Journal of Molecular Cell Biology最新文献

Medium-Frequency Electrotherapy-Driven Remodeling of Tumor Biology and Overcoming Treatment Resistance: Molecular Mechanisms and Clinical Integration. 中频电疗驱动的肿瘤生物学重塑和克服治疗耐药性：分子机制和临床整合。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-10-16 DOI: 10.1093/jmcb/mjag040

Xiumin Wu, Yao Liu, Zhifei He, Hang Du, Hongzhi Ouyang, Huaiqing Luo, Yufei Li, Jun Huang, Yongguang Tao, Li Cong, Yuanbing Chen, Yiqun Jiang

{"title":"Medium-Frequency Electrotherapy-Driven Remodeling of Tumor Biology and Overcoming Treatment Resistance: Molecular Mechanisms and Clinical Integration.","authors":"Xiumin Wu, Yao Liu, Zhifei He, Hang Du, Hongzhi Ouyang, Huaiqing Luo, Yufei Li, Jun Huang, Yongguang Tao, Li Cong, Yuanbing Chen, Yiqun Jiang","doi":"10.1093/jmcb/mjag040","DOIUrl":"https://doi.org/10.1093/jmcb/mjag040","url":null,"abstract":"Electrotherapy exerts antitumor effects by applying specific electric currents or fields to tumor tissues, inducing biological responses through thermal, non-thermal, and electrochemical mechanisms. In recent years, electrotherapy has emerged as a promising approach in cancer treatment. Its therapeutic efficacy is largely determined by key physical parameters, including frequency, voltage, electric field strength, and exposure duration. Among various electrotherapy modalities, medium-frequency electrotherapy, which primarily operates through non-thermal mechanisms, induces biological effects via coordinated regulation of multiple cellular processes, including membrane potential modulation, ion channel activity, and intracellular signaling pathways. This category mainly includes pulsed electric fields and tumor treating fields. This review systematically summarizes the historical development and evolution of electrotherapy, with particular emphasis on the regulatory effects of medium-frequency electrotherapy on malignant tumor biology. We further discuss the molecular mechanisms through which medium-frequency electrotherapy, alone or in combination with surgery, chemotherapy, radiotherapy, and immunotherapy, may overcome tumor treatment resistance. By integrating recent clinical evidence regarding the application of medium-frequency electrotherapy in combination with conventional anticancer therapies, this review proposes a 'physical energy-biological effect-clinical translation' framework. Through elucidating how electrotherapy reshapes tumor biology and attenuates resistance to established treatments, this review provides new insights into the development of multimodal therapeutic strategies for cancer.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A histological staining identifies malignancy-correlated stromal vimentin across human cancer tissues. 组织学染色鉴定恶性相关的间质波形蛋白跨越人类癌症组织。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-10-15 DOI: 10.1093/jmcb/mjag041

Qianyue Chen, Xuedi Gao, Chenglin Miao, Wakam Chang, Wei Wang, Yaming Jiu

引用次数: 0

A Deep Learning system for Automated Quality Control of Medical Questionnaire data in Large-Scale Cohort Studies. 大规模队列研究中医疗问卷数据自动质量控制的深度学习系统。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-10-08 DOI: 10.1093/jmcb/mjag038

Minmin Cao, Yanan Duan, Dong Lang, Pinqi Fang, Zhouyu Guan, Xinming Xu, Qingqing Zheng, Di Cheng, Fusong Jiang, Hua Zhao, Keqing Dong, Shijun Wang, Bin Sheng, Huating Li, Weiping Jia

