PubMed Trending Research Digest — June 24, 2026

Automated digest · 97 articles · 15 research areas · June 24, 2026

Overview

This week’s PubMed highlights a strong convergence around immune regulation and immune–metabolism coupling. Several studies dissect how immune signaling is shaped by cellular metabolic states—ranging from MAVS activation being enabled by lipid droplet–mitochondria tethering (via PLIN3–MFN2) to tumor ferroptosis sensitivity being tuned by STING-driven lipid mediator production in colorectal cancer. In parallel, multiple cancer papers emphasize how immune cell programming (e.g., CD8-derived IFN-γ inducing FDX1 for cuproptosis, or CD8 IL-10 orchestrating early NK recruitment during antiangiogenic plus checkpoint blockade) can be leveraged to overcome immunotherapy resistance.

A second dominant theme is “precision stratification” across diseases using mechanistic biomarkers and refined patient selection. In neurodegeneration, work spans from preclinical oral GLP-1 receptor agonism that targets astrocyte–neuron metabolic coupling to blood-based SECmere RNA biomarkers for Alzheimer’s, and microglial immune reprogramming strategies in APOE4-driven amyloid pathology. In oncology, studies use multi-omics and spatial/proteomic approaches to define vulnerabilities and risk: GATA6 loss and lineage plasticity in colorectal liver metastasis, MED4 as a gatekeeper of metastatic dormancy, and proteomics-defined subtypes in nasopharyngeal carcinoma. Even outside cancer, biomarker-driven approaches appear in cardiometabolic and pulmonary contexts (e.g., FeNO for glucocorticoid response in AECOPD; comparative liver-outcome effectiveness of GLP-1RA vs SGLT2 inhibitors in MASLD with T2D).

Finally, the digest reflects an ongoing shift toward network- and systems-level thinking—whether in genetics (rare-variant network testing for Parkinson’s, immune-cell eQTL mapping for AD risk, and multi-omics epigenetic drivers of glioma progression) or in translational modeling and delivery (brain-on-a-chip platforms, BBB shuttling for CNS ASOs, and biohybrid microrobots for intracavitary chemotherapy). Together, these studies reinforce a broader message: mechanistic understanding at the level of pathways, cell states, and microenvironments is increasingly driving both biomarker development and therapeutic design.

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Innate Immunity & Antiviral Signaling (MAVS/Interferon)

A guardian role of TagA in protecting Mycobacterium tuberculosis from nitrosative killing.

This study used transposon insertion sequencing to identify Mycobacterium tuberculosis (Mtb) genes required for survival inside macrophage subsets and in mice, focusing on nitrosative stress from reactive nitrogen species. TagA was found to be specifically required for Mtb resistance to DNA damage in M1-polarized macrophages and at an early postinfection stage in mice, where macrophages are biased toward an M1 phenotype. These findings define TagA as a key bacterial “guardian” of intracellular DNA integrity under nitrosative killing, highlighting a potential vulnerability of Mtb during macrophage-driven host defense.

Zhang Y, Wang H, Liu Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Parathyroid Hormone Receptor 1 Facilitates Cyst Growth in Genetic Models of Autosomal Dominant Polycystic Kidney Disease.

This study examined the role of Parathyroid Hormone Receptor 1 (PTHR1) in cyst growth using genetic mouse models of autosomal dominant polycystic kidney disease (ADPKD) driven by PKD1 or PKD2 mutations. Using RiboTag-based translational profiling of early cystic kidneys, the authors identified ciliary signaling pathways and implicated PTHR1 as a facilitator of cyst progression in these models. The work is significant because it links a specific ciliary receptor (PTHR1) to ADPKD cyst growth, suggesting a more targeted therapeutic direction within cilia-mediated signaling.

Wu Z, Sun M, Hu M et al. · Journal of the American Society of Nephrology : JASN · (2026) · View on PubMed ↗

Klebsiella genus as driver of human disease: from infections to non-communicable disorders.

This Nature Reviews Microbiology article reviews how Klebsiella species act as drivers of human disease, spanning acute infections (e.g., pneumonia, urinary tract, bloodstream infections) and associations with non-communicable disorders. It synthesizes evidence on Klebsiella taxonomy, molecular features, epidemiology, and the role of multidrug-resistant strains, while also summarizing links between Klebsiella and chronic disease outcomes. The review is significant because it frames Klebsiella as both an infectious pathogen and a pathobiont, guiding future research into mechanisms and interventions across disease categories.

Porcari S, Ferrari M, Melekhova A et al. · Nature reviews. Microbiology · (2026) · View on PubMed ↗

mRAVE governs lysosomal catabolism through basal and mTORC1-regulated V-ATPase assembly.

The study characterized the mammalian RAVE complex (mRAVE) subunits Dmxl1/Dmxl2, Wdr7, and Rogdi to define how V-ATPase assembly is regulated under basal conditions and by mTORC1 in mammalian cells. mRAVE broadly promoted V-ATPase assembly and luminal acidification of endomembrane compartments, and mTORC1 signaling regulated V-ATPase assembly through mRAVE-dependent mechanisms. This advances understanding of how lysosomal catabolism is controlled by coupling organelle acidification to basal and nutrient-responsive mTORC1 regulation.

Siefert NS, Zanotti A, Paneva A et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

Modelling the role of the microbiome in antimicrobial resistance across scales.

This modelling paper studied how the microbiome influences antimicrobial resistance (AMR) dynamics across ecological and evolutionary scales, including resistance-gene reservoirs, microbial competition, and community-mediated selection. It found that existing AMR predictive models often underrepresent microbiome–AMR interactions and proposed a structured framework to incorporate these microbiome-mediated processes into multiscale prediction. Scientifically, the framework aims to improve forecasts of AMR emergence, transmission, and persistence by explicitly modelling microbiome-driven selection and reservoir effects.

Pagani L, León-Sampedro R, Amicone M et al. · Nature microbiology · (2026) · View on PubMed ↗

Structure and substrate recognition by the bacterial twin-arginine translocation (Tat) core complex.

This structural biology study investigated substrate recognition by the bacterial twin-arginine translocation (Tat) core complex using cryo-electron microscopy. It found cryo-EM structures of the resting-state TatBC complex from Escherichia coli and atypical Tat complexes from Nitratifactor salsuginis and Myxococcus xanthus, as well as substrate-bound TatAC/TatBC and TatABC assemblies from E. coli, revealing how substrate binding triggers recruitment of additional TatA protomers to form the transport site. The significance is a mechanistic, structure-based understanding of Tat transport that can inform strategies to target bacterial virulence and related processes dependent on folded-protein export.

Deme JC, Bryant OJ, Batista MRB et al. · Nature microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Molecular basis of host ATP level modulation by actin-dependent secreted bacterial ATPase and its metaeffector.

Legionella pneumophila uses the S-HxxxE-family effector Ceg14, together with the metaeffector AnkJ and host actin, to modulate host ATP levels in infected host cells. Cryo-EM structures show that actin binds the C-terminal α-helix of Ceg14’s catalytic domain, driving N-terminal domain rearrangement and reconfiguring the flexible Lid, while AnkJ and actin together form distinct Ceg14 complexes that regulate Ceg14 ATPase activity. These mechanistic structural insights explain how actin-dependent bacterial ATPase control is implemented at atomic resolution, informing strategies to disrupt pathogen energy exploitation.

Guan H, Li Y, Zhang L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment.

This study used high-resolution single-cell analysis to examine how Mycobacterium tuberculosis adapts at the single-bacterium level to acidic environments and how that affects antibiotic survival, including clinical strains. Mtb increased the fraction of cells entering a growth-arrested state under acidic conditions, and this nongrowing subpopulation showed enhanced tolerance to ethambutol. The results suggest that host-like acidity promotes a drug-tolerant growth-arrest program, informing strategies to prevent or target this state during antibiotic treatment.

Chung ES, Johnson WC, Kamkaew M et al. · PLoS biology · (2026) · View on PubMed ↗ · Free PDF ↗

Lysosome-related organelles employ divergent mechanisms to modulate cytosolic zinc homeostasis.

This study examined how lysosome-related gut granules regulate cytosolic zinc homeostasis in C. elegans under high dietary zinc, focusing on the roles of GLO-1, GLO-3, and CCZ-1. GLO-1 primarily controlled granule biogenesis, while zinc-induced granule expansion used distinct mechanisms involving GLO-3-CCZ-1, with high zinc upregulating GLO-1 activity via increased transcription of GLO-3 and post-translational modification of CCZ-1. These findings clarify divergent molecular control of zinc buffering by lysosome-related organelles, advancing understanding of metal homeostasis and stress adaptation.

Xie C, Luo Y, Zheng Y et al. · PLoS genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Niche-targeted therapy via YAP/TAZ activation enhances hematopoietic regeneration.

