We deliver! Get curated industry news straight to your inbox. Subscribe to Adweek newsletters
HBO’s The Last of Us and Corona are raising a glass to the new season and a new partnership
Heading into the Last of Us Season 2’s premiere in April
Discovery Ad Sales and Corona teamed up for the “La Playa Awaits” campaign
which celebrates Season 2 of the zombie series as well as the alcohol brand’s 100th anniversary
the idea is to have a beach mindset no matter where you are—even if you’re in a post-apocalyptic world overrun by zombies infected by parasitic mushrooms
5 Immersive Brand Collabs for The Last of Us Season 2
The campaign activated around key series events
including providing Corona Extra and non-alcoholic options for guests at the March 24 premiere at the TCL Chinese Theater in Los Angeles
as well as the sponsorship of an influencer pre-screening of the first episode at the Domino Sugar Factory in Brooklyn
Corona also provided the title sponsorship and supporting media in the first and second seasons of The Last of Us on Max
Corona also debuted two 30-second custom ads featuring The Last of Us star Gabriel Luna
The ads show Luna making the most of the post-apocalyptic situation after discovering an ice-cold Corona beer
The spots aired on Max’s ad-supported plan ahead of The Last of Us episodes and across social media via the CoronaUSA and Max accounts
“I’m proud to partner with Corona to help celebrate ‘La Playa Awaits’ through a world that parallels the one I exist in as Tommy on the HBO Original series The Last of Us,” Luna said in a statement to ADWEEK
“‘La Playa Awaits’ represents the beach mindset
inviting people to make the most of the present moment
which is something I strive to do every day
if only Tommy could stumble upon a cold Corona.”
Corona launched a retail activation and sweepstakes with co-branded assets in select retail environments
Fans of the show and the beer brand have the chance to enter a giveaway to win exclusive The Last of Us merchandise
including a special edition Taylor Guitar 314 replica like the one that appeared in the series
“Partnering with the HBO Original series The Last of Us is another way we seek to immerse into our consumers’ passions,” Rob Nelson
‘La Playa Awaits,’ reminds us all of the power of being more present in the moment
which is embodied in this partnership—whether through the characters in the construct of the show itself
or as viewers collectively coming together and tuning into one of the most anticipated seasons in television history.”
In addition to Corona, The Last of Us also recently rolled out collaborations with Four Sigmatic
Saleah Blancaflor is a TV reporter at ADWEEK
Adweek is the leading source of news and insight serving the brand marketing ecosystem
May 5, 2025 3:02 PM EDTAmericans love their beer
but the best-selling beer in the United States is imported from Mexico
Modelo Especial overtook Bud Light to become the top-selling beer brand in America
is still flying off the shelves in the U.S
According to Darren Rovell of cllct media and Kickstand Cocktails, via BevNet
Modelo has been the most purchased beer in America over the last year
Coors ($3.13 Billion) and Corona ($3.12 billion) round out the top five
Both Corona and Modelo Especial are made by the Grupo Modelo brewery south of the border
The best cheap beers in America range from Budweiser to Miller Lite to Corona to Modelo
feeling fresher and more authentic.”
Bernot added that the Mexican imports are "just cooler brands," and their rise is indicative of a surge in Latin American culture in America in other areas
“We see it in music as well,” Bernot said
“Look at Bad Bunny and Nathy Peluso
It matters that these beers have cultural cache at a time when Hispanic cultural exports of all kinds—food
music and art—are enjoying a moment in American mainstream culture.”
As for the American brands, Miller can at least take solace in being named "America's favorite beer" in a recent study by Coffeeness, a German-based website.
Miller was the preferred brew in 30 of 50 states, finishing well ahead of Coors, which placed second as the favored beer in eight states.
By Andrew HolleranAndrew Holleran is a trending news writer on Men's Journal
He's covered sports and pop culture for more than a decade
How to watch California high school boys lacrosse: Loyola vs
May 6Data SkriveWe have an exciting high school game in Los Angeles
with Loyola High School hosting Corona Del Mar High School
How to watch Corona Del Mar vs. Loyola boys lacrosseCorona Del Mar and Loyola will hit the field on Tuesday, May 6, at 5 p.m. PT. Don't miss out on any of the action with NFHS Network
The NFHS Network gives you access to live high school sports around the country
Follow your favorite team and never miss a game
Want to track your alma mater, local team or family member's school throughout the playoffs? NFHS Network has high school lacrosse streaming live
plus on-demand replays and highlights of all the action from thousands of schools across America
Watch Loyola vs. Corona Del Mar on NFHS Network!
All NFHS Network events are available to watch online at and through the NFHS Network Mobile Apps for iOS and Android and TV Apps for ROKU
The team analyzed radio-frequency data from the Parker Solar Probe (PSP) but did not find any spectral distortions that would have been dark-photon evidence
The researchers thus place the strongest limits yet for dark photons with masses around 10−9eV/c2
The dark photon is an appealing dark-matter candidate because it can arise naturally within certain string-inspired theories
these models do not fix the mass of the dark photon
searches have spanned many orders of magnitude in mass from 10−18 to 106 eV/c2
The ultralight dark photon (less than about 1 eV/c2) stands out
as it offers distinctive cosmological effects and novel experimental signatures
Remarkably, we may not be completely blind to the dark photon, as it could interact with normal particles through a phenomenon known as kinetic mixing [4]
This feeble coupling effectively allows dark photons to “oscillate” into ordinary photons and vice versa
much like neutrinos oscillate between different flavors
This oscillation can be enhanced in certain environments
One such environment is the solar corona—a superheated
ionized gas extending millions of kilometers into space around the Sun
The electrons in this plasma interact with normal photons
causing them to behave as if they had a mass
The value of this effective mass depends on the corona’s electron density
which decreases with distance from the Sun
If a dark photon passes through the solar corona
and its mass is equal to the effective mass in a particular region of the plasma
then the dark-to-normal conversion will be dramatically enhanced through a resonant interaction
The resulting photon is highly monochromatic
with an energy equal to the dark photon’s mass
Some of these converted photons will be absorbed or scattered in the plasma, but a fraction of them will escape, leading to an observable “bump” in the spectrum of the corona. Researchers have previously looked for this dark-photon signature using ground-based radio telescopes [5]
These observations have been limited to photon frequencies above 10 MHz
corresponding to dark-photon masses above 10−6 eV/c2
The reason for this limited range is that radio frequencies below approximately 10 MHz are reflected back into space by Earth’s ionosphere
ground-based radio telescopes suffer from an attenuated signal because of the vast distance between the Sun and Earth
To address these limitations, An and his colleagues have used the PSP as an in situ dark-matter detector. The PSP is a NASA mission designed to study the solar corona by flying closer to the Sun than any previous spacecraft (see Special Feature: To Touch the Sun)
the probe reached its closest perihelion distance of approximately 10 solar radii in July 2022
but its highly elliptical orbit has allowed it to study up close the corona’s plasma over a wide range of radii—and thus over a wide range of electron densities
The PSP’s two radio receivers are capable of measuring frequencies ranging from about 20 kHz to 20 MHz
Using these radio data and the orbital path of the probe
An and colleagues could look for spectral bumps corresponding to dark-photon masses between 3 × 10−10 and 8 × 10−8 eV/c2
For smaller dark-photon masses (and equivalently smaller frequencies)
the researchers also considered data from the Solar Terrestrial Relations Observatory (STEREO)
which maintains a fixed orbital distance of 1 astronomical unit from the Sun
The search for dark-photon dark matter remains vigorous
having made significant progress over the past decade
The work of An and colleagues carves out a novel pathway
limiting lightweight dark photons to have either an extremely feeble kinetic mixing parameter or a very low mass (below 10−15 eV/c2)
where the parameter space remains relatively open
An interesting way to improve the sensitivity to ultralight dark photons involves resonant LC circuits—sometimes called dark-matter radios
These experiments aim to detect the dark photon’s tiny
oscillating electric fields by tuning the circuit to the particle’s Compton frequency
allowing dark photons to induce a faint but measurable current
Several such experiments are on the horizon
Paola Arias is a particle physicist based in Santiago
She earned her PhD from the University of Santiago
and has held two postdoctoral research positions: one at the German Electron Synchrotron (DESY) in Germany
as a Humboldt fellow; and another at the Pontifical Catholic University of Chile
Her research focuses on extensions of the standard model
with a particular interest in WISPy particles
She is deeply fascinated by the interplay between particle physics and cosmology
especially in how it can help us uncover the properties of dark matter
Phys. Rev. Lett. 134, 171001 (2025)
The planned MUonE experiment could—in addition to studying the muon’s magnetic moment—search for dark matter particles. Read More »
Measurements of millions of galaxies suggest that dark energy changes over time and is more complicated than previously thought. Read More »
The Euclid satellite released its first trove of galaxy data based on seven days of deep-field observations in three sky areas. Read More »
Researchers have shown that they can distribute quantum keys under realistic conditions using commercial lasers
Student enrollment and guaranteed financial support are expected to fall amid anticipation of federal budget cuts
Two independent teams have searched for axions using x-ray observations of entire galaxies
setting some of the strictest constraints to date on the properties of these dark matter candidates
More Recent Articles »
Sign up to receive weekly email alerts from Physics Magazine
Use of the American Physical Society websites and journals implies that the user has read and agrees to our Terms and Conditions and any applicable Subscription Agreement.
, opens new tab. The levies went into effect on April 4.The move would potentially drive up prices of cocktails
champagne and foreign beers and wipe out jobs in the spirits industry
according to drinks industry bodies and analysts.Late on Wednesday
Trump said he would temporarily lower the hefty duties he had just imposed on dozens of countries while further ramping up pressure on China.Constellation Brands also projected annual enterprise organic net sales between a 2% decline and 1% growth
while forecasting wine and spirits income to slump up to 100%.Beer sales made up nearly 82% of total fiscal 2024 revenue for Constellation Brands
while wine was about 16%.It posted fourth-quarter net sales of $2.16 billion
beating estimates of $2.13 billion.Reporting by Savyata Mishra in Bengaluru; Editing by Maju Samuel
Our Standards: The Thomson Reuters Trust Principles., opens new tab
, opens new tab Browse an unrivalled portfolio of real-time and historical market data and insights from worldwide sources and experts.
, opens new tabScreen for heightened risk individual and entities globally to help uncover hidden risks in business relationships and human networks.
© 2025 Reuters. All rights reserved
— In the first eight years that Bob Mauger taught his auto body course at Corona High
maybe three balls were hit into his classroom area
located well beyond the baseball team’s left-field fence
The peace and quiet to which he’d become accustomed ended on the first day of practice last fall
He stormed up to the field in a huff; his sanctuary was suddenly the site of what felt like target practice
“The balls were just raining down on my classroom,” Mauger recalled
Head baseball coach Andy Wise had started to run toward Mauger’s classroom
This has never happened in all the years I’ve been here.’”
Mauger was certain this was the result of some thoughtless drill
perhaps one that required hitting from the outfield grass
the coaches were taking swings — it had to be them because high schoolers couldn’t hit the ball this far
Corona baseball was built from scratch into one of the nation’s most formidable powerhouses
The best team in the most populous state resides at a school that never could have imagined this level of success
it has three players projected to be first-round MLB Draft picks: pitcher Seth Hernandez
shortstop Billy Carlson and infielder Brady Ebel
it would be the first time in the draft’s history that one high school produced three first-rounders — with an outside chance at a fourth
amid a season that might be once in a lifetime
And there is perhaps no better measure of its prowess than the damage it’s done to one teacher’s classroom
potential new players or fans who have flooded this school
it’s Mauger’s body shop — and the 40-foot fence the school will build to protect the rest of the classrooms — that serves as the most tangible measurement of growth for this program and the players in it
tell everybody,’” Wise said he told Mauger
who initially wanted the principal to step in
Corona faced something it will seldom experience this year: a deficit
was a celebration by the opposition akin to winning a championship
His team wasn’t even using its full complement of starters
the Panthers are 6-0 and have outscored opponents 35-1
They will be every opponent’s biggest game
“I told the team they kind of remind me of us
Los Angeles Dodgers third-base coach Dino Ebel
who often throws BP or fungoes with the team
“We’ve got a target on our backs everywhere we go
The Ebels are a great example of the benefits of building
Dino’s sons transferred from Etiwanda High to play for Corona
They liked the way Wise coached fundamental baseball
He came with his parents to watch Corona’s games before eventually enrolling
who transferred in this season at the suggestion of Hernandez and Carlson
It’s so anomalous to what’s possible that there’s no way it can be sustained at this level
It’s a product of building a culture so strong that the best baseball players from all over will do whatever it takes to get a roster spot
“I was a little freshman kid just trying to make my way
who has been with the program his entire high school career
“To see the growth of Corona and the program is super special.”
Carlson is the only player among Corona’s group of stars who has known only one school
He developed into a prospect and is rated No
Wise made a point to stand behind first base as his shortstop took grounders
highlighting how assured he was by his shortstop’s accuracy
He’s committed to Tennessee and says he’s confident he’ll stick as an infielder in the professional ranks
Hernandez plans to pitch at the next level
Scouts line the bleachers anytime he’s on the mound
5 overall draft prospect and is widely considered the best high school pitcher available
“I think it’s definitely a lot of pressure
but only if you think about it too much,” Hernandez said
turn into a man — some crazy things can happen.”
Bingaman is the player who everyone comes to see
Instead, he’s a relative afterthought in the national conversation surrounding this team because he will have to play his way into the first round this year, whereas his more publicized teammates will have to play their way out of it. The Athletic’s Keith Law had Carlson and Hernandez within his top 30 draft prospects
“There’s no way that you can say anybody in the lineup is better than Ethan Bingaman,” Wise said
Is that a slap in the face to a Brady or a Billy
And it’s one Bingaman — a two-way player with speed
“I could see myself in the first round,” Bingaman said
“I’ve just got to keep proving people wrong.”
San Francisco Giants starting pitcher Tristan Beck will regularly log in to online streams to watch Corona
The seeds of the success date back to veteran MLB reliever Joe Kelly
who graduated from the school nearly 20 years ago
He also played a critical role in bringing the Ebels on board this year
whom Wise credits as being the catalyst for the most recent iteration of Corona High baseball
In the aftermath of his tenure at the school
the team has gotten better and more players have gone to top colleges
“It’s one of the best high school teams of all time
Beck and Kelly are the only big leaguers to come from Corona since 2001
and the school has produced only five in its history
That’s because Corona is not the biggest school
News & World Report ranks it as the sixth-best school in the district and 692nd in the state of California
“This is the lowest socioeconomic school in the district,” Wise said
They don’t come from the prototypical SoCal powerhouse mold — think Harvard Westlake
Junipero Serra and Huntington Beach — but that’s exactly where this is headed
pitcher Ethan Schiefelbein was selected by the Detroit Tigers with the No
Corona hopes to have multiple players drafted
Athletic director Jeff Stevens said the winning has brought a different set of challenges — namely
a lot of people from all over hoping to transfer into the program
He has to explain all the various requirements to parents and stress that playing time won’t be guaranteed
“When we did what we did last year,” Stevens said
referring to Corona’s California Interscholastic Federation Division I championship
“I was getting emails from families in Mexico saying
‘We want to transfer to your school.’ I had a family reach out to me from Puerto Rico.”
It’s remarkable for a school that has no real advantages
and its current building was constructed in 1907
It does not have the resources or amenities
“It makes me feel good that people have the decision of where they want to go,” Wise said
“I ain’t asking or begging or telling nobody to come here.”
Wise’s attention is always getting pulled in different directions
all of whom want to be at games or practices
Wise is the brash but approachable mastermind behind this team’s success
And after losing just three games last year
he believes his program can go undefeated this season
Baseball is a weird game in that failure is inevitable at some point
A bad outing on the mound or a few bats go cold for a day and an upset loss could be the result
That conventional wisdom might not apply to this team
“We should be favored in every game,” Wise said
“If we’re going to run out a pitcher — the other team might have a great pitcher
I feel like we could go undefeated if we play our game the right way,” Brady Ebel said
“Win every tournament we’re in and hopefully become CIF champions back-to-back years.”
