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High-Throughput Prediction and Design of Novel Conopeptides for Biomedical Research and Development

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BioDesign Research 2022年第1期2022卷 38-51页

作者： Bingmiao Gao Yu Huang Chao Peng Bo Lin Yanling Liao Chao Bian jiaan yang Qiong Shi Key Laboratory of Tropical Translational Medicine of Ministry of Education School of PharmacyHainan Medical UniversityHaikouHainan 570102China Shenzhen Key Lab of Marine Genomics Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic AnimalsBGI Academy of Marine SciencesBGI MarineShenzhenGuangdong 518081China BGI-Marine Research Institute for Biomedical Technology Shenzhen Huahong Marine Biomedicine Co.Ltd.ShenzhenGuangdong 518119China Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical UniversityHaikouHainan 570102China Research and Development Department Micro Pharmtech Ltd.WuhanHubei 430075China

Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to theirpharmacological applications in development of marine drugs for treatment of various human diseases. To date, around 800Conus species are recorded, and each of them produces over 1,000 venom peptides (termed as conopeptides or conotoxins).This reflects the high diversity and complexity of cone snails, although most of their venoms are still *** multiomics (such as genomics, transcriptomics, and proteomics) approaches have been recently developed to minediverse Conus venom samples, with the main aim to predict and identify potentially interesting conopeptides in an efficientway. Some bioinformatics techniques have been applied to predict and design novel conopeptide sequences, related targets, andtheir binding modes. This review provides an overview of current knowledge on the high diversity of conopeptides andmultiomics advances in high-throughput prediction of novel conopeptide sequences, as well as molecular modeling and designof potential drugs based on the predicted or validated interactions between these toxins and their molecular targets.

关键词： drugs Con prediction

Characterization and validation of somatic mutation spectrum to reveal heterogeneity in gastric cancer by single cell sequencing

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Science Bulletin 2019年第4期64卷 236-244页

作者： Lihua Peng Rui Xing Dongbing Liu Li Bao Wenxiang Cheng Hongyi Wang Yuan Yu Xiaofeng Liu Lu Jiang Yan Wu Zhongxue An Qiaoyi Liang Ryong Nam Kim Young Kee Shin Huanming yang Jian Wang Jun Yu Xiuqing Zhang Xun Xu jiaan yang Kui Wu Shida Zhu Youyong Lu BGI-Shenzhen China National GeneBank-Shenzhen BGI-Shenzhen Laboratory of Molecular Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Department of Drug Design and Pharmacology University of Copenhagen Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Department of Histology and Embryology Inner Mongolia Medical University Department of Medicine and Therapeutics State Key Laboratory of Digestive Disease Institute of Digestive Disease and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Department of Pharmacy College of Pharmacy Seoul National University James D. Watson Institute of Genome Sciences Micro Pharmatech Ltd Department of Biology University of Copenhagen

Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor ***, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.

关键词： Gastric cancer Single-cell whole exome sequencing SNV Signi-cell mutated gene Heterogeneity

创新型城市建设对制造业企业数字技术创新的影响

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安徽商贸职业技术学院学报 2024年第4期23卷 21-27页

作者：杨嘉安首都经济贸易大学经济学院北京100070

基于2004—2022年我国制造业上市企业的数据,以国家创新型城市试点为准自然实验,运用渐进DID方法评估了创新型城市建设对制造业企业数字技术创新的影响,并探讨了其作用机制。研究发现,国家创新型城市建设对制造业企业的数字技术创新有... 详细信息

基于2004—2022年我国制造业上市企业的数据,以国家创新型城市试点为准自然实验,运用渐进DID方法评估了创新型城市建设对制造业企业数字技术创新的影响,并探讨了其作用机制。研究发现,国家创新型城市建设对制造业企业的数字技术创新有显著促进作用。机制检验表明创新型城市建设能够通过财政支持和人才支持两条路径促进制造业企业的数字技术创新。从企业规模和企业媒体关注度两个方面对创新型城市建设的数字创新效应进行异质性分析,结果显示,创新型城市建设对大规模企业、媒体关注度更高的制造业企业的数字技术创新的促进作用更为明显。研究结论对于推动数字技术与实体经济深度融合、加速制造业转型升级和创新发展、抢占数字经济时代大国竞争的制高点,以及全面落实“创新中国”的重大战略具有一定的政策借鉴意义。

关键词：创新型城市建设数字技术创新制造业企业

高通量筛选高特异性的检测类风湿关节炎的生物探针分子

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湖北大学学报（自然科学版） 2015年第5期37卷 506-512页

