PubMed Trending Research Digest — April 24, 2026

Automated digest · 98 articles · 15 research areas · April 24, 2026

Overview

Across this week’s set, a dominant thread is “metabolism as control logic” for aging, immunity, and cancer. Multiple studies connect mitochondrial lipid/redox regulation (phosphatidylcholine synthesis, ER glutathione export, redox timing) and dietary inputs (intermittent fasting, fructose signaling, plant-forward patterns) to organismal function and disease risk. In parallel, gut microbial metabolites and bile acid ecology repeatedly emerge as actionable levers—ranging from lactate-driven lactylation that tunes intestinal inflammation/cancer, to F. prausnitzii enzyme–PD-L1 trafficking and FMT restoring bile acids to improve outcomes with immunotherapy or recurrent C. difficile.

On the oncology side, the field continues to converge on mechanisms that reshape immune visibility and cell-death susceptibility. Several papers highlight non-apoptotic death programs—especially ferroptosis—through targeted vulnerabilities (PRMT5, FAAH, copper chelation) and broader reviews emphasize how programmed cell death rewires the tumor immune microenvironment. Immunotherapy-focused work spans from biomarkers and engineering (NKG2A blockade in ovarian cancer, IL-2-orthogonal CAR T cells, CAR Treg concepts) to strategies for “cold-to-hot” conversion using low-dose radiotherapy plus checkpoint blockade. Meanwhile, cancer genomics/plasticity (ecDNA, DNA damage response vulnerabilities, splicing dysregulation) and translational modeling (spatially resolved precancer-to-invasion mapping; improved preclinical platforms for glioblastoma) underscore a push toward more precise, mechanism-linked patient stratification.

Finally, neurodegeneration and systemic aging biomarkers are advancing with increasingly multimodal, quantitative tools. Wearable-derived sleep variability and plasma klotho associate with early Alzheimer’s pathology and cognitive trajectories, while new imaging/AI frameworks aim to map MRI signals to cellular ground truth. In parallel, immune–stromal and inflammatory pathways (e.g., macrophage–fibroblast axes in fibrosis/TBI, gut–skin metabolite–immune circuits in atopic dermatitis) reinforce the broader theme that cross-tissue signaling networks—rather than single targets—are likely to determine disease course and therapeutic response.

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Mitochondrial metabolism & redox control

Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging.

This study investigated how aging-associated changes in phosphatidylcholine synthesis affect mitochondrial aging in wild-type Caenorhabditis elegans and long-lived clk-1(qm30) and isp-1(qm150) mitochondrial mutants, using proteomics, lipidomics, genetics, functional assays, and follow-up transcriptomics/metabolomics in humans. The authors found that a decline in phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging. These findings suggest that restoring phosphatidylcholine biosynthesis could be a therapeutic lever to preserve mitochondrial function during aging.

Poliezhaieva T, Li Y, Chaudhari PS et al. · Nature communications · (2026) · View on PubMed ↗

SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis.

This study investigated how the endoplasmic reticulum (ER) maintains redox homeostasis, focusing on glutathione transport in mammalian cells. Using rapid immunopurification of ER fractions for proteome/metabolome profiling combined with CRISPR screening, it identified SLC33A1 as the major ER GSSG exporter, where loss of SLC33A1 causes GSSG accumulation and disrupts ER redox balance. This is significant because it defines a specific transporter mechanism controlling ER oxidative folding conditions, with implications for secretory pathway function and redox-related diseases.

Liu S, Gad M, Li C et al. · Nature cell biology · (2026) · View on PubMed ↗

Redox rhythms promote fitness by modulating ageing-dependent reprogramming.

This study examined how age-related disruption of redox oscillations affects organismal fitness and aging-dependent transcriptional reprogramming in male mice. It found that disrupted redox rhythms are common diurnal alterations in aging across eight peripheral tissues, and that restoring redox rhythms via time-restricted antioxidant and pro-oxidant treatment improves glucose metabolism, motor performance, and aging-related characteristics in liver and skeletal muscle. The significance is that redox timing—not just redox state—can be therapeutically targeted to mitigate aspects of age-associated decline.

Wang X, Cui SS, Li XK et al. · Nature metabolism · (2026) · View on PubMed ↗

Oxytocin signaling in adipocytes is required for normal milk fat production.

Using mouse models with adipocyte-specific deletion of oxytocin receptors (OxtrΔAd), the study examined how oxytocin (OXT) signaling in adipocytes regulates milk fat production and neonatal growth. OxtrΔAd dams produced milk deficient in triglycerides, leading to reduced pup weight gain, and the phenotype was rescued by increasing dietary fat intake, with OXT sourced from oxytocinergic sympathetic neurons. This is significant for understanding neuroendocrine control of lactation and for identifying potential pathways to address lactation failure or metabolic dysfunction in mammals.

Li E, Yuan Y, Sun H et al. · Cell metabolism · (2026) · View on PubMed ↗

Mitochondrial translation elongation controls OXPHOS biogenesis by coordinating synthesis and folding of mitochondrially encoded proteins.

This mechanistic study investigated how mitochondrial translation elongation regulates oxidative phosphorylation (OXPHOS) biogenesis in the fungus Neurospora crassa, centering on the mitochondrial ribosomal RNA methyltransferase MRM1. The key finding was that MRM1 promotes OXPHOS biogenesis by repressing mitochondrial translation elongation through an N-terminal intrinsically disordered region (IDR) that binds both mitochondrial ribosomes and mRNAs, with disruption of either interaction accelerating elongation and increasing synthesis of mtDNA-encoded proteins. Scientifically, it identifies a non-catalytic, dual-binding role for MRM1 in coordinating mitochondrial protein synthesis and respiratory complex biogenesis.

Xie L, Ren S, Zhang L et al. · Molecular cell · (2026) · View on PubMed ↗

Uncovering shared and tissue-specific molecular adaptations to intermittent fasting in liver, brain, and muscle.

This study used comprehensive proteomics and transcriptomics to characterize shared and tissue-specific molecular adaptations to intermittent fasting in male C57BL/6 mice across liver, skeletal muscle, and cerebral cortex after a 16-hour daily fasting regimen for 4 months (IF16). The key finding is that IF improved systemic metabolic markers (e.g., lower blood glucose, HbA1c, cholesterol and higher ketone bodies) while producing distinct organ-specific proteomic and transcriptomic response patterns. These results clarify how intermittent fasting drives both common and tissue-restricted pathways, supporting mechanistic translation of dietary interventions for metabolic health.

Fan Y, De Silva S, Tabassum NI et al. · eLife · (2026) · View on PubMed ↗

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Microbiome, metabolites & gut–immune axes

Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.

This review studied lactate metabolism-driven lactylation as a mechanism that can paradoxically modulate intestinal inflammation and malignancy. The key finding is that lactate-dependent lactylation links metabolic state to epigenetic regulation, influencing both inflammatory and cancer-related processes in the gut. This is significant because it frames lactate metabolism/lactylation as a potential therapeutic target for intestinal inflammatory diseases and gut malignancies.

Liu J, Liu Y, Zhang H et al. · Journal of translational medicine · (2026) · View on PubMed ↗

Faecalibacterium prausnitzii enzyme reprograms PD-L1 trafficking and sensitizes colorectal cancer to immunotherapy in mice.

This study examined how the gut bacterium Faecalibacterium prausnitzii and its enzyme phosphoribosyl pyrophosphate synthetase (fpPRPS) affect colorectal cancer (CRC) outcomes and immunotherapy responses in CRC patient cohorts and mouse CRC models (AOM/DSS and Apcmin/+). F. prausnitzii abundance correlated with improved survival and immunotherapy response, and bacterial fpPRPS inhibited tumor development by reprogramming PD-L1 trafficking to sensitize CRC to immunotherapy. These findings identify a specific microbial enzyme–PD-L1 trafficking axis as a potential strategy to enhance anti–PD-1/PD-L1 immunotherapy efficacy in CRC.

Ji S, Liu Y, Xu Y et al. · Nature microbiology · (2026) · View on PubMed ↗

Oral microbiome signatures predict biological age and host health.

This study evaluated whether oral microbiome composition can serve as a non-invasive biomarker of biological age and health by analyzing oral microbiome data from two NHANES cohorts (N=4,675) and validating in an external cohort (N=1,293). It identified 64 age-dependent bacterial genera and built a machine-learning model to predict chronological age, defining an Oral Microbiome Aging Acceleration (OMAA) score that associated with all-cause mortality and frailty. These findings suggest oral microbiome–based aging clocks could support preventive risk stratification in clinical practice.

Zhao JJ, Hu M, Li S et al. · Nature communications · (2026) · View on PubMed ↗

Efgartigimod in Sjögren’s disease: a phase 2, randomised, placebo-controlled, parallel-group, double-blinded, proof-of-concept study (RHO).

