PubMed Trending Research Digest — September 03, 2026

Automated digest · 96 articles · 15 research areas · September 03, 2026

Overview

Across this week’s PubMed highlights, a dominant theme is “precision by context”: whether in cancer immunotherapy (tracking tumor immune microenvironment transitions during checkpoint blockade, mapping malignant transcriptional archetypes in multiple myeloma, or reprogramming glioblastoma toward dendritic-cell fate), or in other diseases where response depends on biological state (e.g., iNOS/IFNγ effector differences across hosts in tuberculosis, or ORAI1/STIM1-dependent neurovascular coupling sustaining activity-driven blood flow).

A second major thread is mechanistic specificity—often at the interface of metabolism and immunity. Examples include ADAMTSL4-driven latent TGFβ1 activation driving cachexia, ferroptosis/cuproptosis immunogenicity amplified by redox control via GSR–ROS–cGAS-STING, and parasite or bacterial metabolites (KSHV lytic replication via TRAF6–Akt, Vibrio tryptophan–serotonin–IMD signaling, Plasmodium EV-delivered miR-451a suppressing neutrophil function). In parallel, multiple studies emphasize improved measurement and interpretation: from guideline-driven diagnostic workups in refractory atopic dermatitis, to imaging/biomarker frameworks (MS lesion types, aneurysm prevalence trends, ECG foundation models), to methodological rigor in RNA-targeting CRISPR quantification and clearer definitions around “biological age reversal.”

Finally, the digest reflects the field’s accelerating move toward longitudinal and high-resolution data. Long-read proteogenomic atlases, multi-organ and cross-species single-cell atlases, and live-cell transcriptomics approaches all aim to capture dynamics rather than snapshots—supporting better biomarkers, more transferable models, and more actionable mechanistic hypotheses. Together, these studies suggest that next-generation clinical translation will increasingly depend on combining deep biology with robust, state-aware diagnostics and carefully validated computational/experimental tools.

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Cancer therapeutics: Targeted drugs, ADCs, and small-molecule inhibitors

Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer.

This phase 1–2 multicenter dose-escalation/dose-expansion study evaluated daraxonrasib (RMC-6236), an oral RAS(ON) multiselective tri-complex inhibitor of GTP-bound mutant and wild-type RAS isoforms, in previously treated patients with advanced RAS-mutant non-small-cell lung cancer (NSCLC). Daraxonrasib was assessed for safety as the primary endpoint across 10–400 mg orally once daily in 21-day cycles, with efficacy and other secondary outcomes reported in the full article. If clinically active and tolerable, daraxonrasib could provide a new targeted option for RAS-driven NSCLC beyond prior therapies.

Arbour KC, Punekar S, Luo J et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

This phase 2 randomized trial in previously untreated adults with acute myeloid leukemia (AML) compared azacitidine plus venetoclax versus standard induction chemotherapy for patients eligible for induction. The study tested whether hypomethylating therapy plus venetoclax could match or improve outcomes while reducing the toxicity and healthcare burden associated with induction chemotherapy. Establishing a safer, effective induction alternative would directly change first-line treatment for AML patients who are fit for induction but may benefit from venetoclax-based regimens.

Fathi AT, Perl AE, Fell GG et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

DESTINY-Lung06: trastuzumab deruxtecan and pembrolizumab as first-line treatment for HER2-overexpressing, PD-L1 TPS <50% NSCLC.

DESTINY-Lung06 studied first-line trastuzumab deruxtecan plus pembrolizumab in patients with HER2-overexpressing, PD-L1 TPS <50% non-small cell lung cancer (NSCLC). The trial reported improved clinical outcomes for this lower-PD-L1 subgroup compared with expectations for standard pembrolizumab-based approaches, supporting the strategy of combining HER2-targeted antibody-drug conjugation with PD-1 blockade. Clinically, this provides evidence for expanding first-line targeted therapy options beyond PD-L1-high selection in HER2-driven NSCLC.

Jänne PA, Zhou CC, Smit EF et al. · Future oncology (London, England) · (2026) · View on PubMed ↗

Brain-Targeting siRNA Delivery to Tackle Alzheimer’s Disease.

This review examined brain-targeting small interfering RNA (siRNA) delivery strategies for Alzheimer’s disease (AD), focusing on nucleic-acid-based interventions that modulate AD-relevant pathways. It concluded that siRNA can be rationally designed for multi-pathway targeting and that delivery technologies are central to overcoming the main barriers to clinical translation. Scientifically, it frames how improved brain delivery could enable more practical, biomarker-light disease-modifying approaches for AD.

Yang Q, Chen Z, Zhu J et al. · Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · (2026) · View on PubMed ↗

Beyond Zolbetuximab: Next-Generation Targeting Strategies for CLDN18.2.

This review evaluated next-generation CLDN18.2 targeting strategies beyond zolbetuximab for gastric and gastroesophageal junction adenocarcinoma. It highlighted that limitations of the first validated approach—such as antigen heterogeneity, incomplete primary sensitivity, toxicity, and uncertain biomarker persistence—are driving development of ADCs, CAR T cells, bispecific antibodies, and T-cell engagers. Scientifically and clinically, it frames how improved targeting modalities and biomarker strategies may overcome current barriers after progression or in zolbetuximab non-responders.

Sagawa T, Nagashima H, Fujikawa K · Journal of gastrointestinal cancer · (2026) · View on PubMed ↗

Fast tumor accumulation and payload release of c-Met targeting aptamer-drug conjugate enables robust anti-tumor efficacy.

The study developed a c-Met-targeting aptamer-drug conjugate (ApDC) using SL1 linked to monomethyl auristatin E (MMAE) via a cathepsin B–sensitive linker and tested it in c-Met–overexpressing tumor models. The ApDC showed selective binding, fast tumor accumulation, and cathepsin B–triggered payload release to drive robust, MET-independent anti-tumor efficacy. This supports aptamer-drug conjugates as a potential therapeutic strategy for c-Met–overexpressing cancers beyond the MET-mutation–restricted benefit of current inhibitors.

Liu Y, He J, Su M et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia.

The study evaluated XY0206, a sunitinib-derived FLT3-targeting compound, using biochemical assays, multi-omics profiling, and functional experiments in acute myeloid leukemia (AML) models with FLT3-dependent resistance. XY0206 directly engaged FLT3 and suppressed STAT5, AKT, and ERK signaling, inducing apoptosis in FLT3-ITD AML cells while retaining antileukemic activity across models of FLT3-dependent resistance. The significance is that XY0206 may overcome microenvironment- and treatment-emergent resistance that limits current FLT3 inhibitor efficacy in FLT3-driven AML.

Shen L, Yang Y, Xu C et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Sequencing asymmetry: the case for caution before first-line pirtobrutinib in chronic lymphocytic leukemia.

This commentary analyzed evidence from the phase III BRUIN CLL-313 and CLL-314 trials regarding pirtobrutinib, a noncovalent BTK inhibitor, as a candidate first-line therapy in chronic lymphocytic leukemia (CLL). It argues for caution based on an “untested asymmetry”: after failure of covalent BTK inhibitors, pirtobrutinib retains phase III-validated activity, but resistance to first-line pirtobrutinib can arise via kinase-domain mutations (e.g., A428D, L528W) that confer in vitro cross-resistance to covalent agents. The clinical significance is that sequencing of BTK inhibitors may materially affect later options for relapse management, and prospective data are needed to guide first-line use.

Chen B, Qian S · Annals of hematology · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative effectiveness of apalutamide-, abiraterone-, and enzalutamide-based doublets in mHSPC.

The study compared real-world effectiveness of apalutamide-, abiraterone-, and enzalutamide-based doublets added to androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). The key finding was a comparative effectiveness assessment across these androgen receptor pathway inhibitor (ARPI) combinations using eligible real-world studies, addressing the lack of direct head-to-head trials. This helps clinicians choose among ARPI doublets for mHSPC when randomized comparative data are limited.

Valikovics AK, Bacsó D, Samaien N et al. · BJU international · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular disease & Epidemiology (HF, myocarditis, ACS biomarkers, ECG AI)

Global, Regional, and National Burden of Myocarditis and Its Impairment, 1990-2023.

Using Global Burden of Disease (GBD) 2023 data, this study estimated global, regional, and national trends in myocarditis prevalence, incidence, disability-adjusted life years (DALYs), mortality, and mortality-to-incidence ratio (MIR) from 1990–2023 across countries stratified by age, sex, and Socio-demographic Index (SDI) quintiles. The key finding was the detailed characterization of how myocarditis burden has changed over time and differed by geography and demographic strata. These estimates provide an evidence base for public health planning and resource allocation to address myocarditis morbidity and mortality.

Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Development and external validation of a contrastive learning foundation model for ECG-based prediction of cardiovascular diseases and outcomes.

