PubMed Trending Research Digest — September 12, 2026

A curated digest of 98 trending PubMed articles, automatically categorised and summarised across 15 research areas.

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Immunology: T Cells, Checkpoints, and Innate Immune Signaling Cancer Clinical Trials and Treatment Strategies (Non-ADC/Non-TCE) Cardiovascular, Vascular Disease, and Risk Stratification CNS Development, Ciliopathies, and Hydrocephalus Cancer Tumor Biology, Biomarkers, and Mechanisms Aging, Frailty, and Musculoskeletal Function Neurodegeneration, Brain Clearance, and Neuroimmune Interfaces Microbiome, Virome, and Host-Microbe Interactions Immunotherapy and Targeted Protein Degradation (PROTACs/TCEs/Antibodies) Metabolic Disease, Liver Disease, and Obesity-Related Mechanisms Sleep, Circadian, and Insomnia Pharmacology Autoimmune Disease (Non-Cancer) and Real-World Therapeutics Neuroinflammation and Infection-Driven Brain Effects Type 1 Diabetes Prevention and Disease Modification Reproductive Health and Pain Mechanisms

Automated digest · 98 articles · 15 research areas · September 12, 2026

Overview

Across this week’s set of papers, several dominant threads emerge: (1) precision immunology and targeted therapeutics, (2) mechanistic links between metabolism and disease progression, and (3) neurobiology spanning clearance, inflammation, and developmental circuitry.

On the immunotherapy side, multiple studies refine how to modulate immune responses for durable benefit. In cancer, new antibody- and T-cell–based strategies (e.g., bispecific CD3×CD19 in SLE, DLL3×CD3 TCE review, and MPZL1-amplification–driven CAR-T concepts) sit alongside mechanistic work that explains resistance and improves targeting (e.g., HUWE1-driven ASCL1 degradation in SCLC, CRBN-based PROTAC degradation of KRAS mutants, and perioperative myeloid remodeling via TREM2 that can be therapeutically targeted to boost CAR-T efficacy). In parallel, foundational immunology papers clarify checkpoint control (PD-1’s direct inhibition of LAT condensates), innate immune activation (AMBR A1 as an NLRP3 activator; microbial adhesion–Piezo1–LTB4 initiation of neutrophil recruitment), and T-cell bioenergetics (DAHB-driven mitochondrial/PCr reserve requirements for CD8 effector differentiation).

Metabolism and tissue aging also recur strongly. Several studies connect lipid/iron pathways to cancer or systemic dysfunction (ferroptosis–immune axes in MASH; adipocyte oxylipins restraining breast cancer via ferroptosis; ALKBH5–CKB stabilization in cold/adrenergic thermogenesis). Meanwhile, chemotherapy mutagenesis work in pediatric tissues provides high-resolution evidence that platinum exposure can drive tissue-specific, long-term aging risk—complementing broader themes of frailty and functional decline. Finally, neuro-focused research spans multiple scales: from brain clearance systems (glymphatic/meningeal lymphatic roles in AD protein deposition) and neuroimmune interfaces (post-streptococcal encephalitis mechanisms) to developmental ciliopathy/hydrocephalus circuitry (TZ linker defects and microglial GRB2 in ventriculogenesis), underscoring how circuit-level and molecular-level mechanisms converge on disease heterogeneity and therapeutic opportunities.

Immunology: T Cells, Checkpoints, and Innate Immune Signaling

Mitochondrial ATP promotes T cell differentiation through chromatin accessibility.

The study examined how D-α-hydroxybutyrate (DAHB) alters mitochondrial ATP production and chromatin accessibility during differentiation of cytotoxic CD8+ T cells. DAHB increased mitochondrial ATP by shifting metabolism from glycolysis to oxidative phosphorylation supported by fatty acid oxidation, raising phosphocreatine (PCr) and requiring both PCr bioenergetic reserve and oxidative phosphorylation for effector function and chromatin-accessibility changes. These findings suggest a bioenergetic signaling route that can be therapeutically leveraged to enhance T cell effector differentiation in chronic infection and cancer.

Ng C, Fung TS, Li D et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Glycan recognition by a plant damage-sensing immune receptor.

This study examined how the plant damage-sensing immune receptor IGP1 recognizes a cellulose-derived damage-associated molecular pattern (DAMP), specifically the glycan cellotriose, and how its leucine-rich repeat (LRR)-malectin domains contribute to ligand specificity. Structural analyses showed that constitutive LRR-malectin interactions preconfigure IGP1 for ligand binding and that IGP1 contains a highly specific sugar-binding pocket in the LRR domain that discriminates fine glycan structural variations. This advances understanding of plant innate immunity by defining the structural basis for glycan DAMP recognition by IGP1.

Jiménez-Sandoval P, Kentish O, Broyart C et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Unphosphorylated tyrosines mediate PD-1 inhibition of T cell signaling condensate formation.

This study investigated how programmed cell death protein 1 (PD-1) inhibits T cell signaling condensate formation by examining effects on T cell receptor (TCR)-induced LAT (linker of activated T cells) condensation. The key finding was that the cytoplasmic domain of PD-1 directly inhibits LAT condensation in vitro via tyrosine residues in PD-1’s two inhibitory motifs, and that contrary to prevailing models, tyrosine phosphorylation eliminates PD-1 inhibition while tyrosine-to-tryptophan substitution restores inhibition in T cells. Scientifically, it clarifies the molecular rule for PD-1-mediated control of LAT condensates, refining how immune checkpoint signaling suppresses T cell activation.

Sharma M, Katz ZB, Dewitt DC et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.

The study examined how chronic type II interferon (IFN-II) promotes tumor growth in cancer models, focusing on mitochondrial double-stranded RNA (ds-mtRNA) signaling and downstream type I interferon (IFN-I) pathways. Chronic IFN-II induced tumor growth by triggering cytoplasmic release of ds-mtRNA that activated an IFN-I response, which synergized with IFN-II to enhance tumor growth. This mechanistic link suggests that persistent IFN-II can reprogram innate immune signaling (ds-mtRNA→IFN-I) to support tumor immune evasion and growth.

Johnson MA, Varanasi SK, Mangalhara KC et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Upper respiratory tract CD8+ tissue-resident memory T cells protect against viral transmission.

This study examined how CD8+ tissue-resident memory T cells (TRM) protect against respiratory virus transmission in a murine model of parainfluenza virus. Protection mediated by upper respiratory tract (URT) CD8 TRM occurred independently of circulating leukocytes, B cells, and CD4 T cells, and compartment-specific TRM localization shaped the transmission-blocking effect. These findings identify URT CD8 TRM as a mechanistic target for vaccines aiming to reduce viral spread while limiting immunopathology.

Michalets SE, Soto-Vazquez Y, Moore KM et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Microbial adhesion promotes Piezo1 activation to initiate innate immunity.

This Nature Immunology study investigated how microbial adhesion triggers innate immune activation in myeloid cells, using a skin infection model with pathogenic bacteria and fungi and mechanistic experiments focused on the mechanosensitive ion channel Piezo1. It found that neutrophil recruitment occurs in two sequential phases, with an early PRR-independent phase driven by microbial adhesion that activates Piezo1 to promote leukotriene B4 (LTB4) production, which together with IL-1α induces CXCL1 release and neutrophil infiltration. The scientific significance is identifying microbial adhesion–Piezo1–LTB4 as an upstream initiation pathway for innate immunity that could be targeted to modulate inflammatory responses.

Stucchi G, Galli M, Cozzi S et al. · Nature immunology · (2026) · View on PubMed ↗ · Free PDF ↗

AMBRA1 allosterically activates NLRP3 by releasing its autoinhibition.

This study examined how the autophagy-related protein AMBRA1 regulates activation of the inflammasome sensor NLRP3 in the context of NLRP3’s autorepressed conformation. AMBRA1 bound NLRP3, engaged specific NLRP3 subdomains (leucine-rich repeat and helical domain 2) via its β-propeller domain, and allosterically destabilized NLRP3 autoinhibition to promote activation. These findings identify AMBRA1 as a mechanistic activator of NLRP3, providing a potential new target pathway for controlling NLRP3-driven inflammatory disease.

Pan M, Zhou J, Fu S et al. · Nature immunology · (2026) · View on PubMed ↗

Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.

This study determined the structure and transport mechanism of the human sphingosine-1-phosphate (S1P) exporter MFSD2B (major facilitator superfamily domain-containing protein 2B). It reported a 3.0 Å cryo-EM structure of human MFSD2B bound to S1P and used mutagenesis and molecular dynamics simulations to show S1P is deeply buried in the C-domain with its phosphate coordinated by polar residues and its sphingoid tail in a hydrophobic pocket. These structural and mechanistic details clarify how MFSD2B exports S1P from red blood cells and platelets, informing therapeutic strategies targeting S1P signaling and immune trafficking.

Ahmed S, Huang M, Dai Y et al. · Nature communications · (2026) · View on PubMed ↗

Cancer Clinical Trials and Treatment Strategies (Non-ADC/Non-TCE)

Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.

This phase III, open-label randomized trial studied trastuzumab botidotin versus trastuzumab emtansine in adult patients with HER2-positive unresectable/metastatic breast cancer who had prior trastuzumab and a taxane. Trastuzumab botidotin was evaluated for safety and efficacy with progression-free survival as the primary endpoint assessed by blinded independent central review (BICR). If effective, this HER2-directed antibody-drug conjugate could provide a new treatment option for this heavily pretreated patient population.

Zhang J, Ouyang Q, Zhang Q et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancer.

