You’ll soon be able to include a Bigfoot emoji in your chats — even if the organization behind it won’t call it that.
Unicode announced that a “Hairy Creature” emoji will be among the new additions to its standard emoji options when it releases Unicode 17 in September. Here is the full list of emoji that’ll be included in the release.
Trombone
Treasure Chest
Distorted Face
Hairy Creature
Fight Cloud
Apple Core
Orca
Ballet Dancers
Here’s what the emoji look like.
Mashable Trend Report
The fight cloud is kind of funny. Credit: Unicode
As Engadget noted, Unicode — the nonprofit that creates an emoji standard — might call it “Hairy Creature” because it wants the name to be understood globally, where Bigfoot might not be the preferred nomenclature. All eight emoji were among the expected additions for 2025, though a landslide emoji seemingly did not make the cut.
So, soon enough, your chats can officially have a “Hairy Creature” or a Bigfoot — whatever you want to call it.
Distressed birth is linked to an increased risk of physical and mental problems later in life, according to research by 2 University of Miami Patti and Allan Herbert Business School professors.1
Categories of distressed birth evaluated included newborns admitted to neonatal intensive care units, babies with low birth weights, and infants born preterm. These distressed births were more often observed in economically disadvantaged mothers who often had prior health issues.1
“This research has important policy implications, especially as federal and state legislators are debating the future of publicly financed health care programs such as Medicaid,” said Michael T. French, co-author and chair of the Department of Health Management and Policy.1
Focus on long-term health outcomes
According to investigators, prior studies focused on newborn survival, health complications, and use of medical care.2 Therefore, the study was conducted to evaluate physical and mental health in young and middle-aged adults.
The data was published in Medical Care on April 30, 2025.1 According to French, alongside overall health status, the research focused on the presence of chronic health conditions such as hypertension, diabetes, and heart disease.
Participants included respondents of Waves 4 and 5 of the National Longitudinal Survey of Adolescent to Adult Health.2 Outcomes in these patients were determined through multivariate regression models in each wave separately and a mixed-effects model for both waves combined.
Distressed birth and adult health
Comparisons were made for each subgroup of distressed birth with a population of non-distressed births. Neonatal intensive care unit admission, low birth weight, and preterm birth were all linked to significant adverse impacts on physical and mental health in young and middle-aged adults.2
Investigators concluded this data highlights a need for clinicians, policy makers, and public health advocates to invest in additional resources to prevent future distressed births. These interventions may include family planning, prenatal checkups and related care, and incentives for healthy behaviors during pregnancy.2
“If society can either prevent or minimize distressed births, or provide assistance to new mothers and infants soon thereafter, we can perhaps avoid very expensive health care costs related to inpatient hospital stays and emergency room visits,” said French.1
Support evidence finds increased stroke risk
This data is supported by a study published in the European Heart Journal on June 24, 2025, highlighting an increase in long-term stroke risk among women with complications during pregnancy.3 The analysis included over 2 million women assessed across over 40 years.
Preterm birth, small for gestational age, preeclampsia, gestational diabetes, and other hypertensive disorders of pregnancy were considered adverse pregnancy outcomes. For overall stroke, 30-year incidence rates from these outcomes were 1.3%, 1.3%, 1.8%, 1.3%, and 1.5%, respectively.3
For total cumulative incidence, rates were 2.2%, 2.2%, 3.1%,1.9%, and 1.8%, respectively. In comparison, the overall cohort had a 30-year incidence rate of 0.9% and total cumulative incidence rate of 1.6%. This highlighted increased risks among women with complications during pregnancy.3
“Both women and their doctors should now recognize that pregnancy complications are an early signal for future stroke risk. This can help us identify high-risk women long before they suffer a stroke or other cardiovascular disease,” said Casey Crump, MD, PhD, MS, MPH, professor at UTHealth.
References
Research links birth issues to adult health deficits. University of Miami. July 10, 2025. Accessed July 18, 2025. https://www.newswise.com/articles/research-links-birth-issues-to-adult-health-deficits/?sc=dwhr&xy=10023887.
French MT, Mortensen K. Is a distressed birth associated with physical and mental health problems as an adult? Evidence from panel data. Medical Care. 2025. doi:10.1097/MLR.0000000000002156
Krewson C. Pregnancy complications linked to long-term stroke risk. July 8, 2025. Accessed July 18, 2025. https://www.contemporaryobgyn.net/view/pregnancy-complications-linked-to-long-term-stroke-risk.
