检索结果-南通市图书馆

Applications and prospects of cryo-EM in drug discovery

Military Medical Research 2023年第6期10卷 848-861页

作者： Kong-Fu Zhu Chuang Yuan Yong-Ming Du Kai-Lei Sun Xiao-Kang Zhang horst vogel Xu-Dong Jia Yuan-Zhu Gao Qin-Fen Zhang Da-Ping Wang Hua-Wei Zhang Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen 518055GuangdongChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesPeking UniversityBeijing 100191China Department of Structural Biology St.Jude Children’s Research HospitalMemphisTN 38105USA Center for Protein Science and Crystallography School of Life SciencesFaculty of ScienceChinese University of Hong KongHong Kong 999077China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055GuangdongChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055GuangdongChina Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions Shenzhen 518055GuangdongChina Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055GuangdongChina State Key Lab for Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China Cryo‑EM Facility Center Southern University of Science and TechnologyShenzhen 518055GuangdongChina Department of Orthopedics Shenzhen Intelligent Orthopaedics and Biomedical Innovation PlatformGuangdong Provincial Research Center for Artifcial Intelligence and Digital Orthopedic TechnologyShenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen 518000GuangdongChina Guangdong Provincial Key Laboratory of Advanced Biomaterials Southern University of Science and TechnologyShenzhen 518055GuangdongChina

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time-and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy(cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence(AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of mediumresolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

关键词： Cryo-electron microscopy(cryo-EM) Drug discovery Structure-based drug design Fragment-based drug discovery Proteolysis targeting chimeras Drug repurposing Artificial intelligence(AI)

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Enhanced activity and durability of FeCoCrMoCBY nanoglass in acidic hydrogen evolution reaction

引用

Journal of Materials Science & Technology 2024年第3期170卷 212-220页

作者： Mengyang Yan Shuangqin Chen Shangshu Wu Xuechun Zhou Shu Fu Di Wang Christian Kübel horst Hahn Si Lan Tao Feng Herbert Gleiter Institute of Nanoscience School of Material Science and EngineeringNanjing University of Science and TechnologyNanjing 210094China Institute of Nanotechnology Karlsruhe Institute of TechnologyKarlsruhe 76021Germany

In the present work,a multi-element nanoglass(m-NG)of FeCoCrMoCBY is obtained first time by the laser ablation combined with inert gas condensation(laser-IGC)technique.Compared with the conventional rapid-quenched metallic glass(MG)with identical composition,the Fe-based m-NG demonstrates a superior performance as a self-supported electrocatalyst for hydrogen evolution reaction(HER)in acidic solution.The enhanced HER activity of m-NG is proposed to be closely related to its high en-ergy states,which is originated from the unique inhomogeneous nanostructures with a high density of low-coordinated atoms.Additionally,the Fe-based m-NG exhibits an outstanding comprehensive catalytic performance even beyond the commercial Pt/C catalyst in long-term test due to its self-optimization ability.This work not only opens the way to the preparation of m-NGs by the novel laser-IGC technique,but also makes a great contribution to developing low-cost,high-efficient,and super-durable HER electrocat-alysts in acidic environment.

关键词： Nanoglass Inert gas condensations High energy states Hydrogen evolution reactions

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Targeting non-coding RNAs to overcome cancer therapy resistance

引用

Signal Transduction and Targeted Therapy 2022年第5期7卷 1447-1466页

作者： BaoQing Chen Mihnea P.Dragomir Chen Yang Qiaoqiao Li David horst George A.Calin Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Institute of Pathology Charité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlin 10117Germany Berlin Institute of Health Anna-Louisa-Karsch-Straße 210178 BerlinGermany German Cancer Consortium(DKTK) Partner Site BerlinGerman Cancer Research Center(DKFZ)69210 HeidelbergGermany Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Center for RNA Interference and Non-Coding RNAs The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

It is now well known that non-coding RNAs(ncRNAs),rather than protein-coding transcripts,are the preponderant RNA transcripts.NcRNAs,particularly microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation,apoptosis,invasion,metastasis,and genomic instability.Despite recent discoveries in cancer therapy,resistance to chemotherapy,radiotherapy,targeted therapy.

关键词： chemotherapy metastasis RNAs

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A comprehensive research framework for Bitcoin’s energy use:Fundamentals,economic rationale,and a pinch of thermodynamics

引用

Blockchain(Research and Applications) 2023年第3期4卷 98-122页

作者： horst Treiblmaier School of International Management Modul University Vienna1190ViennaAustria

The energy use of Bitcoin is fiercely debated among academics,practitioners,and the general public.This debate is often biased and characterized by a lack of understanding.Therefore,I start this paper with a discussion of the fundamentals of Bitcoin,which includes the clarification of widely held misconceptions.Next,I illustrate how Bitcoin is related to energy and describe the underlying incentive mechanism.In the main body of the paper,I discuss various components of Bitcoin’s energy use,including the amount,composition,and geographical distribution of the energy,as well as emerging positive and negative effects.These components are then combined into a comprehensive framework that provides a solid foundation for future academic research and presents practitioners with the big picture of how and why Bitcoin requires energy and whether this can be justified from an environmental point of view.