In adults with Sjögren’s disease, a phase 2 randomized, double-blind, placebo-controlled multicentre trial (RHO) evaluated intravenous efgartigimod 10 mg/kg once weekly for 24 weeks versus placebo, with efficacy assessed using the CRESS responder composite. Efgartigimod showed proof-of-concept efficacy on the primary CRESS responder endpoint at week 24 and was evaluated for safety across systemic disease activity, patient-reported symptoms, tear/salivary gland function, and serology. If confirmed in larger studies, efgartigimod could represent a targeted immunotherapy option for Sjögren’s disease by improving multiple disease domains.

Peene I, Verstappen GM, Arends S et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

Intestinal dysbiosis exacerbates skin inflammation via microbial metabolite-driven Th2 cell differentiation.

In mice and in human atopic dermatitis (AD) patients, the study tested how intestinal dysbiosis drives skin inflammation through microbial metabolite-driven Th2 differentiation, using Toll-like receptor 4 (TLR4) epithelial deficiency as a mechanistic perturbation. TLR4 deficiency reshaped the microbiome (including reduced Akkermansia muciniphila and enrichment of CutC-expressing bacteria), increased choline-to-trimethylamine conversion and circulating TMAO, and exacerbated AD-like skin inflammation with Th2 skewing; AD patients had higher plasma TMAO correlated with severity. These findings are significant because they identify a gut–metabolite–immune axis (CutC/TMAO) that could be targeted to treat or stratify AD.

Yu L, Peng S, Chen X et al. · Immunity · (2026) · View on PubMed ↗

Improving immunotherapy in solid tumors using FMT.

This study reviewed clinical evidence that fecal microbiota transplantation (FMT) improves first-line immune checkpoint inhibitor efficacy in solid tumors, focusing on renal cell carcinoma, cutaneous melanoma, and non-small cell lung cancer patients. The key finding was that FMT-mediated benefit is associated with functional microbiome remodeling, depletion of deleterious taxa, and systemic immunometabolic modulation that enhances responses to immune checkpoint inhibitors. These results support microbiome-directed therapeutic strategies to improve immunotherapy outcomes in multiple solid-tumor indications.

Davar D, Zarour HM, Trinchieri G · Cell · (2026) · View on PubMed ↗

Effect of Probiotics on the Clinical Outcome and Inflammatory Response in Gastric Cancer Surgery: A Double Blinded Randomized Control Trial.

This double-blinded, randomized, placebo-controlled trial evaluated whether probiotics improve postoperative outcomes and inflammatory/immune responses in gastric cancer patients undergoing open gastrectomy. The key finding was that probiotic administration (for 10 days, per the abstract) was tested for effects on length of hospital stay, nutritional status, and postoperative inflammatory and immune markers compared with placebo. Clinically, the trial addresses whether gut microbiota modulation can reduce postoperative complications and immune dysfunction in gastric cancer surgery patients.

Pal D, Anandhi A, Keerthi AR et al. · Journal of gastrointestinal cancer · (2026) · View on PubMed ↗

Pharmacological interventions targeting the gut-brain axis in neurological disorders: mechanisms and translational applications.

This article reviewed pharmacological interventions that target the gut–brain axis in neurological disorders, focusing on mechanistic pathways linking gut microbiota changes to brain outcomes. The key finding is that gut–brain signaling through neural, immune, endocrine, and metabolic routes can modulate neuroinflammation, neurotransmission, and blood–brain barrier integrity, providing rationale for translational therapeutic strategies. Scientifically, it consolidates evidence supporting gut–brain axis modulation as a potential intervention framework across multiple neurological and psychiatric conditions.

Li X, Zhou W, Yang S et al. · Frontiers in neuroscience · (2026) · View on PubMed ↗

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Cancer cell death & ferroptosis/necrotic pathways

Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.

This review studied programmed cell death (PCD) pathways—especially apoptosis, pyroptosis, ferroptosis, and necroptosis—in lung cancer, including their mechanisms, immune effects, and therapeutic implications. It found that PCD pathways shape tumor immune microenvironment and influence response or resistance to therapies such as immune checkpoint blockade, with tumor immune evasion often linked to altered PCD signaling. This is significant because it frames how combining or targeting specific PCD mechanisms could improve lung cancer treatment outcomes.

Liu Y, Chen Q, Xu J et al. · Apoptosis : an international journal on programmed cell death · (2026) · View on PubMed ↗

FAAH initiates a positive feedback loop to promote lung adenocarcinoma progression through inhibition of ferroptosis.

This study investigated the role of fatty acid amide hydrolase (FAAH) in regulating ferroptosis and lung adenocarcinoma (LUAD) progression in LUAD patient samples and LUAD cell models. FAAH was upregulated in LUAD and promoted progression by inhibiting ferroptosis, mechanistically enhancing STAT3 palmitoylation via conversion of N-palmitoylethanolamine to palmitic acid in a positive feedback loop. Targeting FAAH could therefore restore ferroptotic cell death and provide a therapeutic vulnerability for LUAD.

He X, Tang C, Jiang T et al. · Cell death and differentiation · (2026) · View on PubMed ↗

Cell death in cancer.

This review focused on the cancer hallmark of evading cell death and the therapeutic opportunity of restoring cancer cell death by understanding multiple cell-death programs beyond apoptosis. It summarizes how apoptosis remains the dominant program induced by radiation and chemotherapy, while non-apoptotic pathways such as necroptosis, pyroptosis, and ferroptosis can drive inflammatory signaling and modulate tumor–stroma–immune interactions that affect immunotherapy outcomes. The significance is that selecting or combining therapies to engage specific death programs could improve anti-tumor efficacy and immune engagement.

Conrad M, Strasser A, Jost PJ et al. · Cell · (2026) · View on PubMed ↗

The ecological dynamics of skin microbiota in skin health and diseases.

This review synthesized evidence on how skin microbiota composition and function relate to skin health and diseases, focusing on dysbiosis in conditions such as atopic dermatitis, psoriasis, and acne. It highlights specific microbes (e.g., Staphylococcus aureus and Cutibacterium acnes) that can either promote or protect against disease through effects on host immunity, barrier function, and metabolism. The work frames microbiome-targeted diagnostics and therapies as potential avenues for improving management of inflammatory and infectious skin disorders.

Pu P, Wang Y, Liu X et al. · Clinical microbiology reviews · (2026) · View on PubMed ↗

Rational Design of Schiff Base Copper Chelators as Potent Necroptosis Inducers for Anticancer Therapy.

The study rationally designed and synthesized novel Schiff base copper chelators to induce necroptosis for anticancer therapy, evaluating their activity in cancer models sensitive to copper depletion. The key finding is that specific Schiff base structural modifications improved copper specificity and bioactivity, enabling potent necroptosis induction via copper chelation (“copper addiction” targeting). This provides a drug-design framework for next-generation, more selective copper chelators that could translate into anticancer strategies that trigger regulated necrotic cell death.

Yu LB, Guan QX, Huang ST et al. · Journal of medicinal chemistry · (2026) · View on PubMed ↗

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Cancer immunotherapy & tumor microenvironment

NKG2A inhibition promotes NK cell-CD8+ T cell interactions to improve anticancer immunity in ovarian carcinoma.

This study analyzed NK-cell and CD8+ T-cell interactions in ovarian carcinoma, focusing on NKG2A-expressing dysfunctional NK cells, using transcriptomic/spatial profiling of patient samples and syngeneic mouse models. Inhibiting NKG2A promoted productive NK–CD8+ T-cell crosstalk and improved anticancer immunity, with depletion of either cell type impairing the reciprocal population’s function. The results support NKG2A blockade as a way to rewire innate–adaptive immune cooperation in high-grade serous ovarian carcinoma.

Lanickova T, Angelidou A, Hensler M et al. · Nature communications · (2026) · View on PubMed ↗

Identification of cycling regulatory T cell precursors as conductors of immune escape during breast carcinoma progression.

The study used transcriptomic mapping of immune landscapes across normal breast, ductal carcinoma in situ (DCIS), and invasive breast cancer (IBC) cohorts to define immune-cell programs driving immune escape during the DCIS-to-IBC transition. Cycling regulatory T cell precursors (cycTreg) were identified as orchestrators of immunosuppression in IBC, with cycTreg frequency predicting cytotoxic CD8+ T-cell responses, TCR diversity, disease-specific survival in IBC, and DCIS recurrence, and cycTreg acting as precursors to mature Tregs in a rat breast cancer model. These findings suggest cycTreg as a prognostic biomarker and a mechanistic target to prevent or reverse immune escape during breast cancer progression.

Bui TM, Jimenez ER, Li Z et al. · Cancer cell · (2026) · View on PubMed ↗

Unlocking the potential of T cell engagers in solid tumors.

