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Nanomaterials for neurodegenerative diseases:Molecular mechanisms guided design and applications

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Nano Research 2022年第4期15卷 3299-3322页

作者： Tianzhong Li Xueyan Hou Yu Qi Xiaohan Duan Pengcheng Yan Haoru Zhu Zhongjian Xie Han Zhang Shenzhen International Institute for Biomedical Research Shenzhen 518110China International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhen 518060China School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhou 325035China Institute of Pediatrics Shenzhen Children’s HospitalShenzhen 518038China

Successful treatment of neurodegenerative diseases(NDDs),including Alzheimer’s disease(AD),Parkinson’s disease(PD),and Huntington’s disease(HD),remains a significant challenge for neurologists due to the undesirable curative outcomes.Apart from surgeries,most drugs are only used to relieve the patients’symptoms without a permanent cure of the disease.The development of novel biomaterials targeting NDDs is greatly hindered by the limited understanding of underlying molecular mechanisms.Considering the difficulties in NDD drug development and clinical trials,a comprehensive and up-to-date review of disease pathogenesis and related novel therapies are needed.In the current article,the basic concepts and pathogenic characteristics of NDDs are firstly illustrated.Following the detailed description of molecular mechanisms underlying three common NDDs,recent advances of drug development based on targeting different pathogenic mechanisms are clarified.Hopefully,this review will be beneficial to address the gap between materials and targeted mechanisms while simultaneously provide suggestions for the future design of precise NDD medicine.

关键词： neurodegenerative diseases molecular mechanisms nanomaterials signaling pathways protein aggregation

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 1028-1036页

作者： Zhiting Wei Sheng Zhu xiaohan Chen Chenyu Zhu Bin duan Qi Liu Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration(Tongji University) Ministry of EducationOrthopaedic Department of Tongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Research Institute for Intelligent Autonomous Systems Shanghai 201210China

Transcriptional phenotypic drug discovery has achieved great success,and various compound perturbation-based data resources,such as connectivity map(CMap)and library of integrated network-based cellular signatures(LINCS),have been presented.Computational strategies fully mining these resources for phenotypic drug discovery have been proposed.Among them,the fundamental issue is to define the proper similarity between transcriptional profiles.Traditionally,such similarity has been defined in an unsupervised way.However,due to the high dimensionality and the existence of high noise in high-throughput data,similarity defined in the traditional way lacks robustness and has limited performance.To this end,we present Dr Sim,which is a learning-based framework that automatically infers similarity rather than defining it.We evaluated Dr Sim on publicly available in vitro and in vivo datasets in drug annotation and repositioning.The results indicated that Dr Sim outperforms the existing methods.In conclusion,by learning transcriptional similarity,Dr Sim facilitates the broad utility of high-throughput transcriptional perturbation data for phenotypic drug discovery.The source code and manual of Dr Sim are available at https://***/bm2-lab/Dr Sim/.

关键词： Metric learning Transcriptional profile similarity Drug annotation Drug repositioning LINCS

Sign-Changing Solutions for Superlinear Kirchhoff Type Problem via the Nehari Method

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Journal of Applied Mathematics and Physics 2023年第7期11卷 2093-2102页

作者： Xiaohan Duan Guanggang Liu School of Mathematical Sciences Liaocheng University Liaocheng China

In this paper, we consider a class of Kirchhoff type problem with superlinear nonlinearity. A sign-changing solution with exactly two nodal domains will be obtained by combining the Nehari method and an iterative tech... 详细信息

关键词： Kirchhoff Type Problem Nehari Method Iterative Technique

Solid polymer electrolytes in all-solid-state lithium metal batteries:From microstructures to properties

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能源化学:英文版 2023年第6期81卷 358-378,I0009页

作者： Zongxi Lin Ouwei Sheng xiaohan Cai Dan duan Ke Yue Jianwei Nai Yao Wang Tiefeng Liu Xinyong Tao Yujing Liu College of Materials Science and Engineering Zhejiang University of TechnologyHangzhou 310014ZhejiangChina

