New research published in Marine Ecology Progress Series points to the importance of mid-sized predators, including the bigscale pomfret, in connecting deep and shallow ocean ecosystems. These fish appear to serve as a crucial link between the surface and the depths. Until recently, scientists lacked detailed information about how bigscale pomfret and similar species move through the ocean, limiting understanding of their ecological role.

To close that gap, researchers turned to satellite-based tracking tags. This technology allowed them to follow the movements of bigscale pomfret over time, something that had been difficult to achieve with deep-sea fish.

Tracking Life in the Twilight Zone

“The data shows bigscale pomfret are permanent residents of the ocean’s twilight zone, and follow the pattern of diel migration. This means they stay deep during the day and come to shallower waters to feed at night,” said Martin Arostegui, lead author of the study and a research associate at WHOI.

Tracking enough of these constantly moving fish posed a challenge. “Since these species spend a majority of their life on the move and in hard-to-reach places, it wouldn’t have been possible for us to tag enough of them during a few days at sea. Thus, we collaborated with a commercial longline fisher, Captain Danny Mears, who did that work as part of our research team.”

Collaboration With Commercial Fishers

Mears and his crew were eager to participate in the project. “Bigscale pomfret are so different from the tunas and swordfish we usually catch that we are fascinated by them whenever they show up in our gear,” Mears said. “My crew and I were excited for the opportunity to help with the satellite tagging for this study. It’s been very rewarding to see the data.”

The study also sheds light on how environmental conditions influence bigscale pomfret behavior. When the fish traveled from the Slope Sea into the clearer waters of the Sargasso Sea, researchers observed noticeable changes in their migration patterns. This suggests that water clarity affects how deep these fish swim, which can alter the prey they hunt and their exposure to predators like large sharks.

Why Mid-Sized Fish Matter More Than We Thought

“We always talk about the mesopelagic layer like it’s this giant buffet for big predators — but we’ve been skipping over the species in the middle,” said WHOI biologist Camrin Braun, the study’s senior author and principal investigator of WHOI’s Marine Predators Group. “These mesopelagic fish are doing the hard work of connecting the deep ocean to the surface food web. If we don’t understand them, we’re basically trying to solve a puzzle with the middle pieces missing.”

Together, the findings highlight how overlooked species in the ocean’s twilight zone play an outsized role in shaping marine food webs and the behavior of some of the ocean’s largest predators.

On the CBS sitcom “The Big Bang Theory,” characters Sheldon Cooper and Leonard Hofstadter wrestled with the same idea across three episodes in Season 5. Despite their efforts, the problem remained unsolved in the show.

Now UC physics professor Jure Zupan and his co authors from the Fermi National Laboratory, MIT and Technion-Israel Institute of Technology report a possible solution. Their findings appear in a new study published in the Journal of High Energy Physics.

Why Axions Matter to Dark Matter Research

Axions are theoretical subatomic particles that scientists believe could help explain dark matter. Dark matter is of intense interest because it plays a major role in shaping the universe after the Big Bang nearly 14 billion years ago.

Although dark matter has never been detected directly, physicists think it makes up most of the matter in the universe. Ordinary matter, including stars, planets and people, accounts for only a small fraction. Dark matter earns its name because it does not absorb or reflect light.

Its presence is inferred through gravity. The unusual motions of galaxies and the stars within them suggest that large amounts of unseen matter are exerting gravitational pull. One leading idea is that dark matter consists of extremely light particles known as axions.

Fusion Reactors as a Source of New Particles

In their study, Zupan and his colleagues examined a fusion reactor design that uses deuterium and tritium fuel inside a lithium lined vessel. This type of reactor is being developed through an international collaboration in southern France.

Such a reactor would generate vast numbers of neutrons along with energy. According to the researchers, those neutrons could also lead to the creation of particles linked to the dark sector.

“Neutrons interact with material in the walls. The resulting nuclear reactions can then create new particles,” he said.

Another possible production route occurs as neutrons collide with other particles and slow down. This process releases energy in a phenomenon known as bremsstrahlung, or “braking radiation.”

Through these mechanisms, the reactor could theoretically produce axions or axion like particles. Zupan noted that this is where the fictional physicists on television came up short.

The Big Bang Theory Easter Egg Explained

“The Big Bang Theory” aired from 2007 to 2019, won seven Emmys and remains one of the most watched shows on streaming platforms, according to Nielsen.

