PubMed Trending Research Digest — September 30, 2026

Automated digest · 96 articles · 15 research areas · September 30, 2026

Overview

This week’s digest is dominated by studies linking immune function to metabolism and microenvironmental context across diseases. In cancer, multiple reports emphasize how metabolic state shapes immune efficacy—ranging from immunometabolic profiling of MAIT and CD8+ T cells in checkpoint-treated head and neck cancer to mitochondrial and epigenetic rewiring strategies in AML and glioblastoma stem cells. Complementing this, several tumor microenvironment-focused works highlight how specific cellular niches (e.g., TLS-like structures in bladder cancer, cachexia-associated cellular circuitry in pancreatic cancer, and CAF-driven chemoresistance in lung adenocarcinoma) can be mapped and targeted to improve outcomes.

A second major theme is the gut microbiome as a mechanistic lever for therapy response and systemic disease risk. Evidence spans microbiome–immunotherapy coupling (checkpoint inhibitor outcomes), microbiome–drug metabolism (metformin inactivation via microbial AdhE), and microbiome–neurologic/vascular effects (AHR-dependent immune pathways influencing ischemic stroke severity). Several studies also move toward precision approaches—using spatial transcriptomics, peripheral-blood workflows for neoantigen discovery, and risk-stratified surveillance frameworks—to better capture heterogeneity and tailor interventions.

Finally, the digest includes strong mechanistic and translational advances in neuroinflammation and CNS biology (e.g., microglial lactylation/mitochondrial axes after injury, CSF α-synuclein seeding for Parkinson’s stratification, and CXCR3 blockade in tauopathy), alongside structural and molecular biology that clarifies fundamental processes (vesicle trafficking initiation, organelle mechanotransduction, and toxin pore maturation). Together, these studies reinforce a broader trend: moving from descriptive biomarkers toward actionable, pathway-level targets that can be measured, modeled, and manipulated.

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Cancer immunotherapy & tumor microenvironment

Spatial evolution of a cachexia-promoting microenvironment in pancreatic cancer.

This work studied the spatial evolution of a cachexia-promoting tumor microenvironment in pancreatic cancer by integrating single-cell RNA sequencing, Xenium spatial transcriptomics, multiplex immunohistochemistry, bulk transcriptomics, and functional experiments across human non-cachexia, pre-cachexia, and cachexia samples plus mouse models. It defined a cachexia-associated niche composed of SEMA4A+ tumor cells, AQP9+ macrophages, and LOXL2+ cancer-associated fibroblasts, with SEMA4A signaling promoting BMP2-dependent acquisition of an AQP9-associated macrophage program. These results clarify cellular circuitry driving cancer cachexia and suggest SEMA4A/BMP2/AQP9-axis components as potential therapeutic targets to prevent or treat wasting.

Hu Y, Lv G, Yuan H et al. · Cell · (2026) · View on PubMed ↗

Multiplex Immunofluorescence-defined CXCL13-associated TLS-like Niches Predict Outcome in Bladder Cancer.

This study investigated whether multiplex immunofluorescence-defined CXCL13-associated tertiary lymphoid structure (TLS)-like niches predict outcomes in bladder cancer, analyzing 469 tumors using 41-plex multiplex immunofluorescence (PhenoCycler) plus bulk RNA-seq and computational deconvolution (CIBERSORTx). It identified mTLS-associated immune programs and used Cox modeling with CXCL13 as a continuous variable and spatial neighborhood analysis to link these TLS-like niches to clinical prognosis, with validation in orthotopic bladder cancer mouse models treated with an unspecified agent (truncated abstract). These findings suggest that spatially organized CXCL13-associated TLS-like niches provide prognostic information beyond single markers and could inform immunotherapy stratification in bladder cancer.

Maenosono R, Nishimura K, Tsujino T et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

Real-World Strategies for Biologic Dose Escalation and Reduction in Psoriasis and Psoriatic Arthritis: A Systematic Review.

This systematic review evaluated real-world strategies for biologic dose escalation (DE) and dose reduction (DR) in moderate-to-severe psoriasis and psoriatic arthritis. The key finding was that real-world dosing frequently deviates from standard protocols, with reported success rates and rationales varying across studies and definitions of DE/DR criteria. Clinically, it highlights the need for clearer, evidence-based criteria to optimize long-term efficacy and safety when adjusting biologic dosing in practice.

Crespi O, Giunipero di Corteranzo I, Bongiovanni E et al. · Journal of cutaneous medicine and surgery · (2026) · View on PubMed ↗

Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery.

This study developed a peripheral-blood-only workflow to discover cancer neoantigens and reactive T cells in eight metastatic cancer patients using cell-free DNA whole-exome sequencing plus neoantigen-specific CD4+ and CD8+ T-cell isolation based on PD-1 and CD39 co-expression. The key finding was that the method identified most neoantigens and detected more T-cell reactivities than standard biopsy-based approaches, while also uncovering additional neoantigens missed by tumor biopsy. Scientifically, it expands neoantigen-targeted immunotherapy discovery to a less invasive sampling strategy that may better capture tumor heterogeneity.

Garcia-Garijo A, Creus-González I, Levy PL et al. · Cancer discovery · (2026) · View on PubMed ↗ · Free PDF ↗

Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a detailed safety analysis of the randomized OptiTROP-Breast01 study.

This post-hoc safety analysis studied sacituzumab tirumotecan (sac-TMT), an anti–trophoblast cell-surface antigen 2 (TROP-2) antibody-drug conjugate, in previously treated metastatic triple-negative breast cancer using the randomized OptiTROP-Breast01 study safety set. The key finding was a detailed characterization of adverse event frequencies and patterns, with particular emphasis on hematologic toxicities (exact rates are truncated). Clinically, it refines the risk profile of sac-TMT for treatment planning and monitoring in Chinese patients receiving second-line and later therapy.

Fan Y, Ouyang Q, Yin Y et al. · Breast cancer research : BCR · (2026) · View on PubMed ↗ · Free PDF ↗

A human single-cell atlas identifies OLR1+ scar-associated macrophages as a potential therapeutic target for chronic liver disease.

This study generated a human liver single-cell atlas of 649,295 cells from 42 healthy and 35 chronic liver disease (CLD) patients to identify macrophage states driving fibrosis. The key finding was that disease-expanded TREM2+ scar-associated macrophages include an OLR1+ pro-inflammatory subpopulation that spatially accumulates in the fibrotic niche and is associated with CLD outcomes (association details are truncated). Therapeutically, it nominates OLR1+ scar-associated macrophages as a potential target to treat chronic liver disease–associated fibrosis.

Papachristoforou E, Kong K, Colella F et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer.

This open-label phase 2a trial studied systemic immune reactivation with aglatimagene besadenovec (CAN-2409; a replication-defective adenoviral vector encoding herpes simplex virus thymidine kinase) plus valacyclovir in immune checkpoint inhibitor (ICI)-refractory advanced non-small cell lung cancer patients. Patients receiving two intratumoral CAN-2409 injections plus valacyclovir showed prolonged survival compared with historical expectations for ICI-refractory disease. These results support CAN-2409/valacyclovir as a clinically relevant strategy to induce systemic antitumor immunity in ICI-refractory NSCLC.

Aggarwal C, Sterman D, Dwyer J et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

IL-23-engineered oncolytic vaccinia virus enhances pancreatic cancer control through inflammasome-driven Th17-skewed CD4+ T-cell responses.

This study engineered an oncolytic vaccinia virus with CRISPR-Cas9 to delete thymidine kinase (TK) and B2R and to express IL-23 p40 and p19 subunits (VV-DDIL23) to test whether inflammasome-driven, Th17-skewed CD4+ T-cell responses improve pancreatic cancer control. The IL-23–engineered virus enhanced antitumor efficacy by promoting inflammasome-dependent immune activation and a Th17-biased CD4+ T-cell response. The findings mechanistically support IL-23–programmed oncolytic vaccinia as a way to convert immunologically cold pancreatic tumors into durable adaptive immune responses.

Guo Y, Wang M, Xuan Y et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative clinical outcomes and single-cell profiling of CD19 CAR-T versus blinatumomab for relapsed/refractory B-ALL.

This retrospective study compared CD19 CAR-T therapy versus blinatumomab in 106 relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) patients and used single-cell RNA sequencing (scRNA-seq) on nine post-infusion patient-derived T-cell samples. CD19 CAR-T and blinatumomab showed different clinical outcomes and toxicity profiles, with scRNA-seq revealing distinct post-infusion T-cell states associated with each therapy. These data help refine selection and mechanistic understanding of CD19-targeted immunotherapies in r/r B-ALL.

Wang K, Yu L, Liang X et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

A transient MXD4-dependent proliferative pause enables survival of brain micrometastases.

