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Unveiling E2F4,TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis

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Protein & Cell 2022年第10期13卷 742-759页

作者： Yuting Wang Liping Liu Yifan Song Xiaojie Yu Hongkui Deng School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic DrugsPeking UniversityBeijing 100191China The MOE Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Chemical Oncogenomics School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Senescence,a stable state of growth arrest,affects many physiological and pathophysiological processes,especially *** work has indicated that transcription factors(TFs)play a role in regulating ***,a systematic study of regulatory TFs during replicative senescence(RS)using multiomics analysis is still ***,we generated timeresolved RNA-seq,reduced representation bisulfite sequencing(RRBS)and ATAC-seq datasets during RS of mouse skin fibroblasts,which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and *** integrative analysis and genetic manipulations,we found that transcription factors E2F4,TEAD1 and AP-1 are key regulators of *** of E2f4 improved cellular proliferative capacity,attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites(DMSs).Moreover,knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated *** addition,knockdown of Atf3,one member of AP-1 superfamily TFs,reduced Cdkn2a(p16)expression in pre-senescent *** together,the results of this study identified transcription factors regulating the senescence program through multi-omics analysis,providing potential therapeutic targets for anti-aging.

关键词： transcription factor senescence multiomics

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Uncertainty Representation of Ocean Fronts Based on Fuzzy-Rough Set Theory

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Journal of Ocean University of China 2008年第2期7卷 131-136页

作者： XUE Cunjin ZHOU Chenghu SU Fenzhen ZHANG Dandan The Marine GIS＇s Center of State Key Laboratory of Resources and Environment Information System Chinese Academy of Sciences Beijing 1 O0101 P. R. China graduate School of the Chinese Academy of Sciences Beijing 100039 P. R. China

Analysis of ocean fronts＇ uncertainties indicates that they result from indiscemibility of their spatial position and fuzziness of their intensity. In view of this, a flow hierarchy for uncertainty representation of ocean fronts is proposed on the basis of fuzzy-rough set theory. Firstly, raster scanning and blurring are carried out on an ocean front, and the upper and lower approximate sets, the indiscernible relation in fuzzy-rough theories and related operators in fuzzy set theories are adopted to represent its uncertainties, then they are classified into three sets： with members one hundred percent belonging to the ocean front, belonging to the ocean front＇s edge and definitely not belonging to the ocean front. Finally, the approximate precision and roughness degree are utilized to evaluate the ocean front＇s degree of uncertainties and the precision of the representation. It has been proven that the method is not only capable of representing ocean fronts＇ uncertainties, but also provides a new theory and method for uncertainty representation of other oceanic phenomena.

关键词： fuzzy-rough set upper approximate sets lower approximate sets ocean fronts uncertainties

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Deep-learning-based quality filtering of mechanically exfoliated 2D crystals

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npj Computational Materials 2019年第1期5卷 57-62页

作者： Yu Saito Kento Shin Kei Terayama Shaan Desai Masaru Onga Yuji Nakagawa Yuki M.Itahashi Yoshihiro Iwasa Makoto Yamada Koji Tsuda RIKEN Center for Advanced Intelligence Project(AIP) Tokyo 103-0027Japan Department of Computational Biology and Medical Sciences Graduate School of Frontier SciencesThe University of TokyoKashiwa 277-8561Japan graduate School of Medicine Kyoto UniversityKyoto 606-8501Japan Quantum-Phase Electronics Center(QPEC)and Department of Applied Physics The University of TokyoTokyo 113-8656Japan RIKEN Center for Emergent Matter Science(CEMS) Wako 351-0198Japan Department of Intelligence Science and Technology Kyoto UniversityKyoto 606-8501Japan PRESTO Japan Science and Technology Agency(JST)4-1-8HonchoKawaguchi-shiSaitama 332-0012Japan National Institute for Materials Science(NIMS) Center for Materials Research by Information IntegrationTsukuba 305-0047Japan California NanoSystems Institute University of California at Santa BarbaraSanta BarbaraCA 93106USA

Two-dimensional(2D)crystals are attracting growing interest in various research fields such as engineering,physics,chemistry,pharmacy,and biology owing to their low dimensionality and dramatic change of properties compared to the bulk counter *** the various techniques used to manufacture 2D crystals,mechanical exfoliation has been essential to practical applications and fundamental ***,mechanically exfoliated crystals on substrates contain relatively thick flakes that must be found and removed manually,limiting high-throughput manufacturing of atomic 2D crystals and van der Waals ***,we present a deep-learning-based method to segment and identify the thickness of atomic layer flakes from optical microscopy *** carefully designing a neural network based on U-Net,we found that our neural network based on Unet trained only with the data based on realistically small number of images successfully distinguish monolayer and bilayer MoS2 and graphene with a success rate of 70–80%,which is a practical value in the first screening process for choosing monolayer and bilayer flakes of all flakes on substrates without human *** remarkable results highlight the possibility that a large fraction of manual laboratory work can be replaced by AI-based systems,boosting productivity.