This study tested whether niche-targeted activation of the Hippo pathway effectors YAP/TAZ can enhance hematopoietic regeneration after bone marrow (BM) injury, focusing on endothelial cells (ECs) and mesenchymal stromal cells (MSCs). The authors found that YAP/TAZ are critical for ECs and MSCs to respond to BM injury and that YAP/TAZ activation accelerates BM niche recovery, thereby improving hematopoietic regeneration. Scientifically, it positions YAP/TAZ activation as a strategy to therapeutically restore the BM niche after myeloablative stress.

Uemura S, Yamashita M, Yokomizo-Nakano T et al. · Blood · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Lipid droplet-mitochondria tethering releases MAVS inhibition to potentiate antiviral immunity.

The study examined how viral infection regulates mitochondrial antiviral signaling protein (MAVS) activation in cells by promoting lipid droplet (LD)–mitochondria interactions, focusing on the LD protein PLIN3 and the mitochondrial fusion protein MFN2. It found that LD formation after infection enables PLIN3 to bind MFN2, relieving MFN2-mediated inhibition of MAVS and facilitating MAVS prion-like oligomerization, while LD–mitochondria contact sites support fatty-acid transfer to sustain mitochondrial membrane potential for antiviral signaling. This mechanistic link between lipid metabolism and MAVS activation identifies PLIN3–MFN2–dependent LD–mitochondria tethering as a potential target to potentiate innate immunity against RNA viruses.

Peng Q, Liang W, Wang W et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Psychosocial Determinants & Aging-Related Health

Bibliometric analysis and visualization of the triglyceride-glucose index from 2014 to 2024.

This bibliometric analysis characterized research trends on the triglyceride-glucose (TyG) index from 2014 to 2024 using Web of Science Core Collection records. It assessed publication patterns and research development in the TyG index literature, focusing on how attention and growth have accelerated—especially in cardiovascular research. The study is significant because it maps the evolving evidence landscape for the TyG index, helping researchers identify hotspots and gaps for future clinical and mechanistic work.

He Q, Cong X, Ji A et al. · Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Neuropsychological Factors in Vitiligo: Mechanisms and Clinical Application.

This review examined neuropsychological and neuro-endocrine-immune mechanisms linking psychological stress with vitiligo onset and progression in the general vitiligo population. It found evidence for a self-amplifying pathogenic loop in which stress precedes disease onset and visible depigmentation increases depression and anxiety, mediated through a neuro-endocrine-immune-cutaneous axis. The clinical significance is that neuropsychological assessment and stress-targeted interventions may be translationally relevant adjuncts to vitiligo management.

Ren FF, Zhou J, Zhang W · Clinical reviews in allergy & immunology · (2026) · View on PubMed ↗

Biological aging and generational shifts in early-onset cancer risk.

This population-based study analyzed biological aging and generational shifts in early-onset cancer risk using 154,169 young adults from the UK Biobank. It found that systemic aging measured by PhenoAge increased across birth cohorts and was associated with higher early-onset solid cancer risk (HR per SD 1.08), with effects driven by cancers including lung and gastrointestinal. The significance is that cohort-level changes in aging biology may help explain rising early-onset cancer incidence and could inform risk stratification using aging biomarkers.

Tian R, Zong X, Ren D et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Resetting of epigenetic cold memory through somatic embryogenesis in plant regeneration.

This plant regeneration study examined whether epigenetic cold memory can be reset during asexual propagation by using Arabidopsis somatic embryogenesis. It found that the vernalized state is reprogrammed during somatic embryogenesis, overturning the prior assumption that vernalization cannot be reset through asexual reproduction. The significance is a practical strategy to erase parental epigenetic effects in clonal plant propagation, improving control over developmental timing and traits.

Niu D, Ou Y, Tang LP et al. · Nature plants · (2026) · 1 citations · View on PubMed ↗

Deep brain stimulation of the nucleus accumbens for severe self-injurious behaviour in children: long-term outcomes from a first-in-human pilot trial.

This first-in-human pilot trial studied deep brain stimulation (DBS) of the nucleus accumbens (NAc) for severe self-injurious behaviour (SIB) in children with profound autism and treatment-refractory SIB. In six participants aged 7–14 years, bilateral NAc implantation was followed prospectively for at least 24 months (mean 32.5 months), with one serious adverse event reported (device-related). Clinically, the long-term outcomes support feasibility and inform risk–benefit considerations for NAc DBS as a potential neuromodulation option for pediatric, treatment-refractory SIB.

Mithani K, Breitbart S, Dinger T et al. · Molecular psychiatry · (2026) · View on PubMed ↗

AOC1 regulates labor initiation through spermidine-induced autophagy of placental trophoblast cells via EIF5A hypusination.

The authors studied how placental signaling regulates labor initiation in Src-1/Src-2 double-knockout mice and in placental trophoblast cells, focusing on AOC1-driven spermidine metabolism. Reduced placental AOC1 increased spermidine levels, and spermidine induced autophagy through EIF5A hypusination, lowering estrogen and prostaglandin production, with estrogen/ERα–SRC-1/2 feedback upregulating Aoc1 to maintain placental autophagy. This identifies an AOC1–spermidine–EIF5A hypusination axis as a mechanistic regulator of parturition and a potential therapeutic target to modulate labor timing.

Chen H, Long P, Wang Z et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Reframing diet assessment for geroscience: development and preliminary validation of an anti-aging dietary score.

This paper studied whether an anti-aging dietary score grounded in the Nutrient–Signaling–Senescence (NSS) axis better reflects aging biology than conventional diet indices using NHANES data. The Nutrient-Signaling-Senescence–based anti-aging dietary score (AADS) showed preliminary validation in which higher AADS was significantly associated with lower PhenoAge acceleration, performing comparably to established indices. The work provides a mechanistic, geroscience-oriented framework to translate diet into measurable aging-related outcomes for population studies.

Feng S, Wang T, Yan J et al. · NPJ science of food · (2026) · View on PubMed ↗ · Free PDF ↗

Immune cell-specific genetic architecture of Alzheimer’s disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.

The study integrated single-cell eQTL data from the OneK1K cohort with Alzheimer’s disease (AD) GWAS summary statistics to map immune cell subset–specific genetic architecture and regulatory landscapes, using genetic causal inference and Bayesian colocalization. It identified immune-cell–specific genes whose expression regulation is genetically linked to AD risk, prioritizing candidate therapeutic targets across peripheral immune subsets. These findings support immune-cell–focused target discovery for AD by specifying which immune cell gene programs are most likely to be causally involved.

Gao TL, Geng S, Chen J et al. · Translational psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

Preoperative Risk Evaluation for Cancer Treatment (PREdiCT): protocol for an international cohort study evaluating a trimodal screening tool to predict outcomes following gastrointestinal cancer surgery.

The PREdiCT study protocol describes an international cohort study to evaluate a trimodal, online self-reported preoperative risk screening tool for predicting outcomes after gastrointestinal cancer surgery, addressing limited access to prehabilitation. It will prospectively assess whether the tool can identify high-risk patients within the narrow time window between diagnosis and surgery and enable targeted preoperative interventions. If validated, PREdiCT could improve perioperative risk stratification and equitable allocation of prehabilitation resources in gastrointestinal cancer care.

Reeves J, Koh C, Alexander K et al. · BMJ open · (2026) · View on PubMed ↗ · Free PDF ↗

Trends in colorectal cancer mortality among younger versus older adults in 49 countries.

Using the WHO Mortality database (1990–2023), the study analyzed trends in colorectal cancer (CRC) mortality among younger adults (25–49 years) versus older adults (50–79 years) across 49 countries. CRC mortality among younger adults increased in 18 countries, decreased in 15, and was stable in the remainder, with substantial heterogeneity in the magnitude and direction of trends. These findings highlight an urgent need for age-tailored prevention and early detection strategies in countries where younger-adult CRC mortality is rising.

Sung H, Kelly K, Jiang C et al. · Journal of the National Cancer Institute · (2026) · View on PubMed ↗

Role of an Ayurvedic formulation ‘Kalyanaka Ghrita’ in Mild Cognitive Impairment: A single-patient, quasi-randomized, controlled, open-label N-of-1 trial.

This single-patient, quasi-randomized, controlled N-of-1 trial evaluated the Ayurvedic polyherbal formulation Kalyanaka Ghrita (KG) for efficacy and safety in a patient with mild cognitive impairment (MCI). The study used an N-of-1 design aligned with individualized Ayurvedic decision-making to systematically assess KG’s effects within the single participant. The approach is significant as a proof-of-concept for evaluating traditional formulations in cognitive disorders while accounting for inter-individual variability.

Sharma S, Kaushik A, Chakrabarti SS et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Zhongchi Liu.

This item is a biographical profile of Zhongchi Liu rather than a primary research study with experimental methods or results. No drug, gene, technique, or population-specific scientific findings are provided in the available abstract text. Therefore, it does not support a mechanistic or clinical summary in the format requested for research articles.

