PubMed Trending Research Digest — September 18, 2026

A curated digest of 98 trending PubMed articles, automatically categorised and summarised across 23 research areas.

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Neurodevelopment, Brain Circuits & Neuroinflammation Cardiometabolic Disease & Vascular Risk Hematology & Thrombosis/Platelet Biology AI for Drug Discovery & Clinical Decision Support Cancer Immunotherapy & Immune Evasion Radiation, Myeloid Reprogramming & Radio-Immunotherapy Infectious Disease, Microbiome & Host Defense Cell Biology Mechanisms (Replication, Organelle Dynamics, Signaling) Gene Editing & Genome Engineering (CRISPR/Integrases/Epigenome Editing) AI for Medical Imaging & Diagnostics Neurodegeneration, Dementia & Tau/Amyloid Biology Targeted Cancer Therapies (Small Molecules & Pathway Inhibition) Aging Biology, Senescence & Longevity Modeling Autoimmunity, Inflammation & Immunomodulation Cancer Genomics, Evolution & Biomarkers Reproductive Health & Endometrial/Implantation Biology Gene/Cell Therapy & Regenerative Medicine Chromatin, Transcription & 3D Genome Regulation Respiratory Disease, Pulmonary Fibrosis & Lung Cancer Risk Transplantation, Xenotransplantation & Transfusion Safety Plant Biology & Plant Immunity Musculoskeletal & Tissue Injury/Repair Tumor Microenvironment, Niches & Cell-State Plasticity

Automated digest · 98 articles · 23 research areas · September 18, 2026

Overview

Across this week’s papers, a dominant theme is how modern “systems” approaches—multi-omics, spatial mapping, and AI—are being used to connect mechanism to clinical decision-making. Several studies use large-scale data integration (e.g., longitudinal gut microbiome trajectories during immune checkpoint inhibitor therapy; proteogenomics for idiopathic pulmonary arterial hypertension; and single-cell/spatial multi-omics to define therapy-resistant tumor niches) to identify actionable biomarkers and state-specific vulnerabilities. Complementing this, multiple AI-focused works aim to reduce development attrition and improve diagnostic consistency, including report-supervised annotation-free abdominal CT interpretation and multi-agent AI for therapeutic discovery.

A second major theme is immune modulation and immune escape, spanning both cancer and infection. In cancer, papers describe mechanisms of T-cell evasion (e.g., antigen processing constraints for truncal TP53 neoantigens), radiation-driven reprogramming of myeloid cells to enhance radio-immunotherapy, and niche-level interactions that support multidrug resistance. In infectious disease and host defense, studies highlight how antibiotics can reprogram non-tuberculous mycobacteria fitness, how HBV drives immunosuppressive macrophage differentiation via metabolic-epigenetic remodeling, and how engineered or microbiota-mediated strategies (e.g., lytic phage lysogen prophylaxis; pectin-induced IgA programs) can reshape mucosal immunity.

Finally, the digest shows continued momentum in foundational molecular biology and translational engineering. Multiple articles advance understanding of chromatin/3D genome regulation, transcriptional coupling, and replication stress control—processes that underlie cancer and aging biology. Parallel translational efforts include new genome-editing toolkits (prime assembly, Cas12m epigenome editing, and CRISPR-like programmable DNA targeting) and gene/cell therapy progress (AAV factor IX in adolescents; mini/micro-dystrophin gene therapy synthesis; xenotransplantation feasibility). Together, these studies reinforce a broader trend: moving from descriptive biology to programmable, targetable interventions guided by better models, better biomarkers, and better mechanistic endpoints.

Neurodevelopment, Brain Circuits & Neuroinflammation

Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma.

This study evaluated whether the antiseizure drug levetiracetam improves outcomes in children with diffuse midline glioma (DMG) versus pediatric hemispheric high-grade glioma, and tested its effects in DMG orthotopic xenograft mouse models. Retrospective real-world clinical data showed longer overall survival in DMG patients taking levetiracetam, while preclinical experiments found reduced glioma proliferation and tumor burden with extended survival. These findings support a potential therapeutic role for levetiracetam targeting GABAergic synapses in DMG and justify further mechanistic and clinical investigation.

Barron T, Drexler R, Mochizuki A et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.

In relapsing-remitting multiple sclerosis, this observational study used longitudinal sampling with single-cell RNA sequencing, bulk transcriptomics, multiparameter flow cytometry, and targeted viral RT-qPCR to map immune changes preceding relapse. A reproducible pre-relapse signature in monocytes and B cells emerged up to 3 months before clinical onset and was enriched for host genes responsive to Epstein–Barr virus (EBV) lytic reactivation. This supports EBV reactivation as an upstream trigger of relapse-associated immune perturbations and identifies cellular pathways that could be targeted or monitored.

King DA, Saxena S, Caefer D et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Topographic structure and function of locus coeruleus noradrenaline neurons.

This study mapped the relationship between morphology, gene expression, and activity of noradrenergic neurons in the mouse locus coeruleus during behavior, using circuit-level characterization of individual neurons and activity readouts in a continuous learning task. Axonal projections were extensive but biased to subsets of brain regions, and both projection patterns and graded gene expression correlated with locus coeruleus cell-body location; dorsal locus coeruleus neurons projecting to isocortex were activated during choice switches and by reward-prediction-error signals. The results provide a topographic cellular logic for how locus coeruleus noradrenaline signals are routed to support adaptive learning.

Su Z, Kosillo P, Jung K et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

De novo variants in the poly(rC)-binding protein gene PCBP1 cause a neurodevelopmental disorder.

This study identified genetic causes of neurodevelopmental disorder by analyzing de novo variants in the poly(rC)-binding protein gene PCBP1 across an international multicenter cohort. Sixteen de novo pathogenic PCBP1 variants were found in 17 subjects, with intellectual disability and prominent autism spectrum disorder features, and functional assays in primary hippocampal mouse neuron cultures showed impaired dendritic arborization. The findings establish PCBP1 as a neurodevelopmental disease gene and connect specific variants to neuronal structural phenotypes relevant to cognition and ASD.

Deb W, Besnard T, Desprez F et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Transcriptomic profiling of inner ear hair cell spontaneous regeneration reveals the key role of dlx5a.

This study profiled gene expression during spontaneous regeneration of zebrafish inner ear semicircular canal crista hair cells after injury using single-cell transcriptomic sequencing across a regeneration timeline, with emphasis on the transcription factor dlx5a. It found that regenerated crista hair cells arise from supporting cells via both mitotic and non-mitotic mechanisms and that transcriptomic programs highlight dlx5a as a key driver of the regenerative process. The results identify dlx5a-centered molecular control of hair cell regeneration, offering a candidate pathway for promoting sensory recovery in mammals.

Gong J, Yang C, Zhang G et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Cardiometabolic Disease & Vascular Risk

Exercise-based cardiac rehabilitation for coronary heart disease.

This Cochrane systematic review assessed the clinical and cost-effectiveness of exercise-based cardiac rehabilitation (exercise training alone or with psychosocial/educational components) in people with coronary heart disease (CHD). The review synthesized evidence on effects on mortality, morbidity, and health-related quality of life (HRQoL) compared with no-exercise controls. The results are intended to guide evidence-based CHD rehabilitation strategies and health-economic decision-making.

Dibben G, de Vries FB, Faulkner J et al. · The Cochrane database of systematic reviews · (2026) · View on PubMed ↗

Zonated cholesterol sensing by SIRT2 drives MASLD-HCC.

This Cell Metabolism study investigated how zonated cholesterol sensing drives metabolic dysfunction-associated steatotic liver disease (MASLD) progression to hepatocellular carcinoma (HCC), focusing on sirtuin 2 (SIRT2). Lineage tracing and functional experiments showed that zone 1 hepatocytes are the tumor origin, and that SIRT2 overexpression in zone 1 promotes HCC whereas SIRT2 deletion prevents carcinogenesis by restoring cholesterol/bile acid metabolism and increasing CD8+ T cell recruitment. Mechanistically, cholesterol activates SIRT2, which deacetylates sterol carrier protein 2 (SCP2) at Lys546 to block peroxisome-related pathways, implicating SIRT2 as a zonation-linked therapeutic target.

Zhang Y, Long X, Fu Y et al. · Cell metabolism · (2026) · View on PubMed ↗

Comparative Cardiorenal Efficacy and Safety of Finerenone, SGLT2 Inhibitors, Semaglutide and Their Combination in Diabetic Kidney Disease.

The study compared cardiorenal efficacy and safety of finerenone, SGLT2 inhibitors (dapagliflozin/canagliflozin class), semaglutide, and their combination in adults with diabetic kidney disease (DKD) using a frequentist network meta-analysis of randomized trials. Across 10 randomized datasets totaling 37,923 participants, multiple therapies reduced cardiovascular composite events versus control, and the analysis estimated relative risks for cardiorenal and safety outcomes. This helps clinicians rank treatment options for DKD in type 2 diabetes by integrating comparative evidence across drug classes and combination therapy.

Zhou Z, Fu L, Chen D et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Eyeballing for Frailty Assessment in Elderly Patients Referred for Coronary Angiography.

This prospective observational study evaluated whether physician “eyeballing” of frailty can accurately detect frailty in elderly patients (age ≥70) referred for coronary angiography, using the Fried test as the reference standard. Two blinded cardiologists scored frailty both with a formal Fried test and with an eyeballing approach on a Fried-like scale, and the study assessed the diagnostic accuracy of the eyeballing method. If validated, eyeballing could provide a faster, clinically feasible frailty screen to better risk-stratify older adults undergoing invasive coronary procedures when structured tools are not available.

