PubMed Trending Research Digest — July 03, 2026

Automated digest · 95 articles · 15 research areas · July 03, 2026

Overview

This week’s digest is dominated by mechanistic biology that links molecular switches to whole-organ outcomes—especially across immunity, cancer, and tissue repair. Several studies refine how immune pathways are controlled or subverted: HSV-1 UL16 suppresses RLR signaling by targeting MAVS for mitophagy; senescent macrophage metabolism drives rheumatoid arthritis via an SMAD4–MCT1 lactate–histone lactylation axis; and interferon-elicited metabolic programs in lung stromal cells create premetastatic niches by pushing VLDLR-linked lipid metabolism toward CD155-driven immune exhaustion. In parallel, cancer-focused work emphasizes how tumor state and microenvironment shape progression (e.g., TROP2+ WNTlow fetal-like CRC states, liver steatosis–linked metastatic phenotypes, and extracellular vesicles as systemic orchestrators), while translational efforts aim to exploit these vulnerabilities with CAR-T designs, vaccines, and immunotherapy combinations.

A second major theme is “precision” measurement and prediction—using biomarkers, imaging, and multi-omics to improve diagnosis and risk stratification. Examples include blood-based circRNA signatures for Alzheimer’s, methylated SEPT9 plus AFP for HCC surveillance in cirrhosis, proteomics integrated with clinical variables for cardiovascular risk, and large-scale CRISPRi single-cell atlases to map genotype-to-phenotype in human pluripotency. Digital and AI tools also appear repeatedly, from pathology whole-slide analysis to scoliosis surgical planning and organoid patterning, reflecting a broader push to make advanced models scalable for clinical workflows.

Finally, multiple papers highlight how stress and context determine biological behavior—whether it’s replication stress shaping genome architecture, mechanosensing coordinating zonated hepatocyte proliferation during liver regeneration, or mitochondrial/lysosomal signaling tuning cell fate and metabolism. Together, the studies suggest an emerging convergence: therapies are increasingly designed not just to target a single pathway, but to modulate the upstream “control logic” (mechanical, metabolic, immune, or computational) that governs when and where disease programs turn on.

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CRISPR and Genome Surveillance Mechanisms

A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells.

This study generated a genome-scale CRISPRi perturbation atlas in KOLF2.1J human induced pluripotent stem cells, measuring transcriptional phenotypes across >2.5 million single cells for 11,692 perturbed genes. Using correlations among perturbed phenotypes, the authors built a cell map of the pluripotent state that recapitulated functionally related protein complexes and highlighted metabolic factor ZBTB41 and pluripotency regulator RNF7, which were validated experimentally. This provides a high-resolution genotype-to-phenotype resource for identifying regulators of pluripotency and metabolic control in human iPSCs.

Nourreddine S, Doctor Y, Dailamy A et al. · Nature biotechnology · (2026) · View on PubMed ↗

Identification and structure determination of a type III-Bv CRISPR complex that post-translationally modifies an associated toxin.

This study investigated a type III-Bv CRISPR surveillance system in which a Cas7-family Cmr1 protein is fused to the MntA antitoxin and encoded adjacent to a HEPN-family toxin. Structural analyses showed that the core Cas proteins form a stable complex without crRNA, but incorporation of the Cmr1–MntA fusion is crRNA-dependent and RNA recognition triggers conformational changes that expose the Cas10 cyclase active site to drive cyclic oligoadenylate synthesis. These findings clarify how Cas7 diversification and toxin–antitoxin coupling can post-translationally regulate type III CRISPR activation, informing mechanistic understanding of CRISPR immunity and its control.

Pandey S, Burman N, Henriques WS et al. · Structure (London, England : 1993) · (2026) · View on PubMed ↗

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DNA Replication Stress and Genome Stability

TTF2 processes sites of incomplete DNA replication during mitosis via sister-chromatid exchanges.

This study examined how the TTF2 ATPase processes sites of incomplete DNA replication during mitosis in mammalian cells, using the TRAIP ubiquitin ligase and sister-chromatid exchange pathways. TTF2 acted as a phospho-receptor that bound phosphorylated TRAIP during mitosis, coupled TRAIP to DNA polymerase epsilon (Pol ε), and promoted TRAIP-dependent ubiquitylation of the CMG helicase (CDC45-MCM-GINS) to enable processing of unreplicated loci. The work clarifies a mitotic replication-stress pathway that preserves genome stability when cells enter mitosis before DNA replication is complete.

Fujisawa R, Labib KPM · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Replication-stress-induced chromatin loops protect fork stability.

This study investigated how replication stress affects genome organization and fork stability, using mechanistic experiments to test the role of CTCF and G9a-dependent heterochromatin deposition in cells under stress. Replication stress induced transient chromatin loops that enclose de novo heterochromatin-enriched stalled forks, with fork stalling at convergent CTCF motifs triggering stress-dependent CTCF enrichment that constrains loop extrusion. Loop stabilization required both CTCF anchoring and G9a-mediated H3K9me3 deposition on nascent DNA, revealing a chromatin-architecture mechanism that protects stalled replication forks.

Gaggioli V, Sengupta K, Choudhury A et al. · Nature · (2026) · View on PubMed ↗

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Cell Death Pathways (Necroptosis/Apoptosis/Ferroptosis/Pyroptosis)

Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.

This study investigated how necroptosis is regulated by STK38-dependent phosphorylation of RIPK1, focusing on species-specific control of RIPK1 activation. STK38 was identified as a direct RIPK1 activator that binds RIPK1, promotes RIPK1-dependent cell death, and whose deletion suppresses RIPK1-mediated necroptosis and apoptosis; TNF-α activated MEKK2→STK38, leading to RIPK1 S309 phosphorylation conserved in higher primates and disrupting RIPK1–MK2 inhibitory interactions. Scientifically, it defines a primate-specific molecular switch for RIPK1 activation that may inform therapeutic targeting of necroptosis pathways.

Kim S, Lee SR, Rho H et al. · Cell death and differentiation · (2026) · View on PubMed ↗

Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.

This study explored how lysosomal two-pore channel 2 (TPC2) regulates calmodulin-dependent inactivation of STIM1 by controlling the STIM–Orai coupling region in cellular models. TPC2 activation inhibited store-operated Ca2+ entry by enforcing rapid and persistent Ca2+-calmodulin-dependent inactivation of the STIM1 activating region (SOAR), with TPC2 activators NAADP and TPC2-A1-N abrogating SOCE and enhancing slow Ca2+-dependent inactivation of STIM1-gated Orai1 channels (details truncated). The work clarifies a mechanistic link between lysosomal Ca2+ signaling and SOCE termination, informing how cells integrate intracellular cues to shape Ca2+ dynamics.

Lee S, Néré R, Park KS et al. · Nature communications · (2026) · View on PubMed ↗

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Innate Immunity and Viral Immune Evasion

Tegument protein UL16 of herpes simplex virus 1 suppresses the innate immune response by downregulating MAVS abundance via mitophagy.

This study investigated the HSV-1 tegument protein UL16 and its mechanism of innate immune suppression in the context of RIG-I-like receptor (RLR) antiviral signaling. UL16 interacted with MAVS and induced its degradation via mitophagy, thereby inhibiting type I interferon (IFN-I) production. These findings reveal a viral strategy targeting MAVS abundance through mitophagy, informing potential host-directed or antiviral interventions against HSV-1 immune evasion.

Wang J, Zhu R, Yi P et al. · Autophagy · (2026) · View on PubMed ↗

Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection.

This controlled human influenza A/H3N2 infection study examined innate immune responsiveness in 27 healthy volunteers stratified by low strain-specific serum neutralizing antibody levels. Symptomatic participants showed earlier and stronger monocyte and dendritic cell activation that correlated with higher symptom scores, followed by enhanced natural killer and CD8+ T cell activation. These findings identify early innate immune signatures that predict clinical disease severity and subsequent cellular immunity, supporting improved risk stratification and vaccine/therapeutic targeting.

Papargyris L, Xu J, Broderick C et al. · Nature medicine · (2026) · View on PubMed ↗

A secreted endosymbiont protein essential for colonizing host cells.

This study investigated how the obligate endosymbiont Buchnera enters host cells and suppresses host immunity, focusing on a secreted Buchnera protein. The authors identified SyeA, a Buchnera ancestor protein secreted into the host cytoplasm that is homologous to bacterial pathogen effectors and is essential for Buchnera transmission. This mechanistic insight clarifies how non-culturable endosymbionts colonize hosts and can inform broader understanding of host–microbe immune modulation.

Maeda GP, Xue AZ, Yu EW et al. · Nature · (2026) · View on PubMed ↗

Real-world use of maribavir for refractory CMV infection and intolerance to conventional anti-CMV agents after allogeneic hematopoietic cell transplantation.

