Human T cell leukemia virus type 1, the first human retrovirus ever identified, infects an estimated 5 to 10 million people worldwide, a figure extrapolated from surveys covering only about one-seventh of the global population. The virus inserts a DNA copy of its RNA genome into the chromosomes of host T cells, establishing a lifelong infection that can drive a spectrum of diseases, including adult T cell leukemia/lymphoma, HTLV-1-associated myelopathy, and HTLV-1-associated uveitis, a chronic inflammation inside the eye that is particularly common in endemic regions such as Japan. Despite the scale of the problem, coordinated global action has been slow; the World Health Organization only published technical reports aimed at reducing HTLV-1-related morbidity and mortality in 2021, and no broadly effective intervention has emerged in decades of research.

Current treatment for the ocular disease relies heavily on corticosteroids, delivered as topical drops, injections into the eye, or oral prednisone. This approach has serious shortcomings. Studies indicate that 30 to 60 percent of patients with HTLV-1-associated uveitis experience recurrent episodes, and long-term steroid exposure can trigger cataracts, glaucoma, macular edema, epiretinal membranes, retinal degeneration, optic nerve atrophy, and bullous keratopathy. Most importantly, corticosteroids suppress inflammation without reducing the number of virus-infected cells or halting disease progression. Newer molecular targeted agents, including the anti-CCR4 antibody mogamulizumab and the immunomodulatory drug lenalidomide, have been explored, but treatment-related inflammation and adverse effects remain significant obstacles. This therapeutic gap motivated a team led by Yaru Zou and Koju Kamoi of Tokyo Medical and Dental University to investigate whether an epigenetic drug already approved for blood cancer could address the root of the ocular inflammation.

The drug in question is valemetostat, marketed as EZHARMIA, a dual inhibitor of the enzymes EZH1 and EZH2 that was approved in 2022 for adult T cell leukemia/lymphoma. Both enzymes are the catalytic components of polycomb repressive complex 2, a molecular machine that silences genes by adding three methyl groups to lysine 27 on histone H3, producing the repressive chromatin mark known as H3K27me3. Previous work had shown that EZH1 and EZH2 are overexpressed, and H3K27me3 deposition increased, in ATL cells and in cells expressing the viral oncoprotein Tax. Dual EZH1/2 inhibitors have also been reported to curb the spontaneous proliferation and exaggerated immune responses of HTLV-1-infected cells in patients with HTLV-1-associated myelopathy. What remained unknown was whether such inhibition could benefit the inflamed eye.

To find out, the researchers built a series of laboratory models centered on ARPE-19 cells, a human retinal pigment epithelial cell line chosen because the retinal pigment epithelium forms the outer blood-retinal barrier and governs retinal immune homeostasis. They exposed these ocular cells to three kinds of T cells: MT-2 cells, which carry transcriptionally active HTLV-1 and express the viral protein Tax; TL-Om1 cells, an ATL-derived line in which the virus is largely silent and Tax is low or absent; and Jurkat cells, which are uninfected and served as controls. In parallel, they treated the T cell lines themselves. Western blotting and quantitative PCR revealed that HTLV-1 infection drove significant upregulation of both EZH1 and EZH2, along with elevated H3K27me3, in infected retinal pigment epithelial cells and in MT-2 cells, with EZH1 protein rising roughly 2.5-fold in infected ocular cells and six-fold in MT-2 cells. This was the first demonstration that HTLV-1 infection induces polycomb-mediated epigenetic changes in retinal cells.

The team then treated the models with valemetostat at 0.01, 0.1, and 1 micromolar for 96 hours, concentrations selected in preliminary experiments because they harmed infected T cells while leaving normal ocular cells, including primary human trabecular meshwork cells, unaffected below 10 micromolar. The results were strikingly dependent on the model. In co-cultures of retinal cells with Tax-positive MT-2 cells, and in retinal cells directly infected with HTLV-1, the drug produced modest but statistically significant reductions in cell viability at the highest dose, accompanied by small increases in late-stage apoptosis. No such effects appeared in co-cultures with TL-Om1 or Jurkat cells. Crucially, the absolute magnitude of apoptosis remained limited, typically only 1 to 3 percent above baseline, indicating that valemetostat is not broadly toxic to retinal cells, an important safety consideration given their role in maintaining vision.

The virological findings were equally nuanced. Valemetostat did not significantly reduce the HTLV-1 proviral load in co-culture systems or in directly infected retinal pigment epithelial cells. However, in MT-2 cells themselves, 1 micromolar valemetostat significantly lowered proviral load and suppressed the messenger RNA levels of both Tax and HBZ, the two hallmark transcripts of the virus. Because MT-2 cells represent the transcriptionally active, highly infectious state of HTLV-1, while TL-Om1 represents latency, the results suggest that the drug’s antiviral effect is gated by the transcriptional status of the infected cell. Within the four-day treatment window, the authors conclude, valemetostat’s benefit to the ocular environment is likely indirect, acting primarily by quieting the most virally active cells rather than by eradicating provirus everywhere.

The most clinically relevant effects emerged in the inflammatory readouts. HTLV-1-infected T cells recovered from the eyes of patients with uveitis are known to secrete copious interleukin-6, interleukin-8, and interleukin-10, all implicated in disease. In the new study, valemetostat produced a dose-dependent increase in the anti-inflammatory cytokine IL-10 in MT-2-containing conditions, significant at 1 micromolar in the co-culture system and across all doses in MT-2 cells. This fits a mechanistic expectation: blocking EZH1/2 removes H3K27me3 marks that repress the IL-10 gene, and prior genetic studies showed that loss of EZH2 directly activates IL-10 transcription in several CD4-positive T cell subsets. Meanwhile, pro-inflammatory signals fell in a context-dependent pattern. IL-12p70 and the chemokine CXCL-10 dropped in co-cultures, IL-6 and IL-8 declined mainly in MT-2 cells, and CCL-2 fell at low doses in the MT-2 co-culture, whereas the chemokine CCL-5 was unchanged in every model.

The drug’s influence on NF-kappaB, the central inflammatory pathway that Tax hijacks to drive both viral replication and cytokine production, was more subdued. Valemetostat modestly reduced NF-kappaB p65 phosphorylation in the MT-2 co-culture at the lowest dose and slightly decreased the nuclear-to-cytoplasmic ratio of p65 in retinal cells stimulated with TNF-alpha, but it did not abolish nuclear translocation. The authors attribute this to the overwhelming strength of Tax-driven NF-kappaB activation, which a 96-hour course of EZH1/2 inhibition may be insufficient to counteract, and to the fact that NF-kappaB and cytokine networks are regulated by many factors beyond polycomb complexes. Immunofluorescence confirmed that valemetostat significantly lowered H3K27me3 in retinal cells exposed to MT-2 cells or directly infected, but not in cells co-cultured with TL-Om1 or Jurkat cells, again underscoring the model dependence of the epigenetic response.

The study also carries a cautionary note about IL-10. Although the cytokine is anti-inflammatory, it can promote the survival of HTLV-1-infected T cells and facilitate immune evasion by impairing dendritic cell antigen presentation and downregulating MHC class I molecules, and patients with aggressive ATL often show abnormally elevated IL-10. The authors therefore suggest that combining EZH1/2 inhibition with IL-10 pathway blockade could prove more effective, noting evidence that IL-10 neutralization sensitizes ATL cells to standard therapies. In the TL-Om1 model of ATL-related ocular infiltration, valemetostat failed to reduce H3K27me3, proviral load, or NF-kappaB activation within the malignant cells, yet it suppressed TL-Om1-induced CXCL10 secretion and induced dose-dependent apoptosis, pointing to a benefit mediated through the inflammatory microenvironment rather than direct tumor killing.

