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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期68卷 300-302页

作者： Ze-min Lin Mai Xiang Wen-Hui wei Shu-Hui fan Li chen Jie wang Xiao-Qian Yang Chun-Hao Yang Shi-Jun He Jian-Ping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie chen Hai-Di fan Wan wang Bin wang Ju-Yun Ma Peng-Peng Li Hai-wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年

作者： Dan wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin wang Yongzhen Mo Chunmei fan Yi He Pan chen ming Zhou Bo Xiang wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong Laboratory Cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang Key Laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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List Vertex-arboricity of Planar Graphs without Intersecting 5-cycles

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Acta Mathematicae Applicatae Sinica 2020年第2期36卷 439-447页

作者： wei-fan wang Li HUANG min chen Department of Mathematics Zhejiang Normal UniversityJinhua 321004China

The vertex-arboricity a(G)of a graph G is the minimum number of colors required for a vertex coloring of G such that no cycle is *** list vertex-arboricity al(G)is the list-coloring version of this *** this paper,we prove that every planar graph G without intersecting 5-cycles has al(G)≤*** extends a result by Raspaud and wang[On the vertex-arboricity of planar graphs,European ***.29(2008),1064-1075]that every planar graph G without 5-cycles has a(G)≤2.

关键词： planar graphs list vertex-arboricity intersecting cycles monochromatic cycle

Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda Zhang weimin Yuan Zhixing Ling Yong chen Nanda Rea Arne Rau Zhiming Cai Huaqing cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng wang Lei Yang Bing Zhang chen Zhang Shuang-Nan Zhang Yonghe Zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris Zhou fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers weihua Lei Wenxiong Li Bifang Liu mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng wang Song wang Tinggui wang Zhongxiang wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian Zhang Zipei Zhu Hu Zou Congying Bao fansheng chen Houlei chen Tianxiang chen wei chen Yehai chen Yifan chen chenzhou Cui weiwei Cui Yanfeng Dai Dongwei fan Ju Guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen Jiang Ge Jin chengkui Li Junfei Li Longhui Li Maoshun Li wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao wang Juan wang Lei wang Wenxin wang Yilong wang Yusa wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang Juan Zhang Mo Zhang Wenjie Zhang Zhen Zhang Zhen Zhang Ziliang Zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Sciences University of Chinese Academy of Sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Institute of Space Sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of Sciences Department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University Department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of Sciences Physics Department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas Department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory Department of Astronomy University of Cape Town Department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM Department of Astronomy Guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen Department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC Department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney Department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University Department of Astronomy University of Science and Technology School of Astronomy and Space Sciences University of Science and Technology of China Institute of Deep Space Sciences Deep Space Exploration Laboratory Department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

Is the Cape Stone Forest in Shantou City formed by wave erosion? A comparison of the pedestal rocks on the coasts and the mountains of Queshi in eastern Guangdong, China

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Journal of Mountain Science 2024年第5期21卷 1447-1463页

作者： chen min wang wei School of Geography South China Normal UniversityGuangzhou 510631China

Cape Stone Forest is a group of granite rock pillars(pedestal rocks) towering over Shilin Lake, on the southern shore of Shantou Bay in eastern Guangdong, China. The rock pillars were previously identified as sea stacks because they have marine notch-like concave sidewalls at their base, and more importantly, the lake is immediately adjacent to the bay, which is exposed to the open sea. However, rock pillars similar in shape and size can also be found at the top of Queshi Mountain, which is only about 300 meters northwest of the lake and about 85 meters above sea level. Therefore, the marine origin of Cape Stone Forest is seriously questioned. In this study, 3D imagery and drone technology were used to collect data in the investigations without direct manual measurements in the water or on the mountain. It shows that the concave sidewalls of the rock pillars in the lake and on the mountains occur at different heights and are exposed to different directions, while a natural sea stack on Mayu Island at the mouth of Shantou Bay has a horizontal notch parallel to the sea level, although the granite rock of the sea stack is the same as that of the lake and the mountains. The eastern side of the island, where the sea stack is located, is exposed to the open sea but blocks large waves for the rock pillars in the lake. Therefore, the origin of Cape Stone Forest cannot be explained by wave-based mechanisms. The only satisfactory explanation that takes into account all the field evidence is that the narrow rock pillars of the lake and mountain were formed by chemical weathering that penetrated closely the spaced joints of the granite rock, and the notch-like concave sidewalls were formed by more effective chemical weathering at the base of the pillars.

