Wentao Wang , Qing Wang , Wenming Li , Hao Xu , Xiaolong Liang , Wei Wang , Ning Li , Huilin Yang , Yaozeng Xu , Jiaxiang Bai , Shuli Yang , Dechun Geng
{"title":"Targeting APJ drives BNIP3-PINK1-PARKIN induced mitophagy and improves systemic inflammatory bone loss","authors":"Wentao Wang , Qing Wang , Wenming Li , Hao Xu , Xiaolong Liang , Wei Wang , Ning Li , Huilin Yang , Yaozeng Xu , Jiaxiang Bai , Shuli Yang , Dechun Geng","doi":"10.1016/j.jare.2024.12.033","DOIUrl":"10.1016/j.jare.2024.12.033","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammatory diseases, such as diabetes mellitus, rheumatoid arthritis, and inflammatory bowel disease, lead to systemic immune microenvironment disturbances, contributing to bone loss, yet the mechanisms by which specific receptors regulate this process in inflammatory bone loss remain poorly understood. As a G-protein-coupled receptor, the Apelin receptor plays a crucial role in the regulation of inflammation and immune microenvironment. However, the precise mechanisms governing its role in inflammatory bone loss remain incompletely understood.</div></div><div><h3>Objective</h3><div>This study aims to investigate how APJ regulates macrophage polarization to mitigate inflammatory bone loss.</div></div><div><h3>Methods</h3><div>Lipopolysaccharide induced systemic inflammatory bone loss model in mice was used to explore the relationship between bone loss and osteoclast activation, macrophage polarization and APJ. In vitro studies, Bone marrow derived macrophages and siRNA were used to elucidate the regulatory influence of APJ on the immune microenvironment and osteoclast differentiation, while high-throughput sequencing is leveraged to uncover the underlying mechanisms through which APJ modulates macrophage polarization.</div></div><div><h3>Results</h3><div>Our study established a link between APJ and macrophage M1 polarization in systemic inflammatory bone loss mice. The activation of APJ effectively mitigated M1 polarization in macrophages, suppressed excessive osteoclast activation, and alleviated systemic inflammatory bone loss. In vitro high-throughput sequencing analysis revealed that APJ modulates macrophage polarization, linking to mitochondrial autophagy and the NOD-like receptor signaling pathway and the involvement of the AMPK and MAPK signaling pathways in signal transduction after APJ activation was also suggested. Subsequent experiments substantiated that APJ predominantly enhances mitophagy and diminishes the accumulation of reactive oxygen species by regulating the AMPK/BNIP3/PINK1/PARKIN axis, thereby suppressing the activation of macrophage M1 polarization and osteoclastogenesis.</div></div><div><h3>Conclusion</h3><div>This study elucidated the underlying mechanism by which APJ modulates macrophage polarization, thereby proposing a new therapeutic target for addressing inflammatory bone loss.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 655-668"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884684","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}
Ke Gu , Aimin Wu , Chen Liu , Bing Yu , Jun He , Xin Lai , Junzhou Chen , Yuheng Luo , Hui Yan , Ping Zheng , Junqiu Luo , Junning Pu , Quyuan Wang , Huifen Wang , Daiwen Chen
{"title":"Absence of gut microbiota alleviates iron overload-induced colitis by modulating ferroptosis in mice","authors":"Ke Gu , Aimin Wu , Chen Liu , Bing Yu , Jun He , Xin Lai , Junzhou Chen , Yuheng Luo , Hui Yan , Ping Zheng , Junqiu Luo , Junning Pu , Quyuan Wang , Huifen Wang , Daiwen Chen","doi":"10.1016/j.jare.2024.12.030","DOIUrl":"10.1016/j.jare.2024.12.030","url":null,"abstract":"<div><h3>Introduction</h3><div>Iron overload disrupts gut microbiota and induces ferroptosis, contributing to colitis. However, whether gut microbiota directly drives iron overload-induced colitis and its underlying mechanism remain unclear.</div></div><div><h3>Objectives</h3><div>The study aimed to explore whether gut microbiota can directly regulate iron overload-induced colitis and its underling mechanism.</div></div><div><h3>Methods</h3><div>Male C57BL/6N mice were fed with ferrous sulfate to establish an iron overload model. Antibiotics and dextran sulfate sodium salt (DSS) were used to create germ-free and colitis models, respectively.