PubMed Trending Research Digest — May 29, 2026

Automated digest · 99 articles · 15 research areas · May 29, 2026

Overview

Across this week’s set of papers, a dominant theme is mechanism-first immunology and immune modulation—spanning cancer, autoimmune disease, and infection. Multiple studies connect immune outcomes to specific molecular or cellular “control points,” such as perineural invasion neuroimmune programs in head and neck cancer, lactate–checkpoint resistance pathways in glioblastoma, and metabolic regulation of antigen presentation in hepatocellular carcinoma. In parallel, neuroimmune and inflammatory disease work highlights how immune signaling can be shaped by lipid metabolism (Alzheimer’s), microglia-driven innate immune responses (computational and mechanistic reviews), and B-cell depletion agent–specific immune dynamics in neuroimmunological disease. Even outside classic immunology, studies on STING termination and inflammasome activation emphasize that precise intracellular routing and signaling termination steps can determine whether inflammation escalates or resolves.

A second major thread is the growing integration of high-resolution “omics” and advanced modeling to improve prediction, stratification, and target discovery. Spatial and single-cell atlases (early human embryos, astrocyte functional units, cardiac sarcoidosis regions) and large-scale genomic/epigenomic analyses (HSC inflammatory memory, mtDNA mutation accumulation, PRS tail-architecture) provide new reference frameworks and biological explanations for heterogeneity. Methodology papers further push this trend: AI/ML tools for gene prioritization (SIGnature, MIDAS), improved reliability/quality assessment for clinical prediction (PROBAST+AI, TRUSTGUIDES), and explainable risk models (e.g., postoperative thrombosis). Together, these studies reflect a field moving from “one-size-fits-all” toward more personalized, mechanism-informed risk and treatment decisions.

Finally, several papers underscore how metabolism and organelle biology intersect with disease—especially via mitochondria, lysosomes, and metabolic sensors. Work on mitochondrial stress signaling (SLC25A12), mtDNA replication-error accumulation with age, mitochondrial calcium control of inflammasome cytokine release, and αKG–carnitine axes affecting DNA repair all point to metabolism as both a driver of pathology and a therapeutic lever. In cardiovascular and systemic contexts, studies address how metabolic or inflammatory perturbations translate into clinical risk (e.g., potassium range in heart failure, microplastic effects via gut-heart pathways, and neutrophil mitochondrial programs in severe infections), reinforcing the broader message that cellular energetics and stress responses are central to modern translational medicine.

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Cancer immunotherapy & tumor microenvironment

Circulating Tumor DNA in Early Breast Cancer: A Review.

This JAMA Oncology review examined circulating tumor DNA (ctDNA) minimal residual disease (MRD) assays in patients with early breast cancer. It found that while ctDNA MRD assays show analytical and clinical validity, their optimal clinical utility (eg, how best to guide treatment decisions) remains uncertain. The review highlights the need for prospective evidence to determine when ctDNA-driven “molecular relapse” detection should change management beyond standard imaging and clinical follow-up.

Schlam I, Tolaney SM, Lin NU et al. · JAMA oncology · (2026) · View on PubMed ↗

Intrathecal Allogeneic B7-H3-targeted CAR γδ T Cells for Leptomeningeal Metastasis from Solid Tumors: Safety, Efficacy, and Immunological Dynamics in a Phase 1 Trial.

This phase 1 clinical trial evaluated intrathecal allogeneic QH104, a B7-H3–targeted CAR γδ T-cell therapy, in patients with leptomeningeal metastasis from B7-H3–positive solid tumors. The key finding was that intrathecal administration via lumbar puncture or an Ommaya reservoir was feasible and produced safety/clinical activity signals along with immunological dynamics in a small cohort (N=3). Scientifically, it supports further development of B7-H3 CAR γδ T cells for CNS leptomeningeal disease and provides early pharmacodynamic insights.

Ma P, Zhou Y, Ma W et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗ · Free PDF ↗

Epigenetic Silencing of RFX7 Defines a Transcriptional Axis Linking Lactate Metabolism to Immune Checkpoint Therapy in Glioblastoma.

This mechanistic study investigated how epigenetic silencing of the transcription factor RFX7 regulates a lactate–immune checkpoint therapy axis in glioblastoma (GBM). Using transcriptomic profiling, chromatin immunoprecipitation sequencing (ChIP-seq), metabolic analyses, and gene perturbation experiments, the authors identified an RFX7→PIK3IP1 transcriptional axis and showed that RFX7 expression is reduced in GBM via promoter hypermethylation. Scientifically, this links lactate metabolism to immune checkpoint therapy resistance and suggests RFX7/PIK3IP1 pathway modulation as a potential therapeutic strategy in GBM.

Han L, Zhou J, Zhu G et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Multi-omics investigation of perineural invasion in head and neck squamous cell carcinoma: neuroimmune mechanisms and clinical implications.

This study investigated the molecular and neuroimmune mechanisms of perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) using integrative multi-omics (transcriptomics, proteomics, single-cell and spatial transcriptomics) from public datasets plus an independent clinical cohort. The authors identified PNI-associated molecular patterns and constructed prognostic signatures while characterizing immune infiltration and cell-cell communication, with regulatory elements mapped via super-enhancer analysis and target-gene prediction. These findings provide mechanistic neuroimmune links and potential biomarkers that could help stratify HNSCC patients for prognosis and immunotherapy response.

Deng M, Lin Y, Fang C et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.

This study analyzed tumor biopsies from hepatocellular carcinoma (HCC) patients treated with immune checkpoint blockade (ICB) to determine how OXCT1 (a ketone-body metabolism enzyme) and its substrate β-hydroxybutyrate (BHB) relate to immunotherapy response, and then tested the mechanism in HCC cells. OXCT1 expression was negatively correlated with ICB efficacy, while BHB showed the opposite association, and glucose deprivation activated AMPK to phosphorylate OXCT1 at S113, promoting its nuclear translocation and thereby attenuating histone β-hydroxybutyrylation-driven MHC-I transcription. These findings suggest that the AMPK–OXCT1 axis can reprogram tumor antigen presentation and may represent a metabolic target to improve ICB responsiveness.

Hu Z, Lv W, Wen T et al. · Nature chemical biology · (2026) · View on PubMed ↗

Combating small extracellular vesicle-mediated immunological barriers in the tumor microenvironment via strategically activatable PEGylated peptides.

This study engineered ExoPERM, a pH-activatable PEGylated peptide system designed to disrupt tumor microenvironment–localized small extracellular vesicles (TDEs/EVs) to overcome immunological barriers to cancer immunotherapy. The strategy used a pH-sensitive linker so PEGylation stabilized peptides systemically while enabling selective peptide release and exosome membrane rupture in the mildly acidic tumor microenvironment. By targeting EV-mediated immune evasion, the approach aims to improve the effectiveness of cancer immunotherapies.

Kim CH, Ko H, Lee JA et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

LISS enables immune evasion of colorectal cancers irrespective of MSI status.

This study identified and characterized the lncRNA LISS (lncRNA of IFN-γ-signaling suppressor) in colorectal cancer to determine how it affects immune checkpoint blockade (ICB) responses across microsatellite instability (MSI) and microsatellite stability (MSS). LISS expression was increased in colorectal cancers and associated with poor prognosis and high CD8+ scores, and functional experiments showed that LISS impairs T cell–mediated cytotoxicity. By defining an MSI-independent immune evasion mechanism, the study suggests LISS as a potential target to improve ICB efficacy in colorectal cancer.

Lin Q, Wang X, Zhao W et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

A PI(3,5)P2/CHMP4B axis on lysosomes is essential for microautophagic degradation of STING.

The study investigated how lysosomes encapsulate the innate immune sensor STING for ESCRT-driven lysosomal microautophagic degradation. The authors found that a PI(3,5)P2/CHMP4B axis is essential for STING encapsulation, showing that CHMP4B binds PI(3,5)P2 and that forced recruitment of Pikfyve’s catalytic core (to generate PI(3,5)P2) to early endosomes recruits CHMP4B, with CHMP4B mutants disrupting the process. This provides a defined molecular mechanism for terminating STING signaling, informing strategies to modulate type I interferon responses.

Shoji T, Shinojima A, Kishimoto T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

NF-κB inducing kinase (NIK) deletion accelerates KRAS-driven pancreatic cancer in association with tumor microenvironment remodeling.

The study tested how deletion of NF-κB–inducing kinase (NIK, encoded by MAP3K14) affects KRAS-driven pancreatic cancer and the tumor microenvironment in genetically engineered mouse models. In Pdx1-Cre; KRASG12D (KC) and Pdx1-Cre; KRASG12D; p53fl/fl (KPC) mice, with NIK-deficient counterparts (KNiC and KPNiC) and cerulein-induced pancreatitis to mimic inflammation-driven PDAC, the authors found that NIK deletion accelerated KRAS-driven tumor progression alongside tumor microenvironment remodeling. This indicates that NIK can act as a context-dependent brake on KRAS-driven PDAC and highlights the microenvironmental consequences of targeting non-canonical NF-κB signaling.

