PubMed Trending Research Digest — March 21, 2026
Automated digest · 99 articles · 15 research areas · March 21, 2026
Overview
Across this week’s set, a clear through-line is the push toward scalable, mechanism-informed care: AI-enabled clinical workflows (e.g., stroke CDSS and automated AI-driven patient education) and noninvasive or “liquid/quantitative” biomarkers (ctDNA, liquid biopsy for EBV-positive Burkitt’s lymphoma, PET metabolic tumor volume, retinal imaging atlases, and post hoc MRI biomarker estimation) aim to standardize decisions, shorten time-to-action, and improve risk stratification.
On the biology side, many studies converge on immune regulation as a therapeutic lever—both in cancer and inflammatory disease. Tumor-associated macrophage programs (multiple axes including IGF1/PI3K/Zic1–SHH, CAV1–DOT1L–driven vasculogenic mimicry, HTRA1+ macrophage immune evasion, and Gsα–MAPK signaling) repeatedly emerge as actionable vulnerabilities, while colorectal cancer work highlights how targeting immunosuppressive pathways (e.g., WIP1) can remodel the tumor microenvironment toward anti-tumor immunity. Outside oncology, neuroimmune and immunothrombotic mechanisms (stress–sympathetic–eosinophil circuits in atopic dermatitis, immunothrombosis in NEC, and neuroimmune frameworks linking POTS/ME-CFS/Long COVID) underscore how shared inflammatory pathways may unify seemingly distinct syndromes.
Finally, several papers emphasize metabolism and systemic physiology as upstream drivers—ranging from lactate-driven epigenetic regulation in oral cancer, nutrient stress adaptation in tumors, and ferroptosis-related iron/ion-channel pathways, to microbiome–host metabolic signaling (including microbiota-derived serotonin affecting hepatic vector delivery and diet–microbe axes influencing sepsis risk). Together, these studies reinforce a broad theme: integrating quantitative diagnostics, immune biology, and metabolic control may yield more precise and durable interventions across diverse diseases.
AI & Digital Clinical Decision Support
Effect of a clinical decision support system on stroke care quality and outcomes in patients with acute ischaemic stroke (GOLDEN BRIDGE II): cluster randomised clinical trial.
This multicentre cluster randomised clinical trial studied whether a stroke clinical decision support system (CDSS) using artificial intelligence-assisted imaging analysis, stroke-cause classification, and evidence-based treatment recommendations improves care quality and outcomes in 21,603 patients with acute ischaemic stroke admitted within 7 days across 77 hospitals in China. Hospitals receiving the CDSS support achieved better stroke care quality and improved clinical outcomes compared with control hospitals. The findings support deploying AI-enabled CDSS workflows to standardise acute stroke management at scale and potentially improve patient prognosis.
Zhang X, Ding L, Jing J et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗
Effectiveness of Al-Assisted Patient Health Education Using Voice Cloning and ChatGPT: Prospective Randomized Controlled Trial.
The study evaluated AI-assisted patient health education using voice cloning and ChatGPT in a prospective randomized controlled trial. It compared different voice-cloning strategies and assessed the reliability/effectiveness of automated AI evaluation tools for improving patient education outcomes. If effective, this would support scalable, personalized digital health education workflows that can be implemented with automated assessment.
Sun Y, Xu S, Jin H et al. · Journal of medical Internet research · (2026) · View on PubMed ↗
Clinical Trials & Therapeutics in Neurology
Tavapadon as Adjunctive Treatment for Parkinson Disease: The TEMPO-3 Randomized Clinical Trial.
This randomised clinical trial evaluated tavapadon, an oral once-daily selective D1/D5 agonist, as adjunctive therapy to levodopa in adults with Parkinson disease experiencing motor fluctuations. Tavapadon improved motor control while demonstrating an acceptable safety and tolerability profile compared with placebo/standard adjunctive management (as per the trial design). The results support D1/D5 agonism as a potential approach to reduce motor fluctuations with potentially fewer D2/D3-related adverse events.
Fernandez HH, Isaacson SH, Hauser RA et al. · JAMA neurology · (2026) · View on PubMed ↗
Ritlecitinib for Severe Alopecia Areata: A 24-Week, Multicentre, Real-World Study.
This real-world retrospective multicenter study evaluated ritlecitinib 50 mg/day over 24 weeks in patients aged ≥12 years with severe alopecia areata (SALT ≥50) in Italy. The key finding was the observed effectiveness and tolerability of ritlecitinib in routine clinical practice after 24 weeks. These data support clinical decision-making for ritlecitinib use in severe alopecia areata outside controlled trials.
Starace M, Rapparini L, Pampaloni F et al. · American journal of clinical dermatology · (2026) · View on PubMed ↗
International Expert Opinion on Optimal Switching to Cladribine Tablets from Other High-Efficacy Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: Opportunities and Challenges.
This international expert opinion reviewed evidence and clinical practice for switching relapsing-remitting multiple sclerosis patients to cladribine tablets (CladT) from other high-efficacy disease-modifying therapies. The key finding is that optimal switching strategies depend on prior therapy class (anti-trafficking S1P modulators, natalizumab, or anti-CD20 agents) and require balancing immune reconstitution timing and safety. Clinically, it provides guidance to reduce risks such as disease rebound and infection while maximizing efficacy after switching to cladribine.
Chan A, Alroughani R, Calabrese M et al. · Neurology and therapy · (2026) · View on PubMed ↗
Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression: The BRIGHT-2 Phase 3 Randomized Clinical Trial.
In a double-blind, placebo-controlled phase 3 randomized clinical trial conducted at 64 hospitals in China, patients with hormone receptor–positive, ERBB2 (HER2)-negative advanced breast cancer after endocrine progression were assigned to bireociclib plus fulvestrant versus placebo plus fulvestrant. The final BRIGHT-2 analysis (with additional follow-up) further evaluated efficacy and safety of bireociclib plus fulvestrant in this HR+/ERBB2− population. If confirmed, this regimen could expand targeted options after endocrine therapy failure by improving outcomes through CDK/kinase inhibition combined with estrogen receptor blockade.
Wang J, Zhang Q, Li H et al. · JAMA oncology · (2026) · View on PubMed ↗
Women with epilepsy: Evidence-based counseling across the lifespan.
This evidence-based review synthesized data on women with epilepsy across the lifespan, covering adolescence/transition to adult care and reproductive health topics including contraception, fertility, pregnancy, lactation, menopause, and bone health. The review highlights persistent gaps in integrating sex- and life-stage–specific epilepsy management into routine clinical care despite updated guidelines. The work supports more comprehensive, guideline-aligned counseling to improve outcomes beyond seizure control for women at different reproductive and aging stages.
Tettenborn B, Ramantani G, Flügel D et al. · Epilepsia · (2026) · View on PubMed ↗
Cardiovascular Risk, Prognosis & Clinical Outcomes
USP25 regulates atherosclerosis by restricting RIPK1-mediated inflammatory responses.
This mechanistic study examined how the deubiquitinase USP25 regulates atherosclerosis by restricting RIPK1-mediated inflammatory responses, using human atherosclerotic lesions and ApoE-/- mouse models. USP25 was downregulated in human lesions, and USP25 promoted anti-inflammatory signalling by limiting RIPK1-driven inflammatory pathways, with macrophages identified as a key cellular source. These results position USP25 as a potential therapeutic target to dampen RIPK1-dependent inflammation in atherosclerotic disease.
Su X, Zhou B, Xu Y et al. · EBioMedicine · (2026) · View on PubMed ↗
Prognostic Impact of Elevated Pulmonary Vascular Resistance in Group 2 Pulmonary Hypertension: Insights From a Japanese Multicenter Registry.
This Japanese multicenter registry analysis studied the prognostic impact of elevated pulmonary vascular resistance (PVR) in group 2 pulmonary hypertension (PH) due to left heart disease, using two prospective registries (2012–2016 and 2018–2024; total n=988). Higher PVR was associated with worse real-world outcomes including heart failure hospitalization and death, and the analysis also informed how emerging therapies might be interpreted in relation to PVR. The findings help risk-stratify group 2 PH patients and guide selection/assessment of future treatment strategies.
Satoh T, Sugimura K, Fukumoto Y et al. · Journal of the American Heart Association · (2026) · View on PubMed ↗
Trends in 5-year net survival for women diagnosed with breast, cervical or ovarian cancer in Japan, 2000-14 (CONCORD-3).