This nationwide French cohort study examined whether mRNA COVID-19 vaccination around immune checkpoint inhibitor (ICI) initiation affects survival in 95,015 adults starting ICI therapy between December 2020 and March 2023. Using inverse probability of treatment weighting and cloning-censoring-weighting target-trial emulation, the study evaluated all-cause mortality (with cancer-specific and non-COVID-19 mortality as secondary outcomes) in relation to vaccination within 100 days before versus after ICI start. The findings provide population-level evidence on how timing of COVID-19 vaccination may influence outcomes in patients receiving ICIs, informing clinical guidance for cancer immunotherapy during the pandemic.

Salem JE, Curmin R, Ajrouche A et al. · Nature medicine · (2026) · View on PubMed ↗

Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn’s disease: 5-year follow-up of the PROFILE trial.

This 5-year follow-up analysis of the PROFILE trial compared long-term outcomes of top-down anti-TNF therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn’s disease. The study tested whether the previously observed 48-week advantage of starting infliximab-based top-down treatment translates into durable modification of the disease course over years. The findings inform optimal initial treatment strategy selection for newly diagnosed Crohn’s disease to improve long-term outcomes.

Noor NM, Sharip MT, Zheng H et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

Management of Soft Tissue and Visceral Leiomyosarcomas.

The article provided an evidence-based consensus review on management of soft tissue and visceral leiomyosarcomas, synthesizing diagnostic and therapeutic strategies across clinical and research stakeholders. It emphasizes site-specific management and systemic therapy approaches while identifying clinical uncertainties and research priorities for this heterogeneous malignancy. This consensus aims to harmonize care and guide future trials to close gaps in leiomyosarcoma treatment.

Campos F, Gladdy R, Achee A et al. · JAMA oncology · (2026) · View on PubMed ↗

Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial.

The exploratory analysis evaluated 5-year efficacy and safety of pembrolizumab plus chemotherapy (with or without bevacizumab) in participants with previously untreated persistent, recurrent, or metastatic cervical cancer from the KEYNOTE-826 randomized clinical trial. The abstract confirms durable benefit at final analysis in the parent trial and focuses on long-term outcomes, but the provided text is truncated before detailing the 5-year results. Long-term follow-up strengthens the benefit–risk assessment for pembrolizumab-based regimens in advanced cervical cancer.

Hasegawa K, Colombo N, Tewari KS et al. · JAMA oncology · (2026) · View on PubMed ↗

In a randomized, double-masked, placebo-controlled adaptive phase II trial, the GOLDEN study tested the investigational complement factor B (CFB) antisense oligonucleotide sefaxersen in 332 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The key finding was the trial’s evaluation of whether monthly subcutaneous sefaxersen slows GA progression while assessing pharmacokinetics and safety at interim and 56-week endpoints. If efficacy signals were observed alongside acceptable safety, this would support CFB-targeted antisense therapy as a disease-modifying approach for GA in AMD.

Jaffe GJ, Wykoff CC, McCaleb ML et al. · Ophthalmology science · (2026) · View on PubMed ↗ · Free PDF ↗

Actual Five-year Survival After Neoadjuvant Therapy and Resection for Localized Pancreatic Ductal Adenocarcinoma.

This retrospective cohort study assessed actual 5-year survival after neoadjuvant therapy followed by curative-intent pancreatectomy in patients with localized pancreatic ductal adenocarcinoma (PDAC) treated at two high-volume centers (2015–2021), including only patients with complete follow-up (death or ≥5 years). It aimed to determine actual (not actuarial) 5-year survival from surgery among 660 patients (results truncated). The clinical significance is providing more realistic long-term outcome estimates to better counsel patients and benchmark neoadjuvant strategies for localized PDAC.

De Stefano F, Belfiori G, Wu NF et al. · Annals of surgery · (2026) · View on PubMed ↗

Cardiovascular, Vascular Disease, and Risk Stratification

Out-of-Hospital Intensive Care in Germany - who´s out there? Key issues revealed by the clinical application of the new legislation in Baden Württemberg.

This study assessed the early real-world impact of Germany’s new legislation on out-of-hospital intensive care by examining weaning potential in adult patients referred to a Loewenstein Weaning Center. Among 148 consecutive patients evaluated retrospectively (Oct 2023–Feb 2026), respiratory physicians and therapists characterized key issues related to prescribing and optimizing out-of-hospital intensive care under the new requirements. The results inform how policy changes affect access to intensive care and rehabilitation planning for a vulnerable group needing out-of-hospital intensive support.

Joves B, Kempa A, Rheinhold A et al. · Respiration; international review of thoracic diseases · (2026) · View on PubMed ↗

Familial pulmonary fibrosis: a UK consensus framework for the investigation and management of patients and their relatives.

This UK consensus framework article addressed how to investigate and manage familial pulmonary fibrosis by incorporating genetic predisposition into clinical care for patients and their relatives. It emphasizes that adult-onset monogenic fibrotic interstitial lung disease—often due to telomere maintenance defects or surfactant biology disorders—can have additional intrapulmonary and extrapulmonary features requiring surveillance, and it reflects the impact of newly accessible respiratory-physician genetic testing panels in England. The framework aims to standardize genetic workup and downstream management to improve diagnosis and family counseling.

Bowden AR, Morris-Rosendahl DJ, Hanson H et al. · Thorax · (2026) · View on PubMed ↗

Beyond Heritable PAH: Pulmonary Hypertension in Genetic Syndromes.

This review examined pulmonary hypertension (PH) occurring in genetic syndromes beyond classic heritable pulmonary arterial hypertension, focusing on how PH can present within complex multisystem disorders. It summarizes that PH may be underrecognized when it coexists with congenital heart disease, developmental lung abnormalities, parenchymal lung disease, vascular malformations, or extra-pulmonary manifestations, and it highlights expanding gene discovery from recent human genetics. The article supports broader precision-genomics approaches to identify PH risk and improve diagnosis in diverse genetic syndromes.

Grynblat J, Coulet F, Lacoste-Palasset T et al. · The European respiratory journal · (2026) · View on PubMed ↗

Metabolic Markers of MRI-Confirmed Lacunar Stroke: Observational and Mendelian Randomization Analyses.

This study assessed associations between serum metabolites and MRI-confirmed lacunar stroke, neuroimaging markers of cerebral small vessel disease (SVD), and cognition using NMR spectroscopy in a UK clinical cohort. It also performed genome-wide association analyses and Mendelian randomization to test causal relationships (detailed results truncated in the abstract). If specific metabolites show causal links to lacunar stroke/SVD, they could become biomarkers or targets for preventing vascular cognitive decline.

Ng WH, Aghakishiyeva E, Markus HS et al. · Neurology · (2026) · View on PubMed ↗

Avoiding Vascular Misadventure: Pre-emptive Contralateral Endovascular Access in Revision Total Hip Arthroplasty: A Case Report.

This case report studied a 73-year-old woman undergoing re-revision total hip arthroplasty (THA) with severe acetabular bone loss using a custom triflange acetabular component (CTAC) and pre-emptive contralateral endovascular access. The key finding was that prophylactic contralateral vascular access enabled immediate hemorrhage control risk mitigation when the distal external iliac artery was at risk due to CTAC medialization, with the patient remaining symptom-free at 1 year. Clinically, this supports feasibility and potential safety of planned endovascular access to reduce morbidity and mortality in high-risk revision THA vascular scenarios.

Isaacs D, Byrne C, Du YK et al. · JBJS case connector · (2026) · View on PubMed ↗

Management and Outcomes of Cardiac Sarcoidosis: Insights From the Nationwide MYSTICS Registry.

This nationwide MYSTICS registry study analyzed management and outcomes of cardiac sarcoidosis in 2366 consecutive patients, focusing on 1852 newly diagnosed cases between 2012 and 2021 and stratifying them by diagnostic category (definite, probable, presumed systemic, presumed isolated). The key finding was characterization of real-world treatment patterns and clinical outcomes, including recurrence, across these diagnostic groups. These registry-based insights are significant for improving diagnostic certainty, guiding management strategies, and benchmarking prognosis in a rare but high-risk disease.

Izumi C, Yoshikawa Y, Komuro I et al. · Circulation. Heart failure · (2026) · View on PubMed ↗ · Free PDF ↗

Kidney injury associated with direct oral anticoagulants: a comparative study of direct thrombin inhibitors and factor Xa inhibitors based on literature and database analysis.

This study analyzed kidney injury associated with direct oral anticoagulants in real-world adverse event reports from the FDA FAERS database (2008–2024) and in published case reports, comparing the direct thrombin inhibitor dabigatran with factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. Across 8,116 suspected DOAC-associated kidney injury reports, DTIs had higher disproportional reporting than FXa inhibitors (DTIs: 1,784 reports; FXaIs: 6,332 reports; ROR for DTIs 2.081, 95% CI 1.979–2.189, truncated). These findings suggest a signal for greater kidney-injury reporting with dabigatran versus factor Xa inhibitors, supporting more targeted pharmacovigilance and risk stratification in clinical practice.

Chen S, Shi C, Li X et al. · Renal failure · (2026) · View on PubMed ↗ · Free PDF ↗

Chronic conditions and aortic disease risk: a prospective cohort study with predictive and etiological analyses.

This study assessed associations between 42 chronic conditions, multimorbidity, and incident aortic disease using UK Biobank with external validation in China Kadoorie Biobank, including predictive and etiological analyses. After false discovery rate correction in UKB, 21 chronic conditions were associated with overall aortic disease, with similar patterns in CKB, and aortic atherosclerosis showed the broadest comorbidity profile. The findings improve risk stratification for clinically silent aortic disease by identifying nontraditional comorbidity determinants beyond standard cardiovascular risk factors.