This review article evaluated the current state of T cell engagers (TCEs) for solid tumors, focusing on how target heterogeneity, immunosuppressive tumor microenvironments, on-target toxicity, and safety complexity limit translation from hematologic malignancies. It concludes that improved target selection, protein engineering, and clinical trial design principles will guide next-generation TCE development for solid cancers. Scientifically, it provides a roadmap for optimizing TCE specificity and efficacy while mitigating normal-tissue toxicity in heterogeneous solid tumor settings.

Wingrove E, Bailis JM, Farago AF et al. · Cancer cell · (2026) · View on PubMed ↗

Cancer cachexia: A tumor-driven disorder of whole-body homeostasis.

This review summarized how cancer cachexia is driven by tumor-induced disruption of whole-body homeostasis, emphasizing skeletal muscle atrophy and adipose tissue loss across multiple malignancies. It highlights that cachexia emerges from dynamic interactions among immune, metabolic, endocrine, and neural networks that reshape energy balance and tissue integrity, while effective therapies remain limited due to incomplete mechanistic understanding. Clinically, the work underscores cachexia as a major determinant of functional decline, reduced treatment tolerance, and poor survival, motivating deeper mechanistic and therapeutic development.

Zhang Y, Nipp RD, Janowitz T et al. · Cancer cell · (2026) · View on PubMed ↗

Infusion-Related Reactions from Immune Checkpoint Inhibitors in Solid Tumors: A Proportional and Network Meta-Analysis.

This network meta-analysis and proportional meta-analysis compared infusion-related reactions (IRRs) across immune checkpoint inhibitor (ICI) regimens in solid tumors using phase 3 randomized controlled trials. The key finding was that IRR incidence varies by ICI type and that the study used random-effects network meta-analysis to estimate odds ratios for IRRs across dual ICI combinations, ICI monotherapy, and placebo/observation arms. Clinically, these comparative estimates can inform risk stratification and selection of ICI regimens to mitigate IRRs during cancer immunotherapy.

Fujiwara Y, Takahashi T, Tsuchiya K et al. · Targeted oncology · (2026) · View on PubMed ↗

Viral vector-free generation of orthogonal IL-2-responsive CAR T cells through gene editing of IL-2 and its receptor.

This study developed a viral vector-free gene-editing approach to generate orthogonal IL-2-responsive CAR T cells by editing IL-2 and its receptor, producing orthogonal IL-2Rβ (oIL-2Rβ) mutations via prime editing. It found prime editing achieved ~72% average efficiency, that the mutations were functional and improved CAR T-cell engraftment, efficacy, and toxicity in vivo, and that inserting a CD19-specific CAR into the IL-2 locus (with a chicken β-globin promoter) supported comparable performance to cotransduction-generated orthoCAR T cells. This is significant because it offers a potentially safer, scalable manufacturing route for IL-2-optimized CAR T therapies.

Zhang Q, Wu Y, Yang J et al. · Blood immunology & cellular therapy · (2025) · View on PubMed ↗

One-step knock-in CAR constructs in human NK cells enable scalable, TGFβ1-resistant immunotherapy for solid tumors.

The study engineered primary human NK cells by one-step electroporation of Cas9 ribonucleoprotein plus a dsDNA donor to knock out TGFBR2 and knock in a mesothelin CAR, with cytokine activation (IL-12/15/18), and compared performance against a two-step AAV approach while testing dexamethasone during manufacturing. The key finding is that this scalable one-step knock-in strategy yields TGFβ1-resistant mesothelin CAR NK cells with improved anti-solid-tumor function relative to less resistant configurations. This is significant because it targets a major immunosuppressive barrier in solid tumors (TGFβ signaling) using an efficient genome-editing workflow suitable for broader CAR-NK manufacturing.

Yee SM, Jeong JH, Kim D et al. · Theranostics · (2026) · View on PubMed ↗

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Cancer genomics, DNA damage & cellular plasticity

Mapping intratumor heterogeneity across layers for advancing immunotherapy.

This perspective/review addressed how intratumor heterogeneity across genetic, epigenetic, transcriptional, proteomic, and immunopeptidomic layers shapes immunotherapy responses. It argues that non-mutational heterogeneity and plasticity create dynamic cancer cell states with distinct immune visibility by altering antigen processing and presentation, producing spatially and temporally distinct immunological niches through variation in the immunopeptidome. The significance is that mapping heterogeneity at the immunopeptidome level could better predict and guide immunotherapy targeting strategies.

Marine JC, Bartok O, Sagie S et al. · Cell · (2026) · View on PubMed ↗

A recipe for chaos: Extrachromosomal DNA and the hallmarks of cancer.

This review examined how extrachromosomal DNA (ecDNA) contributes to aggressive cancer phenotypes by enabling rapid genome change and therapy resistance. It proposes integrating ecDNA biology into the hallmarks of cancer framework, emphasizing that oncogenic elements on ecDNA escape Mendelian inheritance, driving genomic chaos, accelerated evolution, and distinct therapeutic vulnerabilities. Scientifically, it reframes ecDNA as a driver of non-traditional vulnerabilities that may require therapies beyond conventional mutation-targeting approaches.

Wong IT, Bailey C, Wu S et al. · Cell · (2026) · View on PubMed ↗

Targeting genomic instability in cancer.

This review analyzed genomic instability as both an engine of cancer evolution and a therapeutic vulnerability, describing how failure of DNA integrity maintenance systems enables accumulation of genetic and epigenetic alterations. It highlights the clinical impact of targeting DNA damage response pathways, including the use of PARP inhibitors in homologous recombination repair-deficient tumors and the emergence of tumor-targeted DNA-damaging platforms such as antibody-drug conjugates (ADCs) and radiopharmaceuticals. The significance is that exploiting genomic instability can guide precision oncology strategies that selectively stress cancer cells’ DNA repair capacity.

Yap TA, Manning HC, Sapra P et al. · Cell · (2026) · View on PubMed ↗

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Cancer signaling networks & targeted vulnerabilities

PRMT5 inhibition sensitizes B-cell lymphoma cells to ferroptosis.

This study examined whether inhibiting PRMT5 affects ferroptosis sensitivity in B-cell lymphoma cell models, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). It found that PRMT5 inhibition sensitizes these cells to ferroptosis by upregulating SLC7A11, which increases cystine import for glutathione (GSH) biosynthesis, via the AKT–MYC–ATF5 signaling axis. This is clinically significant because targeting PRMT5 could be a strategy to overcome ferroptosis resistance in PRMT5-overexpressing B-cell lymphomas.

Liu Y, Chen R, Gao X et al. · Leukemia · (2026) · View on PubMed ↗

Intracellular IL-23R is necessary for mitotic spindle formation and viability in AML.

This research investigated the role of interleukin-23 receptor (IL-23R) in acute myeloid leukemia (AML), focusing on its intracellular localization and interaction partners. It found that intracellular IL-23R is increased in primary AML samples, localizes predominantly intracellularly, and interacts with mitotic spindle proteins identified by BioID mass spectrometry through an IL-23R (S/T)x(I/L)P motif, with IL-23R depletion impairing mitotic spindle formation and AML viability. The scientific significance is that IL-23R functions as a mitosis-supporting intracellular factor in AML, suggesting a potential vulnerability distinct from its canonical T-cell surface cytokine role.

Duong N, Khan DH, Thomas GE et al. · Leukemia · (2026) · View on PubMed ↗

Integrative single-cell analysis reveals endothelial diversity in the vasa vasorum of human atherosclerosis.

This study used integrative single-cell RNA sequencing to characterize endothelial diversity in the vasa vasorum within human atherosclerosis. It found that among 17,367 vascular endothelial cells pooled from five scRNA-seq studies, SULF1+ arterial endothelial cells were the main subcluster undergoing endothelial-to-mesenchymal transition (EndMT), capillary-like endothelial cells were primary mediators of angiogenesis, and a trajectory model supported tip-to-stalk transitions. The significance is that it pinpoints specific endothelial states and transitions that may drive plaque progression and could be targeted to modulate angiogenesis and EndMT.

Wu Y, Xue Z, Sun T et al. · Communications biology · (2026) · View on PubMed ↗

ELMO2 is a therapeutic vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer.

This study tested whether ELMO2 is a therapeutic vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer (NSCLC) using cellular and mechanistic experiments. ELMO2 suppression triggered excessive autophagy and cell death through FAK activity inhibition, and ELMO3 was identified as a compensatory paralog creating a synthetic lethal interaction with ELMO2 loss. Because ZEB1 repressed ELMO3 transcription in mesenchymal-like contexts, ZEB1-high/EMT-associated tumors became more sensitive to ELMO2 blockade, suggesting a targeted strategy for resistant NSCLC.

Li M, Xue Y, Chang Y et al. · Nature communications · (2026) · View on PubMed ↗

Hallmarks of liver cancer: Therapeutic implications.