Liu Z · Current biology : CB · (2026) · View on PubMed ↗

Sustained Reduction in Cardiopulmonary Fitness in Long COVID: A Report from the RECOVER-adult Cohort Study.

This RECOVER-adult cohort digital health substudy studied longitudinal cardiopulmonary fitness using wearable sensor measures in adults with Long COVID at least 6 months after SARS-CoV-2 infection. Over a 6-month window, cardiopulmonary fitness metrics were modeled in relation to survey-derived Long COVID symptoms using linear regression adjusted for wear time, age, sex, and race/ethnicity. The results are significant because they provide evidence for sustained functional impairment after infection and can inform monitoring and rehabilitation trial endpoints.

Vogel JM, Jenkins T, Cerda M et al. · JACC. Advances · (2026) · View on PubMed ↗ · Free PDF ↗

Airway Mucus Plugs in Asthma and COPD: Pathobiology, Imaging, and Implications for Clinical Trials.

This review synthesized current knowledge on airway mucus plugs in asthma and COPD, focusing on pathobiology, imaging approaches, and implications for clinical trials. It describes mucus plug formation as driven by mucus hyperconcentration, altered viscoelasticity, impaired clearance, and mucociliary collapse, and it highlights scoring systems (including bronchopulmonary segment mucus plug score) that associate greater mucus plug burden with worse clinical outcomes such as exacerbations and spirometric decline. The review is important for guiding trial design by identifying measurable mucus-plug phenotypes and potential imaging/quantification endpoints.

Bosma CB, Aaron SD, Celli BR et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Exhaled Nitric Oxide Predicts Glucocorticoid Response in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

This retrospective study assessed whether fractional exhaled nitric oxide (FeNO) measured at admission predicts glucocorticoid response in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Patients with FeNO ≥25 ppb (high FeNO group, n=61) differed from those with FeNO <25 ppb (low FeNO group, n=61) in their response to additional systemic glucocorticoids on top of standard therapy (ICS, SABA, and SAMA). If validated, FeNO could serve as a practical biomarker to stratify AECOPD patients likely to benefit from systemic glucocorticoids.

Chen J, Li J, Wang W et al. · Journal of visualized experiments : JoVE · (2026) · View on PubMed ↗

Loneliness, unhealthy lifestyle, and incident cardiometabolic disease among middle-aged and older adults across 33 countries: a multicohort study.

This multicohort study assessed whether loneliness is associated with incident cardiometabolic disease (CMD) and cardiometabolic multimorbidity across 33 countries in middle-aged and older adults, and whether unhealthy lifestyle and socioeconomic status (SES) explain or amplify these relationships. The key finding was not available because the abstract text provided is truncated before results are reported. Clinically, clarifying whether loneliness independently predicts CMD risk (and through which modifiable pathways such as lifestyle or SES) could inform prevention strategies in aging populations.

Wang DY, Xie L, Wu Q et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗

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Pediatric Obesity & Weight-Loss Interventions

HRS-7535, an oral small-molecule GLP-1 receptor agonist, in Chinese adults with obesity without diabetes: a randomized, double-blind, placebo-controlled phase 2 trial.

This randomized, double-blind, placebo-controlled phase 2 trial studied the oral small-molecule GLP-1 receptor agonist HRS-7535 in Chinese adults with obesity without diabetes. In 235 participants (BMI 28.0–40.0 kg/m²), once-daily HRS-7535 at 30, 60, 120, or 180 mg was compared with placebo to evaluate efficacy and safety, with the primary endpoint being percent change in body weight from baseline. If effective and safe, HRS-7535 could expand oral GLP-1–based obesity treatment options for patients who do not have diabetes.

Gu W, Zhang L, Li L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of Weight-Loss Interventions on Kidney, Cardiometabolic and Anthropometric Outcomes in Adults With CKD and Overweight or Obesity: A Systematic Review and Meta-Analysis.

The study systematically reviewed and meta-analyzed randomized controlled trials of weight-loss interventions (lifestyle, pharmacological, and surgical) in adults with chronic kidney disease (CKD) who were overweight or obese, assessing kidney, cardiometabolic, and anthropometric outcomes. It synthesized evidence on how different weight-loss strategies affect clinically relevant endpoints in this comorbid population. The findings can guide evidence-based selection of weight-loss approaches to improve both renal and cardiometabolic health in CKD patients.

Stamatiou A, Theodorakopoulou MP, Iatridi F et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Impact of weight loss and reduction of ultra-processed foods on liver fat content in MASLD: a randomized controlled trial.

This randomized controlled trial studied whether Mediterranean diet (MeD) or low-carbohydrate, high-protein diet (LCHO) provides benefits beyond weight loss in overweight/obese adults with metabolic dysfunction-associated steatotic liver disease (MASLD). After 6 months, the trial compared changes in liver fat content and metabolic health across the MeD, LCHO, and standard nutritional recommendation arms. The results are clinically relevant for refining dietary prescriptions in MASLD by separating diet-pattern effects from weight-loss effects.

Bo S, Armandi A, Castelnuovo G et al. · JHEP reports : innovation in hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management: A Systematic Review and Network Meta-Analysis.

This systematic review and network meta-analysis compared the effectiveness of health behavior and lifestyle treatment (HBLT), obesity pharmacotherapies, and their combinations for pediatric obesity management in children and adolescents aged 10–19 years. The key finding was not available because the abstract text provided is truncated before the comparative efficacy results are reported. Scientifically and clinically, ranking interventions by weight outcomes could guide evidence-based selection of pharmacotherapy versus structured lifestyle programs for pediatric obesity.

Wan KW, Lei EF, Liu Y et al. · JAMA pediatrics · (2026) · View on PubMed ↗

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Diabetes Timing, Exercise Patterns & Cardiometabolic Outcomes

Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.

The authors integrated whole-genome sequencing with plasma metabolomics to map the genetic architecture of 313 metabolic biomarkers and infer clinical implications in up to 199,138 UK Biobank participants. Single-variant analyses identified 36,105 independent signals (22.20% novel) and 12,361 putative causal variant–trait associations, with rare-variant aggregate testing and improved fine-mapping resolution compared with imputed array-based approaches. This large-scale multi-omics genetics study strengthens causal discovery for metabolite biomarkers and supports downstream risk stratification and precision medicine efforts.

Wang YX, Qiang YX, Ge YJ et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Glucagon-Like Peptide-1 Receptor Agonists and Incident Major Adverse Liver Outcomes in People With Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.

The study compared glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus sodium-glucose cotransporter-2 (SGLT-2) inhibitors for major adverse liver outcomes (MALO), cirrhosis, and all-cause mortality in a Germany claims-based active comparator new-user cohort of people with type 2 diabetes and metabolic dysfunction–associated steatotic liver disease (MASLD). GLP-1 RA and SGLT-2 inhibitor use showed differential effectiveness for liver-related endpoints, informing comparative risk of progression and mortality in this population. The results are clinically relevant for choosing glucose-lowering therapies that may also modify liver outcomes in MASLD with type 2 diabetes.

Maier GA, Hofmann RA, Roden M et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity.

This post hoc analysis evaluated the dual glucagon and GLP-1 receptor agonist survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations of people with type 2 diabetes (metformin-treated) or overweight/obesity with normoglycaemia. Across the two trials, survodutide improved biomarkers of beta-cell function and insulin sensitivity relative to placebo (and was benchmarked against semaglutide in the type 2 diabetes trial), with effects interpreted alongside bodyweight changes. These findings support survodutide’s potential metabolic benefits and help position it among incretin-based therapies for type 2 diabetes and obesity-related dysglycaemia.

Ekinci EI, Maldonado SG, Unseld A et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

COMPARING NAFLD, MAFLD, AND MASLD CRITERIA FOR IDENTIFYING SIGNIFICANT LIVER FIBROSIS: A CROSS-SECTIONAL STUDY.

This cross-sectional study in 360 Vietnamese adults compared NAFLD (exclusion-based), MAFLD (inclusion-based), and MASLD criteria for identifying significant liver fibrosis. Using transient elastography, it assessed concordance between frameworks and evaluated fibrosis detection performance with significant fibrosis defined by liver stiffness measurement (LSM) ≥ 7.0. The findings are important for selecting the most appropriate fatty liver diagnostic framework in settings with high viral hepatitis and alcohol use, where classification can affect fibrosis risk identification.

Dinh HC, Tran TTK, Nguyen HH · Gastroenterologia y hepatologia · (2026) · View on PubMed ↗

The Hepato-Exposome Axis: How Endocrine Disruptors Hijack Liver Receptors to Drive MASLD.

