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LRRK2, gBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 869-882页

作者： Shirley Yin-Yu Pang Rachel Cheuk Nam Lo Philip Wing-Lok ho Hui-Fang Liu Eunice Eun Seo Chang Chi-Ting Leung Yasine Malki Zoe Yuen-Kiu Choi Wing Yan Wong Michelle Hiu-Wai Kung David Boyer Ramsden Shu-Leong ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Institute of Metabolism and Systems Research University of BirminghamBirminghamUK.

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (gBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab gTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in gBA reduce glucocerebrosidase (gCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and gBA influence each other: gCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter gCase activity in gBA mutant cells. Clinically, LRRK2 g2019S mutation seems to modify the effects of gBA mutation, resulting in milder symptoms than those resulting from gBA mutation alone. however, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and gBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate gCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and gCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.

关键词： Parkinson’s disease Interaction LRRK2 gBA gCase Mutation Autophagy α-Synuclein

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Recent advances in polymeric membranes for CO_2 capture

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Chinese Journal of Chemical Engineering 2018年第11期26卷 2238-2254页

作者： Yang Han W.S.Winston ho William g.Lowrie Department of Chemical and Biomolecular Engineering and Department of Materials Science and Engineering The Ohio State University

Membrane and membrane process have been considered as one of the most promising technologies for mitigating CO_2 emissions from the use of fossil fuels. In this paper, recent advances in polymeric membranes for CO_2 capture are reviewed in terms of material design and membrane formation. The selected polymeric materials are grouped based on their gas transport mechanisms, i.e., solution‐diffusion and facilitated transport. The discussion of solution‐diffusion membranes encompasses the recent efforts to shift the upper bound barrier, including the enhanced CO_2 solubility in several rubbery polymers and novel methods to construct shape-persisting macromolecules with unprecedented sieving ability. The carrier-bearing facilitated transport membranes are categorized based on the specific CO_2-carrier chemistry. Finally, opportunities and challenges in practical applications are also discussed, including post-combustion carbon capture(CO_2/N2), hydrogen purification(CO_2/H2), and natural gas sweetening(CO_2/CH4).

关键词： Carbon capture Polymeric membrane gas separation

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Multidimensional thermally-induced transformation of nest-structured complex Au-Fe nanoalloys towards equilibrium

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Nano Research 2022年第1期15卷 581-592页

作者： Jacob Johny Oleg Prymak Marius Kamp Florent Calvo Se-ho Kim Anna Tymoczko Ayman El-Zoka Christoph Rehbock Ulrich Schurmann Baptiste gault Lorenz Kienle Stephan Barcikowski Technical Chemistry I and Center for Nanointegration Duisburg-Essen(CENIDE) University of Duisburg-EssenEssen 45141Germany Inorganic Chemistry and Center for Nanointegration Duisburg-Essen(CENIDE) University of Duisburg-EssenEssen 45141Germany Institute for Materials Science Synthesis and Real StructureKiel UniversityKiel 24143Germany University grenoble Alpes CNRSLiPhyGrenoble 38000France Max-Planck-Institut fur Eisenforschurtg gmbH Diisseldorf40237Germany Department of Materials Royal School of MineImperial College LondonLondon SW72AZUK

Bimetallic nanoparticles are often superior candidates for a wide range of technological and biomedical applications owing to their enhanced catalytic,optical,and magnetic properties,which are often better than their monometallic *** of their properties strongly depend on their chemical composition,crystallographic structure,and phase ***,little is known of how their crystal structure,on the nanoscale,transforms over time at elevated temperatures,even tho.gh this knowledge is highly relevant in case nanoparticles are used in,e.g.,high-temperature ***-Fe is a promising bimetallic system where the low-cost and magnetic Fe is combined with catalytically active and plasmonic ***,we report on the in s/fi;temporal evolution of the crystalline ordering in Au-Fe nanoparticles,obtained from a modern laser ablation in liquids *** in-depth analysis,complemented by dedicated atomistic simulations,includes a detailed structural characterization by X-ray diffraction and transmission electron microscopy as well as atom probe tomography to reveal elemental distributions down to a single atom *** show that the Au-Fe nanoparticles initially exhibit highly complex internal nested nanostructures with a wide range of compositions,phase distributions,and size-depended *** elevated temperature induces a diffusion-controlled recrystallization and phase merging,resulting in the formation of a single face-centered-cubic ultrastructure in contact with a body-centered cubic phase,which demonstrates the metastability of these *** these unique nanostructures with nested features could be highly attractive from a fundamental viewpoint as they could give further insights into the nanoparticle formation mechanism under non-equilibrium ***,the in situ evaluation of the crystal structure changes upon heating is potentially relevant for high-temperature process utilization of bimetallic na