The players say they haven’t allowed themselves to think much about draft day — where they’ll be or who they’ll spend it with
all this attention was brought on so quickly
It wasn’t long ago that Carlson was committed to Vanderbilt
so he switched that commitment to Tennessee
a choice rooted solely in his baseball future
It’s with that understanding that all these players and coaches operate
Not even their names being called on July 13
they’re focused on what’s in front of them: a high school baseball season
the likes of which we have never seen before and might never see again
“It’s going to be history,” Hernandez said of this season and the upcoming draft
“I think that’s pretty cool to leave a legacy behind at this place.”
(Top photo of Billy Carlson: Gia Cunningham / Courtesy of Corona High School)
Sam Blum is a staff writer for The Athletic covering the Los Angeles Angels and Major League Baseball. Before joining The Athletic, he was a sports reporter for the Dallas Morning News. Previously, he covered Auburn for AL.com and the University of Virginia for The Daily Progress in Charlottesville.
Corona celebrates its 100-year anniversary, a remarkable milestone for the iconic brand that has been synonymous with the beach and enjoyed by consumers worldwide for the past century. Since 1925, Corona has cultivated a deep association with the beach; fully embodying a lifestyle connected to nature and relaxation.
In honour of the occasion, Corona invites everyone to live their 'beach side' – a.k.a. their best side – at top-tier beach locations across the globe. The Corona 100 platform includes a film highlighting 100 years of beach culture, a definitive list of the top 100 beaches in the world to visit, and a signed multi-year sponsorship of a renowned concert at Copacabana Beach in Rio de Janeiro — all offering people across the globe opportunities to connect with their beach side.
To honour a century of beach side living, the brand has created its Corona Beach 100 list: a curated guide of the world’s most iconic beaches that best represent Corona’s 'This is Living' expression. From hidden coves to legendary coastlines to remote paradises, these beaches aren’t just destinations; they’re places where people have travelled for centuries to disconnect from the real world and reconnect with nature.
The guide includes sandy beaches from famed hotspots within South Africa, Mexico, and Brazil, as well as showcases some lesser travelled shorelines, such as Chile’s Punta de Lobos, Iceland’s Stokksnes Beach, and Canada’s Cox Bay Beach, among many more.
Additionally, Corona is offering the chance to visit the iconic beaches featured on the Beach 100 list. Anyone of legal drinking age can enter to win a chance to tap into their beach side at one of the 100 crowned coastlines simply by purchasing the special edition 100 Anniversary pack and scanning the QR code. Other instant win items include Corona merchandise, coolers, towels, and digital vouchers.
To access the Beach 100 list – developed in partnership with experiential marketing agency, WINK – and to learn more about how to win Beach 100 prizes, visit Corona.com for more information.
To kick-off the anniversary in grand fashion, Corona will take over one of the most iconic beaches in the world – Copacabana Beach in Rio De Janeiro – as a marquee sponsor of a global concert that will transform the shores of Copacabana Beach into the ultimate celebration. Taking place on May 3rd, the concert will captivate millions of attendees on the beach where each year the concert will feature some of the world’s most popular musical artists and bands.
From its origins in Mexico in 1925, Corona has been dedicated to quality with an emphasis on how the beach lifestyle positively impacts consumers worldwide. Named the World’s Most Valuable Beer Brand in 2024, Corona has turned every sip into a moment of connection through its premium products – brewed with 100% natural ingredients including its iconic lime ritual – and continues to bring more 'This is Living' moments of social connection and relaxation into the world.
To highlight those 100 years of beach culture, Corona has unveiled a branded legacy film, titled 'This is Living Since 1925,' that brings to life many decades unfolding over the course of a day. From the early beginnings of beach side gatherings during the bikini era to swimming and surfing across the globe today, the archival look and feel across the film sets the tone for each decade, which also depicts a variety of beaches and coastlines from around the world.
As seen in the film – created in partnership with Wieden+Kennedy Amsterdam – Corona’s integration within the beach culture is effortless in the scenes over time, a testament to the brand’s natural place on the beach 'Since 1925.'
The 360 platform also features vibrant new digital, trade, and OOH assets that highlight how Corona has remained a staple for beach lovers from around the world for generations — no matter the season or location.
The centennial celebrations will continue throughout 2025, so grab a lime, raise a Corona, and join the brand in commemorating a century of vibrant beachside living. Cheers to 100 years under the sun and to the next century of unforgettable 'This Is Living' moments.
a list of the world’s top 100 beaches and a multi-year sponsorship of a concert at Copacabana Beach in Rio de Janeiro—beginning May 3 with a Lady Gaga show.","type":"text"},{"_id":"5ZW2SIEJ4FE3DAP6E5SFNUDI6Y","additional_properties":{},"content":"The beer brand worked with experiential marketing agency Wink on the beach curation part of the project
free divers and other nature enthusiasts to curate the list
rating each beach based on beachside culture
connection to nature and scenic aesthetics.","type":"text"},{"_id":"27ZC5IZHJFHQ5P4WBLRCTHIDOQ","additional_properties":{},"content":"The list includes well-known hot spots in South Africa
as well as lesser known shorelines such as Chile’s Punta de Lobos
Corona is also set to sponsor concerts at Copacabana Beach in Brazil
The 100th anniversary concert will take place May 3 featuring Lady Gaga
The free show launches “Todo Mundo no Rio,” a new cultural initiative in Rio.","type":"text"},{"_id":"E6Z4C25KDVAODDM7S5I2EJYTCI","additional_properties":{},"content":"“For 100 years
Corona has fully embodied the ‘This is Living’ spirit of the beach lifestyle
inspiring people to disconnect from their everyday routine and reconnect with nature and each other,” said Clarissa Pantoja
“Enjoyed by millions around the world today and still growing
Corona will always remain unwavering in its commitment to the beach
This anniversary is not just a celebration of our legacy
He was previously editor in chief of the Clio Awards and Muse by Clio
and has also served as creative editor at Adweek.","slug":"/author/tim-nudd","native_app_rendering":false,"fuzzy_match":false,"contributor":false,"status":true,"last_updated_date":"2025-03-31T20:40:15.144Z","role":"Creativity Editor"}}}]},"description":{"basic":"Wink helped to build the global Corona Beach 100 experience
backed by a W+K Amsterdam film."},"display_date":"2025-04-29T12:15:13.41Z","distributor":{"category":"other","mode":"custom","name":"crain"},"editor_note":"1
Disregard subheadline field in article template.\n2
Left panel in sepia tone with \"THIS,\" center in soft color with \"IS LIVING,\" and right in modern photo quality with \"SINCE 1925,\" set against various beach backgrounds.","auth":{"1":"43359b663491bb57d4e66a052d55dde4a0f5119819ea30a7fde901c762197125"},"caption":"Wink helped to build the global Corona Beach 100 experience
He previously covered the private equity industry as a reporter for PEI Media
Lindsay Rittenhouse is a senior reporter for Ad Age
covering broad advertising industry trends
He was previously a freelance journalist and podcaster covering pop culture and entertainment as well as a Pilates instructor and a professional dancer
the “Scream” franchise and Halloween costumes
covers household and personal-care marketers
He's based near Cincinnati and has previously written for the Atlanta Journal Constitution
woodworking and graphic design industries and worked in corporate communications for the E.W
Gillian Follett is a general assignment reporter for Ad Age. She writes about a variety of topics including social media
influencer marketing and the creator economy
Gillian graduated from Syracuse University’s S.I
He previously covered corporate communications and public relations agencies as a reporter at PRWeek
Jon Springer covers sports marketing and beverage marketing
He formerly covered the food retail industry for Winsight and Supermarket News
and is a former sports and features writer for The Cecil Whig
He has worked in newspapers from Albany to New York City
He has also worked at every advertising industry trade publication that matters
and he once visited Guatemala and once rode the Budapest Metro
Adrianne Pasquarelli is a senior reporter at Ad Age
She is also a host of the Marketer’s Brief podcast and spearheads special reports including 40 Under 40 and Hottest Brands
Pasquarelli joined Ad Age in 2015 after writing for Crain's New York Business
where she also focused on the retail industry.
Bradley Johnson is Ad Age's director of data analytics
Johnson focuses on data and financial topics related to marketing
Los Angeles and New York including editor at large
overseeing breaking news and daily coverage
He also contributes reporting on the beverage
automotive and sports marketing industries
He is a former reporter for McClatchy newspapers
where he covered business and state government and politics
Jones Krahl is U.S. head of creative and creative fellow at Deloitte Digital
She was previously creative editor at Campaign US
and also served as a writer and reporter at Sidekick by Morning Brew and PRWeek
CHICAGO, April 09, 2025 (GLOBE NEWSWIRE) -- Corona Premier
the only lighter than light beer worthy of being called Corona
announces its partnership with Grammy-nominated artist & entrepreneur Saweetie
to celebrate National Pickleball Month and the launch of their Dink N’ Drink™ activation
As part of the brand’s broader Premier Side of Light campaign
Dink N’ Drink™ provides an interactive post-game experience for players who seek to extend their active lifestyle
giveaways – and even a new signature courtside drink recipe
To bring the Dink N’ Drink campaign to life, Corona Premier teamed up with Break the Love
a next-generation racquet social sports platform from Break Sports
to host an exclusive pickleball event in New York City on April 23rd
designed to connect players of all skill levels
Whether you’re a seasoned pro or just picking up a paddle for the first time
this event invites guests to get comfortable on the court
meet new friends and enjoy surprise giveaways and special activities
Founded by renowned beverage innovators Cody and Camille Goldstein
Muddling Memories has been behind some of the most viral drink sensations
transforming the industry and establishing itself as one of the most sought-after creative agencies
“As a performer and someone who grew up playing sports
I’ve always found it important to celebrate your wins and that’s exactly what this event is about,” said Saweetie
“I’m so excited to team up with Corona Premier to play some pickleball and make this experience even more special for fans and players
With pickleball’s popularity soaring – there were an estimated 19.8 million players in the U.S
marking a 45.8% increase from 20231 – it’s clear that enthusiasts are drawn to more than just the competition
The sport’s accessibility and inherent social nature make it the perfect match for Corona Premier
a brand that celebrates the social side of living an active lifestyle by bringing people together over a premier light beer after the game
we wanted to create a way for players to celebrate post-game,” said Rob Nelson
“Dink N’ Drink is about elevating the best parts of the game – friendly competition
extending the moment with friends after a match with a crisp Corona Premier
We’re excited to be part of National Pickleball Month with a toast to the sport’s growing community.”
And for those who can’t join the event in NYC
Corona Premier is giving fans a chance to bring the Dink N’ Drink experience to their home court
By entering the Corona Premier Dink N’ Drink Sweepstakes
25 lucky winners will have a chance to win a special Corona Premier Dink N’ Drink Kit
complete with pickleball gear and all the ingredients† needed to enjoy this season’s coolest drink with friends (†no alcohol is awarded with prizes; drink ingredients awarded as a $30 Sponsor-specified gift card)
Fans can visit @CoronaUSA to learn how to enter for a chance to win an exclusive Corona Premier Dink N’ Drink Kit
NO PURCHASE NECESSARY TO ENTER THE CORONA PREMIER DINK N’ DRINK SWEEPSTAKES
Starts 12:00 AM ET on 4/9/25 and ends 11:59 PM ET on 4/30/25
Void outside the Eligibility Area and where prohibited
see Official Rules at rules.dja.com/dinkndrink
Corona Premier offers drinkers an exceptionally crisp premium light beer experience
smooth finish and in-the-moment beach vibes that come with Corona
Corona Premier is perfect for casual entertaining
or for those looking to extend any unwind moment
Corona encourages consumers to enjoy its products and drink responsibly
About the Corona Brand Family The Corona brand family is home to Corona Extra
Corona Non-Alcoholic and Corona Sunbrew Citrus Cerveza
The entire Corona portfolio is brewed in Mexico by Constellation Brands and imported and marketed exclusively to the U.S
the flagship brand of the Corona brand family
is a pilsner-style lager with a golden hue that was first brewed in Mexico in 1925
Corona embraces the Mexican beach mindset with “La Playa Awaits” and encourages consumers to live life more presently no matter where they are
The refreshing flavor and carefree attitude of Corona Extra holds a respected place in U.S
1Source: SFIA Top Line Participation Report for 2025
Contact:Constellation BrandsStephanie McGuanestephanie.mcguane@cbrands.com
https://www.globenewswire.com/NewsRoom/AttachmentNg/84c8b110-8a2f-4705-9e84-81c4ef154575
https://www.globenewswire.com/NewsRoom/AttachmentNg/e99e3bf3-4639-408d-ba93-fca395ca893c
https://www.globenewswire.com/NewsRoom/AttachmentNg/8c445f4e-b32a-4904-8022-046d5a6d7296
https://www.globenewswire.com/NewsRoom/AttachmentNg/21d6119c-a2df-4736-978e-823384e76084
AB InBev has officially opened the eco-protected luxury destination it calls “Corona Island” to the public
which was originally debuted by AB InBev in 2021 as an invite-only getaway located 20 km (12 mi) southwest of Cartagena
The destination has been carefully positioned by the beer giant as “symbolic of the brand’s dedication to live in harmony with nature” and offers the chance to “disconnect from daily life and reconnect with nature”
Corona Island is also the world’s first and only island to receive Oceanic Global’s three-star plastic-free Blue Seal for eliminating single-use plastics and adopting sustainable operating best practices at scale
Corona Island features 10 premium waterfront bungalows
nestled amongst tropical forests and beaches
The island also offers all-inclusive overnight stays for two people per bungalow
alongside a limited number of all-inclusive day trip passes that are also available to buy
global vice president of Corona said: “The inspiration to build this experience stems from Corona’s long-standing commitment to nature and is a physical manifestation of our vision for eco-friendly tourism and conservation efforts
Corona now welcomes eco-conscious travellers from around the world to experience the island and truly disconnect to reconnect with nature.”
and traditional building techniques such as bahareque
The island also serves its food with an emphasis on local ingredients
such as baked goods made with fruits native to the region
which are all included in the price of the visit
Also available for guests to enjoy are the full suite of Corona products
including Corona Extra and Corona Cero as well as a variety of relaxation and eco-conscious activities
and kayaking and snorkelling to restore coral reefs and mangrove planting for ecosystem reforestation
Pantoja explained: “As a beer brewed with natural ingredients
Corona has always been associated with nature and relaxation
Corona Island is an extension of that ethos – offering an experience that blends leisure with eco-friendly travel experiences.”
relaxation meets conservation in a natural beachside setting
and a beer brewed with natural ingredients
we believe that our island serves as a perfect extension of our ethos.”
we invite eco-tourists and travel enthusiasts alike to explore this unique setting
where every experience reflects our dedication to preserving the beauty of the natural world.”
