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Comprehensive multi-omics analysis uncovers potential risks of aged sperm on offspring development after short-term storage. 综合多组学分析揭示了短期储存后衰老精子对后代发育的潜在风险。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-22 DOI: 10.1186/s12915-025-02379-5
Yu Cheng, Songpei Zhang, Sayyed Mohammad Hadi Alavi, Rigolin Nayak, Swapnil Gorakh Waghmare, Nururshopa Eskander Shazada, Deepali Rahi Roy, Zhijun Ma, Otomar Linhart, Zuzana Linhartová
{"title":"Comprehensive multi-omics analysis uncovers potential risks of aged sperm on offspring development after short-term storage.","authors":"Yu Cheng, Songpei Zhang, Sayyed Mohammad Hadi Alavi, Rigolin Nayak, Swapnil Gorakh Waghmare, Nururshopa Eskander Shazada, Deepali Rahi Roy, Zhijun Ma, Otomar Linhart, Zuzana Linhartová","doi":"10.1186/s12915-025-02379-5","DOIUrl":"https://doi.org/10.1186/s12915-025-02379-5","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have demonstrated that prolonged sperm storage adversely affects offspring through epigenetics, yet its broader effects on other molecular levels such as transcription and proteomics in progeny have been rarely explored.</p><p><strong>Results: </strong>We employed comprehensive multi-omics approaches to uncover storage-induced epigenetic changes in sperm and their effects on embryonic development and offspring health. Sperm from common carp (Cyprinus carpio) was stored in vitro in artificial seminal plasma for 14 days, and the impacts of storage on functional properties of sperm and progeny development were investigated. We combined DNA methylome, transcriptomic and proteomic data to elucidate the potential mechanisms by which sperm storage influences progeny development. Prolonged in vitro storage significantly reduced sperm motility and fertilising ability which coincided with changes in the DNA methylation pattern. Integrated analyses of the offspring DNA methylome, comparative transcriptomics and cardiac performance measurements revealed storage-induced alterations of genes associated with nervous system development, myocardial morphogenesis and cellular responses to stimuli. Proteomic analyses showed that in addition to visual perception and nervous system function, pathways of the immunity system were also enriched. Results provide strong evidence of the epigenetic inheritance of the offspring's performances when short-term stored sperm was used for fertilisation.</p><p><strong>Conclusions: </strong>Short-term sperm storage induces heritable molecular and phenotypic changes in offspring, raising concerns over the potential intergenerational consequences of assisted reproductive practices in aquaculture and possibly other vertebrates.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"264"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid metabolism in age-related musculoskeletal disorders: insights into sarcopenia and osteoporosis. 脂质代谢与年龄相关的肌肉骨骼疾病:洞察肌肉减少症和骨质疏松症。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-22 DOI: 10.1186/s12915-025-02383-9
Shivum Lal, Shreya Gunji, Pankaj Ahluwalia, Ravindra Kolhe, Wendy B Bollag, William D Hill, Meghan E McGee-Lawrence, Carlos M Isales, Sadanand Fulzele
{"title":"Lipid metabolism in age-related musculoskeletal disorders: insights into sarcopenia and osteoporosis.","authors":"Shivum Lal, Shreya Gunji, Pankaj Ahluwalia, Ravindra Kolhe, Wendy B Bollag, William D Hill, Meghan E McGee-Lawrence, Carlos M Isales, Sadanand Fulzele","doi":"10.1186/s12915-025-02383-9","DOIUrl":"https://doi.org/10.1186/s12915-025-02383-9","url":null,"abstract":"<p><p>Musculoskeletal disorders (MSDs), notably sarcopenia and osteoporosis, profoundly affect aging individuals. This review explores lipid metabolism's role in age-related MSD pathophysiology, highlighting