</div></div><div><h3>Results</h3><div>Results showed that iron overload caused disruption of systemic iron homeostasis via activating pro-inflammation response, which caused induction of ferroptosis and eventually resulted in colitis in mice. Notably, iron overload inhibited System Xc- and activated the nuclear factor E2-related factor 2/heme oxygenase-1 pathway, driving ferroptosis and colitis progression. Similar results were observed in mouse colon epithelial cells, which were treated with high doses ferric ammonium citrate. Additionally, iron overload exacerbated DSS-induced colitis by activating the ferroptosis and increasing harmful bacteria (e.g., <em>Mucispirillum</em>) abundance. Interestingly, eliminating gut microbiota attenuated iron overload-induced colitis, without affecting systemic inflammation through inhibiting ferroptosis of mice. Depletion of the gut microbiota partially mitigated the exacerbating effect of iron overload on DSS-induced colitis through inhibiting ferroptosis of mice.</div></div><div><h3>Conclusion</h3><div>Iron overload activates ferroptosis in colonic cells, increases the relative abundance of harmful bacteria, and exacerbates DSS-induced colitis in mice. Iron overload exacerbates DSS-induced ferroptosis and colitis in a microbiota-dependent manner. Targeting gut microbiota may offer new strategies for managing iron overload-induced colitis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 233-250"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867557","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}
Tong-Ju Eh , Yaxuan Jiang , Mingquan Jiang , Jianxin Li , Pei Lei , Ximei Ji , Hyon-Il Kim , Xiyang Zhao , Fanjuan Meng
{"title":"The role of trehalose metabolism in plant stress tolerance","authors":"Tong-Ju Eh , Yaxuan Jiang , Mingquan Jiang , Jianxin Li , Pei Lei , Ximei Ji , Hyon-Il Kim , Xiyang Zhao , Fanjuan Meng","doi":"10.1016/j.jare.2024.12.025","DOIUrl":"10.1016/j.jare.2024.12.025","url":null,"abstract":"<div><h3>Background</h3><div>Trehalose is a nonreducing disaccharide containing two glucose molecules linked through an α,α-1,1-glycosidic bond. This unique chemical structure causes trehalose levels to fluctuate significantly in plants under stress, where it functions as an osmoprotectant, enhancing plant resistance to stress. Previous studies have confirmed that the trehalose synthesis pathway is widely conserved across most plants. However, the protective role of trehalose is limited only to organelles or tissues where the concentration is sufficiently high.</div></div><div><h3>Aim of review</h3><div>In this review, we summarize previous reports on improving plant stress tolerance (drought, cold, heat, salt, pathogen, etc.) by applying trehalose-6-phosphate (T6P) or trehalose and manipulating the expression of trehalose metabolism-related genes. The molecular mechanisms underlying T6P, trehalose, and their related genes that regulate plant stress resistance are reviewed. More progressive studies on the spatiotemporal control of trehalose metabolism will provide a novel tool that allows for the simultaneous enhancement of crop yield and stress tolerance.</div></div><div><h3>Key scientific concepts of review</h3><div>We introduce the history of trehalose and discuss the possibility of trehalose and its metabolity-related genes binding to T6P to participate in stress response through unknown signaling pathways. In addition, the effects of trehalose metabolism regulation on plant growth and stress resistance were reviewed, and the molecular mechanism was fully discussed. In particular, we came up with new insights that the molecular mechanism of trehalose metabolism to enhance plant stress resistance in the future and we propose the need to use biotechnology methods to cultivate crops with stress resistance and high yield potential.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 57-72"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857865","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}
Siyu Wang , Xingda Zhang , Quanrun Chen , Hao Wu , Shihan Cao , Shilu Zhao , Guozheng Li , Jianyu Wang , Yajie Gong , Xinheng Wang , Da Pang , Song Gao
