PubMed Trending Research Digest — September 26, 2026

Automated digest · 95 articles · 15 research areas · September 26, 2026

Overview

This week’s digest is dominated by mechanistic biology that links signaling and metabolism to disease state transitions. Multiple studies highlight how dysregulated regulatory programs—ranging from post-transcriptional osteogenic switching in CKD vascular calcification (THOC5) to chromatin and epigenetic control in medulloblastoma (KDM2B dependency) and T cell exhaustion (ZMYND8 antagonizing IL-2/STAT5)—can create actionable vulnerabilities. In cancer, several papers converge on microenvironmental and metabolic dependencies: hepatocyte-derived serine supports liver metastasis of serine-dependent PDAC, resident macrophages promote ferroptosis resistance via a selenium transporter axis (Selenop–LRP8), and tumor-intrinsic ceramide metabolism drives colorectal cancer metastasis through YAP activation.

A second major theme is translational and clinical risk stratification using real-world evidence and biomarker frameworks. Real-world effectiveness/safety signals for biologics in asthma and atopic dermatitis (including subgroup-specific response and ocular adverse events) sit alongside cohort and trial designs that aim to personalize therapy—such as NECTIN4 RNA expression for enfortumab vedotin plus pembrolizumab in urothelial cancer, biomarker signatures predicting rheumatoid arthritis flare during tapering, and consensus guidance for autoimmune encephalitis diagnosis and for perioperative systemic therapy trials in hepatocellular carcinoma. In cardiometabolic disease, low-cost indices (SPISE, TyG-based measures) and longitudinal trajectories are repeatedly emphasized as practical tools for earlier prediction of cardiovascular outcomes and multimorbidity.

Finally, the digest includes strong cross-cutting advances in systems biology and computational/structural approaches. Large-scale single-cell atlases and AI scoring frameworks in Alzheimer’s disease and brain disorders (cell-type resolved vulnerability, phenotype-aware cellular characterization, and sTWAS localization) complement mechanistic immune and structural studies (e.g., liver transplant tolerance mediated by EBV-reactive KIR+ CX3CR1+ CD8+ T cells; cryo-EM insights into phage defense and parasite RNA processing). Together, these papers reflect a field moving toward cell-resolved mechanisms, measurable biomarkers, and more rational therapeutic design—spanning from microbiome–gut–brain/respiratory axes to next-generation inhibitor and antibody engineering.

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Diabetes, cardiometabolic risk indices & multimorbidity prediction

Variations in Single-Point Insulin Sensitivity Estimator Index and the Risk of Cardiovascular Disease in Individuals With Cardiovascular-Kidney-Metabolic Syndrome Stages 0 to 3: A National Longitudinal Cohort Study.

This prospective CHARLS cohort study assessed whether longitudinal changes in the single-point insulin sensitivity estimator (SPISE) index—calculated from body mass index, triglycerides, and HDL cholesterol—in individuals with cardiovascular-kidney-metabolic syndrome stages 0 to 3 predicted incident cardiovascular disease (CVD). The key finding was that variations/trajectories in SPISE index were associated with CVD risk in this preclinical population. These results support using dynamic SPISE trajectories as a practical metabolic risk marker for earlier CVD prevention in people with cardiovascular-kidney-metabolic syndrome.

Shi Y, Shen Y · Journal of the American Heart Association · (2026) · View on PubMed ↗ · Free PDF ↗

Diagnosing autoimmune encephalitis in psychiatry: clinical recommendations and unresolved challenges from the GENERATE network.

This GENERATE network consensus paper synthesized interdisciplinary psychiatry–neurology recommendations for diagnosing autoimmune encephalitis (AE) in patients presenting with psychiatric syndromes, including cases with predominant or isolated psychiatric symptoms. The key finding was that standardized diagnostic pathways and clear criteria are needed to reduce variability across clinical settings and to improve identification of AE when psychiatric symptoms are the initial presentation. Clinically, it provides actionable guidance to clinicians on when and how to pursue AE workup in psychiatry to enable earlier, more targeted treatment.

Endres D, von Zedtwitz K, Tebartz van Elst L et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

Expert consensus on clinical trials for use of systemic therapy in patients with hepatocellular carcinoma undergoing surgical and locoregional therapies.

This expert consensus from the HCC-Live Consortium reviewed evidence and proposed trial design considerations for systemic therapy in hepatocellular carcinoma (HCC) patients undergoing surgical and locoregional therapies, focusing on perioperative and combination strategies. The key finding was the establishment of consensus recommendations (>70% approval) on inclusion criteria, risk stratification, treatment arms, and appropriate endpoints for these heterogeneous early/intermediate-stage populations. Scientifically and clinically, it aims to standardize how future trials are designed to generate interpretable results in earlier-stage HCC.

Yarchoan M, Llovet JM, Kelley RK et al. · Gut · (2026) · View on PubMed ↗

Circulating biochemical signatures of neurodegeneration in Alzheimer’s disease.

This review summarized circulating biochemical signatures relevant to neurodegeneration in Alzheimer’s disease (AD) and emphasized that molecular changes occur before behavioral symptoms. The key finding was that blood-based biochemical approaches could complement or extend neuroimaging and cerebrospinal fluid methods for earlier and more accessible monitoring of AD-related neurodegeneration. Clinically, it supports continued development of peripheral biomarkers to enable earlier diagnosis and disease tracking in AD.

Eliazer GR, Kandasamy M · International review of neurobiology · (2026) · View on PubMed ↗

Dynamic changes in plasma biomarkers of Alzheimer’s disease in patients treated with lecanemab: a longitudinal cohort study.

This longitudinal cohort study followed patients with early symptomatic Alzheimer’s disease who were amyloid PET–positive and received biweekly infusions of the anti-amyloid antibody lecanemab, measuring changes in a panel of 130 plasma proteins and relating them to conversion to amyloid PET negativity and cognitive change. Lecanemab treatment was associated with dynamic, time-dependent shifts in neurodegeneration-linked plasma biomarkers, and specific protein trajectories correlated with amyloid PET conversion and cognitive outcomes. These findings support plasma proteomic monitoring as a potential pharmacodynamic readout for anti-amyloid therapy and may help refine biomarker-driven patient tracking in early symptomatic Alzheimer’s disease.

Mu R, Hofmann A, Gong K et al. · The Lancet. Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration.

This study used a single-cell transcriptomic atlas of human brain vasculature to determine how the Alzheimer’s genetic risk factor APOE4 affects cerebrovascular cell states, focusing on pericytes and downstream fibroblast-like populations. In APOE4 carriers, pericyte abundance was reduced and a myofibroblast-like population emerged that co-expressed contraction and extracellular matrix genes, with immunostaining confirming non-vascular myofibroblasts in APOE4 human and mouse brains. The results link APOE4 to a pericyte-to-myofibroblast transition as a cellular mechanism for cerebrovascular degeneration, informing targets to prevent vascular pathology in Alzheimer’s disease.

Schuldt BR, Haworth-Staines D, Perez-Arevalo A et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Androgenetic alopecia drugs and male infertility: Evidence from pharmacovigilance and testicular transcriptomics.

This study investigated whether androgenetic alopecia (AGA) drugs—finasteride, dutasteride, and minoxidil—are associated with male infertility-related adverse events using pharmacovigilance databases (FAERS and EudraVigilance) and explored infertility biology using testicular transcriptomic datasets. The authors reported disproportionality signals linking AGA drugs to infertility-related adverse events and used testicular transcriptomics (including single-cell RNA-seq and intercellular communication analyses) to identify candidate molecular features underlying these associations. These findings suggest a potential drug–infertility risk signal for AGA therapies and provide mechanistic hypotheses to guide future reproductive safety studies.

Gong Z, He J, Feng Q et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Transition to once-weekly growth hormone in paediatric isolated growth hormone deficiency: A real-world experience.

This single-centre retrospective study evaluated real-world auxological and biochemical outcomes in 73 paediatric patients with isolated growth hormone deficiency (52 boys) transitioning from daily recombinant human growth hormone to once-weekly somatrogon. After 6 months (and with additional follow-up at 12 and 18 months for subsets), the key outcomes were changes in height standard deviation score (SDS) and height velocity SDS, indicating how growth response and monitoring parameters evolved after the switch. The results support evidence for the effectiveness and safety monitoring of once-weekly somatrogon in routine clinical care for children with isolated GHD.

Sotiriou G, Moutafi M, Triantafyllou P et al. · European journal of endocrinology · (2026) · View on PubMed ↗

Predictors of trajectories of suicidal thoughts in Texas youth depression and suicide research network youth.

