Journal of advanced research最新文献

{"title":"Montmorillonite@Metal oxide nanocomposites enables multitarget therapy for inflammatory bowel disease treatment.","authors":"Lu Wang, Xiaolong Yang, Xiaofang An, Shiwen Chen, Zihan Xia, Ling He, Xiaohu Gan, Yuanyuan Zhao, Chaoqian Zhang, Chaoxi Chen, Ge Fang, Tao Dai","doi":"10.1016/j.jare.2026.08.008","DOIUrl":"10.1016/j.jare.2026.08.008","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD) is a global health challenge characterized by excessive reactive oxygen species (ROS) accumulation, immune dysregulation, and impaired intestinal barrier integrity. Although montmorillonite (MMT) is clinically used for gastrointestinal protection, its limited anti-inflammatory and ROS-scavenging activities restrict its therapeutic potential in intestinal inflammatory disorders.</p><p><strong>Objectives: </strong>This study aimed to develop a multifunctional clay-supported nanozyme platform and evaluate its therapeutic effects in dextran sulfate sodium (DSS)-induced acute colitis model through the rational construction and screening of MMT-supported metal oxide nanocomposite (MMT@M_xO_y) library.</p><p><strong>Methods: </strong>A library of MMT@M_xO_y was constructed by integrating different metal oxide nanozymes onto MMT. The nanocomposites were screened and optimized by electron-transfer behavior, multienzyme-mimetic activities, and ROS-scavenging performance. Therapeutic efficacy was evaluated in DSS‑induced acute colitis model. Therapeutic mechanisms were investigated using transcriptomic profiling, gut microbiota analysis, biochemical assays, and molecular validation.</p><p><strong>Results: </strong>MMT@MnO₂ was identified as the leading nanocomposite owing to favorable electron-transfer characteristics and enhanced loading-normalized multienzyme-mimetic and ROS scavenging activities. Optimizing Mn precursor feeding ratio produced the lead MMT@MnO₂ formulation, which exhibited favorable biocompatibility. In vivo, MMT@MnO₂₂ alleviated body weight loss, reduced disease activity, preserved colon length, attenuated histopathological injury, and promoted mucus barrier recovery. Improvements in disease-related indices approached the orally administered 5-aminosalicylic acid, although route differences preclude direct pharmacological comparison. Mechanistically, MMT@MnO₂ attenuated oxidative stress and inflammatory responses, promoted macrophage phenotype remodeling toward less inflammatory and more reparative state, restored epithelial tight junction, and partially recovery of gut microbial homeostasis. Transcriptomic analysis and downstream molecular validation supported the involvement of NF-κB-related inflammatory suppression, phagosome-associated immune remodeling, and Rap1/ERK-related epithelial repair.</p><p><strong>Conclusion: </strong>This work established a rational design framework for clay-based nanotherapeutics and identified MMT@MnO₂ as a promising multitarget platform for alleviating DSS-induced acute colitis, offering a basis for future translational development of local nanotherapeutic strategies for intestinal inflammatory diseases.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic application of probiotic extracellular vesicles in inflammatory bowel disease.","authors":"Yining Wang, Zheng Sun, Linna Wang, Hongjun Shi, Shenhong Xiao, Fengming Dong, Ningbo Qin","doi":"10.1016/j.jare.2026.08.016","DOIUrl":"10.1016/j.jare.2026.08.016","url":null,"abstract":"<p><strong>Background: </strong>The chronic, recurring nature of Inflammatory bowel disease (IBD) and the complications associated with conventional drugs have driven the search for next-generation therapies capable of overcoming the limitations of current treatment regimens. As functional proxies of their parent bacteria, probiotic extracellular vesicles (PEVs) have become the focus of attention in recent years because of their great potential in the treatment of IBD.</p><p><strong>Aim of review: </strong>This review summarizes the overview of PEVs and recent advances of PEVs on the therapeutical effect and potential mechanisms in IBD. In addition, the review discusses the possible applications and challenges of PEVs in IBD. Key scientific concepts of review: PEVs facilitate a complex molecular crosstalk that preserves intestinal homeostasis in IBD by concurrently modulating immunological responses, reinforcing intestinal barrier, and stabilizing the gut microbiota. Although PEVs offer powerful innovations for the treatment of IBD, they still face challenges such as high-quality and scaled-up production, purification, safety, target specificity, and bioavailability. Consequently, future investigations will focus on establishing standard procedures of isolation, purification, and quality control while engineering PEVs for enhanced target-specific delivery in IBD treatment.