Science China Life Sciences最新文献

{"title":"Nusap-dependent inhibition of Separase in meiosis.","authors":"Si-Min Sun, Xue-Mei Yang, Jia-Ni Guo, Jing-Yi Qiao, Liu Zhu, Yi-Ke Lu, Yuan-Hong Xu, Bing-Wang Zhao, Catherine C L Wong, Zhen-Bo Wang","doi":"10.1007/s11427-025-3375-1","DOIUrl":"https://doi.org/10.1007/s11427-025-3375-1","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897661","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":"T2T and chromosome-level genome assemblies provide insights into the genetic basis of bioactive compound biosynthesis and environmental adaptation in licorice.","authors":"Shandang Shi, Fei Wang, Tianxin Lu, Guozhi Li, Mengqian Long, Chao Jiang, Rui Tang, Shiyan Cui, Wei Wang, Hua Yao, Xuechi Li, Meng Meng, Jianting Feng, Xifeng Chen, Quanliang Xie, Zhuang Meng, Xiang Jin, Haitao Shen, Hongbin Li","doi":"10.1007/s11427-025-3304-2","DOIUrl":"https://doi.org/10.1007/s11427-025-3304-2","url":null,"abstract":"<p><p>Licorice is an important medicinal herb worldwide, including three Chinese Pharmacopoeia species (Glycyrrhiza uralensis, G. inflata, G. glabra), with bioactive compounds crucial for disease treatment and industrial applications. However, the genetic mechanisms underlying the biosynthesis, diversification, and environmental adaptation of bioactive compounds in Glycyrrhiza species have long remained unclear. Herein, we assembled a gapless telomere-to-telomere (T2T) genome of G. uralensis with resolved telomeres and centromeres and three significantly improved high-quality chromosome-level Glycyrrhiza genomes, alongside a variation map of 188 wild accessions. Population analysis revealed evolutionary divergence among species, with selection signals linked to medicinal compound pathways. We identified 4CL5 as a key gene for stress response and compound synthesis. GWAS validation highlighted the GiPHL1-Gi4CL5 module's role in licochalcone A accumulation and enhanced stress adaptation in G. inflata. This study provides the first T2T Glycyrrhiza genome and insights into medicinal compound biosynthesis and environmental adaptation.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897664","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":"Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.","authors":"Yuhui Zheng, Ze-Hui Ren, Yafei Yang, Wenteng Liu, Fupeng Li, Yajun Zuo, Tao Zeng, Xue Wang, Xiumei Lin, Xinyue Zhu, Baibing Guan, Wenwen Zhou, Yunting Huang, Wangsheng Li, Yu Feng, Xiao Yang, Xin Liu, Xin Jin, Hanjie Li, Ying Ting Sit, Chang Liu, Hongling Zhou, Yuliang Dong, Xiangliang Yang, Xun Xu, Jun Pu, Jianhua Yin, Chuanyu Liu","doi":"10.1007/s11427-025-3398-8","DOIUrl":"https://doi.org/10.1007/s11427-025-3398-8","url":null,"abstract":"<p><p>Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4⁺ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897701","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":"A species-specific protein corona determines osteogenic fate of multi-walled carbon nanotubes by modulating macrophage polarization.","authors":"Yu Wang, Jiangfei Xiao, Luhan Chang, Ying Wang, Wenjia Liu, Jinchao Zhang, Kun Ge, Guoqiang Zhou","doi":"10.1007/s11427-025-3290-4","DOIUrl":"https://doi.org/10.1007/s11427-025-3290-4","url":null,"abstract":"<p><p>Multi-walled carbon nanotubes (MWCNTs) have emerged as promising candidates for bone tissue engineering due to their excellent biocompatibility, mechanical strength, and chemical stability. However, disparities often exist between their osteogenic performance in vitro and in vivo. The formation of protein corona on biomaterials is a key factor that may govern these biological outcomes. This study investigated how the distinct protein corona compositions in mouse serum (MS) and fetal bovine serum (FBS) modulate the immune recognition and osteogenic capacity of MWCNTs, thereby mimicking in vitro and in vivo environments, respectively. It was demonstrated that the MS-derived corona complexes, enriched with immunoreactive proteins such as complement 3, potently induced a pro-inflammatory M1 response via recognizable immune signals in both Raw264.7 cells and a mouse calvarial defect model. In contrast, FBS-derived corona complexes lacked murine-specific \"alarm signals\", thereby attenuating reactive oxygen species generation and polarizing macrophages toward M2 phenotype both in vitro and in vivo. Consequently, the MS-derived corona conferred no significant osteogenic effect, whereas the FBS-derived corona markedly enhanced osteogenic differentiation. We propose that the FBS corona acts as a physical barrier, preventing subsequent adsorption of host alarm signals onto MWCNTs, thereby suppressing immunogenicity and enhancing osteogenesis. These findings highlight a critical limitation of using FBS in conventional in vitro models for predicting in vivo immune responses, and underscore the decisive role of species-specific immune recognition in determining the osteogenic fate of biomaterials.