Journal of Advanced Research最新文献

{"title":"HFPO homologue exposure impairs human sperm function via calcium dyshomeostasis and mitochondrial dysfunction","authors":"Meiling Le,Jiayu Xue,Jing Ding,Lihai Wu,Yangyang Yuan,Liping Zheng,Liaoliao Hu,Dalei Zhang","doi":"10.1016/j.jare.2026.10.013","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.013","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150617","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":"Pluripotent stem cell–specific imprinted genes identified using human uniparental-induced pluripotent stem cells","authors":"Na Young Choi,&nbsp;Seokbeom Ham,&nbsp;Dahee Jeong,&nbsp;Jihye Ryu,&nbsp;Minseong Lee,&nbsp;Abida Raheem,&nbsp;Suk-Won Ahn,&nbsp;Yukyeong Lee,&nbsp;Yerin Kim,&nbsp;Han Sung Hwang,&nbsp;Gwang Jun Kim,&nbsp;Kisung Ko,&nbsp;Chaeyoung Lee,&nbsp;Kinarm Ko","doi":"10.1016/j.jare.2026.01.023","DOIUrl":"10.1016/j.jare.2026.01.023","url":null,"abstract":"<div><div><em>Introduction:</em> Genomic imprinting is an epigenetic mechanism in which gene expression is determined by the parent of origin. Imprinted genes are crucial for mammalian growth and development, and mutations at imprinting sites can lead to developmental disorders and diseases. Therefore, identifying novel imprinted differentially methylated regions (DMRs) is essential for understanding imprinting mechanisms and their implications in human biology.</div><div><em>Objectives:</em> This study aimed to identify new imprinted DMRs using parthenogenetic and androgenetic human induced pluripotent stem cells (PgHiPSCs and AgHiPSCs), derived from mature cystic teratomas and complete hydatidiform moles, respectively.</div><div><em>Methods:</em> Genome-wide DNA methylation profiling via DNA methyl-capture sequencing (MethylCap-seq) was used to identify candidate imprinted DMRs. Subsequent bisulfite sequencing validated the methylation status, and comparative analyses confirmed pluripotency-specific imprinting.</div><div><em>Results:</em> We identified 26 novel imprinted DMRs and excluded 6 that exhibited the absence of allelic imbalance or the presence of potential confounding by expression quantitative trait locus. Among the remaining 20, the DMRs in <em>DOCK4</em> and <em>LYNX1</em> were validated. They had distinct imprinted methylation and expression patterns unique to pluripotent stem cells and absent in fibroblasts and normal adult tissues.</div><div><em>Conclusion:</em> These findings highlight the utility of uniparental iPSCs for discovering imprinted genes specific to the pluripotent state and provide insights into the epigenetic regulation of early human development.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 275-283"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A methylation in ferroptosis regulation: mechanisms, targets, and therapeutic interventions","authors":"Chaoying Wen,&nbsp;Yi Jiao,&nbsp;Zhaoran Wang,&nbsp;Tong Shi,&nbsp;Yan Wang,&nbsp;Jiahe Xu,&nbsp;Tiantian Deng,&nbsp;Guoqiang Zhang,&nbsp;Cheng Xiao","doi":"10.1016/j.jare.2026.01.021","DOIUrl":"10.1016/j.jare.2026.01.021","url":null,"abstract":"<div><h3>Background</h3><div>The dynamic crosstalk between N6-methyladenosine (m6A) RNA methylation and ferroptosis is pivotal for understanding disease pathogenesis. As the most abundant form of eukaryotic mRNA modification, m6A methylation guides RNA metabolism through writers, erasers, and readers. Ferroptosis, an iron-dependent and lipid peroxidation-driven form of cell death, occurs under conditions including dysregulated iron metabolism, compromised antioxidant defences, and lipid peroxidation.</div></div><div><h3>Aim of review</h3><div>This review highlights recent progress in basic research and proposes potential therapeutic targets for diseases of different systems while also addressing current drugs and challenges.</div></div><div><h3>Key scientific concepts of review</h3><div>m6A RNA modification is governed by three types of effector proteins—writers, erasers, and readers—while the molecular mechanisms governing ferroptosis involve three interconnected biological axes: iron metabolism homeostasis, redox balance, and lipid peroxidation dynamics. Studies have indicated that m6A methylation regulates the expression of ferroptosis-related proteins, thus influencing tumorigenesis, progression and pathogenesis. This review also summarizes currently available agents targeting m6A-related targets as well as those associated with both m6A and ferroptosis, aiming to highlight their potential for clinical applications.