关键词： Pedestal rock Granite Closely spaced joints Wave erosion Chemical weathering

Least Absolute Deviation Estimation of Autoregressive Conditional Duration Model

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Acta Mathematicae Applicatae Sinica 2011年第2期27卷 243-254页

作者： wei Liu Hui-min wang min chen Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 China Business School Hohai University Nanjing 210098 China Information Management Center of China minsheng Banking Corp. Ltd. Beijing 100873 China

This paper studies the least absolute deviation estimation of the high frequency financial autoregressive conditional duration （ACD） model. The asymptotic properties of the estimator are studied given mild regularity conditions. Furthermore, we develop a Wald test statistic for the linear restriction on the parameters. A simulation study is conducted for the finite sample properties of our estimator. Finally, we give an empirical study of financial duration.

关键词： least absolute deviation estimation ACD model heavy tail

A density functional study on magnetic exchange interaction between Mn(II)ion and nitronyl nitroxide radical in trans-and cis-metal-radical complexes

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Science China Chemistry 2005年第5期48卷 402-414页

作者： wei Haiyan wang fan chen Zhida State Key Laboratory of Rare Earth Materials Chemistry and Applications College of Chemistry and Molecular Engineering Peking University Beijing 100871 China State Key Laboratory of Rare Earth Materials Chemistry and Applications College of Chemistry and Molecular Engineering Peking University Beijing 100871 China State Key Laboratory of Rare Earth Materials Chemistry and Applications College of Chemistry and Molecular Engineering Peking University Beijing 100871 China

The magneto-structural correlation between a Mn(II) ion, coordinated in an octahe-dral environment, and two nitronyl nitroxide radical ligands in trans- and cis-metal-radical com-plexes is investigated by the broken symmetry (BS) approach within density functional theory (DFT). The dependences of coupling constants J on three structural parameters: (i) bond angle θ (Mn-O-N (nitroxide)); (ii) rotating angle ψ, defined by the nitronyl nitroxide radical plane rotating around the axial Mn-O (nitroxide); (iii) bond distance R (Mn-O (nitroxide)) are directly calculated. Our calculations showed that both trans- and cis-Mn(II)-radical complexes behave a stronger antiferromagnetic interaction, consistent with experiments. In view of molecular orbital theory, the direct exchanges, including σ-type and π-type exchanges, are responsible for the magnetic ex-change pathways. There is a preferable linear correlation between the calculated coupling con-stants J and the overlap integral squares Sa2b between the local magnetic orbitals at the various rotating angle ψ at the fixed bond angle θ and bond distance R, in both trans- and cis-Mn(II)- radical complexes.

关键词： density functional theory, broken-symmetry approach, magnetic exchange, molecular magnetism,Mn(II)-NITR complex.

Understanding the scale-up of fermentation processes from the viewpoint of the flow field in bioreactors and the physiological response of strains

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Chinese Journal of Chemical Engineering 2021年第2期34卷 178-184页

作者： Jianye Xia Guan wang Meng fan min chen Zeyu wang Yingping Zhuang State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China

The production capability of a fermentation process is predominately determined by individual strains,which ultimately affected ultimately by interactions between the scale-dependent flow field developed within bioreactors and the physiological response of these *** these complicated interactions is key for better understanding the scale-up of the fermentation *** review these two aspects and address progress in strategies for scaling up fermentation processes.A perspective on how to incorporate the multiomics big data into the scale-up strategy is presented to improve the design and operation of industrial fermentation processes.

关键词： Fermentation Scale-up Bioreactors Gas-liquid flow Kinetics