关键词： crystals filtering attracting

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Review on the characteristics of liver-pacifying medicinal in relation to the treatment of stroke: from scientific evidence to traditional medical theory

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Journal of Traditional Chinese Medicine 2018年第1期38卷 139-150页

作者： Kyungjin Lee Hyejin Joo Meixiang Sun Minwoo Kim Bumjung Kim Beom-Joon Lee Jae-Heung Cho Jae-Young Jung Jae-Woo Park Youngmin Bu Department of Herbal Pharmacology College of Korean Medicine Kyung Hee University Department of Science in Korean medicine Graduate School Kyung Hee University Division of Allergy Immune and Respiratory System Department of Internal Medicine College of Korean Medicine Kyung Hee University Department of Korean Rehabilitation Medicine College of Korean Medicine Kyung Hee University Department of Internal Medicine College of Korean Medicine Kyung Hee University

OBJECTIVE： To analyze the characteristics of liver pacifying medicinal in the treatment of brain disease to provide scientific evidence in clinical usage on ***： MEDLINE/PubMed, Google Scholar, and China National Knowledge Infrastructure Database were used as the literature sources. The Scientific name, Latin pharmaceutical name, Chinese name of 7 kinds of liver pacifying medicinal including Gouteng （Ramulus Uncariae Rhynchophyllae cure Uncis）, Tianma （Rhizoma Gastrodiae）, Juemingzi （Semen Cassiae Obtusifoliae）, Quanxie （Scorpio）, Wugong （Scolopendra）, Jiangcan （Bombyx Batryticatus）, and Dilong （Pheretima Aspergillum） were used as the keywords to search the databases for relevant publications up to July 2016. Their major compounds were also used as the keywords. The papers were selected based on the pharmacological activities and mechanisms of action related to brain diseases and subsequently, were analyzed and reviewed. We first described the origin, efficacy, and clinical indications of selected medicines, then brain disease specific activities focusing on stroke after the description of the general pharmacological activities. RESULTS： On the basis of the literature of scientific studies and clinical use in traditional medicine, we found and discussed the characteristics of liver pacifying medicinal in stroke treatment. First, liver-pacifying medicinal, or their components, might pass through the blood-brain barrier and act directly on neurons or on the neural network to provide protective effects against brain disease. Second, although it could be used throughout the disease duration, treatment of stroke might be more effective from the subacute up to the convalescent phase than the acute ***： We can suggest that live pacifying medicinal has beneficial pharmacological activities directly or indirectly on neurons in brain disease and is useful for the treatment of stroke from subacute to convalescent phase.

关键词： Stroke Traditional medicine Calming liver wind Review

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Design,synthesis,antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives

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Acta Pharmacologica Sinica 2007年第1期28卷 140-152页

作者： Hai-hong LI~2 Xiu-hua ZHANG~3 Jin-zhi TAN~2 Li-li CHEN~2 Hong LIU~(2,5) Xiao-min LUO~(2,5) Xu SHEN~(2,4) Li-ping LIN~(3,5) Kai-xian CHEN~2 Jian DING~3 Hua-liang JIANG~(2,4)2 Center for Drug Discovery and Design,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,and graduate School,Chinese Academy of Sciences,Shanghai 201203,China 3 Division of Anti-tumor Pharmacology,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China 4 School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China Center for Drug Discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences and Graduate School Chinese Academy of Sciences Shanghai China Division of Anti-tumor Pharmacology Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China School of Pharmacy East China University of Science and Technology Shanghai China

Aim:To design and synthesize a novel class of antitumor agents,featuring the 3,5-substituted indolin-2-one ***:Based on enzyme binding fea-tures of（Z）-SU5402,introducing a β-pyrrole group at the 3-position of the indolin-2-one core,a series of novel 3,5-substituted indolin-2-ones were designed *** human carcinoma cell lines of A-43l,A-549,MDA-MB-468,and Autosomal Dominant Polycystic Kidney disease were chosen for the cellproliferation ***:Twenty new compounds（1a-t）with E configurationhave been designed,synthesized and *** structural features weredetermined by nuclear magnetic resonance（NMR）spectra,low-and high-resolu-tion mass spectra,and confirmed by X-ray *** the enzymeassay showed a weak inhibition effect against the epidermal growth factor receptor,vascular endothelial growth factor receptor,fibroblast growth factor receptor andplatelet-derived growth factor receptor tyrosine kinases,the cell-based antitumoractivity was *** 1 g and lh showed higher inhibitory activitytoward the A-549 and MDA-MB-468 cell lines with IC50of 0.065-9.4 μmol/***:This study provides a new template for further development ofpotent antitumor drugs.