The authors are candid about the limitations. The work relied entirely on in vitro co-cultures and established cell lines, which cannot reproduce the blood-retinal barrier, retinal architecture, or local immune regulation of a living eye, and the intraocular pharmacokinetics of valemetostat after systemic administration remain undefined. Sex as a biological variable could not be assessed because donor-defined primary cells were not used. Even so, the findings establish a proof of concept that an approved epigenetic therapy can counteract HTLV-1-induced chromatin changes in retinal cells, dampen viral transcription in the most active infected cells, and reshape the cytokine milieu that sustains uveitis. Longer treatment studies, in vivo models, and patient-derived systems will be needed to determine whether these modest, context-dependent effects can be translated into a genuine steroid-sparing therapy for one of the most burdensome manifestations of a virus that medicine has long neglected.

Subject of Research: EZH1/2-targeted epigenetic therapy with valemetostat for HTLV-1-associated uveitis

Article Title: Dual impact of EZH1/2-targeted therapy in HTLV-1-associated inflammation: Direct and indirect mechanisms

Article References: Zou, Y., Kamoi, K., Yang, M., Zong, Y., Zhang, J., & Ohno-Matsui, K. (2026). Dual impact of EZH1/2-targeted therapy in HTLV-1-associated inflammation: Direct and indirect mechanisms. iScience, 29(11), Article 117775. https://doi.org/10.1016/j.isci.2026.117775

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117775

Keywords: HTLV-1, valemetostat, EZH1, EZH2, H3K27me3, uveitis, epigenetics, PRC2, Tax, IL-10, NF-kappaB, retinal pigment epithelium

A million-person study points to repeated heat injury in the oesophagus.

Despite major strides in education and conservation efforts, rabies remains a serious public health issue. The Center for Disease Control (CDC) estimates around 90 percent of cases occur in wildlife, but their consequences still reverberate across ecosystems and routinely endanger humans. Combating the viral disease costs the United States over $300 million every year, but the hefty price tag is justified. Contracting one of the oldest known diseases invariably causes severe symptoms like abnormal sensations, violent movements, hydrophobia, and loss of consciousness. Rabies is fatal in virtually every documented case, and still kills around 59,000 people around the world each year.

Once primarily associated with dogs, rabies has since spread to wildlife such as raccoons, skunks, bats, and foxes—making the issue much more difficult to track and control. Since 1995, the United States Department of Agriculture (USDA) has overseen a National Rabies Management Program in cooperation with state and federal departments, university researchers, and other organizations. After over 30 years of work, one of the most preferred mitigation methods is regularly placing oral rabies vaccine (ORV) bait in strategically selected wildlife areas. The easiest way to spread millions of bait blocks across thousands of square miles? Airdrops.

Next month, the USDA will once again begin tossing fishmeal-coated ORV packets from planes throughout the Southeastern states of Virginia, North Carolina, Tennessee, Georgia, and Alabama. These tiny edibles are specifically crafted to target the most prominent rabies variants seen in raccoons, coyotes, and gray foxes.

“The goal is to prevent westward spread of raccoon rabies by creating a continuous vaccine barrier that stays in front of rabies occurrence on the landscape,” a USDA spokesperson recently told FOX Carolina News. The representative added that although the distribution’s scope doesn’t currently include South Carolina, they are “very close to establishing an ORV area in South Carolina counties bordering North Carolina and Georgia in the next few years.”

If all goes as planned, the National Rabies Management Program’s geographic scope will shrink over time as the disease is regionally eliminated. Until then, anyone who accidentally comes into contact with an ORV bait brick shouldn’t worry about contracting the disease. The vaccine inside each brick is proven safe for over 60 animal species, including cats and dogs. If you happen to locate one in a residential area, the USDA recommends to either simply leave it alone, or use gloves to move it to a more remote location for its intended recipients. Always wash your hands thoroughly after handling ORV bait—and try to ignore the pungent odor of fishmeal.

The post It’s almost time to airdrop rabies vaccines again appeared first on Popular Science.

A new virus emerges in rural China. Although those who contract it initially display moderate, flu-like symptoms, their health quickly declines. The mortality rate is unclear, but one aspect is immediately obvious—it’s very contagious. Within three months, nations around the world are planning lockdown protocols and quarantine measures. Politicians seem completely out of their league and ill-equipped. 

The world eventually recovers from the ordeal, but consequences of the virus linger for decades.While society pushes forward, there’s no promise that an even deadlier virus isn’t already lurking out of sight.

This isn’t about COVID-19, by the way. It’s the plot to the novel World War Z—arguably the most realistic depiction of a zombie apocalypse ever created. Released 20 years ago this week, the horror novel by Max Brooks quickly became one of the undisputed cornerstones of walking dead canon. Readers and critics devoured the book (no pun intended), but their responses often worry Brooks. Much like the reception to his first book, The Zombie Survival Guide, many fans seem to misunderstand his intentions. These projects weren’t simply intended to entertain. Max Brooks was trying to warn everyone about the looming threats we would prefer to ignore.

While the 54-year-old writer ostensibly writes books about zombies, Sasquatch, and (soon) an alien invasion, his attention to disaster details and hyperrealism has earned him a parallel career as a security and threat analyst for some of the world’s most respected geopolitical think tanks.

To celebrate World War Z’s 20th anniversary, Popular Science recently spoke with Brooks about the book’s massive impact.

This interview has been edited for length and clarity.

Andrew Paul: Did you anticipate World War Z attaining the legacy it now has in popular culture?

Max Brooks: Oh, God no. Of course not. Especially because I’m never tapped into pop culture. I don’t know what anybody else is doing—even when it was my job writing for Saturday Night Live! I’m good at thinking about what I think about.

AP: Before World War Z, you wrote an actual preparedness handbook called The Zombie Survival Guide. What prompted you to take a hyperreal approach to such a seemingly outlandish subject?

MB: The reason I wrote [them] was because all the zombie stories, even to this day, tend to focus around small groups. To me, it’s like trying to understand World War II from watching Saving Private Ryan. I had big picture questions nobody was answering.

I think the best zombie movie ever made was Dawn of the Dead. To me, the most interesting part was when they’re holed up in the mall watching the news. That window into the wider world was so fascinating, and I wanted more.

AP: But there was a time when World War Z almost never happened, right?

MB: [The publisher] didn’t know what to do with The Zombie Survival Guide. Their marketing strategy almost killed my career before it even launched. They thought, “Well, no one is clearly that much of a loser that he’s actually spent this much time thinking about [zombies]. Clearly, he’s a cool guy making fun of those losers. And because he’s Mel Brooks’ son and he’s coming off SNL, we’re gonna position him as Mel Brooks, Jr. writing Younger Frankenstein.”

But The Zombie Survival Guide really is a disaster preparedness manual. It’s why [soldiers] took it to Afghanistan; people told me it saved their lives when they were lost in the woods. I didn’t make anything up. It’s not Hollywood stuff—it’s all about dehydration and dry socks and shelter.

But [these books were] legitimately the product of years of thinking, “If I was in a zombie world, how would I survive?” It really set me on this path of asking, “What happens when the grown-ups drop the ball?”

AP: And now it’s your job to worry professionally.

MB: I’ve now been part of three military and national security think tanks—the Atlantic Council, the Center for Strategic and International Studies, and the Modern War Institute at West Point. I’m a non-resident senior fellow at all three of them, and it’s my job to study real threats.

For some reason, I was not blessed with the wall of denial. Like, I can’t just say, “That would never happen and I’m just going to go about my merry way.” I’m already terrified! And the way to reduce my anxiety is to study the threat so that it’s not nebulous.

AP: What was the most difficult part in preparing to write World War Z?

MB: You don’t know what you don’t know, so you don’t know what you’re missing. There’s always a fear of groping around in the dark; of not even knowing who to talk to. That was a real struggle, because I’m an insular guy. I’m not a social guy. Part of it was talking to experts, but part of it was reading books—and I’m fully dyslexic. So that was a real slog.

