Science China Life Sciences最新文献

{"title":"Painting dopamine in far-red: a chemigenetic breakthrough.","authors":"Jing Ling, Sohum Mehta, Jin Zhang","doi":"10.1007/s11427-025-3132-9","DOIUrl":"10.1007/s11427-025-3132-9","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1812-1814"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011899","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":"CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.","authors":"Guolong Liu, Xiaoling Tian, Lu Ye, Peijing Han, Qiudao Wang, Yang Cao, Yuxuan Wu, Yuming Lu","doi":"10.1007/s11427-025-3153-9","DOIUrl":"10.1007/s11427-025-3153-9","url":null,"abstract":"<p><p>Sequence-specific gene knockdown technologies are crucial for fundamental research and therapeutic applications. RNA interference and CRISPR interference, while extensively utilized for gene expression manipulation, face limitations due to their ectopic or transient expression. In this study, we developed a generalizable and efficient method to downregulate gene expression in human 293T cells by introducing de novo upstream ATGs (uATGs) of genes using CRISPR-Cas9-mediated genome editing. Through CRISPR library screening, in-depth sequencing, and flow cytometry analysis, we validated that the introduction of uATGs served as an effective method to suppress protein expression. Our findings further revealed that this strategy can be tailored to diminish endogenous gene expression in tumor cells without affecting the mRNA transcription levels. Importantly, by introducing a uATG into the 5' untranslated region (UTR) of the Uox gene, we successfully established a Uox-knockdown (KD) mouse model of hyperuricemia associated with metabolic disorders. This model demonstrated hyperuricemia, with serum uric acid levels that exceeded 400 µmol L^-1, along with renal dysfunction, as indicated by elevated serum creatinine and blood urea nitrogen levels. Examination of the kidneys from 8-week-old Uox-KD mice revealed abnormal histopathological characteristics, including partial dilation of Bowman's capsules and renal tubules, focal nephron collapse and necrosis, and lymphocytic infiltration. In addition, the mice exhibited lipid and glucose metabolism disorders, all while maintaining a normal lifespan. This spontaneous hyperuricemia model has potential as a valuable tool for long-term studies on hyperuricemia and gout. Taken together, we present an efficient approach for the constant suppression of specific gene expression in mammalian cells and the development of a Uox-KD mouse model of hyperuricemia via CRISPR-Cas9-mediated uATG introduction. This offers broad implications for fundamental research and therapeutic applications.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1620-1633"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114193","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":"SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.","authors":"Di Wu, Xinhui Zhao, Yajing Pu, Qianwen Lu, Jiulei Shui, Yichu Chen, Kang Yang, Bangyi Yang, Gaoxiang Li, Hong Zhou, Meng Zhou","doi":"10.1007/s11427-025-3144-0","DOIUrl":"10.1007/s11427-025-3144-0","url":null,"abstract":"<p><p>Graft-versus-host disease (GVHD) remains a major challenge in successful allogeneic hematopoietic stem cell transplantation. Here, we report that inhibiting sphingosine kinase 1 (SPHK1), an enzyme that phosphorylates sphingosine to bioactive sphingosine-1-phosphate (S1P), effectively ameliorates acute GVHD (aGVHD) without compromising the graft-versus-leukemia effect. The absence of SPHK1 in the host exerts a beneficial effect on maintaining gut homeostasis by limiting intestinal epithelial cell (IEC) and intestinal stem cell (ISC) injury. This reduces gut permeability and prevents bacterial translocation, decreasing MHC II levels in IECs and donor T-cell infiltration. Persistent endoplasmic reticulum (ER) stress is observed during GVHD in the gastrointestinal tract and contributes to IEC injury. SPHK1 deficiency attenuates IEC damage by alleviating ER stress, which can be reversed by supplementation with exogenous S1P. FTY720, an S1P receptor antagonist, significantly inhibits ER stress-induced IEC injury. Our findings highlight the pathogenic role of host SPHK1 in gastrointestinal injury during aGVHD and suggest that targeting SPHK1 could be a therapeutic strategy for managing this condition.