This population-based surveillance study used Japanese CONCORD-3 data from 16 cancer registries to analyse trends in 5-year net survival for women diagnosed with breast, cervical, or ovarian cancer from 2000–2014. The authors reported changes over time in survival outcomes stratified by cancer type and age, reflecting improvements and persistent disparities. These long-term trend estimates provide evidence for evaluating cancer control efforts and targeting gaps in outcomes for women in Japan.
Watanabe K, Di Carlo V, Sugiyama H et al. · Japanese journal of clinical oncology · (2026) · View on PubMed ↗
Stroke Risk After Bioprosthetic Aortic Valve Replacement in Aortic Stenosis: Systematic Review and Meta-Analysis.
This systematic review and meta-analysis quantified the proportion of adults with severe aortic stenosis who experienced ischaemic stroke after bioprosthetic aortic valve replacement, including transcatheter AVR (TAVR), surgical AVR, and valve-in-valve (ViV) replacement. Across included studies, the authors estimated stroke risk within and beyond the periprocedural period after bioprosthetic AVR. The results improve counselling and prognostication by providing pooled, procedure-relevant stroke incidence estimates.
Bou Dargham T, Hassani S, Mac Grory BC et al. · Stroke · (2026) · View on PubMed ↗
Inhibiting RhoA Activation Via GDP-State Stabilization to Relieve Heart Failure.
This study aimed to inhibit RhoA activation in heart failure by stabilising the GDP state, addressing RhoA’s “undruggable” nature due to high-affinity nucleotide binding. Using structural comparisons of RhoA-GTP versus RhoA-GDP and surface plasmon resonance-based screening, the authors identified a RhoA inhibitor that reduced pathological RhoA signalling and alleviated heart failure-associated remodelling phenotypes. The work provides a proof-of-concept strategy for targeting small GTPases by nucleotide-state stabilisation to treat heart failure.
Xue M, Liang Y, Yuan Z et al. · Circulation research · (2026) · View on PubMed ↗
Glucagon-like peptide-1 receptor agonists for major cardiovascular and kidney outcomes in type 1 diabetes.
This observational comparative effectiveness study used national electronic health records (n=174,678) and sequential target trial emulation to assess long-term outcomes of GLP-1 receptor agonists in type 1 diabetes. After propensity score weighting, GLP-1RA initiation was associated with lower risks of major adverse cardiovascular events and end-stage kidney disease over 5 years compared with non-initiation. The results provide real-world evidence that GLP-1RAs may confer cardiovascular and renal protection in type 1 diabetes.
Xu Y, Malek ND, Chang AR et al. · Nature medicine · (2026) · View on PubMed ↗
Fibrinogen-Bmal1 signaling as a therapeutic target to limit aortic dissection by preserving VSMC contractility.
This study investigated fibrinogen–Bmal1 signaling as a therapeutic target to limit aortic dissection (AD) progression by preserving vascular smooth muscle cell (VSMC) contractility, building on prior pilot clinical observations linking higher plasma fibrinogen with better outcomes. It found in nonsurgically managed acute AD patients that fibrinogen-related signaling patterns associate with disease course and that fibrinogen–Bmal1 pathways can be leveraged to maintain VSMC function and reduce progression. This provides a translational rationale for targeting fibrinogen/Bmal1 signaling to slow AD beyond surgery.
Zhong X, Li D, Zhao Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗
Integration of Epidemiology and Network Toxicology Revealed the Arrhythmogenic Potential of Neonicotinoid Insecticides.
The study assessed arrhythmogenic potential of neonicotinoid insecticides by measuring urinary neonicotinoids and metabolites in 136 arrhythmia patients and 222 healthy controls. Neonicotinoids were detected in all samples with higher concentrations in patients than controls (except thiamethoxam and clothianidin), and statistical models (quantile g-computation and Bayesian kernel machine regression) suggested that co-exposure to multiple neonicotinoids increased arrhythmia risk. This provides epidemiologic and mixture-toxicity evidence that supports cardiovascular risk assessment for neonicotinoid exposure.
Ge Y, Xiao Q, Fu B et al. · Environmental science & technology · (2026) · View on PubMed ↗
Transradial vs Transfemoral Access for Cerebral Angiography: A Randomized Noninferiority Clinical Trial.
This randomized noninferiority clinical trial compared transradial access (TRA) versus transfemoral access (TFA) for diagnostic cerebral angiography in patients across 13 sites in China. The key finding was the relative efficacy and safety of TRA compared with TFA, assessed with blinded outcome evaluation in an open-label design. Clinically, it informs procedural access-site choice for cerebral angiography to potentially reduce complications while maintaining diagnostic performance.
Ni W, Yang H, Su J et al. · JAMA network open · (2026) · View on PubMed ↗
Immuno-oncology & Tumor Microenvironment
Targeting tumor-associated macrophages-induced IGF1/PI3K/Zic1 axis triggers SHH medulloblastoma regression and chemosensitization.
This study investigated whether targeting tumor-associated macrophages (TAMs)-induced IGF1/PI3K/Zic1 signalling can trigger SHH medulloblastoma regression and chemosensitisation. Using a CD11b-DTR/Ptch1-deficient medulloblastoma mouse model with TAM genetic deletion and pharmacologic inhibition (including the CSF1R inhibitor PLX3397 and PI3K inhibitor buparlisib), the authors showed TAM pathway blockade reduced tumour growth and improved chemosensitivity. The results identify a TAM–IGF1/PI3K/Zic1–SHH axis as a therapeutic vulnerability in medulloblastoma.
Pang YC, Wang C, Qiu JF et al. · Neuro-oncology · (2026) · View on PubMed ↗
Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer.
The study investigated wild-type p53-induced phosphatase 1 (WIP1/PPM1D) as an immunosuppressive driver in colorectal cancer and tested genetic or pharmacologic WIP1 inhibition in CRC models. It found that inhibiting WIP1 suppressed tumor growth by remodeling the tumor microenvironment, increasing infiltration of anti-tumor macrophages and cytotoxic T cells while dampening type I interferon (IFN) signaling. This positions WIP1 as a target to reverse immunosuppression and potentially potentiate immune checkpoint inhibitor responses in CRC.
Chen L, Chen M, Yuan S et al. · Cell death and differentiation · (2026) · View on PubMed ↗
SHR-A1811, a novel HER2-targeting antibody-drug conjugate, in advanced solid tumors (HORIZON-X): a global phase 1 trial.
This first-in-human global phase 1 trial evaluated SHR-A1811, a HER2-targeting antibody–drug conjugate, in adults with advanced solid tumors in the HORIZON-X study (NCT04446260). It found that SHR-A1811 (trastuzumab conjugated via a cleavable linker to a topoisomerase I inhibitor payload) showed substantial antitumor activity in heavily treated HER2-expressing or HER2-mutated tumors, with safety and efficacy assessed across dose-escalation cohorts. Clinically, it supports further development of SHR-A1811 as a next-generation HER2 ADC for refractory metastatic disease.
Yao H, Yan M, Tong Z et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗
CAV1-DOT1L axis in TAM-derived EVs orchestrates VM and sensitises PDAC to combined VM and VEGF targeting.
This Gut study investigated how the CAV1–DOT1L axis in tumor-associated macrophage (TAM)-derived extracellular vesicles (EVs) regulates vasculogenic mimicry (VM) and sensitizes pancreatic ductal adenocarcinoma (PDAC) to combined VM and VEGF targeting. It combined histopathology, 3D tissue clearing, spatial transcriptomics, and single-cell RNA-seq with tissue microarrays, co-culture assays, and xenografts to map VM distribution and TAM contributions. The work identifies a TAM EV–epigenetic signaling pathway (CAV1–DOT1L) as a mechanistic driver of VM and a therapeutic lever to improve anti-vascular strategies in PDAC.
Liu Z, Zhang Y, Wu H et al. · Gut · (2026) · View on PubMed ↗
A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer.
The study developed B6ADC, a nanobody-based bispecific antibody-drug conjugate targeting TROP2 and c-Met, and evaluated it in TROP2/c-Met-expressing pancreatic cancer cell lines and mouse xenograft models. B6ADC showed potent in vitro cytotoxicity and superior in vivo tumor inhibition versus single-target ADCs and combinations, outperforming clinically used TROP2 ADC sacituzumab govitecan and c-Met ADC Teliso-V. This supports bispecific nanobody-drug conjugate design as a strategy to overcome antigen heterogeneity and improve tumor penetration for low-dose, single-administration pancreatic cancer therapy.
Ning W, Liu H, Zeng H et al. · Cell reports. Medicine · (2026) · View on PubMed ↗
Preferences in Cyclin-Dependent Kinase 4/6 Inhibitors for Advanced Breast Cancer Among Medical Oncologists in Latin America.
