{"title":"The dual fate of L-theanine in tea: Metabolic regulation and processing transformations","authors":"Haiyan Cheng, Jinglei Zheng, Linyue Tu, Lin Chen, Weizhong He, Yuefei Wang, Zhonghua Liu, Ping Xu","doi":"10.1016/j.jare.2025.10.002","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.002","url":null,"abstract":"<h3>Background</h3>L-Theanine, the signature non-protein amino acid unique to tea (<em>Camellia sinensis</em>), is crucial for tea’s health benefits and umami taste, yet its biosynthesis and stability face increasing threats from climate change and processing challenges.<h3>Aim of review</h3>This review intends to provide the comprehensive synthesis of L-theanine’s dual fate from biosynthesis to cup by integrating recent breakthroughs in its biosynthesis, transport, stress responses, and processing transformations.<h3>Key scientific concepts of this review</h3>This review systematically elucidated the complete “root-to-shoot” metabolic pathway regulated by key genes and transporters of L-theanine, and summarized stress-adaptive mechanisms where L-theanine serves as both nitrogen reservoir and stress protectant, and further constructed a comprehensive analytical for L-theanine-derived flavor compound formation during tea processing. By bridging fundamental discoveries in plant physiology with practical applications in food chemistry, this work provides new insights into innovative strategies for developing climate-resilient tea varieties through molecular breeding and optimizing processing technologies to enhance product quality.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lactylation: a promising target for musculoskeletal disorders via interactions with chronic inflammation","authors":"Tiantian Wang, Sihan Chen, Zhen Hong","doi":"10.1016/j.jare.2025.09.058","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.058","url":null,"abstract":"Musculoskeletal disorders (MSDs) encompass conditions that affect bones, joints, and muscles, leading to substantial pain and functional impairment and representing a major global health concern. In MSDs, key metabolic processes—such as glycolysis and lactate accumulation under hypoxic conditions—disrupt cellular energy homeostasis. Lactylation, a post-translational modification arising from excessive lactate, modifies both histone and non-histone proteins and has been implicated in inflammation and MSD pathogenesis. Preclinical studies indicate that targeting lactylation holds promise for the treatment of various MSDs. Systemic, chronic, low-grade inflammation (SCLGI) is thought to contribute to both the onset and persistence of many MSDs, with its unresolved state driving chronic disease progression. Promoting the resolution of SCLGI may alleviate symptoms, particularly through specialized pro-resolving mediators (SPMs) derived from dietary essential polyunsaturated fatty acids (PUFAs). Both SPMs and their small-molecule analogs have demonstrated therapeutic benefits in animal models of inflammation-related disorders, including arthropathies, osteoporosis, and muscular dystrophy.This review proposes a novel therapeutic strategy for MSDs that integrates lactylation inhibitors or agonists with agents that facilitate SCLGI resolution. Such a combined approach may enhance the effectiveness of MSD management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Erianin serves as an NFATc1 inhibitor to prevent breast cancer-induced osteoclastogenesis and bone destruction” Adv. Res. 69 (2025) 399-411]","authors":"Jiehuang Zheng, Weili He, Yan Chen, Lihong Li, Qinghe Liang, Wenqi Dai, Ruopeng Li, Fengsheng Chen, Ziye Chen, Yanhui Tan, Xiaojuan Li","doi":"10.1016/j.jare.2025.09.035","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.035","url":null,"abstract":"The authors regret the oversight related to Fig. S2 due to a copy-paste error which resulted in the unintended misplacement of Fig. S2.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydrogen sulfide regulation in redox homeostasis and programmed cell death: mechanistic insights and implications in cancer","authors":"Aoli Deng, Lulu Chen, Hangqi Huang, Qin Tang, Yajuan Lu, Jinghao Cao, Yingchao Liu, Yunyi Wu, Feifan Pan, Yanchun Li, Xiangmin Tong, Jing Du","doi":"10.1016/j.jare.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.001","url":null,"abstract":"Hydrogen sulfide (H<sub>2</sub>S), a key endogenous gaseous mediator derived from sulfur-containing amino acid metabolism, exhibits a concentration-dependent duality in cancer. At physiological concentrations, H<sub>2</sub>S exerts antioxidant effects by activating the NRF2/Keap1 pathway and suppressing lipid peroxidation, thereby promoting tumor cell survival. In contrast, supraphysiological levels of H<sub>2</sub>S induce programmed cell death (PCD) by impairing mitochondrial homeostasis, triggering reactive oxygen species (ROS) bursts, and modifying critical proteins via persulfidation. The complex interplay between H<sub>2</sub>S and PCD pathways highlights its potential as a therapeutic target, with emerging strategies focusing on modulating endogenous H<sub>2</sub>S production and developing targeted H<sub>2</sub>S-releasing compounds. Current pharmacological approaches include inhibiting H<sub>2</sub>S-synthesizing enzymes and exogenous administration of H<sub>2</sub>S donors, which have shown