Corona Island is priced at US$600 per night and US$200 per day-pass – both are all-inclusive
the individual booking sites will provide all prices in the local currency for each potential traveller for ease
Travellers worldwide can secure their stay directly at livecoronaisland.com or through Airbnb
We are using cookies to give you the best experience on our website
You can find out more about which cookies we are using or switch them off in settings
This website uses cookies so that we can provide you with the best user experience possible
Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful
Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings
we will not be able to save your preferences
This means that every time you visit this website you will need to enable or disable cookies again
Please select what you would like included for printing:
Copy the text below and then paste that into your favorite email application
Add to Calendar
Complete the form below to get directions for the Funeral Service for Sherry Corona
Complete the form below to get directions for the Visitation one hour prior to the service for Sherry Corona
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply
Service map data © OpenStreetMap contributors
2025Jared CornickPrep Baseball California Contributor
- Coming into this season being defending Prep Baseball National Champions
the expectations are straightforward for Coach Andy Wise and Corona High School
“Our expectations are to be the best and win everything,” said Andy Wise
head coach of the Corona Panthers since 2009
Wise has taken the high school baseball world by storm with him and his staff’s ability to construct what is to be considered one of the best baseball programs in the entire nation
the team may even be better this year than it was the year prior
“This group is just trying to repeat what that team did
but that does not dictate winning,” said Wise
The talent of this roster is evident on paper
With a lineup containing eight Division One committed players
the Panthers are a team forced to be reckoned with
It starts with three highly touted seniors
and all two time Prep Baseball All-Americans: Seth Hernandez
Seth Hernandez
is the number one ranked pitcher and number two ranked player in the class of 2025
The 6’ 3’’ dual threat can top 100 MPH on the mound
with an exit velocity off the bat reaching upwards of 107.1 MPH
Hernadez serves as the team’s ace as well as a pivotal bat in the lineup
Brady Ebel
a SS committed to play at LSU is the number two-ranked infielder and the number four ranked player in the class of 2025
five-tool prospect has a career OBP of .368 for the Panthers as well as playing exceptional defense at both 3B and SS
Billy Carlson
a SS/RHP committed to play at the University of Tennessee
is the fifth-ranked shortstop and the seventh-ranked player in the class of 2025
A former Prep Baseball Future Games participant
Carlson hit to the tune of a .367 average in his junior season for Corona
as well as clubbing four home runs in the process
Carlson serves as a vital asset in Corona’s bullpen
As for coaching such highly touted prospects
Coach Wise finds it to be pretty easy due to how they take care of their business
“Those guys know one way to play the game both mentally and physically and they just do it," said Wise
but most importantly they are great people.”
In addition to Carlson, Ebel, and Hernadez, the Corona lineup and rotation is bolstered by the likes of other division one commits such as ‘25 RHP/OF Jason Gerfers (Arizona State) and ‘25 OF Joshua Sur (Vanguard)
Leadoff hitter ‘26 OF Anthony Murphy is committed to play at Louisiana State University as well
Brady’s younger brother, INF Trey Ebel
is committed to play at Texas A&M in the fall of 2026
‘25 RHP/INF Ethin Bingamin is committed to Auburn University and will join Ebel
and Carlson in the ever-so-competitive SEC
We are just going to do what we do and our lineup is extremely difficult on pitchers," said Wise
"It’s all about grinding out good-at bats and every guy from top to bottom is a threat.”
The pitching staff is just as equally talented as the bats that Corona puts forth
and a deep reliever pool highlighted by Carlson and Gerfers
Corona’s well-rounded roster provides a tough test for any team that faces the Panthers
“We probably have the best pitching staff and we probably have the best defense going,” said Wise
Wise and his staff have always prioritized a schedule that provides a challenge
The Panthers face competitive schools such as Mater Dei
and Summit High School this season to help them prepare for what they expect to be a deep playoff run
“Even when we were not highly touted and ranked
the philosophy of mine and this program is to be big game hunters and beef up our schedule," said Wise
"We want the best game we can get so we can take something from each good program we play and add it to our own mix.”
The culture that Wise has fostered at Corona has been a long time in the making
a former player at Long Beach State and Santa Ana College
has absorbed the knowledge of what it takes to be an excellent coach from the likes of Dave Snow and Ken Ravizza
“I am really just trying to give my spin with my personality from the coaches that I have played for and worked with," said Wise
"Corona Baseball is a little bit of Santa Ana College
and I couldn't be more honored to represent those programs and those coaches
Just trying to do the same as they did for me.”
Panther alumni is headlined by the likes of Joe Kelly and Tristian Beck
a two-time world series champion with the Los Angeles Dodgers
went on to play for UC Riverside and was drafted by the St
Louis Cardinals in the third round of the 2009 MLB June Amateur Draft
a right-handed pitcher for the San Francisco Giants
attended Stanford University after his time at Corona
and was originally drafted by the Atlanta Braves in the fourth round of the 2018 MLB June Amateur Draft
“It’s a great brotherhood and having alumni come back and share their stories is amazing," said Wise
"All the way from Joe Kelly to Tristian Beck
you can really see how the Corona baseball community and culture has grown and it's fun to watch to see players who have represented our program enter the real world prepared
the Corona Panthers hope to run it back and prove why they are considered to be one of
the Corona Panthers have what it takes to be repeat as Prep Baseball National champions
“We know everyone wants to kick our ass so we’re always getting a team’s best and we wouldn’t want it any other way,” said Wise
+ Prep Baseball California on X+ Prep Baseball California on Instagram+ Prep Baseball California on Facebook+ Prep Baseball California on YouTube
Heritage Wellness Collective won a revocable license to run the market for the next five years following a 6-1 vote by the city council at their meeting Tuesday, with Councilman Erik Weigand as the only member in opposition. The nonprofit will take over after the license with the current manager, Rick Heil, expires on June 30.
The city began soliciting bids for a new operator in August, according to a staff report. Newport Beach officials made their decision based on candidates’ experience running farmer’s markets as well as their ability to create community events and attract quality merchants while retaining existing vendors. Heritage Wellness Collective was chosen out of 8 bidders.
The nonprofit runs seven weekly or bi-monthly farmer’s markets in Orange, Los Angeles, San Bernardino and Riverside counties. Their executive director, Bing Turner, has a background in public health, and told the Daily Pilot during an interview Wednesday he hopes to preserve the Corona Del Mar gathering’s focus on high quality produce while drawing in more families, local businesses and institutions to visit and take part in it.
“Will the market look different than what it currently looks like now? Absolutely yes,” Turner said. “Will the vendors change at the market? That’s going to happen. Are we going to move people out of their market or out of their spaces? No, unless they decide they don’t want to work with us. But we’re there to really enhance and make the space reflective of the community... this isn’t going to be any rock concert.”
Numerous residents who attended Tuesday’s meeting said they feared the merchants supplying their favorite carrots, strawberries, pomegranates, flowers, cuts of meat and more may go away if the market changes management. Current operator Heil claimed that only one of its current vendors had been contacted by Heritage.
Several public speakers cited the adage “if it ain’t broke, don’t fix it.” They said they preferred that the the market remain solely for the exchange of artisan produce. Many worried that adding food vendors, music and public events would make it a larger event that would result in more noise and traffic.
Opponents of the change in vendors claim more than 1,000 people had signed a petition to prevent the move.
“The people are really angry in the community,” Heil told the Pilot at the most recent Corona Del Mar Farmer’s Market on Saturday. “I’ve never seen anything like this where the city council go up against the will of the people who like it and don’t want to change something that’s been there 29 years.”
However, Turner said he has heard from numerous people in the Newport Beach community who want to see the market evolve into a more family-oriented event. He said that includes local chefs and merchants who had been denied after expressing interest in doing business at the market.
Turner also refuted Heil’s claim that only one vendor had been contacted by Heritage. The nonprofit’s executive director said emails were sent prior to Tuesday’s meeting to about 15 or 20 merchants currently doing business at the Corona Del Mar market, and 14 had replied expressing interest in staying under new management. Turner added that he was hesitant to contact them before confirming the new license agreement, but had been advised by city staff to do so.
Concerned Corona Del Mar residents said that email was the first notification they received regarding new management and the city did not reach out to them for input. Many said the preliminary message from Heritage was evidence that the change was a “done deal” even before council members cast their votes.
“We like the Farmers Market the way it is,” said Corona del Mar resident and petition monitor, Carole Geronsin said Saturday. “Everyone we talked to there was not one person that doesn’t absolutely love it the way it is.”
Turner, as well as members of the council, acknowledged that more could have been done to engage residents before the issue came to council. However, he said Heritage’s immediate priority will be building a bridge with the Corona Del Mar Community to ensure the market continues to meet their needs and wants, while growing to include more of their neighbors.
Before voting on the new agreement, Councilman Weigand asked that provisions for the inclusion of live music be removed. Mayor Pro Tem formally backed that amendment, which was seconded by Councilman Noah Blom. Councilmembers also asked city staff to further study potential impacts to traffic.
“I get it they don’t want to lose something they have none of us do once we have it... nobody on this dais ever wants to see food trucks everywhere,” Blom said. “I’m here to give new things a try because sometimes it’s amazing what happens when we take a chance on something new. And I hear the scoffing from people in the room, mainly from the current operator.”
Blom and other councilmembers also noted that the new license is revocable, and can be terminated if new management does not prove satisfactory.
Eric Licas covers Newport Beach for the Daily Pilot. He previously was a crime and public safety reporter and, before that, spent four years as a staff writer with the Orange County Register and the Southern California News Group. He has been on the ground to cover active wildfires, civil unrest and mass shootings. He was born in the Philippines, raised in the San Fernando Valley and is a Cal State Northridge alumnus.
Susan Hoffman is a contributor to Times Community News.
News
Subscribe for unlimited accessSite Map
Corona Henrietta Bucher “Coonie” Essner
at Saint Francis Medical Center in Cape Girardeau
daughter of the late Philip and Leocadia Dirnberger Bucher
Her life was marked by unwavering dedication to her faith
as she served in various capacities throughout her life
she moved from the family farm in New Hamburg to Cape Girardeau where she was an active member of St
Vincent de Paul Catholic Church and the Cathedral of St
She worked at Cape LaCroix Apartments in Cape Girardeau
Lawrence Parish School of Religion and in the church choir
She brought the first Teens Encounter Christ (TEC) conference team to the Diocese of Springfield-Cape Girardeau
many summers at Camp Re-NEW-all in Fredericktown
Coonie was also active in the regional and Diocesan Council of Catholic Women and the Oran KC-ettes
She enjoyed visiting friends in nursing homes
giving rides to those in need and making time for her ladies’ groups which included the New Hamburg Homemakers Club
Red Hat Society and her friend group which met regularly over the past 50 years to celebrate their birthdays
she also volunteered for 20 years in the gift shop at St
receiving the Volunteer of the Year Award in 2018
When she completed her last day of service on Feb
Known affectionately as "Nana" to her grandchildren
creating lasting memories through card games and her famous homemade pumpkin bread
which her grandchildren looked forward to receiving every Christmas along with their nylon pot scrubbers
She was always up for any adventure and there to listen and lend a hand when needed
Survivors include: two sons and a daughter-in-law
and Tim Essner of New Hamburg; daughter-in-law
Texas; Dustin (Amy) Essner of New Hamburg; Kari (James) Wilhelm of Kelso; Kent Essner of Dexter; Leonna (Dean) Heuring of New Hamburg; Michelle (Andy) Silman of Benton; Andrea (Pete) Sampanis of Vienna
Virginia; and Lisa (Jim) Eftink of New Hamburg; 21 great-grandchildren; one great-great-grandson; and many nieces
A funeral Mass will be celebrated at 10 a.m
Lawrence Catholic Church in New Hamburg with the Rev
Pallbearers will be her great-grandsons: Drew Silman
Honorary pallbearer will be her great-grandson
Memorial contributions may be made to SSM Health Cardinal Glennon Children’s Foundation at glennon.org or St
Enter your phone number above to have directions sent via text
tourists will be able to immerse themselves in a Corona experience by holidaying on an island dedicated to the lager
adopting it for the use of “friends and family of the brand,” according to its vice-president
the world was in the grip of the similarly named Coronavirus
the paradise has been opened up to public bookings via Airbnb
Corona Island sits 12 miles off the coast of Cartagena
Its isolation means it needs to offer an all-round hospitality experience and
It’s badged with marine conservation charity Oceanic Global’s three-star plastic-free Blue Seal for eliminating single-use plastics
making it the first and only island to do so
solar energy powers the operation and traditional building techniques such as bahareque have been employed
alongside the use of native plants such as guadua
in addition to well-stocked supplies of Corona
fresh local food and experiences that include yoga and stand-up paddle boarding
You can also take part in snorkeling coral reef restoration projects and planting mangroves
known for their carbon-capturing properties
“It’s more than just relaxing; it’s remembering how important it is to live in harmony with nature and the programs you can choose from include making food with natural ingredients
which helps connect us to the natural world,” says Pantoja
While the experience is choreographed to blend sustainable practices with a reconnection to the natural world
Pantoja is also keen to link this back to the product
which is “brewed with 100% natural ingredients,” she says
is an example to the world of what we believe in as there’s nothing more natural than protecting and being connected to nature,” she adds
Corona is all in with the endeavor and although it hasn’t bought the island
so it does very much belong to the company – for now
drawing attention to sustainably minded endeavors should really be a chance for a company to illuminate its attitude to environmental
social and governance (ESG) as a whole rather than demonstrate one project in isolation
The actions that will really dictate the environmental impact of Corona and its parent company
take place across the whole lifecycle and supply chain of the product
Corona was not able to provide any figures on further efforts the brand is making to reduce its environmental impact
in particular around any journey towards net zero or the environmental impact of its factories
However, since 2021, it has achieved a net zero plastic footprint by recovering more plastic from the environment than it uses
Pantoja also reminds us that all of its bottles have always been glass
with only the ingredients label on the back made of plastic
and that the brand has used engraved bottles for 100 years
She also answered that all-important question: lime in the top of the bottle or no lime
Catch up on the most important stories of the day
Stay up to date with a curated digest of the most important marketing stories and expert insights from our global team
Learn how to pitch to our editors and get published on The Drum
An official website of the United States government
Select a service on this page to check the hours
Wheelchair availability: Wheelchairs are available upon arrival for patients who need them to access the building
We work with Disabled American Veterans and county Veterans Affairs directors to provide transportation for Veterans and authorized caregivers to get to scheduled medical appointments
Many localities in the region provide other van services to Veterans
Learn more about DAV and the other van services available in your county
Corona Public Transit
Beneficiary travel benefits include round-trip transportation from your home to the medical center
Find out if you qualify for beneficiary travel benefits
Our laboratories provide a full range of clinical and diagnostic testing services
Our laboratory and pathology services include:
Our medical center and clinics provide consultation
and treatment for a range of issues that may impact your mental health or emotional well-being
Our confidential outpatient services include individual and group therapy for:
Learn more and connect with a care coordinator
My HealtheVet is a web-based tool you can use to manage your care and improve your health from your computer or mobile device
You can access your personal health records and use tools to manage your care through our My HealtheVet online system
You can also use My HealtheVet to refill your prescriptions
you can contact our coordinator by phone or in person
Learn more and register for My HealtheVet
Our pharmacy provides you and other Veterans with convenient
efficient service to make it easy to get your medications and medical supplies
Learn more about our pharmacy
Your VA primary care provider will work closely with you to plan for all the care you need to stay healthy and well throughout your life
They will also work with family members or caregivers who support you
A strong network of family and internal medicine specialists and services can offer you the best possible care
Internal medicine doctors (internists) prevent
Doctors who specialize in family medicine provide primary health care to the entire family
Your primary care team can coordinate the many services you receive such as:
NOTICE TO PATIENTS: Some of our medical doctors are licensed and regulated by the Medical Board of California. To check up on a license or to file a complaint go to https://www.mbc.ca.gov/, email: licensecheck@mbc.ca.gov
Deportation threats and the potential of job losses have led to decreased spending among Hispanic consumers who make up half of the company’s beer sales
Part of Constellation’s strategy to overcome difficulties in the beer market is to better advertise Modelo beyond the Hispanic market
“We increased our [marketing] spend even though the consumer was pulling back
and we’re seeing that providing great returns to our business,” Newlands said
TD Cowen analyst Robert Moskow pointed to Nielsen data that found the rate of Constellation beer purchases among Hispanic consumers declined between 7% and 9% so far in 2025
He projected immigration and employment issues related to the demographic could weigh on the company for years to come
Constellation's CEO pointed to internal data which found two-thirds of Hispanic consumers are concerned about the price of food
Half are worried about Trump’s actions on immigration
an area where the Hispanic consumer often consumes beer
are declining today as part of these overarching concerns they have,” Newlands said
“We’re going to need and want to see some improvement in the consumer brand health before we’re able to correctly project how long some of these challenges are going to last.”
