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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 light and hypoxia induced gene ZmPORB1 determines tocopherol content in the maize kernel

    Nannan LiuYuanhao DuShijuan YanWei Chen...
    435-448页
    查看更多>>摘要：Tocopherol is an important lipid-soluble antioxidant beneficial for both human health and plant growth.Here,we fine mapped a major QTL-qVE1 affecting γ-tocopherol content in maize kernel,positionally cloned and confirmed the underlying gene ZmPORB1(por1),as a proto-chlorophyllide oxidoreductase.A 13.7 kb insertion reduced the tocopherol and chlorophyll content,and the photosynthetic activity by repressing ZmPORB1 expression in embryos of NIL-K22,but did not affect the levels of the tocopherol precursors HGA(homogentisic acid)and PMP(phytyl monophosphate).Furthermore,ZmPORB1 is inducible by low oxygen and light,thereby involved in the hypoxia response in developing embryos.Concurrent with natural hypoxia in embryos,the redox state has been changed with NO increasing and H2O2 de-creasing,which lowered γ-tocopherol content via scavenging reactive nitrogen species.In conclusion,we proposed that the lower light-harvesting chlorophyll content weakened embryo photosynthesis,leading to fewer oxygen supplies and consequently diverse hypoxic responses including an elevated γ-tocopherol consumption.Our findings shed light on the mechanism for fine-tuning endogenous oxygen concentration in the maize embryo through a novel feedback pathway involving the light and low oxygen regulation of ZmPORB1 expression and chlorophyll content.
      原文链接:
    • 万方数据
    • 维普

    Evolutionary mechanisms and practical significance of reproductive success and clonal diversity in unisexual vertebrate polyploids

    Meng LuLi ZhouJian-Fang Gui
    449-459页
    查看更多>>摘要：Unisexual reproduction is generally relevant to polyploidy,and unisexual vertebrates are often considered an evolutionary"dead end"due to the accumulation of deleterious mutations and absence of genetic diversity.However,some unisexual polyploids have developed strategies to avoid genomic decay,and thus provide ideal models to unveil unexplored evolutionary mechanisms,from the reproductive success to clonal diversity creation.This article reviews the evolutionary mechanisms for overcoming meiotic barrier and generating genetic diversity in unisexual vertebrates,and summarizes recent research advancements in the polyploid Carassius complex.Gynogenetic gibel carp(Carassius gibelio)is a unique amphitriploid that has undergone a recurrent autotriploidy and has overcome the bottleneck of triploid sterility via gynogenesis.Recently,an efficient strategy in which ploidy changes,including from amphitriploid to amphitetraploid,then from amphitetraploid to novel amphitriploid,drive unisexual-sexual-unisexual reproduction transition and clonal diversity has been revealed.Based on this new discovery,multigenomic reconstruction biotechnology has been used to breed a novel strain with superior growth and stronger disease resistance.Moreover,a unique reproduction mode that combines both abilities of ameiotic oogenesis and sperm-egg fusion,termed as ameio-fusiongensis,has been discovered,and it provides an efficient approach to synthesize sterile allopolyploids.In order to avoid ecological risks upon escape and protect the sustainable property rights of the aquaculture seed industry,a controllable fertility biotechnology approach for precise breeding is being developed by integrating sterile allopolyploid synthesis and gene-editing techniques.This review provides novel insights into the origin and evolution of unisexual vertebrates and into the attempts being made to exploit new breeding biotechnologies in aquaculture.
      原文链接:
    • 万方数据
    • 维普

    CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

    Daoyuan HuangQian ZhaoKuan YangJinghui Lei...
    460-474页
    查看更多>>摘要：Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and senescence.To this end,we conducted a comparative aging phenotype analysis by in-dividually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome hMSCs.Among all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence.To investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into hMSCs,we found that CUL2 deletion markedly accelerates hMSC senescence.Importantly,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated de-gradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn down-regulates one of the canonical aging marker-P21wan/cip1,and thereby delays senescence.Our work provides important insights into how CRL2APPBP2-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.
      原文链接:
    • 万方数据

    Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1

    Hao-Xiang YuanYa-Ting ChenYu-Quan LiYan-Sheng Wang...
    475-487页
    查看更多>>摘要：Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury(ALI),including acute respiratory distress syndrome(ARDS),in patients after cardiac surgery.We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles(eEVs)with components of coagulation and acute inflammatory responses.However,the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass,remains unclear.Plasma plasminogen-activated inhibitor-1(PAI-1)and eEV levels were measured in patients with cardiopulmonary bypass.Endothelial cells and mice(C57BL/6,Toll-like receptor 4 knockout(TLR4-/-)and inducible nitric oxide synthase knockout(iNOS-/-))were challenged with eEVs isolated from PAI-1-stimulated endothelial cells.Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass.Plasma PAI-1 eleva-tion was positively correlated with the increase in eEVs.The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS.The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade iden-tified as the Janus kinase 2/3(JAK2/3)-signal transducer and activator of transcription 3(STAT3)-interferon regulatory factor 1(IRF-1)pathway,along with iNOS induction,and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice,ultimately contributing to ALI.ALI could be attenuated by JAK2/3 or STAT3 inhibitors(AG490 or S3I-201,respectively),and was relieved in TLR4-/-and iNOS-/-mice.eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1(FSTL1),and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS.Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs,which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop,leading to ALI/ARDS after cardiac surgery.Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.
      原文链接:
    • 万方数据
    • 维普

    LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

    Xiao FanFangzhou LiuXiang WangYing Wang...
    488-503页
    查看更多>>摘要：Ferroptosis,a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation,has a potential physiological function in tumor suppression,but its underlying mechanisms have not been fully elucidated.Here,we report that the long non-coding RNA(lncRNA)LncFASA increases the susceptibility of triple-negative breast cancer(TNBC)to ferroptosis.As a tumor suppressor,LncFASA drives the formation of droplets containing peroxiredoxinl(PRDX1),a member of the peroxidase family,resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis.Mechanistically,LncFASA directly binds to the Ahpc-TSA domain of PRDX1,inhibiting its per-oxidase activity by driving liquid-liquid phase separation,which disrupts intracellular ROS homeostasis.Notably,high LncFASA expression indicates favorable overall survival in individuals with breast cancer,and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis.Together,our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.
      原文链接:
    • 万方数据
    • 维普

    Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation

    Qi FuYu QianHemin JiangYunqiang He...
    504-517页
    查看更多>>摘要：During the pathogenesis of type 1 diabetes(T1D)and type 2 diabetes(T2D),pancreatic islets,especially the β cells,face significant challenges.These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin,but the exact mechanism needs to be defined.High-fat diet(HFD)and streptozotocin(STZ)treatment are well-established models to study islet damage in T2D and T1D respectively.Therefore,we applied these two diabetic mouse models,triggered at different ages,to pursue the cell fate transition of isletβ cells.Cre-LoxP systems were used to generate islet cell type-specific(a,β,or δ)green fluorescent protein(GFP)-labeled mice for genetic lineage tracing,thereinto β-cell GFP-Iabeled mice were tamoxifen induced.Single-cell RNA sequencing(scRNA-seq)was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice.STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models.β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells,in contrast,α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youth-and adulthood-initiated).In addition to the re-dedifferentiation of β cells,it is also highly likely that these"α or δ"cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery.The analysis of ScRNA-seq revealed that several pathways including mitochondrial function,chromatin modification,and remodeling are crucial in the dynamic transition of β cells.Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.
      原文链接:
    • 万方数据
    • 维普

    Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors

    Meimei LiaoXinwei GaoChen ChenQi Li...
    518-528页
    查看更多>>摘要：The circadian clock coordinates rhythms in numerous physiological processes to maintain organismal homeostasis.Since the su-prachiasmatic nucleus(SCN)is widely accepted as the circadian pacemaker,it is critical to understand the neural mechanisms by which rhythmic information is transferred from the SCN to peripheral clocks.Here,we present the first comprehensive map of SCN efferent connections and suggest a molecular logic underlying these projections.The SCN projects broadly to most major regions of the brain,rather than solely to the hypothalamus and thalamus.The efferent projections from different subtypes of SCN neurons vary in distance and intensity,and blocking synaptic transmission of these circuits affects circadian rhythms in locomotion and feeding to different extents.We also developed a barcoding system to integrate retrograde tracing with in-situ sequencing,allowing us to link circuit anatomy and spatial patterns of gene expression.Analyses using this system revealed that brain regions functioning downstream of the SCN receive input from multiple neuropeptidergic cell types within the SCN,and that individual SCN neurons generally project to a single downstream brain region.This map of SCN efferent connections provides a critical foundation for future investigations into the neural circuits underlying SCN-mediated rhythms in physiology.Further,our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions.
      原文链接:
    • 万方数据
    • 维普

    An effective pharmacological hydrogel induces optic nerve repair and improves visual function

    Lipeng WangShan ZhangYawen HanShuo Tang...
    529-542页
    查看更多>>摘要：Irreversible eye lesions,such as glaucoma and traumatic optic neuropathy,can cause blindness;however,no effective treatments exist.The optic nerve,in particular,lacks the capacity to spontaneously regenerate,requiring the development of an effective approach for optic nerve repair,which has proven challenging.Here,we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC,respectively-packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal in-jection,effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury.Moreover,this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old)of glaucoma.Taken together,our data provide a new,local small molecule-based treatment for the effective induction of optic nerve repair,which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.
      原文链接:
    • 万方数据
    • 维普

    Local field potentials,spiking activity,and receptive fields in human visual cortex

    Lu LuoXiongfei WangJunshi LuGuanpeng Chen...
    543-554页
    查看更多>>摘要：The concept of receptive field(RF)is central to sensory neuroscience.Neuronal RF properties have been substantially studied in animals,while those in humans remain nearly unexplored.Here,we measured neuronal RFs with intracranial local field potentials(LFPs)and spiking activity in human visual cortex(V1/V2/V3).We recorded LFPs via macro-contacts and discovered that RF sizes estimated from low-frequency activity(LFA,0.5-30 Hz)were larger than those estimated from low-gamma activity(LGA,30-60 Hz)and high-gamma activity(HGA,60-150 Hz).We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously.We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity.In sum,this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement,implying the pivotal functions of LGA and HGA in early visual information processing.
      原文链接:
    • 万方数据
    • 维普

    Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12iMax

    Jilong RenTang HaiYangcan ChenKe Sun...
    555-564页
    查看更多>>摘要：The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated gene(Cas)system is continually optimized to achieve the most efficient gene editing effect.The Cas12iMax,a Cas12i variant,exhibits powerful DNA editing activity and enriches the gene editing toolbox.However,the application of Cas12iMax in large domestic animals has not yet been reported.To verify the efficiency and feasibility of multiple gene editing in large animals,we generated porcine fibroblasts with simultaneous knockouts of IGF2,ANPEP,CD163,and MSTN via Cas12iMax in one step.Phenotypically stable pigs were created through somatic cell nuclear transfer technology.They exhibited improved growth performance and muscle quality.Furthermore,we simultaneously edited three genes in bovine fibroblasts.A knockout of MSTN and PRNP was created and the amino acid Q-G in CD18 was precisely substituted.Meanwhile,no off-target phenomenon was observed by sum-type analysis or off-target detection.These results verified the effectiveness of Cas12iMax for gene editing in livestock animals and demonstrated the potential application of Cas12iMax in the field of animal trait improvement for agricultural production.
      原文链接:
    • 万方数据