Hilu R, Arow Z, Barashi R et al. · Journal of the American Geriatrics Society · (2026) · View on PubMed ↗ · Free PDF ↗

Predicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial.

This post hoc analysis of the ATTAIN-1 phase 3 trial assessed how orforglipron (5.5 mg, 9 mg, or 17.2 mg) versus placebo for 72 weeks changes predicted 10-year cardiometabolic risk in adults with overweight or obesity without type 2 diabetes (T2D). Using validated risk engines (Cardiometabolic Disease Staging for T2D risk, Framingham for total CVD risk, and PREVENT for total CVD/ASCVD), the study quantified changes in long-term risk predictions from baseline to week 72. If consistent with actual outcomes, these modeling results could support orforglipron’s role in reducing future T2D and cardiovascular disease risk in high-risk obese/overweight populations.

Shinde S, Kahles F, Vasileva-Metodiev S et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Proteogenomic Profiling of Idiopathic Pulmonary Arterial Hypertension Identifies Sex-Differential Proteins and Candidate Therapeutic Targets.

This proteogenomic study investigated idiopathic pulmonary arterial hypertension (IPAH) by integrating plasma proteomics with genetic evidence to identify sex-differential proteins and candidate therapeutic targets. Using UK Biobank data (44,137 predominantly European-ancestry participants; 252 incident and 141 prevalent IPAH cases) and regression-based protein associations, the authors prioritized proteins supported by cis-Mendelian randomization and reported sex-specific candidates. The findings aim to improve IPAH biomarker specificity and risk stratification while suggesting drug-repurposing targets informed by both protein biology and genetics.

Lin X, Zhang Y, Pu Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis.

This systematic review and comprehensive meta-analysis compared the efficacy and safety of orforglipron maintenance doses of 12 mg versus 36 mg in adults with obesity with or without diabetes. Across included trials, it evaluated outcomes spanning weight change, glycemic measures, cardiometabolic endpoints, and adverse events to determine whether dose-dependent differences exist. The clinical significance is that it provides a head-to-head evidence synthesis to inform optimal dosing of this oral non-peptide GLP-1 receptor agonist for weight and metabolic management.

Hegaz MG, Aboud MYA, Kamel AII et al. · BMC endocrine disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Lipoprotein (a) variability in high cardiovascular risk individuals with hypertriglyceridemia and controlled LDL-C on statin therapy in REDUCE-IT.

This study assessed sources of within-person variability in lipoprotein(a) [Lp(a)] among high cardiovascular risk individuals with hypertriglyceridemia and controlled LDL-C on statin therapy using serial Lp(a) measurements at baseline, 12 months, and 24 months in the REDUCE-IT trial. Lp(a) showed clinically meaningful intraindividual variability over time despite the genetically determined expectation, with variability influenced by participant characteristics in this statin-treated, triglyceride-elevated population. These findings challenge the single-lifetime Lp(a) measurement framework and support more careful interpretation (and potentially repeat testing) of Lp(a) in high-risk patients under lipid-modifying therapy.

Szarek M, Bhatt DL, Miller M et al. · Journal of clinical lipidology · (2026) · View on PubMed ↗ · Free PDF ↗

Associations between specific non-sustained ventricular tachycardia characteristics and sudden cardiac death in hypertrophic cardiomyopathy.

This retrospective, multicentre study evaluated prognostic value of non-sustained ventricular tachycardia (NSVT) characteristics—especially coupling intervals—for sudden cardiac death (SCD) risk stratification in 2,625 patients with hypertrophic cardiomyopathy (HCM). Using 24-hour Holter recordings, specific NSVT coupling interval patterns were associated with higher SCD risk beyond NSVT frequency and duration alone. The results refine HCM risk stratification by identifying more granular Holter-derived NSVT features that could guide clinical decision-making for SCD prevention.

Zhang Y, Qin F, Guan Y et al. · Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Risk Factors and Definition of Younger-Onset Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Cirrhosis.

This study examined genetic and metabolic factors associated with younger-onset metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis in adults with biopsy-proven MASLD enrolled in the NASH CRN. Using DNA genotyping to build a genetic risk score (GRS) based on PNPLA3 and TM6SF2 risk alleles plus the wild-type HSD17B13 allele (and comparing with other published weighted GRSs), it assessed associations with younger-onset cirrhosis defined as the youngest quartile of age among participants. The significance is identifying risk stratification markers for earlier development of MASLD cirrhosis, which could guide earlier surveillance and intervention.

Ajmera V, Schwantes-An L, Díaz LA et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Hematology & Thrombosis/Platelet Biology

State-level burden of chronic respiratory diseases in the USA, 1990-2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023.

This Global Burden of Disease Study 2023 analysis quantified US chronic respiratory disease burden (asthma, chronic obstructive pulmonary disease, and other chronic respiratory conditions) from 1990–2023, identified contributing risk factors, and forecast prevalence to 2050. Using GBD 2023 estimates of prevalence, mortality, and disability-adjusted life-years (DALYs), the study characterized temporal trends and regional disparities across the USA. These projections and risk-factor insights can inform targeted public health interventions and resource planning for chronic respiratory disease.

The Lancet. Respiratory medicine · (2026) · View on PubMed ↗

Germline EGFR T790M mutation and lung cancer risk.

The study assessed whether the germline EGFR T790M variant is associated with lung cancer risk in a large population of over 3.3 million individuals, including analysis of never-smokers and ancestry/geography. Germline EGFR T790M was significantly associated with increased lung cancer risk, with no increased risk for 17 other cancers and no interaction with polygenic risk, and the risk exceeded that conferred by smoking and was several-fold higher in never-smokers. Clinically, this supports EGFR T790M as an inherited lung cancer susceptibility marker that could refine risk stratification beyond smoking history.

LoPiccolo J, Micheletti S, Shi J et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

AI for Drug Discovery & Clinical Decision Support

Clinical activity and safety of rilzabrutinib in patients with previously treated immune thrombocytopenia (LUNA3): results from the open-label period of a phase 3 trial.

This phase 3 LUNA3 open-label analysis studied long-term activity and safety of the BTK inhibitor rilzabrutinib in adolescents and adults (≥18 years) with primary persistent or chronic immune thrombocytopenia (ITP) who had prior response to intravenous or anti-D immunoglobulins or corticosteroids. The key finding was that rilzabrutinib maintained clinically meaningful long-term activity with an overall favorable safety profile during the open-label period. This supports continued use and further development of rilzabrutinib for previously treated ITP patients.

Kuter DJ, Ghanima W, Cooper N et al. · The Lancet. Haematology · (2026) · View on PubMed ↗

An open benchmark and language models for AI in aging biology.

This Cell study developed LongevityBench, an open benchmark of 17 tasks across five biodata domains, to evaluate whether AI models can interpret heterogeneous aging data types. Across 18 frontier AI systems, the study found that no single model dominates all tasks and that omics-based age prediction is consistently the hardest task regardless of model scale. By also fine-tuning multitask Longevity-LLMs, the work provides a public evaluation framework and highlights where AI performance gaps remain in aging biology.

Zhavoronkov A, Naumov V, Sidorenko D et al. · Cell · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

The Virtual Biotech: A multi-agent AI framework for therapeutic discovery and development.

The study developed and evaluated the “Virtual Biotech,” a multi-agent AI framework for therapeutic discovery and development across target discovery, safety assessment, modality selection, and clinical development. Using outcomes from 55,984 trials annotated by 37,000 agents, the system found that targeting cell-type-specific genes was associated with a 48% higher likelihood of reaching market and 32% fewer adverse events, and it integrated multimodal evidence to propose therapeutic strategies at multiple decision points. This provides a scalable AI approach to reduce attrition and improve evidence integration in drug development pipelines.

Zhang HG, Eckmann P, Miao J et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

Evolution and heterogeneity of lethal metastatic bladder cancer subtypes.

The study introduced Paper2Agent, an automated framework that converts research papers into AI agents that act like a “virtual corresponding author” by exposing manuscript, supplementary materials, datasets, code, and workflows as agent-native knowledge. It addresses barriers to reuse by transforming static text into an active system that can support downstream use and discovery. This could improve reliability and interoperability of scientific communication by making published methods and resources directly executable by AI.

Itagi P, Schuster SL, Arora S et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Development of a random background to understand ligand optimization.

The study aimed to develop a random background for ligand optimization by defining how systematic random small substitutions across starting ligands can estimate the probability of achieving substantial improvements in affinity or potency. It was motivated by the lack of an appropriate baseline to compare optimization trajectories and by prior reports suggesting a nontrivial fraction of minor analogues can yield large potency gains. Creating such a random optimization baseline would enable more rigorous evaluation of whether observed improvements reflect true design signal versus chance.

Xu X, Mailhot O, Correy GJ et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.

This study developed machine learning workflows to predict nonspecific binding (polyreactivity) of VHH antibodies while addressing dataset bias from closely related pipeline sequences using cluster-aware validation. It found that incorporating cluster-aware benchmarking improves the ability to generalize predictions to new, less-related VHH sequences compared with conventional validation approaches. The approach supports more reliable developability risk assessment for VHH therapeutics by reducing false confidence from biased training/benchmark datasets.

Stanev V, Devalle F, Boroumand M et al. · mAbs · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer Immunotherapy & Immune Evasion

Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.