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 825-840"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular choreography of vesicle trafficking: Exocyst–SNARE interplay in plant defense","authors":"Muhammad Adnan,&nbsp;Liu Xiaokun","doi":"10.1016/j.jare.2026.01.059","DOIUrl":"10.1016/j.jare.2026.01.059","url":null,"abstract":"<div><h3>Background</h3><div>The plant secretory system operates as a precision logistics network that sustains cellular homeostasis and mobilizes rapid defense against pathogens. Central to this system are SNARE (soluble <em>N</em>-ethylmaleimide-sensitive factor attachment protein receptor) proteins, which catalyze membrane fusion, and the octameric exocyst complex, which tethers <em>trans</em>-Golgi–derived vesicles to defined plasma-membrane domains. Rather than functioning independently, these machineries act as an interdependent module: the exocyst facilitates vesicle tethering and promotes SNARE complex assembly, while SNARE proteins reciprocally stabilize exocyst positioning and activity. This synergy ensures the targeted delivery of immune cargos—including pathogenesis-related proteins, callose synthases, transporters, and specialized metabolites—directly to pathogen attack sites. However, pathogens deploy effectors that disrupt exocyst–SNARE interfaces, weakening these defensive supply lines.</div></div><div><h3>Aim of review</h3><div>This review integrates recent advances that expand the functional repertoire of both complexes across canonical and unconventional secretion pathways. It incorporates regulatory factors such as Rab GTPases, Rho-GTPases of plants (ROPs), phosphoinositides, cytoskeletal elements, and post-translational modifications, offering a comprehensive framework for understanding exocyst–SNARE coordination in plant defense. At the same time, it highlights key unresolved questions, such as the molecular choreography of holo-exocyst–SNARE assemblies in vivo, rules of immune cargo selection, and the dynamic rerouting of pathways during stress.</div></div><div><h3>Key scientific concepts of review</h3><div>A central theme emerging from these insights is the cooperative interaction between exocyst and SNARE proteins as the basis for localized immune delivery. However, the vulnerability of this machinery to pathogen interference underscores the need for deeper mechanistic understanding. This review positions vesicle-fusion control as a promising and tractable strategy for engineering durable disease resistance in crops, framing exocyst–SNARE biology as a critical lever in strengthening plant immunity.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 469-483"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 promotes neutrophil extracellular trap formation via SYK/ERK/MEK signaling during acute lung injury","authors":"Shuhua Luo,&nbsp;Qianqian Zhang,&nbsp;Wending Zhou,&nbsp;Lina Zhang,&nbsp;Chaoxiong Liao,&nbsp;Dan Zeng,&nbsp;Liangqing Zhang,&nbsp;Fu-li Xiang,&nbsp;Jie Xu,&nbsp;Jing Tang","doi":"10.1016/j.jare.2026.01.044","DOIUrl":"10.1016/j.jare.2026.01.044","url":null,"abstract":"<div><h3>Introduction</h3><div>Acute lung injury (ALI) is a life-threatening condition characterized by overwhelming pulmonary inflammation and neutrophil infiltration. Neutrophils play a central role in ALI pathogenesis by releasing proteolytic enzymes, reactive oxygen species, and neutrophil extracellular traps (NETs). Although NETs contribute to pathogen clearance, excessive NET formation exacerbates tissue injury and amplifies inflammation. N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA and plays a pivotal role in immune cell regulation by modulating RNA stability and translation. However, how m6A modification governs NETosis during ALI remains incompletely understood.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the role of METTL3 mediated m6A modification on NET formation and the underlying mechanisms in lung injury in ALI.</div></div><div><h3>Methods</h3><div>The role of METTL3 mediated m6A in ALI was examined in mouse with conditional deletion of METTL3 in myeloid or neutrophil lineages. Histological and flow cytometric analysis, gene interference, overexpression, transcriptomic profiling and m6A-RIP-qPCR were performed to elucidate the underlying mechanisms of METTL3 promoting NETosis via SYK/ERK/MEK signaling axis in vitro and in vivo.