关键词： protein-tyrosine kinase indolin-2-one antitumor drug screening assays drug design molecular models

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Observation constraints of the hard X-ray modulation telescope HXMT

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Science China(Physics,Mechanics & Astronomy) 2010年第S1期53卷 31-35页

作者： LU Yu1,2,ZHANG WenZhao3,QU JinLu1,SONG LiMing1,GAO Jian3,ZHANG HongMei4 & OU Ge4 1 Key Laboratory of Particle Astrophysics,Institute of High Energy Physics,Chinese Academy of Sciences,Beijing 100049,China 2 graduate University of Chinese Academy of Sciences,Beijing 100049,China 3 Department of Astronomy,Beijing Normal University,Beijing 100875,China 4 Computing Center,Institute of High Energy Physics,Chinese Academy of Sciences,Beijing 100049,China Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Beijing China graduate University of Chinese Academy of Sciences Beijing China Department of Astronomy Beijing Normal University Beijing China Computing Center Institute of High Energy Physics Chinese Academy of Sciences Beijing China

The hard X-ray modulation telescope HXMT is a low orbit X-ray space telescope whose main science goals are to accomplish a hard X-ray all sky survey and to study timing and spectral characteristics of X-ray *** has three kinds of science instruments:the high energy X-ray detector(HE),the medium energy X-ray detector(ME) and the low energy X-ray detector(LE).The observation schedule of HXMT is a key to achieving the science goal of HXMT,and the analysis of the observation constraints is one of the first tasks in making the observation *** paper analyzes how the observation constraints influence the sky visibility and the visible time distribution of X-ray sources and discusses the schedule strategy with regard to the observation constraints.

关键词： HXMT observation constraints sky visibility

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Antifeedant and Antiviral Diterpenoids from the Fresh Roots of Euphorbia jolkinii

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Natural Products and Bioprospecting 2014年第2期4卷 91-100页

作者： Chun-Shuai Huang Shi-Hong Luo Yao-Lan Li Chun-Huan Li Juan Hua Yan Liu Shu-Xi Jing Ying Wang Min-Jie Yang Sheng-Hong Li State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China graduate University of Chinese Academy of Sciences Beijing 100049China Institute of Traditional Chinese Medicine and Natural Products Jinan UniversityGuangzhou 510632China

The perennial herbaceous plant Euphorbia jolkinii(Euphorbiaceae)is a noxious weed widely distributed in the grasslands of northwestern Yunnan and has greatly threatened the local *** investigation on the fresh roots of *** afforded six new diterpenoids 1,2,4–6,and 8,together with fifteen known *** structures were elucidated on the basis of 1D and 2D NMR and other spectroscopic ***,lathyrane,abietane,and ent-kaurane diterpenoids were reported from this plant for the first *** compounds were evaluated for their antifeedant and anti-RSV(respiratory syncytial virus)*** 2 and ingenol(3)exhibited moderate antifeedant activity against a generalist insect herbivore,Spodoptera exigua,with EC50 values of 17.88 and 17.71 lg/cm2 *** 19 showed significant anti-RSV activity,with 50%inhibition(IC50)value of 10.0 lM and selective index of *** 1 and 2 were less active against RSV virus,both with IC50 value of 25 lM,and with selective indices of 1.0 and 3.2 *** findings provided new evidence for the biological functions and utilization of the diversified diterpenoid metabolites in the roots of this rich but harmful plant.

关键词： Euphorbia jolkinii Diterpenoids Antifeedant activity Antiviral activity

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Application of flow driven pore-network crack model to Zipingpu reservoir and Longmenshan slip

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Science China(Physics,Mechanics & Astronomy) 2011年第8期54卷 1532-1540页

作者： ZHU BoJing LIU Chang SHI YaoLin SUN DongSheng ZHANG Kai Key Laboratory of Computational Geodynamics of Chinese Academy of Sciences College of Earth Science Graduate University of Chinese Academy of Sciences Beijing 100049 China Laboratoire De Geologie Ecole Norrnale Superieure 24 Rue Lhomond 75231 Paris CEDEX 5 France Institute of Geomechanics Chinese Academy of Geological Sciences Beijing 100081 China Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 China

The study has analyzed the relationship between the water-drainage sluice process of reservoir, stress triggers and shadows of earthquake and porosity variability of fault slip zone. First, the pore pressure, pressure gradient, viscous stress and Reynolds stress to reservoir-earthquake fault slip problem are analyzed, and these are un-negligible factors of the extended coulomb failure stress under ultra-high temperature and pressure condition. Second, the porosity tensor and permeability tensor are studied, the relationship between Zipingpu reservoir and Longmenshan slip has been analyzed, and the extended viscous stress and Reynolds stress as function of time and infiltration process are obtained. Last, some primary conclusions about the flow-solid coupled facture mechanism to the Zipingpu reservoir and Longmenshan slip problem are presented, which can help understand the flow-solid coupled facture mechanism of reservoir-coseismic fault slip problem.