Constellation lowered its anticipated sales growth for its beer business to 0% to 3%
In its most recent financial quarter ending in February, the company’s beer business saw flat growth in net sales and a 1.8% decline in shipments, according to Constellation’s earnings report
Declining demand is just one issue linked to Trump’s policies that has weighed down the Pacifico brewer. Constellation is considered among the brands most vulnerable to the president's tariff policy because imports make up nearly 85% of its annual revenues
Correction: A previous version of this story misidentified the owner of Modelo and Corona
which are distributed by Constellation Brands in the U.S
Get the free daily newsletter read by industry experts
The soda giant’s Red Tree Beverages subsidiary is making a bet that its vodka lemonade can help it gain a stronger foothold in booze
Ingredion and consumer insights platform Tastewise say innovative tech can help companies stay ahead of the latest trends and potential supply chain headwinds
The free newsletter covering the top industry headlines
2025Investigators are searching for an arson suspect who they say caught on fire while he was setting a car ablaze in Corona
(KABC) -- Investigators are searching for an arson suspect who they say caught on fire while he was setting a car ablaze in Corona - an incident that was caught on video
It happened early Tuesday morning in the front yard of a home on Wakefield Avenue
Surveillance footage shows the man standing next to a black sedan before flames suddenly erupt
He is then seen catching fire as well before appearing to jump a fence and fleeing the scene while on fire
The fire destroyed the car and caused some damage to the nearby home
Authorities believe the suspect got away in a newer model white pickup truck with tinted windows and light-colored rims
Anyone with information is urged to call Corona fire investigators at (951) 736-22-119
Research Development and Administration Team
If the price tag on your Modelo or Corona is higher next year
Many economists say that the 25% tariffs President-elect Donald Trump has proposed on imported goods from Mexico and Canada
not to mention additional tariffs on Chinese goods
would be catastrophic for the economy and consumers
an assistant teaching professor of history at Northeastern University whose focus is the history of beer
says they will hit those beer brands particularly hard
“The most popular beer brand in the entire country right now is Modelo,” Purinton says
“The thing is the demand isn’t going to go away
it’s going to dramatically affect the costs of those.”
Read more on Northeastern Global News.
The College of Social Sciences and Humanities combines Northeastern University’s signature focus on experiential learning with the rigorous study of society
CSSH is redefining liberal arts education for the next generation of global thinkers
Your support and partnership can help CSSH and our students continue to lead
CSSHDean@northeastern.edu
Metrics details
The protein corona formed on nanoparticles (NPs) has potential as a valuable diagnostic tool for improving plasma proteome coverage
and nutrients into plasma can induce diverse protein corona patterns on otherwise identical NPs
significantly enhancing the depth of plasma proteome profiling
The protein coronas on polystyrene NPs when exposed to plasma treated with an array of small molecules allows for the detection of 1793 proteins marking an 8.25-fold increase in the number of quantified proteins compared to plasma alone (218 proteins) and a 2.63-fold increase relative to the untreated protein corona (681 proteins)
we discovered that adding 1000 µg/ml phosphatidylcholine could singularly enable the detection of 897 proteins
phosphatidylcholine selectively depletes the four most abundant plasma proteins
thus reducing the dynamic range of plasma proteome and enabling the detection of proteins with lower abundance
Employing an optimized data-independent acquisition approach
the inclusion of phosphatidylcholine leads to the detection of 1436 proteins in a single plasma sample
Our molecular dynamics results reveal that phosphatidylcholine interacts with albumin via hydrophobic interactions
The addition of phosphatidylcholine also enables the detection of 337 additional proteoforms compared to untreated protein corona using a top-down proteomics approach
Given the critical role of plasma proteomics in biomarker discovery and disease monitoring
we anticipate the widespread adoption of this methodology for the identification and clinical translation of biomarkers
Peptides from these high-abundance proteins
tend to dominate mass spectra impeding the detection of proteins with lower abundance
utilizing a single type of NP can streamline the MS analysis process
reducing the time required to analyze large cohorts in plasma proteomics studies
to assess the potential collective effects of these molecules
we analyzed two representative “molecular sauces.” Molecular sauce 1 contained a blend of glucose
employing a wide range of characterizations
to analyze the protein corona of polystyrene NPs
This rigorous optimization ensures highly accurate and reproducible results
Our findings confirm that the addition of these small molecules in plasma generates distinct protein corona profiles on otherwise identical NPs
significantly expanding the range of the plasma proteome that can be captured and detected by simple LC-MS/MS analysis
we discover that the addition of specific small molecules
leads to a substantial increase in proteome coverage
which is attributed to the unique ability of PdtChos to bind albumin and reduce its participation in protein corona formation
PtdChos coupled with NP protein corona analysis can replace the expensive albumin depletion kits and accelerate the plasma analysis workflow by reducing processing steps
our single small molecule-single NP platform reduces the necessity for employing multiple NP workflows in plasma proteome profiling
This approach can seamlessly integrate with existing LC-MS/MS workflows to further enhance the depth of plasma proteome analysis for biomarker discovery
We assessed the effect of eight distinct small molecules, namely, glucose, triglyceride, diglycerol, PtdChos, PE, PtdIns, IMP, and vitamin B complex, on the protein corona formed around polystyrene NPs. The workflow of the study is outlined in Supplementary Fig. 1
a The number of quantified proteins in plasma
and protein coronas in the presence of small molecules and molecular sauces (mean ± SD of three technical replicates)
The cumulative number of unique proteins identified using untreated protein corona and corona treated with various small molecules is also shown using the purple bar
the database was performed individually for each small molecule (the higher the small molecule(s) concentration
b The distribution of averaged normalized abundances of three technical replicates for proteins quantified in the plasma
and protein coronas in the presence of small molecules and molecular sauces (the higher the small molecule(s) concentration
the darker the blue shade; boxplot: center line
median; box limits contain 50%; upper and lower quartiles
greatest value excluding outliers; minimum
more than 1.5 times of upper and lower quartiles)
c Clustered heatmap of the normalized abundance of all 1793 proteins quantified across all samples
d Clustered heatmap of the normalized abundance of 117 shared proteins across all samples
Experiments were performed in three technical replicates
To mitigate the impact of these variables on the interpretation of how small molecules can enhance proteome coverage
we chose to report our data as fold changes in the number of quantified proteins relative to control plasma and untreated corona samples
This approach offers a more objective assessment of the role of small molecules in enhancing proteome analysis
minimizing the confounding effects of different workflows and data analysis techniques that may be employed by various researchers
While most of the enriched pathways were shared
some pathways were specifically enriched for a given molecular sauce
systemic lupus erythematosus (SLE) was only enriched among the top pathways for molecular sauce 2
the small molecules can be potentially used for facilitating the discovery of biomarkers for specific diseases
or for assaying the abundance of a known biomarker in disease detection
To understand whether the quantification of a higher number of proteins in protein corona profiles was due to a lower dynamic range of proteins available in human plasma for NP binding, we plotted the maximum protein abundance vs minimum protein abundance for plasma alone, and plasma-treated with small molecules in Supplementary Fig. 10
The plasma alone showed the highest dynamic range
suggesting that identification of low-abundance proteins would be most difficult from plasma alone
the addition of small molecules was shown to reduce plasma protein dynamic range
thereby allowing for the detection of more peptides and quantification of proteins with lower abundance through the NP protein corona
a Normalized protein abundance (left axis
bar plot) and protein rankings (right axis
b A stream (or alluvial) diagram illustrating the significant depletion of abundant plasma proteins
following the incubation of plasma with NPs and PtdChos (only shared proteins with plasma are included; colors are chosen randomly)
c Total count of proteins identified in plasma
and protein corona treated with PtdChos at various concentrations (colors are chosen randomly; mean ± SD of three technical replicates)
d A stream diagram demonstrating the depletion pattern of abundant plasma proteins
in response to NP addition and enhanced with escalating concentrations of PtdChos (colors are chosen randomly; only shared proteins with plasma are included)
allowing for more robust detection of other proteins with lower abundance
These findings not only validate the enhancement of plasma proteome coverage by PtdChos but also illustrate the capability of PtdChos to facilitate the in-depth profiling of the plasma proteome associated with protein corona formed on the surface of a single type of NP
Since the ratio of the number of quantified proteins through PtdChos spiking is generally around 1.4-fold higher than in the NP corona alone
PtdChos can be incorporated into any LC-MS workflow aiming to boost plasma proteome profiling
More optimized plasma proteomics pipelines
or high-end mass spectrometers such as Orbitrap Astral are envisioned to quantify an even higher number of proteins than those reported in the current study
In total, 637 proteoforms were identified across the two samples (with technical triplicates for each sample) (Fig. 3c)
Data analysis using Perseus software (Version 2.0.10.0) revealed that only 110 proteoforms overlapped between the two samples (the minimum number of valid values for filtering data was set to 1)
The proteoform mass distribution differed between the two samples (Fig. 3d)
Although the average proteoform masses were similar
the box plot indicated a greater number of larger proteoform identifications in the control sample (over 20 kDa)
We hypothesize that PtdChos can bind to large proteins
and due to the high concentration of PtdChos relative to the proteoforms
the signals of these large proteoforms may be obscured
Additional data analyses identified differential proteins in this study (Fig. 3e)
The top-down proteomics approach identified specific gene products that bind to the NP surface in the presence of PtdChos
a Total linear interaction energies between albumin and various number of ligands systems over simulation time
The total energy represents the sum of Lennard-Jones and Coulombic energies
b Effective free energy of binding terms for the different systems over the entire simulation
GGAS represents the energy of the gas phase
c Average root mean square fluctuation of albumin residues for the four systems
d Root mean square deviation of PtdChos over time for the four types of systems
e Bond types present within each simulation
and the x-axis represents the percentage of simulation timestamps when each type of bond is present
The results of our molecular dynamics evaluations of the interactions between PtdChos and albumin were in line with the literature
we found that the simple addition of PtdChos to plasma can significantly reduce albumin adsorption for the surface of polystyrene NPs
thereby creating unique opportunities for the involvement of a broader range of proteins with lower abundance in the protein corona layer
We also observed the same effects of PtdChos on enhancing the proteome coverage using different types of NPs
Not only is PtdChos an economical and simple alternative for conventional albumin depletion strategies
but it can also deplete several other highly abundant proteins as an added advantage
This approach reduces the necessity for employing NP arrays in plasma proteome profiling
and the cost and biases that can occur with albumin depletion
PtdChos can help accelerate plasma analysis workflows by reducing the sample preparation steps
Our study highlights the tremendous potential of leveraging small molecules to enhance the capabilities of protein corona profiles for broader plasma proteome analysis
By introducing individual small molecules and their combinations into plasma
we have successfully created distinct protein corona patterns on single identical NPs
thereby expanding the repertoire of attached proteins
we quantified an additional 1573 unique proteins that would otherwise remain undetected in plasma
This enhanced depth in protein coverage can be attributed
to the unique interactions of each small molecule
allowing for the representation of a diverse set of proteins in the corona
our findings underscore the influence of small molecules on the types and categories of proteins in the protein corona shell
This feature opens exciting possibilities for early disease diagnosis
particularly in conditions such as cardiovascular and neurodegenerative disorders
our study demonstrated that PtdChos preferentially interact with highly abundant plasma proteins
thereby reducing their binding to NP surfaces
This reduction allows low-abundance proteins to contribute more significantly to the protein corona profile
This effect was achieved by reducing the binding of highly abundant proteins and enhancing the representation of low-abundance proteins on the NP surfaces
We acknowledge that the number of human plasma samples used in this study was limited
primarily due to our specific focus on improving proteome coverage through the use of a single pooled plasma sample
This approach effectively allows us to test and validate our hypothesis
given that the most abundant plasma proteins exhibit minimal variability between individuals
for future biomarker discovery applications
it is essential to expand the sample size to a more diverse cohort
This will ensure the platform fully accounts for biological variability and provides a more comprehensive and generalizable assessment of the proteome across different individuals
the depth of analysis can further increase toward the ultimate goal of achieving comprehensive human proteome coverage
Another alternative would be to combine our strategy with tandem mass tag (TMT) multiplexing and fractionation to achieve an even higher plasma proteome depth
We anticipate that this platform will find extensive applications in plasma proteome profiling
providing an unprecedented opportunity in disease diagnostics and monitoring
and diluted to the desired concentration with 55% human plasma
Mass spectrometry-grade lysyl endopeptidase (Lys-C) was sourced from Fujifilm Wako Pure Chemical Corporation
Formic acid and C18 StageTips were purchased from Thermo Fisher Scientific
For protein corona formation in the presence of small molecules
individual or pooled human plasma proteins 55% were first incubated with individual small molecules or in combination by preparing two molecular sauces of individual small molecules at different concentrations (i.e.
each type of polystyrene NPs was added to the mixture of plasma and small molecules solution so that the final concentration of the NPs was 0.2 mg/ml and incubated for another 1 h at 37 °C
It is noteworthy that all experiments are designed in a way that the concentration of NPs
To remove unbound and plasma proteins only loosely attached to the surface of NPs
protein–NP complexes were then centrifuged at 14,000×g for 20 min
the collected NPs’ pellets were washed three times with cold PBS under the same conditions
and the final pellet was collected for further analysis
we used various concentrations of PtdChos (i.e.