</div></div><div><h3>Results</h3><div>Conditional deletion of METTL3 in myeloid or neutrophil lineages significantly reduced lung MPO activity, citrullinated histone H3 levels, and extracellular DNA deposition following lipopolysaccharide (LPS)-induced ALI. METTL3 deficiency attenuated pulmonary inflammation and reduced neutrophil infiltration. In vitro, METTL3-deficient neutrophils exhibited decreased NET formation upon phorbol myristate acetate (PMA) stimulation, along with diminished SYK phosphorylation and downstream ERK/MEK activation. Mechanistically, METTL3 promotes m6A methylation of SYK mRNA, enhancing its stability and transcription. Pharmacological inhibition of either METTL3 or SYK recapitulated the protective phenotype, suppressing NETosis and lung damage in vivo.</div></div><div><h3>Conclusion</h3><div>Collectively, our findings uncover a novel METTL3–SYK epitranscriptomic axis that governs neutrophil effector responses during endotoxin-induced lung injury. These results highlight m6A-dependent post-transcriptional regulation as a potential therapeutic target in ALI and sepsis-associated inflammation.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 367-379"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MetsObesity: a novel classification system for predicting 15-year cardiovascular risk in the UK Biobank population","authors":"Junaid Iqbal,&nbsp;Hui-Xuan Wu,&nbsp;Yan-Xuan Wu,&nbsp;Hong-Li Jiang,&nbsp;Long Li,&nbsp;Xuan-Yu Zhou,&nbsp;Yan-Hong Bu,&nbsp;Hou-De Zhou","doi":"10.1016/j.jare.2026.01.050","DOIUrl":"10.1016/j.jare.2026.01.050","url":null,"abstract":"<div><h3>Background</h3><div>Obesity phenotyping often fails to capture the heterogeneity in cardiovascular risk. Current approaches rely heavily on BMI or conventional metabolic syndrome criteria, which underestimate cardiometabolic risk in a large proportion of population. We aimed to develop and validate a novel, clinically scalable classification system, MetsObesity, to predict long-term cardiovascular outcomes in people with obesity and/or other metabolic abnormalities.</div></div><div><h3>Methods and Findings</h3><div>Using data from 346,001 participants in the UK Biobank (median follow-up: 15 years), we applied random forests and recursive feature elimination algorithms to identify key predictors of cardiovascular events across metabolic, anthropometric, and additional abnormalities domains. The SHapley Additive exPlanations (SHAP) model was employed to explore the interpretability of variables selection. These variables informed a five-tier classification system (MetsObesity Classes 1–5). Cox proportional hazard models were used to assess associations with major adverse cardiovascular events (MACE). Model performance was evaluated using discrimination (C-index), calibration, and decision curve analysis.</div><div>In the validation cohort (n = 173,000), the incidence of MACE was 1.4%, 3.3%, 5.0%, 6.0%, and 8.5% across the five classes, respectively. MetsObesity significantly outperformed BMI, waist circumference, body fat percentage, and existing metabolic syndrome definitions in predicting incident MACE. Participants in Classes 4 and 5 had 2–4-fold higher hazard ratio than traditional obesity classifications. The model demonstrated robust calibration and clinical net benefit across subgroups. Lack of external validation is the key limitation of this study.</div></div><div><h3>Conclusions</h3><div>The MetsObesity offers a novel, interpretable, and implementable framework for cardiovascular risk stratification in people with obesity and metabolic abnormalities. Integration of routinely available clinical variables allows scalable application across healthcare settings. This classification has potential to inform risk-based prevention strategies and redefine cardiometabolic screening in global health systems.