It was also about never trusting the internet. I used it once or twice, like, to research laser weaponry. I literally went to a company’s website, saw their demonstration video, and was like, “Yeah, okay. That is not a practical weapon for hunting zombies. I see how long it takes to burn through something.”

AP: Obviously humanity’s most terrifying challenge in the last 20 years was the COVID-19 pandemic. How do you view that real-world horror in the context of World War Z? 

MB: COVID was scary because I knew it was coming thanks to my friends in the military and biodefense community. I was part of what was called the Blue Ribbon Biodefense Panel for germ attacks way before COVID. So I already had at my fingertips the ability to tell the difference between panic porn in the media and the real deal. I also had to study diseases enough to write about a zombie plague. But also, it came from being on the receiving end of a bioterror attack. When I worked at SNL [from 2001 to 2003], we had the anthrax letters delivered to our building [in October 2001].

So, I knew this was coming, but the question was how to warn people. I had people laughing at me. Ironically, the people who are the worst minds to reach are the smarty-smarts because they think they know everything.

AP: Were you expecting COVID to be much worse than it was?

MB: Oh, much worse. It got me into trouble, because I was prepping for, like, tanks on the street, you know? I was ready for that. I stocked my home with food that would last the longest as opposed to food that my wife would actually eat. 

But the irony is, had it been worse, we might have actually done better. Studying diseases over the years—it’s sort of like the slow zombie versus the fast zombie. The fast zombie is so scary you have to react. The slow zombie gives you the false sense of security. Like, “Oh, I can take ‘em out.” COVID was the slow zombie. It allowed us to be arrogant and dismiss it: “Oh, it’s no worse than the flu.”

AP: How did you see that play out during the quarantine?

MB: It goes back to when COVID hit New York City. I had written a book called The Harlem Hellfighters, which was a true story of African American soldiers in World War I. They’re still an active unit in the National Guard, and I’m friends with their chief medical officer. Their job was to pick up the dead bodies around New York.

He said to me, “If those bodies had been stacked up on the street for everyone to see them, there would have been no argument about masking or distancing or taking the vaccine.” The hiding of it is what allowed naysayers to get way more people killed.

AP: Where did the grown-ups “drop the ball,” as you say?

MB: I think the greatest failure on the part of leadership at every level was not publicizing the dead. Maybe they were afraid of angry letters and backlash and didn’t want to cause a panic, but that’s exactly what they should have done.

A doctor in Los Angeles told me they converted hospital rooms into morgues. He said, “You don’t believe the amount of bodies. We’ve got pyramids of body bags.” And I’m like, “Well, then why is this not on the news every night?”

AP: After experiencing an actual global plague, how do you feel about World War Z’s overall accuracy?

MB: I think it was accurate for the time. I would still have the plague coming from China, 100 percent. I would love to say that was my genius futuristic prediction, but no. I based it on SARS. And this is why it’s unforgivable that it happened again. If I wrote it today, I would really highlight why it was allowed to be [downplayed]—and the reason is our greed. All of our stuff is made in China.

I would also really change the politicization of information. We’re living in a time where all facts have become tribalized. We’ve had 20 years of such dumbing down that I think it would be a central tenant of the book.

AP: Would you change how the United States responded to a zombie outbreak?

MB: I still firmly believe we are a moderate country, but I don’t know how brave we are. In order for a crime to be committed, you don’t need 100 bullies. You just need one bully and 99 cowards.

The psycho fanatics have a microphone now, which was inconceivable 20 years ago. They are hate merchants, and the erosion of our education system has created a demand that the merchants supply.

AP: So you think we would have handled COVID differently in 2006?

MB: If COVID happened 20 years earlier, we would all have gotten vaccinated, because of all the grandmas and grandpas who grew up before the polio vaccine.

AP: What else has changed?

MB: When I talk to people in power, I try to educate them about what I call “uphill influence” versus “downhill influence.” Downhill influence is when there’s a pre-existing bias that you just need to hijack and ride downhill. There’s gravity already there, and that’s not necessarily a bad thing. It was an established fact 20 or 30 years ago that vaccines kept you safe. So, if you were rolling out a vaccine, you could already just ride that existence acceptance downhill. The gravity was with you.

Uphill is when you have to educate before you can even start to persuade. You first have to educate people about just the world that you’re trying to explain. Vaccines have gone from downhill to uphill. The [subjects] we all had to try to stay awake through in seventh grade science class aren’t even there anymore.

I understand [MAHA supporters] want a clean planet, food, and water, and all of that will make you healthier. However, in 1491, the people who lived on this continent had all that, right? The moment the first Javier Bardem-looking Spaniard coughed on them, whole civilizations died.

AP: Both of your zombie books hinge on public education, and that’s now a major aspect of your threat analysis work. Do you know why you keep returning to this theme?

MB: I think one of the reasons I’m so obsessed with education is because I was not a good student. I have such ferocious learning disabilities. I never felt instantly comfortable learning, and I’ve always had to find workarounds. My mother had to help me find workarounds so I could learn. So when I research, it takes so much time and effort and [there’s] so much insecurity. I understand how hard it is to teach something to someone who doesn’t naturally pick it up.

I’m very lucky that I come from two parents who had no formal education, but were both very smart. Most importantly, they were very curious. I became very comfortable with the idea of approaching something as an absolute beginner.

AP: It took 14 years between World War Z and your follow-up sci-fi novel, Devolution. Your next book, The First Hundred Hours: A Story of Alien Invasion, comes out in 2027. Is there a reason for such long pauses between these projects?

MB: I’m not a natural scientist. The amount I’ve had to study for this new book has been excruciating. But it’s very humbling having to talk to the experts and say things like, “Please talk to me like I’m a third grader—and not a smart third grader.”

AP: Would you end World War Z the same if it was set in 2026?

MB: I would still end it on a positive note, and I think that has to do with being an American. We don’t have the luxury of abandoning our ideals, because that’s all we are. We’re not a nation-state—the ideals in America are all that hold this mutt [of a] nation together. We all come from different places and tribes, and we all agree to live under a certain set of guidelines. It’s really critical that we fight for those guidelines.

If there is one takeaway, it’s the central reason I wrote the book in the first place. We’re all stuck on the same planet together, and that planet is not that big anymore. What affects some of us could potentially affect all of us. I think America has some amazing cultural strengths, but one of our weaknesses is our isolationism. That’s built on an outdated notion that we are somehow protected by two oceans and our geography. That’s not true anymore.

The post Max Brooks reflects on 20 years of ‘World War Z’ appeared first on Popular Science.

Endometriosis, a chronic inflammatory condition affecting an estimated one in ten women of reproductive age, has long frustrated clinicians with its stubborn tendency to recur despite surgery and hormone therapy. A new review published in Reproductive Sciences argues that the answer to this therapeutic failure may lie in a single transcription factor: ZEB1, or Zinc Finger E-Box Binding Homeobox 1. Written by Gaurav Doshi and Sanket Shirodkar of SVKM’s Dr. Bhanuben Nanavati College of Pharmacy in Mumbai, the review synthesises evidence from across the field to position ZEB1 as a master molecular integrator—converging hormonal, inflammatory and epigenetic signals into a single programme that drives lesion establishment, invasiveness and drug resistance.

The biological centrepiece of the review is epithelial–mesenchymal transition, or EMT, the process by which epithelial cells lose their adhesive, stationary character and acquire the migratory, invasive traits of mesenchymal cells. In endometriosis, EMT is thought to be essential for the survival of endometrial cells that reflux into the pelvic cavity during menstruation and subsequently implant on peritoneal surfaces, ovaries and other ectopic sites. ZEB1 sits at the apex of this programme. It suppresses CDH1, the gene encoding E-cadherin, the principal adhesion molecule holding epithelial sheets together, and in doing so dismantles the cell–cell junctions that would otherwise keep ectopic cells anchored and vulnerable. The review details how ZEB1 accomplishes this repression by recruiting chromatin-remodelling machinery, notably the SWI/SNF ATPase subunit BRG1, to the E-cadherin promoter, effectively silencing it epigenetically. The result is a stabilised mesenchymal differentiation that permits attachment, invasion and, ultimately, the vascularisation required for a lesion to persist.

