was re-hired after resigning a few weeks ago Previously he came to Ennis as the Assistant Finance Manager after being referenced by his friend so did Muli.In a conversation with Mayor Kameron Raburn PLEASE LOG IN FOR PREMIUM CONTENT. Our website requires visitors to log in to view the best local news. Not yet a subscriber? Subscribe today! Click here to read Ennis News IN SHORT: A graphic that appears to be from the Star news website quoting the president of the Law Society of Kenya on the electoral commissioners' selection committee A graphic on social media in Kenya attributes a quote to Faith Odhiambo, the president of the Law Society of Kenya (LSK) In the graphic, Odhiambo appears to question Koki Muli's suitability for a place on the panel that will select commissioners for the Independent Electoral and Boundaries Commission (IEBC) Ambassador Dr Koki Muli Grignon is a distinguished Kenyan scholar The graphic appears to have been published by Kenyan newspaper the Star and reads: “Koki was thrice rejected as an IEBC commissioner Now she seeks a spot on the selection panel We must investigate her motives and suitability!”  The graphics feature a photo of Odhiambo In October, the opposition Azimio la Umoja coalition selected Muli as its representative on the IEBC selection panel. Muli’s name had previously been submitted to the panel But is the graphic to be trusted Get a weekly dose of facts delivered straight to your inbox Africa Check didn't find any reputable media outlets reporting on the claim in the graphic We compared the graphics with those published by the media outlet on its social media platforms and found inconsistencies The legitimate graphics use a different logo and are dated On 13 December, the publication flagged the suspicious graphic as “fake” “FAKE NEWS ALERT: This online card is not our original version; please ignore,” the Star wrote on X the graphic continues to be shared online as if it came from the Star You can republish the text of this article free of charge, both online and in print. However, we ask that you pay attention to these simple guidelines as in most cases we do not own the copyright 3. Make sure you credit "Africa Check" in the byline and don't forget to mention that the article was originally published on africacheck.org A fact-checker has rated your Facebook or Instagram post as “false” Click on our guide for the steps you should follow The content we rate as “false” will be downgraded on Facebook and Instagram public figures need to be held to account for what they say non-partisan organisation which assesses claims made in the public arena using journalistic skills and evidence drawn from the latest online tools sorting fact from fiction and publishing the results Help us keep it that way by supporting our work Africa Check values your trust and is committed to the responsible management, use and protection of personal information. See our privacy policy. Support independent fact-checking in Africa. Subscribe To The Newsletter to receive relevant stories googletag.cmd.push(function(){googletag.display('div-gpt-ad-hero-single-1');}); jQuery(window).on('load',function(){header_js();});jQuery(document).ready(function(){menu_close_button();});jQuery(document).ready(function(){cookieyes_btn();}); .cky-btn-customize{display:none} NewsErik Santos Set To Drop ‘Pagbigyang Muli – I Will Never Leave You’ Mix Release ‘Greatest Hits Live!’ VinylThe renowned balladeer has a lot in store for his fans in the coming months By photographed by Ellah Plariza and Miggy Rivera Erik Santos will soon be compiling some of his best live performances yet on record Last Tuesday (October 29), the renowned pop balladeer performed a collection of his well-loved ballads at the Ayala Museum in Makati City announced that he would drop a fifteen-track album of the performances next year in February 2025 The artist is also set to release a mix of his hits “Pagbigyang Muli” and “I Will Never Leave You” this November 8 He had previously debuted this mix at his sold-out ‘MilEStone: The 20th Anniversary Concert’ held last October 6 1 for almost one year in almost all the charts since its release back in 2004 and I am so blessed to have been given this very beautiful masterpiece that is also celebrating its 20th anniversary this year.” His Greatest Hits Live! album will be available on double vinyl, and can be pre-ordered here the balladeer is preparing to release a new album by next year and will be releasing a docu-concert that will be available for streaming soon In anticipation of Erik Santos’ “Pagbigyang Muli – I Will Never Leave You” mix listen to “Pagbigyang Muli” here: © 2025 Modern Media Group Inc. is a subsidiary of AGC Power Holdings Corp. All rights reserved. She now stars in the sizzling new Showmax crime drama The Chocolate Empire a young woman from a struggling family who lands a job at JB’s (played by the legendary Jimmy Gathu) nightclub to make ends meet She just might be the next big love interest in this thrilling series.  Ann reflects on meeting her idols and her newest role The audition process was nothing short of intense If you have ever crossed paths with Phillip Bresson you would know he’s as thorough as they come especially since she had two sides: her normal self and a more rebellious version I watched shows like Rockville from South Africa for inspiration It really helped me get into the right mindset before stepping on set.  Playing the “good girl” side was much easier for me because it felt natural Music really helped set the mood and made it all come together.  Day one on set was very intimidating for me Sharing a set with these legends was so iconic Working with the one and only Sanaipei Tande I even attended some of the karaoke nights she hosted.  I had some intense steamy scenes with Jimmy’s character the directors knew how to set the mood – bringing in intimacy coaches to ensure everything was handled with care and professionalism But don’t let the on-screen sparks fool you What looks smooth and sexy on camera is anything but during filming and endless direction all happening at once.  Filming with Sanaipei was no walk in the park who’s both a guiding force and an unyielding obstacle If I had a dollar for every time Margaret slapped me in the show She really instils the fear of God in Lily – it’s powerful and fuels so much of their emotional conflict The raw intensity of these moments was thrilling to dive into Working with Sanaipei fed into that fear and love making those emotional scenes so impactful but channelling that raw emotion takes everything out of you One of the best pieces of advice I have received is to never lose yourself you might give so much of yourself that you forget who you are So always take care of yourself and never compromise your values.  A heart-pounding bungee jump in South Africa I want to feel that adrenaline rush – it’s been on my mind for ages Can you believe I’ve never been to the Maasai Mara at my age Watch Ann Muli in The Chocolate Empire now streaming on Showmax.   TV presenter, actress and singer Ntombee Ngcobo-Mzolo to host The Mommy Club reunion for the second consecutive year. The two part reunion streams on Showmax on 17 and 24 May 2025. Laugh Africa Comedy Festival announces Faizon Love as the festival’s new international headliner, following Deon Cole’s withdrawal due to an unforeseen medical emergency. The star-studded lineup of panelists at the Showmax Roast of Helen Zille includes Patricia de Lille, Loyiso Gola, Zwai Bala, JJ Tabane and more. Look out for your first newsletter in your inbox soon The best of Melbourne straight to your inbox We help you navigate a myriad of possibilities Sign up for our newsletter for the best of the city By entering your email address you agree to our Terms of Use and Privacy Policy and consent to receive emails from Time Out about news Sign up for our email to enjoy Melbourne without spending a thing (as well as some options when you’re feeling flush) Our newsletter hand-delivers the best bits to your inbox Sign up to unlock our digital magazines and also receive the latest news By entering your email address you agree to our Terms of Use and Privacy Policy and consent to receive emails from Time Out about news, events, offers and partner promotions. Melbourne Time Out Melbourne never writes starred reviews from hosted experiences – Time Out covers restaurant and bar bills for reviews so that readers can trust our critique Muli Express offers a unique offering to its predecessors with a brisk but friendly standing-only service style that sets it apart from the crowd We visit late on a Tuesday afternoon yet we’re put on standby as the place is completely full The pint-sized venue does not have a liquor license – there’s just a small fridge full of soft drinks and Heaps Normal – so we duck around the corner for a beer we’re able to snag a spot “at the bar” peering over dozens of live oysters with owner Van Tran as our guide Her eagerness to offer assistance is much appreciated There are roughly twenty oysters on offer at any given time with nicknames like “Rock Hard” “Angel’s Happy Tears” and “Tarzan” While they’re labelled by provenance and sorted by price it’s still tricky to gauge what’s what by name alone The best approach is to let Tran take her pick.  she curated a selection progressing from mild-flavoured and petite to rich and meaty based upon our preferred style and how many oysters we wanted to eat there’s a $38 tasting menu featuring a mixed half-dozen that spans style and region It’s not fair to say that the supersized “Big Boy Sam” from Port Douglas is any better than the “Morning Glory” from Coffin Bay every pick of the bunch was objectively great – mostly because you can taste that they were shucked just seconds before That’s why Tran will likely steer you away from the condiment station she mostly suggested a light spritz of lemon to let the shellfish shine All the oysters are sourced fresh from farmers that the team work with directly (They previously ran Footscray’s D&K Live Seafood.) Eating there is similar to visiting the fresh seafood stalls at Queen Victoria or South Melbourne market where diners can perch at a butcher’s block with their catch of the day at least you’re in a dedicated space designed just for that purpose.  The shop isn’t trying to compete with its neighbours with a fancy fitout or excessive menu focusing on what the team does best: top-tier this standing-room-only spot offers an experience that’s hard to forget Thanks for subscribing! Look out for your first newsletter in your inbox soon! twitterinstagrampinterestAbout us Contact us This website is using a security service to protect itself from online attacks. The action you just performed triggered the security solution. There are several actions that could trigger this block including submitting a certain word or phrase, a SQL command or malformed data. You can email the site owner to let them know you were blocked. Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page. Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the “Treatise on Febrile Diseases” written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study. Volume 14 - 2023 | https://doi.org/10.3389/fendo.2023.1206353 This article is part of the Research TopicBenefits and Risks of Drug Combination Therapy for Chronic Metabolic DiseasesView all 8 articles Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the “Treatise on Febrile Diseases” written by the founding theorist of Traditional Chinese Medicine While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia An adenine diet-induced chronic kidney disease (CKD) model was established in mice we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice as well as the production of insomnia related regulatory proteins and inflammatory factors Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice and Orexin R2 in the hypothalamus of CKD mice decreased significantly while Orexin and its receptors increased remarkably after CLMD intervention reduced neuron loss and improved learning as well as memory ability were observed in CKD mice And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK which further inhibits NF-κB downstream signaling pathways thereby improving the disordered inflammatory state in the central and peripheral system More research is required to confirm the clinical significance of the study Chronic kidney disease (CKD) refers to the reduction of glomerular filtration rate and irreversible damage to renal structure as well as function due to various causes (1) Compared with patients with other chronic diseases CKD patients often require longer and more frequent hospitalizations the incidence of metabolic syndrome is significantly higher than that of the general population the goal of CKD treatment includes not only delaying the progression of the disease but also reducing complications and accompanying symptoms there is an urgent need to develop drugs to improve metabolic disorders in CKD patients while improving their sleep and quality of life The Chaihu-Longgu-Muli decoction (CLMD) was originally recorded in the “Treatise on Febrile Diseases” written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing, 1,800 years ago. CLMD has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, depression, anxiety, and dementia(7–9) indicating that orexin-A might be a therapeutic target of CKD-related insomnia we evaluate the effects of CLMD in insomnia and explore the molecular mechanisms After an adenine diet-induced CKD mouse model was established insomnia-related behaviors were observed after treatment with CLMD We aimed to observe the potential neurobiological mechanisms by observing the orexin-A-related signal pathway in the hypothalamus and hippocampus and effect of treatment with CLMD Specific pathogen-free(SPF)male C57/BL6 mice were raised in the Experimental Animal Center of Chongqing Hospital of Traditional Chinese Medicine The environmental temperature was set at 24 ± 2°C with a relative humidity of 60 ± 5% and the mice ate and drank freely in alternating light and dark for 12 hours The animal experiment methods were based on the Guidelines for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Institutional Committee of Chongqing Hospital of Traditional Chinese Medicine(NO.2020-DWSY-LF) The CLMD formula contained the following: Bupleurum chinense DC Scutellaria baicalensis Georgi(4.5 g) Cinnamomum cassia (L.) J.Presl (4.5 g) All drugs were purchased from the Pharmacy Department of Chongqing Hospital of Traditional Chinese Medicine Figure 1 The quantities of two characteristic pharmaceutically active substances in CLMD preparation for study (A) Reference standards; (B) CLMD preparation Previous studies have shown that administering an adenine diet can lead to chronic kidney damage, such as massive proteinuria, deterioration of renal function, and pathological damage of renal tubules and interstitial tissues. Therefore, this study followed the literature (14) After 60 C57/BL6 mice were fed with a 0.2% adenine diet for 2 weeks four mice were selected for detection of serum creatinine and urea nitrogen indicators and 50 mice were randomly selected to be weighed and enter the follow-up experiment Purine-fed mice were randomly divided into CKD(n=10) and 10 normal diet mice comprised a control group and CLMD-H groups continued the purine diet and CLMD-H groups were also given CLMD by gavage at a dose of 2.36 g/kg and the CKD group was given a normal saline gavage The control group continued the normal diet and were administered saline for 4 weeks 24-hour spontaneous activity monitoring was carried out 3 days before the end of the gavage to evaluate circadian rhythms mice were weighed and then performed a 6-day water maze behavior test four of the mice were deeply anesthetized and perfused transcardially with cold PBS followed by 4% paraformaldehyde and processed for histochemical and immunohistochemical analyses Six of the mice were euthanized and their eyeballs and fresh brain tissue samples were collected for enzyme-linked immunosorbent assay (ELISA) and western blotting (WB) detection The circadian rhythms of the mice were monitored using a spontaneous activity experiment video analyzer set to a 12D/12L light-dark cycle (0–12 h was light-on time and the mouse activity was recorded every 2 h during which the length of time and the number of activities performed by the mice was recorded Activities were recorded over a 3-day period and the difference between the longest and shortest time of activity in each group of mice (recorded as time variability) was compared Changes in mouse circadian rhythms were also analyzed Dilute pentobarbital with 0.9% normal saline to 1%, experimental mice was injected intraperitoneally at a dose of 45mg/kg (15, 16) The time from pentobarbital injection to the disappearance of the righting reflex was recorded as the sleep latency The time from the beginning of sleep to the disappearance of the righting reflex was recorded as the sleep time The sleep latency and sleep time of mice in each group were compared the Morris water maze (MWM) was used to test the spatial learning and memory abilities of the mice in each group The mice were placed in a circular pool with three quadrants An underwater platform was placed in the third quadrant and the mice were placed in the opposite quadrant The mice were placed in the water and the time taken for the mouse to reach the underwater platform was monitored (escape latency If the mouse did not find the platform within 90s it was guided to the platform and made to stay there for 30s a space exploration experiment was conducted on the 6th day after the training The mouse exploration trajectory was recorded within 90s and the number of platform crossings during that time was recorded as well as the percentage of time spent in the target quadrant subsequently incubated for 1 hour and then centrifuged at 4000 rpm for 15 minutes at low temperature The supernatant was collected for further analysis ELISA kits were used to measure levels of the following inflammatory factors: serum creatinine (C011-1-1; Nanjing Jiancheng urea nitrogen (C013-1-1; Nanjing Jiancheng peripheral tumor necrosis factor-alpha (TNF-α) interleukin-6 (IL-6)(H007; Nanjing Jiancheng Fresh brain tissue was also collected from the hippocampal protein homogenate and passed through a bicinchoninic acid (BCA) assay kit (H004; Nanjing Jiancheng Bioengineering Institute) to measure the protein concentration IL-10 and IL-4 expression levels were quantified and orexin receptor2 in the mouse hypothalamus AMPK and their phosphorylated proteins derivatives in the hippocampus were measured The protein expression levels of TNF-α and IL-1β in the hippocampus were also detected The mouse hippocampus tissue protein was extracted according to the experimental procedure The concentration of each sample was calculated using BCA 20 μg of the sample was placed into each well the membrane was transferred and blocked at room temperature for 2h The primary antibody was diluted in different proportions at 4°C overnight washed with triton-X-100 TBS(TBST) (1:10000) for 3×5 min It was then incubated for 2 h at room temperature and placed in ECL luminescent solution to visualize the band Image J 1.41 software was used to measure the mean gray value of the bands and applied for statistical analysis Primary antibodies used were: orexin (ab255294; Abcam orexin R2 (PA5-77567; Thermo Fisher Scientific TNF-α (11948S; Cell Signaling Technology [CST] p-NF-κB P65 (3033S; CST); NF-κB (8242S; CST) AMPK (2532S; CST); and p-AMPK (2535S; CST) Secondary antibodies used were: goat anti- mouse IgG(H+L) (1:10000) (115-005-003; Jackson ImmunoResearch Laboratories Inc. USA) and goat anti-Rabbit