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生物医学工程学杂志 2014年第3期31卷 586-589页

作者：黄戎何红梅皮喜田刁子骥赵素文重庆工业职业技术学院自动化系重庆401120 重庆医科大学附属第二医院胃肠外科重庆400010 重庆大学生物工程学院重庆400040

非药物治疗高血压由于可能克服药物治疗所带来的经济负担和副作用等缺点,逐渐成为研究热点。其中,基于慢呼吸训练的高血压疗法因治疗效果好和操作简便,已成为临床治疗高血压的新型物理疗法之一。本文阐述了基于慢呼吸训练的高血压治疗... 详细信息

非药物治疗高血压由于可能克服药物治疗所带来的经济负担和副作用等缺点,逐渐成为研究热点。其中,基于慢呼吸训练的高血压疗法因治疗效果好和操作简便,已成为临床治疗高血压的新型物理疗法之一。本文阐述了基于慢呼吸训练的高血压治疗方法原理,介绍了便携式高血压治疗仪的总体结构和功能,包括呼吸检测电路、核心控制模块、音频模块、存储模块和人机交互模块。简要介绍高血压治疗仪软件流程。试验样机的测试结果的表明,该治疗仪具有较明显降低血压的治疗效果。

关键词：呼吸传感器微处理器高血压慢呼吸训练

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Assignment of function to a domain of unknown function: DUF1537 is a new kinase family in catabolic pathways for acid sugars

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016年第29期113卷 E4161-E4169页

作者： Zhang, Xinshuai Carter, Michael S. Vetting, Matthew W. Francisco, Brian San zhao, suwen Al-Obaidi, Nawar F. Solbiati, Jose O. Thiaville, Jennifer J. de Crecy-Lagard, Valerie Jacobson, Matthew P. Almo, Steven C. Gerlt, John A. Univ Illinois Inst Genom Biol Urbana IL 61801 USA Albert Einstein Coll Med Dept Biochem Bronx NY 10461 USA Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94158 USA Univ Florida Dept Microbiol & Cell Sci Gainesville FL 32611 USA Univ Illinois Dept Biochem Urbana IL 61801 USA Univ Illinois Dept Chem Urbana IL 61801 USA

Using a large-scale "genomic enzymology" approach, we (i) assigned novel ATP-dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function;Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways for D-threonate, L-threonate, and D-erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, including D-erythronate and L-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism. Sequence similarity networks and genome neighborhood networks were used to identify the enzyme components of the pathways. Conserved genome neighborhoods encoded SBPs as well as permease components of the TRAP transporters, members of the DUF1537 family, and a member of the 4-hydroxy-L-threonine 4-phosphate dehydrogenase (PdxA) oxidative decarboxylase, class II aldolase, or ribulose 1,5-bisphosphate carboxylase/oxygenase, large subunit (RuBisCO) superfamily. Because the characterized substrates of members of the PdxA, class II aldolase, and RuBisCO superfamilies are phosphorylated, we postulated that the members of the DUF1537 family are novel ATP-dependent kinases that participate in catabolic pathways for four-carbon acid sugars. We determined that (i) the DUF1537/PdxA pair participates in a pathway for the conversion of D-threonate to dihydroxyacetone phosphate and CO2 and (ii) the DUF1537/class II aldolase pair participates in pathways for the conversion of D-erythronate and L-threonate (epimers at carbon-3) to dihydroxyacetone phosphate and CO2. The physiological importance of these pathways was demonstrated in vivo by phenotypic and genetic analyses.

关键词： DUF1537 kinase four-carbon acid sugars conserved genome neighborhoods genomic enzymology

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Structure-Based Design of Melanocortin 4 Receptor Ligands Based on the SHU-9119-hMC4R Cocrystal Structure

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JOURNAL OF MEDICINAL CHEMISTRY 2021年第1期64卷 357-369页

作者： Martin, Charlotte Gimenez, Luis E. Williams, Savannah Y. Jing, Yu Wu, Yiran Hollanders, Charlie Van der Poorten, Olivier Gonzalez, Simon Van Holsbeeck, Kevin Previti, Santo Lamouroux, Arthur zhao, suwen Tourwe, Dirk Stevens, Raymond C. Cone, Roger D. Ballet, Steven Vrije Univ Brussel Res Grp Organ Chem B-1050 Brussels Belgium Univ Michigan Inst Life Sci Ann Arbor MI 48109 USA ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Univ Michigan Dept Mol & Integrat Physiol Ann Arbor MI 48109 USA

