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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng huang Yanan Du Wei huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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数字化转型赋能企业绿色技术创新的影响研究——基于中国上市公司的经验数据

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工业技术经济 2025年第1期44卷 96-105页

作者：李刚黄苗苗安徽财经大学经济学院蚌埠233030

在“双碳”目标背景下,企业通过数字化转型推动绿色技术创新,这不仅关乎其自身生存发展,也是促进中国经济可持续发展的微观基础。本文基于2009~2023年沪深A股上市公司数据,实证检验数字化转型对企业绿色技术创新的影响。研究发现:(1)数... 详细信息

在“双碳”目标背景下,企业通过数字化转型推动绿色技术创新,这不仅关乎其自身生存发展,也是促进中国经济可持续发展的微观基础。本文基于2009~2023年沪深A股上市公司数据,实证检验数字化转型对企业绿色技术创新的影响。研究发现:(1)数字化转型有助于提升企业绿色技术创新水平,且估计结果十分稳健;(2)数字化转型通过增强内部能力、提高外部市场关注和增加政府补贴促进企业绿色技术创新;(3)异质性分析表明,在国有企业和环境规制强度高的区域,数字化转型对企业绿色技术创新的推动作用更为显著。本文为理解数字化转型赋能企业绿色技术创新提供经验证据,并为我国推动数字化转型以促进经济可持续发展提供理论和实践参考。

关键词：数字化转型绿色技术创新内部能力外部市场关注政府补贴高维固定效应双碳经济可持续发展

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MOLAP的数据存储设计与实现

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铁路计算机应用 2004年第3期13卷 8-11页

作者：康志钢黄厚宽北京交通大学计算机与信息技术学院北京100044

引入MOLAP的存储机制,自定义子立方体和块的概念,提出并实现了MOLAP中子立方体存储时块的两种存储方法,即直接多维数组存储和压缩多维数组存储。

关键词： MOLAP 数据存储设计子立方体存储时块直接多维数组存储压缩多维数组存储多维数据库

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Merging bound states in the continuum in an open acoustic resonator

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 124-131页

作者： Lujun huang Bin Jia Artem S.Pilipchuk Sibo huang Chen Shen Almas F.Sadreev Yong Li Andrey E.Miroshnichenko School of Physics and Electronic Sciences East China Normal University Institute of Acoustics Tongji University L.V.Kirensky Institute of Physics Department of Mechanical Engineering Rowan University School of Engineering and Technology University of New South Wales at Canberra

Bound states in the continuum （BICs） are perfectly localized resonances despite embedding in the continuum ***,an isolated BIC is very sensitive to the structure ***,we report merging acoustic BICs in a single open resonator,robust against the structure *** find that both symmetry-protected BIC and Friedrich-Wintgen BIC are sustained in a single coupled waveguide-resonator *** varying the height and length of the resonator,these two BICs move toward each other and merge into a single one at a critical *** to an individual BIC,the merged BIC is robust against fabrication error because its Q-factor is proportional to ΔL-4,whereΔL embodies the structure *** essence of this extraordinary phenomenon is perfectly explained by the two-and three-level approximations of the effective nonHermitian ***,we present direct experimental demonstrations of the moving and merging of BICs in a coupled 3D waveguide-resonator,which are evidenced by the vanishing of the linewidth of Fano resonance in the transmission *** results may find exciting applications in designing high-quality acoustic sources,sensors and filters.

关键词： acoustic resonances bound state in the continuum high-Q resonances

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Blue LED-pumped efficient NIR luminescence in Sb3+-doped lead-free metal halides

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Science China Materials 2025年

作者： Xiaoyong huang College of Physics and Optoelectronics Taiyuan University of Technology

Broadband near-infrared （NIR） light sources hold promise for some important NIR spectroscopy applications such as night vision,plant growths,optical communications,remote sensing,biomedical imaging and other noninvasive and nondestructive detections[1–4].Recently,the phosphors-converted NIR lightemitting diodes （LEDs） based on“blue LED chips+broadband NIR phosphors”are widely developed for next-generation costeffective NIR light *** this respect,the performance of NIR phosphors directly determines the overall quality of phosphors-converted NIR LEDs.