This Immunity study investigated how cancers evade T cell detection of truncal TP53 neoantigens by examining immunogenicity and antigen processing across human tumors. Comprehensive immunopeptidomics showed that hotspot TP53 mutations preferentially occur in TP53 regions resistant to antigen processing, leading to reduced presentation of neoantigen peptide–HLA complexes (including for HLA-A02:01 and HLA-B07:02). The work identifies a mechanism of immune escape at the level of antigen processing that could inform neoantigen selection and immunotherapy design.

Haratani K, Reinhold B, Duke-Cohan JS et al. · Immunity · (2026) · View on PubMed ↗

Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia.

This study used an immune checkpoint knockout screen to identify how TIGIT-CD155 signaling modulates adapter CAR-T (AdCAR) cell function in acute myeloid leukemia (AML). The key finding was that the TIGIT–CD155 interaction significantly regulates AdCAR-T activity, thereby altering the immunosuppressive checkpoint control of adapter CAR-T function. Clinically, targeting the TIGIT–CD155 axis could improve the efficacy and durability of AdCAR-T strategies in AML while informing rational checkpoint-combination designs.

Mast AS, Atar D, Ruoff L et al. · Oncoimmunology · (2026) · View on PubMed ↗ · Free PDF ↗

T-cell lymphoma following chimeric antigen receptor-T therapy: a cause for concern?

This review synthesized evidence on T-cell lymphoma occurring after chimeric antigen receptor (CAR) T-cell therapy, drawing on pivotal trials, real-world registries, meta-analyses, pharmacovigilance data, and molecular case reports. The key conclusion was that post–CAR T-cell lymphoma is rare but biologically plausible and clinically important enough to warrant ongoing surveillance and regulatory attention. Scientifically, it highlights mechanisms and incidence patterns that can guide risk mitigation and long-term follow-up strategies for patients receiving CAR T therapies.

Stella F, Fraietta JA, Schuster SJ et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

Identification of broadly tumour-reactive γδ TCRs from multiple myeloma.

This study created PreGame, a machine-learning algorithm to identify tumour-reactive γδ T cells from single-cell CITE sequencing data, and applied it to samples from patients with multiple myeloma. PreGame distinguished tumour-reactive γδ TCR-bearing cells from bystander γδ T cells and enabled the identification of broadly tumour-reactive γδ TCRs across patients. Scientifically and translationally, this provides a way to prioritize γδ TCRs for immunotherapeutic development by reducing the confounding of non-reactive γδ populations.

St Paul M, Hendrikse LD, Ying F et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Immunogenic cell death and tertiary lymphoid structures: bridging tumour cell death and immune organization.

This Perspective reviewed evidence linking immunogenic cell death (ICD) to the formation of tertiary lymphoid structures (TLSs) in tumors. The authors propose that ICD acts as an upstream organizer by releasing tumor antigens and damage-associated molecular patterns that activate innate pathways such as cGAS–STING in dendritic cells, myeloid cells, endothelial cells, and stromal fibroblasts, leading to type I interferons and chemokines (e.g., CCL19/CCL21/CXCL13) that support TLS organization. Conceptually, this framework bridges tumor cell death mechanisms with immune microenvironment architecture and suggests ICD-inducing strategies could improve anti-tumor immunity via TLS formation.

Hanc R, Demuynck R, Krysko DV · Nature reviews. Immunology · (2026) · View on PubMed ↗

Radiation, Myeloid Reprogramming & Radio-Immunotherapy

Myeloid reprogramming generates myeloid-derived activating cells to potentiate radiotherapy and suppress metastasis.

This Cancer Cell study examined how radiation reshapes myeloid cell states to influence radiotherapy response and metastasis, focusing on the role of TET2 in advanced lung cancer treated with radio-immunotherapy. It found that radiation induces TET2 in myeloid-derived suppressor cells, and that myeloid-specific Tet2 deletion after radiotherapy suppresses tumor progression while redirecting monocytes toward antigen-presenting myeloid-derived activating cells (MDACs) that enhance antitumor T cell responses. Mechanistically, a radiation-responsive p53–TET2 axis modulates chromatin methylation (including m5C), linking DNA damage signaling to myeloid reprogramming.

Ji F, Zheng L, Chen D et al. · Cancer cell · (2026) · View on PubMed ↗

Infectious Disease, Microbiome & Host Defense

Dietary pectin remodels commensal bacterial surfaces to promote IgA-mediated protection from intestinal inflammation.

This Cell Host & Microbe study tested whether dietary pectin can induce strain-specific IgA responses that protect against intestinal inflammation, using gnotobiotic mice mono-colonized with Bacteroides uniformis. It found that pectin induces a microbiota-dependent high-IgA phenotype via a pectin-responsive rcsC-associated regulatory program that remodels bacterial surfaces, with HexCer (34:0) as a dominant remodeled lipid recognized by CLEC4E on intestinal neutrophils. The requirement for CLEC4E to drive IgA induction links specific microbial surface remodeling to IgA-mediated mucosal protection.

Tang W, Wang Y, Feng S et al. · Cell host & microbe · (2026) · View on PubMed ↗

Tobramycin enhances Mycobacterium abscessus fitness through whiB7 induction.

The study examined how tobramycin affects Mycobacterium abscessus fitness in the context of cystic fibrosis (CF)–associated chronic airway infection, focusing on whiB7 induction. Tobramycin enhanced M. abscessus fitness by inducing the stress-response gene whiB7. This mechanistic finding suggests that antibiotic exposure can actively reprogram NTM physiology, informing how CF clinicians and researchers should consider antibiotic choice and resistance/fitness tradeoffs in NTM-PD.

Corley JM, Congel JH, Haist KC et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Probiotics in Cardiometabolic Diseases: Current Evidence, Postbiotic Perspectives, and Future Directions.

This narrative review summarized evidence for probiotics in cardiometabolic diseases, discussed emerging “postbiotic” approaches, and outlined future research directions. It focused on how gut microbiome alterations influence cardiometabolic outcomes such as atherosclerosis, hypertension, and diabetes through multiple signaling pathways. The significance is that it frames current clinical and mechanistic knowledge to support more targeted microbiome-based interventions beyond live probiotics.

Yang F, Qin W, Zhang G et al. · Journal of microbiology and biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

FAM134B Restricts African Swine Fever Virus Capsid Assembly via Reticulophagy and Its Antiviral Activity is Antagonized by the Viral Virulence-Associated Factor pMGF300-2R.

This experimental study examined how the reticulophagy receptor FAM134B affects African swine fever virus (ASFV) capsid assembly in infected cells and how ASFV virulence factor pMGF300-2R antagonizes this antiviral effect. The authors found that FAM134B interacts with major ASFV capsid proteins p72 and pA137R to restrict capsid maturation within perinuclear viral factories, and that pMGF300-2R counteracts FAM134B-mediated inhibition. These results identify a host reticulophagy pathway as a mechanistic antiviral defense against a DNA virus and suggest potential targets for ASFV intervention.

Luo R, Zhang J, Huang R et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.

The study engineered non-pathogenic Escherichia coli to carry an engineered prophage that produces obligately lytic phage progeny targeting Salmonella enterica Typhimurium (STm) and tested prophylactic protection in mice. Prophylactic gut colonization with the lytic phage-producing lysogen generated high pre-infection lytic phage levels and overcame STm host defense systems (including restriction–modification), reducing subsequent enteric infection. This provides a pre-emptive, gene-engineering-based strategy for prophylactic lytic phage therapy against enteric pathogens.

Bataglioli RA, Baaziz H, Avalos HF et al. · Nature microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Mutational constraints on RSV F and its neutralization by antibodies.

This study analyzed mutational constraints in the respiratory syncytial virus (RSV) F protein and how those constraints shape neutralization by antibodies, focusing on nirsevimab resistance and subtype differences. Using a biophysical model plus pseudovirus deep mutational scanning, the authors showed that resistance to nirsevimab is more common in RSV subtype B than A due to how bivalent IgG binding buffering and Fab potency interact with F mutations. This work informs antibody-resistance risk assessment and can guide the design or selection of next-generation RSV F immunotherapies.

Simonich CAL, McMahon TE, Juviler G et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Cell senescence emerges as a hallmark and therapeutic target of chronic intracellular infection.

This study examined how chronic intracellular infection by Mycobacterium abscessus reprograms alveolar macrophages toward senescence, using cellular and molecular analyses to define drivers and propagation of the senescent state. It found that Mab-induced DNA damage is the primary trigger of senescence and that senescence-associated secretory phenotype (SASP) factor secretion propagates secondary senescence in neighboring cells. The work positions chronic intracellular infection as a model for senescence emergence and highlights SASP-mediated spread as a potential therapeutic target to limit chronic inflammatory pathology.

Scarpa E, Oliveri D, Rondelli D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

This double-blind, parallel-group, placebo-controlled randomized trial studied whether non-enteric-coated pancreatic enzyme replacement therapy (NEPERT; protease 30,000U, lipase 25,000U, amylase 8,000U per capsule) reduces pain in adults aged 18–60 years with chronic pancreatitis (Mayo Clinic criteria). NEPERT improved pain outcomes measured by change in Izbicki pain score compared with placebo over the 12-week primary assessment period (with follow-up to 24 weeks). The results support NEPERT as a potential therapeutic option for chronic pancreatitis pain, addressing uncertainty about PERT analgesic efficacy.

Talukdar R, Rasheed A, Unnisa M et al. · Gut · (2026) · View on PubMed ↗

HBV induces immunosuppressive macrophages via metabolic and epigenetic reprogramming to facilitate the establishment of chronic persistent infection.