This review synthesized the cancer hallmarks framework and mapped it onto therapeutic implications for primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). It emphasizes HCC hallmarks such as sustaining proliferative signaling, accessing vasculature, and avoiding immune detection, noting improved outcomes in advanced HCC with immunotherapies, while describing iCCA hallmark features including sustaining proliferative signaling (truncated in abstract). The significance is a unifying, hallmark-based rationale to guide targeted and immune-based treatment strategies in HCC and iCCA.

Llovet JM, Pinyol R, Affo S et al. · Cell · (2026) · View on PubMed ↗

Cancer neuroscience: The past, the present, and the road ahead.

This review examined how cancer-intrinsic neural features and nervous system signaling influence cancer initiation, growth, progression, metastasis, and treatment resistance, and how tumors reciprocally reprogram neural circuits to drive neuropsychiatric symptoms. It summarizes evidence for neuro-cancer crosstalk mechanisms such as neuron-to-cancer synapses and neuro-immuno-oncological interactions, and frames the field’s goal of developing neuroscience-instructed cancer therapies. The scientific significance is that targeting neuro-cancer communication may improve both disease control and patient quality of life.

Winkler F, Heuer S, Althammer F et al. · Cell · (2026) · View on PubMed ↗

UFMylation Suppresses Hepatocellular Carcinoma Metastasis by Inhibiting β-catenin-Driven Hybrid EMT and NK Cell Evasion.

This study analyzed human hepatocellular carcinoma (HCC) specimens and mechanistically tested how ubiquitin-fold modifier 1 (UFM1) conjugation (UFMylation) affects metastasis and immune evasion. The key finding was that UFMylation levels correlated with prognosis and metastatic burden, and that Emerin (EMD) was identified as a UFMylation substrate whose loss destabilizes EMD, leading to nuclear β-catenin accumulation, hybrid epithelial–mesenchymal transition (EMT), and enhanced NK cell evasion. Clinically, targeting the UFMylation–EMD–β-catenin axis may reduce HCC metastatic progression and improve antitumor immune responses.

Xu M, Gao X, Zhao J et al. · Cancer research · (2026) · View on PubMed ↗

Long-term effects of plant vs. animal protein supplementation on body composition, muscle strength, physical performance, and cardiometabolic risk factors in adults:a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials studied long-term (≥6 months) supplementation with plant-based protein (PBP) versus animal-based protein (ABP) in adults (≥18 years) and assessed body composition, muscle strength, physical performance, and cardiometabolic risk factors. It pooled evidence to compare the effects of different protein sources on these outcomes over extended durations. Clinically, the findings aim to inform dietary protein recommendations for improving musculoskeletal and cardiometabolic health.

Yimam MA, Roberts J, O’Callaghan A et al. · Frontiers in nutrition · (2026) · View on PubMed ↗

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Translational oncology models & clinical trial evidence

Boron neutron capture therapy (BNCT) for experimental bladder cancer: systemic or intravesical approach.

This preclinical study evaluated boron neutron capture therapy (BNCT) for experimental bladder cancer in Wistar rats, comparing systemic versus intravesical borophenilalanine administration and benchmarking against conventional radiotherapy (cRT). It found that BNCT delivered via the MARK TRIGA-II reactor produced antitumor and pro-inflammatory effects, with outcomes assessed by tumor staging/burden and proliferative and apoptotic indexes in bladder and perivesical tissues. The significance is that it informs how route of boron delivery (systemic vs intravesical) may affect BNCT efficacy and immune activation in bladder cancer models.

Teke K, Özer C, Yaprak Bayrak B et al. · British journal of cancer · (2026) · View on PubMed ↗

Lumen-apposing metal stents vs. self-expandable metal stents for endoscopic ultrasound-guided choledocoduodenostomy: a network meta-analysis of randomized controlled trials.

A network meta-analysis of randomized controlled trials compared lumen-apposing metal stents (LAMS), specifically cautery-enhanced LAMS (CE-LAMS), versus self-expandable metal stents (SEMS) for endoscopic ultrasound-guided choledocoduodenostomy (EUS-CDS) in patients with malignant distal biliary obstruction, using ERCP as a common comparator. The analysis synthesized comparative outcomes related to stent patency and safety between CE-LAMS-based and conventional SEMS-based strategies. This is clinically important because it helps clinicians choose the optimal EUS-CDS stent strategy to balance efficacy and adverse events in malignant biliary drainage.

Spadaccini M, Chen YI, van Wanrooij RLJ et al. · Endoscopy · (2026) · View on PubMed ↗

Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers.

This perspective addressed the rising incidence of early-onset cancers and birth-cohort effects, arguing for accelerating discovery of cancer causes to enable prevention and interception. It reviews milestones and challenges in cause discovery and proposes integrating epidemiologic and mechanistic studies using tissue ecosystem–anchored and other interconnected frameworks (truncated in abstract). The significance is a strategy to translate emerging epidemiology into actionable biological networks and preventive interventions for younger populations.

Shi M, Patti GJ, Gunter MJ et al. · Cell · (2026) · View on PubMed ↗

Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

This study mapped the precancer-to-cancer transition in breast and prostate tumors by imaging intact specimens with lightsheet microscopy and then applying a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics across 51 cases. The key finding was that analysis of 319 spatial assays identified gene-expression programs and structural features defining the shift to invasion, including breast-associated loss of MGP and PLAT and prostate-associated involvement of GDF15, ALDH1A3, ANPEP, and FA-related signals (as reported in the abstract). Clinically, these spatially resolved molecular signatures and transitional junctions could enable earlier detection and more targeted intervention for invasion in hormone-driven adenocarcinomas.

Storrs E, Mo CK, Chou WH et al. · Cancer discovery · (2026) · View on PubMed ↗

A model-based prion vaccine protects a transgenic mouse line carrying a Gerstmann-Sträussler-Scheinker disease mutation.

The study developed and tested a model-based prion vaccine designed to mimic predicted surface immunogenic features of the infectious prion conformer (PrPSc) in a transgenic mouse line carrying a Gerstmann-Sträussler-Scheinker (GSS) disease mutation. The vaccine protected these transgenic mice, shifting immunity toward PrPSc-like targets rather than relying on PrPC immunization alone. This provides a strategy to more specifically target heterogeneous prion aggregates and could improve the translational feasibility of anti-prion immunotherapy.

Fang A, Tang X, Fleming M et al. · Acta neuropathologica · (2026) · View on PubMed ↗

Total marrow irradiation-based conditioning for allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies: A multicenter real-world study.

This multicenter real-world retrospective study evaluated total marrow irradiation (TMI)-based conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematologic malignancies across four Chinese centers from 2017–2024. The key finding is that TMI conditioning was feasible and associated with measurable overall survival and disease control outcomes, with safety assessed through nonrelapse mortality and graft-versus-host disease-related endpoints. Clinically, the study strengthens evidence for TMI as a conditioning option in routine practice and helps define its risk–benefit profile in diverse patient populations.

Zhang Y, Zhang R, Cao X et al. · Cell transplantation · (2026) · View on PubMed ↗

Oropharyngeal cancer mortality in the United States, 1999-2023: a surveillance analysis using CDC WONDER.

This surveillance analysis used CDC WONDER mortality data to examine oropharyngeal cancer (OPC) mortality trends and demographic/geographic disparities in the United States from 1999–2023. The key finding is that age-adjusted OPC mortality rates increased over the period (with joinpoint regression quantifying annual percent change) and that disparities varied across demographic and geographic strata. The results are clinically important for public health planning by identifying where and among whom OPC mortality is worsening.

Deng W, Cao L, Li Z · Frontiers in oncology · (2026) · View on PubMed ↗

Redefining standards: a comprehensive systematic review of practice changing advances in GU oncology from ASCO and ESMO 2025.

This comprehensive systematic review summarized practice-changing advances in genitourinary (GU) oncology from ASCO and ESMO 2025, focusing on pivotal phase II/III randomized controlled trials across bladder, kidney, prostate, penile, and testicular cancers. It aimed to critically evaluate how 2025 trial results with novel mechanisms and refined personalization are redefining treatment standards. The work is significant for clinicians and researchers needing an organized, evidence-graded map of emerging GU oncology therapies.

Ismaili N · Frontiers in endocrinology · (2026) · View on PubMed ↗

Translational Models for Glioblastoma: Revolutionizing Drug Development and Personalized Medicine through Clinical Insights.

This article reviews translational models for glioblastoma (GBM), focusing on how preclinical systems (cell lines, 2D cultures, and animal models) fail to capture GBM tumor microenvironment, blood–brain barrier function, and interpatient heterogeneity in ways that predict clinical trial outcomes. It highlights the development of advanced experimental platforms intended to better model these determinants of therapeutic resistance and to support personalized medicine and drug development. Improving translational fidelity for GBM is clinically significant because it may reduce late-stage trial failures and enable more reliable, patient-tailored therapies.