Crucially, the authors argue that ZEB1 is not merely one EMT factor among many, such as SNAI1, SNAI2 or its paralog ZEB2, but a systems-level hub. Immunohistochemical and molecular studies have repeatedly shown selective upregulation of ZEB1 in ectopic endometriotic lesions compared with matched eutopic endometrium, and its expression is particularly pronounced in deep infiltrating disease. One frequently cited clinical study found ZEB1 expression to be a potential indicator of invasive endometriosis, while a pilot investigation of different disease phenotypes has extended these observations across superficial, ovarian and deep infiltrating subtypes. Measurable ZEB levels have even been detected in plasma and peritoneal fluid of patients with endometriosis and infertility, raising the prospect of ZEB-family proteins as circulating biomarkers.

Perhaps the most consequential section of the review concerns the bidirectional crosstalk between ZEB1 and sex steroid signalling. Endometriosis is a hormone-dependent disease, and its defining therapeutic problem is progesterone resistance: lesions fail to respond to the progestational drugs used to suppress them. The review marshals evidence that oestrogen, specifically 17β-estradiol, induces ZEB1 expression, and that ZEB1 in turn suppresses progesterone receptor pathways. This creates a self-reinforcing circuit in which the oestrogen-ZEB1 axis dismantles the molecular machinery that progesterone therapy depends upon. Experimental work has demonstrated that high ZEB1 expression accompanies 17β-estradiol-induced EMT in endometriotic cells, and parallel findings from other hormone-driven diseases reinforce the mechanism: in breast cancer, ZEB1 induces oestrogen receptor-α promoter hypermethylation and confers antiestrogen resistance, and ZEB-family members have been shown to regulate endocrine therapy sensitivity through both canonical and non-canonical routes. In endometriosis, EMT itself has been shown to contribute to the downregulation of progesterone receptor expression in lesions, and the near-uniform loss of progesterone receptor isoform B in ectopic tissue is a long-standing observation that the ZEB1 framework now helps to explain mechanistically.

The review also devotes substantial attention to the non-coding RNA dimension of ZEB1 regulation, describing a multilayered feedback architecture that locks the mesenchymal state in place. The miR-200 family of microRNAs normally targets the 3′ untranslated regions of ZEB1 and ZEB2 transcripts, holding EMT in check. In ectopic lesions, this double-negative feedback loop is subverted: ZEB1 represses miR-200 transcription, and the resulting loss of miR-200 pressure allows ZEB1 protein to accumulate. Long non-coding RNAs add another tier. The lncRNA AFAP1-AS1, for example, promotes EMT in endometriosis in a ZEB1-correlated manner, and the metastasis-associated transcript MALAT1 has been implicated in the same circuitry, with miR-200c suppressing endometriotic progression in vitro and in vivo by targeting it. Circular RNAs complete the picture. The circRNA circZFPM2 has been shown to promote EMT by sponging miR-205-5p and thereby releasing ZEB1 from repression, while hsa_circ_0063526 acts through the miR-141-5p/EMT axis and circATRNL1 acts upstream by upregulating the EMT cofactor YAP1. Together these competing endogenous RNA networks—a concept also validated in metastatic cancer by J Clin Invest work—build a ceRNA web that perpetuates ZEB1 expression long after the initial pro-EMT stimulus has passed.

The authors then connect ZEB1 to the two great downstream consequences of endometriotic lesions: chronic inflammation and fibrosis. Through interactions with the TGF-β pathway—upstream signals such as TGF-β1 activate SMAD2/3, which cooperate with ZEB1 to drive the mesenchymal programme—ZEB1-linked cells reshape the lesion microenvironment. Fibroblast-to-myofibroblast transdifferentiation, marked by α-smooth muscle actin expression, generates the dense extracellular matrix characteristic of endometriotic implants, and analogous MRTF-A–ZEB1–IRF9 axes have been documented in renal fibrosis. Inflammation completes the loop: pro-inflammatory cytokines such as TNF-α, IL-6 and IL-10, and peritoneal fluid cytokine profiles that differ across endometriosis subphenotypes, feed back into EMT signalling through MAPK, ERK, PI3K/AKT and NF-κB pathways, while immune evasion mechanisms—including indoleamine 2,3-dioxygenase-mediated suppression of natural killer cell cytotoxicity—shield ectopic tissue from immune clearance. ZEB1’s own roles in immune cell biology and in macrophage efferocytosis and mitochondrial dynamics add further dimensions to this immunological interplay.

A distinctive strength of the review is its engagement with modern genomics and the heterogeneity it has revealed. Single-cell transcriptomic analyses of endometriosis, published in Nature Genetics and the Journal of Pathology, have identified distinct hormonal, immunologic and inflammatory signatures among the cell populations constituting lesions, and spatial transcriptomics is beginning to map how intermediate fibroblast and myeloid cell distributions shape lesion architecture. ZEB1 expression, the authors note, is not uniform: it varies by lesion subtype, anatomical site and microenvironmental context, which helps explain why superficial peritoneal, ovarian endometrioma and deep infiltrating disease behave so differently and respond so unevenly to therapy. This heterogeneity argues strongly against a one-size-fits-all anti-ZEB1 strategy and supports the emerging precision-medicine framing of the oestrogen-ZEB1-TGF-β axis as the central therapeutic target.

The review is refreshingly candid about the translational paradox at the heart of any ZEB1-directed therapy. Far from being a purely pathological molecule, ZEB1 has indispensable physiological functions in the female reproductive tract. In vitro studies show that ZEB1 modulates endometrial receptivity through EMT in endometrial epithelial cells, and work in mice demonstrates that it promotes EMT of endometrial epithelium and plays a critical role in embryo implantation. ZEB1 is also detected in granulosa cells of women undergoing IVF, regulates wound angiogenesis and closure, participates in corneal homeostasis, and contributes to endometrial repair during menstruation through epithelial migration and mesenchymal–epithelial transition. Blanking ZEB1 systemically, therefore, risks impairing fertility, tissue regeneration and wound healing—the very outcomes clinicians are trying to protect. Any therapeutic strategy would need to be lesion-specific, temporally controlled and carefully titrated, perhaps by targeting upstream oestrogen-driven induction, the TGF-β/ALK5 arm, the non-coding RNA sponges, or post-translational stabilisation mechanisms such as ZEB1 acetylation, phosphorylation and ubiquitin-proteasome turnover via regulators like USP51 and SIAH1/2.

The authors also stress the need for better experimental models to establish causal rather than merely correlative relevance. shRNA- and siRNA-based knockdown of ZEB1 in endometriotic cells, three-dimensional patient-derived endometriosis models for drug evaluation, and multi-omics approaches that integrate transcriptomic, epigenomic and proteomic data—including recent ubiquitination-focused studies of endometriosis fibrosis—are all highlighted as tools that could convert the ZEB1 hypothesis into testable interventions. Biomarker development is another avenue: ZEB-family levels in plasma and peritoneal fluid, in combination with existing miRNA signatures, could one day support non-invasive diagnosis, a long-standing unmet need given that current detection still relies on laparoscopy.

Ultimately, the review’s central claim is that the oestrogen–ZEB1–TGF-β axis functions as a signalling hub through which the hormonal, inflammatory and epigenetic drivers of endometriosis converge and perpetuate one another. By identifying ZEB1 as the point of integration, the authors provide a mechanistic scaffold that could explain progesterone resistance, fibrotic progression and recurrence within a single framework, and they chart a cautious but concrete path toward mechanism-based, lesion-specific precision therapies. For a disease that has historically been managed with blunt hormonal and surgical instruments, the prospect of intervening at the level of a single, druggable transcriptional circuit represents one of the more compelling conceptual advances in endometriosis research in recent years.

