PubMed Trending Research Digest — August 28, 2026

Automated digest · 98 articles · 15 research areas · August 28, 2026

Overview

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Anticoagulation & Thrombosis (AF/VTE/ATTR-CM)

Beat- and Side-family cell-surface molecules are expressed combinatorially in the partner neurons of the olfactory circuit in Drosophila.

The study investigated combinatorial expression of the IgSF cell-surface gene families beat and side in Drosophila olfactory receptor neurons (ORNs) and their synaptic projection neurons (PNs) using newly generated gene trap transgenic driver lines. Beat/side family genes were found to be expressed in partner neurons in specific combinations, consistent with a Beat–Side IgSF protein interactome that can act as neuron-specific recognition tags during olfactory circuit assembly. This work clarifies how multi-member cell-surface gene families encode synaptic partner identity in vivo, providing a mechanistic framework for complex olfactory wiring in the fly brain.

Duan Q, Okuwa S, Estrella R et al. · PLoS biology · (2026) · View on PubMed ↗

Lesion-Level Subtypes of White Matter Hyperintensity Evolution Beyond Spatial Location.

This longitudinal observational study analyzed 3224 MRI scans from 403 participants across cognitively normal aging and mild cognitive impairment to identify lesion-level white matter hyperintensity (WMH) subtypes beyond spatial location and test associations with neurodegeneration and vascular risk. The key finding was that WMH can be stratified into biologically distinct lesion-level subtypes that show different relationships with subsequent neurodegeneration and vascular risk factors, rather than behaving as a uniform process. Clinically, this supports moving beyond global WMH burden metrics toward lesion-level phenotyping to better predict and understand cerebrovascular contributions to cognitive decline.

Gonzalez-Gomez R, Tagliazuchi E, Campo CG et al. · Neurology · (2026) · View on PubMed ↗

Pregnancy Outcomes in Individuals With Long COVID.

This prospective multicenter cohort study (RECOVER Adult) evaluated whether maternal Long COVID status—classified using the Long COVID Research Index (LCRI)—is associated with adverse pregnancy outcomes in individuals with prior SARS-CoV-2 infection who reported symptom surveys during or before pregnancy. The study found an association between Long COVID classification and pregnancy outcomes, indicating that maternal Long COVID status may influence risk of adverse events. Scientifically and clinically, it highlights the need to account for Long COVID phenotype when counseling and managing pregnancy in patients with a history of COVID-19.

Metz TD, Sandoval GJ, Allshouse AA et al. · Obstetrics and gynecology · (2026) · View on PubMed ↗

Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial.

The DEEPER randomized phase II trial compared modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS/BRAF wild-type metastatic colorectal cancer, and this final analysis evaluated long-term overall survival (OS) and progression-free survival (PFS) with exploratory subgroup analyses in the per-protocol set. The key finding was that the updated long-term survival outcomes did not show differences in PFS and OS between treatment arms in the reported analyses. This informs the durability of benefit (or lack thereof) for m-FOLFOXIRI+cetuximab versus bevacizumab in RAS/BRAF wild-type mCRC, including considerations for left-sided disease and other subgroups.

Sunakawa Y, Shiozawa M, Watanabe T et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Refined Continuous Risk Index for Accurately Predicting Outcomes of Patients With Chronic Lymphocytic Leukemia After Limited-Duration Therapy.

This study developed and validated a refined continuous individualized risk index (CIRI2) for chronic lymphocytic leukemia (CLL) patients treated with fixed-duration targeted therapy by incorporating measurable residual disease (MRD) at interim, end-of-treatment (EoT), and 12 months post-EoT. The key finding was that CIRI2 improves outcome prediction beyond pretreatment-only indices by leveraging dynamic MRD trajectories after limited-duration therapy. Clinically, this supports more accurate risk stratification and potentially better tailoring of follow-up or treatment decisions based on MRD over time.

Al-Sawaf O, Zhang C, Esfahani MS et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

De novo design of RNA pseudoknots with deep learning.

This study demonstrated de novo design of RNA pseudoknots using deep learning generative AI methods that generate accurate pseudoknot secondary structures. The key finding was that AI-designed RNA molecules matched experienced human designers in an Eterna blind competition and were validated by single-nucleotide chemical mapping, compensatory mutagenesis, and cryo-electron microscopy, with correct secondary structures forming well-ordered 3D folds stabilized by noncanonical tertiary interactions. This is significant because it advances the ability to design complex RNA structures despite limitations in 3D structure prediction accuracy.

Townley J, Kladwang W, Baker D et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Autism mutations rewire protein interaction networks to drive neurodevelopmental pathology.

This study investigated how autism spectrum disorder (ASD) mutations rewire protein-protein interaction (PPI) networks by mapping PPIs for 100 high-confidence ASD genes using affinity purification-mass spectrometry and then assessing effects of pathogenic missense mutations with AlphaFold and human-derived model validation. The key finding was convergence onto shared protein complexes in the wild-type state and convergent PPI rewiring driven by independent mutations. Scientifically, it links causal ASD genes to network-level mechanisms, suggesting potential targets at the level of affected protein complexes.

Wang B, Vartak R, Hennick KM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

A tripartite genetic conflict system controls hybrid sterility in rice.

This study dissected the genetic basis of hybrid sterility in interspecific Asian–African hybrid rice and identified RHS3 as a major quantitative trait locus controlling the trait. RHS3 encodes a tripartite toxin–antidote system (MAO, DUN, and JIA) where MAO disrupts mitochondrial function to abort gametes, while DUN and JIA act via selective autophagy to neutralize MAO toxicity, enabling transmission advantage of the African allele. The significance is that it reveals a specific molecular conflict system underlying reproductive isolation and provides insight into the de novo origin of such loci in the AA-genome rice lineage.

He X, Zhao Z, Shao K et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

SGLT2 inhibitors activate pantothenate kinase in the human heart.

This study examined the mechanism of action of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in human heart tissue by testing whether they activate pantothenate kinase 1 (PANK1), the rate-limiting enzyme in coenzyme A (CoA) synthesis. The key finding was that SGLT2i directly bind PANK1 at physiological concentrations, induce conformational changes, increase PANK1 enzymatic activity, and thereby activate CoA synthesis and broadly stimulate fuel use in human cardiac tissue. Clinically, this identifies a direct molecular target (PANK1) that can help explain the cardioprotective effects of SGLT2 inhibitors.

Forelli N, Thome T, Eaton DM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Allele-Specific Mechanisms Guide Salvage Therapy to Overcome Daraxonrasib Resistance in Pancreatic Cancer.

This cancer research study investigated allele-specific resistance mechanisms to daraxonrasib (RMC-6236), a multi-selective RAS(ON) inhibitor, in pancreatic ductal adenocarcinoma (PDAC) models harboring KRASG12D versus KRASG12R. It found that daraxonrasib inhibited KRASMUT mainly via steric occlusion of effector binding with modest engagement of RASWT (~20%), while KRASG12R resistance relied on EGFR/RASWT-GTP signaling as the dominant adaptive route and KRASG12D resistance used a different adaptive pattern. These allele-specific mechanisms are significant because they suggest salvage therapy strategies tailored to the patient’s KRAS mutation subtype to overcome daraxonrasib resistance.

Dorbin D, Herrera J, Davidson R et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗

Single-Nucleus and Multiomics Profiling of Epicardial Adipose Tissue in Atrial Fibrillation Reveals Novel Mechanisms and Translational Biomarkers.

This study profiled epicardial adipose tissue (EAT) in atrial fibrillation (AF) using single-nucleus RNA sequencing and multiomics approaches, integrating population data and genetic evidence from Mendelian randomization. It identified novel cellular and molecular/immune mechanisms in EAT linked to AF and proposed translational biomarkers validated in additional datasets. The significance is that it advances mechanistic understanding of how cardiac visceral fat contributes to AF and supports biomarker development for risk prediction or stratification.

Huang S, Yang Z, Zhong X et al. · Journal of the American Heart Association · (2026) · View on PubMed ↗ · Free PDF ↗

PCNA-RECQL5-RPRD1B recruit repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells.

The study examined how microRNA miR-4485-3p and the repair factor RPRD1B regulate replication-fork stress responses in BRCA1-deficient cancer cells that rely on polymerase theta (POLQ) microhomology-mediated end joining (MMEJ). Re-expression of miR-4485-3p suppressed RPRD1B, and RPRD1B depletion selectively reduced MMEJ and replication fork repair while promoting death of BRCA1-deficient cells, with RPRD1B reported to recruit MMEJ components including 53BP1 and PARP1 to stressed forks. This identifies an miR-4485-3p–RPRD1B axis as a potential synthetic-lethal vulnerability and a mechanistic target to impair replication stress tolerance in BRCA1-deficient tumors.