Lee G, Kim YJ, Ham SJ et al. · Theranostics · (2026) · View on PubMed ↗

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Neurodegeneration, brain imaging & sleep biomarkers

Dysfunction of the episodic memory network in the Alzheimer’s disease cascade.

This study examined episodic memory (EM) network dysfunction across Alzheimer’s disease progression by relating longitudinal fMRI measures from the DZNE DELCODE cohort (over 1000 longitudinal scans) to disease progression model scores. Voxel-wise analyses showed widespread loss of EM deactivation and activation with increasing disease progression, with nonlinear trajectories for deactivation loss. These results link EM network dynamics to biomarker and neurodegeneration progression, supporting EM network fMRI as a functional marker of AD cascade staging.

Lattmann R, Vockert N, Bernal J et al. · Nature communications · (2026) · View on PubMed ↗

Night-to-night rapid eye movement sleep variability: A relevant marker of early amyloid-β deposition.

This study examined cognitively unimpaired older adults with cerebral amyloid deposition to determine whether night-to-night rapid eye movement (REM) sleep variability predicts early amyloid-β (Aβ) deposition. The key finding was that Aβ-positive individuals showed altered sleep patterns, and the abstract indicates that REM sleep variability was associated with regional amyloid deposition and related cognitive/psychoaffective outcomes. Scientifically, it suggests that objective wearable-derived sleep variability could serve as an early, noninvasive marker of preclinical Alzheimer’s disease pathology.

Montagne B, Boulin M, Hamel A et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Elevated plasma klotho levels attenuate Alzheimer’s disease pathologies and cognitive decline in APOE ε4 carriers.

This study assessed 354 older adults to test whether elevated plasma klotho levels are linked to Alzheimer’s disease (AD) biomarkers and cognition, with analyses stratified by APOE ε4 status. The key finding was that higher plasma klotho levels were associated with lower AD-related pathology (including amyloid/tau and neurodegeneration measures as evaluated by PET and plasma biomarkers) and attenuated cognitive decline specifically in APOE ε4 carriers. Clinically, plasma klotho may represent a modifiable or prognostic biomarker for reducing AD risk and progression in a genetically defined high-risk subgroup.

Yang J, Wang J, Chai W et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Voxel-accurate MRI-microscopy Correlation Enables AI-powered Prediction of Brain Disease States.

This study introduced BRIDGE (Brain Radiological Imaging with Deep-learning based Ground-Truth Exploration) to correlate voxel-accurate in vivo MRI with in vivo two-photon microscopy and ex vivo super-resolution microscopy for brain disease state prediction. Using a multi-step iterative co-registration pipeline, it enabled longitudinal, voxel-precise mapping of MRI signals to cellular/anatomical ground truth and supported AI training for predicting brain disease states. The approach is significant because it links imaging biomarkers to biological substrates, improving interpretability and potentially the accuracy of AI-based neurodiagnostics.

Schroers J, Yang Y, Reyhan E et al. · Theranostics · (2026) · View on PubMed ↗

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Neuroimmune disorders & immunotherapy tolerance

CAR Treg therapies for neurodegenerative diseases.

This review examined how chimeric antigen receptor regulatory T cells (CAR Tregs) could be engineered to recognize non-foreign self-antigens and suppress immune responses, with emphasis on neurodegenerative diseases driven by misfolded/aggregated proteins. It highlights that CAR Tregs may be extended to regulate inflammation triggered by protein aggregates that otherwise contribute to neural injury. If translated successfully, CAR Treg targeting could provide a cell-specific immunotherapy strategy to slow or prevent neurodegeneration by restoring immune tolerance to pathogenic protein species.

Stein DN, Gendelman HE · iScience · (2026) · View on PubMed ↗

Nuclear export modulates TDP-43 phase transitions and cytoplasmic aggregation.

This study investigated how nuclear export regulates TAR DNA-binding protein 43 (TDP-43) liquid-to-solid phase transitions and cytoplasmic aggregation using chemical and genome-wide genetic screening in cells expressing an RNA-binding–defective TDP-43 mutant that models an ALS-associated variant. The key finding is that multiple cellular processes—including RNA splicing, protein translation, proteostasis imbalance, and especially nuclear export—modulate TDP-43 phase behavior and aggregation propensity. This is significant because it identifies actionable cellular pathways that could be targeted to reduce TDP-43 aggregation and neurotoxicity in ALS and related disorders.

Chin N, Zhang Q, Zou J et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Exploring medication adherence and illness perception in patients with neuroimmune diseases: a cross-sectional study.

This cross-sectional study examined medication adherence and illness perception in patients with neuroimmune diseases—myasthenia gravis (MG), multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD)—recruited from the outpatient neurology clinic at West China Hospital, Sichuan University (March–August 2025). Using the Eight-Item Morisky Medication Adherence Scale (MMAS-8) and a questionnaire assessing illness perception, it identified factors associated with adherence and evaluated how adherence relates to illness perception. The clinical significance is that understanding these determinants can inform interventions to improve long-term adherence and outcomes in chronic neuroimmune conditions.

Fu R, Wang X, Shi Z et al. · Frontiers in immunology · (2026) · View on PubMed ↗

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Inflammation, fibrosis & immune–stromal signaling

Aberrant laminin signaling drives melanocyte dedifferentiation and unveils a tractable therapeutic target in vitiligo.

This study investigated how laminin signaling drives melanocyte dedifferentiation in vitiligo by analyzing changes in laminin-211 versus laminin-332 interactions and downstream cytoskeletal/niche signaling. In vitiligo, reduced laminin-211 and increased laminin-332 shifted melanocytes toward integrin α3β1–laminin-332 signaling, accompanied by dedifferentiation-like transcriptional and Rho–F-actin remodeling changes involving Hippo pathway alterations. The work uncovers a tractable ECM–integrin signaling target that may be therapeutically leveraged to reverse melanocyte dysfunction in vitiligo.

Yang F, Yang L, Lai S et al. · Nature communications · (2026) · View on PubMed ↗

Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture.

In a subgroup of a randomized controlled trial in patients with recurrent Clostridioides difficile infection, fecal microbiota transplantation (FMT) was compared with oral vancomycin or a 12-strain bacterial mixture, with serial fecal bile acid profiling using 16S rDNA-based analyses. FMT more effectively re-established a bile acid composition closer to a “normal” profile than vancomycin or the defined bacterial mixture, supporting bile acid restoration as a treatment-relevant mechanism. This controlled evidence strengthens the scientific rationale for targeting bile acid ecology to improve outcomes in recurrent C. difficile and helps refine microbiota-based therapeutic strategies.

Rode AA, Duboc H, Lamazière A et al. · Gut microbes · (2026) · View on PubMed ↗

Thiamine deficiency in cancer patients at initial admission to a palliative care unit: a single-centre cross-sectional study.

This single-centre cross-sectional study assessed thiamine deficiency in end-of-life cancer patients at initial admission to a palliative care unit, measuring whole-blood thiamine concentrations by high-performance liquid chromatography. The study quantified the prevalence of thiamine deficiency and identified clinical factors associated with it in this population. These findings are clinically significant because they support routine screening and potential thiamine repletion strategies to address a potentially reversible contributor to morbidity in palliative oncology care.

Sato R, Ishida M, Uchida N et al. · BMJ supportive & palliative care · (2026) · View on PubMed ↗

Gastrointestinal Disorders in Scleroderma.

This article reviewed gastrointestinal disorders in systemic sclerosis (scleroderma), emphasizing how vasculopathy, immune-mediated inflammation, and neuropathy drive GI involvement across the esophagus, stomach, and other segments. It summarizes clinical manifestations and approximate prevalence (e.g., esophageal involvement in ~90% of patients) and links them to underlying pathogenic mechanisms. The review is significant because it consolidates current knowledge to guide clinicians in recognizing, stratifying, and managing GI complications in scleroderma.

Quigley EMM, McMahan ZH, Kulkarni S et al. · Gastroenterology · (2026) · View on PubMed ↗

Orthokeratology for stable mild-to-moderate keratoconus: a pilot study on safety and corneal remodeling via quantitative OCT analysis.

This pilot prospective cohort study evaluated overnight orthokeratology (Ortho-K) using Euclid Emerald Ortho-K lenses in 13 patients (24 eyes) aged 14–21 years with stable mild-to-moderate keratoconus (Amsler-Krumeich grades I–II). The key finding was that safety and corneal remodeling were assessed over 18 months using quantitative OCT analysis, focusing on epithelial and Bowman’s layer structural changes alongside visual and refractive outcomes. Scientifically and clinically, it provides early evidence on whether Ortho-K can safely induce measurable corneal remodeling in keratoconus using OCT-based quantification.

