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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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给水厂典型工艺碳排放特征与影响因素

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环境科学 2024年第1期45卷 123-130页

作者：张翔宇胡建坤马凯高欣慰魏月华韩宏大李克勋天津水务集团有限公司天津300042 南开大学环境科学与工程学院天津300350 天津市自来水集团有限公司天津300040 天津市自来水集团有限公司凌庄水厂天津300381

基于实际运行工况和数据监测基础,对天津市给水厂典型工艺的碳排放特征进行研究.给水厂总碳排放强度(以CO_(2)-eq计)为0.254 kg·m^(-3),其中电耗和药耗碳排放占比分别为81.76%和9.15%.给水厂的关键电耗碳排放环节为送水泵房、超滤膜工... 详细信息

基于实际运行工况和数据监测基础,对天津市给水厂典型工艺的碳排放特征进行研究.给水厂总碳排放强度(以CO_(2)-eq计)为0.254 kg·m^(-3),其中电耗和药耗碳排放占比分别为81.76%和9.15%.给水厂的关键电耗碳排放环节为送水泵房、超滤膜工艺和进水泵房,分别占总电耗碳排放的50.99%~73.51%、17.64%~20.70%和17.97%~22.40%.次氯酸钠对药耗碳排放的贡献率为89.12%~90.30%,其余依次为三氯化铁、聚合氯化铝和硫酸铵.传统净水工艺单元的电耗碳排放强度依次为:进水泵房>快滤池>沉淀池,在深度处理工艺线中依次为:进水泵房>超滤膜>机械混凝>澄清池.快滤池工艺线和超滤膜工艺线的碳排放强度分别为0.0709 kg·m^(-3)和0.1090 kg·m^(-3).超滤膜工艺能节约23%的药剂用量,而电耗碳排放是传统处理工艺的2倍.对关键环节的碳排放影响因素分析结果表明,浊度、pH、氨氮和温度等原水水质参数与次氯酸钠碳排放强度显著相关;出厂水压力、日送水量与送水泵房碳排放强度呈显著的线性回归关系,相关水质和水压调控措施可以有效减少给水厂碳排放.

关键词：碳排放给水厂超滤膜快滤池电耗药耗

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X-ray diagnosis of synchronous multiple primary carcinoma in the upper gastrointestinal tract

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World Journal of Gastroenterology 2011年第14期17卷 1817-1824页

作者： Zhi-Hao Yang Jian-Bo Gao Song-wei yue hua Guo Xue-hua Yang Department of Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 Henan Province China

AIM:To analyze the radiological features of multiple primary carcinoma (MPC) in the upper gastrointestinal (GI) tract,study its biological characteristics and evaluate X-ray examination in its diagnosis. METHODS:Hypotonic double-contrast GI radiography was performed in 59 multiple primary carcinoma cases,pathologically proved by surgery or endoscopy biopsy. Radiological findings were analyzed. RESULTS:Of the 59 cases,esophageal MPC (EMPC) was seen in 24,esophageal and gastric MPC (EGMPC) in 27 and gastric MPC (GMPC) in 8. Of the 49 lesions found in 24 EMPC,hyperplastic type was seen in 23,medullary type in 9. The lesions were located at the upper (n = 17),middle (n = 19) or lower (n = 13) segment of the esophagus. In 27 EGMPC,the esophageal lesions were located at the middle (n = 16) or lower (n = 11) segment of the esophagus,while the gastric le-sions were located at the gastric cardia (n = 16),fundus (n = 1),body (n = 3) and antrum (n = 7). The esophageal lesions were mainly of the hyperplastic type (n = 12) or medullary type (n = 7),while the gastric lesions were mainly of the hyperplastic type (n = 18). A total of 119 lesions in the 59 patients with synchronous multiple carcinoma were proved by surgery or endoscopy biopsy,and preoperative upper radiographic examination detected 100 of them (84.03% sensitivity). Eighteen (52.94%) of the T1 lesions were found during preoperative diagnosis by radiographic examination. Moreover,only 3 (3.53%) of the T2-4 lesions were misdiagnosed. CONCLUSION:Hypotonic double-contrast upper gastrointestinal examination,providing accurate information about lesion morphology,location and size,can serve as a sensitive technique for the preoperative diagnosis of MPC.