作者：李洪伟吴仲岿杨家安赵晓飞武汉理工大学材料科学与工程学院湖北武汉430070 麦科罗医药科技有限公司湖北武汉430075

从靶蛋白-配体特异性结合角度,采用蛋白折叠码(PFSC)技术在PDB数据库中高通量地筛选出与TNFA_HUMAN靶点区结合灵敏度高的分子作为检测类风湿关节炎的生物探针分子.结果显示,小分子307具有相对较高的灵敏度和较低的检出限,可以作为生物... 详细信息

从靶蛋白-配体特异性结合角度,采用蛋白折叠码(PFSC)技术在PDB数据库中高通量地筛选出与TNFA_HUMAN靶点区结合灵敏度高的分子作为检测类风湿关节炎的生物探针分子.结果显示,小分子307具有相对较高的灵敏度和较低的检出限,可以作为生物探针来检测类风湿关节炎.结果显示,蛋白指纹检索技术是一种快速、有效的蛋白质结构检索工具,通过对数据库中海量数据的筛选,可为重大疾病的检测试剂开发提供先导信息.

关键词：蛋白折叠形状码高通量筛选类风湿关节炎生物探针分子

大学生焦虑抑郁情绪及儿时体罚经历与生活满意度的关系

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神经疾病与精神卫生 2022年第7期22卷 505-510页

作者：杨嘉安鞠文静张文琳马龙刘迪哈尔滨医科大学附属第二医院宣传科 150081 哈尔滨市疾病预防控制中心传染性疾病预防控制所 150056 黑龙江省标准化研究院办公室 150036 齐齐哈尔医学院附属第一医院医院办公室 161041 哈尔滨医科大学马克思主义学院研究生思想政治理论课教研室 150086

目的了解大学生焦虑、抑郁情绪及儿时体罚经历与生活满意度的关系。方法于2019年4—5月,采用方便抽样法对哈尔滨市某两所大学部分专业的全体大一、大二学生进行问卷调查。采用一般情况调查表、青少年学生生活满意度量表(CASLSS)、焦虑... 详细信息

目的了解大学生焦虑、抑郁情绪及儿时体罚经历与生活满意度的关系。方法于2019年4—5月,采用方便抽样法对哈尔滨市某两所大学部分专业的全体大一、大二学生进行问卷调查。采用一般情况调查表、青少年学生生活满意度量表(CASLSS)、焦虑自评量表(SAS)、抑郁自评量表(SDS)和亲子冲突解决策略量表中的体罚分量表进行调查。采用二项Logistic回归分析大学生焦虑、抑郁、10岁及以前体罚经历及一般人口学特征对生活满意度的影响。共发放纸质问卷2440份,回收有效问卷2150份,问卷有效回收率为88.11%。结果2150名大学生的CASLSS总分为190(165,210)分。除学业维度外,女大学生CASLSS总分及各维度得分均高于男大学生,差异有统计学意义(P<0.05)。伴有焦虑、抑郁情绪及有10岁及以前体罚经历的大学生CASLSS总分及各维度得分低于无焦虑、无抑郁及10岁及以前无体罚经历的大学生,差异均有统计学意义(均P<0.01)。二项Logistic回归分析显示,焦虑(OR=2.108,95%CI=1.472~3.020)、抑郁(OR=5.831,95%CI=4.595~7.398)、10岁及以前有体罚经历(OR=2.249,95%CI=1.849~2.736)、男性(OR=1.393,95%CI=1.149~1.689)是大学生生活满意度的危险因素(P<0.05),家庭月收入高(OR=0.789,95%CI=0.697~0.892)是大学生生活满意度的保护因素(P<0.05)。结论有焦虑、抑郁情绪及儿时体罚经历大学生的生活满意度较低,应加强对大学生焦虑、抑郁情绪的干预,提高大学生的生活满意度。

关键词：大学生生活满意度焦虑抑郁体罚

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十字孢碱对宫颈癌细胞中Btk表达的影响

医学分子生物学杂志 2011年第4期8卷 318-322页

作者：郑昆杨家安展锐岩葛雅琨赵航国新华施维吉林大学生命科学学院、分子酶学教育部重点实验室长春市130012 吉林化工学院环境与生物工程学院吉林省吉林市132022 桑迪亚医药技术(上海)有限责任公司上海市201203 吉林化工学院化学与制药工程学院吉林省吉林市132022 吉林大学化学学院长春市130012

