PubMed Trending Research Digest — August 23, 2026

Automated digest · 97 articles · 15 research areas · August 23, 2026

Overview

This week’s research landscape is dominated by two converging trends: (1) precision stratification—using biomarkers, multi-omics, and decision-rule frameworks to predict who will benefit (or be at risk), and (2) next-generation therapeutics that combine targeted mechanisms with scalable delivery.

Across infectious disease, respiratory medicine, and cardiometabolic care, several studies emphasize risk prediction and tailoring: symptom burden in asthma (ACQ-5) as a prognostic/predictive tool; real-world comparisons of asthma biologics for respiratory viral risk; and thyroid/aging-adaptation measurements that improve interpretation of labs and biological trajectories. In cancer and neurodegeneration, the same “mechanism-to-decision” logic appears repeatedly: functional mapping of variants, cell-type–specific extracellular vesicle signatures, and causal/trajectory analyses that connect molecular pathways to clinical outcomes.

On the therapeutic side, immuno-oncology continues to mature with durable perioperative PD-1 blockade in early NSCLC and post-chemoradiation dual immunotherapy strategies in esophageal squamous cell carcinoma. Meanwhile, CAR T approaches expand both in efficacy and engineering ambition—targeting toxicity drivers like TNF in CRS models and moving toward in vivo CAR T manufacturing. In parallel, neurodegeneration and brain injury work highlights emerging targets (e.g., NAD+-mitophagy, glial handling of α-synuclein, and transcriptomic risk stratification at birth), reinforcing a broader shift toward earlier, more mechanistically grounded intervention.

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Infectious Diseases & Antimicrobial Therapy

Berberine induces PD-L1 degradation via the autophagy-lysosome pathway through the PI3K-Akt pathway and enhances immunogenic cell death in triple-negative breast cancer.

This study investigated how berberine (BBR) regulates programmed death-ligand 1 (PD-L1) expression and immunogenic cell death in triple-negative breast cancer (TNBC) using MDA-MB-231 and BT-549 cells and mouse models. BBR reduced PD-L1 protein levels in a time- and dose-dependent manner, blocked IFN-γ–induced PD-L1 upregulation, and promoted PD-L1 degradation via the autophagy–lysosome pathway through PI3K–Akt signaling. These findings suggest BBR could enhance anti-tumor immunity by lowering PD-L1 and increasing immunogenic cell death, supporting its potential as an immunomodulatory adjunct in TNBC.

Wei Y, Huang Q, Wei X et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

CD161 serves as a prognostic biomarker and predicts immunotherapy response in head and neck squamous cell carcinoma.

This study assessed whether CD161 expression is a prognostic biomarker and predicts immunotherapy response in head and neck squamous cell carcinoma (HNSCC) by analyzing transcriptomic data from TCGA and four GEO cohorts (GSE6631, GSE102349, GSE159067, GSE103322). CD161 was evaluated for associations with survival outcomes and immune infiltration/immune function signatures, and the study concluded that CD161 stratifies patients by prognosis and likelihood of benefiting from immune checkpoint inhibitor therapy. If validated clinically, CD161 could help personalize immunotherapy in HNSCC by identifying patients with more favorable immune responsiveness.

Mei S, Qian X, Chen H et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Dissecting Alzheimer’s proteomic landscape through NULISA profiling of brain cell-specific extracellular vesicles.

This study profiled brain cell-specific extracellular vesicles (sEVs) from plasma of individuals with normal cognition (CN), mild cognitive impairment (MCI), or Alzheimer’s disease–related dementia (ADRD) using NULISAseq to generate a proteomic landscape. Using sEVs derived from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells, the authors quantified 122 proteins spanning Alzheimer’s pathology, neurodegeneration, and neuroinflammation and reported disease-associated proteomic differences across groups and cell types. This approach advances brain cell–specific, blood-based biomarker discovery for Alzheimer’s disease by improving sensitivity to low-abundance proteins relevant to neuroinflammatory and neurodegenerative processes.

Kumar A, Sharma M, Su Y et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels.

This study examined whether activating the mechanosensitive ion channel Piezo1 can restore anabolic responses to mechanical loading in aged bone, using 19-month-old male mice and the Piezo1 agonist Yoda1. Aged tibiae showed a blunted anabolic response to axial cyclic compressive loading and Yoda1 alone, but chemical activation of osteocytic Piezo1 with Yoda1 rescued the anabolic response to mechanical loading. Mechanistically, the study implicated Piezo1 activation and connexin 43 hemichannels in the rescue pathway, supporting Piezo1/connexin-43 signaling as a potential target to counter age-related loss of bone mechanotransduction.

Zhao D, Fu J, Liu H et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

Dysregulated adult hippocampal neurogenesis in major depressive disorders.

This study investigated adult human hippocampal neurogenesis in major depressive disorder (MDD) by integrating neurogenic trajectory analyses with cell-type/subfield-specific gene expression, chromatin accessibility, and protein expression in nonmedicated individuals. The authors identified a neurogenic lineage in the adult hippocampal subgranular zone and found evidence for a stalled neurogenic process in MDD. These results link human MDD to disrupted hippocampal plasticity at the level of neurogenic programs, highlighting adult neurogenesis as a potential mechanistic target for future therapies.

Peng MS, Jiang J, Polizzi L et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Responsiveness of epigenetic aging biomarkers to longevity interventions in humans.

This study curated TranslAGE, a harmonized database of 51 longitudinal human interventional studies, to test whether epigenetic aging biomarkers (including 16 epigenetic clocks and 94 additional DNA methylation biomarkers) respond to longevity interventions. By calculating consistent biomarker outputs across studies, the authors identified patterns of responsiveness across different intervention types and biomarker measures. The work supports the use of epigenetic clocks as faster surrogate endpoints in aging and longevity trials, while clarifying which clocks/DNAm markers are most responsive.

Sehgal R, Borrus D, Armstrong JF et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Rewiring immunity with in vivo CAR T cell engineering.

This Perspective reviewed in vivo CAR T cell engineering approaches, focusing on generating CAR T cells directly within patients rather than ex vivo manufacturing. It synthesized current principles for lymphocyte targeting, discussed pharmacology and biodistribution, and highlighted emerging safety considerations and translational challenges. The article frames how in vivo CAR T strategies could expand access and simplify manufacturing while guiding the key preclinical and clinical questions needed for safe, effective implementation.

Slaney CY, Xu R, Wu S et al. · Nature cancer · (2026) · View on PubMed ↗

Mutations of the DICER1 gene among children and adolescents with thyroid cancer: a systematic review.

This systematic review evaluated mutations in the DICER1 gene among children and adolescents with thyroid cancer by searching multiple databases and applying PRISMA methodology with ROBINS-1 quality assessment. The study compiled and characterized reported DICER1 mutation patterns in pediatric thyroid cancer cohorts, summarizing the evidence linking DICER1 alterations to disease in this age group. By consolidating mutation prevalence and spectrum, the review supports improved genetic risk assessment and informs future diagnostic and research efforts in pediatric thyroid malignancies.

Dimaki A, Kotanidou EP, Tsinopoulou VR et al. · Pediatric research · (2026) · View on PubMed ↗ · Free PDF ↗

Nutritional Strategies for Targeting Biological Age.

This review summarized how nutritional strategies can modulate biological age in model organisms and humans, emphasizing clinical trials using composite omics-based aging biomarkers. It concluded that interventions such as caloric restriction, Mediterranean diet, intermittent fasting, and micronutrient supplementation are generally associated with reduced biological age, whereas obesity, inflammatory dietary patterns, and malnutrition are linked to accelerated aging depending on population and measurement platform. The review positions nutrition as a practical, potentially measurable lever for targeting aging biology and improving healthspan.

Albright SM, Poganik JR, Gladyshev VN · Annual review of nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Diet in IBD: preventive and therapeutic concepts.

This review discussed dietary concepts for preventing and treating inflammatory bowel diseases (IBD), framing Western dietary patterns as a “rheostat” for gut inflammation. It summarized evidence linking specific dietary patterns and food constituents to IBD development and disease course and highlighted how nutritional immunology and genetic/epidemiologic insights are informing individualized dietary interventions. The article supports diet as a modifiable therapeutic option that may synergize with pharmacologic treatments in IBD management.

Schwärzler J, Tilg H, Adolph TE · Gut · (2026) · View on PubMed ↗ · Free PDF ↗

Activation of the KPNA2-mediated nuclear import of PPARα by KIF13B mitigates alcohol-associated liver steatosis.