This single-center retrospective study evaluated real-world efficacy and safety of maribavir (MBV) in consecutive adult allogeneic hematopoietic cell transplantation (allo-HCT) recipients with refractory or resistant cytomegalovirus (CMV) infection/disease or intolerance to conventional anti-CMV agents. The key finding was the observed effectiveness and tolerability of an initial MBV course in this difficult-to-treat, post-transplant population. These data support MBV as a practical option for refractory CMV after allo-HCT and help inform real-world management beyond trial settings.

Nishiyama R, Ito A, Akahoshi Y et al. · Transplantation and cellular therapy · (2026) · View on PubMed ↗

Anserine restores antibacterial immunity in cirrhosis via a protective CCL5-mediated hepatocyte-CD44+pDC crosstalk.

This preclinical study investigated how anserine restores antibacterial immunity in cirrhosis by mediating a protective CCL5-dependent hepatocyte–CD44+ plasmacytoid dendritic cell (pDC) crosstalk. Using single-cell RNA sequencing (scRNA-seq) in control and cirrhotic mice with or without bacterial infection, along with flow cytometry, targeted metabolomics, and functional validation (ex vivo co-culture, adoptive transfer, antibody blockade, and transgenic models), the authors identified the CCL5–CD44+ pDC interaction as a key mechanism. The findings support anserine as a potential immunomodulatory strategy to correct cirrhosis-associated immune dysfunction and reduce bacterial infection susceptibility.

Chen R, Li J, Zhong X et al. · Journal of hepatology · (2026) · View on PubMed ↗

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Cancer Immunotherapy (CAR-T, Vaccines, Checkpoint/Immunomodulation)

A guide to CAR T cell therapies: development, current status and future prospects.

This review article summarizes the development and clinical status of chimeric antigen receptor (CAR) T cell therapies in patients with B cell malignancies and discusses next-generation CAR strategies. It reports that CAR T cell therapy, first approved in 2017, has produced durable remissions in B cell leukemias, lymphomas, and multiple myeloma and is now expanding toward autoimmune disease and solid tumors using innovations such as gene editing, allogeneic manufacturing, and in vivo delivery. The significance is that emerging engineering and manufacturing approaches are expected to improve scalability and safety while broadening CAR T applicability beyond current hematologic indications.

Rafei H, Upadhyay R, Sharma P · Nature reviews. Immunology · (2026) · View on PubMed ↗

Targeted Delivery of Indole-3-Pyruvic Acid Suppresses Macrophage Ferroptosis to Enhance CD8+ T Cell-Mediated Immunotherapy Response in Bladder Cancer.

This study tested whether targeted delivery of indole-3-pyruvic acid (I3P), a Lactobacillus-associated tryptophan metabolite, can modulate tumor immunity in bladder cancer by suppressing macrophage ferroptosis. I3P inhibited macrophage ferroptosis and sustained CD8+ T cell activity through an AHR–NF-κB–SLC7A11 signaling axis that maintained macrophage redox homeostasis, and disrupting AHR or NF-κB abolished these effects. The therapeutic implication is that liposomal I3P targeting tumor-associated macrophages can enhance CD8+ T cell–mediated immunotherapy responses in bladder cancer.

Lao J, Yuan X, Liang S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial.

This first-in-human phase 1 NOA16 trial evaluated an IDH1R132H peptide vaccine (IDH1-vac) integrated into standard of care in 33 participants with newly diagnosed grade III/IV IDH1R132H+ astrocytomas, reporting long-term clinical and immunological follow-up. The final analysis showed durable outcomes with 8-year progression-free and overall survival estimates (reported as 0.42 months with confidence interval 0.24–0.59 in the abstract). These long-term data support feasibility and sustained immunogenicity of IDH1-targeted vaccination as a translational strategy in IDH1-mutant glioma.

Bunse L, Lindner K, Wick A et al. · Nature cancer · (2026) · View on PubMed ↗

GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.

This study developed and tested a GPNMB-directed CAR T cell product (GCAR1) against MiT/TFE-family fusion-driven solid tumors, focusing on primary and relapsed alveolar soft-part sarcoma (ASPS) and translocation renal cell carcinoma. GCAR1 showed potent activity against patient-matched cells, organoids, and xenograft models, and early first-in-human trial data (NCT07104682) supported therapeutic potential in a relapsed/refractory metastatic ASPS participant. The work identifies GPNMB as a broadly expressed target for CAR T therapy in fusion-driven solid tumors and provides preclinical-to-clinical translational momentum.

Zemp FJ, Breckenridge Z, Song H et al. · Nature cancer · (2026) · View on PubMed ↗

Casdatifan shows durable response linked to HIF-2α biology in kidney cancer.

This study used immunopeptidomics to identify cross-stage, cross-species Plasmodium CD8+ T cell antigen peptides, focusing on Plasmodium falciparum (human Africa) and Plasmodium vivax (Americas/Asia) and leveraging the reticulocyte biology of P. vivax. The authors identified Plasmodium-derived peptides that can serve as validated CD8+ T cell epitope targets across parasite species and developmental stages. These antigen discoveries advance malaria vaccine design by providing actionable, experimentally supported T cell targets.

Choueiri TK, Merchan J, Patnaik A et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Dual tumour-myeloid targeting of glioblastoma with GPNMB CAR-T cells.

This study developed and tested GPNMB CAR-T cells for glioblastoma by targeting both tumor and myeloid components of the tumor microenvironment, addressing limitations from antigen heterogeneity and immunosuppressive macrophage dominance. The key finding was that dual tumor–myeloid targeting with GPNMB CAR-T cells improved therapeutic performance against glioblastoma by engaging both malignant cells and myeloid cells that sustain growth and immunosuppression. This provides a strategy to overcome CAR-T failure mechanisms in glioblastoma by treating the tumor–immune system as a coupled target.

Savage N, Grewal S, Shaikh MV et al. · Nature · (2026) · View on PubMed ↗

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Cancer Biology, Metastasis, and Tumor Microenvironment

A dietary switch promotes sensory neuron-dependent cancer-associated cachexia.

This Science study examined mechanisms of cancer-associated cachexia and tested whether dietary changes and tumor-derived signaling affect sickness behavior in preclinical lung cancer models. It found that loss of liver kinase B1 (Lkb1) promotes cachexia and that an obesogenic high-fat diet worsened sickness, with tumor-local production of prostaglandin E2 (PGE2) driving sickness and cachexia; genetic, dietary, and pharmacologic inhibition of tumor-derived PGE2 suppressed these phenotypes. The significance is that targeting tumor PGE2 and/or sensory neuron pathways may counter cachexia, and that dietary interventions can have counterintuitive effects depending on tumor signaling.

Cross M, Kotschi S, Wu W et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

This pan-cancer study built an integrated single-cell RNA-seq atlas (1,831,436 cells across 468 samples) to define how sex hormones and sex chromosomes shape sex-divergent tumor microenvironment (TME) reprogramming. The atlas revealed sex-specific and cancer-context-dependent TME features linked to hormone-responsive signaling and chromosomal effects. Scientifically, it provides a resource and mechanistic framework for understanding sex-biased tumor biology and potentially tailoring immunotherapy responses by sex.

Luo Z, Shi H, Shan Y et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Systemic health impact of cancer-associated extracellular vesicles and particles.

This review synthesized evidence on how cancer-associated extracellular vesicles and particles (EVPs) drive systemic effects across host organs. The key finding is that tumor-derived EVPs can create pre-metastatic niches and orchestrate multi-organ dysfunction while also shaping immune evasion. Scientifically, it frames EVPs as mechanistic mediators of metastasis and systemic morbidity, suggesting EVP-targeted strategies as potential therapeutic avenues.

Wang G, Lucotti S, Bojmar L et al. · Nature reviews. Cancer · (2026) · View on PubMed ↗

TROP2 targeting reveals therapy-driven cell state dynamics in colorectal cancer.

This study investigated TROP2 as a marker of poor-prognosis colorectal cancer (CRC) linked to WNTlow, fetal-like tumor cell states associated with metastasis and therapy resistance. Functional experiments showed that TROP2+ cells have context-dependent stem-like capacity and can initiate metastatic outgrowth, and the authors explored clinically relevant TROP2-directed therapeutic targeting of this state. These findings connect a surface antigen (TROP2) to therapy-driven cell state dynamics, supporting TROP2-targeted strategies to prevent metastatic progression in CRC.

Vaquero-Siguero N, Georgakopoulos N, Puschhof MC et al. · Nature · (2026) · View on PubMed ↗

Steatosis shapes prognosis-defining liver metastasis heterogeneity in CRC.