Folkestone doesn’t have a pier. It has an Arm. That’s what the harbour’s long walkway into the Channel is called. It is a suitably surreal, even grotesque setting for the Folkestone Triennial artworks that infest its salty nooks and crannies – or armpits and elbow crooks. Laure Prouvost has placed a mutant seabird, with three heads and an electric plug on its tail, on the adjacent concrete stump of the defunct ferry terminal. Surprising? Not really if you have just visited The Ministry of Sewers, an installation by Cooking Sections that documents and protests the poisoning of our rivers and seas.
Poison pen-pushers … The Ministry of Sewers by Cooking Sections at Folkestone Triennial. Photograph: Thierry Bal
There’s nothing like an exhibit on the scale of Britain’s water pollution to kick off a day at the seaside. It’s cloudy when I visit, the cliffs and sea swathed in white mist and the water under the Arm looking like a detergent soup. It all adds to the uncanny mood. And art doesn’t come much more uncanny than the sculpture by Dorothy Cross near the far end of the Arm. You have to go down soaking wet, concrete steps to a recess with a precipitous opening to the evil-looking sea. “Try not to fall in,” says the attendant, who stays up above. Here you find a massive block of blood-coloured marble, as if a giant tuna steak had been stashed here by fish smugglers. The sides are smooth, the top uneven and rough. Out of this earthy hulk Cross has carved several pairs of feet in hyperrealistic detail, nervously walking its beach-like surface. They face out to sea, as if about to make a bold leap into the blue-green water, to find a better life.
Cross has made a monument to migrants. The marble she has used is from Syria, the feet pattering over it full of fear and hope. These lifelike appendages and the surface on which they stand echo Magritte’s surrealist 1934 painting The Red Model, of disembodied feet on red ground, while her use of massive, raw stone to suggest infinite sorrow – the weight of the world – shows she understands Michelangelo. This is a superb sculpture, brilliantly sited. It would be worth visiting Folkestone just to see it.
But there’s more – if you fancy a walk. Up above the cliffs, on steep green downs guarded by Martello towers built to fend off invasion during the Napoleonic wars, are a string of thoughtful, often witty artworks. A monolith that looks as if it were made from glue and plastic stands alone on a mowed hill, facing the sea. Approaching, you read the words “Curse dissolved”. That’s heartening. The brochure describes this piece by South African artist Dineo Seshee Raisibe Bopape as “meditative” but it made me laugh. What is the curse? Who lifted it?
Infinite sorrow … Red Erratic by Dorothy Cross at Folkestone Triennial. Photograph: Thierry Bal
I chew on this as I climb to a white circular tower inside which Katie Paterson also plays with magic. Paterson shows, on curving display tables inside the round room where red-coated soldiers once lived, a collection of mystic charms from different times and places. There are images of ancient Egyptian gods, Buddhist amulets and a tiny figure of the Mesopotamian demon Pazuzu who features in The Exorcist.
Each replica is cast in materials that bear witness to planetary crisis, including space debris from satellites and plastic from the Mariana trench. Paterson has a track record of working with scientists to get her hands on such exotic materials. Her installation is a more refined version of the Ministry of Sewers, a sly way to show us that we are turning everything to crap. These amulets are bluntly satirical. They seem to mock the magical thinking of those who would wish away the Earth’s crisis.
Sweetening the picture …Four-year-old Bram Kimm eats an art ice-cream by Emeka Ogboh at Folkestone Triennial. Photograph: Lia Toby/PA
If you head on to the next Martello tower you might be momentarily cheered up by Jennifer Tee’s wavy picture of a giant kelp, mapped in the grass in brown bricks which also have sea kelp and other life forms imprinted on their surfaces. It makes you look out to the sea below and imagine the threatened life it holds.
There are jollities to be found in this seaside art trail – for the kids, Monster Chetwynd has started building an adventure playground, and down in the harbour you can get Emeka Ogboh’s “artist designed ice-cream”. But then I find huge burial urns littered in the high moorland overlooking the misty Channel. Sara Trillo has modelled these deathly objects on bronze age grave goods. They return you to melancholy: the view from here is as bleak as it is beautiful.
Summers are about big, fun, mind-numbing movies. Great escapes in the best of ways. I need that right now, and maybe you do too. I’m happy to say that Donkey Kong Bananza is here to whisk you off to multilevel worlds of satisfyingly smashing madness, to cheer you up and give you an excuse to punch the heck out of things. It’s a game my 12-year-old son has loved playing along with me, although I’ve had to find ways to wrestle the game back to play for myself.