Late last week, word started leaking that the National Institutes of Health (NIH) had reached an agreement with the Department of Defense that would see part of the NIH's budget used to fund research at the Department of Defense. So, on the Friday just prior to a US holiday weekend, the Department of Defense released a copy of the agreement and confirmed that it had been signed roughly a month earlier. The move is striking for a number of reasons, ranging from the existing budget disparities between the two parties involved to the fact that the money would be used for projects that the current NIH leadership has explicitly rejected.

The agreement itself sets up a system where the NIH would transfer money to the Department of Defense to fund staff and projects that would "support the advanced development of medical countermeasures against pandemic influenza, chemical, biological, radiological, and nuclear (CBRN) threats, and emerging infectious diseases." The money would come out of the budget for the NIH's National Institute of Allergy and Infectious Diseases, or NIAID, to which Congress has allocated $6.6 billion in 2026. The agreement is set to run for a decade.

Left unspecified is just how much of the NIAID budget will be spent on Defense projects. Reporting by Nature suggests that the Department of Defense was looking for up to a third of its total budget but was being told to settle for about 10 percent. There's obviously an enormous disparity between the budgets of these two agencies, given that the 2026 Defense budget is roughly $1 trillion. That budget is under considerable strain, however, due to the open-ended nature of the conflict with Iran. The deal has also been announced at a time when the NIH has been struggling to issue sufficient grants to use the money that Congress allocated to it.

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© Artem Onoprienko

Late last week, word started leaking that the National Institutes of Health (NIH) had reached an agreement with the Department of Defense that would see part of the NIH's budget used to fund research at the Department of Defense. So, on the Friday just prior to a US holiday weekend, the Department of Defense released a copy of the agreement and confirmed that it had been signed roughly a month earlier. The move is striking for a number of reasons, ranging from the existing budget disparities between the two parties involved to the fact that the money would be used for projects that the current NIH leadership has explicitly rejected.

The agreement itself sets up a system where the NIH would transfer money to the Department of Defense to fund staff and projects that would "support the advanced development of medical countermeasures against pandemic influenza, chemical, biological, radiological, and nuclear (CBRN) threats, and emerging infectious diseases." The money would come out of the budget for the NIH's National Institute of Allergy and Infectious Diseases, or NIAID, to which Congress has allocated $6.6 billion in 2026. The agreement is set to run for a decade.

Left unspecified is just how much of the NIAID budget will be spent on Defense projects. Reporting by Nature suggests that the Department of Defense was looking for up to a third of its total budget but was being told to settle for about 10 percent. There's obviously an enormous disparity between the budgets of these two agencies, given that the 2026 Defense budget is roughly $1 trillion. That budget is under considerable strain, however, due to the open-ended nature of the conflict with Iran. The deal has also been announced at a time when the NIH has been struggling to issue sufficient grants to use the money that Congress allocated to it.

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© Artem Onoprienko

A bacterial molecule called gladiolin can disarm invasive Candida albicans and strengthen the effects of a major antifungal drug. Candida albicans usually lives harmlessly in the human body, but under the wrong conditions it can transform into an invasive form capable of damaging tissue and causing life-threatening infection. Researchers from Monash University and the University [...]

Under a new partnership, the Defense Department would play a larger role in biodefense and pandemic preparedness. Democrats warned it could allow a Pentagon cash grab.

Diseases that cause nerve cells in the brain to die over time are known as neurodegenerative diseases. These cells, known as neurons, are vulnerable to DNA damage because they are highly active cells that require large amounts of energy. Neural DNA damage is a normal part of aging as changes to the DNA sequence, called mutations, build up over time. 

Previous scientists have shown that neurons from people with the neurodegenerative diseases Alzheimer’s disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) accumulate unusually high numbers of changes in the DNA sequence, called somatic mutations. However, researchers don’t know what causes the high number of mutations or whether the same process causes them in all 3 diseases. 

To answer these questions, researchers at Boston Children’s Hospital and Harvard Medical School analyzed brain tissue from people who died with and without AD, FTD, or ALS. They compared the processes that cause DNA mutations in the 3 diseases by first accessing the DNA inside individual neurons from healthy and diseased postmortem brain tissue. 

To do this, they broke apart the brain tissue and added a fluorescent marker that identified the center of each neuronal cell where DNA is housed, called its nucleus. They used a sorting machine to separate the nuclei from the rest of the cell material to access the neuron’s DNA. Using a DNA sequencing method called single-cell whole genome sequencing, the team then sequenced each neuron’s DNA to identify mutations. 

They analyzed 159 neurons from people with AD, 61 neurons from people with FTD, 77 neurons from people with ALS, and 232 neurons from healthy individuals. This allowed the team to compare the number and types of DNA mutations between diseased and control (non-diseased) neurons. The researchers found that compared to the control neurons, which typically accumulate only 200 to 300 mutations over an 80-year lifespan, neurons from all 3 diseases contained an unusually high number of 2-base-pair deletions, often exceeding 1,000 mutations per cell. 

When a biological process damages DNA, it leaves behind its own unique signature. By identifying these signatures, scientists can identify the biological process that likely caused the damage. Since these 2-base-pair deletions were so frequent in diseased neurons, the researchers wanted to know whether they were left behind by a biological process. The researchers used a machine learning algorithm to scan DNA sequences for recurring mutation patterns and identified a signature in neuronal DNA, which they named ID-4.

When the researchers compared the ID-4 signature with a database of previously characterized signatures, they found that it was associated with a DNA repair protein called TOP1. TOP1 temporarily cuts and rejoins DNA to relieve the tension that builds up during normal cellular activity. TOP1 typically detaches from the DNA after completing this process. However, if TOP1 fails to detach, it breaks one of the two DNA strands. 

To test whether abnormal TOP1 activity was breaking the DNA, the researchers isolated DNA from control and diseased neurons. They visualized the DNA on a gel, where intact DNA forms bands while broken DNA spreads out into smears. The more fragmented the DNA is, the more intense the smear appears. Using a machine that quantified the intensity of smears, the researchers found that DNA from diseased neurons produced smears that were up to 3.2 times more intense than those from control neurons. They also found that neurons with more DNA fragmentation had more ID-4 signatures. 

Based on these findings, the researchers concluded that abnormal TOP1 activity created frequent single-strand DNA breaks. They proposed that some of these breaks are repaired incorrectly, eventually leading to widespread DNA breaks in all 3 neurodegenerative diseases.

Overall, the researchers found that neurons from these 3 neurodegenerative diseases accumulated excessive DNA mutations despite differences in the disease symptoms and underlying causes. Their findings also provided evidence that abnormal TOP1 activity contributes to this mutation accumulation. Based on these findings, they stated that preventing TOP1 from becoming trapped on DNA, or improving the DNA repair process that removes trapped TOP1, could be a promising way to treat a wide range of neurodegenerative diseases.

The post Common DNA damage could cause neurodegenerative diseases appeared first on Sciworthy.

A multidisciplinary team from Baylor College of Medicine, Rice University and the University of Texas School of Public Health has received the inaugural Climate + Health Excellence award from the Burroughs Wellcome Fund. The five-year, $10 million award will support FORECAST, an ambitious program designed to investigate how climate change, extreme weather and environmental disruption influence the emergence and spread of infectious diseases. Led by infectious disease researcher Dr. Anthony Maresso, the project will combine wastewater surveillance, metagenomic sequencing, climate science, epidemiology and public education to create an early-warning system for pathogen activity across Texas.

