PubMed Trending Research Digest — July 01, 2026

Automated digest · 96 articles · 15 research areas · July 01, 2026

Overview

Across this week’s set, a dominant theme is the use of mechanistic “axes” that connect molecular perturbations to system-level outcomes—spanning aging, cancer, and immune regulation. Several studies highlight lipid- and metabolism-linked pathways (e.g., ferro-aging via ACSL4–lipid peroxidation–senescence; lactate-driven immune evasion via direct STING inhibition; lactate–KAT8–ANT2–PGAM5 control of mitochondrial permeability and PANoptosis; and mitochondrial/lysosomal dysfunction in neurodegeneration and glioblastoma). Together, they emphasize that targeting upstream biochemical nodes can reshape downstream cell fate, immune sensing, and tissue phenotypes.

A second major thread is precision and personalization in oncology and beyond: living guidelines for driver-altered stage IV NSCLC, evidence synthesis for antiplatelet/anticoagulant strategies, and multiple trials/registries testing optimized sequencing or local intensification (e.g., perioperative/systemic therapy around colorectal peritoneal metastases, SBRT as metastasis-directed therapy in oligometastatic CRPC, and response-adaptive or regional nodal radiotherapy strategies in breast cancer). In parallel, translational cancer engineering and immunotherapy platform work (oncolytic adenovirus boosting CD4 responses, biparatopic BCMA CAR-T to overcome antigen heterogeneity, and broader cell-therapy modality reviews) underscores a shift toward modular designs that directly address tumor microenvironment constraints.

Finally, several studies connect host biology to external or ecological inputs—microbiome-derived metabolites shaping immune-metabolic programs, diet patterns (including planetary health diet) relating to IBD outcomes, and pathogen surveillance/diagnostics (avian SARS-CoV-2 VOC-like genomes; sepsis mNGS detection; and long-term CRKP genomic epidemiology). In neuroscience and neuroimmunology, circuit-level and cell-type-specific mechanisms (orexin reward prediction, astrocyte innate immune signaling, and microglial lysosomal pathways affecting α-synuclein propagation) reinforce the broader message that cell-state control—whether by signaling, metabolism, or immune pathways—can be leveraged for therapeutic benefit.

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Aging biology & ferroptosis/senescence axes

Gravitational and mechanical forces shape mitochondrial translation.

The study examined how gravitational and mechanical cues regulate mitochondrial protein synthesis in mammalian cells and Caenorhabditis elegans under microgravity. Genome-wide ribosome profiling showed reduced mitochondrial translation in microgravity, which was linked to attenuated cell adhesion via laminin–integrin signaling and a FAK–RAC1–PAK1–BAD–Bcl-2 family cytosolic relay. These findings identify a mechanotransduction pathway that can control mitochondrial translation and thereby influence cellular stress responses and physiology in altered gravity environments.

Wakigawa T, Kimura Y, Mito M et al. · Nature communications · (2026) · View on PubMed ↗

Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.

The study tested whether covalent inhibition of serine hydroxymethyltransferase 2 (SHMT2) by gambogic acid induces ferroptosis via mitochondrial collapse in triple-negative breast cancer (TNBC). Gambogic acid covalently inhibited SHMT2 and triggered ferroptotic cell death accompanied by mitochondrial structural/functional collapse in TNBC models. This is clinically relevant because it suggests a druggable mitochondrial metabolic vulnerability that could be exploited for TNBC treatment.

Yang T, Qiu C, Li Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Tau protein as a regulator of mitochondrial function and dynamics.

The study assessed the physiological role of wild-type Tau in mitochondrial function and dynamics using Caenorhabditis elegans and mice lacking the Tau-like homolog PTL-1 and Tau, respectively. Tau deficiency shifted mitochondria toward a pro-fusion state with increased mitochondrial activity and altered redox homeostasis, improving stress resistance including heat tolerance. These results support Tau as a regulator of mitochondrial homeostasis and suggest that modulating Tau pathways could influence resilience to neurodegenerative and aging-associated mitochondrial dysfunction.

Tsakiri E, Campos-Marques C, Ploumi C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Reassessing the risk-modifying effects of novel antidiabetic agents on asthma-COPD overlap syndrome: a dose-stratified network meta-analysis of 316,832 adults from 128 randomised trials.

This dose-stratified network meta-analysis evaluated how novel antidiabetic agents modify risk of asthma–COPD overlap syndrome (ACOS) using data from 316,832 adults across 128 randomized trials. It compared respiratory outcomes by specific glucose-lowering drug classes and dose strata to estimate agent-level and dose-specific effects on ACOS risk. The analysis is significant for guiding safer selection and dosing of newer diabetes therapies in patients at risk for chronic obstructive airway disease overlap.

Zeng BY, Hsu CW, Hung CM et al. · EClinicalMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Compositional recalibrations of cardiolipin integrate loss of stearoyl-CoA desaturase 1 activity with mitochondrial decay in lipid-laden pancreatic β-cells.

This work examined how loss of stearoyl-CoA desaturase 1 (SCD1) activity affects cardiolipin composition and mitochondrial decay in lipid-laden pancreatic β-cells relevant to type 2 diabetes. The authors found that compositional recalibrations of cardiolipin integrate SCD1 loss with mitochondrial deterioration, linking altered mitochondrial phospholipid biosynthesis to β-cell failure. These findings identify a lipid–mitochondria coupling mechanism that could help explain early β-cell dysfunction in T2D and suggest potential metabolic targets beyond SCD1 alone.

Janikiewicz J, Lebiedzinska-Arciszewska M, Kendziorek ME et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial quality control in human ageing and longevity.

This review summarizes mitochondrial quality control (MQC) mechanisms in human aging and longevity, focusing on how cells monitor, repair, and remove damaged mitochondria. It explains how MQC failure contributes to chronic diseases including diabetes, metabolic syndromes, and immunosenescence, emphasizing MQC’s importance under metabolic and environmental stress. The synthesis provides a conceptual framework for targeting MQC pathways to promote healthy aging and potentially extend healthspan.

Picca A, Ferrucci L · Nature metabolism · (2026) · View on PubMed ↗

Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.

This mechanistic study investigated how angiogenin (ANG) functions as a mitochondrial tRNA (mt-tRNA) processing enzyme to support mitoribosome biogenesis during cell-cell fusion in myoblasts and osteoclasts. The key finding is that ANG translocates to mitochondria upon fusion initiation, cleaves mt-tRNA 3′ ends, and thereby promotes mitoribosome biogenesis to enable translation of respiratory complex proteins and ATP production needed for fusion. Scientifically, it identifies ANG as a critical mitochondrial RNA-processing regulator of fusion energetics and mitochondrial translation capacity.

Shen K, Zeng Y, Wang J et al. · Bone research · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of proteomic age clocks with lifestyle risk factors, incident chronic diseases and mortality in two European cohorts.

This cohort study assessed associations between plasma proteomic age clocks (SomaScan-based, including organ-specific clocks) and lifestyle risk factors, incident chronic diseases, and mortality in 17,473 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) with replication in the Whitehall II study. The key finding is that the global age gap (an age acceleration score combining proteomic clocks) is associated with smoking, alcohol consumption, physical inactivity, and higher all-cause mortality risk over up to 28 years of follow-up. The significance is that proteomic “biological aging” measures may improve risk prediction and help connect modifiable behaviors to long-term disease and mortality pathways.

Robinson O, Xiao H, Homann J et al. · Nature aging · (2026) · View on PubMed ↗ · Free PDF ↗

Chromosome condensation mechanically primes the nucleus for mitosis.

This cell biology study investigated how chromosome condensation controls the spatial activation of cyclin B1–CDK1 to prime the nucleus for mitosis. The key finding is that chromosome condensation increases nuclear envelope (NE) tension, which is required for cyclin B1 translocation into the nucleus and dynein loading on nuclear pore complexes via SUN proteins, thereby enabling timely mitotic entry. Scientifically, it reveals a mechanical checkpoint that couples chromosome state to nuclear transport and mitotic timing to preserve genome integrity.

Nunes V, Moura M, Silva SF et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting the Ip6k2-Runx2 axis disrupts osteoblast-osteoclast coupling to treat osteoporosis.

The study investigated the Ip6k2–Runx2 signaling axis in bone cells to treat osteoporosis, using conditional knockout models to dissect Runx2 function in osteoblasts versus osteoclasts. The key finding was that Runx2 directly drives osteoclast differentiation by regulating Ctsk transcription, while Ip6k2 interacts with Runx2 to enhance osteoclast-specific Ctsk transcription; deleting Ip6k2 phenocopied osteoclast Runx2 loss by suppressing osteoclastogenesis and increasing bone mass. This is significant because it identifies Ip6k2 as a more osteoclast-selective therapeutic target within the Runx2 pathway to disrupt osteoblast–osteoclast coupling in osteoporosis.

