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A strategy with label-free quantification of the targeted peptides for quantitative peptidome analysis of human serum

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Science China Chemistry 2010年第4期53卷 759-767页

作者： ZHU Jun, WANG FangJun, DONG XiaoLi, ye mingliang & ZOU HanFa Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic Research and Analysis Center Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China Key Laboratory of Separation Sciences for Analytical Chemistry Chinese Academy of Sciences Dalian China National Chromatographic Research and Analysis Center Chinese Academy of Sciences Dalian China Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian China

Peptidomics draws more and more attention in discovering useful biomarkers for early diagnosis of disease. However, there is lack of efficient quantification strategy in peptidome analysis. In this study, a strategy with label-free quantification of the targeted endogenous peptides based on peak intensity using μUPLC-Q-TOF-MS/MS was developed for quantitative peptidome analysis of human serum. Different amounts of standard BSA tryptic digesting peptides were added into the same serum extracts for evaluation of the developed strategy, and it was observed that the average relative error of the targeted peptides was 6.42%, which was superior to the result obtained directly by commercially available software PLGS. It was also demonstrated that this quantification strategy could obviously increase the detection sensitivity of the peptide by DDA analysis. Then, this strategy was applied to comparatively analyze the peptides extracted from the serum of HCC or breast cancer patients and healthy individuals, respectively. Peptides with charge states up to 5 and molecular weight over 4000 can be reliably identified and quantified. This quantitative analysis method based on μUPLC-Q-TOF-MS/MS exhibited superior sensitivity than that by MALDI-TOF-MS commonly used in peptidome analysis. Finally, some interesting endogenous peptides related to corresponding diseases were successfully obtained.

关键词： peptidomics label-free quantification hepatocellular carcinoma breast cancer human serum

Characterization of a small-molecule inhibitor targeting NEMO/IKKβto suppress colorectal cancer growth

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1219-1231页

作者： Zhenlong Yu Jian Gao Xiaolei Zhang Yulin Peng Wenlong Wei Jianrong Xu Zhenwei Li Chao Wang Meirong Zhou Xiangge Tian Lei Feng Xiaokui Huo Min Liu mingliang ye De-an Guo Xiaochi Ma Pharmaceutical Research Center Second Affiliated HospitalDalian Medical UniversityDalian 116000China College of Pharmacy College(Institute)of Integrative MedicineDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Research Center for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Academy of Integrative Medicine Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China Neurology Department Dalian University Affiliated Xinhua HospitalDalian 116021China

NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic ***,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO *** destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in *** addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβ*** study provides some new insights for the development of potent small-molecule PPI inhibitors.

关键词： IKKβ colorectal cancer

An Integrated Platform for Determination of N-and O-linked Endogenous Glycopeptides in Human Serum

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An Integrated Platform for Determination of N-and O-linked E...

2018年中国质谱学术大会（CMSC2018）

作者： Shuyue Wang Hongqing Qin mingliang ye Lianghai Hu CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS) School of Life Sciences Jilin University

Endogenous glycopeptidome in serum was rarely reported due to the low abundance and insufficient enrichment of endogenous glycopeptides. Owing to the low molecular weight(LMW) of peptidome than proteome, ultrafiltration(UF) was diffusely and efficiently used to separate the endogenous peptides from proteins. HILIC approach could generally capture the glycopeptides/glycoproteins without destroying the structure of glycan chains. Hence we combined UF and HILIC to get an integrated goal and comprehensively extract endogenous glycopeptides from mini amount of serum. By utilization of this strategy, 347 N-glycopeptides and 111 O-glycopeptides were identified from 30 □l serum. In the meanwhile, we analyzed clinical serum samples, and identified 59 N-linked and 55 O-linked endogenous glycopeptides from 30 □l serum of hepatocellular carcinoma(HCC) patients. Accepted biomarker glycoproteins, such as ITIH4 and A1 AT, were identified with abnormal glycans. Glycosylation distinction of these endogenous glycopeptides may reflect the cancer formation and development and provide novel source for biomarker discovery.

