New and emerging therapies in type 1 diabetes mellitus: doi.org/10.1172/JCI2... In this Review, Kevan C. Herold  & Carmella Evans-Molina highlight the mechanisms driving T1D and explore strategies to achieve lasting metabolic remission.

Introducing ‘symbiotic exclusivity’ as a conceptual framework in glioblastoma: doi.org/10.1172/JCI1... Zhou et al. report on two genes that cooperate to help aggressive brain tumors grow and evade immunity—and targeting both pathways boosts immune therapy and shrinks tumors in mice.

ICYMI: Conventional type-1 DC density is associated with checkpoint inhibitor response across multiple cancers: doi.org/10.1172/JCI2... Lopez-Janeiro et al. integrate 7 checkpoint inhibitor trials with spatial tissue analyses to test whether cDC1s correlate with clinical benefit across cancers

From earlier this week: A landmark in cardiac metabolism: doi.org/10.1172/JCI2... Jay D. Horton & team find unrestrained fat oxidation in heart cells deplete cardiolipins needed for mitochondrial energy, triggering heart failure in mice and revealing a potential metabolic target

Review: Towards precision medicine for brain arteriovenous malformations: doi.org/10.1172/JCI2... Hale et al. detail the molecular mechanisms, human genetics, models, translational studies & key research supporting a rationale for pharmacologic and gene-editing therapies for bAVMs.

A comprehensive analysis of kidney cancer tumor burden doi.org/10.1172/JCI1... This issue’s Cover features work by Haddad et al. showing that the anatomic distribution of metastases relates to molecular clusters associated with response to specific therapies Illustration by Elsa Pedrosa

A arget for preventing HCC formation in late-stage MASH: doi.org/10.1172/JCI1... William C. Sessa & team report loss of the liver protein NgBR drives fat buildup, inflammation & liver cancer in obese mice—and blocking fat synthesis prevented obesity-induced HCC. @krishb21.bsky.social

Expanding the functional repertoire of macrophages as remote healers: doi.org/10.1172/JCI2... Camille Blériot @gustaveroussy.fr & Florent Ginhoux comment on Salm et al.: doi.org/10.1172/JCI1... #PeritonealMacrophages #WoundHealing

Running Rich: How excess fatty acid oxidation drains the cardiac engine: doi.org/10.1172/JCI2... Steven M. Claypool & Carla M. Koehler comment on Kim et al.: doi.org/10.1172/JCI2...

Advancing our understanding of how metabolism shapes neuronal development: doi.org/10.1172/JCI1... @rjdlab.bsky.social & team generated neural progenitor cells from patients, finding that L2HG epigenetically activates MYC to impair neuronal differentiation—and the effect is reversible

Highlighting an unexpected connection between loss of circadian rhythm and cancer cell diversity: doi.org/10.1172/JCI2... Yang et al. report that targeting Wnt/β-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell-state diversity.

Conventional type-1 DC density is associated with checkpoint inhibitor response across multiple cancers: doi.org/10.1172/JCI2... Lopez-Janeiro et al. integrate 7 checkpoint inhibitor trials with spatial tissue analyses to test whether cDC1s correlate with clinical benefit across cancers

A landmark in cardiac metabolism: doi.org/10.1172/JCI2... Jay D. Horton & team find unrestrained fat oxidation in heart cells deplete cardiolipins needed for mitochondrial energy, triggering heart failure in mice and revealing a potential metabolic target

A new method for the diagnosis and treatment of melanoma lung metastasis: doi.org/10.1172/JCI1... Jiang Yang & team present a label-free, multiscale, photoacoustic imaging technique, using animal models and human tissue, that guides photoablation for melanoma lung metastases.

ICYMI: Progressing the field of tissue repair: doi.org/10.1172/JCI1... Salm et al. show that peritoneal macrophages release fibronectin, accelerating skin wound healing at distant sites and revealing an endocrine role for these cells in systemic tissue repair beyond the abdominal cavity.

Previously shared: There is growing recognition of a role for m6A RNA modification in neurodegenerative diseases Here, Sun Liu et al. reveal a pathogenic feedback loop between m6A deficiency and mitochondrial dysfunction, which may contribute to Parkinson’s disease pathogenesis.

Hitting pause on chemotherapy-induced alopecia: Transient p53 activation as a guardian of the hair follicle: doi.org/10.1172/JCI2... Edward B. Li, Meredith J. Klay & Rui Yi @feinberg.northwestern.edu comment on Gherardini et al.: doi.org/10.1172/JCI1...