Ma G, Chen Y, Cheng S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A trispecific GLP-1/anti-GIPR/FGF21 peptibody exhibits favorable metabolic effects in a diet-induced obesity model.

This preclinical study evaluated a trispecific peptibody that combines GLP-1R agonism, GIPR antagonism, and FGF21 pathway activation in a diet-induced obesity model. The construct showed favorable metabolic effects compared with relevant controls, consistent with simultaneous modulation of multiple obesity and glucose-regulatory pathways. This supports the therapeutic rationale for multi-target incretin/FGF21 pathway engagement as a strategy to improve metabolic outcomes beyond single-target GLP-1 approaches.

Liu Y, Liu X · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · (2026) · View on PubMed ↗ · Free PDF ↗

Vitamin C, ACSL4, and Ferro-Aging: Mechanistic Insights and Translational Perspectives from Primate Studies.

This study examined ferro-aging in non-human primates, focusing on the iron-driven aging axis involving acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) and testing vitamin C (VC) as a potential inhibitor of ACSL4. The authors report that supraphysiological VC can inhibit ACSL4 activity and reverse multi-omic markers of biological age while preserving neural architecture, functional connectivity, and metabolic homeostasis in aged primates. These findings support a translational strategy targeting the ACSL4–lipid peroxidation–senescence pathway to mitigate systemic aging phenotypes.

Li C, Gong Z, Ye J et al. · Aging and disease · (2026) · View on PubMed ↗ · Free PDF ↗

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Precision oncology guidelines & treatment sequencing

Quizartinib in Combination With FLAG-IDA for Relapsed or Refractory Acute Myeloid Leukemia (FLAG-QUIDA): A PETHEMA Phase I-II Trial.

This phase I–II PETHEMA trial studied quizartinib (a FLT3 tyrosine kinase inhibitor) combined with FLAG-IDA in adult patients with first relapsed/refractory acute myeloid leukemia (R/R AML). The trial evaluated recommended phase 2 dose (RP2D) and complete remission outcomes (CR/CRi), reporting early efficacy and safety results across 61 enrolled patients. If confirmed in full analyses, quizartinib+FLAG-IDA could improve remission rates for R/R AML patients by intensifying FLT3-targeted therapy within a chemotherapy backbone.

Bernal T, Zambrano Márquez J, Rodríguez-Veiga R et al. · American journal of hematology · (2026) · View on PubMed ↗

53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.

The study investigated how BRCA1-deficient cells respond to replication-coupled DNA double-strand breaks when the 53BP1–Shieldin pathway components are altered. Loss of Shld2 or Shld3 (but not 53BP1) conferred PARP inhibitor (PARPi) resistance in mouse embryonic stem cells lacking a functional BRCA1 BRCT domain, partially restoring homologous recombination at replication-coupled DSBs with increased RAD51 loading. This reveals a 53BP1-independent Shieldin–BRCA1 antagonism mechanism that could inform biomarkers and resistance management for PARPi therapy.

Feng YL, Wang M, Li G et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A pilot translational study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma.

This pilot phase II translational study evaluated neoadjuvant fulvestrant plus abemaciclib in 15 women with advanced, unresectable low-grade serous carcinoma of the ovary (LGSOC) (NCT03531645), with imaging every 8 weeks to determine resectability and clinical benefit rate (CBR). The study’s key finding (as reported in the abstract) is that the combination was assessed for clinical benefit and biomarker-linked tumor phenotypic changes while also characterizing safety in this chemotherapy-resistant population. Clinically, it tests whether hormone-receptor–targeted CDK4/6 inhibition can improve outcomes in LGSOC, a disease with limited effective neoadjuvant options.

Cobb LP, Dai Y, Molina Ayala M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Outcomes of patients with higher-risk myelodysplastic syndromes/neoplasms treated with hypomethylating agents + venetoclax-an analysis from the International Consortium for MDS (icMDS) VALIDATE database.

This analysis studied outcomes in higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) treated with hypomethylating agents (HMAs) with or without venetoclax (VEN) using data from the International Consortium for MDS (icMDS) VALIDATE database. Among 1907 frontline patients, the study compared response and survival outcomes between HMA monotherapy and HMA/VEN, addressing whether adding VEN benefits specific HR-MDS subsets. The results are clinically significant for refining patient selection for HMA+VEN regimens in HR-MDS where randomized evidence has been mixed.

Bewersdorf JP, Kewan T, Lanino L et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗

Real-world Comparison of Avelumab Maintenance and Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma.

This study compared, in a real-world setting, avelumab maintenance versus enfortumab vedotin plus pembrolizumab (EVP) as first-line strategies for metastatic urothelial carcinoma (mUC) using the TriNetX Global Collaborative Network. The key finding was the relative survival outcomes between cohorts receiving avelumab maintenance after platinum-based chemotherapy and those receiving EVP, addressing whether the maintenance approach is comparable or superior. This is clinically significant for guiding treatment sequencing in mUC outside clinical trials.

Yen TH, Wang SS, Chen CS et al. · Anticancer research · (2026) · View on PubMed ↗

Secukinumab biosimilar BAT2306 versus reference secukinumab in patients with moderate-to-severe plaque psoriasis: a multicentre, double-blind, randomised, active-controlled, phase 3 trial.

This phase 3 randomized, double-blind, active-controlled trial compared the biosimilar BAT2306 to reference secukinumab in adults with moderate-to-severe plaque psoriasis. The key finding was that BAT2306 matched reference secukinumab in safety, efficacy, pharmacokinetics, and immunogenicity based on trial outcomes and biomarker responses. This is significant for expanding evidence-based, lower-cost biologic options while maintaining therapeutic performance in psoriasis patients.

Chen JQ, Chen R, Wu L et al. · The Lancet. Rheumatology · (2026) · View on PubMed ↗

Reirradiation for recurrent head and neck squamous cell carcinoma: international expert consensus recommendations endorsed by the Reirradiation Collaborative Group, the European Society for Radiotherapy and Oncology Reirradiation Focus Group, and the American Society for Radiation Oncology.

This international expert consensus statement reviewed evidence and provided pragmatic recommendations for reirradiation in recurrent head and neck squamous cell carcinoma (HNSCC) occurring within previously irradiated regions. The key finding was that modern conformal techniques (including intensity-modulated radiotherapy, proton therapy, and stereotactic body radiotherapy) can make reirradiation feasible despite heterogeneous evidence and variable toxicity risk. This is clinically significant because it standardizes decision-making in a setting with limited options and substantial inter-patient variability.

Biau J, Beddok A, Sharma M et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

European guideline for imaging of primary paediatric and adult osteosarcoma and Ewing sarcoma: systematic review and joint statement by the FOSTER consortium, Euro Ewing Consortium, European Society of Paediatric Radiology, and the European Association of Nuclear Medicine.

This European guideline, developed by multiple consortia and societies, systematically reviewed and proposed standardized imaging approaches for diagnosing, staging, response assessment, and surveillance in osteosarcoma and Ewing sarcoma across pediatric and adult patients. The key finding from the underlying systematic review was marked heterogeneity in diagnoses, chemotherapy regimens, and imaging protocols, with inconclusive evidence for optimal modalities for detecting bone metastases and no consistent metabolic imaging indices or MRI parameters predicting response or survival. This is significant for harmonizing imaging practice to improve comparability across studies and optimize patient care in these rare cancers.

Adriaansen LME, Merks JHM, van Dalen EC et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Dose escalation with intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO-II): an open-label, multicentre, randomised, controlled, phase 3 trial.

This phase 3 randomized controlled trial studied whether adding intraoperative kilovoltage radiotherapy after maximal resection improves outcomes in adults (18–80 years) with supratentorial glioblastoma (KPS ≥60%) across multiple countries. The key finding was that dose escalation with intraoperative radiotherapy (INTRAGO-II) was tested as an additional treatment beyond standard of care to reduce local recurrence risk. Clinically, the trial’s results are intended to determine whether intraoperative radiotherapy can improve survival and local control in newly diagnosed glioblastoma.

Giordano FA, Ganslandt O, Münter MW et al. · The Lancet. Oncology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Perioperative systemic therapy versus surgery alone for resectable colorectal peritoneal-only metastases (CAIRO6): a randomised, open-label, phase 3 trial.

This open-label phase 3 randomized trial compared perioperative systemic therapy versus surgery alone in adults with resectable colorectal peritoneal-only metastases (WHO performance status 0–1) at Dutch and Belgian tertiary centers. The key finding was the trial’s assessment of whether adding systemic therapy around surgery improves efficacy compared with surgery alone in this selected population. The significance is that it directly informs whether perioperative systemic treatment should become standard for resectable peritoneal-only colorectal metastases.