fatty acid uptake, lipid signaling, and lipotoxicity in muscle deterioration. It further addresses lipid-mediated regulation of osteoclasts, osteoblasts, and bone remodeling, emphasizing age-associated metabolic shifts exacerbating bone loss. Emerging therapeutic strategies targeting lipid pathways for MSD treatment are also discussed. This review integrates recent findings in muscle and bone lipid metabolism to deepen understanding of lipid dysregulation in musculoskeletal disorders and explore potential metabolic intervention strategies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"265"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic formation of lower Yellow River populations in the Han dynasty. 汉代黄河下游种群的基因组形成。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-20 DOI: 10.1186/s12915-025-02377-7
Zhi Ji, Kui Chen, Jiajing Zheng, Chaochao Qin, Suyun Cui, Qu Shen, Hao Ma, Baitong Wang, Xiaolu Mao, Yilan Liu, Hongming Zhou, Xinyue Zou, Xinyi Wang, Jiaxin Tang, Tianlai Ma, Wen Wan, Kongyang Zhu, Le Tao, Haifeng He, Rui Wang, Xiaomin Yang, Yu Xu, Mengting Xu, Tianyou Bai, Yiling Jiang, Shaoqing Wen, Li Jin, Qun Zhang, Chuan-Chao Wang
{"title":"Genomic formation of lower Yellow River populations in the Han dynasty.","authors":"Zhi Ji, Kui Chen, Jiajing Zheng, Chaochao Qin, Suyun Cui, Qu Shen, Hao Ma, Baitong Wang, Xiaolu Mao, Yilan Liu, Hongming Zhou, Xinyue Zou, Xinyi Wang, Jiaxin Tang, Tianlai Ma, Wen Wan, Kongyang Zhu, Le Tao, Haifeng He, Rui Wang, Xiaomin Yang, Yu Xu, Mengting Xu, Tianyou Bai, Yiling Jiang, Shaoqing Wen, Li Jin, Qun Zhang, Chuan-Chao Wang","doi":"10.1186/s12915-025-02377-7","DOIUrl":"10.1186/s12915-025-02377-7","url":null,"abstract":"<p><strong>Background: </strong>As a key region in the lower Yellow River Basin, Shandong Province plays a central role in understanding the genetic history of East Asia. However, detailed ancient DNA data across its historical periods remains limited. This study aims to characterise the genomic profiles of Shandong populations during the Western Han Dynasty and trace their genetic connections with neighbouring regions.</p><p><strong>Results: </strong>Here, we newly generated 14 ancient genomes from the Wenshaobei site of the Western Han dynasty in Shandong Province. Genetic analyses, including principal component analysis (PCA), ADMIXTURE, and f-statistics, revealed that the Wenshaobei population was genetically distinct from Early Neolithic Shandong hunter-gatherers but closely aligned with Middle Neolithic to Iron Age populations from the middle and lower Yellow River Basin. This indicates strong genetic continuity with millet-farming societies from the middle Yellow River, supplemented by minor influences from southern rice-farming groups. Modern Han Chinese in Shandong share a core genetic foundation with ancient populations, such as Wenshaobei.</p><p><strong>Conclusions: </strong>Our findings highlight the role of the lower Yellow River Basin as a nexus of genetic exchange between northern millet-farming and southern rice-farming cultures, with sustained genetic influences from the middle Yellow River shaping the demographic landscape from the Neolithic to the Han Dynasty. The study provides critical insights into the formation of East Asian populations, underscoring the interplay between agriculture, migration, and genetic diversity in this cradle of ancient Chinese civilization.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"260"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multimodal analysis of cell-free DNA enhances differentiation of early-stage breast cancer from benign lesions and healthy individuals. 无细胞DNA的多模态分析增强了早期乳腺癌与良性病变和健康个体的分化。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-20 DOI: 10.1186/s12915-025-02371-z