IgG(H+L) (1:10000) (111-005-003; Jackson ImmunoResearch Laboratories Inc.) After the mice were perfused with paraformaldehyde and then frozen sectioned with a thickness of 20 μm permeabilized with 0.5% Triton for 40 minutes blocked with 5% bovine serum albumin(BSA) for 1 h placed in 1:400 anti-NeuN (26975-1-AP; ProteinTech Group Inc. Secondary donkey anti-rabbit antibody-AF555 (6441-32; SouthernBiotech USA) was added at 1:500 and samples were left for 2 h at room temperature The NeuN positive cells were counted (where four mice in each group were selected for frozen section and hippocampus CA1 area as well as CA3 area were selected for cell count) Student’s t-test or one-way ANOVA were used to analyze the significant differences in groups Data are presented as the Mean ± Standard error of the mean (SEM) P < 0.05 was considered statistically significant Figure 2 Cage activity following CLMD treatment among adenine-induced chronic kidney disease (CKD) mice After 4 weeks of control or CLMD treatment in CKD mice (n=10 in each group) cage activity (A–E) was measured by infrared sensor and video monitoring Time-series activity data are shown with individual plots (A); 2-hour bins (A Time variations are shown as the difference between the highest and lowest activity time of each mouse (E) The dark shadows indicate the time of lights-off (Zeitgeber time; ZT0 is the time of light-on and ZT12 is the time of light-off; ZT12–24) Effects of CLMD on hypnotic response in CKD mice in the pentobarbital-induced sleep test—sleep latency (F) and sleep duration (G)—are shown All values are expressed as individual plots with mean ± standard deviation P values versus control: *P < 0.05; **P < 0.01; P values versus CKD: #P < 0.05; ##P < 0.01; ns P > 0.05 Figure 3 Representative swimming traces and heat map of different CKD mice groups in the MWM test (A) The water maze area was defined by four quadrants The small circle in quadrant 4 was the platform position Quantitative analysis of the time taken to find the platform in the MWM test (B) The number of times a mouse crosses the platform (C) and the percent distance (E) in the quadrant area in the spatial probe test are shown The data are presented as mean ± standard deviation (n = 10/group) NeuN immunofluorescence staining was performed on each group of mice to evaluate the survival of neurons in the hippocampus. The results showed that the number of NeuN positive cells in the CA1 and CA3 regions of the hippocampus of CKD mice was significantly reduced, while doses of CLMD-M and CLMD-H could significantly reduce the number of neurons lost in the CA1 and CA3 regions of the hippocampus in CKD mice (Figure 4) Figure 4 CLMD significantly reduced neuron loss in CKD mice NeuN immunofluorescence staining of the CA1 and CA3 hippocampus region (A) NeuN positive cell count graph of CA1 (B) and CA3 hippocampus region (C) All values are expressed as individual plots with mean ± standard deviation (n = 4/group) P values versus control: **P < 0.01; P values versus CKD: #P < 0.05; ##P < 0.01; ns P > 0.05 Figure 5 CLMD increased the expression of orexin and orexinR2 in the hypothalamus of CKD mice Representative western blot images of protein orexin-A (A) and the quantitative analysis of protein level of orexin-A All values are expressed as individual plots with mean ± standard deviation (n = 6/group) the protein levels of p-CaMKK2 and p-AMPK in CKD mice were significantly down-regulated (P<0.01) while the protein levels of p-NF-κB were significantly up-regulated After intervention with CLMD, the levels of p-CaMKK2 and p-AMPK were partially restored. Compared with the CKD group, the protein levels of p-CaMKK2 and p-AMPK in the CLMD medium- and high-dose treatment groups were elevated significantly (P<0.05 or <0.01). Meanwhile, the phosphorylation level of NF-κB was significantly down-regulated by CLMD treatment (P<0.05 or P<0.01). These results are shown in Figure 6 Figure 6 CLMD activated the CaMKK2/AMPK pathway and inhibited NF-κB pathway Representative western blot images of protein p-CaMKK2 and CaMKK2 (A) and the quantitative analysis of protein levels of p-CaMKK2/CaMKK2 Figure 7 Representative western blot images of protein IL-1β (A),TNF-α (B) and the quantitative analysis of protein levels of IL-1β and the quantitative analysis of hippocampal tissue anti-inflammatory factor IL-4 (C) and IL-10 (D) Figure 8 The quantitative analysis of serum anti-inflammatory factor IL-1β (A) and Serum Urea nitrogen (D) and Serum creatinine (E) Change in body weight (F) All values are expressed as individual plots with mean ± standard deviation (n = 6/group) P values versus control: **P < 0.01 P values versus CKD: #P < 0.05; ##P < 0.01; ns P > 0.05 Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula for neuropsychiatric disorders To study whether CLMD could modulate CKD-related insomnia we used a 0.25%-adenine diet to induce CKD in mice the total activity of mice decreased at night-time our results demonstrate that CLMD can improve sleep disturbances in adenine-induced CKD Further, we performed a preliminary exploration of the mechanisms of CLMD in improvement of sleep disorders. As a key modulator of sleep rhythm, decreases in orexin levels could shorten non-REM and REM sleep periods and increase wakefulness, and also cause anxiety. As mentioned earlier, previous studies have shown that the expression of orexin-A and orexin receptor-1 in the hypothalamus of CKD rats is low (12) the expression of orexin-A and orexin R1 in adenine-induced CKD mice was down-regulated This suggests that CLMD may improve the sleep rhythm of CKD mice by regulating the expression of orexin and orexin receptors in the hypothalamus Our research has also shown that CLMD has a protective effect on neurons while intervening to restore sleep rhythms in CKD mice NeuN immunofluorescence detection on frozen sections of mouse brain showed that CLMD significantly reduced the loss of neurons in the CA1 and CA3 regions of the hippocampus in CKD mice results of the MWM task showed that after CLMD intervention the learning and memory ability and spatial exploration ability of CKD mice were improved and the cognitive function of CKD mice was also significantly improved This indicates that CLMD could improve sleep by increasing the levels of orexin-A and orexin receptor-1 in CKD mice CLMD could increase the phosphorylation levels of the CaMKK2/AMPK pathway in the hippocampus of CKD mice inhibiting the activation of NF-κB and then down-regulating the release of pro-inflammatory factors in the brain to play a neuroprotective role We further tested whether CLMD could affect the peripheral inflammation state of CKD mice The results showed the levels of IL-1β and TNF-α in the peripheral serum of CKD mice after CLMD intervention were also significantly reduced further confirming that CLMD intervention effectively improved the chronic inflammatory state of CKD mice we tested the serum creatinine and urea nitrogen levels of CKD mice and the results showed that not only did CLMD not increase the serum creatinine and urea nitrogen levels but that renal function had a trend toward improvement after intervention with CLMD (no statistical significance) The comparison of the weight of mice before and after treatment also shows that CLMD intervention is beneficial to weight loss in mice in a CKD model and this further confirms that CLMD is safe to apply to sleep disorders in CKD mice this study is just a preliminary pilot animal test and more research is required to confirm the clinical significance of the study our results suggest that CLMD could improve sleep disorders and cognitive levels of CKD mice The mechanism may be related to the up-regulation of orexin-A and increases in the phosphorylation level of CaMKK2/AMPK which further inhibit NF-κB downstream signaling pathways without affecting renal function The original contributions presented in the study are included in the article/supplementary Files further inquiries can be directed to the corresponding author/s The animal study was reviewed and approved by Animal Care and Use Institutional Committee of Chongqing Hospital of Traditional Chinese Medicine FL and MS designed and conducted experiments FL and X-LC participated in experiment design and article proof reading G-BL assisted in data collection and manuscript preparation The final manuscript has been all authors read and approved by all authors This work was supported by Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) Clinical Study on the Mechanism of Regulating Neuroimmune Interaction by Chaihu-Longgu-Muli decoction to Improve CKD (grant number 2022MSXM169) and Depression and Clinical effect of Chaihu-Longgu-Muli decoction combined with electroacupuncture moxibustion on female over-activity of bladder with anxiety(grant number 2023MSXM168) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Calcium/Calmodulin Dependent Protein Kinase Kinase 2; (AMP) Adenosine 5’-monophosphate; AMPK,-activated protein kinase; NF-κB and clinical trials of mortality risk in chronic kidney failure Lancet (London England) (2014) 383:1831–43 Sleep and activity in chronic kidney disease: a longitudinal study PubMed Abstract | CrossRef Full Text | Google Scholar A comparison of quality of sleep between patients with chronic kidney disease not on hemodialysis and end-stage renal disease on hemodialysis in a developing country Inflammation in end- stage renal disease–what have we learned in 10 years Daytime sleepiness in stable hemodialysis patients Am J Kidney Dis (2003) 41(2):394–402 The Orexin/Receptor system: molecular mechanism and therapeutic potential for neurological diseases Involvement of NMDA-AKT-mTOR signaling in rapid antidepressant-like activity of chaihu-jia-Longgu-Muli-tang on olfactory bulbectomized mice Behavioural and psychological symptoms of dementia in an alzheimer's disease case successfully treated with natural medicine: association with gonadotropins Psychogeriatrics (2013) 13(2):124–7 Am Coll Neuropsychopharmacol (2020) 45:6–20 CrossRef Full Text | Google Scholar Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep and ob-r of hypothalamus in rats with chronic renal failure Zhongguo Yi Xue Ke Xue Yuan Xue Bao (2004) 26:56–61 PubMed Abstract | Google Scholar Immediate and persistent antidepressant-like effects of chaihu-jia-Longgu-Muli-tang are associated with instantly up-regulated BDNF in the hippocampus of mice Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice Sleep promoting effect of luteolin in mice via adenosine A1 and A2A receptors Hypnotic effects of lactobacillus fermentum PS150(TM) on pentobarbital-induced sleep in mice Google Scholar Morris water maze: procedures for assessing spatial and related forms of learning and memory Sleep and CKD in Chinese adults: a cross-sectional study Sleep and the Risk of Chronic Kidney Disease: A Cohort Study Sleep apnea and daytime sleepiness in end-stage renal disease PubMed Abstract | CrossRef Full Text | Google Scholar Subjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study Abnormal nocturnal heart rate variability response among chronic kidney disease and dialysis patients during wakefulness and sleep Update on inflammation in chronic kidney disease PubMed Abstract | CrossRef Full Text | Google Scholar Orexin a alleviates neuroinflammation via OXR2/CaMKKβ/AMPK signaling pathway after ICH in mice Orexins as novel therapeutic targets in inflammatory and neurodegenerative diseases China Pharmacopoeia 2015 China Medical Science and Technology Press Google Scholar Keywords: Chaihu-Longgu-Muli decoction (CLMD) Li F and Song M (2023) Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice Received: 15 April 2023; Accepted: 12 June 2023;Published: 27 June 2023 Copyright © 2023 Cao, Peng, Li, Ding, Wang, Wang, Xiong, Xiong, Li and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Fan Li, cnlsMTExNkAxNjMuY29t; Min Song, MjY4MTgzNzhAcXEuY29t †These authors have contributed equally to this work Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish The National Liberal Party (Kenya) party leader Augustus Kyalo Muli on Monday blamed Kalonzo Musyoka’s Wiper party for the hurdle that has halted the reconstitution of the Independent Electoral and Boundaries Commission (IEBC) Speaking in a morning show on Citizen TV, Muli explained the refusal by the Wiper Party to approve his election to the selection panel and instead fronting Koki Muli as his replacement is what led him to challenge the decision in court The NLP party leader maintained that the elections were held according to Section 2(b) of the first schedule of the IEBC Amendment Act 2024 in which he emerged victorious “An election was held in the Azimio Coalition involving all the 23 parties and I won 16 against Koki Muli who got 7 It's clear nobody has ever challenged the elections,” he stated emphasising that no one has replaced him his election was credible as the political party liaison committee facilitated an election that was supervised by the IEBC Augustus noted that the Wiper Party wanted to short-change his victory and have Koki Muli vowed to hold the position because he won through a proper election I am the only one who has a certificate so nobody else has any authority to say that they are selected in the selection panel,” he asserted He linked the refusal to approve his name to powerful vested interests in the elite political class “We know very well that the Wiper leader wants to be a presidential candidate in 2027 and that’s why he wants to be the only person that goes to the selection panel,” he said The NLP boss blasted Kalonzo for misleading Kenyans insisting that his party is responsible for the delay in the appointment of the selection panel that will oversee the reconstitution of IEBC.  “I think it’s time for leaders to become responsible and stop fooling Kenyans Simply because one has a microphone and media attention he should not go cheating Kenyans because we do not have a chance to respond,” he stated This came after civil society groups raised objections in an attempt to replace Augustus Muli Led by Musili Kauta of the Centre for Progressive Leadership and Musembi Kitavi of Kitui Peace Economic Front the civil groups questioned Wiper’s party insistence to replace Augustus who won the elections There has been a lot of pressure on the government to reconstitute the electoral body the government has defended itself by pointing a pending court case has blocked the process Deputy President Kithure Kindiki on Sunday while commenting on the issue called on parties involved in the case to reach an out-of-court settlement to facilitate the reconstitution of the Commission The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V. Electric bicycles have evolved from simple bicycles with an electric motor strapped onto the back wheel into machines entirely their own cargo e-bikes transform the way people move proving that you don’t need a big car to go about your daily commute you'd have to choose from a wide selection of two all of which emphasize practical urban mobility the Muli Motor ST Pro might just be the right bike for you The German bike company specializes specifically on cargo bikes – both electric and otherwise – and the Motor ST Pro represents the very best Muli Cycles has to offer when it comes to versatility the Muli Motor ST Pro breaks the mold when it comes to cargo e-bikes It’s capable of carrying a respectable 195-kilogram (429-pound) load while at the same time boasting a folding frame that lets you load it in the back of a van or even carry it along with you on the subway or bus the bike is fitted with some impressive componentry that not only ensures a reliable ride but injects a touch of excitement into your daily commute Not willing to trade off pedaling efficiency, the Motor ST Pro makes use of a Shimano Nexus five-speed rear hub complete with Di2 automatic mode. As such, the rider can simply pedal away without having to worry about changing gears. While we’re on the topic of efficiency, the bike is powered by a 630-watt-hour battery pack for increased range in between charges. Putting a stop to the versatile e-bike is a pair of four-piston hydraulic brakes which clamp down on large 180-millimeter rotors. ZF's New EV Range Extender Also Powers The Wheels, But Not Like You Think The 2026 Jeep Compass Gets An EV Version With Up To 404 Miles Of Range Toyota And Google's Waymo May Build An Autonomous Car Platform Together Waymo Is Far From Done With The Jaguar I-Pace Nissan's EV Sedan, Frontier PHEV Make Me Wish For A Different Reality Ford Isn't Slowing Down Mustang Mach-E Production, Despite Tariffs The New Hyundai Palisade Hybrid Drives Like An EV. Here's How This ruling had declared Augustus Kyalo Muli as the legitimate representative of small parties on the IEBC selection panel. Ambassador Koki Muli has filed the case, which is scheduled for mention on Thursday, September 26, before Lady Justice Janet Mulwa.  Meanwhile, Augustus Kyalo Muli has announced that his party, the National Liberal Party, will lead 15 small parties in withdrawing from the Azimio la Umoja coalition. It has been over two months since President William Ruto assented to the IEBC Bill, which set the stage for the reconstitution of the electoral body through the appointment of commissioners and a chairperson in preparation for the 2027 general election.  However, the nomination process for the IEBC selection panel, responsible for recruiting the commissioners, has been thrown into disarray. Ambassador Koki Muli and the Azimio la Umoja coalition have appealed against the tribunal's ruling that named Augustus Kyalo Muli as the nominee.  The appellants argue that the tribunal failed to provide Ambassador Koki Muli the opportunity to be heard, lacked jurisdiction under the Political Parties Act to consider the complaint, selected an inappropriate representative for Azimio la Umoja, and did not uphold the two-thirds gender rule.  They contend that the tribunal overstepped its authority by infringing on Azimio's right to choose its nominee for the IEBC selection panel. In response, Augustus Kyalo Muli has labeled the new suit as an act of impunity and an attempt to undermine the electoral body.  "What we are seeing here is impunity. The court has already pronounced itself. Do we want a divided IEBC? Azimio has a significant role in this. I stand for justice. It is time for the president to clarify his position. We are considering withdrawing from Azimio and will elect our own leader, as we represent the majority," he stated. This controversy surrounding the IEBC selection panel nomination comes just a week after National Assembly Speaker Moses Wetangula urged for the swift reconstitution of the electoral body, calling on those obstructing the process to reconsider their stance. The case will be mentioned on Thursday, September 26, before Lady Justice Janet Mulwa. © 2025 Citizen Digital. All rights reserved. A major health scare has prompted a Hamilton man to shed more than 100kg. At his heaviest, Neum Muli’aumaseali’i weighed in at 293kg. In January 2024, the 39-year-old was taken to hospital with sepsis in his blood. Neum Muli’aumaseali’i says he hasn’t set himself a weight goal – he’s focussed on the non-scale victories like being about to "move and groove" again, or fitting in a seat on a plane. (Source: Breakfast) "I had been massive my whole life," he told Breakfast, "but this was a massive wake-up call." He threw himself into a strict regime of diet, exercise and increased water intake, but said he soon "fell off the wagon". At his heaviest, Hamilton man Neum Muli’aumaseali’i weighed in at 293.2 kilograms. (Source: Supplied) Last November, he started again – and this time, he broadcast it on social media. Muli’aumaseali’i has now amassed more than 45,000 followers on TikTok, where he frequently goes live during his early-morning walks. "[Social media] keeps me accountable for sure, but it's also a really positive place with a lot of encouragement." Learning to accept the compliments has been a challenge, Muli’aumaseali’i said, but he keeps going knowing he is inspiring others to make changes in their own lives. His latest weigh-in, on March 22, put him at 188.5kg. While he steps on the scales every 15 days, Muli’aumaseali’i is not setting an ultimate weight goal, saying focusing on the numbers has been his "downfall" in the past. Instead, he's looking at the non-scale victories - being able to "move and groove" again, or fitting in a seat on a plane. Neum Muli’aumaseali’i celebrates victories beyond a number on the scale. (Source: Supplied) His advice? Don't compare your own journey to others you see online. "Remember, comparison is the killer of dreams. In hospital, I could barely walk five steps without collapsing. That was my benchmark." Juliana Herrera's family tell inquest: 'Stop repeating avoidable mistakes' was murdered in January 2022 by her neighbour Health Homegrown music festival's new location revealed New Zealand Good Sorts: The retired Feilding GP running a mobile medical service Dr Warren Nicholls has taken his skills on the road to increase access to healthcare Life-saving heart transplant technology a 'game changer' Doctors at Auckland City Hospital have been using a HOPE box for heart transplants – and they're showing promising results Warning of poisonous shellfish in Western Firth of Thames New Zealand Food Safety said routine tests on shellfish from Waimangu Point have shown levels of the toxins over the safe limit Environment New air ambulance unveiled for Auckland and Northland The Leonardo AW169 swept into action as a welcome service for Auckland and Northland as one of nine new or near-new choppers to replace the ageing fleet Film industry anxiously awaits details on Trump's 100% movie tariff 7:17pm Search underway for Masterton man, 74, missing since Sunday 7:07pm Crooks, culture first order of business for Mike Bush in Victoria 7:05pm Charges filed against Woolworths over pricing, misleading specials 6:45pm Police, experts warn 'emerging risk' of 3D-printed firearms rising 6:33pm Trade war: Sir John Key's 'optimism' on Trump's next tariff moves 7:28pm 1US woman who disappeared for more than six decades found safe Sole survivor of poisoned beef Wellington takes the stand Person dies following morning crash on Auckland motorway US prisons bureau has challenges — reopening Alcatraz is now another Two men's shared name brings years of trouble and a hefty bill to one Photos: Lorde among stars at 2025 Met Gala A$AP Rocky and Rihanna also revealed they are expecting their third child. Two arrested over alleged plot targeting Lady Gaga concert in RioBrazilian police said they thwarted an alleged bomb attack planned for Lady Gaga's concert on Copacabana beach in Rio de Janeiro. Lady Gaga rocks Copacabana Beach with free concert for over 2 million fansSun, May 4 Lorde announces new album name, dateThu, May 1 Kim Kardashian to testify in Paris trial over 2016 armed robberyMon, Apr 28 Chubby Checker, Outkast, Cyndi Lauper join Rock & Roll Hall of FameMon, Apr 28 Kim Kardashian to testify in Paris trial over 2016 armed robberyMon Hamilton has been announced as the new home for the Homegrown music festival In January the festival, which features New Zealand music, confirmed it would be leaving Wellington's waterfront after being there for 18 years From next year it will be held at Hamilton's Claudelands Oval Festival director Andrew Tuck said the move is "about creating something that celebrates our roots and gives back to the region that inspires us" Organisers said that Hamilton offers potential for the festival to expand and evolve as New Zealand's fastest-growing city "Its central location — just a short journey from the Bay of Plenty and the King Country — makes it accessible for a wide range of attendees eager to enjoy Aotearoa's finest musical acts." Tuck said accessibility for as many people as possible is key for the festival and "being close to such a large population makes this dream even more achievable" Hamilton City Council deputy chief executive Sean Murray said the festival returning to the Waikato is "a win for the whole upper North Island" Next year's event will be held on March 14 Tonight's Good Sort is Dr Warren Nicholls a retired GP from Feilding who never quite stopped being a doctor Dr Nicholls took his skills on the road as part of a mobile medical service aimed at increasing access to healthcare There are no appointments needed – people just show up the team checks basic information like weight "There's a huge need for it," Dr Nicholls said The service began with local farmer Dean Williamson who wanted farmers to get more than their tractor checked up "To be able to book a health check in with the doctor you're looking at four or five weeks in advance and goodness knows what the weather's going to be like or what they're going to be doing on farming," Williamson said "I've signed a thousand death certificates but I've also delivered a thousand babies so the ledger of life is balanced," he said One caravan has now turned into a three and they've seen over a thousand patients He said one in four patients need further help "We've got a person who's probably a diabetic with a sugar of 12 and they don't know it." A mental health survey always finishes the visit it's their first doctor's visit in years "I haven't retired yet," Dr Nicholls said he wants to expand his operation into Northland "It's become my glorious obsession now." Taylor Keepa was like every other teenager full of plans for the future beyond the walls of Rototuna Senior High School But undergoing a heart transplantation was never one of them Taylor was in his final year of school in 2023 working a real estate internship and a part-time job at McDonald's when he began experiencing symptoms like shortness of breath and fatigue "I would have to take a break on my walk to school and even just doing nothing I would struggle to breathe," he told 1News What followed was a frustrating series of visits to the doctors and Waikato Hospital where he was initially diagnosed with pneumonia Taylor and his mother Michelle were given a devastating diagnosis – left and right ventricular non-compaction cardiomyopathy a rare condition which was causing his heart to fail that's when we were getting a chopper from Waikato Hospital to Auckland Hospital and then the very next day he was put on life support; he was put on an ECMO machine that took over the function of his heart," Michelle said And I just had to watch it all happen." Taylor was now facing the biggest battle of his life What followed was a series of surgeries to keep the teenager's heart beating as he awaited transplantation Just days after being rushed to Auckland Hospital doctors inserted a Ventricular Assist Device (VAD) – a mechanical pump that helps circulate blood from his heart to the rest of his body "It's kind of like having two satchels and they both cross over you and you kind of wear them like bags There are two wires that attach to your heart and sort of come out of your stomach area and funnel into these batteries," he said including a portable mode which has a 12-hour battery life Taylor would have to plug the batteries – still attached to him – into a power outlet while he slept "They definitely did not make it easy You would constantly be thinking about them Did I charge them correctly?" he said Taylor was eventually put on the urgent donor list "When you're put on the urgent list that's basically saying there isn't much longer we need this now" But seven months later on New Years Day 2024 during an intense card game in the hospital cafeteria with his dad 'I don't want to get your hopes up "It was kind of like a 'finally' type moment a heart was transported from Australia using a Hypothermic Oxygenated Perfusion box A Hypothermic Oxygenated Perfusion box – also known as a HOPE box by staff at Auckland City Hospital – is a specialised device used in organ transplantations The technology helps preserve oxygen and blood flow to a heart keeping the donor organ viable for longer than other traditional methods "It's basically like a really fancy version of a chilly bin It has a cooling device that keeps the heart at 8C and then it is perfused with blood and nutrients to provide exactly what the heart needs," said Dr Jamie O'Loughlin clinical lead for the Auckland Heart and Lung Transplant programme "The cool temperature keeps the metabolic demands low but providing oxygen and blood keeps the heart in the best condition that we can prior to transplant." The device was part of a clinical trial at Auckland City Hospital from March 2021 to December 2022 and has been used for 18 transplantations in New Zealand – five of those involving donor hearts flown in from Australia Dr O'Loughlin described the HOPE box as a "game changer" "We're not up against a time frame knowing that the donor heart is deteriorating over time so it gives us a lot of leeway in terms of how fast we're progressing the operation and the surgeons can take their time and do it really carefully," she said But this type of technology doesn't come cheap The technology is currently funded through donations given to the Auckland Hospital Foundation which means patients must meet strict criteria to qualify Advocates hope the Government will one day help fund the device so more people can access it "It's enabling the teams to build the capacity enabling the teams to build the care pathways and then for it to be adopted in government budgets," said Candy Schroder the director of the Auckland Hospital Foundation The last thing Taylor remembers before his heart transplantation was fist-bumping the surgeons and anaesthesiologists "He'd become quite popular in there," his mum said Taylor had received what he calls "the gift of life" "I remember waking up a couple of days later and I was really high," he laughed "People were coming in and saying hi to me and I was like After surgery he was transferred to Greenlane Hospital's Hearty Towers for recovery and rehabilitation and to connect with other New Zealanders who had also received heart transplants "I'm doing pretty awesome," he said "I'm studying again and I'm working now" When asked about the donor who gave him his heart "I like to think their life continues on in me" His gratitude is echoed by his mother and his wider whānau I wake up and I'm just like 'I still have my son' I'm thankful for everything I have," Michelle said I don't think there are enough words to describe how grateful I am," Taylor added "It's really hard to describe this feeling." People are being warned not to collect or consume shellfish gathered in the Western Firth of Thames region due to the presence of paralytic shellfish toxins The warning extends from the mouth of the Waitakaruru River up to Pakatoa Island and across to the mid-point of the Firth "Affected shellfish include bivalve shellfish such as mussels as well as pūpū (cat's eyes) and Cook's turban," New Zealand Food Safety deputy director-general Vincent Arbuckle said "It's also important to know that cooking the shellfish does not remove the toxin." crab and crayfish if the gut was removed before cooking "New Zealand Food Safety is monitoring shellfish in the region and will notify the public of any changes to the situation," Arbuckle said New Zealand Food Safety said there had been no reported associated illness Commercially harvested shellfish are still safe to eat Symptoms of poisoning appear between 10 minutes and three hours after ingestion and may include: rnz.co.nz Auckland and Northland's emergency medical response capabilities have been boosted with a new air ambulance helicopter Associate Health Minister Hon Casey Costello and ACC Minister Scott Simpson unveiled the new helicopter as part of a national fleet upgrade designed to improve aeromedical services across the country Speaking at Northern Rescue's Ardmore base where the aircraft was now stationed Costello said the helicopter represented a "major advancement" in aeromedical service delivery "We are pleased to see it become operational in this part of the country." the first of its kind to enter service under this initiative important for missions in remote or challenging weather conditions The Auckland/Northland chopper is the third aircraft to be rolled out under the national Emergency Air Ambulance Helicopter Service renewal programme would deliver nine new or near-new helicopters across the country in 2024/25 Ageing helicopters were to be replaced in Auckland "It's great news that this helicopter will support people living in these regions as part of the Government’s investment to upgrade some of New Zealand’s air ambulance fleet." Simpson said the service played a "critical role" in time-sensitive care for people in urgent need particularly in regional and rural communities this is the first helicopter purchased using ACC Investment debt financing which has enabled the ageing helicopter replacement programme to progress at a faster pace "This financing arrangement has contributed to savings of around $500,000 per year." The next helicopter would enter into service in Auckland/Northland in July 2025 A search and rescue operation is underway for a Masterton man in his 70s missing since Sunday John Rafferty was last seen at Masterton Railway Station about midday on May 4 The 74-year-old did not board a train and left on foot about 20 minutes later Matheson said it was possible Rafferty was staying with a friend but police and loved ones "want to know he’s safe" and John doesn’t have his cell phone or wallet," he said A search team and a helicopter has been out looking for the missing man "We are really keen to know that he’s safe." Police have released an image from CCTV showing Rafferty on a station platform on the day of his disappearance He was wearing a blue jacket with 'NASA' written on the back Anyone who saw him was asked to contact police on 111 or online at 105 if there was Information after the fact The next top cop of the troubled Victoria police force embraces his "outsider" status to curb its leadership malaise and has a stern warning for crooks Former New Zealand Police commissioner Mike Bush won the race to become Victoria's chief commissioner after months of top-level staffing woes The 40-year police veteran steps into the role on June 27 with a five-year contract The Kiwi conceded the job will be no picnic with Victoria's crime rate hitting an almost decade-high in 2024 everyone knows that," he told reporters today "These crime issues are actually global they are quite similar wherever you go but it's not good enough just to turn up after the act Rising youth crime and high-profile cases of alleged offenders committing crimes while on bail spurred the Victorian government to strengthen laws in March Bush said he was familiar with the crackdown but bail laws were just one part of the solution to tackling youth crime along with a "prevention mindset" He retired from the NZ police force in 2020 after joining in 1978 and spending his final six years in the top job Whakaari/White Island volcano eruption and Covid-19 pandemic were among the biggest crises Bush confronted during his tenure Bush also made headlines in 2022 after it emerged he had a past drink-driving conviction when unsuccessfully applying to become head of the UK's Metropolitan Police Former New Zealand police minister Stuart Nash describedr Bush as hard but fair He said Bush regularly met with police forces across the Tasman in his previous role and recalled travelling with him to every district across New Zealand once a year to chew the fat with communities and then we all had biscuits and a cup of tea," Nash told AAP "Mike is someone who had deep credibility in policing." The state government has not handed the reins of Victoria Police to an outsider since former NSW Police assistant commissioner Christine Nixon in 2001 The Kiwi was happy to wear the "outsider" tag and is already hatching plans to hit the ground running "I've got a lot to do to come up to speed," Bush said "Culture is a consequence of leadership." establishing relationships with community groups amid rising tensions and increasing police visibility on the beat were among his other top initial priorities Victoria Police was thrust into leadership turmoil in February with a no-confidence vote from officers costing chief commissioner Shane Patton his job Emergency Management Commissioner Rick Nugent became acting chief and expressed an interest in making the move permanent before throwing in the towel in April Deputy Commissioner Robert Hill will serve in an acting capacity until Bush takes over Bush intends to speak with Patton before starting and said he wouldn't shy away from pushing back if he disagreed with the government Premier Jacinta Allan said a recruitment agency was hired and instructed to find a leader capable of addressing the "challenges" plaguing the force "Mike Bush is the best person for the job," she said whose union led the no-confidence vote against Patton following a bitter pay dispute admitted there was a disconnect between members and leaders The state police union secretary welcomed Mr Bush's appointment and pledge to listen to the mounting workforce concerns "We have a police force that is currently under-resourced that needs fresh officers," he said The Commerce Commission has filed criminal charges against Woolworths NZ for alleged inaccurate pricing and misleading specials that may have breached the Fair Trading Act The commission filed the charges against Woolworths in the Auckland District Court It indicated in December last year that it would be filing separate criminal charges against Woolworths and two Pak'nSave supermarkets the commission said there were ongoing issues with pricing in the supermarket sector and the operators may have breached the Fair Trading Act deputy chair Anne Callinan said operators should know what the expectations were "Supermarkets have long been on notice about the importance of accurate and clear pricing and specials and we're not satisfied with the continuing issues we're seeing across the industry "Pricing accuracy is a consumer right and an expectation of a competitive market well-resourced businesses that should invest the time and effort to get pricing and promotions right." She said the charges were filed to remind all supermarkets that they are expected to fix the pricing accuracy issues and implement better processes In a statement when the charges were announced Woolworths managing director Spencer Sonn said it was important customers could trust prices advertised at their supermarkets Woolworths said it has cooperated with the Commerce Commission's pricing investigation for some time rnz.co.nz Former prime minister Sir John Key says he remains optimistic about Donald Trump's domestic economic policy despite opposing the tariff strategy that has sent global markets into turmoil in recent months who served as prime minister for eight years was the keynote speaker at an Auckland business summit earlier today Sir John told 1News he believed Trump would ultimately take a more moderate approach to tariffs than initially proposed "I'm not a fan of tariff policies I don't think they really work," he said as I think the stock market is telling you at the moment that actually there will be a more sensible landing place for the tariffs that he's wanting to impose." Sir John said he "wasn't entirely surprised" at Trump's call to go ahead with the policy "They're just a negotiating point I think he simply put on widespread