The study developed and externally validated an ECG foundation model, ECG-CLIP, using contrastive learning to improve generalizability for cardiovascular disease prediction and outcomes. Using a large retrospective dataset from the Scripps Health GE MUSE system (1.7+ million ECGs; 542,288 patients) with clinician-overread reports, the model was designed to reduce reliance on task-specific labels and better capture ECG representations transferable across tasks. This is significant because it advances clinically deployable, label-efficient ECG AI that can support more robust diagnosis and risk prediction across populations and settings.

Ko M, Gadaleta M, Topol EJ et al. · The Lancet. Digital health · (2026) · View on PubMed ↗ · Free PDF ↗

Lipoprotein(a) and the C-reactive protein-triglyceride-glucose index in relation to coronary lesion burden in patients with acute coronary syndrome.

This retrospective single-center study of 2,836 acute coronary syndrome (ACS) patients who underwent coronary angiography examined whether the C-reactive protein–triglyceride–glucose index (CTI) adds prognostic information to lipoprotein(a) [Lp(a)] for coronary lesion burden. The key finding was that CTI, reflecting systemic inflammation and metabolic stress, was associated with angiographic coronary lesion burden (continuous Gensini score) and could complement Lp(a) in risk characterization. Clinically, it suggests a combined biomarker strategy to better stratify inflammatory-metabolic and inherited atherothrombotic risk in ACS.

Xie P, Wang Z, Huang C et al. · Journal of lipid research · (2026) · View on PubMed ↗ · Free PDF ↗

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the prevalence of unruptured intracranial aneurysms (UIAs) across populations, stratified by comorbidities, risk factors, country, and time period, using cross-sectional and case-control studies published from 2011–2025 plus reanalysis of 68 studies from an earlier 2011 review. The authors aimed to test whether the previously observed decline in aneurysmal subarachnoid hemorrhage incidence (linked to falling smoking and hypertension prevalence) is paralleled by declines in UIA prevalence, and they recompiled and reassessed the evidence base to quantify these trends. Clinically, establishing whether UIA prevalence is changing over time would refine risk forecasting and screening/primary prevention strategies for aneurysm-related hemorrhage.

Dremel J, Rücker V, Badel C et al. · The Lancet. Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

This Global Burden of Disease Study 2023 systematic analysis quantified adolescent health outcomes and risk-factor prevalence across the Asia Pacific region (ages 10–24) at subregional and national levels. It synthesized GBD 2023 estimates of disease burden, mortality, and key adolescent risk factors to identify major contributors to adolescent morbidity and mortality across countries. The findings provide an evidence base to target region-specific adolescent health interventions and policy priorities.

The Lancet. Child & adolescent health · (2026) · View on PubMed ↗ · Free PDF ↗

New Evidence in Heart Failure: 2026 Update.

This 2026 update article reviewed advances in heart failure (HF) epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery, and incorporated updates from the Second Universal Definition of HF. It summarizes how the field has moved beyond traditional ejection fraction–based classification toward a more refined framework. The significance is that clinicians and researchers can align HF diagnosis and research with the latest definitions and evolving concepts of patient outcomes.

Liguori V, Rizzello A, Adamo M et al. · ESC heart failure · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer immunotherapy & Tumor microenvironment (ICI, CAR-T/NK/TCR, TIME, antigen presentation)

Functionally active lymphoid aggregates correlate with improved prognosis in brain metastases.

This study analyzed more than 200 patients with melanoma brain metastases (BM) or lung adenocarcinoma (LUAD) BM to determine whether B-cell infiltration and lymphoid aggregates (LAs)/tertiary lymphoid structures (TLS) relate to prognosis. Functionally active LAs correlated with improved survival in melanoma BM (and were associated with increased intratumoral CD8+ T cells in melanoma compared with LUAD), but this prognostic association was not observed in LUAD BM. The results support LAs/TLS as potential biomarkers of antitumor immunity and prognosis, particularly in melanoma brain metastases.

Nader NE, Glathar AR, Byrnes EV et al. · Cancer discovery · (2026) · View on PubMed ↗

RUNX3+ basal-like malignant cells: architects of an immunosuppressive microenvironment in bladder cancer: a comprehensive bioinformatics analysis of single-cell and spatial transcriptomics.

The study integrated five publicly available bladder cancer single-cell RNA-seq datasets (530,000+ cells from 62 bladder cancer and normal samples) and validated findings with single-nucleus and spatial transcriptomics, using RNA fluorescence in situ hybridization, to characterize RUNX3+ basal-like malignant cells. RUNX3+ basal-like malignant cells were identified as key architects of an immunosuppressive tumor microenvironment, with spatially supported immunosuppressive programs. These results suggest RUNX3+ basal-like states may serve as prognostic biomarkers and potential targets to reprogram immunity in bladder cancer.

Liu S, Wang Y, Peng S et al. · International journal of surgery (London, England) · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.

The work developed a modular γδ TCR-T platform that targets KRAS-derived pMHC while using a re-dosable mRNA engager system to redirect specificity, addressing antigen/HLA heterogeneity in solid tumors. The key finding was that KRAS pMHC targeting can be combined with reprogrammable mRNA-based redirection to maintain functional T-cell engagement despite variable antigen presentation. This supports a flexible immunotherapy design for KRAS-driven cancers where classical αβ TCR specificity is undermined by HLA loss or fluctuating antigen expression.

Ramírez-Fernández Á, Bear AS, Kamali E et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

A phase 1 trial of CD123-directed chimeric antigen receptor T-cell therapy in adults with relapsed/refractory acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm.

This phase 1 trial evaluated CD123-directed CAR T-cell therapy in adults with relapsed/refractory acute myeloid leukemia (r/r AML) or blastic plasmacytoid dendritic cell neoplasm (BPDCN), using dose escalation across two arms for CD123-positive r/r AML and BPDCN. The key finding was the feasibility and clinical activity of autologous or donor-derived CD123 CAR T cells in this heavily pretreated population. Clinically, it supports CD123 as a viable CAR T target and informs dosing and safety considerations for future studies in AML and BPDCN.

Budde LE, Del Real MM, Song J et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial.

The randomized phase 3 NSABP B-59/GeparDouze trial studied whether adding the immune checkpoint inhibitor atezolizumab to sequential neoadjuvant taxane–carboplatin–anthracycline chemotherapy improves outcomes in stage II–III triple-negative breast cancer (TNBC) patients (773 randomized to atezolizumab vs 777 to placebo). Atezolizumab did not significantly improve event-free survival (EFS) (HR 0.80, stratified log-rank P=0.083; ~3.3% difference in 4-year EFS rates), and overall survival also showed no clear benefit (HR 0.86). Scientifically and clinically, the trial indicates that atezolizumab addition to this neoadjuvant regimen is not broadly effective for early TNBC, informing future biomarker-driven immunotherapy strategies.

Loibl S, Tang G, Nekljudova V et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Generation of a highly versatile TCR bispecific scaffold optimized for targeting tumor-specific peptide-HLA antigens.

The study focused on engineering a highly versatile T-cell receptor (TCR) bispecific scaffold designed to target tumor-specific peptide–HLA (pHLA) antigens. The key advance is the development of an optimized scaffold enabling specific redirection of T cells toward pHLA targets, addressing the technical challenge of targeting low-copy, highly promiscuous pHLA epitopes in solid cancers. This is clinically relevant because it expands the feasibility of T-cell-engaging bispecific therapies beyond lineage antigens toward broader solid-tumor antigen landscapes.

Hofmann M, Unverdorben F, Pszolla MG et al. · mAbs · (2026) · View on PubMed ↗ · Free PDF ↗

Patient-reported outcomes with tisotumab vedotin versus chemotherapy in patients with recurrent or metastatic cervical cancer: post hoc analyses from the open-label, randomized, phase 3 ENGOT-cx12/GOG-3057/innovaTV 301 trial.

The study performed post hoc analyses of patient-reported outcomes (health-related quality of life) comparing tisotumab vedotin versus chemotherapy in patients with recurrent or metastatic cervical cancer enrolled in the open-label randomized phase 3 innovaTV 301/ENGOT-cx12/GOG-3057 trial. The key finding was that patient-reported outcomes were assessed as secondary endpoints in the context of a trial where tisotumab vedotin had previously shown survival benefit over chemotherapy. This is clinically important because it informs tolerability and quality-of-life considerations for second- or third-line treatment decisions in this patient population.

Jordan SE, González-Martin A, Morlock R et al. · International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · (2026) · View on PubMed ↗ · Free PDF ↗

Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy.