This study investigated how hepatitis B virus (HBV) drives immunosuppressive macrophage differentiation through metabolic and epigenetic reprogramming to enable chronic persistent infection. Using monocyte-derived macrophages generated from monocytes of chronic HBV-infected patients, healthy controls, and cord blood, the authors showed HBV-associated programming that promotes an immunosuppressive macrophage phenotype. These mechanistic insights identify metabolic–epigenetic pathways as potential targets to disrupt HBV immune evasion and improve strategies to control chronic infection.

Wang Z, Liu N, Li Y et al. · Gut · (2026) · View on PubMed ↗

Longitudinal gut microbiome dynamics during immunotherapy identify microbial features of clinical benefit in advanced primary liver cancer.

This prospective longitudinal shotgun metagenomic study profiled 777 serial stool metagenomes from 315 patients with advanced primary liver cancer receiving immune checkpoint inhibitor (ICI)-based therapy to define gut microbiome trajectories during treatment. Microbial features present during therapy (on-treatment states) improved identification of clinical benefit and enhanced generalizability compared with relying solely on pretreatment biomarker signatures. The findings support microbiome-informed monitoring during ICI therapy as a strategy to better predict response and tailor immunotherapy.

Qian Z, Han J, Lyu B et al. · Gut · (2026) · View on PubMed ↗ · Free PDF ↗

Integrated metabolomic and genetic profiling implicate loss of docosahexaenoic acid in the link between ultra-processed foods and Crohn’s disease.

The study used integrated metabolomic and genetic profiling to investigate how ultra-processed food (UPF) relates to incident Crohn’s disease (CD) in participants from UK Biobank (discovery n=10,229) with internal (n=91,306) and external (n=7,893) validation plus ONE-IBD (n=752). It identified UPF-associated circulating metabolomic features and implicated loss of docosahexaenoic acid (DHA) as a key mediator linking UPF exposure to CD risk. Scientifically, this provides a mechanistic metabolite target (DHA) that could inform prevention strategies and biomarker development for UPF-related CD risk.

Wang S, Dan L, Ruan X et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

IL1B-high macrophages promote ferroptosis-like lipid peroxidation injury in Crohn’s disease intestinal epithelium.

This study integrated longitudinal single-cell and spatial transcriptomics, macrophage–epithelial co-culture, epithelial RNA-seq, GPX4 functional assays, and a TNBS-induced chronic colitis model to define myeloid drivers of epithelial injury in Crohn’s disease. IL1B-high macrophages were associated with ferroptosis-like lipid peroxidation injury in intestinal epithelium, and GPX4 validation supported a causal role in the epithelial damage program. Targeting IL1B-high macrophage states or the ferroptosis-like pathway may offer a strategy to reduce mucosal epithelial injury in Crohn’s disease.

Sun Q, Jiang Z, Chen X et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗

Cell Biology Mechanisms (Replication, Organelle Dynamics, Signaling)

Molecular mechanism of HUWE1-HAPSTR1-USP7-mediated ubiquitin chain amplification on nuclear proteins.

This Molecular Cell study elucidated the mechanism by which the HUWE1–HAPSTR1–USP7 axis amplifies ubiquitin chains on nuclear proteins. It showed that HUWE1 acts as a ubiquitin chain amplifier by capturing pre-ubiquitinated substrates and assembling long ubiquitin chains with K11–K48 branch points, a process regulated by the partners HAPSTR1 and USP7. This mechanistic framework clarifies how HUWE1 achieves substrate selectivity and stress-responsive protein degradation.

Yatskevich S, Mohapatra J, Mroue R et al. · Molecular cell · (2026) · View on PubMed ↗

Splenic regulation of systemic platelet activation state.

The study investigated physiological mechanisms that counteract systemic platelet activation in mice, focusing on splenic regulation of platelet activation state. It found that the spleen filters activated platelets in thrombotic and inflammatory conditions to limit pathology by maintaining platelet quiescence, where glycoprotein VI (GPVI)–dependent activation in splenic red pulp is balanced by inhibitory G6b–perlecan signaling. This identifies a spleen-based inhibitory axis (G6b–ITIM/perlecan) that could be targeted to prevent thromboinflammatory complications without broadly suppressing platelets.

Laun L, Leunig A, Zhang F et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Cohesin reshapes replication fork contacts to aid fork slowing and reversal.

The study investigated how the cohesin complex reshapes replication fork contacts to promote fork slowing and reversal under replication stress. By linking cohesin-mediated genome organization (via loop extrusion) to functional replication fork behaviors, it provided mechanistic insight into how fork contacts contribute to maintaining fork stability and damage tolerance during stress. This improves understanding of replication stress responses relevant to cancer chemotherapeutic sensitivity and genome integrity preservation.

González-Acosta D, Giménez-Llorente D, Rodrigues M et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial fission factor senses and governs ferroptosis.

This study investigated how mitochondrial dynamics regulate ferroptosis by identifying signaling events upstream of mitochondrial fission, using quantitative phosphoproteomics and mechanistic cell-based assays. The authors found mitochondrial fission factor (MFF) as a ferroptosis-selective regulator, where the lipid mediator 17-HETE promotes phosphorylation of MFF at Ser155 to drive coordinated fragmentation and dysfunction of mitochondria and peroxisomes. These mechanistic links connect organelle remodeling to ferroptotic execution and suggest MFF/Ser155 as a potential target to modulate ferroptosis in disease.

Dai S, Dai X, Zhang T et al. · Nature · (2026) · View on PubMed ↗

Profilin promotes lamellipodium protrusion by tuning the antagonistic activities of capping protein and VASP.

This study used genome editing to dissect how profilin (Pfn) coordinates actin dynamics during lamellipodium protrusion by tuning the antagonistic activities of capping protein (CP) and Ena/VASP family polymerases, in the context of Arp2/3-driven branched actin networks. The authors found that Pfn counters Ena/VASP but promotes Arp2/3 complex activity, while Ena/VASP and CP mutually antagonize each other, and that CP’s sensitivity to Pfn removal depends on Ena/VASP presence. These mechanistic insights clarify how actin regulators are balanced to control lamellipodial protrusion, informing broader models of cell migration and motility.

Tang Y, Schaks M, Jiang X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.

This study examined how membrane lipids regulate lysosomal degradative capacity during clearance and recycling of dysfunctional mitochondria, focusing on cholesterol and lysosome-associated lipid signaling in cells. The authors found that cholesterol preserves lysosomal function, with damaged-mitochondria clearance coupled to acute PI4P accumulation on lysosomes via PI4KIIα and subsequent OSBP-mediated cholesterol transport. These findings identify a cholesterol–PI4KIIα–OSBP axis that helps maintain lysosomal catabolism, informing strategies to improve mitochondrial quality control in aging and disease.

Yang H, Matsuhisa K, Wei M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Core nucleosomes are refractory to lentiviral DNA integration.

This study examined lentiviral integration behavior in chromatin by testing native HIV-1 preintegration complexes and in vitro-assembled lentiviral intasomes against chromatinized target DNA with defined histone marks, focusing on the role of LEDGF/p75 and nucleosome structure. It found that while LEDGF/p75 is essential and minimally sufficient to enhance integration into chromatin containing H3K36me3, integration is unexpectedly refractory within the nucleosome core. The work clarifies how lentiviral intasomes engage chromatin and constrains integration site selection, informing mechanistic models of retroviral genome insertion.

Hope J, Punch E, Cook NJ et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Gene Editing & Genome Engineering (CRISPR/Integrases/Epigenome Editing)

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas.

The study characterized an ancestral CRISPR-associated system by identifying Viral Interference Programmable Repeat (VIPR) components—Vipr proteins and VIPR RNAs (vrRNAs)—and determining how vrRNAs recognize DNA. Unlike canonical contiguous guide-target pairing, vrRNAs use a noncontiguous “gapped” code in which alternating GGY/NN motifs collectively specify the target sequence in double-stranded DNA, and natural vrRNA targets suggest action against competing phages. This advances understanding of how early RNA-guided DNA recognition could have evolved and provides a blueprint for designing programmable, noncontiguous DNA-targeting CRISPR-like systems.

Yoon PH, Loi KJ, Zhang ZT et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.

This study engineered and characterized a miniature CRISPR-Cas12m system for epigenome editing, focusing on a structure-guided discovery of a V-M miniature subtype from Pelomicrobium methylotrophicum. The authors showed that PmCas12m recognizes a flexible 5’-YTN-3’ PAM and binds double-stranded DNA robustly while lacking DNA cleavage activity, and they used structural approaches (including cryo-electron microscopy) to support the design. The scientific significance is that this smaller Cas12m variant could be more compatible with AAV delivery for programmable epigenome editing therapies.

Yu T, Ji M, Yu D et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗

Targeted genomic integration and rearrangement using prime assembly.

This study developed prime assembly, a CRISPR-targeted dual flap synthesis method for RNA-programmable, site-specific DNA integration in human cells, and compared its activity in dividing versus non-dividing contexts. Prime assembly enabled targeted installation of single- or double-stranded DNA fragments, including exon recoding, transgene integration, and megabase-scale rearrangements, with performance similar to homology-directed repair but applicable to both cell-cycle states. Clinically, this expands the toolkit for therapeutic genome editing by making medium-to-large genomic modifications more feasible in therapeutically relevant human cells.

Levesque S, Kawashima N, Hwang GH et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

AI for Medical Imaging & Diagnostics

An expert-level generalist AI for abdominal CT diagnosis.

The study developed RADAR, an expert-level generalist vision-language AI model for abdominal CT diagnosis trained on over 400,000 contrast-enhanced abdominal CT exams and 15 million anatomy-wise image-text pairs using clinical reports without manual annotation. Across internal and external multi-center evaluations, RADAR achieved robust generalization for 18 anatomical structures and 146 imaging findings, and a reader study evaluated its assistance in clinical interpretation. This supports the feasibility of report-supervised, annotation-free generalist AI for broad abdominal imaging tasks, potentially improving diagnostic consistency and workflow efficiency.