This study analyzed longitudinal suicidal ideation trajectories in 1,449 youth with depression/suicidality from the Texas Youth Depression and Suicide Research Network and tested baseline clinical and sociodemographic predictors of trajectory membership. Using group mixture models to identify multiple suicidal-thought trajectory groups and random forest analyses to evaluate predictors, the authors identified baseline features that differentiated which youths followed higher- versus lower-risk ideation paths over the subsequent 6 months. Clinically, these trajectory-informed predictors could improve early risk stratification and targeting of preventive interventions for suicidal ideation in depressed youth.

Minhajuddin A, Walker RA, Jha MK et al. · Psychological medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cannabis use is associated with increased risk of violence: A systematic review and meta-analysis.

This systematic review and meta-analysis synthesized evidence from 63 studies (N=265,079) to quantify the association between cannabis use and violence risk, considering cannabis users as perpetrators and/or victims. Random-effects meta-analysis found that cannabis users had a significantly higher risk of perpetrating violent acts, with the association observed in psychiatric patient populations. These results strengthen the evidence base for cannabis use as a violence-related risk factor and support incorporating substance-use history into violence-risk assessment and prevention strategies.

Trotta G, Rodriguez V, Marino P et al. · Psychological medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.

This study used single-nucleus RNA-seq from the Seattle Alzheimer’s Disease Brain Cell Atlas to compare non-neuronal cell transcriptional programs in middle temporal gyrus tissue from donors classified as LATE-NC dominant, ADNC dominant, or mixed LATE-NC/ADNC pathology. The authors report distinct, cell-type-specific single-nucleus RNA-seq changes across these neuropathology groups, indicating that LATE-NC and ADNC leave separable molecular signatures in non-neuronal populations. These findings improve molecular stratification of mixed Alzheimer-spectrum pathology and can guide downstream biomarker and mechanism discovery beyond bulk diagnosis.

Qiao Q, Katsumata Y, Lai HY et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Triglyceride-glucose waist-to-height ratio in relation to prevalent and incident multimorbidity: cross-sectional and prospective evidence from four national studies.

This analysis studied whether the triglyceride-glucose waist-to-height ratio (TyG-WHtR) predicts prevalent and incident multimorbidity in adults aged ≥50 years using cross-sectional and prospective data from NHANES, HRS, CHARLS, and ELSA. The key finding is that higher TyG-WHtR is associated with greater multimorbidity burden and shows a dose-response relationship with an identifiable threshold for risk. Clinically, TyG-WHtR could serve as an inexpensive screening metric for identifying older adults at elevated risk of developing multiple chronic conditions.

Shao Z, Hu H, Ge X et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Integrative plasma proteomic network analysis identifies physical activity-associated protein modules potentially mediating type 2 diabetes risk.

This study investigated whether moderate-to-vigorous physical activity (MVPA) is associated with incident type 2 diabetes (T2D) through specific plasma protein modules in 28,842 diabetes-free UK Biobank participants with baseline proteomics. It reports that MVPA is linked to lower T2D risk and that integrative plasma proteomic network analysis identifies physical-activity-associated protein co-expression modules, with mediation analyses implicating individual proteins in the pathway. These results provide candidate circulating protein targets and mechanistic biomarkers for how MVPA reduces T2D risk.

Wang Z, Su CY, Lu J et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Antecedent, landmark, and two-visit cumulative triglyceride-glucose index and non-traditional lipid measures in relation to incident cardiovascular disease in adults with cardiovascular-kidney-metabolic syndrome (CKM) stages 0-3: a nationwide prospective cohort study.

This nationwide prospective cohort study evaluated whether antecedent, landmark, and two-visit cumulative triglyceride-glucose (TyG) index measures and non-traditional lipid parameters (nTLPs) predict incident cardiovascular disease across cardiovascular-kidney-metabolic (CKM) stages 0–3 using the China Health and Retirement Longitudinal Study. The authors find that TyG and specific nTLPs show longitudinal associations with cardiovascular outcomes and that cumulative/landmark approaches improve prognostic discrimination. Scientifically and clinically, the work supports using low-cost metabolic-lipid indices to refine CVD risk stratification in CKM populations.

Lu A, Xu Q · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data.

This Nature Medicine study used the PsychAD project’s population-scale single-nucleus RNA-seq dataset (6+ million nuclei from >1,000 brains) to develop PASCode, an AI framework for scoring single-cell phenotype associations in Alzheimer’s disease. The key finding is that the model identifies ~1.5 million phenotype-associated cells (PACs) across 584 donors and links these cells to specific AD clinical phenotypes, enabling phenotype-aware cellular characterization. This provides a scalable computational route to connect single-cell molecular states to heterogeneous AD symptoms, supporting more precise phenotype stratification for research and potential clinical translation.

He C, Li AZ, Hanthanan Arachchilage K et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Optimizing the delivery of radiotherapy with artificial intelligence.

The review studied how artificial intelligence (AI) and machine learning are being applied to optimize radiotherapy delivery in radiation oncology workflows and clinical deployment. It reports that AI has already been used for tasks including auto-contouring, geometric adaptation, dose calculation, quality assurance, and outcome prediction, but real-world clinical uptake lags due to technical, practical, ethical, and legal barriers, with newer approaches expanding toward generative AI and foundation models. This matters because improving safe, scalable AI integration could accelerate more personalized and efficient radiotherapy planning and delivery while addressing governance and implementation risks.

Katsoulakis E, El Naqa I · Nature reviews. Clinical oncology · (2026) · View on PubMed ↗

Single-cell atlas of transcriptomic vulnerability across brain disorders.

This study generated a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex using specimens from 1,494 unique donors across neurotypical controls and eight brain disorders including Alzheimer’s disease, diffuse Lewy body disease, and vascular dementia. The key finding is the creation of a large, multi-disorder single-cell resource comprising over 6.3 million nuclei that maps transcriptomic vulnerability across brain disorders. Scientifically, this atlas enables cell-type–resolved comparisons of disease-associated molecular programs and supports discovery of mechanisms and potential biomarkers across neurodegenerative and neuropsychiatric conditions.

Lee D, Koutrouli M, Masse NY et al. · Nature · (2026) · 5 citations · View on PubMed ↗ · Free PDF ↗

Lifespan single-cell transcriptomic atlas of the human prefrontal cortex.

This study investigated how cellular and molecular programs in the human dorsolateral prefrontal cortex change across the lifespan by building a lifespan single-cell transcriptomic atlas. The key finding is that the atlas provides a structured, cell-type–resolved view of age-associated transcriptional programs across early development to late adulthood. This is significant because it improves interpretation of normal aging and clarifies how age-related cellular states may shape vulnerability to psychiatric and neurodegenerative disease.

Yang H, Clarence T, Scott MR et al. · Nature · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

Single-nucleus transcriptome-wide association study of human brain disorders.

This study examined how genetic risk for human brain disorders maps to gene expression in specific cell types by performing a single-nucleus transcriptome-wide association study (sTWAS) using dorsolateral prefrontal cortex single-nucleus profiles from the multi-ancestry PsychAD cohort. The key finding is that single-nucleus, multi-ancestry data can better localize non-coding GWAS risk to cell-type–specific gene expression changes than bulk European-ancestry approaches that average across cellular diversity. This is clinically and scientifically important because it helps connect GWAS loci to mechanistic targets in relevant brain cell types for neuropsychiatric and neurodegenerative disorders.

Venkatesh S, Kosoy R, Wu Z et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Diagnosis and management of Silver-Russell syndrome: second international consensus statement.

This consensus statement studied updated diagnosis and management strategies for Silver-Russell syndrome (SRS) using a Delphi-like process to integrate published evidence and expert opinion. The key finding is that genomic and epigenomic advances support strict, primarily molecular diagnostic criteria, particularly for individuals with maternal uniparental disomy for chromosome 7 (upd(7)mat) or H19/IGF2 imprinting loss of methylation at the IG-DMR on 11p15. Clinically, this standardization improves diagnostic accuracy and guides consistent care for a genetically heterogeneous disorder.

Wakeling E, Davies JH, Giabicani E et al. · Nature reviews. Endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila.

The study investigated how the storage protein Lsp2 regulates nutrient-sensing mTORC1 signaling and translation of 5’-terminal oligopyrimidine (TOP) motif mRNAs in Drosophila, linking these processes to organismal lifespan. Lsp2 was found to connect mTORC1 activity to TOP mRNA translation in a way that tunes translational burden and promotes lifespan outcomes. This identifies Lsp2 as a mechanistic bridge between mTORC1-dependent translational control of ribosomal-protein TOP mRNAs and aging, suggesting a new target axis for lifespan modulation.

Wang J, Cai Z, Gu J et al. · Nature · (2026) · 2 citations · View on PubMed ↗

Lsp2 links early-life diet to adult translation and lifespan in Drosophila.