The study investigated the role of kinesin family member 13B (KIF13B) in alcohol-associated liver disease (ALD) using global and hepatocyte-specific Kif13b knockout mice and primary mouse hepatocytes, with human ALD liver tissue for clinical relevance. KIF13B activated KPNA2-mediated nuclear import of PPARα, thereby mitigating alcohol-associated liver steatosis. These findings support a mechanistic, targetable KIF13B–KPNA2–PPARα axis for developing therapies against ALD-related fatty liver.

Lu K, Mei S, Zhang L et al. · Gut · (2026) · View on PubMed ↗

Glial control of extracellular α-synuclein propagation in LRRK2 Parkinson’s disease.

This review synthesized evidence on how glial cells (microglia and astrocytes) regulate extracellular α-synuclein propagation in the context of LRRK2 Parkinson’s disease, focusing on LRRK2 domain architecture and downstream Rab GTPase signaling. It concludes that LRRK2 mutations disrupt glial handling of extracellular α-synuclein, impairing clearance and promoting prion-like spread. The work highlights glial–LRRK2–Rab pathway dysfunction as a potential therapeutic leverage point to slow α-synuclein propagation in familial PD.

Datta I, Sahu DD · Advances in immunology · (2026) · View on PubMed ↗

Diagnosis and management of acute hyperkalaemia.

This article reviewed the diagnosis and management of acute hyperkalaemia in clinical care settings, emphasizing common high-risk populations such as patients with chronic kidney disease, heart failure, diabetes, and those taking drugs that impair renal potassium excretion. It identifies the major etiologies (reduced renal potassium elimination and transcellular shifts from metabolic acid) and outlines urgent, evidence-based management strategies to prevent malignant arrhythmias and sudden cardiac arrest. Clinically, it provides a practical framework for rapid risk assessment and treatment decisions in acute care and chronic disease comorbidity contexts.

Rech MA, Zimmerman DE, Ray L et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗

Biodegradable versus plastic pancreatic stents for preventing post-ERCP pancreatitis: A multicentre propensity score-adjusted study.

This multicentre retrospective propensity score-adjusted study compared biodegradable versus plastic pancreatic stents in adults undergoing ERCP to prevent post-ERCP pancreatitis. Biodegradable stents were associated with a different (reported in the full text) incidence of post-ERCP pancreatitis after inverse probability of treatment weighting (IPTW) to minimize confounding. The results inform endoscopy practice by evaluating whether biodegradable stents can reduce post-ERCP pancreatitis risk compared with standard plastic stents.

Galanakis V, Moreno-Sanchez M, Braimakis I et al. · Endoscopy · (2026) · View on PubMed ↗

Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study.

This analysis reported 5-year outcomes from the phase 3 randomized KEYNOTE-671 trial in participants with resectable stage II–IIIB (N2) early-stage non-small-cell lung cancer, comparing perioperative pembrolizumab (200 mg every 3 weeks) plus platinum-doublet chemotherapy and surgery versus neoadjuvant chemotherapy and surgery alone with placebo. Perioperative pembrolizumab maintained improved long-term survival outcomes at 5 years compared with the control strategy. These findings strengthen the clinical significance of perioperative PD-1 blockade with chemotherapy as a durable treatment approach for early-stage NSCLC.

Wakelee H, Spicer JD, Gao S et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

Atezolizumab with or without tiragolumab in unresectable esophageal squamous cell carcinoma following definitive concurrent chemoradiotherapy (SKYSCRAPER-07): a randomised, phase III study.

This phase 3 randomized SKYSCRAPER-07 trial evaluated atezolizumab with or without tiragolumab versus placebo in adults with unresectable esophageal squamous cell carcinoma after definitive concurrent chemoradiotherapy (dCRT). The study tested whether adding the TGF-β pathway-targeting agent tiragolumab to atezolizumab improves efficacy beyond atezolizumab alone or placebo. The trial’s results are clinically important for identifying whether dual immunotherapy can improve outcomes in a post-dCRT setting with limited options.

Xu RH, Cho BC, Chen M et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

A multi-center cohort study evaluated hemoglobinuria as a marker of inflammation in IgA nephropathy.

This multicenter retrospective cohort study assessed whether hemoglobinuria (dipstick) can serve as a marker of inflammation in IgA nephropathy (IgAN) by correlating urinary findings with biopsy-proven histology. Hemoglobinuria and hematuria measures were evaluated for associations with Oxford Classification MEST-C components and composite inflammatory lesions. If validated, hemoglobinuria could improve risk stratification in IgAN beyond current reliance on proteinuria and estimated glomerular filtration rate.

Vargas-Brochero MJ, Cara A, Angioi A et al. · Kidney international · (2026) · View on PubMed ↗ · Free PDF ↗

Severe health-care-associated infections and antimicrobial resistance in an Asian Surveillance Network (ACORN-HAI): a multicentre, prospective cohort study.

This large-scale prospective multinational multicentre cohort study in an Asian hospital network (ACORN-HAI) characterized antimicrobial resistance (AMR) epidemiology and estimated disease burden for ventilator-associated pneumonia and hospital-acquired bloodstream infections. It quantified severe health-care-associated infections and linked AMR patterns to attributable burden rather than relying only on cross-sectional microbiology data. The findings are significant for guiding infection-control and antimicrobial stewardship priorities across Asian healthcare systems.

Mo Y, Hao X, Ding Y et al. · The Lancet. Infectious diseases · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Redefining plasma cell leukaemia.

This commentary argued that plasma cell leukaemia should be reclassified not as a separate disease entity but as a high-risk type of multiple myeloma. It bases the argument on the observation that circulating clonal plasma cells are present in nearly all multiple myeloma patients and on proposed changes to diagnostic criteria (stricter high-risk myeloma criteria and relaxed plasma cell leukaemia criteria). The redefinition has clinical implications for diagnosis, prognostication, and treatment selection by aligning terminology with underlying biology and risk.

Rajkumar SV, Kumar S · The Lancet. Haematology · (2026) · View on PubMed ↗

Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial.

This US-based multicentre phase 2 randomized double-blind placebo-controlled trial evaluated once-weekly mazdutide, a glucagon and GLP-1 receptor dual agonist, in adults with obesity or overweight without type 2 diabetes across doses up to 16 mg. The study assessed efficacy, safety, and tolerability outcomes compared with placebo in adults aged 18–75 years. The results are clinically relevant for determining whether mazdutide provides differentiated weight loss with an acceptable safety profile in a broad non-diabetic population.

Hsia SH, Bays HE, Billings LK et al. · The lancet. Diabetes & endocrinology · (2026) · View on PubMed ↗

Rezpegaldesleukin treatment of moderate-to-severe atopic dermatitis (REZOLVE-AD): final results from the 16-week induction period of an international, double-blind, placebo-controlled, randomised phase 2b study.

This phase 2b randomized, double-blind, placebo-controlled study evaluated rezpegaldesleukin (an IL-2 receptor agonist that expands regulatory T cells) in adults with moderate-to-severe atopic dermatitis naive to biological treatments. Rezpegaldesleukin improved efficacy outcomes versus placebo during the 16-week induction period while maintaining an acceptable safety profile. These results support rezpegaldesleukin as a potential Treg-targeted biologic alternative for treating moderate-to-severe atopic dermatitis.

Silverberg JI, Rosmarin D, Bieber T et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Nicotinamide nucleotide transhydrogenase directly couples redox homeostasis to proline biosynthesis in human glioma.

The study investigated how nicotinamide nucleotide transhydrogenase (NNT) couples redox homeostasis to proline biosynthesis in human glioma using in vivo isotope-labeled metabolite tracing in an orthotopic xenograft model. Human gliomas showed extensive proline synthesis, with hypoxia-enhanced proliferative sensitivity to environmental proline that depended on NADH-to-NADPH transhydrogenation. Scientifically, this links mitochondrial redox control via NNT to proline-driven growth under hypoxia, suggesting a potential metabolic vulnerability for glioma therapy.

Vettore LA, Boufersaoui A, Lyu Y et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

Bacterial effector modifies host messenger RNA to promote virulence.

This work studied Legionella pneumophila infection mechanisms by using RNA-interactome capture (RIC) to identify bacterial effectors bound to host messenger RNA in infected host cells. RIC identified the uncharacterized effector FadA (Lpw16921), which localized to the host nucleus, bound host mRNAs at uracil (U)-rich motifs, and used NADPH-oxidase activity to mediate 8-oxo-guanine (oxo8G) RNA modification. These findings reveal a direct bacterial strategy to reprogram host mRNA via RNA oxidation, advancing understanding of how bacterial virulence is controlled at the RNA level.