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Photoinduced radical sulfur dioxide insertion with asymmetric cyclization of alkenes: accessing β-chiral sulfones bearing S-stereocentric cyclic sulfinamides

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Science China Chemistry 2025年第1期68卷 257-263页

作者： Jiapian huang Chenxin Wang Xu Wang Xiaoyu Zhou Wei Xiao Jie Wu School of Pharmaceutical and Chemical Engineering & Institute for Advanced Studies Taizhou University State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences School of Chemistry and Chemical Engineering Henan Normal University

The generation of various β-chiral sulfones bearing chiral cyclic sulfinamides through photoredox-catalyzed sulfur dioxide insertion with asymmetric radical cyclization is described. This method features a broad substrate scope and excellent stereospecificity. Computational studies reveal that the dispersion interaction between sulfinyl group and CH2SO2Ph group plays a crucial role in the stereoselectivity control.

关键词： β-chiral sulfones chiral cyclic sulfinamides sulfur dioxide insertion asymmetric radical cyclization stereoselectivity

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质粒pUC18DNA的螺线管型超螺旋结构

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生物物理学报 2003年第1期19卷 13-17页

作者：齐静张臻峰于春风杨琴黄志刚侯亭黄熙泰南开大学生命科学学院生化与分子生物学系天津300071

理论上,游离的超螺旋DNA可以采取两种结构形式:互缠式超螺旋和螺线管型超螺旋。前者早已被透射电子显微镜和原子力显微术的研究所证实,而后者却仍然缺乏足够的证据。使用温和的清亮裂解液法,从DNA拓扑酶野生型大肠杆菌HB101细胞抽提质粒... 详细信息

理论上,游离的超螺旋DNA可以采取两种结构形式:互缠式超螺旋和螺线管型超螺旋。前者早已被透射电子显微镜和原子力显微术的研究所证实,而后者却仍然缺乏足够的证据。使用温和的清亮裂解液法,从DNA拓扑酶野生型大肠杆菌HB101细胞抽提质粒pUC18 DNA。经CsCl-EB平衡密度梯度超离心分离获得超螺旋pUC18 DNA和松弛型pUC18 DNA(DNA Ⅱ)。纯化DNA分别用疏水性溶剂系统和亲水性溶剂系统的细胞色素单分子层展开技术制备电子显微镜标本。观察结果显示:在疏水性的甲酰胺-水展开系统中,DNA采取通常的互缠式结构;在含有1.5mmol/L醋酸铵的水介质中制备的超螺旋DNA标本,DNA采取线圈型结构,测得pUC18 DNA(单体)分子这种结构的外直径约为43.8nm,内直径约为2nm。在相同亲水介质中松弛型pUC18DNA采取典型的螺线管型结构,其单体平均外直径约为53.1nm,内直径约为17.2nm。表明:在疏水介质中超螺旋DNA趋向于采取互缠式结构,而在亲本介质中DNA则采取螺线管型结构。DNA链之间可能存在非共价相互作用以维持这种结构。螺线管型结构可能是水溶液中的超螺旋DNA分子普遍的存在形式。

关键词： DNA拓扑结构螺线管型超螺旋DNA 螺线管型DNAⅡ 电子显微镜

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng huang zhijun Wu Baitao Liu Hongjie huang Haijun Wang Yongjian Wang Dingge Liu zhihua Zhang Kaiping Liu gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

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World Journal of Clinical Cases 2025年第2期13卷 50-58页

作者： Xiu-Ying Chen Fa Shen Chang Cheng Yu-Han Wang Wen-Chao Cheng De-zhi Yuan Wen huang Department of Neurology Chongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400000China Department of Neurology Xinqiao HospitalThe Army Medical University(Third Military Medical University)Chongqing 400000China

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic *** cerebral fat embolism(CFE)as a complication is rare,it carries serious health *** SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling *** the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided *** physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon *** clinical diagnosis was acute cerebral embolism following facial fat filling *** included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb *** patient showed a significant improvement in symptoms after 2 weeks of *** recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of *** Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial *** prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

关键词： Cerebral fat embolism Mechanical thrombectomy Thrombolysis Steroid therapy Symptomatic treatment Case report

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