This preclinical study engineered primary natural killer (NK) cells to express a CD33-CD73 dual-function CAR-NK construct (enhanced CD33 CAR-NK cells secreting anti-CD73scFv) to counter adenosine-mediated immunosuppression in acute myeloid leukemia (AML). The key finding was that cotargeting CD73 and the adenosine-rich tumor microenvironment overcame adenosine-driven suppression and improved anti-AML efficacy compared with approaches targeting CD39 versus CD73 blockade. The work is significant because it provides a mechanistic CAR-NK design to enhance activity in the immunosuppressive AML microenvironment.

Wang L, Gong S, Wang J et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Tumor immune microenvironment remodeling predicts response to checkpoint inhibitor therapy.

This study analyzed how the tumor immune microenvironment (TIME) changes during immune checkpoint inhibitor (ICI) therapy by building a longitudinal single-cell RNA sequencing atlas of 441 samples from 241 patients across ten cancer entities. It defined 77 immune and stromal subtypes and four conserved TIME states, finding that ~40% of tumors transition between states during therapy and that the transition—especially toward inflamed or B cell-enriched subtypes—was more predictive of outcome than baseline TIME state. Clinically, TIME transition dynamics could serve as a biomarker to predict response to checkpoint inhibitors and guide patient stratification.

Lin Z, Chandra M, Srinivas N et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

CRISPRa-identified transcription factors reprogram glioblastoma into dendritic cell-like cells to elicit systemic antitumor immunity.

This study used a candidate-based CRISPR activation (CRISPRa) functional screen to identify transcriptional regulators that reprogram glioblastoma (GBM) cells toward conventional dendritic cell (cDC) fate. It found that Zfp366/Znf366, Pu.1, Irf8, and Batf3 (collectively ZPIB) are sufficient to convert GBM cells into cDC-like cells, driving global transcriptional and epigenetic remodeling, with downstream single-cell RNA sequencing used to characterize the reprogrammed states. The work suggests a strategy to overcome GBM immune evasion by enhancing antigen presentation and eliciting systemic antitumor immunity.

Liu X, Zhu M, Zou C et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

This prespecified analysis evaluated patient-reported outcomes (PROs) in adults with extensive-stage small cell lung cancer (ES-SCLC) comparing tarlatamab versus standard-of-care platinum-based chemotherapy after first-line platinum therapy in the phase 3 DeLLphi-304 trial. The study assessed changes from baseline and time to deterioration using validated instruments (e.g., EORTC QLQ-C30/LC13, FACT-G, BPI-SF, EQ-5D-5L). The results are significant for determining whether tarlatamab improves or preserves health-related quality of life alongside clinical efficacy in ES-SCLC.

Mountzios G, Lammers PE, Sun L et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗

Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience.

This study analyzed GPRC5D-associated on-target/off-tumor adverse events in adult Chinese patients with heavily pretreated relapsed/refractory multiple myeloma treated with the GPRC5D×CD3 bispecific antibody talquetamab in the MonumenTAL-1 phase I/II cohort. Talquetamab safety outcomes were characterized by incidence, time to onset, duration, and recovery status of GPRC5D-linked adverse events across subcutaneous dosing regimens (0.4 mg/kg weekly or 0.8 mg/kg every 2 weeks). These findings support clinical risk characterization of GPRC5D-directed bispecific therapy in a defined RRMM population and inform monitoring/management of expected on-target/off-tumor toxicities.

An G, Jin J, Cai Z et al. · Hematology (Amsterdam, Netherlands) · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic disease & Nutrition (diabetes, NAFLD/T2D, diet, polyphenols, metabolic therapies)

N-Lactoyl-phenylalanine Improves Cardiac Function in a Mouse Model of Diabetic Cardiomyopathy by Regulating Lipid Metabolism.

In a mouse model of type 2 diabetic cardiomyopathy (DCM), researchers tested whether the endogenous metabolite N-lactoyl-phenylalanine (Lac-Phe) improves cardiac function and investigated mechanisms in H9c2 cardiomyoblast cells exposed to high glucose and palmitic acid. Lac-Phe improved cardiac contractile function, reduced pathological remodeling and cardiac lipid accumulation, and in vitro decreased lipid accumulation by lowering cholesterol synthesis. These findings suggest Lac-Phe as a candidate metabolic therapy for DCM targeting cardiac lipid metabolism.

Zhou Z, Yang X, Li W et al. · Journal of visualized experiments : JoVE · (2026) · View on PubMed ↗

Multi-omics integration identifies APOE as a metabolic regulator of macrophage-fibroblast crosstalk in idiopathic pulmonary fibrosis.

Using multi-omics integration, including two-sample Mendelian randomization (MR) and protein interaction network analyses, this study identified APOE as a metabolic regulator of macrophage–fibroblast crosstalk in idiopathic pulmonary fibrosis (IPF). The key finding was that genetically supported APOE-related metabolic pathways causally link immune remodeling (macrophage heterogeneity) to fibroblast activation in the fibrotic niche. If validated experimentally, APOE-centered metabolic modulation could represent a therapeutic strategy to disrupt macrophage–fibroblast signaling in IPF.

Bai B, Chang L, Cheng Z et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction.

The study investigated whether low maternal serum isthmin-2 (ISM2) measured at ~12 weeks of gestation predicts preeclampsia and fetal growth restriction (FGR) in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study) and was validated in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes). Proteomics of maternal serum identified low ISM2 as the strongest first-trimester protein signal among 2,904 proteins associated with later preeclampsia or FGR, with supportive ISM2 mRNA findings. Clinically, ISM2 could serve as an early biomarker to identify pregnancies at high risk for impaired extravillous trophoblast invasion and enable earlier surveillance or intervention.

Miao R, Gong S, Sovio U et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Antifungal therapy improves microbiome dynamics in inflammatory bowel disease.

This prospective observational study compared oral antifungal therapy (swish-and-spit nystatin; ORNT) versus orogastrointestinal antifungal therapy (fluconazole; GIFT) in patients with inflammatory bowel disease (mild-to-moderate ulcerative colitis or Crohn’s disease) who had mild oral thrush and gut Candida sharing. Antifungal treatment improved gut mycobiome dynamics, indicating that targeting Candida/other fungi can modulate the gut fungal ecosystem in IBD. The findings support antifungal strategies as a potential way to address fungal dysbiosis and refine microbiome-directed adjunct therapies in IBD.

Pan X, Conroy A, Ngima TS et al. · Nature medicine · (2026) · View on PubMed ↗

Nutraceuticals and phytoceuticals for the treatment of major depressive disorder: a systematic review and network meta-analysis.

This systematic review and network meta-analysis evaluated randomized clinical trials of nutraceuticals and phytoceuticals for major depressive disorder (MDD), comparing them against placebo or treatment as usual (TAU, antidepressants) across multiple databases up to 01/07/2025. The analysis synthesized effects on depressive symptom change (standardized mean difference), treatment response, and all-cause discontinuation, aiming to rank interventions by comparative efficacy and acceptability. The work informs evidence-based consideration of dietary/plant-derived compounds as adjunct or alternative options in MDD, while clarifying comparative benefits and tolerability across trial types.

Fornaro M, Di Lorenzo C, Nunez N et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

A self-selected vegan diet reduces skeletal muscle mass in healthy older adults: a randomized controlled trial.

This randomized controlled trial studied 72 healthy adults aged ≥65 years to compare a 12-week self-selected vegan diet versus an omnivorous diet, and versus a self-selected vegan diet combined with resistance exercise (VEG-RE), measuring skeletal muscle mass, strength, and muscle protein synthesis (MPS). The key finding was that the self-selected vegan diet reduced skeletal muscle mass compared with the omnivorous diet, and adding resistance exercise did not fully prevent this loss. Clinically, it highlights a potential nutritional risk of vegan diets in older adults and supports the need for strategies (e.g., protein optimization) to preserve muscle.

Domić J, Grootswagers P, Pinckaers PJ et al. · The American journal of clinical nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial diabetes mellitus: real world insights from the GENOMIT registry-a multinational, longitudinal cohort study.

The GENOMIT registry analysis studied real-world risk factors, clinical course, and antidiabetic treatment use in 2,399 patients with genetically confirmed mitochondrial disease–associated diabetes mellitus (mitochondrial diabetes mellitus, mDM) across German, Austrian, and Italian sites (07/2009–01/2025). The cohort characterization and longitudinal data were used to expand the genetic spectrum of mDM and describe how patients were managed with antidiabetic therapies over time. Clinically, these multinational longitudinal insights aim to inform risk stratification and treatment recommendations for a poorly characterized diabetes subtype.

Semmler L, Büchner B, Kornblum C et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Preclinical evidence and multi-omics insights into the protective effects of epigallocatechin-3-gallate against high-fat diet-induced adverse health outcomes.

