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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall hong-xing wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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Impact of Mo/Ni alloying on microstructural modulation and low-temperature toughness of high-strength low-alloy steel

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Journal of Iron and Steel Research(International) 2024年第7期31卷 1746-1762页

作者： Wei Liu hong-li Zhao Bing-xing wang Yong Tian State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819LiaoningChina

The high-strength low-alloy steel plates with varying Ni/Mo contents were manufactured using the thermos-mechanical control *** investigation was conducted to explore the effect of Ni/Mo microalloying on microstructure evolution and mechanical properties of the *** results revealed that the increase in Ni content from 1 to 2 wt.%reduced the transition temperature of ferrite and the growth range of ferritic grain was narrowed,which promoted grain *** optimized combination of grain size,high-angle grain boundaries(HAGBs),and martensite-austenite(M-A)islands parameter contributed to the excellent impact toughness of S1 steel at-100℃(impact absorbed energy of 218.2 J at-100℃).As the Mo increases from 0 to 2 wt.%,the matrix structure changes from multiphase structure to granular bainite,which increases the average effective grain size to~4.62 pm and reduces HAGBs proportion to~36.22%.With these changes,the low-temperature impact toughness of S3 steel is *** addition,based on the analysis of the characteristics of crack propagation path,it was found that M-A islands with low content(~2.21%)and small size(~1.76 pm)significantly retarded crack propagation,and the fracture model of M-A islands with different morphologies was further ***,correlation between behaviour of delamination and toughness was further analysed by observing delamination size and impact energy parameters.

关键词： High-strength low-alloy steel Microstructural regulation Ni addition Mo addition Crack propagation Low-temperature toughness

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Bunch-length measurement at a bunch-by-bunch rate based on time–frequency-domain joint analysis techniques and its application

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Nuclear Science and Techniques 2024年第4期35卷 165-175页

作者： hong-Shuang wang xing Yang Yong-Bin Leng Yi-Mei Zhou Ji-Gang wang Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China University of Chinese Academy of Sciences Beijing 100049China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230026China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201204China

This paper presents a new technique for measuring the bunch length of a high-energy electron beam at a bunch-by-bunch rate in storage *** technique uses the time–frequency-domain joint analysis of the bunch signal to obtain bunch-by-bunch and turn-by-turn longitudinal parameters,such as bunch length and synchronous *** bunch signal is obtained using a button electrode with a bandwidth of several *** data acquisition device was a high-speed digital oscilloscope with a sampling rate of more than 10 GS/s,and the single-shot sampling data buffer covered thousands of *** bunch-length and synchronous phase information were extracted via offline calculations using Python *** calibration coefficient of the system was determined using a commercial streak ***,this technique was tested on two different storage rings and successfully captured various longitudinal transient processes during the harmonic cavity debugging process at the Shanghai Synchrotron Radiation Facility(SSRF),and longitudinal instabilities were observed during the single-bunch accumulation process at Hefei Light Source(HLS).For Gaussian-distribution bunches,the uncertainty of the bunch phase obtained using this technique was better than 0.2 ps,and the bunch-length uncertainty was better than 1 *** dynamic range exceeded 10 *** technology is a powerful and versatile beam diagnostic tool that can be conveniently deployed in high-energy electron storage rings.

关键词： Bunch-by-bunch diagnostic Bunch-length measurement Synchronous phase measurement Joint time–frequency-domain analysis Longitudinal instability

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Dynamic plugging regulating strategy of pipeline robot based on reinforcement learning

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Petroleum Science 2024年第1期21卷 597-608页

作者： xing-Yuan Miao hong Zhao College of Mechanical and Transportation Engineering China University of PetroleumBeijing102249China

Pipeline isolation plugging robot (PIPR) is an important tool in pipeline maintenance operation. During the plugging process, the violent vibration will occur by the flow field, which can cause serious damage to the pipeline and PIPR. In this paper, we propose a dynamic regulating strategy to reduce the plugging-induced vibration by regulating the spoiler angle and plugging velocity. Firstly, the dynamic plugging simulation and experiment are performed to study the flow field changes during dynamic plugging. And the pressure difference is proposed to evaluate the degree of flow field vibration. Secondly, the mathematical models of pressure difference with plugging states and spoiler angles are established based on the extreme learning machine (ELM) optimized by improved sparrow search algorithm (ISSA). Finally, a modified Q-learning algorithm based on simulated annealing is applied to determine the optimal strategy for the spoiler angle and plugging velocity in real time. The results show that the proposed method can reduce the plugging-induced vibration by 19.9% and 32.7% on average, compared with single-regulating methods. This study can effectively ensure the stability of the plugging process.