The study examined whether early-life protein restriction (ePR) in Drosophila alters adult translation programs and lifespan, using stable-isotope tracing to follow dietary amino acids into adulthood. Early-life protein restriction increased adult lifespan by lowering storage protein levels and by showing that larval-stage amino acids are retained into early adulthood and incorporated into ribosomal components. These findings provide a mechanistic link between juvenile diet, ribosome biogenesis/translation capacity, and lifespan extension.

Kosakamoto H, Okada R, Barker CS et al. · Nature · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

Maternal obesity programs offspring metabolic dysfunction via small extracellular vesicle-mediated epigenetic remodeling.

The study tested whether maternal obesity programs offspring metabolic dysfunction via small extracellular vesicles (sEVs) carrying microRNAs, using a diet-induced obesity (DIO) mouse model and assessing male offspring insulin sensitivity. Maternal circulating sEVs crossed the placenta and delivered obesity-associated miRNAs to fetal liver, where elevated miR-29a-3p targeted DNA methyltransferases and demethylases to remodel DNA methylation, including hypomethylation of the Pgc-1α locus, leading to premature activation of gluconeogenesis-related phenotypes. This provides an intergenerational epigenetic mechanism—sEV miRNA delivery to fetal liver—that could inform prevention or intervention strategies for obesity-linked metabolic disease.

Song H, Li D, Ma L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Tirzepatide versus GLP-1 receptor agonists and stroke in patients with atrial fibrillation and type 2 diabetes.

The study compared stroke outcomes associated with tirzepatide versus GLP-1 receptor agonists in adults with atrial fibrillation and type 2 diabetes using a retrospective, matched-pair cohort from a large international federated electronic health-record network. Among 14,118 matched pairs, tirzepatide initiation was associated with lower risks of any stroke, ischemic stroke, hemorrhagic stroke, and all-cause death compared with other GLP-1 receptor agonists. This suggests a clinically relevant cerebrovascular risk reduction signal for tirzepatide in a high-risk population, warranting prospective confirmation.

Lin CL, Lin KC, Yu JM et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of Life’s Essential 8 cardiovascular health score with prevalent microvascular complications stratified by sex and menopausal status in Chinese adults with type 2 diabetes: a cross-sectional study.

This cross-sectional study assessed associations between the American Heart Association Life’s Essential 8 (LE8) cardiovascular health score and prevalent microvascular complications in Chinese adults with type 2 diabetes, stratified by sex and menopausal status. The key finding was that LE8 score tiers were associated with the burden of microvascular complications and that these associations differed by sex and menopausal status. This is significant for risk stratification and prevention planning in T2DM by using a composite cardiovascular health metric to anticipate microvascular disease patterns.

Qiu L, Feng Y, Zhou Y et al. · BMJ open diabetes research & care · (2026) · View on PubMed ↗ · Free PDF ↗

Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation.

This target trial emulation used linked electronic health records and claims from 10 health systems and two national insurance plans (BESTMED) to compare renal deterioration risk in people with type 2 diabetes treated with SGLT-2 inhibitors versus GLP-1 receptor agonists, stratified by albuminuria status (albumin-to-creatinine ratio ≥30 mg/g). The key finding is the comparative assessment of renal outcomes under these second-line therapies versus other treatments across patients with and without albuminuria, using emulated treatment groups rather than randomization. Clinically, the results aim to clarify which drug class better preserves kidney function in type 2 diabetes depending on baseline albuminuria.

Turchin A, Petito LC, Hegermiller E et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗ · Free PDF ↗

Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study.

This nationwide nested case-control study in Danish registries examined associations between current menopausal hormone therapy use and risks of venous thromboembolism, ischemic stroke, and myocardial infarction in women aged 50–69 years. The key finding is the quantification of thrombotic and cardiovascular event risks associated with current hormone therapy use while excluding women with prior thrombosis, arterial thrombosis, cancer, liver disease, thrombophilia, and several other confounders. The findings are significant for refining risk–benefit decisions for menopausal hormone therapy in real-world populations.

Berggreen J, Pourhadi N, Wood-Kurland H et al. · BMJ (Clinical research ed.) · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

QTc changes and early major adverse cardiovascular events associated with antidepressant treatment for major depressive disorder in adults: individual participant data network meta-regression of double blind randomised trials.

This individual participant data network meta-regression of double-blind randomized trials compared specific antidepressants versus placebo on early (first 8 weeks) QTc changes in adults with major depressive disorder and assessed whether antidepressant-associated QTc effects relate to early major adverse cardiovascular events (MACE). The key finding is the integrated analysis linking antidepressant-specific QTc trajectories to early cardiovascular outcomes using both individual-level and aggregate trial data. Scientifically and clinically, it helps identify antidepressants with higher or lower early cardiac electrical risk and informs safer prescribing in patients vulnerable to arrhythmia or cardiovascular events.

Ostinelli EG, Capocci S, Li Z et al. · BMJ (Clinical research ed.) · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

Results from the Phase 2 Explore-CKD Trial of lorundrostat, a novel aldosterone synthase inhibitor, in participants with uncontrolled hypertension, chronic kidney disease, and albuminuria.

This report presented results from the randomized, double-blind, placebo-controlled crossover Explore-CKD phase 2 trial of lorundrostat, a selective aldosterone synthase inhibitor, added to an SGLT2 inhibitor in adults with uncontrolled hypertension, chronic kidney disease, and albuminuria. The key finding is the trial’s evaluation of lorundrostat 25 mg/day on top of stable SGLT2 inhibitor therapy in this specific high-risk CKD population. If beneficial effects on kidney and blood-pressure outcomes are demonstrated, it would support aldosterone-synthesis targeting as an add-on strategy for CKD patients with albuminuria.

Weir MR, Bhaduri S, Lee K et al. · Kidney international · (2026) · View on PubMed ↗

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Asthma & biologic therapy effectiveness/safety (incl. AERD, ocular AEs)

Distinct intestinal eosinophil subsets in ulcerative colitis and their modulation by advanced inflammatory bowel disease therapies.

This study profiled intestinal eosinophil subsets in ulcerative colitis (UC) using flow cytometry of colonic immune cells (with matched stool fecal calprotectin and eosinophil-derived neurotoxin) and evaluated how advanced inflammatory bowel disease therapies modulated these subsets in a baseline-to-post-induction cohort. The key finding was that distinct eosinophil subsets exist in UC and that advanced therapies differentially modulate these subsets, with changes linked to treatment response defined by Mayo endoscopic subscore 0–1. This provides mechanistic and biomarker-relevant insight into how advanced UC therapies reshape eosinophil biology beyond histology.

Jacobs I, Ceulemans M, Lenfant M et al. · Journal of Crohn’s & colitis · (2026) · View on PubMed ↗

Tezepelumab effectiveness in Aspirin-Exacerbated Respiratory Disease: a real-world multicenter study.

This multicenter retrospective real-world study evaluated tezepelumab effectiveness in patients with severe uncontrolled asthma and aspirin-exacerbated respiratory disease (AERD) versus those without AERD, using tezepelumab 210 mg every 4 weeks for 12 months. Patients with AERD showed clinical outcomes with tezepelumab in routine practice that were assessed against non-AERD comparators, addressing a gap in real-world evidence for this subgroup. Clinically, the findings support evidence-based use of tezepelumab in AERD-associated severe asthma and inform expectations for effectiveness outside randomized trials.

Betancor D, Villalobos-Violan V, Antolin-Amerigo D et al. · Respiratory medicine · (2026) · View on PubMed ↗

Ocular Safety of Dupilumab Compared With IL-5 Inhibitors in Asthma.

This retrospective cohort study compared ocular adverse event (OAE) risk between dupilumab and IL-5 inhibitors (mepolizumab or benralizumab) in adults with asthma using a target trial emulation framework and the TriNetX US Collaborative Network (2018–2025). It found differential OAE risk profiles for dupilumab versus IL-5 inhibitors, addressing uncertainty about comparative ocular safety in asthma. The clinical significance is that it informs risk–benefit decisions for biologic selection in asthma patients concerned about ocular side effects.

Tsao HM, Wu PL, Wang YH et al. · The journal of allergy and clinical immunology. In practice · (2026) · View on PubMed ↗

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Cancer metabolism & tumor microenvironment nutrient coupling

Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial.

In the randomized phase 2 portion of ASPEN-06, this trial studied evorpacept (a CD47–SIRPα interaction blocker) plus trastuzumab, ramucirumab, and paclitaxel versus trastuzumab/ramucirumab/paclitaxel alone in 127 patients with pretreated HER2-overexpressing advanced gastric or gastroesophageal junction cancer. The key finding was that adding evorpacept to the chemotherapy/anti-HER2 regimen improved the primary efficacy signal (investigator-assessed objective response rate) compared with the control arm. Clinically, this supports further development of CD47-targeted phagocytosis enhancement as an immuno-oncology strategy in HER2+ gastric cancer.