This preclinical study investigated whether epigallocatechin-3-gallate (EGCG) protects against high-fat diet (HFD)–induced adverse outcomes relevant to dyslipidemia, NAFLD, and type 2 diabetes mellitus using integrated meta-analysis, machine learning, in vivo experiments, proteomics, and public single-cell RNA sequencing (scRNA-seq). By combining these approaches, it aimed to systematically evaluate EGCG’s efficacy and identify mechanistic signatures across datasets. The scientific significance is that multi-omics and computational integration can clarify EGCG’s pathways and strengthen the evidence base for dietary polyphenols as candidate interventions for metabolic disease.

Liu M, Jiang J, Wang Z et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

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Cancer mechanisms & signaling pathways (non-genetic mechanistic drivers)

MAP3K14 (NIK) synonymous variants drive altered splicing to activate NF-κB in mature B-cell malignancies.

This study characterized two recurrent synonymous variants in MAP3K14 (the gene encoding NF-κB-inducing kinase, NIK) across multiple mature B-cell malignancies (including chronic lymphocytic leukemia, lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia, multiple myeloma, and mantle cell lymphoma). The synonymous changes created splice donor sites that removed the critical TRAF3 binding motif, thereby activating non-canonical NF-κB signaling by enabling NIK to drive ncNF-κB. Functionally defining these “silent” MAP3K14 variants clarifies a mechanism of NF-κB pathway activation and may inform genetic diagnostics and targeted therapeutic strategies in B-cell cancers.

Li EW, Heitink L, Bandala-Sanchez E et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.

The study tested whether glutathione reductase (GSR) deficiency increases the immunogenicity of ferroptosis and cuproptosis by amplifying reactive oxygen species (ROS) and activating the cGAS-STING pathway. Using genetic and pharmacologic perturbations (including genome-wide CRISPR screening to identify regulators), it found that GSR loss potentiated ROS accumulation and enhanced cGAS-STING–dependent immune signaling during these cell death programs. This provides a redox-to-immunity mechanism that could be exploited to improve immunogenic cell death–based cancer therapies.

Deng X, Deng Z, Zhu B et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

YTHDC1 functions as a molecular chaperone to suppress ALS-linked hnRNPA1 mutants from aggregation.

The study investigated the ATP-independent chaperone function of the m6A-binding protein YTHDC1 and how it modulates aggregation of ALS-linked hnRNPA1 mutants in cellular and disease-relevant contexts. YTHDC1 was shown to prevent misfolding and aggregation, unfold kinetically trapped substrates, and resolubilize pre-formed aggregates via a polyaspartate/glutamate (polyD/E) segment, with polyD/E deletion abolishing activity while aromatic-cage mutants retained it, indicating m6A recognition is not required. This is clinically important because it identifies a mechanistic, non-m6A-dependent chaperone pathway that suppresses aggregation of ALS-associated hnRNPA1 variants.

Ren K, Cheng M, Luo Q et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

AML1-ETO hijacks a distal enhancer of NAT10 to reprogram glutathione metabolism and sustain leukemia stem cell stemness.

This study examined how the t(8;21) AML fusion protein AML1-ETO uses chromatin regulatory elements to reprogram metabolism in primary t(8;21) AML CD34+ cells and AML cell lines, focusing on the RNA ac4C writer NAT10. Using CUT&Tag mapping, the authors found AML1-ETO binding at a distal enhancer of NAT10 that drives NAT10 transcription and thereby reprograms glutathione metabolism to sustain leukemia stem cell stemness. These results identify a specific distal enhancer–NAT10 axis as a vulnerability in AML1-ETO–driven leukemia biology.

Li S, He S, Su Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Seeds from ALS patients homozygous for the SOD1 D90A mutation transmit two types of SOD1 aggregation and motor neuron disease.

The study investigated whether seeds derived from ALS patients homozygous for the SOD1 D90A mutation transmit distinct SOD1 aggregation strains and cause motor neuron disease. Seed preparations produced two structurally different SOD1 aggregate types (strains A and B), with strain B associated with homozygous hSOD1D90A and also capable of generating strain A. This supports prion-like propagation of SOD1 aggregates in human-derived material and implies that SOD1 “strain” heterogeneity may influence disease phenotype and progression.

Henne C, Sigfridsson I, Brännström T et al. · Acta neuropathologica · (2026) · View on PubMed ↗ · Free PDF ↗

Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.

The study examined whether the tumor-secreted glycoprotein ADAMTSL4 activates latent TGFβ1 to drive cancer cachexia in preclinical models and in patients with colorectal and lung cancers. ADAMTSL4 overexpression converted non-cachexia tumors into cachexia-inducing tumors, while ADAMTSL4 deletion reduced fat/muscle wasting and cachexia severity by promoting local activation of TGFβ1 at muscle cell membranes. These results identify ADAMTSL4–latent TGFβ1 activation as a mechanistic driver of cachexia and a potential therapeutic target.

Machado J, Karthikaisamy V, Mohr H et al. · Cancer discovery · (2026) · View on PubMed ↗ · Free PDF ↗

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Methods, diagnostics & Clinical trial design/real-world evidence (guidelines, imaging/diagnostics, PROs, RT-qPCR artifacts, AI screening)

ACG Clinical Guideline: Diagnosis and Management of Adenomatous Colorectal Polyposis Syndromes.

This ACG clinical guideline synthesized evidence for diagnosing and managing hereditary adenomatous colorectal polyposis syndromes using personal/family history risk assessment and germline genetic testing, followed by timely surgical and endoscopic management. The key recommendation is that identifying these incurable, systemic cancer-predisposition syndromes early can reduce gastrointestinal cancer incidence and mortality. Clinically, the guideline standardizes care pathways for patients and families at risk for adenomatous polyposis syndromes.

Mankaney G, Idos GE, Stoffel EM et al. · The American journal of gastroenterology · (2026) · View on PubMed ↗

Early-onset colorectal cancer in patients under 30: a case series from Tanzania highlighting an emerging epidemiological shift.

This case series described three patients under age 30 with early-onset colorectal cancer (EOCRC) treated at a tertiary referral center in northern Tanzania. All patients presented after prolonged symptoms with advanced disease, with histopathology showing mucinous adenocarcinoma in two cases and adenocarcinoma not otherwise specified in one, and one patient had a family history suggestive of hereditary predisposition. The report highlights an emerging epidemiological shift toward EOCRC in low- and middle-income settings and underscores the need for earlier recognition and evaluation.

Suleman M, Lodhia J, Rwomurushaka ES et al. · Journal of surgical case reports · (2026) · View on PubMed ↗ · Free PDF ↗

A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.

This study performed a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies to quantify variability in motor neuron (MN) loss assessment and then validated a standardized whole-segment approach using tissue clearing, MN tracing, and multimodal imaging. It found substantial (about 60%) variability in reported MN loss, with spinal cord sampling as a major driver, and showed that ChAT provided robust MN labeling compared with less specific markers like SMI-32 and Nissl. The framework improves cross-study comparability of MN degeneration measurements, strengthening mechanistic and therapeutic interpretation across neurodegenerative disease models.

Sowoidnich L, Norman AL, Gerstner F et al. · Acta neuropathologica communications · (2026) · View on PubMed ↗

Intestinal Ultrasound Predicts Primary Non-Response and Maintenance Relapse in Upadacitinib-Treated Active Crohn’s Disease: A Multicenter, Prospective Cohort Study.

This multicenter prospective cohort study assessed whether intestinal ultrasound (IUS) predicts primary non-response (PNR) and maintenance relapse in 122 patients with active Crohn’s disease treated with upadacitinib (UPA) through week 52. The key finding was that post-induction IUS targets were associated with higher risk of PNR and subsequent maintenance relapse, enabling risk stratification beyond standard clinical and biochemical measures. Clinically, it supports using IUS as a noninvasive monitoring tool to guide early treatment decisions in UPA-treated Crohn’s disease.

He R, Huang Y, Han J et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

AI-enhanced adaptive virtual screening of large libraries for ligand discovery.

This work introduced AdaptiveFlow, an AI-enhanced adaptive virtual screening platform, to improve ultralarge virtual screening (ULVS) for ligand discovery by addressing cost, flexibility, and scalability limits. AdaptiveFlow provides a screening-ready version of the Enamine REAL Space library (69 billion ready-to-dock compounds) and uses an 18-dimensional molecular property grid with optional active learning to reduce computational cost while prioritizing promising chemical subspaces. Scientifically, it advances scalable ML-driven drug discovery workflows for screening massive chemical libraries.

Cecchini D, Nigam A, Tang M et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

A pervasive RT-qPCR artifact inflates RNA knockdown by RNA-targeting CRISPR.