promise in preclinical models and clinical trials for overcoming therapy resistance and enhancing treatment efficacy. This review establishes the integrative framework bridging H<sub>2</sub>S biology with six distinct PCD modalities, focusing on its potential therapeutic applications in cancer therapy. It further investigates the core challenges in clinical translation of H<sub>2</sub>S-based therapies, particularly the dual hurdles of achieving targeted delivery and managing concentration-dependent effects. To overcome these challenges, we outline emerging translational strategies that leverage enzyme-targeted inhibitors, repurpose H<sub>2</sub>S-modulating drugs already approved by the FDA, and integrate novel nano-theranostic platforms capable of stimulus-triggered and spatially precise release of H<sub>2</sub>S. Future research should prioritize developing intelligent delivery systems with precise spatiotemporal control, and deciphering the dynamic regulation of H<sub>2</sub>S-mediated PCD, which will be essential for advancing these mechanistic insights into precision oncology therapeutics.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"349 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome-wide CRISPR screen identifies STK11 as a critical regulator of sialic acid clusters important for influenza A virus attachment","authors":"Huimin Sun, Jiahui Zou, Shaoyu Tu, Didan Luo, Rong Xiao, Yue Du, Chuhan Xiong, Shengsong Xie, Hailong Liu, Meilin Jin, Huanchun Chen, Hongbo Zhou","doi":"10.1016/j.jare.2025.09.059","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.059","url":null,"abstract":"<h3>Introduction</h3>Swine influenza virus (SIV) is a highly contagious respiratory pathogen in pigs that causes substantial economic losses in the pig industry. Importantly, pigs act as “mixing vessels” for diverse influenza A viruses (IAVs), facilitating the emergence of novel pandemic strains through reassortment, which represents a continuous global public health threat. IAV replication relies heavily on host cellular machinery, underscoring the importance of elucidating virus-host protein interactions for the development of targeted antiviral therapeutics.<h3>Objectives</h3>This study aims to identify host genes required for SIV replication via a genome-wide CRISPR screen and elucidate the mechanism by which STK11 modulates viral replication.<h3>Methods</h3>A pig genome-scale CRISPR knockout (PigGeCKO) screen was performed in newborn pig trachea (NPTr) cells to identify host genes required for SIV replication. Candidate genes were further validated by generating knockout cell lines using CRISPR/Cas9-mediated gene editing, followed by assessing their impact on IAV replication. The specific lifecycle stage regulated by STK11 and its mechanistic role in viral attachment were determined via Western blotting, confocal microscopy, transmission electron microscopy, and stimulated emission depletion (STED) imaging. <em>In vivo</em> validation of STK11 knockdown effects on IAV replication was conducted in BALB/c mice treated with STK11-targeting siRNA, with outcomes evaluated by survival analysis, body weight monitoring, lung viral titers quantification, immunofluorescence, and histopathology.<h3>Results</h3>STK11 promotes replication of different IAV subtypes <em>in vitro</em>, and STK11 knockdown significantly suppresses SIV replication <em>in vivo</em>. Mechanistically, STK11 depletion impairs viral attachment by altering the organization of sialic acid clusters, mediated through reduced intracellular actin stress fibers via inhibition of RhoA signaling pathway.<h3>Conclusion</h3>We identify STK11 as a novel regulator of IAV attachment and elucidate its mechanistic role in facilitating viral entry. These findings highlight the potential of STK11 to serve as an ideal antiviral target against IAV infection.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"128 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jihong Wang, Xiangrui Guo, Qiwen Fan, Lin Liu, Kanghui Lin, Rui Shi, Xiahong He, Xianfeng Ye, Yan Huang, Yanling Ji, Lei Zhang, Daniel Wall, Muxing Liu, Zhongli Cui, Zhoukun Li
{"title":"A predator–prey interaction between myxobacteria and fungi mediated by outer membrane vesicles","authors":"Jihong Wang, Xiangrui Guo, Qiwen Fan, Lin Liu, Kanghui Lin, Rui Shi, Xiahong He, Xianfeng Ye, Yan Huang, Yanling Ji, Lei Zhang, Daniel Wall, Muxing Liu, Zhongli Cui, Zhoukun Li","doi":"10.1016/j.jare.2025.10.006","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.006","url":null,"abstract":"<h3>Introduction</h3>Outer membrane vesicles (OMVs) of Gram-negative bacteria mediate diverse functions in natural ecosystems. As a keystone taxon in soil, myxobacteria produce OMVs for cargo packing and microbial predation. However, the roles of OMVs in the interactions of myxobacteria with fungi remain poorly understood.<h3>Objectives</h3>This work aims to clarify the role of outer membrane vesicles in the interaction between myxobacteria and fungi and the regulatory mechanism during the interaction process.<h3>Methods</h3>We found that OMV plays a significant role in the interaction between <em>Myxococcus</em> sp. MP20 and <em>Verticillium dahilae</em> (Vd). We further identified the antifungal metabolites in OMV and verified the regulatory mechanism of OMV in the model strain <em>Myxococcus xanthus</em> DK 1622.