Science China Life Sciences最新文献

{"title":"Glutathione contributes to alleviating hepatic injury via host-microbiome interaction and CAR-dependent pathway.","authors":"Xuan Xiang, Siwei Liu, Houfu Wang, Chenyu Wang, Wentao Zhou, Heshu Chen, Yanzhong Feng, Xinmiao He, Gang Xu, Qiang Zhao, Tiejun Li, Di Liu, Yulong Yin, Liuqin He","doi":"10.1007/s11427-024-2949-8","DOIUrl":"https://doi.org/10.1007/s11427-024-2949-8","url":null,"abstract":"<p><p>Glutathione (GSH) is a potent antioxidant regulating oxidative stress, but whether exogenous GSH supplementation mitigates stress injury through host-microbiome and liver interactions remains unclear. This study aimed to determine the regulatory mechanism of GSH using in vivo (28-day-old weaned piglets) and in vitro (alpha mouse liver 12 (AML12) cells) stress injury models. Thirty-five healthy weaned piglets (mean body weight (9.52±0.20) kg) were fed diets supplemented with 0.01%, 0.03%, or 0.06% GSH for 4 weeks, followed by being injected intraperitoneally with paraquat (PQ) on days 28, 30, and 32. AML12 cells exposed to tert-butyl hydroperoxide (tBHP) were used to evaluate related mechanisms, and CINPA1was used to inhibit constitutive androstane receptor (CAR) activity. Our results showed that PQ challenge induced hepatic morphological and functional impairments, accompanied by suppression of antioxidant capacity and immune function. Notably, exogenous GSH treatment significantly increased CD4⁺/CD8⁺ T lymphocyte ratio, GSH, immunoglobulin A and interleukin-10 levels in serum, reduced the secretion and gene expression of pro-inflammatory factors to alleviate liver injury. Moreover, GSH treatment significantly promoted CAR nuclear translocation and regulated the expression of detoxification genes in response to liver inflammation. Additionally, GSH treatment improved the diversity and relative abundance of colonic probiotic bacteria such as UCG_002, Christensenellaceae_R_7_group, Prevotellaceae_NK3B31_group, Prevotella, Oscillospira, and unclassified_UCG_010. Furthermore, in vitro results showed that 3 mmol L^-1 GSH administration could increase the expression of CAR pathway and antioxidant related genes, and inhibit cellular ROS production in tBHP-induced AML12 cells. However, CAR inhibition by CINPA1 prevented GSH from alleviating tBHP-induced oxidative stress injury in AML12 cells. Our results indicate that exogenous GSH treatment alleviated liver injury in piglets through host-microbiome interaction and a CAR-dependent signaling pathway.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281155","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}

{"title":"AI meets RNA: revolutionizing structure prediction.","authors":"Ruobin Zhao, Shaozhen Yin, Qiangfeng Cliff Zhang, Lei Sun","doi":"10.1007/s11427-025-3079-3","DOIUrl":"https://doi.org/10.1007/s11427-025-3079-3","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281206","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}

{"title":"TurboID-based proximity labeling identifies novel germline proteins that maintain E granule integrity and small RNA homeostasis in C. elegans.","authors":"Kun Li, Xuezhu Feng, Ke Wang, Xiaona Huang, Liang Liu, Chaoyue Yan, Xinya Huang, Chengming Zhu, Quan Wen, Shouhong Guang, Xiangyang Chen","doi":"10.1007/s11427-025-3025-6","DOIUrl":"https://doi.org/10.1007/s11427-025-3025-6","url":null,"abstract":"<p><p>Germ granules are biomolecular condensates composed of RNA and proteins that play crucial roles in RNA metabolism and post-transcriptional gene regulation. C. elegans germ granules consist of multiple distinct subcompartments, including P granules, Mutator foci, Z granules, SIMR foci, P-bodies, D granules, and E granules. Among these condensates, the E granule, which is nonrandomly positioned within the germ granule, is required for the production of a specialized class of small interfering RNAs (siRNAs). However, the mechanisms underlying E granule formation and its functional significance remain largely unexplored. In this study, via the use of TurboID-based proximity labeling technology combined with an RNAi-based reverse genetic screen, we identified two novel components of the E granule, EGC-2/C27B7.5 and EGC-3/F59G1.8, which initiate E granule assembly. The depletion of EGC-2 or EGC-3 disrupts the perinuclear localization of the EGO and PICS complexes, both of which are enriched in E granules and are required for E-class siRNA and piRNA biogenesis, respectively. Small RNAomic analyses revealed that both EGC-2 and EGC-3 promote the production of 5' E-class siRNA, whereas piRNA accumulation is inhibited by EGC-3. Taken together, our results elucidate the roles of EGC-2 and EGC-3 in maintaining E granule integrity and small RNA homeostasis. Additionally, the combination of proximity labeling technology and reverse genetic screening provides a robust strategy for studying the assembly of biomolecular condensates.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281209","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}