and high rates of tariffs on every country to give himself a leverage point and a negotiating point "What I think he actually grossly underestimated was the stock market reaction You can actually make the case that his own strategy hasn't worked The reason the markets have recovered is because he's taken those tariffs off the most part 'I'm going to negotiate case by case'." Sir John suggested Trump's economic policies could still generally be positive for the US but the tariffs could be trickier for the global economy Asked whether he stood by his October comments that Trump would be good for the economy he said: "Do I think he's going to reduce regulatory burden in the United States It depends on where things shake down in terms of tariffs." Sir John acknowledged that for certain industries Trump's policies could be "a really negative thing" particularly if the president's proposed 100% tariff on the film industry were to be implemented "I can't see how it would be cost-competitive to make a movie in New Zealand with a 100% tariff on it," he said noting that films such as The Hobbit would not have been made in New Zealand without government subsidies who now served as a director of US tech company Palo Alto Networks said he had "always been opposed" to Trump's tariff policies but believes they won't be the "dominant part of his economic solutions" "I don't think it's perfect from New Zealand's point of view but I don't think we should panic either and America will still be a very big market for us to sell things to," he said "There are growing markets around the world It's not a great thing from New Zealand's point of view We've got a very sound economy with lots of options in front of us." Sir John suggested a belief that the Republican Trump was was better "on balance" for the US economy than Democratic opponent Kamala Harris he expressed concerns about Trump's tariff approach: "China doesn't pay those tariffs middle-income consumers or consumers in America do because when a tariff goes on a good that you bring into a country He added: "I don't agree with the massive tariffs and I don't think you'll follow through with all of that and I certainly don't agree with this view on trade." Audrey Backeberg disappeared from a small city in south-central Wisconsin after reportedly hitchhiking with her family’s babysitter and catching a bus to Indianapolis Nobody ever knew where she went or what happened to her All that changed last week when she was found alive and safe in another state thanks to the fresh eyes from a deputy who took over the case in February Detective Isaac Hanson discovered an out-of-state arrest record that matched Backeberg which triggered a series of investigative moves that led to finding her alive and safe in another state Turns out Backeberg chose to leave the town of Reedsburg on her own accord – likely due to an abusive husband safe and secure; And just kind of lived under the radar for that long,” he said Hanson was assigned the case in late February and he and other officials met with Backeberg’s family to see if they had a connection with that region They also started digging through Backeberg's sister's Ancestry.com account obituaries and marriage licenses from that region they found an address where a woman was living that Hanson said shared a lot of similarities with Backeberg including date of birth and social security number Hanson was able to get a deputy from that jurisdiction to go to the address "I was expecting the deputy to call me back and say ‘Oh nobody answered the door.’ And I thought it was the deputy calling me I could sense that she obviously had her reasons for leaving.” Most of the information he learned during that call he declined to share saying that it was still important to Backeberg that she not be found “I think it overwhelmed her of course with the emotions that she had having a deputy show up at her house and then kind of call her out and talk with her about what happened and kind of relive 62 years in 45 minutes,” he said Hanson described discovering her safe after more than six decades practically unheard of And while he doesn't know what will happen next in terms of her family reconnecting he said he was happy that she can reach out if she wants to so she has my contact number if she ever wants to reach out or needs anything any phone numbers of family members back here," he said "Ultimately she kind of holds the cards for that.” A person has died following a crash on Auckland's south-western motorway this morning The single vehicle crash was reported to police shortly before 5am the sole occupant of this vehicle died at the scene," a police spokesperson said "Earlier closures of northbound lanes have now lifted and police advise motorists to continue to expect delays as earlier backlogs clear "We appreciate motorists' understanding this morning while emergency services carried out their work." Police said the serious crash unit examined the scene this morning and an investigation was underway into this morning's crash on behalf of the Coroner This is in addition to an earlier crash on Auckland's northern motorway near the Auckland Harbour Bridge Emergency services responded to a two-truck collision on the northern motorway near the Auckland Harbour Bridge shortly after 5am New Zealand Transport Agency (NZTA) said all lanes south on State Highway 1 were open again following this earlier crash with five lanes available on the Harbour Bridge "Allow extra time for delays on the Northern Motorway to slowly ease this morning three lanes going south were now open again between Onewa Rd and the Harbour Bridge," NZTA said Eleven inmate deaths in less than two months A US$3 billion (NZ$5 billion) repair backlog a stunning directive from President Donald Trump for the crisis-plagued federal Bureau of Prisons to “REBUILD AND OPEN ALCATRAZ!” — the notorious penitentiary on an island in San Francisco Bay that last held inmates more than 60 years ago Even as the Bureau of Prisons struggles with short staffing chronic violence and crumbling infrastructure at its current facilities Trump is counting on the agency to fulfill his vision of rebooting the infamously inescapable prison known in movies and pop culture as The Rock Trump declared in a social media post that a “substantially enlarged and rebuilt” Alcatraz will house the nation’s “most ruthless and violent Offenders” Newly appointed Bureau of Prisons Director William K Marshall III said that the agency “will vigorously pursue all avenues to support and implement the President’s agenda” and that he has ordered “an immediate assessment to determine our needs and the next steps” We look forward to restoring this powerful symbol of law and justice,” Marshall said in a statement “We will be actively working with our law enforcement and other federal partners to reinstate this very important mission.” an 8.9-hectare spit of land with views of the Golden Gate Bridge and the San Francisco skyline was once the crown jewel of the federal prison system and home to some of the nation’s most notorious criminals including gangsters Al Capone and George Machine Gun Kelly But skyrocketing repair and supply costs compelled the Justice Department to close the prison in 1963 and the Bureau of Prisons has long since replaced Alcatraz with modern penitentiaries including a maximum-security prison in Florence The former and perhaps future penitentiary is now a popular tourist attraction and a national historic landmark It’s controlled by the National Park Service as part of the Golden Gate National Recreation Area meaning the Bureau of Prisons could be in for an interagency tug of war if it tries to wrest away control of the island Trump’s Alcatraz directive is yet another challenge for the Bureau of Prisons as it struggles to fix lingering problems while responding to the president’s priorities on incarceration and immigrant detention includes taking in thousands of immigration detainees under an agreement with the Department of Homeland Security The problems at the Bureau of Prisons transcend administrations and facilities An ongoing Associated Press investigation has uncovered deep previously unreported flaws within the Bureau of Prisons over the last few years including widespread criminal activity by employees and severe understaffing that has hampered responses to emergencies then-President Joe Biden signed a law strengthening oversight of the agency It remains the Justice Department’s largest agency 155,000 inmates and an annual budget of about US$8 billion (NZ$13.4 billion) but the Trump administration’s cost-cutting measures have eliminated some pay bonuses that were credited with retaining and attracting new staff That has resulted in long overtime shifts for some workers and the continued use of a policy known as augmentation teachers and other workers are pressed into duty to guard inmates A Bureau of Prisons official told Congress at a hearing in February that more than 4000 beds within the system — the equivalent of at least two full prisons — are unusable because of dangerous conditions like leaking or failing roofs a 37-year-old Florida businessman who was found dead April 28 in a suspected suicide at a federal jail in Miami He was awaiting trial on charges that he kidnapped and killed his estranged wife in Spain inmate Ramadhan Jaabir Justice was killed in a fight at the federal penitentiary in Pollock where he was serving a nearly 11-year sentence for a conviction related to an armed robbery As Trump was ordering Alcatraz’s reopening correctional officers at the same Miami jail were fighting to curb the spread of tuberculosis and Covid-19 isolating inmates after they tested positive for the diseases immigration detainees at the facility ripped out a fire sprinkler and flooded a holding cell during a lengthy intake process the Federal Correctional Institution in Dublin has sat idle for more than a year after the Bureau of Prisons cleared it of inmates in the wake of rampant sexual abuse by employees the agency made the closure permanent and idled six prison camps across the country to address “significant challenges crumbling infrastructure and limited budgetary resources” While Trump hails Alcatraz as a paragon of the federal prison system’s cherished past other facilities stand as reminders of its recent troubles They include the federal jail in Manhattan which remains idle after Jeffrey Epstein’s suicide there in 2019 exposed deep flaws in its operations where 23 inmates have been charged in recent months with crimes ranging from smuggling weapons in a Doritos bag to the stabbing last month of a man convicted in the killing of hip-hop legend Jam Master Jay Shane William Pritchard has been charged with crimes he didn’t commit and chased for debts he doesn’t owe That’s because the Dunedin man is not the only Shane William Pritchard in town While the duo’s shared name and age has sometimes been a handy loophole for one Shane for the other it has caused problems for 36 years It’s been years of fearing every knock on the door Years of wondering if he’ll be hand-cuffed and taken to jail to be honest,” says Shane William Pritchard a scout and a member of the Air Training Corp remembers getting quite a shock when her friend called one evening She'd been acting as a referee for a gun licence for Shane whose friend informed her that the police had a long list of offences against Shane’s name Not long after that the police turned up to where Shane was working at the local tannery to arrest him “You're scrambling in your head to think of ways that you can prove it's not you.” Another Shane William Pritchard had been born in Otago They were separated by just two weeks and about 50 miles – one growing up in Mosgiel the other in Milton – but also by the lives they’d been leading To watch the full video story go to TVNZ+ Shane from Milton had huge problems focusing at school He was raised in foster care and then boys’ homes I just wanted to look cool and get in trouble,” he tells Fair Go Milton Shane was used to run-ins with police he got pulled over in his car and asked about his driving licence one’s got a licence and the other hasn’t.’ And I’m like ‘obviously it must be the one with a licence’.” he went to his bank to draw out an ACC payment and was asked which bank account was his He says that at that point he was trying to figure out what was going on “I thought it was just an error.” But he took advantage of the situation and withdrew a large sum of cash Mosgiel Shane became aware of the withdrawal when a scheduled car payment was declined and when Milton Shane turned up at the bank to withdraw more money Identity fraud was considered but Milton Shane was legitimately expecting an ACC payment so the withdrawal appeared to be a genuine mistake and the police couldn’t take any action 'Anything I could get away with Mosgiel Shane thought the bank incident would have alerted police to the problem But his nemesis had cottoned on to the advantages of having a second identity to use Milton Shane acquired a suite of furniture on hire-purchase Milton-Shane clocked up more driving offences Mosgiel Shane thought about changing his name but realised he’d have to provide his previous name in the process the courts and debt collectors such as Baycorp should be able to distinguish between himself and Milton Shane The police first addressed the issue in the 1990s after Mosgiel Shane went to the media He was given a letter to carry with him should he be apprehended He and his parents felt his situation wasn’t being taken seriously Mosgiel Shane went to the media a second time in the mid-2000s the police gave their word that a record in their system would stop the misidentification from happening again This does appear to have worked as far as police action goes But while Mosgiel Shane was given the same reassurance by the Ministry of Justice he continued to receive demands from the courts for unpaid fines He’d also get stopped and questioned whenever he left the country for work trips or holidays It took a huge toll on Mosgiel Shane’s mental health not realising the constant stress it placed on his life John Pritchard says that at times his son felt his life wasn’t worth living worrying about what he was going to do to himself and that really ate me up.” he and his son were in tears as Shane admitted he was at breaking point He described going for days at a time unable to eat or sleep wondering what might happen next "Am I going to be in a position where they've got me in handcuffs or I've got debt collectors coming to the door?" ...You're spiralling into this black hole." He started taking anti-anxiety medication which helped And events regarding Milton Shane seemed to settle Milton Shane was charged for fishing without a licence in Twizel and failing to comply with fisheries officers But a court registrar incorrectly entered the birth date of Mosgiel Shane in the system both Shanes were being chased to pay the $1530 fine It was Mosgiel Shane who spotted the error and rang the court He also sent a statement from his manager saying he’d not been fishing in Twizel that day The reply he got was to say he’d been given the wrong form and that they wouldn’t accept his proof They just wanted to know how I was going to pay the fine.” The first Milton Shane knew about this was when Fair Go told him Mosgiel Shane had been chased for the fine He was told to pay up or face the consequences feeling he shouldn’t have to pay good money to correct someone else’s mistake But it cost Mosgiel Shane over $5000 in legal fees and took months of back and forth between him “Why should anybody have to pay their own money to right somebody else's wrongs and prove who they are I’m sick and tired of proving who I am all the time.” He wanted the Ministry of Justice to take responsibility and reimburse him for his legal costs saying court staff such as the registrar in this case have immunity if they make mistakes such as the one made here and if I make a mistake and it's affecting my client that it's going to cost them money to rectify a mistake that I've made.” he deserves a million apologies from those guys,” she says Milton Shane told Fair Go he still gets in trouble but wants the other Shane to know he doesn’t use his birth date anymore And he had a message for him: “We’ve got to get it sorted for you so you can have a good life with you and your family because I’m trying to get my life together with my son and my grandson” He offers to meet to see if they can sort it out together but I’m not interested in meeting him,.” says Mosgiel Shane He says he doesn’t hold any grudges and accepts Milton Shane’s apology And he believes the only way for that to happen is for the courts and the Ministry of Justice to give him a guarantee that mix-ups won’t occur in the future Fair Go asked the Ministry of Justice to appear in person to apologise and provide reassurance to Shane of its plans to guard against these mistakes The Ministry declined our request to be on camera saying any comment on an individual case would compromise the independence of the courts as the Ministry operates separately But it did send a written apology directly to Mosgiel Shane It also admitted mistakes can occur in clerical records but said instructions were clear and the importance of getting things right had been emphasised to staff Mosgiel Shane isn’t totally convinced that’s the end of it “All I want is for the Ministry of Justice and the courts to do their job I'd like to live without this hanging over me all the time his criminal check has come back showing a clean slate Lady Gaga gave a free concert Saturday night in front of 2 million fans who poured onto Copacabana Beach for the biggest show of her career (...) Thank you for making history with me,” Lady Gaga told a screaming crowd kicked off the show at around 22.10pm local time with her 2011 song Bloody Mary Cries of joy rose from the tightly-packed fans who sang and danced shoulder-to-shoulder on the vast stretch of sand Concert organisers said 2.1 million people attended the show switching between an array of dresses including one with the colours of the Brazilian flag Some fans – many of them young – arrived on the beach at the crack of dawn to secure a good spot “Today is the best day of my life,” said Manoela Dobes a 27-year-old designer who was wearing a dress plastered with a photograph from when she met Lady Gaga in the United States in 2019 Madonna also turned Copacabana Beach into a massive dance floor last year The large-scale performances are part of an effort led by City Hall to boost economic activity after Carnival and New Years’ Eve festivities and the upcoming month-long Saint John’s Day celebrations in June “It brings activity to the city during what was previously considered the low season – filling hotels and increasing spending in bars generating jobs and income for the population,” said Osmar Lima the city’s secretary of economic development in a statement released by Rio City Hall’s tourism department last month Rio’s City Hall said in a recent report that around 1.6 million people were expected to attend Lady Gaga's concert and that the show should inject at least 600 million reais (NZ$178.3 million) into Rio’s economy Similar concerts are scheduled to take place every year in May at least until 2028 Lady Gaga arrived in Rio in the early hours of Tuesday The city has been alive with Gaga-mania since as it geared up to welcome the pop star for her first show in the country since 2012 Rio’s metro employees danced to Lady Gaga’s 2008 hit song LoveGame and gave instructions for today in a video A free exhibition celebrating her career sold out While the vast majority of attendees were from Rio the event also attracted Brazilians from