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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 biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The 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)groups.The 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 groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine 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 analysis.Results: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 response.The developed and externally validated prediction model,which incorporated clinical information,

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

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Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 42-52页

作者： hai-Li huang Guan-Hong Wang liang-liang Niu Xing-Huai Sun Department of Ophthalmology&Visual Science Eye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghai 200031China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China NHC Key Laboratory of Myopia Chinese Academy of Medical Sciencesand Shanghai Key Laboratory of Visual Impairment and Restoration(Fudan University)Shanghai 200031China

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

关键词： choroidal thickness choroidal vascularity index swept-source optical coherence tomography acute primary angle-closure chronic primary angle-closure glaucoma

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Risk Assessment of Deep-Water Horizontal X-Tree Installation

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China Ocean Engineering 2024年第2期38卷 210-220页

作者： MENG Wen-bo FU Guang-ming huang Yi LIU Shu-jie huang liang GAOYong-hai CNOOC China Limited Zhanjiang BranchZhanjiang 524057China Key Laboratory of Unconventional Oil and Gas Development Ministry of Education(China University of Petroleum(East China))Qingdao 266580China

Due to the high potential risk and many influencing factors of subsea horizontal X-tree installation,to guarantee the successful completion of sea trials of domestic subsea horizontal X-trees,this paper established a modular risk evaluation model based on a fuzzy fault tree.First,through the analysis of the main process oftree down and combining the Offshore&Onshore Reliability Data(OREDA)failure statistics and the operation procedure and the data provided by the job,the fault tree model of risk analysis of the tree down installation was established.Then,by introducing the natural language of expert comprehensive evaluation and combining fuzzy principles,quantitative analysis was carried out,and the fuzzy number was used to calculate the failure probability of a basic event and the occurrence probability of a top event.Finally,through a sensitivity analysis of basic events,the basic events of top events significantly affected were determined,and risk control and prevention measures for the corresponding high-risk factors were proposed for subsea horizontal X-tree down installation.

关键词： subsea horizontal X-tree risk assessment fuzzy fault tree modular risk evaluation model

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Energy-information trade-off induces continuous and discontinuous phase transitions in lateral predictive coding

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 79-85页

作者： Zhen-Ye huang Ruyi Zhou Miao huang hai-Jun Zhou Key Laboratory for Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Optics and Photonics Beijing Institute of TechnologyBeijing 100081China Minjiang Collaborative Center for Theoretical Physics Minjiang UniversityFuzhou 350108China

Lateral predictive coding is a recurrent neural network that creates energy-efficient internal representations by exploiting statistical regularity in sensory inputs.Here,we analytically investigate the trade-off between information robustness and energy in a linear model of lateral predictive coding and numerically minimize a free energy quantity.We observed several phase transitions in the synaptic weight matrix,particularly a continuous transition that breaks reciprocity and permutation symmetry and builds cyclic dominance and a discontinuous transition with the associated sudden emergence of tight balance between excitatory and inhibitory interactions.The optimal network follows an ideal gas law over an extended temperature range and saturates the efficiency upper bound of energy use.These results provide theoretical insights into the emergence and evolution of complex internal models in predictive processing systems.

关键词： predictive coding recurrent neural network phase transition internal model free energy

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Design optimization of a hexapod vibration isolation system for electro-optical payload

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Chinese Journal of Aeronautics 2024年第2期37卷 330-342页

作者： Jing LI Weipeng LI Xiaoyan ZHANG hai huang School of Astronautics Beihang UniversityBeijing 100191China

The electro-optical payloads on mobile platforms generally suffer undesirable vibrations generated by maneuvers and turbulence.These vibrations are in six degrees of freedom and cause line-of-sight jitters,resulting in image blurring and loss of tracking accuracy.In this paper,a Hexapod Vibration Isolation System(HVIS)is proposed and optimized to solve this problem.The optimization aims to centralize and minimize the natural frequencies of HVIS,for expanding the vibration isolation bandwidth and improving the vibration isolation in the higher frequency band.Considering that the design space for HVIS is limited and interfered with the frames of the mobile platform,a non-collision algorithm is proposed and applied in the optimization to obtain the feasible optimal design.The optimization result shows that the natural frequency bandwidth has been reduced by 42.9%,and the maximum natural frequency is reduced by 30.2%.The prototypes of initial and optimal designs are manufactured and tested.Both simulated and experimental results demonstrate the validity of the optimization,and the optimal design provides a maximum of 15 dB more isolation in rotation direction than the initial design.

