Journal of Advanced Research最新文献

{"title":"Ganoderma lucidum spore powder enhances IFN-α-mediated antiviral capacity of COVID-19 vaccine boosters revealed by single-cell multi-omics sequencing","authors":"Anyao Li, Xiaoyan Lu, Rongfang Guo, Wenbo Guo, Penghui Yang, He Lou, Jie Chen, Enshan Huang, Ronghua Zhang, Hanbo Wang, Jihong Yang, Zhenhao Li, Xiaohui Fan","doi":"10.1016/j.jare.2025.10.014","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.014","url":null,"abstract":"<h3>Introduction</h3>Reduced vaccine efficacy may hinder stable herd immunity. Traditional herbal ingredients, such as <em>Ganoderma lucidum</em> products, have shown potential as safe and effective adjuvants to improve vaccine efficacy. However, their roles in assisting human epidemiological vaccines remain uninvestigated.<h3>Objectives</h3>This study aimed to evaluate <em>Ganoderma lucidum</em> spore powder (GLSP) as an adjuvant for COVID-19 vaccine boosters and to elucidate its underlying immunomodulatory mechanisms.<h3>Methods</h3>The microneutralization assay was utilized to measure the percentage of Neutralizing antibodies (NAbs) inhibition. The single-cell multi-omics sequencing was performed to investigate the mechanism of GLSP. The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and ultra-performance liquid chromatography multiple reaction monitoring mass spectrometry (UPLC-MRM-MS) were used to characterize the chemical composition of GLSP. The molecular docking and in vitro validated experiments were performed to identify triterpenoids that are active in inducing IFN-α production and signaling.<h3>Results</h3>In comparison with vaccination alone, GLSP significantly enhanced the NAbs percent inhibition in participants with moderate baseline immunity at 90 days post-vaccination. At the cellular level, GLSP substantially expanded the myeloid cell proportions, particularly classical monocytes (CMs), and augmented their interactions with T and B cells. It also promoted a stronger IFN-α response in innate and adaptive immune cells. In innate immunity, GLSP enhanced the transcription factor activity and chromatin accessibility related to IFN-α stimulation. In adaptive immunity, GLSP induced distinct biases for gene usage and clonal expansion of BCRs and TCRs, contributing to stronger antiviral immunity. Crucially, a combination of chemical profiling and functional validation identified the triterpenoid ganoderic acid H (GH) as the key active component responsible for inducing the IFN-α response.<h3>Conclusions</h3>GLSP demonstrates significant potential as a safe, orally administered adjuvant to counteract waning vaccine efficacy by promoting a robust, IFN-α-mediated antiviral state at the multi-omics level","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"43 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283140","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":"Breaking the bottleneck of asthma treatment: the future of omni-targeted therapy","authors":"Kuan Li, Huimin Xie, Dongshuai Shen, Li Li, Huaiyong Chen","doi":"10.1016/j.jare.2025.10.016","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.016","url":null,"abstract":"<h3>Background</h3>Bronchial asthma is a complex, highly heterogeneous disease involving multiple pathological mechanisms and inflammatory pathways. Traditional pharmacotherapies, including glucocorticoids, leukotriene modifiers, β2-adrenergic agonists, and muscarinic antagonists, and new targeted biologics can alleviate symptoms and prevent acute exacerbations; however, achieving clinical remission or a cure remains a major challenge.<h3>Aim of review</h3>To systematically outline the definition, epidemiology, and multifactorial pathogenesis of asthma; to explore potential therapeutic targets incorporating the latest advances from clinical trials and targeted interventions; and to emphasize the development of multi-target (“omni-targeted”) combination strategies based on individualized diagnosis, potentially guided by artificial intelligence (AI), to improve asthma control, clinical outcomes, and exacerbation rates, with an eye toward a definitive cure.<h3>Key scientific concepts of review</h3>We propose that the current therapeutic dilemma largely reflects the inability of single-target therapies to address an individual’s multiple pathogenic pathways. In contrast, multi-target, personalized strategies can modulate diverse pathological pathways simultaneously and precisely. Realizing these strategies will require AI-enabled guidance, precise identification of individual pathogenic mechanisms, and further development of targeted therapeutics.