Tran MT, Williamson EA, Jaiswal AS et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Harnessing the E3 Ligase KLHL12 for Tumor-Selective Protein Degradation.

The research developed KLHL12-recruiting PROTACs using a structure-based macrocyclization strategy, testing tumor-selective degradation of oncogenic BRD4 and EGFR in cell models including A549 lung cancer cells. The lead compound k12bp-1 achieved tumor-selective BRD4(L) degradation, inhibited proliferation, and induced apoptosis while sparing non-targeted effects (as reported in the truncated abstract). This provides a first-in-class approach to improve PROTAC tumor selectivity by leveraging the E3 ligase KLHL12 rather than ubiquitously expressed ligases.

Xu S, Zhang X, Hu S et al. · Angewandte Chemie (International ed. in English) · (2026) · View on PubMed ↗

Mepolizumab Modifies Blood Eosinophil Proteome and Transcriptome in Severe Eosinophilic Asthma.

This study investigated how mepolizumab (an anti-IL5 monoclonal antibody) alters the proteome and transcriptome of circulating blood eosinophils in severe eosinophilic asthma (SEA) patients compared with healthy individuals. Using LC-MS/MS proteomics and Nanostring targeted transcriptomics on isolated eosinophils at baseline and after treatment, the authors aimed to define molecular signatures that persist despite rapid eosinophil count reduction. The work is significant because it may explain why some SEA patients remain symptomatic and could reveal biomarkers or pathways beyond eosinophil abundance that drive ongoing disease.

Miguéns-Suárez P, Vázquez-Mera S, Martelo-Vidal L et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

Epstein-Barr Virus and Multiple Sclerosis: Mechanistic Insights into Virus-Driven Autoimmunity.

This article reviewed mechanistic links between Epstein-Barr virus (EBV) infection and multiple sclerosis (MS), focusing on EBV’s role in virus-driven autoimmunity in the context of MS epidemiology and immunology. It highlights that nearly all people with MS are EBV-seropositive and that longitudinal data show EBV infection precedes MS onset, consistent with a causal contribution via EBV latency in B cells and downstream immune modulation. The significance is that it consolidates mechanistic hypotheses that could guide EBV-targeted prevention or therapeutic strategies for MS.

Bashiardes S, Krashias G, Englezou E et al. · Microorganisms · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review.

This systematic literature review assessed whether the day of the week affects clinical outcomes, adherence, and tolerability of once-weekly GLP-1 receptor agonists semaglutide and tirzepatide in type 2 diabetes mellitus and obesity. The key finding is that the timing-by-day-of-week question remains insufficiently explored in the existing literature, motivating the need for evidence to support personalized scheduling. Clinically, resolving this could improve real-world adherence and tolerability optimization for incretin-based therapies if a meaningful effect is demonstrated.

La Vignera S, Condorelli RA · Medicina (Kaunas, Lithuania) · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Bone Health: Exploring the “Heart-Brain-Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2).

This narrative review synthesized evidence for the “heart–brain–bone” axis and how lipid-soluble nutrients—omega-3 polyunsaturated fatty acids, vitamin D3, and vitamin K2—may modulate shared regulators of calcium handling, inflammation resolution, vascular integrity, and inflammaging. The authors emphasize that the axis is an integrative framework rather than a fully validated physiological entity with agreed diagnostic criteria or proven modifiability. Scientifically, it organizes mechanistic and translational rationale for studying these nutrients across cardiovascular, neurocognitive, and bone outcomes in aging populations.

Fang SC, Huang MK, Shen HE et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

Micronutrition as a Therapeutic Strategy for Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Narrative Review.

This narrative review evaluated micronutrition as a therapeutic strategy for mitochondrial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia, focusing on pathways including oxidative/nitrosative stress, immune dysregulation, and altered NAD+ metabolism. It concludes that micronutrients can support mitochondrial bioenergetics, antioxidant defenses, and immune-metabolic regulation, though the strength of evidence across mechanisms varies. The significance is that it frames testable micronutrient targets for fatigue and pain syndromes where mitochondrial and redox dysfunction are implicated.

Abanades S, Fernández I, Capdevila N et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Weight Loss: Skeletal Muscle Health During Incretin-Based Therapy in Patients with Diabesity.

This narrative review summarized evidence on skeletal muscle health during incretin-based therapy in patients with diabesity, emphasizing older adults at risk for sarcopenia and functional decline. It focuses on how GLP-1 receptor agonists (e.g., semaglutide) and dual GIP/GLP-1 receptor agonists (e.g., tirzepatide) may affect muscle outcomes based on randomized controlled trials and observational studies. The clinical significance is that it highlights the need to balance metabolic benefits with preservation of muscle mass and function during long-term incretin therapy.

Mollero ELM, Dozzani I, Biamonte E et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

T-Cell Engagers Targeting BCMA, GPRC5D, or FcRH5 in Relapsed/Refractory Multiple Myeloma: The Landscape Beyond CAR-T Cell Therapy-A Systematic Review and Network Meta-Analysis.

This systematic review and network meta-analysis compared T-cell engager bispecific antibodies targeting BCMA, GPRC5D, or FcRH5 in relapsed/refractory multiple myeloma (RRMM) beyond CAR-T cell therapy. Across 44 included studies, agents such as talquetamab, teclistamab, elranatamab, and linvoseltamab showed higher odds of objective response rate versus standard of care, with progression-free survival outcomes also assessed (truncated abstract). The significance is that it provides a comparative efficacy/safety landscape to inform treatment selection among non–CAR-T T-cell engager options in heavily pretreated RRMM.

Shambhavi S, Joy AA, Singh H et al. · International journal of molecular sciences · (2026) · View on PubMed ↗ · Free PDF ↗

Detection of TDP-43 Proteinopathies in Brain and Cerebrospinal Fluid Using Seed Amplification Assay.

The study developed and evaluated a streamlined, non-immunoprecipitation-based seed amplification assay using real-time quaking-induced conversion (RT-QuIC) to detect misfolded TDP-43 seeding activity in brain tissue and cerebrospinal fluid (CSF). It assessed diagnostic performance using CSF from patients with TDP-43 proteinopathies and control subjects, aiming to enable broader clinical implementation beyond technically complex workflows. This is significant because it advances practical detection of TDP-43 proteinopathies in CSF, which could improve diagnosis and patient stratification for ALS and frontotemporal lobar degeneration.

Satoh K, Shimamura MI, Fujimoto T et al. · Current issues in molecular biology · (2026) · View on PubMed ↗ · Free PDF ↗

SIOOT® Adjunct Oxygen-Ozone Therapy Against Multidrug-Resistant Bacteria: A Pilot Study of 257 Cases.

This pilot study evaluated standardized SIOOT® oxygen-ozone major autohemotherapy (SIOOT®-O2-O3-MAHT) given alongside conventional antibiotics in patients with chronic multidrug-resistant (MDR) bacterial infections. The adjunct oxygen-ozone therapy was reported to improve clinical and microbiological outcomes while exerting antimicrobial, antibiofilm, and immunomodulatory effects. If confirmed in larger controlled trials, SIOOT®-O2-O3-MAHT could become a non-antibiotic adjunct strategy to help manage MDR chronic infections and biofilm-associated disease.

Franzini M, Chirumbolo S, Ricevuti G et al. · Antibiotics (Basel, Switzerland) · (2026) · View on PubMed ↗ · Free PDF ↗

Cardiac Conduction Disorders in Melanoma Patients Treated with CTLA-4-Containing Versus PD-1-Only Immune Checkpoint Inhibitor Therapy: A Propensity Score-Matched Real-World Analysis.

This retrospective propensity score-matched real-world analysis compared cardiac conduction outcomes in adults with advanced melanoma treated with CTLA-4-containing immune checkpoint inhibitor regimens (ipilimumab plus anti–PD-1) versus anti–PD-1-only therapy (nivolumab or pembrolizumab) using the TriNetX electronic health record network. Patients exposed to CTLA-4 blockade had different (reported) risks of cardiac conduction disorders compared with PD-1-only exposure after matching. These findings are clinically important for selecting and monitoring ICI regimens to mitigate cardiotoxicity in melanoma patients.

Awad A, Khodeir J, AlQudah Q et al. · Cancers · (2026) · View on PubMed ↗ · Free PDF ↗

Current and future therapies for triple-negative breast cancer.

This review summarized current and emerging therapies for triple-negative breast cancer (TNBC) using a three-layer framework spanning tumor-cell-intrinsic vulnerabilities, the local immune/stromal microenvironment, and host-level systemic modifiers. The key message was that durable control is limited because responses are shaped by interacting biological layers rather than by drug class or single molecular subtype alone. Clinically, this framework supports more rational combination strategies and biomarker-driven approaches to improve outcomes in TNBC.

Wang ZX, Liu XY, Wu YX et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Programmable ZBTB7A RNA N6-methyladenosine site-specific demethylation suppresses colorectal cancer liver metastasis.