Du Z, Büttner UFG, Wirth HL et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer genomics, DNA repair & genome stability

A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.

This study used Sleeping Beauty (SB) transposon mutagenesis in a mouse model with prostate-specific loss of Pten and Tp53 (NPp53) to identify genetic drivers of neuroendocrine prostate cancer (NEPC). It found that SB-driven additional mutations accelerated tumor aggressiveness and produced NEPC-like phenotypes with transcriptomic features resembling human NEPC, with recurrent common insertion sites implicating specific driver genes. The significance is that it provides candidate NEPC drivers and mechanistic targets that could guide future therapeutic strategies for aggressive prostate cancer variants.

Nunes de Almeida F, Vasciaveo A, Giacobbe A et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗

Distinct repair outcomes from single and convergent replication fork collapse.

This Nature Structural & Molecular Biology study examined DNA repair outcomes after replication fork collapse by replicating site-specific nicks with single versus convergent replication forks in Xenopus laevis egg extracts. Single fork collapse produced single-ended double-strand breaks that were repaired by homologous recombination to form stable D-loops and end-to-end fusions without restarting DNA synthesis, whereas convergent fork collapse yielded distinct repair/resolution pathways. The results are significant for understanding how replication stress is resolved differently depending on fork geometry, informing models of genome stability maintenance.

Conwell SC, Patel KVN, Weeks-Pollenz SJ et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗ · Free PDF ↗

αKG-mediated carnitine synthesis drives DNA repair via histone acetylation.

The study examined how α-ketoglutarate (αKG)–mediated carnitine synthesis affects DNA repair in homologous recombination (HR)–proficient cancer cells. Using a targeted CRISPR knockout library of 64 αKG-dependent dioxygenases (αKGDDs), the authors found that αKG depletion sensitizes HR-proficient cells to DNA-damaging agents by regulating histone acetylation, implicating αKGDD-dependent control of trimethyllysine hydroxylase epsilon (and related histone acetylation pathways). This links a specific metabolic axis (αKG→carnitine synthesis) to chromatin regulation of DNA repair, suggesting metabolic targeting as a strategy to overcome resistance to DNA-damaging cancer therapies.

Uboveja A, Yang B, Buj R et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Substrate selectivity of the human RNA m5C methyltransferase NSUN2.

The study characterized substrate selectivity of the human RNA cytosine-5 methyltransferase NSUN2 and how it recognizes RNA during its catalytic cycle. The authors found that NSUN2 interacts with RNA substrates at distinct stages of the catalytic cycle and that RNA structure facilitates NSUN2 activity at multiple tRNA positions, explaining how NSUN2 can act on diverse RNA substrates. This improves mechanistic understanding of NSUN2’s epitranscriptomic roles in cancer and neurological disease and can guide efforts to predict or modulate NSUN2-dependent methylation.

Canepa J, Ruiz-Arroyo VM, Schlamowitz NS et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

CDC48A and the UBA-domain protein PUX10 regulate the ubiquitin-dependent degradation of peroxisomal proteins in Arabidopsis.

This study investigated how the AAA-ATPase CDC48A and the UBX-domain cofactor PUX10 regulate ubiquitin-dependent degradation of peroxisomal proteins in Arabidopsis thaliana. The authors found that CDC48A and PUX10 are required for degradation of specific peroxisomal proteins, supporting a model in which a subset of peroxisomal cargo is retrotranslocated/targeted for proteasomal turnover. Scientifically, it clarifies a plant-specific quality-control pathway connecting peroxisome homeostasis to ubiquitin-dependent proteolysis.

Li J, Yu S, Zang X et al. · The Plant cell · (2026) · View on PubMed ↗

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Cancer therapeutics (drugs, targets, preclinical/clinical trials)

Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy: a multi-institution study.

This multi-institution retrospective study evaluated predictors of pathologic complete response (pCR) in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy including pembrolizumab. The key finding was that specific clinical factors and treatment variables were associated with achieving pCR after neoadjuvant chemotherapy plus pembrolizumab in a real-world cohort. This is significant because it can help refine patient selection and expectations for benefit from pembrolizumab-based neoadjuvant regimens beyond the original KEYNOTE-522 trial context.

LeVee A, Santos B, Wong M et al. · Breast cancer research and treatment · (2026) · View on PubMed ↗ · Free PDF ↗

Nucleic Acid Therapeutics for “Undruggable” Cancer Targets: Mechanisms, Challenges, and Prospects.

This review article surveyed nucleic acid therapeutics—including antisense oligonucleotides (ASOs), siRNAs, and miRNA-based approaches—for targeting “undruggable” cancer proteins such as Ras, MYC, and p53. It highlights that nucleic acid modalities act at the mRNA or genomic level, avoiding the need for direct binding to well-defined protein structural domains. The synthesis supports continued translational development of RNA/DNA-targeting strategies to expand immuno-oncology and precision cancer treatment options for previously inaccessible targets.

Xu F, Wang K, Lu K et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.

This preclinical study developed AcTor, a novel mTOR stimulator designed to potentiate the proteasome inhibitor ixazomib in acute myeloid leukemia (AML). By using in silico docking and medicinal chemistry to generate AcTor as a TSC2-targeting agent, the authors found that AcTor increased sensitivity to proteasome inhibition and enhanced ixazomib cytotoxicity across multiple AML cell contexts. The clinical significance is that pharmacologically activating the mTOR axis via TSC2 inhibition may be a strategy to improve proteasome inhibitor efficacy in AML.

Pattanayak SP, Darawshi O, Hajihassani O et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.

This study tested whether inhibiting RNA polymerase II–activating CDKs (CDK9 and CDK12/13) versus cell-cycle CDKs induces apoptosis, using pharmacologic inhibitors in cancer models. Inhibition of CDK9 (AZD4573, atuveciclib) or CDK12/13 (SR4835, THZ531) induced apoptosis by downregulating short-lived anti-apoptotic Bcl-2 family proteins Mcl1 and Bfl1/A1, whereas inhibition of cell-cycle-relevant CDKs (e.g., CDK1, CDK4/6) did not. The work links transcriptional elongation CDK activity to survival protein maintenance, supporting CDK9/CDK12/13 as mechanistically grounded therapeutic targets.

Krings KS, Hatzfeld J, Weller S et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗

Comparison of effectiveness and safety of pembrolizumab plus lenvatinib versus nivolumab plus cabozantinib for metastatic renal cell carcinoma: a real-world study.

This retrospective real-world study compared first-line pembrolizumab plus lenvatinib (Pem-Len) versus nivolumab plus cabozantinib (Nivo-Cabo) in Japanese patients with metastatic renal cell carcinoma treated at Kobe University Hospital and affiliated institutions. Pem-Len and Nivo-Cabo showed differences in clinical outcomes and safety profiles across the 139-patient cohort, with the study designed to directly contrast effectiveness and tolerability between these two standard immunotherapy–TKI combinations. These findings are clinically relevant for selecting first-line therapy in Japanese metastatic RCC patients when randomized trial data may not fully reflect routine practice.

Tobe T, Teishima J, Mita Y et al. · International journal of clinical oncology · (2026) · View on PubMed ↗

Dual Biological Aggressiveness in Gastric MiNEN With Squamous Differentiation: A Case of Rapid Postoperative Peritoneal Dissemination.

This case report studied a rare gastric mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) with squamous differentiation and its clinical behavior. The authors describe an 89-year-old man whose tumor showed dual biological aggressiveness with early peritoneal dissemination within three months after curative resection, alongside pathological heterogeneity. The report is significant because it highlights the potential for rapid metastatic progression in this uncommon histologic subtype, informing clinicians to consider aggressive management and close follow-up.

Iseki S, Aoki T, Yamazaki K et al. · Anticancer research · (2026) · View on PubMed ↗

Real-world Clinical Outcomes of Ivermectin and Mebendazole in Cancer Patients: Results from a Prospective Observational Cohort.

This prospective observational cohort study examined real-world clinical outcomes, safety, and adherence for off-label ivermectin plus mebendazole in cancer patients. Among 197 patients prescribed compounded capsules containing 25 mg ivermectin and 250 mg mebendazole via a U.S. telemedicine platform, outcomes were collected using standardized digital surveys at baseline and 6 months. The significance is that it provides early human effectiveness and tolerability data for a repurposed combination with multi-target anticancer activity, informing feasibility for future trials.

Hulscher N, Victory K, Thorp JA et al. · Anticancer research · (2026) · View on PubMed ↗ · Free PDF ↗

Cenobamate: a new drug that may change the concept of drug-resistant focal epilepsy.

This narrative review studied the clinical development and real-world/clinical-trial performance of cenobamate as an antiseizure medication for focal epilepsy, particularly in patients with drug-resistant disease. The key finding is that cenobamate has demonstrated higher seizure freedom rates in patients who have not responded to two or more prior antiseizure drugs, with tolerability described as similar to earlier-generation options. Scientifically and clinically, the review argues that cenobamate may shift expectations for outcomes in drug-resistant focal epilepsy and supports its role in treatment strategies.