FORECAST will build on Texas’s expanding wastewater-monitoring infrastructure, including the Texas Wastewater Environmental Biomonitoring Network, or TexWEB. The statewide network samples sewage from 15 Texas cities and analyzes biological material shed by communities. Unlike clinical surveillance, which depends on people seeking medical care and receiving diagnostic tests, wastewater epidemiology captures population-level signals from entire communities. Viral genetic fragments, bacterial DNA and other biological markers can appear in sewage before hospitals and clinics register a rise in patients, providing public health officials with valuable time to investigate and respond.

The program will use metagenomic surveillance, a technique that examines genetic material recovered from environmental samples rather than searching only for a predetermined pathogen. In conventional testing, laboratories typically use targeted molecular assays designed to detect a known virus or bacterium. Metagenomic sequencing can survey a much broader range of organisms, including variants and potentially unfamiliar pathogens. Researchers can then compare these signals with clinical data, geographic information and environmental measurements to determine whether changes in temperature, rainfall, flooding, drought or other conditions are associated with shifts in infectious disease activity.

The scientific goal is not simply to identify pathogens after they appear, but to uncover relationships between microbes and the environmental conditions that help them enter or circulate within human populations. Climate change can influence disease transmission through several pathways. Warmer temperatures may expand the geographic range or seasonal activity of mosquitoes and other vectors. Heavy rainfall and flooding can overwhelm sanitation systems and redistribute contaminants, while drought can alter water use and concentrate biological material. Changes in human behavior, animal movement and ecosystems may create additional opportunities for pathogens to cross species boundaries.

Maresso and his colleagues demonstrated during the COVID-19 pandemic that SARS-CoV-2 signals in wastewater could precede increases in clinically diagnosed infections. Viral RNA released in feces entered sewage systems, where researchers tracked changes in concentration over time. Although wastewater measurements cannot determine which individuals are infected, they can reveal whether pathogen activity is increasing or declining within a catchment area. The approach has since been extended to a wider range of targets, including avian influenza, measles, HIV and viruses associated with cancer. FORECAST aims to develop this surveillance capacity into a predictive climate-health platform.

Rice University climate scientist Dr. Sylvia Dee will help connect pathogen observations with weather and climate data. The team plans to examine whether specific environmental patterns consistently occur before increases in particular infectious agents. Such models could eventually function like a public health weather report, indicating when conditions are becoming more favorable for disease transmission. The researchers emphasize that predictive systems will require careful validation because the presence of pathogen genetic material does not necessarily indicate infectious virus, active transmission or a future outbreak. Interpreting the signal will require laboratory studies, clinical evidence and knowledge of local infrastructure.

The project will also investigate diseases transmitted by vectors such as mosquitoes. Dr. Peter Hotez and colleagues at the National School of Tropical Medicine will focus on vector-borne pathogen transmission and the growing health risks associated with changing climate conditions. Texas is particularly relevant for this work because it contains diverse ecological regions and experiences heat waves, hurricanes, flooding and rapid urban growth. These factors can affect mosquito habitats, human exposure and the movement of pathogens across communities. Integrating wastewater findings with vector surveillance could help reveal connections that would remain hidden if either system were used alone.

Education and public communication will form a central part of FORECAST. The team plans to create a “Middle to Medical” climate-health education track extending from middle school through medical training and professional development. Dr. Nancy Moreno, who developed Baylor’s BioEd online program, will lead educational efforts with Rice University’s Dr. Joseph Campana, director of the university’s Center for Environmental Studies and EcoStudio. The curriculum will explain how pathogens spread, how climate conditions alter disease risk and how scientific evidence can guide decisions by students, clinicians, policymakers and communities.

The award is particularly significant because FORECAST was selected as the sole funded project from 161 applications submitted to the new CHEX program. The initiative is intended to strengthen research, education and public engagement at the intersection of climate change and human health. Dr. Eric Boerwinkle, dean of the UT School of Public Health and a project co-investigator, will contribute access to large clinical datasets that can be used to evaluate wastewater and environmental signals against reported illnesses. The investigators say the work could improve outbreak preparedness while advancing the still-developing field of wastewater science.

By combining environmental sequencing with climate modeling and health education, FORECAST seeks to shift infectious disease surveillance from a largely reactive system toward earlier detection and prevention. Its findings may help officials recognize emerging threats before they produce widespread clinical disease, while also clarifying how environmental changes shape viral evolution, transmission and geographic spread. The researchers describe wastewater as an unusually candid public health resource: it aggregates biological information from a population without requiring individual testing. As climate pressures intensify, they argue, that collective signal could become an essential tool for protecting communities and preparing the next generation of scientists.

Subject of Research:
Climate-driven infectious disease emergence, wastewater epidemiology, metagenomic pathogen surveillance and climate-health education.

Article Title:
Texas Researchers Launch FORECAST Program to Link Climate Change With Emerging Viral Threats

Web References:
Baylor College of Medicine; Rice University; University of Texas School of Public Health; Burroughs Wellcome Fund; Texas Wastewater Environmental Biomonitoring Network (TexWEB).

References:
Information provided in the source news release concerning the FORECAST project, the Climate + Health Excellence award and TexWEB wastewater surveillance activities.

Keywords:
Wastewater epidemiology, viral surveillance, metagenomic sequencing, climate change, infectious diseases, pathogen emergence, public health, Texas, SARS-CoV-2, avian influenza, measles, vector-borne disease, climate health, epidemiology, wastewater science

A research team in Japan has won a US$1 million Milestone 2 award in the XPRIZE Healthspan competition for developing engineered “super exosomes,” microscopic biological delivery vehicles designed to target aging and damaged cells. Led by Professor Keisuke Goda of Tohoku University’s SiRIUS Institute of Medical Research and Graduate School of Medicine, in collaboration with researchers from the University of Tokyo’s Department of Chemistry, the team was selected from more than 600 competitors worldwide.

XPRIZE Healthspan is a seven-year international competition focused on extending the period of life people spend in good health. Participating teams are challenged to develop treatments capable of restoring muscle, cognitive, and immune function in adults between 50 and 90 years old. The competition sets a minimum target of reversing at least 10 years of biological decline, while the most ambitious goal is a 20-year improvement within one year or less of treatment. Goda’s team is now moving forward after receiving recognition for results obtained in aged animal studies.

At the center of the research are exosomes, naturally occurring nanoparticles released by cells. These membrane-bound vesicles normally transport proteins, lipids, messenger RNA, and other molecular signals between cells, functioning as part of the body’s communication network. Because exosomes can carry biological cargo and interact with specific tissues, scientists have been investigating them as potential alternatives to synthetic drug-delivery systems. However, naturally produced exosomes often lack sufficient targeting precision, limiting their ability to reach the cells most relevant to a disease or aging process.

The Tohoku-led group attempted to solve that problem by chemically modifying the surface of exosomes with lanthanide ions. Lanthanides are a family of metallic elements with distinctive electronic and chemical properties. According to the researchers, attaching these ions changes the surface behavior of the exosomes and substantially improves their ability to recognize and bind to senescent cells. The resulting particles have been named “super exosomes,” a term that reflects their enhanced targeting and delivery capabilities rather than a new biological category.

Cellular senescence is one of the major biological processes associated with aging. Senescent cells have generally stopped dividing because of accumulated damage or stress, but they do not necessarily disappear. Instead, some remain metabolically active and release inflammatory molecules, growth regulators, and other signals that can disrupt nearby tissues. This collection of secreted factors, often called the senescence-associated secretory phenotype, can contribute to chronic inflammation, impaired tissue repair, and the deterioration of organs. Precisely influencing these cells has therefore become a major objective in longevity research.

The proposed super-exosome platform is designed to deliver regenerative molecular cargo directly to aging tissues after attaching to senescent cells. Potential cargoes include growth factors, messenger RNA, and other genetic materials capable of altering cellular behavior. Rather than distributing such molecules broadly throughout the body, a targeted exosome could concentrate them near damaged or dysfunctional tissue. In theory, this approach could promote repair while reducing unwanted effects in healthy cells, although the degree of targeting and the durability of the response will need to be confirmed in human studies.