across the country and international visitors More than 500,000 tourists poured into the city in the days leading up to the show according to data from the local bus station and Tom Jobim airport Rio’s City Hall said in a statement yesterday made a cross-continent trip from Colombia to Brazil to attend the show “I’ve been a 100% fan of Lady Gaga my whole life,” said Serrano who was wearing a T-shirt featuring Lady Gaga’s outlandish costumes over the years the mega-star represents “total freedom of expression – being who one wants without shame” Rio officials have a history of organising huge concerts on Copacabana Beach Madonna’s show drew an estimated 1.6 million fans last year while 4 million people flooded onto the beach for a 1994 New Year’s Eve show by Rod Stewart in 1994 that was the biggest free rock concert in history sixteen sound towers were spread along the beach Rio state’s security plan included the presence of 3300 military and 1500 police officers Among those present were Lady Gaga admirers who remember their disappointment in 2017 when the artist cancelled a performance scheduled in Rio at the last minute due to health issues “She's the best artist in the world,” the 25-year-old said I love you” in Portuguese rose from the crowd behind him whose real name is Ella Yelich O'Connor which also displayed what appears to be the album cover art — an X-ray of a pelvis "100% written in blood," the website read The new album's announcement came a week after she released her latest single What Was That The song's music video was filmed at a mysterious pop-up event in New York City's Washington Square Park that was initially shut down by police. The event ended up going ahead after all, and fans who stayed got to hear the new song for the first time. View this post on Instagram A post shared by Lorde (@lorde) It was the first sign of a follow-up to Lorde's previous album Her other albums were 2013's Pure Heroine and 2017's Melodrama she collaborated with British singer Charli XCX on a remix of Girl so confusing — on a re-release of the Grammy award-winning Brat Kim Kardashian thought she was going to be raped and killed when criminals broke into her bedroom in central Paris tied her up and stole more than US$6 million in jewellery 10 people will go on trial in Paris over the robbery abduction and kidnapping of the media personality and the concierge of the residence where she was staying during Paris Fashion Week the night of October 2 Kardashian’s lawyers said she will testify in person at the trial starting Monday and scheduled to run through May 23 "Ms Kardashian is reserving her testimony for the court and jury and does not wish to elaborate further at this time," they said "She has great respect and admiration for the French justice system and has been treated with great respect by the French authorities "She wishes the trial to proceed in an orderly fashion in accordance with French law and with respect for all parties to the case." In interviews and on her family’s reality TV show Kardashian has described being terrified as robbers pointed a gun at her In a 2020 appearance on David Letterman’s Netflix show she tearfully recalled thinking: "This is the time I’m going to get raped Twelve people were originally expected in the defendants’ box and another is seriously ill and can't be tried five of the 10 defendants were present at the scene of the robbery The French press has dubbed them The Granddad Robbers because the main defendants are elderly and have careers as bank robbers with long criminal records Kardashian told investigators she was taken to a bathroom next to her bedroom and placed in the bathtub Her attackers fled on bicycles or on foot and she managed to free herself by removing the tape from her hands and mouth She had also removed the tape from her feet and rushed to her stylist’s room She called her sister Kourtney to tell her about the theft Kardashian told investigators that she had not been injured adding that she wanted to leave France as soon as possible to be reunited with her children According to her testimony and that of the concierge at least one of the suspects had a handgun The gangsters stole many pieces of jewellery estimated to be worth more than US$6 million (NZ$10 million) Only one piece of jewellery — a diamond cross on platinum that was lost during the suspects' escape — has been recovered Two of the accused have partially confessed to the crime is one of two suspected robbers who allegedly entered the apartment his genetic profile was found on the tape used to gag Kardashian who was waiting for him in a parked car at a nearby train station The second robber said he tied up the concierge with cables but did not go up to Kardashian’s apartment said he acted as a lookout in the ground-floor reception area He said he was unarmed and did not personally threaten Kardashian but admitted he shared responsibility for the crime Abbas was arrested in January 2017 and spent 21 months in prison before being released under judicial supervision he co-authored a French-language book titled I Sequestered Kim Kardashian is the second alleged robber suspected of entering the flat although he was filmed by CCTV cameras and numerous telephone contacts with the other co-defendants show his involvement The other defendants are suspected of providing information about Kardashian’s presence in the apartment Others are accused of playing a role in the resale of the jewellery in Antwerp Joe Cocker and Bad Company will be inducted into the Rock & Roll Hall of Fame — in a class that also includes pop star Cyndi Lauper the rock duo the White Stripes and grunge masters Soundgarden the first female rap act to achieve gold and platinum status and the late singer-songwriter Warren Zevon will get the Musical Influence Award pianist Nicky Hopkins and bassist Carol Kaye will each get the Musical Excellence Award who sang at Woodstock and was best known for his cover of The Beatles’ With a Little Help From My Friends a member of Elvis Costello & The Attractions who argued that Cocker is "about as rock and roll as it gets" Soundgarden — with the late Chris Cornell as singer — get into the Hall on their third nomination They follow two other grunge acts in the Hall — Nirvana and Pearl Jam Bad Company get in having become radio fixtures with such arena-rock staples as Feel Like Makin’ Love Can’t Get Enough and Rock ‘n’ Roll Fantasy The Ahmet Ertegun Award — given to nonperforming industry professionals who had a major influence on music — will go to Lenny Waronker Some nominees that didn't get in this year included Mariah Carey and subsequent Let’s Twist Again are considered among the most popular songs in the history of rock 'n' roll The 83-year-old has expressed frustration that he hadn't been granted entry before including telling the AP in 2014: "I don’t want to get in there when I’m 85 years old so you better do it quick while I’m still smiling." Lauper rose to fame in the 1980s with hits such as Time After Time and Girls Just Want To Have Fun and went on to win a Tony Award for Kinky Boots have six Grammys and a reputation for pushing the boundaries of hip-hop The White Stripes — made up of Jack White and Meg White — were indie darlings in the early 2000s with such songs as Seven Nation Army Artists must have released their first commercial recording at least 25 years before they’re eligible for induction The induction ceremony will take place in Los Angeles this fall Nominees were voted on by more than 1200 artists historians and music industry professionals The selection criteria include "an artist’s impact on other musicians the scope and longevity of their career and body of work as well as their innovation and excellence in style and technique" Dave Matthews Band and singer-guitarist Peter Frampton were inducted The harbor development works initiated in Muli Island of Meemu atoll are progressing according to schedule The Maldives Transport and Contracting Company (MTCC) said that the harbor basin dredging operations and installation of concrete blocks required for quay wall construction are ongoing MTCC will conduct dredging operations for the harbor basin measuring an area of 33,888 cubic meters as well as dredging operations for a channel measuring 6,254 cubic meters The company will also be constructing a breakwater measuring 465 meters a revetment measuring 89 meters as well as a 479-meter quay wall Muli harbor development project is valued at MVR 61.8 million ($4 million) Daily news and in-depth stories in your inbox Post Courier Former Hela Wigmen premiership-winning coach late Seth Ripp Muli’s body is to be laid to rest today at 9-mile Cemetery in Port Moresby Having a colorful career in rugby league from a player in Mendi Town Southern Highlands province of PNG to head trainer and later becoming the head coach and team manager Late Muli’s casket was officially handed over to his family yesterday was known for his bone-wreaking games with Mendi Muruks as a player before he ended his career and went into management as head training before joining Wigmen in 2017 as strength and condition trainer Late Muli worked his way up to the ranks to head coach in 2022 and won his first premiership in his first year as coach He remained with the club until his untimely death at Port Moresby General Hospital on December 2 after involving in a car accident on November 9 Late Muli’s funeral was hosted yesterday at Sioni Kami Memorial Church where the club officially handed the body to his immediate family in the presence of his friends and fans came to show their respect before his casket was taken to Gerehu Stage Six and handed over to his family Late Muli’s body spent a night at Gerehu and today it will be taken up to Nine Mile cemetery outside Port Moresby and be put to rest former club enforcer and current PNG Hunters player Valentine Richard said Muli was like a father to them In areas in life that you go through there will always be someone that will stand behind you to guide you and today we lost our brother and players from the Water Boy Up and the supporters of Kroton Hela Wingmen club we lost a workaholic person Seth doesn’t sleep he works day and night; he committed his life to rugby league The club has been a champion club for years and Seth Muli has been behind it We are more than a rugby club we are a family once a Wigmen we will always be a Wigmen Members of wigmen players led by their coach Ian Yaro who have taken over the role of head Coach from Muli mid-season this year in their yellow and blue colours as they hand over the late Muli to his family representing the late Muli’s family Ben Pameasi thanked the club for their support to the family throughout the period Muli was involved in the accident to his burial and the opportunity given to him to realize his potential as a coach Get the latest news delivered straight to your inbox A Comancheros member is now facing up to life imprisonment after pleading guilty to having aided the importation of a massive load of methamphetamine disguised as tea bags The haul, initially described as 613kg and worth roughly $245 million, was intercepted at Auckland Airport in 2022 as part of a covert investigation dubbed Operation Weirton Papatoetoe resident Muli Paunga, 35, appeared in the dock in the High Court at Auckland yesterday wearing the gang’s black and gold colours as he admitted two charges of possessing meth for supply He is likely to receive a substantial prison term as a result Justice Layne Harvey denied Paunga’s request to remain on bail while awaiting his sentencing hearing Operation Weirton was launched by the Police National Organised Crime Group in August 2020 focusing on another defendant described in court documents as a consignment imported for on-supply by the Comancheros Motorcycle Club was intercepted by Customs 18 months later after arriving on a flight from Kuala Lumpur described in the agreed summary of facts as a patched member of the gang was arrested a week later after authorities caught him in possession of the fake powder substance that had been secretly swapped out by authorities Audio and tracking devices had been concealed within the haul Court documents state the drugs were retrieved from a shipping company by others on March 1 Five of the 27 boxes were then loaded into a Nissan Navara registered to Paunga’s father and driven to Paunga’s address where they were left inside the fenceline of the property Police started making arrests a short time later “Mr Paunga ran from his address,” court documents state “It is accepted that the defendants knew the consignment was very large — requiring a truck and at least two defendants to move it — but may not have known the precise amount of methamphetamine involved (613 kilograms).” The shipment was described by police as consisting of 27 boxes on a pallet wrapped in black shrink wrap Each box contained 22 to 23 square-shaped items wrapped in tin foil Underneath the layer of tinfoil was a further layer of packaging for green tea Inside each set of packaging was a vacuum-sealed plastic package containing approximately 1kg of methamphetamine The 613kg of methamphetamine was later tested and determined to have a purity of 80% with revised street value of between $98m and $116m Police also located just under 450g of low-purity methamphetamine in Paunga’s home unrelated to the consignment in a Nike shoe box and in a Pyrex container Police also located Comancheros hoodies and patches Other co-defendants have pleaded not guilty and await trial next year Craig Kapitan is an Auckland-based journalist covering courts and justice. He joined the Herald in 2021 and has reported on courts since 2002 in three newsrooms in the US and New Zealand. No one knew he'd fallen after a guard rail gave way while he was loading containers. Aim: Chaihu-jia-Longgu-Muli-tang (CLM) is derived from “Shang Han Lun” and is traditionally prescribed for treating depression. However, there is still a lack of evidence for its antidepressant effects, and the underlying mechanism is also unclear. This study aimed to assess clinical evidence on the efficacy of CLM in patients with depression using a meta-analysis and to explore its underlying antidepressant molecular mechanisms via network pharmacology. Conclusion: Compared to SSRIs/SNRIs alone, CLM is more effective and safe in treating depression. It not only significantly alleviates depressive mood, but improves symptoms such as anxiety and insomnia, with fewer side effects, especially in combination with SSRI. Its antidepressant mechanism may be correlated with the regulation of the PI3K/Akt signaling pathway and inhibiting inflammatory response. Volume 14 - 2023 | https://doi.org/10.3389/fphar.2023.1257617 Aim: Chaihu-jia-Longgu-Muli-tang (CLM) is derived from “Shang Han Lun” and is traditionally prescribed for treating depression there is still a lack of evidence for its antidepressant effects and the underlying mechanism is also unclear This study aimed to assess clinical evidence on the efficacy of CLM in patients with depression using a meta-analysis and to explore its underlying antidepressant molecular mechanisms via network pharmacology Methods: Eight open databases were searched for randomized controlled trials (RCTs) comparing the effects of CLM alone or combined with serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) in patients with depression evaluating the total effective rate of the treatment group (CLM alone or combined with SSRIs/SNRIs) and the control group (SNRIs or SSRIs) inflammation indicators and adverse effects the active ingredients and target genes of CLM were screened through six databases Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network and topology analysis were performed Molecular docking was applied to evaluate the binding affinity between components and predicted targets Results: Twenty-four RCTs with a total of 2,382 patients were included For the efficacy of antidepression and adverse effects whether CLM alone or in combination with SSRIs/SNRIs the treatment group has no inferior to that of the control group the intervention of CLM + SSRI significantly improved the symptoms of anxiety and insomnia and reduced serum IL-6 and TNF-α levels a total of 129 compounds and 416 intersection targets in CLM were retrieved The interaction pathway between CLM and depression is mainly enriched in PI3K-Akt and AKT1 may be the potential targets of Stigmasterol CLM is more effective and safe in treating depression It not only significantly alleviates depressive mood but improves symptoms such as anxiety and insomnia Its antidepressant mechanism may be correlated with the regulation of the PI3K/Akt signaling pathway and inhibiting inflammatory response it is still necessary to find or develop antidepressant treatments with high-efficiency and fewer side effects CLM has a wide range of antidepressant efficacy but with still a lack of clinical evidence and its antidepressant mechanism is still unclear due to the complexity of TCM compound ingredients this study aimed to assess clinical evidence on the efficacy of CLM in patients with depression using a meta-analysis and to explore its underlying antidepressant molecular mechanisms via network pharmacology Clinical trials were searched in the PubMed, Web of Science, MEDLINE, Cochrane Library, China National Knowledge Internet, VIP, Wanfang, and SinoMed databases from the inception of each database until December 2022. This meta-analysis complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Page et al., 2021) (protocol shown in Figure 1). The search strategy is shown in Supplementary Table S1 Flow chart of the investigation of CLM in the treatment of depression Due to the limited exact treatment methods for depression at present physical therapy has the disadvantage of large side effects and poor compliance (e.g. repeated transcranial magnetic stimulation) SSRIs and SNRIs) have exact therapeutic effects and are widely accepted there are still some limitations we mentioned above so we have made the following provisions in the inclusion and exclusion criteria The exclusion criteria were as follows: 1) incomplete data; 2) inclusion of drug-induced secondary depression somatic or psychiatric disease-induced secondary depression or menopausal depression; 3) other comorbid conditions 4) interventions combining other traditional Chinese medicine formulas or physical therapy (e.g. The search terms and their common synonyms in each database were as follows: “Depression OR Depressive” AND “chaihu jia longgu muli decoction OR CLM.” All retrieved studies were imported into Endnote20 software for screening and eliminating duplicates according to abstracts and YY.) extracted the information trial characteristics (study Adverse effects and serum inflammatory factors: TNF-α and IL-6) Two assessors (JW and DZ.) independently evaluated study quality and risk of bias and extracted data using the Cochrane Collaboration Assessment Tool Discrepancies between the assessors were resolved by a third assessor STATA software (v16.0) to analyze this meta-analysis IL-6) and dichotomous outcomes (Total Effective Rate and Adverse Effects) the standardized mean difference (SMD) and risk ratios (RR) were represented The 95% confidence interval (CI) was used to analyze the effects of secondary variables When heterogeneity was high (I2 > 50% or p < 0.05) a random effects model was used; otherwise The subgroup analysis was based on the type of treatment group which included CLM + SSRI (CLM + SSRI vs CLM + SNRI (CLM + SNRI vs SNRI) Egger’s test and funnel plots were used to assess publication bias all screened ingredients were imported into the TCMSP for normalization according to ADME (absorption oral bioavailability ≥30% and