关键词： Endogenous peptide Glycosylation Serum UF

Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3013-3028页

作者： Ziruoyu Wang Yanan Li Wensi Zhao Shuai Jiang Yuqi Huang Jun Hou Xuelu Zhang Zhaoyu Zhai Chen Yang Jiaqi Wang Jiying Zhu Jianbo Pan Wei Jiang Zengxia Li mingliang ye Minjia Tan Haowen Jiang Yongjun Dang Key Laboratory of Metabolism and Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesShanghai Medical CollegeFudan University200032ShanghaiChina CAS Key Lab of Separation Sciences for Analytical Chemistry National Chromatographic Research and Analysis CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences116023DalianChina The Chemical Proteomics Center and State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences201203ShanghaiChina University of Chinese Academy of Sciences 100049BeijingChina Department of Urology Zhongshan HospitalFudan University200032ShanghaiChina Department of Urology Zhongshan Hospital Wusong BranchFudan University200032ShanghaiChina Center for Novel Target and Therapeutic Intervention Chongqing Medical University400016ChongqingChina Department of Urology Huashan HospitalFudan University200040ShanghaiChina

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for ***,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical *** multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in *** the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary *** further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug ***,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft *** integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

关键词： drug PC3 diagnosis operative

MONOLITHIC CAPILLARY COLUMNS FOR EFFICIENT SEPARATION OF BIOLOGICAL SAMPLES

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MONOLITHIC CAPILLARY COLUMNS FOR EFFICIENT SEPARATION OF BIO...

第十三届北京分析测试学术报告会暨展览会(BCEIA 2009)

作者： Hanfa ZOU Fangjun WANG Renan WU mingliang ye CAS Key Laboratory of Separation Science for Analytical Chemistry National Chromatographic R&A Center Dalian Institute of Chemical PhysicsChinese Academy of Sciences

Monolithic columns have been widely applied in capillary liquid chromatography(μLC)and capillary electrochromatography(CEC)due to their easy preparations,low back pressure,convective mass transfer process and high se...

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发动机工况下透平级凹槽叶顶冷却传热性能研究

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西安交通大学学报 2021年第7期55卷 106-116页

作者：于金杏叶明亮晏鑫西安交通大学能源与动力工程学院西安710049

采用数值方法研究了发动机工况下透平级凹槽叶顶的冷却传热性能,获得了3种吹风比(M=0.5,1.0,2.0)和2种气膜孔布置(单排叶顶气膜孔、叶顶+压力面侧气膜孔)下凹槽叶顶的传热系数和气膜冷却效率分布。研究表明:凹槽腔室涡、刮削涡和冲击流... 详细信息

采用数值方法研究了发动机工况下透平级凹槽叶顶的冷却传热性能,获得了3种吹风比(M=0.5,1.0,2.0)和2种气膜孔布置(单排叶顶气膜孔、叶顶+压力面侧气膜孔)下凹槽叶顶的传热系数和气膜冷却效率分布。研究表明:凹槽腔室涡、刮削涡和冲击流是影响凹槽叶顶冷却传热性能的主要流场结构。在凹槽腔室涡的作用下,冷却流对凹槽底部前缘及压力侧形成了有效的冷却。在腔室涡与刮削涡的共同作用下,冲击流导致凹槽底部吸力侧形成高传热区。采用单排叶顶气膜孔时,随着吹风比的增大,凹槽叶顶的传热系数减小,气膜冷却效率提高。采用叶顶+压力面侧气膜孔时,与采用单排叶顶气膜孔相比,在吹风比为2.0的条件下,凹槽肩壁的平均传热系数降低了13.89%,平均气膜冷却效率升高了61.45%。

关键词：凹槽叶顶传热冷却透平级

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隔板位置对凹槽叶顶传热和冷却性能的影响

西安交通大学学报 2018年第5期52卷 55-62页

作者：叶明亮黄琰晏鑫何坤西安交通大学能源与动力工程学院西安710049

采用数值求解RANS方程(Reynolds averaged Navier-Stokes equations)的方法,对3种带隔板的凹槽叶顶间隙内的流动、传热以及冷却特性进行了研究,隔板分别位于凹槽25%、50%和75%弦长处,3种结构分别称为rib25、rib50、rib75,并与无隔板时... 详细信息