{"title":"Toward a comprehensive map of Rab-mediated cargo transport to migrasomes.","authors":"Yiling Wen, Yong Li, Jiayi Chen, Dianxing Liu, Yuanchao Li, Ying Li, Haohao Tang, Peizhen Gao, Wenmin Tian, Ning Shen, Yang Chen","doi":"10.1007/s11427-025-3073-2","DOIUrl":"https://doi.org/10.1007/s11427-025-3073-2","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281188","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}

{"title":"Berberine combined with stachyose protects against obesity by modulating gut microbiota and increasing leptin sensitivity.","authors":"Dan Wu, Feng Zhang, Huiying Wang, Lijun Xie, Bingdong Liu, Shanshan Xiao, Wei Chen, Yuqing Ye, Zhinan Chen, Guanghou Shui, Weimin Zeng, Liwei Xie, Fang Hu","doi":"10.1007/s11427-024-2943-4","DOIUrl":"https://doi.org/10.1007/s11427-024-2943-4","url":null,"abstract":"<p><p>Leptin resistance is a hallmark of obesity. Recent evidence shows that gut microbiota is associated with the development and progression of leptin resistance. However, whether intervention targeting gut microbiota can improve leptin sensitivity remains to be fully established. In the current investigation, we have demonstrated that co-administration of berberine, an isoquinoline alkaloid compound, and stachyose, a prebiotic, could enhance leptin sensitivity and reduce body weight in diet-induced obesity (DIO) mice, via an effect associated with gut microbiota modulation. Notably, the combination of berberine and stachyose significantly increased the abundance of Blautia producta, altered host purine metabolism, and elevated serum and hypothalamic levels of a purine metabolite, inosine. Furthermore, direct supplementation with inosine further ameliorated inflammation and endoplasmic reticulum stress in the hypothalamus and improved leptin sensitivity in obese mice. These findings suggest that berberine combined with stachyose represents a novel leptin sensitizer for obesity, acting through the modulation of gut microbiota and subsequently alteration in host purine metabolism, particularly with the involvement of inosine.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281198","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}

{"title":"Tree of life and conservation of gymnosperms in China.","authors":"Chang-Wang Ma, Dan Xie, Hong Du, Kai-Yuan Huang, Yuan-Yuan Feng, Zhou-Rui Wei, Xin-Quan Liu, Cheng-Ru Li, Jing-Jing Sun, Xiao-Xin Wei, Zhi-Heng Wang, Wei-Hua Xu, Xiao-Quan Wang, Jin-Hua Ran","doi":"10.1007/s11427-024-2988-0","DOIUrl":"https://doi.org/10.1007/s11427-024-2988-0","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281136","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}

{"title":"Unveiling the choroidal immune landscape revealed interferon-gamma and TNF-alpha as novel therapeutic targets in dry AMD.","authors":"Lin Ye, Tujing Zhao, Huaping Tian, Runze Li, Zheng Li, Hongjing Li, Ruilin Liao, Junlan Chuan, Haojue Xu, Liang Zou, Chao Qu, Yi Shi, Zhenglin Yang, Lulin Huang","doi":"10.1007/s11427-025-2951-5","DOIUrl":"https://doi.org/10.1007/s11427-025-2951-5","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD), particularly its atrophic (dry) form, is a leading cause of irreversible blindness in the elderly. Limited treatment efficacy stems from its complex pathogenesis, highlighting an urgent need for novel therapeutic targets. This study investigates the contribution of the choroidal immune microenvironment, focusing on intercellular communication involving resident fibroblasts-a cell type whose role in AMD remains poorly defined. By analyzing single-cell RNA sequencing data from human choroid, we interrogated crosstalk between fibroblasts, macrophages, and NK/T cells, identifying interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) signaling pathways as central mediators. We demonstrate that activated choroidal fibroblasts release key inflammatory mediators, including IL6, CCL2, CSF1, CXCL9, and CXCL10, which functionally recruit macrophages and CD8⁺ T cells, thereby shaping the local immune landscape. Critically, targeting these pathways in vivo using TAPI-1 (inhibiting TNFα processing) and Tofacitinib (inhibiting IFNγ signaling) significantly ameliorated retinal, RPE, and choroidal pathology in a NaIO₃-induced murine model of dry AMD. Our findings underscore the pathogenic role of fibroblast-mediated choroidal inflammation driven by TNFα and IFNγ signaling in dry AMD, presenting these pathways as promising therapeutic targets.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281201","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}

{"title":"Telomere-to-telomere sequence of mouse haploid stem cells.","authors":"Qilin Li, Xiaochun Yu","doi":"10.1007/s11427-025-2919-4","DOIUrl":"10.1007/s11427-025-2919-4","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"3102-3103"},"PeriodicalIF":9.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199887","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}

