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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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Epitaxial growth of Fe/Ag single crystal superlattices and their magnetic properties

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International Journal of Minerals,Metallurgy and Materials 2009年第1期16卷 71-76页

作者： Yu Gu Fei Zeng Fang Lv Yu-li Gu Pei-yong yang feng Pan Laboratory of Advanced Materials Department of Materials Science and Engineering Tsinghua University Beijing 100084 China

Single crystal Fe/Ag（001） superlattices with various periodicities were fabricated using ultrahigh vacuum evaporation deposition. It was found that single crystal bcc Fe layers and single crystal fcc Ag layers can epitaxially grow on a single crystal Ag buffer layer alternately, which was deposited on NaCl single crystal chips by ion beam assisted deposition. The magnetic measurements of the superlattices reveal an oscillation coupling between ferromagnetism and antiferromagnetism as a function of the Ag layer thickness. The oscillation period, which is 1 nm （5 Ag layers）, is in good agreement with the calculated values when the Ag thickness is greater than 1.5 nm. While the thickness of the Ag spacer layer decreases to 1 nm, the oscillation coupling varies from calculations, which can be attributed to the intermixing of the interlayers according to the annealing results.

关键词： Fe/Ag superlattices magnetization oscillating periodicity annealing

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Management of chronic hepatitis B in pregnancy

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World Journal of Gastroenterology 2012年第33期18卷 4517-4521页

作者： Guo-Rong Han Chuan-Lu Xu Wei Zhao yong-feng yang Department of Gynecology and Obstetrics The Second Affiliated Hospital of the Southeast UniversityNanjing 210003Jiangsu ProvinceChina Department of Infectious Diseases The Second Affiliated Hospital of the Southeast UniversityNanjing 210003Jiangsu ProvinceChina

Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in thechild-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.

关键词： Chronic hepatitis B Hepatitis B virus Mother-to-child transmission Perinatal transmission Pregnancy Vertical transmission Antiviral therapy

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Efficient Monolithic Perovskite/Silicon Tandem Photovoltaics

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Energy & Environmental Materials 2024年第3期7卷 268-281页

作者： yong Wang Yu Wang feng Gao Deren yang State Key Laboratory of Silicon Materials and School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027China ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 310014China Department of Physics Chemistry and Biology(IFM)Linköping UniversityLinköping 58183Sweden

Tunable bandgaps make halide perovskites promising candidates for developing tandem solar cells(TSCs),a strategy to break the radiative limit of 33.7%for single-junction solar *** perovskites with market-dominant crystalline silicon(c-Si)is particularly attractive;simple estimates based on the bandgap matching indicate that the efficiency limit in such tandem device is as high as 46%.However,state-of-the-art perovskite/c-Si TSCs only achieve an efficiency of~32.5%,implying significant challenges and also rich *** this review,we start with the operating mechanism and efficiency limit of TSCs,followed by systematical discussions on wide-bandgap perovskite front cells,interface selective contacts,and electrical interconnection layer,as well as photon management for highly efficient perovskite/c-Si *** highlight the challenges in this field and provide our understanding of future research directions toward highly efficient and stable large-scale wide-bandgap perovskite front cells for the commercialization of perovskite/c-Si TSCs.

关键词： 2-terminal electrical interconnection perovskite/silicon tandem photovoltaics photon management wide-bandgap perovskites

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On the Probability of Generating a Primitive Matrix

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Journal of Systems Science & Complexity 2024年第4期37卷 1755-1771页

作者： CHEN Jingwei feng yong LIU yang WU Wenyuan Chongqing Key Laboratory of Automated Reasoning and Cognition Chongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China Chongqing College University of Chinese Academy of SciencesChongqing 400714China Key Laboratory of Advanced Manufacturing Technology of Ministry of Education Guizhou UniversityyGuiyang 550025China Information Science and Engineering Chongqing Jiaotong UniversityChongqing 400074China