and 10000 µg/ml) and used the same protein corona method for the preparation of the samples for mass spectrometry analysis
DLS and zeta potential analyses were performed to measure the size distribution and surface charge of the NPs before and after protein corona formation using a Zetasizer nano series DLS instrument (Malvern company)
A Helium-Neon laser with a wavelength of 632 nm was used for size distribution measurement at room temperature
TEM was carried out using a JEM-2200FS (JEOL Ltd) operated at 200 kV
The instrument was equipped with an in-column energy filter and an Oxford X-ray energy dispersive spectroscopy (EDS) system
Twenty microliters of the bare NPs were deposited onto a copper grid and used for imaging
20 μl of samples was negatively stained using 20 μl uranyl acetate 1%
PC composition was also determined using LC-MS/MS
The collected protein corona-coated NP pellets were resuspended in 20 µl of PBS containing 0.5 M guanidinium-HCl
The proteins were reduced with 2 mM DTT at 37 °C for 45 min and then alkylated with 8 mM IAA for 45 min at room temperature in the dark
5 µl of LysC at 0.02 µg/µl in PBS was added and incubated for 4 h
followed by the addition of the same concentration and volume of trypsin for overnight digestion
the samples were centrifuged at 16,000×g for 20 min at room temperature to remove the NPs
The supernatant was acidified with TFA to a pH of 2–3 and cleaned using C18 StageTips
The samples were then heated at 95 °C for 10 min
and submitted to the core facility for LC-MS analysis
The PtdChos concentration series experiment was performed using the same protocol
and the samples were analyzed over a 120 min gradient
The protein corona-coated NPs (with/without PtdChos) were separately treated in a 0.4% (w/v) SDS solution at 60 °C for 1.5 h with continuous agitation to release the protein corona from the NP surface
the supernatant containing the protein corona in 0.4% SDS was separated from the NPs by centrifugation at 19,000×g for 20 min at 4 °C
the supernatant underwent an additional centrifugation step under the same conditions
The final protein corona sample was then subjected to buffer exchange using an Amicon Ultra Centrifugal Filter with a 10 kDa molecular weight cut-off
effectively removing sodium dodecyl sulfate (SDS) from the protein samples
The buffer exchange process began by wetting the filter with 20 µl of 100 mM ABC (pH 8.0)
followed by centrifugation at 14,000×g for 10 min
200 µg of proteins were added to the filter
and centrifugation was conducted for 20 min at 14,000×g
This step was repeated with the addition of 200 µl of 8 M urea in 100 mM ammonium bicarbonate
followed by centrifugation for 20 min at 14,000×g
and repeated twice to ensure complete removal of SDS and other small molecules
To eliminate urea from the purified protein
the filter underwent three additional rounds of buffer exchange
All procedures were carried out at 4 °C to effectively eliminate urea from the protein corona
the total protein concentration was determined using a bicinchoninic acid (BCA) assay kit from Fisher Scientific (Hampton
The samples were then stored overnight at 4 °C
consisting of 40 µl (without PtdChos initially) and 44 µl (with PtdChos initially) of 100 mM ABC with a protein concentration of 2.8 mg/ml
The RPLC separation was performed using an EASY-nLC™ 1200 system from Thermo Fisher Scientific
A 1-µL aliquot of the protein corona sample (0.3 mg/mL) was loaded onto a home-packed C4 capillary column (75 µm i.d
Sepax) and separated at a flow rate of 400 nL/min
A gradient composed of mobile phase A (2% ACN in water containing 0.1% FA) and mobile phase B (80% ACN with 0.1% FA) was used for separation
The gradient profile consisted of a 105-min program: 0–85 min
The LC system required an additional 30 min for column equilibration between the analyses
resulting in approximately 135 min per LC-MS analysis
The experiments utilized a Q-Exactive HF mass spectrometer
employing a data-dependent acquisition (DDA) method
MS settings included 120,000 mass resolution (at m/z 200)
parameters included 120,000 mass resolution (at 200 m/z)
the top five most intense precursor ions from each MS spectrum were selected in the quadrupole and fragmented using higher-energy collision dissociation (HCD)
Fragmentation occurred exclusively for ions with intensities exceeding 5E4 and charge states of 4 or higher
Dynamic exclusion was enabled with a 30-s duration
and the “Exclude isotopes” feature was activated
Complex sample data were analyzed using Xcalibur software (Thermo Fisher Scientific) to obtain proteoform intensities and retention times
Chromatograms were exported from Xcalibur and formatted using Adobe Illustrator for the final figure presentation
The resulting mass spectra were stored in msalign files
while proteoform feature information was stored in text files
Database searches were carried out using TopPIC Suite against a custom-built protein database (~2780 protein sequences)
which included proteins identified in the BUP data
The search allowed for a maximum of one unexpected mass shift
with mass error tolerances of 10 ppm for precursors and fragments
Unknown mass shifts up to 500 Da were considered
False discovery rates (FDRs) for proteoform identifications were estimated using a target-decoy approach
filtering proteoform identifications at 1% and 5% FDR at the PrSM and proteoform levels
The samples were centrifuged at 14,000×g for 20 min to remove the unbound proteins
The collected NP pellets were washed three times with cold PBS under the same conditions
The samples were resuspended in 20 µl of PBS
and the proteins were reduced with 2 mM DTT (final concentration) for 45 min and then alkylated using 8 mM IAA (final concentration) for 45 min in the dark
5 µl of LysC at 0.02 µg/µl was added for 4 h
followed by the same concentration and volume of trypsin overnight
The samples were then centrifuged at 16,000×g for 20 min at room temperature to remove the NPs then cleaned using C18 cartridges and vacuum dried
Dried peptides were resuspended in 0.1% aqueous formic acid and subjected to LC-MS/MS analysis using an Exploris 480 mass spectrometer fitted with a Vanquish Neo (both Thermo Fisher Scientific) and a custom-made column heater set to 60 °C
Peptides were resolved using an RP-HPLC column (75 μm × 30 cm) packed in-house with C18 resin (ReproSil-Pur C18–AQ
The following gradient was used for peptide separation: from 4% B to 10% B over 7.5 min to 35% B over 67.5 min to 50% B over 15 min to 95% B over 1 min followed by 10 min at 95% B to 5% B over 1 min followed by 4 min at 5% B
Buffer A was 0.1% formic acid in water and buffer B was 80% acetonitrile
The mass spectrometer was operated in DIA mode with a cycle time of 3 s
MS1 scans were acquired in the Orbitrap in centroid mode at a resolution of 120,000 FWHM (at 200 m/z)
and maximum ion injection time mode set to Auto
MS2 scans were acquired in the Orbitrap in centroid mode at a resolution of 15,000 FWHM (at 200 m/z)
quadrupole isolation window of 7 m/z with 1 m/z window overlap
normalized AGC target set to 3000% and a maximum injection time of 22 ms
Peptides were fragmented by HCD with collision energy set to 28% and one microscan was acquired for each spectrum
The acquired RAW files were searched individually using the Spectronaut (Biognosys v18.6) directDIA workflow against a Homo sapiens database (consisting of 20,360 protein sequences downloaded from Uniprot on 2022/02/22) and 392 commonly observed contaminants
For analysis of the impact of PtdChos treated plasma and different NPs
we chose a quicker LC-MS setup (30 SPD) consisting of an Exploris 480 fitted with an Evosep One using the following settings
Dried peptides were resuspended in 0.1% aqueous formic acid
loaded onto Evotip Pure tips (Evosep Biosystems)
and subjected to LC-MS/MS analysis using an Exploris 480 Mass Spectrometer (Thermo Fisher Scientific) fitted with an Evosep One (EV 1000
Peptides were resolved using a performance column—30 SPD (150 μm × 15 cm
Evosep Biosystems) kept at 40 °C fitted with a stainless-steel emitter (30 um
Evosep Biosystems) using the 30 SPD method
Buffer A was 0.1% formic acid in water and buffer B was acetonitrile
The mass spectrometer was operated in DIA mode
MS1 scans were acquired in centroid mode at a resolution of 120,000 FWHM (at 200 m/z)
MS2 scans were acquired in centroid mode at a resolution of 15,000 FWHM (at 200 m/z)
quadrupole isolation window of 12 m/z without window overlap
normalized AGC target set to 3000% and maximum injection time mode set to Auto
The acquired RAW files were searched using the Spectronaut (Biognosys v19.0) directDIA workflow against a Homo sapiens database (consisting of 20,360 protein sequences downloaded from Uniprot on 2022/02/22) and 392 commonly observed contaminants
Default settings were applied except method evaluation was set to TRUE
The top ten unique non-overlapping binding poses were kept for the subsequent molecular dynamics simulations
and 10 ligands systems each were used for the simulations
The protein-ligand systems along with the TIP3P water model and a neutralizing salt concentration of 0.15 M NaCl were energy minimized using 5000 steps with an energy tolerance of 1000 KJ/mol/nm
The systems were subsequently equilibrated in 1 ns NVT and 4 ns NPT steps with a 1 fs timestep
The constant temperature for all runs was 310 K and the Berendsen pressure coupling was used
Production steps were then run for 100 ns with a 2 fs timestep with the Parrinello–Rahman barostat
The residues and ligand atoms within 6 Å were selected for the calculation
were averaged for 1000 frames and plotted for each simulation
The results of the three 1 ligand systems were averaged
All visualizations were made using the visual molecular dynamics (VMD) software113
data were normalized by total protein intensity in each technical replicate
Then all the abundances were transformed into log10 and NA values were imputed by a constant value of −10 (in the heatmap figure)
all samples were analyzed with three technical replicates
there were four individual samples per group with no technical replicates
Statistical t-test with unequal variance were used to compare the differences between groups
Data analysis was performed using R (R version 4.1.0) with the help of ggplot2
All measurements were performed as a triplicate analysis of a given aliquot
The initial DIA analysis was performed in one replicate
The experiments on different NPs with PtdChos and DIA were performed on plasma samples from four individual donors
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
The human plasma proteome draft of 2017: building on the human plasma PeptideAtlas from mass spectrometry and complementary assays
The challenge of the proteome dynamic range and its implications for in‐depth proteomics
Mining the plasma proteome for disease applications across seven logs of protein abundance
In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
Single chain variable fragment displaying M13 phage library functionalized magnetic microsphere-based protein equalizer for human serum protein analysis
Digestion and depletion of abundant proteins improves proteomic coverage
Plasma proteome profiling to detect and avoid sample‐related biases in biomarker studies
Mass spectrometry-based plasma proteomics: considerations from sample collection to achieving translational data
Unbiased identification of the liposome protein corona using photoaffinity-based chemoproteomics
ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery
A streamlined high-throughput plasma proteomics platform for clinical proteomics with improved proteome coverage
high-throughput depletion strategy for deep plasma proteomics
Affinity capture enrichment versus affinity depletion: a comparison of strategies for increasing coverage of low-abundant human plasma proteins
Abundant plasma protein depletion using ammonium sulfate precipitation and protein A affinity chromatography
Depletion of abundant plasma proteins and limitations of plasma proteomics
A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona
Protein corona fingerprinting to differentiate sepsis from non-infectious systemic inflammation
Nanotools for sepsis diagnosis and treatment
Physical–chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles
A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers
Disease-specific protein corona sensor arrays may have disease detection capacity
Rapid plasma proteome profiling via nanoparticle protein corona and direct infusion mass spectrometry
Proteomic analysis reveals distinct protein corona compositions of citrate- and riboflavin-coated SPIONs
How eluents define proteomic fingerprinting of protein corona on nanoparticles
The protein corona from nanomedicine to environmental science
An overview of nanoparticle protein corona literature
The issue of reliability and repeatability of analytical measurement in industrial and academic nanomedicine
Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona
Effects of cholesterol on biomolecular corona
Vitamin B6 metabolism and binding to proteins in the blood of alcoholic and nonalcoholic men
Simultaneous binding of folic acid and methotrexate to human serum albumin: insights into the structural changes of protein and the location and competitive displacement of drugs
Molecular recognition patterns between vitamin B12 and proteins explored through STD-NMR and in silico studies
and expression of the pantothenate permease (panF) gene of Escherichia coli
The tuberculosis structural genomics consortium: a structural genomics approachto drug discovery
In: Advances in Protein Chemistry and Structural Biology (ed
Interaction between carbon dots from folic acid and their cellular receptor: a qualitative physicochemical approach
Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical
Structural analysis and insight into effector binding of the niacin-responsive repressor NiaR from Bacillus halodurans
Variation of protein corona composition of gold nanoparticles following plasmonic heating
Regulation of macrophage recognition through the interplay of nanoparticle surface functionality and protein corona
Protein corona composition of gold nanocatalysts
Optical sensor arrays for chemical sensing: the optoelectronic nose
Irreversible changes in protein conformation due to interaction with superparamagnetic iron oxide nanoparticles
Protein corona composition of superparamagnetic iron oxide nanoparticles with various physico–chemical properties and coatings
Graphene oxide strongly inhibits amyloid beta fibrillation
Hard corona composition and cellular toxicities of the graphene sheets
Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide
Protein-Nanoparticle Interactions: the Bio-nano Interface (Springer Science & Business Media
Zeolite nanoparticles for selective sorption of plasma proteins
Corona protein composition and cytotoxicity evaluation of ultra-small zeolites synthesized from template free precursor suspensions
Personalized protein coronas: a “key” factor at the nanobiointerface
Sex-specific silica nanoparticle protein corona compositions exposed to male and female BALB/c mice plasmas
Nanoscale characterization of the biomolecular corona by cryo-electron microscopy
Measurements of heterogeneity in proteomics analysis of the nanoparticle protein corona across core facilities
A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities
Bacterial effects and protein corona evaluations: crucial ignored factors in the prediction of bio-efficacy of various forms of silver nanoparticles
Exploring cellular interactions of liposomes using protein corona fingerprints and physicochemical properties
Nanoparticles-cell association predicted by protein corona fingerprints
Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line
Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis
Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona
Biomolecular coronas provide the biological identity of nanosized materials
Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology
The need for improved methodology in protein corona analysis
Disease-related metabolites affect protein–nanoparticle interactions
Interactions of triglycerides with phospholipids: incorporation into the bilayer structure and formation of emulsions
Interactions of phosphatidylcholine surface monolayers with triglyceride cores and enhanced ApoA-1 binding in lipid emulsions
Bottom-up and top-down proteomic approaches for the identification
and quantification of the low molecular weight proteome with focus on short open reading frame-encoded peptides
Selected reaction monitoring-based proteomics: workflows
Proteomics by mass spectrometry: approaches
Standardizing protein corona characterization in nanomedicine: a multicenter study to enhance reproducibility and data homogeneity
Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders
Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts
Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells
Plasma concentration gradient influences the protein corona decoration on nanoparticles
The protein corona mediates the impact of nanomaterials and slows amyloid beta fibrillation
Proteoforms as the next proteomics currency
Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells
Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics
Mass spectrometry-based top-down proteomics in nanomedicine: proteoform-specific measurement of protein corona
Understanding biophysicochemical interactions at the nano–bio interface
The crystal structure of human microsomal triglyceride transfer protein
Interaction of C-reactive protein with artificial phosphatidylcholine bilayers
Phosphatidylserine and phosphatidylethanolamine bind to protein Z cooperatively and with equal affinity
Effect of phosphorylation of phosphatidylinositol on myelin basic protein-mediated binding of actin filaments to lipid bilayers in vitro
Structure of human phosphatidylcholine transfer protein in complex with its ligand
Interaction of phosphatidylcholine with bovine serum albumin
Specificity and properties of the complexes
Leakage of sucrose from phosphatidylcholine liposomes induced by interaction with serum albumin
Lipid–protein interactions in the plasma lipoproteins
Mapping the KRAS proteoform landscape in colorectal cancer identifies truncated KRAS4B that decreases MAPK signaling
Progress in Top-down proteomics and the analysis of proteoforms
Rafieioskouei, A., Rogale, K., Dibavar, A. S., Mahmoudi, M. & Bonakdarpour, B. Causality analysis of protein corona composition: phosphatidylcholine-enhances plasma proteome profiling by proteomics. Preprint at bioRxiv https://doi.org/10.1101/2024.09.10.612356 (2024)
IgY14 and SuperMix immunoaffinity separations coupled with liquid chromatography-mass spectrometry for human plasma proteomics biomarker discovery
Deciphering nanoparticle protein coronas by capillary isoelectric focusing-mass spectrometry-based top-down proteomics
Estimating evolutionary rates using time-structured data: a general comparison of phylogenetic methods
TopFD: a proteoform feature detection tool for top-down proteomics
Large-scale qualitative and quantitative top-down proteomics using capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry with nanograms of proteome samples
Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function
Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit
Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone ϕ
ψ and side-chain χ1 and χ2 dihedral angles
gmx_MMPBSA: a new tool to perform end-state free energy calculations with GROMACS
MMPBSA.py: an efficient program for end-state free energy calculations
MD-ligand-receptor: a high-performance computing tool for characterizing ligand-receptor binding interactions in molecular dynamics trajectories
The PRIDE database and related tools and resources in 2019: improving support for quantification data
Download references
gratefully acknowledges financial support from the U.S
National Institute of Diabetes and Digestive and Kidney Diseases (grant DK131417)
was supported by an Ambizione Fellowship from the Swiss National Science Foundation (SNSF grant number: PZ00P3_216203) and a grant from Karolinska Institutet (2-188/2022)
thanks the support from the National Cancer Institute (NCI) through the grant R01CA247863
We acknowledge the support of a Burroughs Wellcome Fund Career Award at the Scientific Interface (CASI) (M.P.L.)
and a polymaths award from Schmidt Sciences
is a Chan Zuckerberg Biohub San Francisco investigator
Open access funding provided by Karolinska Institute
These authors contributed equally: Ali Akbar Ashkarran
Ali Akbar Ashkarran & Morteza Mahmoudi
Department of Medical Biochemistry and Biophysics
Department of Chemical and Biomolecular Engineering
Departments of Bioengineering and Mechanical Engineering
University of Tennessee Health Science Center
Medical College of Georgia at Augusta University
and hypothesis development were done by (A.A.S
performed experimental procedures on the formation and analysis of protein corona; and sent the samples for bottom-up-proteomics analysis and different core facilities
conducted and supervised (respectively) the protein corona analysis using top-down-proteomics
conducted and discussed molecular dynamics analysis
conducted the bottom-up proteomics of the samples
Morteza Mahmoudi discloses that (i) he is a co-founder and director of the Academic Parity Movement (www.paritymovement.org)
a non-profit organization dedicated to addressing academic discrimination
and incivility; (ii) he is a co-founder of Targets’ Tip and Albuderm; and (iii) he receives royalties/honoraria for his published books
The remaining authors declare no competing interests
Nature Communications thanks Amitava Mukherjee and the other
reviewers for their contribution to the peer review of this work
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/s41467-024-53966-z
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.
