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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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    Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A2 receptors

    Yuan WengXinyu YangQiansen ZhangYing Chen...
    986-995页
    查看更多>>摘要：The adenosine subfamily G protein-coupled receptors A2AR and A2BR have been identified as promising cancer immunotherapy candidates.One of the A2AR/A2BR dual antagonists,AB928,has progressed to a phase Ⅱ clinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A2AR complexed with AB928 and a selective A2AR antagonist 2-118.The structures revealed a common binding mode on A2AR,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A2AR and A2BR molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A2BR.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A2BR pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A2BR and A2AR.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A2AR/A2BR for cancer therapy.
      原文链接:
    • 万方数据

    Hemin blocks TIGIT/PVR interaction and induces ferroptosis to elicit synergistic effects of cancer immunotherapy

    Xiaowen ZhouYang LiXiangrui ZhangBeibei Li...
    996-1009页
    查看更多>>摘要：The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8+T cell-mediated cytotoxicity.Immune checkpoint blockade(ICB)could induce tumor ferroptosis through IFN-γ released by immune cells,indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth.However,the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet.In this study,the small molecule Hemin that could bind with TIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay.Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells.Hemin reinvigorated the function of CD8+T cells to secrete IFN-γ and the elevated IFN-γ could synergize with Hemin to induce ferroptosis in tumor cells.Hemin inhibited tumor growth by boosting CD8+T cell immune response and inducing ferroptosis in CT26 tumor model.More importantly,Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model.In summary,our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell fer-roptosis,which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.
      原文链接:
    • 万方数据
    • 维普

    Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

    Ziyue QinYanxing HanYifei DuYixuan Zhang...
    1010-1026页
    查看更多>>摘要：Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this process.Berberine(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic disorders.In this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone loss.CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro.To clarify the underlying mechanism,the bioactive materials were applied to different animal models.We discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the CS.Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats.Colony-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated HBMSCs.Moreover,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab.These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis.Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets.Overall,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.
      原文链接:
    • 万方数据
    • 维普

    Hi-Tag:a simple and efficient method for identifying protein-mediated long-range chromatin interactions with low cell numbers

    Xiaolong QiLu ZhangQiulin ZhaoPeng Zhou...
    1027-1034页
    查看更多>>摘要：Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation.However,these techniques require complex experimental procedures and millions of cells per experiment,which limits their widespread application in life science research.Here,we develop a novel method,Hi-Tag,that identifies high-resolution,long-range chromatin inter-actions through transposase tagmentation and chromatin proximity ligation(with a phosphorothioate-modified linker).Hi-Tag can be implemented using as few as 100,000 cells,involving simple experimental procedures that can be completed within 1.5 days.Meanwhile,Hi-Tag is capable of using its own data to identify the binding sites of specific proteins,based on which,it can acquire accurate interaction information.Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies,particularly in the context of limited cell availability.
      原文链接:
    • 万方数据
    • 维普

    Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

    Yaling WangJingwen ChenXueying HuangBangguo Wu...
    1035-1050页
    查看更多>>摘要：Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced mosaicism.iSTOP enables direct phenotyping in founders'somatic cells,but it remains unknown whether this works in founders'germ cells so as to rapidly reveal novel genes for fertility.Here,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders'germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human"multiple morphological abnormalities of the flagella"syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona pellucida.We further illustrate iSTOP's utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO offspring.We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport.Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.
      原文链接:
    • 万方数据
    • 维普

    Base editor-mediated large-scale screening of functional mutations in bacteria for industrial phenotypes

    Yaomeng YuanXihao LiaoShuang LiXin-Hui Xing...
    1051-1060页
    查看更多>>摘要：Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.
      原文链接:
    • 万方数据
    • 维普

    Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up

    Zhibo ZhangJianbin GuoWeijie TianYe Zhang...
    1061-1068页
    查看更多>>摘要：Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great im-portance globally.However,reports with follow-up＞10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stage Ⅲ-Ⅳ symptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1％)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6％and 8.8％in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2％between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7％.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3％to 28.4％from 5 to 11 years,respectively.Office trimming resolved 80.0％of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring＞3 office procedures or mesh removal in the operating room(5.8％by 11 years)had lower satisfaction rates(P＜0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement ≥2 were 2.5％,3.3％,and 94.2％,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80％of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.
      原文链接:
    • 万方数据
    • 维普

    Interplant communication:an emerging battlefield in plant-aphid-virus interactions

    Yunjing WangQian GongYule Liu
    1069-1071页
      原文链接:
    • 万方数据
    • 维普

    Artificial selection shapes the lower genomic diversity and higher selective pressures on the sex chromosomes of domestic animals

    Meiming WuDongfeng WangMeng-Hua LiFenghua Lv...
    1072-1075页
      原文链接:
    • 万方数据
    • 维普

    Chemical defense mediates population density-driven on anuran brain size evolution

    Ying JiangLianju YuanWenbo Liao
    1076-1078页
      原文链接:
    • 万方数据
    • 维普