Zhang C, Hu Z, Li W et al. · International ophthalmology · (2026) · View on PubMed ↗

Clinical and endocrine effects of pharmacological therapy in endometriosis: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated clinical and endocrine effects of pharmacological therapies for endometriosis, including combined oral contraceptives (COCs), progestins, GnRH analogues, levonorgestrel-releasing intrauterine system (LNG-IUS), and the oral GnRH antagonist relugolix, across 149 clinical trials. It reported that these hormonal and adjunctive treatments produced benefits of varying magnitude, with effect sizes extracted using standardized mean differences (SMD) and assessed with Jadad and GRADE frameworks. The synthesis supports evidence-based selection of endometriosis therapies by clarifying comparative clinical and endocrine effects.

Sun R, Xu H, Ma R et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗

Meningeal macrophages regulate fibroblasts to influence meningeal lymphatic function following traumatic brain injury.

This study examined how meningeal macrophages regulate fibroblasts to influence meningeal lymphatic function after traumatic brain injury (TBI). Using single-cell RNA sequencing, confocal microscopy, and flow cytometry, it identified a distinct meningeal fibroblast population that secretes VEGF-C and assessed how TBI alters this pathway, with mechanistic testing using subdural clodronate liposomes (macrophage depletion) and PDGF-C. The findings are significant because they define an immune–fibroblast signaling axis that could be targeted to restore lymphatic clearance and improve outcomes after TBI.

Guo X, Zhu Y, Gao S et al. · Theranostics · (2026) · View on PubMed ↗

Single-Cell Transcriptomics Reveals Riluzole as an Osteoarthritis Candidate Drug via OB-NE Signaling Modulation and CTSS/NOS1 Inhibition.

This study used single-cell RNA sequencing of human femoral head tissue to identify osteoarthritis (OA) candidate mechanisms and reposition drugs, focusing on osteoblast (OB)–immune cell interactions and OB–NE signaling modulation. It reports that riluzole emerges as an OA candidate drug, with network proximity-based drug repositioning and Mendelian randomization supporting a causal link between drug targets and OA, and it further implicates CTSS and NOS1 inhibition in the mechanism. This is significant because it provides a data-driven rationale for riluzole as a potential OA therapeutic and highlights specific target pathways for further validation.

Liu K, Li JL, Chen Y et al. · Drug design, development and therapy · (2026) · View on PubMed ↗

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Cardiometabolic risk, diet & exercise

Evidence-Based Recommendations on the Use of Inclisiran in Patients With Chronic Kidney Disease.

This article studied evidence and expert guidance for using inclisiran in patients with chronic kidney disease (CKD), focusing on its mechanism as a long-acting small interfering RNA (siRNA) that targets hepatic PCSK9 synthesis. The key finding is a practical, evidence-based stratification approach for inclisiran suitability in CKD patients, integrating clinical trial evidence and specialist opinion. This is significant because it provides a structured way to address dyslipidemia in CKD where statin intolerance and polypharmacy/adherence issues are common.

Sharma S, Kalra S, Sahay M et al. · Nephrology (Carlton, Vic.) · (2026) · View on PubMed ↗

The Effect of Empagliflozin on Renal Outcomes in Patients With Established Cardiovascular Disease: Systematic Review and Meta-Analysis of Randomised Placebo-Controlled Trials.

This systematic review and meta-analysis studied the effect of empagliflozin (an SGLT2 inhibitor) on renal outcomes in patients with established cardiovascular disease by pooling randomized, placebo-controlled trials. The key finding was an overall assessment of renal efficacy and safety, including the magnitude of benefit and potential heterogeneity across CVD populations. Clinically, it supports decision-making on empagliflozin for renal protection in high-risk patients with cardiovascular disease.

Bahardoust M, Rad FN, Mousavi S et al. · Endocrinology, diabetes & metabolism · (2026) · View on PubMed ↗

Effects of GLP-1 Receptor Agonists on Muscle Mass, Strength, and Quality in MASLD: A Systematic Review.

This systematic review studied how GLP-1 receptor agonists affect muscle mass, strength, and muscle quality in adults with metabolic dysfunction-associated steatotic liver disease (MASLD), including studies using CT/MRI, DXA, and bioelectrical impedance. The key finding (from the review’s synthesis) is the current state of evidence on whether GLP-1RA-associated weight loss translates into clinically meaningful changes in muscle-related outcomes in MASLD. Scientifically, it informs risk–benefit counseling for preserving lean mass and function during GLP-1RA therapy in a population prone to sarcopenia.

Iorra F, Jayakar T, Yee M et al. · Liver international : official journal of the International Association for the Study of the Liver · (2026) · View on PubMed ↗

Associations of plant-based diets with all-cause and cause-specific mortality and life expectancy among participants with cardiometabolic disorders from UK, US, and China.

This study examined associations of plant-based diet patterns with all-cause and cause-specific mortality and life expectancy among 78,151 participants with cardiometabolic disorders (obesity, diabetes, or CVD) across UK Biobank, NHANES, and CLHLS. The key finding was the relationship between a plant-based diet index and mortality/life expectancy outcomes in these high-risk cohorts. This is significant for preventive cardiometabolic care by informing whether plant-forward dietary patterns may extend life and reduce specific mortality risks.

Tan B, Li Z, Chen P et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗

GLP-1 therapies and hair loss: A systematic review of current evidence and implications for counseling.

This systematic review studied GLP-1 receptor agonist–specific associations with hair loss by screening 133 studies and including 24 primary articles, with attention to alopecia subtypes and potential mechanisms. The key finding was that semaglutide and tirzepatide showed the highest incidence rates of hair loss and stronger pharmacovigilance signals. Clinically, it supports more informed counseling and monitoring for patients starting GLP-1 therapies who develop alopecia.

Gupta AK, Teasell EM, Economopoulos V et al. · Science progress · (2026) · View on PubMed ↗

Fructose: metabolic signal and modern hazard.

This review studied the metabolic roles and health risks of fructose compared with glucose, focusing on how fructose acts as a signal of metabolic plenty under modern overnutrition. It found that chronic excess fructose promotes triglyceride synthesis and fat accumulation, contributing to metabolic syndrome features, and that emerging evidence links fructose exposure to cancer and dementia. The significance is that it reframes fructose as both a metabolic substrate and signaling driver, informing risk assessment and potential dietary or therapeutic strategies.

Johnson RJ, Lanaspa MA, Tolan DR et al. · Nature metabolism · (2026) · View on PubMed ↗

Dual Roles of Adipose Tissue in Skeletal Muscle Regeneration: Pro-Regenerative Versus Maladaptive.

This review synthesized evidence on how adipose tissue influences skeletal muscle regeneration, contrasting pro-regenerative versus maladaptive effects depending on context and fat distribution. The key finding is that appropriately regulated adipose presence supports local metabolic support and paracrine signaling during repair, whereas excessive or dysregulated ectopic fat accumulation impairs regeneration and function. Scientifically, it frames adipose tissue as a modifiable component of the regenerative microenvironment, informing therapeutic strategies for muscle repair and sarcopenia-related conditions.

Lu C, Lu F, Cai J · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗

Sarcopenic Obesity in Children: An Emerging Complication Evidenced by Clinical Data and a Juvenile Mouse Model.

This study investigated sarcopenic obesity in children by combining clinical assessments in 1447 children (DXA body composition; grip strength in a separate cohort of 349) with a juvenile and adult-onset high-fat diet (HFD) mouse model. The key finding is that childhood obesity is associated with impaired musculoskeletal health consistent with sarcopenic obesity, and the mouse models support mechanistic pathway alterations linked to obesity-driven muscle deficits. This highlights sarcopenic obesity as an emerging pediatric complication and provides preclinical targets for early prevention or intervention.

Wang S, Zhang W, Qin Z et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗

Comparative effectiveness of non-pharmacological traditional Chinese medicine therapies for chronic fatigue syndrome: a systematic review and network meta-analysis.

This systematic review and network meta-analysis compared non-pharmacological Traditional Chinese Medicine (TCM) therapies for chronic fatigue syndrome (CFS) using a broad database search completed January 1, 2026. The key finding is that the analysis synthesized comparative effectiveness across different TCM interventions while applying risk-of-bias assessment and network meta-analysis ranking (via CINeMA). This is significant for guiding evidence-informed selection of non-pharmacological TCM options for CFS, though the strength of conclusions depends on the included study quality.

Zhang Y, Zhou Y, Xu H et al. · Frontiers in medicine · (2026) · View on PubMed ↗

Latest advances and controversies of exercise therapy in the management of type 2 diabetes.

This mini-review synthesized recent evidence and controversies regarding exercise therapy for adults with type 2 diabetes, focusing on exercise modalities and dose optimization. It reports that high-intensity interval training (HIIT) is time-efficient and associated with superior reductions in HbA1c, while concurrent aerobic plus resistance training provides broader metabolic and functional benefits. The review supports practical exercise prescription strategies while highlighting the gap between ideal efficacy and real-world effectiveness.