In preclinical experiments involving several groups of aged mice, the researchers reported statistically significant improvements in frailty, physical performance, and multiple functional measures associated with aging. They also described the treatment’s safety profile as excellent in the studies conducted so far. The team says the overall benefit corresponds to more than 15 additional healthy human years when estimated using cross-species lifespan scaling. Such calculations can help compare biological effects between species, but they are not evidence that a mouse treatment will extend human life by a specific number of years. Human biology, dosing, immune responses, and long-term risks could differ substantially.

The award will support the next stage of development: clinical studies planned in collaboration with Tohoku University Hospital and the Tohoku University Healthspan Research Center. These studies will need to establish how the particles behave in humans, how efficiently they reach senescent cells, what cargoes are most effective, and whether the treatment produces measurable improvements in strength, cognition, immunity, or other healthspan indicators. Researchers will also have to monitor possible immune reactions, unintended effects on healthy tissues, changes in tumor risk, and the persistence of engineered exosomes in the body. These questions are essential before claims of age reversal can move beyond the laboratory.

The platform could eventually be investigated for conditions involving muscle decline, cognitive impairment, immune dysfunction, hair loss, skin aging, and reproductive health. The team plans to commercialize the technology through NanoTitan, with the aim of developing scalable manufacturing and international distribution for exosome-based therapeutics produced in Japan. “Advancing to the XPRIZE Healthspan finals is an important milestone, but our ultimate goal is to translate this technology into therapies that allow people to lead healthy, independent, and active lives longer,” Goda said. The research now enters its most demanding phase: determining whether an impressive result in aged mice can become a safe, reproducible, and clinically meaningful treatment for people.

Subject of Research: Engineered “super exosomes” designed to target senescent cells and deliver regenerative molecular cargo for healthy aging.

Article Title: Japanese Research Team Wins US$1 Million XPRIZE Award for “Super Exosome” Aging Technology

Web References: https://mediasvc.eurekalert.org/Api/v1/Multimedia/673c8fb3-268a-4a90-93b4-a0d531624a52/Rendition/low-res/Content/Public

Image Credits: Goda Lab

Keywords: Super exosomes, exosomes, cellular senescence, healthy aging, longevity research, XPRIZE Healthspan, regenerative medicine, Tohoku University, lanthanide ions, aged mice, healthspan, nanomedicine

Fuchs endothelial corneal dystrophy, a progressive disorder that can gradually cloud the cornea and impair vision, may be driven by a cellular process more complex than simple cell loss. A new study published in Cell Death Discovery reports that ultraviolet-A light can induce chronic hyperploidization in corneal endothelial cells, triggering changes associated with fibrosis. The findings connect long-term genome abnormalities in post-mitotic cells to the structural deterioration observed in this increasingly recognized eye disease.

The cornea depends on a thin inner layer of endothelial cells to maintain its transparency. These cells regulate the movement of fluid between the cornea and the anterior chamber of the eye, preventing the tissue from becoming waterlogged. Unlike many cell types, human corneal endothelial cells have limited ability to divide and replenish themselves. When they are damaged or lost, neighboring cells may enlarge and stretch to cover the affected area, but this compensation has limits. In Fuchs endothelial corneal dystrophy, the endothelial layer progressively becomes dysfunctional, allowing fluid accumulation and producing corneal swelling, haze and visual distortion.

The study focuses on hyperploidization, a condition in which cells acquire extra sets or copies of chromosomes. In a healthy cell cycle, DNA is replicated and then evenly distributed when a cell divides. Post-mitotic cells, however, are not expected to continue cycling through repeated rounds of DNA replication. If DNA replication occurs without successful cell division, the result can be a cell with an enlarged genome and multiple chromosome sets. This state, known as polyploidy or hyperploidization depending on its extent and context, can alter cell size, metabolism, gene activity and responses to stress.

The researchers investigated how ultraviolet-A, or UVA, light affects cells associated with Fuchs endothelial corneal dystrophy. UVA has a longer wavelength than ultraviolet-B and can penetrate biological tissues more deeply. Although the eye possesses protective mechanisms, persistent or excessive exposure to light-generated stress can damage cellular components, including DNA, proteins and mitochondria. The study indicates that UVA exposure does not merely cause an acute injury that cells either repair or fail to survive. Instead, it can establish a chronic hyperploid state in cells that no longer divide normally.

That distinction is important because a cell can remain alive while becoming increasingly dysfunctional. Hyperploid cells may continue to produce proteins, communicate with neighboring cells and modify their surrounding environment, even as their enlarged genomes disrupt normal regulation. In the corneal endothelium, such persistent abnormalities could interfere with the machinery responsible for maintaining fluid balance and tissue transparency. The research links this long-lasting cellular state to the activation of fibrotic processes, suggesting that damaged endothelial cells may help remodel the cornea rather than simply disappearing.

Fibrosis is the formation or accumulation of excessive connective-tissue components, particularly extracellular matrix proteins such as collagens. During wound healing, matrix production can provide temporary structural support. When the response persists, however, the tissue can stiffen, become disorganized and lose its normal optical properties. In the context of Fuchs endothelial corneal dystrophy, fibrosis may contribute to the loss of corneal clarity and the progression of visual impairment. The study’s central message is that chronic hyperploidization may act as an upstream signal that pushes post-mitotic cells toward this pathological remodeling.

The findings also help explain why a disease affecting a specialized, non-dividing cell population can progress over time. A conventional view of cellular damage often emphasizes apoptosis, necrosis or the gradual depletion of functional cells. The new work highlights another possibility: injured cells may survive in a permanently altered condition and actively influence disease progression. By retaining metabolic activity while carrying abnormal quantities of DNA, these cells could produce signals that encourage inflammation, matrix deposition or changes in the behavior of nearby cells.

The UVA connection raises questions about how environmental stress interacts with inherited susceptibility. Fuchs endothelial corneal dystrophy has genetic and age-related components, and the disease does not arise from a single universal cause. The study does not establish that UVA exposure alone causes the disorder, but it provides a mechanism through which light-associated stress could worsen cellular instability in vulnerable corneal tissue. This may help researchers examine whether cumulative exposure, cellular antioxidant capacity and pre-existing genetic changes combine to determine how rapidly the disease advances.

From a treatment perspective, the work points toward targets beyond replacing lost endothelial cells. Future strategies might seek to prevent abnormal DNA replication, stabilize genome integrity, suppress the fibrotic signals released by hyperploid cells or protect the corneal endothelium from chronic light-induced stress. Such approaches would require careful testing, because polyploidy can serve useful roles in some normal tissues, and broadly blocking cell-cycle or repair pathways could produce harmful effects. The challenge will be to distinguish pathological hyperploidization from adaptive genome changes that help cells survive.

The study ultimately presents Fuchs endothelial corneal dystrophy as a disease of cellular identity as well as cellular survival. UVA-induced chronic hyperploidization appears to place post-mitotic corneal endothelial cells in a persistent state of genomic imbalance, where they can contribute to fibrosis and tissue failure. By connecting light stress, abnormal DNA content and corneal scarring, the research offers a new framework for understanding why the disease can continue even after the initial injury has passed—and provides a potential roadmap for therapies designed to interrupt the process before vision is permanently compromised.