drug-likeness ≥0.18 as the most commonly used pharmacokinetic parameters to measure drug properties The keyword “depression” was searched to obtain potential targets related to depression from the GeneCards (Stelzer et al., 2016) and DisGeNET (Pinero et al., 2017) databases. To forecast CLM’s therapeutic targets for treating depression, the common targets of compounds and depression were sorted out, and a Venn diagram was obtained using the Venn 2.1.0 platform (Heberle et al., 2015) The intersection targets were entered into Cytoscape software (v 3.8.2) to construct Herb-Compound-Target (H-C-T) networks For KEGG and GO enrichment analyses, we uploaded intersection targets into the Metascape platform (http://metascape.org/Homo sapiens, p < 0.05, and p-values were corrected by the Benjamini–Hochberg procedure) (Zhou et al., 2019) To further evaluate the core of regulatory targets in the treatment of depression and discover potential connections, intersection targets were uploaded to the STRING database (H. sapiens, minimum required interaction score: 0.9) to construct a PPI network (Szklarczyk et al., 2019) to evaluate the topological characteristics of the nodes the three parameters of “betweenness centrality” (BC) “closeness centrality” (CC) and “degree centrality” (DC) were computed and the torsion angles in the ligand were identified and the Kollman atomic charges were assigned to the protein using Autogrid4 and Autodock4 The “Local Search Parameters” algorithm was used for the docking operation we constructed the docking interaction pattern diagram and displayed the docking findings via PyMoL (v2.4.0) PRISMA flow diagram and risk-of-bias assessment; (A) literature screening process; (B) risk-of-bias summary Twenty-four RCTs with a total of 2,382 patients with depression were included (1195 cases in the treatment group According to the intervention in the treatment group 13 trials on CLM + SSRI included 1337 patients 3 trials on CLM + SNRI included 280 patients and 8 trials on CLM alone included 765 patients The treatment duration varies from 2 to 12 weeks Comparative forest plots of total effective rate; (A) forest plot showing the total effective rate of CLM alone or anti-depressant drug therapy on depression; Treatment: CLM alone or combined with pharmaceutical anti-depressants; Control: pharmaceutical anti-depressants; (B) funnel plot of total effective rates and PSQI scores; (A) HAMD scores; (B) SDS scores; (C) HAMA scores; (D) SAS scores; (E) PSQI scores Two trials reported HAMA scores for CLM and CLM + SNRI respectively. According to heterogeneity testing (p = 0.387, I2 = 0.0%), the fixed effects model was applied. The HAMA scores of the group of patients receiving CLM or combined with antidepressant drugs were significantly lower than those of the control group (SMD = −0.37%, 95% CI [−0.66, −0.07], Figure 4C) Three trials reported PSQI scores, all of included were for CLM + SSRI. According to heterogeneity testing (p = 0.930, I2 = 0.0%), the fixed effects model was applied. The PSQI scores of the treatment group were significantly lower than those of the control group (SMD = −2.53, 95% CI [−2.89, −2.18], Figure 4E) Comparative forest plots of indicators of inflammation; (A) TNF-α; (B) IL-6 there was no statistical significance between CLM + SNRI and SNRI alone Comparative forest plots of adverse effects; Treament: CLM alone or combined with pharmaceutical anti-depressants; Control: pharmaceutical anti-depressants We obtained 129 active compounds from the four databases, including Radix Bupleuri (16 compounds), Radix Scutellariae (29 compounds), Pinelliae Tuber (10 compounds), Ginseng radix (35 compounds), Hoelen (12 compounds), Zingiber rhizoma (5 compounds), Zizyphi fructus (25 compounds), Radix et Rhizoma Rhei (7 compounds), and Cinnamomi cortex (7 compounds). The primary active components of CLM are listed in Supplementary Table S3 There were 2356 targets screened from the 129 active compounds CLM using the Swiss, TCMSP, HERB, and BATMAN-TCM databases. In addition, 1490 depression-related targets were identified using the DisGeNET and GeneCards databases. The intersection of drug targets and depression targets resulted in a total of 416 CLM treatment depression targets, as shown in the Venn diagram (Figure 7A) Venn diagram and H-C-T network; (A) Venn diagram of the active ingredients of CLM and potential treatment targets; 2356 predicted targets of CLM and 416 targets intersected; (B) H-C-T network of CLM; BX: Ban Xia RS: Ren Shen; A–H: Common components of different drugs Basic information of the top five degree of the compounds For GO enrichment analysis, a total of 3516 items were selected, and the top 20 significant terms in the BP, CC, and MF categories are shown in Figure 8A The intersected target proteins in the BP category mainly included responses to hormones The MF category mainly included kinase binding and CC categories in GO analysis of 416 intersection targets; (B) top 20 signaling pathways in KEGG enrichment analysis of 416 intersected targets For KEGG enrichment analysis, the top 20 items were selected for visualization according to the criteria above (Figure 8B) The results mainly involved neuroactive ligand-receptor interactions Interaction network diagram of 416 predicted targets and topology analysis; (A) PPI network of 416 predicted targets; (B) topology analysis; BC: betweenness centrality; CC: closeness centrality; DC: degree centrality; (C) network of the top 28 core proteins; (D) top 28 targets ranked by degree values Specifc information of the 28 key target genes Based on the above results in H-C-T, GO, and PPI network analysis, molecular docking analysis was performed between the top five compounds of CLM and the top seven key targets. The docking visualizations and scores are shown in Figures 10A,B The stronger the binding force between the compound and the protein the lower the docking score (the higher the negative number) When the docking score is ≤ −5.0 kJ/mol the exertion of a strong binding effect is suggested The results showed that 35 pairs of active compounds and ligands were relatively stable and AKT1 (PDB: 1UNP) might be potential therapeutic targets for depression using CLM among which stigmasterol (MOL000449) had the highest binding energy with PIK3R1 Molecular docking analysis of main compounds binding to key targets; (A) molecular docking models of main chemical components; (B) heat map showing values of docking affinity CLM is derived from “Shang Han Lun” and has a significant effect on depression the mechanism of action of this prescription has not been fully clarified The results of present study indicated that the antidepressant efficacy of CLM whether administered alone or in combination with antidepressants was significantly higher than that of antidepressants alone whether in CLM alone or CLM + SSRI/SNRI and insomnia in patients with depression were significantly improved comparing antidepressants alone CLM and CLM + SSRI also showed fewer adverse reactions than SSRI alone Five compounds in CLM and seven of its key targets were shown to be related to antidepressant activity in the present analysis This means that a good treatment strategy for patients with depression seems to be relieving anxiety and insomnia while adjusting mood both CLM alone and combined with SSRI/SNRI markedly reduced the scores of HAMD and SDS results indicated that the synergistic effect of CLM and SSRI was significantly better than that of SSRI alone due to the limited literature on CLM alone and CLM + SNRI the synergistic effect of CLM alone or with SNRI may need further exploration CLM alone or in combination is not inferior to antidepressants alone whether CLM alone or in combination with SSRI the incidence of adverse reactions is significantly fewer than that of SSRI alone It is worth noting that the incidence of adverse reactions in CLM combined with SNRI is the same as that of SNRI alone which may be the reason for only including one trial CLM could not only improve the symptoms of depression but can also reduce the incidence of adverse responses caused by commonly used antidepressants anti-inflammatory treatments may be effective for depression The present results indicated that CLM dramatically decreased the levels of TNF-α and IL-6 in the peripheral blood of patients with depression compared to antidepressant treatment groups The above research provides a pharmacological basis for the clinical efficacy of CLM in depression although the effect of CLM on depression has been revealed directly or indirectly through the above ingredients the specific mechanisms have not been clarified we assessed the relevant pathways for CLM in the treatment of depression using KEGG and GO enrichment analyses we speculate that the antidepressant effect of CLM may be related to the activation of PI3K/Akt and its downstream signaling pathways Although CLM likely exerts anti-depressant effects via the PI3K/Akt it remains urgently necessary to clarify the therapeutic targets of CLM which may contribute to the development of novel therapeutic strategies according to the PPI network and molecular docking analyses and PI3KR1 were potential antidepressant targets of CLM Similar to the above results from the network pharmacology analysis stigmasterol showed high binding energy with PI3KR1 suggesting that CLM alleviates depression via modulation of the PI3K/Akt signaling pathway the above evidence suggests that CLM is a safe and effective antidepressant prescription with multiple pathways and targets Its mechanism is likely related to the regulation of neuronal synaptic plasticity the number of trials included in this study was insufficient to clearly state the specific efficacy of some subgroup analyses such as HAMA and SAS so part results have to be roughly concluded by assessing the comprehensive efficacy of CLM alone or in combination with antidepressants part of literature included by allocation concealment and blinding is not yet clear TCM has the characteristics of personalized treatment which is limited to the unique odor and color making it difficult to implement blind methods screening the active ingredients based on OB and DL may exist inconsistency with the precise ingredients and the predicted targets are likely to be limited by the hot spots of current research the specific mechanism in this study still needs to be verified by further vivo and vitro experiments This study analyzed the effectiveness and mechanism of CLM in the treatment of depression Our findings revealed that compared to antidepressants CLM had better clinical efficacy and fewer side effects Its mechanism in treating depression may be related to regulating neuronal synaptic 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Full Text | Google Scholar 42 cases of depression treated with paroxetine combined with Chaihu and longgu oyster soup Google Scholar Li J and Guo W (2023) The pharmacological mechanism of chaihu-jia-longgu-muli-tang for treating depression: integrated meta-analysis and network pharmacology analysis Received: 12 July 2023; Accepted: 05 September 2023;Published: 21 September 2023 Copyright © 2023 Zhao, Xu, Wang, Zhou, Liu, Sun, Yuan, Li and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use *Correspondence: Jianxiang Li, bGp4MDI5NTA0QG5qdWNtLmVkdS5jbg==; Weifeng Guo, Z3dmd2ZnMjAwM0BuanVjbS5lZHUuY24= †These authors have contributed equally to this work and shared the first authorship Burundi’s Rodrigue Kwizera and Kenya’s Lucy Mawia Muli captured respective wins at the Cross Internacional de Soria – the third Gold standard meeting of this season’s World Athletics Cross Country Tour – held in the altitude (1100m) of Soria While Kwizera beat three top 10 athletes from the 2019 World Athletics Cross Country Championships in Aarhus Muli got the better of Ethiopia’s Likina Amebaw Ayel the men’s 10km race opened at a quick pace set by the Ugandan duo of Thomas and Joel Ayeko with only five athletes – Burundi's Thierry Ndikumwenayo and Kwizera Eritrea’s Yemane Hailesilassie and Spain's Juan Antonio Perez and Ibrahim Chakir – able to stay with them the contest became a three-way battle between Thomas and Joel Ayeko and Kwizera and some 12 minutes into the race Kwizera moved to the front for the first time Thomas Ayeko ran comfortably on his shoulder and Joel managed to maintain contact but seemed to be in trouble the leading trio reached the bell 40 seconds clear of Hailesilassie himself clearly ahead of a large group of pursuers when the 22-year-old Kwizera found another gear and easily left his rivals behind to cross the finish line unopposed in 28:47 some seven seconds ahead of Thomas Ayeko Joel Ayeko in third was another eight seconds adrift Spain’s Nassim Hassaous secured a surprise fourth as he overtook Hailesilassie down the home straight who runs for the Spanish team Playas de Castellon and was fresh from another victory at a low-key cross country permit in Castellon last Sunday The rain made the race tough but I’m very satisfied with my win as I beat two world-class athletes." The women’s 8km contest kicked off at a moderate rhythm the large leading group reaching the opening kilometre in 3:30 Burundi’s Francine Niyomukunzi and Amebaw broke away easily from the rest and it became clear that the crown would return to Africa after Mariana Machado of Porugal’s win in the last edition It was the 21-year-old Portuguese athlete who headed the chasing group alongside her compatriot Lia Lemos and Spain’s Cristina Ruiz Muli took charge of the pacing duties closely followed by Niyomukunzi while Amebaw remained conservatively in third By half way the leading trio had built a sizeable 18-second margin over the chasing group and some 800m later Amebaw unleashed a terrific change of speed which could only be followed by Muli while Niyomukunzi was way back to lose any winning chances Once Amebaw realised that Muli had stayed tucked behind her she slowed her frantic pace as the leading duo covered the 1800m lap in 5:48 compared to a previous split of 5:55 Muli and Amebaw remained ahead of Niyomukunzi Lemos and Ruiz travelled another 80 metres adrift Muli ran 10 metres ahead of Amebaw but the Ethiopian never looked likely to threaten the Kenyan Muli increased her advantage over the closing 500m to finish in style while Niyomukunzi completed the podium as a distant third the 2019 European U20 cross country bronze medallist Machado proved to be the strongest and kept Ruiz at bay to cross the finish line in fourth The 22-year-old winner Muli said: "I expected to be on the podium but the win has been a surprise for me." Women1 Lucy Mawia Muli (KEN) 27:222 Likina Amebaw Ayel (ETH) 27:293 Francine Niyomukunzi (BUR) 28:114 Mariana Machado (POR) 28:305 Cristina Ruiz (ESP) 28:326 Rosalia Tarraga (ESP) 28:347 Marta Perez (ESP) 28:378 Lia Lemos (POR) 28:389 Lidia Campo (ESP) 28:4210 Azucena Diaz (ESP) 29:00 Men1 Rodrigue Kwizera (BUR) 28:572 Thomas Ayeko (UGA) 29:043 Joel Ayeko (UGA) 29:124 Nassim Hassaous (ESP) 29:575 Thierry Ndikumwenayo (BUR) 30:036 Zakaria Boufaliat (ESP) 30:077 Ibrahim Chakir (ESP) 30:158 Juan Antonio Perez (ESP) 30:199 Andreu Blanes (ESP) 30:2510 Ayad Lamdassem (ESP) 30:30 Habte and Niyomukunzi take the spoils in Amor.. Arter and Milner victorious at Cardiff Cross .. Azimio has picked Koki Muli as its representative in the IEBC Selection Panel, paving the way for the gazettement and swearing-in of a team tasked with recruiting new commissioners. Mulwa also directed Azimio to conduct a fresh election for the minority coalition cluster in compliance with the law of the First Schedule of IEBC (Amendment) Act 2024, within 48 hours from the date of the ruling.  "The court further directs and orders that Fresh Election for Minority Coalition Cluster for nominees to the IEBC selection panel be held in strict compliance with provisions of Sections 2(B) and 2(C) of the First Schedule of IEBC (Amendment) Act 2024, within 48 hours of this judgment/orders, and in any event not later than 3.00 pm on 24/10/2024,’’ Mulwa said. US Ambassador to Kenya Meg Whitman had warned that Kenya’s democracy was in jeopardy due to the delay in recruitment of new IEBC commissioners. Speaking on Wednesday during a high-level meeting with IEBC Commission Secretary and CEO Marjan Hussein Marjan, Ambassador Whitman emphasised the vital role of IEBC in ensuring free and fair elections and called for immediate action to secure its stability. “IEBC Kenya’s ability to support democracy in Kenya is at risk without the recruitment of commissioners or parliamentary action to provide IEBC funding for voter registration, by-elections, and other election activities,” the US Embassy in Nairobi said in a statement on X. Methods: The OB model was first characterized with depression-like behaviors and the time course changes of the behaviors. The fast onset of antidepressant effect of CLM was evaluated using sucrose preference test, tail suspension test and forced swim test in OB mice after a single administration. The expression of synaptic proteins of AMPA and NMDA subunits as well as Akt/mTOR signaling in the prefrontal cortex, and hippocampal BDNF was evaluated with the immunoblotting method. Conclusion: CLM elicited rapid antidepressant-like effects in the OB model mice, and CLM reversal of the abnormality in PFC expression of AMPA and NMDA receptors and associated Akt-mTOR signaling may underlie the effects. Volume 9 - 2018 | https://doi.org/10.3389/fphar.2018.01537 Background: Fast-onset antidepressants are urgently needed has been used for antidepressant treatment with long history Olfactory bulbectomization (OB) model is validated for identification of rapid antidepressant efficacy Here we used OB model for investigating the rapid onset activity of CLM in mice and also tested the involvement of prefrontal Akt-mTOR and associated AMPA/NMDA receptors as well as hippocampal BDNF in the rapid antidepressant-like effect of CLM Methods: The OB model was first characterized with depression-like behaviors and the time course changes of the behaviors The fast onset of antidepressant effect of CLM was evaluated using sucrose preference test tail suspension test and forced swim test in OB mice after a single administration The expression of synaptic proteins of AMPA and NMDA subunits as well as Akt/mTOR signaling in the prefrontal cortex and hippocampal BDNF was evaluated with the immunoblotting method Results: A single dose of CLM significantly improved the deficiency in the sucrose preference and decreased the immobility time in the tail suspension test in OB mice there was lower expression level of the AMPA receptor subunit GluR1 the expression of NMDA subunit NR1 was up-regulated in OB mice whereas mTOR and its upstream Akt signalings were both down-regulated These deficiencies were reversed by a single dose of CLM The CLM treatment also attenuated the expressions of NMDA receptor subunits NR2A and NR2B expressions of GluR1 and brain derived neurotrophic factor (BDNF) were both up-regulated in OB mice Conclusion: CLM elicited rapid antidepressant-like effects in the OB model mice and CLM reversal of the abnormality in PFC expression of AMPA and NMDA receptors and associated Akt-mTOR signaling may underlie the effects - The olfactory bulbectomization (OB) mice showed abnormal NMDA-Akt-mTOR-AMPA signaling - A single dose of CLM reversed the abnormal NMDA-Akt-mTOR-AMPA signaling - CLM elicited rapid antidepressant-like effect in OB mice likely via remedy of NMDA-Akt-mTOR-AMPA signaling safe and effective antidepressants is urgently needed The NMDA-Akt-mTOR-AMPA signaling in the PFC and BDNF expression in the hippocampus are probably responsible for the rapid antidepressant-like effect Clinical observations also suggested a relatively fast antidepressant action of