Thi Tuong Vi Van, Trung Hieu Tran, Thi Hue Hanh Nguyen, Van Thien Chi Nguyen, Dac Ho Vo, Giang Thi Huong Nguyen, Trong Hieu Nguyen, Kim Sang To, Anh Luan Nguyen, Cao Hong An Tran, Thanh Xuan Jasmine, Thi Loan Vo, Thi Huong Thoang Nai, Thuy Trang Tran, My Hoang Truong, Ngan Chau Tran, Thi Loc Le, Thi Hong Nhung Nguyen, Ngoc Hieu Tu, Thanh Son Tran, Bao Toan Le, Van Phong Tang, Pham Thanh Nhan Nguyen, Khac Tien Nguyen, Van Chien Ho, Xuan Vinh Nguyen, Nhu Nhat Tan Doan, Thi Trang Tran, Thi Minh Thu Tran, Vu Uyen Tran, Minh Phong Le, Thi Luyen Vu, Ba Linh Tieu, Huu Tam Phuc Nguyen, Luu Hong Dang Nguyen, Ngoc Minh Phan, Thi Van Phan, Thi Thanh Thuy Do, Thi Huyen Dao, Hung Sang Tang, Duy Sinh Nguyen, Hoa Giang, Minh Duy Phan, Hoai-Nghia Nguyen, Duc Hieu Vo, Le Son Tran
{"title":"Multimodal analysis of cell-free DNA enhances differentiation of early-stage breast cancer from benign lesions and healthy individuals.","authors":"Thi Tuong Vi Van, Trung Hieu Tran, Thi Hue Hanh Nguyen, Van Thien Chi Nguyen, Dac Ho Vo, Giang Thi Huong Nguyen, Trong Hieu Nguyen, Kim Sang To, Anh Luan Nguyen, Cao Hong An Tran, Thanh Xuan Jasmine, Thi Loan Vo, Thi Huong Thoang Nai, Thuy Trang Tran, My Hoang Truong, Ngan Chau Tran, Thi Loc Le, Thi Hong Nhung Nguyen, Ngoc Hieu Tu, Thanh Son Tran, Bao Toan Le, Van Phong Tang, Pham Thanh Nhan Nguyen, Khac Tien Nguyen, Van Chien Ho, Xuan Vinh Nguyen, Nhu Nhat Tan Doan, Thi Trang Tran, Thi Minh Thu Tran, Vu Uyen Tran, Minh Phong Le, Thi Luyen Vu, Ba Linh Tieu, Huu Tam Phuc Nguyen, Luu Hong Dang Nguyen, Ngoc Minh Phan, Thi Van Phan, Thi Thanh Thuy Do, Thi Huyen Dao, Hung Sang Tang, Duy Sinh Nguyen, Hoa Giang, Minh Duy Phan, Hoai-Nghia Nguyen, Duc Hieu Vo, Le Son Tran","doi":"10.1186/s12915-025-02371-z","DOIUrl":"10.1186/s12915-025-02371-z","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) remains the second leading cause of cancer-related mortality among women worldwide. Liquid biopsy based on circulating tumor DNA (ctDNA) offers a promising noninvasive approach for early detection; however, differentiating malignant tumors from benign abnormalities remains a significant challenge.</p><p><strong>Results: </strong>Here, we developed a multimodal approach to analyze cfDNA methylation and fragmentomic patterns in 273 BC patients, 108 individuals with benign breast conditions, and 134 healthy controls. Genome-wide analyses revealed distinct cfDNA copy number alterations and cytosine-enriched cleavage sites in BC patients. Targeted sequencing further revealed unique methylation patterns, including hypermethylation in GPR126, KLF3, and TLR10 and hypomethylation in TOP1 and MAFB. Our machine-learning model achieved an AUC of 0.90, with 93.6% specificity and 62.1-66.3% sensitivity for stage I-II cancers. In symptomatic populations, sensitivities were 50.0%, 68.2%, and 64.7% for BI-RADS categories 3, 4, and 5, respectively, with 96.1% specificity.</p><p><strong>Conclusions: </strong>These findings underscore the potential of cfDNA biomarkers to enhance BC detection and reduce the rate of unnecessary biopsies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"259"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adaptive genetics reveals constraints on protein structure/function by evolving E. coli under constant nutrient limitation. 适应性遗传学揭示了在持续的营养限制下,大肠杆菌进化对蛋白质结构/功能的限制。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-20 DOI: 10.1186/s12915-025-02331-7
Katja Schwartz, Margie Kinnersley, Charles Ross Lindsey, Gavin Sherlock, Frank Rosenzweig
