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MiR-186-5p carried by M2 macrophage-derived exosomes downregulates TRPP2 expression in airway smooth muscle to alleviate asthma progression

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INTERNATIONAL IMMUNOPHARMACOLOGY 2025年 148卷 114107页

作者： Wang, Zunyun Ren, Yan Li, Yicong Zhang, Yuxin Bai, suwen Hou, Wenxuan Zhang, Wenjun Yao, Yanheng zhao, Hongxian Wang, Minghua Luo, Yumei Pang, Gang Du, Juan Chinese Univ Hong Kong Ciechanover Inst Precis & Regenerat Med Sch Med Shenzhen Guangdong Peoples R China Anhui Med Univ Sch Basic Med Sci Hefei Anhui Peoples R China Chinese Univ Hong Kong Shenzhen Affiliated Hosp 2 Sch Med Shenzhen Guangdong Peoples R China Longgang Dist Peoples Hosp Shenzhen Shenzhen Guangdong Peoples R China

Bronchial asthma (asthma) is a chronic inflammatory disease of the airways that remains an unresolved problem. Reportedly M2 macrophages and exosomes play a role in inflammation, including asthma. We investigated the roles of M2 macrophage-derived exosomes (M2-Exos) effect in asthmatic progression by using ovalbumin (OVA) induced asthmatic mice model. M2-Exos significantly ameliorated the pulmonary inflammatory response and airway hyperresponsiveness in asthmatic mice and suppressed aberrant proliferation and transient receptor potential polycystic protein 2(TRPP2) expression in LPS-stimulated primary airway smooth muscle cells (ASMCs). Then, we found that miR-186-5p of M2-Exos could target TRPP2 through online database analysis. However, miR-186-5p downregulation by miR-186-5p inhibitors decreased the protective effect of M2-Exos in asthmatic mouse and cellular models. miR-186-5p was identified and selectively combined with the polycystin-2 gene encoding TRPP2 protein, inhibited TRPP2 protein production, and downregulated TRPP2 expression. A reduction in the number of TRPP2 calcium (Ca) channels formed on the cell membrane leads to a decreased intracellular Ca2+ concentration ([Ca2+] i), causing reduced ASMC contraction and proliferation, thereby improving airway hyperresponsiveness and airway remodeling in asthma. Collectively, we conclude that M2 exosomal miR-186-5p to alleviate asthma progression and airway hyperresponsiveness though downregulating TRPP2 expression. These results may offer a novel insight to the treatment and drug delivery of asthma.

关键词： M2 macrophages Exosomes Transient receptor potential polycystic protein MiR-186-5p Asthma

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基于生物反馈的便携式高血压治疗仪的研究

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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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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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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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The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules

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CELL REPORTS 2024年第7期43卷 114505页

作者： Jiang, Kexin Zheng, You Zeng, Liting Wang, Ling Li, Fei Pu, Jun Lu, Yingli zhao, suwen Xu, Fei ShanghaiTech Univ iHuman Inst Shanghai Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China Kunming Med Univ Dept Neurosurg Affiliated Hosp 2 Kunming Peoples R China Shanghai Jiao Tong Univ Shanghai Peoples Hosp 9 Inst & Dept Endocrinol & Metab Sch Med Shanghai Peoples R China Shanghai Clin Res & Trial Ctr Shanghai Peoples R China

Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

关键词： CP: Neuroscience

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Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

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NATURE COMMUNICATIONS 2017年第1期8卷 15383页