关键词： Multiple primary carcinoma Upper gastrointestinal tract Radiography

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Microneedle patch loaded with ferritin-nanocaged doxorubicin for locally targeted drug delivery and efficient skin cancer treatment

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Particuology 2024年第5期88卷 282-289页

作者： Feng Li Yuan Yang hua yue Shuang Wang Xiao Zhang wei wei State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190China Key Laboratory of Biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China

Ferritin has emerged as a promising nanocarrier for delivering therapeutic agents to ***,the limited drug loading and the off-target impacts after systemic administration remain challenges for cancer treatment with ferritin-based ***,we develop a microneedle patch loaded with ferritin-nanocaged doxorubicin(DoxFe@Fn/MN)for skin cancer ***,doxorubicin(Dox)is encapsulated in ferritin(Fn)using an iron core-assisted strategy,which results in a 3.4-fold increase in Dox loading compared to the direct loading ***,a polyvinyl alcohol-based microneedle(MN)patch is used for the transdermal delivery of DoxFe@Fn,enabling targeted tumour accumulation of DoxFe@Fn and preventing off-target *** released DoxFe@Fn can bind to CD71 highly expressed on skin cancer cells,facilitating its *** a result,the DoxFe@Fn/MN therapy presents a robust antitumour effect in a melanoma tumour model,showing its potential as a promising therapeutic modality for skin cancer treatment.

关键词： Ferritin Microneedle Skin cancer Drug delivery

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Micro segment analysis of supercritical methane thermal-hydraulic performance and pseudo-boiling in a PCHE straight channel

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Petroleum Science 2024年第2期21卷 1275-1289页

作者： Qian Li Zi-Jie Lin Liu Yang yue Wang yue Li wei-hua Cai Laboratory of Thermo-Fluid Science and Nuclear Engineering Northeast Electric Power UniversityJilin132000JilinChina School of Energy and Power Engineering Northeast Electric Power UniversityJilin132000JilinChina

The printed circuit heat exchanger(PCHE) is receiving wide attention as a new kind of compact heat exchanger and is considered as a promising vaporizer in the LNG process. In this paper, a PCHE straight channel in the length of 500 mm is established, with a semicircular cross section in a diameter of 1.2 *** simulation is employed to investigate the flow and heat transfer performance of supercritical methane in the channel. The pseudo-boiling theory is adopted and the liquid-like, two-phase-like, and vapor-like regimes are divided for supercritical methane to analyze the heat transfer and flow *** results are presented in micro segment to show the local convective heat transfer coefficient and pressure drop. It shows that the convective heat transfer coefficient in segments along the channel has a significant peak feature near the pseudo-critical point and a heat transfer deterioration when the average fluid temperature in the segment is higher than the pseudo-critical point. The reason is explained with the generation of vapor-like film near the channel wall that the peak feature related to a nucleateboiling-like state and heat transfer deterioration related to a film-boiling-like state. The effects of parameters, including mass flow rate, pressure, and wall heat flux on flow and heat transfer were *** calculating of the averaged heat transfer coefficient of the whole channel, the traditional method shows significant deviation and the micro segment weighted average method is adopted. The pressure drop can mainly be affected by the mass flux and pressure and little affected by the wall heat flux. The peak of the convective heat transfer coefficient can only form at high mass flux, low wall heat flux, and near critical pressure, in which condition the nucleate-boiling-like state is easier to appear. Moreover,heat transfer deterioration will always appear, since the supercritical flow will finally develop into a filmboiling-like state. So hea

关键词： Printed circuit heat exchanger Vaporization Supercritical methane Pseudo-boiling Micro segment analysis

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Synthesis of poly(thiourethane-alt-thioester)by alternating ring-opening copolymerization of N-thiocarboxyanhydrides and episulfides