“The general idea from our paper was discussed in ‘The Big Bang Theory’ years ago, but Sheldon and Leonard couldn’t make it work,” Zupan said.

In one episode, a white board displays an equation and diagram that Zupan said represent how axions are produced in the sun. In a later episode, a different equation appears on another board. Under the calculations, drawn in a different marker color, is a clear sad face — a visual sign of failure.

Zupan explained that the equation compares the chances of detecting axions from a fusion reactor with those coming from the sun — and the comparison is not encouraging.

“The sun is a huge object producing a lot of power. The chance of having new particles produced from the sun that would stream to Earth is larger than having them produced in fusion reactors using the same processes as in the Sun. However, one can still produce them in reactors using a different set of processes,” he said.

The show never explicitly mentions axions or explains the white boards. These details serve as inside jokes for scientists, fitting a series known for weaving concepts like Schrodinger’s cat and the Doppler effect into its plots, along with appearances by Nobel Prize winners and “Star Trek” alumni.

“That’s why it’s fantastic to watch as a scientist,” Zupan said. “There are many layers to the jokes.”

In a new study from Ben-Gurion University of the Negev (BGU), researchers examined how diet-induced obesity and later weight loss affected young adult mice compared with mid-aged mice. In both groups, weight loss successfully restored healthy blood glucose control, showing that key metabolic improvements occur regardless of age. However, the scientists also observed an unexpected difference. In mid-aged mice, weight loss led to increased inflammation in the hypothalamus, a part of the brain involved in regulating appetite, energy use, and other essential functions.

Brain Inflammation Raises New Questions

This increase in brain inflammation was detected at the molecular level and through detailed microscopic imaging of microglia (the brain’s immune cells). The inflammatory response lasted for several weeks before gradually declining. While the long-term effects of this response are still unclear and may even play a role in achieving metabolic improvements, the findings raise important concerns. Persistent or poorly regulated inflammation in the brain has been linked to memory problems and neurodegenerative conditions such as Alzheimer’s. As a result, the study highlights new questions about how weight loss during midlife may interact with brain health.

Researchers Urge a More Nuanced View of Midlife Weight Loss

“Our findings show that losing weight in midlife is not a simple copy-and-paste of what works in young adulthood,” said Alon Zemer, an M.D.-Ph.D. candidate and the first author of this paper. “Weight loss remains essential for restoring metabolic health in obesity, but we need to understand the impact of weight loss on the mid-age brain and ensure brain health is not compromised.”

Dr. Alexandra Tsitrina added: “Our study characterizes the body’s adaptive response to weight loss through two complementary dimensions — molecular and structural. This high-end imaging by advanced microscopy and image analysis with advanced computational analysis enable detection of sensitive changes with potential health ramifications.”

Next Steps for Protecting Brain Health

The research team stresses the importance of additional studies to better understand why this temporary but concerning brain inflammation occurs during midlife weight loss. Future work could help scientists develop approaches that maintain the metabolic advantages of weight loss while also protecting brain health as people age.

The study, titled, “Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice” was published in GeroScience and supported by an internal grant at BGU (with the Ilse Katz Institute of Nanoscale Science and Technology), and grants from theUS-Israel Binational Science Foundation (Grant no. 2021083) and the Israel Science Foundation (Grant No. 194/24).

The study, published in The American Journal of Clinical Nutrition, adds clarity to long-standing debates about vitamin D’s links to colorectal cancer and other diseases. These questions have gained attention due to mixed results from major studies, including the VITAL trial. The new findings also reinforce earlier research from 2013 by the same team, which found that people with low magnesium intake often had low vitamin D levels as well.

New Evidence of a Regulating Effect

Beyond confirming earlier observations, the trial uncovered an additional insight. Magnesium did not simply raise vitamin D across the board. Instead, it appeared to act as a regulator, lowering vitamin D levels in participants whose levels were already high. This is the first clinical evidence suggesting magnesium may help optimize vitamin D levels rather than just increase them, which could be important for reducing disease risk linked to vitamin D imbalance.

Qi Dai, MD, PhD, Ingram Professor of Cancer Research and lead author of the study, explained that the healthiest vitamin D range appears to fall in the middle of a U-shaped curve. Previous observational studies have linked this middle range to the lowest risk of cardiovascular disease.