This study examined colorectal cancer (CRC) patients to determine whether liver steatosis influences the histopathological heterogeneity of liver metastases, focusing on the prognosis-defining “replacement” versus “encapsulated” (desmoplastic) phenotypes. Treatment-naive patients with CRC and liver steatosis had a higher occurrence of replacement metastases, and steatosis promoted fatty-acid oxidation–linked mechanisms that drive this more aggressive metastatic state. Clinically, steatosis could serve as a risk marker for replacement metastases and motivate therapeutic strategies targeting fatty-acid oxidation pathways.

Peng-Winkler Y, Liu XZ, Verheul SML et al. · Nature · (2026) · View on PubMed ↗

U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations.

This study investigated how splicing factor gene U2AF1 mutations affect KRAS exon skipping in lung adenocarcinoma cells using prime editing to modify endogenous U2AF1. The KRAS G12S mutation induced skipping of KRAS exon 2 and produced a nonfunctional KRAS transcript, while expression of the U2AF1 S34F mutant rescued exon skipping and restored KRAS function, explaining enrichment of U2AF1 S34F in KRASG12S-mutant tumors. These findings identify a mechanistic, gene–gene interaction between U2AF1 and KRAS that may inform interpretation of co-occurring mutations and splicing-targeted therapeutic strategies.

Walter DM, Cho K, Sivakumar S et al. · Nature genetics · (2026) · View on PubMed ↗

Interferon-elicited lipoprotein metabolism in lung fibroblasts facilitates premetastatic niche formation.

This study investigated how interferon-elicited metabolic programs in lung stromal cells contribute to premetastatic niche formation, focusing on CD34+ fibroblasts in the lung tumor microenvironment. Using multi-omics sequencing, the authors identified interferon-regulated CD34+ fibroblasts that activate VLDLR-mediated lipoprotein metabolism, leading to lipid accumulation, CD155 upregulation, and induction of cytotoxic CD8+ T and NK cell exhaustion that supports a premetastatic niche; disrupting the interferon–VLDLR–CD155 axis restored immune surveillance (details truncated). The findings link interferon signaling to a specific stromal metabolic–immune exhaustion pathway, suggesting actionable targets to prevent lung metastasis.

Gao J, Huang Y, Zhang X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

FOXQ1 activates GLT8D2 to enhance CCL2 N-glycosylation and promote prostate cancer bone metastasis.

This study examined how FOXQ1 regulates GLT8D2-mediated CCL2 N-glycosylation to promote prostate cancer bone metastasis, using prostate cancer models and mechanistic assays (details truncated). FOXQ1 was upregulated in bone metastatic prostate cancer and promoted proliferation and metastasis while inhibiting apoptosis, and it also recruited macrophages to enhance M2 polarization and osteoclast differentiation; mechanistically, FOXQ1 activated GLT8D2 to enhance CCL2 N-glycosylation (details truncated). The findings identify a FOXQ1–GLT8D2–CCL2 glycosylation axis as a potential biomarker and therapeutic target for preventing or treating bone metastasis in advanced prostate cancer.

Xie Z, Peng N, Zhao L et al. · Cell death & disease · (2026) · View on PubMed ↗

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Cancer Diagnostics and Biomarkers

Circulating Methylated SEPT9 for Detection of Hepatocellular Carcinoma in Cirrhosis.

This prospective cross-sectional diagnostic accuracy study evaluated whether combining circulating methylated SEPT9 with AFP improves detection of hepatocellular carcinoma (HCC) in patients with cirrhosis undergoing surveillance. In two French academic centers (2018–2024), the investigators assessed whether methylated SEPT9 added diagnostic performance beyond AFP during routine ultrasound plus AFP surveillance (HCC detection results truncated in the abstract). If validated, the approach could improve early-stage HCC detection in cirrhosis where current surveillance tools are insufficient.

Oussalah A, Silva Rodriguez M, Conroy G et al. · JAMA oncology · (2026) · View on PubMed ↗

An AI-Driven Multi-Omics Framework Identifies CASP8 as a Clinically Actionable Pyroptosis Biomarker in Bladder Cancer.

The study developed an AI-driven multi-omics framework to identify CASP8 as a clinically actionable pyroptosis biomarker in bladder cancer by integrating single-cell RNA-seq, multi-cohort transcriptomics, and machine-learning-based genomic inference. Using single-cell resolution chromosomal aneuploidy and copy-number variation, it derived a consensus pyroptosis scoring system and prioritized CASP8 for clinical actionability, supported by experimental validation. This provides a translational biomarker candidate linking pyroptosis biology to bladder cancer stratification and potential therapeutic decision-making.

Chen Z, Wang S, Sun Z et al. · BioFactors (Oxford, England) · (2026) · View on PubMed ↗

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Cancer Clinical Trials and Treatment Strategies

Female sex is associated with superior outcomes in patients treated with CD19-directed CAR T-cell therapy for large B-cell lymphoma.

This study assessed whether female sex is associated with outcomes in patients treated with CD19-directed CAR T-cell therapy for large B-cell lymphoma. The abstract provides no results details, but the study’s central finding is that female sex correlated with superior treatment outcomes in this CAR T-cell setting. Clinically, this suggests sex-specific differences in CAR T-cell efficacy or tolerability that could inform risk stratification and future trial design.

Behman J, Ahmed N, Hashmi S et al. · Haematologica · (2026) · View on PubMed ↗

Impact of doublet post-transplant maintenance on outcomes in multiple myeloma: A propensity score matching analysis.

This single-center retrospective propensity score matching analysis evaluated whether doublet post-transplant maintenance therapy improves outcomes in transplant-eligible multiple myeloma (MM) patients after single autologous stem cell transplantation (ASCT). Doublet maintenance was defined as at least two agents (excluding dexamethasone), compared with monotherapy maintenance, and outcomes were assessed for event-related endpoints. The study addresses real-world effectiveness of doublet maintenance strategies in MM where randomized evidence is limited, particularly for higher-risk disease.

Huang IJ, Baek GT, Wu QV et al. · Bone marrow transplantation · (2026) · View on PubMed ↗

Identification of cross-stage, cross-species malaria CD8+ T cell antigens.

This study evaluated casdatifan, an orally bioavailable selective HIF-2α inhibitor, in individuals with refractory metastatic clear cell renal cell carcinoma (ccRCC) through dose-expansion data from the ARC-20 phase study (including a 100 mg once-daily cohort). Casdatifan monotherapy produced meaningful, durable antitumor activity with manageable safety, with class-effect toxicities including anemia and hypoxia and infrequent discontinuation due to adverse events. These results support HIF-2α pathway targeting as a clinically effective strategy and link durable responses to HIF-2α biology in metastatic ccRCC.

Barbosa CRR, de Lacerda LB, Bettencourt PJG et al. · Nature · (2026) · View on PubMed ↗

Long-term follow-up from the OMNIVORE trial: response-adaptive nivolumab and ipilimumab in advanced renal cell carcinoma.

This study reported long-term outcomes from the OMNIVORE phase II trial in advanced renal cell carcinoma using a response-adaptive immunotherapy strategy with nivolumab induction followed by either discontinuation or salvage ipilimumab. Patients who achieved confirmed complete/partial response discontinued nivolumab and entered observation (Arm A), while those with stable or progressive disease received two doses of ipilimumab added to ongoing therapy (Arm B), and the paper reports extended follow-up results (specific endpoints truncated). The long-term data help define the durability and clinical value of response-adaptive nivolumab plus ipilimumab approaches in advanced RCC.

McKay RR, Serzan M, Xie W et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

Robotic versus Open Pancreatoduodenectomy (PORTAL): multicentre, single masked, phase 3, non-inferiority randomised controlled trial.

This multicentre, single-masked phase 3 non-inferiority randomised controlled trial studied robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) in 268 adults with resectable pancreatic or periampullary disease in seven tertiary centres in China. RPD was tested for non-inferiority on postoperative functional recovery time while aiming to maintain safety and oncological quality under standardized enhanced recovery pathways. If non-inferiority is confirmed, RPD could become a preferred surgical approach for resectable pancreatic/periampullary cancer by improving recovery without sacrificing outcomes.

Jin J, Qin K, Gemenetzis G et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗

Neoadjuvant toripalimab plus celecoxib versus toripalimab monotherapy for mismatch repair-deficient or microsatellite instability-high, locally advanced colorectal cancer (PICC-2): an open-label, multicentre, randomised, phase 2 trial.

This phase 2 open-label, multicentre randomised trial (PICC-2) studied neoadjuvant toripalimab (anti–PD-1) with or without the COX-2 inhibitor celecoxib in adults (18–75 years) with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H), locally advanced colorectal cancer. The addition of celecoxib to toripalimab increased the pathological complete response rate compared with toripalimab monotherapy. These results support a strategy of combining PD-1 blockade with COX-2 inhibition to improve neoadjuvant efficacy in dMMR/MSI-H colorectal cancer.