Yu L, Lu P, Yang M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

CNS Development, Ciliopathies, and Hydrocephalus

Infantile Maculopapular Cutaneous Mastocytosis: A Case Report with an Integrative Unani Medicine Perspective.

This case report studied a 9-month-old male infant with infantile maculopapular cutaneous mastocytosis using an integrative Unani medicine perspective alongside standard diagnostic evaluation. Clinical findings including multiple hyperpigmented macules with a positive Darier’s sign were confirmed by serum tryptase measurement, histopathology, and immunohistochemistry consistent with cutaneous mastocytosis. The report highlights the importance of accurate diagnostic work-up to exclude systemic mastocytosis in infants presenting with cutaneous mast cell disease.

Khanum S, Ilyas J, Eram F · Advances in mind-body medicine · (2026) · View on PubMed ↗

‘Leave no one behind’: cochlear implantation under regional anaesthesia in a humanitarian setting - a case series.

This case series studied feasibility, safety, and outcomes of cochlear implantation performed under regional anesthesia (RA) in a humanitarian setting. The authors report that RA can avoid general anesthesia (GA) logistical and safety barriers, enabling cochlear implantation for patients who might otherwise be ineligible due to comorbidities. The findings support RA as a practical approach to expand access to hearing restoration in low-resource humanitarian missions.

Aljazeeri I, Alzahrani MF, Halawani RT et al. · Journal of global health · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluating AI-assisted detection of fetal intracranial malformations in prenatal ultrasound practice: a multicentre, self-crossover, randomised controlled trial in China.

This multicentre, self-crossover, randomised controlled trial in China assessed whether the Prenatal Ultrasound Diagnosis Artificial Intelligence Conduct System (PAICS) improves detection of AI-recognisable fetal intracranial malformations in high-risk singleton pregnancies (11–32 weeks) examined by sonographers. The trial tested PAICS-assisted performance and also whether it helps identify anomalies outside its recognition scope. If effective, PAICS could support earlier and more consistent prenatal detection of fetal brain malformations in real-world ultrasound practice.

Lei T, Shang N, Xie B et al. · The Lancet. Digital health · (2026) · View on PubMed ↗ · Free PDF ↗

In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.

This study investigated the molecular architecture of the human ciliary transition zone (TZ) in multiciliated epithelial cells and how linker defects cause primary ciliary dyskinesia (PCD), focusing on the genes ECT2L and DZANK1. Using in situ cryo-electron tomography with subtomogram averaging, the authors resolved TZ doublet microtubules and identified ECT2L and DZANK1 as major linker complexes; biallelic loss-of-function variants in either gene disrupted TZ structure and produced microtubular abnormalities consistent with PCD. Scientifically, it links specific TZ protein defects to motile ciliopathy pathogenesis and provides mechanistic targets for diagnosis and future interventions.

Zhou H, Terbeck L, Berical A et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Tmem216 deficiency induces hydrocephalus via impaired ciliogenesis and disrupted ependymal planar polarity in mice.

The study tested the role of the ciliopathy gene Tmem216 in mice by inactivating Tmem216 in the central nervous system and assessing cilia formation and ependymal planar polarity. Tmem216 deficiency caused severe postnatal hydrocephalus due to impaired ciliogenesis and disrupted ependymal planar polarity, with TMEM216 localizing to the transition zone (TZ) of motile cilia in ependymal cells and primary cilia in radial glia cells. This establishes TMEM216 as a critical regulator of multiciliated ependymal function and CSF flow, linking TZ defects to congenital hydrocephalus.

Gong Q, Lv Z, Dou Z et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Microglial GRB2 is essential for brain ventriculogenesis and CSF homeostasis.

This study examined the genetic and cellular basis of congenital hydrocephalus (CH) by identifying damaging missense variants in the SH3-binding domain of GRB2 in patients and testing microglial GRB2 function in brain development. Microglial GRB2 was essential for brain ventriculogenesis and cerebrospinal fluid (CSF) homeostasis, and GRB2 variants were linked to CH. The work implicates microglial GRB2 signaling as a driver of ventricular development defects, informing potential molecular diagnostics and therapeutic targets for pediatric hydrocephalus.

Duy PQ, Reeves BC, Sun H et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗

A single-nucleus transcriptomic atlas of human inner ear development.

This study generated a single-nucleus RNA-seq atlas of human inner ear development (HIEDRA) covering the first and second trimesters to map sensory and nonsensory cell types and their developmental programs. The atlas defined multiple inner ear populations, including undercharacterized secretory cells important for ion homeostasis, and provided a reference for how human disease genes may affect cell-type formation. This resource supports improved interpretation of genetic risk and accelerates development of targeted therapies, including gene therapies, for human hearing and balance disorders.

van der Valk WH, Udayappan SD, van Beelen ESA et al. · Nature neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer Tumor Biology, Biomarkers, and Mechanisms

T-cell engagers in small cell lung cancer.

This review examined the role of T-cell engagers (TCEs) in small cell lung cancer, focusing on the DLL3 target and the approved DLL3×CD3 TCE tarlatamab. It summarizes how DLL3-directed TCEs bypass the immunosuppressive tumor microenvironment to promote T-cell-mediated tumor cell lysis while also addressing real-world challenges such as toxicity management. The review frames how DLL3 TCE therapy is reshaping SCLC treatment and what future strategies may be needed to optimize safety and implementation.

Cooper AJ, Sands J · Cancer · (2026) · View on PubMed ↗

Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma.

This study examined how perioperative myeloid remodeling affects CAR-T cell efficacy in glioblastoma (GBM) using both male mice and human GBM ex vivo models. The key finding was that surgical resection induced rapid, sustained tumor microenvironment remodeling with upregulation of TREM2 in myeloid cells, followed by emergence of T cell exhaustion-like phenotypes; in mice, targeting TREM2 reshaped the perioperative TME and potentiated antigen-specific CAR-T responses, improving intratumoral persistence, proliferation, effector differentiation, and survival. The results identify TREM2-driven perioperative myeloid changes as a modifiable determinant of CAR-T performance in GBM.

Pedard M, Castillo Cantero L, Ghasemi A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

PTEN homozygous deletion is a negative prognostic factor in tumor treating fields-treated glioblastoma, IDH wildtype patients.

This study evaluated whether PTEN homozygous deletion predicts outcomes in glioblastoma (IDH wildtype) patients treated with tumor treating fields (TTFields) after surgery and radiochemotherapy. In a reassessed cohort of TTFields-treated GBM, IDH-wildtype tumors with molecular profiling (DNA methylation profiling and TSO500 DNA/RNA panel sequencing), PTEN homozygous deletion was associated with worse prognosis. These findings suggest PTEN loss could be a clinically actionable biomarker to help stratify GBM patients for TTFields initiation.

Nückles J, Jelgersma C, Siewert C et al. · Brain pathology (Zurich, Switzerland) · (2026) · View on PubMed ↗ · Free PDF ↗

A HUWE1 regulatory helix gates ASCL1 degradation through its C-terminal phospho-degron in small cell lung cancer.

This mechanistic study in small cell lung cancer (SCLC) used genome-wide CRISPR knockout screening and base editor tiling screens with an endogenous knock-in reporter of the lineage transcription factor ASCL1 to determine how the HECT E3 ligase HUWE1 targets ASCL1 for degradation. The authors found that a HUWE1 regulatory helix gates ASCL1 degradation through a C-terminal phospho-degron. This provides a molecular rule for targeted protein degradation of ASCL1, a key SCLC driver, potentially informing future therapeutic strategies.

Masuzawa K, Dong KD, XiaoYang Hu C et al. · Genes & development · (2026) · View on PubMed ↗

A stem-like chromatin program in small-cell lung cancer is associated with poor outcomes after chemoimmunotherapy.

This study profiled tumor-intrinsic chromatin accessibility in small-cell lung cancer (SCLC) using patient-derived xenograft (PDX) biobank data and validated recurrent chromatin programs in bulk and single-cell transcriptomic datasets (>800 tumors, including ~300 extensive-stage) from patients treated with chemoimmunotherapy. It identified three recurrent chromatin programs—neuroendocrine (ASCL1/NEUROD1), immunogenic (IRF-associated), and stem-like (TEAD/OCT)—and reported that a stem-like program is associated with poor outcomes after chemoimmunotherapy. Clinically, TEAD/OCT-marked stem-like chromatin states could help stratify SCLC patients for prognosis and potentially guide therapy selection beyond established clinical biomarkers.

Kumar R, Desai P, El Meskini R et al. · Cell reports. Medicine · (2026) · View on PubMed ↗

Evaluation of anti-tumor drugs by simulating physiological absorption and metabolism with a multi-organoid system.

The authors developed an intestine–liver–tumor multi-organoid system to simulate physiological intestinal absorption and hepatic metabolism when evaluating anti-tumor drugs, addressing limitations of single-organoid tumor models. In fluidic conditions, the system maintained viability and showed intestinal and liver organoids with superior cellular diversity and transcriptional resemblance to native tissues, enabling more physiologically relevant efficacy and toxicity assessment (specific drug outcomes truncated). This platform could improve preclinical prediction of drug exposure and metabolism-driven efficacy/toxicity, supporting more reliable translational drug development.

Xiao C, Guo Y, Li C et al. · Cell systems · (2026) · View on PubMed ↗

Target Antigen Identification for Antibody Drug Conjugate Therapy in Biliary Tract Cancer.