Rovers KP, Bakkers C, van den Heuvel TBM et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial.

This long-term unplanned overall survival analysis evaluated whether adding metastasis-directed therapy (SBRT) to abiraterone acetate plus androgen deprivation therapy (ADT) improves survival versus abiraterone acetate plus ADT alone in oligometastatic castrate-resistant prostate cancer (ARTO trial). The key finding was the extended overall survival impact of SBRT-based MDT on top of systemic androgen-axis therapy. This is significant because it tests whether early local control via SBRT translates into durable survival benefit in oligometastatic CRPC.

Francolini G, Di Cataldo V, Caini S et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Internal mammary chain and medial supraclavicular lymph node irradiation in stage I-III breast cancer (EORTC trial 22922/10925): an unplanned subset analysis of 20-year outcomes in patients with node-negative breast cancer.

This unplanned subset analysis of the EORTC trial 22922/10925 studied internal mammary chain and medial supraclavicular (IM-MS) nodal irradiation in patients with stage I–III node-negative breast cancer (pathological N0) over 20-year follow-up. The key finding was the long-term effect of adding IM-MS regional nodal irradiation on disease outcomes, including distant metastasis and breast cancer-related mortality, with variable overall survival effects. The significance is that it provides decades-long evidence to guide whether IM-MS irradiation should be used in node-negative breast cancer after surgery.

Kaidar-Person O, Weltens CG, Fortpied C et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Tailoring radiotherapy in cT1-2N1 breast cancer to nodal response on primary chemotherapy (RAPCHEM: BOOG 2010-03): 10-year follow-up results of a Dutch, prospective, registry study.

This Dutch prospective registry study (RAPCHEM: BOOG 2010-03) investigated whether tailoring postoperative radiotherapy in cT1-2N1 breast cancer based on nodal response to primary chemotherapy improves long-term outcomes. The key finding from the 10-year follow-up was that nodal-response–tailored radiotherapy maintained excellent locoregional control compared with less individualized approaches. This is significant because it supports response-adaptive radiotherapy decisions to optimize benefit while potentially limiting overtreatment.

Mauritz AJW, de Munck L, Simons JM et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by olaparib in stage III breast cancer (SUBITO): an open-label, randomised, controlled, phase 3 trial.

This open-label phase 3 randomized trial (SUBITO) studied stage III HER2-negative breast cancer with homologous recombination deficiency (HRD), comparing intensified chemotherapy with autologous stem cell rescue (IACT) versus standard chemotherapy followed by olaparib. The key finding was the prospective assessment of whether IACT remains superior for 4-year overall survival compared with a contemporary HRD-targeting regimen using the PARP inhibitor olaparib. This is clinically significant because it directly informs optimal first-line treatment strategy for HRD-positive, HER2-negative stage III breast cancer.

Seefat RL, Vliek SB, de Jong VMT et al. · The Lancet. Oncology · (2026) · 1 citations · View on PubMed ↗

Adverse Events After Same-Day COVID-19 and Influenza Vaccination Versus Influenza Vaccination Alone : A Target Trial Emulation.

This target trial emulation study used U.S. Department of Veterans Affairs electronic health care data to compare 90-day adverse events after same-day coadministration of COVID-19 and influenza vaccines versus influenza vaccination alone across bivalent, XBB-adapted, and KP-adapted COVID-19 vaccine periods. It assessed risks for adverse events in vaccinated populations receiving both vaccines on the same day compared with those receiving influenza vaccine alone. The results provide updated real-world safety estimates relevant to immune-experienced populations and variant-era formulations.

Xie Y, Choi T, Al-Aly Z · Annals of internal medicine · (2026) · View on PubMed ↗

Performance of Lung Cancer Risk Prediction Models in Different Racial and Ethnic Groups in the United States: Results From the Lung Cancer Cohort Consortium.

This cohort study evaluated how 16 lung cancer risk prediction models perform for determining screening eligibility across racial and ethnic groups in the United States using data from the Lung Cancer Cohort Consortium. Among 641,830 participants aged 50–80 with smoking histories (including Asian, Hispanic, non-Hispanic Black, and non-Hispanic White groups), it quantified calibration and discrimination and then computed screening-related metrics after applying model thresholds. The findings clarify whether existing risk models generalize across populations, informing equitable lung cancer screening strategies.

Feng X, Guida F, Guenoun A et al. · Annals of internal medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.2.

This ASCO living guideline systematically reviewed evidence to define therapy recommendations for patients with stage IV non-small cell lung cancer (NSCLC) harboring driver alterations. The key finding is that the guideline provides continuously updated, evidence-ranked treatment recommendations tailored to specific actionable driver mutations and evolving trial data. Clinically, it standardizes decision-making for precision oncology in stage IV NSCLC while explicitly accounting for the rapid pace of new evidence.

Puri S, Ismaila N, Azar IH et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

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Cancer structural biology & genotype–phenotype mapping

Thick filament molecular interfaces play a critical role in the pathogenesis of hypertrophic cardiomyopathy.

This study mapped 233 missense variants in hypertrophic cardiomyopathy genes—MYH7, MYBPC3, MYL2, and MYL3—onto a cryo-EM-based atomic model of the human cardiac thick filament to define structural consequences at molecular interfaces. The authors found that pathogenic HCM variants cluster in 30 molecular interfaces of the thick filament interactome, implicating specific interface disruptions in disease mechanism. Scientifically, the work links genotype to thick-filament structural pathology and provides a framework for interpreting variant-specific effects in HCM.

Dutta D, Kim Y, Ho CY et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Zoonotic and viral surveillance (SARS-CoV-2 and others)

Structural basis for host membrane binding and remodeling by invading malaria parasites.

The study determined the endogenous structural basis of host membrane binding and remodeling by invading Plasmodium falciparum parasites, focusing on the moving junction complex. Cryo-structural analysis of invasion-stalled parasites revealed a sailboat-shaped 1:1:1:1 assembly of PfAMA1 with PfRON2, PfRON4, and PfRON5, including PfRON2 transmembrane helices that anchor the complex in the red blood cell membrane and an extracellular handle for PfAMA1 binding. These structural insights clarify how PfAMA1–PfRON interactions mechanically couple parasite invasion to RBC membrane remodeling, informing rational antimalarial target development.

Haile MT, Kaxiras DA, Zhen J et al. · Cell · (2026) · View on PubMed ↗

Enhanced invasiveness promotes the dominance of a widely-distributed carbapenem-resistant virulence-plasmid-carrying Klebsiella pneumoniae sublineage.

The study analyzed a decade of surveillance data and performed whole-genome sequencing on 1513 clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, integrating fine-scale genome analysis of 60,724 additional genomes. The key finding was identification of a predominant, widely distributed ST11-KL64 sublineage carrying plasmids with hypervirulence factors and showing enhanced invasiveness, with seasonal associations (e.g., influenza peaks) and international dissemination. This is significant because it pinpoints a high-risk CRKP sublineage and virulence-plasmid context that can inform infection control and antimicrobial resistance surveillance.

Yang Y, Qin J, Feng Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Genomic and structural evidence of SARS-CoV-2 and MERS-CoV in migratory birds.

This study investigated whether migratory birds carry coronaviruses by sequencing and analyzing almost full-length SARS-CoV-2 genomes from Tundra swans using genomic and structural comparisons to known variants. It identified three SARS-CoV-2 variant-of-concern–like genomes (IMCAS_M1, IMCAS_M2, IMCAS_M3) with spike receptor-binding domain mutation patterns matching Beta (K417N/E484K/N501Y) and Gamma (K417T/E484K) lineages. The findings are significant for zoonotic surveillance, showing that SARS-CoV-2 VOC-like viruses can be detected in avian reservoirs and may inform risk assessment of cross-species transmission.

Cao J, Liu S, Su C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroscience of motivation, circuits, and neuromodulation

Prevalence of Insomnia in Healthcare Profession - PIHEP Study: A Large-Scale National Study in Vietnam.

The PIHEP study conducted a nationwide multi-region cross-sectional survey to estimate the prevalence of insomnia among 1,655 Vietnamese healthcare professionals and identify associated nocturnal symptoms, daytime impairment, and clinical factors. Insomnia prevalence and correlates were quantified using structured questionnaire data across occupational and health-related variables. These results are important for occupational health planning and targeted interventions to reduce sleep disturbance in healthcare workers in Southeast Asia.

Duong-Quy S, Nguyen-Thi-Thu D, Hoang-Thi-Xuan H et al. · Nature and science of sleep · (2026) · View on PubMed ↗ · Free PDF ↗

TRPC4/TRPC5 are critical for neuronal modulation by transcranial focused ultrasound in retrosplenial cortex in male mice.