The melanocortin receptors (MC1R-MC5R) belong to class A G-protein-coupled receptors (GPCRs) and are known to have receptor-specific roles in normal and diseased states. Selectivity for MC4R is of particular interest due to its involvement in various metabolic disorders, including obesity, feeding regulation, and sexual dysfunctions. To further improve the potency and selectivity of MC4R (ant)agonist peptide ligands, we designed and synthesized a series of cyclic peptides based on the recent crystal structure of MC4R in complex with the well-characterized antagonist SHU-9119 (Ac-Nle(4)-c [Asp(5)-His(6)-DNal (2' )(7)-Arg(8)-Trp(9)- Lys(10)]-NH2). These analogues were pharmacologically characterized in vitro, giving key insights into exploiting binding site subpockets to deliver more selective ligands. More specifically, the side chains of the Nle(4), DNal(2')(7), and Trp(9) residues in SHU-9119, as well as the amide linkage between the Asp(5) and Lys(10) side chains, were found to represent structural features engaging a hMC4R/hMC3R selectivity switch.

关键词： Peptides and proteins Agonists Ligands Selectivity Receptors

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?406.4mm尾管悬挂技术在深水钻井中的应用

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石油钻采工艺 2015年第1期37卷 103-106页

作者：赵苏文黄小龙熊爱江赵德中海油能源发展股份有限公司工程技术深圳分公司广东深圳518606

针对深水钻井水下井口系统的表层套管尺寸限制后续套管层次的问题,介绍了?406.4 mm超大尺寸尾管悬挂技术以及与其对应的注水泥工艺。悬挂装置由承载环和配套的悬挂器组成,承载环最大外径508 mm,最小内径445.8 mm,出厂前预制在?508 mm套... 详细信息

针对深水钻井水下井口系统的表层套管尺寸限制后续套管层次的问题,介绍了?406.4 mm超大尺寸尾管悬挂技术以及与其对应的注水泥工艺。悬挂装置由承载环和配套的悬挂器组成,承载环最大外径508 mm,最小内径445.8 mm,出厂前预制在?508 mm套管上;配套的悬挂器上卡环坐入?508 mm套管承载环上的对应卡槽内,连接?406.4 mm尾管串。对作业过程中可能出现的一些问题进行了分析总结,提出了建议。该技术有助于优化井身结构,从而更好地应对复杂地层钻井难题,对今后类似井的作业具有很好的借鉴作用。

关键词：深水钻井井身结构尾管悬挂器井口头防喷器

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Crystal Structure of the Human Cannabinoid Receptor CB₁

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CELL 2016年第3期167卷 750-+页

作者： Hua, Tian Vemuri, Kiran Pu, Mengchen Qu, Lu Han, Gye Won Wu, Yiran zhao, suwen Shui, Wenqing Li, Shanshan Korde, Anisha Laprairie, Robert B. Stahl, Edward L. Ho, Jo-Hao Zvonok, Nikolai Zhou, Han Kufareva, Irina Wu, Beili zhao, Qiang Hanson, Michael A. Bohn, Laura M. Makriyannis, Alexandros Stevens, Raymond C. Liu, Zhi-Jie ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China Chinese Acad Sci Inst Biophys Natl Lab Biomacromol Beijing 100101 Peoples R China Northeastern Univ Dept Pharmaceut Sci Ctr Drug Discovery Boston MA 02115 USA Northeastern Univ Dept Chem & Chem Biol Boston MA 02115 USA Univ Southern Calif Dept Biol Sci Bridge Inst Los Angeles CA 90089 USA Univ Southern Calif Dept Chem Bridge Inst Los Angeles CA 90089 USA Scripps Res Inst Dept Mol Therapeut Jupiter FL 33458 USA Scripps Res Inst Dept Neurosci Jupiter FL 33458 USA Univ Calif San Diego La Jolla CA 92093 USA Chinese Acad Sci Shanghai Inst Mat Med CAS Key Lab Receptor Res Shanghai 201203 Peoples R China GPCR Consortium San Marcos CA 92078 USA

Cannabinoid receptor 1 (CB1) is the principal target of Delta(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 angstrom crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.