Shitara K, Wainberg Z, Tabernero J et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Pretreatment Tumor NECTIN4 RNA Expression Is Associated with First-line Enfortumab Vedotin Plus Pembrolizumab Efficacy in Metastatic Urothelial Cancer.

This retrospective real-world study evaluated whether pretreatment tumor NECTIN4 RNA expression and tumor mutational burden (TMB) predicted outcomes in 322 patients with metastatic urothelial cancer receiving first-line enfortumab vedotin plus pembrolizumab (EV + P). The key finding was that NECTIN4-high tumors were associated with better overall survival and higher best overall response compared with NECTIN4-low tumors. This supports NECTIN4 RNA expression as a potential predictive biomarker to refine patient selection for EV + P in metastatic urothelial cancer.

Cho BA, Perry CJ, Yoo SK et al. · European urology · (2026) · View on PubMed ↗

Resident tissue macrophages transfer selenium transporter protein to protect pancreatic cancer from ferroptosis.

Using single-cell profiling, spatial analysis, lineage tracing, and selenium tracing, this study investigated how resident tissue macrophages (RTMs) influence ferroptosis resistance in pancreatic ductal adenocarcinoma (PDAC). RTMs localized preferentially to the tumor border and promoted EMT, tumor growth, and metastasis by transferring the selenium transporter Selenop to EMT-high tumor cells via LRP8-dependent uptake, thereby increasing tumor-cell selenium and suppressing ferroptosis. The work identifies an RTM–Selenop–LRP8 axis as a mechanistic vulnerability that could be targeted to sensitize PDAC to ferroptosis-based therapies.

Guo W, Li Z, Chen Q et al. · Cell · (2026) · View on PubMed ↗

Ceramide synthesis mediates colorectal cancer metastasis through a YAP-driven regenerative program.

This study investigated how tumor-intrinsic ceramide metabolism drives colorectal cancer metastasis, using mechanistic experiments linking dietary fat exposure to ceramide biosynthesis and downstream signaling. Dietary fat increased de novo ceramide synthesis via the enzyme dihydroceramide desaturase Degs1, leading to ceramide accumulation that activated YAP through PP2A-mediated dephosphorylation and promoted a durable YAP-driven regenerative program (including Basp1) that enhanced metastasis. The work connects a specific metabolic pathway (Degs1–ceramide) to YAP activation as a targetable driver of metastatic progression in colorectal cancer.

Goswami S, Zhang Q, Yildiz AB et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Senescence-directed nanotherapy ameliorates fibrosis and overcomes immune exclusion in cancer.

Using a nanoparticle-based approach, this study tested whether senescence-directed targeting can modulate fibrotic and immunosuppressive tumor microenvironments by focusing on P-selectin–expressing senescent-like cells. Fucoidan-based nanoparticles that bind P-selectin (senescence-modulating nanoparticles, SMNPs) selectively targeted these disease-associated senescent-like states and produced antifibrotic and immunomodulatory effects while overcoming immune exclusion. The findings suggest a strategy to improve immunotherapy responsiveness by functionally reprogramming senescence-associated cells in fibrosis and cancer.

Hinterleitner C, Barthet VJA, Goldberg HV et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Mammals produce cyclo-octasulfur to suppress lipid peroxidation and ferroptosis.

This study explored sulfur metabolism in mammals by identifying the presence, biosynthesis, and function of cyclo-octasulfur (S8) in mouse and human cells. S8 accumulated to millimolar levels in mitochondrial membranes and lipid droplets, was produced via a lipid droplet–associated nitric oxide synthase source, and limited lipid peroxidation to suppress ferroptosis. The discovery of an S8-based antioxidant mechanism provides a new metabolic pathway that could be leveraged to prevent ferroptosis-related tissue damage.

Barayeu U, Ogata S, Takata T et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Targeting an atypical G protein-coupled receptor signaling pathway for cardiac fibrosis therapy.

This study used a multidimensional drug discovery pipeline centered on a human induced pluripotent stem cell (iPSC) platform to identify and characterize therapies for cardiac fibrosis. It identified CGS15943 (CGS) as a lead antifibrotic compound that inhibited fibrotic remodeling in human cardiac fibroblasts, 3D engineered heart tissues, and animal models of heart failure, acting through an atypical adenosine receptor (AR) signaling pathway that converges on Gβγ. The work provides a candidate small molecule and a defined receptor–G-protein mechanism for developing targeted anti-fibrotic therapies in heart failure.

Zhang H, Shivnaraine RV, Ren L et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Search for leukemia-restricted targets: a new paradigm for precision immunotherapy in acute myeloid leukemia.

This article reviewed the rationale and emerging strategies for identifying leukemia-restricted targets to enable precision immunotherapy in acute myeloid leukemia (AML). The key finding is a proposed “new paradigm” emphasizing the discovery of targets preferentially expressed in AML (and not in essential normal tissues) to overcome the limitations of prior immunotherapy approaches in high-risk AML subtypes. Scientifically, this framework aims to improve the therapeutic index of AML immunotherapies and guide target selection for more effective, safer precision treatments.

Meshinchi S, Locatelli F · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

Rituximab maintenance following frontline bendamustine-rituximab in mantle cell lymphoma: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated rituximab maintenance after frontline bendamustine-rituximab in mantle cell lymphoma. Although the abstract was not available, the study’s purpose was to synthesize comparative evidence on efficacy and safety outcomes associated with rituximab maintenance strategies. The findings are intended to inform clinical decision-making on whether and how to use rituximab maintenance following initial bendamustine-rituximab induction in MCL.

Wang J, Yi D, Gao Y et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis.

Using the Center for International Blood and Marrow Transplant Research registry, this study assessed real-world outcomes of frail versus nonfrail patients receiving commercial ciltacabtagene autoleucel (cilta-cel), an anti-BCMA CAR-T therapy, for relapsed/refractory multiple myeloma. Among 541 patients with frailty status, 183 (33.8%) were frail and overall response rates were comparable between frail (82.8%) and nonfrail (88.5%) groups, with the study evaluating broader efficacy and safety endpoints. These results support the feasibility of cilta-cel in frail RRMM patients and help clinicians weigh benefit–risk in a population often underrepresented in trials.

Mian H, Faisal MS, Chen T et al. · Cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Randomized phase II trial of liposomal cytarabine and daunorubicin with or without pomalidomide in newly diagnosed acute myeloid leukemia myelodysplasia-related.

This randomized phase II trial evaluated liposomal cytarabine plus daunorubicin with or without pomalidomide in newly diagnosed acute myeloid leukemia with myelodysplasia-related changes. The abstract was not available, but the study design indicates a direct comparison of adding pomalidomide to standard liposomal chemotherapy to test efficacy and safety in this specific AML-MR population. If positive, the trial could establish a new combination strategy for newly diagnosed AML-MR by improving outcomes beyond chemotherapy alone.

Peters DT, Koenig K, Ivanova A et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

The Role of EVs in the Aging Hematopoietic System.

This review examined how extracellular vesicles (EVs) mediate communication within the aging hematopoietic system, focusing on bone marrow niche cells and hematopoietic stem/progenitor cells (HSPCs). It finds that aging-driven senescence and telomere attrition remodel EV biogenesis and cargo, with aged EVs (notably from senescent mesenchymal stromal cells and osteoblasts) showing altered microRNA profiles and reduced antioxidant protection that perpetuates niche dysfunction. The work highlights EV cargo as a mechanistic link between aging and impaired hematopoiesis and suggests EV-targeted interventions as potential therapeutic strategies.

Kosebent EG, Havranek N, Kollmann K et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

The emerging roles of disulfidptosis in cancer.

This systematic review and reconstructed individual patient data meta-analysis compared neoadjuvant chemoimmunotherapy (NCIT) versus standard neoadjuvant chemoradiotherapy (NCRT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). The analysis reports differences in efficacy and safety endpoints—particularly pathological response measures such as pCR and MPR—along with reconstructed overall survival and progression-free survival estimates from Kaplan–Meier curves. Clinically, the findings help determine whether adding immunotherapy to neoadjuvant strategies can improve outcomes beyond chemoradiotherapy in resectable LA-ESCC.

Zhu YH, Liu YX, Liu YX et al. · Apoptosis : an international journal on programmed cell death · (2026) · View on PubMed ↗

Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy.

This article reviews emerging evidence on disulfidptosis, a regulated cell death program driven by disulfide stress and characterized by metabolic dependence on cystine handling and redox balance. It highlights a mechanistic framework in which pathological intracellular cystine accumulation and NADPH depletion (reducing equivalents) trigger disulfidptosis, offering a distinct vulnerability compared with other cell death pathways. The scientific significance is that disulfidptosis may be exploitable for cancer therapy, potentially overcoming resistance mechanisms tied to conventional apoptosis pathways.

