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中国科学:生命科学（英文版）
中国科学:生命科学（英文版）

周光召

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中国科学:生命科学（英文版）/Journal Science China(Life Sciences)CSCDCSTPCDSCI
查看更多>>《中国科学》是中国科学院主办、中国科学杂志社出版的自然科学专业性学术刊物。《中国科学》任务是反映中国自然科学各学科中的最新科研成果，以促进国内外的学术交流。《中国科学》以论文形式报道中国基础研究和应用研究方面具有创造性的、高水平的和有重要意义的科研成果。在国际学术界，《中国科学》作为代表中国最高水平的学术刊物也受到高度重视。国际上最具有权威的检索刊物SCI，多年来一直收录《中国科学》的论文。1999年《中国科学》夺得国家期刊奖的第一名。
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    The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

    Peidong ZhangPeiwei LiMuya TangRyan C.Gimple...
    1549-1562页
    查看更多>>摘要：Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogramming.However,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched.Herein,we sys-tematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)databases.All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes.Each subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical outcome.We further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents.Collectively,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.
      原文链接:
    • 万方数据
    • 维普

    CD146,a therapeutic target involved in cell plasticity

    Zhenzhen WuYuzhe ZangChuyi LiZhiheng He...
    1563-1578页
    查看更多>>摘要：Since its identification as a marker for advanced melanoma in the 1980s,CD146 has been found to have multiple functions in both physiological and pathological processes,including embryonic development,tissue repair and regeneration,tumor progression,fibrosis disease,and inflammations.Subsequent research has revealed that CD146 is involved in various signaling pathways as a receptor or co-receptor in these processes.This correlation between CD146 and multiple diseases has sparked interest in its potential applications in diagnosis,prognosis,and targeted therapy.To better comprehend the versatile roles of CD146,we have summarized its research history and synthesized findings from numerous reports,proposing that cell plasticity serves as the underlying mechanism through which CD146 contributes to development,regeneration,and various diseases.Targeting CD146 would consequently halt cell state shifting during the onset and progression of these related diseases.Therefore,the development of therapy targeting CD 146 holds significant practical value.
      原文链接:
    • 万方数据
    • 维普

    Computational tools for plant genomics and breeding

    Hai WangMengjiao ChenXin WeiRui Xia...
    1579-1590页
    查看更多>>摘要：Plant genomics and crop breeding are at the intersection of biotechnology and information technology.Driven by a combination of high-throughput sequencing,molecular biology and data science,great advances have been made in omics technologies at every step along the central dogma,especially in genome assembling,genome annotation,epigenomic profiling,and transcriptome profiling.These advances further revolutionized three directions of development.One is genetic dissection of complex traits in crops,along with genomic prediction and selection.The second is comparative genomics and evolution,which open up new opportunities to depict the evolutionary constraints of biological sequences for deleterious variant discovery.The third direction is the development of deep learning approaches for the rational design of biological sequences,especially proteins,for synthetic biology.All three directions of development serve as the foundation for a new era of crop breeding where agronomic traits are enhanced by genome design.
      原文链接:
    • 万方数据
    • 维普

    Genetic regulation of m6A RNA methylation and its contribution in human complex diseases

    Kexuan ChenJiuhong NanXushen Xiong
    1591-1600页
    查看更多>>摘要：N6-methyladenosine(m6A)has been established as the most prevalent chemical modification in message RNA(mRNA),playing an essential role in determining the fate of RNA molecules.Dysregulation of m6A has been revealed to lead to abnormal physiological conditions and cause various types of human diseases.Recent studies have delineated the genetic regulatory maps for m6A methylation by mapping the quantitative trait loci of m6A(m6A-QTLs),thereby building up the regulatory circuits linking genetic variants,m6A,and human complex traits.Here,we review the recent discoveries concerning the genetic regulatory maps of m6A,describing the methodological and technical details of m6A-QTL identification,and introducing the key findings of the cis-and trans-acting drivers of m6A.We further delve into the tissue-and ethnicity-specificity of m6A-QTL,the association with other molecular phenotypes in light of genetic regulation,the regulators underlying m6A genetics,and importantly,the functional roles of m6A in mediating human complex diseases.Lastly,we discuss potential research avenues that can accelerate the translation of m6A genetics studies toward the development of therapies for human genetic diseases.
      原文链接:
    • 万方数据