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897597","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":"Broad-spectrum chemical defense by phytoalexins: from pathway elucidation to metabolic organization.","authors":"Guoyi Yang, Le Mi, Shanshan Zhao, Jianguo Wu","doi":"10.1007/s11427-026-3451-3","DOIUrl":"https://doi.org/10.1007/s11427-026-3451-3","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876132","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":"CD22⁺-apoptotic vesicles from cardiac fibroblasts provide endogenous cardioprotection against myocardial ischemia-reperfusion injury.","authors":"Chan Zhang, Hao Hao, Nan Mu, Yishi Wang, Yin Yue, Lu Yu, Heng Ma","doi":"10.1007/s11427-025-3251-7","DOIUrl":"https://doi.org/10.1007/s11427-025-3251-7","url":null,"abstract":"<p><p>Apoptotic vesicles (ApoVs) facilitate intercellular communication. Cardiac fibroblasts (CFbs) undergo apoptosis during myocardial ischemia-reperfusion (MI/R), but their ApoVs' role in cardiomyocyte survival is unknown. Here, CFbs-ApoVs were isolated from fibroblast conditioned medium (FCM). Transmission electron microscopy, nanoparticle tracking analysis, and protein blotting were used to characterize the properties of CFbs-ApoVs. Bioinformatics screening and experimental validation identified the molecular markers of CFbs-ApoVs. Enriched CFbs-ApoVs were explored in their effects and mechanisms on cardiomyocytes in vitro and in vivo. This study identified and characterized the apoptotic CFbs-derived ApoVs subtypes: CD22⁺-CFbs-ApoVs. The results showed that CD22⁺-CFbs-ApoVs were efficiently homed to cardiomyocytes. Mechanistically, miR-1246, which is enriched in CD22⁺-CFbs-ApoVs, effectively inhibits p53 protein expression and the translocation of p53 from the nucleus to mitochondria in MI/R-injured cardiomyocytes, rescues mitochondrial damage, and suppresses cardiomyocyte apoptosis. Overexpression of miR-1246 or inhibition of p53 enhanced the protective effect of CD22⁺-CFbs-ApoVs on injured cardiomyocytes. We found that CD22⁺-CFbs-ApoVs are effective endogenous cardioprotective vectors that can target cardiomyocytes for fusion, and we also revealed the dual inhibitory effect on p53 mediated by miR-1246. This study revealed a previously unidentified cell-to-cell communication mechanism of apoptotic CFbs that serves to promote cardiomyocyte survival during MI/R, and it also implies the potential use of ApoVs for combating MI/R injury.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857287","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":"METTL18-catalyzed histidine methylation of YTHDF2 promotes mRNA stability.","authors":"Wen-Lan Yang, Meng-Xia Liu, Yue Han, Xing-Xing Li, Ye Gu, Xinyuan Tian, Mengqian Mu, Xiaolin Zhang, Yanzhe Wang, Xinyu Li, Yu-Sheng Chen, Chun-Chun Gao, Weiyi Lai, Ang Li, Jiazhi Li, Yajing Hao, Hailin Wang, Yong-Liang Zhao, Yun-Gui Yang, Ying Yang","doi":"10.1007/s11427-025-3420-3","DOIUrl":"https://doi.org/10.1007/s11427-025-3420-3","url":null,"abstract":"<p><p>RNA N⁶-methyladenosine (m⁶A), as the most prevalent and abundant RNA modification on mRNAs, plays indispensable roles in biological processes and development by modulating the fate of target RNAs. However, whether other METTL proteins, besides dominant METTL3 and METTL14, participate in the intricate dynamic regulation of mRNA m⁶A remains elusive. Here, we reveal that METTL18 catalyzes the methylation of histidine within the YTHDF2 protein, which in turn facilitates the stability of m⁶A-modified RNAs. Mechanistically, METTL18 directly interacts with YTHDF2 and catalyzes the methylation of histidine at position 437 of YTHDF2, attenuating its binding to m⁶A-modified target RNAs, thereby safeguarding these RNAs from degradation. Our findings not only demonstrate the crucial roles of METTL family proteins but also deepen our understanding of the intricate regulatory dynamics of m⁶A modification.