CLM has not been scientifically investigated using appropriate animal models It is believed that OB led to dysregulated NMDA-AMPA and Akt-mTOR signaling in PFC similar to other models we investigated whether a single dose of CLM was able to elicit rapid antidepressant-like activity; furthermore we tested the association of NMDA-AMPA receptors and related Akt-mTOR signaling in PFC or increase in hippocampal BDNF with the rapid antidepressant-like action of CLM in OB mice Kunming mice weighing between 20 and 25 g were purchased from China Academy of Military Medical Sciences (Beijing) Mice aged approximately 6 weeks old and were housed in cages for 7 days before behavioral testing and OB Animals were maintained in a temperature and humidity-controlled environment (temperature 22 ± 2°C and room humidity 50 ± 10%) under a 12: 12 h light/dark cycle All the mice were offered ad libitum access to food and water All procedures in this study conformed to the Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at Nanjing University of Chinese Medicine these 11 dried herbal and mineral drugs were soaked in water for 30 min and then were decocted two times with boiling water in the ratio of 1:8 for 2 h placed in a water bath at 60°C and evaporated to a target concentration for frozen storage The yield of the preparation was about 42% The solutions of the herb preparation and vehicle were administered to mice via intragastric administration at a dosage of 0.1 mL/10 g (body weight) and the concentration of the solutions for administration was 210mg/ml Olfactory bulbectomy was performed according to the mouse brain anatomy map mice were anesthetized with Chloral hydrate (3.8% 0.1 ml/10 g an incision was made in the overlying skin after which holes were drilled on both sides of the midline (4.5 mm anterior fontanelle; 0.8 mm by the middle line; 2.5–3.0 mm depth) The olfactory bulbs were then bilaterally aspirated using a blunt hypodermic needle (1.0–1.2 cm long with a rounded tip that was 0.80–1.2 mm in diameter) attached to a 10-ml syringe that was used to create suction Care was taken to avoid damaging the frontal cortex the holes were filled with swabs and covered with dental cement 70% alcohol solution was used to eliminate contamination during all of the surgical procedures The mice were allowed to recover under a warming lamp to help with body temperature maintenance Each animal was given 14 days to recover from the surgery prior to undergoing any further treatment Open field test estimated locomotor activity and anxiety-like behavior Mice were freely explore for 5 minutes in a well-illuminated (∼300lux) plastic cage (40 cm × 40 cm × 40 cm) A camera was placed in the top of the box for recording the activity Both the distance traveled (cm) and time spent in central area(s) were analyzed by a computer-based tracking system Testing apparatus was thoroughly cleaned with 75% ethanol between each test The SPT followed a procedure published before with minor modifications mice were housed and exposed to a sucrose solution (2% in tap water) for 72 h followed by 24 h of water deprivation and mice were offered two individual bottles containing either tap water or 2% sucrose solution for 2 h Liquid consumption from each bottle was measured by comparing the differences in bottle weight before and after a 2hr exposure Sucrose preference was measured by the percentage of sucrose solution intake versus total (water + sucrose liquid) intake The apparatus is consisted of 6 chambers which allowed 6 animals to be videotaped and tested at one time In a chamber which is isolated acoustically and visually an individual mouse was individually suspended 1cm from the tip of the tail to the vertical bar with adhesive tape A camera positioned in front of the TST box was used to record the animal’s behavior for 6 min Total immobility time during the last 4 min was analyzed by ANY-maze software No animal climbed its tail during the test After the mouse behavioral test was finished The entire hippocampus and PFC were lysed in RIPA buffer containing protease inhibitors and phosphatase inhibitors Protein concentration was determined colorimetrically by BCA assay (Pierce Protein lysates were separated by SDS-PAGE electrophoresis and were transferred onto polyvinylidene difluoride (PVDF) membranes the membranes were incubated with primary antibodies 1 : 2000) were used at 4°C overnight blots were washed three times in TBST and incubated with horseradish peroxidase conjugated anti-mouse or anti-rabbit secondary antibody (1:3000) for 1 h the bands were visualized using the Super Signal West Pico Chemiluminescent Substrate (Thermo Fisher Scientific Inc.) NR2B and GluR1 were all normalized to β-Tubulin bands p-Akt bands were normalized to total protein levels then expressed as a percentage All data are presented as means ± SEM Two-sample comparisons were carried out using two-tailed Student’s t-test Others was performed by one-way analysis of variance (ANOVA) followed by the Bonferroni multiple comparison tests A value of p < 0.05 was considered statistically significant Behavioral effects at different time points after a single ketamine and CLM treatment on OB mice Control animals (CTL) received vehicle treatment and animals exposed to olfactory bulbectomy received a single administration of vehicle (OB) Chaihu-jia Longgu-Muli decoction (CLM) or ketamine (KET) and 4 weeks after olfactory bulbectomy surgery (T-test ∗p < 0.05 and n = 6–10/group) and n = 7–8/group) was tested at 24 h and n = 8–9/group) was tested at 72 h (E,F) OFT was performed 24 h post administration of CLM Western blotting detection of expressions of Glur1 and NMDA receptor subunits in the PFC of OB mice at 24 h post a single administration of CLM or KET F(3,19) = 8.797; Data are means ± SEM Western blotting detection of expressions of AKT and mTOR signaling in the PFC of OB mice at 24 h post a single administration of CLM or KET Western blotting detection of expressions of BDNF and GluR1 in the hippocampus in OB mice at 24 h post a single administration of CLM or KET We aimed to test a traditional Chinese herbal medicine CLM for a rapid antidepressant activity and to examine associated neuromolecular substrate We found a single dose of CLM instantly induced an antidepressant-like action we found the deficits in sucrose preference in OB mice which was reversed by a single dose of CLM mice with OB showed decreased level of expression of GluR1 and increased level of NR1 There was also remarked deficiency in Akt and mTOR signaling regulating neural plasticity in OB mice which was ameliorated by a single dose of CLM These results suggested that normalization of NMDA and AMPA receptors and related Akt-mTOR signaling may account for the rapid antidepressant-like activity of CLM the results from this study suggest the fast-onset antidepressant-like effect of CLM these molecular deficits were still repairable by a single dose of CLM or ketamine the hippocampal BDNF level in OB mice failed to alter by a single dose of CLM These observations suggest that rapid normalization of the ratio of AMPA to NMDA receptors may represent an important mechanisms underlying the rapid reverse of depression-like behavior in OB mice by CLM The present study demonstrated the fast-onset antidepressant-like activity of CLM An equivalent to half of clinical dose of CLM elicited an antidepressant effect on OB mice post an acute administration and the effect lasted for 3 days a single dose of CLM rescued the deficient Akt-mTOR signaling which controls the expression of synaptic proteins including GluR1 the dysregulations of the subunits of NMDA was also reversed by CLM These findings suggest that the activation of Akt-mTOR signaling and normalization of AMPAR/NMDAR ratio in the PFC may underlie the rapid antidepressant-like effect of CLM in OB mice XW and GC conceived and designed the experiments and GC contributed to the writing of the manuscript The study was supported by the National Science Foundation of China (81673625) National Science Youth Fund of China (81603089) the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Open Project Program of Key Subject of TCM Encephalopathy Jiangsu Administration of Traditional Chinese Medicine (NBKF201607) The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2018.01537/full#supplementary-material α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Gang Chen, aGRuXzIwMDFAeWFob28uY29t; Y2hlbmdhbmdAam51LmVkdS5jbg== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. CECM ICT, Education and Internship, Elizabeth Muli toured Kiima Kiu Kalanzoni Ward to evaluate the progress of various ongoing projects aimed at enhancing Education and Skill development in the region. The visit underscores H.E Governor Mutula Kilonzo Jnr’s commitment to improving the lives of Makueni County residents through strategic investments in quality Education and Infrastructure. By focusing on transformative projects, Governor Mutula seeks to empower communities, promote economic growth, and ensure access to modern learning facilities for all. Among the key initiatives inspected was the construction of the Kwa Ndeke ECDE center, designed to offer a modern, supportive environment for early childhood education. CECM Elizabeth also toured the newly completed Kisse ECDE facility, which is already providing high-quality early education and addressing the needs of the surrounding community. Additionally, she visited Enzai Community Technical Training Institute (CTTI), a vital hub equipping young people with practical skills to enhance their employability and drive economic empowerment across the region. Volume 10 - 2022 | https://doi.org/10.3389/feart.2022.898629 This article is part of the Research TopicNew Advances in Light Oil/Condensate GeochemistryView all 8 articles The discovery of gas hydrates in the Muli Depression has made the South Qilian Basin (SQB) a hotspot for oil and gas exploration Although many studies have been carried out on the gas hydrates the geochemical characteristics have rarely been reported which can effectively indicate the genetic type the molecular composition and carbon isotopes of alkane gases were collected from gas hydrates and free gases in drilled boreholes of the Muli Depression The results show that the majority of natural gases are oil-type gases The natural gases have undergone biodegradation leading to a decrease in the propane content and an increase in the methane content with a heavier carbon isotope of propane and a lighter carbon isotope of methane Some of the natural gases have experienced diffusion resulting in a decrease in the methane content and an increasing value of Δ(δ13C1-δ13C2) the wet gases from natural gases were derived from the cracking of kerogen and crude oil at the thermal maturity stage The dry gases in small quantities were produced by biodegradation of the wet gases We propose that the potential for light oil and condensate exists in the Jurassic Yaojie Formation Our new findings on the geochemical characteristics of natural gases provide new constraints for the study of petroleum systems and deeply buried sediments in the SQB which can be used to evaluate the origin of natural gas the thermal maturity and secondary alteration of gas hydrates have not been studied in detail which in turn leads to a debate on the formation and enrichment model of natural gas in the Muli Depression In this contribution, we systematically analyzed the molecular and stable carbon isotopic composition of natural gas collected from newly drilled boreholes in the Muli Depression to identify the genetic type, thermal maturity, and secondary alteration (biodegradation and diffusion) of natural gases by the diagrams proposed by Chung et al. (1998), Milkov (2021), Prinzhofer and Huc (1995) the potential of primary light oil and condensate were discussed in the Jurassic strata of the Muli Depression Our new findings not only lay a theoretical basis for exploring the relationship between natural gas and source rocks but also provide a new perspective on the enrichment and reservoir formation mechanism of Jurassic natural gas in the Muli Depression and the Jurassic strata were deposited locally in the northern part of the basin Simplified geological map with the distribution of natural gas boreholes in the Muli Depression of the South Qilian Basin and gas indications are mainly distributed in the Yaojie Formation Distribution and stratification of gas hydrates in the Muli Depression Geochemical data on natural gases were collected from previous studies (Lu et al., 2010; Lu et al., 2015; Liu et al., 2012; He et al., 2015; Huang et al., 2016) and the natural gases were collected from coarse sandstones (n = 5) A total of 190 molecular compositions and 174 methane and 43 propane carbon isotopes were collected from 11 boreholes A large number of samples (n = 145) were free gases and desorbed gases from sandstones A few samples (n = 45) were collected from natural gases produced by gas hydrate decomposition It is noteworthy that the free gases were obtained by different methods the sub-surface depth of the gas samples varied from 55.3 to 487.3 m we utilize molecular and isotopic gas data produced by two laboratories using various instruments and practices regarding calibration and normalization of raw δ values over a period from 2009 to 2016 All of the carbon isotopes are within ±0.05‰ accuracy The molecular compositions from gas hydrates and free gases in the Muli Depression contain carbon dioxide The carbon dioxide content ranges from 0.05% to 79.40% the CO2 content ranges from 2.16% to 6.28% and the content ranged from 0.23% to 76.76% Alkane gas is the primary component of natural gas in all boreholes and the content ranged from 16.50% to 99.90% The drying coefficients of the alkane gas ranged from (C1/∑C1-5) 18.24%–99.84% and most of the drying coefficients were concentrated in the range of 60%–99% The samples where the drying coefficients of natural gas was greater than 95% account for approximately 40% and were mainly distributed in DK5 the drying coefficient of alkane gas is more variable the drying coefficients were relatively concentrated between 60% and 98% Ethane content ranged from 0.16% to 20.57% of alkane gas primarily concentrating between 0.20% and 15% Propane content ranged from 0.15% to 37.93% primarily concentrating between 0.01% and 10% Butane (including n-butane and isobutane) content ranges from 0.01% to 29.57% primarily concentrated between 0.01% and 10% The content of pentane (including n-pentane and isopentane) ranged from 0.01% to 15.81% primarily concentrated between 0.01% and 5% the results show a gradual decrease of each component with an increase in the carbon number in the majority of samples the molecular composition of some samples from DK1 and DK13–11 show the order of methane > ethane < propane Δ(δ13C2-δ13C1) (B) of alkane gas also indicating that the alkane gases from gas hydrates and free gases in the Muli Depression are organic in origin FIGURE 4. δ13Cn-1/n chart for identifying genetic types of natural gases FIGURE 5. Genetic-type identification diagram of δ13C2 vs. δ13C1 for natural gases (After Milkov, 2021) indicating that the natural gases in the Muli Depression are mainly thermogenic gases with biodegradation most of the natural gases show δ13C2 < -28‰ and a few samples show δ13C2 > -28‰ from DK5 and DK6 indicating that alkane gases are mainly oil-type gases with a little coal-type gas in DK5 and DK6 most of the alkane gases are located in the oil-type gases and other natural gases from DK5 are located in the coal-type gas area with a few samples in the secondary biogenic gas area indicating that the alkane gases are mainly the oil-type gases with a small amount of coal-type gases and secondary biogenic gases most of the samples are distributed at the intersection area of secondary microbial gases and thermogenic gases with a few samples found entirely in the area of secondary microbial gases further suggesting that biodegradation of natural gases has occurred in the Muli Depression Diagrams of gas dryness (C1/∑C1–3) vs the iC4/nC4 ratios from a large portion of the natural gases are greater than 0.8 and iC4/n-C4 ratios increase as the carbon isotope of methane becomes lighter which further confirms that biodegradation occurred in most natural gases pieces of evidence show that alkane gases in the Muli Depression underwent biodegradation Discrimination diagram of alkane gas diffusion and biodegradation (After Prinzhofer and Huc Δ(δ13C1-δ113C2) (B) for natural gases The molecular composition responds significantly to the diffusion of natural gases the molecular composition of the gas without diffusion decreases with carbon number the relative content of methane and ethane decreases and the relative content of propane increases The molecular composition of some samples from DK1 and DK13–11shows an order of methane > ethane < propane The order can be reasonably explained by the relative enrichment of propane due to diffusion This may be due to the fact that biodegradation leads to a sharp while diffusion leads to only a slightly heavier carbon isotope of methane Those natural gases that were both biodegraded and diffused also show the trends of biodegraded natural gas in iC4/nC4 ratios and methane carbon isotopes the δ13C2 values increase with decreasing Δ(δ13C2-δ13C1) values of alkane gases from DK2 and DK5 further proving the presence of diffusion in these two boreholes multiple lines of evidence from molecular composition and carbon isotopes show that the diffusion of natural gases occurred in the Muli Depression indicating that natural gas is a product of kerogen cracking at most FIGURE 9. Diagram showing C2/C3 vs. δ13C2-δ13C3 for the identification of kerogen-cracking gas and oil cracking gas at different thermal evolution stages (Modified after Lorant et al., 1998) The results show that Ro values of a large amount of samples range from 0.6 to 1.2% which is consistent with the thermal maturity of coal-type gases in the DK2 The Ro values of the alkane gases from humic kerogen in DK5 and DK6 are higher than 1.2% the methane would derive from secondary cracking of wet gases most of the natural gases are distributed in the area of the mature stage with a small number of natural gases from DK5 in the area of the high mature stage Considering the effect of biodegradation on the methane carbon isotopes of the natural gases from DK6 this would lead to a low assessment of its thermal maturity The natural gases from DK6 are coal-type gases and the ethane carbon isotopes are close to those from DK5 indicating that the natural gases from DK6 are also a product at the high maturity stage With further increase in thermal maturity (RO% = 2.0–3.5%) the liquid hydrocarbons are almost completely cracked resulting in a partial or complete reversal trend of the carbon isotopes (δ13C1 > δ13C2) FIGURE 10. Sketch map of geochemical patterns for natural gases (After Clayton, 1998) Most of the natural gases in the Muli Depression have the following characteristics: 1) they contain small amounts of carbon dioxide and nitrogen, and the alkane gas is wet gas; 2) the carbon isotope values of methane are lighter than those of ethane, and the ethane carbon isotope decreases with thermal maturity (Figure 3B); 3) the δ13C2 values range from -40‰ to -28‰ close to δ13C2 values of the mature to high-maturity stage These pieces of evidence indicate that the natural gases are mainly derived from the sapropelic kerogen and crude oil cracking The Ro values of coal-type gases in the Muli Depression exceed 1.3% the humic kerogen can generate a large amount of dry gases by secondary cracking of wet gases it is inferred that coal-type gas is the product of wet gas cracking gas multiple lines