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactiplantibacillus plantarum WY2401 promotes myogenesis via riboflavin-mediated modulation of METTL3-dependent mRNA m⁶A methylation.","authors":"Jiaqi Liu, Tongyudan Yang, Fangfang Lou, Wei Chen, Zimeng Xin, Shun Chen, Ruiti Ren, Xinxia Wang","doi":"10.1016/j.jare.2026.08.015","DOIUrl":"10.1016/j.jare.2026.08.015","url":null,"abstract":"<p><strong>Introduction: </strong>Lactiplantibacillus plantarum (L. plantarum) is a well-characterized probiotic with a long history of safe application, exhibiting prominent potential in improving skeletal muscle function. As the most prevalent and plentiful mRNA modification in eukaryotes, extensive research has highlighted the non-negligible role of N⁶-methyladenosine (m⁶A) in regulating various aspects of skeletal muscle biology. However, the underlying mechanisms through which L. plantarum-derived signals regulate host myogenic programs, as well as whether m⁶A modification is involved in this process, remain unclear.</p><p><strong>Objective: </strong>To explore the microbe-host regulatory axis through which L. plantarum promotes skeletal muscle regeneration and whether m⁶A modification is involved in this process.</p><p><strong>Methods: </strong>The cardiotoxin-induced muscle injury mouse model was constructed to investigate the impact of L. plantarum WY2401 on skeletal muscle regeneration. Untargeted metabolomics analysis was used to screen out L. plantarum WY2401-derived key metabolite. The changes in m⁶A modification were determined using dot blot and MeRIP-qPCR.</p><p><strong>Results: </strong>We identified L. plantarum WY2401 as a pro-myogenic probiotic that promotes skeletal muscle regeneration. Specifically, L. plantarum WY2401 strongly alters circulating metabolomic profiles, particularly elevating the production of microbiota-derived riboflavin. Upregulated riboflavin is transported to skeletal muscle through the bloodstream, where it modulates the expression of the m⁶A methyltransferase METTL3 in a stage-dependent manner during myogenesis. This modulation promotes myoblast proliferation by enhancing the stability of Cdk2 and Ccnd1 mRNAs through the METTL3-m⁶A-YTHDF1 pathway. It also facilitates myoblast differentiation by increasing Mef2a mRNA stability through the METTL3-m⁶A-YTHDF2 pathway.</p><p><strong>Conclusion: </strong>Our findings reveal a novel microbe-host regulatory axis through which L. plantarum WY2401 promotes skeletal muscle regeneration via stage-specific epigenetic modulation of myogenesis. This work highlights the potential of L. plantarum as a functional probiotic supplement for improving skeletal muscle development and provides new insights into probiotic-mediated regulation of muscle regeneration.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence of things-enhanced automated surveillance system for global antimicrobial resistance in food supply chain.","authors":"Jinxin Liu, Marti Z Hua, Xinyu Yan, Luyao Ma, Shenmiao Li, Yang Wang, Tian Yang, Yihan He, Michael E Konkel, Greta Gölz, Thomas Alter, Jinsong Feng, Qian Liu, Xiaonan Lu","doi":"10.1016/j.jare.2026.08.019","DOIUrl":"10.1016/j.jare.2026.08.019","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) threatens food safety across the farm-to-fork continuum. Real-time surveillance is crucial to mitigate its global escalation, yet conventional antimicrobial susceptibility testing (AST) remains slow, labor-intensive, and impractical for large-scale monitoring.</p><p><strong>Objectives: </strong>We developed an Artificial Intelligence of Things (AIoT)-integrated multiplex microfluidic platform enabling automated AMR surveillance ofpathogens in food supply chain.</p><p><strong>Results: </strong>Each node combines a single-board AIoT controller (Orange Pi 5B), portable incubator, chromogenic microfluidic chips, and environmental sensors, reducing costs by 98% compared with standard AST. A lightweight YOLO model embedded in the controller achieved > 99% accuracy in identifying bacterial growth and inhibition under antibiotic pressure, showing 96% and 95% agreement with standard results forSalmonella andCampylobacter, respectively. Data are synchronized to a cloud server for real-time aggregation and early resistance warning.