This study aimed to identify actionable targets for antibody-drug conjugate therapy in biliary tract cancer by profiling antigen expression in resected primary tumors and matched metastases. Using tissue microarrays and immunohistochemistry (IHC) for CLDN18.2, c-MET, Nectin-4, TROP2, and HER2, with a subset analyzed by targeted next-generation sequencing using MSK-IMPACT, the authors assessed how target prevalence and genomic alterations relate to recurrence-free and overall survival. The work is significant for improving ADC patient selection by clarifying target expression heterogeneity and its clinical-genomic correlates in biliary tract cancer.

Dhyani A, Tezcan N, Chou JF et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗ · Free PDF ↗

The PROM1+SMAD5+ Tumor-Initiating Subpopulation Shapes Premetastatic Niches through Spatial Multi-Omics Landscapes in HER2-Positive Breast Cancer.

This study investigated how a PROM1+SMAD5+ tumor-initiating subpopulation shapes premetastatic niches in HER2-positive breast cancer using integrated spatial multi-omics approaches including spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics. It found that the PROM1+SMAD5+ cells create spatially organized microenvironmental programs that promote metastatic niche formation. These findings are significant because they pinpoint a specific tumor-initiating cell state (PROM1+SMAD5+) and its microenvironmental mechanisms as potential targets to prevent HER2+ metastasis.

Yin H, Wang W, Ge J et al. · Cancer communications (London, England) · (2026) · View on PubMed ↗

Targeting USP7 lactylation suppresses NSCLC tumorigenesis by promoting PINK1 ubiquitination and degradation.

This mechanistic cancer study investigated how USP7 lactylation regulates mitophagy and tumorigenesis in non-small cell lung cancer (NSCLC) using integrated proteomic/lactylomic analyses of clinical NSCLC specimens and matched adjacent normal tissues, plus USP7 knockout or inhibition of USP7 lactylation in cellular models. USP7 was upregulated and USP7 K1084 lactylation increased in NSCLC, and blocking USP7 or its lactylation impaired cellular mitophagy, causing mitochondrial damage and reducing NSCLC tumorigenicity, with downstream effects involving PINK1 ubiquitination/degradation. Scientifically, it identifies USP7 lactylation as a potential therapeutic target to suppress NSCLC via restoration of mitophagy and mitochondrial quality control.

Wang Z, Li C, Zhu R et al. · Autophagy · (2026) · View on PubMed ↗

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.

This international retrospective cohort study evaluated the relationship between baseline severity of hypercortisolism and survival outcomes in 101 patients with adrenocortical carcinoma (ACC) presenting with overt Cushing’s syndrome. Patients had markedly elevated urinary free cortisol (median 6.4× ULN), and the study assessed whether the degree of hypercortisolism predicted progression-free survival, disease-free survival, and overall survival (results truncated). Clinically, clarifying prognostic impact of hypercortisolism severity could refine risk stratification and management strategies for ACC-associated Cushing’s syndrome.

Araujo-Castro M, Bancos I, Detomas M et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.

This review article examined the von Hippel–Lindau (VHL) gene as a therapeutic target beyond the canonical VHL–HIF oxygen-sensing axis in clear cell renal cell carcinoma (ccRCC) and broader pan-cancer contexts. It argues that resistance and non-responsiveness to HIF-2α inhibitors (e.g., belzutifan-centered approaches) can be addressed by targeting non-canonical VHL substrates and pathways, summarizing evidence-graded novel VHL targets and next-generation therapeutics (truncated). The scientific significance is expanding the target landscape for VHL-driven tumors to overcome limitations of HIF-centric therapies.

Deng R, Wang B, Zou M et al. · Biomarker research · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.

This review focused on how E3 ubiquitin ligases mechanistically regulate tumor radiosensitivity and immunoresponsiveness, with the goal of informing clinical translation for tumor radioimmunotherapy. It synthesizes pathways by which E3 ubiquitin ligases control protein stability across DNA repair, immune signaling, and stress-response networks that influence response to combined radiation and immunotherapy (details truncated). The significance is identifying actionable ubiquitin-ligase nodes that could be targeted to improve durable efficacy of radioimmunotherapy.

Yang Q, Xing X, Wang Y et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Aging, Frailty, and Musculoskeletal Function

Dynamic frailty exposure and cognitive aging trajectories: A multicohort study.

This multicohort study analyzed how dynamic frailty exposure relates to cognitive aging trajectories in older adults across three nationally representative cohorts (n=19,586). Using longitudinal mixed-effects models with exposure-by-time interactions, it evaluated associations of baseline frailty status, two-wave frailty change, and mean frailty burden with annual global and domain-specific cognitive change. The results clarify whether changes in frailty over time predict cognitive decline patterns, informing risk stratification for cognitive aging.

Wang X, Hao H, Jiang T et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Phenomic profiles and disease patterns of 1.9 million participants from Our Future Health.

This Nature Medicine report analyzed baseline phenomic data from >1.9 million participants enrolled in the UK Our Future Health prospective cohort to characterize disease patterns and compare them with national estimates and the UK Biobank. The key finding was that sociodemographic, lifestyle, and health-related characteristics largely mirrored UK population patterns, enabling robust mapping of diagnoses, medications, healthcare utilization, cancer registry data, and cause of death across a very large cohort. Scientifically, this establishes a high-resolution phenotyping resource for discovering and translating prevention, detection, and treatment strategies at scale.

Straub VJ, Benonisdottir S, Bentivoglio GS et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

InsP3R signaling and actomyosin-dependent mitochondrial dynamics play essential roles in mitochondrial stress-induced longevity.

This study investigated the molecular requirements for mitochondrial stress-induced longevity, focusing on inositol 1,4,5-trisphosphate receptor (InsP3R) signaling and actomyosin-dependent mitochondrial dynamics. Using C. elegans with longevity induced by mitochondrial Complex I/nuo-6 mutation, the key finding was that longevity depended on the ER Ca2+ channel InsP3R, while testing candidate Ca2+-mitochondrial links showed that mitochondrial calcium uniporter (MCU)-dependent respiration stimulation was dispensable for the longevity pathway. Scientifically, it clarifies how ER Ca2+ signaling and mitochondrial dynamics integrate to produce adaptive longevity under mitochondrial dysfunction.

Feng G, Ruark EM, Mulligan AG et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies.

This review addressed the clinical problem that incretin-based therapies (including GLP-1 receptor agonists and related multi-agonists) can cause weight loss accompanied by reductions in lean mass, raising concerns about sarcopenia. The key finding emphasized that lean mass loss does not necessarily equate to loss of contractile skeletal muscle or true sarcopenia, and therefore assessment should distinguish fat loss from muscle quality/functional decline during incretin treatment. The review’s significance is to guide clinicians and researchers toward better evaluation and mitigation of muscle-related adverse outcomes as incretin therapies expand beyond fat loss.

Kim JY, Kim NH · Diabetes & metabolism journal · (2026) · View on PubMed ↗ · Free PDF ↗

This work investigated the role of programmed cell death ligand 2 (PD-L2) in age-associated cellular senescence by analyzing PD-L2 expression in senescent human cells and aging, using PD-L2 knockout mice and anti-PD-L2 therapy. PD-L2 was upregulated in senescent cells and during aging, and blocking PD-L2 reduced senescent cell accumulation in old PD-L2 knockout mice, improving insulin sensitivity and grip strength. These findings suggest PD-L2 is a therapeutic target for senescent-cell–driven age-related dysfunction, extending senolytic/immune-modulatory strategies beyond cancer.

Chaib S, Langhi Prata LGP, Suda M et al. · Cell metabolism · (2026) · View on PubMed ↗

Platinum chemotherapy ages the liver.

This study investigated how platinum chemotherapy affects liver aging in children treated for cancer. The key finding was that platinum-based drugs induce mutations and promote liver aging, consistent with chemotherapy-driven genomic damage contributing to long-term tissue aging. Clinically, it supports a mechanistic link between platinum exposure and late adverse outcomes, motivating strategies to mitigate mutagenic effects.

Vasudevan SA, Parsons DW · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Extensive and differential platinum chemotherapy mutagenesis in livers of children.

This study investigated chemotherapy mutagenesis in normal pediatric tissues in childhood cancer survivors, focusing on platinum chemotherapy effects in the liver and using duplex sequencing (NanoSeq) to detect mutations from single DNA molecules. The key finding was that platinum chemotherapeutics increased mutation burdens in normal pediatric tissues to adult-like levels and produced a liver-specific mutational signature absent from other tissues, with gene-focused duplex sequencing revealing diverse nonsynonymous variants with potential functional impact. Scientifically and clinically, it provides high-resolution evidence that platinum therapy drives tissue-specific mutagenesis that may underlie late adverse effects.

Wenger A, Vannier JB, Lee-Six H et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

The complete telomere-to-telomere sequence of a mouse Y chromosome.

This study assembled and analyzed a telomere-to-telomere (T2T) mouse Y chromosome (mT2T Y) in C57BL/6 mice to resolve gaps and errors in the GRCm39 reference. The key finding was that the new 95.21 Mb mT2T Y assembly filled all gaps, corrected structural errors, and added over 8.70 Mb of previously unassembled sequence, including annotation of 142 previously unidentified genes and mapping of homologous recombination loci in the pseudoautosomal region (PAR). Scientifically, it improves the reference for Y-linked genetics and enables more accurate studies of Y chromosome dosage compensation and recombination.

Li Q, Liu J, Chen S et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Sustained Activation of CaMKII Promotes Skeletal Muscle Contractile Dysfunction in Aging.

This work studied how sustained CaMKII (Ca2+/calmodulin-dependent protein kinase II) activation affects skeletal muscle contractile function in aging, using mouse models with increased CaMKII abundance in aged muscle and experimental CaMKII activation in young muscle. It found that sustained CaMKII activation impairs contractile function before major atrophy develops and, with prolonged activation, drives progressive muscle dysfunction. The results implicate maladaptive CaMKII signaling as a mechanistic driver of sarcopenia-related functional decline and a potential target for intervention.