    LncRNA CCRR maintains Ca2+homeostasis against myocardial infarction through the FTO-SERCA2a pathway

    Hua YangLina XuanShengjie WangHuishan Luo...
    1601-1619页
    查看更多>>摘要：Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic IncRNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR over-expressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca2+overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective IncRNA that acts by maintaining the function of FTO,thereby reducing the m6A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.
      原文链接:
    • 万方数据

    DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation

    Yunde DouRusong ZhaoHan WuZhiheng Yu...
    1620-1634页
    查看更多>>摘要：Polycystic ovary syndrome(PCOS)is a complex disorder.Genome-wide association studies(GWAS)have identified several genes associated with this condition,including DENND1A.DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport.However,the specific role of DENND1A in reproductive hormone abnormalities and follicle devel-opment disorders in PCOS remain poorly understood.In this study,we investigated DENND1A expression in ovarian granulosa cells(GCs)from PCOS patients and its correlation with hormones.Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases,which was positively correlated with testosterone levels.To further explore the functional implications of DENND1A,we generated a transgenic mouse model overexpressing Dennd1a(TG mice).These TG mice exhibited subfertility,irregular estrous cycles,and increased testosterone production following PMSG stimulation.Additionally,the TG mice displayed diminished responsiveness to FSH,characterized by smaller ovary size,less well-developed follicles,and abnormal expressions of FSH-priming genes.Mechanistically,we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor(FSHR),promoting its internalization and inhibiting recycling.These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms,thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.
      原文链接:
    • 万方数据
    • 维普

    High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

    Feng-Qi LiuQing-Yuan QuYing LeiQi Chen...
    1635-1647页
    查看更多>>摘要：To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upre-gulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th1 7 cell subsets.Taking a platelet count of 30×109 L-1 as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.
      原文链接:
    • 万方数据
    • 维普

    Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

    Jie GaoXiaoyi ShiYaohui SunXudong Liu...
    1648-1665页
    查看更多>>摘要：Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored.Here,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 patients.BHMT was to be frequently found(86.6％)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC.Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt-/-)produced the opposite effect.We combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt-/-promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models.In contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis.Additionally,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of G6PD.Protein sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246.Furthermore,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed hepatocarcinogenesis.Taken to-gether,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.
      原文链接:
    • 万方数据
    • 维普

    Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease:A dietary salt-intervention trial

    Zhennan LinJianxin LiFangchao LiuJie Cao...
    1666-1675页
    查看更多>>摘要：Individuals with a high degree of salt sensitivity(SS)have a greater risk of cardiovascular disease(CVD),but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear.This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs,based on the MetaSalt study,which was a dietary salt-intervention trial conducted at four centers in China in 2019.A total of 528 participants were recruited and underwent 3 days of baseline observations,a 10-day low-salt intervention,and a 10-day high-salt intervention.Plasma untargeted metabolomics,lipidomics,and BP measurements were scheduled at each stage.Participants were grouped into extreme SS,moderate SS,and salt-resistant(SR)individuals according to their BP responses to salt.Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness.Mendelian randomization(MR)analyses were applied to establish the causal pathways among the SS-related metabolites,BP,and CVDs.Among the 713 metabolites,467 were significantly changed after the high-salt intervention.Among them,the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups.Of the remaining nonsalt-related metabolites,the baseline levels of 11 metabolites were related to SS.These 41 metabolites explained 23％of the variance in SS.Moreover,SS and its metabolomics signature were positively correlated with arterial stiffness.MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP,indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause.Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs.This study provides insight into understanding the biology and targets of SS and its role in CVDs.
      原文链接:
    • 万方数据
    • 维普

    Dynamic intrauterine crosstalk promotes porcine embryo implantation during early pregnancy

    Xupeng ZangShengchen GuWenjing WangJunsong Shi...
    1676-1696页
    查看更多>>摘要：Dynamic crosstalk between the embryo and mother is crucial during implantation.Here,we comprehensively profile the single-cell tran-scriptome of pig peri-implantation embryos and corresponding maternal endometrium,identifying 4 different lineages in embryos and 13 cell types in the endometrium.Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations,showing development from undifferentiated trophectoderm to polar and mural trophectoderm.Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation.Then,we developed a novel tool,ExtraCellTalk,generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges.Through cross-species comparisons,we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells.These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.
      原文链接:
    • 万方数据
    • 维普