Phospholipase PLA2G5-triggered hemolysis emerges as a contributor to sepsis lethality: doi.org/10.1172/JCI2... Jean-Marc Cavaillon @pasteur.fr provides a Commentary on Takahama et al.: doi.org/10.1172/JCI1... #Sepsis

www.jci.org/articles/vie.... Now out in @jci.org, estrogen exerts cardio protective effects via microtubule modulation!

Read the media release about this study, which paves the way for new approaches to predicting and treating wound healing disorders after surgery: mediarelations.unibe.ch/media_releas... @unibe.ch @inselgruppe.bsky.social

✅Clear association with disease severity ✅Mechanistic insight ✅Robust multi-platform design doi.org/10.1172/JCI1... @deepakarao.bsky.social & team implicate CD57+ TEM cells as a driver of lung injury in systemic sclerosis-interstitial lung disease & potentially other forms of ILD

Towards preventing intravascular hemolysis in sepsis: doi.org/10.1172/JCI1... Takahama et al. report on bloodborne PLA2G5, which damages red blood cells during sepsis and predicts disease severity and mortality in humans (from blood levels)—and blocking it improves survival in mice.

🎉 Congratulations to Jason Nideffer on his paper published today in the Journal of Clinical Investigation! Jason's work defines a novel surface marker profile — CXCR6⁺ CD127⁻ — that identifies Type 1 regulatory T (Tr1) cells in the context of P. falciparum infection. www.jci.org/articles/vie...

Presenting a novel topical approach for protecting healthy hair follicles from chemotherapy-induced hair loss: doi.org/10.1172/JCI1... Ralf Paus & team show ALRN-2624 activates the p53/p21 signal without protecting p53 mutant cancer cells, using ex vivo human scalp hair follicle culture

Review: Neuroendocrine and neural control of bone mass in health and disease: doi.org/10.1172/JCI203623 Mone Zaidi et al. discuss the medical consequences arising from dysfunction of two neural pathways regulating bone mass & explore promising therapeutic targets.

Progressing the field of tissue repair: doi.org/10.1172/JCI1... Salm et al. show that peritoneal macrophages release fibronectin, accelerating skin wound healing at distant sites and revealing an endocrine role for these cells in systemic tissue repair beyond the abdominal cavity.

How do monogenic disorders drive calcification? doi.org/10.1172/JCI1... Arjun Deb & team @dgsomucla.bsky.social find the liver regulates ectopic calcification of target tissues in Pseudoxanthoma elasticum models by altering the metabolome and cellular respiration of target organs.

#Immune #cells in the peritoneal cavity can speed up the healing of distant #skin #wounds – via fibronectin in the #blood. 🩸 New findings based on mouse and patient data from @inselgruppe.bsky.social & #unibern open up ways to better predict impaired wound healing 👇 sohub.io/vcxb

Review: Smoldering in the sanctuary: HIV-associated brain injury in the ART era: doi.org/10.1172/JCI2... Paraskevas Filippidis & Shelli F. Farhadian highlight single-cell multiomics and liquid biopsy approaches in understanding the CNS reservoir and discuss CNS-targeted cure strategies.

Highlighting a bench-to-bedside evidence-based study doi.org/10.1172/JCI1... Here, Jonathan J. Rios & team identify MAPK pathway activation in the pathogenesis of osteofibrous dysplasia and demonstrate efficacy of the MEK inhibitor mirdametinib in a pediatric patient.

Purpose, persistence, and progress: building the next generation of physician-scientists: doi.org/10.1172/JCI2... Through personal account, Cynthia Y. Tang celebrates 20 years of annual meetings @a-p-s-a.bsky.social and discusses the requirements for sustaining the workforce.

There is growing recognition of a role for m6A RNA modification in neurodegenerative diseases Here, Sun Liu et al. reveal a pathogenic feedback loop between m6A deficiency and mitochondrial dysfunction, which may contribute to Parkinson’s disease pathogenesis.

ICYMI: Tiffany C. Scharschmidt @scharschmidtlab.bsky.social & team @ucsanfrancisco.bsky.social report on the early life window for immune tolerance, finding naïve CD4+ T cells in cord blood have distinct metabolic traits that enable their regulatory potential: doi.org/10.1172/JCI2...