</p><p><strong>Conclusion: </strong>This fully automated and low-cost system minimizes human error and workload, providing a scalable sample-to-answer solution for AMR surveillance in global agri-food system.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth differentiation factor 15 impairs periodontal ligament stem cell proteostasis via integrated stress response to drive diabetic periodontitis.","authors":"Xiaoyu Yang, Han Li, He Wang, Houxuan Li, Shuhong Li, Yiyao Hu, Deping Zeng, Junji Xu, Jinlin Song, Jie Li","doi":"10.1016/j.jare.2026.08.007","DOIUrl":"10.1016/j.jare.2026.08.007","url":null,"abstract":"<p><strong>Introduction: </strong>Periodontitis progresses more rapidly and severely in individuals with type 2 diabetes mellitus (T2DM), yet whether the integrated stress response (ISR) contributes to the progression of diabetic periodontitis has not been elucidated.</p><p><strong>Objectives: </strong>This study aims to clarify the impact and mechanisms of growth differentiation factor 15 (GDF15) in diabetic periodontitis.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on periodontal tissues and integrated the datasets with bidirectional Mendelian randomization to identify ISR-related alterations associated with impaired periodontal regeneration under diabetic conditions. Functional analyses were conducted in periodontal ligament stem cells (PDLSCs) subjected to diabetic-inflammatory conditions. Genetic deletion, antibody-based neutralization of GDF15, and ISR inhibition were used to evaluate therapeutic rescue effects in diabetic mice.</p><p><strong>Results: </strong>We identify GDF15 as an important effector of ISR signaling in PDLSCs. T2DM induces sustained PERK-eIF2α activation accompanied by GDF15 induction, leading to translational repression, loss of proteostasis, and impaired osteogenic differentiation. Mechanistically, GDF15 silencing preserved BiP-PERK complex stability and attenuated downstream PERK-eIF2α activation under diabetic-inflammatory stress. Genetic ablation or pharmacologic neutralization of GDF15, as well as ISR inhibition, partially restores PDLSC proteostasis and bone-forming capacity, preserving periodontal tissue regenerative capacity in diabetic mice.</p><p><strong>Conclusion: </strong>These findings suggest that GDF15 contributes to ISR-mediated PDLSC dysfunction and impaired periodontal regeneration under diabetic conditions. Targeting pathological GDF15-ISR signaling may provide mechanistic insight for future strategies to improve periodontal regenerative outcomes in T2DM.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Tissue engineering ECM-enriched controllable vascularized human microtissue for hair regenerative medicine using a biomimetic developmental approach\" [J. Adv. Res., 38 (2022) 77-89].","authors":"Peng Chen, Yong Miao, Feifei Zhang, Zhexiang Fan, Junfei Huang, Xiaoyan Mao, Jian Chen, Zhiqi Hu, Jin Wang","doi":"10.1016/j.jare.2026.07.064","DOIUrl":"https://doi.org/10.1016/j.jare.2026.07.064","url":null,"abstract":"","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valine modulates Alzheimer's disease risk in APOE ε4 carriers: evidence from two cohorts.","authors":"Ze-Lin Yang, Can Zhang, Shi Tang, Xin-Yu Zhang, Liang-Yu Huang, Lan Tan, Wei Xu","doi":"10.1016/j.jare.2026.08.014","DOIUrl":"10.1016/j.jare.2026.08.014","url":null,"abstract":"<p><strong>Introduction: </strong>The apolipoprotein E ε4 (APOE ε4) allele confers the greatest genetic risk for sporadic Alzheimer's disease (AD).</p><p><strong>Objectives: </strong>To identify APOE ε4-associated metabolic factors related to AD risk and to provide preliminary insights into their biological and nutritional context.</p><p><strong>Methods: </strong>We leveraged multi-omics analyses across two independent cohorts to characterize biomarkers associated with AD. The effects of metabolite × APOE ε4 interactions were tested on incident AD and the ε4-specific metabolic signatures were pinpointed. Multimodal analyses were used to test the underlying mechanisms, including neuroimaging, cerebrospinal fluid (CSF), and PET biomarkers within the A/T/N framework, as well as plasma proteomics combined with bioinformatics enrichment analyses.