Zhang Q, Zhang J, Cao W et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Neurodegeneration, Dementia & Tau/Amyloid Biology

Effective amyloid clearance with lecanemab in a female with Alzheimer’s disease: A case report.

The case report studied an 81-year-old woman with amnestic mild cognitive impairment (MCI) due to Alzheimer’s disease treated with the anti-amyloid monoclonal antibody lecanemab for 18 months in a real-world clinical setting. Lecanemab was associated with effective amyloid clearance as assessed by imaging outcomes reported in the case. This provides real-world evidence complementing trials on the effectiveness of lecanemab outside controlled study settings, while highlighting the need for continued monitoring of long-term safety and durability.

Noguchi-Shinohara M, Ono K · Radiology case reports · (2026) · View on PubMed ↗ · Free PDF ↗

Rethinking tau-targeted therapy in Alzheimer’s disease: Toward a dual biomarker strategy.

This article reviewed tau-targeted therapeutic strategies in Alzheimer’s disease, focusing on how soluble phosphorylated tau biomarkers (p-tau262, p-tau356, and p-tau217) and the monoclonal antibody posdinemab should be interpreted in relation to clinical outcomes. It argues that decreases in certain CSF soluble p-tau measures may reflect disease-stage biology rather than treatment efficacy, and highlights that p-tau217 lowering with posdinemab was not accompanied by clinical benefit. The proposed dual-biomarker framework aims to improve trial design and biomarker interpretation so tau-targeted therapies are evaluated against the right biological endpoints.

Teunissen CE, Pini L, Imbimbo BP · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.

This study investigated whether APOE genetic variants remodel astrocyte lipid droplet proteomes and lipid droplet degradation dynamics using human induced pluripotent stem cell-derived astrocytes treated with oleic acid. It found that APOE genotype differentially shapes the lipid droplet proteome/lipidome and alters lipid droplet dynamics and turnover, consistent with genotype-specific regulation of lipid storage and degradation pathways. These data link APOE risk alleles to glial lipid droplet biology relevant to late-onset Alzheimer’s disease and suggest genotype-tailored therapeutic opportunities.

Cuní-López C, Root JT, Hao Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Inflection points and transitions in Alzheimer’s disease.

This Perspective article proposes that Alzheimer’s disease progresses through discrete molecular, cellular, and network phases centered on biological inflection points rather than a single linear cascade from amyloid-β to tau and neurodegeneration. It argues that stress-driven loss of homeostasis causes qualitative state transitions that spread across brain tissue domains and culminate in cognitive decline, with amyloid-associated tau phosphorylation marking a key inflection point. The framework is significant because it reframes timing and targeting of interventions toward phase-specific mechanisms and thresholds.

De Strooper B, Karran E · Nature · (2026) · View on PubMed ↗

Targeted Cancer Therapies (Small Molecules & Pathway Inhibition)

RAS-targeted therapies for pancreatic cancer.

The review summarized current and emerging RAS-targeted therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC), a RAS-driven cancer with poor prognosis. It highlighted the development of KRASG12C inhibitors enabled by the switch-II pocket discovery and discussed broader approaches including pan-RAS inhibition such as daraxonrasib. This synthesis frames how new structural insights into RAS druggability are translating into clinical trial strategies for PDAC.

Chan LL, Kwong TT, Yau JCW et al. · ESMO gastrointestinal oncology · (2026) · View on PubMed ↗ · Free PDF ↗

RBM25 Drives Hepatocellular Carcinoma Progression by Stabilizing YAP Through Regulating Oncogenic Splicing-switch of MYPT1.

This study identified RNA-binding motif protein 25 (RBM25) as an oncogenic driver in hepatocellular carcinoma (HCC) by stabilizing YAP through regulation of oncogenic alternative splicing of MYPT1. RBM25 was overexpressed in HCC and promoted tumor progression across in vitro models, xenografts, and patient-derived organoids, with mechanistic data showing RBM25 recruits PRPF40A to facilitate MYPT1 exon 13 inclusion. The significance is that the RBM25–PRPF40A–MYPT1 splicing axis provides a concrete therapeutic target and biomarker pathway for YAP-driven HCC progression.

Zhang W, Zhi L, Huang T et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Bias from within: intracellular allosterism and the ICL2 hub.

This article reviews how intracellular allosteric modulators (AMs) of G protein-coupled receptors (GPCRs) exploit the TM3–ICL2–TM4 intracellular pocket (the ICL2 site) to control transducer-selective signaling bias. It highlights structural and mechanistic evidence that the ICL2 hub governs conformational control, enabling biased signaling and noncanonical receptor activation relevant to intracellular AM drug discovery. Scientifically, it provides a framework for designing more selective GPCR therapeutics by targeting intracellular signaling determinants rather than only orthosteric sites.

Zhou Y, Long A, Gross JD et al. · Trends in pharmacological sciences · (2026) · View on PubMed ↗

Final Biomarker and Efficacy Analyses of Lorlatinib in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer in a Phase 2 Study.

This phase 2 study evaluated lorlatinib in patients with ALK-positive advanced non-small cell lung cancer (NSCLC) who had progressed after failure of a second-generation ALK tyrosine kinase inhibitor (TKI), using prospectively collected plasma for biomarker analyses across multiple treatment-experience cohorts (EXP1, EXP2-3A, EXP3B-5). It analyzed circulating tumor DNA (ctDNA) and tumor ALK fusion subtypes and co-mutations to correlate molecular features with lorlatinib outcomes and to infer potential resistance mechanisms. The significance is refining predictive biomarkers and resistance understanding to better select patients and anticipate mechanisms of failure on lorlatinib.

Bauer TM, Martini JF, Besse B et al. · Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · (2026) · View on PubMed ↗

Chemotherapy-free phase 1/2 trial of HRS-4642 plus adebrelimab in previously treated metastatic KRAS G12D-mutant pancreatic cancer.

This phase 1/2 clinical trial tested the combination of HRS-4642, a selective KRAS G12D inhibitor, plus the PD-L1 antibody adebrelimab in 48 previously treated patients with metastatic KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC). Dose escalation established the recommended phase 2 dose (RP2D) with no dose-limiting toxicities and no treatment-related deaths, and in the RP2D cohort (n=37) the confirmed objective response rate was 43.2%. Clinically, the results support further development of KRAS G12D targeted therapy combined with PD-L1 blockade as a chemotherapy-free option for this molecularly defined PDAC subgroup.

Shi S, Wei M, Du N et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

Allosteric modulation of YTHDFs by ellagic acid suppresses triple-negative breast cancer via non-canonical activation of the HIF-1α pathway.

This study investigated ellagic acid (EA) as a small-molecule modulator of YTHDF RNA readers in triple-negative breast cancer (TNBC). EA allosterically bound a conserved histidine-dependent site shared by YTHDF paralogs, disrupted YTHDF–m6A RNA interactions, and inhibited all three YTHDF proteins without escape, suppressing TNBC via non-canonical activation of the HIF-1α pathway. The results support EA (or related allosteric YTHDF inhibitors) as a potential targeted approach for YTHDF-overexpressing TNBC.

Zhou J, Li Y, Chen X et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Aging Biology, Senescence & Longevity Modeling

Gut microbiota dysbiosis shapes brain T-cell immunity in accelerated aging.

This preclinical study examined how gut microbiota dysbiosis shapes brain T-cell immunity during accelerated aging using senescence-accelerated SAMP8 mice versus senescence-resistant SAMR1 controls across young and aged stages. In SAMP8 mice, accelerated aging was associated with behavioral decline and brain transcriptomic changes alongside altered fecal microbiota composition and brain T-cell profiles, linking gut dysbiosis to age-related immune remodeling in the CNS. These findings support a mechanistic gut–brain axis model for neuroinflammation and cognitive decline and suggest microbiota-targeted strategies as potential interventions for age-associated immune dysfunction.

Peschke L, Nguyen TT, Leite JA et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Sex-specific biological aging clocks across organs and omics.

The study developed 38 sex-specific biological aging clocks across 15 organ systems using AI-predicted age minus chronological age and evaluated genetic parameters and Mendelian randomization for sex-dependent aging liability. Sex-stratified training produced sex-specific healthy normative references and revealed marked divergence between female and male aging clocks, with organ-specific aging relationships supported by genetic and Mendelian randomization analyses. These sex-specific clocks improve interpretation of aging risk and may refine prediction of sex-differential disease trajectories such as Alzheimer’s disease.

Song Z, Feng D, Rahman NA et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence.

This study used mass spectrometry-based quantitative proteomics to map dynamic proteome changes during progression of replicative cellular senescence in human cells. It showed that senescence-associated proteome remodeling is coordinated, including widespread depletion of chromatin-associated proteins and depletion of cytoplasmic translation machinery alongside increased insolubility of mitochondrial proteins. The results provide a systems-level molecular framework for how replicative senescence reorganizes cellular function, supporting proteomic biomarkers and targets for anti-senescence interventions.

Da Silva Fernandes N, Kielisch F, Fulzele A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

CK2α restriction of STING accumulation underlies systemic aging.