{"title":"Adaptive genetics reveals constraints on protein structure/function by evolving E. coli under constant nutrient limitation.","authors":"Katja Schwartz, Margie Kinnersley, Charles Ross Lindsey, Gavin Sherlock, Frank Rosenzweig","doi":"10.1186/s12915-025-02331-7","DOIUrl":"10.1186/s12915-025-02331-7","url":null,"abstract":"<p><strong>Background: </strong>Evolution of microbes under laboratory selection produces genetically diverse populations, owing to the continuous input of mutations and to competition among lineages. Whole-genome whole-population sequencing makes it possible to identify mutations arising in such populations, to use them to discern functional modules where adaptation occurs, and then map gene structure-function relationships. Here, we report on the use of this approach, adaptive genetics, to discover targets of selection and the mutational consequences thereof in E. coli evolving under chronic nutrient limitation.</p><p><strong>Results: </strong>Replicate bacterial populations were cultured for ≥ 300 generations in glucose limited chemostats and sequenced every 50 generations at 1000X-coverage, enabling identification of mutations that rose to ≥ 1% frequency. Thirty-nine genes qualified as high value targets of selection, being mutated far more often than would be expected by chance. A majority of these encode regulatory proteins that control gene expression at the transcriptional (e.g., RpoS and OmpR), post-transcriptional (e.g., Hfq and ProQ), and post-translational (e.g., GatZ) levels. The downstream effects of these regulatory mutations likely impact not only acquisition and processing of limiting glucose, but also assembly of structural elements such as lipopolysaccharide, periplasmic glucans, and cell surface appendages such as flagella and fimbriae. Whether regulatory or structural in nature, recurrent mutations at high value targets tend to cluster at sites either known or predicted to be involved in RNA-protein or protein-protein interactions.</p><p><strong>Conclusions: </strong>Our observations highlight the value of experimental evolution as a proving ground for inferences gathered from traditional molecular genetics. By coupling experimental evolution to whole-genome, whole-population sequencing, adaptive genetics makes it possible not only the genes whose mutation confers a selective advantage, but also to discover which residues in which genes are most likely to confer a particular type of selective advantage and why.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"261"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CoREST3 exhibits isoform specific expression in Alzheimer's disease and regulation of HDAC2. CoREST3在阿尔茨海默病和HDAC2调控中表现出同种异构体特异性表达。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-15 DOI: 10.1186/s12915-025-02349-x
Simon Maksour, Helena Targa Dias Anastacio, Jeremy S Lum, Samara Walpole, Kelly A Newell, Calista Turner, Adile Kaban, Rachelle Balez, Julia Lim, Greg T Sutherland, Lezanne Ooi, Mirella Dottori
{"title":"CoREST3 exhibits isoform specific expression in Alzheimer's disease and regulation of HDAC2.","authors":"Simon Maksour, Helena Targa Dias Anastacio, Jeremy S Lum, Samara Walpole, Kelly A Newell, Calista Turner, Adile Kaban, Rachelle Balez, Julia Lim, Greg T Sutherland, Lezanne Ooi, Mirella Dottori","doi":"10.1186/s12915-025-02349-x","DOIUrl":"10.1186/s12915-025-02349-x","url":null,"abstract":"<p><strong>Background: </strong>The epigenetic regulator, histone deacetylase 2 (HDAC2), is dysregulated in Alzheimer's disease (AD), resulting in disruption to neuronal dynamics, memory and cognition. The transcriptional repressor, REST corepressor 3 (CoREST3) has a potential binding site upstream of Hdac2 and therefore we hypothesised CoREST3 would directly regulate HDAC2 and that CoREST3 expression would be altered in the AD brain.