{"title":"FTO activates PD-L1 promotes immunosuppression in breast cancer via the m6A/YTHDF3/PDK1 axis under hypoxic conditions","authors":"Siyu Wang , Xingda Zhang , Quanrun Chen , Hao Wu , Shihan Cao , Shilu Zhao , Guozheng Li , Jianyu Wang , Yajie Gong , Xinheng Wang , Da Pang , Song Gao","doi":"10.1016/j.jare.2024.12.026","DOIUrl":"10.1016/j.jare.2024.12.026","url":null,"abstract":"<div><h3>Introduction</h3><div>Altered epigenetic reprogramming enables breast cancer cells to adapt to hypoxic stress. Hypoxic microenvironment can alter immune cell infiltration and function, limiting the effectiveness of immunotherapy.</div></div><div><h3>Objectives</h3><div>The study aimed to identify how fat mass and obesity-associated protein (FTO) helps breast cancer cells cope with the hypoxic microenvironment and the mechanisms behind breast cancer cell resistance to tumor immunity.</div></div><div><h3>Methods</h3><div>Clinical samples were utilized to analyze the impact of FTO on breast cancer progression and the effect of programmed cell death protein 1/ programmed cell death 1 ligand 1(PD-1/PD-L1) immune checkpoint inhibitor treatment. Utilized MeRIP-seq and mRNA-seq to analyze the downstream genes regulated by FTO under hypoxia. Methylation modification regulation of PDK1 by FTO was clarified using RIP. Then mouse models were utilized to analyze the efficacy of inhibiting FTO and 3-Phosphoinositide-dependent protein kinase 1(PDK1) in combination with PD-1/PD-L1 immune checkpoint inhibitor treatment.</div></div><div><h3>Result</h3><div>N6-Methyladenosine(m<sup>6</sup>A) demethylase FTO was transcriptionally activated by hypoxia inducible factor 1α(HIF-1α). PDK1 was identified as a potential target of FTO under hypoxic conditions through high-throughput sequencing. Mechanistically, overexpression of FTO decreases m<sup>6</sup>A modification sites on PDK1 mRNA, preventing YTH domain family 3(YTHDF3) from recognizing and binding to these sites, thereby inhibiting the degradation of PDK1 mRNA. Overexpression of PDK1 activates the AKT/STAT3 pathway, leading to enhanced PD-L1 expression. Targeting the FTO and PDK1-AKT pathways with FB23 and BX-912 inhibit breast cancer growth, enhance cytotoxic T lymphocyte (CTL) activity, and enhance the effectiveness of the PD-1/PD-L1 checkpoint inhibitor Atezolizumab.</div></div><div><h3>Conclusion</h3><div>This study reveals that HIF-1α promotes FTO transcription under hypoxic conditions, thereby increasing PD-L1 expression through the PDK1/AKT/STAT3 axis. Inhibition of FTO and PDK1 under hypoxic conditions could serve as a promising immunotherapeutic strategy for breast cancer.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 191-206"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841526","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}
Weiwei Zeng , Huan Deng , Yuning Luo , Shilong Zhong , Min Huang , Brian Tomlinson
{"title":"Advances in statin adverse reactions and the potential mechanisms: A systematic review","authors":"Weiwei Zeng , Huan Deng , Yuning Luo , Shilong Zhong , Min Huang , Brian Tomlinson","doi":"10.1016/j.jare.2024.12.020","DOIUrl":"10.1016/j.jare.2024.12.020","url":null,"abstract":"<div><div><strong>Background:</strong> Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Statins are the cornerstone of preventing and treating cardiovascular disease and can reduce LDL cholesterol by more than 60%. Although statins have high tolerability and safety, as the number of users increases, their adverse reactions in the liver, kidneys, skeletal muscles, and their potential to induce diabetes have also received widespread attention.</div><div>Aim <strong>of review:</strong> How to maximize the lipid-lowering effect of statins, reduce the incidence of adverse reactions, promote the rational application of statins in the clinic, and improve the risk–benefit level, in order to benefit more cardiovascular patients and provide reference for the related basic research of statins.</div><div><strong>Key scientific concepts of review:</strong> This article provides a comprehensive review of the clinical manifestations of statin-related adverse reactions (associated myopathy, hepatotoxicity, nephrotoxicity, glycemic effects, central nervous system, hemorrhagic stroke, etc.), risk factors for triggering adverse reactions, statin interactions with other drugs (food), potential etiopathological mechanisms and common interventions in the clinic. Genetic diversity is strongly associated with statin adverse effects, and thus, in the future genetic testing may also be key to mitigating statin adverse effects.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 781-797"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820952","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}