Subject of Research: Ultraviolet-A light-induced chronic hyperploidization and fibrosis in post-mitotic corneal endothelial cells affected by Fuchs endothelial corneal dystrophy

Article Title: Ultraviolet-A light-induced chronic hyperploidization causes fibrosis in post-mitotic cells affected by Fuchs endothelial corneal dystrophy

Article References: Adhikari, Y., Parekh, M., Deshpande, N. et al. Ultraviolet-A light-induced chronic hyperploidization causes fibrosis in post-mitotic cells affected by Fuchs endothelial corneal dystrophy. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03292-8

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41420-026-03292-8

Keywords: Fuchs endothelial corneal dystrophy, ultraviolet-A, UVA, hyperploidization, polyploidy, corneal endothelial cells, fibrosis, post-mitotic cells, genome instability, corneal disease

Gut bacteria helped some adults tolerate peanuts in a first human trial.

Researchers say breakthrough offers hope for new medicines but also raises urgent biosecurity questions

Scientists have made the first viruses designed by artificial intelligence in a milestone that raises hopes for new medicines but also concerns over how to ensure the technology remains safe.

The viruses are specific kinds known as bacteriophages, which only infect bacteria and are used around the world to treat patients with persistent infections. In lab tests, a cocktail of the AI-designed viruses killed E coli bugs that were resistant to natural bacteriophages.

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© Photograph: Samyukta Lakshmi/Bloomberg/Getty Images

© Photograph: Samyukta Lakshmi/Bloomberg/Getty Images

© Photograph: Samyukta Lakshmi/Bloomberg/Getty Images

Scientists at Imperial College London and The University of Manchester have developed a promising new way to create

Senator Rand Paul said the committee he leads would vote next week on whether to hold Dr. Fauci in contempt of Congress.

Neonatal necrotizing enterocolitis (NEC) remains one of pediatrics’ most devastating intestinal disorders, and safer, mechanism-driven therapies are urgently needed. New findings suggest that tiny vesicles naturally present in human breast milk—exosomes—may offer protection by delivering a specific regulatory microRNA.

Researchers report that exosomes enriched with miR-144-5p can help restore the intestinal tight junction barrier, a key defense line that collapses during NEC. By focusing on miR-144-5p, the team moves beyond earlier observations that breast milk exosomes can reduce NEC severity and instead pinpoints a molecular cargo likely responsible for part of that benefit.

The study centers on how NEC damages epithelial integrity and promotes inflammatory signaling. Tight junction disruption is associated with increased permeability, bacterial translocation, and worsening inflammation—conditions that accelerate disease progression in vulnerable newborns. The investigators therefore examined whether miR-144-5p could counter these barrier failures in NEC contexts.

Mechanistically, the work links miR-144-5p action to the TLR4/NF-κB pathway, a well-known inflammatory axis. Toll-like receptor 4 (TLR4) senses danger-associated cues and can trigger NF-κB activation, driving transcription of pro-inflammatory mediators. In NEC, exaggerated signaling through this route contributes to tissue injury and impaired repair.

By modulating this cascade, miR-144-5p appears to dampen downstream inflammatory responses while promoting recovery of junctional structure. The paper’s data indicate that exosomal delivery is central: miRNAs packaged within vesicles can be taken up by recipient cells more efficiently than naked RNA, enabling functional gene regulation in target intestinal compartments.

Together, the results support a model in which breast milk exosomal miR-144-5p alleviates NEC by suppressing TLR4-driven NF-κB activation, thereby reducing inflammatory injury and enabling tighter regulation of epithelial junctions. If translated, such a cargo-guided approach could complement existing supportive NEC treatments.

While additional work will be required to confirm efficacy across models and to evaluate safety, the study provides a clear mechanistic roadmap: therapeutic exosomes or miRNA mimics that bias TLR4/NF-κB activity may be a promising strategy for protecting the neonatal gut.

Subject of Research: Neonatal necrotizing enterocolitis (NEC), breast milk-derived exosomes, miR-144-5p, tight junction barrier repair, TLR4/NF-κB signaling.

Article Title: Human milk exosomal-miR-144-5p alleviates neonatal necrotizing enterocolitis by regulating the TLR4/NF-κB pathway.

Article References: Chen, Z., Chen, C., Hu, X. et al. Human milk exosomal-miR-144-5p alleviates neonatal necrotizing enterocolitis by regulating the TLR4/NF-κB pathway. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05305-9

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05305-9

Keywords:

A new Bayesian system called ALADYNOULLI is designed to forecast how multiple diseases unfold over time from longitudinal electronic health record (EHR) histories. The work targets a central challenge in longitudinal modelling: evaluating prediction without “information leakage,” so that future diagnoses never influence training for past timepoints. By explicitly simulating real clinical follow-up, the researchers aim to make risk estimates more trustworthy for decision-making.

In the primary assessment, ALADYNOULLI produced dynamic 1-year forecasts at 10 fixed moments during follow-up, starting at enrollment and extending to years 1 through 9. At each timepoint, models were retrained using only data available up to that moment, then tested on 1-year outcomes. The key metric was the median area under the receiver operating characteristic curve (AUC) across these dynamic evaluations, summarizing how predictive accuracy changes as new diagnoses accumulate.

The study spans 28 diseases and reports robust discrimination for several clinically important endpoints. Performance was strong for atherosclerotic cardiovascular disease (ASCVD), breast cancer, atrial fibrillation, heart failure, and Parkinson’s disease, with AUC values of 0.879, 0.867, 0.801, 0.811, and 0.796, respectively. Importantly, the evaluation excluded people with prevalent disease at prediction time, aligning the comparisons with prospective risk.

ALADYNOULLI was also benchmarked against established clinical risk tools where feasible. At enrollment, static models trained only on baseline information were compared for both 1-year and 10-year horizons. While longer-term predictions naturally degraded, ALADYNOULLI retained meaningful power—for example, for ASCVD at 10 years—highlighting the advantage of learning from longitudinal EHR trajectories rather than relying solely on cross-sectional inputs.

Calibration analyses further supported reliability: predicted and observed event rates matched closely across millions of at-risk patient-time observations. The researchers report a mean squared error on calibration of 4.67 × 10⁻⁷, with mean predicted rates (5.55 × 10⁻⁴) closely tracking mean observed rates (5.45 × 10⁻⁴). This suggests not only ranking accuracy, but also quantitative risk realism.

To test whether results were driven by subtle temporal artifacts, the team ran sensitivity analyses that excluded events occurring shortly before prediction and varied washout windows. They also examined alternative horizons and a dynamic 10-year rolling interpolation strategy, which updates risk estimates as annual information becomes available. Together, these checks help confirm that temporal patterns are being learned in a causally aligned manner.

Overall, the findings position ALADYNOULLI as a clinically relevant framework for multi-disease risk forecasting, combining longitudinal EHR modelling with predictive discrimination and calibration. By rigorously preventing leakage and validating dynamic follow-up scenarios, the approach offers a pathway toward more actionable, time-aware risk prediction in real-world healthcare settings.

Subject of Research: Longitudinal EHR-based multi-disease risk prediction using Bayesian modelling and genetic/EHR integration
Article Title: A Bayesian framework for longitudinal EHR and genetic discovery.
Article References: Urbut, S.M., Ding, Y., Nakao, T. et al. A Bayesian framework for longitudinal EHR and genetic discovery. Nature (2026). https://doi.org/10.1038/s41586-026-10780-5
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41586-026-10780-5
Keywords: longitudinal EHR, Bayesian framework, disease risk prediction, dynamic forecasting, temporal validation, calibration, AUC, ASCVD

Lettuce and salad greens have become the prime suspects in an explosive outbreak of the diarrheal parasite Cyclospora, which is surging nationwide but erupting to extraordinary heights in Michigan.

In recent years, Michigan has typically reported around 50 cases of cyclosporiasis, which causes urgent bouts of watery diarrhea, abdominal cramps, and nausea. But, this year, as of July 14, the state has reported 3,309 cases of the food-borne pathogen. Of those 44 have been hospitalized.

Based on interviews with more than 1,000 people sickened in Michigan, the latest data is pointing to leafy greens as the source, according to the Michigan Department of Health and Human Services (MDHHS).

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