This study investigated how the nuclear envelope (NE) regulates STING activity during aging by identifying lamin A/C (LMNA) as a scaffold that recruits STING and Casein Kinase 2 alpha (CK2α) in myeloid cells and in systemic aging models. It showed that LMNA promotes CK2α-dependent phosphorylation of STING at Ser366, which increases STING turnover, restricts STING accumulation, attenuates cGAS–STING pathway activation, and mitigates senescence and systemic aging phenotypes. These findings define an LMNA–CK2α–STING regulatory mechanism that could be targeted to reduce inflammaging driven by chronic innate immune activation.

Zhang J, Jin M, Rao D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

HMGA1-HP1β axis regulates premature aging in Hutchinson-Gilford progeria syndrome through chromatin remodeling.

This study investigated the HMGA1–HP1β chromatin remodeling axis in Hutchinson–Gilford progeria syndrome using LmnaG609G/G609G progeria mice and Hmga1 knockout models. It found that HMGA1 correlates with HP1β in multiple tissues, HP1β decreases in Hmga1−/− mice, and HMGA1 mitigates HGPS cellular senescence in an HP1β-dependent manner. These findings connect specific chromatin regulators to LMNA-driven premature aging mechanisms, suggesting chromatin-targeted approaches for HGPS.

Hu Q, Sun Q, Xiang W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Autoimmunity, Inflammation & Immunomodulation

Comparative Safety of Common Immunosuppressant Therapies in Systemic Lupus Erythematosus: A Target Trial Emulation Study.

This target trial emulation study compared infection-related hospitalization risk among non-renal systemic lupus erythematosus (SLE) patients initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAA) using Optum Labs Data Warehouse claims (March 2011–September 2023). Across intention-to-treat and per-protocol analyses, the study estimated time to first infection-related hospitalization for each immunosuppressant strategy. The results are intended to guide safer immunosuppressant selection in non-renal SLE by quantifying real-world infection hospitalization risk differences between commonly used therapies.

Duarte-García A, Sandino-Bermúdez MJ, González-Treviño M et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗ · Free PDF ↗

Post-marketing safety assessment of mirvetuximab soravtansine: a disproportionality analysis based on the FDA Adverse Event Reporting System.

This study assessed post-marketing adverse events for mirvetuximab soravtansine (MIRV), an anti–folate receptor-alpha antibody-drug conjugate used in platinum-resistant ovarian cancer, using the FDA Adverse Event Reporting System (FAERS) from Q4 2022 to Q4 2025. Disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) identified safety signals for specific adverse event categories associated with MIRV. These findings provide hypothesis-generating, real-world pharmacovigilance evidence to guide clinicians and regulators in monitoring MIRV’s risk profile after approval.

Tan H, Ou X, Luo L et al. · Journal of gynecologic oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Pathophysiology and Emerging Therapies in Chronic Inflammation Demyelinating Polyneuropathy.

This review summarized the pathophysiology and emerging therapies for chronic inflammatory demyelinating polyneuropathy (CIDP), contrasting classical macrophage-mediated demyelination with distinct autoimmune nodopathies driven by IgG4 antibodies against nodal/paranodal proteins. It highlighted that therapies such as corticosteroids, intravenous immunoglobulins, and plasma exchange remain effective for many patients, while newer targeted strategies are being developed for antibody-defined subtypes (e.g., neurofascin 155, contactin 1, Caspr1). The synthesis helps clinicians stratify CIDP-like disorders by mechanism and guides selection of emerging treatments tailored to immunologic targets.

Yoshikawa M, Ide T, Koike H · Internal medicine (Tokyo, Japan) · (2026) · View on PubMed ↗ · Free PDF ↗

In a phase 2A randomized, double-blind, placebo-controlled multicentre trial, adults aged 18–70 years with severe fibromyalgia were studied to test rozanolixizumab, an IgG-lowering monoclonal antibody targeting the neonatal Fc receptor. The trial evaluated efficacy using pain-related endpoints (including Brief Pain Inventory-Short Form interference and Pain Numeric Rating Scale measures) and assessed safety across treatment arms. The clinical significance is that if effective, IgG-mediated mechanisms could become a therapeutic rationale for severe fibromyalgia using FcRn inhibition.

Goebel A, Meisner P, Rydevik G et al. · The Lancet. Rheumatology · (2026) · View on PubMed ↗ · Free PDF ↗

This single-centre, randomized, double-blind, intra-patient-controlled phase 2 trial evaluated topical ruxolitinib 1.5% cream for epidermal or superficially sclerotic cutaneous chronic graft-versus-host disease (cGVHD) in patients aged 12 years or older after allogeneic hematopoietic stem cell transplantation. The study aimed to measure clinical activity and safety of the topical JAK1/2 inhibitor as an alternative to topical corticosteroids, which are limited by adverse effects. The significance is potential expansion of targeted, localized JAK inhibition for cutaneous cGVHD with improved tolerability.

Markova A, Ostojić J, Rotemberg V et al. · The Lancet. Haematology · (2026) · View on PubMed ↗ · Free PDF ↗

Local sympathetic signal enables the immune evasion of hepatic stellate cells.

This study examined human liver fibrosis patients and mouse models to test how local sympathetic signaling affects hepatic stellate cells (HSCs) during fibrosis. Sympathetic axon density correlated with fibrosis severity, and sympathetic ablation reduced CCl4-induced liver fibrosis while chemogenetic activation worsened disease; mechanistically, HSCs expressed the norepinephrine receptor ADRA1B and HSC-specific Adra1b deletion protected mice. The findings implicate the ADRA1B–norepinephrine axis as a potential therapeutic target to limit fibrogenesis.

Li T, Zhou X, Wang G et al. · Neuron · (2026) · View on PubMed ↗

Peri-operative glucagon-like peptide-1 receptor agonist use and outcomes: a national prospective multicentre cohort study.

This national prospective multicentre cohort study evaluated adults undergoing elective or emergency anesthesia to determine peri-operative GLP-1 receptor agonist (GLP-1 RA) use and related outcomes, focusing on aspiration/regurgitation risk. It screened patients for GLP-1 RA use within the prior 3 months and collected peri-operative management and outcome data including pulmonary aspiration and regurgitation. The study informs peri-operative risk stratification and management policies for patients taking GLP-1 RAs.

Potter TE, Cronin JN, Kua J et al. · Anaesthesia · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Cancer Genomics, Evolution & Biomarkers

Impact of maintenance therapy on survival after autologous stem cell transplant for multiple myeloma regardless of response: a global analysis.

This global real-world analysis evaluated how different maintenance therapies affect survival after autologous hematopoietic cell transplantation (AHCT) in newly diagnosed multiple myeloma (NDMM) patients regardless of response. Using Worldwide Network for Blood and Marrow Transplantation (WBMT) registry data for transplants performed in 2013–2017 (n≈8,269), the study compared overall survival and progression-free survival with landmark Cox models and assessed non-relapse mortality and relapse/progression incidence. The findings aim to inform post-AHCT maintenance selection by clarifying which maintenance approaches improve survival outcomes across response strata.

Cowan AJ, Gras L, Cassano R et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

Liquid biopsy for early detection of pancreatic ductal adenocarcinoma.

The study developed and validated a blood-based microRNA (miRNA) assay and composite score, PANXEON, integrating a defined panel of miRNAs (including hsa-miR-142-3p, hsa-miR-30c-5p, hsa-miR-335-5p, hsa-miR-340-5p, hsa-miR-200b-3p, hsa-miR-1260b, hsa-miR-145-3p, hsa-miR-145-5p, hsa-miR-429, hsa-miR-200a-3p) with carbohydrate antigen 19-9 for early detection of early-stage pancreatic ductal adenocarcinoma (PDAC). In an international multicenter observational prospective biomarker study, the assay was tested for performance in detecting early-stage disease (with the composite score designed to improve clinical relevance over CA19-9 alone). This advances a clinically actionable liquid biopsy approach for earlier PDAC detection, potentially improving outcomes by enabling earlier diagnosis.

Xu C, Mannucci A, Han H et al. · Nature medicine · (2026) · View on PubMed ↗

Reimagining research papers as interactive and reliable AI agents.

The study analyzed metastatic bladder cancer using a metastatic bladder cancer rapid autopsy program enriched for histological subtypes to reconstruct evolutionary histories across terminal patients. It found that metastasis-to-metastasis seeding dominated the spread pattern and that increased polyclonal migration predicted worse prognosis, with genomic alteration burden, heterogeneity, and timing differing by histological subtype. These findings clarify how lethal metastatic urothelial cancer evolves and may guide subtype-specific prognostic stratification and therapeutic targeting.

Miao J, Davis JR, Zhang Y et al. · Nature · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

Genomic and transcriptomic features of relapsed small cell lung cancer.

The authors profiled relapsed small cell lung cancer (SCLC) by comparing 54 relapsed samples with 27 treatment-naive samples (including 26 patient-matched pairs when available) using whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing (RNA-seq). They generated a comprehensive genomic and transcriptomic landscape of relapsed SCLC to characterize treatment resistance-associated alterations. Scientifically, this defines candidate pathways for functional validation and potential new therapeutic targets for relapsed SCLC.

Devarakonda S, Hoang M, Sankararaman S et al. · Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · (2026) · View on PubMed ↗

Pembrolizumab plus chemotherapy as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma: 4.5-year follow-up from the randomized phase III KEYNOTE-859 study.

This report provides 4.5-year follow-up from the randomized phase III KEYNOTE-859 trial evaluating pembrolizumab plus chemotherapy as first-line treatment for untreated locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. Among 1579 participants, pembrolizumab 200 mg plus chemotherapy improved overall survival compared with placebo plus chemotherapy regardless of PD-L1 status. Long-term efficacy data strengthen the clinical rationale for incorporating pembrolizumab with chemotherapy as a standard first-line regimen in this patient population.