Poza JJ · Neurologia · (2026) · View on PubMed ↗ · Free PDF ↗

Adjuvant chemoradiotherapy versus completion total mesorectal excision after local excision for early rectal cancer (TESAR): a multicentre, randomised, controlled, phase 3, non-inferiority trial.

This multicentre, open-label, randomized phase 3 non-inferiority trial studied adjuvant chemoradiotherapy versus completion total mesorectal excision (cTME) after local excision for early rectal cancer in patients with high-risk pT1 and low-risk pT2 tumors. The key finding is the trial’s design and primary objective to determine whether organ-preserving chemoradiotherapy can achieve oncological outcomes that are not worse than cTME while reducing morbidity and functional impairment. If chemoradiotherapy is non-inferior, it could change standard management toward less invasive treatment for selected early rectal cancer patients.

Moolenaar LR, Ali M, Aufenacker TJ et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

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Hematology & hematopoietic cell therapy

The 2024 EBMT activity report: crossing one million HCTs and 20,000 CAR-T. A landmark in cellular therapy.

This EBMT activity report analyzed global hematopoietic cell therapy (HCT) registry data to characterize trends in transplant volumes and indications in 2024, including CAR-T expansion. The key finding is that 2024 surpassed one million total HCTs reported since 1990, with 47,204 HCTs in 2024 and CAR-T reaching 6,082 patients (and over 20,000 since 2018). This is significant for benchmarking the clinical growth and shifting indications of allogeneic, autologous, and CAR-T therapies across 53 countries.

Greco R, Sánchez-Ortega I, Risitano AM et al. · Bone marrow transplantation · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration, neuroinflammation & neuroimmune mechanisms

Lipid metabolic regulation of neuroinflammation in Alzheimer’s disease.

This article reviewed how lipid metabolic regulation shapes neuroinflammation in Alzheimer’s disease (AD), focusing on microglial activation and inflammatory cascades. It highlights that dysregulated fatty acid composition, apolipoprotein E (ApoE) isoforms, lipoprotein lipase activity, and lipid-derived signaling mediators can drive sustained neuroinflammatory states alongside β-amyloid and tau pathology. The work supports lipid metabolism as a modifiable scientific target for understanding and potentially treating AD-associated neuroinflammation.

Li T, Guo K, Ma Y et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

AI-driven insights into protein misfolding and innate immunity in neurodegenerative diseases.

This review synthesized AI-driven approaches to study protein misfolding and innate immune responses mediated largely by microglia across neurodegenerative diseases including Alzheimer’s, Parkinson’s, and pediatric neuronal ceroid lipofuscinoses (NCLs), Niemann-Pick type C (NPC), and infantile neuroaxonal dystrophy (INAD). It emphasizes that aggregated proteins such as β-amyloid (Aβ), tau, α-synuclein, and TDP-43 can engage innate immune pathways and that AI can help extract mechanistic insights from complex biological data. The significance is that computational methods may accelerate identification of immune-relevant misfolding mechanisms and therapeutic hypotheses across multiple neurodegenerative disorders.

Deng HX, Cao JL, Wu Y et al. · Frontiers in immunology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.

The study examined how thyroid-stimulating hormone receptor (TSHR) mediates peripheral-to-central neuroimmune crosstalk in autoimmune thyroid diseases, focusing on Graves’ disease (GD) and Graves’ orbitopathy (GO). The authors report that TSHR-driven pathological signaling links peripheral immune activation to CNS-relevant neuroimmune pathways, providing a mechanistic bridge for extended systemic features beyond the thyroid and orbit. This work is significant because it identifies TSHR as a potential target for therapies aimed at neuroimmune complications in GD/GO rather than treating only local tissue pathology.

Zhang H, Jiang S, Zhu T et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis.

This study evaluated the antiretroviral combination Triumeq (abacavir/dolutegravir/lamivudine) in a doxycycline-suppressible rNLS8 TDP-43 mouse model of amyotrophic lateral sclerosis (ALS) to test whether treatment affects TDP-43 pathology. In the TDP-43-driven model, Triumeq was assessed for its impact on cytoplasmic TDP-43 accumulation and ALS disease phenotypes. If effective, repurposing Triumeq would provide a mechanistic, ERV-linked therapeutic strategy for TDP-43-mediated ALS.

Fowler M, Carr JM, Gold J et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology.

This study used transgenic mice expressing human caspase-4 (CASP4) to model how cytoplasmic TDP-43 pathology develops with age. CASP4 transgenic mice showed cytoplasmic accumulation of TDP-43 and age-dependent neuropathology, consistent with CASP4-mediated cleavage of TDP-43 into mislocalizing fragments. The model improves relevance of cytoplasmic TDP-43 mechanisms for neurodegenerative disease research and potential therapeutic testing.

Jia Q, Zhu L, Li D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

The multiple scales of astrocytic functional units.

This Nature Neuroscience study investigated how astrocyte functions are organized across spatial scales by analyzing astrocytic morphological features and molecular heterogeneity. The authors define multiple spatial scales of astrocytic functional units, ranging from fine perisynaptic structures to broader domains and networks, rather than a single uniform unit size. This work is significant because it provides a framework for linking astrocyte structure to specific modes of neuron–glia communication and brain circuit function.

Oliveira JF, Agarwal A, Beckervordersandforth R et al. · Nature neuroscience · (2026) · View on PubMed ↗

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Neurodevelopment & neurogenetics

Spatiotemporal transcriptome atlas of human embryos after gastrulation.

This Nature study generated a spatiotemporal transcriptome atlas of human embryos after gastrulation using Stereo-seq across 77 sagittal sections of 13 whole embryos (Carnegie stages 12–23) and integrated the data with single-nucleus RNA sequencing. The key finding is that spatial gene-expression patterns reveal cellular heterogeneity driving organ-specific differentiation and provide regulatory profiles for development of 50 organs and 198 substructures. This is significant because it creates a high-resolution reference map for early human organogenesis that can guide mechanistic studies of developmental disorders.

Pan J, Li Y, Lin Z et al. · Nature · (2026) · 6 citations · View on PubMed ↗ · Free PDF ↗

Transcription factor codes patterning neuronal groundplans of the cerebrum.

The study investigated how transcription factor combinations pattern neuronal groundplans in the cerebrum by analyzing transcriptional contexts of neuronal lineages in Drosophila melanogaster. By embedding well-studied mating-regulating neurons into their lineage transcriptional programs and comparing transcription within and between lineages, the authors identified large sets of transcription factors expressed in combinatorial codes that delineate cerebral hemilineage organization. This advances a gene-regulatory “code” for building complex brain region identities, providing a framework for mapping how transcriptional programs generate neural circuit diversity.

Elkahlah NA, Lin Y, Pan Y et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Defective ventral neurogenesis due to midfetal Chd8 mutation drives autistic-like behavior in mice.

This study examined how embryonic Chd8 mutations in mice affect ventral neurogenesis timing and specific cell types, and how those developmental changes produce autistic-like behaviors. The authors found that inducing a Chd8 mutation at embryonic day 14.5 caused ASD-like phenotypes (including abnormal social interaction and increased anxiety-like behavior) by disrupting ventral neurogenesis during a critical developmental window. These results strengthen a causal link between CHD8-dependent midfetal ventral developmental defects and ASD-relevant circuit dysfunction, supporting CHD8 as a mechanistic target for understanding neurodevelopmental risk.

Nitahara K, Kawamura A, Tashiro A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroimaging, biomarkers & brain structure/function

Associations of Retinal Curvature With Choroidal Thickness and OCTA-Derived Choroidal Flow-Density Metric in High Myopia: A Two-Center OCTA Study of Interocular Asymmetry.

This two-center cross-sectional OCTA study examined associations between retinal curvature (RC) and choroidal structure (choroidal thickness) and perfusion-density metrics in high myopia, including interocular asymmetry. It found that RC correlated with OCTA-derived choroidal flow-density and choroidal thickness measures, and that inter-eye differences were more closely linked to perfusion-density differences than to structural differences. The clinical significance is that RC and OCTA metrics may help characterize and quantify choroidal involvement in high myopia, potentially improving risk assessment for disease progression.

Wang ZX, Wei B, Li R · Translational vision science & technology · (2026) · View on PubMed ↗ · Free PDF ↗

Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.

This case-control study examined whether putative glymphatic dysfunction relates extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis (ALS). In 146 ALS patients and 149 matched healthy controls, glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS), and associations were tested with multimodal MRI measures and comprehensive clinical assessments. The significance is that it links glymphatic impairment to structural brain changes and clinical heterogeneity, suggesting a potential mechanistic biomarker pathway in ALS.

Jin X, Fu Y, Qiu T et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Lifespan normative modeling of brain microstructure.

This study developed a lifespan normative model of brain white-matter microstructure using diffusion MRI from 19 international datasets (N=54,583; ages 4–91 years). Using standardized extraction of regional DTI metrics and hierarchical Bayesian regression, the model characterized age-related trajectories across the lifespan. This provides a reference framework to detect and quantify white-matter abnormalities in neurodevelopmental, psychiatric, and degenerative disorders.