Kethidi N, Pothukuchi S, Aleman A et al. · Nature medicine · (2026) · View on PubMed ↗

NLRX1 is a critical neutrophil checkpoint modulating ferroptosis and suppressing NETosis to attenuate joint damage in arthritis.

This study investigated the role of the mitochondrial innate immune receptor NLRX1 in neutrophil regulation of ferroptosis and neutrophil extracellular trap (NET) formation in rheumatoid arthritis (RA) and joint damage. It found that NLRX1 is dysregulated in RA, that NLRX1 deficiency (including neutrophil-specific loss) expands neutrophils and accelerates arthritis with increased NETosis and joint injury, and that single-cell RNA sequencing supports a mechanistic link to pathways controlling these inflammatory cell states. The significance is that NLRX1 functions as a neutrophil checkpoint and could represent a therapeutic target to limit NET-driven pathology in arthritis.

Feng Z, Liu R, Hou J et al. · Cell death and differentiation · (2026) · View on PubMed ↗ · Free PDF ↗

Hepatocytes promote liver metastasis of pancreatic cancer by providing serine.

The study examined how hepatocytes support liver metastasis of pancreatic ductal adenocarcinoma (PDAC) by providing serine, focusing on PDAC cells with PHGDH loss that depend on exogenous serine. It found that hepatocyte-derived serine promotes metastatic colonization of exSer-dependent PDAC cells in the liver microenvironment. This identifies a specific metabolic coupling (hepatocyte serine supply–tumor serine dependence) that could be therapeutically targeted to limit liver metastasis.

Ganguly K, Yamamoto K, Rodencal J et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Antibody-drug conjugate engineering: from design to efficacy and safety.

This article reviewed how antibody-drug conjugates (ADCs) are engineered for efficacy and safety, emphasizing the interdependent roles of antigen selection, antibody engineering, linker chemistry, and payload pharmacology. It highlights recent advances where AI and computational biophysics enable more rational ADC design by integrating genomic, transcriptomic, and proteomic data to improve optimization beyond empirical approaches. The review’s significance is providing a framework for accelerating ADC development and improving therapeutic index through data-driven, mechanistic design strategies.

Ocana A, Espinosa JR, Alonso-Moreno C et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.

This review examined how cuproptosis and ferroptosis—two metal-dependent regulated cell death pathways—operate in cells and contribute to disease, focusing on their shared and distinct signaling mechanisms. It found that although cuproptosis is driven by copper-mediated disruption/aggregation of lipoylated mitochondrial proteins and ferroptosis by iron-dependent phospholipid peroxidation, the pathways intersect via mitochondrial metabolism, redox imbalance, iron–sulfur cluster biology, and organelle crosstalk. The synthesis highlights lysosome–mitochondria–endoplasmic reticulum interactions as therapeutic target opportunities for diseases where these death programs are dysregulated.

Li YY, Tay FR · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Butyrylcholinesterase alleviates hepatic stellate cell activation via paracrine muscarinic signalling.

This experimental study investigated whether butyrylcholinesterase (BuChE) modulates hepatic stellate cell activation and fibrosis through paracrine muscarinic acetylcholine (ACh) signaling in human biopsies and mouse models. It found that BuChE expression in patient tissue and BuChE genetic manipulation (Buche ΔHep and Buche KI/KI-Hep mice), together with pharmacologic inhibition and recombinant/mutant BuChE conditioned media, altered ACh bioavailability and downstream muscarinic receptor signaling to alleviate stellate cell activation. The results are clinically relevant because they identify a cholinergic paracrine mechanism that could be therapeutically targeted to reduce liver fibrogenesis.

Tao L, Liu N, Zhang W et al. · Gut · (2026) · View on PubMed ↗

SPP1+ macrophage-induced CD74+ tumor cells promote adrenocortical carcinoma tumor thrombus via the SPP1/CD44/JAK/STAT signaling.

This study examined how SPP1+ macrophage signaling promotes venous tumor thrombus formation in adrenocortical carcinoma through CD74+ tumor cells and the SPP1/CD44/JAK/STAT pathway. Using integrated single-cell RNA sequencing and spatial transcriptomics on paired primary tumor and tumor thrombus samples from an ACC patient, followed by in vitro and in vivo functional validation, it found that a CD74+ tumor cell subcluster enriched in the VTT head region drives thrombus-promoting behavior and that CD74 enhances ACC via SPP1/CD44/JAK/STAT signaling. The work is significant because it identifies a mechanistic axis that could be targeted to prevent or treat ACC-associated tumor thrombus.

Zhang H, Xu K, Zhen L et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.

This single-center phase II trial studied first-line ivonescimab (PD-1/VEGF bispecific) plus paclitaxel and carboplatin in treatment-naïve patients with stage IVb advanced thymic carcinoma, with biomarker analyses. The key finding reported in the abstract is that the regimen was evaluated with ivonescimab given at 20 mg/kg every 3 weeks for 4–6 cycles followed by ivonescimab maintenance, aiming to improve outcomes beyond the <40% response rates typical of platinum chemotherapy and the inconsistent efficacy of checkpoint inhibitors alone. If efficacy and biomarker signals are confirmed, this strategy could establish a new chemo-immunotherapy standard for advanced thymic carcinoma by combining PD-1 blockade with VEGF inhibition.

Ma JT, Sun L, Zhang LY et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Deletion of protein FSTL3 unravels the role of activin signaling in regulating macrophage L-arginine metabolism and kidney injury.

This study investigated the role of the activin antagonist FSTL3 in kidney injury by combining human biomarker measurements with mechanistic mouse and macrophage experiments. The key finding is that deletion of FSTL3 disrupts activin signaling and alters macrophage L-arginine metabolism (including ARG1-related pathways), thereby influencing kidney injury processes induced by folic acid or cisplatin in mice. Scientifically, it identifies FSTL3–activin signaling as a regulator of macrophage metabolic programs that could be targeted to modulate kidney injury and repair.

Xing F, Xiang L, Yan J et al. · Kidney international · (2026) · View on PubMed ↗

Novel human neutralizing monoclonal antibodies against Pregnancy-Associated Plasma Protein A for the treatment of Autosomal Dominant Polycystic Kidney Disease.

This preclinical study generated novel human neutralizing monoclonal antibodies against pregnancy-associated plasma protein A (PAPPA) to treat autosomal dominant polycystic kidney disease (ADPKD), using yeast-based expression platforms and testing efficacy in mouse models of early and advanced PKD. The key finding is that pan-selective PAPPA antibodies were designed to neutralize PAPPA-mediated cleavage of IGFBP2, IGFBP4, and IGFBP5, building on prior evidence that PAPPA suppression ameliorates polycystic disease in Pkd1RC/RC mice. The significance is that these human PAPPA-mAbs could provide a translational therapeutic approach by blocking PAPPA-driven IGF signaling in ADPKD.

Hu E, Gardener MJ, Wang X et al. · Kidney international · (2026) · View on PubMed ↗ · Free PDF ↗

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Extrachromosomal DNA (ecDNA) & genome amplification vulnerabilities

Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency.

This study used multi-modal chromatin profiling (integrating histone modification maps with mutational, DNA methylation, and transcriptomic data) across medulloblastoma subgroups to identify subgroup-specific chromatin states and dependencies. The key finding was that a bivalent/poised enhancer (EnhBiv) state enriched at neurodevelopmental gene promoters in Group 3/4 medulloblastoma revealed aberrant KDM2B binding and a selective dependency on KDM2B. Scientifically, it implicates KDM2B as a tractable chromatin regulator vulnerability in specific medulloblastoma chromatin contexts.

Tao R, Erkek-Ozhan S, Xu B et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion.

This study examined how the chromatin reader ZMYND8 regulates IL-2 receptor (IL-2R)–STAT5 signaling and T cell exhaustion by using in vivo single-cell CRISPR screens in the context of CD8+ T cell dysfunction. The key finding is that ZMYND8 antagonizes IL-2R–STAT5 signaling, restraining effector-like states, and that targeting ZMYND8 can unleash IL-2 signaling to override T cell exhaustion. This is clinically significant because it identifies a potential epigenetic intervention to restore IL-2 responsiveness and improve anti-tumor or anti-viral T cell function.

Wang Y, Shi H, Chapman NM et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

MMEJ repair of breaks at TA repeats maintains ecDNA and cancer fitness.

The study tested which DNA repair pathways maintain extrachromosomal DNA (ecDNA) by inhibiting microhomology-mediated end joining (MMEJ) and comparing effects to NHEJ and homologous recombination in cancer cells dependent on ecDNA-driven oncogene amplification. It found that MMEJ inhibition selectively depletes ecDNA, induces ecDNA-specific damage, and drives ecDNA sequestration into micronuclei, reducing cancer cell fitness. This identifies MMEJ as a pathway vulnerability for targeting ecDNA-mediated tumor aggressiveness and therapy resistance.