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Science China Chemistry 2024年第9期67卷 3091-3097页

作者： wei Xiong Tianjun yue Haiwang Lai Chunyan Lyu weimin Ren hua Lu Beijing National Laboratory for Molecular Sciences Center for Soft Matter Science and EngineeringKey Laboratory of Polymer Chemistry and Physics of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116081China

Polythiourethanes(PTU)and polythioesters(PTE)derived from renewable sources are emerging sustainable polymers for their excellent degradability and ***,P(TU-alt-TE)copolymers have been rare and challenging to ***,we report the efficient synthesis of novel P(TU-alt-TE)copolymers via the alternating copolymerization of N-thiocarboxyanhydrides(NTA)/episufides(ES)and provide mechanistic insight into the alternating chain propagation process via density functional theory(DFT)*** incorporation of ESs into traditional peptide backbone is capable of adjusting the glass transition temperature below thermal decomposition temperature,which confers better thermal processability by regulating the rigidity of the backbone and the hydrogen bond interaction among the polymer *** PTUs with tailored properties are accessible by altering the feeding ratio of NTAs and(bifunctional)***,the thiourethane in the backbone can endow interesting underwater adhesion properties to the *** the broad scope of NTA and ES monomers,this method is expected to provide a promising and general route to a wide range of P(TU-alt-TE)copolymers with diverse properties.

关键词： poly(thiourethane-alt-thioester) alternating ring-opening copolymerization N-thiocarboxyanhydrides episulfides

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Elite Dung Beetle Optimization Algorithm for Multi-UAV Cooperative Search in Mountainous Environments

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Journal of Bionic Engineering 2024年第4期21卷 1677-1694页

作者： Xiaoyong Zhang wei yue The College of Marine Electrical Engineering Dalian Maritime UniversityDalian116026China

This paper aims to address the problem of multi-UAV cooperative search for multiple targets in a mountainous environment,considering the constraints of UAV dynamics and prior environmental ***,using the target probability distribution map,two strategies of information fusion and information diffusion are employed to solve the problem of environmental information inconsistency caused by different UAVs searching different areas,thereby improving the coordination of UAV ***,the task region is decomposed into several high-value sub-regions by using data clustering *** on this,a hierarchical search strategy is proposed,which allows precise or rough search in different probability areas by adjusting the altitude of the aircraft,thereby improving the search ***,the Elite Dung Beetle Optimization Algorithm(EDBOA)is proposed based on bionics by accurately simulating the social behavior of dung beetles to plan paths that satisfy the UAV dynamics constraints and adapt to the mountainous terrain,where the mountain is considered as an obstacle to be ***,the objective function for path optimization is formulated by considering factors such as coverage within the task region,smoothness of the search path,and path *** effectiveness and superiority of the proposed schemes are verified by the simulation.

关键词： Mountainous environment Multi-UAV cooperative search Environment information consistency Elite dung beetle optimization algorithm(EDBOA) Path planning

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Manipulation of internal blockage in triangular triple quantum dot

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Chinese Physics B 2024年第5期33卷 588-593页

作者：齐月魏建华 Department of Physics Renmin UniversityBeijing 100876China

We utilize the calculation of hierarchical equations of motion to demonstrate that the spin-dependent properties between adjacent quantum dots(QDs)can be changed by breaking the internal symmetry configuration,corresponding to the inversion of dominant chiral *** the linear triple quantum dots(LTQDs)connected to two electron reservoirs,we can observe that the blockage appears at the triangle triple quantum dots(TTQDs)by gradually increasing the coupling strength between next-nearest double *** the initial coupling between LTQDs has altered,the internal chiral circulation also undergoes the corresponding transform,thus achieving qualitative regulation and detection of the blocking *** also investigate the response of the chiral circulation to the dot–lead coupling strength,indicating the overall robust chiral circulation of the TTQDs frustration.