关键词： Bitcoin Energy Energy use Energy consumption Proof of work Sustainability

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Function of lateral line canal morphology

引用

Integrative Zoology 2015年第1期10卷 111-121页

作者： Adrian KLEIN horst BLECKMANN Institute for Zoology University of BonnPoppelsdorfer SchlossBonnGermany

Fish perceive water motions and pressure gradients with their lateral line.Lateral line information is used for prey detection,spatial orientation,predator avoidance,schooling behavior,intraspecific communication and station holding.The lateral line of most fishes consists of superficial neuromasts(SNs)and canal neuromasts(CNs).The distribution of SNs and CNs shows a high degree of variation among fishes.Researchers have speculated for decades about the functional significance of this diversity,often without any conclusive answers.Klein et al.(2013)examined how tubules,pore number and pore patterns affect the filter properties of lateral line canals in a marine teleost,the black prickleback(Xiphister atropurpureus).A preliminary mathematical model was formulated and biomimetic sensors were built.For the present study the mathematical model was extended to understand the major underlying principle of how canal dimensions influence the filter properties of the lateral line.Both the extended mathematical model and the sensor experiments show that the number and distribution of pores determine the spatial filter properties of the lateral line.In an environment with little hydrodynamic noise,simple and complex lateral line canals have comparable response properties.However,if exposed to highly turbulent conditions,canals with numerous widely spaced pores increase the signal to noise ratio significantly.

关键词： filter lateral line morphology noise sensor

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Lateral line system of fish

引用

Integrative Zoology 2009年第1期4卷 13-25页

作者： horst BLECKMANN Randy ZELICK Institute of Zoology University of BonnBonnGermany Department of Biology Portland State UniversityPortlandUSA

The lateral line is a sensory system that allows fishes to detect weak water motions and pressure gradients.The smallest functional unit of the lateral line is the neuromast,a sensory structure that consists of a hair cell epithelium and a cupula that connects the ciliary bundles of the hair cells with the water surrounding the fish.The lateral line of most fishes consists of hundreds of superficial neuromasts spread over the head,trunk and tail fin.In addition,many fish have neuromasts embedded in lateral line canals that open to the environment through a series of pores.The present paper reviews some more recent aspects of the morphology,behavioral relevance and physiology of the fish lateral line.In addition,it reports some new findings with regard to the coding of bulk water flow.

关键词： central integration hydrodynamic reception lateral line object localization teleost fish.

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

完全可吸收封堵器——结构性和先天性心脏病治疗的关键进展?

引用

Science Bulletin 2023年第16期68卷 1733-1734页

作者： Kerstin Piayda Stefan Bertog Kolja Sievert horst Sievert CardioVascular Center Frankfurt Frankfurt 60389Germany Department of Cardiology and Angiology Universitätsklinikum Gieûen und MarburgGieûen 35391Germany

Over the past decades,transcatheter therapy has become the primary option for the treatment of simple congenital heart diseases with the advantages of minimal invasiveness and rapid recovery.However,currently used metal occluders may cause nickel allergies,inflammation,and erosion.In the treatment of ventricular septal defects(VSD),due to the close proximity of the electrical conduction tissue,implantation of conventional occluders may cause conduction abnormalities.Complete atrioventricular block can occur in up to 2%of patients undergoing percutaneous perimembranous VSD closure with conventional devices[1].The timing of this event varies,ranging from immediate/intraprocedural to years after the procedure.Most commonly,it is observed within the first five days[1],however,late-onset atrioventricular block is fairly common.For this reason,no perimembranous VSD closure device has been approved by the US Food and Drug Administration[2].The complicated anatomical structure of VSDs and its anatomical relationship to the atrioventricular node complicates device design and development.In this context,bioresorbable occluders have potential advantages.It is conceivable that,due to implant degradation over time and native cardiac tissue coverage,surrounding tissue compression and persistent arrhythmias are less prevalent.

关键词：先天性心脏病 closure conduction

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Microstructure and magnetic properties evolution of Al/CoCrFeNi nanocrystalline high-entropy alloy composite

引用

Rare Metals 2022年第6期41卷 2038-2046页

作者： Jun-Jie Wang Zong-De Kou Shu Fu Shang-Shu Wu Si-Nan Liu Meng-Yang Yan Di Wang Si Lan horst Hahn Tao Feng School of Material Science and Engineering Herbert Gleiter Institute of NanoscienceNanjing Universily of Science and TechnologyNanjing 210094China Institute of Nanotechnology Karlsruhe Institule of TechnologyKarlsruhe 76021Germany