I was wowed by Bananza during an early preview a few weeks ago, but after a few weeks of play at home, it’s even better. This is my favorite Switch game since… I have no idea when. Maybe since Super Mario Odyssey.
The catch is that you need the new Nintendo Switch 2 console to play it. Donkey Kong Bananza won’t work on the original Switch — or on any other gaming device. Of course, that’s the whole idea.
Nintendo needed home run games for its new Switch 2 console, and it hit a grand slam with the new Donkey Kong. I still haven’t finished the game, but I already know it’s the best reason to buy a Switch 2 yet.
Donkey Kong Bananza is available for $70 from Nintendo.com and other retailers. We’re also keeping track of Nintendo Switch 2 restocks if you’re still seeking a console.
Bananza is about punching tons of stuff, and also about questing.
Nintendo
Smashing story with co-op options
In a lot of ways, Bananza feels like Zelda and Mario met in the middle.
The story’s weird, but what Mario (or Nintendo) game isn’t? Donkey Kong’s world has been threatened by a sinister bunch of apes, after a large meteor knocks a mining company deep into the planet’s core. The adventure involves diving down into those sublevels — it’s Donkey Kong Hollow Earth, or Journey to the Center of the Kongiverse. The big difference in this game is that you can destroy just about anything, burrowing and tunneling throughout the game’s large 3D maps.
Technically, this isn’t a true collaborative co-op game, but there’s a mode where Pauline — a young girl who mysteriously fell from the sky and becomes Donkey Kong’s friend — can throw her voice, literally, at things to destroy them. A second player takes over as Pauline and aims and shoots words at enemies, and can absorb material powers from nearby rocks and objects. It’s more engaging than the hat-throwing co-op in Odyssey.
You can Game Share Bananza with a local Switch 2 or Switch 1 in co-op mode to play on two screens, or just play on one. For this review, I wasn’t allowed to Game Share to a second Switch.
The Mario mojo
Bananza is made by the Super Mario Odyssey team, and its 3D platforming feels like a Mario sequel. You can wander through large but still self-contained sublevels that remind me of the Kingdoms in Super Mario Odyssey. As you descend to new levels, the characters you meet and the level’s game mechanics shift up a bit. The levels aren’t as drastically different or quite as weirdly whimsical as the ones in Odyssey, but they feel a lot busier.
Jumping and punching are the main ways to control things, but there are plenty of other moves. There’s also a skill tree of abilities to unlock and power up, which uses points you accumulate by collecting giant, crystal bananas (just go with it). Donkey Kong can also buy new outfits, much like Mario Odyssey, but these outfits (or pieces of outfits) give extra perks, like cold resistance or faster energy recovery.
Each of the levels has goals and sub-bosses to fight, but also secret subchallenges to discover — some of them 3D, some 2D side-scrolling. There are other things to find, in every direction, on any potential hillside or surface, if you just pummel your fists and dig. The free-digging usually involves either finding more crystal bananas or various-sized fossils, which can be collected and redeemed for costumes. There’s gold to accumulate, too, which acts as general currency. But even as I rush to the next goal on any level, I’m equally tempted to just start digging around and see what’s going on somewhere else.
You’ll be studying a lot of 3D map terrain.
Nintendo
The Zelda zeitgeist
Here’s where Bananza really starts to feel like a lower-key Zelda game, especially when it comes to finding characters and following sub-missions. You can talk to lots of the strange characters in each sublevel, and some share important news. You’ll get directed to a particular goal, and on a 3D map, you can track your progress or warp to other spots. But as the game’s progress starts to wind up and down through sublevels, it begins to feel a lot more quest-y than any Mario game.
Zelda: Tears of the Kingdom kept coming to mind for me. That game’s vast overworld and underworld — and its various ways of finding passages between — is very much like Bananza. Also, like recent Zelda games, you can climb just about anywhere (or surf chunks of rock you rip out of the ground). The outfit perks feel Zelda-like, and so does the game’s sense of real-time, chaotic physics. Some puzzles involve understanding the environment and manipulating it, much like I did many times in Tears.
There’s also a sense of persistence in Bananza. You can create little home bases that let you rest up and change outfits. You’ll meander off and come back to locations. Mario Odyssey had some of this too, but Bananza feels more lived in.