The study examined how RNA-targeting CRISPR knockdown is quantified by RT-qPCR in experimental settings where guide RNAs may be present during RNA extraction. The authors found that guide RNAs copurify and inhibit RT-qPCR for amplicons spanning or upstream of the guide RNA binding site, systematically inflating apparent knockdown efficiency across all CRISPR systems tested. This work is significant because it provides a concrete RT-qPCR artifact mechanism and recommends using a processive, strand-displacing reverse transcriptase and orthogonal validation to ensure accurate RNA-targeting CRISPR quantification.

Watkins L, Zhu A, Wu B · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Live-cell transcriptomics with engineered virus-like particles.

This study developed live-cell transcriptomics using engineered virus-like particles (VLPs) that export mRNA from mammalian cells so transcriptional states can be sampled repeatedly without lysing the cells. The key finding was that VLP-mediated mRNA export from VLP-producing cultures faithfully captured evolving transcriptional dynamics during acute inflammatory stimulation of primary cell spheroids and across multi-day differentiation of pluripotent stem cells. Scientifically, this enables longitudinal measurement of gene-expression trajectories in the same biological system, improving studies of dynamic processes such as inflammation and differentiation.

Najia MA, Le A, Borrajo J et al. · Cell · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗

Ratiometric transcriptional activation by protein degradation.

This study explored synthetic gene-regulatory circuit design principles that convert protein degradation events into transcriptional outputs in live cells, introducing a ratiometric transcriptional activation strategy. The key finding was that controlling the ratio between a transcription factor and a protein-of-interest fused to its inhibitor enables sensitive detection of protein abundance changes at scale, with degradation-driven transcriptional activation following defined design rules. This provides a programmable framework for building cells that report protein dynamics more robustly than transcription-only or non-ratiometric approaches.

Gray MA, Randal KL, Co JA et al. · Cell · (2026) · View on PubMed ↗

De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles.

This paper describes de novo design of pan-rhodamine fluorescent binders (“Rhobin”) for fluorescence microscopy, enabling reversible binding across diverse rhodamine fluorophores. The key finding was that Rhobin provides a compact, bright, reversible labeling system that works for live- and fixed-cell imaging in mammalian cells and remains stable across diverse conditions, with performance surpassing prior approaches (as reported in the abstract). Technically, this expands the toolkit for multiplexed and robust fluorescence imaging beyond what existing fluorescent protein tags can achieve.

Chen Y, Yserentant K, Hong K et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Vornorexant versus Lemborexant for Insomnia Disorder: A Systematic Review and Network Meta-analysis.

This systematic review and frequentist network meta-analysis compared vornorexant (VOR) versus lemborexant (LEM) for adults with insomnia disorder, focusing on efficacy, tolerability, and safety. It evaluated subjective time to sleep onset (sTSO) at week 2 as a primary endpoint and also compared outcomes such as sTST, sWASO, sleep efficiency, discontinuation due to adverse events, and safety events including somnolence and falls. The clinical significance is that it provides comparative evidence to guide selection between dual orexin receptor antagonists for insomnia based on both effectiveness and adverse-effect profiles.

Kishi T, Sakuma K, Kitajima T et al. · The international journal of neuropsychopharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Mechanism of gating and isoform-specific inhibition in renal CLC chloride channels.

This study investigated the molecular basis for gating and isoform-specific inhibition of renal CLC chloride channels, focusing on the selective inhibitor BIM1 and the CLC-Ka versus CLC-Kb distinction. The key finding was that BIM1 preferentially inhibits CLC-Ka over CLC-Kb, and the authors used mechanistic analyses to explain how this selectivity arises at the level of channel gating/inhibition. This provides a clearer pharmacologic mechanism for designing safer, isoform-selective CLC-Ka inhibitors to address hyponatremia.

Chien CT, Sobecks-Doherty BL, Powers AS et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Investigating the Pharmacokinetics, Injection Speed, and Usability of Subcutaneous Efgartigimod PH20 Administered with a Prefilled Syringe.

The study investigated the pharmacokinetics, injection speed, and usability of a subcutaneous efgartigimod PH20 formulation delivered via a prefilled syringe (PFS), compared with the original vial plus separate syringe approach. It focused on efgartigimod PH20 SC, where efgartigimod is an IgG1 Fc fragment that blocks the neonatal Fc receptor (FcRn) to reduce circulating IgG, including pathogenic autoantibodies. The significance is that optimizing delivery (PFS usability and injection characteristics) can improve patient experience and potentially support broader clinical adoption of PH20 SC therapy.

De Muynck C, Noukens J, Allosery K et al. · Advances in therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Guidelines for diagnostic testing in adults with presumed atopic dermatitis refractory to treatment.

The study developed evidence-based guidelines for diagnostic testing in adults with presumed atopic dermatitis (AD) that is refractory to optimized treatment. The key finding was a structured, multidisciplinary diagnostic workup approach to identify misdiagnosis and comorbid conditions contributing to treatment failure in refractory adult AD. Clinically, this provides a practical framework to improve diagnostic accuracy and reduce inappropriate therapy in patients not responding to standard AD management.

Sidbury R, Wu PA, Alikhan A et al. · Journal of the American Academy of Dermatology · (2026) · View on PubMed ↗

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Neurobiology: Synaptic plasticity, neural circuits, and neurovascular coupling

RNA-Binding Protein MBNL2 Drives Cardiac Hypertrophy and Dysfunction by Facilitating TPM3 Splicing.

This mechanistic study investigated how RNA-binding protein MBNL2 drives cardiac hypertrophy and dysfunction by regulating TPM3 splicing, using adeno-associated virus serotype 9 to overexpress MBNL2 in cardiomyocytes and generating cardiomyocyte-specific MBNL2 knockout mice. MBNL2 overexpression and loss-of-function experiments showed that MBNL2 facilitates TPM3 alternative splicing in ways that promote hypertrophic remodeling and impaired cardiac function. Defining the MBNL2–TPM3 splicing axis identifies a potential molecular target to prevent or treat pathological cardiac hypertrophy.

Shi Y, Sheng S, Wang B et al. · Circulation research · (2026) · View on PubMed ↗

The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.

The study examined whether the medial prefrontal cortex (mPFC)–reuniens–hippocampus pathway causally regulates neural plasticity and antidepressant-like responses in a mouse model of stress-induced depression. Chemogenetic activation of the infralimbic cortex (IL) produced rapid antidepressant-like effects and engaged top-down control over the hippocampus, restoring long-term potentiation deficits, improving state-dependent ventral hippocampal network dynamics, and enhancing structural plasticity. This is important because it defines a specific brain circuit mechanism connecting antidepressant response to hippocampal plasticity.

Veleanu M, Schuberth L, Kilias A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.

The study investigated how the glial-enriched polyamine transporter ATP13A4 controls extracellular polyamine availability and thereby regulates excitatory synaptogenesis, focusing on astrocyte biology. ATP13A4 was found to import polyamines into cells, reducing extracellular spermidine availability; loss of ATP13A4 simplified astrocyte morphology and increased astrocyte-promoted excitatory synapse formation, while adding spermidine reproduced the synapse-promoting phenotype. This is significant because it identifies extracellular spermidine as a functional synaptogenic signal governed by ATP13A4, linking polyamine homeostasis to synapse development.

van Veen S, Meeus E, Irala D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

ORAI Ca2+ channels and STIM1 drive capillary-to-arteriole communication in neurovascular coupling.

This study investigated how ORAI1 Ca2+ channels and the ER Ca2+ sensor STIM1 mediate capillary-to-arteriole communication during neurovascular coupling in vivo. Endothelial-specific knockout of Stim1 or Orai1 disrupted capillary Ca2+ signals, impaired sustained capillary-driven arteriole dilation, and reduced whisker-stimulation–evoked blood flow increases in the somatosensory cortex. The findings identify ORAI1/STIM1 store-operated Ca2+ entry as a critical signaling pathway sustaining cerebral blood flow during neuronal activity.

Lavanderos B, Sanchez-Solano A, Zhu W et al. · Science signaling · (2026) · 1 citations · View on PubMed ↗

MGRN1 preserves transiently damaged mitochondria for antioxidant-mediated repair.

The study used a cell-based system to induce transient mitochondrial stress and then tracked recovery dynamics to determine how cells decide between repair versus elimination. It identified the E3 ubiquitin ligase MGRN1 (mahogunin ring finger 1) as a damage-threshold sensor that, during transient stress, associates with the outer mitochondrial membrane via MFN1 to restrain mitophagy and preserve mitochondria for repair. This mechanistic insight suggests MGRN1–MFN1–mitophagy control as a potential target to modulate mitochondrial quality control in aging and mitochondrial disease.

Chen N, Li Z, Wang X et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

Ceramide transfer protein regulates G-protein-coupled phospholipase signalling in photoreceptors.