This study analyzed how metastasis-initiating cancer cells survive early brain colonization, using models of brain micrometastases to define the role of the MYC antagonist MXD4. It found that metastatic cells transiently enter an MXD4-dependent proliferative pause before vascular co-option-associated outgrowth, and genetic disruption of MXD4 impaired micrometastasis survival and progression to macrometastases. The results indicate that a temporary MXD4-controlled cell-cycle buffering program is a vulnerability for preventing brain metastasis establishment.

García-Gómez P, Retana D, Hernández-Oliver C et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

Concomitant medications and outcomes of bispecific T-cell engager therapy: A propensity-matched study of tarlatamab in ES-SCLC.

This retrospective propensity-matched study evaluated whether concomitant medications influence safety and outcomes of the bispecific T-cell engager tarlatamab in patients with extensive-stage small cell lung cancer (ES-SCLC). Using TriNetX (April 2024–May 2026), patients receiving tarlatamab were stratified by exposure to commonly used concomitant drugs within 3 months of treatment initiation, with overall survival as the primary endpoint and cytokine release syndrome/toxicity measures as secondary endpoints. The findings are intended to guide real-world medication management during tarlatamab therapy by identifying drug exposures that may alter survival or immune-related toxicity risk.

Eysha M, Green A, Khamis MM et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗

A Paired Tumor Organoid-Stroma Biobank Reveals PLAU⁺ Fibroblasts as Drivers of Chemoresistance in Lung Adenocarcinoma.

This study created a paired tumor organoid–stroma biobank from patient-derived lung adenocarcinoma (LUAD) to determine how cancer-associated fibroblasts (CAFs) drive chemoresistance. Co-culture with CAFs reduced organoid chemosensitivity, and PLAU (plasminogen activator urokinase)-positive fibroblasts were identified as a chemoresistance-associated CAF marker linked to poor survival in LUAD patients. These results support PLAU+ CAFs as both a mechanistic driver and a potential biomarker/therapeutic target to overcome chemotherapy resistance in LUAD.

Li S, Zhang Z, Lv Q et al. · Cancer research · (2026) · View on PubMed ↗

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Cancer genomics, biomarkers & precision oncology

Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents.

This narrative expert review synthesized evidence on gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, covering approved therapies, oral formulations, and late-stage pipeline agents. It concluded that nausea, vomiting, diarrhea, and constipation are common limitations leading to discontinuation, and it summarized incidence, mechanisms, and clinical implications across trial and pharmacovigilance data (specific rates and agent-by-agent comparisons are not shown in the truncated abstract). The review is clinically significant for guiding patient counseling, mitigation strategies, and selection of therapies to improve adherence in type 2 diabetes and obesity.

Singhani V, Ehsan M, Valencia S et al. · Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Daraxonrasib and the era of pan-RAS inhibition: mechanisms, clinical advances, and resistance landscapes.

This review article synthesized preclinical and clinical evidence on daraxonrasib (RMC-6236), a tri-complex inhibitor that targets the active, GTP-bound state of multiple RAS isoforms, across RAS-mutant cancers. The key finding was that pan-RAS inhibition via RAS(ON) tri-complex mechanisms has advanced clinical development and revealed emerging resistance landscapes across tumor types (mechanistic and resistance details are truncated). This is significant because it frames how next-generation RAS(ON) inhibitors may overcome prior “undruggable” limitations and guide combination strategies.

Lou J, Zhang D · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Germline homologous recombination deficiency influences TP53-mutant clonal hematopoiesis fitness during platinum and PARP inhibitor treatment.

The study examined how germline homologous recombination deficiency (gHRD) affects TP53-mutant clonal hematopoiesis (CH) fitness during platinum chemotherapy and poly(ADP-ribose) polymerase inhibitor (PARPi) treatment in patients undergoing serial blood sampling. DDR-driven CH was frequently observed after PARPi therapy and expanded during carboplatin exposure and to a lesser extent during PARPi treatment, with expansion linked to prior carboplatin exposure. These findings suggest that inherited HRD and TP53-mutant DDR clones can be selected by DNA-damaging therapy, informing risk stratification and monitoring for therapy-related myeloid neoplasms (tMN).

Baeten JT, Chan ICC, Moukarzel L et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.

This study investigated resistance to PI3-kinase (PI3K) inhibition in acute myeloid leukemia (AML) by testing dependencies of leukemic stem cells (LSCs) and the role of epigenetic adaptation. It found LSCs are particularly dependent on the p110α PI3K isoform, and that PI3K inactivation triggers adaptive downregulation of EZH2/PRC2 function via reduced EZH2 protein levels as a non-genetic resistance mechanism. This is significant because targeting the PI3K–EZH2 adaptive axis could improve strategies to prevent relapse by better eliminating therapy-resistant LSCs.

Glushakow-Smith SG, Kaur I, Sidoli S et al. · Leukemia · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of HER2 directed therapies for advanced HER2-mutant non-small-cell lung cancer - a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated efficacy and safety of HER2-directed therapies—including HER2 tyrosine kinase inhibitors (TKIs) and HER2 antibody-drug conjugates (ADCs)—for advanced HER2-mutant non-small cell lung cancer based on prospective trials. The analysis found clinically meaningful activity across approved HER2-directed agents, while highlighting that evidence is largely from single-arm studies with limited direct comparative data. This supports ongoing efforts to define optimal sequencing and selection of HER2 TKIs versus HER2 ADCs in distinct clinical contexts.

Li MSC, Soon YY, Au-Yeung PY et al. · Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · (2026) · View on PubMed ↗

ATM safeguards DNA replication by restraining pathological repriming at endogenous base lesions.

This work investigated the mechanism of PARP inhibitor (PARPi) cytotoxicity in mammalian ATM-deficient cells, focusing on DNA replication stress and repriming at endogenous base lesions. In the absence of ATM, unrestrained PRIMPOL-dependent repriming at oxidative base lesions created post-replicative DNA gaps that activated PARP, driven by aberrant BRCA1 recruitment to stalled replication forks and suppression of HLTF/ZRANB3-mediated repriming control. Clinically, the study clarifies why ATM loss sensitizes tumors to PARPi and identifies replication-pathway nodes (PRIMPOL/BRCA1/HLTF-ZRANB3) that could be targeted to refine synthetic-lethal strategies.

Sommerova L, King A, Chapman JR · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

The Polycystic Kidney Disease Cyst Transcriptome Defined by Integrating Spatial, Single Nuclear, and Bulk Transcriptomics.

This study integrated 10x Genomics Visium spatial transcriptomics with single-nucleus and bulk transcriptomics to define the cyst transcriptome in an autosomal dominant polycystic kidney disease (ADPKD) patient sample while preserving cyst morphology. It demonstrated that ADPKD cysts exhibit size-based transcriptional heterogeneity that can be mapped spatially, overcoming limitations of dissociation-based single-cell approaches. The resulting spatially resolved cyst transcriptome provides a framework for identifying cyst-size–specific molecular pathways and potential therapeutic targets in ADPKD.

Khan MI, Robichaud JH, Afrin H et al. · Kidney360 · (2026) · View on PubMed ↗

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Cancer metabolism & immunometabolism

AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.

This mechanistic study investigated how AARS2-mediated DLD K445 lactylation and SIRT5 delactylation regulate cuproptosis resistance in therapy-resistant glioblastoma stem cells (GSCs). It found that lactylome profiling identified dihydrolipoamide dehydrogenase (DLD) as a key lactylation target, with AARS2 catalyzing DLD K445 lactylation and SIRT5 reversing it via NAD+-dependent delactylation, thereby promoting resistance to copper-dependent cuproptosis. Scientifically, it links a specific lactylation switch (AARS2–DLD K445–SIRT5) to mitochondrial lipoylated-protein aggregation biology, suggesting potential targets to sensitize GSCs to cuproptosis-based therapies.

Ding M, Xu H, Liu C et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Cotranslational membrane protein biogenesis by an EMC-bound translocon.

This study examined how cotranslational membrane proteins are biogenetically processed by an ER membrane translocon that is bound to the ER Membrane Complex (EMC) in human cells. Using selective ribosome profiling, cryo-electron tomography, and site-specific photocrosslinking, it revealed how EMC and the multipass translocon components are deployed during synthesis of nascent multipass membrane proteins. The mechanistic insight is significant for understanding the fundamental choreography of membrane protein biogenesis and for identifying potential targets to modulate ER protein folding and trafficking.

Rollins MG, Tang J, Wan Y et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗ · Free PDF ↗

CPT1A-mediated IDO1 succinylation shapes EGFRvIII-driven resistance to tumor electric field therapy in glioblastoma.

