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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）

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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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    Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

    Chengcheng SongYingying QinYan LiBingyi Yang...
    1325-1337页
    查看更多>>摘要：Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78％of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111+/-).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
      原文链接:
    • 万方数据
    • 维普

    Plant regeneration in the new era:from molecular mechanisms to biotechnology applications

    Chunli ChenYuxin HuMomoko IkeuchiYuling Jiao...
    1338-1367页
    查看更多>>摘要：Plants or tissues can be regenerated through various pathways.Like animal regeneration,cell totipotency and pluripotency are the molecular basis of plant regeneration.Detailed systematic studies on Arabidopsis thaliana gradually unravel the fundamental mechanisms and principles underlying plant regeneration.Specifically,plant hormones,cell division,epigenetic remodeling,and transcription factors play crucial roles in reprogramming somatic cells and reestablishing meristematic cells.Recent research on basal non-vascular plants and monocot crops has revealed that plant regeneration differs among species,with various plant species using distinct mechanisms and displaying significant differences in regenerative capacity.Conducting multi-omics studies at the single-cell level,tracking plant re-generation processes in real-time,and deciphering the natural variation in regenerative capacity will ultimately help understand the essence of plant regeneration,improve crop regeneration efficiency,and contribute to future crop design.
      原文链接:
    • 万方数据
    • 维普

    Advances in environmental DNA monitoring:standardization,automation,and emerging technologies in aquatic ecosystems

    Suxiang LuHonghui ZengFan XiongMeng Yao...
    1368-1384页
    查看更多>>摘要：Environmental DNA(eDNA)monitoring,a rapidly advancing technique for assessing biodiversity and ecosystem health,offers a non-invasive approach for detecting and quantifying species from various environmental samples.In this review,a comprehensive overview of current eDNA collection and detection technologies is provided,emphasizing the necessity for standardization and automation in aquatic ecological monitoring.Furthermore,the intricacies of water bodies,from streams to the deep sea,and the associated challenges they pose for eDNA capture and analysis are explored.The paper delineates three primary eDNA survey methods,namely,bringing back water,bringing back filters,and bringing back data,each with specific advantages and constraints in terms of labor,transport,and data acqui-sition.Additionally,innovations in eDNA sampling equipment,including autonomous drones,subsurface samplers,and in-situ filtration devices,and their applications in monitoring diverse taxa are discussed.Moreover,recent advancements in species-specific detection and eDNA metabarcoding are addressed,highlighting the integration of novel techniques such as CRISPR-Cas and nanopore sequencing that enable precise and rapid detection of biodiversity.The implications of environmental RNA and epigenetic modifications are considered for future applications in providing nuanced ecological data.Lastly,the review stresses the critical role of standardization and automation in enhancing data consistency and comparability for robust long-term biomonitoring.We propose that the amalgamation of these technologies represents a paradigm shift in ecological monitoring,aligning with the urgent call for biodiversity conservation and sustainable manage-ment of aquatic ecosystems.
      原文链接:
    • 万方数据
    • 维普

    A phase separation-fortified bi-specific adaptor for conditional tumor killing

    Yuyan LiuYuting ZhuWeifan XuPilong Li...
    1385-1397页
    查看更多>>摘要：A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal transduction.Leveraging the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor cells.Despite their simplicity,these"triggers",named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPS-mediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor cells.The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction.This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.
      原文链接:
    • 万方数据
    • 维普

    Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy

    Shuxiang WangHongmei CaoCui-Cui ZhaoQian Wang...
    1398-1412页
    查看更多>>摘要：Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist radiotherapy.Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy.Therefore,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O2)and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced radiotherapy.After administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O2 and Pt(Ⅳ).O2 introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress.Moreover,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments.Consequently,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7％.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.
      原文链接:
    • 万方数据
    • 维普

    Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance

    Xueyan ChenWeilin WuJi-Hak JeongMatjaz Rokavec...
    1413-1426页
    查看更多>>摘要：Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive(ER+)breast cancer.However,the efficacy of agents such as tamoxifen(Tam)is often compromised by the development of resistance.Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER+breast cancer by inducing the expression of FAT10,and that the expression of FAT10 and nuclear IKKα in primary ER+human breast cancer was correlated with lymphotoxin β(LTB)expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam.IKKα activation or enforced FAT10 expression pro-motes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity.The induction of FAT10 by IKKα is mediated by the tran-scription factor Pax5,and coordinated via an KKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10.Thus,our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER+breast cancer.
      原文链接:
    • 万方数据
    • 维普

    Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

    Hongfeng GuoQihang SunXiaoli HuangXiaohao Wang...
    1427-1440页
    查看更多>>摘要：Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of aNSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrin a6(Itga6),an upstream regulator of the PI3k-Akt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.
      原文链接:
    • 万方数据
    • 维普

    The key role of myostatin b in somatic growth in fishes derived from distant hybridization

    Qingfeng LiuLujiao DuanBei LiXuanyi Zhang...
    1441-1454页
    查看更多>>摘要：The basic mechanism of heterosis has not been systematically and completely characterized.In previous studies,we obtained three eco-nomically important fishes that exhibit rapid growth,WR(WCC ♀ × RCC ♂),WR-Ⅱ(WR ♀ × WCC ♂),and WR-Ⅲ(WR-Ⅱ ♀ × 4nAU ♂),through distant hybridization.However,the mechanism underlying this rapid growth remains unclear.In this study,we found that WR,WR-Ⅱ,and WR-Ⅲ showed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species(RCC and WCC).Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes.Notably,the mRNA level of mstnb(myostatin b),which is a negative regulator of myogenesis,was significantly reduced in WR,WR-Ⅱ,and WR-Ⅲcompared with the parent species.To verify the function of mstnb,a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique.The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57％compared with that in wild-type siblings.Moreover,the area and number of muscle fibers were significantly increased in mstnb-deficient RCC,indicating hypertrophy and hyperplasia.Furthermore,the muscle protein and fat contents were significantly increased in mstnb-deficient RCC.The molecular regulatory mechanism of mstnb was then revealed by transcription profiling,which showed that genes related to myogenesis(myod,myog,and myfi),protein synthesis(PI3K-AKT-mTOR),and lipogenesis(pparγ and fabp3)were highly activated in hybrid fishes and mstnb-deficient RCC.This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis,protein synthesis,and lipogenesis in hybrid fishes and mstnb-deficient RCC,which provides evidence for the molecular mechanism of heterosis via distant hybridization.
      原文链接:
    • 万方数据
    • 维普

    Two sex pheromone receptors for sexual communication in the American cockroach

    Na LiRenke DongHuanchao ZengYan Zhang...
    1455-1467页
    查看更多>>摘要：Volatile sex pheromones are vital for sexual communication between males and females.Females of the American cockroach,Periplaneta americana,produce and emit two sex pheromone components,periplanone-A(PA)and periplanone-B(PB).Although PB is the major sex attractant and can attract males,how it interacts with PA in regulating sexual behaviors is still unknown.In this study,we found that in male cockroaches,PA counteracted PB attraction.We identified two odorant receptors(0Rs),0R53 and 0R100,as PB/PA and PA receptors,respectively.OR53 and 0R100 were predominantly expressed in the antennae of sexually mature males,and their expression levels were regulated by the sex differentiation pathway and nutrition-responsive signals.Cellular localization of OR53 and OR100 in male antennae further revealed that two types of sensilla coordinate a complex two-pheromone-two-receptor pathway in regulating cockroach sexual behaviors.These findings indicate distinct functions of the two sex pheromone components,identify their receptors and possible regulatory mechanisms underlying the male-specific and age-dependent sexual behaviors,and can guide novel strategies for pest management.
      原文链接:
    • 万方数据
    • 维普

    AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken

    Jiang DengJia-Cheng YangYue FengZe-Jing Xu...
    1468-1478页
    查看更多>>摘要：Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic animals.The hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide(AFBO)in chicks.However,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown.Dual-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1(SP1)and activator protein-1(AP-1)motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 promoter.Furthermore,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6.Moreover,bioactivation of AFBi to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregu-lation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen species.Additionally,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of AFB1.In conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.
      原文链接:
    • 万方数据
    • 维普