Cellular plasticity as a therapeutic vulnerability: HNF4α is a key target in lung adenocarcinoma: doi.org/10.1172/JCI2... Raymond Ho and Jason C. Mills @the-asci.org provide a Commentary on Dadzie et al. doi.org/10.1172/JCI1...

Review: Emerging roles of the cGAS/STING pathway in cardiovascular diseases by Wataru Saitoh et al. Inflammation plays a key role in cardiovascular disease pathogenesis, and accumulating evidence implicates the cGAS/STING pathway: doi.org/10.1172/JCI2...

A special congratulations to our first author, Dr. Abdualrahman Abdualkader, whose dedication and perseverance were instrumental in driving this project and uncovering a previously unrecognized mechanism by which SGLT2 inhibitors directly activate hepatic HMGCS2 to enhance ketogenesis.

Super proud of my former #PDF Rami Al Batran, & all the work he's been doing since starting his lab in 2020. He's been on a killer run w/ several grants from #CIHR @heartandstroke.bsky.social, promotion to AssociateProfessor, with many key papers, including this one @jci.org jci.org/articles/vie...

As part of the JCI’s series on the cGAS-STING pathway: DNA sensing in health and disease: Min-Guk Cho et al. present: Molecular mechanisms regulating cGAS-STING activation in health and disease: doi.org/10.1172/JCI2...

Invasive mucinous adenocarcinoma (IMA) is a unique lung adenocarcinoma subtype featuring profound pulmonary-to-gastric lineage switch during its progression doi.org/10.1172/JCI1... Here, Eric L Snyder & team discover HNF4α controls growth, identity & KRAS inhibitor response in IMA models

As part of the JCI’s series on The cGAS-STING pathway: DNA sensing in health and disease: Mahajan et al. present: Therapeutic targeting of the cGAS–STING pathway in human disease: doi.org/10.1172/JCI2...

BARI spotlight: Alexis Combes and team turned routine biopsy samples into rich maps of what’s happening in inflamed guts. Their work highlights cellular patterns linked to treatment success, offering new paths to help patients with ulcerative colitis get the right therapy sooner. #GutHealth #IBD

How might SGLT2 inhibitors mediate cardiorenal benefits beyond glucose lowering? doi.org/10.1172/JCI1... Rami Al Batran & team report that SGLT2 inhibitors boost ketone production by directly activating a liver enzyme.

BCG has been used to treat bladder cancer for over 50 years. doi.org/10.1172/JCI2... Here, @joshmeeks.bsky.social & team analyzed the tumor microenvironment in patients with bladder cancer, identifying dynamic regulation of myeloid-T cell interactions as a critical for outcomes of BCG.

Beyond neuronal degeneration: oligodendroglial dysfunction as a driver of spinocerebellar ataxia type 1 pathogenesis Associate Editor Puneet Opal discusses compelling evidence from Lee et al. that substantially expands current models of SCA1 pathogenesis: doi.org/10.1172/JCI2...

Can circadian-based therapies promote recovery after ischemic injury? doi.org/10.1172/JCI2... Maiken Nedergaard, @laurenhablitz.bsky.social & team find tactics that reinforce daily rhythmicity after stroke can increase glymphatic flow, lower brain inflammation & improve outcomes in mice

ASCI member Rosas et al. report on its contribution to the profibrotic responses in activated lung fibroblasts & show macropinocytosis inhibition has potent anti-fibrotic effects in pulmonary fibrosis models: doi.org/10.1172/JCI1...

A shared atherogenic mechanism across multiple non-LDL lipoproteins that contribute to residual cardiovascular risk: doi.org/10.1172/JCI1... Cabodevilla et al. identify a region in APOB critical for atherosclerosis development & generate a peptide that reduces atherosclerosis in mice.

From earlier this week: Explaining the clinical association between hyperglycemia and autoimmune skin disease Pan Kang et al. report hyperglycemia aggravates vitiligo through succinate, a metabolite that facilitates CD8+ T cell hyperactivation and skin homing: doi.org/10.1172/JCI2...

Bittersweet: how hyperglycemia exacerbates vitiligo progression through the succinate/SUCNR1 axis: doi.org/10.1172/JCI2... Kaitlyn G. O'Donnell & I. Caroline Le Poole provide a Commentary on Kang et al. doi.org/10.1172/JCI2...