Billing D, Selvaraj M, Kelley ME et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.

The study investigated the molecular mechanism of resistance to mTOR inhibitors (everolimus and temsirolimus) in clear cell renal cell carcinoma (ccRCC), focusing on SPOP-mediated ubiquitination of the histone modifier ZMYND8. SPOP (CULLIN3-RING E3 ligase substrate receptor) promoted K63-linked polyubiquitination of ZMYND8 at lysine 398, which prevented ZMYND8 phase separation, enhanced ZMYND8–ZHX2 transactivation complex formation, and drove mTOR inhibitor resistance. This reveals a specific SPOP–ZMYND8 ubiquitination/phase-separation pathway as a potential therapeutic vulnerability to overcome mTOR inhibitor resistance in ccRCC.

Tang B, Sun R, Shao J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

The study investigated the role of autophagy signaling in multiple myeloma (MM) by identifying ULK3 as a progression-associated autophagy gene and testing whether pharmacologic ULK3 inhibition affects MM survival. ULK3 supported MM cell survival through the ULK-ATG13-FIP200 complex, and small-molecule ULK3 inhibitors (SG3-014/MA9-060) with nanomolar potency (confirmed by co-crystallization) reduced MM burden in vivo and improved survival despite multikinase activity. This positions ULK3 as a druggable autophagy dependency in MM and provides preclinical evidence for therapeutic targeting to delay relapse.

Tauro M, Li T, Sudalagunta PR et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.

The study examined how mutant TP53 (DNA-binding domain mutations) promotes immune evasion in cancer by hijacking the RNA-splicing factor RBM28, using mouse tumor models and human esophageal cancer development data. Mutant p53 drove RBM28 overexpression, causing excessive splicing of transposon elements that reduced double-stranded RNA formation and suppressed dsRNA-triggered type I interferon signaling and antitumor immunity. This identifies a mutant p53–RBM28–dsRNA/IFN axis as a key mechanism of immune suppression and a potential target for restoring antitumor immunity.

Xiang T, He Z, Hu X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Distinct molecular signature in relapsed patients with ANCA-associated vasculitis.

This study investigated whether relapsing versus new-onset ANCA-associated vasculitis (microscopic polyangiitis and granulomatosis with polyangiitis) has distinct molecular signatures. Using whole-blood RNA sequencing and differential expression/functional enrichment in 21 patients (treatment-naïve, off-therapy relapsed, and remission on/off maintenance) versus 12 matched healthy controls, it found a distinct gene-expression profile in relapsed patients compared with new-onset disease. The findings are significant because they suggest relapse-associated molecular pathways that could inform biomarker development and improved management of MPA/GPA.

Gialouri CG, Valakos D, Moustafa S et al. · RMD open · (2026) · View on PubMed ↗ · Free PDF ↗

Integrated serum proteomics and autoantibody analyses reveal a biomarker signature predictive of flare during biologic tapering in rheumatoid arthritis.

This study aimed to identify serum biomarker signatures predictive of rheumatoid arthritis flare during biologic DMARD tapering in patients in sustained remission. Using a two-stage design with discovery mass spectrometry on OPTIBIO trial baseline samples (n=44) followed by ELISA validation and anti-cytokine autoantibody analyses, it found a circulating protein biomarker signature that could predict flare risk during tapering. This is clinically important because it moves toward personalized tapering decisions to reduce flare incidence in RA.

Blanco FJ, Quaranta P, Domínguez-Guerrero P et al. · RMD open · (2026) · View on PubMed ↗ · Free PDF ↗

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Gut–lung axis & respiratory microbiome immunology

The microbiota-gut-brain axis in epilepsy: Mechanistic insights and emerging probiotic-based therapeutics.

This review examined mechanistic links between the microbiota-gut-brain axis and epilepsy, focusing on how gut dysbiosis can influence immune signaling, neurotransmitter pathways, and gut–brain barrier integrity. The key finding was that epilepsy is associated with altered gut microbial composition (including reduced Lactobacillus, Bifidobacterium, and Faecalibacterium) and that probiotic-based therapeutics are emerging as potential adjunct treatments. This provides a rationale for microbiome-targeted interventions to reduce seizure burden or improve pharmacoresistance in epilepsy.

Matta T, Bishnoi M, Chopra K et al. · International review of neurobiology · (2026) · View on PubMed ↗

Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial.

In the REFIT2 randomized, double-blind, placebo-controlled phase 3 trial, investigators studied faecal microbiota transplantation (FMT) versus placebo in adults with moderate-to-severe irritable bowel syndrome (IBS) meeting Rome IV criteria and an IBS-SSS score ≥175. The key finding was the trial’s efficacy and safety assessment of FMT for improving IBS outcomes compared with placebo (with results reported in the full article). If effective and safe, FMT could represent a disease-modifying microbiome therapy for IBS beyond standard symptom-directed treatments.

Johnsen PH, Juul FE, Hoff DAL et al. · Lancet (London, England) · (2026) · 1 citations · View on PubMed ↗

Fibroblasts restrain gut inflammation by IGF1-dependent regulation of innate lymphocytes.

This study examined how fibroblast heterogeneity regulates intestinal immune responses by focusing on insulin-like growth factor 1 (IGF1)–expressing fibroblasts in inflammatory bowel disease (IBD). IGF1-expressing fibroblasts were reduced in IBD patients, and in mouse models IGF1 signaling limited group 3 innate lymphoid cell (ILC3) CXCL10 production and reduced recruitment of plasmacytoid dendritic cells (pDCs), thereby restraining gut inflammation. The results support a conserved fibroblast–ILC3–pDC regulatory axis that could be therapeutically targeted to treat chronic intestinal inflammation.

Lin Q, Liu RE, Wang Q et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Molecular insights into GLP-1 receptor agonists and emerging metabolic-inflammatory targets in hidradenitis suppurativa.

This review synthesized molecular insights into glucagon-like peptide-1 receptor (GLP-1R) agonists and other emerging metabolic–inflammatory targets in hidradenitis suppurativa (HS). The authors highlighted immunometabolic mechanisms linking HS to obesity-associated and obesity-independent metabolic dysfunction (including insulin/IGF-1 signaling and chronic low-grade inflammation), and discussed how targeting upstream metabolic drivers may improve treatment responses, particularly where biologics are less effective in obesity. The review supports a mechanistic basis for considering GLP-1R agonists and metabolic–inflammatory pathways as therapeutic targets in HS.

Brogaard E, Nielsen VW, Pedersen NH et al. · Expert opinion on therapeutic targets · (2026) · View on PubMed ↗

Baloxavir marboxil versus oseltamivir for influenza A in children aged 5 years and older: a community-based prospective cohort study.

This community-based prospective cohort study compared baloxavir marboxil (single dose) versus oseltamivir (5-day course) for influenza A in 750 children aged 5–14 years with RT-PCR-confirmed infection in Chongqing, China. The key finding is that baloxavir marboxil was associated with a shorter fever duration and comparable safety relative to oseltamivir in this real-world pediatric setting. The results support baloxavir as an effective, simpler antiviral option for children with influenza A in community practice.

Li W, Zhou M, Ye H et al. · BMC infectious diseases · (2026) · View on PubMed ↗ · Free PDF ↗

TRAM promotes Toll-like-receptor-free myddosome signal transduction.

This study investigated how Toll-like receptor (TLR) signaling proceeds from membrane-proximal proto-myddosomes to receptor-free cytosolic myddosomes by identifying factors that regulate proto-myddosome maturation. The key finding is that TRAM promotes Toll-like-receptor-free myddosome signal transduction, as revealed through a genetic screen in macrophages and mechanistic characterization of the maturation process. This is significant because it clarifies a control point in innate immune signaling that could be leveraged to modulate inflammatory responses.

Fisch D, Ohri V, Anastasakou E et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Lebrikizumab in Atopic Dermatitis: Associations of Patient Characteristics and Treatment History with Clinical Outcomes.

This multicenter observational real-world study evaluated lebrikizumab effectiveness and safety in adults with moderate-to-severe atopic dermatitis treated for at least 16 weeks across eight Italian university hospitals. The key finding was that clinical outcomes (including EASI75 at week 16 as the primary endpoint) varied across patient characteristic and treatment-history subgroups, indicating differential response patterns in routine care. These results support more tailored use of lebrikizumab by identifying which adult AD subgroups are more likely to achieve meaningful eczema improvement during treatment.

Gori N, Galluzzo M, Ippoliti E et al. · Dermatitis : contact, atopic, occupational, drug · (2026) · View on PubMed ↗

Near pan-alphavirus neutralization by an antibody-nanobody bispecific.