{"title":"A Deep Learning system for Automated Quality Control of Medical Questionnaire data in Large-Scale Cohort Studies.","authors":"Minmin Cao, Yanan Duan, Dong Lang, Pinqi Fang, Zhouyu Guan, Xinming Xu, Qingqing Zheng, Di Cheng, Fusong Jiang, Hua Zhao, Keqing Dong, Shijun Wang, Bin Sheng, Huating Li, Weiping Jia","doi":"10.1093/jmcb/mjag038","DOIUrl":"https://doi.org/10.1093/jmcb/mjag038","url":null,"abstract":"Recent advances in natural language processing combined with deep learning have transformed disease prediction, diagnosis, and treatment, yet their application in automated quality control of medical questionnaire data remains largely unexplored. Here, we present an end-to-end system tailored for large-scale cohort interview data. A fine-tuned Whisper model was developed for automatic audio-to-text transcription and optimized for recognizing domain-specific medical terminology and regional dialects, achieving an accuracy of over 91%. Using the DeepSeek framework, we jointly analyzed transcribed texts, interviewer records, and questionnaire content from 522 medical interviews to identify quality issues, achieving the area under the receiver operating characteristic curve (AUC) values of 0.893, 0.953, and 0.973 for omitted question stems, response-record inconsistencies, and insufficient follow-up, respectively. The system achieved high agreement with the senior specialist reference (F1 = 0.843, Kappa = 0.835) and significantly outperformed the junior specialist group (P < 0.01). Evaluation on an independent validation dataset (n = 96), which was collected using a structurally distinct brain health questionnaire, further demonstrated robust performance and generalizability (F1 = 0.831, Kappa = 0.821). Collectively, this framework enhances the efficiency and reliability of medical questionnaire data processing and offers a practical artificial intelligence-driven solution for quality control in global health data, especially in low-resource dialect settings.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wdr5 Modulates Synaptic Development and Memory Consolidation in the Hippocampus and Cerebral Cortex. Wdr5调节海马和大脑皮层突触发育和记忆巩固。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-09-29 DOI: 10.1093/jmcb/mjag037

Huishan Wang, Wei Li, Pengcheng Ma, Yuwei Li, Pengju Huang, Zhibiao Zhang, Jiayi Li, Zhibi Zhang, Bingyu Mao

{"title":"Wdr5 Modulates Synaptic Development and Memory Consolidation in the Hippocampus and Cerebral Cortex.","authors":"Huishan Wang, Wei Li, Pengcheng Ma, Yuwei Li, Pengju Huang, Zhibiao Zhang, Jiayi Li, Zhibi Zhang, Bingyu Mao","doi":"10.1093/jmcb/mjag037","DOIUrl":"https://doi.org/10.1093/jmcb/mjag037","url":null,"abstract":"WD-repeat domain 5 (Wdr5), a core component of the SET1/MLL family of histone methyltransferases, is widely involved in the regulation of development, epigenetic control, transcription, and cell division. Wdr5 has been linked to neurodevelopmental disorders characterized by intellectual disability and developmental delay-yet its regulatory roles in neurons remain poorly understood. Here, we report that postnatal deletion of Wdr5 in excitatory forebrain neurons impairs learning and memory in male Wdr5fl/fl; CaMKIIα-iCre conditional knockout (Wdr5 cKO) mice. We showed that the conditional Wdr5 knockout affects dendritic spine as well as synapse development in cortex and hippocampus. In addition, the expression profile of the hippocampus in response to contextual fear-conditioning tests was dysregulated in the Wdr5 cKO mice, including genes related to Notch signaling and mitochondrial respiratory. The recovery of the expression of the immediate early genes was also impaired in the Wdr5 cKO mice compared to the wild-type mice. Collectively, these findings identify Wdr5 as a critical regulator of synaptic development and memory consolidation.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune licensing of exercise: B cells wire a liver-muscle glutamate axis. 运动的免疫许可：B细胞连接肝脏-肌肉谷氨酸轴。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-09-01 DOI: 10.1093/jmcb/mjag036

Yiqi Yu, Rong Rong, Weiwei Dai

引用次数: 0

MAD2B guides chromosome stability in mitosis via the MAD2B-CIP2A signaling axis. MAD2B通过MAD2B- cip2a信号轴引导有丝分裂中的染色体稳定性。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-29 DOI: 10.1093/jmcb/mjag034

Umer Ejaz, Fangyuan Xiong, Hengyi Shao, Tahir Ullah, Xuebiao Yao, Liangyu Zhang, Zhen Dou