The study examined how ceramide transfer protein (CERT), encoded by dcert in Drosophila, regulates G-protein-coupled phospholipase signaling in photoreceptors. Loss of dcert increased short-chain ceramides and reduced phosphoethanolamine ceramide, accompanied by a diminished electrical light response in photoreceptors. These findings establish CERT-mediated ceramide trafficking at membrane contact sites as a functional regulator of phototransduction signaling and suggest lipid-transfer control as a potential target for sensory dysfunction.

Mishra S, Khan A, Nath VR et al. · The Journal of cell biology · (2026) · View on PubMed ↗

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Genetics, genomics & molecular regulation (splicing/APA, QTLs, telomeres, rare variants)

RNF213 regulates palmitate signaling through AAA+ and RZ-finger domains, a process enhanced by gain-of-function moyamoya disease-associated mutations.

The study investigated how RNF213 regulates palmitate signaling via its AAA+ ATPase and RZ-finger domains and how gain-of-function moyamoya disease-associated mutations enhance this process. RNF213 activity was shown to be functionally linked to palmitate-driven signaling, with disease mutations amplifying the pathway. These mechanistic insights clarify how lipid-stress signaling may contribute to moyamoya disease and related vascular occlusive disorders.

Huang Q, Tezuka T, Iida K et al. · The FEBS journal · (2026) · View on PubMed ↗

Whole-exome sequencing in individuals with obsessive-compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes.

Using whole-exome sequencing, the study analyzed 3,964 individuals with obsessive-compulsive disorder (OCD), chronic tic disorders (CTDs), or both (including 2,418 trios) to identify rare, large-effect genetic risk factors. It found an excess of de novo and rare protein-damaging mutations and identified 36 high-confidence risk genes (FDR <0.1), including four previously known genes (CELSR3, CHD8, SCUBE1, WWC1) and additional genes overlapping OCD GWAS loci (BRWD1, CELSR3, QRICH1, SYNE1). These results expand the genetic architecture of OCD/CTDs and provide targets for mechanistic studies and improved risk stratification.

Wang B, Tran MN, Wang S et al. · Nature neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.

The study generated a long-read proteogenomic atlas of human neuronal differentiation by integrating deep long-read RNA sequencing and proteomics in induced pluripotent stem cell (iPSC)-derived cortical neurons. It identified 182,371 mRNA isoforms (with over half previously unknown) and provided direct peptide evidence for translation of hundreds of novel protein-coding sequences, with population genetics showing variants affecting novel exons/splice sites under negative selection. This is significant for neurodevelopmental risk biology because it links developmental splicing/isoform diversity to genetic constraint and provides experimentally supported targets for disease mechanism studies.

Xu N, Rynard KM, Radley E et al. · Nature communications · (2026) · View on PubMed ↗

Decoding anterior-posterior patterning cues into embryo-wide binary fate decisions through recruitment-mediated targeting.

This study in Caenorhabditis elegans investigated how quantitatively asymmetric Wnt/β-catenin signals (anterior POP-1/TCF and posterior SYS-1/β-catenin) are converted into embryo-wide binary fate decisions. The authors show that the transcription factor ZIP-7/DBP, with stage-specific posterior-exclusive expression, is essential for multiple posterior fate decisions and resolves Wnt/β-catenin cues into switch-like regulatory outputs. Scientifically, it clarifies a recruitment-mediated mechanism for turning graded morphogen signaling into discrete gene-regulatory states.

Xiao L, Cong Y, Qi H et al. · Genes & development · (2026) · View on PubMed ↗ · Free PDF ↗

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

This study investigated how genetic variants regulate CPEB3-mediated alternative polyadenylation (APA) and how these APA quantitative trait loci (apaQTL) relate to survival in hepatocellular carcinoma (HCC). Using TCGA genotype and APA profiling with prognosis-apaQTL analyses and two-stage survival validation in 848 Chinese and 369 TCGA LIHC patients, it identified prognostic APA events and performed functional validation. The significance is that CPEB3-associated APA genetic regulation could provide new prognostic markers and mechanistic targets for HCC progression.

Wang H, Zhang S, Zhang C et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗

Actin depolymerization factor (ADF) moonlighting: Nuclear immune regulation by interacting with WRKY transcription factors and shaping the transcriptome.

This study investigated nuclear “moonlighting” functions of Arabidopsis actin depolymerization factors (ADFs) and how they interact with WRKY transcription factors to shape immune-related gene expression. The key finding was that ADFs act in the nucleus by partnering with WRKY proteins to reprogram the transcriptome beyond their canonical cytosolic role in actin filament severing/depolymerization. This mechanistic link advances understanding of how plant actin regulators can directly control transcriptional programs during plant immunity.

Li P, Kelley B, Xie X et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Reexamining the activation mechanisms of adhesion G protein-coupled receptors.

This review/reanalysis study focused on adhesion G protein-coupled receptors (aGPCRs) and reexamined how these receptors are activated, challenging the traditional tethered agonist (TA) model. The key finding is that accumulating structural, functional, and biophysical evidence suggests TA exposure alone does not fully explain aGPCR activation, implying additional or alternative activation mechanisms. This reframing is significant for guiding future experiments and for drug discovery targeting aGPCRs.

Araç D, Kordon SP · Science signaling · (2026) · View on PubMed ↗

Multi-organ single-cell transcriptomic atlas identifies QrIAA14 as a candidate negative regulator of adventitious root development in Quercus robur.

The study generated a multi-organ single-cell RNA-seq atlas of leaf, stem, and root tissues in the woody plant Quercus robur to map cellular developmental trajectories and regulators of adventitious root development during vegetative propagation. It identified QrIAA14 as a candidate negative regulator of adventitious root development, supported by cell-type/trajectory-specific transcriptional evidence across the three organs. This provides a cell-resolved regulatory target (QrIAA14) that could be leveraged to improve rooting efficiency in oak propagation systems.

Hui W, Li J, Li H et al. · PLoS genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Hypomorphic Lig4 gene mutation in mice predisposes to Th1-skewed intestinal inflammation.

The study created and characterized mice carrying the hypomorphic DNA ligase IV (Lig4) missense mutation p.W447C (Lig4W447C/W447C) to model LIG4 syndrome and its DNA double-strand break repair defects. Mutant mice showed functional impairment of LIGIV, growth retardation, increased radiosensitivity, and a predisposition to Th1-skewed intestinal inflammation. Scientifically, it provides an in vivo mechanism linking hypomorphic DSB repair (LIG4) to Th1-biased gut inflammation, supporting the relevance of DNA repair defects to immune dysregulation.

Yamashita Y, Kosako H, Kato T et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration & Dementia (Alzheimer spectrum, MS imaging, and biomarkers)

Symptomatic treatment for Alzheimer disease: current evidence and future directions.

This Nature Reviews Neurology article synthesized evidence on symptomatic treatments for Alzheimer disease, covering both pharmacological options (including cholinesterase inhibitors and memantine) and non-pharmacological interventions (e.g., cognitive training, physical exercise, cognitive stimulation therapy, and multimodal lifestyle programmes). Overall, non-pharmacological approaches show small-to-moderate benefits—particularly in mild cognitive impairment—while established drugs provide modest but significant symptomatic effects on cognition and related outcomes. The review highlights practical implementation challenges and frames how symptomatic care remains essential alongside emerging disease-modifying therapies.

Ballard C, Doherty P, Ismail Z et al. · Nature reviews. Neurology · (2026) · View on PubMed ↗

The Gut Microbiota and Gut-Brain Axis in Alzheimer’s Disease: From Pathogenesis to Treatment.

This narrative review synthesized evidence on the gut microbiota and the microbiota–gut–brain axis in Alzheimer’s disease (AD), linking gut dysbiosis to amyloid-β deposition, tau pathology, neuroinflammation, and neurovascular dysfunction. The key finding is that modifiable peripheral factors (diet, medications, aging, intestinal physiology) may influence barrier homeostasis, immunometabolic state, neural afferent signaling, and brain responses to pathology. The review is significant because it frames microbiome-targeted interventions as potential therapeutic avenues for AD beyond traditional amyloid/tau-centric approaches.

Wang J, Luo L, Zhang J et al. · Ageing research reviews · (2026) · View on PubMed ↗

Cross-species single-cell atlas of the striatum defines cell-type and subregion disease vulnerabilities.

This study generated a cross-species single-cell atlas of the striatum using single-nucleus RNA sequencing across 109 human and 22 mouse samples spanning dorsal and ventral striatum. It identified cell-type and subregion-specific neuronal specialization, including rare neuronal subpopulations and transcriptional gradients along the dorsolateral–ventromedial axis, with notable differences between species that map to disease vulnerabilities. The atlas helps pinpoint which striatal cell states may be most relevant to neurodegenerative and neuropsychiatric disorders and supports translational targeting across model systems.