Unlike recent Zeldas, though, this game’s challenges are relatively contained. You won’t have long lists of subquests or stories to lose track of. After spending months away from Zelda, and coming back not remembering what I was meant to do next, I appreciate Bananza’s simpler vibe.
Pauline literally throws her words as weapons.
Nintendo
A whole new yet familiar feel
Most importantly, Bananza just feels fresh. I get a little tired, sometimes, of diving back into new Zeldas and Marios that layer legends on top of legends. Donkey Kong’s universe is different from previous Kong games, especially the giant, wrinkled Elders who preside over subworlds like spirits, granting extra transformation powers. This is where the “Bananza” name comes in.
Accumulating enough gold triggers a chance to become a spirit animal. There’s a Bananza version of Kong that has stronger punches, an ostrich that can fly and drop egg bombs, and a zebra that can run fast over ice and water. (I haven’t unlocked any others yet.)
After a week-plus of playing, I’m still consistently surprised by what I’m encountering. But I’m also finding it familiar and comfortable, just like a big summer movie. And that’s what this is: Nintendo’s big blockbuster summer game, one of the best I can remember. Something I don’t want to end, and I’m glad to have more to explore.
I’m also surprised by other things: there’s no online mode, which I don’t mind but feels surprising after Super Mario Wonder’s clever additions. The game download size is only 8GB, shockingly small compared to Switch 2 launch games like Cyberpunk 2077, which were nearly 60GB. I was getting worried about how much storage space I’d have on the Switch 2 over time, but if more games are like Bananza, things will be OK.
My youngest son was instantly interested in Bananza, so much so that he didn’t want me playing without him. I had to, though, so I could carve enough time out to play. We’re going to backtrack and play again, and he’ll start playing, too. Will Bananza feel as replayable and infinitely fun as many of Nintendo’s best? I can’t entirely tell yet, but there’s already so much I’ve skipped over in so many levels, I don’t doubt it. There’s also a 3D art mode thrown in as a bonus where you use the Joy-Cons to sculpt and paint ape heads and bunches of bananas.
DK meeting one of the massive Elders.
Nintendo
Donkey Kong makes it worth buying a Switch 2
Bananza is a great sign for where Nintendo’s heading with the Switch 2. It feels like a more evolved version of many Switch games of the past, but just like Mario Kart World, the other major Switch 2 exclusive, it takes the good ideas even further. Bananza is also an extension of Nintendo’s universe, including the Super Mario Movie, which has a Donkey Kong that looks like this one, and Super Nintendo World, which has a Donkey Kong land, too. And yes, Super Nintendo World’s Donkey Kong Power-Up bands even work like Amiibo with this game.
This is a game as vibrant and kinetic as Sony’s fantastic Astro Bot and similarly full of things to search for and do. In comparison, Super Mario Odyssey now seems surprisingly quiet and chill.
And yes, this game is worth getting a Switch 2 for — that was the idea all along. It’s nice to see that Nintendo really pulled it off, though. Combined with Mario Kart World, this is a heck of a one-two punch. I’d still love a proper 3D Mario sequel someday, but Bananza is practically that right now.
UFC BJJ 2: TACKETT vs CANUTO will take place Thursday, July 31 and will stream live and free on UFC’s YouTube channel beginning at 8 pm ET/5 pm PT.
Media members wishing to apply for credentials may sign up here.
UFC BJJ welterweight champion Tackett (competing out of Austin, Texas) intends to make another statement and defend his title for the first time. Considered one of the best grapplers competing today, Tackett won the inuagural belt with a dominant first-round submission over Andy Varela less than a month ago. He now aims to make the most of his main event spot and prove that he can submit anyone at 170-pounds.
Canuto (competing out of Las Vegas, Nev.) has made a name for himself as one of the most exciting submission threats in Brazilian Jiu-Jitsu. Stepping onto the UFC BJJ mats for the first time, he has already shown his talent in victories over Oliver Taza, Jason Nolf and PJ Barch. Canuto now looks to upset Tackett and claim the UFC BJJ welterweight championship in highlight-reel fashion.
The always exciting Fowler (competing out of Fresno, Calif.) makes his UFC BJJ debut with his sights set on securing the inaugural UFC BJJ light heavyweight championship. A dynamic and versatile grappler, Fowler has wowed fans with submissions over Christiano Troisi, Pedro Marinho and Haisam Rida. He now plans to stake his claim as the best light heavyweight on the planet and raise UFC BJJ gold.