This work investigated how CPT1A-mediated IDO1 succinylation affects resistance to tumor electric field therapy (TEFT) in glioblastoma, focusing on EGFRvIII-driven mechanisms in TEFT-treated patients and experimental models. TEFT activated an AMPK–PPARα–CPT1A bioenergetic stress axis, while EGFRvIII primed IDO1 transcription via NF-κB; CPT1A then stabilized IDO1 by promoting succinylation at lysine 377 through a non-canonical LSTase-related activity, reducing TRIM21-dependent ubiquitination and proteasomal degradation. Clinically, this links EGFRvIII status to TEFT resistance and identifies the CPT1A–IDO1 succinylation axis as a potential therapeutic target to overcome resistance.

Feng B, Li B, Zhang Q et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Immunometabolic Profiling of T Cells and Innate Lymphoid Cells Uncovers Therapeutic Targets to Enhance Immunotherapy in Head and Neck Cancer.

This study used functional-metabolic flow cytometry to profile tumor-infiltrating MAIT cells, CD8+ T cells, and innate lymphoid cells (ILCs) from head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant anti-PD-1 alone or anti-PD-1 plus anti–interleukin-8 (IL-8). It found that CD39-negative OX40+ MAIT cells and CD8+ tumor-infiltrating lymphocytes were metabolically fit and less exhausted, whereas OX40− populations showed altered metabolic features consistent with poorer antitumor fitness. These immunometabolic signatures suggest OX40+ MAIT and CD8+ T-cell metabolic states as therapeutic targets to improve checkpoint blockade responses in HNSCC.

Rajakumar SA, Nanda N, Kim C et al. · Cancer immunology research · (2026) · View on PubMed ↗

Targeting ClpP Rewires the Metabolic-Immune Axis in Acute Myeloid Leukemia.

This study investigated how targeting the mitochondrial caseinolytic protease P (ClpP) rewires the metabolic–immune axis in acute myeloid leukemia (AML), focusing on tumor-intrinsic and immune effects. It showed that elevated ClpP expression marks advanced AML and that IMP125, a ClpP agonist, produced dual antileukemic and anti–tumor immune effects by altering mitochondrial metabolism and immune suppression. These findings support ClpP agonism as a strategy to couple mitochondrial metabolic targeting with enhancement of antitumor immunity in AML.

Xiang X, Luo B, Zhao L et al. · Cancer research · (2026) · View on PubMed ↗

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Radiotherapy & radiation oncology

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer (CHN HYPOPMRT): 10-year outcomes from a randomised, non-inferiority, open-label, phase 3 trial.

This randomized, non-inferiority, open-label phase 3 trial studied long-term outcomes of hypofractionated versus conventional fractionated postmastectomy radiotherapy in women aged 18–75 with high-risk breast cancer who underwent modified radical mastectomy and axillary dissection in China. The key finding was the 10-year comparative efficacy and adverse-event profile supporting whether hypofractionation is non-inferior to conventional fractionation for high-risk disease with regional nodal irradiation. Clinically, this informs durable radiotherapy regimen selection to optimize outcomes and potentially improve convenience and resource use.

Sun GY, Chen SY, Tang Y et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Surgery and tile-based radiation therapy versus surgery and stereotactic radiation for newly diagnosed brain metastases (ROADS): a randomized, open-label, phase 3 trial.

This randomized, open-label phase 3 trial (ROADS; NCT04365374) studied whether surgery plus cesium-131 collagen tile-based radiation therapy (R+TBRT) is non-inferior to surgery plus stereotactic radiation (R+SRT) for newly diagnosed brain metastases requiring resection. Patients were randomized 1:1 across 32 US centers, and the trial compared safety and efficacy outcomes between the two post-operative radiation strategies. If TBRT matches SRT outcomes, it could offer a logistical and immediate post-resection radiation alternative for resected brain metastases.

Weinberg JS, Imber BS, DiNapoli V et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

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Surgery, staging & clinical trial design

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients Presenting With Locally Advanced Breast Cancer.

This prospective study evaluated sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy in patients with locally advanced breast cancer who had nodal complete response (cN0) and underwent dual-tracer SLNB without routine nodal clipping. It aimed to determine the false-negative rate (FNR) of SLNB, with FNR calculations based on patients with adequate mapping (≥3 SLNs or <3 SLNs plus clipped node) and all participants receiving completion axillary lymph node dissection. If confirmed, the results could refine axillary staging and reduce overtreatment by validating SLNB accuracy after NAC in this high-risk clinical setting.

Barrio AV, Mautner S, Capko D et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Risk-Stratified Surveillance for Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Comparison With the RETREAT-Guided Surveillance Protocol.

This single-center retrospective study evaluated risk-stratified surveillance for recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) in patients whose explants showed specific AJCC tumor stage, grade, and vascular invasion (2013–2023), and compared adherence/effectiveness against the RETREAT-guided surveillance protocol. The key finding was that the risk-stratified approach (and its modified cutoffs/strategies) performed differently from RETREAT in predicting surveillance adherence and/or recurrence detection, with performance varying by risk group and protocol cutoff. These results support tailoring post-LT HCC surveillance intensity to explant pathology risk to improve detection of recurrence while optimizing follow-up resources.

Dharia IP, Leven EA, Schmidt N et al. · Clinical transplantation · (2026) · View on PubMed ↗

Atezolizumab Plus Bevacizumab Treatment for Patients With Hepatocellular Carcinoma in the Barcelona Clinic Liver Cancer B2 Stage.

This retrospective analysis studied treatment patterns associated with survival beyond a previously validated prognostic model in 113 patients with Barcelona Clinic Liver Cancer (BCLC) stage B2 hepatocellular carcinoma between 2017 and 2024. The key finding was that certain systemic or combined treatment modalities were associated with survival exceeding model-predicted outcomes in this intermediate-stage subgroup (specific regimen details are truncated in the provided abstract). Clinically, it informs evidence generation for selecting therapies beyond transarterial chemoembolization in BCLC-B2 patients.

Ouchi K, Ninomiya M, Tsuruoka M et al. · Journal of gastroenterology and hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical and oncological outcomes of gastroduodenal neuroendocrine tumours after endoscopic resection in the Western setting - a target trial emulation.

This multinational retrospective target-trial emulation compared long-term clinical and oncological outcomes after endoscopic resection (ER) of gastroduodenal neuroendocrine tumors (GD-NETs) across Western centers, including comparisons of ER techniques such as endoscopic submucosal dissection (ESD) versus conventional endoscopic mucosal resection (EMR). The key findings focused on rates of curative (R0) resection, residual disease, and local recurrence after different ER approaches. These results help clinicians choose the most effective endoscopic technique to optimize oncologic outcomes for GD-NETs.

Mendes F, Vieira RJ, Alípio M et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

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Infectious agents & cancer prevention

Postpandemic Trends in Pediatric Respiratory Virus Hospitalizations: A Multicenter Study, 2019-2025.

This multicenter retrospective study analyzed postpandemic trends in pediatric respiratory virus hospitalizations in Italy (2019–2025) across 16 hospitals, with special attention to the 2024–2025 RSV season after nirsevimab immunoprophylaxis. Hospitalization patterns for viruses such as RSV and influenza showed marked temporal variability, and the introduction of nirsevimab provided an opportunity to evaluate changes in RSV hospitalization trends. The results are clinically important for anticipating healthcare burden and assessing real-world impact of RSV immunoprophylaxis in children.

Attaianese F, Campani S, Trapani S et al. · Influenza and other respiratory viruses · (2026) · View on PubMed ↗ · Free PDF ↗

Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.

This worldwide incidence analysis studied the global cancer burden attributable to infections in 2024 by estimating population-attributable fractions (PAFs) and age-standardized incidence rates using the GLOBOCAN Cancer Today database. It quantified the number and incidence of new cancers attributable to 12 IARC Group 1 carcinogenic infectious agents. The significance is that it provides an evidence-based target list for prevention programs aimed at reducing infection-driven cancers.

Rumgay H, Georges D, Huang Y et al. · The Lancet. Oncology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Neuroinflammation, neurodegeneration & CNS immune signaling

Beyond weight loss: a narrative review of tirzepatide’s impact on muscle and lean mass in people with overweight and obesity.

This study investigated lactate-driven histone lactylation signaling in microglia after spinal cord injury (SCI), focusing on H4K12 lactylation and its regulation of NDUFS7. It found that SCI increases lactate, which promotes histone H4 lysine 12 lactylation (H4K12la) that directly upregulates NDUFS7 (a mitochondrial Complex I subunit), driving mitochondrial reverse electron transport (RET), reactive oxygen species (ROS) burst, and a pro-inflammatory microglial phenotype. These findings identify an H4K12la–NDUFS7–RET axis as a potential therapeutic target to limit neuroinflammation and secondary injury after SCI.

Wilkinson T, Ramzan R · Current medical research and opinion · (2026) · View on PubMed ↗ · Free PDF ↗

α-Synuclein Seeding Discriminates Between LRRK2 G2019S Variant Carriers with and Without Parkinson’s Disease.

