Science China Life Sciences最新文献

{"title":"The gut microbiome modulate response to immunotherapy in cancer.","authors":"Shan-Shan Jiang, Zi-Ran Kang, Ying-Xuan Chen, Jing-Yuan Fang","doi":"10.1007/s11427-023-2634-7","DOIUrl":"10.1007/s11427-023-2634-7","url":null,"abstract":"<p><p>Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"381-396"},"PeriodicalIF":8.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133629","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":"Genome-wide CRISPR screens identify CLC-2 as a drug target for anti-herpesvirus therapy: tackling herpesvirus drug resistance.","authors":"Fayu Yang, Nan Wei, Shuo Cai, Jing Liu, Qingping Lan, Hao Zhang, Lu Shang, Bo Zheng, Mi Wang, Yingchun Liu, Lifang Zhang, Chenzhong Fei, Wu Tong, Changlong Liu, Ersheng Kuang, Guangzhi Tong, Feng Gu","doi":"10.1007/s11427-023-2627-8","DOIUrl":"10.1007/s11427-023-2627-8","url":null,"abstract":"<p><p>The emergence of drug resistance to virus (i.e., acyclovir (ACV) to herpesviruses) has been termed one of the common clinical issues, emphasizing the discovery of new antiviral agents. To address it, a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening was performed in mouse haploid embryonic stem cells infected with pseudorabies virus (PRV), an α-herpesvirus causing human and pig diseases. The results demonstrated that type 2 voltage-gated chloride channels (CLC-2) encoded by one of the identified genes, CLCN2, is a potential drug target for anti-herpesvirus therapy. CLC-2 inhibitors, omeprazole (OME) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), can efficiently inhibit infection of multiple herpesviruses in cellulo (i.e., PRV, HSV and EBV), and effectively treat murine herpes simplex encephalitis (HSE). Additionally, DIDS was found to inhibit HSV-1 replication by blocking the PI3K/Akt pathway. Most importantly, both DIDS and OME were able to inhibit ACV-resistant HSV-1 strain infection. The study's findings suggest that targeting host-cell factors such as CLC-2 may be a promising approach to tackling herpesvirus drug resistance. The discovery of CLC-2 as a potential drug target for anti-herpesvirus therapy provides a new direction for the development of novel antiviral agents.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"515-526"},"PeriodicalIF":8.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473720","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":"Optimized inner ear organoids for efficient hair cell generation and ototoxicity response modeling.","authors":"Xuanhe Qin, Liping Fu, Chunying Li, Xilin Tan, Xiaolei Yin","doi":"10.1007/s11427-024-2803-1","DOIUrl":"https://doi.org/10.1007/s11427-024-2803-1","url":null,"abstract":"<p><p>Hair cells in the mammalian cochlea are highly vulnerable to damage from drug toxicity, noise exposure, aging, and genetic mutations, with no capacity for regeneration. Progress in hair cell protection research has been limited by the scarcity of cochlear tissue and suitable in vitro models. Here, we present a novel one-step, self-organizing inner ear organoid system optimized with small molecules, which bypasses the need for multi-step expansion and forced differentiation protocols. This approach efficiently generates hair cells and supporting cells that recapitulate the molecular, cellular, and structural characteristics of the inner ear. Single-cell RNA sequencing revealed the diversity and fidelity of cell populations within the organoids. Utilizing this platform, we validated the protective effects of candidate compounds against hair cell damage, highlighting its potential as a powerful tool for drug discovery and mechanistic studies of hair cell protection.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041556","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":"Decoupled responses of soil microbial diversity and ecosystem functions to successive degeneration processes in alpine pioneer community.","authors":"Yazhou Zhang, J Aaron Hogan, Yaojun Ye, Xin Liu, Minshu Song, Jianguo Chen, Hang Sun","doi":"10.1007/s11427-024-2692-5","DOIUrl":"https://doi.org/10.1007/s11427-024-2692-5","url":null,"abstract":"<p><p>Many alpine ecosystems are undergoing vegetation degradation because of global changes, which are affecting ecosystem functioning and biodiversity. The ecological consequences of alpine pioneer community degradation have been less studied than glacial retreat or meadow degradation in alpine ecosystems. We document the comprehensive responses of microbial community characteristics to degradation processes