This review examined how endocrine-disrupting chemicals (EDCs) drive metabolic dysfunction-associated steatotic liver disease (MASLD) by hijacking hepatic nuclear receptors and metabolic transcriptional networks. It proposes the “hepato-exposome axis,” mapping specific EDC families to nuclear receptors and downstream pathways relevant to lipid metabolism, glucose homeostasis, and mitochondrial dysfunction. The framework is scientifically significant because it links environmental exposures to mechanistic receptor targets that could guide future MASLD prevention and therapy.

Martín-Grau M, Kamstra JH, Hyötyläinen T et al. · Journal of hepatology · (2026) · View on PubMed ↗

A translational model of MASLD-associated HFpEF defines mitochondrial dysfunction and cardiac plasticity during disease progression and regression.

This translational preclinical study developed a MASLD-associated HFpEF model to define mitochondrial dysfunction and cardiac plasticity during disease progression and regression. Using Alms1-/- (Foz/Foz) models and left-ventricular functional and transcriptomic analyses, it characterized pathways linked to HFpEF-like cardiac dysfunction and its reversibility. The work is significant because it provides a mechanistic platform for understanding how liver metabolic disease drives HFpEF and how cardiac changes may be reversed.

Ganguly S, Gunes B, Gu Y et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗

Timing of Antidiabetic Medication Initiation and Risk of Cardiovascular Events and Mortality.

This target trial emulation cohort study evaluated whether the timing of antidiabetic medication (ADM) initiation within 3, 6, or 12 months after newly meeting type 2 diabetes (T2D) diagnostic criteria is associated with major adverse cardiovascular events (MACE) and all-cause mortality among adults in Korea (2013–2022). The key finding was not available because the abstract text provided is truncated before results are reported. If earlier ADM initiation reduces MACE and mortality, it would support tighter clinical timelines for starting therapy after T2D diagnosis.

Ko HY, Shin JY, Jung K et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Long-Term Resistance Training and Risk of Type 2 Diabetes.

This prospective cohort study investigated how long-term resistance training patterns—volume, consistency, and integration with aerobic activity and sedentary behavior—relate to incident type 2 diabetes (T2D) using US cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study). The key finding was not available because the abstract text provided is truncated before results are reported. Establishing dose- and pattern-specific resistance training guidance could improve T2D prevention recommendations alongside aerobic activity and sedentary behavior management.

Zhang T, Zhang Y, Lee DH et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Youth Sports, Brain Health & Biomarkers

Youth Soccer Participation and Brain Health Outcomes in Adolescent Athletes.

This prospective longitudinal cohort study tested whether participation in one season of youth soccer is associated with changes in cognition, behavior, balance, brain structure/function, or blood biomarkers compared with noncontact sports in male adolescent athletes across European centers (Munich, Leuven, Oslo). The key finding was not available because the abstract text provided is truncated before results are reported. If soccer participation produces measurable early brain or biomarker changes, it would inform youth sports safety policies and monitoring for repetitive head impacts.

Koerte IK, Wiegand TLT, Bonke EM et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Genetics of Kidney Disease & Transplant Outcomes

Fabry Disease: Current Perspectives on Diagnosis and Management Strategies.

This narrative review summarized current perspectives on diagnosis and management of Fabry disease, an X-linked lysosomal storage disorder caused by deficient α-galactosidase A leading to globotriaosylceramide accumulation. It emphasized that diagnosis relies on clinical suspicion plus enzymatic assays and genetic testing, and it contrasted classic (type 1) childhood-onset with late-onset (type 2) adult-predominant cardiac/renal disease. The review is clinically significant for improving early recognition and guiding management strategies in a rare, multisystem condition.

Norouzi S, Ghozloujeh ZG, Lerma E et al. · Advances in kidney disease and health · (2026) · View on PubMed ↗

NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson’s disease.

This study introduced NERINE, a hierarchical model-based rare variant association test that incorporates gene network topology to improve rare-variant gene-network analyses across phenotypes. The key finding was that NERINE identified rare variant associations in gene networks and implicated an SNCA–PRL–LRRK2 subnetwork in Parkinson’s disease. This bridges statistical genetics with mechanistic network models, prioritizing specific gene subnetworks for follow-up in PD biology.

Nazeen S, Wang X, Morrow AR et al. · Cell genomics · (2026) · View on PubMed ↗ · Free PDF ↗

Pathogenic variants in ACTRT3 lead to male infertility characterized by fertilization defects.

This study investigated whether pathogenic variants in ACTRT3 cause male infertility characterized by fertilization defects in affected men with normal sperm motility. The authors identified ACTRT3 as a novel primary disease gene, linking ACTRT3 dysfunction to fertilization failure despite preserved motility. These findings expand the genetic basis of male infertility and implicate an actin-related testis pathway (ACTRT3 interacting with Profilin3 during spermatogenesis) as a mechanistic target for diagnosis and future intervention.

Zhu H, Shi R, Zou G et al. · Human reproduction (Oxford, England) · (2026) · View on PubMed ↗

Apolipoprotein L1 Gene Genotype and Kidney Outcomes After Living Kidney Donation.

This retrospective cohort study examined whether apolipoprotein L1 (APOL1) gene polymorphisms are associated with worse kidney outcomes after living kidney donation among Black and White US donors who donated from 2000–2008. The key finding was not available because the abstract text provided is truncated before results are reported. Clinically, identifying APOL1-associated post-donation risk could refine donor evaluation and long-term follow-up strategies for living kidney donors.

Hsu CY, Gao Y, Freedman BI et al. · JAMA internal medicine · (2026) · View on PubMed ↗

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Bipolar Depression Pharmacotherapy (Dose/Age Effects)

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar depression: A systematic review and dose-related network meta-analysis across different age groups.

This study systematically reviewed randomized controlled trials of pharmacological interventions for acute bipolar depression (type I/II/other) and performed a dose-related network meta-analysis to compare efficacy, response, and acceptability across different age groups. The key finding was that treatment effects varied by dose and that comparative efficacy/response and tolerability profiles were not uniform across age strata. These results support more age- and dose-informed selection of acute bipolar depression therapies to improve both symptom outcomes and acceptability.

Fornaro M, Di Lorenzo C, Oliva V et al. · Journal of affective disorders · (2026) · View on PubMed ↗

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Cancer Immunotherapy & Combination Strategies

Darolutamide versus abiraterone acetate-based triplets in patients with hormone-sensitive prostate cancer: real-world, head-to-head comparison from the ARON-3 study.

This real-world, head-to-head comparative study from the ARON-3 cohort evaluated darolutamide plus docetaxel plus androgen deprivation therapy (DARO+DOCE+ADT) versus abiraterone acetate plus docetaxel plus ADT (ABI+DOCE+ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Across 247 patients treated in 37 institutions across 14 countries, outcomes such as progression-free survival (PFS), overall survival (OS), PSA kinetics, and safety were compared using propensity score adjustment and Cox modeling. The findings are clinically relevant for selecting among triplet intensification regimens in routine practice, where comparative effectiveness and tolerability between darolutamide- and abiraterone-based triplets remain important.

Rescigno P, Taha T, Fita MJ et al. · Minerva urology and nephrology · (2026) · View on PubMed ↗

Fate induction through asymmetric T cell division is modulated by chimeric antigen receptor costimulatory domains.

The study examined how CAR T cell costimulatory domains (CD28 vs 4-1BB) regulate early memory fate acquisition by analyzing asymmetric T cell division outcomes after CAR engagement. CD28 CAR T cells showed higher CAR surface expression and enhanced surface proteome asymmetry after the first division, yet paradoxically acquired memory fate less efficiently than 4-1BB CAR T cells. This clarifies how specific CAR costimulatory signaling programs asymmetric division to shape long-lived memory formation, informing CAR T design to reduce relapse.

Frazee CS, Chen S, Berry CT et al. · Nature immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Acquisition of Vimentin by trogocytosis inhibits the NK cell-mediated immune response against circulating tumour cells (CTCs).

This study examined an immune-evasion mechanism in which tumor cells acquire vimentin and transfer it to NK cells, focusing on NKp46-dependent trogocytosis and circulating tumor cells (CTCs) from oral cancer patients. It found that vimentin delivered via NKp46-dependent trogocytosis impairs NK cell cytotoxicity, with non-endogenous vimentin detected in NK cells isolated from CTC-positive patients, supported by high-throughput proteomics, flow cytometry, and confocal microscopy. The significance is that blocking the NKp46–trogocytosis/vimentin transfer axis could restore NK-mediated clearance of CTCs and improve anti-tumor immunity.

Zhao L, Li R, Meng XY et al. · Cellular & molecular immunology · (2026) · View on PubMed ↗

IL-10 secretion by CD8 T cells orchestrates early NK cell recruitment and antitumor immunity after anti-VEGFR-2/PD-1 therapy.

The study investigated how IL-10 secretion by CD8 T cells regulates early natural killer (NK) cell recruitment and antitumor immunity after combined anti-VEGFR-2/PD-1 therapy in preclinical colorectal cancer models. It showed that CD8 T cells respond early to VEGFR-2 inhibition and orchestrate NK recruitment via IL-10, preceding later overt cytotoxic immune changes. These mechanistic insights suggest that IL-10–dependent CD8-to-NK crosstalk is a key driver of early immune activation during antiangiogenic plus checkpoint blockade therapy.