目的探讨十字孢碱对宫颈癌细胞生长及酪氨酸激酶Btk（tyrosine kinase）基因和蛋白表达的影响。方法用不同浓度的十字孢碱处理宫颈癌HeLa细胞24h，采用MTT比色法分析IC50。用不同浓度十字孢碱处理HeLa细胞24h，Real—time PCR检测酪氨... 详细信息

目的探讨十字孢碱对宫颈癌细胞生长及酪氨酸激酶Btk（tyrosine kinase）基因和蛋白表达的影响。方法用不同浓度的十字孢碱处理宫颈癌HeLa细胞24h，采用MTT比色法分析IC50。用不同浓度十字孢碱处理HeLa细胞24h，Real—time PCR检测酪氨酸激酶BtkmRNA表达的变化，Western印迹检测酪氨酸激酶Btk蛋白表达的变化。结果随着十字孢碱浓度及处理时间的增加，宫颈癌HeLa细胞生长抑制率升高；随着十字孢碱剂量的增加，酪氨酸激酶BtkmRNA及蛋白的表达水平逐渐减少。结论十字孢碱可呈剂量依赖性抑制HeLa细胞的生长，呈浓度依赖性减少酪氨酸激酶BtkmRNA及蛋白的表达。

关键词：十字孢碱宫颈癌酪氨酸激酶Btk

A new look at the Lagrange method for continuous-time stochastic optimization

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Science China Mathematics 2012年第11期55卷 2247-2258页

作者： CHENG Xue YAN jiaan School of Mathematical Sciences Center for Statistical SciencePeking UnivevsityBeijing 100871China Institute of Applied Mathematics Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China

We formulate a Lagrange method for continuous-time stochastic optimization in an appropriate normed space by using a proper stochastic process as the Lagrange *** obtained optimality conditions are applied to different types of *** examples selected from control theory and economic theory are studied to test and illustrate the potential applications of the method.

关键词： stochastic optimization Lagrange method extremal point optional projection Fr^chet derivative subdifferential

An overview of representation theorems for static risk measures

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Science China Mathematics 2009年第7期52卷 1412-1422页

作者： SONG YongSheng YAN jiaan Center for Financial Engineering and Risk Management Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China

In this paper,we give an overview of representation theorems for various static risk measures:coherent or convex risk measures, risk measures with comonotonic subadditivity or convexity, law-invariant coherent or conv... 详细信息

关键词： Choquet integral (concave) distortion law-invariant risk measure stochastic orders 46N10 60E05 60E15 91B28 91B30

Differential gene expression profiling in the developed ovaries between the parthenogenetic and bisexual female rice water weevils,Lissorhoptrus oryzophilus Kuschel(Coleoptera:Curculionidae)

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Chinese Science Bulletin 2009年第20期54卷 3822-3829页

作者： yang Pu ZHOU WenWu ZHANG Qin CHENG jiaan ZHU ZengRongx WAY MO State Key Laboratory of Rice Biology Key Laboratory of Molecular Biology of Crop Pathogens and Insects Ministry of Agriculture Institute of Insect Sciences Zhejiang University Hangzhou 310029 China Department of Plant Protection College of Biosafety Science and Technology Hunan Agricultural University Changsha 410128 China Texas A & M University Agricultural Research and Extension Center 1509 Aggie Dr. Beaumont TX 77713 USA

The rice water weevil,Lissorhoptrus oryzophilus Kuschel(Coleoptera:Curculionidae),reproduces by sex in the Southeastern United States,but reproduces by parthenogenesis in California and other invaded regions in Asia and *** objective of this study was to create a parthenogenetic gene expression profile of the rice water weevil in order to gain a better insight into the molecular mechanisms of parthenogenesis in the *** subtractive hybridization(SSH) technique was employed for profiling differential gene expression in the developed ovary between the parthenogenetic and bisexual female rice water weevils.A total of 70 contigs were obtained,and the BLASTX search identified putatively 28 genes with differential *** to the cytological process of parthenogenesis,the tubulin alpha-1 chain and signal transduction genes *** selected for real time quantitative RT-PCR analyses,and their possible functions related to the molecular mechanism of parthenogenesis were *** tubulin alpha-1 chain and some signal transduction genes may be related to the molecular mechanisms of parthenogenesis of the rice water weevil.

关键词：基因差异表达稻水象甲发达国家象虫科鞘翅目卵巢女性抑制性消减杂交