This biomarker study evaluated whether α-synuclein seed amplification assay (aSyn SAA) in cerebrospinal fluid (CSF) can discriminate Parkinson’s disease (PD) status among LRRK2 p.G2019S variant carriers. It found that α-synuclein seeding results differed between affected and unaffected LRRK2 G2019S carriers, indicating that aSyn SAA can stratify LRRK2-related PD pathology, and it also examined links to mitochondrial genetic burden. Scientifically, it advances CSF seeding assays as a tool for identifying prodromal/manifest PD pathology in genetically defined cohorts.

Lüth T, Gabbert C, Kleinz T et al. · Movement disorders : official journal of the Movement Disorder Society · (2026) · View on PubMed ↗ · Free PDF ↗

The influence of anti-CD20-directed B cell depletion across different agents on Epstein-Barr virus-specific humoral and cellular immunity in patients with multiple sclerosis.

This cross-sectional study compared Epstein-Barr virus (EBV)-specific humoral and cellular immunity in multiple sclerosis patients receiving anti-CD20-directed B-cell depletion therapy (BCDT) across different agents versus untreated people with MS at diagnosis and age- and sex-matched healthy controls. The key finding was that anti-CD20 B-cell depletion differentially impacts EBV-specific CD4+ and CD8+ T-cell responses and EBV-related humoral immunity depending on the BCDT agent (specific comparative results are truncated). Scientifically and clinically, it clarifies how B-cell depletion modulates EBV immunity, informing infection-risk considerations and mechanistic understanding of MS immunobiology.

Stögbauer J, Bronder S, Saenz Kämpfer N et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

CD38-activated macrophages drive age-related placental senescence by depleting NAD+ in decidual stromal cells.

The study examined age-related placental senescence in humans and mouse/pig models by integrating metabolomics, single-cell RNA sequencing, and spatial transcriptomics, and then testing macrophage CD38 function using pharmacological and genetic perturbations. Aged placentas showed increased CD38 expression in macrophages and NAD+ deficiency, and macrophage CD38 depleted NAD+ in decidual stromal cells, promoting senescence. This identifies the macrophage CD38–NAD+ axis as a mechanistic driver of placental aging and a potential intervention point for age-related reproductive complications.

Hua L, Yang X, Gao D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

ALKBH5-mediated microglia-neuron crosstalk inhibits sympathetic innervation and adipocyte browning in male mice.

The study investigated how ALKBH5-mediated m6A demethylation in microglia regulates neural–adipose crosstalk in male mice, using microglia-specific ALKBH5 knockout (MCKO) and single-nuclear RNA sequencing plus brain slice electrophysiology and tissue pathology. Microglial ALKBH5 in the hypothalamic PVH region inhibited cold-induced adipocyte browning in subcutaneous white adipose tissue by modulating sympathetic activation. Scientifically, it identifies ALKBH5 as a microglial regulator of sympathetic innervation and browning, pointing to RNA epigenetic control of neuro-metabolic responses.

Yang YF, Li Y, Chen MH et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Insomnia as risk factor for brain, mental and general health consequences: an umbrella systematic review.

This umbrella systematic review evaluated whether insomnia predicts later brain, mental, and general health outcomes by synthesizing systematic reviews with meta-analysis (SMRAs) on endpoints including dementia, stroke, depression, suicide, death, and hospitalization. Across included SMRAs, insomnia consistently predicted dementia, depression, and suicide, while death was not consistently associated with insomnia. The evidence supports insomnia as a clinically meaningful risk marker for multiple adverse outcomes and underscores the value of insomnia screening and treatment.

Vignatelli L, Leone MA, Pupillo E et al. · Sleep medicine reviews · (2026) · View on PubMed ↗ · Free PDF ↗

Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy.

This mouse study examined whether peripheral CXCR3 blockade can reduce T cell infiltration and neurodegeneration in a tauopathy model. Genetic deletion or antibody-mediated blockade of CXCR3 prevented IFNγ-induced CXCL10 upregulation and brain T cell infiltration, and chronic systemic anti-CXCR3 treatment reduced parenchymal CD4+ and CD8+ T cells, attenuated neurodegeneration, and improved cognition. The significance is that targeting the CXCR3 chemokine axis may be a therapeutic strategy for inflammatory components of tau-driven neurodegeneration.

Emmerson JT, Hu H, Savani V et al. · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗

BAG3 coordinates astrocytic proteostasis of Alzheimer’s disease-linked proteins via proteasome, autophagy, and retromer interactions.

This study assessed how the astrocyte-enriched proteostasis regulator BAG3 coordinates handling of Alzheimer’s disease-linked proteins by proteasome, autophagy, and retromer interactions, using single-nucleus RNA sequencing, CRISPR/Cas9 editing in human induced pluripotent stem cells, and proteomic/transcriptomic profiling. BAG3 loss caused greater disruption of astrocytic proteostasis pathways, implicating BAG3 as a coordinator of multiple degradation/trafficking systems relevant to AD-linked protein homeostasis. The work supports BAG3 as a mechanistic node in astrocyte proteostasis that could be targeted to mitigate neurodegenerative protein dysregulation.

Augur ZM, Fogo GM, Benoit CR et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Hearing Intervention for Older Adults With Mild Cognitive Impairment: The CHOICE Randomized Clinical Trial.

This multicenter, parallel-group, open-label randomized clinical trial tested whether a hearing intervention could reduce dementia-level impairment incidence in older adults with coexisting hearing loss and mild cognitive impairment (MCI). The key finding was that hearing intervention did not significantly reduce the incidence of dementia-level impairment over follow-up compared with control. Clinically, the results suggest that hearing intervention alone may be insufficient to prevent dementia progression in this specific high-risk MCI population, informing future prevention strategies.

Chen Y, Shi H, Xiang M et al. · JAMA neurology · (2026) · View on PubMed ↗

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Pain & neurobiology of chronic conditions

A microglial SPP1-ITGB1 feedback loop sustains thalamic hyperexcitability and post-stroke pain.

This study investigated mechanisms of central post-stroke pain (CPSP) in mice by focusing on microglial secreted phosphoprotein 1 (SPP1) and integrin β1 (ITGB1) signaling. Hemorrhage-induced ATP activated P2X7 receptors to induce microglial SPP1, which engaged an autocrine, self-amplifying SPP1–ITGB1 feedback loop that sustained a pro-nociceptive milieu and CPSP-like behaviors. The scientific significance is identifying a specific microglial chronification switch that could be targeted to prevent transition from acute injury to chronic pain.

Dai R, Wu W, Zhou X et al. · Neuron · (2026) · View on PubMed ↗

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Genetic disorders & neurodevelopment

Large-scale genetic profiling of hereditary ataxias in China: implications for a stepwise molecular diagnostic strategy.

This large-scale genetic profiling study examined hereditary ataxias in China to inform a stepwise, epidemiology-informed molecular diagnostic strategy, focusing on the regionally variable genetic landscape despite the predominance of spinocerebellar ataxia type 3 (SCA3). The key finding was that comprehensive, up-to-date profiling supports implementing a diagnostic algorithm that reflects local mutation frequencies rather than a one-size-fits-all testing order (full algorithm specifics are truncated). This is significant for improving diagnostic yield, genetic counseling accuracy, and cost-effective testing in Chinese hereditary ataxia patients.

Yu JY, Sun YM, Dong Y et al. · Translational neurodegeneration · (2026) · View on PubMed ↗ · Free PDF ↗

Mepolizumab long-term remodeling effect in severe asthma responders: the MESILICO study.

This retrospective ESID registry-based analysis assessed real-world treatment indications, clinical course, immunologic changes, and tolerability in activated PI3K-delta syndrome (APDS) patients treated with leniolisib (a selective PI3Kδ inhibitor) and/or rapamycin. The key finding is that these targeted and off-label immunomodulatory approaches were used in routine care with measurable immunologic effects and variable tolerability across patients. These real-world data help guide management of APDS where prospective comparative evidence remains limited.

Porpodis K, Tsiouprou I, Bakakos P et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Monoallelic variants in BRSK1 are associated with a neurodevelopmental disorder with or without epilepsy.

This study investigated monoallelic BRSK1 variants in individuals identified through Texome Project and GeneMatcher, using genomic diagnosis pipelines including AI-MARRVEL. Affected participants with rare heterozygous BRSK1 missense variants showed neurodevelopmental phenotypes including developmental delay, anxiety, ADHD, autism, and variable epilepsy. The clinical significance is that BRSK1 expands the genetic basis of neurodevelopmental disorders and supports improved molecular diagnosis and counseling.

Deng M, Ma M, Gomez VA et al. · American journal of human genetics · (2026) · View on PubMed ↗

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Imaging diagnostics & radiology consensus

Use of MRI in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease - MAGNIMS consensus recommendations.