Bene MR, Chung T, Luczak ED et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

Neurodegeneration, Brain Clearance, and Neuroimmune Interfaces

Retromer-targeted therapy for neurodegenerative diseases.

This narrative review studied the therapeutic potential of retromer-targeted strategies across neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. It links retromer dysfunction to shared endosomal-lysosomal system (ELS) mechanisms—proteostasis/protein misfolding, mitochondrial dysfunction, neurotransmission, and neuroinflammation—and discusses how these pathways may be interconnected in disease progression. The review supports retromer as a cross-disease molecular node and motivates retromer-focused interventions for neurodegeneration.

Persico M, Tuithung S, Lorenzo A et al. · Molecular neurodegeneration · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.

This structural biophysics study investigated how metabotropic glutamate receptor 8 (mGluR8) couples to β-arrestins (β-arrs) during receptor activation and desensitization. Using negative-stain EM and cryo-EM structures of mGluR8 alone and bound to G proteins or β-arrestin-1 (β-arr1), the authors identified tail- and core-bound complex orientations and stoichiometries that define active-state coupling. The work provides a mechanistic structural framework for understanding mGluR8 β-arrestin engagement, which can guide rational design of drugs targeting GPCR desensitization pathways.

Marx DC, Huynh K, Gonzalez-Hernandez AJ et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Astrocyte-derived extracellular vesicle phosphorylated TDP-43 as a blood-based biomarker for amyotrophic lateral sclerosis.

This study evaluated a blood-based liquid biopsy biomarker for amyotrophic lateral sclerosis (ALS) by measuring astrocyte-derived extracellular vesicles (ADEVs) carrying TDP-43 and hyperphosphorylated phospho-Ser409 TDP-43 (pTDP-43). It assessed diagnostic performance of these ADEV-associated forms to improve non-invasive detection and potentially support patient stratification for clinical trials. If validated, phosphorylated TDP-43 in ADEVs could reduce diagnostic delay and help monitor treatment response in ALS.

Butt TH, Strait M, Marcinczyk L et al. · Neurobiology of disease · (2026) · View on PubMed ↗

Architecture of the serotonergic projectome in the mouse brain.

This study mapped the serotonergic projectome in mouse brain using systematic whole-brain axon tracing combined with integrated analyses. It found that serotonin neuron targets are organized by functional relatedness rather than physical proximity, with dorsal and median raphe neurons partitioning into five projectomic groups preferentially innervating major brain regions (e.g., hippocampus, basal ganglia, cortex, medial interbrain). Scientifically, this provides a circuit-level framework for how diffuse serotonin signaling supports differentiated functions and may inform mechanistic models of psychiatric disorders.

Song JH, Friedmann D, Wu Y et al. · Cell · (2026) · View on PubMed ↗

Lipid flip-flop in biological membranes: through the lens of TMEM16F.

This article is a mechanistic review focusing on lipid flip-flop (phospholipid translocation across membrane leaflets) and specifically discusses the Ca2+-activated phospholipid scramblase TMEM16F. It synthesizes how lipid asymmetry is maintained despite thermodynamic instability, why cells invest energy to preserve it, and what happens when lipid organization breaks down in health and disease. The significance is that TMEM16F-centered insights clarify fundamental membrane biology and can guide therapeutic thinking for disorders involving disrupted membrane lipid asymmetry.

Shan KZ, Lowry AJ, González Torres MA et al. · Physiological reviews · (2026) · View on PubMed ↗

Noncoding transcription controls the developmental dynamics of long-range gene regulation.

This work studied how noncoding transcription shapes developmental long-range gene regulation dynamics in Drosophila embryos, using live imaging and single-allele co-visualization of enhancer activity and ncRNA transcription. The key finding was that sequential transcription of ncRNAs from distinct regulatory elements underlies gene activation, and that disrupting enhancer-associated ncRNAs causes precocious gene activation, indicating ncRNAs control the timing of gene expression. Scientifically, it reframes enhancer output as a timing mechanism driven by ncRNA transcription rather than solely by enhancer activity levels.

Batut PJ, Levine MS · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Novel Therapeutic Insights Into Alzheimer’s Disease: Glymphatic System and Meningeal Lymphatic Vessels.

This study reviewed how the glymphatic system (GS) and meningeal lymphatic vessels (mLVs) in the human/animal brain clear Alzheimer’s disease (AD)–associated proteins such as amyloid-β and tau via cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange. It reports that GS dysfunction can promote or worsen pathological protein deposition, thereby contributing to AD pathogenesis. These mechanistic insights support therapeutic strategies aimed at restoring GS/mLV clearance to slow or prevent AD progression.

Song B, Wang W, Liu S et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer’s disease.

This post-mortem genetic association study examined whether the TMEM106B coding variant rs3173615 and APOE diplotypes (rs429358, rs7412) modulate TDP-43 co-pathology risk in 2604 individuals with a primary neuropathologic diagnosis of Alzheimer’s disease. The key finding was that the TMEM106B risk variant was significantly enriched in AD cases with TDP-43 co-pathology (with logistic regression linking genetic modifiers to co-pathology risk). This identifies TMEM106B as a selective genetic modulator of TDP-43 pathology, helping explain AD heterogeneity and informing risk stratification for mixed pathology.

Reeves MM, Calliari A, Todd TW et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Conceptualizing cognition and behaviour across amyotrophic lateral sclerosis and frontotemporal dementia.

This article conceptualized how cognition and behavior evolve across a clinical continuum spanning frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), including clinically silent, prodromal (mild cognitive impairment/mild behavioral impairment), and manifest stages. It highlights that ALS and FTD share overlapping cognitive/behavioral manifestations despite differences in syndrome presentation. The framework is significant for improving phenotyping, clinical trial design, and biomarker targeting across neurodegenerative disease spectra.

Benatar M, Huey ED, Onyike CU et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis.

This study investigated how nuclear speckle architecture controls the timing and spatial release of long-lived intron-retained RNAs across the cell cycle in human pluripotent stem cells. It identified a nuclear RNA niche at the periphery of nuclear speckles that couples intron retention to cell-cycle-timed RNA release, using compartment-resolved transcriptional inhibition, deep learning, and single-molecule/super-resolution RNA imaging. The work links intron retention to nuclear compartmentalization and mitotic resolution, clarifying a regulatory layer that coordinates RNA availability with genome regulation programs.

Biayna J, Baranovskii A, Chaudhuri A et al. · Nature cell biology · (2026) · View on PubMed ↗ · Free PDF ↗

TDP-43 controls RNA structure through high affinity lattice interactions.

This study investigated how the neurodegeneration-associated RNA-binding protein TDP-43 interacts with GU dinucleotide repeat RNAs to control RNA structure. TDP-43 bound GU repeats with very high affinity and specificity, prevented formation of the pUG fold (an intramolecular quadruplex), and conversely pUG fold formation blocked TDP-43 binding; the authors further showed TDP-43 recognizes RNA as a 1D lattice where overlapping binding sites enable efficient initial capture. These mechanistic insights explain how TDP-43 can reshape repeat-containing RNAs at the structural level, informing models of RNA dysregulation in TDP-43 proteinopathies.

Vivek R, Kume T, Roschdi S et al. · Nature communications · (2026) · View on PubMed ↗

ARID5A RNA-binding coordinates microglial defense and ferroptosis in iPSC-derived models.

This study examined how the RNA-binding protein ARID5A coordinates microglial defense and ferroptosis using iPSC-derived models and integrated multi-omics analyses of ARID5A RNA/DNA/protein interactions. ARID5A regulated splicing and translation of RNA targets enriched in lysosomal, immune, and iron metabolism pathways, and ARID5A-dependent regulation influenced microglial functional outcomes relevant to ferroptosis. By linking a specific RBP (ARID5A) to immune-lysosomal-iron control in CNS-relevant cells, the work identifies a candidate molecular axis for modulating neuroinflammatory and ferroptotic processes.

Schafer DM, Blue SM, Xu S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Microbiome, Virome, and Host-Microbe Interactions

Virobiome-mediated regulation of microbiota-gut-brain axis signaling and neuroimmune homeostasis.

This review studied how the virome—particularly bacteriophages and eukaryotic viruses—may regulate the microbiota-gut-brain axis and neuroimmune homeostasis. It synthesizes evidence that viral components can influence microbial and immune balance and thereby modulate signaling relevant to neurological health. The work highlights the virome as a potential target for future microbiome-based interventions to maintain or restore neuroimmune equilibrium.

Afkhamian A, Saffari Natanzi A, Jafaridarabjerdi M et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Commensal bacteria inhibit viral infections via a tryptophan metabolite.

This study identified how specific commensal bacteria inhibit viral infections via a tryptophan metabolite pathway, using HIV as a model system. The key finding was that viral replication inhibition required aromatic amino acid aminotransferase (ArAT) to convert tryptophan into 3-indolelactic acid, which agonizes the aryl hydrocarbon receptor (AhR). Clinically and scientifically, it links defined gut microbial metabolism to antiviral effects through an AhR-dependent mechanism, suggesting potential microbiome- or metabolite-based adjunct strategies.

Jiang D, Soo N, Tan CY et al. · Nature communications · (2026) · View on PubMed ↗

Mechanism of membrane perforation in rotavirus cell entry.