Vitamin D Research Remains Mixed

Despite earlier findings, vitamin D did not show a clear link to cardiovascular disease in the recent VITAL trial. Dai and co-author Martha Shrubsole, PhD, a research professor of Medicine in the Division of Epidemiology, are now examining whether magnesium could help explain these inconsistent results. Their work is part of the ongoing Personalized Prevention of Colorectal Cancer Trial.

“There’s a lot of information being debated about the relationship between vitamin D and colorectal cancer risk that is based upon observational studies versus clinical trials,” Shrubsole said. “The information is mixed thus far.”

Why Magnesium May Matter More Than Expected

The researchers turned their attention to magnesium after noticing that vitamin D supplements do not work equally well for everyone. Some people fail to raise their vitamin D levels even when taking high doses.

“Magnesium deficiency shuts down the vitamin D synthesis and metabolism pathway,” Dai said.

The study included 250 adults considered at higher risk for colorectal cancer, either due to known risk factors or because they had previously had a precancerous polyp removed. Participants received either magnesium supplements or a placebo, with dosages tailored to their usual dietary intake.

Magnesium Deficiency Is Common in the U.S.

Shrubsole noted that vitamin D insufficiency is widely recognized as a public health concern in the United States, and many patients are advised to take supplements based on blood test results.

“Vitamin D insufficiency is something that has been recognized as a potential health problem on a fairly large scale in the U.S.,” Shrubsole said. “A lot of people have received recommendations from their health care providers to take vitamin D supplements to increase their levels based upon their blood tests. In addition to vitamin D, however, magnesium deficiency is an under-recognized issue. Up to 80 percent of people do not consume enough magnesium in a day to meet the recommended dietary allowance (RDA) based on those national estimates.”

Food Sources of Magnesium

Shrubsole emphasized that magnesium intake in the study matched RDA guidelines and suggested that diet is the best way to increase magnesium levels. Foods rich in magnesium include dark leafy greens, beans, whole grains, dark chocolate, fatty fish such as salmon, nuts and avocados.

Additional Vanderbilt co-authors on the study include Xiangzhu Zhu, MD, Hui Nian, PhD, Harvey Murff, MD, MPH, Reid Ness, MD, MPH, Douglas Seidner, MD and Chang Yu, PhD.

That species is the zombie worm, formally known as “the bone devourer” Osedax. Its disappearance may signal deeper trouble ahead, including species loss and weakening ecosystems linked to long-term climate change.

A Decade-Long Deep-Sea Experiment

Fabio De Leo, a senior staff scientist with Ocean Networks Canada (ONC) and an adjunct assistant professor in the University of Victoria’s (UVic) Department of Biology, co-led a long-term experiment off the coast of British Columbia (BC). The study placed humpback whale bones on the deep ocean floor and monitored them for signs of life.

After years of observation, researchers found no trace of zombie worms, despite their well-known role in breaking down whale bones and supporting deep-sea food webs.

How Zombie Worms Feed Without a Digestive System

Osedax worms are unusual creatures. They lack a mouth, anus, and digestive tract, yet they survive by drilling root-like structures into bone. Inside those roots live microbes that extract nutrients, which then nourish the worms.

Because of this unique role, Osedax is considered an ecosystem engineer, helping recycle nutrients and create conditions that allow other species to move in.

Why the Absence Is So Concerning

Over 10 years of high-resolution underwater camera footage from ONC failed to capture any zombie worm colonization. In scientific terms, this kind of outcome is known as a negative result, and it can be just as meaningful as a positive finding.

“This was a remarkable observation in such a long-term experiment,” De Leo says. He adds that the absence may be linked to unusually low oxygen levels at the study site.

Low Oxygen Zones and Whale Falls

The whale bones were placed in Barkley Canyon, nearly a thousand meters below the Pacific Ocean surface. This area lies within a naturally low-oxygen zone and along migration routes used by humpback and grey whales.

When whales die from natural causes or human-related threats such as ship strikes or fishing net entanglements, their bodies sink to the seafloor. These events create “whale falls,” which normally provide a sudden surge of food that supports rich biodiversity. The lack of zombie worms at Barkley Canyon suggests that expanding oxygen minimum zones (OMZs) in the northeast Pacific and beyond may be disrupting these ecosystems.

Early data from ongoing whale fall research near another ONC NEPTUNE site points to similar concerns elsewhere.