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1634-1649"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106994","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":"Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys.","authors":"Chunyu Liu, Chaofeng Tu, Peng Li, Huan Wu, Feng Wan, Yong Lu, Shuyan Tang, Xin Li, Kuokuo Li, Jiaxiong Wang, Yang Gao, Xinyan Geng, Lanlan Meng, Dapeng Zhou, Yiling Zhou, Zixue Zhou, Haibin Guo, Yunxia Cao, Li Jin, Zheng Li, Xiaojin He, Yue-Qiu Tan, Qiang Sun, Feng Zhang","doi":"10.1007/s11427-025-3186-2","DOIUrl":"10.1007/s11427-025-3186-2","url":null,"abstract":"<p><p>Primate-specific genes (PSGs), important contributors to the origin of adaptive evolutionary novelties, are abundantly expressed in the testis. However, the specific roles of PSGs in the male reproductive system of humans and other primates are largely unknown. Here, we employed whole-exome sequencing and identified deleterious variants of TFDP3, an X-linked PSG, in eight infertile men with oligoasthenoteratozoospermia. All of the male subjects harboring TFDP3 variants presented dramatic reductions in sperm concentration, motility, and abnormal sperm morphology. Furthermore, Tfdp3-knockdown (KD) in the testes of cynomolgus monkeys confirmed the important role of TFDP3 in normal spermatogenesis in primates. Consistently, dramatic decreases in sperm concentration, motility, and abnormal sperm morphology were also observed in Tfdp3-KD male cynomolgus monkeys. More importantly, further functional studies revealed that TFDP3 deficiency activated E2F1 induced apoptosis and thus led to decreased sperm count and motility. In addition, five of the eight couples underwent intra-cytoplasmic sperm injection treatment and achieved a successful pregnancy, indicating a potentially good outcome of assisted reproduction for those with TFDP3 deficiency-mediated oligoasthenoteratozoospermia. Collectively, our genetic analyses and experimental observations in humans and cynomolgus monkeys highlight the crucial role of TFDP3, an inhibitor of apoptosis, in normal spermatogenesis. These findings expand the spectrum of pathogenic variants for oligoasthenoteratozoospermia-associated male infertility and also reveal the special significance of primate-specific TFDP3 for the human male reproductive system, thus providing important guidance for genetic counseling and the clinical diagnosis of male infertility.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1594-1603"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114146","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":"Functional traits shape gut microbial assembly beyond phylogeny in estuarine fish.","authors":"Lei Zhou, Pengfei Wang, Chuanbo Guo, Tianxu Kuang, Xinye Chen, Jianjun Zuo, Jun Wang, Zelong Zhao, Xiaoyong Zhang","doi":"10.1007/s11427-025-3143-x","DOIUrl":"10.1007/s11427-025-3143-x","url":null,"abstract":"<p><p>Host-specific patterns of symbiotic microbiomes are ubiquitous in nature, yet the intricate interplay among host phylogeny, functional traits, and gut microbiota remains insufficiently explored and debated. In this study, the gut microbiota of 61 fish species inhabiting the sympatric Pearl River Estuary, China, was examined by integrating host phylogeny and functional traits to elucidate the mechanisms underlying microbiota assembly. While substantial interspecies differences in gut microbiota composition were evident, the influence of phylosymbiosis was minimal. Instead, functional traits emerged as pivotal mediators of gut microbiota differentiation, emphasizing their roles in adaptive and ecological functions, such as habitat preferences, feeding strategies, and digestive efficiencies. Clustering and machine learning analyses identified three distinct enterotypes within the fish gut microbiota strongly associated with feeding habits and migratory behaviors. Gut microbiota diverged among fishes differing in estuarine use, feeding strategies, and resilience traits. Functional profiling of the gut microbiota unveiled enterotype-specific metabolic adaptations, encompassing pathways related to nutrient utilization and stress resistance. Notably, redundancy analysis indicated that functional traits-such as eye size, oral gape shape, and gut length-played significant roles in influencing enterotype clustering. Our findings introduce the concept of \"functsymbiosis\", defined as the functional-trait-driven congruence between hosts and their symbiotic microbiota, indicating that host functional traits, rather than phylogenetic lineage, predominantly govern gut microbiota assembly. This study highlights the complex interactions between host traits and gut microbiota in fish, providing novel insights into the adaptive mechanisms underpinning host-microbiota dynamics and the ecological significance of gut microbiota in shaping host fitness and niche differentiation.