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 947-957"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmasking human T cell receptor germline diversity: 335 novel alleles identified in 47 Pangenome reference individuals using the gAIRR Suite","authors":"Yu-Hsuan Yang,&nbsp;Chi-Yuan Yao,&nbsp;Mao-Jan Lin,&nbsp;Kuan-Ta Huang,&nbsp;Yu-Hui Lin,&nbsp;Yi-Hui Huang,&nbsp;I-Hsuan Chiu,&nbsp;Sheng-Kai Lai,&nbsp;Chih-Yeh Chen,&nbsp;Ya-Chien Yang,&nbsp;Chia-Lang Hsu,&nbsp;Jacob Shujui Hsu,&nbsp;Chien-Yu Chen,&nbsp;Pei-Lung Chen","doi":"10.1016/j.jare.2026.01.053","DOIUrl":"10.1016/j.jare.2026.01.053","url":null,"abstract":"<div><h3>Introduction</h3><div>The adaptive immune receptor repertoire (AIRR), also referred to as expressed AIRR (exprAIRR) for clarity, comprises V(D)J-recombined T cell receptors (TR) and immunoglobulins (IG), and is central to adaptive immunity. Accurate exprAIRR profiling depends on a comprehensive and population-representative germline gene set encoding AIRR (gAIRR). In addition to serving as the reference for AIRR-seq, gAIRR alleles themselves are increasingly recognized as contributors to immune-related phenotypes, including disease susceptibility, variable vaccine responsiveness, and adverse immune events.</div></div><div><h3>Objectives</h3><div>Current germline TR references form an essential foundation, but based on scientific inference, likely represent only a portion of true human diversity. Some alleles lack flanking genomic information, and several populations remain underrepresented—constraints rooted in earlier sequencing methodologies. This study aims to substantially expand these references by resolving full-length TR alleles and their flanking regions across ancestrally diverse individuals.</div></div><div><h3>Methods</h3><div>We analyzed 47 high-quality, phased diploid genomes from the Human Pangenome Reference Consortium (HPRC) using the gAIRR Suite. All novel alleles were crosschecked using two orthogonal pipelines: gAIRR-annotate (assembly-based annotation) and gAIRR-seq/gAIRR-call (targeted short-read sequencing and genotyping).</div></div><div><h3>Results</h3><div>We identified 335 novel TR alleles—305 TRV and 30 TRJ—representing 91.6% and 30.9% increases over IMGT records (v3.1.41; accessed 2025–04-19), respectively. Many novel alleles occurred at substantial frequencies, particularly among individuals of African ancestry. We further established a comprehensive flanking sequence database, including recombination signal sequences (RSS), and documented allele-specific variations in these regions. Functional annotation showed that several novel alleles exhibit altered coding potential, including transitions to pseudogene or open reading frames (ORFs) status.</div></div><div><h3>Conclusion</h3><div>This study significantly expands the known landscape of human TR germline diversity and provides a rigorously validated, population-diverse resource comprising novel alleles, flanking sequences, RSS profiles, and supporting analytical tools. These improved gAIRR references are essential for accurate germline genotyping and exprAIRR profiling, and will enable improved detection of immunogenetic associations. Our findings advance precision immunogenomics and support the development of ancestry-independent yet diversity-comprehensive genotyping, vaccines, and immunotherapies.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 437-452"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts","authors":"Zhengbin Zhang,&nbsp;Ziqian Wang,&nbsp;Liwen Zhu,&nbsp;Tong Chen,&nbsp;Rundu Chen,&nbsp;Zhengfeng Wu,&nbsp;Jie Chen,&nbsp;Honghong Zhang,&nbsp;Mingyi Wang,&nbsp;Jie Liu,&nbsp;Ning Hua,&nbsp;Shunying Hu,&nbsp;Yundai Chen","doi":"10.1016/j.jare.2026.01.073","DOIUrl":"10.1016/j.jare.2026.01.073","url":null,"abstract":"<div><h3>Introduction</h3><div>Senescent mesenchymal stem cells (MSCs) exhibit impaired self-renewal, limiting their therapeutic potential. While multi-omics have revealed downregulation of pan-tissue <em>Fbn1</em> with aging, particularly in MSCs, the role of its derivative asprosin in MSC senescence is unknown.</div></div><div><h3>Objectives</h3><div>To elucidate the regulation of senescence/reparative function in aged MSCs by asprosin and evaluate its therapeutic potential for aged MSC-mediated cardiac repair after myocardial infarction (MI).</div></div><div><h3>Methods</h3><div>Serum asprosin levels were measured by enzyme-linked immunosorbent assay, and asprosin expression in MSCs was determined by western blotting. <em>Fbn1</em> expression<!--> <!-->dynamics with aging were assessed using public transcriptomic/single-cell datasets. Gain/loss-of-function (lentiviral overexpression/CRISPR-Cas9 knockout) studies were employed to validate the role of asprosin. The effects of recombinant asprosin on senescent MSC proliferation, migration, and pro-angiogenic secretion were tested. Glycolytic flux (Seahorse), metabolites (glucose uptake, G-6-P, lactate), and lactylation (pan-lysine, H3K18la) were measured. Integrated H3K18la CUT&amp;Tag/RNA-seq was performed to identify downstream<!