作者： Zhang, Xianjun zhao, Fei Wu, Yiran Yang, Jun Han, Gye Won zhao, suwen Ishchenko, Andrii Ye, Lintao Lin, Xi Ding, Kang Dharmarajan, Venkatasubramanian Griffin, Patrick R. Gati, Cornelius Nelson, Garrett Hunter, Mark S. Hanson, Michael A. Cherezov, Vadim Stevens, Raymond C. Tan, Wenfu Tao, Houchao Xu, Fei ShanghaiTech Univ IHuman Inst 2F Bldg 699 Haike Rd Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Biol Sci Inst Biochem & Cell Biol Shanghai 200031 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Fudan Univ Sch Pharm Dept Pharmacol Shanghai 201203 Peoples R China Univ Southern Calif Dept Chem Los Angeles CA 90089 USA Univ Southern Calif Dept Biol Sci Los Angeles CA 90089 USA Univ Southern Calif Dept Phys & Astron Los Angeles CA 90089 USA Chinese Acad Sci Shanghai Inst Mat Medica Univ Chinese Acad Sci 555 Zuchongzhi Lu Bldg 3Room 426 Shanghai 201203 Peoples R China Chinese Acad Sci Shanghai Inst Biol Sci Univ Chinese Acad Sci CAS MPG Partner Inst Computat Biol Shanghai 200031 Peoples R China Scripps Res Inst Dept Mol Therapeut 130 Scripps Way Jupiter FL 33458 USA MRC Mol Biol Lab Biomedical CampusFrancis Crick Ave Cambridge 33458 England MRC Mol Biol Lab Biomedical CampusFrancis Crick Ave Cambridge England Arizona State Univ Dept Phys Tempe AZ 85287 USA SLAC Natl Accelerator Lab Linac Coherent Light Source 2575 Sand Hill Rd Menlo Pk CA 94025 USA

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 angstrom. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

关键词： Developmental biology Nanocrystallography

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基于样本优化选取的光谱重建方法研究

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影像科学与光化学 2017年第1期35卷 88-96页

作者：龙艳群王慧琴王可王展赵素文西安建筑科技大学信息与控制工程学院陕西西安710055 西安建筑科技大学管理学院陕西西安710055 陕西文物保护研究院陕西西安710075

针对光谱反射率重建中已有样本选取方法的不足,提出了一种基于核模糊C聚类的样本优化选取方法。该方法综合考虑了光谱反射率空间的广泛性和色度空间的相似性,较大程度满足了光谱重建的精度。首先采用已有样本选取法在光谱反射率空间选取... 详细信息

针对光谱反射率重建中已有样本选取方法的不足,提出了一种基于核模糊C聚类的样本优化选取方法。该方法综合考虑了光谱反射率空间的广泛性和色度空间的相似性,较大程度满足了光谱重建的精度。首先采用已有样本选取法在光谱反射率空间选取C个样本作为聚类初始点,再将原光谱转化到色度空间进行聚类,同时引入核函数将二维色度空间映射到三维特征空间,使得特征数据线性可分,从而达到更好的划分效果。实验结果表明,使用该方法选取训练样本进行光谱反射率重建能够进一步提高光谱重建精度,色度评价和光谱评价结果均好于已有方法。

关键词：光谱学核模糊C聚类样本选取光谱重建

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Structure-Based Ligand Discovery Targeting the Transmembrane Domain of Frizzled Receptor FZD7

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JOURNAL OF MEDICINAL CHEMISTRY 2023年第17期66卷 11855-11868页

作者： Li, Cuixia Wu, Yiran Wang, Wenli Xu, Lu Zhou, Yan Yue, Yang Wu, Tingting Yang, Meifang Qiu, Yanli Huang, Minhao Zhou, Fangfang Zhou, Yiqing Hao, Piliang Lin, Zhixiong Wang, Ming-Wei zhao, suwen Yang, Dehua Xu, Fei Tao, Houchao ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Shenzhen Jingtai Technol Co Ltd XtalPi Shenzhen 518045 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med Natl Ctr Drug Screening CAS Key Lab Receptor Res Shanghai 201203 Peoples R China Shanghai Univ Tradit Chinese Med Innovat Res Inst Tradit Chinese Med Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China Changshu Inst Technol Sch Biotechnol & Food Engn Suzhou 215500 Peoples R China Fudan Univ Sch Basic Med Sci Dept Pharmacol Shanghai 200032 Peoples R China