Rha SY, Wyrwicz LS, Yañez P et al. · ESMO open · (2026) · View on PubMed ↗ · Free PDF ↗

Reproductive Health & Endometrial/Implantation Biology

SAV1 in Cooperation With FKBP52 Participates in Implantation.

This mechanistic study investigated how Salvador homolog 1 (SAV1), a Hippo pathway scaffold, regulates implantation by coordinating progesterone (P4) and estrogen (E2) signaling in the uterus. The key finding was that deletion of Sav1 disrupts the temporal coordination required for endometrial receptivity during the implantation window. Clinically, identifying SAV1 as a regulator of implantation competence suggests a potential molecular target for improving reproductive outcomes in disorders of endometrial receptivity.

Shao Y, Lu Y, Jia Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Nutrition care and Dietetic Practice in Managing Metabolic and Endocrine Dysfunction in Polyendocrine Metabolic Ovarian Syndrome (PMOS): Implications and Opportunities in the Context of the Name Change of Polycystic Ovarian Syndrome (PCOS) to PMOS.

This article discusses nutrition care and dietetic practice for polyendocrine metabolic ovarian syndrome (PMOS), a condition affecting 8–13% of women across the lifespan, in the context of the recent renaming from polycystic ovary syndrome (PCOS) to PMOS. It highlights that dietary intervention is first-line for targeting metabolic risk and that the PMOS terminology better reflects the syndrome’s endocrine and metabolic dysfunction rather than an ovarian-centric framing. The clinical significance is improved alignment of guidelines and dietetic management with the broader metabolic comorbidity risk profile of affected women.

Vine D, Moran L, Teede H et al. · Advances in nutrition (Bethesda, Md.) · (2026) · View on PubMed ↗ · Free PDF ↗

Gene/Cell Therapy & Regenerative Medicine

Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.

This review examined biomimetic scaffold-based three-dimensional (3D) tumor models designed to better replicate the tumor microenvironment compared with conventional 2D cultures and animal models. It summarizes how engineered biomaterials can reproduce key physical and biochemical cues (e.g., architecture and spatial organization) to enable more faithful cancer biology readouts and therapeutic testing. The work is significant because it consolidates current scaffold-based 3D modeling approaches that may improve translational relevance for precision oncology.

Zhao H, Han Y, Li J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial.

This phase 1 multicenter, single-arm trial evaluated AAV-mediated factor IX Padua gene therapy (BBM-H901) in 11 Chinese adolescents (ages 12–18) with severe or moderately severe hemophilia B (FIX:C ≤2 IU/dl). At a dose of 5×10^12 vector genomes/kg, no dose-limiting toxicity was observed during a 52-week follow-up, with safety as the primary endpoint. The results extend evidence for AAV factor IX Padua therapy from adults to adolescents, informing pediatric hemophilia B dosing and risk assessment.

Xue F, Zhang A, Ju M et al. · Nature medicine · (2026) · View on PubMed ↗

Developmental xenocortication using human-derived organoids in mice.

The study established a developmental xenocortication platform by transplanting human-derived neural organoids into mice while using a genetic strategy to deplete glutamatergic neurons from mouse neocortex and hippocampus (apallial) to improve organoid integration. This approach enabled in vivo modeling of aspects of human neurodevelopment and circuit function with behavioral phenotyping of host animals. The platform provides a more tractable way to study human brain development and disease-relevant circuit formation in vivo.

Kaganovsky K, Kelley KW, Gschwind T et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Safety and efficacy of AAV-based mini- and micro-dystrophin gene therapies in Duchenne muscular dystrophy: a systematic review and meta-analysis of clinical trials.

This systematic review and meta-analysis evaluated AAV-based mini- and micro-dystrophin gene therapies for Duchenne muscular dystrophy (DMD) by pooling clinical trial evidence on functional efficacy and safety outcomes. Across included trials, the therapies demonstrated overall clinical activity with a safety profile characterized by AAV-related adverse effects, while efficacy varied by regimen and endpoints. Clinically, the synthesis supports ongoing optimization of AAV mini/micro-dystrophin approaches and informs risk–benefit considerations for DMD patients entering gene therapy trials.

Nassour H, Al Shbailat SA, Ibrahim AS et al. · Journal of medical genetics · (2026) · View on PubMed ↗ · Free PDF ↗

H3K27M drives OPC stemness and intrathecal therapeutic vulnerability in brainstem glioma organoids.

Researchers created patient-derived brainstem glioma organoids (BSGO) to study H3K27M-mutant diffuse midline gliomas (DMGs) and their oligodendrocyte precursor cell (OPC) stemness. Multi-omics and functional assays showed that H3K27M drives OPC stemness through dysregulated ACTIVIN signaling and that this creates an intrathecal therapeutic vulnerability. The scientific significance is identifying ACTIVIN pathway dependence and a delivery strategy (intrathecal) that may improve targeting of otherwise inaccessible brainstem DMGs.

Xie L, Jiang Z, Zhou H et al. · Cell stem cell · (2026) · View on PubMed ↗

Chromatin, Transcription & 3D Genome Regulation

The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.

This review synthesized evidence on how chromatin remodeling and three-dimensional (3D) genome organization contribute to cancer biology and how these mechanisms are being leveraged for emerging therapies. It highlights that chromatin remodelers are frequently mutated in cancer and discusses translational challenges in moving from 2D chromatin concepts to 3D genome–informed therapeutic strategies. The significance is that it frames current mechanistic insights and treatment options while outlining key barriers for clinical implementation.

Luo C, Xia N, Hui SY et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Cohesin preservation across mitosis contributes to restart transcription via Cdk9-mediated activation of RNAPol2.

This study used in vivo labeling and cell-cycle synchronization in human cells to determine how cohesin is transmitted through mitosis and how it affects transcription restart. Cohesin complexes persisted through mitosis, and the inherited Rad21 pool dominated in telophase-G1; acute Rad21 depletion at mitotic exit impaired expression of hundreds of genes, and the restart mechanism involved Cdk9-mediated activation of RNAPol2. These findings clarify a mitosis-to-interphase continuity role for cohesin in gene reactivation programs relevant to tissue growth and development.

Contreras-Pérez A, Espinosa H, Sayago EI et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

A dual-module ECAS complex couples transcription elongation and RNA processing.

This study used native chromatin proteomics in human cells to identify a chromatin-associated complex that couples RNA polymerase II elongation with co-transcriptional RNA processing. It discovered ECAS, a dual-module assembly linking an elongation module (AFF4–ELL2–EAF1) to a U2 snRNP-associated intron binding complex, distinct from the canonical P-TEFb-containing super elongation complex (SEC). Perturbing Aquarius (AQR)/XAB2-dependent ECAS impaired productive gene-body elongation, highlighting a specific molecular mechanism coordinating elongation and splicing.

Xiang Y, Wang H, Yin Z et al. · Molecular cell · (2026) · View on PubMed ↗

Respiratory Disease, Pulmonary Fibrosis & Lung Cancer Risk

This case series and literature review characterized organizing pneumonia (OP) occurring in multiple sclerosis patients treated with ocrelizumab. Among 626 ocrelizumab-treated MS patients at the authors’ center, five OP cases were identified and compared with 17 published cases, describing clinical, radiologic, laboratory, treatment, and outcome patterns. The study is significant because it clarifies a rare but important potential pulmonary adverse effect of ocrelizumab and supports earlier recognition and management of drug-associated OP.

Petza E, Guerrieri S, Marino V et al. · Journal of neurology · (2026) · View on PubMed ↗

Transplantation, Xenotransplantation & Transfusion Safety

Orthotopic liver xenotransplantation from gene-modified pig to decedent human.

This report described an orthotopic pig-to-human liver xenotransplantation performed in a brain-deceased human recipient using a gene-modified pig. Over an 11-day observation period, the xenograft produced continuous albumin and bile with normal composition (though at relatively low levels) and the recipient maintained systemic hemodynamic stability despite suboptimal hepatic function. The significance is that it provides early translational evidence that gene-modified porcine livers can support key metabolic functions in a human orthotopic xenotransplant setting.

Tao K, Yang Z, Zhang X et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

Infectious risks of transfusion: a 10-year look back and perspectives.

This review summarizes infectious risks in blood transfusion over the past decade, building on lessons from the post–transfusion-transmitted HIV era. It highlights changes in donor selection, pathogen testing, and pathogen reduction, including refined bacterial testing and expanded pathogen reduction to mitigate bacterial contamination risks in platelets, while also addressing emerging/re-emerging threats such as Zika virus, Plasmodium, Babesia, and SARS-CoV-2. The review is clinically important for guiding transfusion policy and risk-management strategies as pathogen landscapes evolve.

Bloch EM, Drews SJ, Jacobs JW · Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine · (2026) · View on PubMed ↗

Plant Biology & Plant Immunity

Sex without crossovers mimics clonal reproduction in Rhynchospora tenuis.

This study investigated meiotic recombination in the flowering plant Rhynchospora tenuis, using genomics plus molecular experiments to test whether crossovers occur in male and female meiosis. The authors found obligate, genome-wide achiasmy in both sexes, with sex without crossovers mimicking clonal reproduction despite normal early meiotic axis formation. These results establish a rare sexual-species example of complete crossover absence and provide a new framework for understanding chromosome segregation and genome evolution under achiasmy.

Zhang M, Castellani M, Steckenborn S et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Transcriptional activation of plant immunity by salicylic acid.