Villalón-Reina JE, Zhu AH, Nabulsi L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Indications, contraindications, and step-by-step methodology for performing carotid sinus massage in patients presenting with syncope : A scientific statement of an Ad Hoc Syncope Consortium endorsed by: the European Autonomic Society (EFAS), Gruppo Italiano Multidisciplinare Syncope (GIMSI) and European Geriatric Medicine Society (EuGMS).

This scientific statement addressed carotid sinus massage (CSM) in patients presenting with syncope, providing indications, contraindications, and a step-by-step methodology endorsed by European and Italian autonomic/syncope societies. The key finding is that CSM is essential for diagnosing recurrent unexplained reflex syncope—particularly cardioinhibitory mechanisms that other tests can miss—yet it is underused and variably performed/interpreted, reducing diagnostic yield. Standardizing CSM technique and interpretation is significant because it enables mechanism-based, personalized treatment for patients with unexplained reflex syncope.

de Lange FJ, Brignole M, Benditt DG et al. · Clinical autonomic research : official journal of the Clinical Autonomic Research Society · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular disease & cardiac mechanisms

Adverse Effects and Treatment Discontinuation of Blood Pressure-Lowering Drugs and Combinations: A Network Meta-Analysis.

This JAMA network meta-analysis reviewed short-term randomized clinical trials to compare adverse effects and treatment discontinuation across major classes of blood pressure–lowering drugs and combinations. It found differential rates of adverse events and discontinuation among drug classes (including ACE inhibitors, ARBs, beta-blockers, calcium channel blockers, and thiazide-type diuretics) and their combinations. The results are significant for optimizing antihypertensive selection to improve tolerability and adherence while achieving better blood pressure control.

Wang N, Van Der Hoorn S, Pant R et al. · JAMA · (2026) · View on PubMed ↗

Can Lactate Values Predict Postoperative Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery? A Prospective Observational Study.

This prospective observational study assessed whether routinely measured serum lactate values predict postoperative atrial fibrillation (POAF) after isolated coronary artery bypass grafting (CABG) in 250 patients. It found no statistically significant difference in key baseline and perioperative characteristics between patients with and without POAF, and the lactate time-course did not clearly establish lactate as a reliable predictor (based on the reported comparisons). Clinically, the study suggests that serum lactate—despite being easy to measure—may have limited utility for POAF risk stratification after CABG.

Temiztürk Z, Beyazal OF, Topçu AC et al. · Brazilian journal of cardiovascular surgery · (2026) · View on PubMed ↗

Optimal serum potassium concentrations in heart failure: an individual patient data meta-analysis.

This individual patient data meta-analysis pooled 12 randomized controlled trials to determine the optimal safe serum potassium range in heart failure (HF), stratifying outcomes in HF with reduced ejection fraction (HFrEF) versus HF with preserved ejection fraction (HFpEF). Baseline serum potassium was analyzed in predefined categories and as a continuous variable using restricted cubic splines, with all-cause mortality as the primary endpoint. Clinically, defining an evidence-based potassium target range could improve risk management and guide safer use of therapies that affect potassium in large HF populations.

Ono R, Chimura M, Docherty KF et al. · European heart journal · (2026) · View on PubMed ↗

Microplastic Exposure Aggravates Cardiomyopathy Under Hemodynamic Stress Through the Gut-Heart Axis.

This experimental study tested whether microplastic exposure worsens cardiomyopathy under hemodynamic stress and whether the gut-heart axis mediates the effect, focusing on bisphenol F (BPF) as the microplastic-associated compound. Using germ-free mouse models and fecal microbiota transplantation to establish microbiota dependence, along with untargeted and spatial metabolomics and single-cell sequencing to identify damaged cardiac cell types, the authors showed BPF aggravates cardiovascular injury via gut microbiota–linked metabolic changes. The work suggests that targeting the gut microbiome or BPF-related metabolic pathways could mitigate cardiovascular risk in settings of mechanical stress.

Wang J, Xu J, Mai H et al. · Circulation · (2026) · View on PubMed ↗ · Free PDF ↗

Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury.

This study tested Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, in male Wistar albino rats subjected to lower extremity ischemia-reperfusion (I/R) injury induced by abdominal aortic clamping. Compared with I/R alone, BPC 157 given intraperitoneally at 20 µg/kg at the onset of reperfusion improved outcomes associated with oxidative stress, inflammation, and apoptosis (as assessed in the truncated abstract). The findings support BPC 157 as a potential pharmacologic candidate to reduce peripheral I/R injury relevant to peripheral arterial disease.

Yıldırım AK, Demirtaş H, Özer A et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Phosphoproteomics distinguishes disease-specific mechanisms for human phospholamban cardiomyopathy reversible by RNA therapy.

This study performed phosphoproteomics on cardiac tissue from patients with phospholamban (PLN) p.Arg14del (R14Δ/+) cardiomyopathy (N=6) compared with other dilated cardiomyopathy causes (N=10), and validated findings in CRISPR-Cas9-engineered R14Δ/+ iPSC-derived cardiomyocytes. It identified disease-specific phosphoproteomic mechanisms and assessed how PLN-targeted RNA therapy reverses them. These results connect human PLN R14Δ/+ molecular pathology to measurable therapeutic reversibility, strengthening the translational rationale for RNA therapy in inherited cardiomyopathy.

Deiman FE, Bömer N, Davidsson P et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Current and Future Perspectives of LDL-C Lowering Therapies 2026.

This review studied the current and future landscape of LDL-C–lowering therapies for preventing atherosclerotic cardiovascular disease (ASCVD). It summarizes how statins, ezetimibe, PCSK9-targeting agents, bempedoic acid, and emerging modalities enable attainment of guideline LDL-C targets while increasing complexity of clinical decision-making. The significance is practical: it provides an updated framework to guide therapy selection and sequencing in ASCVD prevention.

Tada H, Sakata K, Usui S et al. · Journal of atherosclerosis and thrombosis · (2026) · View on PubMed ↗ · Free PDF ↗

Design of VICTORION-2 Prevent: a randomized double-blind, placebo-controlled trial, assessing the impact of inclisiran on major adverse cardiovascular events in patients with established cardiovascular disease.

This phase 3 randomized, double-blind, placebo-controlled trial design studied inclisiran (a small interfering RNA targeting hepatic PCSK9/“proprotein convertase subtilisin/kexin type 9” mRNA) in patients with established atherosclerotic cardiovascular disease (ASCVD) receiving high-intensity statin therapy. The key finding is the trial’s planned evaluation of whether inclisiran reduces major adverse cardiovascular events (MACE) compared with placebo in a formal outcomes framework (VICTORION-2 Prevent; NCT05030428). If successful, the results would provide definitive evidence for inclisiran’s cardiovascular event prevention benefit beyond its established LDL-C–lowering effect.

Steg PG, Goodman SG, Jukema JW et al. · American heart journal · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Efficacy and Safety of Catheter Ablation Energy Modalities for Atrial Fibrillation: A Network Meta-Analysis of Randomized Trials.

This network meta-analysis studied comparative efficacy, procedural efficiency, and safety of atrial fibrillation catheter ablation energy modalities—radiofrequency ablation (RFA), cryoballoon ablation (CBA), laserballoon ablation (LBA), pulsed field ablation (PFA), and lattice-tip dual-energy (LTD)—using randomized trials. The key finding was a synthesized comparison across these five modalities using random-effects network meta-analysis (search through March 15, 2026), yielding relative differences in outcomes and safety profiles. Clinically, the analysis helps clinicians choose among ablation technologies by clarifying trade-offs in effectiveness and risk.

Karakasis P, Fragakis N, Tzeis S et al. · Heart rhythm · (2026) · View on PubMed ↗

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Infectious disease: tuberculosis & other pathogens

A pair of DNA glucosyltransferases elevate counter-defense in bacteriophage T4.

This biochemical and genetic study examined how two DNA glucosyltransferases, α-GT and β-GT, provide counter-defense for bacteriophage T4 against host restriction-modification and CRISPR-Cas systems. The authors showed that β-GT and α-GT post-replicatively glucosylate hydroxymethylated deoxycytosines (5-hmC) on phage DNA in distinct conformations (α- and β-forms), with β-GT exhibiting higher catalytic activity. Understanding this phage counter-defense mechanism clarifies host–phage coevolution and can inform engineering of phage DNA modifications for biotechnology and phage therapy.

Ramirez-Chamorro L, Bonhomme F, Wolff ALI et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Molecular basis of type VI secretion system effector loading.

The study resolved the molecular basis of effector loading in bacterial type VI secretion systems (T6SSs), focusing on Pseudomonas aeruginosa and its Hcp ring assemblies. Using cryo-electron microscopy, the authors determined the structure of the Tce1 cargo loaded into an Hcp3 ring from the P. aeruginosa H3-T6SS and showed that a single Tce1 monomer interacts asymmetrically with and is enclosed by two hexameric Hcp3 rings via residues on the inner Hcp3 disc surface. This is significant because it provides a structural mechanism for how T6SS effectors are recruited and loaded, informing strategies to disrupt T6SS-mediated bacterial virulence.