Garmo (competing out of Detroit, Mich.) is determined to claim the biggest victory of his career. An accomplished athlete, he has gained recognition for his exciting and crowd-pleasing style whenever he steps on to the mats. Garmo now seeks to put his skills on display by defeating Fowler and taking the UFC BJJ light heavyweight championship for his own.
Additional matches on the card include:
An exciting middleweight match sees William Tackett (competing out of Austin, Texas) battle Kyle Chambers (competing out of Oceanside, Calif.)
Raquel Canuto (competing out of Las Vegas, Nev.) faces Mo Black (competing out of Colorado Springs, Colo.) in a women’s featherweight match
Lightweight action sees Ademir Barreto (competing out of Columbus, Ohio) take on Kennedy Maciel (competing out of Los Angeles, Calif.)
Aurelie Le Vern (competing out of French Guiana) meets Maggie Grindatti-Lira (competing out of Miami, Fla.) in a women’s featherweight bout
Tammi Musumeci (competing out of Las Vegas, Nev.) aims to impress in her UFC BJJ debut when she goes toe-to-toe with Leilani Bernales (competing out of Miami, Fla.) in a women’s flyweight bout
Bantamweights Everton Teixeira (competing out of Atlanta, Ga.) and Jalen Fonacier (competing out of Los Angeles, Calif.) aim to put on a show
For the latest information on additional bouts for this event, please visit www.ufc.com. All bouts are live and subject to change.
Vitamin C may be best known for its immune-boosting powers, helping you fight off colds, control infections, and heal wounds, says Jessica Levinson, M.S., R.D.N., C.D.N., culinary nutrition expert. But the nutrient does so much more than that. It also supports collagen and neurotransmitter production, helping your body and your nervous system function properly. And since it’s an antioxidant, it’s thought to protect against certain kinds of cancers and heart disease, according to the National Institutes of Health (NIH).
The problem? “[Vitamin C] is a water-soluble vitamin, which means it isn’t stored well in the body,” Levinson says. “Therefore it’s a nutrient we need to consume (or supplement) enough of on a daily basis.”
And not getting enough can have serious downsides, explains Jessica Zinn, M.S., R.D.N., C.D.N, registered dietitian. “Vitamin C deficiency can lead to scurvy, which causes anemia, bleeding gums, poor wound healing and bruising,” she says. (Scurvy is generally rare in the U.S., but research suggests it may be becoming more common.)
According to the NIH, women should get 75 milligrams of vitamin C per day and men should get 90 milligrams—though some groups, like pregnant women, may need more than others. Thankfully, lots of foods are rich in vitamin C. And here are four major benefits you might enjoy if you start eating more of them, per nutritionists.
Vitamin C Health Benefits
Boosted Immune System
Vitamin C plays a key role in immune function, according to the NIH. It supports your body as it fights off infections. And since it also supports collagen production, it helps your body heal wounds.
Muscle Growth
Vitamin C helps your body absorb nonheme iron—a type of iron found in plant-based foods that’s less bioavailable than the kind found in animal foods, says Jackie Newgent, R.D.N., C.D.N., a plant-forward culinary nutritionist. Iron supports your metabolism, muscles, brain, and more, according to the NIH. So vitamin C is especially great to have in your diet if you’re vegan or vegetarian.
Collagen Production
“Vitamin C is needed to make collagen, a fibrous protein in connective tissue that helps build and maintain skin, joints, and bones,” Levinson explains. Because collagen strengthens your skin, muscles, bones, and tissues, low levels can lead to sore muscles, stiff joints, and saggy skin, according to the Cleveland Clinic. Zinn adds that you also need vitamin C to create blood vessels and muscles, so it helps keep your body in working order.
Longevity
Vitamin C is an antioxidant, and according to the NIH, it’s thought to limit the damaging effects of free radicals—unstable atoms or molecules inside the body that may cause stress or cell damage. “Free radicals are caused by pollution, smoke, and toxic chemicals, which can build up in the body and cause health issues, such as cancer, heart disease, and inflammatory diseases like arthritis,” explains Zinn.
Foods Rich in Vitamin C
While citrus fruits are well-known for their vitamin C content, the nutrient can be found in many different foods. Foods rich in vitamin C include:
If you’re concerned about getting enough vitamin C, you can also consider taking a supplement. But talk to your doctor first—too much vitamin C can cause nausea, diarrhea, and stomach cramps, according to the NIH.