Why Bone Devourers Matter

If the “bone devourer” is missing, the chain reaction can affect many other species. Without Osedax to break down bones and kick-start the ecological succession process, fewer organisms may be able to access nutrients stored in whale remains.

Whale falls are “almost like islands,” De Leo explains, calling them “a stepping-stone habitat for this and many other whale bone specialist species.”

The Risk of Species Loss

“Basically, we’re talking about potential species loss,” De Leo says. Adult Osedax typically live on whale bones, while their larvae travel long distances through ocean currents to colonize new whale falls, sometimes hundreds of kilometers away.

If those habitats disappear or stop functioning properly, connectivity between whale fall sites breaks down. Over time, this could lead to declining diversity of Osedax species across entire regions.

Other Deep-Sea Engineers Also Affected

The research team also found signs that another ecosystem engineer may be under stress. Wood-boring Xylophaga bivalves were present on submerged wood samples at Barkley Canyon, but their colonization rates were far lower than in oxygen-rich waters.

Slower colonization could delay carbon decomposition and reduce habitat formation for the many species that typically live inside Xylophaga burrows.

“It looks like the OMZ expansion, which is a consequence of ocean warming, will be bad news for these amazing whale-fall and wood-fall ecosystems along the northeast Pacific Margin,” said Craig Smith, professor emeritus from University of Hawaii, who co-led the experiment.

How Scientists Collected the Data

De Leo and Smith relied on ONC’s NEPTUNE observatory Barkley Canyon Mid-East video camera platform, along with oceanographic sensors and high-definition video collected by remotely operated vehicles.

Additional findings are expected in the coming months from a whale fall currently being monitored at NEPTUNE’s Clayoquot Slope site.

The research was supported by the Canada Foundation for Innovation Major Science Initiative Fund and partly by a US National Science Foundation grant. It also aligns with United Nations Sustainable Development Goal 14, life below water.

Mapping Hidden Heat Beneath Greenland

The project was carried out at the University of Ottawa in partnership with researchers from the University of Twente in the Netherlands and the Geological Survey of Denmark and Greenland (GEUS). To build their models, the team combined satellite observations with data collected on the ground. They then ran hundreds of thousands of computer simulations using high-performance systems, including resources from the Digital Research Alliance of Canada.

The results reveal that heat deep inside the Earth is not evenly distributed beneath Greenland. According to the study’s lead author, these variations are closely tied to Greenland’s geological journey across a powerful volcanic region in the past.

“Our new regional temperature models reveal significant lateral variations in the Earth’s thermal structure beneath Greenland, which provide important information on the island’s passage over the Iceland hotspot,” explains uOttawa’s PhD graduate Parviz Ajourlou, the study’s first author. “These variations help us better interpret Greenland’s tectonic history and the influence of this history on the geophysical properties of the underlying rocks.”

Why Underground Heat Matters for Ice and Land

The temperature of the rocks beneath the ice plays a major role in how the ice sheet behaves today. Warmer conditions at the base can affect how ice slides, how the ground beneath it moves, and how scientists interpret satellite measurements of Earth’s surface.

Glenn Milne, Chair and Full Professor within the Department of Earth and Environmental Sciences at uOttawa and the study’s principal investigator, highlighted the broader importance of these findings.

“This research advances our understanding of the Earth’s internal structure beneath Greenland. Temperature variations directly influence the interaction between the ice sheet and the bedrock, which must be quantified to interpret observations of land motion and gravity changes. These observations tell us how the ice sheet is responding to recent climate warming.”

Improving Predictions of Future Sea Level Rise

To create their 3D temperature model, the researchers analyzed a wide range of geophysical data, including seismic velocities, gravity anomalies, and heat flow. This comprehensive approach not only provides new insight into Greenland’s geological past but also strengthens scientists’ ability to model how the ice sheet may change in the future.

By better accounting for how heat inside the Earth interacts with ice above it, researchers can improve simulations of ice loss and refine estimates of Greenland’s contribution to global sea level rise.

“This work is a good illustration of how our knowledge of the solid Earth enhances our ability to understand the climate system,” says Ajourlou. “By improving how we model ice-earth interactions, we can better forecast future sea level rise and plan accordingly.”