The study surveyed 116 medical oncologists across 15 Latin American countries to characterize preferences and decision-making patterns for CDK4/6 inhibitors in advanced hormone receptor–positive, HER2-negative breast cancer. Ribociclib was the preferred agent (56.8%), with preferences driven by factors related to availability and clinical decision scenarios. These findings highlight regional prescribing/access patterns that can inform guideline implementation and equitable access strategies.
Villarreal-Garza C, Meraz-Brenez A, Reyes Morales A et al. · JCO global oncology · (2026) · View on PubMed ↗
Overcoming T cell tolerance to tumor self-antigens through catch-bond engineering.
The study engineered catch-bond T cell receptors (TCRs) to overcome central tolerance to tumor self-antigens by targeting the nonmutated tumor-associated antigen prostatic acid phosphatase (PAP). It identified a catch-bonding hotspot mutation that increased TCR–pMHC bond lifetime while preserving physiological affinities and fine specificity, leading to vastly improved T cell expansion, effector phenotypes, and tumor elimination in tumors. This provides a mechanistically grounded TCR engineering strategy to enhance anti-tumor immunity against self-antigens.
Chen X, Mao Z, Kolawole EM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Long-term outcomes of eribulin‑based neoadjuvant chemotherapy for triple‑negative breast cancer patients stratified by homologous recombination deficiency status: results of the randomized JBCRG-22 study.
This randomized JBCRG-22 study reported long-term outcomes of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) stratified by homologous recombination deficiency (HRD) and germline BRCA mutation status. The key finding was the differential long-term outcome of eribulin-containing regimens across HRD-positive versus HRD-negative (and gBRCA-mutated when available) strata. The significance is that HRD/gBRCA status may help personalize neoadjuvant eribulin strategies in TNBC.
Masuda N, Yasojima H, Bando H et al. · Breast cancer research and treatment · (2026) · View on PubMed ↗
Gsα deficiency in macrophages promotes tumor progression via the MAPK signaling pathway.
This study examined whether Gsα (the G protein alpha subunit) deficiency in tumor-associated macrophages (TAMs) promotes cancer progression through MAPK signaling. In mouse models using B16 and MC38 tumor cells, the authors found that Gsα-deficient TAMs accelerated tumor growth and metastasis, with mechanistic data implicating MAPK pathway activation. The significance is that restoring or targeting Gsα–MAPK signaling in TAMs could represent a strategy to reprogram the tumor microenvironment for cancer immunotherapy.
Yan W, Yang J, Tan S et al. · Journal of molecular medicine (Berlin, Germany) · (2026) · View on PubMed ↗
HTRA1+ macrophages induce T cells egress through CRIP1/NF-κB/CXCL12 to limit the effects of immunotherapy in triple-negative breast cancer.
In triple-negative breast cancer (TNBC), this study used single-cell and spatial transcriptomics to identify a macrophage subpopulation characterized by high HTRA1 expression that influences immunotherapy response. HTRA1+ macrophages induced T cell egress via a CRIP1/NF-κB/CXCL12 signaling axis, limiting the effectiveness of immunotherapy. Mechanistically defining this pathway suggests a targetable immune-evasion mechanism to improve CD8+ T cell–mediated responses in TNBC.
Weng J, Xu W, Wang F et al. · Cancer immunology research · (2026) · View on PubMed ↗
Albumin-Bound STING Agonist Reprograms HSPCs to Antitumor Neutrophils Enhancing CD8+ T Cell Immunity.
This preclinical study tested an albumin-bound STING agonist, Nano ZSA-51D, to reprogram hematopoietic stem and progenitor cells (HSPCs) into antitumor neutrophils and enhance CD8+ T cell immunity. Nano ZSA-51D expanded HSPCs, shifted differentiation toward granulocyte-monocyte progenitors, increased MHC I–mediated CD8+ T cell responses, and sensitized tumors to α-PD1 immunotherapy. The findings support STING-agonist–driven myeloid reprogramming as a strategy to overcome resistance to checkpoint blockade.
Tao J, Zhao HY, Li C et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗
Cancer Biomarkers, Diagnostics & Imaging
Liquid biopsy for the diagnosis of EBV-positive Burkitt's lymphoma in endemic areas.
This diagnostic study evaluated liquid biopsy approaches for Epstein–Barr virus (EBV)-positive Burkitt’s lymphoma in endemic settings by testing blood-based assays in 377 children and young adults with suspected lymphoma across hospitals in Tanzania and Uganda. Using circulating tumor DNA markers (including MYC mutations, MYC–immunoglobulin translocations, and EBV fragmentomics) alongside clinical features, the authors trained models to improve diagnostic accuracy and reduce turnaround time compared with delayed pathology. The findings support scalable, pathology-light diagnostic strategies for EBV-positive BL in resource-limited regions.
Chamba C, Christopher H, Josephat E et al. · Nature medicine · (2026) · View on PubMed ↗
Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications.
The study reviewed how extrachromosomal DNA (ecDNA) drives genomic instability and tumor evolution in urothelial carcinoma and how ecDNA can be detected using sequencing/imaging and liquid biopsy or histopathology-based inference. It found that ecDNA amplifies oncogenes, alters 3D chromatin interactions, reprograms transcription, and shapes the tumor–immune interface, thereby accelerating APOBEC3-associated mutational evolution and promoting aggressive intratumour heterogeneity. These mechanisms and detection approaches support ecDNA as a clinically actionable biomarker and potential therapeutic target in urothelial cancer.
Li C, Hu Z, Zhang W et al. · Nature reviews. Urology · (2026) · View on PubMed ↗
Prognostic Significance of MSI and EBV Positivity in PD-L1 Positive Gastric Cancer: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis assessed the prognostic significance of microsatellite instability (MSI), Epstein–Barr virus (EBV) positivity, and PD-L1 expression specifically in PD-L1–positive gastric cancer. It synthesized studies (Jan 2010–Dec 2024) using MSI testing (PCR), PD-L1 immunohistochemistry, and EBV in situ hybridization to evaluate overall survival and other endpoints. The analysis aims to refine risk stratification and immunotherapy-related decision-making in gastric cancer using combined biomarker status.
Petrelli F, Antista M, Ghidini A et al. · Cancer medicine · (2026) · View on PubMed ↗
A predictive atlas of disease onset from retinal fundus photographs: a modelling study using data from population-based cohorts.
This modeling study used retinal fundus photographs from population-based cohorts to build a predictive atlas for incident disease onset across the human phenome. It found that retinal imaging can predict future onset of multiple diseases and can add value beyond baseline clinical information (as benchmarked in the study). This supports retinal fundus photography as a scalable, non-invasive screening tool for early identification of individuals at high risk for diverse conditions.
Buergel T, Loock L, Steinfeldt J et al. · The Lancet. Digital health · (2026) · View on PubMed ↗
Risk Assessment in Large B-Cell Lymphoma Using Metabolic Tumor Volume: Real-World Data from a Multicenter Cohort of Patients Undergoing CAR T-Cell Therapy.
This real-world multicenter cohort study evaluated whether PET-derived metabolic tumor volume (MTV) improves risk assessment in large B-cell lymphoma (LBCL) patients undergoing CAR T-cell therapy compared with the International Prognostic Index (IPI). It analyzed 18F-FDG-avid lymphoma burden/MTV-based risk scores in 111 patients to predict outcomes and identify potential nonresponders before infusion. Scientifically and clinically, it supports MTV quantification as a more informative biomarker for pre-treatment stratification in CAR T workflows.
Voltin CA, Flossdorf S, Kurch L et al. · Journal of nuclear medicine : official publication, Society of Nuclear Medicine · (2026) · View on PubMed ↗
Clinical practice guideline for long COVID prevention and treatment.
This multicentre study developed and validated a multimodal fusion model to non-invasively prognosticate survival in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolisation (TACE). It enrolled 1448 patients and used pre-treatment contrast-enhanced CT images integrated with hypoxia- and immune-phenotype information derived from single-cell RNA-seq and TCGA to improve generalisability and biological interpretability over existing scores. The model could enable more precise, biologically grounded survival prediction to guide TACE management.
Cao B, Soriano JB, Wang Q et al. · The European respiratory journal · (2026) · View on PubMed ↗
Post hoc estimation of a quantitative restriction spectrum imaging biomarker for prostate cancer detection using conventional MRI.