Linville RM, James BT, Galani K et al. · Cell · (2026) · View on PubMed ↗

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis estimated the prevalence of slowly expanding lesions (SELs) among T2 lesions and among patients with multiple sclerosis (MS), and quantified overlap between SELs and paramagnetic rim lesions (PRLs) on susceptibility-sensitive MRI. It used conventional MRI criteria for SELs (linear, concentric expansion over time) and PRL identification based on a paramagnetic rim, synthesizing evidence across studies. The clinical significance is improved understanding of chronic active lesion burden in MS and how SELs relate to PRLs, which may inform prognosis and imaging biomarkers.

Liampas A, Artemiadis A, Tseriotis VS et al. · Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Longitudinal Dynamics of the Blood Proteome Within the Alzheimer Spectrum in Down Syndrome.

This longitudinal proteomics study measured plasma protein trajectories across the Alzheimer spectrum in adults with Down syndrome (DS) to assess potential links to disease pathophysiology. Building on prior cross-sectional findings, it focused on longitudinal dynamics of proteins previously implicated (including CBLN4, CD14, CXCL17, EDA2R, GFAP, IGFBP2, NFL, SEPTIN3, and SPON1). The significance is that longitudinal blood proteome changes may yield candidate biomarkers for early Alzheimer disease risk and progression in DS.

Wagemann O, Nuebling GS, Sandkühler K et al. · Neurology · (2026) · View on PubMed ↗

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Infectious disease & Host–Pathogen interactions (TB, malaria, cholera, HIV, bacteria/EVs)

Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy.

This study examined HIV-1 reservoir persistence during long-term suppressive antiretroviral therapy by analyzing >6,000 proviral DNA amplicons from 104 individuals. Carriers of HLA-C2 allotypes (which educate NK cells via KIR2DL1 interactions) had lower frequencies of intact proviruses, with no protective effect observed during untreated infection, suggesting selective vulnerability of reservoir cells to NK-cell-mediated activity under ART. The findings support an “innate immune imprinting” model and point to NK-cell education pathways (HLA-C2/KIR2DL1) as potential levers for reservoir-targeting strategies.

Tan TS, Sun W, Gao C et al. · Nature immunology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Vibrio cholerae-synthesized tryptophan activates innate immune signaling in enteroendocrine cells via phosphorylation of the nuclear receptor ultraspiracle.

The study examined how Vibrio cholerae–produced tryptophan activates innate immune signaling in enteroendocrine cells (EECs) through phosphorylation of the nuclear receptor ultraspiracle. It showed that V. cholerae tryptophan drives host enterocyte serotonin synthesis, which then signals to EECs to activate the TNF-like immune deficiency pathway IMD via a serotonin GPCR subset involving Gαq, phospholipase C, and protein kinase C. This is significant because it connects bacterial tryptophan metabolism to host neuroendocrine immune activation through a defined serotonin–IMD signaling axis.

Ding X, Watnick PI · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Cefepime versus piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa pneumonia.

This single-center retrospective cohort study compared cefepime versus piperacillin-tazobactam for treating pneumonia caused by Pseudomonas aeruginosa in hospitalized patients. The key finding was that the two regimens differed in outcomes assessed by 30-day mortality and a desirability of outcome ranking (DOOR) incorporating clinical failure, resistance, acute kidney injury (AKI), and recurrence, with overlap-weighted analyses used to address confounding. Clinically, it informs empiric and targeted antibiotic selection for P. aeruginosa pneumonia by evaluating both effectiveness and safety endpoints.

Pallotta RH, Wangchinda W, Sallerson SR et al. · Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · (2026) · View on PubMed ↗ · Free PDF ↗

Oxygen-responsive bacterial glycosphingolipid links symbiont fitness and immune development in neonatal host.

This work investigated how the neonatal gut symbiont Bacteroides fragilis colonizes early-life hosts, focusing on the oxygen-responsive role of the bacterial glycosphingolipid alpha-galactosylceramide (BfaGC). Genome-wide fitness profiling showed that BfaGC biosynthesis is selectively required during early life when transient oxygenation bottlenecks strict anaerobes, and mechanistically BfaGC reduces membrane proton permeability to sustain proton-motive force for aerobic respiration while generating a host-facing immunomodulator. These results link a specific bacterial lipid adaptation to both symbiont fitness and immune development in the neonatal host.

Heo K, Jung DJ, Yoo JS et al. · Cell · (2026) · View on PubMed ↗

The TRAF6-Akt axis is required for efficient lytic replication of KSHV.

This study explored how the host ubiquitin ligase TRAF6 supports Kaposi’s sarcoma–associated herpesvirus (KSHV) lytic replication. Mechanistically, during lytic replication TRAF6 promoted K63-linked polyubiquitination and activation of Akt, and CRISPR knockout or pharmacologic inhibition of TRAF6 or Akt reduced KSHV replication efficiency. This defines a TRAF6–Akt axis as a host dependency for efficient viral lytic growth, suggesting potential host-targeted antiviral strategies.

Liu Z, Guo Q, Wang W et al. · PLoS pathogens · (2026) · View on PubMed ↗ · Free PDF ↗

Plasmodium falciparum subverts neutrophil function via host miR-451a loaded extracellular vesicles driving bacterial and fungal superinfection susceptibility.

This study examined how Plasmodium falciparum uses extracellular vesicles (EVs) to manipulate human neutrophil function and promote bacterial/fungal superinfection susceptibility. The key finding was that iRBC-derived EVs deliver host miR-451a to neutrophils, suppressing ROS production and microbicidal activity against Salmonella typhimurium and impairing neutrophil chemotaxis and swarming in microfluidic assays. This reveals a specific parasite-driven EV–miRNA mechanism for innate immune dysfunction that could contribute to malaria-associated superinfections.

Babatunde KA, Ngara M, Martinez Murillo P et al. · PLoS pathogens · (2026) · View on PubMed ↗ · Free PDF ↗

Mycobacterial vaccination of fish and human tuberculin skin test reactivity: a testable One Health interface.

This article reviewed and analyzed how mycobacterial vaccination in fish and humans affects tuberculin skin test (TST) reactivity, focusing on the One Health interface between aquaculture and human tuberculosis diagnostics. It highlights that TST interpretation is confounded by BCG vaccination, exposure to environmental non-tuberculous mycobacteria (NTM), PPD antigen complexity, cutoff selection, and local epidemiology. The significance is that better cross-species vaccination and diagnostic interpretation frameworks are needed to avoid misclassification of mycobacterial sensitization in both aquaculture and human populations.

Mataragka A · Future microbiology · (2026) · View on PubMed ↗

Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.

The study compared IFNγ-induced inducible nitric oxide synthase (iNOS) responses across species using Mtb-infected myeloid cells, including human cells, to determine how iNOS activity relates to IFNγ effector function. iNOS expression and nitric-oxide output differed by species, with species-specific patterns distinguishing epithelial versus myeloid IFNγ responses to tuberculosis. This clarifies when IFNγ-driven iNOS is likely to be a dominant antimicrobial mechanism in natural hosts and can inform translational interpretation of TB immunology and vaccine strategies.

Stei F, McCaffrey EF, Zessin B et al. · American journal of respiratory cell and molecular biology · (2026) · View on PubMed ↗

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Aging biology & Biological age measurement

How telomere attrition protects against cancer.

This Nature Reviews Genetics article reviewed evidence that telomere attrition acts as a tumor-suppressor barrier by limiting cell proliferation and preventing emerging cancers when telomeric DNA becomes depleted. It emphasized how telomere length at birth influences lifelong cancer risk, how telomere length is regulated, and how telomerase activation can allow malignant cells to bypass telomere attrition. The review reframes telomere shortening as protective in normal contexts and highlights mechanistic pathways relevant to cancer prevention and therapy.

Stuart A, Zhang B, Hockemeyer D et al. · Nature reviews. Genetics · (2026) · View on PubMed ↗

Aging vs. biological age: Conceptual considerations for age reversal claims.

This article examined the conceptual meaning and evidentiary requirements for claims of “biological age reversal” versus “aging reversal” in the aging field. It argues that the burden of proof depends on how biological age is defined and measured, and it highlights foundational issues in the language used to debate reversal claims. Scientifically, it provides a framework to improve rigor and reduce overinterpretation in studies proposing interventions that reverse biological age.

Poganik JR, Moldakozhayev A, Justice JN et al. · Cell metabolism · (2026) · View on PubMed ↗

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Cancer genomics, evolution, and single-cell atlases (including metastasis tropism)

A single-cell atlas of multiple myeloma defines malignant archetypes and proliferative states.

The study generated a clinically annotated, population-scale single-cell atlas of multiple myeloma (MM) from 341 individuals across the disease and treatment continuum to define malignant transcriptional archetypes and proliferative states. It identified five recurrent malignant transcriptional archetypes and an orthogonal proliferative program linked to genomic features, therapeutic resistance, and clinical outcomes, with validation in the independent CoMMpass cohort showing robustness and prognostic relevance. This single-cell framework supports improved MM classification and a target-discovery pipeline for precision therapy development.