{"title":"MAD2B guides chromosome stability in mitosis via the MAD2B-CIP2A signaling axis.","authors":"Umer Ejaz, Fangyuan Xiong, Hengyi Shao, Tahir Ullah, Xuebiao Yao, Liangyu Zhang, Zhen Dou","doi":"10.1093/jmcb/mjag034","DOIUrl":"https://doi.org/10.1093/jmcb/mjag034","url":null,"abstract":"Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, monitored by the spindle assembly checkpoint machinery, which prevents precocious chromosome segregation and reduces the risk of aneuploidy. MAD2B, a homologue of MAD2, is critical for mitotic quality control and DNA damage repair. However, it remains elusive how MAD2B guides genome surveillance during the cell cycle. Here, we show that MAD2B safeguards genome integrity through interactions with CIP2A in a context-dependent manner. To delineate the molecular mechanisms underlying MAD2B-dependent signaling in mitosis, we carried out affinity purification of FLAG-MAD2B followed by mass spectrometry to identify MAD2B-associated proteins. Our biochemical characterization uncovered a previously uncharacterized interaction between MAD2B and CIP2A, mediated by the N-terminus of CIP2A. Importantly, MAD2B depletion resulted in DNA damage response and replication stress phenotypes, leading to aberrant mitotic DNA synthesis primarily in HeLa cells. Notably, loss of MAD2B disrupted CIP2A recruitment to γH2AX-marked DNA lesions and attenuated DNA damage repair. Together, these results establish MAD2B as a context-sensitive regulator of genome stability that links replication stress surveillance to mitotic chromosome repair via the MAD2B-CIP2A signaling axis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Jer1-Ga2-LpR1 axis mediates upstream input of alpha-mannosidosis. Jer1-Ga2-LpR1轴介导α -甘露甘露病的上游输入。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-29 DOI: 10.1093/jmcb/mjag035

Wenting Li, Shengnan Li, Qi Wang, Xiuxiu Ti, Zhaoliang Shan, Yuxue Gao, Qing Zhang

{"title":"Jer1-Ga2-LpR1 axis mediates upstream input of alpha-mannosidosis.","authors":"Wenting Li, Shengnan Li, Qi Wang, Xiuxiu Ti, Zhaoliang Shan, Yuxue Gao, Qing Zhang","doi":"10.1093/jmcb/mjag035","DOIUrl":"https://doi.org/10.1093/jmcb/mjag035","url":null,"abstract":"Alpha-mannosidosis (AMD) is a well-known lysosomal storage disorder caused by the loss of α-mannosidase activity due to the mutation of the MAN2B1 gene. Defective α-mannosidase cannot completely degrade the sugar chains of upstream input glycoproteins, leading to the accumulation of oligosaccharides with α-mannosidic linkages in lysosomes, finally causing AMD. However, till now, the upstream input mediating AMD remains elusive, which hinders the development of alternative therapeutic treatments. To address this question, we establish the first Drosophila model of AMD and, through genetic screen, identify three novel upstream factors named Jer1, Ga2, and LpR1. We demonstrate that knocking down either of them can rescue the lethal phenotype of AMD flies and they mediate upstream input of AMD through a Jer1-Ga2-LpR1 axis. Mechanistically, Jer1 recruits the E3 ligase Ga2, which mediates the ubiquitination of the glycoprotein LpR1 for subsequent lysosomal degradation. Therefore, knockdown of Jer1 or Ga2 downregulates LpR1 ubiquitination and prevents it from degradation in lysosomes, reducing the burden on lysosomes and alleviating the symptoms of AMD. Importantly, our study further demonstrates that IPP, UBE3C, and VLDLR, the mammalian counterparts of Jer1, Ga2, and LpR1, respectively, are functionally conserved during evolution, suggesting that they can be used as potential therapeutic targets for the treatment of AMD.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LAMTOR1 sorts APP to late endosomes via AP-3-mediated trafficking. LAMTOR1通过ap -3介导的运输将APP分类到晚期核内体。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-26 DOI: 10.1093/jmcb/mjag033

Chenqian Zhou, Wenyuan Cao, Rixu Cong, Chunyan Shan, Yonglu Tian, Sizheng Xu, Weiran Feng, Yuanjun Li, Xun Wang, Junlin Teng, Pengli Zheng, Ning Huang, Jianguo Chen