The study investigated whether transient receptor potential canonical 4 (TRPC4) and TRPC5 channels mediate transcranial focused ultrasound (tFUS)-induced neuronal modulation in the retrosplenial cortex of male mice. tFUS desensitized mechanical/thermal sensitivity and induced early growth response 1 (Egr1) expression, with transcriptomic enrichment of Trpc4 in tFUS-activated Egr1-positive cells and inhibition of tFUS-induced Egr1 ensembles blocking somatic sensory effects. These findings identify TRPC4/TRPC5 as mechanistic targets linking tFUS stimulation to activity-dependent gene programs, informing safer and more precise neuromodulation strategies.

Wu C, You J, Sheng T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Two parallel neuronal circuits involving electrical synapse and DAF-7/TGF-β signaling regulate muscle autophagy in C. elegans.

This study in C. elegans identified two parallel neuronal circuits that regulate autophagy-lysosome pathway activity in body wall muscle during development. It found that UNC-7/UNC-9 electrical synapses (AVA interneurons to A-type motor neurons) promote autophagy by inhibiting neuropeptide release, while the TGF-β-like ligand DAF-7 from ASI sensory neurons activates autophagy via the canonical TGF-β pathway, with both converging on cytosolic Ca²⁺ regulation to maintain lysosomal integrity. The significance is that it reveals how coordinated neuronal signaling controls muscle autophagy through defined synaptic and DAF-7/TGF-β mechanisms.

Zheng H, Zhao H, Zhang H · Developmental cell · (2026) · View on PubMed ↗

Reward prediction is encoded by orexin neuron activity during motivated behavior.

This study examined how orexin neurons encode reward prediction during motivated behavior in transgenic rats using cell type-specific fiber photometry, optogenetic manipulation, and chemogenetics. It found that activating orexin neurons increases motivation for reward and that orexin neuron activity dynamically rises during reward prediction and falls after reward delivery. These results are significant because they causally link temporally structured orexin neuron activity to computational aspects of motivated behavior.

Dong Y, Rahaman SM, Zhu W et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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GPCR/Hedgehog pathway mechanisms & targeted signaling

The mechanism for ligand activation of the Smoothened G protein-coupled receptor.

This study elucidated the ligand activation mechanism of the Smoothened (SMO) G protein-coupled receptor in the Hedgehog signaling pathway by analyzing the sequence of G protein and cholesterol (CHL) ligand binding steps. The key finding supports a G protein-first activation model in which CHL binds first to the cysteine-rich domain (CRD) of inactive SMO, followed by spontaneous G protein binding that drives progression toward activation. Mechanistically, this clarifies how SMO transitions from inactive to active states and informs therapeutic targeting of SMO in Hedgehog-driven cancers.

Yu RD, Vo AP, Kim SK et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroprotection & dementia risk reduction

Sodium-Glucose Cotransporter 2 Inhibitors and Dementia Risk in Patients With Psychiatric Disorders.

This cohort study used US Veterans Affairs data to evaluate whether sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment is associated with reduced incident dementia in adults aged ≥65 years with mood or psychotic disorders. SGLT2 inhibitor use was associated with a lower risk of developing dementia compared with non-use (target trial emulation design). These findings suggest a potential neuroprotective effect of SGLT2 inhibitors in higher-risk psychiatric populations and support further mechanistic and prospective evaluation.

Liebers DT, He T, Betensky RA et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Geriatric oncology and treatment in older adults

Efficacy, safety, and treatment feasibility of pembrolizumab plus lenvatinib in patients aged 75 years or older with advanced renal cell carcinoma: a Japanese multicenter retrospective study.

This Japanese multicenter retrospective study compared efficacy, safety, and treatment feasibility of pembrolizumab plus lenvatinib as first-line therapy in patients with advanced/metastatic renal cell carcinoma aged ≥75 years versus <75 years. Older patients (≥75) had different treatment exposure and adverse event patterns than younger patients, with clinical outcomes assessed via best overall response, progression-free survival, and overall survival. The results inform real-world geriatric decision-making for immunotherapy–TKI combinations in advanced RCC.

Yamashita S, Yamasaki T, Ueda K et al. · International journal of clinical oncology · (2026) · View on PubMed ↗

Clinical Outcomes of Pola-R-CHP Therapy in Patients Aged >80 Years With Diffuse Large B-Cell Lymphoma.

This retrospective study assessed real-world clinical outcomes of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) as first-line therapy in patients with diffuse large B-cell lymphoma (DLBCL) aged over 80 years. The key finding was the reported progression-free survival (PFS) and safety outcomes in this older cohort, stratified against patients aged ≤80 years within the same dataset. These data are important for determining feasibility and expected benefit of Pola-R-CHP in frailer, underrepresented elderly populations.

Baba Y, Fukumura S, Tanai S et al. · Anticancer research · (2026) · View on PubMed ↗

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Cardiovascular therapeutics: antiplatelets & anticoagulants

Antiplatelet Therapy in the Management of Atherosclerotic Cardiovascular Disease: 2026 ACC Scientific Statement: A Report of the American College of Cardiology.

This 2026 ACC scientific statement reviewed evidence on antiplatelet therapy for atherosclerotic cardiovascular disease (ASCVD), focusing on aspirin and dual antiplatelet therapy (DAPT) strategies in the context of evolving drug-eluting stents and contemporary trials. It concludes that routine aspirin use for primary prevention in unselected populations lacks benefit and should be reserved for those at highest ischemic risk, while emphasizing updated recommendations for secondary prevention and DAPT duration. Clinically, the statement provides an evidence-based framework to optimize antiplatelet selection and duration to balance ischemic and bleeding risks.

Kumbhani DJ, Gibson CM, Kinlay S et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Direct Oral Anticoagulants in Primary and Secondary Prevention of Thrombotic Events: 2026 ACC Scientific Statement: A Report of the American College of Cardiology.

This 2026 ACC scientific statement synthesized evidence on direct oral anticoagulants (DOACs) for primary and secondary prevention of thrombotic events, comparing their use to vitamin K antagonists across major clinical scenarios. It emphasizes that DOACs have become preferred oral anticoagulants for most patients with atrial fibrillation and venous thromboembolism, while noting persistent gaps such as underuse and inappropriate dosing in higher-risk and historically underrepresented populations. The statement’s significance is to guide safer, more consistent DOAC implementation and dosing practices across diverse real-world settings.

Kumbhani DJ, Armbruster AL, Cheng RK et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Low-density lipoprotein cholesterol management and goal attainment at 1 year in patients with diabetes, pre-diabetes and normoglycaemia: results from the European, prospective, observational SANTORINI study.

The SANTORINI prospective observational study examined low-density lipoprotein cholesterol (LDL-C) management, lipid-lowering therapy (LLT) use, and 1-year LDL-C goal attainment across adults stratified by diabetes status (diabetes, pre-diabetes, and normoglycaemia). The key finding was how LDL-C goal attainment and LLT patterns differed by diabetes status over one year in high- and very-high cardiovascular risk patients. This is significant for improving cardiovascular prevention strategies by identifying gaps in achieving guideline LDL-C targets in different metabolic risk groups.

Toplak H, Komen JJ, Bardet A et al. · BMJ open · (2026) · View on PubMed ↗ · Free PDF ↗

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Interventional cardiology outcomes in substance use

Opioid use disorder and clinical outcomes following percutaneous coronary intervention for acute coronary syndromes.

This single-center retrospective cohort study assessed how opioid use disorder (OUD), identified using ICD-9/ICD-10 codes, affects clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndromes in 5,875 patients. Patients with OUD had worse outcomes across multiple follow-up windows (in-hospital, 30-day, 6-month, and 1-year) after adjustment using multivariable logistic regression, propensity score matching, and time-to-event analyses. The findings highlight the need for targeted risk stratification and integrated OUD management in ACS patients undergoing PCI.

Awad A, Hamza M, Smith-Villegas A et al. · Journal of thrombosis and thrombolysis · (2026) · View on PubMed ↗

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Infectious disease diagnostics & sepsis pathogen detection

Effects of a clinical metagenomics intervention on clinical outcomes, healthcare costs, and health-related quality of life in patients with sepsis or septic shock: results of the randomized-controlled DigiSep trial.

The DigiSep randomized controlled trial studied whether metagenomic next-generation sequencing (mNGS) detection of microbial circulating cell-free DNA, added to standard-of-care microbiology, improves outcomes in adults with sepsis or septic shock across 24 German ICUs. The intervention was designed to improve the primary endpoint of Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotics without increasing healthcare costs. If effective, this approach would support earlier pathogen identification to guide antibiotic stewardship and improve patient-centered outcomes in sepsis.