Zada M, Kurilovich A, Shapira N et al. · Nature genetics · (2026) · View on PubMed ↗

Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer.

This integrated clinicogenomic analysis examined over 7,000 consecutively sequenced colorectal cancer (CRC) samples to characterize genetic evolution and metastatic tropisms. The key finding was that evolutionary genomic changes (e.g., clonal mutations and oncogenic mutant allelic imbalance) selectively amplify the impact of recurrent oncogenic alterations, and that metastatic timing differs by molecular context—such as late brain and adrenal metastases in microsatellite stable CRC—while certain metastatic sites cluster together (e.g., lung, bone, brain). Scientifically and clinically, mapping the temporal order of metastasis alongside genomic drivers can improve prognostic modeling and may inform surveillance and therapeutic targeting.

Manca P, Walch H, Xu J et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

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Reproductive health & Pregnancy (preeclampsia/FGR, PGT-A, cervical HPV statements)

FIGO/IGCS Statement on the efficacy of topical treatments for high-risk human papillomavirus in preventing CIN 3+ lesions.

The study is a FIGO/IGCS position statement that critically appraised evidence for topical treatments aimed at clearing high-risk human papillomavirus (HR-HPV) and preventing CIN 3+ lesions. The key conclusion is that the available evidence base is limited—no randomized controlled trial was identified in the provided excerpt—leading to evidence-based recommendations for clinical practice and future research. This is significant because it guides clinicians and researchers on the current effectiveness and evidentiary gaps for topical HR-HPV therapies in preventing high-grade cervical disease.

Pareja R, Heredia F, Sánchez-Díaz E et al. · International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · (2026) · View on PubMed ↗ · Free PDF ↗

International Papillomavirus Society statement on reputed treatments for human papillomavirus infection and human papillomavirus-related diseases: evidence, risks, and standards for clinical evaluation.

This International Papillomavirus Society statement reviewed evidence for reputed therapies for human papillomavirus (HPV) infection and HPV-related diseases, focusing on how such interventions should be clinically evaluated worldwide. It concludes that no HPV therapy has yet demonstrated proven, durable efficacy for eradication of HPV infection or consistently effective treatment of HPV-related disease, and it outlines risks and standards for clinical trials. The guidance is clinically significant because it sets evidence-based benchmarks to prevent adoption of unproven HPV “treatments,” especially in low-resource settings lacking ablative/excisional procedures.

Arroyo Mühr LS, Mungo C, Chatzistamatiou K et al. · International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · (2026) · View on PubMed ↗ · Free PDF ↗

Multicenter Assessment of Outcomes After Intended or Non-selective Transfer of Whole Chromosome and Segmental Aneuploid Embryos.

This multicenter retrospective cohort study assessed clinical outcomes after intended or non-selective transfer of preimplantation genetic testing for aneuploidy (PGT-A) classified embryos—non-mosaic whole chromosome aneuploid (WCA) versus segmental aneuploid (SA)—using data from eight centers in the IRMET network. The key finding was that embryo classification by PGT-A (WCA vs SA) was associated with differences in clinical outcome potential across 250 documented embryo transfers. Scientifically, it informs how PGT-A results should be interpreted for embryo transfer decisions when non-mosaic aneuploidy is involved.

Viotti M, Madjunkova S, Besser A et al. · Fertility and sterility · (2026) · View on PubMed ↗

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Dermatology & Allergy (atopic dermatitis, pruritus)

RANDOMIZED CONTROLLED STUDY OF NEMOLIZUMAB IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND ASSOCIATED PRURITUS: NIKAIA-1.

This 12-week randomized, placebo-controlled trial (NIKAIA-1) evaluated nemolizumab, an anti–IL-31 monoclonal antibody, in 258 hemodialysis patients with chronic kidney disease–associated pruritus (CKD-aP) using 30 mg or 60 mg every 4 weeks. The key finding was that nemolizumab improved pruritus severity and related outcomes (including sleep disturbance and quality of life) compared with placebo. Scientifically and clinically, it supports IL-31 blockade as an effective therapy for uremic pruritus in CKD patients.

Mathur VS, Fishbane S, Ständer S et al. · Journal of the American Academy of Dermatology · (2026) · View on PubMed ↗ · Free PDF ↗

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Immunology & Autoimmunity (Tregs, lupus, SLE, innate immune pathways)

The renaissance of hydroxychloroquine: bridging antimicrobial immunity and autoimmunity in rheumatic diseases.

This narrative review summarized the immunomodulatory mechanisms of hydroxychloroquine (HCQ) in rheumatic diseases, emphasizing endosomal/lysosomal alkalinization and downstream effects on Toll-like receptor 7/9 and cGAS–STING signaling. The key finding is that HCQ bridges antimicrobial immunity and autoimmunity through these innate immune pathways, with additional proposed effects on CD3ζ/CD4 endocytic turnover. Clinically, it reinforces HCQ’s mechanistic rationale for foundational use in systemic lupus erythematosus (SLE) and related rheumatic conditions.

Szabó M, Perl A, Nagy G et al. · Autoimmunity reviews · (2026) · View on PubMed ↗

Rbp-Jκ controls NK cell late maturation and migration via chromatin landscape remodeling.

This study tested the role of the Notch transcriptional regulator Rbp-Jκ in NK cell maturation and migration using NK cell–specific deletion (Ncr1iCre × Rbp-Jκfl/fl; Rbp-JκΔNK) in vivo. Rbp-Jκ-deficient NK cells showed impaired terminal maturation and defective migration (reduced circulating NK cells and decreased migration mediators CD62L, S1pr5, and Cx3cr1), leading to failure to control B16F10 lung metastases due to impaired tissue mobilization. The work links Notch/Rbp-Jκ–dependent chromatin remodeling to functional NK cell trafficking, informing strategies to improve NK-based anti-tumor immunity.

Peng H, Yang Y, Liu Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

The SLC15A4-TASL complex is essential for lupus development in mice.

This study evaluated the requirement of the SLC15A4–TASL signaling complex for lupus development in mice using genetic SLC15A4/TASL pathway perturbations across three complementary SLE models. The key finding was that SLC15A4–TASL signaling was broadly required for disease pathogenesis, with Tasl knockout (TaslKO) and Tasl2 paralogue knockout (TaslDKO) ameliorating or fully preventing autoimmune manifestations in Faslpr loss-of-function contexts. These results establish the SLC15A4–TASL axis as a cross-model driver of SLE-like disease and a potential therapeutic target.

Drobek A, Delacrétaz M, Vasilakou A et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

CD8⁺ Regulatory T Cells Shorten Neutrophil Lifespan to Reduce Hemorrhagic Transformation After Ischemic Stroke.

The researchers examined patient samples and used a murine ischemic stroke model to test how CD8⁺ regulatory T cells (CD8 Tregs) influence neutrophil behavior and hemorrhagic transformation (HT). They found that CD8 Tregs shorten neutrophil lifespan (rather than changing proliferation, bone marrow release, or direct cytotoxicity) by modulating HIF-1α-dependent glycolytic activity and relieving PD-L1–mediated effects, thereby reducing endothelial disruption and HT. Clinically, this identifies CD8 Tregs and their metabolic/PD-L1–linked pathways as potential therapeutic levers to lower HT risk after ischemic stroke.

Lu J, Zhang Q, Chen J et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Enhancing Treg persistence by inhibiting necroptosis restrains autoimmune pathology.

The study used an in vitro system modeling the inflammatory CNS milieu of multiple sclerosis (MS) and a pooled shRNA screen to identify pathways that limit regulatory T (Treg) cell persistence, then validated findings in a mouse MS model and in patients with MS. It found that necroptotic signaling drives Treg cell death and reduces functional persistence, with MS Tregs showing preferential susceptibility to RIPK1 kinase-dependent necroptosis. This supports inhibiting necroptosis (via RIPK1-dependent mechanisms) as a strategy to enhance Treg durability and restrain autoimmune pathology.

Wu Q, Cui N, Gao L et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Early Use of Fostamatinib in Immune Thrombocytopenia.

This multicenter real-world study assessed effectiveness and safety of fostamatinib, an oral SYK inhibitor, as second- or third-line therapy in adult patients with immune thrombocytopenia (ITP) in Spain. In 72 adults treated across 22 centers, the study evaluated treatment responses and adverse events (AEs) to characterize outcomes in earlier-line use. The significance is that it informs how fostamatinib performs outside clinical trials when used earlier in the treatment pathway for adult ITP.

González-López TJ, Bermejo-Vega N, Cardesa-Cabrera R et al. · Advances in therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on September 03, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.