McCaffrey K, Gaussmann S, Ng GZ et al. · Cell host & microbe · (2026) · View on PubMed ↗ · Free PDF ↗

Long-term outcomes of anti-CD19 CAR T cell therapy in refractory myasthenia gravis: A case series.

This case series studied long-term outcomes of autologous fully human anti-CD19 CAR T cell therapy in three patients with refractory generalized myasthenia gravis. All three patients achieved rapid, sustained clinical remission for at least 19 months, enabling treatment-free remission. Clinically, the durability observed in this small cohort supports anti-CD19 CAR T cells as a promising targeted option for treatment-refractory, B-cell–mediated MG.

Hegelmaier T, Motte J, Walther D et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer.

This study evaluated whether PARP inhibition can enhance the antitumor activity of the HER3-targeting antibody-drug conjugate HER3-DXd in non-small cell lung cancer (NSCLC). The authors found significant synergy between HER3-DXd and PARP inhibitors, consistent with improved DNA damage response and cell-cycle effects. These results support combination strategies pairing HER3-DXd with PARP inhibitors as a potential therapeutic approach for NSCLC.

Lin L, Moradi N, Lähdeniemi IA et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Proteo-genomics-guided interpretation of somatic mutations in cancer genomes.

This proteo-genomics analysis integrated protein structural information with somatic mutation data from 139,818 patients to map functional effects of mutations across 173 cancer genes in 18+ tumor types. The study generated detailed functional maps showing that oncogenic mutations cluster in significantly mutated regions aligned with key protein functions (e.g., DNA-binding domains in FOXA1, ligand-binding sites in ERBB2, catalytic domains in EP300). Scientifically, this provides a framework to interpret cancer variants mechanistically and prioritize mutations for functional follow-up and precision oncology.

Hyeon DY, Zhou Y, Chung WK et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial.

This study assessed the prognostic and predictive value of the APUC-6 six-gene androgen pathway expression panel (HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, CYP17A1) in metastatic castration-sensitive prostate cancer using transcriptomic data from 160 patients in the phase III CHAARTED trial. Patients were stratified by APUC-6 and androgen receptor (AR) gene expression, and the analysis tested associations with clinical outcomes such as time to clinical progression and time to castration resistance. If validated, APUC-6 could help refine risk stratification and treatment selection in mCSPC beyond AR status alone.

Shi X, Shetty AC, Wang J et al. · JCO precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Androgen signaling via sympathetic neurons regulates allergic pulmonary inflammation.

This study examined how androgen signaling through sympathetic neurons regulates allergic pulmonary inflammation in male mice exposed to repeated early-life allergen challenges. Increased endogenous androgen production mitigated pulmonary type 2 inflammation, and androgen signaling promoted pulmonary sympathetic innervation that dampened inflammation via norepinephrine; ablation of androgen signaling in sympathetic neurons disrupted establishment of this protective pathway. These findings connect sex hormone signaling to neuroimmune regulation of asthma-like inflammation, suggesting new targets for modulating type 2 immunity.

Tu X, Chen H, Ma X et al. · Science immunology · (2026) · View on PubMed ↗

CAR T cell-derived TNF is an early determinant of cytokine release syndrome severity.

This study investigated what initiates cytokine release syndrome (CRS) severity in CAR T cell therapy by selectively disrupting tumor necrosis factor (TNF) signaling in a mouse CRS model. CAR T cell-derived TNF promoted accumulation of pro-inflammatory monocyte-derived macrophages at the tumor site and induced host cytokines including IL-6 and IL-1β, and TNF was identified as an early determinant of CRS severity. Mechanistically, this supports TNF as an upstream driver of CRS and provides a rationale for early TNF-targeted interventions to reduce toxicity.

Lindenbergh PL, Giavridis T, Vivier O et al. · Science immunology · (2026) · View on PubMed ↗

Cinnamon plays a key role in the anti-obesity action of Hachimijiogan by ameliorating leptin resistance in the hypothalamus.

This preclinical study tested whether cinnamon is a key component of the anti-obesity effects of the traditional herbal formulation Hachimijiogan (MIX8) by focusing on leptin resistance in the hypothalamus in diet-induced obese C57BL/6J mice. Modified MIX8 formulations lacking processed aconite root (MIX7) or lacking processed aconite root and cinnamon (MIX6) were compared, and the results indicated that cinnamon-containing MIX8 improved hypothalamic leptin sensitivity and ameliorated leptin resistance. These findings identify cinnamon as a likely bioactive contributor to MIX8’s anti-obesity mechanism and highlight hypothalamic leptin signaling as a therapeutic target.

Kagawa S, Tanabe K, Ogawa K et al. · The Journal of pharmacy and pharmacology · (2026) · View on PubMed ↗

A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.

The study evaluated the orally bioavailable small molecule 5-tetradecyloxy-2-furoic acid (TOFA) as a multi-functional modulator of energy and lipid metabolism for obesity and related metabolic disorders. TOFA promoted energy expenditure and rebalanced lipid synthesis, significantly alleviating obesity, abnormal glucose homeostasis, and fatty liver-related disease without reducing food intake or muscle mass. These findings support TOFA as a potential non-incretin therapeutic strategy that targets metabolic pathways to treat obesity while avoiding common gastrointestinal side effects and muscle wasting.

Lee JY, Zhu C, Boldridge MA et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Large-scale proteomics to identify novel biomarkers linking social determinants of health to heart failure risk.

This study assessed whether social determinants of health (SDOH) are linked to incident heart failure (HF) risk through plasma protein biomarkers in 9879 participants from the ARIC cohort. Using an aptamer-based SomaLogic platform to measure 4955 plasma proteins and deriving an SDOH factor (income, education, and area deprivation index) in Black and white participants, the authors identified multiple proteins significantly associated with both the SDOH factor and incident HF (36 in Black participants, 126 in white participants, and 12 overlapping). The work provides a large-scale proteomics framework for connecting SDOH to HF biology and for discovering candidate biomarker targets for risk stratification.

Ramonfaur D, Zierath R, Yang Y et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Geneformer-guided multiomics integration identifies Pbx1 as a network hub of hematopoietic stem cell aging.

The study used Geneformer-guided multiomics integration with single-cell RNA-seq and developmental time-series analyses to identify transcriptional network structure underlying hematopoietic stem cell (HSC) aging and to nominate Pbx1 as a key regulator. Geneformer analysis and single-cell programs indicated that old HSCs contain two transcriptional programs (a megakaryocyte-shared program and a primitive HSC program), with primitive features rising prenatally and megakaryocytic priming emerging after birth, and Pbx1 functioning as a network hub. This positions Pbx1 as a mechanistic control point for HSC aging programs and suggests a target for interventions aimed at restoring age-associated hematopoietic imbalance.

Kobayashi H, Watanuki S, Shiozawa Y et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic-epigenetic rewiring of CCR5hi monocytes sustains long-term trained immunity against lethal sepsis.

The study investigated how BCG plus bacterial lipoprotein (BLP) vaccination induces long-term trained immunity against lethal polymicrobial sepsis and what metabolic-epigenetic mechanisms sustain it, focusing on CCR5hi monocytes. Single-cell RNA sequencing showed that protection is mediated by expansion of CCR5hi memory-like monocytes, and mechanistically vaccination activated the AKT–mTOR–HIF-1α axis to drive glycolytic reprogramming and associated epigenetic changes that maintain antimicrobial function. These results link a defined metabolic-epigenetic rewiring to durable trained immunity, informing vaccine strategies for early-life to adulthood protection.

Xu L, Hao W, Yang Y et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Orthogonal DNA barcoding enables subpopulation-resolved extracellular vesicle miRNA profiling.

The study developed DEEPER, an orthogonal DNA barcoding platform using aptamers to enable subpopulation-resolved extracellular vesicle (EV) miRNA profiling. DEEPER used four aptamers targeting CD44, EGFR, HER2, and PD-L1 to generate orthogonal DNA barcodes distinguishing 15 tumor-derived EV subpopulations, followed by targeted membrane fusion with liposome probes for sensitive in situ miRNA analysis. This provides a technique to overcome EV heterogeneity and improve the feasibility of EV-miRNA liquid biopsy by resolving clinically relevant tumor EV subtypes.