Brenner T, Skarabis A, Schaller SJ et al. · Intensive care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic disease therapeutics (GLP-1/GIP/FGF21/SGLT2 and diabetes)

Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study.

Using TriNetX real-world data, this retrospective propensity-matched cohort study compared clinical outcomes and safety between tirzepatide and semaglutide in adults >40 years with obesity (BMI ≥30 kg/m²) and type 2 diabetes (HbA1c ≥6.5% or fasting glucose ≥125 mg/dL). Outcomes were evaluated for events occurring between May 1, 2022 and November 21, 2024 after cohort construction based on treatment initiation. The study helps quantify comparative effectiveness of the dual GIP/GLP-1 agonist tirzepatide versus the GLP-1 receptor agonist semaglutide in routine care.

Qadeer A, Khalid MB, Syed R et al. · Diabetes & vascular disease research · (2026) · View on PubMed ↗ · Free PDF ↗

Emergence of invasive Escherichia coli pathobionts in gut microbiome promotes cancer stemness via targeting Hippo pathways.

This preclinical study investigated how invasive Escherichia coli pathobionts emerging from gut microbiota promote cancer stemness by targeting Hippo signaling pathways in the context of intestinal tumorigenesis. In Apc(Min/+) mice, dysbiosis and invasive pathobionts were linked to increased epithelial stemness through Hippo pathway modulation, consistent with the role of Wnt/Apc/β-catenin and Hippo in tumor growth. The findings suggest a microbiome–Hippo axis mechanism by which barrier dysfunction and specific pathobionts can enhance colorectal cancer stem-like properties.

Yu LC, Wei SC, Lin BR et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative effectiveness of individual-level psychosocial interventions for nurse burnout and its core dimensions: A systematic review and network meta-analysis.

This systematic review and network meta-analysis compared individual-level psychosocial interventions for nurse burnout and its dimensions (emotional exhaustion, depersonalization, and personal achievement). Across studies published up to January 15, 2026, it synthesized relative efficacy using a network meta-analytic framework to determine which intervention types most effectively reduce burnout outcomes. The findings help prioritize psychosocial strategies for healthcare systems aiming to reduce nurse burnout and improve workforce wellbeing and patient care quality.

Liu X, Wang H, Tian S et al. · International journal of nursing studies · (2026) · View on PubMed ↗

Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes : A Phase 2b Randomized Clinical Trial.

This phase 2b randomized clinical trial compared weekly and biweekly bofanglutide dosing regimens with semaglutide in Chinese adults with type 2 diabetes (T2DM), including drug-naïve participants or those on stable oral antidiabetic therapy. Participants were randomized to multiple bofanglutide titration groups (12, 18, or 24 mg with biweekly dosing) versus semaglutide, to evaluate efficacy and safety outcomes over the trial period. The study informs dosing schedules and comparative performance of bofanglutide versus semaglutide for glycemic control and weight-related metabolic benefits in T2DM.

Liu M, Cheng Z, Lu L et al. · Annals of internal medicine · (2026) · View on PubMed ↗

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Microbiome, metabolites, and immune modulation

IL-17A deficiency in HLA-DR3 transgenic mice enriches beneficial Prevotella species in gut to promote Tregs and reduce CNS autoimmunity.

This study used HLA-DR3 transgenic mice deficient in IL-17A to test how IL-17A loss reshapes gut microbiota and CD4+ Treg/Th17 balance to affect CNS autoimmunity. IL-17A deficiency enriched beneficial Prevotella species, promoted regulatory T cells (Tregs), and reduced CNS autoimmune pathology in the HLA-DR3 humanized model. The findings support a microbiota–IL-17A–Treg axis as a potential lever for modulating autoimmune disease risk and severity in genetically susceptible hosts.

Shahi SK, Ghimire S, Jensen SN et al. · Microbiome · (2026) · View on PubMed ↗ · Free PDF ↗

Multiomics analysis of primary metabolism reveals the genetic basis of nitrogen partitioning modulated by ZmAVT1A-1 in maize.

This multi-omics genetics study integrated genomic, transcriptomic, and metabolomic data from 1,404 maize progenies derived from 24 diverse founders to dissect causal genes underlying quantitative trait loci for primary metabolism and nitrogen partitioning. The key finding is that the framework prioritized ZmAVT1A-1, encoding a putative amino acid transporter, as a key regulator of amino acid accumulation, supported by natural variation and transgenic analyses. The significance is that it provides a systems-level route to identify actionable genes for improving maize nutritional quality and nitrogen-use–related traits.

Jin M, Yan S, Wu Y et al. · Nature genetics · (2026) · View on PubMed ↗

Impaired IFNγ responsiveness of monocyte-derived lung cells limits immunity to Mycobacterium tuberculosis.

The study examined lung mononuclear phagocyte subsets during chronic Mycobacterium tuberculosis infection to determine why some cells restrict Mtb poorly. The key finding was that CD11c^lo monocyte-derived lung cells express lower interferon-gamma (IFNγ) signaling proteins, show reduced IFNγ responsiveness, and that type I IFN signaling suppresses IFNγ-driven MHC class II expression, limiting antigen-specific CD4 T cell activation. This is significant because it identifies an IFNγ-pathway impairment mechanism that could be targeted to improve immunity against Mtb in the lung.

Zheng W, Limberis JD, Howard ZP et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Aligning patient and planetary health: planetary health diet adherence and inflammatory bowel disease prognosis across Western and Eastern cohorts.

The study evaluated whether adherence to a planetary health diet (PHD) predicts inflammatory bowel disease (IBD) outcomes, using 1455 participants from UK Biobank and 205 from the ONE-IBD cohort with dietary questionnaires and carbon footprint estimates. The key finding was that PHD adherence was assessed across multiple algorithms and related to IBD prognosis endpoints (including surgery, colorectal cancer, readmission/recurrence, and mortality) using Cox models with hazard ratios. This is significant because it tests whether a sustainability-oriented diet can also serve as a practical dietary strategy to influence long-term IBD clinical outcomes.

Dan L, Shu H, Sun Y et al. · NPJ science of food · (2026) · View on PubMed ↗ · Free PDF ↗

Reactive species as regulators of immune cell metabolism, tolerance, and autoimmunity.

This review article examined how reactive oxygen and nitrogen species (ROS/RNS) regulate immune cell metabolism, tolerance, and autoimmunity. The key finding was that spatially restricted ROS/RNS act as signaling regulators by modulating receptor signaling thresholds and mitochondrial activity, while antioxidant systems maintain a “signaling window” through NADPH-dependent recycling pathways. The significance is that dysregulated ROS/RNS balance (e.g., hydroxyl radical and peroxynitrite accumulation) can drive inflammatory signaling and autoimmune disease, linking redox biology to immune-metabolic control.

Kobayashi T, Brenner D · Cell metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

The interplay between the microbiome and immune cells in metabolic homeostasis and disease.

This review studied how microbiome-derived metabolites influence immune cells to shape metabolic homeostasis and disease. The key finding was that metabolites such as short-chain fatty acids, bile acids, indoles, and lipopolysaccharides modulate immune-metabolic programs via mechanisms including epigenetic remodeling and mitochondrial reprogramming, with effects on mTOR and AMPK signaling. The significance is that it connects specific microbial metabolite classes to immune regulation of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease.

Shapiro H, Jickeli B, Niv I et al. · Cell metabolism · (2026) · View on PubMed ↗

Targeted genomic editing of human gut Bacteroides species based on CRISPR-associated transposases.

This study developed STIB, a ShCAST-based transient insertion genome-editing system derived from CRISPR-associated transposases, to edit human gut Bacteroides species. STIB achieved >97% on-target site-specific insertions while minimizing plasmid cointegration and did so without homologous recombination by fusing a nicking homing endonuclease to the transposase and an ATPase to Cas12k. This provides a broadly applicable, high-efficiency genetic tool for manipulating gut Bacteroides to enable mechanistic microbiome research and potential therapeutic engineering.

Hu Y, Li Q, Li Y et al. · Cell systems · (2026) · View on PubMed ↗

Histidine metabolic reprogramming drives oxidative stress induced mtDNA release to promote necroptosis and airway inflammation in severe asthma.

This study examined how histidine metabolic reprogramming contributes to oxidative stress–induced mitochondrial DNA (mtDNA) release, necroptosis, and airway inflammation in severe asthma using clinical cohort and multi-omics analyses, primary human airway epithelial cells, and TDI- and HDM/LPS-induced mouse models. Histidine levels were elevated in induced sputum from asthma patients, and the mechanistic pathway linked histidine-driven oxidative stress to mtDNA release that promoted necroptosis and inflammatory responses. The results connect a specific metabolic program to a defined cell-death and inflammatory mechanism, supporting histidine-pathway modulation as a potential strategy for severe asthma.