Paracuellos P, Bexter A, Patkowski JB et al. · Nature microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Temperate phages enhance bacterial host fitness via RNA-guided flagellar remodelling.

This study examined how temperate phages enhance bacterial host fitness by RNA-guided remodeling of flagella, using a human clinical Enterobacter isolate carrying a Flagellin Remodeling prophage (FRφ). It showed that FRφ exploits the phage-encoded RNA-guided transcription factor TldR and a specific flagellin isoform to alter flagellar composition, increasing motility and enabling mammalian immune evasion. The findings are significant because they reveal a phage-driven mechanism for immune escape and fitness optimization that could influence how bacterial infections persist and spread.

Walker MWG, Richard E, Wiegand T et al. · Nature microbiology · (2026) · View on PubMed ↗

Long-term spatiotemporal evolution of drug-resistant Mycobacterium tuberculosis in China.

This study analyzed more than 18,000 Mycobacterium tuberculosis genomes to reconstruct the long-term spatiotemporal evolution of drug resistance across China. Resistance mutations to different antibiotics repeatedly emerged, generating hundreds to over a thousand small drug-resistant clades that mostly arose within the past two decades, with transmission largely sustained within provinces but capable of geographic expansion. The results provide a population-level evolutionary map of resistance emergence and spread that can guide surveillance and control strategies for TB drug resistance.

Chen Y, Liang J, Liu D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

African swine fever virus B66L drives extracellular mitochondrial release to promote systemic inflammation in mice.

This study investigated how African swine fever virus (ASFV) protein B66L triggers systemic inflammation in mice by promoting extracellular mitochondrial release. In primary porcine alveolar macrophages, B66L enhanced autophagosome capture of damaged mitochondria while blocking autophagosome–lysosome fusion, leading to extracellular mitochondrial accumulation that was detectable in mouse serum and bronchoalveolar lavage fluid in B66L-expressing animals. The findings identify B66L-driven mitochondrial extracellular release as an upstream inflammatory mediator, suggesting a mechanistic pathway that could be targeted to mitigate ASFV-associated inflammation.

Lin L, Hu Z, Xing G et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease: HIV & viral immunotherapy

Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection.

This study evaluated bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, in adults with noncirrhotic chronic HBV infection enrolled in two replicate phase 3, double-blind trials (B-Well 1 and B-Well 2) who were receiving stable nucleos(t)ide analogue therapy. Bepirovirsen given subcutaneously at 300 mg weekly for 24 weeks was assessed for achieving a functional cure defined by sustained HBV DNA below the lower limit of quantification and loss of hepatitis B surface antigen (HBsAg) after fixed-duration treatment. If effective, this approach could provide a finite, transcript-targeting therapy that increases the likelihood of functional cure beyond long-term nucleos(t)ide analogue suppression.

Hou J, Lim SG, Buti M et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial.

This double-blind, randomized, placebo-controlled trial studied the duration of ART-free HIV control after infusion of Fc-engineered long-acting broadly neutralizing antibodies (LS-bNAbs) 3BNC117-LS and 10-1074-LS versus placebo during analytical treatment interruption (the RIO trial). The key finding is the focus on time to HIV rebound as the primary efficacy endpoint, comparing how long viral suppression persists off ART with LS-bNAbs in adults with early-stage HIV who were virally suppressed and had no evidence of viral insensitivity to 10-1074. Clinically, the results inform how effective and durable long-acting bNAb strategies may be for maintaining HIV control without continuous ART.

Lee MJ, Cherrill LR, Zacharopoulou P et al. · The lancet. HIV · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease: malaria & parasitology

Efficacy and safety of RTS, S and R21 malaria vaccines in children under five in Africa: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis synthesized randomized controlled trials of RTS,S and R21 malaria vaccines in African children under five years old. It pooled efficacy against first/only malaria episodes, multiple episodes, and severe malaria, and also summarized the incidence of severe adverse events following vaccination. The significance is that it provides consolidated, evidence-based estimates to guide vaccine policy and deployment for young children at high malaria risk.

Nurani KM, Kadernani N, Korir E et al. · Malaria journal · (2026) · View on PubMed ↗ · Free PDF ↗

Structural and mechanistic insights into the inhibition of Plasmodium falciparum MDR1.

The study examined the structural basis for inhibition of the Plasmodium falciparum drug-resistance transporter PfMDR1 by the clinical-phase antimalarial candidate ACT-451840. Using cryo-electron microscopy, the authors determined a 3.42 Å structure of PfMDR1 in complex with ACT-451840 and identified how the drug engages the transporter in a way relevant to resistance to first-line antimalarials such as mefloquine and chloroquine. This structural mechanism can guide rational development of next-generation MDR1 inhibitors to counter multidrug resistance in malaria.

Zhao Z, Li J, Wang X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Autoimmunity, inflammatory diseases & immunomodulation

Validation of a 2-Gene Blood Test for Kawasaki Disease in Febrile Children.

This multicenter diagnostic study validated a 2-gene whole-blood qPCR assay measuring IFI27 and MCEMP1 expression to distinguish Kawasaki disease from other febrile illnesses in children in Taiwan and Shanghai. The key finding was that the IFI27/MCEMP1 qPCR test could discriminate Kawasaki disease from alternative pediatric febrile diagnoses with diagnostic performance sufficient for clinical validation. Scientifically and clinically, an objective molecular test could enable earlier identification and timely intravenous immunoglobulin therapy to reduce coronary artery complication risk.

Kuo HC, Xue X, Liu F et al. · JAMA network open · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Evaluation of the safety profile of glucagon-like peptide-1 receptor agonists: a focus on thyroid cancer-related adverse events by using the European pharmacovigilance database.

This pharmacovigilance study analyzed individual case safety reports from the European database to assess thyroid cancer–related adverse events associated with GLP-1 receptor agonists and tirzepatide. It found signals/associations between specific GLP-1 RAs (eg, semaglutide, liraglutide, exenatide, lixisenatide, dulaglutide) and thyroid cancer–related adverse event reports, with emphasis on the pattern of reported cases. The study’s significance is that it informs post-marketing safety surveillance and risk communication while guiding clinicians and regulators on monitoring thyroid-related outcomes.

Anatriello A, Liguori V, Pentella C et al. · Pharmacological reports : PR · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer Surveillance in Lynch Syndrome: A Scoping Review of International and National Guidelines.

This scoping review mapped and compared international and national cancer surveillance, risk-reducing surgery, and chemoprevention guidelines for individuals with Lynch syndrome (LS). It found wide variation across guidelines in recommended surveillance modalities, timing, intervals, and evidence grading despite consensus that colonoscopy and risk-reducing strategies reduce morbidity and mortality. The results identify areas of agreement and evidence gaps that can inform harmonized, higher-evidence surveillance recommendations for LS-associated cancers.

McKenzie M, Quinn M, Stockley C et al. · Genetics in medicine : official journal of the American College of Medical Genetics · (2026) · View on PubMed ↗

Integrative Molecular Analyses of Inflammatory and Autoimmune Signals in Cardiac Sarcoidosis.

This study used comprehensive single-cell and spatial transcriptomic analyses to characterize inflammatory and autoimmune signals across preserved, granulomatous, and fibrotic regions in human cardiac sarcoidosis (CS) hearts. The authors identified clonally expanded cardiac B cells with rearranged immunoglobulin sequences and reconstructed antibody features, alongside mapping region-specific cellular gene expression programs. These findings support a more defined immune mechanism in CS and may enable biomarker-driven or antibody-targeted approaches for diagnosis and treatment.

Neyazi M, Venturini G, Brown KJ et al. · Circulation · (2026) · View on PubMed ↗

Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK Signaling Pathway.

This preclinical study tested whether semaglutide, a long-acting GLP-1 receptor agonist, prevents osteoblast ferroptosis in a diabetic periodontitis model by modulating the Wnt5a/Ror2/p38 MAPK signaling pathway. In MC3T3-E1 osteoblasts exposed to high glucose plus palmitic acid (HGHP) to mimic a diabetic microenvironment, semaglutide was evaluated for effects on osteoblast function and ferroptosis-related outcomes while targeting the Wnt5a/Ror2/p38 MAPK axis. If translatable, semaglutide could represent a therapeutic strategy to protect alveolar bone by reducing ferroptosis-driven osteoblast dysfunction in diabetes-associated periodontitis.

Zhang Z, Niu D, Qiu W et al. · Drug design, development and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Real-world comparison of anti-CD20 therapies: efficacy, infections, and immune profiles in a German cohort.

This real-world cohort study compared anti-CD20 therapies—ocrelizumab, ofatumumab, and rituximab—in 262 patients with neuroimmunological diseases, tracking relapses, infections, and immunoglobulin levels over a median of 36 months. The key finding was that different anti-CD20 agents show distinct dynamics in humoral and cellular immune profiles alongside differences in infection risk and clinical outcomes. Clinically, these comparative immune and safety data can inform selection and monitoring of B-cell-depleting therapy in neuroinflammation, including CNS involvement.