Zhang Y, Zhu Y, Zhang Y et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

YAP1-Driven PLCβ1 Impairs MHC-I Antigen Presentation and Limits Anti-Tumor Immunity in Gastrointestinal Cancer.

The study examined how YAP1-driven PLCβ1 affects immune evasion and resistance to immune checkpoint blockade in gastrointestinal cancer. It identified PLCβ1 as a central driver of tumor progression by impairing antigen presentation, via PLCβ1 interaction with ERC1 that promotes ERC1 ubiquitin-proteasomal degradation, leading to reduced NF-κB-dependent MHC-I transcription. This mechanistic axis (YAP1→PLCβ1→ERC1→MHC-I) highlights a potential therapeutic target to enhance anti-tumor immunity and improve ICB responses in GI malignancies.

Zhang Y, Su P, Yu T et al. · Cancer research · (2026) · View on PubMed ↗

Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila.

This study investigated how Hippo signaling regulates cuticle pigmentation and dopamine metabolism in the fruit fly Drosophila melanogaster. The authors reported that Hippo pathway activity influences expression and/or function of dopamine biosynthesis components involved in melanization, including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc), thereby altering cuticle pigmentation. These findings extend Hippo pathway biology beyond growth control to developmental metabolic regulation of neurotransmitter-derived pigmentation.

Gibson SB, Deal SL, Park YJ et al. · PLoS genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Tox regulates hair cell stereocilia development and Cdh23 expression in mice and zebrafish.

The study identified the transcription factor Tox as a regulator of auditory hair cell (HC) development and examined its role in stereocilia development and Cdh23 expression in both mice and zebrafish. Tox was highly expressed in HCs across species and increased along developmental pseudotime after Atoh1 and before Myo7a, and Tox mutant models showed disrupted HC development with altered Cdh23 expression. This establishes Tox as a conserved component of the HC regulatory network and links transcriptional control to structural maturation of stereocilia.

Zhang J, Gong J, Zhou J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Panitumumab-Based EGFR Blockade in SMARCB1-Deficient Renal Medullary Carcinoma: Preclinical Basis and Prospective Clinical Activity.

The study evaluated whether EGFR is a therapeutically actionable dependency in SMARCB1-deficient renal medullary carcinoma (RMC) and translated this into a panitumumab-based clinical approach. EGFR expression was assessed by CLIA-certified immunohistochemistry and by integrated RNA- and chromatin immunoprecipitation sequencing, and panitumumab was compared with erlotinib using patient- and cell line-derived xenograft models. The results provide a preclinical rationale for targeting wild-type EGFR with panitumumab in this ultra-rare, treatment-refractory cancer subtype.

Zacharias NM, Rupe ES, Chen X et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

Targeting the PHB2-ACSL3 Lipid-Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer.

The study investigated how targeting the PHB2–ACSL3 lipid-remodeling axis can overcome cisplatin resistance by restoring ferroptosis in gastric cancer. Integrated transcriptomics of cisplatin-resistant xenografts and NCI-60 pharmacogenomic analyses identified Prohibitin-2 (PHB2) as a determinant of resistance, where PHB2 upregulation promoted ACSL3 activity via an AMP-binding-domain interface (W244/H254/E260) to enhance monounsaturated fatty acid incorporation into phospholipids and suppress ferroptosis. This supports PHB2–ACSL3 pathway inhibition as a strategy to resensitize gastric tumors to cisplatin through ferroptosis restoration.

Xu L, Xiang W, Wang X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Insights into the recruitment of the H3K4me3 reader Spp1 by the meiotic double-strand break protein Mer2.

This study investigated how the meiotic double-strand break (DSB) factor Mer2 recruits the H3K4me3 reader Spp1 to meiotic chromosome loop-axis structures in the context of Spo11-driven DSB formation. Using AlphaFold modeling, biochemical reconstitution, and biophysical validation, the authors mapped rotationally symmetrical binding sites within the tetrameric Mer2 coiled-coil domain that coordinate Mer2–Spp1 interactions with DNA-bound complexes. These mechanistic insights clarify how epigenetic marks (H3K4me3) are coupled to DSB machinery assembly, informing broader models of meiotic genome organization and recombination control.

Liloku P, Melo DA, Gisbert VG et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Transmurality and Autonomic Effects of Pulsed Field Ablation on the Mitral Isthmus.

This study evaluated pulsed field ablation (PFA) transmurality and autonomic effects on the mitral isthmus (MI) in patients undergoing atrial fibrillation ablation, using real-time vein of Marshall (VOM) epicardial electrograms and VOM high-frequency stimulation. In a prospective cohort (n=71) treated with FaraPulse (n=31), PulseSelect (n=9), or Affera (n=31), the key finding was the characterization of endocardial-to-VOM PFA transmurality and its autonomic impact as measured by VOM electrogram changes and stimulation responses. Clinically, this helps determine whether PFA can reliably achieve MI lesion formation while modulating local autonomic innervation compared with existing MI ablation strategies.

Patel A, Kocharian A, Lopez-Martinez H et al. · Circulation. Arrhythmia and electrophysiology · (2026) · View on PubMed ↗

Left Atrial Appendage Closure Versus Oral Anticoagulation in Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis compared left atrial appendage closure (LAAC) versus oral anticoagulation (OAC) for stroke prevention in adults with atrial fibrillation using randomized controlled trials, with an emphasis on individual clinical outcomes rather than only composite endpoints. The key finding was that LAAC and OAC differed in efficacy and safety across specific outcomes when analyzed separately, rather than being obscured by composite endpoints. This supports more precise clinical decision-making for AF patients by clarifying which individual endpoints may favor LAAC or OAC.

Rao A, Ravi V, Murthi M et al. · Circulation. Arrhythmia and electrophysiology · (2026) · View on PubMed ↗

Global research landscape and emerging trends of respiratory microbiota and asthma: a bibliometric analysis.

This bibliometric analysis studied the global research landscape and emerging trends in respiratory microbiota and asthma from 2000–2025 using publications indexed in Web of Science Core Collection and Scopus. Using tools including Bibliometrix, VOSviewer, and CiteSpace, the authors identified publication trends, collaboration networks, and co-citation/keyword structures that reveal core contributors and fast-emerging topics. Scientifically, this maps where the field is concentrating mechanistic and clinical microbiome work, helping researchers target high-impact gaps in respiratory microbiota–asthma research.

Wang Q, Yu Y, Liang B et al. · Frontiers in cellular and infection microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of fasting on thyroid hormone profiles: a systematic review and meta-analysis of TSH, FT3, FT4, and total T3 responses.

This systematic review and meta-analysis assessed how fasting affects thyroid hormone profiles—TSH, FT3, FT4, and total T3—in human adults undergoing fasting interventions lasting at least 24 hours. Across included pre–post studies, the key finding was the quantified direction and magnitude of standardized changes in these thyroid parameters after fasting. Clinically, these results improve interpretation of thyroid labs during fasting and inform understanding of endocrine adaptation mechanisms to energy restriction.

Ulupınar S, Kaya K, Çamlı A et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

The evaluation of cytokine profiles in atopic dermatitis patients treated with dupilumab: association with ocular complications.

This study evaluated whether plasma cytokine profiles differ between adult atopic dermatitis (AD) patients treated with dupilumab who develop dupilumab-associated ocular surface disease (DAOSD) versus those without ocular complications. Using complex dermatologic examination to define ocular involvement and plasma cytokine profiling to compare groups, the key finding was identification of cytokine differences associated with DAOSD risk after dupilumab. This is significant because it seeks upstream epithelial immune markers that could predict or stratify patients for ocular complications during dupilumab therapy.

Čelakovská J, Čermáková E, Boudkova P et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting ADAR stability: a novel approach to combat glioblastoma.

This study investigated mechanisms regulating adenine deaminase acting on RNA (ADAR) protein stability and function in glioblastoma (GBM), integrating pan-cancer expression analyses with GBM-specific experiments. Using TCGA-based bioinformatics, single-cell RNA sequencing data, and molecular assays including co-immunoprecipitation and ubiquitination detection, the key finding was that ADAR stability is controlled by specific regulatory mechanisms that influence GBM biology. Targeting ADAR stability is therefore proposed as a novel therapeutic strategy for GBM, potentially disrupting RNA editing pathways that support tumor progression.

Fei Q, Huang J, Zhang Y et al. · Frontiers in oncology · (2026) · View on PubMed ↗ · Free PDF ↗

In vivo CAR T cells on the highway: a roadmap for the next decade.