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283141","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":"A ventral hippocampus-basolateral amygdala circuit regulates the unconditioned stimulus retrieval-induced reconsolidation of remote fear memory","authors":"Dan Guo, Zhong Wang, Fanglin Liu, Wenhao Chen, Xuejiao Gao, Shihao Huang, Serik Tabarak, Yuan Yao, Shiya Zhang, Jie Shi, Lin Lu, Ying Han","doi":"10.1016/j.jare.2025.10.015","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.015","url":null,"abstract":"<h3>Introduction</h3>Memory is retrieved and updated during reconsolidation, which provides a potential target for therapeutic intervention. Reconsolidation blockade following unconditioned stimulus (US) retrieval has shown increasing promise in disrupting persistent remote fear memory, yet the underlying neural mechanisms remain poorly understood.<h3>Objectives</h3>This study aims to elucidate the neural mechanisms involved in US retrieval-induced reconsolidation of remote fear memory.<h3>Methods</h3>We established a rat model of contextual fear conditioning to investigate recent and remote fear memory with reconsolidation induced by US or conditioned stimulus (CS) retrieval. Pharmacological intervention, retrograde tracing, immunofluorescence, fiber photometry, as well as chemogenetic manipulation were employed to identify and manipulate key circuits involved in reconsolidation of fear memory.<h3>Results</h3>In this study, we show that pharmacological disruption of the US retrieval-induced reconsolidation of fear memory had a relatively long-lasting effect and was also effective for remote fear memory. We further reveal that activity of ventral hippocampal CA1 (vCA1)–basolateral amygdala (BLA) circuit specially contributes to US retrieval-induced reconsolidation of remote fear memory. Specifically, pharmacological interventions and inhibition of this circuit after US retrieval effectively disrupted remote fear memory, which showed long-term efficacy and resistance to reinstatement. Conversely, activating this circuit blocked the disruptive effect of propranolol on the remote fear memory reconsolidation.<h3>Conclusion</h3>Our findings suggest that the vCA1-BLA circuit becomes increasingly important for remote fear memory reconsolidation, particularly induced by US retrieval. This study highlights the potential for targeting specific circuits involved in reconsolidation of remote fear memory for therapeutic interventions in fear-related disorders.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283139","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":"Postmortem energy metabolism and meat quality development: Advances in basic pathways, endogenous regulatory factors, and exogenous management strategies","authors":"Chao Ma, Wangang Zhang, Jian Zhang, Lei Zhou, Lujuan Xing, Rui Liu","doi":"10.1016/j.jare.2025.10.010","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.010","url":null,"abstract":"<h3>Background</h3>A complex series of biochemical processes is involved during the transformation of muscle into meat, among which postmortem energy metabolism that contributes to adenosine triphosphate regeneration remains paramount. Thus, a timely and thorough overview of postmortem energy metabolism is essential for developing high-quality fresh meat.<h3>Aim of review</h3>The present work reviewed three basic pathways of postmortem energy metabolism and their impacts on meat quality development with special attention to mitochondria aerobic metabolism. In addition, endogenous factors and their mechanisms as well as exogenous strategies for regulating postmortem energy metabolism were also comprehensively summarized.<h3>Key scientific concepts of review</h3>Postmortem mitochondria, especially from livestock, remain metabolically active and exhibit oxygen consumption, which further mediates changes in muscle pH. Adenosine monophosphate-activated protein kinase and hypoxia inducible factor-1α, as energy-controlling hubs, contribute notably to the activation of postmortem glycolysis. Several protein posttranslational modifications (e.g., S-nitrosylation and lactylation) also show crucial regulatory roles for postmortem energy metabolism by altering the structure and function of metabolic enzymes. Exogenous techniques like electrical stimulation and advanced chilling can improve meat quality by optimizing energy metabolism process, while emerging technologies such as ultrasound hold promise. This work integrated existing knowledge, identified research gaps, and proposed a scientific outlook on species-specific postmortem energy metabolism","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"13 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283138","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":"Mitigation of renal tubular injury by SIRT6 may improve individual outcomes in diabetic kidney disease-potential mechanisms involving epigenetic repression of inflammatory responses","authors":"Qi Jin, Lanfang Li, Peng Qu, Fang Ma, Ping Li, Yuan Qiao, Yijia Zhang, Shuman Ran, Xinyu Li, Tongtong Liu, Liping Yang, Qian Li, Huimin Mao, Yuyang Wang, Feihong Ren, Yongli Zhan, Liang Peng","doi":"10.1016/j.jare.2025.10.008","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.008","url":null,"abstract":"<h3>Introduction</h3>Progressive tubulointerstitial injury plays a critical role in the progression of diabetic kidney disease (DKD), but the epigenetic mechanisms driving this process remain largely unclear.