This study evaluated whether restriction spectrum imaging (RSI) metrics (RSIrs) for prostate cancer detection can be estimated post hoc from conventional MRI diffusion-weighted imaging (DWI) rather than requiring dedicated multi–b-value acquisitions. The key finding was the accuracy/validity of post hoc RSI-derived quantitative biomarkers for detecting clinically significant prostate cancer (csPCa). If validated, this would enable broader deployment of RSI-like quantitative biomarkers using standard MRI protocols.
Do DD, Conlin CC, Bagrodia A et al. · Journal of applied clinical medical physics · (2026) · View on PubMed ↗
Machine Learning-Based Sleep Electroencephalographic Brain Age Index and Dementia Risk: An Individual Participant Data Meta-Analysis.
This individual participant data meta-analysis assessed whether a machine learning-based sleep EEG brain age index (BAI) predicts incident dementia in community-dwelling populations. Pooling data from five longitudinal cohorts, the study tested the association between sleep EEG-based brain age (deviation from chronological age) and future dementia risk. The significance is that sleep EEG BAI could serve as a scalable, quantitative risk biomarker for dementia stratification.
Sun H, Milton S, Fang Y et al. · JAMA network open · (2026) · View on PubMed ↗
Diagnostic Performance of Anti-Epstein-Barr Virus BNLF2b in Suspected Nasopharyngeal Carcinoma.
This prospective, multicenter outpatient study evaluated the diagnostic performance of the novel anti–EBV BNLF2b total antibody (P85-Ab) assay for suspected nasopharyngeal carcinoma (NPC) and compared it head-to-head with EBV VCA-IgA, EBV EA-IgA, and EBNA1-IgA. P85-Ab showed diagnostic accuracy for suspected NPC that was benchmarked against established EBV serologic markers. Clinically, identifying the most reliable EBV biomarker could improve early NPC detection and reduce misdiagnosis in routine outpatient practice.
Li SC, Li FG, Wu SJ et al. · JAMA oncology · (2026) · View on PubMed ↗
Use of ctDNA in Older Women with ER+ Breast Cancer to Facilitate Surgical De-escalation: A Prospective, Hybrid-Decentralized Trial with Correlative Studies.
In a prospective, hybrid-decentralized trial (NCT05914792; n=43) of older women with ER+ breast cancer, researchers used circulating tumor DNA (ctDNA) to determine whether ctDNA levels predict tumor progression in patients who chose surgical de-escalation (forgoing breast cancer surgery in favor of primary endocrine therapy). ctDNA was evaluated as a prognostic biomarker to facilitate safe treatment de-escalation, with correlative tissue analyses integrated into the study. If validated, ctDNA-guided selection could reduce overtreatment while maintaining oncologic safety in older patients with competing comorbidities.
Carleton N, Chang AC, Chen F et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗
Molecular Mechanisms of Cancer (Metabolism/Epigenetics/Signaling)
Hijacking ERAD for targeted degradation of transmembrane proteins.
This study developed a targeted protein degradation (TPD) platform that hijacks ER-associated degradation (ERAD) to degrade transmembrane proteins, creating ERAD-engaging chimeras (ERADECs), and tested it by targeting programmed death-ligand 1 (PD-L1) in cells. The authors identified desonide as a binder of the ER E3 ligase SYVN1 and showed ERADECs efficiently degraded PD-L1 by recruiting SYVN1-mediated ERAD. This provides a mechanistic route to drug discovery for otherwise hard-to-degrade transmembrane targets using ERAD machinery.
Song H, Wang W, Mei T et al. · Cell · (2026) · View on PubMed ↗
Lactylation Converts ABHD6 into a Mitochondrial Regulator that Drives Lenvatinib Resistance in Hepatocellular Carcinoma.
This cancer biology study investigated how lactylation alters ABHD6 function to drive lenvatinib resistance in hepatocellular carcinoma (HCC), focusing on mitochondrial dynamics and the ABHD6 S148 catalytic site. Lactylation converted ABHD6 into a mitochondrial regulator that promotes lenvatinib resistance through a pro-resistance scaffolding function that is independent of ABHD6 catalytic activity but requires an unoccupied S148 site. The work suggests targeting ABHD6 lactylation-dependent switching or its mitochondrial effects as a strategy to overcome lenvatinib resistance in HCC.
Sun Y, Luo C, Yang H et al. · Cancer research · (2026) · View on PubMed ↗
Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis.
This study evaluated whether lactate-dependent histone lactylation regulates pyrimidine metabolism to promote oral squamous cell carcinoma (OSCC) and tested the mechanism in oral leukoplakia (OLK) and OSCC. It found that histone lactylation levels were increased in OLK/OSCC and that blocking lactylation via glycolysis inhibitors or silencing LDHA (lactate dehydrogenase A) promoted anti-tumor effects, supported by CUT&Tag, scRNA-seq, and ChIP-qPCR analyses. Scientifically, it links a lactate-driven epigenetic mark to metabolic reprogramming in oral carcinogenesis, suggesting lactylation/metabolism as a therapeutic vulnerability.
Wang Y, Geng Y, Chen Y et al. · Cell death & disease · (2026) · View on PubMed ↗
Mitoxyperilysis: fasting-induced cell death in immunometabolism and disease.
This review summarized evidence for mitoxyperilysis, a fasting-induced lytic cell death mechanism driven by mitochondrial proximity-dependent rupture of the plasma membrane. It concluded that mitoxyperilysis is triggered by immune agonists combined with fasting/nutrient starvation and has therapeutic implications in sepsis and cancer. The concept links immunometabolism to a distinct cell-death pathway that could be exploited for treatment.
Al-Zidan R, Gautam M, Man SM · Trends in biochemical sciences · (2026) · View on PubMed ↗
A CHKA-PML autophagy checkpoint enables tumors to evade glutamine starvation.
This study examined how glutamine scarcity affects tumor-cell survival mechanisms involving choline kinase alpha (CHKA) and promyelocytic leukemia (PML) in cancer models. The authors found that glutamine deprivation upregulates CHKA, whose monomerization drives noncanonical kinase activity that phosphorylates PML at tyrosine 339 to promote cytoplasmic PML, thereby enabling tumors to evade a glutamine-starvation autophagy checkpoint. These findings identify a CHKA–PML compartment-specific signaling switch as a potential therapeutic target to block tumor adaptation to nutrient stress.
Wang R, Cao L, He X et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Unveiling the multifaceted roles of BCL3: biological functions and disease implications.
This review detailed the multifaceted roles of the NF-κB pathway regulator BCL3 (B-cell CLL/lymphoma 3) in normal biology and disease. The key finding is that BCL3, unlike classical IκB proteins, predominantly localizes to the nucleus and can bidirectionally regulate NF-κB–dependent transcription, with phosphorylation and other post-translational modifications tuning its activity. Scientifically, it frames BCL3 as an oncogenic driver in multiple hematologic malignancies and a potential therapeutic target.
Guo X, Guo R, Wang W et al. · Apoptosis : an international journal on programmed cell death · (2026) · View on PubMed ↗
Disruption of iron homeostasis by HERC2-FTL axis leads to chondrocyte loss and exacerbates osteoarthritis.
This study investigated how disruption of iron homeostasis via the HERC2–FTL axis affects chondrocyte survival and osteoarthritis (OA) progression. Using ATDC5 chondrocytes treated with IL-1β or the ferroptosis inducer erastin, the authors found that altering HERC2 (knockdown/overexpression) modulated ferroptosis, autophagy, oxidative stress, and cartilage matrix protein expression, linking HERC2-driven iron regulation to chondrocyte loss. Scientifically, it identifies the HERC2–FTL pathway as an upstream regulator of ferroptosis in OA and a potential therapeutic target.
Zhong Y, Duan J, Chen Z et al. · Apoptosis : an international journal on programmed cell death · (2026) · View on PubMed ↗
The therapeutic potential of Piezo1 channel-mediated ferroptosis and its inhibitor.
This review described the therapeutic potential of Piezo1 channel-mediated ferroptosis and discussed how ferroptosis inhibition might be leveraged. It explains that Piezo1 activation increases Ca2+ influx, reprograms iron metabolism through TfR1-dependent iron uptake, DMT1-mediated transport, and NCOA4-regulated ferritinophagy, leading to ROS accumulation and lipid peroxidation that culminates in ferroptosis. The significance is that Piezo1–ferroptosis signaling could be targeted to induce tumor cell death or modulated to protect tissues depending on context.
Nan K, Zhang L, Zhao Y et al. · Apoptosis : an international journal on programmed cell death · (2026) · View on PubMed ↗
Phospholipid Glutathione Peroxidase Overexpression Mitigates Cancer Cachexia by Protecting Muscle Mass and Lowering Inflammation.