Geindreau M, Pignol C, Coënon L et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Addition of ipilimumab to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (PRODIGE 81-FFCD 2101-TRIPLET HCC): phase 2 results from a randomised, multicentre, open-label, phase 2-3 trial.

This phase 2-3 randomized, multicentre, open-label trial enrolled adults with unresectable, treatment-naïve hepatocellular carcinoma to test whether adding ipilimumab to atezolizumab plus bevacizumab improves outcomes (PRODIGE 81-FFCD 2101-TRIPLET HCC). The key finding from the preplanned phase 2 results was the triple combination’s survival efficacy signal together with a defined safety profile in the first-line setting. Clinically, the study informs whether CTLA-4 intensification (ipilimumab) meaningfully improves benefit over the established atezolizumab–bevacizumab backbone.

Merle P, Blanc JF, Le Malicot K et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

Immune checkpoint blockade augments lymphodepleting chemotherapy-induced antitumor immunity by expanding effector CD8+ T cell clones.

This study evaluated how immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 modulates cyclophosphamide (CTX)-induced antitumor immunity by expanding effector CD8+ T cell clones. The key finding was that ICB augments CTX-driven homeostatic proliferation and expands effector CD8+ T cell clonotypes, thereby strengthening antigen-specific antitumor responses. This supports a mechanism-based combination strategy pairing CTX with checkpoint inhibition to improve efficacy and potentially overcome resistance to ICB.

George MM, Hamadene L, Marouf Y et al. · Cancer research · (2026) · View on PubMed ↗

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Autoimmunity & Inflammatory Disease Continuum (IBD/SpA)

Biologic drugs for induction and maintenance of remission in Crohn’s disease: a network meta-analysis.

This network meta-analysis synthesized evidence on biologic and advanced therapies for induction and maintenance of remission in Crohn’s disease, comparing multiple drug mechanisms and ranking their relative efficacy and safety. The study’s objective was to clarify which biologics best achieve and sustain remission, using a comprehensive search of major databases up to June 2025 and network meta-analytic methods. The results are significant for evidence-based treatment selection in Crohn’s disease, where many patients fail to reach or maintain remission with conventional therapies.

Gordon M, Sinopoulou V, Akobeng AK et al. · The Cochrane database of systematic reviews · (2026) · View on PubMed ↗

The at-risk-to-early continuum of enteropathic spondyloarthritis.

This article synthesized epidemiological, imaging, and biomarker evidence to define an at-risk-to-early continuum for enteropathic spondyloarthritis in people with inflammatory bowel disease. The key finding was that high-risk IBD phenotypes with early extraintestinal manifestations and non-specific pain can progress through subclinical MRI/ultrasound sacroiliac/enthesial inflammation to early clinical enteropathic spondyloarthritis, often after prolonged diagnostic ambiguity. Scientifically and clinically, it provides a framework for earlier identification and potentially preventable intervention before overt synovitis/enthesitis/inflammatory back pain develops.

Caso F, Nardone OM, Costa L et al. · The Lancet. Rheumatology · (2026) · View on PubMed ↗

Challenges and Future Trends in Large Vessel Vasculitis.

This Circulation review summarized challenges and future trends in diagnosing and managing large vessel vasculitis (LVV), focusing on giant cell arteritis and Takayasu arteritis. It emphasizes that LVV pathogenesis is multifactorial—combining genetic predisposition, environmental/geographic triggers, immune dysregulation, and immune/vascular senescence—and that diagnosis based on clinical presentation alone can be difficult. The article is important for guiding future research and improving diagnostic and therapeutic approaches for LVV, particularly given sex differences in prevalence.

Sandovici M, van der Geest KSM, Reitsema RD et al. · Circulation · (2026) · View on PubMed ↗

Gingival Fibroblast-Driven Osteoimmunology via the IL-33-ILC2-IL-13 Axis.

This study investigated the cellular and molecular mechanisms of alveolar bone regeneration after tooth extraction, focusing on gingival fibroblast-driven osteoimmunology via the IL-33–ILC2–IL-13 axis. Using single-cell RNA sequencing and flow cytometry, the authors identified group 2 innate lymphoid cells (ILC2s) as pivotal regulators of post-extraction alveolar bone regeneration. The work links fibroblast-immune signaling to bone repair, suggesting IL-33/ILC2/IL-13 pathway modulation as a potential therapeutic approach for improving regeneration after dental procedures.

Sato Y, Kondo T, Otake K et al. · Journal of dental research · (2026) · View on PubMed ↗

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Cancer Metastasis Biology & Lineage Plasticity

Longitudinal changes in DNA methylation in IDH-mutant glioma fuel disease progression through altered cell state differentiation.

The study profiled a longitudinal cohort of 36 IDH-mutant glioma samples from 19 patients using joint-capture single-nucleus multi-omics (single-nucleus DNA methylation and single-nucleus RNA-seq) plus bulk exome sequencing to define epigenetic drivers of progression. IDH-G progression was associated with increased malignant stem-like states, decreased differentiation, and methylation loss that was uniformly present across malignant cells within individual tumors and linked to worse clinical outcomes. These findings implicate progressive, cell-state–linked methylation erosion as a mechanistic fuel for IDH-G aggressiveness and a potential prognostic biomarker.

Nomura M, Raviram R, Schiffman JS et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Mediator subunit MED4 enforces metastatic dormancy in breast cancer.

The study investigated how the Mediator subunit MED4 regulates metastatic dormancy in breast cancer using an unbiased genome-scale genetic screen and functional testing in metastatic models. MED4 was identified as a cancer cell–intrinsic gatekeeper of metastatic reactivation, and MED4 haploinsufficiency was common in metastatic breast cancer and associated with poorer clinical outcomes, while syngeneic mouse metastasis models showed MED4 enforces dormancy. These results position MED4 as a potential therapeutic target or biomarker for preventing metastatic outgrowth from dormant disseminated cells.

Bae SS, Ling HH, Zhang J et al. · Nature cell biology · (2026) · 1 citations · View on PubMed ↗

Sympathetic immunomodulation suppresses liver metastasis by maintaining the balance between norepinephrine concentration and the α2a/β2-AR ratio.

This preclinical study investigated sympathetic immunomodulation in a colorectal cancer liver metastasis model, focusing on norepinephrine (NE) concentration and the α2a/β2-adrenergic receptor (α2a/β2-AR) balance. It found that hepatic sympathetic nerve activity and moderately increased NE occur early in metastasis, and that only daily low-dose NE maintaining moderate hepatic NE levels suppressed metastatic tumor growth, whereas extremely low NE (induced by 6-hydroxydopamine, 6-OHDA) or other conditions disrupting the NE/α2a/β2-AR balance reduced the anti-metastatic effect. Clinically, the work suggests that timing and dosing that preserve an optimal NE–receptor signaling window could be a therapeutic concept for limiting liver metastasis.

Gao L, Li J, Li B et al. · Cellular & molecular immunology · (2026) · View on PubMed ↗

MiT fusions, TSC1-TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa.

This study used comprehensive multi-omic profiling to classify ultra-rare perivascular epithelioid cell neoplasms (PEComas) and identify genetic drivers in an unselected PEComa cohort. Frequent MITF rearrangements were found involving actin gene partners (ACTA2, ACTG1, ACTB), and transcriptomics defined four subtypes (melanocytic, mesenchymal, adipogenic) with distinct lineage programs and vulnerabilities, including TFE3/MITF rearrangements enriched in non-gynecologic tumors. The results provide a molecular framework for PEComa origin and potential targeted therapy selection based on MITF/TFE3 fusion status and pathway dependencies.

Gantzer J, Lu X, Charon-Barra C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting.

The study used large-scale, high-resolution mass spectrometry–based proteomics and phosphoproteomics on nasopharyngeal carcinoma (NPC) and non-cancerous nasopharyngeal tissues to define molecular subtypes. It classified NPC into two proteomic/phosphoproteomic subtypes (S1 and S2), with S2 showing stronger immune-suppressive characteristics and greater clinical heterogeneity. This proteomics-defined stratification could enable more precise therapeutic targeting and patient selection in NPC.

Wu YP, He YH, Hu GS et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Yorkie/Scalloped-OVOL-Rac1 axis controls insect wing development by promoting cell proliferation.

This study investigated how the Yorkie/Scalloped (Yki/Sd)–OVOL–Rac1 regulatory axis controls insect wing development by promoting cell proliferation. It identified the zinc finger transcription factor OVOL as a critical mediator of Hippo signaling and showed that OVOL is required for normal wing formation in Locusta migratoria and Drosophila melanogaster, regulating cell proliferation and trichome patterning. The findings are significant because they connect conserved Hippo pathway outputs to OVOL and Rac1-driven growth control in a tractable insect model.