This MAGNIMS expert recommendation studied how MRI should be used for diagnosis, monitoring, and treatment decisions in patients with aquaporin-4 positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). It provides consensus guidance to address challenges such as overlapping imaging features, variable lesion evolution, and lack of standardized acquisition protocols. The recommendations are significant for improving consistency of imaging practice and comparability of outcomes across clinical trials and real-world care.

Cortese R, Hacohen Y, Arrambide G et al. · Nature reviews. Neurology · (2026) · View on PubMed ↗

Interobserver agreement among pathologists in the histological diagnosis of coeliac disease: a systematic review supports the British Society of Gastroenterology guidelines’ integrated approach to diagnosis.

This systematic review assessed interobserver agreement among pathologists for histological diagnosis and classification of coeliac disease (CD) using duodenal biopsy findings, and it evaluated evidence in relation to the British Society of Gastroenterology integrated diagnostic approach. It found that reproducibility of histological interpretation varies across diagnostic features, supporting the need for standardized, guideline-aligned integrated assessment rather than histology alone. This is significant for improving diagnostic consistency and patient management in CD by informing how pathology results should be interpreted within an integrated framework.

Feghali CEF, Baby J, Murray ER et al. · Journal of clinical pathology · (2026) · View on PubMed ↗ · Free PDF ↗

MRI Characteristics of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Review.

This review summarized MRI characteristics and lesion evolution patterns used in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), distinguishing it from multiple sclerosis and AQP4+ neuromyelitis optica spectrum disorder. It highlighted hallmark MRI findings across optic nerve and other CNS regions and emphasized how imaging variability and parameter differences can delay diagnosis and treatment. Scientifically and clinically, the article supports more consistent MRI interpretation aligned with the 2023 MOGAD diagnostic criteria.

Flanagan EP, Banwell BL, Cacciaguerra L et al. · JAMA neurology · (2026) · View on PubMed ↗

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Kidney disease & renal therapeutics

EASL-EASD-EASO Guidance for the Use of Resmetirom and Semaglutide as MASH-Targeted Therapy.

This EASL-EASD-EASO guidance synthesized evidence on non-invasive fibrosis assessment and pharmacotherapy selection for adults with MASLD/MASH, focusing on resmetirom and semaglutide use. The key recommendation is to use non-invasive tests such as VCTE, MRE, or ELF to identify patients at higher risk for major adverse liver-related outcomes (MALO) and consider targeted therapy accordingly. Scientifically and clinically, it standardizes how to stratify patients without biopsy and when to deploy these MASH-directed drugs.

Journal of hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Prospective 96-week study to evaluate efficacy and safety of tacrolimus and glucocorticoid against mycophenolate and glucocorticoid as continuous induction-maintenance treatment for Class III/IV without or with Class V lupus nephritis.

This prospective Asian multicenter randomized controlled trial studied continuous induction-maintenance regimens of tacrolimus plus glucocorticoids versus mycophenolate mofetil plus glucocorticoids in 130 biopsy-proven patients with active class III/IV lupus nephritis with or without class V. The primary endpoint was sustained renal response at week 96, comparing renal efficacy and safety between tacrolimus (target trough 6–8 ng/mL) and MMF (1 g twice daily) strategies. The results inform evidence-based selection of calcineurin inhibitor–based versus antimetabolite-based maintenance approaches for lupus nephritis.

Yap DYH, Navarra SV, Ni Z et al. · Kidney international · (2026) · View on PubMed ↗

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Cardiovascular, hemodynamics & vascular biology

Disparities in pathways for anaemia care and recovery among women after major abdominal surgery: secondary analysis of a prospective cohort study in 29 countries.

This secondary analysis studied disparities in pathways for anaemia care and recovery among women after major abdominal surgery across 29 countries, using a prospective cohort of women from 427 hospitals. It assessed preoperative anaemia prevalence and management differences by surgical pathway (gynaecology vs non-gynaecology), examined associations with 30-day outcomes, and estimated potential benefit of anaemia correction (full quantitative findings are not visible in the truncated abstract). The findings are significant for improving equitable perioperative anaemia recognition and treatment strategies to reduce postoperative morbidity in women.

Kamarajah SK, Hapangama D · BJS open · (2026) · View on PubMed ↗

Permissive Blood Pressure Targets in Pediatric Critical Care: The PRESSURE Randomized Clinical Trial.

The PRESSURE randomized clinical trial studied permissive mean arterial pressure (MAP) targets in critically ill, invasively ventilated children receiving vasoactive drugs for hypotension across 23 pediatric intensive care units in 3 countries. The key finding was that adopting a permissive MAP strategy reduced vasoactive drug exposure while maintaining 30-day outcomes (details truncated in the provided abstract). This supports a practice-changing, physiology-guided approach to hemodynamic management in pediatric critical care to potentially lessen harm from vasoactive therapy.

Inwald DP, Laing E, Broomhall JM et al. · JAMA · (2026) · View on PubMed ↗

Targeting the aldosterone-mineralocorticoid receptor pathway in cardiovascular-kidney-metabolic syndrome.

This review synthesized evidence on targeting the aldosterone–mineralocorticoid receptor (MR) pathway across the cardiovascular–kidney–metabolic (CKM) syndrome continuum. It concludes that inappropriate MR activation drives maladaptive remodeling and that both steroidal MR antagonists and non-steroidal MR antagonists (including finerenone) improve cardiorenal outcomes by mitigating MR signaling. Scientifically and clinically, it supports MR pathway inhibition as a unifying strategy for CKM syndrome management and highlights finerenone as a key non-steroidal option.

Sánchez-Bayuela T, Barrera-Chimal J, Jaisser F · Nature reviews. Nephrology · (2026) · View on PubMed ↗

Shear Stress-Stimulated Trafficking of Endothelial Piezo1 to Splenic Capsule Boosts Spleen Contraction and Exercise Endurance.

This study investigated how shear stress signaling in endothelial cells regulates spleen physiology and exercise performance via the mechanosensitive ion channel Piezo1. It showed that shear stress triggers release of medium/large extracellular vesicles from endothelial cells through Piezo1 activation, promotes Piezo1 translocation to the cell periphery, and enables trafficking to smooth muscle cells in the splenic capsule where Piezo1 acts downstream of the α1-adrenergic receptor to boost spleen contraction and exercise endurance. The work links vascular mechanotransduction to systemic exercise benefits and suggests Piezo1/EV pathways as targets for improving functional capacity.

Lou J, Yang M, Hu Y et al. · Journal of extracellular vesicles · (2026) · View on PubMed ↗ · Free PDF ↗

2026 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

This article is a guideline development report that studied the evidence base for perioperative cardiovascular evaluation and management in adult patients undergoing noncardiac surgery, synthesizing literature from August 2022 to March 2023 across major databases. It produced the 2026 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM recommendations for perioperative cardiovascular management. Clinically, it provides an updated, evidence-based framework to standardize risk assessment and management strategies around surgery, aiming to reduce perioperative cardiovascular complications.

Thompson A, Fleischmann KE, Smilowitz NR et al. · Circulation · (2026) · View on PubMed ↗

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Metabolic disease, obesity & incretin therapies

Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.

Retatrutide, a GIP/GLP-1/glucagon receptor agonist, was studied in adults with obesity and type 2 diabetes enrolled in the international phase 3 TRIUMPH-2 double-blind randomized placebo-controlled trial. Retatrutide improved efficacy outcomes with an acceptable safety profile compared with placebo (full effect sizes and adverse-event details are not visible in the provided abstract text). These findings support retatrutide as a potential multi-receptor incretin-based therapy for adults with obesity plus type 2 diabetes, a population with high unmet needs for weight and glycemic control.

Bellido V, le Roux CW, Ekinci EI et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Potential bone marrow-driven reduction of circulating inflammatory monocytes by semaglutide in Type 2 diabetes.

This human translational study assessed whether semaglutide reduces circulating inflammatory monocytes via a bone marrow–cardiovascular–hematopoietic axis in people with type 2 diabetes (n=16). The key finding was that semaglutide was associated with a reduction in inflammatory monocyte measures consistent with a bone marrow-driven mechanism, aligning with GLP-1 receptor agonist anti-inflammatory effects observed experimentally. Clinically, it provides mechanistic support for semaglutide’s cardioprotective benefits in T2D by implicating modulation of hematopoiesis and monocyte-driven inflammation.

Teunis CJ, Collins TJC, Oostveen RF et al. · European heart journal · (2026) · View on PubMed ↗

Indirect comparative efficacy and safety of tirzepatide vs semaglutide for the treatment of obesity or overweight in patients without type 2 diabetes.

This indirect comparative efficacy and safety study evaluated tirzepatide (5, 10, 15 mg weekly) versus semaglutide 2.4 mg weekly in adults with obesity or overweight without type 2 diabetes using adjusted and unadjusted indirect treatment comparisons across STEP 1 and SURMOUNT-1 endpoints. It compared outcomes at primary endpoints (Week 68 for STEP 1 and Week 72 for SURMOUNT-1) under a shared background of reduced-calorie diet and increased physical activity. The results are clinically relevant for informing relative benefits and risks of these anti-obesity therapies when head-to-head trials are unavailable.