Jiangtao Dong , Guoquan Wang , Xiaona Li , Aohui Han , Wanpeng Zhang , Yuhang Yue , Yue Yang , Yishan Wang , Bowen Yuan , Jiahui Wang , Yuhui Peng , Runqiang Liu , Si Chen , Xuezhong Du
{"title":"Bio-friendly multi-stimuli responsive α-CD polymer-gated mesoporous carbon nanoherbicides for enhanced paraquat delivery","authors":"Jiangtao Dong , Guoquan Wang , Xiaona Li , Aohui Han , Wanpeng Zhang , Yuhang Yue , Yue Yang , Yishan Wang , Bowen Yuan , Jiahui Wang , Yuhui Peng , Runqiang Liu , Si Chen , Xuezhong Du","doi":"10.1016/j.jare.2024.12.005","DOIUrl":"10.1016/j.jare.2024.12.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Weeds seriously affect crop yield in global agricultural production. Paraquat (PQ), as one of low cost and highly effective herbicide, is forbidden or severely restricted in production and sales owing to its lethal toxicity to humans. Creating an efficient and bio-friendly PQ formulation is crucial to facilitate the open use of PQ in world’s agriculture.</div></div><div><h3>Objectives</h3><div>This study aims to construct one intelligent and bio-friendly mesoporous carbon nanoparticles (MCN) nanoherbicides coated with α-CD polymer (CDP) gatekeepers.</div></div><div><h3>Methods</h3><div>MCN was prepared through the low-concentration hydrothermal way, calcined and carbonized. PEG stalks were immobilized on MCN surface by amidation reaction. The PQ was trapped in the MCN pores via physical diffusion adsorption and the robust π–π effects between electron-deficient PQ and electron-rich MCN. CDP gatekeepers were fastened via host–guest effects between the chamber of α-CD units and PEG stalks.</div></div><div><h3>Results</h3><div>The PQ-loaded MCN-PEG@CDP nanoherbicides integrated with multi-stimuli responses to amylase, elevated temperature under sunlight, and competitors at leaf interface to control the PQ release for efficient weed control, while appeared low PQ leakage under the simulated human gastric or intestinal conditions, low cytotoxicity to human normal cells <em>in vitro</em>, and high mouse survival rate <em>in vivo</em>. Even through the nanoherbicides inevitably contact with water or intake by beneficial insects, they appear good biosafety on zebrafish (<em>D. rerio</em>) and honeybees (<em>Apis mellifera L</em>.).</div></div><div><h3>Conclusion</h3><div>The as-prepared nanoherbicides have high herbicidal efficacy and low risks to non-target species, and could promote the open use of PQ in agriculture.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 1-16"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809721","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}
Jing Yu , Lili Feng , Zhanhao Luo , Jingyi Yang , Qiang Zhang , Chen Liu , Dayi Liang , Yanchun Xie , Hongmin Li , Junli Gong , Zhen He , Ping Lan
{"title":"Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis","authors":"Jing Yu , Lili Feng , Zhanhao Luo , Jingyi Yang , Qiang Zhang , Chen Liu , Dayi Liang , Yanchun Xie , Hongmin Li , Junli Gong , Zhen He , Ping Lan","doi":"10.1016/j.jare.2024.11.024","DOIUrl":"10.1016/j.jare.2024.11.024","url":null,"abstract":"<div><h3>Introduction</h3><div>The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.</div></div><div><h3>Methods</h3><div>The impact of <em>Il10</em> deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of <em>Parabacteroides distasonis</em> (<em>P. distasonis</em>) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in <em>P. distasonis</em> inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both <em>in vivo</em> and <em>in vitro</em>. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.</div></div><div><h3>Results</h3><div>We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, <em>Il10</em>-deficiency (<em>Il10<sup>−/−</sup></em>) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, <em>Il10<sup>−/−</sup></em> mice reshaped gut microbiota composition, notably enriching <em>P. distasonis</em>. The enriched <em>P. distasonis</em> produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of <em>VEGFA</em>, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both <em>in vitro</em> and <em>in vivo</em> lung metastasis mouse models.