At CERN’s Large Hadron Collider (LHC), proton collisions generate temperatures more than 100,000 times hotter than the Sun’s core. For years, researchers did not understand how delicate particles like deuterons and antideuterons could exist in such intense heat. A deuteron contains just one proton and one neutron, held together by a relatively weak force. Under these conditions, such a light atomic nucleus should break apart almost instantly. Even so, experiments kept detecting them. Researchers have now shown that roughly 90 percent of the observed (anti)deuterons form through this newly identified process, rather than surviving the initial blast.

New Insight Into the Strong Interaction

TUM particle physicist Prof. Laura Fabbietti, a member of the ORIGINS Cluster of Excellence and SFB1258, highlights the importance of the discovery. “Our result is an important step toward a better understanding of the ‘strong interaction’ — that fundamental force that binds protons and neutrons together in the atomic nucleus. The measurements clearly show: light nuclei do not form in the hot initial stage of the collision, but later, when the conditions have become somewhat cooler and calmer.”

Dr. Maximilian Mahlein, a researcher at Fabbietti’s Chair for Dense and Strange Hadronic Matter at the TUM School of Natural Sciences, adds that the findings have broader implications. “Our discovery is significant not only for fundamental nuclear physics research. Light atomic nuclei also form in the cosmos — for example in interactions of cosmic rays. They could even provide clues about the still-mysterious dark matter. With our new findings, models of how these particles are formed can be improved and cosmic data interpreted more reliably.”

CERN and the Large Hadron Collider

CERN (Conseil Européen pour la Recherche Nucléaire) is the world’s largest center for particle physics research. Located near Geneva on the border between Switzerland and France, it is home to the LHC, a 27-kilometer-long underground ring accelerator. Inside the LHC, protons are smashed together at nearly the speed of light. These collisions recreate conditions similar to those shortly after the Big Bang, reaching temperatures and energies not found anywhere else today. This allows scientists to study matter at its most basic level and test the fundamental laws of nature.

ALICE and the Birth of Matter

One of the LHC’s key experiments is ALICE (A Large Ion Collider Experiment), which focuses on understanding the strong interaction that holds atomic nuclei together. ALICE functions like an enormous camera, able to track and reconstruct up to 2000 particles produced in a single collision. By doing so, researchers aim to recreate the universe’s earliest moments and learn how a hot mixture of quarks and gluons eventually formed stable atomic nuclei and, ultimately, all matter.

Exploring Cosmic Origins and Fundamental Forces

The ORIGINS Cluster of Excellence studies how the universe and its structures came into being, from galaxies and stars to planets and the basic components of life. Its research follows the path from the smallest particles in the early universe to the development of biological systems. This includes searching for environments that could support life beyond Earth and gaining deeper insight into dark matter. In May 2025, a second funding phase for ORIGINS, proposed by TUM and Ludwig-Maximilians-Universität München (LMU), was approved under Germany’s Excellence Strategy.

The Collaborative Research Center “Neutrinos and Dark Matter in Astro- and Particle Physics” (SFB 1258) concentrates on fundamental physics questions, with particular attention to the weak interaction, one of the four fundamental forces of nature. The third funding period of the SFB1258 began in January 2025.

By combining modern laboratory techniques with previously published data from vaccinated individuals, the team uncovered a two-stage immune response. In this process, the vaccine activates one type of immune cell, which then stimulates another. Together, these immune reactions drive inflammation that can damage heart muscle cells and set off additional inflammatory effects.

Vaccines Remain Highly Safe and Effective

The findings come despite the fact that mRNA COVID-19 vaccines have been given billions of times worldwide and continue to show an excellent safety record, said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute.

“The mRNA vaccines have done a tremendous job mitigating the COVID pandemic,” said Wu, the Simon H. Stertzer, MD, Professor and a professor of medicine and of radiology. “Without these vaccines, more people would have gotten sick, more people would have had severe effects and more people would have died.”

mRNA vaccines are considered a major advance because they can be developed quickly, adjusted as viruses change, and tailored to target very different pathogens. Still, as with any medical intervention, reactions are not identical for everyone.

Understanding Vaccine-Associated Myocarditis

One uncommon but documented side effect of mRNA COVID-19 vaccines is myocarditis, which refers to inflammation of the heart muscle. Symptoms can include chest pain, shortness of breath, fever and heart palpitations. These symptoms occur without a viral infection and typically appear within one to three days after vaccination.