This study investigated whether overexpressing phospholipid glutathione peroxidase (GPx) can mitigate cancer cachexia by protecting muscle mass and reducing inflammation. Phospholipid GPx overexpression lowered inflammatory burden and preserved muscle, counteracting cachexia-associated muscle wasting. The results position lipid-peroxidation control via phospholipid GPx as a candidate therapeutic approach for cancer cachexia.
Duggan E, Fuqua JD, Hagy B et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗
Regulation of YAP activity by nuclear G-actin binding.
This mechanistic study investigated how nuclear G-actin binding regulates the activity of YAP, a transcriptional co-activator in the Hippo pathway. The authors showed that binding of monomeric actin (G-actin) in the nucleus modulates YAP activity and thereby influences YAP-dependent transcriptional programs. Understanding this actin–YAP regulatory mechanism clarifies how cytoskeletal dynamics and mechanotransduction control proliferation and cancer-related behaviors.
Wang H, Jayawardana IM, Fleisch JM et al. · Nucleic acids research · (2026) · View on PubMed ↗
Infectious Disease & Host–Virus Interactions
LRP8 is a functional receptor for yellow fever virus.
This study identified LRP8 (APOER2) as a functional receptor for yellow fever virus (YFV) by performing a barcoded genome-wide human open reading frame library screen. LRP8 expression increased infection by the live-attenuated 17D vaccine strain and clinical strains (BJ01 and Asibi) by promoting viral entry, and LRP8 expression in mouse liver via adeno-associated virus worsened infection and pathology for BJ01. The work clarifies receptor usage differences among YFV strains and suggests LRP8 as a potential target to modulate infection.
Mei M, Yang Y, Zhang Z et al. · Nature microbiology · (2026) · View on PubMed ↗
ALG6 orchestrates coronavirus replication via the endoplasmic reticulum stress-autophagy axis.
This study investigated the host factor alpha-1,3-glucosyltransferase ALG6 and its relationship to ER stress and autophagy during coronavirus replication, using transmissible gastroenteritis virus (TGEV) models. ALG6 catalytic activity was required for TGEV replication, and ALG6 knockout inhibited viral entry by downregulating the receptor aminopeptidase N (ANPEP) while also triggering ER stress that suppressed viral replication. The work positions ALG6 as a druggable node linking ER stress–autophagy pathways to coronavirus life cycle control.
Fu Y, Gao M, Fu Z et al. · Cell reports · (2026) · View on PubMed ↗
Association between COVID-19 vaccination and sudden death in apparently healthy younger individuals: A population-based case-control study.
This population-based case-control study assessed whether COVID-19 vaccination is associated with sudden death in apparently healthy younger individuals aged 12–50 years in Ontario, Canada using linked administrative datasets. The key finding was the estimated association between vaccination exposure and sudden death risk in this age group (with the study designed to quantify whether any increased risk is detectable despite rarity). Clinically, the results inform risk-benefit counseling and post-vaccination safety surveillance for rare but serious outcomes in younger populations.
Abdel-Qadir H, Bhatt HA, Swayze S et al. · PLoS medicine · (2026) · View on PubMed ↗
Gene Editing & Functional Genomics Tools
Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.
This study developed embedded CRISPR interference (emCRISPRi) in Drosophila melanogaster by engineering transcriptional repression domains (Mxi and TRD) into a flexible region of catalytically inactive Cas9 (dCas9). emCRISPRi significantly increased gene-silencing efficiency and repression amplitude, especially for coding genes and cis-regulatory elements near transcription start sites (TSS). The platform improves the reliability of CRISPRi functional genomics in flies and enables more robust interrogation of TSS-proximal regulatory mechanisms.
Fu P, Zhang X, Zhou Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗
Human DHX29 detects nonoptimal codon usage to regulate mRNA stability.
The study investigated how the human RNA helicase DHX29 detects nonoptimal codon usage to regulate mRNA stability. Using genome-wide CRISPR screening plus cryogenic electron microscopy and selective ribosome profiling, it showed DHX29 directly interacts with the A-site entrance of the translating 80S ribosome to monitor aminoacyl-tRNA sampling. This clarifies a human mechanism linking codon usage to mRNA decay control, informing how translation quality shapes gene expression.
Hia F, Wu Y, Yoshinaga M et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Unstructured transcription factor interactions enable emergent specificity.
The study examined how intrinsically disordered regions (IDRs) enable emergent specificity in transcription factor interactions and chromatin binding. Using proximity-assisted photoactivation (PAPA) in live cells, it found that the Sp1 DNA-binding domain interacts weakly with chromatin, while IDR fusion enhanced interaction and conferred sharp locus specificity on an otherwise nonspecific DNA-binding domain. This demonstrates an experimental framework for understanding how IDRs tune transcription factor targeting in vivo.
Abidi AA, Cattoglio C, Tang NN et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Neuroimmunology & Neuroinflammation
Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.
This article is a mechanistic synthesis proposing that postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Long COVID can be conceptualised as neuroimmune disorders with overlapping pathophysiology. It emphasises shared contributors such as autonomic dysfunction, immune dysregulation/autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. The framework may help unify research and guide development of targeted therapies across these related syndromes.
Blitshteyn S, Doherty TA, Steinman L · ImmunoTargets and therapy · (2026) · View on PubMed ↗
CD177⁺ neutrophil-platelet aggregates contribute to thromboinflammation via NETs in necrotizing enterocolitis.
This study examined necrotizing enterocolitis (NEC) pathogenesis by focusing on CD177+ neutrophil–platelet aggregates and their contribution to thromboinflammation via neutrophil extracellular traps (NETs) in premature infants and neonatal mouse models. It found that NEC is characterized by immunothrombosis with infiltrating CD177+ neutrophils and activated platelets, and that these aggregates promote NET-driven thromboinflammatory processes. The findings identify a specific immunothrombotic cell interaction axis as a potential mechanistic target to prevent or treat NEC.
Lan C, Tian B, Shi Y et al. · Nature communications · (2026) · View on PubMed ↗
Quantifying immune dysregulation in pneumonia and sepsis with a parsimonious machine-learning model: a multicohort analysis across care settings and reanalysis of a hydrocortisone randomised controlled trial.
This multicohort analysis developed a parsimonious machine-learning model to quantify immune dysregulation in pneumonia and sepsis and reanalyzed data from a hydrocortisone randomized controlled trial. It aimed to measure dysregulation directly rather than rely solely on clinical severity for immunomodulation trial enrollment, thereby addressing heterogeneity in treatment response. The approach supports biologically informed prognostication and could help identify patients most likely to benefit from immune-targeted therapies.
Michels EHA, Dequin PF, Butler JM et al. · The Lancet. Respiratory medicine · (2026) · View on PubMed ↗
Psoriasis modulates inflammatory bowel disease risk and intestinal epithelium lipid metabolism via IL-1β-producing macrophages.
The study investigated how psoriasis affects inflammatory bowel disease risk and intestinal epithelial lipid metabolism, combining a clinical cohort with experimental psoriasis mouse models and intestinal organoid assays. Psoriasis severity inversely correlated with postprandial plasma apolipoprotein B48 levels, and the authors used a recombinant photoconvertible apolipoprotein B reporter to show real-time chylomicron production changes driven by IL-1β-producing macrophage–linked mechanisms. This links psoriasis-associated immune activity to impaired intestinal lipid handling, providing mechanistic insight into the psoriasis–IBD comorbidity.
Wu J, Liu S, Dan W et al. · Cell metabolism · (2026) · View on PubMed ↗
A neuroimmune circuit links stress to skin inflammation.
The study investigated a neuroimmune mechanism connecting stress to skin inflammation, focusing on sympathetic neurons and eosinophils in atopic dermatitis flare contexts. It found that sympathetic neurons activate eosinophils during stress, worsening atopic dermatitis inflammation. This identifies a stress-responsive neuroimmune circuit as a potential therapeutic target for inflammatory skin disease.
Gaudenzio N, Basso L · Science (New York, N.Y.) · (2026) · View on PubMed ↗
A sympathetic-eosinophil axis orchestrates psychological stress to exacerbate skin inflammation.
The study defined how psychological stress exacerbates skin inflammation through a sympathetic-eosinophil axis in mouse models of atopic dermatitis-like disease. It identified prodynorphin-positive (Pdyn+) noradrenergic sympathetic neurons innervating hairy skin that worsen inflammation in an eosinophil-dependent manner, with CCL11–CCR3 signaling mediating eosinophil recruitment. These mechanistic insights connect specific neuronal subtypes and chemokine pathways to stress-driven immune pathology in dermatitis.