using field-based sampling, conduct soil microcosm experiments to simulate the effects of global change on microorganisms, and explore their relationships to ecosystem functioning across stages of alpine pioneer community degradation. Our work provides the first evidence that alpine pioneer community degradation led to declines of 27% in fungal richness, 8% in bacterial richness, and about 50% in endemic microorganisms. As vegetation degraded, key ecosystem functions such as nutrient availability, soil enzymatic activity, microbial biomass, and ecosystem multifunctionality progressively increased. However, soil respiration rate and carbon storage exhibited unbalanced dynamics. Respiration rate increased by 190% during the middle stage of degradation compared with the primary stage, and it decreased by 38% in the later stage. This indicates that soil carbon loss or emission increases during the mid-successional stage, whereas in later successional stages, alpine meadows become significant carbon sinks. Compared with microbial community characteristics (such as richness of total and functional taxa, and network complexity), community resistance contributes more significantly to ecosystem functions. Especially, the bacterial community resistance is crucial for ecosystem functioning, yet it is greatly impaired by nitrogen addition. Based on microbial network, community assembly, and community resistance analyses, we conclude that fungi are more vulnerable to environmental changes and show smaller contributions to ecosystem functions than bacteria in degrading alpine ecosystems. Our findings enhance the knowledge of the distinct and synergistic functional contributions of microbial communities in degrading alpine ecosystems and offer guidance for developing restoration strategies that optimize ecosystem functioning of degraded alpine plant communities.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041501","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":"SLC39A10 is a key zinc transporter in T cells and its loss mitigates autoimmune disease.","authors":"Yichang Shao, Qingdian Mu, Rong Wang, Hongbin Luo, Zijun Song, Pengfei Wang, Jingshu Song, Chaodong Ge, Jiyan Zhang, Junxia Min, Fudi Wang","doi":"10.1007/s11427-024-2817-y","DOIUrl":"https://doi.org/10.1007/s11427-024-2817-y","url":null,"abstract":"<p><p>Zinc homeostasis plays an essential role in maintaining immune function and is tightly regulated by zinc transporters. We previously reported that the zinc transporter SLC39A10, located in the cell membrane, critically regulates the susceptibility of macrophages to inflammatory stimuli; however, the functional role of SLC39A10 in T cells is currently unknown. Here, we identified two SNPs in SLC39A10 that are associated with inflammatory bowel disease (IBD). We then generated transgenic mice with T cell-specific deletion of Slc39a10 (cKO) and found that its loss not only protects against disease progression in IBD and experimental autoimmune encephalomyelitis (EAE), but also induces massive apoptosis via a p53/p21- and Bcl2-independent process. Mechanistically, we show that Slc39a10 serves as a key zinc importer upon activation of T cell receptor to safeguard DNA replication. Together, these findings provide new mechanistic insights and potential targets for the development of new therapeutic strategies for the treatment and/or prevention of T cell-mediated autoimmune diseases.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041558","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":"Pilot work of the 10K Chinese People Genomic Diversity Project along the Silk Road suggests a complex east-west admixture landscape and biological adaptations.","authors":"Guanglin He, Hongbing Yao, Shuhan Duan, Lintao Luo, Qiuxia Sun, Renkuan Tang, Jing Chen, Zhiyong Wang, Yuntao Sun, Xiangping Li, Liping Hu, Libing Yun, Junbao Yang, Jiangwei Yan, Shengjie Nie, Yanfeng Zhu, Chuan-Chao Wang, Bing Liu, Lan Hu, Chao Liu, Mengge Wang","doi":"10.1007/s11427-024-2748-4","DOIUrl":"https://doi.org/10.1007/s11427-024-2748-4","url":null,"abstract":"<p><p>Genomic sources from China are underrepresented in the population-specific reference database. We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups (1,081 Sinitic, 56 Mongolic, 40 Turkic, and 30 Tibeto-Burman people) living in North China included in the 10K Chinese People Genomic Diversity Project (10K_CPGDP) to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China. We observed a population split between Northwest Chinese minorities (NWCMs) and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs. The observed population substructures among ethnically/linguistically diverse NWCMs suggested that differentiated admixture events contributed to the differences in their genomic and phenotypic diversity. We estimated that the Dongxiang, Tibetan, and Yugur people inherited more than 10% of the Western Eurasian ancestry, which is much greater than that of the Salar and Tu people (<7%), while Han neighbors showed less West Eurasian ancestry (∼1%-3%). Male-biased admixture introduced Western Eurasian ancestry in the Dongxiang, Tibetan, and Yugur populations. We found that the eastern-western admixture in NWCMs occurred ∼800-1,100 years ago, coinciding with intensive economic and cultural exchanges during the Tang and Song dynasties. Additionally, we identified the signatures of natural selection associated with cardiovascular system diseases or lipid metabolism and developmental/neurogenetic disorders. Moreover, the EPAS1 gene showed relatively high population branch statistic values in NWCMs. The well-fitted demographical models presented the vast landscape of complex admixture processes of the Silk Road people, and the newly reported functionally important variations suggested the importance of including ethnolinguistically diverse populations in Chinese genetic studies for uncovering the genetic basis of complex traits/diseases.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041557","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":"Clinical biomarkers of perioperative neurocognitive disorder: initiation and recommendation.","authors":"Jianhui Liu, Cheng Li, Junyan Yao, Lei Zhang, Xuan Zhao, Xin Lv, Zhiqiang Liu, Changhong Miao, Yingwei Wang, Hong Jiang, Weifeng Yu, Tianlong Wang, Dongxin Wang, E Wang, Xiaoping Gu, Hailong Dong, Junli Cao, Yuan Shen, Weihong Song, Shengdi Chen, Yanjiang Wang, Guanghui Liu, Zhongcong Xie, Lize Xiong, Jialin C Zheng","doi":"10.1007/s11427-024-2797-x","DOIUrl":"https://doi.org/10.1007/s11427-024-2797-x","url":null,"abstract":"<p><p>Perioperative neurocognitive disorder (PND) is a significant neurological complication in aging perioperative patients that impacts post-operative cognition. PND is currently diagnosed through cognitive function testing, which is limited by its subjectivity and time requirements. Thus, the identification of biomarkers to assess PND onset is a priority to identify at-risk individuals and enable interventions and treatments to patient outcomes. This article synthesizes expert perspectives on brain aging and PND, presents the latest clinical evidence on PND biomarkers (imaging, electroencephalography, and molecular biomarkers), and delves into the relationship between PND and other age-related cognitive disorders. Thorough review of PND research identified several biomarkers with high sensitivity and specificity, offering a solid scientific foundation to predict and diagnose PND. These biomarkers not only enhance diagnostic accuracy for clinicians but also provide opportunities for earlier intervention and more effective treatment, potentially enhancing patient outcomes and quality of life.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365926","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":"No association between SARS-CoV-2 infection and embryo chromosomal abnormalities: a prospective cohort study.","authors":"Tianxiang Ni, Yang Liu, Weiran Cui, Siying Chen, Hongchang Li, Yueting Zhu, Wenjie Jiang, Qian Zhang, Wei Zhou, Zi-Jiang Chen, Yan Li, Guangyong Zhang, Junhao Yan","doi":"10.1007/s11427-024-2765-8","DOIUrl":"https://doi.org/10.1007/s11427-024-2765-8","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041522","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":"An extra X chromosome: dissecting its role in male fetal germ cell maturation.","authors":"Shuyan Tang, Feng Zhang, Yanhua Wu","doi":"10.1007/s11427-024-2825-3","DOIUrl":"https://doi.org/10.1007/s11427-024-2825-3","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041490","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":"Exposure to zearalenone exacerbates the decrease in calcium transport via selective regulation to estrogen receptor α/β in estrogenic deficient model.","authors":"Qingxiu Liu, Leli Wang, Yafei Liu, Shimeng Huang, Lihong Zhao, Yulong Yin, Qiugang Ma","doi":"10.1007/s11427-024-2785-8","DOIUrl":"https://doi.org/10.1007/s11427-024-2785-8","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041504","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}