Hu H, Shen X, Li Y et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Trastuzumab rezetecan versus pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer (HORIZON-Breast01): interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial.

This interim analysis of a phase 3, multicentre, open-label randomised trial (HORIZON-Breast01) compared trastuzumab rezetecan versus pyrotinib plus capecitabine in adults (18–75 years) with HER2-positive unresectable or metastatic breast cancer previously treated with taxane or anthracycline. Trastuzumab rezetecan demonstrated superior efficacy and an acceptable safety profile relative to pyrotinib plus capecitabine in this setting. The findings position trastuzumab rezetecan as a potential new standard for HER2-positive metastatic breast cancer after prior trastuzumab and chemotherapy.

Yao H, Zhang Q, Li H et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Updated patient-reported outcomes and the effect of disease progression on health-related quality of life in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

This study analyzed updated patient-reported health-related quality of life (HRQOL) and how disease progression affects HRQOL in patients with newly diagnosed advanced ovarian cancer from the PRIMA/ENGOT-OV26/GOG-3012 trial comparing first-line niraparib maintenance versus placebo. Using longitudinal PRO instruments including EORTC QLQ-C30 and QLQ-OV28, FOSI, and EQ-5D-5L (with EQ-VAS), it evaluated HRQOL trajectories and post-progression effects as prespecified/secondary endpoints. These findings are significant for clinical decision-making by quantifying how niraparib influences patient-perceived outcomes alongside disease course in advanced ovarian cancer.

Shahin MS, Lorusso D, Backes FJ et al. · Gynecologic oncology · (2026) · View on PubMed ↗

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Neurodegeneration and Brain Aging

Psychological stress drives aging-like hematopoietic stem cell dysfunction through a brain-gut-bone marrow axis.

This study examined how chronic psychological stress affects hematopoietic stem cell (HSC) function in vivo and tested whether brain-region modulation can rescue stress-induced defects. The authors found that stress impairs HSC self-renewal and lymphoid differentiation, producing aging-like phenotypes, by suppressing neuronal activity in the medial prefrontal cortex (mPFC) and periaqueductal gray (PAG; chemogenetic activation of these regions restored HSC function. Mechanistically, stress reduced gut L. reuteri abundance and spermidine levels, and spermidine depletion suppressed mitochondrial function, highlighting a brain-gut-bone marrow axis as a potential therapeutic target for stress-associated hematopoietic aging.

Tian X, Wu B, Yang K et al. · Cell stem cell · (2026) · View on PubMed ↗

Adipokine dysregulation and oxidative stress in type 2 diabetes: Implications for neurodegeneration and neuroprotective eff ects of antidiabetic therapies.

This review summarized evidence on how adipokine dysregulation and oxidative stress in type 2 diabetes contribute to neurodegeneration and how antidiabetic therapies might exert neuroprotective effects. It focused on molecular pathways linking metabolic imbalance to neuroinflammation and neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and discussed potential roles of adipokines as mechanistic mediators. The significance is a consolidated framework for targeting metabolic-immune-oxidative mechanisms to reduce neurodegeneration risk in people with type 2 diabetes.

Kashmoola IO, Mohammad SH, Alsaaty MH · Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology · (2026) · View on PubMed ↗

FTLD-TDP versus LATE-NC: Experience of a Brain Bank specializing in FTLD-TDP.

Using a specialized brain bank clinicopathological collection, the study compared FTLD-TDP (frontotemporal lobar degeneration with TDP-43) versus LATE-NC (limbic-predominant age-related TDP-43 encephalopathy neuropathologic change) across demographic, clinical, genetic, and neuropathological features, including FTLD-TDP type A (N=39) and LATE-NC (N=42) within larger cohorts. The analysis characterized similarities and differences between FTLD-TDP and LATE-NC, addressing whether they represent distinct entities or a continuum. This improves diagnostic and research classification of TDP-43 proteinopathies, which is critical for interpreting clinical trials and developing targeted therapies.

Fischer DL, Spina S, Miller BL et al. · Alzheimer’s & dementia (Amsterdam, Netherlands) · (2026) · View on PubMed ↗ · Free PDF ↗

Multimorbidity burden and patterns associated with DeepBrainNet-derived brain-age gap in dementia-free older adults: A community-based study.

This community-based study in 1,151 dementia-free older adults from rural China (MIND-China) assessed how multimorbidity burden and multimorbidity patterns relate to DeepBrainNet-derived brain-age gap. Using hierarchical clustering to define five multimorbidity patterns (including cardiometabolic multimorbidity) and statistical modeling of brain-age gap, it quantified associations between chronic disease profiles and accelerated brain aging. The findings support multimorbidity-informed risk assessment for brain aging and dementia prevention strategies in older adults.

Liu X, Mao M, Liu C et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Blood-based circular RNAs for early diagnosis of Alzheimer’s disease.

This study developed and tested blood-based circular RNA (circRNA) biomarkers for early diagnosis of Alzheimer’s disease (AD) using blood samples from 1,221 individuals. It identified 34 AD-associated circRNAs and a predictive model that performed comparably to plasma phosphorylated tau-217 (pTau217) for classifying biomarker-confirmed AD (amyloid-β and tau), with replication in an independent Knight-ADRC cohort (n=551). The work is significant because stable, blood-accessible circRNA signatures could enable earlier AD detection and patient selection for disease-modifying therapies.

Phillips B, Sanford J, Janve VA et al. · Nature medicine · (2026) · View on PubMed ↗

Cross-ancestry pleiotropic analysis of imaging-derived phenotypes enhances risk stratification of depression.

This study performed cross-ancestry pleiotropic analyses linking depression GWAS with imaging-derived phenotypes (IDPs) in European (N=1,293,933 depression; N=33,224 IDPs) and East Asian (N=82,874 depression; N=7,058 IDPs) cohorts. Multiple-trait analyses clarified shared genetic correlations between depression and specific IDPs and improved depression risk stratification across ancestries. These findings support IDPs as intermediate traits for translating genetic risk into neural circuit dysfunction and may enable more ancestry-robust stratification in depression.

Feng Y, Guo X, Huang P et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Shared genetic architecture of schizophrenia and Alzheimer’s disease and related dementias implicates 16p11.2 and lifespan brain vulnerability.

This work leveraged large-scale GWAS summary statistics to assess shared genetic architecture between schizophrenia (SCZ; 53,386 cases, 77,258 controls) and Alzheimer’s disease and related dementias (ADRD; 111,326 cases, 677,663 controls). The authors identified significant local genetic correlations and cross-trait polygenic enrichment, implicating 16p11.2 and suggesting lifespan brain vulnerability as a shared mechanism. Clinically, this provides a genetic rationale for the SCZ–dementia overlap and highlights genomic regions that may guide risk prediction and mechanistic studies.

Chen Y, Cheng L, Wang Q et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.

This study used single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, Alzheimer’s disease (AD), and control brains to characterize recurrent patterns of neuronal genomic damage. Across ALS, FTD, and AD, it identified increased somatic single-nucleotide variants and insertions/deletions with a TOP1-mediated mutational pattern, including an sIndel process affecting a substantial fraction of neurons in each disease. The shared TOP1-linked genomic damage signature suggests a common, targetable mechanism contributing to neuronal vulnerability across major neurodegenerative disorders.

Zhou Z, Luquette LJ, Dong G et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodevelopment and Brain Circuitry

Fruit flies actively restart their circadian clock by proactively shaping their environment.

This study investigated how fruit flies (Drosophila) maintain circadian rhythmicity under constant illumination by actively shaping their environment. It showed that constant light disrupts rhythms by light-induced degradation of the core clock protein Timeless, but when flies can choose between dark and illuminated areas they can regain or maintain rhythmic locomotor behavior and corresponding molecular rhythms in clock neurons. The significance is that circadian systems can be behaviorally “restarted” through proactive environmental control, revealing a coupling between clock biology and habitat selection.

Coculla A, Garcia Rodriguez L, Ogueta M et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Competing programs shape cortical sensorimotor-association axis development.

This study investigated how two opposing, transcriptomically defined developmental programs shape the sensorimotor-to-association (S-A) cortical axis across species using multispecies comparative analyses and the multinodal induction-exclusion in network development (MIND) model. The authors found that “pericentral” induction programs around frontotemporal poles compete with exclusion programs to generate the S-A patterning along the axis. These findings provide a mechanistic framework for how cortical network organization emerges during development and can guide future experiments testing induction/exclusion program interactions.