All-solid-state lithium(Li)metal batteries(ASSLMBs)are considered one of the most promising secondary batteries due to their high theoretical capacity and high safety performance.However,low room-temperature ionic conductivity and poor interfacial stability are two key factors affecting the practical application of ASSLMBs,and our understanding of the mechanisms behind these key problems from microscopic perspective is still limited.In this review,the mechanisms and advanced characterization techniques of ASSLMBs are summarized to correlate the microstructures and properties.Firstly,we summarize the challenges faced by solid polymer electrolytes(SPEs)in ASSLMBs,such as the low roomtemperature ionic conductivity and the poor interfacial stability.Secondly,several typical improvement methods of polymer ASSLMBs are discussed,including composite SPEs,ultra-thin SPEs,SPEs surface modification and Li anode surface modification.Finally,we conclude the characterizations for correlating the microstructures and the properties of SPEs,with emphasis on the use of emerging advanced techniques(e.g.,cryo-transmission electron microscopy)for in-depth analyzing ASSLMBs.The influence of the microstructures on the properties is very important.Until now,it has been difficult for us to understand the microstructures of batteries.However,some recent studies have demonstrated that we have a better understanding of the microstructures of batteries.Then we suggest that in situ characterization,nondestructive characterization and sub-angstrom resolution are the key technologies to help us further understand the batteries'microstructures and promote the development of batteries.And potential investigations to understand the microstructures evolution and the batteries behaviors are also prospected to expect further reasonable theoretical guidance for the design of ASSLMBs with ideal performance.

关键词： Lithium metal batteries Solid polymer electrolytes Microstructures Properties

Inhibiting collagen Ⅰ production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

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Acta Pharmaceutica Sinica B 2022年第2期12卷 939-951页

作者： Yan Yan Cancan Du Xixi duan xiaohan Yao Jiajia Wan Ziming Jiang Zhongyu Qin Wenqing Li Longze Pan Zhuoyu Gu Fazhan Wang Ming Wang Zhihai Qin Medical Research Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China Department of Urology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Changzhi Medical College Changzhi 046000China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China

The lung is one of the most common sites for cancer metastasis.Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells.Therefore,down-regulating the production of collagens may contribute to the inhibition of lung metastasis.It has been suggested that mi R-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens.Indeed,our clinical lung tumor data shows that mi R-29 a-3 p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’outcomes.However,suitable carriers need to be selected to deliver this therapeutic mi RNA to the lungs.In this study,we found that the chemotherapy drug cisplatin facilitated mi R-29 a-3 p accumulation in the exosomes of lung tumor cells,and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation.To scale up the preparation and simplify the delivery system,we designed a lung-targeting liposomal nanovesicle(by adjusting the molar ratio of DOTAP/cholesterol-mi RNAs to 4:1)to carry mi R-29 a-3 p and mimic the exosomes.This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo,thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

关键词： Lung metastasis miR-29a-3p CollagenⅠ Liposomal nanovesicle Exosomes Fibroblasts Pre-metastatic niche

Low genetic diversity in the endangered marine alga Silvetia siliquosa(Ochrophyta:Fucaceae)and the implication to conservation

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Journal of Oceanology and Limnology 2022年第1期40卷 216-225页

作者： Yanshuo LIANG Jie ZHANG xiaohan SONG Han-Gil CHOI Xu GAO Delin duan Zi-min HU CAS and Shandong Province Key Laboratory of Experimental Marine Biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China University of Chinese Academy Sciences Beijing 100049China Faculty of Biological Science and Institute for Environmental Science Wonkwang UniversityIksan 54538Korea Ocean School Yantai UniversityYantai 264005China

Although signifi cant research eff orts have been targeted toward conservation and management of endangered terrestrial fl ora and fauna,attempts have been limited to conserve threatened seaweeds.Silvetia siliquosa is an ecologically and commercially vital brown alga that is uniquely distributed in the Yellow-Bohai Sea and along the southwest coast of Korea.A massive decline in its distribution range and biomass from the mid-1990s onward indicates that this species has become endangered.In the present study,we used nuclear internal transcribed spacer and concatenated mitochondrial cytochrome oxidase I subunit+intergenic spacer to estimate the genetic diversity,population connectivity,and degree of genetic diff erentiation of S.siliquosa in China and Korea.The molecular results exhibited strikingly low levels of haplotype/ribotype and nucleotide diversity in S.siliquosa populations,with only three mitochondrial haplotypes and nuclear ribotypes detected in 136 and 143 specimens,respectively.The analysis of molecular variance revealed 85%-95%of genetic variance among populations.Population diff erentiation coeffi cient(F_(ST))and gene fl ow(N_(m))suggested that two populations(JIN and GWA)along the southern coast of Korea are highly divergent from the others,with weak genetic exchange.No signifi cant genetic diff erentiation was observed among populations either in China or along the geographically proximate west coast of Korea.Thus,four independent management units were designated for sustainable management:the LII and RUS populations in China,the YEO and CHA populations along the west coast of Korea,and each of the GWA and JIN populations along the south coast of Korea.We suggest that artifi cial cultivation and transplantation of S.siliquosa are the eff ective approaches for restoration and conservation.