Tian J, Cao Y, Li Y et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Hypothalamic clock governs circadian pain.
The study investigated how the hypothalamic circadian clock regulates pain by measuring nociceptive threshold rhythms in a mouse model of neuropathic pain. It found that daily oscillations are driven by a circuit from the suprachiasmatic nucleus (SCN) to descending analgesia pathways, where daytime increased SCNVIP activity raises nociceptive sensitivity and nighttime reduced activity decreases pain. This links hypothalamic clock neurons (VIP) to circadian pain control, suggesting timing-based approaches for pain management.
Wei HR, Lou Q, Li LX et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
From chronic pain to depression: Neurogenesis-driven microglial remodeling in the hippocampal dentate gyrus.
The study examined how chronic pain transitions to depression by integrating human neuroimaging (UK Biobank) with a rodent model and hippocampal dentate gyrus analyses. It found biphasic hippocampal remodeling—volume increases early with cognitive improvements but declines with comorbid depression—and that dentate gyrus lesions prevented affective symptoms. In rodents, increased dentate gyrus activity drove hyperactive newborn neurons and microglial recruitment/remodeling, implicating neurogenesis-driven microglial remodeling as a mechanistic bridge from pain to depression.
Ding M, Xiang S, Zhang Y et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Astrocytes at the crossroads of obstructive sleep apnea and Alzheimer's disease: from oxygen sensing to neurodegeneration.
This review examined mechanistic links between obstructive sleep apnea (OSA) and Alzheimer’s disease (AD) with a focus on astrocytes, oxygen sensing, and neurodegeneration. It synthesizes evidence that intermittent hypoxia and sleep fragmentation can drive astrocyte-mediated pathways that contribute to neuroinflammation and AD-relevant pathology. The significance is that astrocytes are proposed as a mechanistic bridge connecting OSA risk to AD progression, suggesting potential intervention points.
Cabot J, Soriano JB, Alonso-Fernández A et al. · Sleep & breathing = Schlaf & Atmung · (2026) · View on PubMed ↗
Interplay of oxidative stress and neuroinflammation in alzheimer's: insights into age-driven pathogenesis.
This article reviewed how oxidative stress and neuroinflammation interact in Alzheimer’s disease (AD) with emphasis on age-driven mechanisms. It highlights that mitochondrial dysfunction increases reactive oxygen species (ROS), promotes amyloid-β accumulation and cognitive decline, and that inflammasome signaling involving NLRP3 and NF-κB in microglia/astrocytes sustains a neuroinflammatory environment. The significance is that targeting the oxidative stress–neuroinflammation axis may offer disease-modifying opportunities in age-associated AD.
Firdous SM, Chakrabortty S, Undale VR et al. · Inflammopharmacology · (2026) · View on PubMed ↗
Therapeutic Potential of Somatostatin and Its Analogues in Alzheimer's Disease: From Molecular Mechanisms to Preclinical Studies.
This review evaluated the therapeutic potential of somatostatin (SST) and somatostatin analogues (SSAs) in Alzheimer’s disease, integrating molecular mechanisms with preclinical evidence. It highlights that SST receptors (SSTR1–5) influence amyloid-β metabolism, tau phosphorylation, neuroinflammation, and synaptic plasticity, and that SSAs may enhance amyloid clearance via neprilysin activation and attenuate tau pathology and inflammatory signaling in preclinical studies. The clinical significance is that SSAs could be repurposed as multitarget disease-modifying candidates for AD beyond symptomatic therapies.
Liu K, Zhang XY, Wang YT et al. · Molecular neurobiology · (2026) · View on PubMed ↗
Meat Consumption and Cognitive Health by APOE Genotype.
This population-based cohort study in the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K) tested whether meat consumption is associated with cognitive health differently by APOE genotype (ε3/ε4 and ε4/ε4 vs other genotypes) over 15 years. Higher meat consumption was linked to cognitive health benefits specifically in APOE ε4 carriers (APOE34/44), with genotype-dependent differences compared with non-ε4 genotypes. These findings support genotype-informed dietary prevention strategies for Alzheimer disease risk in older adults.
Norgren J, Carballo-Casla A, Grande G et al. · JAMA network open · (2026) · View on PubMed ↗
Transcriptomic Insights Into Alzheimer's Disease: Differentially Expressed Genes and Cholesterol Metabolism.
This computational study applied Mendelian randomization and advanced machine learning to transcriptomic data to characterize differentially expressed genes and cholesterol metabolism pathways in Alzheimer disease. It identified transcriptomic features linking AD biology to cholesterol-related dysregulation. Scientifically, these integrative analyses suggest candidate pathways and gene targets that could support earlier diagnosis and mechanistic stratification of AD.
Sun R, Wang X, Wang Z et al. · CNS neuroscience & therapeutics · (2026) · View on PubMed ↗
The relationship between dietary patterns and neuroinflammation.
This critical review examined how dietary patterns modulate neuroinflammation through immunometabolic mechanisms affecting the central nervous system (CNS). It synthesizes evidence that nutrient quality/composition/timing can influence glial activation, microglial inflammatory signaling, and vulnerability to neuroinflammatory disorders such as Alzheimer disease and major depression. The review supports dietary pattern interventions as potential modulators of neuroinflammation and highlights mechanistic targets for future research.
Medoro A, Scapagnini G, Hu FB et al. · Critical reviews in food science and nutrition · (2026) · View on PubMed ↗
Early-Life Melatonin Supplementation Reduces the Long-Term Behavioral, Morphological, and Molecular Alterations in a Rat Model of Autism Spectrum Disorder.
In a rat model of autism spectrum disorder (ASD), this study tested whether early-life melatonin supplementation reduces long-term behavioral, morphological, and molecular abnormalities. Melatonin administration mitigated persistent ASD-like alterations across behavioral and biological readouts. These findings suggest early melatonin as a potential neuroprotective, anti-inflammatory/antioxidant intervention strategy for ASD-related pathology.
Hernández-Sierra LJ, Salgado-Delgado RC, Ibáñez-Sandoval O et al. · Journal of pineal research · (2026) · View on PubMed ↗
Microbiome–Gut–Brain/Host Metabolism
How gut microbiota contribute to neuropsychiatric disorders: evidence from neuroimaging studies.
This review synthesised evidence from neuroimaging studies on how gut microbiota contribute to neuropsychiatric disorders via the microbiota–gut–brain axis. It highlights multimodal imaging approaches—including MRI, PET, and diffusion tensor imaging—that link microbial alterations to brain structure and function across neurodevelopmental, neurodegenerative, autoimmune, and psychiatric conditions. The review frames neuroimaging biomarkers as tools to clarify mechanisms and stratify patients in microbiome-related neuropsychiatric research.
Jia C, Zhu W, Yuan Y et al. · Frontiers in microbiology · (2026) · View on PubMed ↗
Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors.
The study examined how gut microbiota–derived serotonin production affects in vivo delivery efficiency of intestinal epithelial–triggered hepatic delivery systems for synthetic and viral vectors. It showed that disrupting commensal-host interactions improves IDS-based delivery by reducing hepatic IDS clearance, and that transient serotonin signaling suppression (via receptor blockade or diet) mitigates clearance and increases delivery efficiency by more than threefold. This provides a microbiome-informed strategy to enhance gene/drug vector delivery in vivo.
Wang Q, Chen Z, Zhang G et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Gut microbe-derived N-acyl serinol lipids shape host postprandial metabolic homeostasis.
The study investigated how gut microbe-derived N-acyl serinol lipids influence host postprandial metabolic homeostasis. It focused on N-acyl amide lipid metabolites produced by gut bacteria after meals and assessed their physiological roles in postprandial metabolic responses. This supports a specific diet–microbe–host signaling axis that could be leveraged for microbiome-inspired metabolic therapies.
Dutta S, Mahen KK, Massey WJ et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Metabolic Disease, Obesity & Systemic Risk
Joint TOS/OMA/OAC expert guidance statement on the pharmacological management of United States adults with overweight or obesity using the GRADE approach.
This expert guidance statement used the GRADE approach to synthesise evidence and provide recommendations for pharmacological management of US adults with overweight or obesity, including the role of FDA-approved obesity medications. The guidance addresses clinical decision-making in the context of barriers such as underdiagnosis, limited clinician training, stigma, and reimbursement restrictions. The statement is intended to standardise evidence-based obesity pharmacotherapy and improve access and outcomes at the population level.
Alexander L, Purnell JQ, Burridge K et al. · Obesity pillars · (2026) · View on PubMed ↗
Skeletal muscle metabolism in health and disease: Mechanisms, interventions, and clinical perspectives.
