Traumatic spinal cord injury(SCI)is a devastating central nervous system(CNS)disorder characterized by significant neurological dysfunction and sensory loss,and effective therapies that prevent neuronal loss and funct...Traumatic spinal cord injury(SCI)is a devastating central nervous system(CNS)disorder characterized by significant neurological dysfunction and sensory loss,and effective therapies that prevent neuronal loss and functional recovery remain elusive.After SCI,lesions are surrounded by neuroprotective borders formed by newly proliferated reactive astrocytes.Astrocyte proliferation and activation mediate the formation and function of the glial scar and influence the balance between protection and inflammation.展开更多
随着社会经济的发展和林业管理需求的增加,林权不动产权籍调查的重要性日益凸显。然而,传统的手工制图和制表方式往往耗时耗力,且容易出现数据错误,不仅影响了调查结果的可靠性,而且增加了后续管理的复杂性。为此,基于C#与ArcGIS Pro SD...随着社会经济的发展和林业管理需求的增加,林权不动产权籍调查的重要性日益凸显。然而,传统的手工制图和制表方式往往耗时耗力,且容易出现数据错误,不仅影响了调查结果的可靠性,而且增加了后续管理的复杂性。为此,基于C#与ArcGIS Pro SDK平台,通过创建模板数据、数据准备、加载图层、追加数据、加载布局、检查数据、图层逻辑检查、一键成果8个模块,设计并实现了一套林权不动产权籍调查自动化制图制表工具。通过实际应用案例,对该工具的性能进行评估。结果表明,该工具显著提升了林权不动产权籍调查的工作效率,减少了人为因素导致的错误,为林业管理提供了有力的数据支持和决策依据。展开更多
The main protease(Mpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been validated as a therapeutic target for antiviral drug development,given its critical role in the viral life cycle.SARS-Co...The main protease(Mpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been validated as a therapeutic target for antiviral drug development,given its critical role in the viral life cycle.SARS-CoV-2 Mprocontains 12 cysteine residues,which are susceptible to covalent modification by nucleophilic entities.In this study,we showcase an efficient strategy to uncover the key covalent inhibitors of SARS-CoV-2 Mprofrom herbal extracts and decipher their synergistic anti-Mpromechanisms.Preliminary screening identified Rhodiola crenulata root(RCR),a well-known Tibetan herb,showing the most potent time-dependent inhibition against SARS-CoV-2 Mpro.By integrating fluorescence resonance energy transfer(FRET)-based biochemical assay with phytochemical and chemoproteomic profiling,we efficiently identified thirteen Mprocovalent inhibitors from the crude extract of RCR.Among these,rhodiosin and gallic acid were validated as the key anti-Mproconstituents,due to their strong anti-Mproeffects and high abundance in RCR.Remarkably,their combination exhibited a pronounced synergy in Mproinhibition.Further intact protein mass measurements and top-down mass spectrometry(MS)analysis,complemented by biophysical methods,elucidated how these two compounds work in concert.Our findings revealed that rhodiosin functions as an allosteric inhibitor,disrupting Mprodimerization and significantly facilitating the covalent modification of Mproby gallic acid.Collectively,the covalent SARS-CoV-2 Mproinhibitors are efficiently identified from a Tibetan herb,while a phytochemical combination with synergistic anti-Mproeffects and their unique allosteric-induced cooperative modification mechanism are revealed.展开更多
目的基于国产Insight NM/CT Pro SPECT/CT设备建立正常骨骼标准化摄取值(SUV)参考值范围,并探讨影响SUV的相关因素。资料与方法前瞻性纳入2024年3月-2025年7月内蒙古医科大学附属医院初诊发现占位性病变筛查骨转移的219例患者资料,使用I...目的基于国产Insight NM/CT Pro SPECT/CT设备建立正常骨骼标准化摄取值(SUV)参考值范围,并探讨影响SUV的相关因素。资料与方法前瞻性纳入2024年3月-2025年7月内蒙古医科大学附属医院初诊发现占位性病变筛查骨转移的219例患者资料,使用Insight NM/CT Pro SPECT/CT行骨显像,使用基于CT的人工智能分割自动提取各骨区感兴趣区,并计算最大、平均标准化摄取值(SUVmax、SUVmean),建立正常骨骼的SUV参考值范围,并分析性别、年龄、身高、体重、体重指数等因素对SUV的影响。结果各骨区SUV差异有统计学意义(H=1162.289、1278.004,P均0.05)。SUVmax和SUVmean与年龄呈负相关(r=-0.718~-0.162,P均<0.05),与体重(r=0.277~0.523)、体重指数(r=0.246~0.505)呈正相关(P均<0.05)。除肋骨、颈椎、胸椎、肱骨(r=-0.200~0.242,P均<0.05),其他各骨区和总骨区SUVmax、SUVmean均与身高无相关性。结论本研究基于国产Insight NM/CT Pro SPECT/CT骨定量技术获得正常骨骼SUV参考值范围,可为骨病变诊断及评估提供参考,为国产设备的推广应用提供依据。展开更多
基金supported by a Grant-in-Aid of AMED under Grant Numbers(JP22gm1510009)to RM.