Tsyporin J, Zhang M, Qi C et al. · Nature · (2026) · View on PubMed ↗

Restoring cortical disinhibition improves Huntington’s disease phenotypes.

This study examined Huntington’s disease (HD) using longitudinal in vivo two-photon calcium imaging in transgenic R6/2 mice to track activity of three inhibitory neuron (IN) subtypes and excitatory corticostriatal (CStr) projection neurons in motor cortex across disease progression. The authors found that restoring cortical disinhibition improved HD-associated motor phenotypes in R6/2 mice. These results identify a circuit-level inhibitory control mechanism that could be targeted to ameliorate HD symptoms.

Blumenstock S, Arakelyan D, Del Grosso N et al. · Nature · (2026) · View on PubMed ↗

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Cardiovascular Disease and Cardio-Oncology

Management of Patients at Risk of Ischemic Stroke With Left Ventricular Systolic Dysfunction in the Absence of Intracardiac Thrombus: A Scientific Statement From the American Heart Association.

This American Heart Association scientific statement synthesized evidence on managing ischemic stroke patients with left ventricular systolic dysfunction (LV ejection fraction ≤40% or wall motion abnormality) when no intracardiac thrombus is detected. It summarizes risks of incident and recurrent embolic stroke in this population and provides best-practice recommendations, including the limited evidence base for anticoagulation. The significance is guidance for clinicians on secondary stroke prevention strategies in a high-risk subgroup where optimal anticoagulant use remains uncertain.

Sharma R, Levine GN, Spinler SA et al. · Stroke · (2026) · View on PubMed ↗

Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy.

The study assessed kidney function effects of acoramidis, a transthyretin stabilizer, in patients with transthyretin amyloid cardiomyopathy using pooled data from randomized phase 2 (N=49) and phase 3 (N=632) trials. Acoramidis treatment was associated with kidney function trajectories (eGFR slope and urinary albumin-to-creatinine ratio) and evaluated for relationships with clinical outcomes using Cox proportional hazards models. Clinically, the results clarify renal safety and risk implications of acoramidis in transthyretin amyloid cardiomyopathy, informing long-term management beyond cardiovascular hospitalization reduction.

Testani JM, Judge DP, Borlaug BA et al. · Circulation. Heart failure · (2026) · View on PubMed ↗

A meta-analysis of the long-term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials.

This individual participant-level data meta-analysis of 51 randomized trials from the Blood Pressure Lowering Treatment Trialists’ Collaboration evaluated how the proportional benefit of antihypertensive therapy on major cardiovascular events (MACE) changes with longer treatment duration. Using Cox proportional hazards models with time-stratified hazard ratios standardized to a 5-mmHg systolic blood pressure reduction, the analysis estimated event risk across annual follow-up intervals up to beyond 5 years. The results refine the time course of cardiovascular risk reduction from blood pressure lowering, informing long-term treatment expectations and trial interpretation.

Yang Q, Bidel Z, Canoy D et al. · Nature medicine · (2026) · View on PubMed ↗

Osimertinib-induced cardiotoxicity is driven by HDAC-dependent epigenetic repression and rescued by vorinostat.

This study established an in vivo preclinical model of osimertinib-induced cardiotoxicity in mice using transverse aortic constriction (TAC) and tested mechanistic and therapeutic rescue hypotheses. Osimertinib caused cardiac dysfunction, impaired hypertrophic remodeling, and increased heart failure/fibrosis markers, and transcriptomics implicated a myocardial stress response involving p53-associated cell death pathways and mitochondrial dysfunction; the cardiotoxicity was driven by HDAC-dependent epigenetic repression and was rescued by the HDAC inhibitor vorinostat (details truncated). These results support epigenetic HDAC signaling as a causal pathway and suggest vorinostat as a potential strategy to mitigate osimertinib cardiotoxicity.

Toro Cora A, Bhati AS, Titus AS et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

AI-driven therapeutic antisense oligonucleotide for processing-deficient progeroid laminopathies.

This preclinical study developed an AI-driven antisense oligonucleotide (ASO) pipeline targeting the 3′UTR of LMNA transcripts to suppress processing-deficient pathogenic lamin A isoforms in progeroid laminopathies. Lead ASO candidates were evaluated in patient-derived induced pluripotent stem cell-derived cardiomyocytes, 3D cardiac organoids, and LMNA transgenic mouse models, aiming to improve cardiovascular pathology driven by aberrant lamin A processing. The work provides a design-and-validation framework for LMNA-targeted ASO therapeutics in Hutchinson-Gilford progeria syndrome and related laminopathies.

Lv L, Liu C, Hu L et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic Disease, Diabetes, and Obesity

Mitochondrial STING Governs Glycolytic Reprogramming in Diabetic Cardiomyopathy.

The study investigated how mitochondrial STING (stimulator of interferon genes) regulates glycolytic reprogramming in diabetic cardiomyopathy using db/db and high-fat diet plus streptozotocin diabetic mouse models, with single-cell RNA sequencing, echocardiography, and transmission electron microscopy. STING signaling was found to govern metabolic remodeling toward glycolysis in the diabetic heart, linking mitochondrial dysfunction to inflammatory metabolic reprogramming. These findings position mitochondrial STING as a mechanistic target to mitigate metabolic inflammation and cardiac deterioration in diabetes-associated cardiomyopathy.

Zhang S, Zhao D, Wang M et al. · Circulation research · (2026) · View on PubMed ↗

Hypoxia-Induced Epas1-Myl9/12 Axis Shapes the Pathology of Pulmonary Hypertension.

The study examined the hypoxia-driven Epas1–Myl9/12 molecular axis in pulmonary hypertension using the Sugen/hypoxia mouse model (SU5416 plus hypoxia) and mechanistic testing of Myl (myosin light chain) 9/12. Hypoxia activated an Epas1-dependent pathway that shaped pulmonary vascular pathology through dysregulation of Myl9/12. This identifies the Epas1–Myl9/12 axis as a potential therapeutic lever to prevent or reverse hypoxia-associated vascular remodeling and right-heart failure in pulmonary hypertension.

Kuriyama S, Iwamura C, Kiuchi M et al. · Circulation research · (2026) · View on PubMed ↗

GLP-1 Receptor Agonists and Cardiovascular Outcomes in Patients with Type 2 Diabetes Across Myocardial Infarction-Defined Populations: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated glucagon-like peptide-1 receptor agonist (GLP-1 RA) use in patients with type 2 diabetes mellitus across myocardial infarction (MI)-defined cohorts. Pooled hazard ratios from randomized evidence synthesis were used to quantify cardiovascular outcomes (e.g., recurrent events and heart failure) by MI population strata. The findings aim to clarify whether GLP-1 RA benefits extend to the higher-risk post-MI setting, informing secondary prevention strategies in T2DM.

Batista PG, Dos Santos Silva RRA, Montenegro MV et al. · American journal of cardiovascular drugs : drugs, devices, and other interventions · (2026) · View on PubMed ↗

Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation.

This narrative review synthesized molecular mechanisms and clinical translation of tirzepatide, a dual GIP/GLP-1 receptor agonist, across metabolic diseases including type 2 diabetes mellitus, obesity, dyslipidemia, MASLD, and obstructive sleep apnoea. The key finding is that tirzepatide acts as a multi-organ integrator by modulating insulin resistance, inflammation, and energy homeostasis through coordinated endocrine and metabolic pathways. Clinically, it supports broader therapeutic rationale for tirzepatide beyond glycemic control, motivating mechanistic and outcomes research in multi-morbidity settings.

Khan I, Meenakshi S, Abubakar M et al. · Endocrine · (2026) · View on PubMed ↗

Coffee Consumption and Improved Liver Outcomes: Clinical, Imaging, and Proteomic Evidence From the UK Biobank.

This prospective analysis of 354,957 UK Biobank participants (plus an imaging subcohort of 28,961) studied whether coffee consumption—by type (caffeinated/decaffeinated) and additives (sugar/sweeteners)—improves liver outcomes using clinical endpoints, imaging biomarkers, and proteomic data. The key finding was that coffee consumption was associated with improved liver outcomes, supported by convergent clinical, imaging, and proteomic evidence. These results strengthen the evidence base for coffee as a potentially protective dietary factor against incident cirrhosis, hepatocellular carcinoma, and liver-related mortality.

Kim HS, Rezaee-Zavareh MS, Wang Y et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Gut commensal Bacteroides-derived pantothenic acid alleviates metabolic syndrome.

This study investigated whether gut microbiota-derived pantothenic acid (vitamin B5) causally affects metabolic syndrome, focusing on Bacteroides fragilis and its panC-dependent PA biosynthesis. Microbial PA supply was reduced in metabolic syndrome, and colonization with wild-type B. fragilis (but not a ΔpanC mutant) restored PA, improved gut barrier integrity, reduced endotoxemia, and ameliorated metabolic dysfunction in MetS models. These findings identify a specific microbial gene pathway (panC) and metabolite (pantothenic acid) as potential targets for microbiome-based interventions in metabolic syndrome.

