检索结果-内蒙古大学图书馆

Development of Yin-Yang ligand for cannabinoid receptors

BIOORGANIC CHEMISTRY 2023年第1期133卷 106377页

作者： Qiu, Yanli zhao, Yitian Hu, Tao Yang, Meifang Li, Fei Li, Cuixia Gu, Weiliang Yang, Xiaodi zhao, suwen Tao, Houchao Shanghai Univ Tradit Chinese Med Innovat Res Inst Tradit Chinese Med Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Shanghai Univ Tradit Chinese Med Sch Pharm Dept Pharmacol Shanghai 201203 Peoples R China Shanghai Univ Tradit Chinese Med Shanghai 201203 Peoples R China ShanghaiTech Univ Shanghai 201210 Peoples R China

Cannabinoid receptors (CBs), including CB1 and CB2, are the key components of a lipid signaling endocannabinoid system (ECS). Development of synthetic cannabinoids has been attractive to modulate ECS functions. CB1 and CB2 are structurally closely related subtypes but with distinct functions. While most efforts focus on the development of selective ligands for single subtype to circumvent the undesired off-target effect, Yin-Yang ligands with opposite pharmacological activities simultaneously on two subtypes, offer unique therapeutic potential. Herein we report the development of a new Yin-Yang ligand which functions as an antagonist for CB1 and concurrently an agonist for CB2. We found that in the pyrazole-cored scaffold, the arm of N1-phenyl group could be a switch, modification of which yielded various ligands with distinct activities. As such, the ortho-morpholine substitution exerted the desired Yin-Yang bifunctionality which, based on the docking study and molecular dynamic simulation, was proposed to be resulted from the hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. Our results demonstrated the feasibility of structure guided ligand evolution for challenging Yin-Yang ligand.

关键词： Cannabinoid receptors Docking and simulation Drug design Subtype selectivity Yin -Yang ligand

来源：评论

学校读者我要写书评

暂无评论

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

引用

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

来源：评论

学校读者我要写书评

暂无评论

Localization of site-specific delivery capsule in vivo with alternating electromagnetic field

Localization of site-specific delivery capsule in vivo with ...

引用

Proceedings of the Biannual World Automation Congress

作者： Xitian Pi suwen zhao Hongying Liu Bin Xia Xiaoquan Shi Xiaolin Zheng Microsystem Center of Chongqing University China Key Laboratory of Optoelectronic Technology and Systems of the Education Ministry of China Chongqing University Chongqing University Chongqing China College of Bioengineering Chongqing University China Chongqing University Chongqing Sichuan CN

Site-specific delivery capsule (SSDC) is a robotic capsule. It can load with drug and deliver the drug to the selected sites of human or animalspsila gut. In order to know whether the capsule have moved into the selected sites, we use receiving coils to detect the magnetic field generated by the eddy current in batteries of the capsule when the capsule exists in the alternating magnetic field. Experiment in simulative conditions of gastrointestinal (GI) tract is carried out and the result verifies the effectiveness of this method.

关键词： In vivo Electromagnetic fields Drugs Magnetic fields Robots Humans Coils AC generators Eddy currents Batteries

来源：评论

学校读者我要写书评

暂无评论

《鱼儿佛》杂剧改编者寓山居士为祁彪佳考辨

引用

绍兴文理学院学报（哲学社会科学版） 2001年第2期21卷 8-11页

作者：赵素文浙江大学人文学院，浙江杭州310028

祁彪佳在明末曲坛上有重要地位，他的戏曲论著《远山堂曲品剧品》虽然受到了一些重视，但他本人以及他的戏曲活动却很少受到研究者的关注，同时也存在着一些误解。本文在广泛搜求各方资料的基础上，对学术界以寓山居士为释湛然的传统说... 详细信息

祁彪佳在明末曲坛上有重要地位，他的戏曲论著《远山堂曲品剧品》虽然受到了一些重视，但他本人以及他的戏曲活动却很少受到研究者的关注，同时也存在着一些误解。本文在广泛搜求各方资料的基础上，对学术界以寓山居士为释湛然的传统说法提出质疑，认为《鱼鱼佛》杂剧的改编者寓山居士就是祁彪佳，并进而考订出祁氏改编此剧的大概时间和背景，对祁氏的戏曲活动和创作也作了初步探讨。