引用次数: 0

Topoisomerase 1 initiates biliary-derived liver regeneration through the Dnmt1-p53 axis. 拓扑异构酶1通过Dnmt1-p53轴启动胆汁源性肝脏再生。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-19 DOI: 10.1093/jmcb/mjag031

Chuanfang Qian, Zhuolin Yang, Xuemeng Xu, Kaiwen Dang, Qi Dong, Haojie Yu, Lingfei Luo, Jianbo He

{"title":"Topoisomerase 1 initiates biliary-derived liver regeneration through the Dnmt1-p53 axis.","authors":"Chuanfang Qian, Zhuolin Yang, Xuemeng Xu, Kaiwen Dang, Qi Dong, Haojie Yu, Lingfei Luo, Jianbo He","doi":"10.1093/jmcb/mjag031","DOIUrl":"https://doi.org/10.1093/jmcb/mjag031","url":null,"abstract":"In end-stage liver disease, impaired hepatocyte proliferation prevents regeneration. Biliary epithelial cell transdifferentiation thus becomes a critical alternative for liver repair, yet its efficiency remains low in mammals. Elucidating the initiation mechanisms of this process may unlock novel therapeutic targets for end-stage liver disease treatment. By leveraging the zebrafish severe liver injury model and its transparency, as well as the availability of small-molecule research, we identified that topoisomerase 1 (Top1) is essential for the initiation of biliary-derived liver regeneration. Top1 upregulation occurred early after liver injury. Moreover, genetic knockout (top1 mutants) or pharmacological inhibition (topotecan) impeded liver regeneration by suppressing cholangiocyte dedifferentiation, promoting cell apoptosis, and blocking the redifferentiation of bipotential progenitor cells into hepatocytes and cholangiocytes. Mechanistically, Top1 activates DNA methyltransferase 1 (Dnmt1) in cholangiocytes, thereby depressing p53 during dedifferentiation, which subsequently maintains the activity of mTOR signalling in cholangiocytes to trigger regeneration initiation. These findings suggest that the Top1-Dnmt1-p53 axis orchestrates the initiation of biliary-driven liver regeneration.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FBXO6 ubiquitinates MAOA to promote monoamine neurotransmitter accumulation and tumor growth in HCC. FBXO6泛素化MAOA促进HCC中单胺类神经递质积累和肿瘤生长。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-08-17 DOI: 10.1093/jmcb/mjag029

Chunming Li, Yujun Zhang, Xiao-Tong Lin, Jie Zhang, Lei-Da Zhang, Jianping Gong, Chuan-Ming Xie

{"title":"FBXO6 ubiquitinates MAOA to promote monoamine neurotransmitter accumulation and tumor growth in HCC.","authors":"Chunming Li, Yujun Zhang, Xiao-Tong Lin, Jie Zhang, Lei-Da Zhang, Jianping Gong, Chuan-Ming Xie","doi":"10.1093/jmcb/mjag029","DOIUrl":"https://doi.org/10.1093/jmcb/mjag029","url":null,"abstract":"Monoamine neurotransmitters dopamine and 5-hydroxytryptamine (serotonin, 5-HT), traditionally implicated in the central nervous system, are increasingly recognized as contributors to hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms remain unclear. Here, we demonstrate that the E3 ubiquitin ligase F-box-only protein 6 (FBXO6) is highly expressed in HCC patients. FBXO6 promotes accumulation of 5-HT and dopamine in HCC by mediating K48-linked ubiquitination and degradation of monoamine oxidase A (MAOA). Elevated monoamine levels activate their cognate receptors, triggering the PI3K/AKT/mTOR signaling axis. Simultaneously, these neurotransmitters induce transglutaminase 2 (TGM2)-dependent histone monoaminylation (H3Q5ser and H3Q5dop), forming a synergistic oncogenic circuit that drives HCC development. Clinical specimens reveal a strong inverse correlation between FBXO6 and MAOA protein levels, validating this regulatory axis. Preclinical studies demonstrate that combined treatment with the mTOR inhibitor everolimus and the TGM2 inhibitor GK921 exerts synergistic antitumor effects against FBXO6-driven HCC, providing a rational therapeutic strategy for patients with FBXO6 overexpression.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0