Previously shared: Gasdermin E: a missing link in muscle regeneration: doi.org/10.1172/JCI2... Swathy Krishna & Jill A. Rafael-Fortney provide a Commentary on Cao et al.: doi.org/10.1172/JCI1... #MuscleRegeneration #aging

A promising target in #HuntingtonsDisease: doi.org/10.1172/JCI1... On the Cover: Lu et al. report on SHMT2 downregulation in mitochondrial 1C metabolism leading to homocysteine accumulation that disrupts histone lactylation & transcription & drives neurodegeneration in HD models.

Metabolic syndrome and excessive alcohol consumption lead to liver fibrosis doi.org/10.1172/JCI1... ASCI member David A. Brenner & team @sbpdiscovery.bsky.social discover LARP6 as a master coordinator of hepatic stellate cell activation & fibrosis in human livers with MASH and MetALD

SLC26A4-gene mutations are a frequent cause of hereditary hearing loss doi.org/10.1172/JCI1... Tsai et al. show targeted AAV delivery restores auditory physiology and ameliorates cochlear pathology in a mouse model of Slc26a4-related deafness.

This Research Article evaluated a large MASLD clinical cohort (n=417,657): doi.org/10.1172/JCI2... Luca V.C. Valenti & team @unimont.bsky.social show how different types of apolipoprotein B (APOB) mutations affect the risk of developing cirrhosis and liver cancer.

Tiffany C. Scharschmidt @scharschmidtlab.bsky.social & team @ucsanfrancisco.bsky.social report on the early life window for immune tolerance, finding naïve CD4+ T cells in cord blood have distinct metabolic traits that enable their regulatory potential: doi.org/10.1172/JCI2...

New work from Niccolo Mencacci @feinberg.northwestern.edu et al., with contribution from @depaceraffa.bsky.social in our lab at the NIH, identifies pathogenic variants in BORCS5, encoding a subunit of the BORC complex, as a cause of a severe neurodevelopmental disorder. www.jci.org/articles/vie...

This Research Article raises caution for integrin-targeted therapies in HIV-driven neuroinflammation: doi.org/10.1172/JCI1... Smita S. Iyer @smitaiyer.bsky.social & team find blocking α4 integrin in SIV infection impairs CD8 T cell access to the brain, weakening antiviral defense.

ICYMI: Why are damaged muscles more likely to generate fatty tissue as we age? doi.org/10.1172/JCI1... Pei Wang & team find gasdermin E signaling unexpectedly promotes skeletal muscle repair by sustaining tissue-resident macrophage function and restraining maladaptive adipose tissue remodeling.

ICYMI: Challenging the view of glutathione as a protector in liver disease: doi.org/10.1172/JCI1... Liu et al. show glutathione depletion in the liver surprisingly prevents fatty liver disease by selectively oxidizing certain proteins involved in fat production, rather than causing broad damage.

Expanding clones, expanding aneurysms through macrophage-to-osteoclast differentiation: doi.org/10.1172/JCI2... Jessica A. Regan & Svati H. Shah @dukemedschool.bsky.social comment on Yonekawa et al.: doi.org/10.1172/JCI1...

Gasdermin E: a missing link in muscle regeneration: doi.org/10.1172/JCI2... Swathy Krishna & Jill A. Rafael-Fortney provide a Commentary on Cao et al.: doi.org/10.1172/JCI1... #MuscleRegeneration #aging

Diet’s rapid effects on the thyroid gland challenge unidirectional assumptions about hypothyroidism and energy balance: doi.org/10.1172/JCI2... Arturo Hernandez & Francesco S. Celi comment on Rampy et al.: doi.org/10.1172/JCI1...

For those interested in the link between clonal hematopoiesis and cardiovascular disease👇 doi.org/10.1172/JCI1... Yoshimitsu Yura & team find clonal hematopoiesis accelerates aortic aneurysm growth by driving immune cells to become osteoclast-like and destructive.

Proposing a strategy for treating dominant neurodevelopmental disorders: doi.org/10.1172/JCI1... @kaininghu.bsky.social & team report on alternatively spliced exons in brain that trigger mRNA decay, noting modulation of such exons in disease-causal genes may treat NDDs.

Why are damaged muscles more likely to generate fatty tissue as we age? doi.org/10.1172/JCI1... Pei Wang & team find gasdermin E signaling unexpectedly promotes skeletal muscle repair by sustaining tissue-resident macrophage function and restraining maladaptive adipose tissue remodeling.

Rethinking what comes first in obesity and thyroid dysfunction buff.ly/8VyjAYt Nancy Carrasco & team find diet-induced obesity causes remarkable histological adaptation in the thyroids of mice & humans but ultimately induces hypothyroidism by directly impairing thyroid hormone production & action.