关键词： quantum dots chiral topology blocking

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EPR-Net: constructing a non-equilibrium potential landscape via a variational force projection formulation

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National Science Review 2024年第7期11卷 135-147页

作者： yue Zhao wei Zhang Tiejun Li Center for Data Science Peking University Zuse Institute Berlin Department of Mathematics and Computer Science Freie Universit?t Berlin Laboratory of Mathematics and Applied Mathematics(LMAM)and School of Mathematical Sciences Peking University Center for Machine Learning Research Peking University

We present EPR-Net, a novel and effective deep learning approach that tackles a crucial challenge in biophysics: constructing potential landscapes for high-dimensional non-equilibrium steady-state ***-Net leverages a nice mathematical fact that the desired negative potential gradient is simply the orthogonal projection of the driving force of the underlying dynamics in a weighted inner-product ***, our loss function has an intimate connection with the steady entropy production rate(EPR),enabling simultaneous landscape construction and EPR estimation. We introduce an enhanced learning strategy for systems with small noise, and extend our framework to include dimensionality reduction and the state-dependent diffusion coefficient case in a unified fashion. Comparative evaluations on benchmark problems demonstrate the superior accuracy, effectiveness and robustness of EPR-Net compared to existing methods. We apply our approach to challenging biophysical problems, such as an eight-dimensional(8D)limit cycle and a 52D multi-stability problem, which provide accurate solutions and interesting insights on constructed landscapes. With its versatility and power, EPR-Net offers a promising solution for diverse landscape construction problems in biophysics.

关键词： high-dimensional potential landscape non-equilibrium system entropy production rate dimensionality reduction deep learning

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Treg Immunomodulation Contributes to the Anti-atherosclerotic Effects of Huxin Formula in ApoE-/- Mice

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Chinese Journal of Integrative Medicine 2024年第10期30卷 896-905页

作者： OU Xiao-min CAI Jing HU Xiao-yue ZENG Qiao-huang LAN Tao-hua JIANG wei The Second Clinical College of Guangzhou University of Chinese Medicine Department of Cardiology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases

Objective: To explore the effects of Huxin formula（HXF） in curtailing atherosclerosis and its underlying mechanism. Methods: According to random number table method, 24 specific pathogen free male ApoE-/-mice were randomly divided into model group, HXF low-dose（HXF-L） group（8.4 g/kg daily）, HXF high-dose（HXF-H） group（16.8 g/kg daily）, and pravastatin（8 mg/kg daily） group in Experiment Ⅰ（n=6 per group）. C57BL/6J mice served as the control group（n=6）. ApoE-/-mice in HXF-L, HXF-H, pravastatin groups were fed a Western diet and administered continuously by gavage for 12 weeks, while C57BL/6J mice in the control group were fed conventional lab mouse chow for 12 weeks. Further, Tregs were depleted by weekly intraperitoneal injection of purified anti-mouse CD25 antibody（PC61, 250 μg per mouse） for 4 weeks in Experiment Ⅱ（n=6 per group）. Oil Red O and Masson staining were used to evaluate the plaque area and aortic root fibrosis. The CD4+CD25+Foxp3+Treg counts in the lymph nodes and spleen cells were detected using flow cytometric analysis. The transforming growth factor-β1（TGF-β1）, interleukin（IL）-10, and IL-6 serum levels were examined by MILLIPLEX?MAP technology. Quantitative real-time reverse transcription PCR（qRT-PCR） and Western blot were utilized to assess the expression of TGF-β mRNA and protein in the aorta. The expression of CD4+T lymphocytes, macrophages and smooth muscle cells in the aortic root were detected by immunofluorescence staining. Results: HXF reduced plaque area in ApoE-/-mice（P0.05）. Also, HXF upregulated the expression of TGF-β mRNA and protein in the aorta（P<0.05）. Additionally, HXF attenuated CD4+T lymphocytes, macrophages and smooth muscle cells in aortic root plaque（P<0.01）. Furthermore, the depletion

关键词： Huxin Formula Tregs atherosclerosis immune responses inflammation

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