Chen Y, Huang J, Gong Z et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗

A preS2 aa1-26-specific humoural response marks functional cure in chronic HBV infection.

This study profiled HBV-specific humoural immune responses in 65 patients with chronic hepatitis B undergoing PEG-IFNα-induced functional cure, focusing on the preS2 aa1–26 epitope. Using phage immunoprecipitation sequencing (PhIP-seq) with epitope mapping and validating with longitudinal ELISA and ex vivo B-cell phenotyping, it found that a preS2 aa1–26-specific humoural response marks functional cure. This epitope-resolved biomarker could improve prediction and monitoring of interferon-induced functional cure in chronic HBV.

Wang YY, Fu JL, Wang WX et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer immunotherapy engineering & cell therapy platforms

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

This review synthesized recent advances in cancer cell therapy, spanning T cell receptor-engineered T (TCR-T), tumor-infiltrating lymphocytes (TILs), γδ T cells, CAR-NK, CAR-macrophages, dendritic cell/B cell approaches, and stem-cell–based strategies. It highlights the translational shift from early CAR-T successes in hematologic malignancies toward multiplatform, engineered immune-cell modalities under active development. The work is significant for guiding future clinical trial design and identifying where next-generation cell therapies may overcome current limitations in solid and heterogeneous tumors.

Zi G, Zhang L, Zhou L et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.

This preclinical study engineered humanized biparatopic nanobody-based CAR-T cells targeting B-cell maturation antigen (BCMA) to overcome antigen heterogeneity and soluble BCMA (sBCMA) inhibition in multiple myeloma. Biparatopic Nab5822 CAR-T cells showed improved function in patient-derived multiple myeloma cells and xenograft models compared with monospecific designs, supporting better tolerance to low BCMA density and reduced sBCMA-mediated suppression. The work suggests a concrete CAR design (biparatopic VHHs) that may enhance persistence and antitumor activity in BCMA-variable multiple myeloma.

Zhou J, Wu K, Lei B et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

An ICOSL-armed oncolytic adenovirus activates CD4+ T cell to potentiate antitumor immunity and synergizes with anti-PD-1 or CAR-T cell therapy in colorectal cancer.

The study engineered an oncolytic adenovirus (ADV-ICOSL) expressing inducible T cell co-stimulator ligand (ICOSL) and tested it in murine colorectal cancer models (MC38 and CT26). ADV-ICOSL expanded CD4+ T cells in the tumor microenvironment and enhanced antitumor immunity, synergizing with anti-PD-1 therapy and CAR-T cell therapy. This provides a mechanistic immunotherapy strategy to overcome a key limitation of oncolytic adenoviruses in colorectal cancer by boosting CD4+ T cell–mediated responses and improving combination efficacy.

Liu W, Ren X, Zhang Y et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.

This study examined the role of Nur77 (NR4A1) agonism in natural killer (NK) cell–mediated immunity against hepatocellular carcinoma (HCC) using spatial and single-cell transcriptomics in human and mouse tumors. The key finding is that NR4A1 expression correlates with NK cell proliferation and activation of immunostimulatory AP-1 gene regulons and with improved disease-free survival, and that conditional ablation of Nr4a1 in NK cells disrupts NK homeostasis and anti-tumor function. Clinically, it supports targeting the Nur77 pathway to “invigorate” off-the-shelf NK cell responses in the solid tumor microenvironment.

Neo SY, Mei Y, Chong J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer.

This engineering study developed an engineered circular RNA (circRNA) platform capable of complete nucleoside modification and rolling circle translation (RCT) using a cap-independent translation enhancer (CITE) element from black beetle virus (BBV). The key finding is that BBV drives translation of nucleoside-modified RNA and supports RCT of engineered circRNAs, and that an in vitro transcription (IVT) method enables “scarless” circRNA production for vaccine applications. The significance is a potentially more effective circRNA vaccine design, reported to outperform an m1ψ-mRNA vaccine in inhibiting tumor growth (as indicated in the abstract).

Wang X, Pan Q, Yin J et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

The evolving role of cytokines for CAR-T cell manufacturing and beyond.

This narrative review analyzed the evolving role of cytokines in CAR-T cell manufacturing, focusing on how cytokines are used during ex vivo production and how these choices affect product characteristics. The key finding is that across 292 clinical reports there has been a progressive reduction of interleukin-2 (IL-2) exposure, linked to its association with unfavorable cell characteristics. The significance is that it synthesizes evidence to guide cytokine selection and optimization for CAR-T manufacturing and potentially other cell-based therapies.

Guaza-Lasheras M, Nimmerfroh J, Schwarz D et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

Off‑the‑shelf, engineered non-living stem cell strategy for advancing cellular therapies.

The study developed an off-the-shelf, engineered non-living stem cell therapeutic platform using mesenchymal stem cell-derived HealTEC that is lyophilized and inactivated with tannic acid for translational cellular therapy. The key finding was that the HealTEC manufacturing strategy—tannic-acid-engineered cell inactivation plus low-temperature condensation and advanced lyophilization—produced highly efficient active non-living cells designed to preserve function while improving manufacturability and reducing cellular content loss/structural damage. This provides a scalable “bio-reservoir” approach that could enable more reliable delivery of stem-cell-derived functions without living-cell manufacturing constraints.

Nguyen TT, Nguyen NN, Nguyen L et al. · Nature biomedical engineering · (2026) · 1 citations · View on PubMed ↗

Tetrahedral DNA nano-PROTACs enable enhanced ocular penetration and efficient nucleolin degradation for choroidal neovascularization therapy.

The study evaluated tetrahedral DNA nano-PROTACs designed to enhance ocular penetration and promote nucleolin (NCL) degradation for treating choroidal neovascularization in ocular disease models. The key finding was that the tetrahedral DNA nano-PROTAC platform improved delivery to the eye and enabled efficient NCL degradation, supporting therapeutic activity against VEGF-driven endothelial changes in choroidal neovascularization. This provides a delivery-and-targeting strategy that could reduce reliance on repeated intravitreal anti-VEGF injections by enabling more selective molecular intervention.

Song J, Wei X, He K et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Tumor microenvironment, immune evasion, and targeted immunomodulation

AARS1 promotes tumor progression and immune evasion via ATF6 lactylation-mediated tryptophan metabolism in hepatocellular carcinoma.

The study investigated how alanyl-tRNA synthetase 1 (AARS1) promotes hepatocellular carcinoma (HCC) progression and immune evasion through ATF6 lactylation–mediated tryptophan metabolism. Integrated single-cell and spatial transcriptomics linked AARS1 upregulation to higher glycolytic flux (18F-FDG PET/CT), poor prognosis, and resistance to immunotherapy, and hepatocyte-specific AARS1 knockout suppressed tumor growth in murine models. This mechanistic and clinical association positions the AARS1–ATF6 lactylation–tryptophan axis as a potential metabolic-immune target to improve HCC immunotherapy responses.

Wang Y, Li F, Li J et al. · Cell metabolism · (2026) · View on PubMed ↗

Lactate binds and inhibits the innate immune sensor STING to promote tumor immune evasion.

The study examined how tumor-derived lactate regulates innate immune sensing by targeting STING in the tumor microenvironment. Lactate directly bound the cGAMP-binding domain of STING, blocking cGAMP binding, STING activation, and IRF3-dependent cytokine expression, and it linked lactate production to EGFR-driven phosphorylation of LDHA by PKM2. This identifies lactate–STING direct molecular inhibition as a mechanism of tumor immune evasion and a potential therapeutic lever to restore interferon signaling.

Guo D, Meng Y, Yang Q et al. · Immunity · (2026) · View on PubMed ↗

Lactate-Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo-Immunotherapy by Suppressing Tumor PANoptosis.

The study investigated how lactate-driven metabolic changes promote resistance to chemo-immunotherapy in TNBC by suppressing tumor PANoptosis. Using single-cell transcriptomics and quantitative lactylome profiling, it found that elevated tumor lactate broadly suppresses PANoptosis, and mechanistically KAT8 lactylated the inner mitochondrial membrane ADP/ATP translocator ANT2 at K92 under chemotherapeutic stress, enabling ANT2 to recruit PGAM5 to dephosphorylate CypD. This delineates a lactate–KAT8–ANT2(K92)–PGAM5–CypD axis that restrains mitochondrial permeability transition and PANoptosis, offering targets to overcome therapy resistance.

Zhong S, Chen W, Liu F et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming.