Most affected individuals show elevated levels of cardiac troponin in their blood, a widely used marker of heart muscle injury. (Cardiac troponin is normally found exclusively in the heart muscle. When found circulating in blood, it indicates damage to heart muscle cells.)

The condition occurs in roughly one out of every 140,000 people after a first vaccine dose and increases to about one in 32,000 after a second dose. Rates are highest among males age 30 and younger, where it affects about one in 16,750 vaccine recipients.

Outcomes Are Usually Mild and Temporary

Wu emphasized that the majority of myocarditis cases linked to vaccination resolve quickly, with heart function either fully preserved or restored.

“It’s not a heart attack in the traditional sense,” he said. “There’s no blockage of blood vessels as found in most common heart attacks. When symptoms are mild and the inflammation hasn’t caused structural damage to the heart, we just observe these patients to make sure they recover.”

In rare instances, however, severe inflammation can cause serious injury, leading to hospitalization, intensive care treatment or death.

“But COVID’s worse,” Wu said. He noted that a COVID-19 infection is about 10 times more likely to cause myocarditis than an mRNA-based COVID-19 vaccine, in addition to the many other risks posed by the disease.

A Closer Look at the Immune Response

Wu is a senior author of the study, publisded Dec. 10 in Science Translational Medicine, along with Masataka Nishiga, MD, PhD, a former Stanford postdoctoral scholar now at The Ohio State University. The study’s lead author is Xu Cao, PhD, also a postdoctoral scholar at Stanford.

“Medical scientists are quite aware that COVID itself can cause myocarditis,” Wu said. “To a lesser extent, so can the mRNA vaccines. The question is, why?”

Suspects Identified

To answer that question, the team analyzed blood samples from vaccinated individuals, including some who developed myocarditis. When they compared these samples with those from people who did not develop heart inflammation, two proteins stood out.

“Two proteins, named CXCL10 and IFN-gamma, popped up. We think these two are the major drivers of myocarditis,” Wu said.

Both CXCL10 and IFN-gamma are cytokines, signaling molecules that immune cells use to communicate and coordinate their activity.

How Immune Cells Interact After Vaccination

The researchers grew human immune cells called macrophages in laboratory dishes and exposed them to mRNA vaccines. Macrophages act as early responders in immune defense.

After exposure, the macrophages released multiple cytokines, with especially high levels of CXCL10. Their behavior closely matched immune responses previously documented in vaccinated people.

When T cells were added to the system, either directly or by exposing them to fluid from the macrophage cultures, the T cells began producing large amounts of IFN-gamma. In contrast, T cells exposed to the vaccine alone did not show this spike. These findings showed that macrophages primarily produce CXCL10, while T cells are the main source of IFN-gamma following vaccination.

How the Cytokines Affect the Heart

To determine whether these cytokines directly harm the heart, the team vaccinated young male mice and observed increased cardiac troponin levels, indicating heart muscle injury.

They also found that immune cells, including macrophages and neutrophils, had entered heart tissue. Neutrophils are short-lived immune cells that respond aggressively to threats and are a major component of pus. Similar immune cell infiltration is seen in people who develop myocarditis after vaccination.

Blocking CXCL10 and IFN-gamma reduced the number of these immune cells entering the heart and limited damage to healthy tissue.

The researchers also detected increased levels of adhesion molecules in heart blood vessels. These molecules help immune cells latch onto vessel walls, making it easier for them to move into heart tissue.

Together, these findings confirmed that CXCL10 and IFN-gamma directly contribute to heart injury. Blocking them preserved much of the immune response to vaccination while lowering signs of heart damage.

Testing Human Heart Tissue Models

Wu’s lab specializes in converting human skin or blood cells into stem-like cells that can become heart muscle cells, immune cells and blood vessel cells. These cells can be assembled into small, beating clusters that mimic aspects of heart function.

When these cardiac spheroids were exposed to CXCL10 and IFN-gamma collected from vaccinated immune cells, markers of heart stress rose sharply. Using inhibitors to block the cytokines reduced this damage.

Measures of heart function, including contraction strength and beating rhythm, were impaired by the cytokines but improved once the signaling was blocked.

Saved by a Soybean

Wu suspected that a widely available dietary compound might help protect the heart. Since myocarditis is more common in males and estrogen has anti-inflammatory effects, he revisited genistein, a soy-derived compound his team had studied previously.