</p><p><strong>Results: </strong>Across both cohorts, valine emerged as the only metabolite associated with a reduced risk of incident AD specifically among APOE ε4 carriers (P < 0.005). Significant interaction effects between valine and APOE ε4 were detected in both cohorts (P for meta-analyses < 0.005). Higher levels of valine were associated with greater total white matter and posterior cingulate cortex volumes, as well as with lower levels of CSF tau proteins. Higher valine levels also predicted a slower decline in FDG-PET metabolism. No association was found between valine and Aβ. Mediation analyses of plasma proteomic data suggested statistically significant mediation effects involving GFAP, NEFL, and APOE (P < 2 × 10^-16).</p><p><strong>Conclusion: </strong>Valine is a metabolite associated with lower AD risk in APOE ε4 carriers, with potential associations with tau pathology, neurodegeneration, and neuroinflammation-related processes. As this was an observational study, causality cannot be inferred.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific metabolite profiling reveals diverse metabolic response under N deficiency and high temperature stress in soybean.","authors":"Hamza Tariq, Muhammad Saqib Bilal, Lei Wang, Alisdair R Fernie, Mohsin Tanveer","doi":"10.1016/j.jare.2026.08.017","DOIUrl":"10.1016/j.jare.2026.08.017","url":null,"abstract":"<p><strong>Introduction: </strong>Climate change has increased the incidence of compound stresses, including the co-occurrence of nitrogen deficiency (-N) and high temperature (HT), which severely reduce plant productivity. Studies have primarily focused on single plant tissues to decipher tolerance mechanisms; however, tissue-specific metabolic reprogramming remains poorly examined.</p><p><strong>Objectives: </strong>This work aimed to examine the distinct metabolic reprogramming in roots and leaves under whole-plant nitrogen deficiency (-N) and high temperature (HT), applied individually or combined. We hypothesized that roots and leaves exhibit complementary metabolic profiles, while combined stress triggers a unique metabolic signature associated with plant growth regulation.</p><p><strong>Methods: </strong>Soybean plants were subjected to control, -N, HT, and HT-N conditions, and later whole-plant physiological assessment and untargeted metabolites profiling of roots and leaves were performed and analyzed by machine learning analyses (e.g., t-SNE, UMAP, WGCNA, and random forest regression), qPCR and absolute quantification of identified key metabolites.</p><p><strong>Results: </strong>Combined HT-N stress caused severe growth inhibition, reduced shoot length (67%), root fresh weight (52%), and photosynthetic efficiency (Fv/Fm; by 51%) compared to control. Metabolomic analysis revealed stress specific responses in different tissues, with roots prioritizing N assimilation (accumulating glutamate, proline and aspartate) under -N, while leaves showed higher accumulation of flavonoids under HT. Under combined HT-N, tissue-specific responses were additive, with roots focusing on amino acid and proline metabolism and leaves on phenylpropanoid and glutathione metabolism. Our machine learning analyses (t-SNE, UMAP), WGCNA and RFR showed distinct tissue-specific metabolic signatures for each stress, and identified glucose, flavonoids, proline, and specific amino acids among key candidate metabolites associated with physiological resilience. Later, exogenous application of proline, quercetin, and L-arginine recovered soybean growth under stress, but in a stress-specific manner.</p><p><strong>Conclusion: </strong>Soybean employs distinct metabolic strategies in roots and leaves to manage multiple stresses. The identified key metabolites represent candidate hubs in the stress response network, offering candidate targets that warrant further investigation for breeding climate-resilient crops.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP7-mediated mono-ADP-ribosylation stabilizes MYH9 to ensure actin cap integrity and chromosome segregation in mouse oocytes.","authors":"Guangyi Cao, Sipei Liu, Yanbo Liu, Anqi Chen, Qian Xu, Lina Yu, Aolei Guo, Yan Mao, Ganggui Lou, Chaojun Li, Luhong Wen, Guijun Yan, Haixiang Sun","doi":"10.1016/j.jare.2026.08.012","DOIUrl":"10.1016/j.jare.2026.08.012","url":null,"abstract":"<p><strong>Introduction: </strong>Oocyte meiotic maturation requires highly asymmetric cell division, governed by spindle migration and actin cap formation. However, the upstream mechanisms that regulate the precise coordination of these events remain unclear.