{"title":"(Z)-Ligustilide alleviates intervertebral disc degeneration by suppressing nucleus pulposus cell pyroptosis via Atg5/NLRP3 axis.","authors":"Jiale Wang, Chunyang Fan, Yao Zhang, Di Hua, Zhongwei Ji, Wei He, Yongkang Deng, Dechun Geng, Xiexing Wu, Haiqing Mao","doi":"10.1007/s11427-024-2907-7","DOIUrl":"10.1007/s11427-024-2907-7","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) represents one of the most prevalent degenerative disorders, significantly impairing quality of life and overall health. The inflammatory cascade and dysregulated degradation of the extracellular matrix (ECM) triggered by pyroptosis are considered key mechanisms underlying the pathogenesis of IVDD. Research has highlighted the potential of Chuanxiong Rhizoma (CX), a traditional Chinese medicine, in exerting anti-pyroptotic effects; nevertheless, the exact mechanisms and pathways through which it modulates inflammation, as well as its potential role in the context of IVDD, remain unknown. Network pharmacology analysis was initially employed to identify the principal components and targets of Chuanxiong Rhizoma (CX) in the treatment of IVDD, ultimately selecting LIG as the key active ingredient responsible for its therapeutical effect. To explore the therapeutic effects of LIG on IVDD, we established a rat acupuncture model to simulate IVDD in vivo. Additionally, we used lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce NPC degeneration model in vitro. In vitro experiments revealed that LIG treatment promotes the expression of anabolic markers such as Collagen II and Aggrecan while inhibiting the expression of catabolic markers MMP9 and MMP13 in nucleus pulposus cells (NPCs). Furthermore, LIG was also shown to inhibit cell pyroptosis and the secretion of inflammatory cytokines, which was mediated by NLRP3/caspase-1/GSDMD-N activation. Molecular docking and co-immunoprecipitation further demonstrated that LIG acts as a ligand for the Atg5 protein, inhibiting its degradation and promoting its interaction with the NLRP3 protein, ultimately leading to the suppression of pyroptosis activation in NPCs. It was also found that knocking down Atg5 reverses the protective effects of LIG and exacerbates pyroptosis-mediated inflammation in IVDD. In addition, in vivo experiments also showed that LIG delayed acupuncture-mediated IVDD development. Therefore, this paper confirmed that LIG has the ability to protect NPCs against pyroptosis through Atg5/NLRP3 axis and exert its therapeutic application to ameliorate disc degeneration in vivo. This may shed new insights into the role of LIG in IVDD treatment and offer a mechanistic basis for targeting NLRP3-mediated pyroptosis.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2965-2981"},"PeriodicalIF":9.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560972","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}

{"title":"SUMO-activating enzyme subunit 1 (SAE1) promotes non-small cell lung cancer metastasis by promoting the epithelial-mesenchymal transition through the SUMOylation of N-cadherin.","authors":"Yaru Wang, Xijun Wang, Huan Zhao, Jie Song, Wenhao Hou, Zhenrong Liu, Xin Yang, Sheng Ma, Ruiqi Zheng, Huiqin Guo, Wantao Ying, Ting Xiao","doi":"10.1007/s11427-023-2662-y","DOIUrl":"10.1007/s11427-023-2662-y","url":null,"abstract":"<p><p>Protein SUMOylation is a newly discovered process similar to protein ubiquitination and is crucial for protein stability and protein localization. SAE1 is an important enzyme that initiates protein SUMOylation, but its role in the progression of non-small cell lung cancer remains unknown. We analyzed the protein expression profiles of non-small cell lung cancer tissues and single-cell sequencing data and confirmed that SAE1 is highly expressed in non-small cell lung cancer cells and is associated with a malignant phenotype. Knockdown of SAE1 decreased the growth, cell cycle progression, and metastasis of non-small cell lung cancer cells both in vitro and in vivo. Mechanistically, using the protein expression profile of non-small cell lung cancer cell lines with altered SAE1 expression, we showed that SAE1, a key molecule mediating protein SUMOylation, can SUMOylate the epithelial-mesenchymal transition-related protein N-cadherin, stabilize N-cadherin and promote the occurrence of the EMT in non-small cell lung cancer cells, leading to lung cancer invasion and metastasis. In clinical application, we used sputum samples from patients with lung cancer or chronic pulmonary obstructive pulmonary disease for protein profiling and further used sputum-based thin-slice technology for experimental verification, which confirmed the application potential of SAE1 in the diagnosis of lung cancer patients. In summary, our findings reveal a critical role for SAE1 as an oncogene in lung cancer cells and suggest that SAE1 may be used for the diagnosis of lung cancer patients.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2950-2964"},"PeriodicalIF":9.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609271","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}