This article reviewed the emerging strategy of generating CAR T cells in vivo (“on the highway”) to reduce the logistics of ex vivo manufacturing and lymphodepleting chemotherapy. The key finding across the cited preclinical and early clinical work is that advances in lipid nanotechnology, RNA chemistry, and viral particle targeting can enable delivery of CAR components directly in the patient’s bloodstream. This is significant because it outlines a translational roadmap for making CAR T therapy more scalable and accessible for broader patient populations.

Barden M, Harrer DC, Abken H · Expert opinion on biological therapy · (2026) · View on PubMed ↗

DECREASE study: A European pool-analysis of patients with significant reductions in concomitant antiseizure medications in cenobamate Early Access Programs.

This pooled analysis evaluated the effectiveness and tolerability of cenobamate in European patients enrolled in cenobamate Early Access Programs (EAPs) who had significant reductions in concomitant antiseizure medications (ASMs). Using anonymized real-world registry data (n=69, per the truncated results), the key finding was the degree of cenobamate effectiveness and tolerability in patients who converted toward cenobamate monotherapy or reduced to a single concomitant ASM. Clinically, it supports how cenobamate performs when used in real-world medication-reduction pathways, informing treatment optimization for patients with polytherapy.

Villanueva V, Lattanzi S, Peña-Ceballos J et al. · Epilepsia open · (2026) · View on PubMed ↗ · Free PDF ↗

Four new Duchenne muscular dystrophy mouse models with clinically relevant exon deletions in the human DMD gene.

This study developed four new humanized Duchenne muscular dystrophy (DMD) mouse models carrying clinically relevant exon deletions (exons 44, 45, 51, or 53) in the human DMD gene on an mdx mouse dystrophin-negative background (exon 23 nonsense mutation). Using an optimized CRISPR-Cas9 prescreening pipeline, the key finding was successful generation and validation of these exon-deletion models that enable testing of mutation-specific therapies such as exon skipping or gene editing. These models are scientifically significant because they improve translational relevance for evaluating human-sequence-targeted DMD interventions.

van Putten M, Linssen M, de Winter CT et al. · Disease models & mechanisms · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond the Cochrane review: Re-evaluating anti-amyloid therapy in Alzheimer’s disease.

This article re-evaluates anti-amyloid therapy for Alzheimer’s disease (AD) in the context of a 2026 Cochrane review, focusing on amyloid beta (Aβ)-targeting monoclonal antibodies and newer plaque-directed approaches in AD clinical trial populations. The authors argue that the Cochrane analysis may be biased by a “dilution effect,” where combining monomer-selective antibodies with newer toxic plaque–targeting therapies adds statistical noise that can obscure cognitive preservation signals. The re-analysis is clinically significant because it challenges the conclusion that Aβ-targeted drugs lack benefit and highlights methodological considerations that should guide future meta-analyses and trial interpretation.

Bernath MM, Brosch J, Saykin AJ et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of Self-Guided Digital Mindfulness Interventions on the Mental Health of Health Care Workers: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis evaluated self-guided digital mindfulness interventions delivered without professional or in-person support among health care workers (HCWs). It found that self-guided digital mindfulness programs can improve mental health and well-being outcomes in HCWs compared with control conditions across randomized controlled trials included in the DeLiGHT project. The findings are significant for scalable occupational mental health interventions because they support an effective, low-resource format that does not require facilitators.

Sasaki N, Inoue A, Iida M et al. · JMIR mHealth and uHealth · (2026) · View on PubMed ↗ · Free PDF ↗

Chronic stress-induced brain-derived small extracellular vesicles promote colorectal cancer through Treg differentiation.

This study investigated whether chronic stress–induced brain-derived small extracellular vesicles (BD-sEVs) promote colorectal cancer (CRC) by driving regulatory T cell (Treg) differentiation using chronic restraint stress (CRS) mouse models with MC38 and CT26 tumors. The key finding is that CRS increases BD-sEV activity that enhances Treg differentiation and thereby promotes CRC progression in both subcutaneous and orthotopic settings. This is scientifically significant because it identifies a neuroimmune mechanism—BD-sEV–mediated Treg polarization—linking HPA-axis/sympathetic stress signaling to tumor immune escape.

Ni H, Ling Y, Tang T et al. · Clinical and translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of GLP-1 agonists on the gut microbiota in type 2 diabetes mellitus: a systematic review.

This prospective observational case-control study assessed microvascular remodeling and endothelial dysfunction across the post-COVID-19 spectrum using retinal vessel analysis (RVA) in never-infected individuals, SARS-CoV-2–recovered participants, and post-COVID-19 syndrome (PCS) patients, including a subgroup meeting ME/CFS criteria. The study found that PCS (and particularly those fulfilling ME/CFS criteria) showed worse retinal microvascular and endothelial parameters than never-infected and recovered groups, indicating persistent microvascular impairment after infection. The clinical significance is that RVA provides an accessible, quantifiable tool for stratifying long-term cardiovascular risk and microvascular health in post-viral syndromes.

Santos Dantas R, Souza Santos LV, Carvalho de Oliveira AG et al. · The FEBS journal · (2026) · View on PubMed ↗ · Free PDF ↗

Subtype-specific outcome after allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: a registry study of the European competence network on mastocytosis.

This registry study analyzed outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) in 631 patients with advanced systemic mastocytosis (AdvSM) across subtypes (aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated hematological neoplasm). The key finding is that post-transplant survival and benefit vary by AdvSM subtype and that prognostic factors can identify patient subgroups most likely to benefit from allo-HCT in the era of KIT-targeted tyrosine kinase inhibitors (TKIs) such as midostaurin and avapritinib. This is clinically significant because it informs risk-adapted selection of allo-HCT rather than treating AdvSM as a single uniform disease entity.

Haug S, Sperr WR, Wehr C et al. · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

A cardiometabolic perspective on post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID.

This article provides a cardiometabolic conceptual framework for post-exertional malaise (PEM) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. It argues that PEM may reflect disrupted coordination across physiological systems over different post-exertional timescales, leading to altered post-exertional trajectories with potential cardiometabolic consequences. The significance lies in guiding future longitudinal and mechanistic studies that could connect PEM biology to measurable cardiovascular/metabolic outcomes.

Westermeier F, Pretorius E, Untersmayr E et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Microvascular remodeling and endothelial dysfunction across the post-COVID-19 spectrum: a prospective observational case-control study.

This prospective observational case-control study used retinal vessel analysis (RVA) to compare dynamic and static microvascular parameters among never SARS-CoV-2–infected individuals, SARS-CoV-2 recovered participants, and post-COVID-19 syndrome (PCS) patients, including an ME/CFS-criteria subgroup. The key finding is that microvascular remodeling and endothelial dysfunction are detectable across the post-COVID-19 spectrum and are most pronounced in PCS/ME-CFS–criteria participants. This is significant because it supports microcirculatory dysfunction as a measurable biological feature of long COVID and ME/CFS that may underpin persistent cardiovascular risk.

Wallraven T, Günthner R, Lethen I et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

POSTN⁺ CAF-SPP1⁺ macrophage crosstalk is associated with immune exclusion and poor prognosis in lung adenocarcinoma.

This study examined lung adenocarcinoma (LUAD) tumor microenvironment interactions by focusing on POSTN+ cancer-associated fibroblasts (CAFs) and SPP1+ macrophages and their relationship to immune exclusion and prognosis. Using integrated bulk RNA-seq, single-cell RNA-seq, spatial transcriptomics, multiplex immunofluorescence, and functional in vitro assays, the authors found that POSTN+ CAF–SPP1+ macrophage crosstalk promotes stromal barrier formation that limits immune infiltration and is associated with poor patient outcomes. The scientific significance is that it identifies a spatially organized stromal–immune axis that could be targeted to improve immunotherapy responsiveness in LUAD.

Zhu A, Huang J, Zhang J et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Challenges in Studying Synapses in Alzheimer’s Disease.

This article discusses challenges in studying synapses in Alzheimer’s disease (AD), focusing on how ApoE4, amyloid-β (Aβ) peptides, phospho-tau, and neuroinflammation may drive synapse loss. The key conceptual finding is that free Aβ peptides can be synaptogenic whereas aggregated Aβ species are synaptotoxic, and it remains unclear whether AD is driven primarily by loss of free Aβ, gain of aggregated Aβ, or both, including how ApoE4 modulates synaptic effects. The significance is that clarifying which Aβ species and pathways govern synapse failure is essential for developing mechanism-based AD therapies.