Hao J, Zhang H · Frontiers in endocrinology · (2026) · View on PubMed ↗

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Bone, osteoporosis & bone–brain connections

Romosozumab Versus Teriparatide for the Treatment of Postmenopausal Osteoporosis: An Overview of Systematic Reviews With Direct and Indirect Meta-Analyses.

This overview of systematic reviews studied the comparative efficacy and safety of romosozumab versus teriparatide for postmenopausal osteoporosis using direct and indirect meta-analyses from literature searched through November 2023. The key finding was that romosozumab did not show a significant difference in fall risk over 12–24 months compared with teriparatide (as reported in the available abstract). This matters for osteoporosis treatment selection by clarifying relative outcomes between anabolic therapies beyond fracture endpoints.

Bandeira TFGS, Aguiar PM, Vianna CMM et al. · International journal of rheumatic diseases · (2026) · View on PubMed ↗

Romosozumab versus teriparatide for risk of dementia in individuals with osteoporosis: a target trial emulation study.

This target-trial emulation study used Japanese longitudinal claims data from 69,543 individuals with osteoporosis to compare dementia risk after initiating romosozumab versus initiating teriparatide as an active comparator. Romosozumab initiation was associated with a lower risk of incident dementia than teriparatide initiation. If confirmed prospectively, the findings strengthen the bone–brain connection and support further evaluation of romosozumab for neurocognitive outcomes in osteoporosis.

Hatano M, Okada A, Sasabuchi Y et al. · Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · (2026) · View on PubMed ↗

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Cardiovascular therapeutics & critical care

Brain age gap as biomarker linking cardiovascular diseases genetic susceptibility and causality.

This study used T1-weighted MRI data from UK Biobank to train a 3D vision transformer (3D-ViT) model that predicts brain age and computes brain age gap (BAG), then tested causal relationships between BAG and cardiovascular disease (CVD) using bidirectional Mendelian randomization (MR). The key finding is that brain–heart interactions were supported, with specific CVD outcomes (including acute myocardial infarction and chronic ischemic heart disease) associated with decelerated brain aging in the MR framework. This is important because BAG may serve as an imaging-derived biomarker linking genetic susceptibility to causal cardiovascular risk and systemic aging processes.

Lyu S, Zhang R, Peng K et al. · iScience · (2026) · View on PubMed ↗

Experts’ recommendations for the management of adult patients with cardiogenic shock.

This article developed expert, GRADE-based recommendations for managing adult patients with cardiogenic shock (CS), produced by French Intensive Care Society (SRLF) and French Society of Cardiology (SFC) with SFAR and other stakeholders. It synthesizes evidence and proposes updated, etiology-agnostic clinical management standards for adult CS. These recommendations are intended to standardize care and improve outcomes in a high-mortality ICU population.

Aissaoui N, Delmas C, Merdji H et al. · Annals of intensive care · (2026) · View on PubMed ↗

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Infectious diseases & antifungal/antibiotic decision-making

Clinical and Microbiological Insights Into Invasive Fusariosis Following Allogeneic Hematopoietic Stem Cell Transplantation: A 15-Year Single-Center Analysis.

This 15-year single-center retrospective analysis studied invasive fusariosis (IF) in 2,359 allogeneic hematopoietic stem cell transplant (HSCT) recipients for hematological malignancies (2010–2024), identifying proven IF cases using multigene sequencing and antifungal susceptibility testing. Seventeen proven IF cases (7.2/1000) were identified, with patients more often having prior HSCT than those without IF. Clinically, the work highlights the need for heightened surveillance and tailored antifungal management in HSCT recipients—especially those with prior transplant exposure.

Yamamoto J, Ogura S, Takagi S et al. · Transplant infectious disease : an official journal of the Transplantation Society · (2026) · View on PubMed ↗

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Genetics, splicing & developmental biology

Diagnostic Criteria and Management of MELAS and Stroke-Like Episodes: Consensus-Based Statements.

This consensus statement studied diagnostic criteria and management strategies for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and mitochondrial stroke-like episodes (SLE) across pediatric and adult populations using an international Delphi process through ERN EURO-NMD and the US Mitochondrial Medicine Society. The key outcome was standardized, consensus-based recommendations for defining, diagnosing, and treating MELAS/SLE to reduce variability in clinical practice. Scientifically and clinically, these criteria should improve recognition of mitochondrial stroke-like episodes and support more consistent, evidence-aligned management.

Mancuso M, Bellusci M, Carelli V et al. · European journal of neurology · (2026) · View on PubMed ↗

Tools and tactics for studying alternative splicing.

This review studied how alternative splicing is mapped and functionally tested across model systems, emphasizing recent advances in long-read sequencing, CRISPR-based splicing assays, population genetics, and deep learning. It found that long-read sequencing now enables isoform-resolved profiling at bulk, single-cell, and spatial levels, while CRISPR perturbations can directly assess the functional impact of specific splicing isoforms. These developments are significant because they accelerate mechanistic discovery of splicing dysregulation in diseases such as cancer and rare genetic disorders and improve the ability to interpret splicing variation and “splicing language” from sequence.

Sousa-Luís R, Carmo-Fonseca M · Nature reviews. Genetics · (2026) · View on PubMed ↗

A transgene-free, human peri-gastrulation embryo model presents trilaminar embryonic disc-, amnion- and yolk sac-like structures.

This study developed a transgene-free human peri-gastrulation embryo model (peri-gastrulation trilaminar embryonic disc, PTED) derived from primed human pluripotent stem cells. It found that PTED embryoids form trilaminar embryonic disc-like, amnion-like, and yolk sac-like structures and show primitive hematopoiesis, with lineage tracing supporting mesodermal organization between dorsal amnion and ventral definitive yolk sac. The significance is that PTED provides a tractable in vitro system to study early human embryogenesis and peri-gastrulation events that are otherwise difficult to access directly.

Sun S, Zheng Y, Kim YS et al. · Nature cell biology · (2026) · View on PubMed ↗

A single-cell and spatial atlas of early human olfactory development.

This study mapped early human olfactory development using integrated single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics with multiplexed error-robust fluorescence in situ hybridization (MERFISH) in male and female fetal nasal tissue from 7–12 post-conceptional weeks. The atlas resolved 32 distinct cell types and localized gene-expression dynamics across the olfactory epithelium and adjacent tissues, identifying developmental markers and spatially patterned programs. This resource provides a high-resolution framework for understanding human olfactory lineage specification and for interpreting developmental defects affecting smell.

Mbouamboua Y, Lebrigand K, Nampoothiri S et al. · Nature communications · (2026) · View on PubMed ↗

UK BioCoin: swift trait-specific summary statistics regression for UK Biobank.

This study developed UK BioCoin (UKC), a computational method for generating trait-specific summary statistics regression for UK Biobank while allowing user-specified covariate adjustments without individual-level data access. Using UK Biobank data (505 traits, ~10 million SNPs), UKC produced summary statistics closely matching individual-level analyses with ~80× improved computational efficiency. The method enables more flexible, trait-tailored genetic association analyses for large biobank studies.

He J, Qi G, Ying J et al. · Nature communications · (2026) · View on PubMed ↗

Biallelic mutations in ANAPC13 cause female infertility characterized by oocyte maturation arrest both in humans and mice.

Researchers investigated the causal role of biallelic ANAPC13 mutations in female infertility by combining human genetic/clinical characterization with functional studies in mice, focusing on oocyte maturation arrest. ANAPC13 mutations produced an oocyte maturation arrest phenotype in both humans and mice, implicating ANAPC13 as a required APC/C component for proper meiotic progression. This work is significant for diagnosing a previously under-recognized genetic cause of infertility and for advancing mechanistic understanding of cell-cycle control in oocyte development.

Wang Y, Ding Z, Liu X et al. · American journal of obstetrics and gynecology · (2026) · View on PubMed ↗

MRE11 proximal polyadenylation site-mediated looping impacts transcription and genomic stability.

The study investigated how the proximal polyadenylation site (pPAS) of the DNA damage response gene MRE11 regulates transcription and genome stability by promoting PAS–promoter looping. Deleting the MRE11 pPAS disrupted looping, reduced MRE11 transcription and MRN complex (MRE11-RAD50-NBS1) levels, and caused phenotypes resembling hypomorphic MRE11 mutations, including ectopic DNA replication and reduced viability under overgrowth conditions. This mechanistic insight is significant because it links alternative polyadenylation control of MRE11 to DDR function and genomic stability.

Huang K, Brault ME, Cong K et al. · Molecular cell · (2026) · View on PubMed ↗

A bidirectional brain-fat body axis for pathogen avoidance.

In Drosophila melanogaster, the study identified a bidirectional brain–fat body communication pathway that mediates pathogen avoidance, using immune receptors and an antimicrobial peptide (AMP) as functional nodes. Pathogen-sensing octopaminergic neurons activated fat body calcium signaling via an octopamine receptor, triggering fat body dopamine release that acted through Dop1R1 to suppress pathogen intake, with reciprocal requirements in both tissues. This is significant because it reveals a conserved-like neuroimmune metabolic circuit for behavioral pathogen avoidance that could inform broader principles of how immune detection shapes behavior.