This iScience review summarised skeletal muscle metabolism in health and disease, focusing on mechanisms of metabolic flexibility and how disruptions in pathways such as insulin, AMPK, mTOR, and PGC-1α contribute to mitochondrial dysfunction, lipid dysregulation, and muscle wasting. It also discussed interventions and clinical perspectives relevant to metabolic disorders including obesity, type 2 diabetes, and sarcopenia. The review integrates molecular regulation with translational opportunities for improving muscle and systemic metabolic health.
Lin D, Zhang L, Huang C et al. · iScience · (2026) · View on PubMed ↗
Type 2 diabetes mellitus.
This Nature Reviews Disease Primer synthesized evidence on type 2 diabetes mellitus (T2DM) across populations, focusing on epidemiology, risk factors, and disease progression patterns including early-onset T2DM. It concluded that rising obesity is a major driver of increasing T2DM prevalence and that diagnosis before age 40 is linked to more aggressive progression, higher complication burden, and greater lifetime morbidity than later-onset disease. Clinically, this supports earlier risk identification and tailored prevention strategies for younger patients at high risk.
Davies MJ, Lim S, Slater T et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗
Adherence to the EAT-Lancet Diet and Risk of Sepsis: A Prospective Cohort Study from the UK Biobank.
This prospective cohort study in 199,085 UK Biobank participants assessed whether adherence to the EAT-Lancet diet is associated with sepsis risk, incorporating genetic susceptibility and proteomic mechanisms. It found that higher EAT-Lancet diet adherence was associated with a reduced risk of sepsis (HR 0.85, 95% CI 0.78–[truncated]). The results suggest diet quality may be a modifiable factor influencing sepsis risk through metabolic/inflammatory pathways relevant to precision prevention.
Nan W, Huang Q, He B et al. · NPJ science of food · (2026) · View on PubMed ↗
The efficacy and safety of cannabinoids for the treatment of mental disorders and substance use disorders: a systematic review and meta-analysis.
This systematic review and meta-analysis evaluated the efficacy and safety of cannabinoids as primary treatments for mental disorders and substance use disorders (SUDs) based on randomized controlled trials. It concluded that the evidence base from RCTs was assessed across multiple databases (1980–May 13, 2025) to determine treatment effects and adverse outcomes for cannabinoid interventions. The findings aim to clarify whether cannabinoids provide clinically meaningful benefit and acceptable safety profiles for psychiatric and SUD indications.
Wilson J, Dobson O, Langcake A et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗
The relationship between sarcopenia and all-cause and cardiovascular mortality risk among middle-aged and older adults across stages 0-3 of cardiovascular-kidney-metabolic syndrome: evidence from NHANES and CHARLS.
The study analyzed associations between sarcopenia and all-cause and cardiovascular mortality across cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 using NHANES (2011–2018) and CHARLS (2011–2020). Using multivariable Cox regression, it evaluated whether sarcopenia status modifies mortality risk within CKM stage strata in middle-aged and older adults. This helps refine risk stratification by linking body composition (sarcopenia) to mortality outcomes in CKM disease trajectories.
Chen Y, Liu Y, Liu S et al. · Cardiorenal medicine · (2026) · View on PubMed ↗
MASLD as a systemic metabolic disease: expanding the scope of cardiovascular-kidney-metabolic (CKM) syndrome.
This article reviewed metabolic dysfunction-associated steatotic liver disease (MASLD) as a systemic disease and argued for its inclusion within the cardiovascular–kidney–metabolic (CKM) syndrome framework. The key finding is that MASLD increases cardiovascular and renal complications through shared mechanisms such as insulin resistance, low-grade inflammation, oxidative stress, dyslipidemia, and procoagulant states. Clinically, reframing MASLD as part of CKM syndrome could improve cross-specialty screening and management strategies.
Zhou XD, Fan QY, Targher G et al. · Science China. Life sciences · (2026) · View on PubMed ↗
International Dermoscopy Society consensus recommendations for the management of lentigo maligna.
This consensus statement from the International Dermoscopy Society provided evidence-based recommendations for managing lentigo maligna (LM), a melanoma in situ subtype common on chronically sun-damaged skin in elderly patients. It addresses practical diagnostic and management guidance in settings where evidence is limited and lesions may have subclinical peripheral extension. The recommendations aim to standardize dermoscopic evaluation and treatment decisions to reduce under- or overtreatment of LM.
Forsea AM, Pampena R, Akay BN et al. · Journal of the European Academy of Dermatology and Venereology : JEADV · (2026) · View on PubMed ↗
Renal & Urogenital Disease Mechanisms/Outcomes
Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression.
The study explored how host-derived nitrate fuels microbial indole production to drive chronic kidney disease progression in adenine-induced CKD mice. It showed that impaired indoxyl sulfate clearance increases iNOS expression, elevates luminal nitrate, and promotes Escherichia coli growth via nitrate respiration, while CKD patient fecal microbiota produced more indole under anaerobic conditions. This connects host nitrogen metabolism, E. coli nitrate respiration, and indole/indoxyl sulfate pathways to CKD progression.
Lee JY, Mahan SP, Parente de Carvalho T et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Proteomic analyses of human islets reveal potential markers of β-cell dysfunction during prediabetes.
This study used proteomics to identify markers of pancreatic β-cell dysfunction during prediabetes in humans. Researchers isolated islets from non-diabetic subjects undergoing partial pancreatectomy, characterized glucose tolerance and insulin function, then used laser capture microdissection (LCM) and HPLC-MS proteomic profiling to detect changes associated with impaired glucose tolerance (IGT). The key finding was that IGT islets showed reductions in proteins involved in glycolysis and lipid metabolism and other pathways relevant to β-cell dysfunction, suggesting candidate predictive biomarkers for diabetes onset.
Cefalo CMA, Mezza T, Quero G et al. · JCI insight · (2026) · View on PubMed ↗
Identification and Validation of miR-206-3p Targeting WT-1 Promotes Membranous Nephropathy Through a Comprehensive Bioinformatics and Machine Learning Algorithm.
Using public datasets and bioinformatics/ML pipelines, this study identified microRNA-206-3p (miR-206-3p) as a regulator targeting WT-1 and then validated its role in membranous nephropathy (MN). miR-206-3p targeting of WT-1 promoted MN-associated pathology, supported by differential expression analyses and mechanistic validation. These results nominate the miR-206-3p/WT-1 axis as a potential therapeutic target and biomarker pathway for MN.
Wang X, Zhou F, Fu C et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗
Pulmonary Vascular Disease & Respiratory Critical Care
Epidemiology, ventilation, and outcomes of acute respiratory failure in immunocompromised patients from 103 intensive care units in 26 countries: a retrospective observational study.
This retrospective observational study characterized acute respiratory failure (ARF) in immunocompromised adults across 103 ICUs in 26 countries and assessed predictors of mortality and intubation. It found that contemporary epidemiology and management patterns vary internationally and that specific clinical factors related to underlying immunosuppression and ARF cause/oxygenation strategy are associated with outcomes (details truncated). The results provide evidence to improve risk prediction and ICU decision-making for immunocompromised patients with ARF.
Azoulay E, McEvoy C, Castro P et al. · The Lancet. Respiratory medicine · (2026) · View on PubMed ↗
Efficacy and Safety of Remimazolam Tosylate versus Propofol for Sedation of Postoperative Mechanically Ventilated Patients in Intensive Care Units: a Multicenter, Randomized, Single-blind, Non-inferiority, Phase 3 trial.
The study compared remimazolam tosylate versus propofol for sedation in postoperative mechanically ventilated ICU patients in a multicenter, randomized, single-blind, non-inferiority phase 3 trial (NCT06222294). Patients were randomized to IV remimazolam tosylate (loading 0.08 mg/kg; maintenance 0–2.0 mg/kg/h) or propofol (loading 0.3–0.5 mg/kg; maintenance 0.3–4.0 mg/kg/h) targeting RASS -2 to 1. Demonstrating non-inferior safety/efficacy would support remimazolam as an alternative sedation strategy in mechanically ventilated postoperative patients.
Guan X, Liu N, Lin F et al. · Anesthesiology · (2026) · View on PubMed ↗
Musculoskeletal, Bone & Rehabilitation
FGF21-Mediated Upregulation of SIRT1 Delays Intervertebral Disc Degeneration by Promoting PINK1/Parkin Dependent Mitophagy Through Deacetylation of FOXO3.