Südhof TC · Annals of neurology · (2026) · View on PubMed ↗

Evidence-based guidelines for the diagnosis and management of adult-onset IgA vasculitis.

This article provides evidence-based guidelines for diagnosing and managing adult-onset IgA vasculitis (IgAV), an immune complex–mediated small-vessel vasculitis affecting skin, gastrointestinal tract, kidneys, and joints. The key finding is that adult IgAV requires structured assessment despite the lack of validated adult-specific diagnostic criteria and standardized disease activity scores, with short-term outcomes largely driven by gastrointestinal complications and kidney involvement determining progression risk. The clinical significance is that it standardizes care for a high-risk adult population to improve recognition, monitoring, and management of organ-threatening disease.

Audemard-Verger A, Pillebout E, Baier E et al. · Nature reviews. Rheumatology · (2026) · View on PubMed ↗ · Free PDF ↗

Toward the clinical application of long-read sequencing in repeat-expansion disorders.

This article reviews how long-read sequencing (LRS) can be applied to repeat-expansion disorders (REDs) caused by short tandem repeat (STR) expansions in affected patients. It highlights that LRS can resolve features that short-read sequencing and standard diagnostics often miss—such as multi-kilobase expansions, noncanonical secondary structures, somatic instability, repeat interruptions, and allele-specific methylation. Clinically, this improved molecular characterization could enable better prognosis and potentially inform therapeutic decision-making in REDs.

Benarroch L, Pešović J, Rossato M et al. · Nature genetics · (2026) · View on PubMed ↗

Distinguishing different psychiatric disorders using DDx-PRS.

This study developed and evaluated differential diagnosis-polygenic risk score (DDx-PRS) to genetically distinguish related psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder) versus controls using polygenic risk scores and diagnostic prior probabilities. DDx-PRS jointly models variance–covariance across disorders to estimate posterior probabilities for each diagnostic category, improving genetic differentiation among clinically overlapping conditions. Scientifically, it provides a framework for probabilistic, genetics-informed differential diagnosis that can be applied to large psychiatric cohorts such as those from the Psychiatric Genomics Consortium.

Peyrot WJ, Panagiotaropoulou G, Olde Loohuis LM et al. · Nature genetics · (2026) · View on PubMed ↗

Automated joint segmentation enables quantitative molecular imaging of degeneration with [¹⁸F]FDG and [¹⁸F]NaF PET/CT.

This work studied an automated joint segmentation approach for quantitative PET/CT imaging of weight-bearing joints using [18F]FDG (metabolism) and [18F]NaF (bone remodeling) in healthy volunteers (75 FDG, 80 NaF). The method uses CT-based segmentation with the TotalSegmentator model and defines joint regions between adjacent bones within a distance threshold to standardize quantification. This enables more reliable, scalable measurement of joint metabolism and inflammation than manual methods, supporting research and potentially clinical monitoring of degenerative joint disease.

Lee WK, Patil S, Patel DH et al. · European journal of nuclear medicine and molecular imaging · (2026) · View on PubMed ↗ · Free PDF ↗

Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism.

This study investigated how the branched-chain amino acids isoleucine and valine promote prostate cancer progression through propionyl-CoA-mediated cholesterol metabolism in prostate cancer cells and models. It found that isoleucine/valine catabolism is the primary intracellular source of propionyl-CoA, and that propionyl-CoA acts as a signaling molecule that stabilizes nuclear sterol regulatory element-binding protein (SREBP) to drive cholesterol homeostasis and stress adaptation. These findings identify a metabolic signaling axis that could be therapeutically targeted to limit aggressive prostate cancer lipid remodeling.

Li Z, Liu S, Jin W et al. · Nature metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Proteogenomics in human populations.

This review summarizes proteogenomics in human populations, focusing on how integrating genomic variation with proteomic measurements identifies protein quantitative trait loci (pQTLs). It reports that pQTL discovery has accelerated due to high-throughput proteomics, large biobank datasets, and cross-cohort meta-analyses, expanding mechanistic and translational insight into disease biology. Scientifically, proteogenomics strengthens causal links from genetic variants to protein abundance and function, improving interpretation of human genetic risk.

Zhai R, Mälarstig A, Shen X · Nature reviews. Genetics · (2026) · View on PubMed ↗

Diagnosis of hypochondroplasia: international Delphi consensus recommendations.

This article presents international Delphi consensus recommendations for diagnosing hypochondroplasia, a skeletal dysplasia caused by pathogenic variants in FGFR3, across clinical settings and patient ages. It addresses diagnostic uncertainty—especially in early childhood and mild/atypical presentations—and proposes standardized diagnostic guidance to reduce delays and improve multidisciplinary management and counseling. Clinically, the consensus aims to improve diagnostic accuracy and care planning for individuals with FGFR3-related hypochondroplasia.

Dauber A, Cheung MS, Hoover-Fong J et al. · Nature reviews. Endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Analysing long-read CRISPR experiments with CRISPRLungo.

This study introduced CRISPRLungo, a computational pipeline for analyzing long-read CRISPR experiments using long-read amplicon sequencing of gene-edited samples. It found that CRISPRLungo’s unique molecular identifier (UMI)-based error correction and statistical filtering can distinguish true editing outcomes (including complex indels) from PCR/sequencing errors and background noise. This improves detection of gene-editing allelic outcomes that are difficult to resolve with short-read methods, supporting more accurate interpretation of CRISPR experiments.

Hwang GH, Vyshedskiy B, Barry T et al. · Nature biomedical engineering · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting soluble misfolded oligomers in anti-amyloid research.

This review examines chemical strategies to target soluble misfolded oligomers implicated as cytotoxic species in amyloidoses such as Alzheimer’s disease, Parkinson’s disease, type 2 diabetes, and Huntington disease. It emphasizes that soluble oligomers are transient, heterogeneous, and low-abundance, making them difficult to detect and analyze with conventional approaches, and surveys emerging tools for their detection, separation, and characterization. Scientifically, improving oligomer-targeting and measurement could accelerate development of therapies aimed at the most toxic conformational species rather than only insoluble amyloid plaques.

Vosbein P, Mao H, Lou C · Nature reviews. Chemistry · (2026) · View on PubMed ↗

GLP-1 and dual GIP/GLP-1 receptor agonists’ psychopharmacology and putative neuropsychiatric associated effects: a Bradford Hill-informed, systematic, evaluation.

This Bradford Hill-informed systematic evaluation reviews evidence linking GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists to neuropsychiatric outcomes in populations exposed for type 2 diabetes mellitus and obesity. It synthesizes post-marketing surveillance signals and translational research to assess potential causal relationships with adverse CNS and neuropsychiatric effects. Clinically, the review helps frame risk assessment and monitoring considerations for incretin-based therapies as their use expands.

Schifano F, De Luca MA, Bonaccorso S et al. · Current psychiatry reports · (2026) · View on PubMed ↗ · Free PDF ↗

Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.

This study investigated how inhibiting cyclin D1–CDK6 affects senescence-associated inflammatory programs and age-related functional decline in models of cellular senescence. It found that CCND1 and CDK6 drive SASP and interferon-stimulated gene (ISG) expression by promoting DNA damage, leading to cytoplasmic chromatin fragments that activate cGAS–STING signaling. These results suggest that targeting CCND1/CDK6 could suppress inflammatory senescence and mitigate functional decline during aging.

Rajesh A, Havas AP, Arnold R et al. · Nature aging · (2026) · 1 citations · View on PubMed ↗

Dual regulatory mechanisms of the ZI-LHb circuit in SPS&S model mice: dissociable control of aversion and anxiety through distinct downstream targets.

This study examined how the zona incerta (ZI)→lateral habenula (LHb) circuit is regulated in single prolonged stress and shock (SPS&S) model mice, focusing on distinct downstream targets within the LHb. SPS&S weakened ZI–LHb connectivity during the expression phase and revealed dissociable control of aversion versus anxiety through different downstream LHbL-related mechanisms. These findings clarify circuit-level separation of PTSD-like symptoms and identify specific ZI–LHb pathway components as potential targets for more precise neuromodulation strategies.

Liu Y, Qian J, Wu W et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

The hallmarks of skeletal muscle health.

This article studied skeletal muscle health by proposing a unifying conceptual framework of seven interconnected “hallmarks” (metabolism/bioenergetics, proteostasis, genomics, excitability, structure, regeneration, and cross-talk) across the lifespan. The key finding is that each hallmark is mechanistically grounded, quantifiable, and potentially modifiable, providing an integrative structure for research and intervention. This framework is significant because it can standardize how muscle quality is defined and measured, accelerating development of therapies to preserve muscle integrity and resilience.