Ciudin A, Johansson E, Zimner-Rapuch S et al. · International journal of obesity (2005) · (2026) · View on PubMed ↗ · Free PDF ↗

Sarcopenia as a manifestation of systemic energetic failure with ageing.

This Personal View examined whether sarcopenia in older adults should be conceptualized as a disorder of skeletal muscle alone versus a systemic process of age-related energetic failure. The authors propose that disrupted coordination of energetic demand and supply across integrated physiology drives progressive muscle dysfunction, reframing sarcopenia as a manifestation of systemic energetic failure. This shift could improve diagnosis and treatment strategies by targeting whole-body energy regulation rather than treating sarcopenia as purely intrinsic to muscle.

Ferrucci L, Donega S, Picca A et al. · The lancet. Healthy longevity · (2026) · View on PubMed ↗ · Free PDF ↗

Mild caloric restriction accelerates atherosclerosis via dysregulated cholesterol homeostasis and lipogenesis in HCHF-fed ApoE-deficient mice.

The study examined whether mild caloric restriction (MfR; ~5% lower body-weight gain) accelerates atherosclerosis in ApoE-deficient mice fed a high-cholesterol/high-fat (HCHF) diet, using histologic atherosclerotic burden quantification and hepatic lipidomics by ESI-MS/MS alongside plasma lipidomics from cardiovascular disease (CVD) patients. MfR improved insulin sensitivity but produced dysregulated cholesterol homeostasis and increased lipogenesis, leading to greater pro-atherogenic lipid remodeling and accelerated atherogenesis. These findings suggest that modest weight loss can paradoxically worsen cardiovascular risk in susceptible metabolic contexts, highlighting lipid-homeostasis pathways as potential targets for risk stratification and therapy.

Zhu Y, Xu Y, Liebisch G et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome, gut metabolites & therapy response

Microbial aldehyde-alcohol dehydrogenase degrades metformin to limit therapeutic response in type 2 diabetes.

The study investigated whether gut microbial metabolism directly inactivates metformin, focusing on a gut microbial aldehyde-alcohol dehydrogenase gene AdhE from Eubacterium species enriched in low metformin responders with type 2 diabetes. AdhE converted metformin into pharmacologically inactive products, reducing intestinal and systemic metformin exposure, and genetic deletion or phage-mediated depletion of AdhE-producing Eubacterium hallii MD1 restored metformin exposure and glycemic control in mice. This mechanistic microbiome finding identifies AdhE as a target to improve metformin efficacy and motivates precision strategies (e.g., microbiome modulation) for variable drug response.

Zhao Y, Peng C, Xia Y et al. · Cell metabolism · (2026) · View on PubMed ↗

Gut microbiota primes stroke severity via the AHR in intestinal dendritic cells.

The study examined how gut microbiota influences ischemic stroke severity via the aryl hydrocarbon receptor (AHR) in intestinal dendritic cells, using mouse models and patient association data enriched for indole-producing Escherichia coli. Microbial indole activated an AHR-dependent dendritic-cell response, and DC-specific AHR deletion improved stroke outcomes while preserving intestinal conventional type 1 DCs. Clinically, this supports AHR signaling in intestinal DCs as a mechanistic bridge between gut microbes and stroke severity and suggests that AHR inhibition could modulate immune trafficking to the meninges.

Delgado Jiménez R, Ruggles A, Adedokun MA et al. · Cell · (2026) · View on PubMed ↗

Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort.

This study analyzed gut microbiome signatures linked to cancer and treatment adverse events in a real-world mixed-cancer cohort (Mayo Clinic Cancer Microbiome) including 1,364 cancer patients and 287 healthy controls. Using a framework to account for non-specific associations with cancer, comorbidities, and demographics, it identified 341 cancer-associated species across five cancer classes as plausible contributors to cancer pathogenesis, and it further related microbiome patterns to adverse events within cancer classes (specific adverse-event results are not fully shown in the truncated abstract). The work advances microbiome biomarker development by improving specificity for cancer-related signals and enabling risk stratification for treatment-related complications.

Yang L, Singh V, Gawey BJ et al. · Cell · (2026) · View on PubMed ↗

VI Spanish Consensus Conference on the treatment of Helicobacter pylori infection.

This VI Spanish Consensus Conference synthesized evidence and produced 25 recommendations for treating Helicobacter pylori infection in the Spanish population. The key finding was consensus-driven guidance reflecting updated treatment regimens and the current evidence base, derived from a systematic literature search and iterative expert voting. Clinically, it provides an updated national framework to standardize H. pylori eradication therapy and improve outcomes such as ulcer prevention and gastric cancer risk reduction.

Gisbert JP, Alcedo J, Amador J et al. · Revista espanola de enfermedades digestivas · (2026) · View on PubMed ↗

Differential Sperm DNA Methylation Profiles in Healthy Men With High Versus Low Adherence to the Mediterranean Diet in the Led-Fertyl Study.

This cross-sectional Led-Fertyl study examined whether high versus low adherence to the Mediterranean diet (MedDiet) is associated with differential sperm DNA methylation profiles in 60 healthy men aged 18–40 years. The key finding was that MedDiet adherence level correlated with distinct sperm DNA methylation patterns, consistent with diet-related modulation of the sperm epigenome. This supports a mechanistic link between maternal/partner lifestyle and potential offspring health via heritable epigenetic marks.

Agarwal R, Babio N, Davila-Cordova E et al. · Andrology · (2026) · View on PubMed ↗ · Free PDF ↗

Polymeric alpha-1 antitrypsin perturbs Paneth cell proteostasis and exacerbates intestinal inflammation.

This study tested whether polymeric alpha-1 antitrypsin (AAT), relevant to SERPINA1 PiZ/AAT deficiency, disrupts intestinal epithelial proteostasis and worsens inflammation using PiZ transgenic mouse models. Polymeric AAT perturbed Paneth cell proteostasis and exacerbated intestinal inflammatory phenotypes. The findings support a mechanistic link between AATD and inflammatory bowel disease biology, suggesting that targeting AAT polymerization/proteostasis pathways could be therapeutic.

Annunziata F, Dos Santos Matos F, Relvini I et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer and the microbiome: from association to intervention.

This review studied how the gut microbiome influences cancer therapy outcomes, focusing on evidence from patients receiving immune checkpoint inhibitors (ICIs) across cancers such as melanoma, non-small-cell lung cancer, and renal cell carcinoma. It reports that higher microbial diversity, ecological stability, and enrichment of immunostimulatory pathways are associated with improved ICI response and survival, while antibiotics and other microbiome-disrupting factors can worsen outcomes. The scientific significance is that microbiome modulation may become a clinically actionable strategy to improve efficacy and reduce toxicity of systemic cancer treatments.

Moradi A, Winayak R, Pal SK · The Lancet. Oncology · (2026) · View on PubMed ↗

Opposing functions of gut immunomodulatory metabolites on CAR-T therapy.

This study examined how gut immunomodulatory metabolites and antibiotic exposure affect outcomes of CAR-T cell therapy in 129 patients with hematologic malignancies treated across three German centers. Shotgun metagenomics and targeted mass spectrometry showed that lower short-chain fatty acids—especially valeric acid—before CAR-T predicted higher risk of disease progression, while higher indole metabolites (indole-3-carboxaldehyde, indole-3-acetic acid) and the branched-chain fatty acid isovaleric acid were associated with different (opposing) effects on progression risk. These findings suggest metabolite-specific gut modulation could be used to improve CAR-T efficacy and stratify patients by pre-treatment microbiome chemistry.

Perl M, Guetter S, Shah D et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Extracellular Vesicle-Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism.

This study investigated how extracellular vesicle (EV)-encapsulated small RNAs from the probiotic bacterium Clostridium butyricum modulate host intestinal lipid metabolism in piglets. Piglets with higher crude fat digestibility showed increased lipid absorption/oxidation and reduced C. butyricum abundance in ileal mucosa, while oral C. butyricum suppressed lipid absorption and oxidation by inhibiting PPARα signaling, and C. butyricum-derived EVs delivered small RNAs into intestinal epithelial cells to mediate these effects. The work provides a mechanistic basis for microbiota-derived EV small RNAs as regulators of lipid uptake and suggests potential for targeted microbiome-based metabolic interventions.

Hu H, He Y, Liang J et al. · Journal of extracellular vesicles · (2026) · View on PubMed ↗ · Free PDF ↗

Personalized whole-body modeling links gut microbiota to metabolic perturbations in Alzheimer’s disease.