关键词： Pipeline isolation plugging robot Plugging-induced vibration Dynamic regulating strategy Extreme learning machine Improved sparrow search algorithm Modified Q-learning algorithm

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Gut Microbiota-brain Axis

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Chinese Medical Journal 2016年第19期129卷 2373-2380页

作者： hong-xing wang Yu-Ping wang Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Center of Epilepsy Beijing Institute for Brain Disorders Laboratory of Brain Disorders Capital Medical University Beijing 100069 China

Objective：To systematically review the updated information about the gut microbiota-brain *** Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study ***：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully *** microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous ***,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain *** microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut ***：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

关键词： Gut Microbiota Gut Microbiota-brain Axis Metagenomics Microbiome

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Extracorporeal membrane oxygenation versus cardiopulmonary bypass during transcatheter aortic valve implantation: a meta-analysis of survival benefits

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World Journal of Emergency Medicine 2024年第4期15卷 306-310页

作者： Huiruo Liu Liangshan wang xing Hao Zhongtao Du Chenglong Li hong wang Xiaotong Hou Centre for Cardiac Intensive Care Beijing Institute of HeartLung and Blood Vessel DiseasesBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Since its approval by the Food and Drug Administration in 2011,transcatheter aortic valve implantation(TAVI)has rapidly evolved to become the preferred ultimate intervention for high-and intermediate-risk patients with severe symptomatic aortic stenosis.[1]This is due to its non-open-heart,minimally invasive and off-pump advantages.[1]Nevertheless,as a result of the frequent frailty and comorbidity profiles of patients undergoing TAVI,such as advanced cardiac dysfunction and extensive coronary artery disease,or technically difficult anatomy for the procedure itself,[2-4]it is common for these patients to experience critical circulatory collapse *** factors are linked to elevated mortality rates,necessitating suitable mechanical circulatory support(MCS)to reverse the disastrous situations.[5]

关键词： anatomy bypass elevated

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： hong Weng Kang-Ping Xiong wang wang Kai-Yu Qian Shuai Yuan Gang wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu xing Huang Hang Zheng xing-Huan wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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GPa-level pressure-induced enhanced corrosion resistance in TiZrTaNbSn biomedical high-entropy alloy

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China Foundry 2024年第3期21卷 265-275页

作者： Xiao-hong wang Yu-lei Deng Qiao-yu Li Zhi-xin Xu Teng-fei Ma xing Yang Duo Dong Dong-dong Zhu Xiao-hong Yang Key Laboratory of Air-driven Equipment Technology of Zhejiang Province Quzhou UniversityQuzhou 324000ZhejiangChina School of Materials Science and Engineering Taizhou UniversityTaizhou 318000ZhejiangChina

TiZrTaNb-based high-entropy alloys(HEAs)are research frontier of biomedical materials due to their high hardness,good yield strength,excellent wear resistance and corrosion ***,as an essential trace element in the human body that plays a significant role in physiological *** has stable chemical properties and a low elastic *** this study,a new material,TiZrTaNbSn HEAs,was proposed as a potential biomedical *** Ti_(35)Zr_(25)Ta_(15)Nb_(15)Sn_(10)biomedical high-entropy alloys(BHEAs)were successfully prepared through an arc melting furnace and then remelted using a German high-temperature and high-pressure apparatus under GPa-level(4 GPa and 7 GPa).The precipitation behavior of the needle-like HCP-Zr_(5)Sn_(3)phase that precipitates discontinuously at the grain boundary was successfully *** phase constitution,microstructure,and corrosion resistance of the alloy were *** results show that the needle-like HCP-Zr_(5)Sn_(3)phase is eliminated and the(Zr,Sn)-rich nano-precipitated phase is precipitated in the microstructure under high pressure,which leads to the narrowing of grain boundaries and consequently improves the corrosion resistance of the *** addition,the formation mechanisms of(Zr,Sn)-rich nanoprecipitates in BHEAs were *** Zr and Sn dissolve in the matrix due to the effect of high pressure,during the cooling process,they precipitate to form a(Zr,Sn)-rich nano-precipitated phase.