Wang Y, De Backer JF, Muria A et al. · Neuron · (2026) · View on PubMed ↗

Decoding RNA splicing pathology: Alternative splicing in amyotrophic lateral sclerosis and its therapeutic potential.

This review article summarized how alternative RNA splicing pathology contributes to amyotrophic lateral sclerosis (ALS) and discussed therapeutic opportunities targeting splicing-related mechanisms. The key finding was that ALS-associated RNA-processing genes—including TARDBP, FUS, EWSR1, TAF15, SOD1, and C9orf72—drive disease through disrupted RNA metabolism, altered alternative splicing, and toxic nuclear-to-cytoplasmic mislocalization. Scientifically, it frames splicing dysregulation as a tractable therapeutic axis for developing interventions that correct or mitigate aberrant RNA processing in ALS.

Priya R, Tanti GK, Jain BP · Biochemical and biophysical research communications · (2026) · View on PubMed ↗

Development of a DUX4-targeting antibody oligonucleotide conjugate as a therapy for FSHD.

This preclinical/therapeutic development study created Delpacibart braxlosiran (del-brax, AOC 1020), an antibody–oligonucleotide conjugate designed to treat facioscapulohumeral muscular dystrophy (FSHD) by targeting DUX4 expression in skeletal muscle. The key finding is that the construct—TfR1-targeting monoclonal antibody conjugated to DUX4 mRNA-targeting siRNA (siDUX4.6)—reduces DUX4 mRNA and supports therapeutic activity by improving siRNA delivery to muscle cells. This is significant because it advances a targeted gene-silencing approach for FSHD, addressing a major unmet need with a delivery strategy aimed at muscle specificity.

Malecova B, Sala D, Melikian GM et al. · Nucleic acids research · (2026) · View on PubMed ↗

Targeting Tumour Microtubes to Disrupt Glioma Networks.

This preclinical study investigated how glioma stem cells (GSCs) build tumor microtubes (TMs) to form tumor–tumor and neuron–tumor communication networks that support growth and therapy resistance. Using coordinated proteomics and functional screening, it identified the inner mitochondrial component FASTKD2 as essential for TM-dependent local protein synthesis, and targeting FASTKD2 reduced tumor stemness and growth while disrupting coordinated mitochondrial function. Scientifically, it provides a mechanistic TM vulnerability and a potential therapeutic target to break glioma network communication.

Rich J, Huang T, Zhang P et al. · Research square · (2026) · View on PubMed ↗

Molecular architecture of the ciliary base in mammalian multiciliated cells.

This preprint studied the molecular architecture of the ciliary base in mammalian multiciliated cells from the mammalian trachea. Using cryo-FIB milling and cryo-electron tomography for in situ 3D ultrastructure, together with in situ cross-linking mass spectrometry (XL/MS) and ultrastructure expansion microscopy (U-ExM) for molecular identification, it reports new structural and molecular insights into the transition zone and basal body/ciliary environment. The findings are scientifically significant because they clarify how ciliary base components are organized to support motile cilia function, informing mechanisms of ciliopathies.

McCafferty CL, Brunet M, van den Hoek H et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Whole-organism spatial transcriptomics at single-cell resolution in C. elegans.

This preprint studied whole-organism spatial transcriptomics at single-cell resolution in Caenorhabditis elegans to overcome limitations of spatial resolution and multiplexing in existing worm transcriptomic methods. It reports a workflow enabling mapping of gene expression patterns across intact worms with single-cell spatial detail, leveraging C. elegans’ transparency, compact anatomy, and genetic tractability. The approach is significant because it enables linking molecular and cellular changes to circuit function and behavior within the same animal.

Aguirre Aguilera JD, Wan X, Tischbirek CH et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

WNT5a-Mediated Aberrant Actin Filament Dynamics Drive Cardiac Pathogenic Phenotypes in LMNA-Related Emery-Dreifuss Muscular Dystrophy.

This study investigated LMNA-related Emery-Dreifuss muscular dystrophy (EDMD) by recruiting five patients with LMNA sequence variations and generating patient-specific induced pluripotent stem cells (iPSCs) to model disease-relevant cardiac phenotypes. It identifies a WNT5a-mediated mechanism in which aberrant actin filament dynamics drive pathogenic cardiac features in LMNA-related EDMD. The scientific and clinical significance is that it connects a defined signaling axis (WNT5a) to cytoskeletal dysfunction in a rare genetic cardiomyopathy, suggesting potential mechanistic targets to mitigate disease progression.

Fan H, Wang X, Liu X et al. · Circulation · (2026) · View on PubMed ↗

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Other

Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.

This study assessed the role of histone deacetylase 11 (Hdac11) in idiopathic pulmonary fibrosis (IPF) by using IPF lung analyses, genetic Hdac11 ablation, and adoptive transfer of Hdac11-deficient macrophages. Hdac11 was upregulated in IPF and its loss markedly attenuated fibrosis by reducing M2 macrophage polarization, macrophage–myofibroblast transition-like reprogramming, myofibroblast accumulation, and profibrotic gene expression, mechanistically via impaired Parkin-dependent mitophagy. Targeting Hdac11–Parkin mitophagy signaling could therefore represent a therapeutic approach to limit macrophage-driven fibrogenesis in IPF.

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Combinatorial delivery of low-dose radiotherapy and immunotherapy to patients with immune-excluded tumors enhances CD8+ T cell functionality.

In a multi-cohort phase I clinical trial (RACIN), the investigators studied 25 patients with multimetastatic immune-excluded solid tumors treated with low-dose radiotherapy combined with immune-based regimens including nivolumab plus ipilimumab and additional agents (aspirin or celecoxib) plus low-dose cyclophosphamide. The combined approach enhanced CD8+ T cell functionality, improving immune responses in tumors characterized by low intraepithelial T-cell infiltration. This supports a clinically actionable strategy to convert “cold” tumors into more immunologically responsive ones using LDRT plus checkpoint blockade and immunomodulatory drugs.

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Single-mRNA imaging and modeling reveal coupled translation initiation and elongation rates.

This eLife study used SunTag live-cell single-mRNA imaging and a TASEP-based hidden Markov model to quantify translation initiation and elongation rates across mRNAs with diverse coding sequences. It found strong coupling between initiation and elongation such that ribosome density remained consistently low (≤12% occupancy), and this homeostatic coupling persisted during pharmacological inhibition of the elongation factor eIF5A. The results clarify how translation machinery self-regulates protein output and provide quantitative tools for modeling translational control.

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Exposure to air pollution and risk of gastrointestinal diseases: a systematic review and meta-analysis of epidemiological evidence.

This retrospective diagnostic/prognostic study enrolled 95 patients with Aspergillus detected by blood fungal metagenomic next-generation sequencing (mNGS) and compared infection versus colonization using modified EORTC/MSGERC criteria. Higher blood mNGS fungal load (reads per million) and specific serological biomarkers (galactomannan and 1,3-β-D-glucan) helped distinguish invasive pulmonary aspergillosis from colonization and carried prognostic information. The findings support using blood mNGS alongside GM/BDG to improve clinical decision-making in Aspergillus-positive patients.

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The diagnostic and prognostic utility of blood metagenomic next-generation sequencing for invasive pulmonary aspergillosis.

This cross-sectional global survey characterized the medical mycology workforce by leveraging the ESCMID Fungal Infection Study Group (EFISG) as a representative international network. It aimed to map workforce composition and related needs in the context of invasive fungal infections, antifungal resistance, and diagnostic/therapy access disparities. The results are significant for guiding coordinated research and education efforts in medical mycology worldwide.

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Transcatheter Intra-Arterial Delivery of a Platelet-Derived Extracellular Vesicle-Enriched Preparation for Attenuating Skeletal Muscle Ischaemia-Reperfusion Injury in a Rodent Forelimb Model.

This rodent forelimb model study tested transcatheter intra-arterial delivery of a platelet-derived extracellular vesicle (EV)-enriched preparation to attenuate skeletal muscle ischemia-reperfusion injury (IRI). The EV-enriched treatment reduced the sterile inflammatory and oxidative injury associated with limb IRI compared with control conditions. These preclinical data support platelet EVs as candidate therapeutics for reperfusion-related complications after limb revascularization or transplantation.

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Safety and Efficacy of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Cerebrovascular Ischemic Outcomes in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis compared direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for cerebrovascular ischemic outcomes in non-valvular atrial fibrillation. Across included randomized evidence, DOACs were evaluated for differences in ischemic stroke and transient ischemic attack risk and related safety outcomes. The synthesis informs anticoagulant selection for stroke prevention in non-valvular AF by consolidating comparative efficacy and safety evidence.

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