<h3>Results</h3>We discover that <em>Myxococcus</em> sp. MP20 uses fungal networks and cotton root exudates for spatial dispersal. MP20 deploys the antifungal metabolites myxothiazole via OMVs to inhibit Vd growth by fusing the OMVs with fungal cells, thus restraining fungal invasion. Containment of myxothiazol within OMVs maintains an effective antifungal concentration on target cells. Furthermore, we demonstrate that the release of OMVs from MP20 was suppressed by iron via a newly discovered ABC transport system. In turn the lower number of OMVs reduced the antifungal behavior of MP20, suggesting that iron acquisition regulates OMVs-mediated competition between myxobacteria and fungi. Our findings thus unravel a novel antifungal tactic employed by myxobacteria to suppress fungi prey and control Verticillium wilt, which also provides new insights for understanding predator–prey interactions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"112 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of capsaicin, circadian clock genes, and TRPV1 in colorectal carcinogenesis: Lessons and future directions","authors":"Qiuyan Zhang, Yujia Lu, Yuchen Zhao, Chi-Tang Ho, Yuhao Zhang, Yu Fu","doi":"10.1016/j.jare.2025.10.004","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.004","url":null,"abstract":"Disruptions in rhythm-regulating genes, termed circadian misalignment, have been increasingly associated with the progression of colorectal cancer (CRC), a significant global health challenge. Capsaicin (CAP), a bioactive compound found in chili pepper, has emerged as a promising modulator of clock genes, exhibiting anti-CRC potential. We propose a previously unrecognized dual-pathway mechanism where CAP may modulate circadian clock genes via both transient receptor potential vanilloid 1 (TRPV1)-dependent and TRPV1-independent pathways to inhibit colorectal carcinogenesis. Although the role of CAP in CRC prevention via clock gene regulation is compelling, direct mechanistic evidence remains limited. This paper also identifies several research gaps to underscore the necessity for further research to unlock its therapeutic potential and develop novel preventive strategies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"13 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanhong Fu, Tong Yu, Xiao Ma, Zhuo Liu, Chunjin Li, Shaoqin Shen, Rong Zhou, Yingchao Zhang, Xiaoming Song
{"title":"Comprehensive genomic analysis and database construction for Apiales","authors":"Yanhong Fu, Tong Yu, Xiao Ma, Zhuo Liu, Chunjin Li, Shaoqin Shen, Rong Zhou, Yingchao Zhang, Xiaoming Song","doi":"10.1016/j.jare.2025.10.007","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.007","url":null,"abstract":"<h3>Introduction</h3>The Apiales order harbors a rich variety of species, including vegetables, spices, and medicinal herbs, that possess diverse morphological characteristics and are globally distributed. Apiaceae and Araliaceae, being the two principal families within the Apiales order, have been the focus of extensive attention and research efforts on account of their significant value.<h3>Objectives</h3>Although the species in Apiales are important and there is a large amount of genomic data available, there is currently a lack of large-scale genomic analysis and database platform at the Apiales order level. Therefore, this study aims to conduct a comprehensive genomic analysis and database construction for Apiales.<h3>Methods</h3>This study performed comprehensive comparative genomic analysis by bioinformatics methods. The database was constructed with MySQL database management, the Django framework, and multiple programming languages.<h3>Results</h3>The present study was designed to clarify the phylogenetic associations and the phenomenon of paleo-polyploidization within Apiales species. Subsequently, an in-depth exploration was carried out to determine the ancestral karyotypes and to analyze the evolutionary pathways of chromosomes. In this research endeavor, genomic and transcriptomic data were employed to execute a comprehensive bioinformatic analysis. Eventually, through the integration of genomic data and bioinformatics findings, this study established the Apiales Genome Resources Database (TAGR), which is freely accessible at <span><span>http://tagr.bio2db.com/index.html</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Conclusion</h3>The research project carried out a profound investigation into the genomic evolution and chromosomal karyotypes of Apiales species, unraveling their evolutionary history from a genomic perspective. In addition, this study established the TAGR, which will offer researchers convenient access to and efficient utilization of these omics data resources, facilitating genomic analysis and molecular breeding initiatives.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"77 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Gao, Tao Chen, Yong Xu, Yijie Wu, Kunhong Liu, Weihong Qiu, Weimin Ye