PM, Libyan Commander-in-Chief discuss bilateral cooperation RADIO PAKISTAN
COAS Munir, Libyan armed forces’ chief agree on defence industrial collaboration: ISPR Dawn
Libyan Commander in Chief calls on CNS Admiral Naveed Ashraf Ptv.com.pk
Lieutenant General Saddam Khalifa Haftar, Commander in Chief of Libyan Armed Forces called on Field Marshal Syed Asim Munir, NI (M), Chief of Army Staff at General Headquarters dailyindependent.com.pk
Pakistan and Libya to expand defense industrial collaboration after top military meeting Arab News
Glenn Phillips’ latest injury has ruled him out of New Zealand’s T20I tri-series in Zimbabwe and the two-Test series that follows. The all-rounder suffered a groin strain during the MLC final for Washington Freedom on July 13 and is expected to be sidelined for several weeks, as per reports.
While fans are disappointed by his absence from the field, attention has naturally shifted toward his life off it. From highlight reels to quiet weekends in Dunedin, Phillips shares much of that life with his wife, Kate Victoria—a name now drawing growing curiosity. Between scenic proposal spots and match-day selfies, fans want to know everything about this cricket couple.
From Hooker Valley to happily married
Kate and Glenn started dating in 2021. Just over a year later, he popped the question during a hike at Hooker Valley Track, one of New Zealand’s most breathtaking locations. Kate had shared photos of the moment on her Instagram, in August 2022.
Having been together nearly four years, they officially became husband and wife on February 10, 2025. As of now, they don’t have kids, but their life is packed with travel, time outdoors, and plenty of cricket.
Creative, stylish and always present
Off the grass, Kate is not just the wife in the stands; she’s her own force. According to Zee News, she has worked in event planning and has a clear creative streak. Her feed definitely reflects it: a mix of fashion-forward looks, scenic travel snaps, and hiking trails that inspire her 14K+ followers.
As Phillips gears up to return with sixes and stunning catches, Kate will likely be right by his side during his recovery process. Together, the couple have the means of becoming one of cricket’s most quietly compelling duos—no drama, just support, style, and serious chemistry.
ALSO READ:Is Ishan Kishan dating model Aditi Hundia? Cheering from stands to her cryptic notes, all you need to know about Indian cricketer’s rumored girlfriend
As millions of people know firsthand, the most common side effect of mRNA vaccines like the COVID-19 shot is inflammation: soreness, redness and a day or two of malaise. But what if mRNA vaccines could be redesigned to sidestep that response altogether?
In a new paper in Nature Biomedical Engineering, researchers at the University of Pennsylvania show that tweaking the structure of the ionizable lipid, a key component of the lipid nanoparticles (LNPs) that deliver mRNA, not only reduces inflammation but also boosts vaccine effectiveness for preventing or treating a range of diseases, from COVID-19 to cancer.
The key change? Adding phenol groups, chemical compounds with anti-inflammatory properties famously found in foods like olive oil. “By essentially changing the recipe for these lipids, we were able to make them work better with fewer side effects,” says Michael J. Mitchell, Associate Professor in Bioengineering (BE) and the paper’s senior author. “It’s a win-win.”
Revising the recipe
Until now, the ionizable lipids in LNPs — one of four types of lipids in LNPs, and arguably the most important — have largely been synthesized using chemical reactions that combine two components into a new molecule, much like two halves of a sandwich coming together.
“Because these processes have been so successful, there hasn’t been much effort to look for alternatives,” says Ninqiang Gong, a former postdoctoral fellow in the Mitchell Lab and co-first author of the paper.
Looking back at the history of chemistry, the team found an alternative approach: the Mannich reaction, named after the German chemist who discovered it more than a century ago.
Rather than two components, the Mannich reaction combines three precursors, allowing for a greater variety of molecular outcomes. “We were able to create hundreds of new lipids,” says Gong.
Exploring that “library” of lipids led the team to discover that adding a phenol group — a combination of hydrogen and oxygen connected to a ring of carbon molecules — substantially reduced inflammation.
“It’s kind of like the secret sauce,” says Gong. “The phenol group not only reduces the side effects associated with LNPs, but improves their efficacy.”
The power of phenols
Previous studies have found that phenol-containing compounds reduce inflammation by negating the harmful effects of free radicals, molecules with unpaired electrons that can disrupt the body’s chemistry.