This study investigated an antibody–nanobody bispecific designed to achieve near pan-alphavirus neutralization across human-infecting alphaviruses. The key finding was that the bispecific format enabled sufficiently potent neutralization against multiple alphaviruses by combining broad antibody recognition (including the previously identified SKT05) with nanobody neutralizing activity. This provides a promising single-therapeutic strategy for stockpiling against emerging alphavirus threats such as chikungunya and Venezuelan equine encephalitis.

Pletnev S, Gardner CL, Sutton MS et al. · mAbs · (2026) · View on PubMed ↗ · Free PDF ↗

Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.

This narrative review summarized emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy, focusing on how iron homeostasis is regulated by transferrin, ferritin, ferroportin, hepcidin, and the iron responsive element/iron regulatory protein system. The key finding is that dysregulated pulmonary iron handling can drive oxidative injury and contribute to multiple lung diseases, spanning inflammatory and infectious conditions. The significance is that targeting iron pathways may represent a therapeutic opportunity across pulmonary disorders where iron-dependent oxidative stress is central.

Galaris A, Toumpanakis D, Galaris D et al. · European respiratory review : an official journal of the European Respiratory Society · (2026) · View on PubMed ↗ · Free PDF ↗

Right ventricular-protective ventilation in acute respiratory distress syndrome: phenotypes, monitoring and ventilatory management.

This European Respiratory Review article examined right ventricular (RV) protective ventilation in ARDS, emphasizing ARDS phenotypes, monitoring approaches, and ventilatory management strategies. The key finding is that RV dysfunction is common in ARDS and is consistently associated with worse outcomes, making RV-focused physiology an important determinant beyond lung-protective ventilation alone. Clinically, it supports incorporating RV monitoring and RV-protective ventilatory adjustments to improve outcomes in ARDS patients with pulmonary vascular injury.

Peng C, Yang L, Wu Y et al. · European respiratory review : an official journal of the European Respiratory Society · (2026) · View on PubMed ↗ · Free PDF ↗

Small airways dysfunction: associated factors, clinical aspects and new perspectives.

This nonsystematic narrative mini-review evaluated small airways dysfunction (SAD), comparing spirometry thresholds used to define SAD with other diagnostic techniques and summarizing associated factors and clinical aspects. The key finding is that maximal mid-expiratory flow, particularly values below the lower limit of normal (LLN), appears to be the most accurate and reproducible spirometric measure for assessing SAD, while no single gold-standard spirometric definition has been universally endorsed. The significance is that it guides clinicians and researchers toward more consistent SAD measurement and highlights gaps for future standardization.

Touilloux B, Cartellà A, von Garnier C et al. · European respiratory review : an official journal of the European Respiratory Society · (2026) · View on PubMed ↗ · Free PDF ↗

The Gut-Lung Axis in Respiratory Diseases: Mechanisms, Microbiome Dysbiosis, and Therapeutic Implications. A Comprehensive Review.

This narrative review studied the bidirectional gut–lung axis in respiratory diseases, focusing on how intestinal microbiota, immune cell trafficking, microbial metabolites (including short-chain fatty acids), vagal neuroimmune signaling, and epigenetic regulation influence pulmonary immunity and homeostasis. It reports that microbiome dysbiosis and altered metabolite signaling can drive respiratory inflammation and that lung perturbations can reciprocally impair gut barrier integrity and microbial composition. The review’s significance lies in outlining mechanistic targets and therapeutic implications (e.g., microbiome- and metabolite-based strategies) for respiratory disease management.

Qaid EYA, Long I · Respiratory medicine · (2026) · View on PubMed ↗

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Microbial/archaeal cell-wall enzymes & microbial tools

Targeting a site of vulnerability on circumsporozoite protein inhibits Plasmodium vivax malaria infection.

This study examined protective B cell epitopes on Plasmodium vivax circumsporozoite protein (PvCSP) by screening inhibitory plasma from P. vivax–infected individuals and isolating a monoclonal antibody against identified epitopes. It identified two PvCSP B cell epitopes—PvCSP-A and PvCSP-B/NAGG—located in the N- and C-terminal regions (distinct from the canonical central repeat region), and showed that targeting a vulnerability site on PvCSP inhibits P. vivax malaria infection. These findings advance PvCSP epitope mapping for next-generation P. vivax vaccines and therapeutic antibody design beyond the central repeat region.

Visweswaran GRR, Mahdavi P, Vijayan K et al. · Immunity · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis of step II spliced leader RNA trans-splicing in trypanosomatid parasites.

This study investigated the structural and mechanistic basis of step II spliced leader (SL) RNA trans-splicing in kinetoplastid parasites by determining cryogenic electron microscopy structures of the SL trans-splicing machinery from Leishmania tarentolae. The key finding is that the reported cryo-EM structures reveal how the SL exon ligates to the 5′ end of target mRNAs during step II trans-splicing. This is significant because it provides a molecular blueprint for a fundamental gene-expression process in Trypanosoma/Leishmania pathogens and may inform future therapeutic targeting of SL trans-splicing.

Nadenoen T, Biglione FA, Vandevenne M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A methanogen hydrolase reveals the structure of archaeal peptidoglycan.

The study identified and characterized ArmA, a glycosyl hydrolase from Methanobrevibacter smithii, as the first dedicated enzyme for archaeal peptidoglycan (pseudomurein/archaeal PG) analysis. Using ArmA-mediated digestion, it revealed an unexpected archaeal PG architecture that revises the prevailing model of the glycan backbone. This advances structural understanding of archaeal cell-wall polymers and improves tools for studying archaeal biology and potential antimicrobial targets.

Smith R, Pende N, Rifflet A et al. · Nature · (2026) · View on PubMed ↗

Divergent SAGA complexes shape the Toxoplasma transcriptome for lytic cycle progression and host interaction.

The study examined how Toxoplasma gondii organizes histone acetyltransferase machinery to shape the transcriptome during lytic cycle progression and host interaction, focusing on a plant-like SAGA variant built around TgGCN5b. Interactome and structural analyses showed a modular acetyltransferase complex integrating multiple GNAT enzymes with chromatin-reader proteins (PHD/PZP domains) and Apetala-related regulators, and TgGCN5b drove selective acetylation that promoted lytic transcriptional programs. This defines a parasite-specific SAGA architecture that could be exploited to disrupt Toxoplasma virulence and host interaction.

Cannella D, Pachano B, Shahinas M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Phage terminase recognition by the bacterial immune sensors Avs2 and Upx.

The study investigated how bacterial immune sensors Avs2 and Upx recognize phage terminase proteins, focusing on the structural mechanism for Avs2 sensing of the large terminase subunit in Escherichia coli. A cryo-EM structure at 2.3 Å showed EcAvs2 forms a flat, C4-symmetric tetramer in which each protomer binds a terminase moiety, providing a direct structural basis for terminase recognition. This advances understanding of how phage defense systems detect infection at the molecular level and could guide engineering of bacterial immune sensors.

Evans SA, Chiu C, Wilkinson ME et al. · Nature communications · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Sailing to a deeper understanding of malaria parasite invasion.

This commentary/review studied malaria parasite RBC invasion by focusing on a newly reported atomic-level structure of the invasion protein complex. It found that structural insights clarify how the parasite engages host erythrocytes, informing mechanistic understanding of invasion steps. The work is significant because it guides rational development of next-generation antimalarials targeting the invasion machinery.

Tobin AB · Trends in parasitology · (2026) · View on PubMed ↗ · Free PDF ↗

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Genome stability & chromosome biology (centromeres, recombination)

In-cell structures visualize human pre-ribosome assembly in the nucleolus.

This study used cryogenic correlative light and electron tomography to visualize in-cell pre-ribosome assembly within human nucleoli in HeLa cells. It captured structural snapshots of ribosomal subunit precursors including the SSU processome and pre-60S, revealing known interaction states and additional partners such as the RNA exosome, rixosome, and the nuclear export receptor CRM1–RanGTP. These in-cell structural maps provide mechanistic insight into human ribosome biogenesis and identify molecular components that can be targeted to disrupt nucleolar assembly in disease contexts.

Zhao X, Hayashi Y, Fung HKH et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

SNI1/NSE5 is a cold-sensitive brake on class II crossovers in Arabidopsis.

This study examined how cold temperature alters meiotic recombination pathway choice in Arabidopsis by focusing on the SNI1/NSE5 locus. The key finding is that cold shifts crossovers toward subtelomeric regions and increases class II crossover output, with genetic mapping identifying a 15.6 kb interval containing SNI1 (the NSE5 orthologue) within the SMC5/6 complex; reduced SNI1 function changes the temperature-responsive crossover landscape. This is significant because it reveals a specific gene module that couples environmental temperature to recombination control, informing how plants adapt genome shuffling under stress.