Given a k×n integer primitive matrix A(i.e.,a matrix can be extended to an n×n unimodular matrix over the integers)with the maximal absolute value of entries‖A‖bounded by an integer λ from above,the authors study the probability that the m×n matrix extended from A by appending other m-k row vectors of dimension n with entries chosen randomly and independently from the uniform distribution over{0,1,…,λ-1}is still *** authors present a complete and rigorous proof of a lower bound on the probability,which is at least a constant for fixed m in the range[k+1,n-4].As an application,the authors prove that there exists a fast Las Vegas algorithm that completes a k×n primitive matrix A to an n×n unimodular matrix within expected O(n^(ω)log‖A‖)bit operations,where O is big-O but without log factors,ω is the exponent on the arithmetic operations of matrix multiplication.

关键词： Integer matrix matrix completion probabilistic algorithm unimodular matrix

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Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis

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World Journal of Gastroenterology 2008年第5期14卷 764-770页

作者： Yin-Ying Lu Chun-Ping Wang Lin Zhou Yan Chen Shu-Hui Su yong-Yi feng yong-Ping yang Department of Gastroenterology 302 Hospital of Chinese PLA Beijing 100039 China

AIM:To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS:Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS:A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis.

关键词： Platelet activating factor Kupffer cells Receptor Cirrhosis

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Hepatic stellate cells may be potential effectors of platelet activating factor induced portal hypertension

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World Journal of Gastroenterology 2008年第2期14卷 218-223页

作者： Yan Chen Chun-Ping Wang Yin-Ying Lu Lin Zhou Shu-Hui Su Hong-Jun Jia yong-Yi feng yong-Ping yang Department of Gastroenterology 302 Hospital of PLA Beijing 100039 China

AIM: To determine platelet activating factor (PAF) receptor expression in cirrhotic hepatic stellate ***: Hepatic stellate cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium after overnight culture. We determined the PAF receptor in hepatic stellate cells by saturation binding technique and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the effects of PAF and its antagonist BN52021 on prostaglandin E2 (PGE2) release by stellate ***: Scatchard analysis indicated the presence of PAF receptor with dissociation constant (Kd) of 4.66 nmol/L and maximum binding capacity (Bmax) of 24.65 fmol/μg in cirrhotic stellate cells. Compared with the control, the maximum PAF binding capacity increased significantly (Bmax: 24.65 ± 1.96 fmol/μg. DNA, R = 0.982 vs 5.74 ± 1.55 fmol/μg. DNA, R = 0.93; P 0.05). Consistent with the receptor binding data, the mRNA expression of PAF receptor was increased significantly in cirrhotic stellate cells. PAF in a concentration-dependent manner induced PGE2 synthesis in cirrhotic hepatic stellate cells, but the effects were blocked significantly by ***: Cirrhosis sensitizes hepatic stellate cells to PAF by elevating its receptor level and hepatic stellate cells maybe potential effectors of PAF induced portal hypertension.

关键词： Platelet activating factor Hepatic stellate cells Kupffer cells Cirrhosis Receptor

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Molecular Dynamics Simulation Studies on the Micromorphology and Proton Transport of Nafion/Ti_(3)C_(2)T_(x) Composite Membrane

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Chinese Journal of Polymer Science 2024年第3期42卷 373-387,I0009页

作者： Zhi-Yue Han Su-Peng Pei Chun-yang Yu yong-feng Zhou School of Chemical and Environmental Engineering Shanghai Institute of TechnologyShanghai 201418China School of Chemistry&Chemical Engineering Frontiers Science Center for Transformative MoleculesShanghai Key Laboratory of Electrical Insulation and Thermal AgingShanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Green and High-end Utilization of Salt Lake Resources Chinese Academy of SciencesXining 810008China