This study investigated how programmable N6-methyladenosine (m6A) site-specific demethylation of the m6A-modified transcription factor ZBTB7A affects colorectal cancer liver metastasis (CRLM), focusing on the METTL3–ZBTB7A axis. The authors reported that ZBTB7A demethylation suppresses CRLM progression by interfering with METTL3-mediated m6A regulation of ZBTB7A. Scientifically, it supports precise epitranscriptomic editing as a potential non-pharmacologic precision approach to overcome metastatic progression and therapy resistance.

Chen X, Zhao S, Liu B et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.

This integrative multi-omic study profiled over 300 lung neuroendocrine tumors (NETs/carcinoids) using whole-genome sequencing, transcriptome profiling, and DNA methylation arrays, followed by archetype analysis. It found molecularly distinct entities that are not captured by the current WHO grade-1 typical versus grade-2 atypical classification based on mitotic count and necrosis. The work is significant because it suggests a more molecularly grounded taxonomy that could improve clinical management and future targeted trial design for lung NETs.

Sexton-Oates A, Mathian É, Candeli N et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Cytotoxic CD4+ T cells induce age-associated myelopoiesis through CCL5-CCR5 signaling.

This study examined how cytotoxic CD4+ T cells drive age-associated myelopoiesis in aging mice, focusing on mitochondrial stress, STING activation, and CCL5–CCR5 signaling. The authors reported that T cell receptor-dependent mitochondrial stress and STING upregulated CCL5, while age-associated upregulation of CCR5 on hematopoietic stem cells and myeloid progenitors promoted myelopoiesis and increased the neutrophil-to-lymphocyte ratio. These findings are important for understanding mechanisms behind age-related immune skewing and for identifying CCR5/CCL5 as potential therapeutic targets to reduce mortality-associated inflammation.

Gabandé-Rodríguez E, Soto-Heredero G, Carrasco E et al. · Nature aging · (2026) · View on PubMed ↗ · Free PDF ↗

Contractile myografts confer systemic anti-aging benefits.

This preclinical study developed subcutaneous transplantation of differentiated autologous myocytes (“contractile myografts”) in mice to test whether they confer systemic anti-aging effects. The myografts formed mature, vascularized, continuously self-contracting tissue and improved whole-body muscle mass/function as well as metabolic and regenerative outcomes in aging and obese mouse models. If translatable, contractile myografts could represent an alternative to exercise for improving systemic aging phenotypes when exercise is contraindicated or insufficient.

Liu X, Yao Z, Zhang L et al. · Nature aging · (2026) · 2 citations · View on PubMed ↗

Large eukaryotic DNA viruses encode ESCRT machinery for membrane remodelling.

This study investigated membrane-remodeling capabilities of large eukaryotic DNA viruses by identifying ESCRT machinery components encoded by viruses that infect unicellular eukaryotes. The authors discovered homologues of ESCRT-III and the ATPase Vps4 in mirusviruses and some Nucleocytoviricota viruses, suggesting these viruses encode ESCRT-like functions for membrane budding/scission. This is significant because it expands understanding of viral evolution and reveals how viruses can independently acquire core host membrane-remodeling systems.

Medvedeva S, Guyet U, Koonin EV et al. · Nature microbiology · (2026) · View on PubMed ↗

Desiccation promotes DNA damage and rifampin resistance in Mycobacterium tuberculosis.

This experimental study assessed how desiccation during aerosol droplet formation affects Mycobacterium tuberculosis (Mtb) by exposing Mtb on filters to different humidity levels and measuring transcriptomic and metabolomic responses. Desiccation increased oxidative stress and oxidative DNA damage, including double-stranded DNA breaks, and activated DNA repair pathways required for survival, with increased expression of the transcription-coupled repair factor mfd contributing to rifampin resistance. The findings are important for understanding transmission biology and for anticipating how environmental stressors can promote antibiotic resistance in Mtb.

Brown CD, Lee BM, Liu HM et al. · Nature microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Systems vaccinology and the architecture of human immunity.

This article is a review describing systems vaccinology approaches to map human immunity using vaccines as controlled probes. It highlights how multi-omics and computational analyses identify molecular signatures that predict the magnitude and durability of immune responses and reveal new aspects of human biology, including roles of host genetics and metabolism. The significance is that these frameworks can guide next-generation vaccine design and biomarker-driven development to improve efficacy and longevity of protection.

Pulendran B · Nature · (2026) · View on PubMed ↗

Recombinant shingles vaccination and the risk of cardiovascular events.

The study conducted a natural experiment around the US transition from the live attenuated shingles vaccine to the recombinant shingles vaccine, comparing adults aged ≥60 years vaccinated immediately before versus immediately after the switch. The recombinant vaccine was associated with a 9% decrease in a composite cardiovascular endpoint (ischemic heart disease, heart failure, or ischemic stroke) over the follow-up period. This provides clinically relevant evidence that recombinant shingles vaccination may reduce cardiovascular burden in older adults while mitigating confounding from non-randomized comparisons.

Corsi-Zuelli F, Li F, Upthegrove R et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer.

This study evaluated whether oncogenic KRAS* inhibition with MRTX1133 or daraxonrasib in pancreatic ductal adenocarcinoma (PDAC) can synergize with immune checkpoint blockade in tumor-bearing models. KRAS* targeting recruited diverse T-cell infiltrates (including Tregs, effector, and exhausted T cells) and created a therapeutic window in which anti-CTLA4—but not anti-PD1, anti-Tim3, anti-Lag3, anti-Vista, or 4-1BB agonist combinations—enhanced anti-tumor immunity. These findings support combining KRAS* inhibitors with CTLA4 blockade as a rational strategy to improve durable responses in KRAS-driven PDAC by reshaping the tumor immune microenvironment.

Mahadevan KK, Maldonado AS, Li B et al. · Nature communications · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Inflammatory biomarkers of asymptomatic and symptomatic tuberculosis.

This study characterized blood transcriptomic and proteomic inflammatory biomarkers distinguishing asymptomatic versus symptomatic tuberculosis (TB) using South African community screening and health-facility triage cohorts. Asymptomatic TB shared core innate/interferon/inflammatory pathway upregulation and T/B cell pathway downregulation with symptomatic TB, but integrated multi-omics revealed two asymptomatic sub-clusters with differing bacterial burden. These results suggest that asymptomatic TB has biologically distinct inflammatory states that could inform risk stratification and targeted diagnostics or interventions.

Awany D, Ariefdien DT, Mendelsohn SC et al. · Nature communications · (2026) · 1 citations · View on PubMed ↗

Heritable transgenic schistosomes as a living platform for SARS-CoV-2 neutralizing antibody secretion.

This study engineered heritable transgenic Schistosoma mansoni to secrete a SARS-CoV-2 neutralizing antibody by inserting a VHH-IgG1 Fc transgene (C5-Fc) into a predicted genomic safe-harbor using multiplexed CRISPR/Cas-mediated homology-directed knock-in. Infected Biomphalaria glabrata produced parental P0 lines, and serial passage through snail and mouse hosts generated an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. This provides a proof-of-concept platform for in vivo, heritable delivery of functional neutralizing antibodies using schistosomes.

Ittiprasert W, Smout MJ, Mann VH et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Structural and functional studies of inward rectifier Kir7.1 and its regulation by the Melanocortin-4 receptor.

This study investigated the structure and function of the inward rectifier potassium channel Kir7.1 and how it is regulated by the melanocortin-4 receptor (MC4R), motivated by Kir7.1-linked retinal diseases such as retinitis pigmentosa and Leber congenital amaurosis. The work focused on characterizing the Kir7.1–MC4R complex to explain how a GPCR can directly regulate an ion channel in a G protein-independent manner. Understanding this regulatory mechanism is significant for elucidating disease biology in Kir7.1 channelopathies and for identifying potential therapeutic targets within the MC4R–Kir7.1 axis.

Peisley A, Hernandez CC, Dahir NS et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Temporal drift of sleep-wake representations in hypothalamic neuronal ensembles.

This study examined whether hypothalamic neuronal ensembles that regulate wakefulness, NREM, and REM sleep maintain stable, state-specific activity patterns by performing longitudinal single-cell calcium imaging in freely moving sleeping male mice. Inhibitory, excitatory, hypocretin/orexin-, and melanin concentrating hormone (MCH)-expressing neurons did not show stable state-specific activities; instead, their activity patterns drifted across sleep-wake states over time. These findings challenge the idea of invariant neuronal substrates for sleep states and suggest that sleep regulation relies on dynamic ensemble coding rather than fixed state modules.

Yan Y, Calcini N, Rusterholz T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH.