</p><p><strong>Results: </strong>CoREST3 exhibited three distinct bands at ~ 70 kDa (band I), ~ 60 kDa (band II) and ~ 55 kDa (band III), which were consistent with CoREST3, as shRNA mediated knockdown reduced levels of all three bands. CoREST3 protein levels (band II) in AD post mortem brain tissue were significantly decreased in the superior temporal gyrus (STG), inferior temporal gyrus (ITG) and precuneus (PRE), whereas CoREST3 Band III was significantly increased in the PRE and primary visual cortex (PVC). Additionally, HDAC2 was significantly decreased by > 50% in the STG, PRE and PVC. CoREST3 bound upstream of the transcription start site of HDAC2 in induced pluripotent stem cell (iPSC)-derived cortical neurons, and gene knockdown of CoREST3 resulted in a significant increase in HDAC2 expression (p < 0.01). Through the overexpression of each of the six CoREST3 isoforms we demonstrated that Band I represents isoform A and isoform E, Band II is likely a combination of isoform B and isoform C and Band III is isoform D and isoform F. The overexpression of CoREST3 isoform A (RCOR3-variant 1 led to a significant twofold increase in HDAC2 protein levels in cortical neurons (p < 0.05), conversely CoREST3 isoform F overexpression resulted in the opposite effect, reducing HDAC2 levels by 48% (p < 0.05).</p><p><strong>Conclusions: </strong>Together these data suggest that CoREST3 plays an isoform specific and direct role in repressing HDAC2, with dysregulated CoREST3 expression in AD possibly contributing to altered HDAC2 levels involved in AD pathogenesis.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"255"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of insertion bias into piRNA clusters on the invasion of transposable elements. 插入偏置对转座因子侵袭的影响。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-15 DOI: 10.1186/s12915-025-02370-0
Shashank Pritam, Almorò Scarpa, Robert Kofler, Sarah Signor
{"title":"The impact of insertion bias into piRNA clusters on the invasion of transposable elements.","authors":"Shashank Pritam, Almorò Scarpa, Robert Kofler, Sarah Signor","doi":"10.1186/s12915-025-02370-0","DOIUrl":"10.1186/s12915-025-02370-0","url":null,"abstract":"<p><strong>Background: </strong>In our current understanding of transposable element (TE) invasions, TEs move freely until they accidentally insert into a piRNA cluster, where they are silenced by the production of piRNA cognate to the TE. Under this model, one would expect that selection might favor TEs that avoid piRNA clusters. However, empirical observations show that some TEs, such as the P-element, insert into piRNA clusters preferentially. We were thus wondering if such a bias, by minimizing harm to the host, could facilitate the spread of TEs throughout a population.</p><p><strong>Results: </strong>We performed extensive forward simulations of TE invasions with different insertion biases into piRNA clusters to determine if there was ever a situation in which the insertion bias was beneficial to the TE. We found that insertion bias significantly altered the invasion dynamics of TEs, primarily by changing the number of TE copies in individuals before silencing. Insertion into a piRNA cluster reduced the deleterious effects of TEs to the host population, but we found that TEs avoiding piRNA clusters out-compete TEs with a bias toward cluster insertions. Insertion bias was only beneficial to the TE when there was negative selection against TEs and a lack of recombination.</p><p><strong>Conclusions: </strong>Different TEs show different insertion biases into piRNA clusters suggesting they are an attribute of the TE not the host, yet scenarios in which this is beneficial for TE propagation are quite limited. This opens up an interesting area for future research into the dynamics of insertion bias during TE invasions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"258"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