Pelé A, Sáez Zárate E, Kbiri N et al. · Nature plants · (2026) · View on PubMed ↗ · Free PDF ↗

The mutational dynamics of the Arabidopsis centromeres.

The study quantified centromere mutational dynamics in Arabidopsis thaliana by analyzing replicated genome assemblies from mutation accumulation lines to define the centromere-specific mutation spectrum. It found frequent kilobase-scale insertion-deletion mutations that preserve tandem-repeat arrays by adding/removing complete repeat units, while point mutations accumulated at ~10× higher rates than elsewhere in the genome. These results clarify how centromere repeat structure is maintained despite ongoing mutation, informing models of chromosome segregation evolution.

Dong X, Jiao WB, Goldkuhle L et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

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Evolutionary genomics & phylogenomics (bats, regulatory evolution)

PURE: An interpretable framework for prioritizing candidate regulators of differential gene expression in plants.

This paper introduced PURE (Plant Unified Regulation Explorer), an interpretable computational framework to prioritize candidate transcription factors (TFs) driving differential gene expression in plants. PURE ranks TF candidates by integrating co-expression patterns with sequence motifs and experimental binding evidence, using gradient boosting to model sparse/imbalanced regulatory matrices and SHAP to translate model contributions into TF-level importance scores. This provides a practical, interpretable way to infer regulatory regulators from transcriptomic data in crops and non-model species where experimental TF validation is challenging.

Li C, Yang L, Lin K et al. · Plant communications · (2026) · View on PubMed ↗ · Free PDF ↗

The gene-regulatory evolution of the human skeleton.

The study mapped human-specific gene-regulatory changes underlying human skeletal evolution by performing massively parallel reporter assays (MPRAs) in human chondrocytes and integrating results with human–ape hybrid cell differentiation into osteochondral progenitors. It identified 15,077 loci with human-specific regulatory activity from 561,410 human-derived promoter/enhancer substitutions and used hybrid-cell integration to connect regulatory evolution to skeletal developmental programs. These findings provide a high-resolution regulatory atlas for how promoter/enhancer evolution may have shaped the human skeleton and inform future functional studies of skeletal trait evolution.

Yan Y, Mishol N, Lange K et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Reference genomes and fossils revise bat family phylogeny and biogeography.

The study reconstructed bat family phylogeny and biogeography using chromosome-level, long-read genome assemblies from 103 bat species spanning all 21 bat families, including 42 newly generated assemblies. It produced a revised bat phylogeny, placing Myzopodidae as the earliest branch within Vespertilionoidea and resolving yangochiropteran relationships with Emballonuroidea and Vespertilionoidea as sister groups. This improved genomic framework clarifies evolutionary relationships that underpin the origins of key bat traits such as powered flight and echolocation.

Morales AE, Liang Y, Thomas WR et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Neuroinflammation & TSC–mTORC1 astrocyte reactivity

mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis.

The study investigated whether mTORC1 signaling drives cell-autonomous astrocyte reactivity in tuberous sclerosis complex (TSC) using human brain organoid models carrying TSC1/TSC2-mutated progenitor lineages in the absence of seizures. It found that mTORC1 activity is sufficient to promote astrocyte reactivity driven by mutated progenitor fate rather than requiring seizure activity. This supports a causal glial mechanism in TSC pathology and strengthens the rationale for targeting the TSC–mTORC1 axis to mitigate neuroinflammation and related disease features.

Li TL, Blair JD, Yoo T et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

HOXD13 links positional identity to primary cilia-dependent signalling in synovial fibroblasts.

This study examined how the transcription factor HOXD13 links positional identity to primary cilia-dependent signaling in synovial fibroblasts from rheumatoid arthritis, osteoarthritis, and noninflammatory donors. It found that HOXD13 (along with HOXD10/HOXD11) regulates gene programs in synovial fibroblasts and that HOXD13-dependent effects align with primary cilia presence and cilia-dependent Hedgehog signaling, supported by HOX gene silencing, RNA sequencing, and functional assays (proliferation/cell-cycle/DNA damage). The findings are significant because they connect HOX positional identity to adult synovial signaling pathways that may contribute to inflammatory joint disease.

Mirrahimi M, Klein K, Cebrián CC et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗ · Free PDF ↗

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Brain lipidomics & spatial membrane organization

The lipidomic architecture of the mouse brain.

The study characterized the spatial organization of the adult mouse brain lipidome by mapping membrane-lipid architecture at micrometric scale across sexes and during pregnancy. It revealed fine-grained lipid “lipizones” in which membrane-lipid spatial heterogeneity forms territories that align with functional anatomy. This provides a spatial lipid atlas that can guide mechanistic links between lipid distribution and brain function or neuropathology.

Fusar Bassini L, Schede HH, Capolupo L et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Infectious disease emergence & outbreak risk modeling

The anthropogenic fingerprint on emerging infectious diseases.

The study analyzed how anthropogenic drivers shape outbreak risk by consolidating 58,319 outbreak event records for 32 emerging infectious diseases and testing 16 social/environmental predictors while accounting for detection/reporting biases. It found outbreak risks are highest in mosaic landscapes where people and livestock coexist with forests and fragmented ecosystems. These results quantify how human land-use patterns influence zoonotic and vector-borne emergence and can inform risk mapping and surveillance prioritization.

Gibb R, Ryan SJ, Pigott DM et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

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Kinase inhibitor design & resistance (bitopic inhibitors)

A design approach for bitopic kinase inhibitors.

The study developed a design framework for bitopic kinase inhibitors using ABL1 and EGFR as model targets to systematically vary ligand choice, linkage vector, and linker length. It showed that bitopic potency depends on inter-ligand cooperativity and linker entropy, and it applied the approach to address resistance constraints affecting ABL1 inhibitors in BCR::ABL1-driven leukemia. This provides actionable principles for engineering next-generation kinase inhibitors that improve potency/selectivity and potentially overcome resistance.

Stevenson JW, Lou K, Reynolds JA et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

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Vascular calcification & CKD osteogenic reprogramming

The osteogenic regulator THOC5-dependent post-transcriptional control maintains vascular smooth muscle cell homeostasis against chronic kidney disease related vascular calcification.

This study investigated THOC5-dependent post-transcriptional regulation of vascular smooth muscle cell (VSMC) osteogenic transdifferentiation in chronic kidney disease (CKD)–associated vascular calcification using patient arterial tissues and CKD mouse/in vitro VSMC calcification models. THOC5 was found to maintain VSMC homeostasis by controlling osteogenic switching at the post-transcriptional level, thereby counteracting vascular calcification under CKD conditions. These findings identify THOC5 as a mechanistic regulator and potential therapeutic target to prevent CKD-related vascular calcification by blocking osteogenic VSMC reprogramming.

Cheng A, Wang Y, Liu Y et al. · Kidney international · (2026) · View on PubMed ↗

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Satellite cell culture & skeletal muscle regeneration

Revisiting Culture Conditions of Satellite Cells In Vitro for Skeletal Muscle Regeneration and Therapeutic Applications.

This review examined how satellite cell (SC) culture conditions in vitro affect skeletal muscle regeneration and translational therapeutic outcomes, with emphasis on SC behavior relevant to diseases such as Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS), and myasthenia gravis. It synthesizes evidence that specific culture parameters (e.g., media composition, substrate/coating, and growth/differentiation cues) critically determine SC quiescence, activation, proliferation, and myogenic differentiation. The work is significant because optimizing SC culture conditions could improve the reliability and scalability of cell-based therapies for muscle-wasting and neuromuscular disorders.

Kumari P, Raval A, Rana P et al. · Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft · (2026) · View on PubMed ↗

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Transplant immunology & tolerance (liver transplant)

EBV-reactive KIR+ CX3CR1+ CD8+ T cells mediate liver transplantation tolerance.

This study investigated immune mechanisms of liver transplantation (LT) tolerance by profiling EBV-reactive KIR+ CX3CR1+ CD8+ T cells using single-cell transcriptomics/TCR profiling, flow cytometry, in vitro killing assays, and HLA-E peptidome analyses in a cohort of 347 LT recipients plus murine LT models and a prospective pediatric immunosuppressant withdrawal trial. It found that EBV-reactive KIR+ CX3CR1+ CD8+ T cells mediate LT tolerance, linking their cytotoxic/recognition features to a tolerogenic immune state. The results are significant because they identify a specific EBV-reactive T-cell population and HLA-E–related recognition pathway as a potential biomarker and mechanistic target to reduce immunosuppression after LT.

Liu Y, Wang B, Sun D et al. · Journal of hepatology · (2026) · View on PubMed ↗

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Generated automatically on September 26, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.