<h3>Objectives</h3>This study aimed to investigate the role of the histone deacetylase SIRT6 in renal tubular epithelial cells (TECs) during DKD progression and to explore its potential as a therapeutic target.<h3>Methods</h3>We employed digital spatial profiling (DSP) to perform spatially resolved mRNA quantification in proximal renal tubular tissue from DKD patients. Additionally, we used genetic and pharmacological approaches in DKD mouse models to assess the effects of SIRT6 deficiency or overexpression on renal injury. Mechanistic studies included RNA-sequencing (RNA-seq) and Cleavage Under Targets and Tagmentation (CUT&amp;Tag) sequencing, which to identify SIRT6-regulated genes and epigenetic modifications.<h3>Results</h3>Our findings revealed a significant reduction of SIRT6 in TECs from DKD patients, with its expression inversely correlating with disease severity. TEC-specific SIRT6 deficiency worsened renal injury and proteinuria in DKD mice, whereas SIRT6 overexpression or pharmacological activation provided renoprotection. Mechanistically, SIRT6 directly repressed <em>Nlrp3</em> transcription by deacetylating histone 3 lysine 9 acetylation (H3K9ac), thereby inhibiting NLRP3 inflammasome activation and subsequent TEC injury.<h3>Conclusion</h3>These findings highlight SIRT6 as a protective epigenetic factor in DKD and suggest its potential utility for disease stratification, early therapeutic intervention, and precision medicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"40 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255358","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":"MK8722 alleviates osteoarthritis by activating Sesn2 and transcriptionally upregulating BNIP3 to promote mitophagy and inhibit chondrocyte ferroptosis","authors":"Haochen Wang, Ze Zhao, Jianbang Su, Wenzheng Chen, Haoyan Shi, Tianqi Gao, Minghao Yu, Lunhao Bai, Peng Dong, Qian Zhang, Chao Ji, Jingyu Yang, Yang Liu, Yingliang Wei","doi":"10.1016/j.jare.2025.09.060","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.060","url":null,"abstract":"<h3>Introduction</h3>Osteoarthritis (OA) is commonly accompanied by irreversible destruction of articular cartilage and is difficult to effectively relieve, primarily due to the unclear pathogenesis and the lack of effective therapeutic interventions. Sestrin 2 (Sesn2) is a highly conserved protein that regulates oxidative stress and cellular metabolism; however, its impact on the progression of OA and the detailed mechanisms underlying this process have not been elucidated.<h3>Objectives</h3>To investigate the critical role of Sesn2 in OA cartilage degradation and to clarify the underlying mechanism by which MK8722 promotes mitophagy and inhibits chondrocyte ferroptosis through the activation of Sesn2.<h3>Methods</h3>We utilized multi-omics data from both human and mouse models to investigate a potential association between Sesn2 and chondrocyte ferroptosis. We established a murine OA model through destabilization of the medial meniscus surgery. Various molecular biological techniques, including western blot, immunofluorescence and flow cytometry, in combination with histological analyses, were employed to elucidate the pivotal role of Sesn2 in the progression of OA.<h3>Results</h3>Sesn2 expression is decreased in OA articular cartilage, and Sesn2 is a key gene regulating chondrocyte ferroptosis. Intra-articular injection of adeno-associated virus overexpressed Sesn2 in chondrocytes to alleviate OA cartilage damage by inhibiting ferroptosis. In addition, we identified a drug that activates Sesn2, MK8722, which inhibits chondrocyte senescence and ferroptosis by promoting mitophagy to alleviate cartilage destruction. MK8722 activates Sesn2 and transcriptionally upregulates bcl-2 interacting protein 3 (BNIP3), promoting nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression, and then promoting mitophagy. Upregulation of mitophagy subsequently reduces cellular oxidative stress and ferroptosis, thereby alleviating OA cartilage degeneration.<h3>Conclusion</h3>This study underscores the role of Sesn2 as a novel protein that maintains chondrocyte metabolic homeostasis and redox balance, and demonstrates that MK8722, which activates Sesn2, may serve as a promising therapeutic approach for OA.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255559","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":"Bacteroides vulgatus alleviates heart failure via butyric acid-TGF-β1/MAPK pathway","authors":"Zhiyong Du, Wenxin Zhang, Yu Wang, Xinlan Fang, Yifan Zhang, Yuling Xiao, Xiangrui Zeng, Shuo Yuan, Yong Jiang, Xiaoyu Guo, Kun Hua, Xiubin Yang, Xuedong Zhao, Yuhua Liu, Yingyuan Lu, Pengfei Tu","doi":"10.1016/j.jare.2025.09.057","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.057","url":null,"abstract":"<h3>Introduction</h3>The gut microbiota plays a vital role in the progression of heart failure (HF), making it a potential strategy for treating HF. The <em>Bacteroides</em> genus has shown promising potential for treating HF. However, further research is needed to identify specific beneficial <em>Bacteroides</em> strains for treating HF and elucidate their potential mechanisms.