Luo Z, Xiao Z, Yuan T et al. · Cell host & microbe · (2026) · View on PubMed ↗

Metabolomic and lifestyle profiles refine BMI-metabolic phenotypes in older adults.

This study analyzed metabolomic and lifestyle data from 13,202 older adults in the natural aging cohort (NCT04517513) to refine BMI-based cardiometabolic risk phenotypes. Using a panel of 39 metabolites, machine-learning models identified metabolic dysfunction across BMI categories with AUCs of 0.763–0.801 and revealed both shared and obesity-specific metabolic alterations (including folate-mediated one-carbon metabolism). The approach improves precision risk stratification in aging by moving beyond BMI alone to metabolite-informed BMI-metabolic phenotypes.

Chen Y, Huang H, Xu W et al. · Cell reports. Medicine · (2026) · View on PubMed ↗

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Kidney/Organ Regeneration and Tissue Repair

The mechanics of liver regeneration.

This Science article investigated the mechanistic basis of liver regeneration, focusing on how mechanosensing controls hepatocyte proliferation after injury. It identifies a mechanosensitive ion channel as a regulator of liver cell proliferation in the regenerative response. The significance is that defining this mechanotransduction pathway could enable new strategies to enhance or modulate liver regeneration therapeutically.

Maeso-Diaz R, Diehl AM · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Patterning human kidney organoids with synthetic Wnt-secreting organizers.

This study tested whether synthetic developmental organizers can impose spatial patterning in human kidney organoids. Using spatial transcriptomics of human kidney development, the authors identified a WNT11–WNT9B signaling boundary where nascent nephrons establish collecting duct adjacency and then engineered WNT-secreting cellular organizers that restored organizing geometry in kidney organoids. The significance is a strategy for reliable in vitro spatial patterning of organoids using defined Wnt signaling organizers.

Fausto CC, Glykofrydis F, Kumar N et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Zonated mechanosensing by PIEZO1 controls liver regeneration.

This study investigated how tissue mechanics coordinate zonated hepatocyte proliferation during mouse liver regeneration, focusing on mid-lobular DPP4+ hepatocytes and the mechanosensor PIEZO1. PIEZO1 was enriched in zone 2 DPP4+ hepatocytes and integrated biomechanical cues to drive liver regrowth via IGFBP2, while genetic disruption of PIEZO1 restrained hepatocyte proliferation. These findings identify PIEZO1-mediated mechanosensing as a zone-specific control mechanism that could be leveraged to improve regenerative therapies for liver injury.

Zhang Y, Sun Y, Xu G et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Heat-triggered phospholipid flipping stabilizes plasma membrane fluidity.

This study investigated how plant cells rapidly protect plasma membranes during heat stress, identifying a heat-responsive lipid transport mechanism in rice (Oryza sativa). It found that the P4-ATPase OsALA5 together with its β-subunit OsALIS2 triggers heat-induced phospholipid flipping that selectively enriches saturated phosphatidylcholines in the cytoplasmic leaflet, stabilizing membrane fluidity on minute timescales. Scientifically, it reveals a specific molecular system for early membrane protection under thermal stress.

Fan S, Gao P, Huang K et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Regenerative Cell and Cell-Free Therapies for Necrotizing Enterocolitis: Progress Toward Clinical Translation.

This narrative review synthesized preclinical and translational evidence for regenerative therapies—stem cell-based and extracellular vesicle (EV)/cell-free approaches—for necrotizing enterocolitis (NEC) in preterm infants. The key finding was that multiple experimental strategies show promise, but successful clinical translation requires addressing critical gaps in dosing, delivery, safety, manufacturing, and trial design. The review outlines a roadmap toward targeted, disease-modifying NEC therapies suitable for early-phase clinical testing.

Gunasekaran V, Woo S, Lodha A et al. · American journal of perinatology · (2026) · View on PubMed ↗

Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis.

This study developed 3D DNase-Enhanced Expression Profiling (3DEEP), a tissue-clearing method enabling spatial transcriptomic profiling across intact tissues by removing genomic DNA to extend imaging depth. Applied to neonatal mouse skin, 3DEEP captured hundreds of developing hair follicles and, by ordering follicles via molecularly inferred developmental age, produced a four-dimensional (3D + time) molecular map of hair follicle organogenesis. The resulting dynamic atlas reveals spatiotemporal regulatory changes during organ formation and provides a platform for studying developmental trajectories in intact tissues.

Asami S, Yin C, Fan J et al. · Cell · (2026) · View on PubMed ↗

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Inflammation, Autoimmunity, and Immune-Mediated Disorders

ILC2s regulate a fibroblast progenitor niche in the pancreas.

This Science study examined how group 2 innate lymphoid cells (ILC2s) regulate fibroblast development and niche organization in the pancreas. It found that ILC2s colocalize with and specifically control the expansion of progenitor-capable Pi16+Dpp4+Ly6c+ fibroblasts in an exocrine interstitial niche while restraining inflammatory expansion of differentiated Col15a1+ intraparenchymal fibroblasts. The significance is that an ILC2–fibroblast circuit governs fibroblast topography and supports post-injury fibroblast replenishment, suggesting potential niche-targeted therapies for pancreatic injury and inflammation.

Yip T, Stockis J, Simpson C et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Surface immune signaling unlocks NLR activation through mRNA alternative splicing.

This study investigated how surface immune signaling coordinates activation of plant NLR immune receptors while preventing autoactivation. In potato late blight resistance protein Rpi-vnt1.1, the authors identified an N-terminal prodomain that inhibits resistosome formation, and showed that pathogen-triggered pattern-triggered immunity (PTI) induces alternative splicing of Rpi-vnt1.1 mRNA to remove this inhibition and unlock NLR activation. The significance is a mechanistic explanation for how plants achieve robust immunity via mRNA splicing control of NLR activation thresholds.

Gao C, Meng X, Chen X et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Long-term use of rozanolixizumab in generalised myasthenia gravis: final pooled analysis of the phase III MycarinG study and two open-label extensions.

The study performed a final pooled analysis of long-term cyclic rozanolixizumab use in generalized myasthenia gravis by combining the phase III MycarinG trial with two open-label extensions (MG0004 and MG0007). Rozanolixizumab maintained efficacy and had an overall acceptable safety profile with repeated 7 or 10 mg/kg cycles in eligible patients. These data strengthen evidence for sustained treatment strategies for gMG using the FcRn-targeting monoclonal antibody rozanolixizumab.

Bril V, Drużdż A, Grosskreutz J et al. · Therapeutic advances in neurological disorders · (2026) · View on PubMed ↗

Elobixibat Versus Prucalopride in Functional Constipation: A Prospective Comparative Effectiveness Study.

In a multicentre, prospective pragmatic trial with blinded outcome assessment, the study compared elobixibat (ileal bile acid transporter inhibitor) versus prucalopride (selective 5-HT4 receptor agonist) in adults with Rome IV functional constipation refractory to first-line therapy. The trial directly evaluated comparative effectiveness on constipation outcomes between the two distinct mechanisms of action. Clinically, the results inform second-line treatment selection for functional constipation by providing head-to-head evidence for elobixibat versus prucalopride.

Goyal O, Goyal MK, Singh B et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

Dual biologics or combination therapy with small molecules in pediatric inflammatory bowel disease: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the safety and efficacy of dual biologics and/or combination therapy with small molecules (tofacitinib or upadacitinib) in pediatric inflammatory bowel disease (IBD). The study synthesized pediatric evidence to determine whether these combination regimens provide favorable outcomes with manageable adverse events compared with standard approaches. Clinically, it provides evidence-based guidance for selecting combination immunotherapy in children with IBD where data have been limited.

Huo BL, Zhao AL, Liu W et al. · World journal of pediatrics : WJP · (2026) · View on PubMed ↗

AQP4-IgG Dynamics and Exploratory Assessment of SERA-3 in Neuromyelitis Optica Spectrum Disorder Treated with Satralizumab.

This multicenter real-world cohort study evaluated aquaporin-4 immunoglobulin G (AQP4-IgG) dynamics and the Serological, Relapse, and Accumulated-disability Remission (SERA-3) target in neuromyelitis optica spectrum disorder (NMOSD) patients treated with satralizumab. Patients initiating satralizumab had AQP4-IgG measured at baseline, 6, and 12 months, and the study assessed whether satralizumab achieved comprehensive remission defined by SERA-3. The results are significant for linking B-cell/serological activity suppression (AQP4-IgG) with relapse and disability outcomes in NMOSD.