m6A-modified circZNF548 regulates exosomal miR-7108-3p to activate CD3+CD8+ T cells and suppress NSCLC growth by JMY. m6a修饰的circZNF548调节外泌体miR-7108-3p激活CD3+CD8+ T细胞,通过JMY抑制NSCLC生长。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-15 DOI: 10.1186/s12915-025-02355-z
Yu-Long Zhao, You-Jie Li, Chun-Xia Wu, Ning Xie, Xi-Yan Li, Dian-Chao Cao, Yang Guo, Yan Liang, Yan-Mei Li, Jiang-Nan Xue, Hong-Fang Sun, Qin Wang, Xiao-Hua Li, Ping-Yu Wang, Shu-Yang Xie
{"title":"m6A-modified circZNF548 regulates exosomal miR-7108-3p to activate CD3<sup>+</sup>CD8<sup>+</sup> T cells and suppress NSCLC growth by JMY.","authors":"Yu-Long Zhao, You-Jie Li, Chun-Xia Wu, Ning Xie, Xi-Yan Li, Dian-Chao Cao, Yang Guo, Yan Liang, Yan-Mei Li, Jiang-Nan Xue, Hong-Fang Sun, Qin Wang, Xiao-Hua Li, Ping-Yu Wang, Shu-Yang Xie","doi":"10.1186/s12915-025-02355-z","DOIUrl":"10.1186/s12915-025-02355-z","url":null,"abstract":"<p><strong>Background: </strong>Communication between cancer cells and tumor microenvironment (TME) plays a complicated role in cancer malignancy. Circular RNAs (circRNAs), known for their stability and conservation, contribute to TME remodeling in various cancers. This study aims to investigate the role of N6-methyladenosine (m6A)-modified circZNF548 in the proliferation and migration of non-small cell lung cancer (NSCLC) within the TME.</p><p><strong>Results: </strong>circZNF548 expression is lower in NSCLC tissues than that in adjacent normal controls, and the higher circZNF548 levels correlate with the improved patient survival. circZNF548 overexpression suppresses NSCLC cell proliferation and migration, whereas siRNA-mediated downregulation promotes proliferation and migration. METTL14 overexpression decreases circZNF548 levels through m6A modification, whereas siRNA-mediated METTL14 downregulation increases them. circZNF548 interacts with and regulates the abundance of exosomal miR-7108-3p. CD8A and junction-mediating and regulating Y protein (JMY) are identified as downstream targets of miR-7108-3p. Exosomal miR-7108-3p suppresses the activation of CD3<sup>+</sup>CD8<sup>+</sup> T cells by decreasing CD107a levels and downregulating the production of IFN-γ, perforin 1, and granzyme B in TME. circZNF548 promotes CD3 + CD8 + T cell-mediated cytotoxicity and inhibits NSCLC cell proliferation by modulating exosomal miR-7108-3p and the JMY-p53 pathway.</p><p><strong>Conclusions: </strong>m6A-modified circZNF548 suppresses NSCLC cell proliferation and migration by enhancing anti-tumor immunity via exosomal miR-7108-3p and the JMY-p53 pathway. These findings suggest new therapeutic targets for NSCLC.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"257"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gustatory receptors interact with the serotonin pathway to regulate silkmoth stereotyped courtship behavior. 味觉受体与血清素通路相互作用,调节家蚕的刻板求爱行为。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-15 DOI: 10.1186/s12915-025-02352-2
Zhongjie Zhang, Xiaojing Liu, Mengdan Chen, Chenxin Sun, Dalin Zhu, Jialong Lei, Qingyun He, Qi Yan, Shuanglin Dong, Anjiang Tan
{"title":"Gustatory receptors interact with the serotonin pathway to regulate silkmoth stereotyped courtship behavior.","authors":"Zhongjie Zhang, Xiaojing Liu, Mengdan Chen, Chenxin Sun, Dalin Zhu, Jialong Lei, Qingyun He, Qi Yan, Shuanglin Dong, Anjiang Tan","doi":"10.1186/s12915-025-02352-2","DOIUrl":"10.1186/s12915-025-02352-2","url":null,"abstract":"<p><strong>Background: </strong>Gustatory receptors (GRs) are known to mediate responses to various chemical stimuli including sugars and bitter compounds and sex pheromones. Although numerous types of GRs have been identified across insect species, the physiological roles of most GRs remain largely unknown. The silkworm, Bombyx mori, is representative of the order Lepidoptera, which includes over 70% of agriculturally important pest species. A notable feature of GRs in B. mori is that most GRs are organized in clusters, making them highly suitable for large-scale genetic studies.