采用数值求解RANS方程(Reynolds averaged Navier-Stokes equations)的方法,对3种带隔板的凹槽叶顶间隙内的流动、传热以及冷却特性进行了研究,隔板分别位于凹槽25%、50%和75%弦长处,3种结构分别称为rib25、rib50、rib75,并与无隔板时的常规凹槽叶顶间隙内的总压损失、传热和冷却特性进行了对比。结果表明:随着叶顶间隙的增大,叶顶表面传热系数逐渐增大;rib75结构的气动损失最小,在无气膜冷却条件下,rib75结构的叶顶比纯凹槽叶顶的总压损失低0.16%,对于叶顶带中弧线气膜冷却工况,rib75结构叶顶的总压损失比带常规凹槽叶顶的叶栅低0.15%;随着隔板向前缘方向移动,凹槽底部前缘吸力面侧的高传热区明显减小,在常规凹槽、rib25、rib50、rib75这4种叶顶结构中,rib25结构的叶顶平均传热系数与常规凹槽叶顶相近;加入叶顶中弧线气膜孔后,带隔板的叶顶可使冷气流更易聚集在凹槽底部区域,冷却效果显著提高,其中rib25结构具有最佳的冷却效果,比常规凹槽叶顶的平均冷却系数约高21.5%。

关键词：燃气轮机凹槽叶顶传热气膜冷却

BRAF Oncogenesis Study with in situ Protein Activation and Phosphoproteomics

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BRAF Oncogenesis Study with in situ Protein Activation and P...

第十届全国化学生物学学术会议

作者： Yicheng Weng Yating Yao mingliang ye Peng R.Chen Peking-Tsinghua Center for Life Sciences BeijingChinaAcademy for Advanced Interdisciplinary StudiesPeking University Key laboratory of Separation Sciences for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS) Department of Chemical Biology College of Chemistry and Molecular EngineeringPeking University

BRAF is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling *** of BRAF,over 90%V600 E,can be detected in a wide range of human *** understanding of oncogenesis in BRAF mutated cells leads more efficient therapy for these *** cleavage reaction between TCOK and Me Tz has been reported for kinase activation in ***,we combined this strategy and phosphoproteomics to investigate how BRAF protein induces tumorigenesis.

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压力侧冷却流对凹槽叶顶气膜冷却与传热性能的影响

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西安交通大学学报 2022年第3期56卷 160-172页

作者：于金杏叶明亮何坤晏鑫西安交通大学能源与动力工程学院西安710049

为了降低凹槽叶顶整体热负荷并提高高传热区的气膜冷却效率,研究了压力侧冷却射流对透平级凹槽叶顶冷却传热性能的影响。通过数值计算获得了2种压力侧气膜孔形状(圆孔、扩张孔)和5种压力侧射流角(20°~40°)条件下,透平级凹槽叶顶的传... 详细信息

为了降低凹槽叶顶整体热负荷并提高高传热区的气膜冷却效率,研究了压力侧冷却射流对透平级凹槽叶顶冷却传热性能的影响。通过数值计算获得了2种压力侧气膜孔形状(圆孔、扩张孔)和5种压力侧射流角(20°~40°)条件下,透平级凹槽叶顶的传热系数和气膜冷却效率分布。研究表明:前缘压力侧冷却流进入凹槽,增强了凹槽底部的冷却效果;中部和尾缘压力侧冷却流对凹槽肩壁和叶顶尾缘进行了冷却,增强了叶顶高热负荷区域的冷却效果。在所研究的射流角范围内,射流角越小,凹槽叶顶的冷却效果越好。当采用扩张孔、射流角由20°增大到40°时,肩壁的面积平均传热系数增大了6%,面积平均气膜冷却效率减小了14.3%;叶顶压力侧的面积平均传热系数增大了36%,面积平均气膜冷却效率减小了37.2%。在小射流角条件下,扩张孔的叶顶和压力侧冷却效果优于圆孔。射流角为20°时,与圆孔相比:扩张孔使凹槽肩壁面积平均传热系数减小了2%,面积平均气膜冷却效率增大了5.9%;扩张孔使叶顶压力侧的面积平均传热系数减小了22.6%,面积平均气膜冷却效率增大了43.3%。

关键词：燃气轮机凹槽叶顶传热气膜冷却扩张孔射流角