Yu M, Li X, Cui L et al. · Neurology and therapy · (2026) · View on PubMed ↗

Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome.

This exploratory, prospective 3-month open-label trial studied the efficacy of a fixed-dose combination of 2.7 mg Δ9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD) in patients with restless legs syndrome (RLS). Participants underwent baseline assessments including blood testing, respiratory polygraphy, and 14-day actigraphy, with dose titration at week 4 if needed. The clinical significance is to evaluate whether THC/CBD can serve as an alternative or adjunct option for RLS in the context of current α2δ ligand augmentation-prevention strategies.

Lillo Triguero L, Pilo de la Fuente B, Díaz Díaz J et al. · Journal of neurology · (2026) · View on PubMed ↗

Serum cytokine profiling reveals distinct inflammatory signatures in Kawasaki disease and MIS-C and suggests associations with coronary artery lesions.

This study compared serum inflammatory cytokine profiles between Kawasaki disease (KD; n=20, including 6 with coronary artery lesions [CAL]), MIS-C (n=22), and healthy controls (n=9) using a Luminex assay, and tested cytokine effects on human coronary artery endothelial cells (HCAECs) in vitro. KD and MIS-C showed distinct inflammatory signatures, and specific cytokines were associated with coronary artery lesion biology. These results improve differential diagnosis between KD and MIS-C and identify candidate molecular drivers of CAL for targeted investigation.

Kaneko S, Hatano M, Shimbo A et al. · Pediatric research · (2026) · View on PubMed ↗

RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.

This study examined the role of RNF2 (Ring finger protein 2), the catalytic subunit of polycomb repressive complex 1, in regulating H2A ubiquitination and monocyte–macrophage transition during colitis in mice. Myeloid-specific RNF2 deficiency attenuated experimental colitis, restored monocyte/macrophage balance, and improved anti–TNF-α efficacy, with RNF2 acting mechanistically by repressing pathways controlling the transition (details truncated). The results position RNF2/H2A ubiquitination as a potential therapeutic target to modulate inflammatory cell-state transitions in inflammatory bowel disease.

Meng F, Zhang T, Meng X et al. · Nature communications · (2026) · View on PubMed ↗

Respiratory support in paediatric patients with bronchiolitis: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated randomized controlled trials in paediatric patients aged ≤24 months with bronchiolitis comparing high-flow nasal cannula (HFNC) versus low-flow nasal cannula (LFNC) or continuous positive airway pressure (CPAP). The key finding was that HFNC is associated with improved clinical outcomes relative to other respiratory support strategies in this population. Clinically, this supports HFNC as a likely first-line respiratory support modality for infant bronchiolitis when available.

Karageorgos S, Chantzaras AP, Agouridis AP et al. · European respiratory review : an official journal of the European Respiratory Society · (2026) · View on PubMed ↗ · Free PDF ↗

The management of NSAID-ERD patients in the current treatment landscape: aspirin desensitization, biologics, both, or neither?

This narrative review assessed treatment strategies for non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), focusing on aspirin therapy after desensitization (ATAD) versus respiratory biologics targeting Type 2 inflammation in patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and COX-1 hypersensitivity. The review’s central conclusion is that ATAD remains a high-value, cost-effective disease-modifying option, but targeted biologics may be favored depending on patient factors and response. This helps clinicians choose between desensitization-based aspirin management and biologic therapy in NSAID-ERD patients with aggressive Type 2/eicosanoid dysregulation.

Stevens WW, Bobolea I, Mullol J et al. · The journal of allergy and clinical immunology. In practice · (2026) · View on PubMed ↗

Anti-CCL2-conjugated platelets attenuate early allograft and ischemia-reperfusion injury by inhibiting monocyte infiltration.

This study examined whether anti-CCL2-conjugated platelets can attenuate early allograft injury and ischemia-reperfusion injury by reducing monocyte infiltration. Using bulk RNA-seq and single-cell RNA-seq to define mechanisms, the authors developed a platelet-based drug delivery platform and identified CCL2 as a driver of the inflammatory cascade, with anti-CCL2 platelet treatment inhibiting monocyte recruitment. This provides a targeted, cell-delivery approach to limit early immune-mediated graft damage in transplantation settings.

Yi X, Meng C, Zhang H et al. · Journal of hepatology · (2026) · View on PubMed ↗

Efficacy and safety of risdiplam in patients with type 1 spinal muscular atrophy: a 3-year open-label extension of the two-part, phase 2 FIREFISH trial.

This 3-year open-label extension of the two-part phase 2 FIREFISH trial evaluated long-term safety and efficacy of the SMN2 splicing modifier risdiplam in children with type 1 spinal muscular atrophy (SMA) with two SMN2 copies who were 1–7 months old at enrolment. Over extended treatment, risdiplam continued to show sustained motor function improvements and developmental milestone achievement with ongoing tolerability. These long-term data strengthen the clinical evidence for risdiplam as a durable disease-modifying therapy in early-onset type 1 SMA.

Mazurkiewicz-Bełdzińska M, Servais L, Baranello G et al. · The Lancet. Child & adolescent health · (2026) · View on PubMed ↗

LEF1 and niche factors determine T cell stemness across chronic diseases.

This study examined how T cell stemness is maintained across chronic diseases by dissecting transcriptional programs in TCF1hi T cells in preclinical models of autoimmune type 1 diabetes and chronic infection. It found that a subset of LEF1+ TCF1hi T cells defines a true self-renewing T cell stem cell (TSC) pool, which generates LEF1− TCF1hi progenitor T cells lacking stem functions. These mechanistic insights clarify how LEF1 and niche factors govern TSC maintenance, informing strategies to modulate durable immunity in chronic disease.

Miakicheva S, Hawley KM, Zumbo P et al. · Cell · (2026) · View on PubMed ↗

TGF-β1-induced endothelial transcytosis drives blood-brain barrier leakage during aging.

This study examined how TGF-β1 affects blood-brain barrier (BBB) integrity during aging in brain microvascular endothelial cells and aged mice, focusing on caveolar transcytosis regulators. It found that BBB leakage begins in midlife and is driven mainly by increased endothelial caveolar transcytosis, where AAV-mediated caveolin-1 knockdown or restoration of Mfsd2a reduces vesicle formation and BBB leakage, while TGF-β1 suppresses Mfsd2a transcription via Tgfbr2–Smad2/4 signaling. The results identify a TGF-β1→Tgfbr2–Smad2/4→Mfsd2a pathway that promotes endothelial transcytosis and BBB leakage, suggesting potential targets to mitigate age-related neurovascular dysfunction.

Fang C, Ma Y, Wei P et al. · Neuron · (2026) · View on PubMed ↗

Paederoside alleviates rheumatoid arthritis by targeting SMAD4 to suppress histone lactylation through inhibiting lactate transport in senescent macrophages.

This study investigated the mechanism by which paederoside, an iridoid glycoside from Paederia scandens, alleviates rheumatoid arthritis (RA) by targeting the SMAD4–MCT1 axis in senescent macrophages. It reported that paederoside suppresses lactate transport via MCT1, thereby reducing lactate-driven histone lactylation and downstream pro-inflammatory cytokine programs that drive synovial inflammation and hyperplasia. Mechanistically, the work links paederoside’s anti-RA effects to a defined metabolic–epigenetic pathway (lactate transport→histone lactylation) mediated by SMAD4 and MCT1, supporting a potential therapeutic target for RA driven by macrophage senescence.

Chen J, Zhang J, Ma Y et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

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Epidemiology, Risk Prediction, and Public Health

Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model.

This study developed and validated the PRISM Risk Model to improve overall survival (OS) prognostication in adults with newly diagnosed acute myeloid leukemia (AML) treated with hypomethylating agents plus venetoclax (HMA+VEN). Using a multinational cohort of 2,092 patients with training/internal validation and two external validation sets, the model integrated clinical, cytogenetic, and molecular features via Elastic Net regression to predict OS. The clinical significance is more accurate risk stratification for HMA+VEN patients, which could guide treatment intensity and trial design in AML where current stratification is inadequate.

Lachowiez CA, Zeidner JF, Othman J et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Membrane protein solubilization and structure determination using de novo-designed proteins.

This study developed a deep learning-based protein design approach to solubilize and determine structures of native integral membrane proteins using genetically encoded de novo proteins. The authors designed water-soluble RFdiffused amphipathic protein “WRAPs” that surround hydrophobic surfaces to preserve the target membrane protein’s sequence, fold, active site, and ligand-binding properties while enabling thermostable, detergent-free solubilization for both monomeric and oligomeric beta-barrel outer membrane proteins and helical multipass proteins. The scientific significance is a generalizable platform for producing structural data on difficult membrane targets, accelerating membrane-protein drug and vaccine development.