关键词：《鱼儿佛》释湛然寓山居士祁彪佳改编者考证戏曲文学研究改编时间明代

来源：评论

学校读者我要写书评

暂无评论

Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering

引用

CELL RESEARCH 2024年第9期34卷 630-647页

作者： Cheng, Peng Mao, Cong Tang, Jin Yang, Sen Cheng, Yu Wang, Wuke Gu, Qiuxi Han, Wei Chen, Hao Li, Sihan Chen, Yaofeng Zhou, Jianglin Li, Wuju Pan, Aimin zhao, suwen Huang, Xingxu Zhu, Shiqiang Zhang, Jun Shu, Wenjie Wang, Shengqi Bioinformat Ctr AMMS Beijing Peoples R China Nanjing Med Univ Womens Hosp Nanjing Matern & Child Hlth Care Hosp State Key Lab Reprod Med & Offspring Hlth Nanjing Jiangsu Peoples R China Zhejiang Lab Hangzhou Zhejiang Peoples R China ShanghaiTech Univ IHuman Inst Shanghai Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China

Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from similar to 160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type);and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Assignment of polar states for protein amino acid residues using an interaction cluster decomposition algorithm and its application to high resolution protein structure modeling

引用

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 2007年第4期66卷 824-837页

作者： Li, Xin Jacobson, Matthew P. Zhu, Kai zhao, suwen Friesner, Richard A. Columbia Univ Dept Chem New York NY 10027 USA Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94143 USA

We have developed a new method (Independent Cluster Decomposition Algorithm, ICDA) for creating all-atom models of proteins given the heavy-atom coordinates, provided by X-ray crystallography, and the pH. In our method the ionization states of titratable residues, the crystallographic mis-assignment of amide orientations in Asn/Gln, and the orientations of OH/SH groups are addressed under the unified framework of polar states assignment. To address the large number of combinatorial possibilities for the polar hydrogen states of the protein, we have devised a novel algorithm to decompose the system into independent interacting clusters, based on the observation of the crucial interdependence between the short range hydrogen bonding network and polar residue states, thus. Significantly reducing the computational complexity of the problem and making our algorithm tractable using relatively modest computational resources. We utilize an all atom protein force field (OPLS) and a Generalized Born continuum solvation model, in contrast to the various empirical force fields adopted in most previous studies. We have compared our prediction results with a few well-documented methods in the literature (WHATIF, REDUCE). In addition, as a preliminary attempt to couple our polar state assignment method with real structure predictions, we further validate our method using single side chain prediction, which has been demonstrated to be an effective way of validating structure prediction methods without incurring sampling problems. Comparisons of single side chain prediction results after the application of our polar state prediction method with previous results with default polar state assignments indicate a significant improvement in the single side chain predictions for polar residues.

关键词： protonation state mis-assignment hydrogen bond all-atom force field side chain prediction generalized born model

来源：评论

学校读者我要写书评

暂无评论

Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y₁and P2Y₁₂ receptors

引用

SCIENTIFIC REPORTS 2018年第1期8卷 8084-8084页

作者： Liu, Xuyang Gao, Zhan-Guo Wu, Yiran Stevens, Raymond C. Jacobson, Kenneth A. zhao, suwen ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Biol Sci CAS MPG Partner Inst Computat Biol Key Lab Computat Biol Shanghai 20031 Peoples R China Univ Chinese Acad Sci 19A Yuquan Rd Beijing 100049 Peoples R China NIDDK Mol Recognit Sect Lab Bioorgan Chem NIH Bethesda MD 20892 USA

Many hemorheologic Traditional Chinese Medicines (TCMs) that are widely-used clinically lack molecular mechanisms of action. We hypothesized that some of the active components of hemorheologic TCMs may function through targeting prothrombotic P2Y(1) and/or P2Y(12) receptors. The interactions between 253 antithrombotic compounds from TCM and these two G protein-coupled P2Y receptors were evaluated using virtual screening. Eleven highly ranked hits were further tested in radioligand binding and functional assays. Among these compounds, salvianolic acid A and C antagonized the activity of both P2Y(1 )and P2Y(12) receptors in the low mu M range, while salvianolic acid B antagonized the P2Y(12) receptor. These three salvianolic acids are the major active components of the broadly-used hemorheologic TCM Danshen (Salvia militorrhiza), the antithrombotic molecular mechanisms of which were largely unknown. Thus, the combination of virtual screening and experimental validation identified potential mechanisms of action of multicomponent drugs that are already employed clinically.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Identification of an Underside Binding Site in Smoothened Receptor

Identification of an Underside Binding Site in Smoothened Re...