关键词： Electro-optical payload Vibrations Isolation system Hexapod Optimization Non-collision design

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun hai huang Wei-Lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Transfer of Highest Weight Modules and Small Unipotent Representations

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Acta Mathematica Sinica,English Series 2024年第3期40卷 772-791页

作者： hai An HE Jing Song huang Kayue Daniel WONG Department of Mathematics College of SciencesShanghai UniversityShanghai 200444P.R.China Newtouch Center for Mathematics of Shanghai University Shanghai 200444P.R.China Mathematics Research Center School of Science and EngineeringThe Chinese University of Hong KongShenzhen 518172P.R.China

We study the transfer between small special unipotent representations for all equal rank real forms of type E_(6) and E_(7). As a consequence, one can verify these modules are unitarity using the results of Wallach an... 详细信息

关键词： Unipotent representations Wallach representations Transfer of unitary modules

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Species profile and reactivity of volatile organic compounds emission in solvent uses,industry activities and from vehicular tunnels

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Journal of Environmental Sciences 2024年第1期135卷 546-559页

作者： haimei huang Zhangwei Wang Chunhao Dai hai Wu Jia Guo Chunjie Wang Xiaoshan Zhang State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China Hunan Agricultural University Changsha 430106China National Institute of Metrology Beijing 100029China

A survey was conducted of the volatile organic compounds(VOCs)released from sources of solvent use,industry activities and vehicle emissions in Guiyang,a capital city of China.Samples were collected by canisters and analyzed by GC-MS-FID.The species profiles of VOCs emitted from sources were obtained.Results showed that xylenes,ethylbenzene,acetone and dichloromethane were the characteristics species for painting,2-propanol and ethyl acetate for printing,α-pinene for solid wood furniture manufacturing,and 2-butanone for biscuit baking.These characteristics species could be as tracers for the sources respectively.In most of samples from the solvent use,the benzene/toluene(B/T)ratio was less than 0.3,indicating that the ratio could be as the indicator for tracing the solvent use related sources.The results also suggested that the toluene/xylene(T/X)ratio be as the indicator to distinguish the VOCs sources of painting(2).Aromatics contributed the most to ozone formation potential(OFP)of most painting and non-paper printing sources,and oxygen-containing VOCs(OVOCs)were major species contributing to OFP of the sources from food production and paper printing.The OFP of the VOCs emissions from vehicle in tunnels and from other manufactures were dominated by both aromatics and alkenes.Theα-pinene could explain 56.94%and 32.54%of total OFP of the VOCs sources from filing cabinet and solid wood furniture manufacturing,which was rarely been involved in previous studies of VOCs source profiles,indicating that the species of concern for VOCs sources are still insufficient at present.

关键词： Volatile organic compounds(VOCs) Species profile BTEX ratio Source reactivity

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Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 420-434页

作者： Liu-Hui huang Jiao Lyu Sheng Chen Ting-Yi liang Yu-Qing Rao Ping Fei Jing Li hai-Ying Jin Pei-Quan Zhao Department of Ophthalmology Shanghai Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Ophthalmology Shanghai Tenth People’s Hospital Affiliated with Shanghai Tongji University School of MedicineShanghai 200072China Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVictoria 3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVictoria 3002Australia Shenzhen Eye Hospital Shenzhen Key Laboratory of OphthalmologyAffiliated Shenzhen Eye Hospital of Jinan UniversityShenzhen 518040Guangdong ProvinceChina Department of Ophthalmology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased auto

关键词： cataract posterior capsular opacification lens epithelial cell hyperosmotic stress autophagy apoptosis transient receptor potential vanilloid 1

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Who could and should give exercise prescription:Physicians,exercise and health scientists,fitness trainers,or ChatGPT?

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Journal of Sport and Health Science 2024年第3期13卷 368-372页

作者： Weimo Zhu Wenguang Geng Lingling huang Xiong Qin Zezhao Chen hai Yan Yunnan Plateau Thermal Health Industry Innovation Research Institute Tengchong 679100China Department of Kinesiology&Community Health University of Illinois at Urbana-ChampaignUrbanaIL 61801USA Department of Physical Education Nanjing Agricultural UniversityNanjing 210095China School of Sports Engineering Beijing Sport UniversityBeijing 100084China School of Strength and Conditioning Training Beijing Sport UniversityBeijing 100084China

Benefits of exercise for personal health,as well as preventing and treating chronic diseases,have been well documented during the past several decades.1 Exercise prescription is a specialized field that involves assessing an individual’s health status,fitness level,and specific goals to create a tailored exercise program based often on the FITT-VP principle.

关键词： prescription diseases assessing

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