GPR182 and the reframing of lacteal chylomicron uptake: doi.org/10.1172/JCI2... Liqing Yu provides a Commentary on Sun et al. doi.org/10.1172/JCI2...

Neuropathic pain affects millions of people and is extremely difficult to treat. doi.org/10.1172/JCI1... Here, Daniela Menichella & team report a sex-specific role of skin Langerhans cells during the development of neuropathic pain in a mouse model of painful diabetic neuropathy.

Defining key players of a classical endocrine feedback loop, the liver–α-cell axis: doi.org/10.1172/JCI1... Here, E. Danielle Dean & team show that the arginine transporter SLC7A2 plays a critical role in the regulation of insulin and glucagon secretion and α cell proliferation.

Chylomicrons were thought to slip passively into intestinal lymphatics through button-like gaps between cells: doi.org/10.1172/JCI2... Sun et al. now reveal the receptor GPR182 actively drives their transport—and GPR182 KO in mice leads to resistance to high-fat-diet–induced obesity.

NAD+ deficiency is associated with lung fibrosis Here, ASCI member Paul W. Noble & team boost a key NAD+ enzyme, NAMPT, to restore lung cell regeneration and reduce fibrosis, offering a potential treatment for idiopathic pulmonary fibrosis: doi.org/10.1172/JCI1...

Despite treatment with CFTR modulators, inflammation often persists in CF doi.org/10.1172/JCI1... Here, Camilla Margaroli & team report the epidermal growth factor receptor influences how airway neutrophils clear bacteria in CF, revealing a novel mechanism in neutrophil biology.

Metabolic disturbances are a common side effect of ADT for prostate cancer doi.org/10.1172/JCI2... Here, @nimasharifimd.bsky.social & team unveil a surprising link between a common inherited enzyme variant that drives prostate cancer mortality & its effects on bile acid regulation.

📣We're excited to announce an increase in JCI's impact factor to 14.3 (from 13.6, 2024). Thank you authors, reviewers, and readers!

Explaining the clinical association between hyperglycemia and autoimmune skin disease Pan Kang et al. report hyperglycemia aggravates vitiligo through succinate, a metabolite that facilitates CD8+ T cell hyperactivation and skin homing: doi.org/10.1172/JCI2...

The 1st study to integrate Lp(a)-specific proteomic signatures with long-term outcomes starting in young adulthood: doi.org/10.1172/JCI2... Goonewardena et al. find these signatures, reflecting immune & vascular pathways, predict ASCVD risk & mortality, independent of Lp(a) concentration

From earlier this week: What integrins in the cell junction are doing without classical extracellular matrix ligands: doi.org/10.1172/JCI1... Sipilä et al. present ANGPT2 in complex with TIE2 and α5β1-integrin via integrative structural biology techniques.

ICYMI: SCA1 is a neurodegenerative disease driven by polyQ expansion in ATXN1 doi.org/10.1172/JCI1... @limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.

Rewriting the cancer proteome: Targeting selective translation as a therapeutic frontier: doi.org/10.1172/JCI2... Davide Ruggero comments on Misra et al. doi.org/10.1172/JCI1...

New paper from @limlabyale.bsky.social: first author Changwoo (Chris) Lee and lab members show that neurons are not the whole story in ataxia: oligodendrocytes contribute to the development of the disease.

Aging reprograms microglia toward an inflammasome-linked response to traumatic brain injury: doi.org/10.1172/JCI2... Josh M. Morganti and Adam D. Bachstetter comment on Lu et al. doi.org/10.1172/JCI1...

Review: Polyendocrine metabolic ovarian syndrome (PMOS)/polycystic ovary syndrome (PCOS): current and future trends: doi.org/10.1172/JCI2... Jessica L. Chan, Irene Masini & Margareta D. Pisarska discuss the proposed pathophysiology of PMOS from a translational perspective.

Circadian interventions (light, small molecules targeting the clock, food) can improve glymphatics, improve stroke recovery, and reduce neuroinflammation! This was a 5 yr effort from Hablitz Lab (with the assist from Nedergaard lab) out now in JCI! Hope you enjoy! www.jci.org/articles/vie...