<h3>Objectives</h3>This study aimed to elucidate the therapeutic effect and mechanism of <em>Bacteroides</em> strain on HF.<h3>Methods</h3>This study comprehensively used pharmacological evaluation, 16S rRNA genetic sequencing, SCFA targeted metabolomics, transcriptome, and molecular biology methods to investigate the efficacy and mechanism of <em>Bacteroides vulgatus</em> (<em>B. vulgatus</em>) in the treatment of HF.<h3>Results</h3>We observed a significant decrease in the abundance of <em>B. vulgatus</em> in both HF patients and mice, and dysbiosis of the gut microbiota could cause cardiac dysfunction in mice. The administration of <em>B. vulgatus</em> to mice with HF significantly improved their cardiac function and significantly increased the levels of SCFAs, especially butyric acid. Meanwhile, we also observed a significant reduction in the levels of butyric acid in the serum of HF patients, and the cardiac function of HF mice improved after the administration of butyric acid. Compared to patients with higher butyric acid level, patients with lower butyric acid level had a significantly increased incidence of endpoint events. Moreover, the transcriptome results revealed that <em>B. vulgatus</em> significantly regulated the mitogen-activated protein kinase (MAPK) pathway. After further molecular biology verification, <em>B. vulgatus</em> was confirmed to regulate the TGF-β1/MAPK pathway in the heart through butyric acid, thereby exerting anti-HF effects.<h3>Conclusion</h3>This study provides evidence that <em>B. vulgatus</em> improves heart function by regulating SCFA metabolism and subsequently modulating the TGF-β1/MAPK pathway in myocardial tissue, confirming the potential therapeutic role of <em>B. vulgatus</em> in HF.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"33 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255357","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":"Rural-urban disparities in cardiovascular and other competing risk of death among cancer patients","authors":"Tianwang Guan, Jiaqi He, Liangjia Zeng, Ruoyun Zhou, Kaiyi Chi, Yanhua Yang, Xueqi Xiao, Long Pan, Haowen Liang, Zhijuan Luo, Renyu Li, Jiapeng Wang, Xiaolin Gao, Rundong Tai, Huiwan Chen, Jujian Ye, Yushen Ke, Zhilin Deng, Qingyi Wei, Kang Zhang, Caiwen Ou","doi":"10.1016/j.jare.2025.10.011","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.011","url":null,"abstract":"<h3>Introduction</h3>Rural-urban disparity of cancer is a major public health problem, with an unclear gap in noncancer death. It is important to evaluate rural–urban disparities in cardiovascular diseases (CVDs) and other competing death among cancer patients.<h3>Objectives</h3>Observing urban–rural disparities and trends in noncancer deaths in the U.S. cancer population.<h3>Methods</h3>To address rural–urban disparities, we used proportions of deaths, age-adjusted mortality rates (AAMR), cumulative mortality rates, subdistribution hazard ratio (sHR), standardized mortality ratios (SMRs), absolute excess risks (AERs) and mediation analysis.<h3>Results</h3>Between 1990 and 2017, there were 2,022,482 patients of 24 cancer sites, with a median follow-up of 11·8 years. Rural proportions of noncancer and CVD deaths in cancer patients were higher than urban ones. Rural AAMR of noncancer and CVD deaths surpassed urban one in cancer patients, who had higher cumulative mortality rates than urban counterparts in noncancer (sHR:1·21, 95 % confidence interval [CI]:1·19-1·22), CVDs (sHR:1·25, 95 % CI: 1·23-1·28), diabetes mellitus (sHR:1·24, 95 % CI:1·15-1·34), Alzheimer’s disease (sHR:1·30, 95 % CI:1·21-1·39), pneumonia and influenza (sHR:1·30, 95 % CI:1·21-1·39) and chronic obstructive pulmonary disease and allied cond (sHR:1·32, 95 % CI:1·26-1·39). Compared with the general population, both rural (SMR:4·58, AER:218·03) and urban (SMR: 3·74, AER: 166·61) cancer patients had higher risks of noncancer death. Mediation analyses identified median household income and SEER stages as the mediators.<h3>Conclusion</h3>Rural cancer patients had higher risks of noncancer death than urban counterparts, especially CVD-related deaths. Future targeted policy and public health interventions are needed to diminish the rural–urban gap in such death disparities.