</div></div><div><h3>Conclusions</h3><div>These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-<em>VEGFA</em> axis mediated by gut <em>P. distasonis</em>, suggesting that <em>P. distasonis</em> or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 467-479"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673783","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":"The significance of urine extracellular vesicle DNA methylation detection in the diagnosis and classification of prostate cancer","authors":"Ting Ding, Yanjun Diao, Ruiqing Fu, Chengxiang Gong, Qiye He, Weixiang He, Longlong Zhang, Xiaojian Yang, Xianfei Zeng, Lijuan Yu, Jiayun Liu, Weimei Shi, Kang Zhang, Xiaoke Hao","doi":"10.1016/j.jare.2025.09.056","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.056","url":null,"abstract":"<h3>Introduction</h3>As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA in tumor diagnosis have gradually attracted the attention of researchers. However, methylation detection, which is more advantageous than mutation detection in tumor diagnosis, has not been widely practiced in EV DNA, and its value in PCa diagnosis also remains underexplored.<h3>Objectives</h3>This study aims to establish and optimize an EV DNA methylation detection system and evaluate its diagnostic and classification potential for PCa.<h3>Methods</h3>We characterized EV DNA biological properties, optimized pretreatment strategies, validated its correlation with genomic DNA methylation, and explored urine EV DNA methylation targets in 86 benign prostatic hyperplasia (BPH) and 109 PCa patients across three cohorts (screening: 30 BPH/33 PCa; training: 27 BPH/30 PCa; validation: 29 BPH/46 PCa).<h3>Results</h3>Heterogeneous biological characteristics were observed among DNA from different subtypes of EV, but methylation profiles remained consistent across subtypes and post-DNase I treatment. EV DNA accurately reflected the methylation state of source cell genomic DNA. By combining our screening results with data from the TCGA database and previously reported, we developed a panel consisting of 667 PCa-specific methylation targets for detection. Among these, six methylation sites (MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25) demonstrated high diagnostic value for PCa, enabling construction of PCa and aggressive PCa differential diagnosis model with AUCs up to 0.74 and 0.91 respectively. The diagnostic value of these six markers was further confirmed using methylight PCR in the validation cohort which also displayed promising performance as a tool for diagnosing PCa.<h3>Conclusion</h3>This study highlights the potential of urine EV DNA methylation as a novel diagnostic marker for PCa and lays a foundation for future EV DNA research.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195107","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}
Dongdong Li , Jianan Li , Hao Li , Zhendong Bai , Chujian Ma , Haodong Bai , Dingfeng Luo , Zuren Li , Lianyang Bai
{"title":"Design of highly leaf-adhesive and anti-UV herbicide nanoformulation for enhanced herbicidal activity","authors":"Dongdong Li , Jianan Li , Hao Li , Zhendong Bai , Chujian Ma , Haodong Bai , Dingfeng Luo , Zuren Li , Lianyang Bai","doi":"10.1016/j.jare.2024.12.034","DOIUrl":"10.1016/j.jare.2024.12.034","url":null,"abstract":"<div><h3>Introduction</h3><div>Conventional pesticide formulations have been widely used to boost agricultural productivity, but their weak foliar adhesion and instability under UV light during spraying lead to low utilization rates and potential environmental and health hazards. To counter these challenges, the development of nanoformulations represents a pivotal strategy. These advanced formulations are designed to enhance the efficacy of active ingredients (AIs) and reduce ecological impacts, thereby addressing the need for sustainable agricultural development.</div></div><div><h3>Objectives</h3><div>The study aims to fabricate a highly leaf-adhesive and anti-UV herbicide nanoformulation, designed to enhance the herbicidal activity and utilization rates of AIs.</div></div><div><h3>Methods</h3><div>Herein, the herbicide nanoformulations (Called CB@MSNs-TA-Fe) are synthesized by incorporating cyhalofop-butyl into tannic acid-Fe (III) ions-coated functionalized mesoporous silica. The foliar retention performance of the samples was assessed integrating SEM observation and HPLC analysis.