Zhang J, Zhang Y, Chang BH et al. · Journal of genetics and genomics = Yi chuan xue bao · (2026) · View on PubMed ↗

Lineage plasticity driven by GATA6 loss fuels colorectal cancer metastasis.

This study investigated genetic and epigenetic drivers of colorectal cancer liver metastasis using a pro-metastatic organoid library generated by serial orthotopic transplantation of liver metastasis-derived organoids. Integrative RNA-seq and ATAC-seq identified multilineage transcriptional plasticity programs and implicated GATA6 loss as a key regulator of the epigenetic reprogramming that fuels metastasis. These findings highlight GATA6 as a mechanistic vulnerability and support targeting lineage-plasticity pathways to limit metastatic progression.

Goto S, Deshpande V, Yilmaz ÖH et al. · Cell stem cell · (2026) · View on PubMed ↗

Neuron-Derived MIF Engages VCAM1 to Fuel a Self-Amplifying CXCL8 Loop That Drives Perineural Invasion and Metastasis in Gastric Cancer.

This study examined how neuron-derived macrophage migration inhibitory factor (MIF) promotes perineural invasion and metastasis in gastric cancer through a VCAM1-driven self-amplifying CXCL8 loop. Integrating TCGA/GEO transcriptomics with validation in surgical specimens and using neuron–tumor co-culture plus siRNA/lentiviral perturbations, the authors implicated MIF–VCAM1 signaling in driving CXCL8 amplification and enhanced nerve invasion, supported by sciatic nerve invasion xenografts and orthotopic gastric cancer models using neuron-specific MIF conditional knockout mice. The work is clinically significant because it identifies a tumor–nerve crosstalk signaling circuit (MIF/VCAM1/CXCL8) that could be targeted to reduce perineural spread in gastric cancer.

Li X, Zhai Z, Yu H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Multivalent assembly of PAR-3/aPKC complexes establishes cell polarity in Caenorhabditis elegans zygotes.

This PNAS study investigated how multivalent assembly of PAR-3/aPKC complexes establishes cell polarity in Caenorhabditis elegans zygotes. Using in vivo and ex vivo single-molecule techniques with genetic perturbations, the authors showed cooperativity between PAR-3 oligomerization and PAR-3 binding to aPKC/PAR-6, and they provided evidence that aPKC and PAR-6 bind PAR-3 via independent sites. The findings are significant because they clarify the molecular logic linking scaffold oligomerization to polarity complex formation during early embryonic development.

Hsu SP, Dickinson DJ · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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GPCR Signaling & Biased Agonism

Molecular mechanisms of naturally encoded signaling bias at the complement anaphylatoxin receptors.

This work examined molecular mechanisms of naturally encoded biased agonism at human and mouse complement anaphylatoxin receptors C5aR1 and C5aR2. The key finding was that the naturally occurring C5a variant C5a-d-Arg produces robust G-protein coupling bias at C5aR1 with attenuated β-arrestin recruitment, driven by distinct conformational changes in TM7/helix 8 that impair GRK recruitment and receptor phosphorylation. Scientifically, it clarifies how endogenous ligands encode signaling bias, informing GPCR drug discovery strategies that aim for pathway-selective therapeutics.

Tiwari D, Sawada K, Dalal A et al. · Molecular cell · (2026) · View on PubMed ↗

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Neurodegeneration & Brain Metabolic Therapeutics (AD/PD)

Brain-on-a-Chip and Blood-Brain Barrier-on-a-Chip Modeling for Neurodegenerative Disorders: Recent Progress.

This review summarizes recent advances in microfluidic “brain-on-a-chip” and “blood-brain barrier (BBB)-on-a-chip” platforms for modeling neurodegenerative disorders and BBB dysfunction. It highlights that BBB-on-a-chip systems can recreate neurovascular unit transport and inflammatory disruption relevant to neurodegeneration, while also emphasizing ongoing challenges in translating these models to effective BBB-crossing neurotherapeutics. The article is significant because it consolidates engineering and biological progress toward more predictive in vitro models for studying disease mechanisms and testing treatments that must cross the BBB.

Kempuraj D, Shi H, Truong TD et al. · The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · (2026) · View on PubMed ↗

Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation.

This target trial emulation used TriNetX US electronic health records to compare real-world safety and effectiveness of lecanemab versus acetylcholinesterase inhibitors (AChEIs) in patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD). After 1:1 propensity score matching and Cox modeling, the study estimated comparative risks for clinical outcomes following initiation of lecanemab or AChEIs between July 2023 and September 2025. The findings are important for understanding how lecanemab performs in routine care relative to symptomatic AChEI therapy, particularly regarding safety and effectiveness in real-world populations.

Lee CY, Hsu CW, Tseng PT et al. · Alzheimer’s research & therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of ASO conjugation and receptor binding affinity on intracellular transport of mono- and bispecific TfR- and CD98-BrainshuttleTM variants.

This experimental study tested how antisense oligonucleotide (ASO) conjugation and receptor binding affinity affect intracellular transport of mono- and bispecific TfR- and CD98-BrainshuttleTM variants. By varying ASO cargo linkage and binding properties to transferrin receptor (TfR1) and CD98, the authors evaluated how these design parameters change cellular trafficking relevant to blood-brain barrier (BBB) shuttling. The results are significant for CNS ASO drug development because they provide mechanistic guidance for optimizing BrainshuttleTM constructs to improve delivery across the BBB.

Sela T, Wirth T, Sommer A et al. · mAbs · (2026) · View on PubMed ↗ · Free PDF ↗

Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.

The study developed co-expression network–based eQTL prediction models (INGENE and MODULE) using RNA-seq from six human post-mortem brain regions to capture distal (trans) regulatory effects for transcriptome-wide association studies in schizophrenia. Incorporating trans-acting variant influences within gene coexpression networks improved gene-expression prediction and highlighted new schizophrenia-associated genes beyond cis-only approaches. This provides a more complete framework for mapping non-coding genetic risk to brain regulatory mechanisms relevant to schizophrenia.

Rossi F, Sportelli L, Kikidis GC et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.

This review studied how trace-element dyshomeostasis and toxic metal exposure contribute to neurotoxicity across major neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ALS. It found that metal imbalance can act as a primary pathogenic driver in AD and PD and as an amplifier or risk modifier in HD and ALS, interacting with oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation. Scientifically, it supports targeting metal homeostasis and toxic metal exposure as potential prevention or therapeutic strategies across neurodegenerative disorders.

Tang M, Fleming E, Gu J et al. · Biological trace element research · (2026) · View on PubMed ↗

SECmeres outperform extracellular vesicles as potential blood RNA biomarkers for Alzheimer’s disease.

This study investigated whether SECmeres—sub-50 nm extracellular nanoparticles enriched for brain-specific markers—can serve as blood RNA biomarkers for Alzheimer’s disease (AD) compared with conventional extracellular vesicles/particles. SECmere-associated RNAs discriminated AD cases from controls with higher significance than small EVs, while large EVs showed no differences, and the discriminating RNAs were enriched for brain-associated signals. These findings suggest SECmeres as a more informative blood-based RNA source for AD biomarker development than small EVs.

Gonzalez-Kozlova E, Tichkule S, Nose Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

PARylation in Parkinson’s disease: a bridge between Lewy body formation and neuronal cell death.

This study investigated the role of PARylation, driven by PARP1, in Parkinson’s disease by analyzing post-mortem human PD brains for links between Lewy body formation and neuronal cell death. High-resolution imaging showed PAR accumulation in cytoplasm in PD-affected regions before α-synuclein oligomer formation, and PAR together with stress granules contributed to Lewy body formation. These findings position PARylation as a mechanistic bridge between early Lewy body pathology and downstream neuronal degeneration, suggesting PARP1/PAR pathways as potential intervention targets.

Novello C, Giampietro F, Calogero AM et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗

A α-synuclein aggregation inhibitor exerts neuroprotective effects via mitochondrial resilience in Parkinson’s disease.

The study evaluated A14, a novel small-molecule modulator, for its ability to inhibit α-synuclein (α-Syn) fibrillization and protect mitochondria in models of Parkinson’s disease. A14 was identified via structure-based virtual screening and shown to exert neuroprotective effects by enhancing mitochondrial resilience while disrupting the α-Syn aggregation–mitochondrial collapse pathogenic loop. This dual-action strategy supports A14 as a disease-modifying candidate targeting both toxic α-Syn structural formation and downstream bioenergetic failure in Parkinson’s disease.

Peng Y, Ye J, Wang H et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Neuroinflammation-centered pathophysiology and therapeutic strategy design in Alzheimer’s disease: Cutting-edge developments.