{"title":"Accurate fatty liver disease diagnosis with a multi-source feature fusion model on the segmented tongue image dataset","authors":"Jie Gao, Tao Chen, Yong Xu, Yijie Wu, Kunhong Liu, Weihong Qiu, Weimin Ye","doi":"10.1016/j.jare.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.003","url":null,"abstract":"<h3>Introduction</h3>More than 100 million individuals in rural areas of China are suffered from Fatty Liver Disease (FLD). However, health clinics in remote regions often lack the necessary professional expertise and expensive ultrasound equipment for regular liver disease screening. Delayed treatment frequently leads to liver cirrhosis and cancer, imposing substantial economic burden on both public health systems and affected families.<h3>Objectives</h3>Traditional Chinese Medicine emphasizes the strong association between tongue characteristics and liver health. Leveraging machine learning to model the relationship between tongue images and FLD can enable rapid, non-invasive, large-scale screening in medically underserved areas. However, existing studies in this domain often rely on small-scale private datasets, which can result in unverifiable model performance. Moreover, most studies have employed generic convolutional neural networks for feature extraction, causing a lack of interpretability. The goal of our research is to address above-mentioned questions.<h3>Methods</h3>In this study, we first introduced a Multi-source Feature Fusion-based Tongue Diagnosis Framework for FLD diagnosis (MFF-TDF). In addition, we developed and released a standardized tongue image dataset with physiological indicators and FLD annotations, comprising 5,717 samples, which to our knowledge is the largest public dataset in this domain. Finally, we evaluated the effectiveness of the proposed method through extensive experiments and enhanced model interpretability using shapley additive explanations and counterfactual analysis.<h3>Results</h3>When conducting fusion modeling with tongue images and some basic physiological indicators (such as sex, age, height, etc.), FLD’s prediction performance in the population reached F1-score 0.797, Recall 0.847, and AUC 0.924. This performance significantly exceeds that of the state-of-the-art methods published in this domain.<h3>Conclusion</h3>This study developed an automated and explainable method for tongue diagnosis that facilitated the low-cost, speedy screening of FLD in large-scale populations, and contributed the largest public dataset to support future modeling research in this field.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhu , Haojie Yin , Xianli Zhong , Qin Zhang , Li Wang , Rong Lu , Ping Jia
{"title":"Exploring the mediating roles of depression and cognitive function in the association between sarcopenia and frailty: A Cox survival analysis approach","authors":"Yan Zhu , Haojie Yin , Xianli Zhong , Qin Zhang , Li Wang , Rong Lu , Ping Jia","doi":"10.1016/j.jare.2024.12.021","DOIUrl":"10.1016/j.jare.2024.12.021","url":null,"abstract":"<div><h3>Background</h3><div>Despite earlier research indicating a potential link between the development of sarcopenia and an elevated risk of frailty, the lack of comprehensive prospective data on the correlation between sarcopenia and frailty incidence leaves open the question of whether depression and cognitive function mediate this association.</div></div><div><h3>Objective</h3><div>The principal aim of the current investigation was to evaluate the intricate interplay among sarcopenia, depression, and cognitive function collectively influence the risk of developing frailty.</div></div><div><h3>Methods</h3><div>The participants included in this study were obtained from three waves of the China Health and Retirement Longitudinal Study (CHARLS), which collectively encompassed a total of 3,108 participants. To examine the interrelationships among sarcopenia, depression, cognitive function, and the incidence of frailty, we employed Cox regression models along with structural equation modelling, while making necessary adjustments for baseline demographic characteristics and various lifestyle factors.</div></div><div><h3>Results</h3><div>During a 4-year follow-up, we documented 753 frailty events. Compared to those with nonsarcopenia, those with possible sarcopenia and sarcopenia presented risk ratios for frailty events of 1.354 (95 % CI: 1.156, 1.586) and 1.514 (95 % CI: 1.203, 1.907), respectively. Stratified analyses by different statuses of sarcopenia further revealed that the significant effect of depression on frailty was present across all groups (nonsarcopenia, possible sarcopenia and sarcopenia), whereas the effect of cognitive function on frailty was limited to the non-sarcopenia and possible sarcopenia groups. Mediation analysis showed that sarcopenia was correlated not only with frailty through depression and cognitive function separately but also through a chain-mediated effect of depression and cognitive function together.</div></div><div><h3>Conclusions</h3><div>Sarcopenia is associated with frailty, depression and cognitive function playing partial, mediating roles. Frailty’s susceptibility to depression and cognitive function differs based on sarcopenia status. Therefore, comprehensive interventions that include sarcopenia screening, interventions, improvements in depression, the promotion of mental health, and delays in cognitive decline will be more effective in preventing and delaying frailty. This effectiveness is particularly relevant for middle-aged and older adults who reside in China.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 605-613"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}