Stögbauer J, Bewarder M, Groß L et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

A decade of clinical data with vedolizumab: the past, present, and future.

This narrative review summarized a decade of clinical experience with vedolizumab in inflammatory bowel disease (IBD), covering how treatment strategies and endpoints have evolved over time. It highlights the shift toward treat-to-target approaches using objective measures such as endoscopy and histology/transmural healing, while positioning vedolizumab within modern therapeutic algorithms for ulcerative colitis and Crohn’s disease. The significance is that it consolidates evidence to guide current and future use of vedolizumab as IBD management becomes more endpoint-driven and personalized.

Jairath V, Armuzzi A, Agboton C et al. · Therapeutic advances in gastroenterology · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial activity promotes neutrophil degranulation and endothelial dysfunction in systemic infections.

This work studied how mitochondrial activity regulates neutrophil degranulation and endothelial dysfunction in systemic infections by comparing neutrophil proteomes from patients with severe malaria and sepsis and linking these profiles to functional outcomes. The authors found upregulated mitochondrial pathways associated with increased mitochondrial respiration and neutrophil immaturity, and they showed that neutrophil degranulation degrades the endothelial glycocalyx and increases endothelial permeability. The results identify mitochondrial programs as potential therapeutic targets to limit immunopathology driven by excessive neutrophil activation in severe systemic infections.

Zakrzewski P, Rice CM, Naveh C et al. · EMBO molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds.

This study developed a removable cell-based cytokine patch using engineered human retinal epithelial cells embedded in alginate within a polydimethylsiloxane device, and tested it in rodent and porcine full-thickness wound models. The patch continuously released native, tissue-repair-relevant cytokines and accelerated healing compared with controls. Clinically, this platform offers a translational strategy to restore dysregulated immune and matrix-remodeling signals that contribute to chronic wound progression.

Schreib CC, Kelley EL, Audia G et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

From inflammation to fibrosis and cancer: the emerging role of AIEC-derived metabolites in intestinal disease progression.

This review synthesized evidence on how metabolites derived from adherent-invasive Escherichia coli (AIEC) influence intestinal disease progression, connecting dysbiosis-driven inflammation to downstream fibrosis and colorectal cancer risk in inflammatory bowel disease (IBD). The authors highlight AIEC-derived metabolic drivers as contributors to the transition from inflammation to fibrosis and malignancy, and discuss emerging therapeutic implications. The significance is that targeting AIEC metabolism may offer new interventions for IBD patients at high risk of fibrotic and neoplastic complications.

Ahn JH, Hazelton A, Nguyen J et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Autoantibodies to IL-1Ra and PGRN in severe COVID-19 are associated with inflammation-induced hyperphosphorylated antigen isoforms.

This study examined severe COVID-19 patients for autoantibodies against IL-1 receptor antagonist (IL-1Ra) and progranulin (PGRN) and assessed how these relate to antigen phosphorylation and inflammatory signaling. Autoantibodies to hyperphosphorylated IL-1Ra (Thr111) and PGRN (Ser81) formed immune complexes, reduced circulating antigen levels, and enabled enhanced IL-1 and TNF signaling. These findings identify a mechanism-driven autoimmunity signature in severe COVID-19 that could support targeted immunomodulatory approaches.

Thurner L, Fadle N, Thurner B et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

PRELP negatively regulates IL-17A-mediated proliferation and the inflammatory response in psoriasis.

This study investigated the role of proline/arginine-rich end leucine-rich repeat protein (PRELP) in psoriasis, focusing on how it modulates IL-17A-driven keratinocyte proliferation and inflammation. PRELP was negatively regulated by IL-17A in keratinocytes, and PRELP expression was upregulated in psoriasis lesions after treatment with IL-17A inhibitors (secukinumab, ixekizumab, and brodalumab). These results suggest PRELP as a psoriasis-relevant regulatory factor that may help explain therapeutic responses to IL-17A blockade.

He CC, Lei MX, Jiang JW et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Autoimmune gastritis: a hidden gateway to cardia and oesophageal cancers beyond non-cardia gastric adenocarcinoma.

This review studied the evidence linking autoimmune gastritis (AIG) and pernicious anemia to cancers beyond the traditional association with non-cardia gastric adenocarcinoma, specifically cardia/gastro-oesophageal junction (GOJ) adenocarcinoma and oesophageal cancers. It synthesizes epidemiological and clinical data and proposes mechanisms involving corpus-predominant atrophy, intestinal metaplasia, immunologic changes, and vitamin B12 deficiency. The work is significant because it broadens the recognized oncogenic footprint of AIG, informing risk stratification and surveillance considerations for upper GI malignancies.

Lenti MV, DiPaolo RJ, Di Sabatino A et al. · Gut · (2026) · View on PubMed ↗

Guidance on JAK inhibitor treatment for inborn errors of JAK-STAT signaling (2026). An international consensus statement on behalf of the ESID/EBMT-IEWP and ERN-RITA.

This international consensus guideline studied evidence and expert recommendations for using JAK inhibitors (JAKi) to treat inborn errors of JAK-STAT signaling with gain-of-function (JAK-STAT GOF IEI) across all age groups. The key finding is the development of evidence- and consensus-based treatment recommendations despite the lack of licensed JAKi for these rare conditions and limited high-quality trial data. Clinically, the guideline aims to standardize off-label JAKi use to improve immune dysregulation and reduce complications such as autoimmunity, malignancy risk, and infection susceptibility.

Olbrich P, Fischer M, Deyà-Martinez A et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗

Real-world comparison of herpes zoster risk among five Janus kinase inhibitors in rheumatoid arthritis: the ANSWER cohort study.

This real-world cohort study analyzed herpes zoster risk among rheumatoid arthritis patients treated with five Janus kinase inhibitors (tofacitinib, baricitinib, peficitinib, upadacitinib, and filgotinib) in the multicenter ANSWER cohort. The key finding was the calculation of herpes zoster incidence rates per 100 patient-years and comparative time-to-event/retention analyses using Kaplan–Meier methods and hazard ratios across the different JAKi exposures. Clinically, the results provide comparative safety evidence to guide JAKi selection and risk mitigation for herpes zoster in RA patients.

Etani Y, Okita Y, Maeda Y et al. · Joint bone spine · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic regulation, mitochondria & aging

Mitochondrial calcium uptake drives organelle remodeling to promote inflammasome-dependent cytokine release.

The research investigated how mitochondrial calcium uptake regulates organelle remodeling to drive inflammasome-dependent cytokine release in lipopolysaccharide-primed macrophages. It found that Ca2+ entry via the mitochondrial calcium uniporter (MCU) is required for mitochondrial fragmentation and subsequent NLRP3 inflammasome-mediated IL-1β release, with fragmentation depending on organelle fission machinery but not on the mitochondrial permeability transition pore. This is significant because it positions MCU as a mechanistic control point for IL-1β–driven inflammation and suggests a potential therapeutic lever for inflammatory diseases such as those involving monosodium urate (MSU) crystals.

Gherardi G, Spinelli F, Sbrissa M et al. · Cell death and differentiation · (2026) · View on PubMed ↗ · Free PDF ↗

Glycogen drives the sensory activation of POMC neurons.

This study examined how hypothalamic POMC neurons sense food-related sensory cues, focusing on the role of glycogen metabolism in activation. Genetic depletion of glycogen in POMC neurons rendered them unresponsive to food-associated sensory stimuli, altering consummatory behavior, hepatic physiology, and cephalic insulin release and producing a prediabetic-to-overweight/diabetes phenotype under high-calorie conditions. The findings are significant because they identify glycogen as a sensory transduction mechanism in POMC neurons, linking neural food perception to systemic metabolic disease progression.

Gómez-Valadés AG, Meseguer D, Varela L et al. · Nature metabolism · (2026) · View on PubMed ↗

tRNA m1A modification ensures HSPC production via modulating Nrf1 translation in zebrafish.

This study investigated how tRNA N1-methyladenosine (m1A) modification controls hematopoietic stem and progenitor cell (HSPC) production during embryogenesis in zebrafish. It identified tRNA m1A58 as a key modification for HSPC fate, showing that depletion of trmt61a reduces tRNA m1A58 levels and compromises HSPC production in the aorta-gonad-mesonephros (AGM) region via p53-dependent apoptosis, linked to altered Nrf1 translation. The work is significant because it reveals a translational control mechanism (Trmt61a–tRNA m1A58–Nrf1) that governs early HSPC development, suggesting new targets for regulating hematopoiesis.

Dong Z, Li P, Liu M et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Mitigating copper toxicity in Carthamus tinctorius L. through 6-benzylaminopurine during seed germination and vegetative growth.