关键词： biodiversity conservation endangered seaweed genetic diversity habitat loss Silvetia siliquosa

Considerable molecular interactions enable robust electrochemical properties:hydrogen bonds in lithium-ion batteries

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Science China Chemistry 2023年第7期66卷 1905-1923页

作者： Dan duan xiaohan Cai Cong Ma Zongxi Lin Yao Wang Jianwei Nai Tiefeng Liu Jianmin Luo Yujing Liu Xinyong Tao College of Materials Science and Engineering Zhejiang University of TechnologyHangzhou 310014China

Lithium-ion batteries(LIBs)have been in a dominant position in the new energy industry because of their excellent comprehensive performance.The performance of LIBs highly depends on the microstructures of the materials that constitute LIBs.Particularly,the relatively“weak”molecular interactions instead of the common-discussed strong chemical-bonding always affect the structures and the consequent properties of the components in LIBs.As a typical example,the hydrogen bonds,which widely exist inside LIBs,greatly improved the mechanical strength,lithium ion(Li^(+))transport rate and the intrinsic stabilities towards boosting performance of LIBs.This review starts from the interaction force between molecules,and especially summarizes the correlation between the formation of hydrogen bonds and the properties of the typical components in LIBs(cathode,anode,electrolyte,separator).In addition,how the formation of hydrogen bonds affects the performance of LIBs components is discussed.Finally,the strategies of combining hydrogen bonds with LIBs components in the future are prospected,which provide guidance for the rational design of high-performance LIBs.

关键词： hydrogen bonds lithium-ion batteries electrochemical performance

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低温堆供热控制研究

原子能科学技术 2023年第1期57卷 165-174页

作者：张乐贾玉文段天英刘勇崔晓涵中国原子能科学研究院核工程设计研究所北京102413

核能作为清洁、高效的能源,可以取代燃煤用于冬季供暖,从而实现供暖过程中“减污降碳”的目标。针对热网提出的供热需求指标,本文基于MATLAB/Simulink仿真平台,建立了池式低温堆全厂主系统模型,并提出了可用于反应堆功率调节的供热控制... 详细信息

核能作为清洁、高效的能源,可以取代燃煤用于冬季供暖,从而实现供暖过程中“减污降碳”的目标。针对热网提出的供热需求指标,本文基于MATLAB/Simulink仿真平台,建立了池式低温堆全厂主系统模型,并提出了可用于反应堆功率调节的供热控制方案。文中主要针对功率定值调节过程和热网事故小扰动工况反应堆响应过程作了详细分析。仿真研究结果显示,该控制方案能够根据热网对负荷的需求,调整反应堆功率,调节过程中反应堆各温度参数都在安全限值以内,并能够将用户室内温度维持在一个相对稳定的范围内。同时,该控制方案具有一定的抗事故工况负荷小扰动能力。在热网管网断裂等事故造成的负荷阶跃小扰动时,能够维持反应堆功率不变,使各回路温度在安全允许的范围内缓慢改变并重新达到稳定,且用户室内温度稍微变化后即可重新稳定。因此,该供热控制方案具有一定的设计参考价值。

关键词：核能供热池式低温堆变流量功率控制负荷扰动

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成都市土地利用时空结构变化研究

四川林业科技 2021年第2期42卷 77-81页

作者：魏晓涵段林森成都理工大学旅游与城乡规划学院四川成都610059

随着经济的高速发展,城市化对土地利用结构变化的影响较大,土地利用时空结构变化研究对土地规划及可持续发展具有重要意义。本文对成都市2000—2020年的土地利用数据进行处理,计算土地利用年变化率(R)、土地利用程度综合指数和土地利用... 详细信息

随着经济的高速发展,城市化对土地利用结构变化的影响较大,土地利用时空结构变化研究对土地规划及可持续发展具有重要意义。本文对成都市2000—2020年的土地利用数据进行处理,计算土地利用年变化率(R)、土地利用程度综合指数和土地利用变化量(S),得出以下结论:(1)耕地和建设用地变化幅度较大,总体呈增大的趋势;林地和其他土地总体呈减小趋势;水域面积呈现先减少后增加的趋势;(2)2000—2020年以来,土地利用程度综合指数整体呈上升趋势,土地利用日趋集约化,土地利用类型更加单一化;(3)成都市在2000—2005年、2005—2010年和2015—2020年土地处于发展期;而在2010—2015年,土地处于衰退期;并简要分析得到对土地利用结构的主要影响为人口变动、自然因素、产业调整等方面。

关键词：土地利用结构变化时空变化成都