Print El Sobrante Landfill managers informed air quality regulators last year that a chemical reaction brewing underground was causing broiling temperatures and toxic sulfur pollution.Waste Management
said the chemical reaction hasn’t interfered with daily operations and is about 3,000 feet from the section of the landfill that would receive disaster debris
state regulators say the landfill will no longer accept fire debris
The Eaton and Palisades fires had barely broken out when Waste Management offered to accept the inevitable disaster debris at its El Sobrante Landfill near Corona
8 for an emergency waiver to accept the wildfire rubble
landfill staffers had been struggling for months to control a fiery situation of their own
El Sobrante managers informed the South Coast Air Quality Management District that a chemical reaction brewing inside the landfill was causing broiling temperatures and producing toxic sulfur pollution
Waste Management sought approval to increase its tonnage capacity to take in wildfire debris anyway
which Riverside County officials granted the next day
Riverside County officials are now requesting help from state officials for technical assistance with the situation
They acknowledge that they were notified by environmental regulators about the elevated temperatures
but declined to address whether granting the waiver was appropriate
So far, no fire debris has been taken to the landfill, according to the U.S. Army Corps of Engineers, the federal agency overseeing the debris cleanup. But, as of Thursday morning, it had remained on a list of sites that were eligible to accept this material
Since The Times inquired about the chemical reaction at El Sobrante
state environmental regulators say they have ruled out allowing fire debris to be taken there
“Debris from this year’s fires has not been sent to the El Sobrante landfill nor is the site under consideration for future use for this purpose,” said Nefretiri Cooley
a spokesperson for the California Environmental Protection Agency
“We are currently investigating this incident and will provide additional details as they are available.”
Waste Management executives say the chemical reaction has not interfered with daily operations at the 1,322-acre landfill
is about 3,000 feet from the section of the landfill where they had planned to dump disaster debris
were irked that the landfill had even sought permission
“I’m shocked and appalled that El Sobrante would take ash when it knows that its landfill is on fire,” said Jane Williams
executive director of California Communities Against Toxics
“You greatly increase the public health danger to the communities surrounding when landfills are being operated like this
An out-of-control landfill can emit more [toxic] benzene than an oil refinery.”
The situation at El Sobrante Landfill underscores the checkered compliance history at many Southern California landfills that are poised to receive an estimated 4.5 million tons of potentially hazardous ash
rubble and soil from the federal cleanup efforts
With such problems as excessive air pollution and insufficient inspections
state and local environmental regulators have handed down dozens of violations to these waste disposal facilities in the last year alone
El Sobrante is the second landfill in Southern California in recent years to experience this type of scorching-hot chemical reaction — commonly called an underground landfill fire. Since 2022, operators of the since-closed Chiquita Canyon Landfill in Castaic struggled to contain noxious fumes and contaminated runoff caused by an underground garbage fire
These underground dump fires cannot be easily extinguished and often take years to peter out
these incidents have called into question the environmental oversight of California’s landfills
The California Department of Resources Recycling and Recovery
El Sobrante staff members told the local air district that the landfill had experienced a rise in highly flammable hydrogen gas and lung-aggravating dimethyl sulfide emissions — both telltale signs of abnormal temperatures inside the landfill
Waste Management executives said in August that the pollution was emanating from a two-acre “area of concern” where landfill staff had observed temperatures climbing above 200 degrees
Staff members also reported cracks on the landfill’s surface
landfill workers began extracting liquid waste from the reaction area to alleviate the heat and pressure
transporting it to a waste treatment facility
“South Coast AQMD continues to conduct unannounced on-site inspections at the landfill and responds to all public complaints,” said Nahal Mogharabi
The conditions at El Sobrante Landfill mirror issues at Chiquita Canyon Landfill
where residents called in thousands of odor complaints to the local air district
Air district inspectors found white smoke venting from cracks on the landfill’s surface and liquid waste bursting onto the surface in a geyser-like fashion. The Environmental Protection Agency said the reaction posed an “imminent” danger to public health and the environment
County officials eventually helped organize a temporary relocation program for residents who wanted to escape the stench and toxic fumes
Waste Connections, the owner of Chiquita Canyon, closed the landfill in December and is focusing on managing the reaction area
Federal and state environmental regulators suspected the Chiquita Canyon reaction was caused by oxygen intrusion
landfills have an extensive network of underground wells that are used to extract gases produced as buried waste decomposes
But if this system fails or overdraws these gases
these wells can introduce oxygen into the waste
speeding up waste decomposition and producing heat
the extreme heat has the potential to damage the protective liner underneath the landfill that prevents liquid waste from seeping into the groundwater beneath and migrating to neighboring areas
2:36 p.m. Feb. 28, 2025A previous version of the article stated that CalRecycle inspectors identified several violations at El Sobrante Landfill. Riverside County inspectors, who work in partnership with CalRecycle, found those violations.
In the last year, El Sobrante Landfill has been cited several times for excessive air pollution by the local air district. In that time, Riverside County inspectors also identified violations for elevated levels of flammable methane, improper signage and failure to conduct sufficient truck inspections to ensure hazardous wastes aren’t disposed at the site.
Tony Briscoe is an environmental reporter with the Los Angeles Times. His coverage focuses on the intersection of air quality and environmental health. Prior to joining The Times, Briscoe was an investigative reporter for ProPublica in Chicago and an environmental beat reporter at the Chicago Tribune.
World & Nation
Climate & Environment
and yachting from her home on the Côte d’Azur
where she has lived for nearly two decades
Her stories have appeared in Condé Nast Traveler
She is also a contributing author to four Lonely Planet guidebooks
TechThe Famous Group
Corona Extra team on MLB Opening Day mixed-realty activationThe 30-second spot appeared during the fourth inning of Dodgers-Tigers on ESPN
ESPN’s Opening Day broadcast of Dodgers-Tigers included a unique mixed-reality activation developed by The Famous Group in partnership with Corona Extra and Initiative
the beer brand’s paid media agency of record
introduced the 30-second spot by declaring
“Playa is always just a lime away,” in line with Corona’s popular tagline
Dodger Stadium was then transformed into an animated beachfront by The Famous Group’s new “Virtual Camera” mixed-reality system
centering on two beach chairs and a bucket of beers
four cameras were positioned around Dodger Stadium
This is the second mixed-reality spot TFG has executed at Dodger Stadium, joining a Denzel Washington-narrated Jackie Robinson tribute ahead of the 2022 All-Star Game (using its old system)
TFG’s mixed-reality initiatives are led by the company’s Creative Dir Hemu Karadkar and VP/Production Technology Erik Beaumont
Metrics details
Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts
The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona
which varies patient-to-patient and as a function of disease state
This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions
NP coronas alter cell associations in a disease-dependent manner
induce differential co-stimulatory and co-inhibitory molecule expression
Integrated multi-omics analysis of proteomics
and cytokine datasets highlight a set of differentially enriched TLR4 ligands that correlate with dynamic NP corona-mediated immune activation
Pharmacological inhibition and genetic knockout studies validate that NP coronas mediate this response through TLR4/MyD88/NF-κB signaling
Our findings illuminate the personalized nature of corona formation under a dynamic inflammatory condition and its impact on NP-mediated immune activation profiles and inflammation
suggesting that disease progression-related alterations in plasma composition can manifest in the corona to cause unintended toxicity and altered therapeutic efficacy
a Schematic representation of the endotoxemia mouse model and plasma extractions for NP corona formation. Plasmas were extracted after varying time-points to assess different inflammation severities (n = 10 mice per timepoint) and used to coat NPs for subsequent macrophage treatments. Created in BioRender. Shaw, J. (2025) https://BioRender.com/s80i128
b Pro-inflammatory cytokine profiles of pooled whole mouse plasma after 0
and 16 h-post LPS injection (representing 3 measurements of n = 10 pooled mouse plasmas per timepoint)
c Total protein quantified in whole plasma over time using a bicinchoninic acid (BCA) protein assay (n = 3 biological replicates)
d Nanoparticle Tracking Analysis (NTA) of NP corona diameter size distributions after washing off excess plasma
Plots are representative of n = 3 measurements of 30 second recordings
Error bars are represented as red-shaded regions
Mean size and zeta-potential are presented for each condition
and 8hrPlas samples were eluted and run through an SDS-PAGE gel and stained with Coomassie for total protein
f Quantification of proteins eluted from NP coronas using a 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) protein assay
represented as ng of protein per mg NP (n = 3 independent replicates)
Significance was calculated using a one-way ANOVA with Tukey post hoc test
g Uptake/association kinetic analysis of Cy5.5-labeled PLGA NPs or NP corona-treated macrophages up to 24 h
quantified using flow cytometry (n = 3 biological replicates)
Significance was determined in the final 24-hour timepoint using a one-way ANOVA with Tukey’s post-hoc test (PLGA:NaivePlas_PLGA
*P < 0.05; **P < 0.01; ***P < 0.001
Source data are provided as a Source Data file
a Flow cytometry mean fluorescence intensity (MFI) quantification of macrophage surface markers CD86
and PD-L1 after treatment with pristine PLGA NPs or NP coronas for 30-min or 24-h (n = 3 biological replicates per timepoint)
Representative histograms of 24-hour timepoints are shown below
Statistical significance was determined with a two-way ANOVA using a Dunnett’s test with No Treatment set as control
b TNFα secretions over time from macrophages after PLGA NP or NP corona treatment (n = 3 biological replicates per timepoint)
c Multiplex cytokine analysis in the supernatants of NP corona-treated macrophages after 3-hour incubation (n = 3 biological replicates)
Statistical significance was determined with a two-way ANOVA using Tukey post hoc test
d Spearman correlation matrix of the macrophage multiplex cytokine analysis
indicating a strong positive correlation between sample cytokines
e Organ biodistribution of Cy5.5-labeled PLGA NPs coated in various plasma coronas 3-h post i.v
and brain were isolated and analyzed via in vivo imaging system (IVIS) for NP fluorescence
Representative organ samples are presented from saline (S)
Percent of total radiant efficiency is presented in the graph below (n = 2 mice per group)
No fluorescence was detected in brain samples
f TNFα plasma concentration from NP corona-treated IVIS mice (n = 2 mice per group
Significance was calculated using a two-way ANOVA with Tukey post hoc test
The difference for 8hrPlas compared to the in vitro findings can be attributed to 8hrPlas NP coronas likely stimulating other immune cells in vivo
these findings demonstrate the differential immunostimulatory capabilities of various NP coronas caused by NP composition and disease state dynamics
suggesting that the differential presence of biomolecules in coronas are contributing to the measured alterations in immunological profiles
k Upstream network effects that were supervised to predict 3hrPlas corona-induced cytokines
Color key and symbols are reported in the legend
although the host plasma is laden with pro-inflammatory molecules at the 8hrPlas timepoint
their lack of cellular association could reduce the induction of pro-inflammatory cellular responses when compared to 3hrPlas_PLGA samples
these results show that there is likely a compilation of biomolecules either specific to
or significantly elevated in the 3hrPlas NP coronas that have the propensity to induce inflammatory cytokines
and while 8hrPlas NP coronas also contain similar pro-inflammatory biomolecules
the marked reduction in opsonins may reduce their potency
Significance for all graphs were calculated using a one-way ANOVA with Tukey’s post-hoc test
Although it is possible that LPS may contribute to the inflammatory response
our data supported that it is unlikely to be the driving biomolecule in the 3hrPlas NP coronas
a Upstream network prediction further restricted to 3hrPlas-specific corona biomolecules that induce TLR4/MyD88/NF-kB activation. b Schematic representation of recombinant protein pre-coatings to evaluate potential pro-inflammatory biomolecules. Created in BioRender. Shaw, J. (2025) https://BioRender.com/u64r124
c Pro-inflammatory TNFα secretion of macrophages treated with various pre-coated NP coronas
NP coronas evaluated include hemoglobin (20 mg/mL) coatings (HbHigh_PLGA)
fibrinogen normal (2 mg/mL) and high (10 mg/mL) (FbNorm_PLGA
3hrPlas_PLGA spiked with Paquinimod S100A9 inhibitor
along with healthy (Naïve) plasma coatings spiked with hemoglobin or fibrinogen
(Measurements are from n = 3 biological replicates for all samples
Significance was calculated using a one-way ANOVA with Tukey’s post-hoc test
*P < 0.05; **P < 0.01; ***P < 0.001
although there is previous literature demonstrating disease-specific protein corona composition differences in human plasmas
evaluating the effects of disease dynamics on corona-dependent immune recognition in additional disease models could help to fine-tune the administration of NPs by identifying an optimal therapeutic window where coronas do not induce immune activation or possibly limit therapeutic efficacy
it is likely that many patients will be medicated with other therapeutic agents that could affect the composition of the NP corona and corresponding responses
this work demonstrates that NP coronas are formed differentially due to disease progression
which significantly affects corona formation
and corresponding immune activation profiles
These findings contribute to the nanomedicine field by providing evidence that disease-relevant NP coronas should be assessed on a formulation-specific basis to enhance preclinical testing and potential clinical translation
previously unsuccessful NP formulations may benefit from re-evaluation with more precise classifications of patient subpopulations and disease-relevant corona characterization
Acid-terminated 50:50 PLGA (∼0.17 dL/g inherent viscosity in hexafluoro-2-propanol; approximately MW 4.2 kDa) and acid-terminated poly(DL-lactide) (PLA) (approximately MW 11.3 kDa) with low inherent viscosity between 0.16–0.25 dL/g (Product No
B6014-1) were purchased from Lactel Absorbable Polymers (Birmingham
Poly(ethylene-alt-maleic anhydride) E400 (PEMA
105564) was received as a gift from Vertellus™ (Indianapolis
Poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG5k) (Product No
LPS from Escherichia Coli serotype O111:B4
FITC-conjugated LPS from Escherichia coli serotype O111:B4
and acetone were obtained from Sigma-Aldrich (St
HY-139397) was purchased from MedChemExpress (Monmouth Junction
Endotoxin quantification assay (Product No
C6667) were purchased from Thermo Fisher Scientific (Waltham
RAW-Blue™ cells and QUANTI-Blue™ solution (Cat
raw-sp) were purchased from InvivoGen (San Diego
Female C57BL/6 mice (5–6 weeks old) were purchased from the University of Maryland Vet Resources (Baltimore
TLR4-/- K/O C57BL/6 J (B6(Cg)-Tlr4tm1.2Karp/J) mice were gifted by S
Mice were housed on a 12-hour light/12-hour dark cycle at ambient temperature (65–75oC)
and n-propanol were purchased from Fisher Scientific (Pittsburg
and formic acid was purchased from Sigma Aldrich (St
EquiSPLASH lipidomix was purchased from Avanti Polar Lipids
Flow rate ratio of 1 was used during NP synthesis to achieve consistent size distributions
PLGA and PLA NPs were then subjected to centrifugation at 13,000xg
while PLGA-PEG5k NPs were centrifuged at 50,000xg to eliminate excess surfactant by washing thrice with cold H2O
Sucrose (4% w/v) and mannitol (3% w/v) were added to the NP suspensions as a cryoprotectant
The NPs were then frozen at -80 °C and lyophilized for later storage at RT in a desiccator
The size and zeta potential of PLGA NPs and coronas were determined in 1x PBS by dynamic light scattering (DLS) using a Malvern Zetasizer Nano ZSP and Nanoparticle Tracking Analysis (NTA) using a Malvern Nanosight NS300 (Malvern
UK) set to n = 3 recording measurements at a flow rate of 20 µL/minute
Final NP corona pellets were resuspended in 1x PBS for use in subsequent experiments