The study tested whether personalized whole-body metabolic models that link gut microbiota to blood metabolic perturbations in Alzheimer’s disease (AD) can predict outcomes in real AD cohorts, using data from AD dementia patients and individuals with mild cognitive impairment (MCI) and probable AD. The authors evaluated prior model predictions against observed metabolic perturbations in these clinical groups to validate the gut–metabolism link in AD. If confirmed, this approach could enable microbiome-informed, patient-specific metabolic risk modeling and guide interventions targeting gut communities to alter AD-related metabolic dysfunction.

Hensen T, Khatib L, Patel L et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Screen Use and Child and Adolescent Development and Mental Health Outcomes: A Quantitative Umbrella Review.

This quantitative umbrella review synthesized and quantified meta-analytic evidence linking screen-based media exposure with developmental outcomes and mental health in children and adolescents (≤18 years). It found that screen exposure was associated with measurable but variable effects across outcomes, with the strength and direction depending on outcome type and study design. The consolidated estimates help policymakers and clinicians interpret the evidence base for screen-related risks and guide more targeted recommendations.

Al-Jbouri E, Nivison MD, Neville RD et al. · JAMA pediatrics · (2026) · View on PubMed ↗

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Molecular/cellular mechanisms & structural biology

Complexome profiling of mitochondria in the myzozoan parasite of oysters, Perkinsus marinus.

The study used complexome profiling proteomics to characterize mitochondrial complex composition in the myzozoan oyster parasite Perkinsus marinus, addressing whether enlarged/divergent mitochondrial complexes seen in apicomplexans are conserved across broader unicellular eukaryote lineages. It profiled components of mitochondrial electron transport chain complexes, ATP synthase, mitochondrial ribosome, and the TOM complex to define the parasite’s mitochondrial complex architecture (details are truncated in the provided abstract). This work improves understanding of mitochondrial evolution and may reveal lineage-specific vulnerabilities relevant to controlling parasitic infections in aquaculture.

Maclean AE, Iorillo O, Faktorová D et al. · PLoS pathogens · (2026) · View on PubMed ↗

The role of organelles as mechanotransducers.

This narrative review summarized evidence that intracellular organelles act as mechanotransducers, extending mechanotransduction beyond plasma membrane receptors, focal adhesions, and the cytoskeleton. The key finding was that organelles including the endoplasmic reticulum, nucleus, Golgi apparatus, mitochondria, and endolysosomal system can sense and transduce both external mechanical forces (e.g., matrix stiffness, shear stress) and internal forces (e.g., actomyosin contractility). This reframes mechanobiology toward organelle-centered signaling, guiding future research on how mechanical cues regulate cellular function and disease.

Rawal S, Marwaha R, Das T · The FEBS journal · (2026) · View on PubMed ↗

A metabolic-epigenetic switch governs multicellular cardiac repair following succinate dehydrogenase inhibition.

This study investigated how a metabolic-epigenetic switch governs multicellular cardiac repair after succinate dehydrogenase (SDH) inhibition using malonate and integrated single-nucleus RNA sequencing with ATAC-seq. The key finding was that SDH inhibition triggers coordinated transcriptional and chromatin reprogramming across cell types, and that cardiomyocyte-specific Sdhb deletion increased cardiomyocyte proliferation transiently but did not improve post–myocardial infarction function, implicating non-cardiomyocyte contributions (myofibroblast-related results are truncated). Scientifically, it identifies cell-type-specific regulatory logic that could be targeted to enhance adult heart regeneration.

Fan Y, Nuttall DJ, Zhao Y et al. · Nature cardiovascular research · (2026) · View on PubMed ↗

PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.

This mechanistic study identified a pathway linking mitochondrial depolarization to GSDME-dependent pyroptosis via the PINK1–Parkin axis and regulation by PTEN-L. The key finding was that PTEN-L inhibits this process, whereas mitochondrial depolarization activates PINK1-Parkin signaling to promote MCL-1 ubiquitination/degradation, cytochrome c release, caspase-3 activation, and GSDME cleavage and membrane targeting. This is significant because it connects mitochondrial quality-control signaling to inflammatory cell death, offering potential targets to modulate pyroptosis in disease.

Yan C, Huang C, Liu X et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Accelerated discovery of thermostable mRNA-lipid nanoparticle vaccines using data-efficient AI.

This work studied an AI-guided, data-efficient experimental framework (AGENT: Algorithm-Guided Experimental design for lipid Nanoparticle Thermostabilization) to discover thermostable mRNA-lipid nanoparticle (LNP) formulations. AGENT used high-throughput experimentation with Bayesian optimization to rapidly identify lipid compositions that improve mRNA-LNP thermostability for more practical storage and distribution. The approach is significant because it accelerates development of temperature-tolerant mRNA vaccines and can broaden deployment to delivery platforms such as microneedle patches.

Tian J, Tran KTM, Pogostin BH et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing.

The study investigated whether incorporating large RNA cargo size into ionizable lipid screening can improve in vivo genome editing using lipid nanoparticles (LNPs) in animal models. A 384-lipid combinatorial screen using a 5.7-kb ABE-NanoLuc reporter mRNA identified large-cargo-optimized lipids led by LC-1, which produced higher Cas9 knockout and ABE-mediated reporter correction than comparator LNPs (including LP-01 and ALC-0315) after intravenous, intrathecal, and intratracheal dosing. This is clinically important because it enables more potent delivery of large mRNAs for genome editing across multiple tissues and administration routes.

Dong S, Gong F, Thomson T et al. · Nature biotechnology · (2026) · View on PubMed ↗

Cell atlas of the developing human meninges reveals a dura-like nature of meningiomas.

This study examined the cellular origins of meningiomas by generating a comprehensive single-cell and spatial transcriptomic atlas of human fetal meninges from postconception weeks 5–13. It found that meningeal layer development and molecular features support a dura-like nature of meningiomas, providing molecular evidence linking meningiomas to dura-associated biology. The atlas is significant because it clarifies meningioma lineage and may guide future targeted therapies for tumors that currently lack effective medical treatments.

Vinsland E, Marco Salas S, Kapustová I et al. · Nature cell biology · (2026) · View on PubMed ↗ · Free PDF ↗

Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics.

This work studied human meningeal development by constructing paired single-nuclei RNA-seq and ATAC-seq (scRNA + snATAC) atlases from 6 to 21 postconception weeks across cranial regions, integrating spatial transcriptomics. The multiomics analysis resolved meningeal cell types, defined gene regulatory networks for blood-brain barrier endothelial identity, and supported a yolk sac origin for meningeal myeloid lineages including perivascular macrophages primed for barrier immunity. These findings are significant because they map lineage and regulatory dynamics that can be leveraged to understand and model meningeal disease progression.

To K, Pett JP, Dufva O et al. · Nature cell biology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death.

This study investigated the molecular switch that converts RIPK1 from a prosurvival scaffold in TNFR1 complex I to a prodeath kinase in cytosolic complex II. It identified the E3 ligase HERC4 as the determinant of prodeath signaling by binding S166-phosphorylated, kinase-active RIPK1 and ubiquitinating it within the death domain. This is significant because it clarifies how TNF-induced cell death is licensed at the ubiquitination level, offering potential intervention points for inflammatory and degenerative diseases driven by dysregulated RIPK1 signaling.

Lu H, Du T, Li L et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗ · Free PDF ↗

Profiling extracellular vesicle glycoRNAs defines their function in vesicular communication.

The study profiled extracellular vesicle (EV) glycosylated RNAs (glycoRNAs) in cells by metabolically tagging glycoRNAs with bioorthogonal handles, enriching EV-associated glycoRNAs, and sequencing them, alongside proximity-based imaging to track transfer. EVs carried glycoRNAs with distinct sequence diversity, vesicle-type specificity (large vs small EVs), and cell-type/passage-dependent transfer dynamics, revealing vesicle-specific sorting signatures. These findings expand the EV glycoRNA landscape and provide a mechanistic framework for how glycoRNAs mediate vesicular communication, potentially enabling glycoRNA-based biomarkers or therapeutic targeting.

Chen X, Hao C, Chen X et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗

Recoding by N1-methylpseudouridine guides rational mRNA vaccine design.

The research studied how N1-methylpseudouridine (m1Ψ) affects translational frameshifting during mRNA translation to guide rational mRNA vaccine design, using dual-fluorescence reporter mRNAs in cells, fully in vitro reconstituted translation, and single-molecule FRET. m1Ψ increased +1 frameshifting on UUUC motifs, and the work mapped the mechanism underlying this recoding behavior. This is significant for vaccine engineering because it quantifies and mechanistically explains a potential source of unintended antigenicity, informing safer mRNA modification strategies.

Poulis P, Robecchi G, Kurochkina AO et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Treatment of Canine Atopic Dermatitis: Updated Guidelines From the International Committee on Allergic Diseases of Animals (ICADA).