关键词： G protein-coupled receptor cannabinoid receptor CB1 crystal structure marijuana THC stabilizing antagonist cell signalling AM6538 rimonabant

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Cytoophidia coupling adipose architecture and metabolism

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CELLULAR AND MOLECULAR LIFE SCIENCES 2022年第10期79卷 534-534页

作者： Liu, Jingnan Zhang, Yuanbing Zhou, Youfang Wang, Qiao-Qi Ding, Kang zhao, suwen Lu, Pengfei Liu, Ji-Long ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China Chinese Acad Sci Shanghai Inst Biol Sci Inst Biochem & Cell Biol Shanghai Peoples R China Univ Chinese Acad Sci Beijing Peoples R China ShanghaiTech Univ Human Inst Shanghai Peoples R China Univ Oxford Dept Physiol Anat & Genet Oxford OX1 3PT England

Tissue architecture determines its unique physiology and function. How these properties are intertwined has remained unclear. Here we show that the metabolic enzyme CTP synthase (CTPS) form filamentous structures termed cytoophidia along the adipocyte cortex in Drosophila adipose tissue. Loss of cytoophidia, whether due to reduced CTPS expression or a point mutation that specifically abrogates its polymerization ability, causes impaired adipocyte adhesion and defective adipose tissue architecture. Moreover, CTPS influences integrin distribution and dot-like deposition of type IV collagen (Col IV). Col IV-integrin signaling reciprocally regulates the assembly of cytoophidia in adipocytes. Our results demonstrate that a positive feedback signaling loop containing both cytoophidia and integrin adhesion complex couple tissue architecture and metabolism in Drosophila adipose tissue.

关键词： CTP synthase Cell adhesion Integrin Fat body Drosophila

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Structural and Functional Evaluation of Decellularized Jellyfish Matrices for Cell Culture and Wound Repair

SSRN

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SSRN 2022年

作者： zhao, Jie Yu, Wenjun Zhang, Qi Li, Xiaojing zhao, suwen Huang, Yongjie Li, Tao Li, Yang Shan, Hong Guangdong Provincial Key Laboratory of Biomedical Imaging Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai519000 China Department of Radiology The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai519000 China Cardiac Surgery and Structural Heart Disease Unit of Cardiovascular Center The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai519000 China Department of Interventional Medicine The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai519000 China

Extracellular matrices decellularized from marine animal tissues are emerging scaffolds in tissue engineering. Jellyfish tissues are suitable for making functional and safe decellularized matrices thanks to their simple structure, high water content, and low risk of pathogen transmission to humans. Jellyfish are one of the most prevalent marine animals, but their decellularized matrices remained largely undeveloped to date. Here we evaluated the structures and functions of the jellyfish (R. esculentum) matrices decellularized with seven different detergents. Scanning electron microscopy revealed that the decellularized matrices mostly retained the native microstructures, whereas only SDS and SNL distorted the matrices’ multilayered and fibrous architecture. The collagen hybridizing peptide fluorescence staining showed that SDS, SNL, Triton X-100, IGEPAL, and Tween-20 denatured the jellyfish collagen molecules to varying degrees while CHAPS and SD protected the collagen’s conformation. Importantly, we demonstrated that the decellularized jellyfish matrices supported the adhesion and proliferation of human dermal and corneal fibroblasts and mouse chondrocytes in vitro, and facilitated wound healing in vivo through reducing inflammation while promoting angiogenesis and tissue remodeling. Our collagen immunohistochemistry supported that the jellyfish’s primitive collagen has similarities to mammalian collagen types I, II, and IV, implying that their matrices could be utilized to engineer a variety of tissues. Taken together, our study demonstrated that the decellularized jellyfish matrices are an easy-to-prepare, biocompatible, and potentially versatile scaffold for regenerative medicine. © 2022, The Authors. All rights reserved.

关键词： Collagen

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Hybrid Spectral Library Combining DIA-MS Data and a Targeted Virtual Library Substantially Deepens the Proteome Coverage

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ISCIENCE 2020年第3期23卷 100903-100903页

作者： Lou, Ronghui Tang, Pan Ding, Kang Li, Shanshan Tian, Cuiping Li, Yunxia zhao, suwen Zhang, Yaoyang Shui, Wenqing ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Chinese Acad Sci Interdisciplinary Res Ctr Biol & Chem Shanghai Inst Organ Chem Shanghai 201210 Peoples R China

Data-independent acquisition mass spectrometry (DIA-MS) is a powerful technique that enables relatively deep proteomic profiling with superior quantification reproducibility. DIA data mining predominantly relies on a spectral library of sufficient proteome coverage that, in most cases, is built on data-dependent acquisition-based analysis of the same sample. To expand the proteome coverage for a pre-determined protein family, we report herein on the construction of a hybrid spectral library that supplements a DIA experiment-derived library with a protein family-targeted virtual library predicted by deep learning. Leveraging this DIA hybrid library substantially deepens the coverage of three transmembrane protein families (G protein-coupled receptors, ion channels, and transporters) in mouse brain tissues with increases in protein identification of 37%-87% and peptide identification of 58%-161%. Moreover, of the 412 novel GPCR peptides exclusively identified with the DIA hybrid library strategy, 53.6% were validated as present in mouse brain tissues based on orthogonal experimental measurement.