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1738-1750"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373186","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":"Light-at-night exposure drives myopia via melanopsin signalling.","authors":"Jiaxin Li, Congying Li, Meijun Wang, Jianjun Meng, Jiajia Dang, Ying Huang, Di Shi, Xinyu Li, Shan Cai, Tianli Peng, Yunfei Liu, Yuting Kang, Tianyu Huang, Lipo Guo, Zhaocang Yu, Haihua Chen, Ningli Wang, Yi Song, Shi-Ming Li","doi":"10.1007/s11427-025-3255-8","DOIUrl":"10.1007/s11427-025-3255-8","url":null,"abstract":"<p><p>Myopia poses a growing global public health challenge, with its underlying mechanisms not yet fully understood. While insufficient daytime light exposure is a recognized protective factor, the role of nighttime light exposure remains contentious. Through a murine model, we uncover a novel melanopsin-dependent pathway by which light-at-night (LAN) exposure disrupts the expression of core circadian clock genes (including Arntl, Cry1, Per1, and Per2) and downregulates melanopsin expression in intrinsically photosensitive retinal ganglion cells (ipRGCs). These alterations are associated with axial elongation. Crucially, melanopsin-knockout mice exhibit resistance to myopic changes induced by LAN, indicating that melanopsin-dependent pathways mediate ocular growth responses. Supporting these experimental findings, our epidemiological analysis demonstrates that LAN exposure significantly increases the risk of incident myopia onset in humans. Together, these results establish a functional link between environmental light exposure and the molecular pathogenesis of myopia, identifying LAN as a modifiable risk factor for myopia. Our study provides important insights into the light-mediated myopia development and suggests melanopsin signaling as a potential target for preventive and therapeutic strategies.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1546-1561"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344905","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":"Dehydroepiandrosterone activates ADGRG2 to regulate chloride homeostasis and sperm motility via Gs-cAMP pathways.","authors":"Dan Jiang, Ji-Fei Han, Xian-Zheng Guo, Yu-Qi Ping, Fan Yang, Peng Xiao, Jin-Peng Sun, Xiao Yu, Zhao Yang, Hui Lin","doi":"10.1007/s11427-025-3122-7","DOIUrl":"10.1007/s11427-025-3122-7","url":null,"abstract":"<p><p>Dehydroepiandrosterone (DHEA), a steroid hormone critical to reproductive health, is widely used to improve outcomes in assisted reproductive technologies, though its molecular targets and mechanisms remain incompletely defined. In our previous studies, we identified DHEA as a ligand for the male reproductive-related receptor ADGRG2 and elucidated the recognition mechanism between DHEA and ADGRG2 using Cryo-EM structure of ADGRG2 in complex with DHEA and Gs. However, it remains unclear whether DHEA acts as a physiological ligand for ADGRG2 to regulate its functions. Using ADGRG2-deficient mice and in vitro reconstitution assays, we demonstrated that DHEA activated the Gs signaling pathways of ADGRG2 in efferent ductal cells, which facilitated synergistic coupling with cystic fibrosis transmembrane conduction regulator (CFTR) to regulate chlorine homeostasis. Strikingly, ADGRG2 is selectively expressed in X chromosome-bearing (X) sperm, where DHEA enhances motility via a Gs-cAMP signaling axis. This functional bias enables efficient enrichment of X sperm through DHEA-induced motility enhancement, achieving 80.5% XX embryos in in vitro fertilization (IVF). These findings reveal ADGRG2-dependent mechanisms underlying male reproductive physiology and position DHEA-ADGRG2 axis as a promising therapeutic target for precision management of infertility and sex-controlled reproductive technologies.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1650-1661"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133079","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":"Condensed matter biology: from phase separation to percolated network.","authors":"Wen Jia, Pilong Li","doi":"10.1007/s11427-025-3151-0","DOIUrl":"10.1007/s11427-025-3151-0","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1807-1809"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857650","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":"Engineering probiotics as living biotherapeutics: a novel paradigm of restoring physiological barriers via targeted short-chain fatty acid delivery.","authors":"Guangbo Kang, Biao Zhang, Jiahao Wu, Lina Wang, He Huang","doi":"10.1007/s11427-025-3185-y","DOIUrl":"10.1007/s11427-025-3185-y","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1789-1792"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846731","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":"Repositioning ACLY in liver cancer: from metabolic enzyme to a regulator of antitumor immunity.","authors":"Shuhan Zhao, Jing Tang, Jun Xue","doi":"10.1007/s11427-025-3179-x","DOIUrl":"10.1007/s11427-025-3179-x","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"1817-1819"},"PeriodicalIF":9.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146066391","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}