This study examined how the plant defense hormone salicylic acid (SA) activates transcriptional immunity through the SA receptor NPR1 in plants, using NPR1 interactome/proxiome approaches and structural predictions. SA stabilized the SA-binding domain of NPR1 and allosterically promoted NPR1 interaction with MED15A (Mediator complex), including a direct NPR1–MED15A KIX-domain interaction that links SA sensing to transcriptional activation. These findings clarify the molecular mechanism of NPR1-mediated SA signaling and identify a specific Mediator subunit interface that could be targeted to modulate plant immunity.

Zhang S, Gish M, Li H et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Mechanisms of Transcriptional Regulation by Salicylic Acid Receptors.

This Nature study elucidated transcriptional regulation mechanisms downstream of salicylic acid (SA) receptors in Arabidopsis, focusing on the NPR1 (NIM1) and NPR3/NPR4 SA receptor system. It identified MED15A as a bridge that enables SA-induced direct interaction between NPR1 and the Mediator complex, while SA relieves NPR3/NPR4-mediated transcriptional repression to activate defense genes. These mechanistic and structural insights clarify how SA binding is translated into defense gene expression, advancing understanding of plant immune signaling.

Peng Y, Tian H, Ming Z et al. · Nature · (2026) · View on PubMed ↗

3D chromatin remodeling during domestication defines novel targets for crop improvement.

This study used population-scale Hi-C profiling of 34 semi-wild and 267 cultivated allotetraploid cottons to map 3D genome architecture changes (TADs and chromatin loops) during domestication. It identified 105 TAD reconfigurations and 58 loop rewirings that were linked to fiber quality, increasing heritability estimates for fiber strength by 16% and fiber length by 20%. These domestication-defined 3D chromatin targets provide actionable regulatory loci for crop improvement in cotton breeding programs.

Huang X, Peng Y, Hu X et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Musculoskeletal & Tissue Injury/Repair

Cellular senescence of fibro-adipogenic progenitors by STAT5A/GFPT2/O-GlcNAcylation impairs muscle recovery after glucocorticoid-induced injury.

Researchers studied how glucocorticoid-induced skeletal muscle injury affects fibro-adipogenic progenitors (FAPs) and recovery mechanisms in experimental models, focusing on STAT5A-driven pathways. They found that glucocorticoids induce FAP cellular senescence via increased GFPT2 expression through STAT5A, which elevates O-GlcNAcylation and promotes senescence, and that inhibiting the STAT5A–GFPT2-mediated O-GlcNAcylation reduces senescent FAP burden. Clinically, targeting this STAT5A/GFPT2/O-GlcNAcylation axis may improve muscle recovery after glucocorticoid therapy.

Li B, Xiang W, Qi W et al. · Pharmacological research · (2026) · View on PubMed ↗ · Free PDF ↗

Tumor Microenvironment, Niches & Cell-State Plasticity

Single-cell and spatial multi-omics reveal a recurrent multicellular niche at the tumor-stroma interface in multidrug resistance.

This study analyzed paired therapy-naive and multidrug-resistant (MDR) melanoma specimens from a clinical trial using integrated single-cell and spatial multi-omics, supported by additional datasets across 10 cancer types. It identified a recurrent MDR-associated multicellular niche at the tumor-stroma interface composed of CXCL14+ inflammatory CAFs (iCAFs), TREM2+ tumor-associated macrophages (TAMs), and AXL+ dedifferentiated tumor cells. Defining this spatial nexus provides a mechanistic framework for MDR evolution and suggests niche-targeting strategies to improve therapy durability.

Shen K, Wang L, Gao Z et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Generated automatically on September 18, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.

← All Trending Digests

PubMed Trending Research Digest — September 18, 2026

PubMed Trending Research Digest — September 18, 2026

Overview

Neurodevelopment, Brain Circuits & Neuroinflammation

Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma.

EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.

Topographic structure and function of locus coeruleus noradrenaline neurons.

De novo variants in the poly(rC)-binding protein gene PCBP1 cause a neurodevelopmental disorder.

Transcriptomic profiling of inner ear hair cell spontaneous regeneration reveals the key role of dlx5a.

Cardiometabolic Disease & Vascular Risk

Exercise-based cardiac rehabilitation for coronary heart disease.

Zonated cholesterol sensing by SIRT2 drives MASLD-HCC.

Comparative Cardiorenal Efficacy and Safety of Finerenone, SGLT2 Inhibitors, Semaglutide and Their Combination in Diabetic Kidney Disease.

Eyeballing for Frailty Assessment in Elderly Patients Referred for Coronary Angiography.

Predicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial.

Proteogenomic Profiling of Idiopathic Pulmonary Arterial Hypertension Identifies Sex-Differential Proteins and Candidate Therapeutic Targets.

Efficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis.

Lipoprotein (a) variability in high cardiovascular risk individuals with hypertriglyceridemia and controlled LDL-C on statin therapy in REDUCE-IT.

Associations between specific non-sustained ventricular tachycardia characteristics and sudden cardiac death in hypertrophic cardiomyopathy.

Risk Factors and Definition of Younger-Onset Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Cirrhosis.

Hematology & Thrombosis/Platelet Biology

State-level burden of chronic respiratory diseases in the USA, 1990-2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023.

Germline EGFR T790M mutation and lung cancer risk.

AI for Drug Discovery & Clinical Decision Support

Clinical activity and safety of rilzabrutinib in patients with previously treated immune thrombocytopenia (LUNA3): results from the open-label period of a phase 3 trial.

An open benchmark and language models for AI in aging biology.

The Virtual Biotech: A multi-agent AI framework for therapeutic discovery and development.

Evolution and heterogeneity of lethal metastatic bladder cancer subtypes.

Development of a random background to understand ligand optimization.

Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.

Cancer Immunotherapy & Immune Evasion

Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.

Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia.

T-cell lymphoma following chimeric antigen receptor-T therapy: a cause for concern?

Identification of broadly tumour-reactive γδ TCRs from multiple myeloma.

Immunogenic cell death and tertiary lymphoid structures: bridging tumour cell death and immune organization.

Radiation, Myeloid Reprogramming & Radio-Immunotherapy

Myeloid reprogramming generates myeloid-derived activating cells to potentiate radiotherapy and suppress metastasis.

Infectious Disease, Microbiome & Host Defense

Dietary pectin remodels commensal bacterial surfaces to promote IgA-mediated protection from intestinal inflammation.

Tobramycin enhances Mycobacterium abscessus fitness through whiB7 induction.

Probiotics in Cardiometabolic Diseases: Current Evidence, Postbiotic Perspectives, and Future Directions.

FAM134B Restricts African Swine Fever Virus Capsid Assembly via Reticulophagy and Its Antiviral Activity is Antagonized by the Viral Virulence-Associated Factor pMGF300-2R.

Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.

Mutational constraints on RSV F and its neutralization by antibodies.

Cell senescence emerges as a hallmark and therapeutic target of chronic intracellular infection.

Impact of non-enteric-coated pancreatic enzyme replacement therapy (NEPERT) on pain in patients with chronic pancreatitis: a double-blind, parallel-group, placebo-controlled, randomised trial.

HBV induces immunosuppressive macrophages via metabolic and epigenetic reprogramming to facilitate the establishment of chronic persistent infection.

Longitudinal gut microbiome dynamics during immunotherapy identify microbial features of clinical benefit in advanced primary liver cancer.

Integrated metabolomic and genetic profiling implicate loss of docosahexaenoic acid in the link between ultra-processed foods and Crohn’s disease.

IL1B-high macrophages promote ferroptosis-like lipid peroxidation injury in Crohn’s disease intestinal epithelium.

Cell Biology Mechanisms (Replication, Organelle Dynamics, Signaling)

Molecular mechanism of HUWE1-HAPSTR1-USP7-mediated ubiquitin chain amplification on nuclear proteins.

Splenic regulation of systemic platelet activation state.

Cohesin reshapes replication fork contacts to aid fork slowing and reversal.

Mitochondrial fission factor senses and governs ferroptosis.

Profilin promotes lamellipodium protrusion by tuning the antagonistic activities of capping protein and VASP.

Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.

Core nucleosomes are refractory to lentiviral DNA integration.

Gene Editing & Genome Engineering (CRISPR/Integrases/Epigenome Editing)

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas.

Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.

Targeted genomic integration and rearrangement using prime assembly.

AI for Medical Imaging & Diagnostics

An expert-level generalist AI for abdominal CT diagnosis.

Neurodegeneration, Dementia & Tau/Amyloid Biology

Effective amyloid clearance with lecanemab in a female with Alzheimer’s disease: A case report.

Rethinking tau-targeted therapy in Alzheimer’s disease: Toward a dual biomarker strategy.

APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.

Inflection points and transitions in Alzheimer’s disease.

Targeted Cancer Therapies (Small Molecules & Pathway Inhibition)

RAS-targeted therapies for pancreatic cancer.

RBM25 Drives Hepatocellular Carcinoma Progression by Stabilizing YAP Through Regulating Oncogenic Splicing-switch of MYPT1.

Bias from within: intracellular allosterism and the ICL2 hub.

Final Biomarker and Efficacy Analyses of Lorlatinib in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer in a Phase 2 Study.

Chemotherapy-free phase 1/2 trial of HRS-4642 plus adebrelimab in previously treated metastatic KRAS G12D-mutant pancreatic cancer.

Allosteric modulation of YTHDFs by ellagic acid suppresses triple-negative breast cancer via non-canonical activation of the HIF-1α pathway.

Aging Biology, Senescence & Longevity Modeling

Gut microbiota dysbiosis shapes brain T-cell immunity in accelerated aging.

Sex-specific biological aging clocks across organs and omics.