This study tested how hepatic acetyl-CoA synthetase short-chain family member 2 (ACSS2) contributes to progression from MASLD to MASH by acting as an epigenetic regulator, focusing on the ACSS2–KAT5 complex and histone crotonylation. ACSS2 upregulation in patients promoted MASH progression and, mechanistically, the ACSS2–KAT5 complex drove histone crotonylation to orchestrate a pro-inflammatory transcriptional program independent of ACSS2’s canonical lipogenic role. These results identify a specific epigenetic mechanism that could be targeted to prevent or treat inflammatory progression in MASLD/MASH.

Wen X, Wu K, Wang M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Single-fraction or multi-fraction stereotactic ablative body radiotherapy followed by atezolizumab in advanced triple-negative breast cancer: a randomized phase II trial.

This randomized phase II trial (AZTEC; NCT03464942) studied whether single-fraction (20 Gy) versus multi-fraction SABR (24 Gy in three fractions) followed by atezolizumab (anti–PD-L1) improves outcomes in 54 women with advanced triple-negative breast cancer (TNBC). The trial compared progression-free survival as the primary endpoint between the two SABR fractionation strategies when combined with atezolizumab. If one fractionation approach proves superior, it would directly inform how to optimize radiotherapy scheduling to enhance systemic immune responses in TNBC.

David S, Savas P, Siva S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Loss of Nemp1 disrupts female meiosis and activates a conserved ATM-CHK2 checkpoint.

This study investigated the role of NEMP1 (Nuclear Envelope Membrane Protein 1) in female meiosis using Drosophila and mouse models. Loss of NEMP homologs disrupted female meiosis and activated a conserved DNA damage checkpoint pathway involving ATM and CHK2. These findings link nuclear envelope structural proteins to genome integrity surveillance during oogenesis and help explain mechanisms underlying fertility defects.

Hakim BA, Tsatskis Y, Zhang L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Intercellular Mitochondria Transfer in Lung Diseases: New Mechanisms, Risks, Therapeutic Boundaries.

This review synthesized current evidence on intercellular mitochondrial transfer (MT) in lung diseases, focusing on mechanisms, risks, and therapeutic boundaries. It highlights that MT can modulate mitochondrial quality control, redox homeostasis, immune-cell metabolism, and cell-death susceptibility, with potential benefits such as attenuating pulmonary fibrosis, but also potential risks in cancer contexts where mitochondrial acquisition may enhance metastatic fitness and immune escape. The review frames when MT-based strategies may be therapeutic versus when they could be harmful, guiding safer translational development.

Zhu J, Lai X, Lv W et al. · Antioxidants & redox signaling · (2026) · View on PubMed ↗

[Clinical practice and research of chronic inflammatory demyelinating polyneuropathy: current status and future].

This article reviews the clinical practice and research landscape for chronic inflammatory demyelinating polyneuropathy (CIDP), including current diagnostic categorization and treatment implications. It summarizes epidemiologic data from a 2021 Japanese national survey and emphasizes that CIDP is managed using international (2021) and Japanese (2024) guidelines that classify CIDP into typical CIDP and distinct variants (e.g., multifocal, distal, pure motor/sensory). The significance is improved clinical decision-making for a rare but immunotherapy-responsive disease by aligning practice with guideline-based phenotyping.

Kuwabara S, Doi M, Ukai M et al. · Rinsho shinkeigaku = Clinical neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Updated 2026 Japanese Diagnostic Criteria for Takayasu Arteritis.

This article updated the Japanese diagnostic criteria for Takayasu arteritis (TAK) from the 2017 to the 2026 version using a 3-round modified Delphi process with 21 expert panelists. The key finding was that the 2026 criteria introduced three major changes, including added new symptoms and a new qualifying statement, and incorporated additional refinements such as pulmonary artery involvement criteria (as described in the abstract). Clinically, the updated criteria standardize diagnosis for Japanese practice and guideline use, potentially improving case identification and consistency across centers.

Yoshifuji H, Uchida HA, Onishi Y et al. · Circulation journal : official journal of the Japanese Circulation Society · (2026) · View on PubMed ↗ · Free PDF ↗

Predictive Power of Pulmonary Artery Stiffness - Right Ventricular Interplay, but not Pulmonary Vascular Resistance, in Mild Pulmonary Hypertension: A PVRI GoDeep meta-registry analysis.

This PVRI GoDeep meta-registry analysis assessed whether pulmonary artery stiffness components—pulmonary artery compliance (PAC), arterial elastance (Ea), and right-ventricular stroke volume index (SVI)—predict mortality in patients with mild pulmonary hypertension independently of pulmonary vascular resistance (PVR). The key finding was that pulmonary artery stiffness–right ventricular interplay (rather than PVR alone) had prognostic value for mortality in early/mild disease. This suggests that incorporating pulsatile load measures (PAC/Ea) and RV functional adaptation may improve risk stratification beyond resistance-based metrics.

Yogeswaran A, Fünderich M, Kiely DG et al. · Chest · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Effectiveness and Outcomes of Direct Oral Anticoagulants vs. Vitamin K Antagonists (VKA) in Atrial Arrhythmias Patients with Isolated Lupus Anticoagulant Without Antiphospholipid Syndrome: A Real-World Cohort Analysis.

This real-world cohort study used TriNetX data to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in adults with atrial fibrillation/flutter who had isolated lupus anticoagulant (LA) positivity without meeting antiphospholipid syndrome (APS) criteria. DOAC use showed comparable effectiveness and safety to VKA therapy in this isolated LA population (with APS-coded patients excluded). These findings support the clinical use of DOACs in AF/flutter patients with isolated LA but no APS, addressing a key uncertainty about anticoagulant choice in this subgroup.

Obeidat O, Alhuneafat L, Ismail MF et al. · The American journal of the medical sciences · (2026) · View on PubMed ↗

ERN ReCONNET-SLICC-SLEuro consensus on the therapeutic management of rare systemic lupus erythematosus manifestations (part 2).

This international ERN ReCONNET–SLICC–EULAR consensus project gathered 77 participants to develop therapeutic management recommendations for 22 additional rare systemic lupus erythematosus (SLE) manifestations beyond previously covered 24. The key output was an evidence-informed consensus framework specifying treatment strategies for rare organ- and phenotype-specific SLE presentations. Clinically, it standardizes care for uncommon SLE manifestations where trial data are limited and practice variation is high.

Arnaud L, Monticielo OA, Piga M et al. · The Lancet. Rheumatology · (2026) · View on PubMed ↗

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SLE & Autoimmune Consensus/Management

Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: Five-year results from the phase III KEYNOTE-564 study.

This report provides five-year outcomes of adjuvant pembrolizumab versus placebo in adults with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence from the phase III KEYNOTE-564 trial (NCT03142334). The key finding was that the survival and disease-control benefits observed in earlier analyses persisted with a minimum follow-up of five years. Clinically, long-term confirmation supports adjuvant pembrolizumab as a durable standard of care for high-recurrence-risk ccRCC after nephrectomy.

Haas NB, Powles TB, Tomczak P et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

Outcomes from the International Society of Nephrology Forum on Complement Therapeutics in C3G & IgAN.

This article summarizes outcomes and discussion from the 2025 International Society of Nephrology Forum on Complement Therapeutics in C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), and addresses implications for IgA nephropathy (IgAN). The key finding was that complement alternative pathway inhibitors have shown trial success in complement-driven disorders (C3G and IC-MPGN) and that emerging evidence supports complement as a secondary contributor in IgAN, raising questions about real-world use. Scientifically and clinically, the forum consolidates evidence to guide how complement-targeted therapies should be implemented across these distinct glomerular diseases.

Kavanagh D, Alladin-Karan A, Alexander S et al. · Kidney international · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic Liver Disease (MASH/MASLD)

ALG-055009 in non-cirrhotic adults with metabolic dysfunction-associated steatohepatitis (HERALD): a randomised, double-blind, placebo-controlled, phase 2a trial.

In the randomized, double-blind, placebo-controlled phase 2a HERALD trial, non-cirrhotic adults with presumed metabolic dysfunction–associated steatohepatitis (MASH) with F1–F3 fibrosis were assigned to oral thyroid hormone receptor beta (THR-β) agonist ALG-055009 at doses of 0·3–0·9 mg or placebo. ALG-055009 improved metabolic and liver-related endpoints consistent with THR-β–mediated reductions in hepatic fat and atherogenic lipids, with dose-dependent pharmacokinetic/pharmacodynamic effects and an acceptable safety profile for a phase 2a study. Scientifically and clinically, it advances a targeted THR-β approach for treating MASH in non-cirrhotic patients.

Loomba R, Wang S, Desai D et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome & Live Biotherapeutics (IBD/colitis)

Defined human Clostridia consortia reverse colitis via dual effects of tryptophan metabolites on microbiota and immunity.