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857627","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":"Respiratory viral sepsis: rethinking fluid resuscitation and antibiotic stewardship.","authors":"Dong Liu, Mengwei Yan, Di He, Zai Wang, Yeming Wang, Bin Cao","doi":"10.1007/s11427-026-3496-6","DOIUrl":"https://doi.org/10.1007/s11427-026-3496-6","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857645","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":"Autoimmune disease patients with comorbid cancer exhibit prominent immunometabolic crosstalk.","authors":"Xu Jiang, Yangzhige He, Naixin Liang, Xiangyi Shen, Ziyue Zhou, Dan Yang, Jiana Chen, Jiaqi Xu, Mengyuan Wang, Yiyi Gong, Xiaoyan Si, Li Zhang, Lidan Zhao, Yunyun Fei, Fengchun Zhang, Mengtao Li, Huaxia Yang","doi":"10.1007/s11427-026-3465-2","DOIUrl":"https://doi.org/10.1007/s11427-026-3465-2","url":null,"abstract":"<p><p>Patients with autoimmune diseases (AIDs) are at an increased risk of developing cancer; however, the immunometabolic programs that shape this comorbidity remain incompletely defined. We integrated targeted serum metabolomics with multiplex profiling of cytokines, chemokines, and immune checkpoint proteins in patients with five major AIDs-idiopathic inflammatory myopathies, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis-with or without cancer. A total of 49 patients with AID and comorbid cancer (AID-CA), 47 patients with AID alone, and 15 healthy controls were enrolled. Compared with AID alone, AID-CA was associated with coordinated remodeling of amino acid and nucleotide metabolism, dominated by the alanine, aspartate, and glutamate pathways. Decreased L-glutamine and increased L-glutamic acid levels were consistently observed and remained significant after the false discovery rate correction. Immune profiling revealed modest but consistent differences, including higher levels of CXCL9 and Galectin-9 and lower levels of selected checkpoint molecules in AID-CA. The effects of major metabolites and immune mediators were directionally stable after adjusting for age, sex, treatment exposure, and autoimmune disease subtype. Integrative analyses revealed stronger associations between metabolites and immune mediators in AID-CA, centered on CXCL9 and Galectin-9, and linked to amino acid and pyrimidine metabolism. In ex vivo assays, perturbation of glutamine or arginine availability preferentially modulated the release of CXCL9 and Galectin-9 from peripheral blood mononuclear cells of patients with AID-CA. Together, these findings define an internally consistent immunometabolic pattern associated with cancer comorbidities in patients with AIDs. They nominated amino acid metabolism and CXCL9/Galectin-9-centered immune signaling as candidates for mechanistic investigation and biomarker development, while underscoring the need for validation in larger, longitudinal, and disease-specific cohorts.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857301","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":"IFITM1 enhances anti-tumor function of unconventional TCRαβ double negative T cells by upregulating mitophagy.","authors":"Xiaotong Han, Xiaonan Du, Longyang Zhou, Zihan Zhang, Jingjing Zhu, Xiyu Wang, Yuan Jiang, Jie Sun, Yue Tian, Songlin Wang, Zhongtao Zhang, Guangyong Sun, Dong Zhang","doi":"10.1007/s11427-025-3424-5","DOIUrl":"https://doi.org/10.1007/s11427-025-3424-5","url":null,"abstract":"<p><p>Unconventional TCRαβ⁺ CD4^-CD8^- double negative T cells (DNT) can effectively impede the progression of leukemia, lymphoma, and solid tumors, highlighting their potential as a novel and effective cell therapy approach for cancer. However, the intrinsic mechanisms regulating DNT homeostasis and anti-tumor functions remain unclear. In this study, we discovered that DNT highly expressed IFITM1 (interferon-induced transmembrane protein 1) and further demonstrated that IFITM1 actively regulated the anti-tumor function of DNT both in vitro and in vivo. Furthermore, our investigation revealed that IFITM1⁺ DNT exhibited elevated expression of key molecules involved in immune cell-mediated anti-tumor responses, such as perforin, granzyme B, and NKG2D. Overexpression of IFITM1 promoted DNT anti-tumor activity. Notably, IFITM1 regulated mitophagy, which contributed to the improved mitochondrial function in DNT. Mechanistically, IFITM1 in the mitochondria of DNT interacts with the autophagosomal cargo protein p62/SQSTM1, recruiting more p62/SQSTM1 to the mitochondria, thereby promoting mitophagy. It is worth noting that IFITM1 is also highly expressed in activated human DNT (hDNT), and its regulatory effect on DNT mitophagy, homeostasis, and anti-tumor function has been validated. In conclusion, IFITM1 has emerged as a crucial player in enhancing DNT-mediated anti-tumor activity by regulating mitophagy and mitochondrial function. These findings suggested that upregulating IFITM1 expression in DNT may enhance mitophagy and promote DNT survival and cytotoxic functions, ultimately providing better control over cancer.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857610","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}