The study examined how phosphorylated DEK sustains leukemia stem cells (LSCs) through PBX3-driven transcriptional reprogramming in acute myeloid leukemia (AML). Phosphoproteomic profiling of normal HSPCs versus LSC-enriched populations identified DEK phosphorylation as a leukemogenesis-associated modification, and DEK deletion impaired LSC maintenance and AML progression in MLL-AF9 and HOXA9/MEIS1 mouse models and in patient-derived xenografts, increasing chemosensitivity to azacitidine-based standard-of-care combinations. This is significant because it links a specific post-translational event (DEK phosphorylation) to LSC transcriptional control and therapeutic vulnerability.

Lei Y, Lai Y, Li Y et al. · Blood · (2026) · View on PubMed ↗

Dysregulated methylation‒ubiquitination crosstalk accelerates intervertebral disc degeneration via MED12 destabilization and cGAS/STING activation.

The study investigated how dysregulated methylation–ubiquitination crosstalk accelerates intervertebral disc degeneration (IVDD) via MED12 destabilization and activation of the cGAS/STING pathway. It reported that PRMT2 deficiency disrupted the arginine-methylation component of this regulatory axis, leading to MED12 destabilization and downstream cGAS/STING activation in nucleus pulposus cells (NPCs) associated with senescence-driven degeneration. These findings are clinically relevant because they connect a defined epigenetic/proteostasis mechanism to innate immune activation in IVDD, suggesting potential targets to slow or reverse disc degeneration.

Liang H, Zhu D, Du Z et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗

The epidemiological burden and societal cost of 14 respiratory conditions in the World Health Organization European region: systematic evidence map and economic analysis.

This study systematically mapped lung-condition epidemiology and estimated societal costs for 14 respiratory conditions across 53 World Health Organization Europe countries using Global Burden of Disease (GBD) outputs for nine conditions (including asthma and COPD). It identified key evidence gaps in age/sex-specific incidence, prevalence, mortality, years of life lost, years lived with disability, and DALYs, and produced bespoke economic burden estimates to support resource allocation. These findings provide an evidence-and-cost framework to prioritize where surveillance and health-economic data collection for European lung diseases should be strengthened.

Harnan S, Franklin M, Angus C et al. · ERJ open research · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

Monocyte-Derived LGMN+ Macrophages Divert Lung Injury Outcomes toward Fibrosis through Matrix Remodeling.

This research analyzed monocyte-derived LGMN+ macrophages in idiopathic pulmonary fibrosis by profiling 75 patient lungs and identifying a conserved profibrotic macrophage subset with high legumain (LGMN) expression and matrix-remodeling gene signatures. LGMN+ macrophages localized to fibroblastic foci and were associated with disease progression and poor prognosis, implicating LGMN-driven matrix remodeling in the repair-to-fibrosis transition. Clinically, targeting the LGMN+ macrophage program could represent a strategy to slow or prevent fibrosis progression in idiopathic pulmonary fibrosis.

Li Z, Zhang Y, Yang K et al. · Research (Washington, D.C.) · (2026) · View on PubMed ↗ · Free PDF ↗

Multi-omics integration and in vitro validation identify IL4R, IMPA2, and PRR4 as key therapeutic targets in chronic rhinosinusitis with nasal polyps.

This study used multi-omics integration of single-cell RNA sequencing (GSE276503) and bulk transcriptome datasets (GSE136825, GSE179265) to identify therapeutic targets in chronic rhinosinusitis with nasal polyps (CRSwNP), followed by in vitro validation. It nominated IL4R, IMPA2, and PRR4 as key therapeutic targets among 43 druggable candidates derived from 4460 differentially expressed genes and 732 hub genes. These results provide specific, testable molecular targets for developing IL4R/IMPA2/PRR4-directed therapies in CRSwNP.

Wei B, Gan W, Li J et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Focal adhesion kinase FAK interplays with ROR1 in the aggressiveness of chronic lymphocytic leukemia.

This study investigated how focal adhesion kinase (FAK) interacts with receptor tyrosine kinase-like orphan receptor 1 (ROR1) to drive aggressiveness in chronic lymphocytic leukemia (CLL), with emphasis on IGHV-unmutated disease. Using stimulation of CLL cells (including Wnt5a-related pathway perturbation, as described in the abstract) to assess bidirectional FAK–ROR1 associations, it linked FAK activation to aggressiveness-associated signaling networks that converge on Lyn substrates (HS1 and cortactin) and ROR1 pathways. These mechanistic connections support FAK–ROR1 axis targeting as a potential therapeutic approach for high-risk CLL.

Castronuovo M, Capasso G, Beltrame A et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

This article reviewed and proposed mechanistic modeling approaches to decode glioblastoma (GBM) clonal evolution and heterogeneity, integrating multi-omics evidence about genetic, epigenetic, transcriptional, spatial, and immune microenvironment remodeling. It emphasizes that GBM may originate from aberrant neural stem/progenitor cells (including subventricular zone populations) and that glioblastoma stem cells (GSCs) contribute to tumor propagation and therapeutic resistance. The scientific significance is that mechanistic, evolution-aware models could improve clinical translation by identifying actionable vulnerabilities tied to specific evolutionary states.

Jiang H, Zhao W, Zhou H et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

Acidosis-associated gene signature defines novel subtypes and dual-target therapeutic candidates in breast cancer.

This study integrated GEO datasets, sgRNA-seq data, and breast cancer gene sets to define an acidosis-associated gene signature and classify novel breast cancer subtypes based on acidosis tolerance. It identified dual-target therapeutic candidates linked to the acidic tumor microenvironment (lactate-driven metabolic reprogramming) and used the signature to stratify tumors with distinct biology and treatment implications. These results suggest that targeting acidosis-tolerance pathways could improve precision therapy for breast cancer patients with acid-adapted tumors.

Li Y, Wu D, Shi Z et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Dissecting oral premalignant carcinogenesis: spatial omics mechanisms and nanomedicine-driven therapeutic innovation.

This work focused on oral premalignant disorders (OPMD) and their progression to oral squamous cell carcinoma (OSCC), using spatial omics to map cellular heterogeneity and microenvironmental remodeling across precancerous stages. It highlighted multistep epithelial plasticity, fibroblast heterogeneity with extracellular matrix remodeling, immune suppression/inflammatory reprogramming, and coupled metabolic/redox alterations, and framed these mechanisms for nanomedicine-driven therapeutic innovation. The clinical significance is that spatially resolved, mechanism-based targets could enable earlier interception strategies and guide nanomedicine approaches to prevent OPMD progression to OSCC.

Cai X, Cui Y, Ding C et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Hypoxic CA9-high mesenchymal-like glioma stem cells promote ANXA1-FPR1-dependent macrophage polarization in recurrent glioblastoma.

The study investigated hypoxic carbonic anhydrase 9 (CA9)-high mesenchymal-like glioma stem cells in recurrent glioblastoma and their effects on tumor-associated macrophages (TAMs). CA9-high mesenchymal-like GSCs promoted ANXA1-FPR1-dependent macrophage polarization, worsening the immunosuppressive microenvironment in recurrent glioblastoma. This highlights a CA9-linked, ANXA1–FPR1 macrophage-education axis as a potential therapeutic target to disrupt myeloid remodeling in recurrent GBM.

Gao H, You G, Huang J et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

Association of the atherogenic index of plasma and its integrative novel adiposity-based composites with all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome: novel adiposity-derived AIP indices provide modest incremental prognostic information.

This study assessed whether the atherogenic index of plasma (AIP) and integrative novel adiposity-based composites (including body roundness index, weight-adjusted waist index, and body shape index) predict all-cause and cardiovascular mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome. The authors reported that AIP-based adiposity composite indices provided modest incremental prognostic information for mortality across the CKM spectrum. Clinically, these indices could improve risk stratification using readily available anthropometric and lipid measures, though the added value appears limited.

Wei S, Qiu J, Liu Y et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

BRD4-mediated histone H4K12 lactylation drives ovarian cancer progression by activating the Ube2v1-DDX3X ubiquitination axis.

The research examined how BRD4-mediated histone H4K12 lactylation drives epithelial ovarian cancer progression by regulating the Ube2v1–DDX3X ubiquitination axis. Using CUT&Tag and RNA-seq, the authors identified Ube2v1 as a key gene regulated by H4K12 lactylation and showed that H4K12la increases Ube2v1 expression via BRD4-dependent mechanisms, activating downstream ubiquitination involving DDX3X. This mechanistic link between epigenetic lactylation and a specific ubiquitination pathway provides a potential molecular target set for therapeutic intervention in ovarian cancer.

Jiang Y, Lyu T, Zhou T et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction.

This study aimed to define a plasma proteomic signature of cancer-related sarcopenia using cohorts from the MATCH-R study (including advanced cancer patients treated with immunotherapy) and an independent metastatic castration-resistant prostate cancer (mCRPC) validation cohort. The authors identified circulating protein patterns associated with muscle dysfunction and implicated the IGFBP axis as a mediator of sarcopenia-related pathology. The resulting proteomic and pathway insights could enable more practical, biology-informed assessment of sarcopenia risk in routine oncology care.