Too many free radicals and too few antioxidants result in “oxidative stress,” which degrades proteins, damages genetic material and can even kill cells.
By checking various markers associated with oxidative stress, the researchers compared the inflammatory effects of LNPs formulated using different lipids.
“The best-performing LNP, which we built using a phenol-containing ionizable lipid produced by the Mannich reaction, actually caused less inflammation,” says Emily Han, a doctoral student in BE and co-author of the paper.
Less inflammation, higher performance
With these encouraging signs of reduced inflammation, the researchers next tested whether the new lipids also improved vaccine performance.
Across multiple experiments, C-a16 LNPs, which incorporated the most anti-inflammatory lipid, outperformed LNPs used in on-the-market mRNA technologies.
“Lowering oxidative stress makes it easier for LNPs to do their job,” says Dongyoon Kim, a postdoctoral fellow in the Mitchell Lab and co-first author of the paper.
C-a16 LNPs not only produced longer-lasting effects, but also improved the efficacy of gene-editing tools like CRISPR and the potency of vaccines for treating cancer.
Fighting genetic disease, cancer and COVID-19
To test how well the new C-a16 lipids worked in an animal model, the researchers first used them to deliver into cells the gene that makes fireflies glow — a classic experiment for checking the strength of genetic instructions.
The glow in mice was about 15 times brighter compared to the LNPs used in Onpattro, an FDA-approved treatment for hereditary transthyretin amyloidosis (hATTR), a rare genetic liver disease.
The C-a16 lipids also helped gene-editing tools like CRISPR do a better job fixing the faulty gene that causes hATTR. In fact, they more than doubled the treatment’s effectiveness in a mouse model compared to current delivery methods.
In cancer treatments, the results were just as striking. In an animal model of melanoma, an mRNA cancer treatment delivered with C-a16 lipids shrank tumors three times more effectively than the same treatment delivered with the LNPs used in the COVID-19 vaccines. The new lipids also gave cancer-fighting T cells a boost, helping them recognize and destroy tumor cells more efficiently — and with less oxidative stress.
Finally, when the team used the C-a16 lipids for preparing COVID-19 mRNA vaccines, the immune response in animal models was five times stronger than with standard formulations.
“By causing less disruption to cellular machinery, the new, phenol-containing lipids can enhance a wide range of LNP applications,” says Kim.
Old chemistry, new frontiers
Besides investigating the immediate potential of the new lipids to reduce side effects in mRNA vaccines, the researchers look forward to exploring how overlooked chemical processes like the Mannich reaction can unlock new LNP-enhancing recipes.
“We tried applying one reaction discovered a century ago, and found it could drastically improve cutting-edge medical treatments,” says Mitchell. “It’s exciting to imagine what else remains to be rediscovered.”
Reference: Gong N, Kim D, Alameh MG, et al. Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity. Nat Biomed Eng. 2025. doi: 10.1038/s41551-025-01422-8
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Kirkland & Ellis is advising Advent on its agreement to invest in Reckitt’s Essential Home portfolio (“Essential Home”), whereby Advent will acquire a 70% stake to facilitate the company’s accelerated growth and innovation over the years to come as a standalone business. The carve-out of Essential Home will create a dedicated global home care platform with an iconic portfolio of leading brands – including Air Wick, Calgon, Woolite, Cillit Bang and SBP.
The transaction values Essential Home at an enterprise value of up to US$4.8 billion (including up to US$1.3 billion of contingent and deferred consideration). As part of the transaction, Reckitt will continue to support Essential Home by retaining a significant minority interest of 30%. The transaction remains subject to customary closing conditions and regulatory approvals.
Read Advent’s press release
The Kirkland team includes corporate lawyers Adrian Maguire, Vincent Bergin, Dan Clarke, Claire Rushton, Charles Hébert, Douglas Collins, Luke Forryan, James Whybrow, Athena Chuang, Yumiko Wong and Martin Floro; carve-out and separation lawyers André Duminy, Joanna Thomson, Jenni Polson, Samantha Bradley, Saif Khan, Lana Khoury, Julia Ostendorf and Nara Yoo; debt finance lawyers Christopher Shield, Leon Daoud, Thomas Raftery, Aman Nath and Aram Valesyan; and tax lawyers Mavnick Nerwal, Jared Rusman, Siv Devakumar, Sam Trowbridge, Rikesh Gandhi, Natasha Haftke, Bryan Leighton, Joe Morley and Alexandria Solomou.