Vainshtein A, Blaauw B, De Bock K et al. · Nature metabolism · (2026) · View on PubMed ↗

Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response.

This review studied how brain barriers regulate glioma immune surveillance and thereby shape immunotherapy responses in the context of CNS immune privilege. It found that specialized brain barriers compartmentalize immune-cell and immune-mediator access, directing immune surveillance toward the subarachnoid and perivascular spaces rather than uniformly across the parenchyma. This is clinically significant because it reframes limited glioma immunotherapy efficacy as partly barrier-mediated and highlights barrier-targeting as a potential strategy to improve immune access and treatment response.

Engelhardt B, Platten M · Nature reviews. Cancer · (2026) · View on PubMed ↗

Breastfeeding and viral infections in preterm infants: a multicenter cohort study.

This multicenter cohort study evaluated whether breastfeeding status up to 6 months affects the incidence of viral infections during the first year of life in preterm infants. Using Japanese National Hospital Organization NICU registry data (2010–2014 and 2016–2018) and modified Poisson regression, it assessed infection risk ratios across breastfeeding exposures collected by parental questionnaire at 1 year. The results are significant for informing early-life nutrition guidance in preterm populations to potentially reduce viral morbidity.

Kamiya Y, Takeuchi A, Nakamura K et al. · Pediatric research · (2026) · View on PubMed ↗

Cancer pain.

This Nature Reviews Disease Primers article studied the mechanisms underlying cancer pain across cancer types and stages, emphasizing contributions from both neuronal and non-neuronal cells. It found that cancer pain arises from multiple processes—peripheral nociception, central sensitization, and maladaptive neuroplasticity—regulated importantly by immune cells, Schwann cells, and central glia. This mechanistic synthesis is significant because it supports more targeted pain interventions beyond broad analgesia, potentially improving quality of life and outcomes.

Villalba-Riquelme E, Zhang C, Sikandar S et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗

AI-enabled discovery and biochemical optimization of minibinders targeting cancer cell-surface proteins.

This study investigated an AI-enabled workflow for discovering and biochemically optimizing “minibinders” against cancer cell-surface proteins using mammalian cell-surface display. Screening thousands of AI-designed candidates identified several high-affinity PD-L1 minibinders but far fewer for CD276 (B7-H3) and VTCN1 (B7-H4), and predicted interface template modeling scores (Chai-1 with ESM embeddings) correlated with binding success and deleterious interface mutations. The approach is significant because it provides a scalable, target-dependent pipeline for generating functional binders that can be validated by fluorophore labeling and flow cytometry.

Broske B, McEnroe BA, Frechen SC et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Structural origins of species-specific differences in TRPV2 activation.

This study examined why human TRPV2 (hTRPV2) is less sensitive than rodent TRPV2 to stimuli such as 2-aminoethoxydiphenyl borate (2-APB) and heat. By combining electrophysiology with cryo-electron microscopy, it found structural differences at the voltage sensor-like domain (VSLD) that align with graded functional activity across human, mouse, and rat TRPV2. This is significant because it pinpoints the structural basis for species-specific TRPV2 pharmacology, informing translational drug development and interpretation of rodent data.

Fricke TC, Pumroy RA, Rocereta JA et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models.

This study developed and tested AChR chimeric autoantibody receptor (CAAR) T cells engineered to eliminate autoreactive B cells producing anti–acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG) models. The key finding was that T cells co-transduced with CAARs containing extracellular domains of AChRα1 or β1 enabled recognition of a broad range of pathogenic anti-AChR antibodies and selectively eliminated AChR-specific B cells. This is clinically significant because it offers a more targeted alternative to broad immunosuppression for achieving sustained remission in MG.

von Wardenburg N, Spagni G, Reincke SM et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer.

This study investigated how glycolysis-linked epigenetic modification regulates quiescent breast cancer stem-like cells in triple-negative breast cancer (TNBC), focusing on ENO1-driven H4K12 lactylation. Using a dual-reporter system (NANOG-EGFP plus H2B-mCherry pulse-chase) and corroborating evidence from scRNA-seq of TNBC patient samples, it found that active BCSCs (aBCSCs) are enriched for glycolysis and lactylation signatures and that ENO1 expression positively correlates with elevated histone H4 lysine 12 lactylation (H4K12la). This is significant because it links a specific metabolic enzyme to a specific histone lactylation mark that may control the transition from quiescence to activation in TNBC.

Liu S, Ma Y, Zeng Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of loneliness, social isolation and healthy lifestyle with life expectancy free of major physical disease and mental disorder.

This study examined associations of loneliness and social isolation with life expectancy free of major physical disease and mental disorder in 277,489 UK Biobank adults initially free of seven major chronic diseases. It found that loneliness and social isolation were more strongly associated with life expectancy free of mental disorder than with life expectancy free of physical disease. This is significant because it suggests that psychosocial factors may disproportionately affect mental-health trajectories and overall healthspan, informing prevention and intervention priorities.

Wang X, Ma H, Heianza Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Azithromycin with or without cefixime for suspected or culture-confirmed uncomplicated typhoid fever in Nepal, Bangladesh, and Pakistan (ACT-South Asia): a double-blind, parallel-group, randomised, placebo-controlled, phase 4 trial.

This phase 4, double-blind, parallel-group randomized placebo-controlled trial studied azithromycin with or without cefixime in adults and children with suspected or culture-confirmed uncomplicated typhoid fever in Nepal, Bangladesh, and Pakistan. The trial tested whether adding cefixime to azithromycin would reduce treatment failure rates compared with azithromycin alone, based on the hypothesis that azithromycin’s intracellular activity plus cefixime’s extracellular activity would improve tissue sterilisation. If effective, the azithromycin–cefixime combination could address high typhoid treatment failure rates and inform WHO-aligned first-line regimens in South Asia.

Basnyat B, Adhikari S, Shrestha P et al. · The Lancet. Infectious diseases · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical Prediction, Decision Rules & Target Trial Emulation

From prediction to decision: prediction-based decision rules and target trial emulation in ADHD.

This Personal View evaluated how to translate ADHD prediction models into clinical practice by defining prediction-based decision rules and using target trial emulation to emulate actionable treatment decisions from prediction outputs. It argues that most ADHD prediction studies report discrimination (e.g., AUC) without specifying what clinicians should do differently for high- versus low-risk patients, leaving models clinically “inert.” Establishing explicit model-to-action decision rules and target trial emulation could improve the real-world implementation of prediction models for ADHD.

Garcia-Argibay M, Faraone SV, Chang Z et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗

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Orthopedics & Joint Replacement Technologies

Robotic-arm-assisted versus conventional total knee replacement (RACER-Knee): a pragmatic, multicentre, participant-masked and assessor-masked, superiority, randomised controlled trial.

This pragmatic, multicentre, participant-masked and assessor-masked superiority randomized controlled trial compared robotic-arm-assisted total knee replacement using the Mako system versus conventional instruments for advanced knee osteoarthritis in patients across 10 hospitals in Great Britain. The study aimed to determine whether robotic assistance improves clinical outcomes and cost-effectiveness after TKR compared with conventional TKR. Positive results would support adoption decisions for robotic TKR technology by linking efficacy and economic impact.

Parsons H, Metcalfe A, Griffin J et al. · Lancet (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

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Respiratory Disease: Asthma Prognosis & Biologics

Cardiometabolic Effects of Dual GLP-1 and Glucagon Receptor Agonists: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This retrospective cohort study using the TriNetX US Collaborative Network compared respiratory virus infection risk among adults with asthma newly initiating biologics—benralizumab, omalizumab, dupilumab, or mepolizumab—using an active-comparator new-user design with 1:1 propensity score matching. It found differential risk of a composite respiratory virus outcome (including COVID-19, influenza, RSV infection, and viral pneumonia) across biologic classes when benralizumab was compared with each other therapy. These comparative real-world data are clinically significant for selecting biologic treatment in severe asthma patients where minimizing respiratory viral morbidity is important.

Roessler J, Nauck MA, Haghikia A · Diabetes care · (2026) · View on PubMed ↗

Symptom burden to characterise, predict, and prevent asthma attacks: a patient-level meta-analysis of randomised trials and translational prospective studies.