关键词： Zipingpu reservoir 2008 Wenchuan earthquake coulomb failure stress diffusion pore stress diffusion fluid flow driven pore-network crack model

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Calculation and Simulation of Evapotranspiration of Applied Water

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Journal of Integrative Agriculture 2012年第3期11卷 489-501页

作者： Richard L Snyder Shu Geng Morteza Orang Sara Sarreshteh Department of Land Air and Water Resources University of California Davis CA 95616 USA School of Environment and Energy Shenzhen Graduate School Peking University Shenzhen 518055 P.R.China Department of Plant Sciences University of California Davis CA 95616 USA California Department of Water Resources Division of Statewide Integrated Water Management Water Use and Efficiency SacramentoCA 94236 USA

The University of California, Davis and the California Department of Water Resources have developed a weather generator application program “SIMETAW” to simulate weather data from climatic records and to estimate reference evapotranspiration （ETo） and crop evapotranspiration （ETc） with the generated simulation data or with observed data. A database of default soil depth and water holding characteristics, effective crop rooting depths, and crop coefficient （Kc） values to convert ETo to ETc are input into the program. After calculating daily ETc, the input and derived data are used to determine effective rainfall and to generate hypothetical irrigation schedules to estimate the seasonal and annual evapotranspiration of applied water （ETaw）, where ETaw is the net amount of irrigation water needed to produce a crop. in this paper, we will discuss the simulation model and how it determines ETaw for use in water resources planning.

关键词： weather generator water balance crop water requirements water resource planning crop coefficient

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Registration of intervention trials of Traditional Chinese Medicine for four neurological diseases on Chinese Clinical Trial Registry and Clinical ***:a narrative review

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Journal of Traditional Chinese Medicine 2022年第1期42卷 148-153页

作者： WEI Jingjing GUO Rongjuan FU Guojing LIANG Xiao XU Zhenmin JIA Min ZENG Zixiu DU Wanqing JIAO Weiwei SUN Linjuan LIU Hongmei GUO Chunli TONG Chenguang ZHANG Yunling LIAO Xing graduate school Beijing University of Chinese MedicineBeijing 10029China Center for Evidence Based Chinese Medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical SciencesBeijing 100700China Department of Neurology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Department of Neurology Dongfang HospitalBeijing University of Chinese MedicineBeijing 100078China

OBJECTIVE:To analyze the current status of clinical trial registration of Traditional Chinese Medicine(TCM)for the treatment of neurological ***:Interventional clinical trials of TCM treatment for ischemic stroke,hemorrhagic stroke,vascular cognitive impairment,tension-type headache before September 22,2020 on the platform of Chinese Clinical Trial Registry(Chi CTR),and Clinical *** were *** researchers independently selected the literature and extracted ***:A total of 180 interventional clinical trials were included for *** of 180 trials,127 were from Chi CTR and 53 from Clinical *** countries primary sponsoring the included trials were China(176,97.8%),and the common categories of primary sponsors were hospital(131,72.8%).Among the study design,the largest proportion of allocation was randomized(172,95.6%),interventional model assignment was parallel(163,90.6%),masking was double blind 49(27.2%),and the sample size was≤400(144,80.0%).The trials were most carried out at a single center(102,56.7%).Among the included studies,112(62.2%)registered on Chi CTR attached the ethical approval *** terms of trial stages,50(27.7%)studies were in phaseⅣ.The mostly used intervention was Chinese herbal medicines(99,55%),acupuncture(68,37.8%)was the *** searching the registration number on China National Knowledge Infrastructure Database and Pub Med,38(21.1%)registered trials were published,including 25 protocol studies and 14 research results with one(NCT02275949)published both the protocol and the ***:Irregular and inadequate reporting,untimely update and publication,insufficient information on traditional medicine unique characteristics,and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological *** efforts need to be made from the above aspects to standardize and improve th

关键词： medicine Chinese traditional ischemic stroke cognitive dysfunction tension-type headache hemorrhagic stroke Chinese Clinical Trial Registry Clinical Trials.gov critical appraisal

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