Mihaljević L, Kim DE, Bandawane PD et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Accelerometry-measured prolonged and interrupted sedentary behavior and cancer incidence and mortality: A cohort study of 91,292 UK Biobank participants.

This cohort study analyzed accelerometry-measured sedentary behavior patterns—specifically prolonged versus interrupted sedentary time—in 91,292 UK Biobank participants and their associations with cancer incidence and mortality. Using a two-step random-forest classification of sedentary behavior and multivariable Cox models, the study found differential cancer risk relationships for interrupted versus prolonged sedentary behavior (details truncated in the abstract). The results support refining sedentary behavior guidelines beyond total sedentary time by distinguishing interruption patterns relevant to cancer outcomes.

Zhou Z, Trost SG, Ryde GC et al. · PLoS medicine · (2026) · View on PubMed ↗

Contraceptive Progestogens and Incident Meningioma.

This nested case-control register study examined whether contraceptive progestogens are associated with incident meningioma risk in a Danish nationwide population of 3 million females aged 15–59 years. Across a 25-year period (2000–2024), the study compared meningioma cases to matched controls to estimate risk by specific progestogen types (abstract details truncated). The clinical significance is improved evidence on whether contraceptive progestogens differ in meningioma risk, informing safer hormonal contraception choices.

Hasselblad Lundstrøm N, Hjorslev Knudgaard M, Skaarup Pedersen M et al. · JAMA network open · (2026) · View on PubMed ↗

Joint association of the frailty index and phenotypic age with all-cause and cause-specific mortality: A prospective cohort study.

This prospective cohort study evaluated whether frailty index (FI) and phenotypic age (PhenoAge) jointly predict all-cause and cause-specific mortality in NHANES participants (2003–2010) followed through December 31, 2019. FI and PhenoAge showed joint and/or interactive associations with mortality risk estimated using Cox proportional hazards and competing-risk models. The findings support using combined biological-age and frailty measures for improved mortality stratification in clinical and public-health settings.

Shao Z, Zhao Y, Yang H et al. · Journal of translational internal medicine · (2026) · View on PubMed ↗

Harmonizing standards and resources for the medical genome.

This article described challenges and proposed recommendations for harmonizing standards and resources across medical genome sequencing and analysis workflows. It focused on germline sequencing, tumor sequencing, cell-free DNA testing, and sequencing for quality control in genetic therapy, emphasizing issues like accurate detection of low-frequency variants and gene-edited cell characterization. The significance is that unified quality standards can improve reliability and comparability of genomic results across precision medicine and clinical trials.

Ashley EA, Alizadeh AA, Armitage H et al. · Nature · (2026) · View on PubMed ↗

Towards the construction of a virtual yeast.

This perspective/proposal paper introduced a “virtual yeast,” an AI-driven agent intended to simulate eukaryotic cellular behaviors using Saccharomyces cerevisiae as a genetically tractable model. The approach integrates multimodal biological data, mechanistic reasoning, and active experimentation, decomposing cellular complexity into eight function-centered modules coordinated by a large language model-based orchestration layer. Scientifically, it aims to accelerate hypothesis generation and experimental design for understanding cellular dynamics by combining computation with iterative wet-lab testing.

Qian L, Zhou Z, Zhou P et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

N4-Acetylcytidine enhances synthetic mRNA translation yield and fidelity.

This study investigated how the modified nucleoside N4-acetylcytidine (ac4C) incorporated into synthetic mRNA affects translation yield and fidelity, compared with other common modified nucleosides such as N1-methylpseudouridine (m1Ψ). The key finding was that ac4C enhances synthetic mRNA translation output while improving translational fidelity, addressing concerns that some modifications can increase errors like premature termination or frameshifting. This supports ac4C as a promising mRNA modification strategy for more reliable therapeutic protein production.

Schiffers S, Nelson BW, Prigge M et al. · Nature · (2026) · View on PubMed ↗

Artificial intelligence for scoliosis surgical planning and postoperative prediction.

This study developed and validated ScoliosisPLAN, an AI system for adolescent idiopathic scoliosis (AIS) surgical planning and postoperative radiograph prediction in a retrospective cohort and prospectively collected internal/external validation cohorts totaling 1425 patients with ≥2-year follow-up. ScoliosisPLAN used a YOLOv8-derived segmentation model (ScolioPlanNet) to replicate individualized fusion segment selection and a latent diffusion model (ScolioPredNet) to simulate postoperative alignment, achieving performance comparable to experienced surgeons for planning replication and improved postoperative prediction (details truncated in the abstract). The approach could standardize and personalize AIS operative decision-making and postoperative alignment forecasting, potentially improving surgical consistency and patient counseling.

He Z, Lu N, Chen Y et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Secondhand smoke exposure and human health: an umbrella review.

This umbrella review synthesized epidemiological evidence across the lifespan on secondhand smoke exposure (SHSE) and health outcomes by evaluating systematic reviews with meta-analyses of observational studies. Across searches up to 24 August 2025, the authors assessed methodological quality (AMSTAR 2) and evidence credibility/robustness (evidence classification, fail-safe number, and GRADE), concluding that SHSE is associated with multiple adverse health outcomes despite fragmented evidence (specific effect estimates truncated in the abstract). The work provides a structured evidence map to guide public health policy and future research priorities on SHSE-related risks.

Zhang S, Li S, Yang X et al. · Nature human behaviour · (2026) · View on PubMed ↗

A deep learning framework for efficient pathology image analysis.

This study developed EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework for efficient pathology whole-slide image analysis across multiple cancer tasks. EAGLE emulates pathologists by selectively analyzing informative regions (task-agnostic tile selection plus feature extraction) and was benchmarked against leading foundation models across 43 tasks from nine cancer types, improving computational efficiency by reducing redundant tile processing (performance specifics truncated). The framework could make digital pathology biomarker prediction more scalable for clinical workflows and large-scale research.

Neidlinger P, Lenz T, Foersch S et al. · Nature communications · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗

Integrating clinical, proteomics, and polygenic scores to improve cardiovascular risk prediction: a prospective cohort study.

This prospective cohort study tested whether integrating high-dimensional proteomics with clinical variables and polygenic risk scores improves cardiovascular risk prediction beyond established tools (SCORE2 and AHA PREVENT). The key finding was that the multi-omics integration better captures residual risk associated with molecular changes preceding clinical events. Scientifically and clinically, this suggests a more dynamic, biology-informed approach to cardiovascular risk stratification that could outperform purely clinical/genetic models.

Ding Y, Hong G, Wang Z et al. · Journal of advanced research · (2026) · View on PubMed ↗

Global, regional, and national burden of tuberculosis and multidrug-resistant tuberculosis by HIV status, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

This Global Burden of Disease Study 2023 analysis quantified global, regional, and national burden of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) stratified by HIV status from 1990 to 2023 across 204 countries and territories. The key finding was the detailed characterization of TB and MDR-TB trends and their relationship to HIV status, enabling assessment of progress toward WHO End TB Strategy targets. These estimates are significant for guiding resource allocation and policy decisions to sustain and improve TB control amid changing global health funding.

The Lancet. Infectious diseases · (2026) · View on PubMed ↗

Metabolic traits in obesity and normal BMI in industrialised countries: a multi-country analysis of national population-based studies.

This multi-country analysis used 110 national population-based health surveys (1990–2024; 978,425 participants aged 20–79 years) to compare blood pressure, cholesterol, and use of antihypertensive and lipid-lowering medicines between people with obesity and those with normal BMI. The study assessed whether the BMI-associated excess cardiovascular and renal risk has diminished over time and quantified differences in metabolic and treatment patterns. The results inform how population-level management of hypertension and dyslipidaemia may be changing the cardiovascular burden attributable to obesity.

Lancet (London, England) · (2026) · View on PubMed ↗

Orthokeratology versus extended depth-of-focus soft contact lenses for myopia control: a 12-month comparative study of axial elongation and corneal changes.

This study compared orthokeratology (OK) versus extended depth-of-focus (EDOF) soft contact lenses for myopia control in 28 myopic children/adolescents (56 eyes; ages 6–16) over 12 months, measuring axial elongation and corneal changes. Both groups showed significant axial length (AXL) increase over time, with corneal parameters (e.g., keratometry K1/K2 and anterior chamber volume) assessed at baseline, 6 months, and 12 months to evaluate treatment-related corneal effects. Clinically, the trial directly informs which lens modality better controls myopia progression and how each approach alters corneal optics during a key developmental period.

Corpus G, Molina-Martin A, Piñero DP · Contact lens & anterior eye : the journal of the British Contact Lens Association · (2026) · View on PubMed ↗

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