关键词： Analytical Chemistry Biological Sciences Classification of Proteins Proteomics

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High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening

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CHEMICAL SCIENCE 2018年第12期9卷 3192-3199页

作者： Qin, Shanshan Meng, Mengmeng Yang, Dehua Bai, Wenwen Lu, Yan Peng, Yao Song, Gaojie Wu, Yiran Zhou, Qingtong zhao, suwen Huang, Xiping McCorvy, John D. Cai, Xiaoqing Dai, Antao Roth, Bryan L. Hanson, Michael A. Liu, Zhi-Jie Wang, Ming-Wei Stevens, Raymond C. Shui, Wenqing ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China Nankai Univ Coll Pharm Tianjin 300071 Peoples R China Chinese Acad Sci Natl Ctr Drug Screening CAS Key Lab Receptor Res Shanghai Inst Mat Med Shanghai 201203 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201202 Peoples R China Univ N Carolina Chapel Hill Sch Med Dept Pharmacol Chapel Hill NC 27599 USA GPCR Consortium San Marcos CA 92078 USA Fudan Univ Sch Pharm Shanghai 201203 Peoples R China

G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Therefore, significant effort has been put towards the identification of novel ligands that can modulate the activity of a GPCR target with high efficacy and selectivity. However, due to limitations inherent to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and effective ligand screening methods especially for the identification of potential allosteric modulators. Here we present a high-throughput, label-free and unbiased screening approach for the identification of small molecule ligands towards GPCR targets based on affinity mass spectrometry. This new approach features the usage of target-expressing cell membranes rather than purified proteins for ligand screening and allows the detection of both orthosteric and allosteric ligands targeting specific GPCRs. Screening a small compound library with this approach led to the rapid discovery of an antagonist for the 5-HT receptor and four positive allosteric modulators for GLP-1 receptor that were not previously reported.

关键词： Mass spectrometry

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ZMYND8 Reads H3K36me2 to Activate CEBPE Transcription and Suppress Multiple Myeloma Progression through the Inhibition of Adaptive UPR Pathways

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ADVANCED SCIENCE 2025年 e2409219页

作者： Xu, Jiaxuan Dong, Xiaoqing Peng, Yue Yan, Jie Xu, Peipei Li, Feiyu Zhang, suwen Chen, Lanxin Meng, Xingjun Wang, Kangning Xing, Mengying Li, Wenyang Huang, David C. S. zhao, Quan Chen, Bing Nanjing Univ Nanjing Drum Tower Hosp Clin Coll Nanjing Univ Chi China Australia Inst Translat Med Sch Life Sci Affiliated HospMed SchDept HematolState Key Lab Nanjing 210023 Peoples R China Nanjing Univ Chinese Med Sch Hlth Preservat & Rehabil Nanjing 210023 Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Inst Basic Med Sci Beijing 100005 Peoples R China Univ Melbourne Walter & Eliza Hall Inst Med Res Dept Med Biol Melbourne Vic 3052 Australia

Multiple myeloma (MM) pathogenesis is closely associated with aberrant epigenetic regulation and resulting modifications, such as dimethylation of lysine 36 in histone H3 (H3K36me2). However, the recognition signature of H3K36me2 and its functional role in MM remain largely unknown. Here, the zinc-finger MYND-type-containing 8 (ZMYND8) is identified as a potential reader of the H3K36me2 mark that suppresses MM progression. ZMYND8 knockdown promotes the proliferation and invasion of MM cells. Combined transcriptomic and epigenomic analyses reveal that CCAAT/enhancer-binding protein epsilon (CEBPE) is a direct downstream target of ZMYND8. CEBPE modulates adaptive unfolded protein response (UPR) pathways through the transcriptional repression of ERN1, XBP1, and ATF6 to impair cell survival. Coimmunoprecipitation and chromatin immunoprecipitation assays show that ZMYND8 activates CEBPE expression in an H3K36me2-dependent manner and that its Pro-Trp-Trp-Pro domain is required for binding H3K36me2 modules, leading to CEBPE transcription. Low ZMYND8 expression is significantly correlated with adverse clinicopathological features and poor survival outcomes in MM patients. Furthermore, ZMYND8 upregulation increases the sensitivity of MM cells to carfilzomib. Taken together, these findings demonstrate that ZMYND8 epigenetically activates CEBPE transcription and suppresses MM cell growth by inhibiting the adaptive UPR, suggesting that ZMYND8 can be a novel therapeutic target for patients with MM.

关键词： carfilzomib CEBPE multiple myeloma ZMYND8

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