</p><p><strong>Results: </strong>Here we developed a transcription activator-like effector nuclease-mediated gene cluster replacement system, enabling functional studies beyond single-gene resolution. Using this system, we deleted the GR27-31 cluster in B. mori, which includes 12 GRs spanning approximately 82 kb of genomic sequence. Loss of GR27-31 function results in significant time retardation of courtship by impairing the ability of male silkmoths to seek female silkmoths. Electroantennogram analysis revealed that GR27-31 mutant male silkmoths did not change their responses to volatile sex pheromones of bombykol and bombykal compared with wild-type silkmoths, indicating that GR27-31 mutation did not affect male-female sex pheromone responses at the peripheral level. Subsequent molecular analysis revealed that mRNA relative expression of serotonin receptors was significantly affected in mutant silkmoths.</p><p><strong>Conclusions: </strong>The current study provides the first genetic and phenotypic evidence that GRs modulate male-female courtship in B. mori. Furthermore, the results revealed for the first time that the serotonin pathway is associated with GR regulation of courtship behavior in insects.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"256"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DualNetM: an adaptive dual network framework for inferring functional-oriented markers. DualNetM:用于推断功能导向标记的自适应双网络框架。
IF 4.5 1区 生物学
BMC Biology Pub Date : 2025-08-12 DOI: 10.1186/s12915-025-02367-9
Bingjie Dai, Hanshuang Li, Peizhuo Wang, Pengwei Hu, Jixiang Xing, Yanan Hu, Qilemuge Xi, Yongchun Zuo
{"title":"DualNetM: an adaptive dual network framework for inferring functional-oriented markers.","authors":"Bingjie Dai, Hanshuang Li, Peizhuo Wang, Pengwei Hu, Jixiang Xing, Yanan Hu, Qilemuge Xi, Yongchun Zuo","doi":"10.1186/s12915-025-02367-9","DOIUrl":"10.1186/s12915-025-02367-9","url":null,"abstract":"<p><strong>Background: </strong>Understanding how genes regulate each other in cells is crucial for determining cell identity and development, and single-cell sequencing technologies facilitate such research through gene regulatory networks (GRNs). However, identifying important marker genes within these complex networks remains difficult.</p><p><strong>Results: </strong>Consequently, we present DualNetM, a deep generative model with a dual-network framework for inferring functional-oriented markers. It employs graph neural networks with adaptive attention mechanisms to construct GRNs from single-cell data. Functional-oriented markers are identified from bidirectional co-regulatory networks through the integration of gene co-expression networks. Benchmark tests highlighted the superior performance of DualNetM in constructing GRNs, along with a stronger association with biological functions in marker inference. In the melanoma dataset, DualNetM successfully inferred novel malignant markers, and survival analysis results showed that multiple novel markers were associated with lethality in malignant melanoma. Additionally, DualNetM identified stage-specific functional markers and clarified their specific roles in mouse embryonic fibroblast reprogramming. DualNetM's marker inference function demonstrated stronger biological relevance during primed reprogramming.</p><p><strong>Conclusions: </strong>In summary, DualNetM effectively facilitated the inference of functional-oriented markers from complex GRNs.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"254"},"PeriodicalIF":4.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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