This study examined whether FGF21-mediated upregulation of SIRT1 delays intervertebral disc degeneration by promoting PINK1/Parkin-dependent mitophagy through deacetylation of FOXO3, using human and rat degenerated intervertebral discs and in vitro assays. FGF21 was downregulated in degenerated discs, and restoring the FGF21–SIRT1 axis enhanced PINK1/Parkin mitophagy and reduced senescence-related pathology via FOXO3 deacetylation. These findings identify a FGF21–SIRT1–FOXO3–PINK1/Parkin pathway as a potential therapeutic target for slowing intervertebral disc degeneration.
Wu ZL, Ran R, Xie QQ et al. · Aging cell · (2026) · View on PubMed ↗
Velocity Loss During Resistance Training: Implications for Concurrent Training Adaptations.
The study examined how different velocity loss (VL) thresholds during resistance training affect adaptations to concurrent training in 41 moderately trained men over 8 weeks. Concurrent training with VL thresholds of 0%, 15%, or 40% (plus endurance training) was compared with endurance training alone, focusing on strength, endurance, neuromuscular, and hypertrophic outcomes. The results inform how to set VL targets to optimize concurrent training adaptations without sacrificing key performance domains.
Tundidor-Duque RM, Loturco I, Paéz-Maldondado JA et al. · Scandinavian journal of medicine & science in sports · (2026) · View on PubMed ↗
Managing Bone Fragility in Older Adults with Diabetes: Pathophysiology, Assessment, and Therapeutic Considerations.
This review summarized how diabetes in older adults (type 1 and type 2) contributes to bone fragility and fracture risk, focusing on differences in pathophysiology and implications for assessment and therapy. The key finding is that T1D-related fragility is often driven by reduced bone mineral density from insulinopenia, whereas T2D fragility can occur despite normal/high BMD due to impaired bone quality, microarchitecture changes, advanced glycation end products (AGEs), and low turnover. The clinical significance is improved fracture-risk stratification and more tailored therapeutic considerations for diabetic older adults.
Bahat G, Erdogan T, Ozturk S et al. · Drugs & aging · (2026) · View on PubMed ↗
Effects of Diactive-1-Supported Progressive Resistance Training on Body Composition in Youth With Type 1 Diabetes.
This randomized/controlled exercise study evaluated the effects of Diactive-1–supported progressive resistance training on body composition in youth with type 1 diabetes (ages 8–18). Resistance training supported by the mHealth application improved specific body composition outcomes compared with baseline/controls. Clinically, it supports scalable digital-health–assisted resistance exercise as a strategy to counter diabetes-associated adverse body composition changes.
Muñoz-Pardeza J, López-Gil JF, Hormazábal-Aguayo I et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗
Rare Diseases, Genetics & Translational Platforms
Apoptotic extracellular vesicles derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by enhancing cell activity and regulating immunity microenvironment.
This preclinical study tested whether apoptotic extracellular vesicles (ApoEVs) derived from mesenchymal stem cells (MSCs) exposed to hypoxic and inflammatory conditions can slow intervertebral disc degeneration by enhancing nucleus pulposus cell activity and modulating the immune microenvironment. The authors reported that these MSC-derived ApoEVs improved disc degeneration phenotypes and regulated immune-related pathways in the degenerative context. The findings support ApoEV-based cell-free therapies as a strategy to overcome challenges of MSC survival and apoptosis in vivo.
Zhang W, Ma X, Yin H et al. · Materials today. Bio · (2026) · View on PubMed ↗
Cryo-EM structure of TRPM1 reveals a non-canonical architecture with an inverted transmembrane domain.
This structural biology study examined the vision-related ion channel TRPM1 in the context of congenital stationary night blindness by isolating TRPM1 and determining its structure using cryogenic electron microscopy (cryo-EM). It found that TRPM1 forms a non-canonical architecture with an inverted transmembrane domain while maintaining a canonical tetrameric intracellular-domain fold consistent with other TRPM family members. This clarifies TRPM1’s molecular basis for ion-channel function and provides a structural framework for interpreting disease-causing mutations.
Fabrizio M, Brewer M, Bogdanović N et al. · Nature communications · (2026) · View on PubMed ↗
Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models.
The study tested a mitochondrial transplantation method in mice and monkeys by encapsulating mitochondria in vesicles derived from erythrocyte plasma membranes. Encapsulated mitochondria efficiently entered somatic tissues, complemented mitochondrial DNA loss/deletion/mutations, and rescued bioenergetic and biochemical defects in patient-derived mitochondrial disorder cells. These findings advance mitochondrial delivery as a potential therapeutic platform for mitochondrial diseases by improving exogenous mitochondrial uptake and functional restoration.
Du S, Long Q, Zhou Y et al. · Cell · (2026) · View on PubMed ↗
Resetting of a tandem microRNA156 enables vegetative perennial growth in rice.
The study identified the genetic basis of perennial growth habit in rice by analyzing introgression lines of wild and cultivated rice. It mapped perennial growth to the EBT1 locus containing tandem microRNA156 genes (MIR156BC), showing that the wild allele (EBT1W1943) resets MIR156BC expression in tiller buds via altered chromatin accessibility and reduced H3K27me3. This advances understanding of microRNA-driven epigenetic regulation of vegetative propagation and floral reversion in crop domestication.
Dai B, Lv D, Chen E et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗
Phase separation of Rht8-derived RNHL1 integrates ethylene and gibberellin signaling to regulate wheat internode elongation.
This study analyzed how the wheat semi-dwarfing gene Rht8, encoding RNHL1 (ribonuclease H-like 1), regulates internode elongation by integrating ethylene and gibberellin signaling. RNHL1 was shown to form nuclear liquid-liquid phase separation condensates via intrinsically disordered regions that interact with the ethylene signaling transcription factor TaEIL1 to create functional transcriptional hubs controlling growth. Scientifically, it reveals an LLPS-based transcriptional mechanism by which RNHL1 coordinates hormone crosstalk to shape plant architecture.
Dong C, Cheng X, Yuan M et al. · The Plant cell · (2026) · View on PubMed ↗
Stage-specific transcriptomics of a leader cell reveals cell machineries driving collective invasion.
This study generated stage-specific transcriptomic data for the Caenorhabditis elegans gonadal leader cell, the distal tip cell (DTC), comparing invasive larval-stage DTCs with noninvasive adult-stage DTCs. The resulting in vivo signature revealed molecular programs and cell-invasion “machineries” that drive collective invasion. The dataset provides a mechanistic framework for how leader cells coordinate invasion, informing broader understanding of development and metastasis.
Agarwal P, Maimon Zielonka I, Gingold H et al. · The Journal of cell biology · (2026) · View on PubMed ↗
ECM1 produced by hepatic stellate cells serves as gate keeper of liver homeostasis in hepatic fibrosis.
Using inducible hepatic stellate cell (HSC) ablation in Lrat-iDTR mice and multi-parametric analyses across two fibrosis models (CCl4-driven injury and MASH induced by choline-deficient high-fat diet, CD-HFD), this study examined how HSC homeostatic functions relate to fibrosis. The authors identified ECM1 produced by hepatic stellate cells as a “gatekeeper” of liver homeostasis during hepatic fibrosis. Targeting ECM1 could preserve beneficial HSC homeostatic activity while limiting fibrogenic progression.
Yang A, Yan X, Wang Y et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗
Onasemnogene Abeparvovec in Type I Spinal Muscular Atrophy: 24-Month Follow-Up From the Italian Registry.
This 24-month prospective observational study from the Italian registry followed spinal muscular atrophy type I (SMA I) patients treated with onasemnogene abeparvovec (AAV9 gene therapy). Outcomes were characterized in real-world practice, including how patients were categorized by treatment status (monotherapy vs bridge from nusinersen/risdiplam vs switch after >3 months). Longer-term registry data are clinically important for counseling families and understanding response variability beyond trial timeframes.
Pane M, Coratti G, Cutrì C et al. · Annals of clinical and translational neurology · (2026) · View on PubMed ↗
A Rare RIPK3 Variant Enhances Necroptosis and Promotes Inflammation in a Still's Disease-like Autoinflammatory Syndrome.
In a three-generation family with a Still’s disease–like autoinflammatory syndrome, this study used whole-exome sequencing to identify a rare RIPK3 variant (p.Q134K) and then performed functional assays. The RIPK3 p.Q134K variant enhanced kinase activity, increased necroptosis, and promoted inflammatory signaling, supported by peripheral blood transcriptomic profiling. This links a specific RIPK3 genetic change to disease mechanism, informing precision diagnosis and potential necroptosis-targeted therapies.
Chen L, Dai Q, Xiao Y et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗
Generated automatically on March 21, 2026 from PubMed's trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.