A systematic microstructure-oriented magnetic property investigation for Al/CoCrFeNi nanocrystalline high-entropy alloys composite(nc-HEAC)is presented.In the initial state,the Al/CoCrFeNi nc-HEAC is composed of face-centered cubic(FCC)-Al,FCC-CoCrFeNi and hexagonal close-packed(HCP)-CoNi phases.High energy synchrotron radiation X-ray diffraction and high-resolution transmission electron microscopy were used to reveal the relationship between microstructure evolution and mag-netic mechanism of Al/CoCrFeNi nc-HEAC during heat treatment.At low-temperature annealing stage,the mag-netic properties are mainly contributed by the HCP-CoNi phase.With the increase of temperature,the diffusion-in-duced phase transition process including the transformation of AlCoCrFeNi HEA from FCC to BCC structure and the growth of B2 phase plays a dominant role in the magnetic properties.It was found that the magnetic properties can be effectively regulated through the control of the thermal diffusion process.The nano dual-phase thermal diffusion-induced phase transition behavior of nanocomposites pre-pared based on laser-IGC technology provides guidance for the diffusion process and microstructure evolution of two phases in composites.

关键词： Nanocry salline high-entropy alloy composites Diffusion-induced phase transition Magnetic Laser-inert gas condensation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Different characteristics of chronic dibutyltin dichloride-induced pancreatitis and cholangitis in mouse and rat

引用

Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 169-174页

作者： Friederike Lütt Luise Ehlers horst Nizze Robert Jaster Department of Medicine II Division of GastroenterologyRostock University Medical CenterE.-Heydemann-Str.618057 RostockGermany Institute of Pathology Rostock University Medical CenterStrempelstraβ1418057 RostockGermany

Background:Current animal models of chronic pancreatitis(CP)often provide only limited pathophysio-logical insights since they incompletely reflect the human disease.CP induced by injection of dibutyltin dichloride(DBTC-pancreatitis)shares with human CP the important feature of extended fibrosis and would be an even more attractive model if it could be transferred from rats to mice,as recently sug-gested in the context of combined ethanol and DBTC application.This study aimed to evaluate the effects of DBTC in pancreas and liver of C57BL/6 mice,a strain commonly used to engineer genetic mouse mod-els.Methods:C57BL/6 mice and Lewis rats were exposed to variable doses of DBTC.After an investigation period of up to 4 weeks,laboratory findings and histopathological changes of pancreas and liver were evaluated.Results:Chronic DBTC-pancreatitis in rats was characterized by acinar cell damage,ductal changes,fi-brosis,and inflammatory cell infiltrates.Mice treated with DBTC at 6–8 mg/kg body weight,the standard doses in rats,showed transient increases of lipase activities but no morphological signs of chronic DBTC-pancreatitis 4 weeks after injection of the drug.Increased doses of 10–12 mg/kg DBTC were intolerable due to their high toxicity.In contrast,mice and rats presented with a similar histopathology of the liver that can be characterized as a chronic-proliferative DBTC-cholangitis with predominating damage and proliferation of the small bile ducts as well as secondary portal inflammatory cell infiltrates and a begin-ning portal fibrosis.Conclusions:The DBTC-model cannot be transferred from rats to C57BL/6 mice with respect to chronic DBTC-pancreatitis,but might be of interest to study DBTC-cholangitis in both species.

关键词： Animal models Cholangitis Pancreatitis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells

引用

Cellular & Molecular Immunology 2016年第3期13卷 277-292页

作者： Andrea Kristina horst Katrin Neumann Linda Diehl Gisa Tiegs Institute of Experimental Immunology and Hepatology Center for Experimental Medicine University Medical Center Hamburg-Eppendorf Martinistrasse 52Hamburg D-20246 Germany

The liver is a tolerogenic organ with exquisite mechanisms of immune regulation that ensure upkeep of local and systemic immune tolerance to self and foreign antigens, but that is also able to mount effective immune responses against pathogens. The immune privilege of liver allografts was recognized first in pigs in spite of major histo-compatibility complex mismatch, and termed the ＂liver tolerance effect＂. Furthermore, liver transplants are spontaneously accepted with only low-dose immunosuppression, and induce tolerance for non-hepatic co-transplanted allografts of the same donor. Although this immunotolerogenic environment is favorable in the setting of organ transplantation, it is detrimental in chronic infectious liver diseases like hepatitis B or C, malaria, schistosomiasis or tumorigenesis, leading to pathogen persistence and weak anti-tumor effects. The liver is a primary site of T-cell activation, but it elicits poor or incomplete activation of T cells, leading to their abortive activation, exhaustion, suppression of their effector function and early death. This is exploited by pathogens and can impair pathogen control and clearance or allow tumor growth. Hepatic priming of T cells is mediated by a number of local conventional and nonconventional antigen-presenting cells （APCs）, which promote tolerance by immune deviation, induction of T-cell anergy or apoptosis, and generating and expanding regulatory T cells. This review will focus on the communication between classical and nonclassical APCs and lymphocytes in the liver in tolerance induction and will discuss recent insights into the role of innate lymphocytes in this process.

关键词： innate immunity liver tolerance nonconventional

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

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

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

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

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

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：