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"122 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255359","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":"Beyond chromosomes: exploring the diverse functions of extrachromosomal circular DNA","authors":"Yaling Chen, Jian Wang, Xudong Liu, Xinxin Li, Zhuanjian Li, Hui Li","doi":"10.1016/j.jare.2025.10.005","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.005","url":null,"abstract":"Extrachromosomal circular DNA (eccDNA) is defined as a form of circular DNA that is widespread across various biological contexts and exists independently of chromosomal structures. The current distribution of total eccDNA identified in both healthy and tumor tissues shows genomic coverage ranging from 1.18% to 30.73%. EccDNAs are double-stranded, covalently closed, circular DNA molecules that originate from mechanisms such as somatic rearrangements, genomic instability, and hypertranscription. EccDNA possesses an open chromatin structure, which can participate in transcriptional regulation across the entire genome and mediate extensive interactions between eccDNAs and between eccDNA and chromosomes. EccDNAs vary from a few dozen base pairs to megabases (Mb) and may include anything from small non-coding sequences to entire genes and regulatory elements. Current research methods limit the ability to knock down or knock out eccDNA like genomic DNA. Overexpressing individual eccDNAs is also challenging, making it difficult to explore their molecular function. This review examines the underexplored potential functions of eccDNA, with particular emphasis on its role as an enhancer and its involvement in the production of transcribed mRNAs and non-coding RNAs (ncRNAs). In addition, we provided a method for in <em>vitro</em> synthesis of eccDNA and a method for generating eccDNA in cells based on CRISPR/Cas9 technology, which provides a research foundation for elucidating its biological functions and mechanisms of action. Finally, this paper presents innovative prospects from a forward-looking perspective regarding the functional mechanisms and potential applications of eccDNA in various biological scenarios.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"114 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261006","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":"Navel orange postharvest resistance towards Penicillium digitatum − role of histone demethylase CsJMJ12","authors":"Jing Zeng, Ting Li, Mengting Liu, Jiechun Peng, Xiaoyan Duan, Zhiwei Li, Guoxiang Jiang, Jianbo Xiao, Yueming Jiang, Xuewu Duan","doi":"10.1016/j.jare.2025.10.012","DOIUrl":"https://doi.org/10.1016/j.jare.2025.10.012","url":null,"abstract":"<h3>Introduction</h3>Histone methylation is essential for plant growth and development, and adaptation to biotic and abiotic stresses. However, its role in postharvest disease resistance in fruits remains poorly understood. The study aimed to investigate the involvement of histone demethylase CsJMJ12 in enhancing postharvest resistance to <em>Penicillium digitatum</em> in Navel orange (<em>Citrus sinensis</em>).<h3>Methods</h3>Jumonji (JmjC) domain-containing proteins (JMJs) potentially involved in resistance to <em>P. digitatum</em> in Navel orange were identified using bioinformatics analysis, artificial inoculation and RT-qPCR<em>.</em> The role of JMJ12 in disease resistance and its underlying mechanism were further investigated through a series of assays, including subcellular location, Western blotting, immunofluorescence staining, transient overexpression, RNA-seq, widely targeted metabolomics, chromatin Immunoprecipitation (ChIP)-qPCR.<h3>Results</h3>A total of 17 JMJs were identified from the citrus genome. In Navel orange infected with <em>P. digitatum</em>, the expression of <em>CsJMJ12</em> was significantly upregulated. CsJMJ12 is localized to the nuclei and functions as a site-specific H3K27me3 histone demethylase. Overexpressing <em>CsJMJ12</em> transiently in fruit resulted in increased resistance to <em>P. digitatum</em>, accompanied by reduced global H3K27me3 levels. Transcriptome sequencing revealed that CsJMJ12 regulates multiple defense pathways, including phenylpropanoid biosynthesis, lignin biosynthesis, cell wall organization, pathogenesis-related protein, and hormone signaling. Metabolomics showed that CsJMJ12 regulates the accumulation of disease-resistant metabolites such as dihydrocoumarin, caffeoylputrescine, prenylnaringenin, quinic acid and syringic acid in phenylpropanoid biosynthesis pathways. Furthermore, CsJMJ12 promoted the expression of key defense-associated genes, including <em>POD, COMT1, LAC7L, SAME, SAMT, CHI, GT2</em> and <em>CSL5</em>, by demethylating H3K27me3 at their chromatin loci, thereby enhancing fruit resistance to <em>P. digitatum</em>.<h3>Conclusions</h3>This study identifies CsJMJ12 as a potential epigenetic regulator of <em>P. digitatum</em> resistance in Navel orange. Our findings provide valuable insights into the molecular mechanism of pathogen defense in sweet orange (<em>Citrus sinensis</em>). Further studies are needed to explore its broader application in agricultural practices and postharvest disease management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"114 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255360","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}