This study investigated the mechanism of membrane perforation during rotavirus cell entry in the context of nonenveloped dsRNA virus translocation, using cryogenic electron tomography to visualize the full entry pathway. The key finding was that time-resolved cryo-tomograms and subtomogram averaging connect high-resolution structures of rhesus rotavirus and its subviral particles to the sequential stages of entry from attachment through release. Scientifically, it provides a structural basis for how rotavirus breaches cellular membranes during infection.

de Sautu M, Leistner C, Kirchhausen T et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

African swine fever virus impairs porcine alveolar macrophages bactericidal function by disrupting lysosomal acidification and cathepsin activity.

The research investigated how African swine fever virus (ASFV) affects porcine alveolar macrophages (PAMs) bactericidal function, particularly lysosomal acidification and cathepsin activity. ASFV impaired PAM killing by disrupting lysosomal acidification and reducing cathepsin function, providing a mechanistic explanation for severe secondary bacterial infections despite reported increases in phagocytosis. These findings identify lysosome/cathepsin dysfunction as a key targetable vulnerability in ASFV-associated bacterial co-infections.

Xu Z, Shi F, Xiang Z et al. · PLoS pathogens · (2026) · View on PubMed ↗

Recurrent synapses between CO2-sensitive olfactory sensory neurons enable robust CO2 detection in Aedes aegypti mosquitoes.

The study mapped neural circuitry for carbon dioxide (CO2) detection in Aedes aegypti by imaging glomeruli innervated by maxillary palp, using automated serial-section transmission electron microscopy (EM) and neuronal reconstruction. CO2-sensitive olfactory sensory neurons (OSNs) formed high levels of recurrent synaptic connections with each other, enabling robust CO2 detection. This provides a circuit-level mechanism for how mosquito olfactory networks integrate CO2 information to drive host-seeking behavior.

Bao J, Alford W, Khandelwal A et al. · PLoS biology · (2026) · View on PubMed ↗

Bacteria synthesize a bacteriocin within the cell membrane.

This study investigated the mechanism of TMcins, a recently discovered class of ribosomally synthesized and post-translationally modified peptide (RiPP) bacteriocins, focusing on where bacteriocin synthesis occurs. The authors report that TMcins are synthesized within the bacterial cell membrane, challenging the prior paradigm that RiPP precursor processing occurs in the cytoplasm followed by secretion across the membrane. This mechanistic insight expands understanding of bacterial antimicrobial biosynthesis and may inform engineering of membrane-associated RiPPs.

Nur FH, Antwi AN, Dickey SW · mBio · (2026) · View on PubMed ↗ · Free PDF ↗

Immunotherapy and Targeted Protein Degradation (PROTACs/TCEs/Antibodies)

A bispecific CD3×CD19 antibody for systemic lupus erythematosus: a phase 1 trial.

This phase 1 trial studied A-319, a bispecific CD3×CD19 antibody, in patients with systemic lupus erythematosus (SLE) to evaluate early safety and clinical activity. In the intravenous treatment arm, the study enrolled 12 patients and aimed to assess deep B cell depletion without the infrastructure demands of CAR T cell therapy. If tolerable and effective, A-319 could offer an off-the-shelf alternative strategy for refractory SLE requiring profound B cell targeting.

Xu J, Mei C, Guan X et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer-driver-agnostic targeting of amplified surface proteins identifies MPZL1 for selective CAR-T cell therapy.

This study developed a cancer-driver-agnostic CAR-T strategy by targeting amplified surface proteins and focused on MPZL1 (myelin protein zero-like 1) across solid tumors. The key finding was that MPZL1 is amplified in up to 75% of patients with certain solid tumor types, is abundantly expressed on tumor cell surfaces across diverse cancers, and is largely absent from healthy tissues, enabling a monoclonal antibody and MPZL1-targeted CAR-T cells to selectively recognize tumor cells. Clinically, it supports MPZL1 as a broadly applicable CAR-T antigen and demonstrates a generalizable approach for targeting amplified, surface-exposed proteins beyond canonical driver mutations.

Jiménez-Vázquez S, Berthel A, Patsis C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in Multiple Myeloma: 30 Years in the Making.

This review traced the 30-year evolution of immunomodulatory drugs (IMiDs) in multiple myeloma and connected their clinical development to cereblon (CRBN) as a druggable E3 ligase substrate receptor. It describes how thalidomide’s repurposing led to lenalidomide-based regimens and how CRBN biology enabled next-generation IMiD modulators, including the need for scalable oral agents active in IMiD-refractory, triple-class-exposed disease. The significance is mechanistic and translational: CRBN/E3 ligase modulation provides a unifying framework for designing and deploying improved therapies in multiple myeloma.

Bazarbachi AH, Lentzsch S, Facon T et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Discovery of Highly Efficacious CRBN-Based KRAS Degraders Targeting Cancers with KRAS G12D and G12V Mutations.

This work studied cereblon (CRBN)-based PROTACs designed to degrade KRAS proteins in cancer models carrying KRAS G12D or KRAS G12V mutations. The lead compound CW-10201 induced low-nanomolar degradation of KRASG12D and KRASG12V in cells and produced 2–4 nM growth-inhibition IC50 values in corresponding mutant cancer cell lines. The results support CRBN-based induced protein degradation as a potent strategy to therapeutically target otherwise difficult KRAS mutant cancers.

Wang C, Ghosh P, Jin S et al. · Journal of medicinal chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Discovery of Highly Potent and Selective, Orally Bioavailable BTK-Targeting PROTACs Featuring Novel CRBN-Binding Warheads.

This study developed and evaluated orally bioavailable BTK-targeting PROTACs using novel CRBN-binding warheads to overcome resistance and reduce off-target toxicity from kinase inhibition. The optimized PROTACs showed high potency against both wild-type and mutant BTK, with linker and warhead design aimed at minimizing unintended protein degradation associated with thalidomide-derived anchors. Scientifically, it advances PROTAC design principles for safer, mutation-resilient BTK degradation as a next-generation approach for hematologic malignancies.

Mantsyzov AB, Zhao P, Kruse CG et al. · Journal of medicinal chemistry · (2026) · View on PubMed ↗

ALKBH5 activates creatine-driven thermogenesis by stabilizing CKB mRNA in response to cold.

This study investigated how the m6A demethylase ALKBH5 regulates cold-induced, non-shivering thermogenesis by stabilizing CKB mRNA in adipose tissue, using fat-specific Alkbh5 knockout and overexpression models in mice and correlational analyses in humans. The key finding was that ALKBH5 responds to cold and adrenergic stimulation to drive UCP1-independent thermogenesis, with Alkbh5 loss reducing thermogenic capacity and worsening obesity susceptibility and glucose homeostasis, while Alkbh5 overexpression increased energy expenditure and improved systemic metabolism. These results identify an ALKBH5–CKB mRNA stabilization axis as a potential therapeutic target for obesity and metabolic disease.

Zhang Y, Du C, Qiao W et al. · Nature metabolism · (2026) · View on PubMed ↗

This review synthesized evidence on how ferroptosis and immune activation interact in metabolic dysfunction-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma (HCC). It proposes a bidirectional, self-amplifying ferroptosis–immune axis in which ferroptotic rupture releases damage-associated molecular patterns that activate myeloid cells and pro-inflammatory cytokines, further promoting ferroptosis. These mechanistic insights highlight potential therapeutic targets at the ferroptosis–immunity interface to prevent or slow MASH-related HCC.

Kuchay MS, Cubero FJ, Ramos-Molina B · Gut · (2026) · View on PubMed ↗

Regulation of hepatic mitochondrial function by AIBP mitigates MASLD development.

This study investigated whether apolipoprotein A-I binding protein (AIBP) preserves hepatic mitochondrial function to mitigate metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The authors reported that mitochondrial AIBP expression is reduced in patients with MASLD and demonstrated protective effects on mitochondrial function that counteract MASLD development. These findings position AIBP as a potential therapeutic target or biomarker pathway for limiting metabolic liver disease progression.

Choi SH, Sharma S, Choi S et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗

ENERGIZE-T studied the oral pyruvate kinase allosteric activator mitapivat in adults (≥18 years) with transfusion-dependent α-thalassaemia or β-thalassaemia across 19 countries in a double-blind, randomized, placebo-controlled phase 3 trial. The trial evaluated mitapivat’s efficacy and safety versus placebo, with patients randomized 2:1 to mitapivat or placebo (central randomization; detailed results truncated in the abstract). If mitapivat improves transfusion burden and clinical outcomes with acceptable safety, it would provide a disease-modifying oral option for both α- and β-thalassaemia populations that currently lack comparable oral therapies.

Cappellini MD, Sheth S, Taher A et al. · Lancet (London, England) · (2026) · View on PubMed ↗

CARDIOVASCULAR EFFECTS OF INCRETIN RECEPTOR AGONISTS: BEYOND GLYCEMIC CONTROL.

This review evaluated cardiovascular effects of incretin receptor agonists—covering GLP-1 receptor agonists, dual GLP-1/GIP agonists, and triple GLP-1/GIP/glucagon receptor agonists—emphasizing mechanisms beyond glycemic control. Mediation analyses of major CV outcomes suggested glycemic improvement explains only ~15–20% of reductions in major adverse cardiovascular events, with the remainder attributed to weight loss, lipid remodeling, blood pressure changes, systemic inflammation, and direct myocardial protection. Clinically, it supports a multi-mechanistic rationale for cardiovascular benefit that extends beyond glucose lowering when selecting incretin-based therapies.

Ravic M, Srejovic IM, Milosavljevic I et al. · Canadian journal of physiology and pharmacology · (2026) · View on PubMed ↗

Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis.