引用

第十一届全国化学生物学学术会议

作者： Fang Zhou Kang Ding Yiqing Zhou Yang Liu Youli Xiao suwen zhao Houchao Tao iHuman Institute ShanghaiTech University CAS Key Laboratory of Synthetic Biology Institute of Plant Physiology and EcologyShanghai Institutes for Biological SciencesChinese Academy of Sciences

An underside binding site was identified in the transmembrane domain of smoothened receptor(SMO) by a colocalization *** structurally complementary photoaffinity probes were designed by appending azide group at two ends of a known ligand *** on the comprehensive analysis of digestive MS data,the binding was determined which was further corroborated by docking and simulation *** key interactions include two pairs of hydrogen bonds,a stable cage involving several π-π interactions,and hydrophobic interaction between Allo-1 and its contacting *** results reveal the molecular base of Allo-1 binding and more importantly,the possible mechanism for its anti-drug resistance activity.

关键词： Smoothened receptor colocalization strategy binding site drug resistance

来源：评论

学校读者我要写书评

暂无评论

基于分片聚合编码的云存储策略的研究

引用

南开大学学报（自然科学版） 2014年第2期47卷 1-8页

作者：邵秀丽许杨赵素文刘瑞琴南开大学计算机与控制工程学院天津300071 天津航海仪器研究所天津300131

针对HDFS采用的完全复制存储方案会占据较多的存储空间,且对数据的恶意窃取和攻击缺少防御措施,提出了基于分片聚合编码的HDFS数据存储策略,其中采用STAR码对数据进行编码处理,产生编码数据片,然后通过聚合操作将每个数据段中位置相同... 详细信息

针对HDFS采用的完全复制存储方案会占据较多的存储空间,且对数据的恶意窃取和攻击缺少防御措施,提出了基于分片聚合编码的HDFS数据存储策略,其中采用STAR码对数据进行编码处理,产生编码数据片,然后通过聚合操作将每个数据段中位置相同的数据片聚合组成一个存储数据块,实现了HDFS文件的存储.模拟实验表明基于分片聚合编码的文件存储策略相比原HDFS存储方案在数据分布方面更安全有效.

关键词： HDFS STAR码数据块解码编码

来源：评论

学校读者我要写书评

暂无评论

Fishing out GPCR ligands from natural product extracts by affinity mass spectrometry

Fishing out GPCR ligands from natural product extracts by af...

引用

2018年中国质谱学术大会（CMSC 2018）

作者： Bingjie Zhang Haijie Cao Yiran Wu Yan Lu Shanshan Qin suwen zhao Wenqing Shui iHuman Institute ShanghaiTech University School of Life Science and Technology ShanghaiTech University

G protein-coupled receptors(GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Serotonin receptors belong to the aminergic GPCR subfamily and are involved in physiological and psychological activities, including mood regulation, memory, appetite, and others. Due to the high similarities of the ligand binding pockets among the 5-HT2 subfamily, most of the approved drugs target these receptors suffer from low specificity which results in serious side effects. It is of considerable importance and challenge to find highly selective ligands that target 5-HT2 C receptor particularly. Affinity mass spectrometry(MS) has emerged as a high-throughput, label-free and unbiased screening approach for rapid identification of novel ligands from complex compound mixtures towards a GPCR target. Therefore, we combine affinity MS and cell bioactivity assays for identification of novel ligands for 5-HT2 C receptor from natural product extracts. Screening a panel of crude extracts with this strategy led to the discovery of two selective agonists and two antagonists for 5-HT2 C receptor.

关键词： GPCR 5HT2C receptor screening affinity MS novel ligand

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：