Plasma was collected into K2 EDTA coated tubes and pooled at 3
and 16-h-post LPS injection for plasma analysis and subsequent ex-vivo NP corona formation
Mice were housed under specific pathogen-free conditions in a facility at the University of Maryland
All mice experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Maryland
NP corona organ distribution: Cy5.5-labeled PLGA NP coronas were injected intravenously through the tail vein at 2 mg per mouse
Mice were then sacrificed after 3 h; organs and plasmas were isolated for Xenogen in vivo imaging system (IVIS) analysis of organ distribution and ELISA plasma cytokine quantification
Total radiant efficiency was calculated for all organs on a per-mouse basis and used to calculate the percent of NP amount in each organ
To determine the concentration of total plasma protein
a Pierce BCA Protein Assay Kit (Thermo Fisher Scientific
Plasma samples were diluted 1000-fold before protein quantification following manufacturers protocol
The protein concentration was determined by comparing the absorbance at 562 nm to a standard curve prepared using bovine serum albumin (BSA) using a SpectraMax iD3 Microplate Reader (Molecular Devices
PLGA NPs were incubated in various plasmas to form coronas as described above
NP coronas were then dissolved in DMSO at a concentration of 20 mg/mL to solubilize the polymer and adsorbed proteins
10 µL of dissolved NP corona samples were mixed with 10 µL of 5 mM ATTO-TAG CBQCA reagent
and 125 µL of 0.1 M sodium borate buffer (pH 9.3)
and measured for fluorescence at an excitation of 465 nm and emission at 550 nm
Quantification of endotoxin was accomplished by a 1:1000 dilution of whole plasma or NP corona samples following the manufacturer’s protocol
0.5 mgs of NPs per condition were mixed with Laemmli buffer (0.277 M Tris-HCl
0.02% bromophenol blue) and heated to 95 °C for 5 min
Samples were then centrifuged at 13,000 xg to separate denatured proteins from solid NPs
and supernatants containing eluted corona proteins were run through a 4%-15% gradient SDS/PAGE gel
A molecular weight protein standard (Product No
gels were stained for total protein with Coomassie for 2 h and destained in a solution of 50:40:10 water:methanol:acetic acid
Images were taken using a ThermoFisher iBright imaging system and processed on ImageJ (Version 1.54 h)
Protein identification was filtered to achieve a 1% false discovery rate (FDR) in peptide spectra match (PSM)
This FDR was determined using the Percolator algorithm embedded in PD
The resulting protein abundances were analyzed using Perseus software (version 1.6.14.0)
data was further filtered to include only proteins identified without any missing values in all the biological replicates
The quantitative protein data were log2 transformed and normalized using median centering
Differentially expressed proteins from various conditions were identified using ANOVA-based analysis or Two-tailed student’s t-test (adjusted p-value < 0.05)
a mixture of 400 µL cold methanol and 10 µL internal standard (EquiSPLASH lipidomix) was added to each sample
followed by orbital shaking at 4 °C for 15 min
and the samples were incubated at 4 °C for 1 hour with orbital shaking
and the resulting extract was incubated at 4 °C for 15 min with orbital shaking
Samples were then centrifuged at 6010x g for 8 min at 4 °C to allow for phase separation
The upper organic phase was carefully collected and kept on ice
while the lower aqueous phase was re-extracted with 200 µL of MTBE followed by 15 min of incubation at 4 °C with orbital shaking
After an additional centrifugation at 6010x g for 8 min at 4 °C
the upper organic phase was removed and combined with the first organic extract
Organic extracts were then dried under a steady stream of nitrogen at 30 °C to remove solvents
and the recovered lipids were dissolved in 200 µL of chloroform:methanol (1:1
v/v) containing 200 µM of butylated hydroxytoluene
samples were diluted 4 fold with acetonitrile:isopropanol:water (1:2:1
The lower aqueous phase was used to determine the protein content via a BCA kit (bicinchoninic acid assay
Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) on an Agilent 1290 Infinity LC coupled to an Agilent 6560 Quadrupole Time-of-Flight (Q-TOF) mass spectrometer was used to analyze total lipid extracts
The separation was carried out using a C18 CSH (1.7 µm; 2.1 ×100 mm) column (Waters
Mobile phase A was 10 mM ammonium formate with 0.1% formic acid in water/acetonitrile (40:60
v/v) and mobile phase B was 10 mM ammonium formate with 0.1% formic acid in acetonitrile/isopropanol (10:90
The gradient was ramped from 40% to 43% B in 1 min
the gradient was returned to initial conditions in 0.5 min and held constant for 1.6 min at a flow rate of 0.4 mL/min
The column was heated to a temperature of 55 °C and the auto-sampler was kept at 5 °C during the analysis
A 2 µL injection volume was used for all samples analyses
Two workflows were used for mass spectrometry analysis
lipid identification of a pooled sample using an iterative MS/MS acquisition
lipid semi-quantitation of all samples using high-resolution
The MS parameters for the iterative workflow were employed as described: extended dynamic range
m/z 980.0164 (–); MS and MS/MS Range m/z 100–1700; acquisition rate
narrow ( ~ 1.3 m/z); collision energy 20 eV (+)
5,000 counts and 0.001%; active exclusion enabled yes; purity
common organic molecules; static exclusion ranges
The MS parameters for the MS1 workflow were the same for source and reference mass parameters and differed only for acquisition (selection of MS (same parameters) not Auto MS/MS)
Univariate analysis performed using Prism 6 (GraphPad
Isolated bone marrow was then subjected to ACK lysis
and residual stem cells were cultured in complete RPMI 1640 media containing penicillin (100 units/mL)
10% heat-inactivated fetal bovine serum (VWR
and 20% L929 cell conditioned medium (containing M-CSF) to induce BMDM differentiation
BMDMs were allowed to differentiate for 8 days
with cell conditioned media changes on days 3 and 6
BMDMs from Naïve mice or TLR4 K/O mice (1 × 105 cells/well) were seeded in a sterile 24-well plate and treated with 300 μg/mL of PLGA NPs or the different NP coronas at 37 °C and 5% CO2
Supernatants were taken after 3 h of incubation
Cytokine profiles in cell culture supernatants and diluted mouse plasmas were analyzed using an enzyme-linked immunosorbent assay (ELISA) (BioLegend
CA) for TNFα or a custom 7-plex Luminex panel for IL-1β
and IFN-β following the manufacturer’s protocols and analyzed using the Luminex xPONENT software (Thermo Fisher
Heatmap and PCA plots were generated using MetaboAnalyst 5.0
BAY 11-7082 was used to inhibit NF-κB where cells were pre-treated at 10 μM for 30 min prior to NP corona treatment for 3 h
TJ-2010-5 was used to inhibit MyD88 activation where cells were pre-treated at 30 µM for 2 h prior to NP corona treatment
RAW-Blue cells were cultured in DMEM (4.5 g/L glucose
Pen-Strep (100 U/mL) following the manufacturer protocol
Cells were treated with 300 µg/mL PLGA NPs or NP coronas
Supernatants from cells were collected 24-h post-stimulation
20 μL of supernatant was mixed with 180 μL of QUANTI-Blue solution and allowed to react in the dark at 37 °C for two hours
Secreted alkaline phosphatase (SEAP) activity was measured by reading the absorbance at 620 nm using a microplate reader
Day 8 BMDMs (1 × 105 cells/well) were seeded in a sterile 24-well plate and treated with 300 μg/mL of Cyanine-5.5 labeled PLGA NP samples
After NP corona treatment for 30 min or 24 h
cells were washed with fresh media and lifted with Versene solution
Lifted cells were incubated with anti‐CD16/32 (1:500
Clone 93) antibody to block nonspecific binding before staining with anti-mouse CD11b-Pacific Blue (1:500
Clone 10 F.9G2) antibodies from BioLegend (San Diego
Cell viability was measured with propidium Iodide (PI) from BioLegend
The stained cells were measured on a Cytek Aurora flow cytometer (Fremont
CA) and analyzed using FCS Express 7 De Novo Software (Glendale
P-values were corrected using a two-way ANOVA with a Benjamini-Hochberg algorithm FDR correction
The list of differentially abundant biomolecules (proteins
and metabolites) between 3hrPlas_PLGA and NaivePlas_PLGA coronas
were uploaded into the IPA software (Qiagen)
The “core analysis” function was used to interpret the datasets
Causal network analysis was supervised based on the observed BMDM cytokine profiles in order to predict 3hrPlas corona-mediated pathway activation
Further TLR4 ligand prediction was done by using the pathway “grow” feature
to identify direct binders from the 3hrPlas_PLGA NP coronas
Purified hemoglobin at 10 mg/mL and fibrinogen (Fb) at 2 mg/mL (FbNorm) or 10 mg/mL (FbHigh)
were incubated with PLGA NPs at 37 °C for 1 hour
purified hemoglobin or fibrinogen was spiked into Naïve plasma at a final concentration of 10 mg/mL
then incubated with NPs to attempt to simulate 3hrPlas concentrations
All NPs were then washed thrice with cold 1x PBS as described earlier and BMDM cells were treated with 300 µg/mL for 3 h before supernatant TNFα cytokine analysis
Paquinimod was added into whole 3hr-post LPS plasma at a final concentration of 30 µM
Samples were allowed to incubate for 1 hour to allow for inhibitor binding
Inhibited 3 hr plasma was then used to coat PLGA NPs as stated above
Washed NP coronas were then used to treat BMDM cells at 300 µg/mL for 3 h before supernatant cytokine analysis
The data analysis was performed using GraphPad Prism 10.4.1 (GraphPad Software Ins.)
Results are presented as mean ± standard deviation of n = 3 independent experiments unless stated otherwise
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
On the issue of transparency and reproducibility in nanomedicine
Nanoparticle Size Is a Critical Physicochemical Determinant of the Human Blood Plasma Corona: A Comprehensive Quantitative Proteomic Analysis
Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles
Binding of blood proteins to carbon nanotubes reduces cytotoxicity
Interplay of protein corona and immune cells controls blood residency of liposomes
Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation
Formation of the Protein Corona: The Interface between Nanoparticles and the Immune System
Ju, Y. et al. Person-Specific Biomolecular Coronas Modulate Nanoparticle Interactions with Immune Cells in Human Blood. ACS Nano https://doi.org/10.1021/acsnano.0c06679 (2020)
Personalized liposome–protein corona in the blood of breast
Personalized protein corona on nanoparticles and its clinical implications
Triad of Acute Infusion-Related Reactions Associated with Liposomal Amphotericin B: Analysis of Clinical and Epidemiological Characteristics
Can the biomolecular corona induce an allergic reaction?—A proof-of-concept study
Roadmap and strategy for overcoming infusion reactions to nanomedicines
Applying lessons learned from nanomedicines to understand rare hypersensitivity reactions to mRNA-based SARS-CoV-2 vaccines
Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts
Precision Nanomedicine Development Based on Specific Opsonization of Human Cancer Patient-Personalized Protein Coronas
Nanoparticle-Enabled Enrichment of Longitudinal Blood Proteomic Fingerprints in Alzheimer’s Disease
Gold Nanoparticle-Enabled Blood Test for Early Stage Cancer Detection and Risk Assessment
Analysis of the Human Plasma Proteome Using Multi-Nanoparticle Protein Corona for Detection of Alzheimer’s Disease
An investigation on the role of plasma and serum opsonins on the evternalization of biodegradable poly(D,L-lactic acid) nanoparticles by human monocytes
Time-dependent changes in opsonin amount associated on nanoparticles alter their hepatic uptake characteristics
and pharmacokinetics of polymeric nanoparticles
Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles
PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases
Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation
Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance
Tolerogenic Immune Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in NOD Mice
PLGA-based nanoparticles: an overview of biomedical applications
TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized
Microfluidic-Generated Immunomodulatory Nanoparticles and Formulation-Dependent Effects on Lipopolysaccharide-Induced Macrophage Inflammation
Serum albumin as a risk factor for death in patients with prolonged sepsis: An observational study
Plasma protein levels are markers of pulmonary vascular permeability and degree of lung injury in critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome
Nanoparticle Uptake: The Phagocyte Problem
Differential Roles of the Protein Corona in the Cellular Uptake of Nanoporous Polymer Particles by Monocyte and Macrophage Cell Lines
Effects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells
Corona Composition Can Affect the Mechanisms Cells Use to Internalize Nanoparticles
Changes in target ability of nanoparticles due to protein corona composition and disease state
Polymeric particle-based therapies for acute inflammatory diseases
Biomaterial-Driven Immunomodulation: Cell Biology-Based Strategies to Mitigate Severe Inflammation and Sepsis
In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance
Cargo-less nanoparticles program innate immune cell responses to Toll-like receptor activation
Immunomodulatory Nanoparticles Mitigate Macrophage Inflammation via Inhibition of PAMP Interactions and Lactate-Mediated Functional Reprogramming of NF-κB and p38 MAPK
Therapeutic Inflammatory Monocyte Modulation Using Immune-Modifying Microparticles
Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery
On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles
Engineering precision nanoparticles for drug delivery
Time Evolution of the Nanoparticle Protein Corona
In situ analysis of nanoparticle soft corona and dynamic evolution
IgG and fibrinogen driven nanoparticle aggregation
Omo-Lamai, S. et al. Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions. bioRxiv 2023.07.21.550080 https://doi.org/10.1101/2023.07.21.550080 (2023)
An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System
Biological Features of Nanoparticles: Protein Corona Formation and Interaction with the Immune System
Understanding Protein–Nanoparticle Interaction: A New Gateway to Disease Therapeutics
The complement system testing in clinical laboratory
Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime
Complement activation in severely ill patients with sepsis: no relationship with inflammation and disease severity
Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo
The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system
Targeting of MyD88 Homodimerization by Novel Synthetic Inhibitor TJ-M2010-5 in Preventing Colitis-Associated Colorectal Cancer
Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 21
Sensitivity of mice to lipopolysaccharide is increased by a high saturated fat and cholesterol diet
Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant
Identification of Human S100A9 as a Novel Target for Treatment of Autoimmune Disease via Binding to Quinoline-3-Carboxamides
TLR4 Signaling by Heme and the Role of Heme-Binding Blood Proteins
Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function
Understanding the Lipid and Protein Corona Formation on Different Sized Polymeric Nanoparticles
Quantitative profiling of the protein coronas that form around nanoparticles
Multimodal nanoparticle-containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation
Quantification of particle-conjugated or particle-encapsulated peptides on interfering reagent backgrounds
Effects of multiple stressors on pancreatic human islets proteome reveal new insights into the pathways involved
Effect of PTFGRN Expression on the Proteomic Profile of A431 Cells and Determination of the PTGFRN Interactome
Comparative Evaluation of MaxQuant and Proteome Discoverer MS1-Based Protein Quantification Tools
Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics
Spinal cord injury disrupts plasma extracellular vesicles cargoes leading to neuroinflammation in the brain and neurological dysfunction in aged male mice
MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights
Download references
Research reported in this publication was supported the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM142752 (R.M.P)
PhRMA Foundation Predoctoral Fellowship in Drug Delivery under award number 2022 PDDL 877305 (N.T.)
University of Maryland School of Medicine’s & Greenebaum Comprehensive Cancer Center’s Flow Cytometry Core–Baltimore
This publication was supported by funds through the Maryland Department of Health’s Cigarette Restitution Fund Program and the National Cancer Institute - Cancer Center Support Grant (CCSG) - P30CA134274
University of Maryland School of Medicine’s Center for Translational Research in Imaging – Baltimore
University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-IQB2014)
The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health
Marlene and Stewart Greenebaum Comprehensive Cancer Center
conceived the project and wrote the manuscript
designed and performed the in vitro experiments
performed in vivo experiments and sample processing
performed the mass spectrometry studies with the supervision of M.A.K
performed computational and statistical analyses
R.M.P acquired funding and supervised the project
All authors edited and approved the final manuscript
The authors declare no competing interests
Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work
Download citation
DOI: https://doi.org/10.1038/s41467-025-56210-4
Renee Corona is an integral part of the team at San Diego SOAR Academy East Mesa.
including teacher and administrative assistant
She is currently working as a classroom assistant.