The perfluorosulfonic acid(PFSA) membrane doped with two-dimensional conductive filler Ti_(3)C_(2)T_(x) is a fuel cell proton exchange membrane with high application potential. Experimental studies showed that the proton conductivity of Nafion/Ti_(3)C_(2)T_(x) composite membrane is improved significantly compared with that in pure Nafion. However, the microscopic mechanism of doping on the enhancement of membrane performance is remain unclear now. In this work, molecular dynamics simulation was used to investigate the microscopic morphology and proton transport behaviors of Nafion/Ti_(3)C_(2)T_(x) composite membrane at the molecular level. The results shown that there were significant differences about the diffusion kinetics of water molecules and hydroxium ions in Nafion/Ti_(3)C_(2)T_(x) at low and high hydration levels in the nanoscale *** the increase of water content, Ti_(3)C_(2)T_(x) in membrane was gradually surrounded by ambient water molecules to form a hydration layer, and forming a relatively continuous proton transport channel between Nafion polymer and Ti_(3)C_(2)T_(x) monomer. The continuous proton transport channel could increase the number of binding sites of proton and thus achieving high proton conductivity and high mobility of water molecules at higher hydration level. The current work can provide a theoretical guidance for designing new type of Nafion composite membranes.

关键词： Nafion/Ti_(3)C_(2)T_(x)composite membrane Proton transport Molecular dynamics simulation

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Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells

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World Journal of Gastroenterology 2006年第30期12卷 4859-4865页

作者： Chun-Ping Wang Lin Zhou Shu-Hui Su Yan Chen Yin-Ying Lu Fei Wang Hong-Jun Jia yong-Yi feng yong-Ping yang Department of Gastroenterology 302 Hospital of Chinese PLA Beijing 100039 China

AIM： To observe the effects of augmenter of liver regeneration （ALR） on Kupffer cells and to determine whether ALR promotes hepatocyte proliferation induced by Kupffer cells. METHODS： Kupffer cells and hepatocytes were cultured in vitro and various concentrations of recombinant rat ALR （rrALR） were added. ^3H-thymidine, BrdU and ^3H-leucine incorporation was determined in cultured Kupffer cells and hepatocytes, in hepatocytes conditioned by Kupffer cells, and in associated medium, rrALR was labeled by iodination and used to determine its binding activity by Scatchard analysis in Kupffer cells and primarily cultured rat hepatocytes. RESULTS： rrALR stimulated DNA replication in Kupffer cells and protein synthesis both in cells and in medium in a non-concentration-dependent manner. The effect was significant at the concentration of 1μg/L ALR. However, rrALR had no effect on primarily cultured hepatocytes, when hepatocytes were cultured with the Kupffer cell medium conditioned by ALR, DNA replication and protein synthesis in hepatocytes increased significantly at the concentration of 1μg/L ALR. When the ALR concentration was increased, its effect on hepatocyte proliferation decreased to the basal level. Scatchard analysis indicated the presence of a single class of high affinity receptors with a dissociation constant （Kd） of 0.883 nmol/L and a maximum binding capacity （Bmax） of 126.1 pmol/g protein in the rat Kupffer cells. CONCLUSION： ALR can promote hepatocyte proliferation induced by Kupffer cells, which is associated with the concentration of ALR, suggesting that Kupffer cells play a dual role in liver regeneration.

关键词： Liver regeneration Augmenter of liver regeneration Kupffer cell

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Overview of radar detection methods for low altitude targets in marine environments

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Journal of Systems Engineering and Electronics 2024年第1期35卷 1-13页

作者： yang yong yang Boyu School of Electronic Science National University of Defense TechnologyChangsha 410073China

In this paper,a comprehensive overview of radar detection methods for low-altitude targets in maritime environments is presented,focusing on the challenges posed by sea clutter and multipath *** performance of the radar detection methods under sea clutter,multipath,and combined conditions is categorized and summarized,and future research directions are outlined to enhance radar detection performance for low-altitude targets in maritime environments.

关键词： radar sea clutter multipath scattering detection low altitude target

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