Revealing a new type of translation inhibitor in prostate cancer: doi.org/10.1172/JCI1... Andrew C. Hsieh & team report on targeting the eIF4E cap-binding domain in prostate cancer models to drive basal-to-luminal lineage reprogramming and restore sensitivity to AR pathway inhibitors.

Biological aging metrics offer a promising path for evaluating interventions that target aging processes. Review by Douglas E. Vaughan & colleagues: Functional, molecular, and digital measurements of biological age doi.org/10.1172/JCI2...

Providing a promising translatable strategy for older patients with traumatic brain injury: doi.org/10.1172/JCI1... Peipei Gong & team find aging-related inflammatory microglia worsen outcomes of traumatic brain injury and reveal a targetable axis in mouse models.

Host-directed immune therapies: a second front in the battle against sepsis: doi.org/10.1172/JCI2... In this Review, Richard S. Hotchkiss & Guillaume Monneret make a case for reducing sepsis mortality through restoration of the patients’ immune competence.

What if stroke recovery is partly a cleaning problem? #URochesterResearch suggests that restoring circadian rhythms improves the brain's glymphatic system, helping clear inflammatory signals & supporting recovery @laurenhablitz.bsky.social @urochestersmd.bsky.social 👉 www.jci.org/articles/vie...

Glad to see @jci.org featuring our study on endothelial RTK/integrin crosstalk—where ANGPT2 simultaneously engages two receptors! Big thanks to @[email protected] and all co-authors and funders. @HelsinkiUniMed @helsinkiuni doi.org/10.1172/JCI1... #vascularbiology

New study from Pipsa Saharinen’s lab @pipsasaharinen.bsky.social at #WRIHelsinki, featured on the cover of @jci.org: Integrin conformational switching regulates ANGPT2/TIE2/FOXO1 signaling at endothelial cell junctions.👇

SCA1 is a neurodegenerative disease driven by polyQ expansion in ATXN1 doi.org/10.1172/JCI1... @limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.

Immune responses in aging adults: doi.org/10.1172/JCI2... In this Review, Cornelia M. Weyand & Jörg J. Goronzy highlight recent advances revealing how immune aging contributes to immune dysregulation and functional decline, as well as to the onset and progression of autoimmune disease.

What integrins in the cell junction are doing without classical extracellular matrix ligands: doi.org/10.1172/JCI1... Sipilä et al. present ANGPT2 in complex with TIE2 and α5β1-integrin via integrative structural biology techniques.

CoA regulation is important for its central roles in metabolism, yet most studies have focused on its biosynthesis. doi.org/10.1172/JCI2... Here, Jen-Tsan Chi & team discover the phosphatase MESH1 degrades CoA, increasing vulnerability to oxidative damage and driving muscle loss.

ICYMI: Reporting on 2 unrelated patients with a rare inborn error affecting CD48: doi.org/10.1172/JCI1... Milanesi et al. characterize the variants in humans & mice, revealing the importance of CD48 in regulating T-cell responses during infections & in the prevention of excessive inflammation

ICYMI: Providing an in vivo model for MPLW515L-positive myeloproliferative neoplasms (MPNs) doi.org/10.1172/JCI1... Baobing Zhao & team report a megakaryocyte HSC subpopulation as the disease-initiating compartment, driving essential thrombocythemia‑like MPN that resists JAK inhibitor therapy

Sinusoidal endothelial cells control liver inflammation and fibrosis: doi.org/10.1172/JCI2... Yingfen Chen and Yong He provide a Commentary on Gan et al. doi.org/10.1172/JCI1...

Presenting a preclinical and translational evaluation of a bispecific antibody–drug conjugate in advanced prostate cancer: doi.org/10.1172/JCI2... Yao Zhu & team report on a targeted therapy against EGFR & HER3 that delivers a cytotoxic payload and demonstrates effectiveness in mCRPC.

This urine test has the potential to reduce the need for intrusive & costly cystoscopy exams: doi.org/10.1172/JCI2... Joseph C. Liao & team present a highly sensitive urine biomarker test for the detection & surveillance of bladder cancer with the potential to refine cystoscopy selection

The progression of liver cirrhosis has long been studied, yet the events triggering immune cell recruitment have been unclear doi.org/10.1172/JCI1... Gan et al. identify distinct inflammatory niches in liver sinusoidal endothelial cells that amplify pro-inflammatory signaling & fibrosis