This patient-level meta-analysis studied whether asthma symptom burden measured by the 5-item Asthma Control Questionnaire (ACQ-5) predicts future severe asthma attacks and response to anti-inflammatory therapy across randomized trials and translational prospective cohorts. Using ORACLE2 on 6513 control-group participants from 22 randomized trials, it quantified the prognostic and predictive value of ACQ-5 symptom burden for subsequent severe exacerbations and treatment response. If symptoms reliably predict attacks and therapy response, ACQ-5 could be used to stratify risk and tailor anti-inflammatory management to prevent severe asthma exacerbations.

Couillard S, Meulmeester FL, Charland P et al. · The Lancet. Respiratory medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiometabolic Pharmacology (GLP-1/GIP/dual agonists) & Obesity

Recent Advances in Diabetes Therapies in Asia.

This systematic review and random-effects meta-analysis of randomized controlled trials evaluated whether dual glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonists produce different cardiometabolic effects compared with selective GLP-1R agonism in trial populations. Across included RCTs, dual GLP-1R/GCGR agonism showed cardiometabolic benefits (including improvements in weight and cardiometabolic risk factors) with effects summarized across study outcomes. The results help clinicians and guideline developers understand whether adding GCGR activity meaningfully changes cardiometabolic efficacy beyond GLP-1R–targeted therapies.

Qian L, Surmont F, Ji L · Diabetes care · (2026) · View on PubMed ↗

Not Just for Diabetes: The Next Frontier for GLP-1 Agonists.

This narrative article reviewed evidence for GLP-1 agonists beyond diabetes, focusing on semaglutide’s cardiovascular benefits in non-diabetic individuals with obesity and pre-existing cardiovascular disease. It highlights that semaglutide reduces adverse cardiovascular outcomes even without diabetes. The clinical significance is expanding the therapeutic role of GLP-1 agonists toward cardiovascular risk reduction in broader populations with obesity.

Colangelo H, Nestler A, Lyon C · Journal of the American Board of Family Medicine : JABFM · (2026) · View on PubMed ↗ · Free PDF ↗

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Sarcopenia, Exercise & Musculoskeletal Aging

The role of preventive cardiology in children.

This narrative review summarized preventive cardiology strategies for children and adolescents, focusing on dyslipidemia, hypertension, and obesity and how these risk factors track into adulthood. It emphasized the American Heart Association’s Life’s Essential 8 framework—covering health behaviors and health factors—as a practical approach to prevention and risk optimization in pediatric care. The review is significant because it links early identification and intervention in childhood to reducing long-term cardiovascular disease burden.

Degen MG, Lyon SM · Current opinion in pediatrics · (2026) · View on PubMed ↗

Aging-, obesity-, and diabetes-related sarcopenia: Pathogenesis and interventions.

This review summarized how aging-, obesity-, and diabetes-related mechanisms contribute to sarcopenia pathogenesis and evaluated interventions. It emphasizes resistance exercise as a foundational and effective nonpharmacological strategy, with strength-based training programs improving muscle mass and strength. Clinically, the synthesis supports exercise-based prevention and treatment approaches tailored to sarcopenia risk driven by aging, obesity, and type 2 diabetes.

Han S, Xiong Q, Wu Q et al. · Chinese medical journal · (2026) · View on PubMed ↗ · Free PDF ↗

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Radiation Oncology & Treatment-Related Toxicity

Association of pulmonary artery radiation with pulmonary hypertension after lung cancer radiotherapy.

This multi-institutional retrospective cohort study assessed whether radiation dose to pulmonary arteries is associated with subsequent pulmonary hypertension in patients with non-small cell lung cancer treated with thoracic radiotherapy. It segmented pulmonary arteries and distal vasculature, extracted dose metrics (mean, maximum, and Vx in 5 Gy increments), and used AUROC and Fine–Gray regression to evaluate dose–PH relationships. Identifying pulmonary artery radiation predictors could enable radiotherapy planning that reduces pulmonary hypertension risk after lung cancer treatment.

Atkins KM, Zhang SC, Kehayias CE et al. · Thorax · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodevelopmental & Neonatal Brain Injury Biomarkers

Whole-Blood Gene Expression and Hypoxic-Ischemic Encephalopathy at Birth.

This case-control study used whole-blood gene expression measured at birth in infants enrolled from the COMET (Cooling in Mild Encephalopathy) pilot randomized clinical trial to relate transcriptomic profiles to hypoxic-ischemic encephalopathy (HIE) severity (mild, moderate, or severe) and to track changes over the first 72 hours versus matched healthy controls. Whole-blood gene expression at birth was associated with subsequent HIE severity and revealed differential biological pathways with time-dependent expression changes during early postnatal evolution. These findings support transcriptomic risk stratification at birth to improve early identification and potentially guide more precise treatment intensity for HIE.

Montaldo P, Herberg J, Uppal S et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Rheumatology: Viral-Associated Inflammatory Disease & Remission

Acute parvovirus B19-associated inflammatory musculoskeletal disease: clinical phenotypes and remission trajectories from the GIRRCS Network.

This non-interventional multicentre observational study in adults with new-onset inflammatory musculoskeletal disease tested within 4 weeks of symptom onset and positive anti-parvovirus B19 IgM characterized clinical phenotypes, imaging findings, and remission trajectories from the GIRRCS rheumatology network. The study reported distinct clinical patterns and time-to-first rheumatologist-confirmed remission trajectories across patients with acute parvovirus B19-associated inflammatory musculoskeletal disease. Clinically, defining phenotype and remission course can inform prognosis and follow-up strategies for this immune-mediated viral condition.

Ruscitti P, Costa L, Mastrangelo A et al. · Rheumatology (Oxford, England) · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurology & Neurodegeneration (AD/PD/HIE/brain mechanisms)

Cell Type-Specific Extracellular Vesicles in Mouse Brain: Proteomic Signatures Highlight Astrocytic GlialCAM Network and GPCR Enrichment.

This mouse brain study performed cell type-specific extracellular vesicle (EV) isolation using magnetic immunocapture and characterized proteomic signatures by LC-MS/MS for neuronal EVs (NDEVs), microglial EVs (MDEVs), and astrocyte-derived EVs (ADEVs). Each EV subtype showed distinct molecular fingerprints, with ADEVs highlighting an astrocytic GlialCAM network and enrichment of GPCR-related proteins. These proteomic signatures support the use of cell type-specific EV cargo as biomarkers and mechanistic clues for astrocyte involvement in brain health and disease.

Lucart-Sanchez AM, Sellés-Climent E, Navarro-Calvo J et al. · Glia · (2026) · View on PubMed ↗ · Free PDF ↗

From gut to brain: data-driven evidence suggests causal contribution of gut-microbiota to major depressive disorder in humans.

This human study used data-driven causal inference approaches to test whether gut microbiota contributes causally to major depressive disorder (MDD), addressing prior limitations of small samples and cross-sectional designs. The analysis supported a causal contribution of gut microbiome features to MDD risk in humans, extending earlier microbiome–depression association findings. Scientifically, it strengthens the rationale for microbiome-targeted interventions and for designing future trials that can test causality more directly.

Fehse L, Ribeiro AH, Winter NR et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Brain-computer interface training for motor recovery after stroke.

This Cochrane systematic review assessed the effects of brain-computer interface (BCI) training for motor recovery in people after stroke by searching multiple databases and trial sources for relevant studies. It evaluated whether BCI-based closed-loop neurorehabilitation improves motor outcomes compared with control interventions, synthesizing the evidence across included trials. The review is clinically important because it clarifies the current effectiveness and evidence quality for BCI training to guide rehabilitation practice and future research.

Qin Y, Li M, Li Y et al. · The Cochrane database of systematic reviews · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

A combined artificial intelligence-wet lab approach identifies a pivotal role of the NAD+-mitophagy axis on aging and neurodegeneration.

This combined artificial intelligence and wet-lab study analyzed transcriptomic data from 12 human brain regions across 77 integrated datasets to identify NAD+-mitophagy axis alterations in aging and neurodegeneration, with emphasis on Alzheimer’s disease (AD). Key NAD+-mitophagy targets were validated in Caenorhabditis elegans, a human Tau cell model, and iPSC-derived cortical neurons, supporting a pivotal role for the NAD+-mitophagy axis in neurodegenerative processes. These findings are significant because they nominate NAD+-mitophagy pathway components as potential therapeutic targets and provide a translational pipeline from human omics to experimental validation.

Lautrup S, Cao SQ, Long X et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on August 23, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.