</p><p><strong>Objectives: </strong>This study aimed to elucidate the role of PARP7, a mono-ADP-ribosyltransferase, in regulating actin cytoskeletal dynamics and chromosomal stability during mouse oocyte meiosis.</p><p><strong>Methods: </strong>Metabolomic profiling was performed to assess NAD⁺ dynamics during meiosis. PARP7 expression and localisation were analysed using genetic knockdown and pharmacological inhibition approaches. Multi-omics analyses were performed to identify PARP7 targets and map MARylation sites within the motor domain. Protein stability was evaluated following PARP7 suppression and site-directed mutagenesis.</p><p><strong>Results: </strong>PARP7 was identified as the most abundant PARP family member in oocytes and localised to the actin cap during anaphase I. PARP7 inhibition disrupted meiotic progression, resulting in cytokinesis failure, aberrant polar body extrusion, and increased aneuploidy. These defects were attributed to impaired actin cap formation. MYH9 was identified as a PARP7 target, and MARylation was found to be critical for its stability; loss of this modification accelerated MYH9 degradation.</p><p><strong>Conclusion: </strong>PARP7-mediated MARylation stabilises MYH9 to maintain actin cap integrity and chromosomal segregation in mouse oocytes. These findings provide novel insights into the aetiology of oocyte aneuploidy and age-related reproductive decline.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRF-28-ZJ47D112Z4DZ suppresses gastric cancer progression via Ago2-mediated regulation of the CCND1-associated cell cycle pathway and serves as a complementary plasma biomarker.","authors":"Xiuchong Yu, Jianing Tong, Yaoyao Xie, Zhimin Hao, Zhilong Yan, Jiaxin Ge, Junming Guo","doi":"10.1016/j.jare.2026.08.022","DOIUrl":"10.1016/j.jare.2026.08.022","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, highlighting the need for improved non-invasive biomarkers for early detection and prognostic evaluation. tRNA-derived fragments (tRFs) have emerged as regulatory non-coding RNAs in cancer, but their biological and clinical significance in GC remains unclear.</p><p><strong>Objectives: </strong>To evaluate the diagnostic, prognostic, and biological significance of tRF-28-ZJ47D112Z4DZ (tRF-28) in GC and investigate its underlying molecular mechanism.</p><p><strong>Methods: </strong>tRF-28 was identified using a stepwise screening strategy, and an absolute quantification assay was established for plasma detection. Receiver operating characteristic (ROC) analysis, survival analysis, and Cox regression models were used to evaluate its clinical significance. Gain- and loss-of-function studies in GC cells, together with xenograft overexpression models, were performed to investigate its biological functions. RNA immunoprecipitation, dual-luciferase reporter assays, rescue experiments, and immunohistochemistry were used to explore the underlying mechanism.</p><p><strong>Results: </strong>Plasma tRF-28 levels progressively decreased from healthy controls to precancerous lesions and GC patients. tRF-28 demonstrated diagnostic value for precancerous lesions (AUC = 0.713) and showed moderate but reproducible diagnostic performance for GC in both the training and validation cohorts (AUC = 0.762 in the training cohort). Reduced plasma tRF-28 levels were associated with poor differentiation, deeper invasion, and unfavorable overall survival, and multivariate Cox analysis identified tRF-28 as an independent protective prognostic factor. Functionally, tRF-28 inhibited GC cell proliferation, colony formation, invasion, migration, and cell cycle progression while promoting apoptosis. Mechanistically, tRF-28 associated with Argonaute 2 (Ago2) and directly targeted the 3' untranslated region of CCND1 mRNA, thereby suppressing the Cyclin D1/CDK4/p-Rb signaling pathway. Xenograft studies further confirmed its tumor-suppressive effect in vivo.</p><p><strong>Conclusions: </strong>tRF-28 suppresses GC progression through regulation of the CCND1-associated cell cycle pathway and may serve as a complementary plasma biomarker for GC diagnosis and prognostic assessment.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}