Despite the essential roles of Frizzled receptors (FZDs) in mediating Wnt signaling in embryonic development and tissue homeostasis, ligands targeting FZDs are rare. A few antibodies and peptide modulators have been developed that mainly bind to the family-conserved extracellular cysteine-rich domain of FZDs, while the canonical binding sites in the transmembrane domain (TMD) are far from sufficiently addressed. Based on the recent structures of FZDs, we explored smallmolecule ligand discovery by targeting TMD. From the ChemDiv library with similar to 1.6 million compounds, we identified compound F7H as an antagonist of FZD7 with an IC50 at 1.25 +/- 0.38 mu M. Focusing on this hit, the structural dissection study, together with computing studies such as molecular docking, molecular dynamics simulation, and free energy perturbation calculations, defined the binding pocket with key residue recognition. Our results revealed the structural basis of ligand recognition and demonstrated the feasibility of structure-guided ligand discovery for FZD7-TMD.

关键词： Foams Free energy Ligands Mixtures Receptors

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基于地应力与岩石抗压强度变异性的岩体爆破响应特征研究

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水力发电 2021年第6期47卷 34-38,90页

作者：林岳张昆赵苏文杭州市地铁集团有限责任公司浙江杭州310019 浙江华东建设工程有限公司浙江杭州310030 海洋岩土工程勘察技术与装备浙江省工程研究中心浙江杭州310014

为研究不同地应力和不同抗压强度对岩体爆破效果的影响,采用颗粒流软件进行数值模拟,监测岩石试样不同位置处的应力峰值变化及岩体爆破破坏特征。结果表明,地应力的增加使测量点的峰值应力明显增加,同时也抑制了裂缝的发展;随着抗压强... 详细信息

为研究不同地应力和不同抗压强度对岩体爆破效果的影响,采用颗粒流软件进行数值模拟,监测岩石试样不同位置处的应力峰值变化及岩体爆破破坏特征。结果表明,地应力的增加使测量点的峰值应力明显增加,同时也抑制了裂缝的发展;随着抗压强度的提高,剪切裂缝的数量不断增加,拉伸裂缝的数量不断减少,23.5~43.5 MPa时的效果最为明显;抗压强度的变化对应变能的峰值影响较大。

关键词：地应力岩体爆破爆破特征抗压强度

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Virtual screening for nucleic acid aptamer

Virtual screening for nucleic acid aptamer

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第11届世界华人药物化学研讨会（ISCMC 2018）

作者： Qingtong Zhou Liping Yang Wei Wei Xianbao Sun Haojun Liang Eugene Shakhnovich zhaofeng Luo suwen zhao Human institute ShanghaiTech University School of Life Science University of Science and Technology of China Department of Polymer Science and Engineering University of Science and Technology of China Department of Chemistry and Chemical Biology Harvard University

Aptamers[1-2]are short,single stranded oligonucleotides that bind potently and selectively to their targets,which has been explored thoughtfully for analytical chemistry and biological ***,the ligand-binding specificity of aptamer is crucial for the aptamer-based biosensor detection,while to what extent aptamer bind multiple ligands are far from ***,the ligand discovery for aptamer,as one typical nucleic acid with flexible conformations,is of great interest in nucleic acid-targeted drug ***,we selected the L-argininamide-binding aptamer[3]and extend the concept of SELEX in silico[4-5]for the aptamer-targeted ligand *** virtual screening consisted of three steps:the high-throughput molecular docking,molecular dynamic simulation and binding free energy ***,verified by experiment,one compound named TPT-260 can bind L-argininamide（L-Arm）-binding aptamer with much higher affinity（K ～10μM） than the original ligand L-Arm（K ～100 uM）.We further analysis the binding pose of TPT-260 with the aptamer and successfully optimized the aptamer sequence with abolished L-Arm binding while retain TPT-260 *** results demonstrate the multi-point mapping between certain sequence and the chemical space and provide one practical approach in nucleic acid-targeted drug discovery.

关键词： Aptamer nucleic acid virtual screening MD simulation

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