摘要Traumatic spinal cord injury(SCI)is a devastating central nervous system(CNS)disorder characterized by significant neurological dysfunction and sensory loss,and effective therapies that prevent neuronal loss and functional recovery remain elusive.After SCI,lesions are surrounded by neuroprotective borders formed by newly proliferated reactive astrocytes.Astrocyte proliferation and activation mediate the formation and function of the glial scar and influence the balance between protection and inflammation.
基金supported by the National Key Research and Development Program of China(No.2021YFD1800300 to FY)the National Natural Science Foundation of China of China(32473064 to WZ)+5 种基金the Fundamental Research Funds for the Central Universities,the Scientific Funds of Gansu Province(23JRRA547 to WJC)the Science and Technology Major Project of Gansu Province(No.22ZD6NA001 to HXZ)the Joint Research Foundation of Gansu Province(No.25JRRA1088,24JRRA804,No.24JRRA813 to FY)the Gansu Province ResearchProduction Integration Technology Breakthrough Empowerment Plan(25FNNA002 to HXZ)the Earmarked Fund(CARS-35 to HXZ)the Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(No.NCTIP-XD/C03 to HXZ).
摘要Foot-and-mouth disease virus(FMDV),a highly contagious picornavirus,employs multifaceted strategies to evade host innate immunity,with viral proteins 3Cprotease(3Cpro)and 2B serving as key immune antagonists.The stimulator of interferon genes 1(STING1)is a critical innate immune adaptor;however,its role and regulatory mechanisms during FMDV infection remain incompletely understood.Here,we report that STING1 inhibits FMDV replication through an interferon(IFN)-independent mechanism,while FMDV counteracts this antiviral effect by degrading STING1 via 3Cproand 2B.Mechanistically,FMDV 3Cpromediates STING1 degradation in a protease activity-dependent manner;this STING1-degrading activity is conserved among 3Cproproteins of poliovirus,enterovirus 71,and coxsackievirus,but not senecavirus A.In contrast,FMDV 2B suppresses STING1 expression at the mRNA level,and neither proteasomal,lysosomal,nor caspase pathways are involved in 3Cpro/2B-mediated STING1 downregulation.Furthermore,the STING1 stabilizer SB24011 enhances endogenous STING1 expression,dose-dependently inhibits FMDV replication by targeting viral internal ribosome entry site(IRES)-mediated translation,and exhibits broad-spectrum antiviral activity against multiple picornaviruses.In vivo,SB24011 treatment alleviates virus-induced histopathological lesions.Collectively,our findings reveal a novel IFNindependent antiviral role of STING1 against FMDV,identify 3Cproand 2B as FMDV-encoded STING1 antagonists,and highlight the potential of SB24011 as a broad-spectrum anti-picornavirus therapeutic agent.