This study examined whether lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis, focusing on the adipocyte-secreted lipid 9S-hydroxyoctadecadienoic acid (9S-HODE). The key finding was that mammary adipocytes secrete less 9S-HODE in obesity, and that 9S-HODE induces ferroptosis in breast cancer cells by disrupting iron homeostasis; ferroptosis inhibition accelerated tumor growth in lean mice, while restoring 9S-HODE suppressed tumor growth in obese mice, with an inverse correlation between human mammary 9S-HODE and BMI. Clinically, it identifies a potentially targetable lipid–ferroptosis axis that may help explain obesity-associated breast cancer aggressiveness.

Curtin MC, Jackson AE, Lee MD et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Exercise stress echocardiography for diagnosis of heart failure with preserved ejection fraction: a multicentre study.

This systematic review and random-effects meta-analysis evaluated whether sunlight exposure is associated with breast cancer risk across 31 epidemiologic studies, including analyses by hormone-receptor subtype. Higher sunlight exposure was associated with lower breast cancer incidence (pooled OR 0.80, 95% CI 0.74–0.86), with stronger effects in studies using personal exposure measures and weaker effects in studies using ambient-ultraviolet proxies. The protective association was most evident for estrogen-receptor-negative and triple-negative breast cancer subtypes, suggesting sunlight-related exposures may differentially influence tumor biology by receptor status.

Harada T, Reddy YNV, Sorimachi H et al. · European heart journal · (2026) · View on PubMed ↗

Genomic meta-analyses of binge-eating behavior and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

This genomic meta-analysis studied binge-eating behavior (BE) and anorexia nervosa (AN) using genome-wide association data from 39,279 BE cases and 1,227,436 controls, alongside AN datasets totaling 24,223 cases and 1,243,971 controls (European ancestries). It identified six BE-associated loci and eight AN loci (with validation of six), and polygenic risk score analyses supported shared and distinct genetic architecture across eating disorder phenotypes. The results are significant for refining biological pathways underlying BE versus AN and for improving genetic risk prediction across eating disorder subtypes.

Termorshuizen JD, Davies HL, Lee SH et al. · Nature. Mental health · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Use of incretin receptor agonists in patients submitted to metabolic bariatric surgery - a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated weight-loss outcomes and adverse events associated with incretin receptor agonists—liraglutide, semaglutide, and tirzepatide—in patients who previously underwent metabolic bariatric surgery. The key finding was the synthesis of available evidence on whether these agents improve weight loss or mitigate weight regain after surgery, while characterizing safety profiles. This is clinically significant because it informs pharmacotherapy options for post-bariatric patients with suboptimal response.

Santos-Pereira M, Frutuoso JF, Pereira SS et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Postpartum GLP-1 receptor agonists and SGLT-2 therapies in women with prior gestational diabetes: current evidence and uncertainties.

This review summarized current evidence and uncertainties regarding postpartum use of GLP-1 receptor agonists and SGLT-2 inhibitors in women with prior gestational diabetes mellitus (GDM), a group at high risk for future type 2 diabetes. It frames the clinical rationale that postpartum glucose often normalizes but early prediabetes confers substantially increased T2DM risk, while existing prevention strategies (including lifestyle and metformin) have limited effectiveness (truncated). The clinical significance is guiding future prevention strategies for cardiometabolic risk reduction in women with prior GDM using GLP-1 RA and SGLT-2 therapies.

Vanlaer Y, Van de Cauter E, Embo N et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

SMRT regulation of nuclear receptors orchestrates bile acid homeostasis.

This study examined the role of the co-repressor SMRT in regulating the constitutive androstane receptor (CAR) to maintain bile acid homeostasis in mice. Targeted disruption of SMRT’s nuclear receptor-interacting domain (SMRTmRID1) increased CAR target gene expression involved in bile acid export, and SMRTmRID1 mice showed altered bile acid homeostasis under high-fat diet challenge. These results establish SMRT–CAR co-regulation as a key control point for bile acid metabolism, with implications for metabolic disease and therapeutic modulation of nuclear receptor pathways.

Kim K, Fang S, Hong SH et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Sleep, Circadian, and Insomnia Pharmacology

Corticotropin-releasing hormone neurons in the bed nucleus of the stria terminalis control wakefulness in physiological and stressful conditions in mice.

This mouse study examined how corticotropin-releasing hormone (CRH) neurons in the bed nucleus of the stria terminalis (BNST) regulate wakefulness under physiological and stressful conditions, using optogenetic activation of BNST neuronal subpopulations. The key finding was that optogenetic activation of CRH-expressing BNST neurons promoted wakefulness, whereas activation of BNST cholecystokinin- or somatostatin-expressing neurons did not. Scientifically, it delineates a specific BNST CRH circuit controlling arousal during stress, offering mechanistic insight relevant to insomnia and sleep-wake disorders.

Zhang KL, Xu W, Sun P et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

Dual orexin receptor antagonist-assisted dose reduction of benzodiazepines and benzodiazepine receptor agonists: a mirror-image analysis of insurance claims data.

This study evaluated whether initiating or continuing dual orexin receptor antagonists (DORAs)—specifically suvorexant or lemborexant—enables dose reduction of benzodiazepines or benzodiazepine receptor agonists (BZ/BZRAs) in long-term users with chronic insomnia. In a self-controlled mirror-image analysis of Japanese health insurance claims (Dokenpo database, 2019–2024), the authors compared changes in bedtime BZ/BZRA dose (diazepam equivalents) before versus after DORA treatment. If effective, this approach would provide a real-world, safety-conscious strategy to reduce benzodiazepine exposure in chronic insomnia patients.

Matsui K, Sugiura K, Shimura A et al. · Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · (2026) · View on PubMed ↗

Autoimmune Disease (Non-Cancer) and Real-World Therapeutics

Sequential disease activity assessment for predicting future treatment trajectories in patients with rheumatoid arthritis treated with JAK inhibitors: a group-based trajectory and landmark analysis.

This registry-based study analyzed 843 rheumatoid arthritis patients treated with Janus kinase (JAK) inhibitors to define disease activity trajectories using Clinical Disease Activity Index (CDAI) over 52 weeks. Group-based trajectory modeling identified distinct CDAI patterns, and landmark analyses at weeks 4 and 12 tested whether early disease activity predicts longer-term treatment trajectories. The results could enable earlier risk stratification and treatment adjustment in RA patients starting JAK inhibitor therapy.

Terabe K, Asai S, Yoshioka Y et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

Rheumatoid Arthritis in Adults: A Review.

This JAMA review summarized epidemiology, clinical features, and diagnostic considerations for rheumatoid arthritis (RA) in adults, including autoantibody prevalence (rheumatoid factor and anticitrullinated peptide antibodies). It highlights that RA affects synovial joints and can involve extra-articular disease, with peak incidence in older adults and a female predominance. As a synthesis of current knowledge, it supports clinicians in recognizing disease patterns and informing evidence-based management.

Smolen JS, Kerschbaumer A, Aletaha D et al. · JAMA · (2026) · View on PubMed ↗

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

This randomized placebo-controlled trial tested whether probiotic supplementation with VSL#3 alters gut-immune signaling and improves disease activity in children with oligoarticular or RF-negative polyarticular juvenile idiopathic arthritis (JIA). After 3 months, probiotics increased fecal TLR4 agonists but did not improve clinical disease activity compared with placebo. The findings indicate that while probiotics can modulate innate immune ligands in the gut, this does not necessarily translate into therapeutic benefit in early JIA.

Durand C, Eveillard LA, Labouret M et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Real-World Effectiveness and Safety of Upadacitinib in Patients With Crohn’s Disease-A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD).

The UPGRADE-CD prospective multicentre observational study evaluated real-world effectiveness and safety of upadacitinib, an oral selective JAK1 inhibitor, in advanced therapy-experienced (AT-experienced) patients with Crohn’s disease across 38 Italian centres. The key finding was the study’s demonstration of clinically meaningful response/remission and safety outcomes at weeks 12 and 24 in this real-world AT-experienced population (including steroid-free outcomes and biomarker/endoscopic measures). This supports upadacitinib’s effectiveness and tolerability in routine care for difficult-to-treat Crohn’s disease patients beyond trial settings.

Barberio B, D’Amico F, Laterza L et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

Practical Guidance on Initiating and Switching Targeted Immunotherapies in Generalised Myasthenia Gravis: A German-Austrian Expert Opinion Paper.

This German-Austrian expert opinion paper reviewed and synthesized evidence on initiating and switching targeted immunotherapies in adults with generalized myasthenia gravis (gMG), focusing on complement C5 inhibitors and neonatal Fc receptor inhibitors. It provides practical guidance for patient selection, therapy sequencing, and integration into routine care based on early post-approval real-world experience in Germany and Austria. The clinical significance is improved decision-making for how to start and switch C5 inhibitors and FcRn inhibitors in gMG to better match heterogeneous real-world outcomes.

Meisel A, Marina AD, Doksani P et al. · European journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Risk of Coeliac Disease After Immune Checkpoint Inhibitor Exposure in Patients With Cancer.

This study used the TriNetX US Collaborative Network to evaluate the risk of developing celiac disease (CeD) after immune checkpoint inhibitor (ICI) exposure in adults with malignancy, excluding patients with pre-existing CeD. It compared cohorts exposed to ICIs (including nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, tremelimumab, or avelumab) versus non-exposed groups and estimated CeD incidence/risk (methods/results truncated). Scientifically and clinically, it informs immune-related adverse event risk assessment and surveillance for CeD in cancer patients receiving ICIs.

Aburumman R, Alsakarneh S, Choung RS et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

Neuroinflammation and Infection-Driven Brain Effects

Loberamisal for Acute Ischemic Stroke: The LAIS Randomized Clinical Trial.