In a 2022 study published in Cell, the researchers showed that genistein has anti-inflammatory properties and can counter marijuana-related damage to blood vessels and heart tissue.

“Genistein is only weakly absorbed when taken orally,” Wu said. “Nobody ever overdosed on tofu.”

Testing Genistein’s Protective Effects

The team repeated their experiments while pre-treating cells, cardiac spheroids and mice (the latter by oral administration of large quantities) with genistein. This treatment reduced much of the heart damage caused by either mRNA vaccination or the CXCL10 and IFN-gamma combination.

The form of genistein used in the study was more purified and concentrated than supplements commonly sold in stores.

“It’s reasonable to believe that the mRNA-vaccine-induced inflammatory response may extend to other organs,” Wu said. “We and others have seen some evidence of this in lung, liver and kidney. It’s possible that genistein may also reverse these changes.”

Broader Implications Beyond COVID Vaccines

Heightened cytokine signaling may be a broader feature of mRNA vaccines. IFN-gamma, in particular, plays a critical role in defending the body against foreign DNA and RNA, including viral genetic material.

“Your body needs these cytokines to ward off viruses. It’s essential to immune response but can become toxic in large amounts,” Wu said. Excessive IFN-gamma can lead to myocarditis-like symptoms and breakdown of heart muscle proteins.

This risk is not limited to COVID vaccines alone.

“Other vaccines can cause myocarditis and inflammatory problems, but the symptoms tend to be more diffuse,” Wu said. “Plus, mRNA-based COVID-19 vaccines’ risks have received intense public scrutiny and media coverage. If you get chest pains from a COVID vaccine you go to the hospital to get checked out, and if the serum troponin is positive, then you get diagnosed with myocarditis. If you get achy muscles or joints from a flu vaccine, you just blow it off.”

Funding and Support

The study was supported by the National Institutes of Health (grants R01 HL113006, R01 HL141371, R01 HL141851, R01 HL163680 and R01 HL176822) and the Gootter-Jensen Foundation.

Mitraphylline is part of a small and unusual family of plant chemicals known as spirooxindole alkaloids. These molecules are defined by their distinctive twisted ring shapes, which help give them powerful biological effects, including anti tumor and anti inflammatory activity.

For years, scientists knew these compounds were valuable but had little understanding of how plants actually assembled them at the molecular level.

Solving a Long Standing Biological Mystery

Progress came in 2023, when a research team led by Dr. Thu-Thuy Dang in UBC Okanagan’s Irving K. Barber Faculty of Science identified the first known plant enzyme capable of creating the signature spiro shape found in these molecules.

Building on that discovery, doctoral student Tuan-Anh Nguyen led new work to pinpoint two key enzymes involved in making mitraphylline — one enzyme that arranges the molecule into the correct three dimensional structure, and another that twists it into its final form.

“This is similar to finding the missing links in an assembly line,” says Dr. Dang, UBC Okanagan Principal’s Research Chair in Natural Products Biotechnology. “It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process.”

Why Mitraphylline Is So Hard to Obtain

Many promising natural compounds exist only in extremely small quantities within plants, making them expensive or impractical to produce using traditional laboratory methods. Mitraphylline is a prime example. It appears only in trace amounts in tropical trees such as Mitragyna (kratom) and Uncaria (cat’s claw), both of which belong to the coffee plant family.

By identifying the enzymes that construct and shape mitraphylline, scientists now have a clear guide for recreating this process in more sustainable and scalable ways.

Toward Greener Drug Production

“With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value,” says Nguyen. “This is a result of UBC Okanagan’s research environment, where students and faculty work closely to solve problems with global reach.”

Nguyen also emphasized the personal impact of the work. “Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing,” he says. “UBC Okanagan’s mentorship and support made this possible, and I’m excited to keep growing as a researcher here in Canada.”

Global Collaboration and Future Directions

The project was a collaborative effort between Dr. Dang’s laboratory at UBC Okanagan and Dr. Satya Nadakuduti’s team at the University of Florida.

Funding came from several sources, including Canada’s Natural Sciences and Engineering Research Council’s Alliance International Collaboration program, the Canada Foundation for Innovation, and the Michael Smith Health Research BC Scholar Program. Additional support was provided by the United States Department of Agriculture’s National Institute of Food and Agriculture.

“We are proud of this discovery coming from UBC Okanagan. Plants are fantastic natural chemists,” Dr. Dang says. “Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds.”