摘要随着社会经济的发展和林业管理需求的增加,林权不动产权籍调查的重要性日益凸显。然而,传统的手工制图和制表方式往往耗时耗力,且容易出现数据错误,不仅影响了调查结果的可靠性,而且增加了后续管理的复杂性。为此,基于C#与ArcGIS Pro SDK平台,通过创建模板数据、数据准备、加载图层、追加数据、加载布局、检查数据、图层逻辑检查、一键成果8个模块,设计并实现了一套林权不动产权籍调查自动化制图制表工具。通过实际应用案例,对该工具的性能进行评估。结果表明,该工具显著提升了林权不动产权籍调查的工作效率,减少了人为因素导致的错误,为林业管理提供了有力的数据支持和决策依据。
基金supported by the National Natural Science Foundation of China(Grant Nos.:82141203,82273897,U23A20516,82204606,and 82104281)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine,China(Grant No.:2023YZZ02)+6 种基金Shanghai Municipal Health Commission's TCM Research Project,China(Grant No.:2022CX005)Shanghai Science and Technology Innovation Action Plans,China(Grant No.:21S21900600)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine,China(Grant No.:2023YZZ02)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-D-202004)Shanghai Talent Development Fund,China(Grant No.:2019093)Shanghai Sailing Program,China(Program No.:22YF1441500)Three-year Action Plan for Shanghai TCM Development and Inheritance Program,China(Grant No.:ZY(2021-2023)-0401).
摘要The main protease(Mpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been validated as a therapeutic target for antiviral drug development,given its critical role in the viral life cycle.SARS-CoV-2 Mprocontains 12 cysteine residues,which are susceptible to covalent modification by nucleophilic entities.In this study,we showcase an efficient strategy to uncover the key covalent inhibitors of SARS-CoV-2 Mprofrom herbal extracts and decipher their synergistic anti-Mpromechanisms.Preliminary screening identified Rhodiola crenulata root(RCR),a well-known Tibetan herb,showing the most potent time-dependent inhibition against SARS-CoV-2 Mpro.By integrating fluorescence resonance energy transfer(FRET)-based biochemical assay with phytochemical and chemoproteomic profiling,we efficiently identified thirteen Mprocovalent inhibitors from the crude extract of RCR.Among these,rhodiosin and gallic acid were validated as the key anti-Mproconstituents,due to their strong anti-Mproeffects and high abundance in RCR.Remarkably,their combination exhibited a pronounced synergy in Mproinhibition.Further intact protein mass measurements and top-down mass spectrometry(MS)analysis,complemented by biophysical methods,elucidated how these two compounds work in concert.Our findings revealed that rhodiosin functions as an allosteric inhibitor,disrupting Mprodimerization and significantly facilitating the covalent modification of Mproby gallic acid.Collectively,the covalent SARS-CoV-2 Mproinhibitors are efficiently identified from a Tibetan herb,while a phytochemical combination with synergistic anti-Mproeffects and their unique allosteric-induced cooperative modification mechanism are revealed.
摘要目的基于国产Insight NM/CT Pro SPECT/CT设备建立正常骨骼标准化摄取值(SUV)参考值范围,并探讨影响SUV的相关因素。资料与方法前瞻性纳入2024年3月-2025年7月内蒙古医科大学附属医院初诊发现占位性病变筛查骨转移的219例患者资料,使用Insight NM/CT Pro SPECT/CT行骨显像,使用基于CT的人工智能分割自动提取各骨区感兴趣区,并计算最大、平均标准化摄取值(SUVmax、SUVmean),建立正常骨骼的SUV参考值范围,并分析性别、年龄、身高、体重、体重指数等因素对SUV的影响。结果各骨区SUV差异有统计学意义(H=1162.289、1278.004,P均0.05)。SUVmax和SUVmean与年龄呈负相关(r=-0.718~-0.162,P均<0.05),与体重(r=0.277~0.523)、体重指数(r=0.246~0.505)呈正相关(P均<0.05)。除肋骨、颈椎、胸椎、肱骨(r=-0.200~0.242,P均<0.05),其他各骨区和总骨区SUVmax、SUVmean均与身高无相关性。结论本研究基于国产Insight NM/CT Pro SPECT/CT骨定量技术获得正常骨骼SUV参考值范围,可为骨病变诊断及评估提供参考,为国产设备的推广应用提供依据。