The LAIS phase 3 randomized clinical trial studied intravenous loberamisal in adults (18–80 years) with acute ischemic stroke across 32 Chinese hospitals, evaluating functional outcomes and safety. The abstract indicates loberamisal was designed to dual-target the PSD-95 pathway and α2-GABAA receptors, but the provided text is truncated before reporting efficacy and safety results. If effective, targeting PSD-95 and α2-GABAA signaling could represent a novel neuroprotective/neuroreparative strategy for acute ischemic stroke.

Li S, Feng B, He D et al. · JAMA · (2026) · View on PubMed ↗

Th17 effector cytokines induce shared and distinct microglial and endothelial cell responses in a mouse model for post-streptococcal encephalitis.

This study tested how Group A Streptococcus (GAS) infection drives brain immune and vascular responses in a mouse model of post-streptococcal encephalitis, focusing on Th17 effector cytokine effects. Using mouse genetics, single-cell RNA sequencing, and spatial transcriptomics, the authors found GAS-induced inflammatory programs in microglia and brain endothelial cells, including loss of blood-brain barrier gene expression in female mice, with microglia clustering near infiltrating CD4+ T cells. The study also connected mouse chemokine changes to patient sera and showed that deleting GM-CSF in CD4+ T cells partially reduced effects, supporting a cytokine-driven mechanism linking peripheral infection to neuroinflammation.

Wayne CR, Akcan U, Faust TE et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Type 1 Diabetes Prevention and Disease Modification

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process.

The Diabetologia consensus guidance developed recommendations for general-population screening for islet autoantibodies (IAbs) to diagnose early-stage type 1 diabetes, using a nominal group technique process. It addresses the rising global incidence of type 1 diabetes and the clinical burden at diagnosis (including DKA and ICU admission in a substantial fraction of children/adolescents), arguing that early IAb detection enables monitoring and education to prevent severe presentations. This guidance could standardize population screening strategies to reduce DKA and enable earlier intervention in type 1 diabetes.

Ziegler AG, Rewers MJ, Achenbach P et al. · Diabetologia · (2026) · View on PubMed ↗

Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial.

The PROTECT randomized trial studied whether teplizumab preserves beta-cell function in children and adolescents (age 8–17) with newly diagnosed stage 3 type 1 diabetes, using a pre-specified per-protocol analysis of participants with adequate treatment adherence. Teplizumab showed greater preservation of stimulated C-peptide (beta-cell function) than placebo in the per-protocol population, supporting efficacy beyond the intent-to-treat estimate. This strengthens the clinical rationale for teplizumab to delay beta-cell decline in stage 3 type 1 diabetes in pediatric patients.

Herold KC, Dayan CM, Chatenoud L et al. · Diabetologia · (2026) · View on PubMed ↗

Reproductive Health and Pain Mechanisms

Endometriosis Pain: Genes linked to Inflammation Distinguish Symptomatic from Asymptomatic Disease.

The authors investigated gene-expression differences underlying endometriosis pain by performing RNA sequencing on formalin-fixed, paraffin-embedded peritoneal biopsies from symptomatic versus asymptomatic subjects. They found 890 differentially expressed genes, with the most significant changes enriched for inflammatory signaling pathways (including IL16, IL17RA, JAK3, SMPD3, and RELT) and cell-adhesion-related genes (e.g., OLFML1). This suggests that inflammation-linked transcriptional programs distinguish symptomatic from asymptomatic endometriosis and could guide biomarker development or targeted therapies for pain.

Mamillapalli R, Li HJ, Apelian S et al. · Molecular human reproduction · (2026) · View on PubMed ↗

Generated automatically on September 12, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.

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PubMed Trending Research Digest — September 12, 2026

PubMed Trending Research Digest — September 12, 2026

Overview

Immunology: T Cells, Checkpoints, and Innate Immune Signaling

Mitochondrial ATP promotes T cell differentiation through chromatin accessibility.

Glycan recognition by a plant damage-sensing immune receptor.

Unphosphorylated tyrosines mediate PD-1 inhibition of T cell signaling condensate formation.

Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.

Upper respiratory tract CD8+ tissue-resident memory T cells protect against viral transmission.

Microbial adhesion promotes Piezo1 activation to initiate innate immunity.

AMBRA1 allosterically activates NLRP3 by releasing its autoinhibition.

Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.

Cancer Clinical Trials and Treatment Strategies (Non-ADC/Non-TCE)

Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.

COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancer.

Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn’s disease: 5-year follow-up of the PROFILE trial.

Management of Soft Tissue and Visceral Leiomyosarcomas.

Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial.

GOLDEN: Efficacy and Safety of Complement Factor B Antisense, Sefaxersen, in Geographic Atrophy due to Age-Related Macular Degeneration.

Actual Five-year Survival After Neoadjuvant Therapy and Resection for Localized Pancreatic Ductal Adenocarcinoma.

Cardiovascular, Vascular Disease, and Risk Stratification

Out-of-Hospital Intensive Care in Germany - who´s out there? Key issues revealed by the clinical application of the new legislation in Baden Württemberg.

Familial pulmonary fibrosis: a UK consensus framework for the investigation and management of patients and their relatives.

Beyond Heritable PAH: Pulmonary Hypertension in Genetic Syndromes.

Metabolic Markers of MRI-Confirmed Lacunar Stroke: Observational and Mendelian Randomization Analyses.

Avoiding Vascular Misadventure: Pre-emptive Contralateral Endovascular Access in Revision Total Hip Arthroplasty: A Case Report.

Management and Outcomes of Cardiac Sarcoidosis: Insights From the Nationwide MYSTICS Registry.

Kidney injury associated with direct oral anticoagulants: a comparative study of direct thrombin inhibitors and factor Xa inhibitors based on literature and database analysis.

Chronic conditions and aortic disease risk: a prospective cohort study with predictive and etiological analyses.

CNS Development, Ciliopathies, and Hydrocephalus

Infantile Maculopapular Cutaneous Mastocytosis: A Case Report with an Integrative Unani Medicine Perspective.

‘Leave no one behind’: cochlear implantation under regional anaesthesia in a humanitarian setting - a case series.

Evaluating AI-assisted detection of fetal intracranial malformations in prenatal ultrasound practice: a multicentre, self-crossover, randomised controlled trial in China.

In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.

Tmem216 deficiency induces hydrocephalus via impaired ciliogenesis and disrupted ependymal planar polarity in mice.

Microglial GRB2 is essential for brain ventriculogenesis and CSF homeostasis.

A single-nucleus transcriptomic atlas of human inner ear development.

Cancer Tumor Biology, Biomarkers, and Mechanisms

T-cell engagers in small cell lung cancer.

Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma.

PTEN homozygous deletion is a negative prognostic factor in tumor treating fields-treated glioblastoma, IDH wildtype patients.

A HUWE1 regulatory helix gates ASCL1 degradation through its C-terminal phospho-degron in small cell lung cancer.

A stem-like chromatin program in small-cell lung cancer is associated with poor outcomes after chemoimmunotherapy.

Evaluation of anti-tumor drugs by simulating physiological absorption and metabolism with a multi-organoid system.

Target Antigen Identification for Antibody Drug Conjugate Therapy in Biliary Tract Cancer.

The PROM1+SMAD5+ Tumor-Initiating Subpopulation Shapes Premetastatic Niches through Spatial Multi-Omics Landscapes in HER2-Positive Breast Cancer.

Targeting USP7 lactylation suppresses NSCLC tumorigenesis by promoting PINK1 ubiquitination and degradation.

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.

Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.

Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.

Aging, Frailty, and Musculoskeletal Function

Dynamic frailty exposure and cognitive aging trajectories: A multicohort study.

Phenomic profiles and disease patterns of 1.9 million participants from Our Future Health.

InsP3R signaling and actomyosin-dependent mitochondrial dynamics play essential roles in mitochondrial stress-induced longevity.

Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies.

Blocking PD-L2 prevents senescent cell accumulation and age-related dysfunction.

Platinum chemotherapy ages the liver.

Extensive and differential platinum chemotherapy mutagenesis in livers of children.

The complete telomere-to-telomere sequence of a mouse Y chromosome.

Sustained Activation of CaMKII Promotes Skeletal Muscle Contractile Dysfunction in Aging.

Neurodegeneration, Brain Clearance, and Neuroimmune Interfaces

Retromer-targeted therapy for neurodegenerative diseases.

Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.

Astrocyte-derived extracellular vesicle phosphorylated TDP-43 as a blood-based biomarker for amyotrophic lateral sclerosis.

Architecture of the serotonergic projectome in the mouse brain.

Lipid flip-flop in biological membranes: through the lens of TMEM16F.

Noncoding transcription controls the developmental dynamics of long-range gene regulation.

Novel Therapeutic Insights Into Alzheimer’s Disease: Glymphatic System and Meningeal Lymphatic Vessels.

TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer’s disease.

Conceptualizing cognition and behaviour across amyotrophic lateral sclerosis and frontotemporal dementia.

The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis.

TDP-43 controls RNA structure through high affinity lattice interactions.

ARID5A RNA-binding coordinates microglial defense and ferroptosis in iPSC-derived models.

Microbiome, Virome, and Host-Microbe Interactions

Virobiome-mediated regulation of microbiota-gut-brain axis signaling and neuroimmune homeostasis.

Commensal bacteria inhibit viral infections via a tryptophan metabolite.

Mechanism of membrane perforation in rotavirus cell entry.

African swine fever virus impairs porcine alveolar macrophages bactericidal function by disrupting lysosomal acidification and cathepsin activity.

Recurrent synapses between CO2-sensitive olfactory sensory neurons enable robust CO2 detection in Aedes aegypti mosquitoes.

Bacteria synthesize a bacteriocin within the cell membrane.