This study tested two live biotherapeutic products (LBPs)—human Clostridia consortia 17-mix and 11-mix—in murine models of established colitis, including T cell–mediated chronic colitis and gnotobiotic colitis driven by human-derived pathobiont combinations. Both LBPs reduced colitis severity and reshaped host immunity, with metagenomic and metabolomic analyses identifying tryptophan metabolite–mediated dual effects on microbiota and immune pathways. The work supports a mechanistic basis for Clostridia-based microbiome therapies in inflammatory bowel disease by linking specific microbial metabolites to immune modulation.

Oka A, Bongers G, Mishima Y et al. · Cell host & microbe · (2026) · View on PubMed ↗ · Free PDF ↗

Long-lasting extracellular matrix modifications reshape intestinal stem cell fate and promote chronic inflammation.

This study used temporal multi-omics, biomechanical profiling, and spatial fate mapping in gut colitis models to determine how extracellular matrix (ECM) changes persist after inflammation and affect intestinal stem cell (ISC) fate. It showed that inflammation induces long-lasting modified ECM (modECM) characterized by collagen XVIII accumulation and immune-driven proteolysis, which redirects ISCs toward a wound-associated, pro-inflammatory epithelial state by suppressing Wnt signaling and promoting immune recruitment. The findings identify ECM reprogramming as a driver of chronic intestinal inflammation and suggest ECM-targeted strategies to prevent maladaptive regeneration.

Adir I, Sochen C, Gelb S et al. · Immunity · (2026) · View on PubMed ↗

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Neurodegeneration & Proteinopathies (AD/FTD/ALS/Tau/TDP-43)

Disruption of sphingolipid metabolism promotes tau seeding through endolysosomal membrane rigidification and rupture.

This study examined how disruption of sphingolipid metabolism affects tau seeding and toxicity in Caenorhabditis elegans and human cell culture models of tauopathies. It found that silencing sphingolipid metabolism genes reduces endolysosomal membrane fluidity, increases endolysosomal rupture, and promotes a feed-forward cycle where aggregated tau in endolysosomal vesicles further rigidifies and damages endomembranes while enhancing seeded tau aggregation. Scientifically, it links sphingolipid/endolysosomal membrane integrity to tau propagation mechanisms, suggesting potential targets to slow tau spread in Alzheimer’s disease–related tauopathies.

Tittelmeier J, Sandhof CA, Martin N et al. · eLife · (2026) · View on PubMed ↗ · Free PDF ↗

Engineered autophagy receptors administered with extracellular vesicles eliminate pathological Tau and TDP-43.

Engineered autophagy receptors were created by fusing LC3A (an autophagosome recruitment protein) to cytoplasm-stable antibodies targeting pathological Tau or TDP-43, and delivered via extracellular vesicles to eliminate these proteins in disease-relevant models. The approach enabled selective recognition and autophagic elimination of pathological Tau and TDP-43 species despite challenges of crossing cellular barriers and handling large inclusions. This supports a translational strategy for treating frontotemporal dementia and ALS by coupling targeted antibody recognition to autophagosome-mediated clearance.

Guo H, Savard A, Manser C et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

Aberrant excitatory neuronal ERBB4 promotes Alzheimer’s disease pathology.

In a mouse model of Alzheimer’s disease (AD), single-nucleus RNA-seq and synapse phagocytosis analyses were used to identify early-responsive excitatory neurons (EREN) and to determine how astrocytes and microglia alter excitatory versus inhibitory synapse elimination during disease progression. The study found that early AD progression is associated with increased phagocytic elimination of excitatory synapses (with reduced elimination of inhibitory synapses) and emergence of EREN characterized by ectopic expression of the ERBB4 pathway. This suggests that aberrant excitatory ERBB4-driven neuronal programs can promote AD synapse loss and pathology, pointing to ERBB4/EREN as potential therapeutic targets.

Lee SY, Park E, Lee HE et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

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Genetic Risk & Variant Interpretation (CNVs/eQTLs/recombination/aging clocks)

Genomic predisposition is associated with the direction of sex chromosome evolution.

This comparative genomics study used chromosome-level genomes from 19 gecko species to test how genomic predisposition relates to the direction of sex chromosome evolution (XY versus ZW). It found that sex chromosome origins are nonrandom in timing and direction, with ancestral gene content patterns predicting evolutionary direction—testis-enriched regions tending toward ZW and testis-depleted regions toward XY—across multiple amniote origins. The scientific significance is that it provides a mechanistic genomic basis for why different lineages evolve different sex chromosome systems.

Zhou Y, Jin J, Jiang C et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

The Joint Effects of Life’s Essential 8 and Genetics on Mild Cognitive Impairment and Dementia Risk in People With Diabetes: Findings From the UK Biobank and All of Us.

This study examined how cardiovascular health (Life’s Essential 8, LE8) and genetic risk jointly relate to mild cognitive impairment and dementia risk in people with diabetes using UK Biobank and All of Us cohorts. It found that LE8 status and Alzheimer disease genetic risk (APOE ε4 and Alzheimer PRS) were associated with cognitive outcomes, with combined effects informing risk stratification. The results are clinically important for identifying modifiable cardiovascular health targets that may mitigate genetic susceptibility to cognitive decline in diabetes.

Wu X, Zu Y, Lu Y et al. · Diabetes care · (2026) · View on PubMed ↗

Prediction of human missense variant effects from functional evidence.

FuncVEP, a missense variant effect predictor, was trained on diverse functional datasets to estimate functional impact of human missense variants and evaluated against 48 existing predictors on functional and clinical benchmarks. FuncVEP generalized across datasets and improved performance from 78.8% to 84.6% on functional benchmarks and from 90.1% to 92.4% on clinical benchmarks. This provides a more generalizable, function-evidence-based framework for variant interpretation that reduces reliance on population/clinical outcome circularity.

Kayaalp B, Çil K, Conil C et al. · Nature genetics · (2026) · View on PubMed ↗

Insights into longevity and virus-driven adaptation from Myotis bat genomes.

Near-complete genome assemblies and cell line experiments across eight closely related Myotis bat species were used to study longevity, cancer resistance, and viral tolerance, integrating genome-wide positive selection scans, structural variation analyses, and functional assays in primary cells. The study identified distinct adaptation modes to DNA versus RNA viruses compared with other mammals and highlighted genetic patterns contributing to longevity, cancer resistance, and viral interactions. These results clarify evolutionary mechanisms behind extreme mammalian lifespan and antiviral/anti-cancer phenotypes, guiding hypotheses for human aging and infection biology.

Vazquez JM, Lauterbur ME, Mottaghinia S et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Long-read sequencing reveals pre-meiotic gene conversion in sperm.

Long-read sequencing of sperm was used to detect both crossovers and non-crossovers, enabling analysis of pre-meiotic gene conversion from a single male using high-fidelity long reads. The study identified a consistent component of non-crossovers with properties distinct from PRDM9-induced recombination and not associated with meiotic PRDM9-driven mechanisms. This provides a new, scalable way to study gene conversion processes in humans and refines understanding of recombination-related genome variation.

Schweiger R, Lee S, Zhou C et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Construction and Validation of Plasma Protein-Based Musculoskeletal Biological Age and Genetic and Environmental Risk Profiles.

This study constructed and validated plasma-protein–based musculoskeletal biological age clocks (MSKAge and MSKAgeMort) and tested genetic and environmental risk profiling using proteomic data from 21,070 UK Biobank participants. The key finding was that the clocks’ acceleration metrics (MSKAgeAccel and MSKAgeMortAccel) quantified deviations from chronological age and showed associations with musculoskeletal aging risk (with positive values indicating accelerated musculoskeletal aging). These validated proteomic aging biomarkers could improve prediction of musculoskeletal decline and help disentangle genetic versus environmental contributions to musculoskeletal aging.

Zhong Y, Xia M, Zhao X et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

Proteomic landscape of pan-tissue neuroendocrine carcinomas defines subtype-specific functional architectures, biomarkers and therapeutic targets.

This study performed comprehensive proteomic and phosphoproteomic profiling of 267 pan-tissue neuroendocrine carcinomas (NECs) across 26 anatomical sites to define subtype-specific functional architectures and biomarkers. The key finding was that integrated proteogenomic analysis recapitulated five ANHPY transcriptional subtypes driven by master transcription factors ASCL1, NEUROD1, HNF4A, POU2F3, and YAP1, each with distinct functional programs. This provides a mechanistic framework for biomarker discovery and therapeutic target selection tailored to NEC subtype biology.

Ge F, Wang Z, Zheng S et al. · Gut · (2026) · View on PubMed ↗

Exome analysis of 22,319 individuals links extremely rare copy-number variants and 22q11.21 dosage to Alzheimer risk.