This article reviewed Alzheimer’s disease (AD) neuroinflammation-centered mechanisms and how they inform therapeutic strategy design. It highlights neuroinflammation as a central driver interacting dynamically with amyloid-β and tau pathology, emphasizing microglial activation pathways including TREM2 signaling, NLRP3 inflammasome activation, and complement cascade dysregulation. The synthesis is clinically relevant by identifying actionable inflammatory targets that may improve disease-modifying approaches in AD.

Li D, Zhang Z, Lu L et al. · Cellular signalling · (2026) · View on PubMed ↗

Oral GLP-1 receptor agonist promotes astrocyte-neuron lactate and lipid transfer with neuroprotective effects.

This study tested whether an oral, blood-brain barrier-penetrant GLP-1 receptor agonist (OHP2) can protect against Alzheimer’s disease by acting on brain cell metabolism. The key finding was that OHP2 primarily activates GLP-1R on astrocytes to increase aerobic glycolysis and lactate release, which is then taken up by neurons to elevate histone H3K9 lactylation (H3K9la) and promote neuroprotective effects. Clinically, it provides preclinical support for an orally deliverable GLP-1R agonist strategy that targets astrocyte–neuron metabolic coupling in AD.

Du Y, Sun C, Wu L et al. · Cell metabolism · (2026) · View on PubMed ↗

Lilrb4a Suppression Reprograms Microglia to Mitigate APOE4-Associated Amyloid Plaques and Cerebral Amyloid Angiopathy in Association With a PPAR-Linked Pro-Clearance State.

This study tested whether suppressing the mouse gene Lilrb4a (human LILRB4 ortholog) can mitigate APOE4-associated amyloid pathology in 5xFAD mice carrying human APOE4. Using genetic deletion or antisense oligonucleotide treatment, Lilrb4a reduction significantly decreased cortical amyloid plaque burden and APOE4-associated cerebral amyloid angiopathy without changing amyloid-β (Aβ) production, and transcriptomics supported a PPAR-linked pro-clearance state. These findings are significant because they suggest a microglial immune-reprogramming strategy targeting LILRB4/Lilrb4a to reduce vascular amyloid in APOE4-driven Alzheimer’s disease.

Nie C, Yang R, Wang X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Viral Immunology & Monoclonal Antibodies (WNV/HBV/Other)

Memory regulatory T cells reprogram into protective TFH cell-like effectors in recurrent malaria.

The study investigated how memory regulatory T cells (mTreg) respond during recurrent Plasmodium infection by combining longitudinal human and mouse analyses to track antigen-driven expansion and epigenetic reprogramming. During reinfection, mTreg cells underwent inflammation-induced epigenetic changes and transitioned into protective T follicular helper (TFH)-like effectors rather than maintaining purely FOXP3+ suppressive function. This reveals a mechanism by which recurrent malaria converts regulatory cells into protective effectors, suggesting targets to improve immunity without excessive immunopathology.

Charles-Chess NAE, Ruberto AA, Bowers C et al. · Nature immunology · (2026) · 1 citations · View on PubMed ↗

Survival Following Paralytic Rabies Encephalomyelitis in a Toddler: Challenges in Confirmation of Diagnosis.

This case report studied paralytic rabies encephalomyelitis in a toddler and focused on the diagnostic challenges of confirming rabies after possible post-exposure vaccination. The child survived despite rabies encephalomyelitis, highlighting that atypical paralytic presentations can lack classic furious-rabies features and that antibody-based confirmation may be confounded while molecular testing is technically limited. Clinically, the report underscores the need for rapid, reliable rabies confirmation strategies (including molecular detection when feasible) and aggressive supportive care even when rabies diagnosis is difficult.

James A, Varanasi SV, Jain S et al. · Indian journal of pediatrics · (2026) · View on PubMed ↗

Functional anti-preS1 antibody responses associated with viral control in chronic hepatitis B.

The study characterized circulating hepatitis B virus (HBV) preS1 antigen and anti-preS1 IgG in chronic HBV infection by developing ELISAs and testing functional neutralizing activity against HBV and hepatitis D virus (HDV) in 549 chronic HBV patients, 107 individuals with functional cure, and 110 vaccinated healthy controls. It found that functional anti-preS1 antibody responses were associated with viral control, linking serological specificity to virological and neutralizing function. This supports preS1-targeted antibody responses as potential biomarkers and mechanistic contributors to immune control in chronic hepatitis B.

Wang B, Li Y, Li F et al. · Gut · (2026) · View on PubMed ↗

Analysis of West Nile disease convalescents identifies human monoclonal antibodies protective against West Nile and related orthoflaviviruses.

This study analyzed antibodies from West Nile virus convalescent individuals to identify human monoclonal antibodies protective against West Nile and related orthoflaviviruses. The key finding was that potent neutralizing monoclonal antibodies included W010, which targets a distinct epitope in envelope protein domain III (EDIII) and conferred pre- and post-exposure protection in a murine WNV model. This supports development of EDIII-directed human monoclonals as prophylaxis or treatment candidates for WNV and related orthoflaviviruses.

Cervantes Rincón T, Frckova T, Contejean ZI et al. · Immunity · (2026) · View on PubMed ↗ · Free PDF ↗

Hepatitis B virus genome packaging and replication are coordinated by a polymerase-responsive RNA switch in the RNA element epsilon.

This PNAS study explored how hepatitis B virus (HBV) genome packaging and replication are coordinated by a polymerase-responsive RNA switch within the pgRNA epsilon (ε) element. The authors used in silico analyses of ε-like elements from related nakednaviruses to identify a distinct RNA rearrangement that occurs upon formation of functional ε–polymerase (P protein) complexes, coordinating minus-strand DNA synthesis and coencapsidation of pgRNA with the P protein. The work is significant because it advances mechanistic understanding of HBV RNA–polymerase regulation, informing strategies to disrupt replication and packaging.

Niklasch M, Wingert I, Fogeron ML et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Addition of blood-stage antibody enhances anti-sporozoite antibody protection in a humanized mouse model of Plasmodium falciparum infection.

This study used a humanized mouse model of Plasmodium falciparum infection to test whether adding a blood-stage antibody improves protection beyond circumsporozoite protein (CSP)-targeted immunity. The authors found that combining anti-CSP monoclonal antibodies with an additional blood-stage antibody enhanced anti-sporozoite antibody protection against breakthrough infection compared with CSP-only approaches. These results provide preclinical evidence that multistage antigen combinations (e.g., CSP plus blood-stage targets such as RH5) may improve malaria vaccine or therapeutic design.

Kirtley P, Martinson T, Donnellan FR et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell Death Pathways & Tumor Immunity (Cuproptosis/Ferroptosis/FUN)

Immune cell-intrinsic STING activation drives tumor ferroptosis via AA-mediated suppression of ACSL4 lactylation in colorectal cancer.

This work investigated how immune cell-intrinsic STING signaling regulates colorectal cancer (CRC) ferroptosis by linking STING to lipid metabolism and posttranslational modifications in the tumor microenvironment. STING activation in immune cells activated TBK1-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2) at Ser505, increasing arachidonic acid (AA) release and suppressing tumor ferroptosis by modulating AA-dependent pathways including ACSL4 lactylation. The study supports a mechanistic immune–tumor metabolic axis in which STING-driven signaling can tune ferroptotic sensitivity, informing strategies to manipulate ferroptosis for antitumor immunity in CRC.

Ding L, Du W, Zhu J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

OMA1 protects from liver injury and tumorigenesis during aging by controlling hepatic immunogenicity.

The study tested the role of the mitochondrial stress integrator OMA1 in aging-associated liver injury and tumorigenesis by using Oma1 knockout mice and assessing oxidative stress signaling, immune exhaustion, and tumor outcomes. Loss of OMA1 increased hepatic primary tumor incidence and reduced survival, with persistent KEAP1–Nrf2 oxidative stress pathway activation driving early liver injury that progressed to chronic inflammation and fibrosis during aging. The study also linked Oma1 deficiency to gradual accumulation of exhausted CD8+ and CD4+ T cells and showed that adoptive transfer/bone marrow approaches supported an immunogenic mechanism. This identifies OMA1 as a regulator of hepatic immunogenicity that protects against age-related liver cancer development.

Martí-Mateos Y, Muñoz-Hernández MDM, Gómez de Las Heras MM et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

Glucose starvation induces fumarate hydratase succinylation and inhibits ferroptosis to maintain colon cancer cell proliferation.

This study examined how glucose starvation affects colorectal cancer cell survival by focusing on fumarate hydratase (FH) succinylation and ferroptosis control. Under glucose starvation, FH protein was downregulated, leading to abnormal accumulation of upstream metabolites and altered FH succinylation, which in turn inhibited ferroptosis and supported colon cancer cell proliferation. The work links nutrient stress–driven post-translational regulation of FH to ferroptosis resistance, highlighting a potential vulnerability in CRC metabolic adaptation.