Dall’Olio FG, Zrafi WS, Song X et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Dysregulation of the TFEB-ATP6V0C axis in microglia exacerbates α-synuclein pathology through impaired lysosomal acidification in Parkinson’s disease.

The study explored how dysregulation of the TFEB–ATP6V0C axis in microglia affects α-synuclein pathology in Parkinson’s disease. It found that α-synuclein preformed fibrils impair lysosomal acidification in microglia by interfering with ATP6V0C (a V-ATPase V0 subunit), leading to defective autophagic flux, reduced α-syn degradation, and increased pathogenic extracellular vesicle secretion. These results connect microglial lysosomal dysfunction to α-synuclein propagation and suggest that restoring TFEB–V-ATPase/ATP6V0C function could be a therapeutic direction.

Wang Y, Ma Z, Jin Z et al. · Cell death and differentiation · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammatory immune modulators of AML lung infiltration and respiratory failure.

This study mapped the acute myeloid leukemia (AML) lung microenvironment at spatial and single-cell resolution to understand mechanisms of leukemia infiltration and respiratory failure. The key finding is that steroid treatment significantly reduces AML lung burden and improves oxygenation and pulmonary function, and that the inflammation-triggered S-type lectin Lgals9 mediates cell-cell interactions within infiltrated lungs. Scientifically and clinically, it links inflammatory remodeling to lung dysfunction in AML and highlights Lgals9 as a potential therapeutic target or biomarker for intervention.

Paraskevopoulou V, Lin Z, Casado-Pelaez M et al. · Nature immunology · (2026) · View on PubMed ↗

Multi-omics reveals tumor microenvironment heterogeneity and therapeutic vulnerabilities in peritoneal metastasis of gastric cancer.

This study used multi-omics approaches to characterize peritoneal metastasis of gastric cancer (PMGC), focusing on tumor microenvironment heterogeneity and therapeutic vulnerabilities. The key finding is that single-cell RNA sequencing (scRNA-seq) defined cellular composition and epithelial developmental trajectories and mapped intercellular communication networks, with spatial transcriptomics and multiplex immunohistochemistry validating targets and mouse models testing therapeutic efficacy. Clinically, it aims to enable more precise, targetable treatment strategies for PMGC, where current systemic therapies have limited effectiveness.

Xie W, Wang Z, Lv P et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

Innate immune signaling and functions in astrocytes.

This Nature Immunology review analyzed innate immune signaling pathways in astrocytes, focusing on pattern recognition receptors (including Toll-like receptors), nucleic acid sensors, and inflammasomes and their downstream interferon, NF-κB, and STAT3 signaling. The key finding was that astrocytes can mount antiviral and inflammatory programs (e.g., cytokine secretion, phagocytosis) through these innate pathways, but dysregulation drives pathological astrocyte reactivity. The work is significant because it frames astrocytes as active regulators of CNS immunity and highlights mechanistic targets for neuroinflammatory disease modulation.

Guo AX, Fisher TM, Comandante-Lou N et al. · Nature immunology · (2026) · View on PubMed ↗

Adaptive immunity in the pathogenesis of neurodegeneration.

This Nature Immunology review summarized evidence for adaptive immune system involvement in neurodegeneration across diseases such as Alzheimer’s, Parkinson’s, and ALS. The key finding was that, beyond innate CNS immune activation (microglia and astrocytes), genetic, neuropathological, and experimental studies support a contributory role for adaptive immunity in disease pathogenesis. This is clinically significant because it supports exploring adaptive immune pathways as therapeutic targets and biomarkers in neurodegenerative disorders.

Li Y, Ulrich JD, Holtzman DM · Nature immunology · (2026) · View on PubMed ↗

A nucleolar stress gene signature enables quantitative scoring across multi-omics contexts.

The study investigated nucleolar stress biology by integrating literature curation with multi-dataset screening to define a nucleolar stress gene signature and create a quantitative nucleolar stress score (NuS) across bulk and single-cell multi-omics. The key finding was that NuS enables quantitative scoring of nucleolar stress in colorectal cancer models and can be applied across transcriptomics, proteomics, and spatial transcriptomics contexts. This is significant because it replaces morphology-only inference with a scalable gene-expression/proteomic framework for nucleolar stress measurement in cancer research and potentially patient stratification.

Chen J, Xiao S, Hao Z et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

Imaging the hallmarks of cancer.

This Nature Reviews Cancer article studied how imaging technologies can monitor the “hallmarks of cancer” and how biomarkers can stratify patients for therapies targeting those hallmarks. The key finding was that non-invasive imaging approaches are increasingly necessary to track tumor heterogeneity and therapy-induced hallmark changes, enabling clinical translation of hallmark-targeted strategies. This is significant because it links mechanistic cancer concepts to practical diagnostic/response-monitoring tools for precision oncology.

Grimm J, Kiessling F, Brindle KM et al. · Nature reviews. Cancer · (2026) · View on PubMed ↗

Transcriptome analysis in osteoarthritis primary tissues identifies high-confidence effector genes.

The study performed transcriptome analysis of primary knee osteoarthritis tissues from patients, mapping cis- and trans- transcriptional regulation in macroscopically intact (low-grade) and degenerated (high-grade) cartilage, synovium, and fat pad. The key finding was identification of 10,166 unique eQTL-associated genes and a large fraction of previously unreported eQTL-associated genes, along with high-confidence effector genes distinguishing disease states. This is significant because it provides a high-resolution regulatory atlas that can prioritize molecular targets and biomarkers for osteoarthritis progression.

Katsoula G, Arruda AL, Tutino M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Lithocholic acid-activated VDR in macrophages promotes HCC recurrence post-ablation via SOCS3-mediated suppression of CXCL16.

The study investigated how lithocholic acid (LCA)-activated vitamin D receptor (VDR) signaling in macrophages promotes hepatocellular carcinoma (HCC) recurrence after incomplete thermal ablation (iTA), focusing on SOCS3-mediated suppression of CXCL16. Using orthotopic and subcutaneous HCC models subjected to iTA, the authors combined bile acid metabolomics with multicolor flow cytometry and immunofluorescence to show that LCA accumulation drives an immunosuppressive macrophage program that facilitates recurrence via SOCS3-dependent downregulation of CXCL16. This mechanistic link is clinically significant because it identifies a post-ablation metabolic-immune pathway that could be targeted to reduce local HCC recurrence.

Li R, Luo W, Li Z et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Novel strategies to overcome the blood-brain barrier in triple-negative breast cancer brain metastases.

This Review examined how triple-negative breast cancer (TNBC) brain metastases breach the blood-brain barrier (BBB) and evaluated emerging BBB-targeting strategies in the context of TNBC. It found that shifting from simply circumventing the BBB to actively targeting and exploiting BBB biology—using a three-pillar framework of physical/focal BBB disruption and BBB-relevant biological mechanisms—could improve clinically actionable therapeutic delivery. This is significant because it reframes translational research for TNBC brain metastases toward mechanism-based BBB exploitation rather than barrier avoidance.

Fan Y, Zhang H, Tang S et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Arc mediates intercellular tau transmission via extracellular vesicles.

This study investigated whether the neuronal gene Arc mediates intercellular tau transmission via extracellular vesicles (EVs) in mouse models and human brain-derived EVs. Arc directly interacted with tau to promote tau release and co-packaging into EVs, and Arc knockout in rTg4510 tau transgenic mice reduced EV tau seeding potential, with Arc EV levels correlating with phosphorylated EV-tau in human Alzheimer’s disease brains. These findings identify Arc as a mechanistic driver of EV-mediated tau spread, suggesting a potential target to slow neurodegenerative propagation.

Tyagi M, de Hoog E, Grega M et al. · Cell · (2026) · View on PubMed ↗

Xian-Lian-Jie-Du Decoction suppresses colorectal cancer liver metastasis by inhibiting Plaur/Hbegf/EGFR-mediated actin cytoskeleton remodeling.

This study assessed the anti-metastatic effects of Xian-Lian-Jie-Du Decoction (XLJDD) on colorectal cancer liver metastasis using a CT26 intrasplenic mouse model, integrated transcriptomic/proteomic analyses, and single-cell RNA sequencing (scRNA-seq) to define mechanisms. XLJDD suppressed liver metastasis by inhibiting Plaur/Hbegf/EGFR-mediated actin cytoskeleton remodeling, and it identified Plaur-targeting active constituents as key drivers of the effect. This mechanistic evidence supports XLJDD (and its Plaur-directed components) as a candidate therapeutic approach to limit CRLM progression.

Zhang Q, Shi Z, Qian J et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

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Generated automatically on July 01, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.