Using exome data from 22,319 individuals (4,150 early-onset AD, 8,519 late-onset AD, and 9,650 controls), this study performed harmonized rare copy-number variant (CNV) calling and gene-set burden analyses to assess Alzheimer disease risk. It found that extremely rare CNVs and 22q11.21 dosage are associated with increased Alzheimer risk, with early-onset AD showing enrichment for rare CNVs affecting coding genes, particularly deletions in AD-related genes. These results refine the genetic architecture of non-monogenic AD and highlight specific CNV regions (including 22q11.21) for risk stratification and future functional studies.

Quenez O, Schramm C, Cassinari K et al. · American journal of human genetics · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Genomics, Tumor States & Targeted Therapies (incl. KRAS/PROTAC/PROTAC/biomarkers)

Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer.

Single-cell master regulator (MR) analysis was used across multiple human pancreatic ductal adenocarcinoma (PDA) cohorts to define malignant epithelial cell states and their regulatory determinants, including MAPK-responsive transcription factors and developmental-lineage regulators. The study identified three co-existing malignant states corresponding to distinct developmental lineage programs, including a poorly differentiated, epithelial–mesenchymal-transition (EMT)-driven state and two well-differentiated states with different morphologies/spatial architecture and associated genetic dependencies. These findings mechanistically link MAPK-responsive and developmental transcriptional programs to pancreatic cancer plasticity and state-specific vulnerabilities, informing more precise therapeutic targeting.

Laise P, Turunen M, Curiel-Garcia A et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

A binding-to-release strategy for targeted anticancer drug delivery.

A binding-to-release (BTR) strategy for targeted anticancer drug delivery was developed, using a phosphorus(V)-phenol exchange (PhoPEx) electrophile design to enable direct cleavage by a proximal nucleophilic residue within a binding pocket, thereby decoupling payload release from receptor-mediated endocytosis. The key finding is that BTR conjugates overcome the internalization-to-release (ITR) limitation of poorly internalizing targets by positioning an electrophile for proximal, binding-pocket cleavage. This provides a generalizable chemical design principle to improve efficacy of drug conjugates (including ADC/SMDC-like systems) against low-internalization receptors.

Wen Z, Xu M, Yan Z et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Ultrafast and reference-free sequence discovery in single-cell data.

The study developed Malva, a computational, ultrafast, reference-free method for discovering RNA sequences from single-cell and spatial transcriptomics datasets in large-scale consortia-style data. Malva enables sequence-level search/discovery across petabyte-scale single-cell profiles where standard reference-based pipelines typically retain only gene or isoform counts. This provides a scalable way to interrogate RNA sequence diversity, splicing, isoforms, structure, and modifications for downstream biological targeting and discovery.

León-Periñán D, Karaiskos N, Rajewsky N · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M.

The study examined how cell-autonomous regional differences shape oligodendrocyte lineage development and responses to the oncohistone H3.3 K27M mutation using conditional K27M knock-in mice. K27M reduced oligodendrocyte differentiation and altered oligodendrocytic cell-state proportions in a region-specific manner, with in vivo EdU labeling showing greater K27M-driven proliferation in pons/midline/hindbrain than in telencephalon. This identifies why DMG with H3.3 K27M preferentially arises in certain brain regions and links mutation-driven chromatin effects to developmental and proliferative differences.

Andrews JM, Budd KM, Kwon CH et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Immuno-oncology & Combination Immunotherapy (ICI/biologics/radiation synergy)

Pre-existing systemic immune state and dynamic myeloid remodeling shape response to neoadjuvant PD-L1 blockade.

This phase II window-of-opportunity study (PIONEER trial, NCT04939480) evaluated how a pre-existing systemic immune state and dynamic myeloid remodeling shape response to neoadjuvant PD-L1 blockade using a single dose of atezolizumab in patients with resectable head and neck squamous cell carcinoma. The key finding was that immune cell dynamics after PD-L1 inhibition were linked to treatment response, highlighting myeloid remodeling as a determinant of immunologic outcome. Clinically, these findings support immune-state–based prediction of benefit from neoadjuvant PD-L1 blockade and inform rational combination strategies.

Kasper S, Winkel H, Höing B et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

AdvanTIG-301: a phase III study of ociperlimab plus tislelizumab and concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer.

This phase III AdvanTIG-301 trial tested ociperlimab plus tislelizumab combined with concurrent chemoradiotherapy (cCRT) in treatment-naïve patients with stage III unresectable non-small cell lung cancer (NSCLC). The key finding (trial-level) is that multiple randomized multiarm strategies were compared—ociperlimab+tislelizumab+cCRT followed by dual maintenance, tislelizumab+cCRT followed by tislelizumab maintenance, or cCRT followed by durvalumab—using safety and efficacy endpoints. The results are intended to determine whether adding ociperlimab to tislelizumab improves outcomes beyond standard chemoradiotherapy-based regimens in this high-need population.

Xing L, Kato T, Levy A et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical Trials & Treatment Strategies (rehab/CBT/oncology regimens)

Cognitive Behavior vs Bright Light Therapy for Insomnia in Women Undergoing Chemotherapy for Breast Cancer: A Randomized Clinical Trial.

This randomized clinical trial studied cognitive behavior therapy for insomnia (CBT-I) versus bright light therapy (BLT), alone and in combination, in women undergoing chemotherapy for breast cancer. The key finding was the comparative effect of these behavioral and circadian interventions on insomnia and fatigue symptoms over a 6-week 2×2 factorial design. Clinically, it informs evidence-based nonpharmacologic treatment selection for chemotherapy-associated insomnia and fatigue in this population.

Do TT, Maccora J, Wallace R et al. · JAMA network open · (2026) · View on PubMed ↗

Sex and Gender Differences in Physical Activity, Sedentary Behavior, and Sleep During Traumatic Brain Injury Recovery: A Narrative Review.

This narrative review studied sex and gender differences in physical activity, sedentary behavior, and sleep during traumatic brain injury (TBI) recovery. It highlighted that these determinants are under-investigated yet likely contribute to heterogeneity in recovery trajectories and long-term outcomes after TBI. The review is significant for shaping future research and for designing sex- and gender-informed rehabilitation and sleep/behavior interventions in TBI care.

España-Irla G, Perko M, Tinney EM et al. · European journal of sport science · (2026) · View on PubMed ↗ · Free PDF ↗

2026 Guideline for Adult Stroke Rehabilitation and Recovery: A Guideline From the American Heart Association and American Stroke Association.

This article presents the 2026 American Heart Association/American Stroke Association guideline for adult stroke rehabilitation and recovery, synthesizing evidence from human-participant studies published since the 2016 guideline. The key finding is an updated, comprehensive set of evidence-based recommendations covering rehabilitation and recovery practices for adults after stroke. Clinically, it standardizes care for physicians, allied health professionals, and caregivers and is intended to improve outcomes by aligning practice with the most current evidence.

Richards LG, Ifejika NL, Stein J et al. · Stroke · (2026) · 4 citations · View on PubMed ↗

Toward autonomous artificial intelligence agents in sports science: a modular framework for development, validation, and implementation.

This article examined inappropriate use of GLP-1–based antiobesity medications, including GLP-1 receptor agonists and GIP/GLP-1 dual agonists, focusing on medically inappropriate weight-loss practices and their consequences. The key finding is that harms associated with inappropriate agents (including reports involving tirzepatide) may stem not only from drug toxicity but also from inappropriate dietary restriction and related behaviors. The significance is that it reframes prevention efforts toward achieving appropriate weight reduction strategies rather than focusing solely on regulatory compliance or off-label/illegal acquisition concerns.

Dergaa I, Barbaria S, Dhahbi W et al. · Biology of sport · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗

Shaping the future of early-onset colorectal cancer prevention.

The study reviewed evidence on early-onset colorectal cancer (EOCRC) prevention, focusing on individuals under age 50 and the roles of lifestyle, early-life exposures, and gut microbial-related factors. It highlights key gaps in identifying additional risk factors and in determining when and how exposures act individually or collectively to initiate or promote colorectal cancer at younger ages. This roadmap informs the development and implementation of prevention strategies tailored to younger populations with EOCRC.

Tian R, Azadnajafabad S, Waters EA et al. · Nature reviews. Cancer · (2026) · View on PubMed ↗

Walk-and-talk versus conventional psychotherapy for men with depressive symptoms: study protocol of a randomised controlled trial.

This protocol describes a randomized controlled trial comparing walk-and-talk therapy versus conventional indoor psychotherapy for men with depressive symptoms. The key finding (as a study design) is that the trial will test whether the outdoor, activity-integrated approach yields clinically meaningful benefits and improved engagement relative to conventional psychotherapy, aiming to reduce dropout. If effective, this could offer a gender-preference–aligned behavioral intervention to improve depression treatment adherence and outcomes in men.

Regan CP, Dickmeyer A, O’Hara R et al. · BMJ open · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiometabolic Drugs & Kidney Outcomes (SGLT2/GLP-1/semaglutide/AKI-D/ADPKD)

Early Sodium-Glucose Cotransporter-2 Inhibitor Use After Acute Kidney Injury in Type 2 Diabetes.