关键词： biomedical HEAs precipitation grain boundary corrosion resistance TiZrTaNbSn

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Corrosion resistance behavior of gradient microstructure induced by punching deformation and recovery treatment on cupronickel alloy surface

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Rare Metals 2017年第12期36卷 971-976页

作者： Xiang-Yang Mao Hao Chen hong-Yan Yang Yao Yao hong-xing wang Jiangsu Key Laboratory of Advanced Structural Materials and Application Technology School of Materials EngineeringNanjing Institute of Technology Nanjing 211167 China

In this study, the gradient grain induced by punching deformation and recovery treatment on a cupronickel alloy surface sample were investigated, and their effects on corrosion resistance were measured by atom force microscopy(AFM), X-ray diffraction(XRD),electrochemical measurement, electron work function(EWF), and contact electrical resistance(CER). The cupronickel alloy surface experienced punching deformation for 60 min and recovery at 300 ℃ for 1 h to produce gradient surface. The grain size measured by XRD is bigger than that measured by AFM, due to X-ray intensity of95 % produced at the depth of 12-20 μm for the crystal planes of(111),(200), and(220). The gradient grain surface, compared to the original surface, shows a 13.7-fold decrease in passivation current density(i), and corrosion potential(Ec) increases by approximately 9.8 %. These results are attributable to the increase in EWF and formation of passivation film with better adhesion and compactness after treatment.

关键词： Gradient grain Corrosion resistance Electron work function Punching deformation

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Numerical and Experimental Analysis of the Aerodynamic Torque for Axle-Mounted Train Brake Discs

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Fluid Dynamics & Materials Processing 2024年第8期20卷 1867-1882页

作者： Nan Liu Chen hong Xinchao Su xing Jin Chen Jiang Yuqi Shi Bingkun wang Brake System Laboratory CRCC(Qingdao)Vehicle Inspection Station Co.Ltd.Qingdao266031China Brake System Laboratory CRRC Qingdao Sifang Rolling Stock Research Institute Co.Ltd.Qingdao266031China The State Key Laboratory of Heavy-Duty and Express High-Power Electric Locomotive Central South UniversityChangsha410075China Key Laboratory of Traffic Safety on Track of Ministry of Education School of Traffic&Transportation EngineeringCentral South UniversityChangsha410075China National&Local Joint Engineering Research Center of Safety Technology for Rail Vehicle Changsha410075China

As the velocity of a train increases,the corresponding air pumping power consumption of the brake discs increases *** the present experimental study,a standard axle-mounted brake disc with circumferential pillars was analyzed using a 1:1 scale model and a test rig in a wind *** particular,three upstream velocities were selected on the basis of earlier investigations of trains operating at 160,250,and 400 km/h,***,3D steady computational fluid dynamics(CFD)simulations of the flow field were conducted to compare with the wind tunnel test *** results for a 3-car train at 180 km/h demonstrated:(1)good agreement between the air resistance torques obtained from the wind tunnel tests and the related numerical results,with differences ranging from 0.95%to 5.88%;(2)discrepancies ranging from 3.2 to 3.8 N·m;(3)cooling ribs contributing more than 60%of the air resistance torque;(4)the fast rotation of brake discs causing a significantly different flow field near the bogie area,resulting in 25 times more air pumping power loss than that obtained in the stationary brake-disc case.

关键词： Axle-mounted train brake disc aerodynamic torque wind tunnel test numerical simulation

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