This study examined whether 6-benzylaminopurine (6-BAP) can mitigate copper (Cu) toxicity in Carthamus tinctorius during seed germination and vegetative growth using a factorial design across multiple CuSO4 and BAP concentrations. High Cu reduced germination and growth traits, photosynthetic pigments, root/shoot protein content, and peroxidase (POX) activity while increasing Cu accumulation and altering oxidative-stress-related enzyme activities such as PPO, and BAP was tested for its ability to counter these effects. The significance is that BAP may enhance plant Cu tolerance by modulating growth, antioxidant/oxidative pathways, and Cu accumulation under metal stress.

Liavoli HA, Najafi F, Shirkhani Z · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Open-channel block of human TRPV6 by polyamine spermine.

This study investigated how the polyamine spermine regulates human TRPV6 using calcium imaging, electrophysiology, cryo-electron microscopy, mutagenesis, and molecular dynamics simulations. Spermine produced a voltage-dependent open-channel block of TRPV6-mediated currents, and the structural/biophysical work aimed to define the underlying binding mechanism. These findings clarify a structural basis for polyamine modulation of TRPV6, informing how TRPV6 activity may be tuned in physiology and diseases such as cancer and inflammation.

Neuberger A, Veretenenko II, Shalygin A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A transport-independent role for SLC25A12 in mitochondrial stress signalling.

This Nature Cell Biology study investigated the mitochondrial carrier SLC25A12 and found it has an integrated stress response (ISR)-related role in mitochondrial stress signalling that is independent of its transport activity. The key finding is that SLC25A12 interacts with mitochondrial components to trigger stress signalling even when its metabolite transport function is not required. This is significant because it identifies a non-transport mechanism for SLC25A12 in cellular stress adaptation, with implications for diseases linked to mitochondrial carrier dysfunction.

Jiang L, Li L, Guan J et al. · Nature cell biology · (2026) · View on PubMed ↗

Human haematopoietic stem cells remember inflammatory stress.

This Nature study examined how human hematopoietic stem cells (HSCs) adapt to inflammatory stress by using xenograft inflammation–recovery models and single-cell multiomics on xenografted human HSCs. The key finding is identification of two transcriptionally and epigenetically distinct HSC subsets, including an HSC inflammatory memory (HSC-iM) subset that retains molecular memory of prior inflammatory treatments and shows quiescence with restrained hematopoietic output. This is significant because it provides mechanistic evidence for long-term functional reprogramming of human HSCs after inflammation, with implications for aging and malignancy risk.

Zeng AGX, Nagree MS, Jakobsen NA et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Mechanism of age-related accumulation of mtDNA mutations in human blood.

This Nature study investigated the mechanism of age-related accumulation of mitochondrial DNA (mtDNA) mutations in human blood using whole-genome sequencing from ~750,000 individuals to quantify mtDNA sequence, mtDNA abundance, and heteroplasmic variants. The key finding is that mtDNA single-nucleotide variants (mtSNVs) accumulate sharply around age 60, show low heteroplasmy levels, little evidence of positive selection, and a mutational spectrum consistent with mtDNA replication errors rather than oxidative lesions. This is significant because it identifies replication error as a likely driver of age-associated mtDNA mutagenesis, informing models of aging biology and mitochondrial disease risk.

Gupta R, Durham TJ, Chau G et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Cellular water-potential sensing through biomolecular condensation.

The study investigated how cells sense changes in water potential under water-deficient conditions, focusing on a sterile alpha motif (SAM)-containing protein called SAM8. The authors found that SAM8 undergoes water-potential-dependent liquid-liquid condensation in vivo and in vitro, and that SAM8 hydration is governed by a negatively charged patch that prevents macroscopic condensation, making SAM8 crucial for hyperosmotic stress tolerance and seed germination. These findings identify a molecular mechanism for water-potential sensing via biomolecular condensation, with implications for understanding stress adaptation in plants and other organisms.

Wang Y, Zhu L, Yang Y et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Universal transcriptomic hallmarks of mammalian ageing and mortality.

The study integrated transcriptomic data from more than 11,000 samples across over 25 tissues in four mammals (mouse, rat, macaque, and human) to define universal transcriptomic hallmarks of mammalian ageing and mortality. The key finding was that ageing-associated gene-expression changes are conserved across species and cell types and can be used to build interpretable biomarkers of chronological age and expected mortality, including signatures involving CDKN1A and LGALS3. This provides cross-species, clinically relevant molecular predictors of lifespan and intervention effects, enabling more systematic evaluation of rejuvenation and age-modifying strategies.

Tyshkovskiy A, Kholdina D, Davitadze M et al. · Nature · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

β-Arrestin condensates regulate G-protein-coupled receptor function.

The study examined how β-arrestins regulate G-protein-coupled receptor (GPCR) function by testing whether β-arrestin condensates form and control signaling. The authors found that β-arrestin 1/2 undergo liquid-liquid phase separation to form condensates that regulate GPCR function, with condensation specific to visual arrestins and β-arrestins and β-arrestin oligomerization occurring near the GPCR. This mechanistic link between phase separation and GPCR regulation suggests new ways to modulate GPCR signaling therapeutically by targeting condensate formation or dynamics.

Anderson PJ, Xiao P, Zhong YN et al. · Nature · (2026) · View on PubMed ↗

Cuproptosis inducers mediate cold lethality via SLCR-46.1 in C. elegans.

This study tested whether cuproptosis contributes to cold-induced lethality in Caenorhabditis elegans and identified the relevant copper-handling gene SLCR-46.1. A slcr-46.1 lysosomal copper transporter mutant showed defective cold tolerance due to copper accumulation in the pharyngeal muscle, and this phenotype was suppressed by disrupting copper homeostasis or cuproptosis-signaling genes; chelating copper rescued cold tolerance, while inhibiting cuproptosis signaling reduced cold-induced lethality in wild-type worms. These results establish cuproptosis as a functional driver of environmental cold sensitivity and position SLCR-46.1–dependent copper overload as a key upstream trigger.

Yamashiro S, Mizuno S, Motomura H et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Gallstones: Physiopathology and treatment of cholelithiasis (part 1).

This article reviewed the physiopathology and treatment approaches for cholelithiasis (gallstones), focusing on mechanisms of bile composition imbalance and gallbladder stasis. It summarizes that cholesterol gallstones (most common) and pigment gallstones arise from factors such as cholesterol oversaturation, low bile acids, and impaired gallbladder emptying, with risk factors including age, female sex, rapid weight fluctuations, pregnancy, and conditions like diabetes, obesity, cirrhosis, and Crohn’s disease. Clinically, the review consolidates current understanding of stone types and risk profiles to guide selection of appropriate diagnostic and therapeutic strategies.

Golse N, Boulard P, Ciacio O et al. · Journal of visceral surgery · (2026) · View on PubMed ↗ · Free PDF ↗

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Genetics, polygenic risk & epidemiologic risk prediction

Multi-omics pleiotropic association analyses reveal functionally relevant genes and druggable pathways for ovarian aging.

This Genome Biology study performed multi-omics pleiotropic association analyses integrating ovarian aging genome-wide association studies with multi-omics summary data to prioritize functionally relevant genes and druggable pathways. Using Mendelian randomization and cross-omics association approaches, it identified key proteins, gene expression signals, splicing events, and metabolites linked to ovarian aging, including conserved genes across species. The scientific significance is that it generates candidate targets and pathways that may enable development of interventions for ovarian aging.

Lian X, Song S, Lou C et al. · Genome biology · (2026) · View on PubMed ↗ · Free PDF ↗

Obesity and the experienced cultural, economic, and climate variations among immigrants to high-income countries: An umbrella review of the literature.

This umbrella review synthesized evidence from systematic reviews and meta-analyses on cultural, socioeconomic, and environmental determinants of obesity among adult immigrants (including economic migrants, students, and refugees) in high-income countries. Across included studies, obesity and weight gain were associated with multifactorial exposures spanning acculturation-related cultural factors, socioeconomic conditions, and climate/environmental context. The findings are clinically and public-health significant because they support more tailored, multilevel obesity prevention strategies for immigrant populations in high-income settings.

Abed Al Ahad M, Fenyk M · Public health nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

A Global Update on the Status of Prevention of Folic Acid-Preventable Spina Bifida and Anencephaly in Year 2024.

This study estimated the global proportion of folic-acid-preventable spina bifida and anencephaly (FAP SBA) prevented in 2024 through mandatory folic acid fortification of cereal grains (wheat flour, maize flour, and rice). Using country-specific fortification data from the Food Fortification Initiative for 2024 (69 countries with complete data), the authors modeled prevention assuming maternal folic acid intake above a threshold (>150 mcg/day) during early pregnancy. The results are significant for guiding policy by quantifying how much mandatory fortification is likely preventing these neural tube defects worldwide in 2024.

Kancherla V, Wagh K, Pachón H · Birth defects research · (2026) · View on PubMed ↗

Association between loneliness trajectories and chronic diseases as well as chronic comorbidities among middle - aged and elderly chinese: based on the group - based trajectory modeling method.