This cohort study used target trial emulation with TriNetX electronic health records to compare outcomes of early versus later initiation of SGLT-2 inhibitors after discharge in adults with type 2 diabetes recovering from dialysis-requiring acute kidney injury (AKI-D). The key finding was the difference in clinical outcomes between SGLT-2 inhibitor prescriptions within 30 days versus 31–90 days after discharge. Scientifically and clinically, it helps define safer and more effective timing for SGLT-2 inhibitor use after AKI-D in routine practice.

Chou YT, Chen JY, Jiang ZH et al. · JAMA network open · (2026) · View on PubMed ↗

Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension.

This post hoc analysis studied cardiovascular-related mortality and hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis 80 mg, drawing participants from the phase 3 ATTR-ACT trial and its long-term extension. Tafamidis treatment reduced cardiovascular-related events (including cardiovascular mortality and recurrent cardiovascular hospitalizations) compared with placebo in ATTR-ACT, with outcomes assessed across up to 60 months. The findings reinforce tafamidis’ long-term clinical benefit on high-risk cardiovascular outcomes in ATTR-CM.

Damy T, Witteles R, Cappelli F et al. · Cardiology and therapy · (2026) · View on PubMed ↗

Comparative Effectiveness of Combination Therapy in Patients with Chronic Kidney Disease and Diabetes mellitus Type 2 using Real World Data.

This real-world comparative effectiveness study analyzed patients with chronic kidney disease (CKD) and type 2 diabetes using TriNetX data to evaluate different combination therapies involving RAAS inhibitors plus SGLT-2 inhibitors and/or GLP-1 receptor agonists. The key finding was the relative effectiveness of these drug combinations on kidney outcomes in an eGFR 20–60 mL/min population after target-trial emulation with propensity score matching. This is significant for guiding evidence-based selection of additive or comparative renoprotective regimens in routine care.

Casper J, Doricic J, Tian Z et al. · Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · (2026) · View on PubMed ↗

Association of semaglutide use with kidney outcomes in adults with ADPKD: A propensity score-matched real-world study.

This propensity score-matched real-world study used TriNetX to evaluate semaglutide use in adults with autosomal dominant polycystic kidney disease (ADPKD) between 2000 and 2024, excluding users of SGLT2 inhibitors, tolvaptan, and other GLP-1 receptor agonists. Semaglutide users were matched 1:1 to non-users, and kidney outcomes were assessed using creatinine-based estimated glomerular filtration rate (eGFR) trajectories. If confirmed by the reported results, the study would provide clinically actionable evidence on whether semaglutide slows kidney decline in ADPKD, a population with limited disease-modifying options.

Chen TP, Tsai SF · Science progress · (2026) · View on PubMed ↗ · Free PDF ↗

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Rare Disease Diagnostics & Clinical Criteria (WHO/Delphi/diagnostic updates)

Nonviral delivery of chemically modified tRNA rescues nonsense mutations in cystic fibrosis.

The study investigated whether nonviral delivery of chemically modified suppressor transfer RNAs (sup-tRNAs) can rescue cystic fibrosis caused by nonsense mutations in vivo, using N1-methyladenosine–modified sup-tRNAs packaged in pulmonary lipid nanoparticles (LNPs). N1-methyladenosine incorporation improved premature termination codon (PTC) readthrough, increased tRNA aminoacylation, prolonged functional persistence, and reduced innate immune activation, with an optimized ionizable lipid LNP formulation tailored to the sup-tRNA. This supports a clinically relevant strategy to enhance sup-tRNA potency and delivery for nonsense-mutation cystic fibrosis without viral vectors.

Chen J, Zhou M, Dong S et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Cutaneous lymphomas - an update.

This article updates the classification of primary cutaneous lymphomas (CL) and lymphoproliferative disorders (LPD) in the context of the WHO 5th edition and the International Consensus Classification, focusing on T- and B-cell entities defined by integrated clinical, histopathological, immunophenotypic, and genetic criteria. It highlights that several previously provisional cutaneous lymphoma entities—such as primary cutaneous small/medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, and Epstein-Barr virus–positive mucocutaneous ulcer—are now established. The significance is improved diagnostic precision and standardized molecular-clinicopathologic criteria for clinicians and pathologists managing heterogeneous cutaneous T- and B-cell neoplasms.

Kempf W, Mitteldorf C · Histopathology · (2026) · View on PubMed ↗

Neuroimaging Abnormalities and Genotype-Phenotype Correlations in Noonan Syndrome: A Multicenter Cohort Study.

This multicenter retrospective cohort study analyzed brain MRI findings and genotype–phenotype relationships in 130 children with genetically confirmed Noonan syndrome. The key finding is that neuroimaging abnormalities are common and show associations with specific genetic variants and clinical features across the cohort. The significance is that it provides a more precise spectrum of pediatric NS brain MRI abnormalities and supports genotype-informed risk stratification for neurologic involvement.

Patti G, Maiorano NG, Piccoli F et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Chelonid alphaherpesvirus 5 qPCR of archived blood and skin samples underpredicts infections in juvenile green turtles Chelonia mydas.

This study evaluated whether quantitative PCR (qPCR) for Chelonid alphaherpesvirus 5 (ChHV5) in archived blood and skin samples underestimates infection prevalence in juvenile green turtles (Chelonia mydas) with fibropapillomatosis. The key finding is that archived samples (>1 year) and storage/age effects can yield negative qPCR results even when individuals are infected, meaning qPCR underpredicts true infection status. Scientifically and for surveillance, it shows that negative ChHV5 qPCR from aged specimens does not reliably indicate absence of infection, affecting interpretation of epidemiologic studies and diagnostics.

Kelley JR, Lee T, Martin KR et al. · Diseases of aquatic organisms · (2026) · View on PubMed ↗

Clinical Reasoning: A 28-Year-Old Man with Subacute-Onset Ataxic Gait.

This clinical case report studied the diagnostic reasoning for a 28-year-old man with subacute-onset ataxic gait and systemic features including intermittent fever and unintentional weight loss, with prior evaluation for a poorly differentiated right tibial tumor. The key finding is that the patient’s neurologic presentation—subacute ataxic gait with peripheral neuropathy signs (e.g., stocking-glove sensory loss, absent lower-extremity reflexes)—illustrates the complexity of diagnosing subacute progressive polyneuropathy with systemic involvement. Clinically, it emphasizes the need for a structured diagnostic approach in patients with combined neurologic and systemic symptoms, particularly when malignancy is suspected.

Benetti M, Caiza-Zambrano F, Reisin R et al. · The Neurohospitalist · (2026) · View on PubMed ↗ · Free PDF ↗

Long-Term Effectiveness and Safety of Direct Oral Anticoagulants in Japanese Patients With Venous Thromboembolism　- Extended Follow-up Results From the KUROSIO Study.

This prespecified extended follow-up analysis of the KUROSIO study evaluated long-term effectiveness and safety of direct oral anticoagulants (DOACs) in Japanese real-world patients with acute venous thromboembolism (VTE) over 156 weeks. The key finding was that cumulative incidence estimates for symptomatic recurrent VTE and major bleeding were assessed through 156 weeks in 993 eligible patients, extending prior 52-week results. Scientifically and clinically, the longer observation period informs durability of benefit and bleeding risk for DOAC use in Japanese VTE populations.

Umetsu M, Tsujita K, Nakamura M et al. · Circulation journal : official journal of the Japanese Circulation Society · (2026) · View on PubMed ↗ · Free PDF ↗

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Gene Therapy & Safety Surveillance

Delphi consensus on gene therapy of spinal muscular atrophy with onasemnogene abeparvovec in Germany, Austria and Switzerland - part II - expert based recommendations for surveillance and management of side-effects.

This Delphi consensus article studied how to implement gene therapy safety surveillance and side-effect management for children with spinal muscular atrophy (SMA) treated with onasemnogene abeparvovec across Germany, Austria, and Switzerland. It produced expert-based, structured recommendations for long-term monitoring and clinical management of safety alerts to standardize care where protocols were previously lacking. The guidance is significant for improving patient safety, harmonizing follow-up practices, and increasing clinician confidence in real-world gene therapy delivery for SMA.

Ziegler A, Weiß C, Vill K et al. · Journal of neuromuscular diseases · (2026) · View on PubMed ↗

Parkinsonism-like delayed neurotoxicity after idecabtagene vicleucel therapy for multiple myeloma: clinicopathological, cerebrospinal fluid, and autopsy analyses.