of evidence suggest that the oil-type gas is the production of primary cracking gas and secondary cracking of oil at the thermal maturity stage by sapropelic kerogen and the coal-type gas is the production of secondary cracking of wet gas generated by humic kerogen at the high maturity stage The oil and gas that have been discovered in the SQB indicate that the petroleum’s basic conditions for forming oil and gas reservoirs are in existence providing petroleum systems for the generation of light oil and condensate widely developed in the Lower Jurassic period are mostly type I and II kerogens with high organic matter abundance (TOC greater than 2.0%) also suggesting high generation potential and expulsion efficiency of hydrocarbon Jurassic source rocks in the mature to over-mature stage have the thermal maturity to form light oil and condensate Jurassic natural gas is a predominantly oil-type gas of the mature to over-mature stage which is consistent with the geological conditions for the generation of light oil and condensate and OGIs related to natural gas show the existence of light oil and condensate in the Jurassic Yaojie Formation 1) The natural gas in the Muli Depression of the SQB is mainly oil-type gas 2) The natural gases have undergone secondary alteration (biodegradation and diffusion) Biodegradation results in lighter carbon isotopes and a relative increase in the molecular content of methane in the alkane gases The diffusion leads to heavier carbon isotopes and a relative decrease in the molecular content of methane 3) Most of the natural gases were generated from sapropelic kerogen directly and crude oil cracking to wet gas with a small number of natural gases from DK5 and DK6 derived from wet gas cracking gas 4) Light oil and condensate may exist in the Jurassic strata of the Muli Depression The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding authors This research was financially supported by the National Natural Science Foundation of China (41702144; 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use *Correspondence: Yang Li, bGl5YW5neGJkeEAxNjMuY29t; Jingli Wang, d2FuZ2psQHN0dW1haWwubnd1LmVkdS5jbg== Metrics details The Muli area is the only permafrost region on the Chinese mainland wherein gas hydrates have been discovered The gas hydrates are present in the fractures and pore spaces of the host rocks with a lamellar or micro-disseminated structure we describe the thickness of the permafrost layer and the well log responses of the gas hydrate reservoir and calculate the porosity and gas hydrate saturation We then analyze the advantages and disadvantages of different logging methods for evaluating gas hydrate reservoirs Our results indicate that (1) gas hydrates are present below the permafrost in the Muli area (2) gas hydrates predominantly occur in rock fractures (3) the apparent resistivity is sensitive to gas hydrates present in pore spaces and both apparent resistivity and acoustic logs are sensitive to gas hydrates present in fractures (4) a density log is more appropriate for calculating porosity and (5) gas hydrate saturation can be effectively calculated by the Archie equation This study focuses on the data from well logs which were collected using a Micro-Logger II system (Robertson Geologging Ltd. Well logging included the production of electrode resistivity logs The purpose of well logging evaluations is to transform well logging data into reservoir parameters such as porosity and gas hydrate saturation which are critical for the evaluation and production of gas hydrate resources we develop a set of well logging methods that can be used to evaluate high-altitude permafrost gas hydrate reservoirs Temperature logs from seven boreholes (DK6 Temperature logs indicated that there were two dominant patterns of temperature with depth (Fig. 2) in which temperatures were higher at the shallowest depths and finally increased to their highest values with increasing depth (e.g. The other pattern observed was the “L” curve in which temperatures were steady in the top section and then increased in the lower section (e.g. all temperature logs could be used to determine the thickness of the permafrost region gas hydrates occur in cracks in rocks with lamellar structures or in the pore spaces of rocks with micro-disseminated structures The lithology of the gas hydrate reservoir in this study is predominantly mudstone The occurrence of gas hydrates varied with lithology and structure so it is reasonable to analyze the log responses of the reservoir according to its lithology The accumulated thickness of the gas hydrate-bearing sandstone gas hydrates in the study area occur predominantly in fractures within mudstone and shale as both lithologies are characterized by low porosity We evaluated the well log responses of each lithology by computing the resistivity and density anomalies for each of the 67 gas hydrate-bearing layers and comparing them to layers without gas hydrates Well logs of sandstone (borehole DK8) with and without gas hydrate (red triangle indicates the gas hydrate layer) and (c) density (g/m3) responses of sandstone reservoirs with (blue bars) and without (green bars) gas hydrate in the study area Well logs of the mudstone (borehole DK8) with and without gas hydrate (red triangle indicates the gas hydrate layer) and (c) density (g/m3) responses of mudstone reservoirs with (blue bars) and without (green bars) gas hydrate in the study area Well logs of the shale (borehole DK9) with and without gas hydrate (red triangle indicates the gas hydrate layer) and (c) density (g/m3) responses of shale reservoirs with (blue bars) and without (green bars) gas hydrate in the study area Similar to well logs from another permafrost region, represented by the Northwest Eileen State-2 well, and the marine well from the Deep Sea Drilling Project (DSDP), Leg 84, Site 570 (Table 3) the resistivity logs increased in the gas hydrate-bearing units in the Muli area the acoustic and density logs of pore-type gas hydrate-bearing reservoirs in the study area showed no anomalies the acoustic and density logs of fracture-type gas hydrate-bearing reservoirs show similar anomalies to these other regions The caliper log was slightly increased in the Muli area; however the anomalies were weaker due to the lithology and low volume of gas hydrates (b) Gas hydrate saturations estimated from the four models employed The gas hydrate saturation calculated by the empirical equation based on the resistivity log performed better than that based on the acoustic log; thus resistivity logs are more suitable for the evaluation of gas hydrate saturation in the Muli area and the Indonesian equation to compute gas hydrate saturation Using the DK8 well as an example, core analysis at a depth of 154 m revealed a gas hydrate saturation of ~50%. Figure 9b illustrates the calculated gas hydrate saturation of the pore-type fine sandstone at a depth interval of 148–155 m indicating that the values calculated by the Archie equation and the Indonesian equation were close to those derived from the core tests and therefore suitable for evaluating gas hydrate saturation in the Muli area the Indonesian equation appeared to be suitable for units with low salinity waters where resistivity of the formation water Rw = 3 Ωm The modified Archie equation and the Indonesian equation can be used for units with high clay contents (Vsh ≥ 10%) because the equations contain correction terms to overcome the effect of clay As the drilling process can change the temperature and pressure conditions of the host rock and lead to decomposition of gas hydrates both gas hydrate and gas are present in the pores leading to a greater gas hydrate saturation when calculated by an acoustic log the acoustic log must be corrected before being used to compute gas hydrate saturation The correction equation can be obtained by laboratory experiments The selection of a gas hydrate saturation model depends upon the distribution of gas hydrates and clay it will plan an important role in the evaluation of gas hydrate reservoirs in the future We tested three models in the Muli area and achieved reasonable results which can provide insights into the evaluation of gas hydrate saturation in areas with similar geologic histories The range of the permafrost thickness in the Muli area is from 70 to 120 m The pore-type gas hydrate reservoir can be identified by apparent resistivity logs while the fracture-type gas hydrate reservoir can be identified by apparent resistivity and acoustic logs The gas hydrate-bearing rocks of the study area are predominantly fracture-type reservoirs which exhibit lower apparent resistivity values (75–250 Ωm) and higher densities (2.36–2.6 g/cm3) than the pore-type reservoirs The pore-type gas hydrate reservoir has an apparent resistivity of 370–490 Ωm Using the density log is a particularly effective method for calculating reservoir porosity in this area Our study indicates that the Archie equation is suitable for evaluating the gas hydrate saturation in formations with low clay contents (Vsh < 10%) while the modified Archie equation and the Indonesian equation are both suitable for formations with high clay contents (Vsh ≥ 10%) The thickness of the permafrost was determined using temperature logs obvious variations in the geothermal gradient were observed which indicated the bottom depth of the permafrost Schematic of the borehole temperature variation in the permafrost region CNL and NMR have not been previously applied in the study area; therefore, in this study, density and acoustic logs were used to compute the porosity of gas hydrate reservoirs (Table 5) and compared to porosity determined by core tests The composition and structure of gas hydrate-bearing reservoirs are very complex; therefore we simplified the model structure during calculation it was prudent to use multiple models to improve the accuracy of our interpretations As the gas hydrate-bearing reservoir was below the permafrost gas hydrate saturation was evaluated as a function of the primary matrix (i.e. where ϕ is porosity and Rt is rock unit resistivity. The resulting Rw of the study borehole is ~3 Ωm. To obtain the resistivity of the units saturated by water (Ro), we used the following equation (Eq. 2): and n were obtained by core tests and the other empirical parameters were from the literature Well log evaluation of natural gas hydrates Review of natural gas hydrates as an energy resource: Prospects and challenges Resource potential and reservoir distribution of natural gas hydrate in permafrost areas of China Gas Hydrates in the Qilian Mountain Permafrost Basic geological characteristics of gas hydrates in Qilian Mountain permafrost area Main achievements of gas hydrate exploration technology in permafrost regions of China Downhole well log characterization of gas hydrates in nature-a review The 7th International Conference on Gas Hydrates: United Kingdom (2011) Well Log Characterization of natural Gas-Hydrates The SPWLA52nd Annual Logging Symposium: Colorado (2011) Downhole well log and core montages from the Mount Elbert Gas Hydrate Stratigraphic Test Well Gulf of Mexico Gas Hydrate Joint Industry Project Leg II logging-while-drilling data acquisition and analysis Semi-quantitative gas hydrate assessment from petroleum industry well logs in the northern Gulf of Mexico Well logging assessment of natural gas hydrate reservoirs and relevant influential factors Physical Analysis with the Logging data on Natural Gas Hydrate in Qilian Mountain permafrost area Hydrate petroleum system approach to natural gas hydrate exploration A seepage gas hydrate system in northern South China Sea: Seismic and well log interpretations Anomlous wireline logging data caused by gas hydrate dissociation in the Shenhu area Elevated gas hydrate saturation within silt and silty clay sedimentsin the Shenhu area Review on Logging Technology Evaluation Methods of Nature Gas Hydrate Estimating pore-space gas hydrate saturations from well log acoustic data Gas hydrate saturations estimated from fractured reservoir at SiteNGHP-01-10 Pore- and fracture-filling gas hydrate reservoirs in the Gulf of Mexico Gas Hydrate Joint Industry Project Leg II Green Canyon 955 H well Well Logging Evaluation of Gas Hydrates in Shenhu Area Permeability and porosity of hydrate-bearing sediments in the northern Gulf of Mexico Research on Logging Interpretation Method of Gas Hydrates Numerical Simulation of Saturation Parameters in Gas Hydrate-bearing Reservoirs Gas hydrate saturation and distribution in the Kumano Forearc Basin of the Nankai Trough sedimentation characteristics and distribution of gas hydrate in Muli Coalfield of Qilian Mountain China University of Geosciences: China Beijing (2012) A Sequence Stratigraphic Discussion of the Jurassic Coal Measures in the Juhugeng Coalmine Area in Qinghai Province Study on the accumulation pattern for permafrost-associated gas hydrate in sanlutian of Muli Logging identification and evaluation methods for gas hydrate Method of estimating the amount of in situ gas hydrate in deep marine sediments Download references This research was supported by the National 863 Plan [Grant No the National Special Research Fund (Gas Hydrate Resource Exploration and Production Testing Project) [Grant No and the National Nature Science Foundation of China [Grant No We thank Drs Miao Luo and Sinan Fang for their constructive suggestions Institute of Geophysical and Geochemical Exploration provided technical guidance for the writing of the manuscript was involved in well logging and prepared Figures 3 All authors reviewed and consented to the publication of the manuscript The authors declare no competing interests Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-018-30795-x Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Connor Muli knows what it takes to become a region champion Muli won the Region 7 championship at 103 pounds so he learned early what it felt like to reach the top of the podium He will get his last chance to become a two-time region champion this weekend at the Region 7 tournament at Robbinsville High School The quarterfinals will be held tonight at 5:30 followed by a full day of competition on Saturday The region finals are scheduled to begin at 5 on Saturday 2 seed behind top-seeded Justin McTamney of Bordentown McTamney won the 132-pound title last season with a 9-2 win over top-seeded Muli in the region final “But I didn’t feel like I wrestled my best so I feel good now and I just want to take it one match at a time and get back to the finals again.” his only loss coming to Camden Catholic’s Mark McCormick with a 4-3 decision on Feb Shawnee coach Tom Mann believes Muli is in good position to have a successful postseason run “He’s really turned it on the last half of the season.” The coach thinks wrestling against some top competition in the regular season will help all his remaining Renegades deal better with the pressures to come “I really think going to the Garden State Duals — competing against Delbarton and Bergen Catholic was beneficial for us,” he said “It put us against some quality teams and I think that environment helps This will be his fourth time in the regions and it would be his third time in Atlantic City so he’s confident because none of this is new to him anymore.” One thing that Muli has had this season that he’s lacked in the past couple is a sense of consistency “In my freshman year I was pretty consistent,” he said “But in my sophomore and junior years I was pretty inconsistent the weight-cutting — it hasn’t been a problem If there was a low point to Muli’s career it came in the beginning of his junior year and he didn’t come out of the team at the start of the season I cut a lot of weight for national tournaments and mentally I wasn’t in the right place to start the season with the team,” he said I had a pretty good showing at the end of the year.” So I’m just working to get back there one match at a time.” Reach Don Benevento at dbenevento@gannett.com Francine Diaz and Seth Fedelin embody the crumbling relationship at the center of Ace Banzuelo’s Muli Related: TikTok Strikes Again: Ace Banzuelo’s ‘Muli’ Is The Internet’s New Favorite OPM Jam When Ace Banzuelo released Muli in October 2020 (yes as does any artist when revealing their work to the world the breakup anthem isn’t like most OPM breakup songs you hear and not to mention a killer guitar rift for a breakup tune that hits harder than most What Ace probably didn’t expect though was that it would take over two years for Muli to finally get the praise and recognition it deserves after it went viral on TikTok Millions of new streams and hundreds of thousands of plays on TikTok later Muli finally got its highly anticipated music video And one of the top OPM songs in the country right now deserves a top tier lead cast And that came in the form of one of the most promising love teams of today Ever since they first appeared in Kadenang Ginto years ago a strong subset of fans hoped for Francine and Seth to finally have an official project together And fans got their wish with the announcement of their new show fans got an extra special treat as the two play the leads of Ace Banzuelo’s Muli music video Seth and Francine aren’t strangers to appearing in music videos. While this isn’t the first time that they’ve appeared in a music video together Muli is the first time they appear together as an official love team and they’re swinging right out of the gate in an emotionally charged music video people were curious to see what Ace would serve up for the music video to his surprise hit and the young OPM artist really brought out the big guns Set mostly in grassy fields and produced by Chapters the video’s narrative follows Seth and Francine as a young couple their relationship encounters rocky waters as they try to put their love back before its eventually crumbles The visual captures the disintegration of what used to be a promising relationship with FranSeth struggling to process their pain What’s interesting about the video is that it also features a strong use of abstract symbolism the video employs imagery to show a house on fire The mostly muted color palette of the music video allows for its cinematography The two Gen Z stars really bring out the emotion of the song and the chemistry is felt but we have to give a shout out to Seth Fedelin who really delivered on the assignment of a man collapsing out of love Ace himself also appears in the video where he and Seth play the same character with Ace embodying the inner conflicting emotions of Seth but still reflects the intensity of the song,” said Jake Soriano This actually isn’t the first time Soriano has worked with both Francine and Seth this project was the first time that he witnessed the loveteam deliver a nuanced performance and showcase their range as dramatic actors We always get a good laugh during shoots.” he initially was open to doing the music video by himself But the clamor from the fans led him to change his mind I was okay to do the music video alone with what I had and messages from multiple fans that they wanted to see me collaborate with local actors.” Ace who had involved in the brainstorming and creative process of the music video had his team reach out to FranSeth’s team and to his joy Working with Seth and Francine was super fun I’m proud that we were able to capture the vision of song and present it through the long-awaited video.” If you’re itching for more FranSeth content keep an eye out for their first show together the singer-songwriter and producer is currently working on his debut full length album which is set to drop later this year Continue Reading: Francine Diaz Is A Lover In Mourning In Zack Tabudlo’s ‘As You Are’ Music Video