Sun LT, Qin XH, Zheng YD et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗

Cuproptosis-immunity crosstalk informs strategy to overcome immunotherapy resistance.

This study explored how cuproptosis intersects with antitumor immunity to overcome immunotherapy resistance, focusing on the role of ferredoxin 1 (FDX1)-dependent protein lipoylation. The key finding was that CD8+ T cell-mediated immunity increases tumor susceptibility to cuproptosis, and cuproptotic tumor cell death enhances dendritic cell activation and antitumor immunity, with CD8-derived IFN-γ upregulating FDX1 transcription in tumor cells. Scientifically, it suggests a combinatorial strategy pairing immunocompetent antitumor immunity with cuproptosis inducers to improve therapeutic responses.

Lei G, Lu Z, Xu Z et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

S100A9 modulates USP7-mediated stabilization of NCOA4 to promote ferroptosis in sepsis-associated acute lung injury.

This study investigated how the DAMP S100A9 regulates USP7-mediated stabilization of NCOA4 to drive ferritinophagy-dependent ferroptosis in sepsis-associated acute lung injury (SALI), focusing on macrophage cell death mechanisms. The authors identified an S100A9–USP7–NCOA4 axis that links inflammatory signaling to increased NCOA4 stability and ferroptosis execution during sepsis-associated lung injury. These mechanistic insights are scientifically significant because they nominate a druggable regulatory pathway (S100A9/USP7/NCOA4) to potentially limit ferroptosis-driven lung damage in sepsis.

Wei Y, Gu A, Wang B et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Cell-Intrinsic Resistance & Targetable Mechanisms

Machine-intelligent multimodal algebot for intracavitary chemotherapy.

The study engineered biohybrid magnetic algae microrobots with hierarchical nanoporous structure and an “algebot” machine-intelligent image-feedback system to perform non-contact convective transport for intracavitary chemotherapy in bladder cancer. The approach enabled autonomous navigation, reconfigurable swarming, selective drug release, and ultrafast tissue penetration to improve tumor targeting and drug delivery across tissue barriers. This provides a translational platform combining robotics, imaging control, and drug release for more effective intracavitary treatment.

Lin L, Li H, Zhou Q et al. · Nature nanotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Intravitreal Faricimab for Retinal Vein Occlusion: Real-World Outcomes from the Multicenter FARTURK-RVO Study in Türkiye.

The study evaluated real-world efficacy and safety of intravitreal faricimab for macular edema secondary to retinal vein occlusion (branch or central RVO) using retrospective multicenter data from 17 centers in Türkiye with up to 52 weeks follow-up. Patients receiving at least one faricimab injection with complete ophthalmic and OCT data showed clinical outcomes assessed by best-corrected visual acuity and OCT measures over a minimum 4-week period. These real-world results support the effectiveness and tolerability of faricimab in routine care for RVO-associated macular edema.

Akkan F, Görgün E, Erden B et al. · Ophthalmology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Proteomics reveals spatial and molecular heterogeneities in advanced atherosclerotic carotid artery plaques.

The study used histomorphology-guided spatial proteomics on 112 human carotid endarterectomy specimens to map molecular programs associated with plaque vulnerability, comparing thin-cap versus thick-cap atherosclerotic plaques. Differences were largely localized to the necrotic core and fibrous cap and were enriched for inflammation, lipid handling, extracellular matrix remodeling, and ossification/calcification pathways. This spatially resolves protein-level determinants of cap phenotype, improving mechanistic understanding of plaque rupture risk.

Sinha A, Sachs N, Kratz E et al. · Nature cardiovascular research · (2026) · View on PubMed ↗ · Free PDF ↗

An intelligent MRI-based all-in-one diagnostic strategy for axillary lymph node status in breast cancer.

This study developed and evaluated an MRI-based hierarchical multitask deep learning model (BCALN-Net) to predict axillary lymph node status in breast cancer patients, using 6,271 cases. BCALN-Net simultaneously predicted sentinel lymph node (SLN) metastasis, SLN metastatic burden, and non-SLN (NSLN) metastasis with high accuracy and robust performance across molecular subtypes and clinical stages. Clinically, this all-in-one imaging strategy could support axillary surgery de-escalation by improving preoperative identification of patients who need less extensive nodal treatment.

Zhang X, Qiu Y, Su Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Hepatic artery infusion pump chemotherapy for unresectable intrahepatic cholangiocarcinoma: Pooled individual patient-level analysis of four clinical trials.

This pooled individual patient-level analysis studied hepatic artery infusion pump (HAIP) chemotherapy using floxuridine (FUDR), with or without systemic therapy, in patients with unresectable, liver-confined intrahepatic cholangiocarcinoma (iCCA) from four phase II trials. Across 142 patients, the analysis evaluated long-term overall survival (OS) for those treated with HAIP-FUDR, including cases with or without resectable regional lymph node metastases. The work is significant because it strengthens evidence for HAIP-FUDR as a liver-directed option for unresectable iCCA and informs long-term expectations beyond initial trial outcomes.

Rousian M, Alessandris R, Schleimer L et al. · Journal of hepatology · (2026) · View on PubMed ↗

Optimal Retention Duration of Prophylactic Pancreatic Duct Stents Placed During Endoscopic Retrograde Cholangiopancreatography: A Multicenter Randomized Controlled Trial.

This multicenter randomized controlled trial studied the optimal retention duration of prophylactic 5-Fr single-pigtail unflanged pancreatic duct stents (PDS) placed during ERCP to prevent post-ERCP pancreatitis (PEP). Adults undergoing ERCP were randomized to scheduled PDS assessment at 2 weeks versus 4 weeks to minimize the need for endoscopic stent removal without compromising safety. The results are clinically important because they aim to standardize PDS management to reduce procedural burden while maintaining PEP prevention efficacy.

Jang DK, Choi YH, Kim EJ et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Sex-based differences in tolerability of developmental antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC).

This monocentric phase I–II cohort study evaluated sex-based differences in tolerability of developmental antibody–drug conjugates (ADCs) in advanced non-small-cell lung cancer (NSCLC) patients treated at Gustave Roussy between 2018 and 2023. Clinically significant treatment-related adverse events (grade ≥2, CTCAE v5.0), dose modifications, hospitalisations, and survival outcomes were analyzed by sex using univariate and multivariate methods. The findings are clinically important for improving sex-disaggregated safety assessment and optimizing ADC dosing strategies in NSCLC.

Parisi C, Banini M, Mantuano F et al. · ESMO open · (2026) · View on PubMed ↗ · Free PDF ↗

Phase 2 Trial of Intravesical Gemcitabine and Docetaxel as First-Line Treatment of Bacillus Calmette-Guérin (BCG)‒Naïve Nonmuscle-Invasive Urothelial Carcinoma: Updated, 3-Year Outcomes.

This prospective, single-arm, open-label phase 2 trial studied first-line intravesical gemcitabine plus docetaxel (Gem/Doce) in BCG-naïve high-risk nonmuscle-invasive urothelial carcinoma (NMIBC), reporting updated 3-year outcomes. Patients received weekly induction for 6 weeks followed by monthly maintenance for 2 years, and the study updated recurrence-free survival and related endpoints beyond the previously reported 1-year results. The long-term efficacy and durability of Gem/Doce in BCG-naïve HR NMIBC are clinically important for expanding bladder-sparing options when BCG is not yet used or is not applicable.

Garman TS, Lokeshwar S, Campbell J et al. · The Journal of urology · (2026) · View on PubMed ↗

EGFR N-Glycosylation Catalyzed by NDST2 Promotes Lenvatinib Resistance in Hepatocellular Carcinoma.

This study investigated mechanisms of lenvatinib resistance in hepatocellular carcinoma (HCC) by testing the role of EGFR N-glycosylation in patient-derived organoids (PDOs) and orthotopic xenograft models. Resistant PDOs showed increased EGFR N-glycosylation, higher EGFR protein expression, and a link to EGFR N-glycosylation catalyzed by NDST2. Clinically, this identifies an actionable resistance mechanism—EGFR glycosylation driven by NDST2—that could guide biomarker development and combination therapies to overcome lenvatinib resistance.

Gu H, Li F, Chen Y et al. · Cancer research · (2026) · View on PubMed ↗

Difelikefalin-associated adverse drug event signals: a real-world pharmacovigilance study from the FAERS database.

This real-world pharmacovigilance study analyzed adverse drug event (ADE) signals for difelikefalin, a peripherally acting selective κ-opioid receptor agonist, in hemodialysis patients using the FDA Adverse Event Reporting System (FAERS) from 2022–2025. The key finding was the identification of difelikefalin-associated ADE signals in this vulnerable population to generate hypotheses for subsequent clinical validation. This supports safer clinical use of difelikefalin by highlighting potential risks detectable through large-scale spontaneous reporting data.

Zhao J, Qiu Q, Zhang J et al. · Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · (2026) · View on PubMed ↗

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Generated automatically on June 24, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.