This report investigated Parkinsonism-like delayed neurotoxicity after idecabtagene vicleucel (ide-cel) therapy in patients with multiple myeloma using clinicopathological evaluation, cerebrospinal fluid (CSF) analyses, and autopsy findings. The key finding is that ide-cel–associated delayed neurotoxicity can manifest with a Parkinsonism-like syndrome and measurable CNS involvement detectable via CSF and neuropathology. Clinically, it underscores the need for vigilance and mechanistic understanding of late neurologic adverse events following CAR T-cell therapy with ide-cel.

Yoshino H, Imi T, Nukii Y et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

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RNA Therapeutics & RNA Engineering (tRNA/sup-tRNA/RNA design)

Automated prototyping of genetic codes.

The study introduced AGENTEX (automated genetic tRNA expansion) to automate multiplexed robotic prototyping of new-to-nature genetic codes in cell-free translation systems. By leveraging two Watson-Crick interactions in the ribosomal LSU that recognize the tRNA 3’ CCA end, AGENTEX quantified how alternative non-CCA-3’ tRNAs are excluded during translation and used this to guide genetic code expansion. This accelerates engineering of organisms and cell-free systems with recoded genomes for new chemistries and therapeutic protein production.

Radford F, Sapers N, Burgess HM et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell Death, Inflammation & Immune Signaling (pyroptosis/necroptosis/IL-5 eosinophils)

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease.

This work studied epithelial cell death signaling in inflammatory bowel disease (IBD) patients, focusing on how nascent inflammation alters epithelial transcriptional programs and death pathways. It found that inflammation skewed epithelial cells toward an M1-macrophage-like transcriptional state that promoted RIPK1-independent necroptotic signaling, which then triggered inducible nitric oxide–related downstream inflammatory effects. The results identify a necroptotic-to-apoptotic signaling axis as a persistent pathogenic mechanism in IBD even during remission/advanced therapy, suggesting potential targets beyond cytokine modulation.

Pang J, Al-Ani AH, Patel KM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Gasdermin D-mediated delivery of caspase inhibitors to suppress pyroptosis.

The study tested covalent caspase inhibitors delivered via gasdermin D (GSDMD) pore–mediated uptake to suppress pyroptosis and IL-1β secretion in relevant cellular models of inflammatory cell death. The inhibitors selectively blocked the pyroptosis/IL-1β pathway while not preventing caspase-driven apoptosis, and mechanistic experiments indicated GSDMD pores enabled inhibitor entry into cells. This suggests a strategy to overcome prior failures of cell-permeable caspase inhibitors by exploiting pyroptotic membrane permeabilization for targeted delivery.

Groborz KM, Truong ME, Stowe I et al. · Nature · (2026) · View on PubMed ↗

T cell fate is dictated by different antigen-presenting cells in response to dietary versus gut epithelial self-antigen.

In mouse experiments, this study compared ovalbumin (OVA)-specific CD4+ T cell fates under different antigen contexts by feeding mice OVA or expressing secreted (s), cytosolic (c), or transmembrane (tm) epithelial OVA, then assessing responses at baseline and after reovirus infection. Helminth infection induced Th2 polarization in sOVA and tmOVA models but not cOVA or OVA-fed mice, while BATF3+ antigen-presenting cells were required for CD4+ proliferation only in cOVA mice and promoted Treg differentiation across epithelial OVA models. The work clarifies how antigen-presenting cell pathways differentially shape dietary versus epithelial self-antigen–driven immunity, informing mechanisms relevant to gut autoimmunity.

Zhou YD, Brown H, Schaffer E et al. · Immunity · (2026) · View on PubMed ↗

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Systems Biology, Omics & Computational Methods (single-cell/AI agents/proteomics/vaccinology)

Inappropriate use of GLP-1-based antiobesity medications: beyond appropriate drug use toward appropriate weight reduction.

This review studied how to develop, validate, and implement autonomous artificial intelligence (AI) agents in sports science, contrasting them with existing passive analytics and conversational systems. The key finding is a proposed modular framework aimed at enabling 24/7 monitoring, independent reasoning, and proactive intervention execution in sports-science workflows. The significance is that it provides a structured pathway for turning AI from human-supervised tools into autonomous systems that can be tested and deployed more rigorously.

Ogawa W, Nishikage S, Nomura K et al. · Diabetology international · (2026) · View on PubMed ↗ · Free PDF ↗

Cell-type-specific eQTLs underlie the genetic architecture of complex traits.

A variance component model was applied to population-scale single-cell RNA-seq data from peripheral blood mononuclear cells (OneK1K cohort) to map cell-type-specific expression quantitative trait loci (eQTLs) underlying complex trait genetic architecture. The study showed that cell-type-specific eQTLs capture additional regulatory effects compared with bulk approaches and better explain how genetic variants influence complex traits through gene expression in specific immune cell types. This advances trait-to-gene inference by incorporating cellular context, improving interpretability of noncoding variation.

Chen M, Wang X, Krockenberger L et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Primate-specific regulation of the human glycosphingolipid gatekeeper UGCG.

In freely moving mammals, endocannabinoid (eCB) signaling was tested using in vivo physiological recordings, imaging, genetic tools, and machine learning to determine whether eCBs implement retrograde gain control that supports motivated behavior. The key finding is that eCB-mediated retrograde gain control facilitates reward engagement by dynamically tuning excitatory/inhibitory fast synaptic transmission. This links a canonical neuromodulatory mechanism to behaviorally relevant computation in vivo, with implications for understanding motivation and psychiatric disorders.

Wu C, Jin S, Xu J et al. · Nature · (2026) · 1 citations · View on PubMed ↗

Endocannabinoids facilitate reward engagement through retrograde gain control.

Cryogenic electron microscopy (cryo-EM) structures were determined for full-length UGCG (UDP-glucose ceramide glucosyltransferase), the human glycosphingolipid gatekeeper, to define its mechanism and regulation, including primate-specific regulatory features. The key finding is that primate-specific regulation of UGCG controls how the enzyme governs glycosphingolipid diversity by modulating the committed glycosylation step. This provides structural and evolutionary insight into a therapeutic target for diseases involving glycosphingolipid dysregulation.

Marcus DJ, English AE, Chun G et al. · Nature · (2026) · View on PubMed ↗

RNA synthesis and substrate analogue inhibition in the CCHFV polymerase.

The study determined high-resolution structural snapshots of the full-length Crimean-Congo haemorrhagic fever virus (CCHFV) L polymerase, including a 3.0 Å polymerase elongation complex, to understand RNA synthesis and substrate analogue inhibition. The structures reveal how large insertions and additions in the endonuclease RdRP and cap-binding regions extend RNA-binding paths around the active site, clarifying mechanisms of early versus late elongation. These mechanistic insights support rational design and optimization of nucleotide analogue inhibitors targeting the CCHFV polymerase.

Jia H, Tang B, Liu S et al. · Nature · (2026) · View on PubMed ↗

PIWI proximity proteome reveals Set1-mediated piRNA biogenesis for transposon silencing at telomeres.

The study used PIWI proximity proteomics in Drosophila ovaries to map proteins associated with PIWI-clade Argonaute proteins Piwi, Aub, and Ago3 and to define factors required for transposon silencing at telomeres. Functional screening identified Set1, an H3K4me3 writer and transcriptional coactivator, as an indispensable repressor in the PIWI-piRNA silencing pathway, supported by transcriptome analyses showing Set1’s requirement for repression of transposon activity. This advances mechanistic understanding of how PIWI-piRNA complexes recruit chromatin-modifying machinery to protect genome integrity in the germline.

Isshiki W, Kozuka-Hata H, Oyama M et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Dual apical methyltransferases orchestrate motility initiation in apicomplexan parasites.

The study investigated motility initiation in apicomplexan parasites, focusing on Toxoplasma gondii, and identified a dual apical methyltransferase mechanism involving TgPCKMT. TgPCKMT (a PreConoidal ring-associated lysine methyltransferase) anchored the actin nucleator Formin-1 (TgFRM1) at the conoid, enabling conoid protrusion and F-actin assembly, and loss of TgPCKMT disrupted TgFRM1 recruitment and blocked motility initiation. This reveals a specific upstream epigenetic-like control step that couples apical signaling to mechanical force generation in parasite invasion-related behaviors.

Qin P, Kumar T, Koczy O et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Next-generation multiplexed targeted proteomics quantifies post-translational modifications in disease and compound-protein interactions with high throughput.

The study developed GoDig 2.0, a next-generation multiplexed targeted proteomics platform for high-throughput quantification of post-translational modifications and compound–protein interactions using mass spectrometry. GoDig 2.0 increased multiplexing up to 35-fold, improved time efficiency without manual scheduling or synthetic standards, and quantified >99% of 800 peptides in a single run while enabling flexible library generation from different MS data types. This enables large-scale profiling of phosphorylation sites (including 23,989 human phosphorylation sites) to compare kinase signaling across cell lines and characterize disease-relevant modification patterns.

Shuken SR, Frere GA, Beard CR et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on August 28, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.