“Her dedication and desire to go the extra mile for our community here at East Mesa makes her an invaluable part of our team,” said Matt Kruger
a teacher who works with Corona at SOAR Academy
I cannot imagine our site without her.”
That dedication has spurred some of the students at the site to give her the nickname “School Mom.”
“Her commitment to students’ education is tangible and inspiring,” Kruger said
Corona to bounce ideas with has made my job easier and more fun.”
Principal Nathan Head said that Corona embodies the resilience and adaptability needed to meet the challenges in the dynamic educational environment at the juvenile detention facility.
“She consistently demonstrates a commitment to and focus on our students by navigating emerging educational platforms
and providing essential direct support to our at-promise youth,” he added
“She believes in the success of all our students and assists our entire educational staff.”
May is a time when we take a step back to acknowledge and celebrate the many people in education who work hard to ensure students
and families are thriving — from principals and teachers to all the staff members behind the scenes — with recognition days and weeks.
Chrys Miller fosters an environment where everyone feels valued
Her commitment to the well-being and growth of students and families is why she was chosen SDCOE's 2025 Early Education Teacher of the Year
Removing barriers to learning for our students is paramount to helping them succeed but many students don’t realize that poor vision is holding them back
Escondido Union High School District is proud to announce and celebrate a historic achievement: three outstanding seniors from Del Lago Academy
and Escondido High School who have been selected as 2025 recipients of The Gates Scholarship
full-ride scholarship that is granted exceptional high school seniors nationwide each year
a virtual event designed to empower students aged 13 and above with practical and creative ways to share their stories and discuss mental health
California Pacific Charter Schools’ Junior Leadership Team has been recognized as a 2025 ASCA Student Council School of Excellence by the National Association of Elementary School Principals
Metrics details
We investigated healthcare avoidance during the first COVID-19 wave in a Dutch region with high infection rates
multiphase study used (1) primary care electronic health records to identify patients
(2) questionnaires to capture patients with unreported COVID-19 symptoms
a natural language model estimated COVID-19 incidence from routine care data
535 (23%) reported COVID-19 symptoms; 180 sought help
Care-seeking rates did not differ significantly between those with or without relatives who experienced severe illness or death before their own illness (p = 0.270)
Interviews showed the main barriers were feeling not ill enough and concerns about an overstressed healthcare system
Only a third of participants with symptoms sought help
Serious illness or death of loved ones had no significant impact
Findings highlight the need for clear communication and accessible healthcare
The underlying reasons for avoiding care during the COVID-19 pandemic remain insufficiently explored
the aim of this study was to investigate the impact of COVID-19 on seeking help at the GP during the initial wave of the pandemic
We hypothesized that healthcare-seeking behaviour could be influenced by factors such as the serious illness or death of loved ones
particularly focused on cases where individuals did not seek help despite having COVID-19 complaints
Description of the different phases of our mixed-method study
The study population comprised all patients registered at one of the three different general practices in the Dutch municipality Hasselt as of March 2020
meaning the population had slightly changed since 2020 due to factors such as relocation or mortality
all inhabitants are registered with one GP
Baseline characteristics (March 2020) of all patients were extracted from the electronic health records of the participating practices. Patients with a registered email-address received an online invitation and questionnaire, while others were sent the same materials by post in September 2022 (Supplementary File 1)
a reminder was sent to those who received the online questionnaire
but not those who received the postal invitation
the study was promoted in the local newspaper “De Stentor”
The questionnaire was designed to identify patients who experienced COVID-19 symptoms during the first wave but did not seek medical care for their COVID-19 complaints
it was an unvalidated questionnaire developed by several experts in the field
we identified a subgroup of COVID-19 cases who did not seek medical help
participants from this subgroup were randomly selected and stratified across the three different practices
they were invited to participate in individual
face to face semi-structured interviews at their homes
An interview guide was developed based on expert opinion and some available literature at that time to explore the participants’ experiences and needs during the first lockdown period
Interviews were conducted by experienced interviewers (AR and ALP) from the regional Community Health Service until no new themes emerged in two consecutive interviews
The interviewers were independent of the patients
and had no personal interest in study’s outcomes
Statistical analysis was performed using SPSS statistics 27.0 software
Characteristics of the study population measured on a continuous scale were represented as either mean ± SD or median (interquartile range)
Categorical variables were presented as the total number of observations with corresponding percentages
Data comparing participants and non-responders were analyzed by using Mann-Whitney U test or Chi Square tests
P-values < 0.05 were considered statistically significant
The study has been approved by the Medical Ethics Committee of the Isala Hospital
The study was conducted in accordance with the Declaration of Helsinki
Informed consent was obtained from all participants
In total, 6123 patients aged over 16 years were extracted from three different general practices. 143 patients were excluded due to missing data, leaving 5980 patients in the study population. The response rate of the questionnaire was 39% (n = 2361). Baseline characteristics of participants and non-responders are shown in Table 1
The median age of participants was higher than the non-responders (median 57 years
the proportion of females was higher in the participant group (58%) compared to the non-responder group (44%)
and malignancies exhibited higher response rates
those with asthma or COPD had lower response rates
Lower response rates were observed in individuals identified by the AI model as having COVID-19 symptoms
4207 have had contact with their GP at least once
Information about COVID-19 was discovered in 3400 unique medical records
1508 patients participated in the questionnaire
the AI model predicted the presence of COVID-19
Among all participants, 23% (n = 535) reported experiencing any COVID-19 related symptoms (Table 2)
139 participants (26%) actually had a positive PCR-test by testing at the community health service
The most frequently reported symptoms were cough (56%)
180 participants (33.6%) reported seeking help for COVID-19
Four patients went directly to the hospital without involving the GP
Of the 535 participants with complaints during the first wave
80 participants (15%) reported experiencing symptoms for more than 24 months
there was no significant difference in the percentage of relatives or acquaintances who experienced severe COVID-19 symptoms or passed away before their own illness
between those who sought care and those who did not (48% vs
as mentioned in the free-text section of the questionnaire
included ‘due to the wave of participants’
‘we waited at home to reduce the severity of complaints to a bearable level’ and ‘the government’s advice at the time was: only seek for help if you have severe shortness of breath’
Cross-sectional thematic network of the interrelated themes before the interviews (light grey) and the additional themes resulting from the qualitative analysis (dark grey) of the interviews (n = 12)
A key reason for not seeking help was participants’ assumption that they were not seriously ill
One participant (#1) said: I do not go to the GP very often
and being sick for three weeks and feeling flu-like does not necessarily mean that I will consult a doctor.One participant indicated that he was experiencing ongoing complaints but did not want to burden the GP too much due to the high workload for GPs at that time
Participant #5 reflected on the challenging situation for the GPs: But the knowledge that the GP’s were just in such a crisis and were so terribly busy
and that you indeed first heard one ambulance after another arriving and later one death bell after another
because it was like that.While most participants were satisfied despite not receiving healthcare
they were able to manage their symptoms on their own
Some indicated they would have sought help if their symptoms had persisted a little longer
The mental impact was mainly attributed to the broader COVID-19 crisis in general
Several participants described the number of deaths on Hasselt as profoundly impactful and intense
Some older participants noted that the infection and crisis had a less impact on them overall
as they were already retired and engaged in fewer activities
And I have a wife who could always step in if necessary
Participants frequently cited social limitations and changes in social interactions as significant factors
A participant (#6) commented on the difficult social limitations as well
a huge number of people around you have passed away
and that had much more impact than me not being able to do my own thing
many participants expressed frustration regarding the lack of clarity from the national government and the frequent changes in COVID-19 regulations
noting that clearer communication could have alleviated these issues
One participant (#4) mentions the lack of appropriate resources to provide good care: But the fact that it just takes a very long time before they realize that you have corona
If they had just tested everyone back then
And then you could have taken targeted actions
but now it was just a bit of muddling through
Participants expressed varied preferences for assistance or care
but faced barriers like limited complaints and high GP workload
They also highlighted healthcare system bottlenecks worsened by COVID-19
such as limiting PCR testing capacity and insufficient aftercare for long-term COVID-19 effects
Suggestions for improvement included a 24-h helpline
and better guidance on managing complaints and medication use
various factors contributed self-direction and self-management among participants
Acceptance of their illness and the inability to visit a GP were common themes
the majority experienced spontaneous improvement through rest
One participant (#5) described the situation as: I am positively surprised by my own ability to deal with it and also to trust the signals my body was giving me and to think
I do not need a caregiver at this moment because I am managing
Informal support from partners or children
including task assistance and emotional support
Participants appreciated healthcare workers despite challenges in arranging immediate assistance
many understood the crisis constraints and did not blame GPs
given the limited understanding of COVID-19 at the time
I would just much rather talk directly to a GP
but that simply was not there back then either
This mixed-methods study suggests that only one-third of patients who experienced COVID-19 related symptoms during the first wave sought medical care
no difference was found between healthcare seeking and the presence of serious illness or death of loved ones
The primary reason for not seeking help was participants’ belief that they were not sick enough
compounded by an overstressed healthcare system
Participants generally expressed contentment
with most managing the situation by themselves
Suggested improvements for future health crises included: sufficient availability of PCR-tests
improved access to health advice (possibly through telephone or digital means)
and enhanced information on managing complaints
and unclear COVID-19 related regulations as key determinants affecting their mental health
This study provided meaningful insights in healthcare-seeking behavior in a region heavily impacted by infections during the first wave of the COVID-19 pandemic
we did not determine how many people would have actually wanted to seek help
Probably some participants who did not seek for help
actually had no desire to seek for help because of few complaints
the severity of the participants’ complaints remain unknown
the questionnaires were sent more than a year after the first wave
Applying the AI model on the routine care data resulted in a higher number of participants with a probable COVID-19 episode than the participants themselves recalled
meaning the self-reported incidence of COVID-19 could have been underestimated
The COVID-19 pandemic has greatly hastened healthcare system transformations
Our study findings can enhance care structures for future pandemics
emphasizing the need for clear communication and accessible healthcare
Data is stored in the online portal ResearchManager
Prevalence and determinants of healthcare avoidance during the COVID-19 pandemic: a population-based cross-sectional study
E Lockdown policies and the dynamics of the first wave of the Sars-CoV-2 pandemic in Europe
Cancer has not gone away: a primary care perspective to support a balanced approach for timely cancer diagnosis during COVID-19
Effects of the COVID-19 pandemic on primary care-recorded mental illness and self-harm episodes in the UK: a population-based cohort study
Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review
A Primary health care during the COVID-19 pandemic: A qualitative exploration of the challenges and changes in practice experienced by GPs and GP trainees
The role of socio-demographic and health factors during COVID-19 in remote access to GP care in low-income neighbourhoods: a cross-sectional survey of GP patients
The general practitioners perspective regarding registration of persistent somatic symptoms in primary care: a survey
AR Impact of COVID-19 on Mental Health in Adolescents: A Systematic Review
Epidemiology of mental health problems in COVID-19: a review
A natural language processing model for COVID-19 detection based on Dutch general practice electronic health records by using bidirectional encoder representations from transformers: development and validation study
Data Resource Profile: Registry of electronic health records of general practices in the north of The Netherlands (AHON)
Impact of COVID-19 pandemic on mental health in the general population: A systematic review
R The association between uncertainty and mental health: a scoping review of the quantitative literature
Postponed healthcare in The Netherlands during the COVID-19 pandemic and its impact on self-reported health
Revolution in UK general practice due to COVID-19 pandemic: A cross-sectional survey
Rural use of health service and telemedicine during COVID-19: The role of access and eHealth literacy
Download references
The authors thank the participating GPs in Hasselt (Robert van Kleef
Nico Tuinstra and Gabriëlle Rook) for sharing their data and for their assistance in contacting the patients
Special thanks are extended to Fokko Douma for his IT-support
Acknowledgement is also given to Marieke Jansen for conducting the interviews
we extend our appreciation to Lilian Peters
Maarten Brilman and Karina Sulim for their contributions in running the AI model
wrote the manuscript in consultation with E.A.G.
was responsible for conducting and processing the interviews
assisted us with obtaining the questionnaires and processing the data
The Hasselt Corona Impact Study has been approved by the Medical Ethics Committee of the Isala Hospital Zwolle (registration number 20211017)
Download citation
DOI: https://doi.org/10.1038/s41533-025-00426-w
Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.
No one has been better than star pitcher Seth Hernandez. He entered Monday having struck out 15 with no walks and no runs in eight innings. Against Norco, he hit a three-run home run and struck out 12 and gave up two hits and a walk over five innings in a 9-0 victory over Norco in the Panthers’ Big VIII League opener.
Anthony Murphy also homered for the Panthers. Ethin Bingaman and Brady Ebel each had two hits.
Corona Centennial 7, Corona Santiago 6: The Huskies, trailing 6-0, scored five runs in the fifth inning, one in the sixth and got a walk-off bases loaded walk in the seventh to win the Big VIII League game. Mason Lear had a three-run double.
High School Sports
Louis Lappe, star of 2023 Little League World Series champion El Segundo, will play high school baseball at Harvard-Westlake.
King 5, Eastvale Roosevelt 4: A three-run sixth inning helped King win.
Castaic 6, West Ranch 4: Freshman Orion Gonzalez contributed a home run, double, single and four RBIs to help Castaic win its Foothill League opener. Gio Foster also homered. Ty Diaz led West Ranch with three RBIs.
Sylmar 13, San Fernando 1: The Spartans opened Valley Mission League play with an impressive win. Victor Espinoza and Martin Magana each had two RBIs. Alex Martinez struck out seven in 4 1/3 innings and had three RBIs.
Sun Valley Poly 10, Kennedy 0: Mark Cesena allowed one hit and struck out eight in 6 2/3 innings for Poly. Gael Garcia had two hits and three RBIs.
Fullerton 3, Villa Park 2: Playing at Angel Stadium, Miguel Velasquez of Fullerton hit a memorable first-inning home run for Fullerton. Declan Fitzgerald struck out eight in six innings for Fullerton.
Calabasas 11, Taft 1: Connor Pink hit two home runs to lead Calabasas. Luc Olson threw five scoreless innings.
Banning 4, Carson 0: Anthony Camarena threw six shutout innings with seven strikeouts and also had two hits for Banning in the Marine League win.
San Pedro 13, Narbonne 5: The Pirates won their Marine League opener. Anthony Solis hit two doubles and had five RBIs and Braydon Griffin finished with three hits.
Granada Hills 10, Newbury Park 2: Tristan Jennings had three hits and Anthony Castro and Landon Tuch each had three RBIs for Granada Hills.
Royal 14, Oak Park 2: Brady Hewitt and Isaiah Tillman each had two hits and three RBIs for Royal.
Summit 10, Beckman 0: Isaac Castanon had a home run and three RBIs for Summit.
Orange. Lutheran 9, Las Vegas Centennial 0: Brady Murrietta and Josiah Hartshorn hit home runs for the Lancers in Las Vegas.
Arcadia 6, Damien 4: The Apaches improved to 10-0 with a win at Angel Stadium. Tyler Swilling got the save.
Los Altos 6, Simi Valley 1: Freshman Kaylahni Duenas struck out nine for 6-1 Los Altos.
Chaminade 11, Oak Park 4: Norah Pettersen hit a home run and had three RBIs for Chaminade.
Eric Sondheimer is the prep sports columnist for the Los Angeles Times. He has been honored seven times by the California Prep Sportswriters Assn. for best prep sports column.
85%;">Corona 100 This Is Living Since 1925
View source version on businesswire.com: https://www.businesswire.com/news/home/20250425804516/en/
Already have an account? Login