--> <!-->targets, and therapeutic efficacy was assessed in an MI mouse model using intramyocardial injection of asprosin-overexpressing aged MSCs.</div></div><div><h3>Results</h3><div>Circulating asprosin was correlated with adipose mass in young obese mice but was attenuated in aged obese mice. Consistently, human cohorts (normal body mass index) showed an inverse age-asprosin correlation. Systemic and MSC-specific asprosin expression significantly declined with aging. Asprosin knockout intensified H₂O₂-induced MSC acute premature senescence, whereas its overexpression restored MSC self-renewal. Human recombinant asprosin protein (requiring post-translational modifications for bioactivity) enhanced proliferation, migration, and paracrine angiogenesis in senescent MSCs. Mechanistically, asprosin activated the PI3K/Akt-HIF-1 pathway to upregulate VEGF/TIMP1 (angiogenesis) and drive the glycolysis-lactate-H3K18la axis (proliferation/migration). H3K18la CUT&amp;Tag/RNA-seq identified targets regulating DNA repair, proliferation, and migration. Asprosin deficiency impaired DNA repair. In MI mice, asprosin-overexpressing aged MSCs significantly improved retention and left ventricular ejection fraction, attenuated cardiac remodeling, and promoted <em>peri</em>-infarct angiogenesis.</div></div><div><h3>Conclusion</h3><div>Asprosin is a novel MSC-specific rejuvenation factor that antagonizes senescence through metabolic-epigenetic interplay. Targeting the asprosin-driven “Glycolysis-Lactylation-Epigenetics” axis offers a transformative strategy to enhance MSC-based therapies for ischemic heart disease.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 1055-1075"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic vulnerabilities in ovarian cancer decoding the nexus between nutrient adaptation and therapy resistance","authors":"Xiaoyu Guo,&nbsp;Zongang Liu,&nbsp;Xiaoman Li,&nbsp;Bingzheng Zhou,&nbsp;Jingyi Chen","doi":"10.1016/j.jare.2026.01.047","DOIUrl":"10.1016/j.jare.2026.01.047","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) is a leading cause of gynecologic cancer-related mortality, primarily due to frequent therapy resistance and disease recurrence. Growing evidence indicates that metabolic reprogramming serves as a critical adaptive mechanism, allowing cancer cells to survive therapeutic stress.</div></div><div><h3>Aim of review</h3><div>This review aims to decode the interplay between nutrient adaptation and therapy resistance in OC. It examines how alterations in key metabolic pathways contribute to treatment resilience and disease progression, and explores the potential of targeting metabolic vulnerabilities to improve therapeutic outcomes.</div></div><div><h3>Key scientific concepts of review</h3><div>We discuss how OC cells utilize metabolic pathways—including glycolysis, OXPHOS, glutamine metabolism, and lipid utilization—to promote survival, DNA repair, and immune evasion. Metabolic plasticity enables shifts between nutrient sources, driving resistance to platinum-based agents, PARP inhibitors, and anti-angiogenic therapies. These adaptations vary across subtypes, such as high-grade serous and clear cell carcinomas, and are influenced by specific mutations. Targeting metabolic enzymes—such as GLS, CPT1, OXPHOS complexes, or NAD⁺ synthesis—offers a promising strategic direction. Metabolic profiling may allow stratification of OC patients and pave the way for precision medicine approaches to overcome treatment resistance.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 589-610"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative genomics decoding DNA methylation-mediated genetic control of complex traits in pigs","authors":"Yiting Wang,Zitao Chen,Manting Fan,Cheng Liu,Jiamin Gu,Pengfei Yu,Wanghao Jin,Zhenyang Zhang,Shuyan Xie,Tao Yang,Jinyun Jiang,Zhe Zhang,Zhen Wang,Zhe Zhang,Lingzhao Fang,Yuchun Pan,Qishan Wang","doi":"10.1016/j.jare.2026.10.001","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.001","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"3 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090562","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}