This study assessed associations between loneliness trajectories and chronic diseases/comorbidities among middle-aged and elderly Chinese adults using group-based trajectory modeling. In 8,935 participants (age ≥45) from the China Health and Retirement Longitudinal Study (2011–2020), three loneliness trajectories (low, moderate, high) were identified and logistic regression tested their associations with chronic disease outcomes. The results are significant because they quantify how persistent loneliness patterns relate to multimorbidity risk, supporting loneliness as a potential target for chronic disease prevention interventions.

Pang Y, Jiang Y, Sa N et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Genomic and population analyses reveal asymmetric subgenome evolution and local adaptation in the polyploid Lycopus lucidus.

This study generated a chromosome-level genome assembly and population genomic datasets for the polyploid medicinal plant Lycopus lucidus to characterize subgenome evolution and local adaptation after a recent whole-genome triplication. It found strong asymmetry among three subgenomes in transposable element accumulation, gene retention, and evolutionary rates, with subgenome B stabilized under purifying selection while subgenomes A and C showed dynamic reorganization. These results clarify how asymmetric subgenome evolution can shape ecological adaptation in polyploid plants.

Zhang R, Wang M, Jiang F et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

Distinct genetic architecture in the tails of complex traits.

This Nature study analyzed how genetic architecture varies along the trait continuum by developing a polygenic risk score–based approach to detect departures from common-variant architecture in the tails of complex traits. The key finding is widespread evidence that one or both tails of 74 quantitative traits show distinct genetic architecture, replicated across ancestries, cohorts, and repeated measures, and supported by a family-based alternative approach. This is significant because it refines how selection and rare variants shape extreme phenotypes, improving interpretation of genetic risk across the full trait distribution.

Souaiaia T, Wu HM, Ori APS et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Polygenic scores for risk of pancreatic ductal adenocarcinoma: evaluation of novel and published models.

The study evaluated polygenic risk score (PRS) models for pancreatic ductal adenocarcinoma (PDAC) risk, comparing novel Bayesian PRSs (LDpred2, PRS-CS) and p-value thresholding (PRSice-2) against 13 published models for performance and cross-ancestry transferability. Using GWAS summary statistics from 7,531 PDAC cases and 10,631 controls and testing in an independent set of 4,508 PDAC cases and 46,189 controls with adjustment for established PDAC risk factors, the authors identified PRS models with more robust predictive performance across ancestries. This supports improved genetic risk stratification for PDAC and highlights which PRS designs generalize better across populations.

Antwi SO, Coombes BJ, Carlson EE et al. · NPJ precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Predictive Role of PSA Kinetics in Oncological Outcomes of Metastatic Castration-sensitive Prostate Cancer.

This study evaluated whether PSA kinetics predict oncological outcomes in metastatic castration-sensitive prostate cancer (mCSPC) treated with upfront androgen receptor signaling inhibitor (ARSI) doublet therapy. Using the ULTRA-J database, the authors retrospectively analyzed 352 high-risk mCSPC patients and assessed PSA nadir, PSA response rate, and time to PSA nadir (TTN) for associations with outcomes. The significance is that PSA kinetics may provide real-world prognostic stratification to refine risk assessment and follow-up strategies in mCSPC treated with ARSI doublets.

Yamamoto Y, Matsumura N, Fujimoto S et al. · Anticancer research · (2026) · View on PubMed ↗

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Methodology, AI/ML & clinical prediction tools

Test-Retest Reliability of Standardized Diagnostic Interviews for Common Adult Psychiatric Disorders: A Systematic Review and Meta-Analysis.

This JAMA Network Open systematic review and meta-analysis evaluated test-retest reliability of standardized diagnostic interviews (SDIs) for classifying common adult psychiatric disorders across studies. It reported pooled estimates of SDI reliability and examined differences by disorder and study-level factors contributing to heterogeneity. Clinically, the findings inform how consistently SDIs can be used for diagnosis and research classification, supporting more dependable psychiatric phenotyping.

Xie W, Nordgaard J, Sheldrick RC et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Immunotherapy drug target identification using machine learning and patient-derived tumour explant validation.

This study developed MIDAS (Mining Immunotherapy Drug tArgetS), a multimodal graph neural network system for immunotherapy drug target identification, and validated candidate targets using patient-derived tumour explants. MIDAS integrates gene interactions, multi-omic patient profiles, immune cell biology, antigen processing, disease associations, and phenotypic consequences of genetic perturbations, and it generalizes to time-sliced data while outperforming baselines including OpenTargets. The approach aims to accelerate discovery of immuno-oncology targets for patients less likely to respond to existing therapies by enabling explant-based functional validation.

Augustine M, Nene NR, Fu H et al. · Nature machine intelligence · (2026) · View on PubMed ↗ · Free PDF ↗

Quality and performance of machine learning versus logistic regression for predicting IVIG resistance in Kawasaki disease: a PROBAST+AI systematic comparison.

This PROBAST+AI systematic comparison evaluated the methodological quality and predictive performance of machine learning (ML) versus logistic regression (LR) models for predicting intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Across included prediction studies, the authors assessed risk of bias and applicability and synthesized discrimination using random-effects meta-analysis of logit-transformed AUC values. The significance is that it provides evidence-based guidance on whether ML models offer reliable advantages over LR for clinical prediction of IVIG resistance in KD.

Zhang J, Wang D, Dong J et al. · BMC medical research methodology · (2026) · View on PubMed ↗ · Free PDF ↗

Scoring gene importance by interpreting single-cell foundation models.

The paper introduced SIGnature, a computational framework for scoring gene importance by interpreting attributions from single-cell RNA-sequencing (scRNA-seq) foundation models. Using attribution scores rather than raw expression, the method reduces technical noise, highlights regulatory genes, and enables cross-dataset gene set searches, demonstrated with the MS1 monocyte signature. This is significant for single-cell biology because it provides a practical way to prioritize genes functionally across large scRNA-seq atlases using foundation-model interpretability.

Gold MP, Reyes M, Diamant N et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Deep chemical structure graph learning deciphers the lipotoxicity code of hypertriglyceridemic pancreatitis.

This study investigated lipotoxicity mechanisms in hypertriglyceridemic acute pancreatitis (HLAP) by developing DeepLipiDecipher, a knowledge-guided graph neural network that integrates lipid chemical structures with metabolic topology, and evaluated it in a retrospective cohort of 433 subjects. DeepLipiDecipher outperformed conventional lipidomics based on linear abundance by identifying latent HLAP-specific lipotoxic features, achieving AUC = 0.810 for distinguishing HLAP from the metabolic background of hypertriglyceridemia. Scientifically and clinically, the approach improves risk stratification by decoding a “lipotoxicity code” that standard lipidomics cannot resolve.

Huang A, Yuan Q, Chen J et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Personalised thrombo-embolic risk prediction after endometrial cancer surgery: an explainable AI approach using SHAP.

This study used perioperative data from 841 endometrial cancer surgery patients to build an explainable AI model for personalized postoperative lower-extremity deep vein thrombosis (LEDVT) risk prediction, comparing 26 machine learning algorithms. A support vector machine (SVM) model with recursive feature elimination selected four variables—postoperative D-dimer, age, fibrinogen, and clinical stage—and achieved strong discriminative performance (AUC reported as superior in the truncated abstract). Clinically, the SHAP-based explainability and compact feature set could enable individualized thrombosis risk stratification and targeted prophylaxis after surgery.

Zhou Q, Liu F, Li J et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Multi-cytokine based TWAS for seven inflammatory skin disorders identify candidate causal genes in keratinocytes.

This study performed multi-cytokine transcriptome-wide association studies (TWAS) in human keratinocytes stimulated with eight pro-inflammatory cytokines to identify genetically regulated expression (GReX) and candidate causal genes for seven inflammatory skin disorders (atopic dermatitis, psoriasis, acne, alopecia areata, systemic sclerosis, SLE, and vitiligo). The authors reported that the multi-condition TWAS approach identified 274 loci and highlighted candidate causal genes with evidence consistent with keratinocyte-relevant inflammatory biology. These findings suggest that modeling GReX across multiple cytokine contexts can improve causal gene discovery for complex inflammatory skin diseases and prioritize targets for downstream functional validation.

Zhang H, Patrick MT, Sarkar MK et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗

Assessing the trustworthiness of health guidelines recommendations: the Transparent, Rigorous, Usable, Standardised and Trustworthy Guide (TRUSTGUIDES) tools development.

This methodological study developed and validated the TRUSTGUIDES tools (Transparent, Rigorous, Usable, Standardised and Trustworthy Guide) to assess the trustworthiness of individual health guideline recommendations. The key finding is that TRUSTGUIDES addresses shortcomings of existing appraisal tools by incorporating broader, up-to-date guideline methodology elements (including living guidelines, GRADE, adaptation, and AI-related considerations) to evaluate recommendation-level trustworthiness. Scientifically and clinically, the tool supports more reliable guideline interpretation and implementation by improving transparency, rigor, and consistency in how recommendations are judged.

Arienti C, Neumann I, Akl EA et al. · Journal of clinical epidemiology · (2026) · View on PubMed ↗

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Generated automatically on May 29, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.