These updated ICADA guidelines reviewed evidence for treating canine atopic dermatitis (cAD) and organized recommendations into reactive therapy to resolve existing pruritus/lesions and proactive therapy to prevent flares. The key finding is a mechanism-of-action–based, two-phase treatment framework intended to standardize individualized short- and long-term management. Clinically, this provides a practical evidence-informed approach for veterinarians to reduce symptoms and maintain remission in genetically and immunologically complex cAD.

Mueller RS, Banovic F, Bensignor E et al. · Veterinary dermatology · (2026) · View on PubMed ↗ · Free PDF ↗

Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis.

This MESILICO long-term follow-up study evaluated whether mepolizumab (an anti–IL-5 biologic) produces sustained airway remodeling changes in severe asthma responders using bronchoscopy-based tissue sampling at 3 years. The study measured remodeling indices and tissue markers including submucosal eosinophils, Muc-5AC, E-cadherin, and FOXP3+ regulatory-like cells to characterize longer-term structural effects. Clinically, it extends understanding of whether IL-5 blockade yields durable modification of airway pathology beyond symptom control.

Rivalta B, Wolkewitz M, Kusters M et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of garetosmab, an activin A-blocking antibody, in fibrodysplasia ossificans progressiva (OPTIMA): a randomised, double-blind, placebo-controlled, phase 3 trial.

This phase 3 randomized, double-blind, placebo-controlled trial studied garetosmab, an activin A-blocking antibody, in adults with fibrodysplasia ossificans progressiva (FOP) caused by heterozygous gain-of-function ACVR1/activin receptor type 1A mutations. Garetosmab was evaluated for efficacy and safety to prevent or reduce heterotopic ossification driven by aberrant activin A (ActA) signaling through ACVR1. If effective, this would provide a targeted disease-modifying therapy for FOP by blocking the ActA–ACVR1 pathway.

Papa R, Rhee S, Delai P et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Cargo crosslinking nucleates AP-1 lattice formation.

This structural biology study used cryo-electron microscopy to determine how cargo nucleates adaptor protein complex AP-1 lattice formation. It revealed that a single cargo molecule with tandem sorting motifs can bridge two neighboring human AP-1 complexes, promoting AP-1 lattice assembly at resolutions of 3.5–4.0 Å. The significance is a mechanistic, cargo-driven explanation for how coat assembly is initiated, informing models of vesicle trafficking and cargo selection.

Deng H, Jia G, Yang Q et al. · Cell · (2026) · View on PubMed ↗

Non-invasive control of gene editing in vivo by photoswitchable Cas12f and focused ultrasound.

This in vivo study developed a photoswitchable CRISPR system using compact photoswitchable Cas12f (psCas12f) co-delivered with its sgRNA in a single AAV particle and activated non-invasively with focused ultrasound. The key finding was that psCas12f activity could be controlled spatiotemporally in deep tissues in vivo using focused ultrasound to trigger photoswitching, enabling restricted gene editing. The clinical/scientific significance is a step toward safer, externally controllable gene editing compatible with AAV delivery.

Song D, Malinao MG, Wu X et al. · Cell · (2026) · View on PubMed ↗

H3K27me3 loss and METTL3-m6A converge to upregulate SOX11/SMARCA4 and drive H3K27-altered spinal cord glioma stemness and proliferation.

This study examined how loss of the histone mark H3K27me3 and METTL3-mediated m6A RNA modification cooperate to drive stemness and proliferation in H3K27-altered spinal cord glioma. Using patient-derived spinal cord H3-DMG stem-like spheres and differentiated cells, the authors applied multi-omics (single-cell RNA-seq, spatial transcriptomics, RNA m6A profiling, CUT&Tag, and ATAC-seq) to show convergence of H3K27me3 loss with METTL3-m6A upregulation of SOX11 and SMARCA4, promoting glioma stem-like behavior and growth. The findings connect epigenetic and epitranscriptomic regulation to key transcriptional drivers (SOX11/SMARCA4), highlighting METTL3-m6A and H3K27 pathways as potential therapeutic leverage points.

Yan H, Jin J, Chang Y et al. · Neuro-oncology · (2026) · View on PubMed ↗

Effectiveness, safety, and clinical outcomes of treatment with the oral α4-integrin antagonist carotegrast methyl in patients with active ulcerative colitis: a multicenter observational study (CANAL study).

This multicenter retrospective CANAL study evaluated the real-world effectiveness and safety of the oral α4-integrin antagonist carotegrast methyl in patients with active ulcerative colitis who had inadequate response to 5-aminosalicylate (5-ASA). The primary endpoint was clinical response at week 8, with remission and response/remission outcomes assessed through up to 52 weeks and adverse drug reactions tracked during and after treatment. The study informs how carotegrast methyl performs outside clinical trials and supports evidence for its clinical utility in 5-ASA–inadequate responders.

Hirai F, Matsuoka K, Watanabe K et al. · Inflammatory bowel diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Nuclear cGAS inhibits stimulation-induced inflammatory gene transcription via HDAC1.

This work studied nuclear cyclic GMP-AMP synthase (cGAS) in macrophages stimulated with lipopolysaccharide (LPS) to determine how nuclear cGAS regulates inflammatory transcription independently of STING. Nuclear cGAS acted as a transcriptional repressor that selectively suppressed primary response inflammatory genes such as Cxcl1 and Tnf, requiring nucleosome binding but not cGAS enzymatic signaling. The results identify a STING-independent, chromatin-associated mechanism by which cGAS can dampen innate immune gene programs, informing how cGAS biology might be therapeutically modulated to control inflammation.

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

Zinc mediates the allosteric activation of Shiftless to suppress programmed -1 ribosomal frameshifting.

The study investigated how zinc regulates the interferon-stimulated restriction factor Shiftless (SHFL) to suppress programmed -1 ribosomal frameshifting (-1 PRF) across viral and cellular contexts. SHFL orthologs inhibited -1 PRF broadly and conservedly in mammals, with inhibition requiring zinc ions and SHFL zinc finger domains. This mechanistic link between zinc-dependent SHFL activity and frameshifting suppression provides a clearer molecular basis for antiviral restriction and potential host-targeted strategies.

He ST, Zheng Y, Ying R et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Cnidarian mechanosensory cells as ancestors of vertebrate hair cells: Molecular targeting of an ancient mechanotransduction complex.

Researchers examined the evolutionary relationship between cnidarian mechanosensory nematocytes and vertebrate hair cells by molecularly targeting an ancient mechanotransduction complex, focusing on mechanotransduction components such as TMC1/TMC2. The study found that cnidarian mechanosensory structures and associated molecular features resemble vertebrate hair-bundle mechanotransduction components, supporting an ancestral origin of the METC. These findings advance understanding of how vertebrate hearing/balance machinery evolved and identify conserved mechanotransduction elements that can guide comparative functional studies.

Banday ZZ, Randich AM, Hulse RE et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Human antibody heavy chain variable region exon interacts with the 3’ regulatory region to form a stable somatic hypermutation center.

The study investigated how the human immunoglobulin heavy chain variable region exon interacts with the 3’ regulatory region (3’RR) to form a stable somatic hypermutation center (SHM-C), using a human RAMOS germinal center B-cell SHM model. The authors tested a cohesin-mediated loop extrusion model that juxtaposes enhancers including the 3’ Igh regulatory region with the V(D)J exon to create privileged AID access for SHM. Establishing a structural/functional basis for SHM-center formation clarifies how genome architecture directs antibody diversification and may inform engineering or therapeutic modulation of adaptive immunity.

Guan Y, Mikhova M, Yang Z et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Step-by-step maturation mechanism of the binary toxin pore revealed by cryo-EM analysis.

This work used cryo-electron microscopy (cryo-EM) to determine the step-by-step maturation mechanism of the binary toxin pore formed by the membrane-binding component Ib from a bacterial binary toxin system. The authors resolved multiple oligomeric structures of Ib that illuminate how the pore forms initially and progresses toward a functional translocation state. These structural insights improve mechanistic understanding of binary toxin entry and can support rational development of inhibitors or vaccines targeting early pore-formation steps.

Yamada T, Nakanishi R, Sugita Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

PfATG18 links V-ATPase assembly to endocytic membrane dynamics in malaria parasites.

The study examined how the malaria parasite autophagy-related protein 18 (PfATG18) regulates digestive vacuole membrane dynamics by linking V-ATPase assembly to endocytic membrane trafficking, using conditional reverse genetics, quantitative live-cell imaging, and 3D electron microscopy in Plasmodium falciparum. PfATG18 loss caused vacuole fragmentation and impaired coordination between vacuolar membrane homeostasis and hemoglobin-filled vesicle influx, with downstream effects on hemoglobin processing relevant to parasite survival and drug susceptibility. These findings identify PfATG18 as a mechanistic regulator of vacuolar function and a potential target for antimalarial strategies that disrupt hemoglobin processing.

Schmitz Y, Sengupta M, Schneider C et al. · PLoS pathogens · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on September 30, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.