</div></div><div><h3>Results</h3><div>The CB@MSNs-TA-Fe with rough outer surface displays typical core–shell structure featuring an average diameter of about 118 nm. After amino modification, the CB@MSNs-TA-Fe shows enhanced loading rate for CB (14.4 ± 0.2 %) and superior thermal stability. The release rate of CB within CB@MSNs-TA-Fe under acidic conditions is higher compared to that under alkaline and neutral conditions. Upon UV irradiation, the half-life of CB within CB@MSNs-TA-Fe nanoparticles is 12.4 times higher than that of CB technical (CB TC). Enhanced foliar adhesion of CB@MSNs-TA-Fe on hydrophobic leaf surfaces is observed, which can effectively mitigate the risk of wash-off by rainfall. The CB@MSNs-TA-Fe displays enhanced herbicidal efficacies against barnyard grass under UV irradiation or simulated rainwater scouring, compared with CB TC and CB oil dispersion. Furthermore, the TA-Fe-coated MSNs-NH<sub>2</sub> nano-carrier (MSNs-TA-Fe) reveals excellent biosafety on rice, zebrafish, and earthworms.</div></div><div><h3>Conclusion</h3><div>The developed TA-Fe-functionalized herbicide nanoformulations, with high foliar adhesion and anti-UV properties, effectively improve the utilization efficiency of AIs, thus offering innovative solutions for the development of efficient pesticide formulations.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 109-118"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874688","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}
Yang-Xi Hu , Hong-Min You , Mei-Rong Bai , Wen-Heng Yue , Fang-Fang Li , Bo-Wen Hu , Ya-Sha Chen , Xiang-Yu Shen , Yue Wu , Jia-Mei Wang , Zhi-Qing He , Xia Tao , Qing Jing , Chun Liang
{"title":"Macrophage P2Y12 regulates iron transport and its inhibition protects against atherosclerosis","authors":"Yang-Xi Hu , Hong-Min You , Mei-Rong Bai , Wen-Heng Yue , Fang-Fang Li , Bo-Wen Hu , Ya-Sha Chen , Xiang-Yu Shen , Yue Wu , Jia-Mei Wang , Zhi-Qing He , Xia Tao , Qing Jing , Chun Liang","doi":"10.1016/j.jare.2024.12.019","DOIUrl":"10.1016/j.jare.2024.12.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Iron retention is commonly observed in atherosclerotic plaques and is believed to be detrimental to atherosclerosis. Platelet P2Y12 is a target of antiplatelet therapy in preventing thrombotic complications of atherosclerosis. The protective effect of P2Y12 on hematopoiesis reported by our previous work implies the involvement of P2Y12 in iron metabolism.</div></div><div><h3>Objectives</h3><div>This study further investigated the role of P2Y12 in the iron metabolism of macrophages, the key player in systemic iron homeostasis and atherosclerosis.</div></div><div><h3>Methods</h3><div>The association between serum iron and the use of P2Y12 inhibitors was evaluated by a case-control study in human. Secondary iron overload and atherosclerosis animal models were established in <em>P2Y12</em>-deficient zebrafish to explore the role of P2Y12 in macrophage iron metabolism <em>in vivo</em>. Both iron-overloaded murine primary peritoneal macrophages (PMs) and ox-LDL–treated PMs with <em>P2Y12</em> knockdown were used for <em>in vitro</em> studies. RNA sequencing and pharmacological approaches were performed to investigate the downstream mechanisms.</div></div><div><h3>Results</h3><div>Increased serum iron level was positively associated with P2Y12 inhibitor usage [odds ratio (OR) = 10.333 (1.281–83.370)]. Elevated serum iron level and transferrin saturation, reduced hepatic and splenic iron content, and decreased iron staining in macrophages were observed in secondary iron overload <em>P2Y12</em>-deficient zebrafish. Deficiency of <em>P2Y12</em> in <em>ApoEb<sup>-/-</sup></em> zebrafish fed a high-fat diet reduced atherosclerosis progression and intraplaque iron retention. Furthermore, reduced ferritin, restored cell viability and expression of ferroptosis marker proteins, and decreased ROS formation and inflammatory cytokines were observed in both iron-overloaded and ox-LDL–treated PMs with <em>P2Y12</em> knockdown <em>in vitro</em>, while reversed phenotypes were observed after agonist-induced P2Y12 activation. Mechanistically, <em>P2Y12</em> inhibition in iron-overloaded or ox-LDL–treated PMs suppressed NF-κB p65 phosphorylation and hepcidin expression, both of which were reversed by P2Y12 activation.</div></div><div><h3>Conclusion</h3><div>P2Y12 inhibition decreased hepcidin autocrine through repressing NF-κB p65 phosphorylation in macrophages, preventing intracellular iron retention and atherosclerosis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 585-603"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809722","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}