关键词： nanoparticles in situ atom probe tomography diffusion recrystallization atomistic simulation

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Artificial cilia for soft and stable surface covalent immobilization of bone morphogenetic protein-2

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Bioactive Materials 2023年第6期24卷 551-562页

作者： Qi gan Lina Chen ho-Pan Bei Sze-Wing Ng Han guo guoqiang Liu Hao Pan Changsheng Liu Xin Zhao Zijian Zheng Laboratory for Advanced Interfacial Materials and Devices School of Fashion and TextilesThe Hong Kong Polytechnic UniversityKowloon99077Hong Kong Special Administrative Region of China Key Laboratory for Ultrafine Materials of Ministry of Education School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237PR China Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong Kong Special Administrative Region of China Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai201204PR China Department of Applied Biology and Chemical Technology Faculty of ScienceThe Hong Kong Polytechnic UniversityKowloon99077Hong Kong Special Administrative Region of China

Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great ***,we develop a stable and soft surface modification strategy to address this ***-2(a model growth factor)is covalently immobilized onto homogeneous poly(glycidyl methacrylate)(PgMA)polymer brushes which are grafted onto substrate surfaces(Au,quartz glass,silica wafer,or common biomaterials)via surface-initiated atom transfer radical *** surface modification method multiplies the functionalized interfacial area;it is simple,fast,gentle,and has little effect on the loaded protein owing to the cilia *** immobilized BMP-2(i-BMP-2)on the surface of homogeneous PgMA polymer brushes exhibits excellent bioactivity(-87%bioactivity of free BMP-2 in vitro and 20%-50%higher than scaffolds with free BMP-2 in vivo),with conformation and secondary structure well-preserved after covalent immobilization and ethanol ***,the osteogenic activity of i-BMP-2 on the nanoline pattern(PgMA-poly(N-isopropylacrylamide))shows-110%bioactivity of free *** is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic *** polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds,which facilitates in situ immobilization of growth factors,and accelerates repair of a wide range of tissue types.

关键词： Polymer brush Poly(glycidyl methacrylate) Surface modification Protein immobilization Bioactivity

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5-Demethylnobiletin and its major metabolites:efficient preparation and mechanism of their anti-proliferation activity in hepg2 cells

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Food Science and Human Wellness 2022年第5期11卷 1191-1200页

作者： Yanping Xin Ting Zheng Man Zhang Ruiqiang Zhang Siyue Zhu Dongli Li Denggao Zhao Yanyan Ma Chi-Tang ho Qingrong Huang School of Biotechnology and health Sciences Wuyi UniversityJiangmen 529020China International healthcare Innovation Institute(Jiangmen) Jiangmen 529020China Department of Food Science Rutgers UniversityNew Jersey 08901USA

5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,3’-didemethylnobiletin(5,3’-DDMN),5,4’-didemethylnobiletin(5,4’-DDMN)and5,3’,4’-tridemethylnobiletin(5,3’,4’-TDMN).however,the anti-cancer effects of 5-DMN and its in vivo metabolites against hepg2 cells remain *** this study,an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites,and their molecular structures were confirmed by;H NMR and ***,cell cycle arrestment,apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on hepg2 *** results showed that all 4 compounds inhibited the proliferation of hepg2 cells in a concentration-dependent *** anti-proliferative activity was exerted through inducing g2/M phase arrestment,cell apoptosis and promoting expression of a key apoptotic protein called cleaved *** results indicated that 5,3’-DDMN and5,3’,4’-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN,followed by 5,4’-*** expression of cleaved caspase-3 was the highest in cells treated with 5,4’-DDMN,implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution *** research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.

关键词： Hydroxylated polymethoxyflavones Chemical synthesis hepg2 Cell cycle Apoptosis

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Development of a Concentration Measurement Technique for Steady State Solid-liquid Mixing using a Neural Network

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Journal of Thermal Science 2013年第5期22卷 478-483页

作者： Deog hee Doh Joo ho Yum gyeong Rae Cho Myung ho Kim gyong Won Ryu Masahiro Takei Division of Mechanical and Energy Systems Engineering Korea Maritime UniversityYeongdo-gu Busan Korea graduate School Korea Maritime UniversityYeongdo-gu Busan Korea R&D Institute-5 Agency for Defense DevelopmentJochiwongil 462Yuseong Daejeon 305-152 Korea graduate School of Mechanical Engineering Artificial Science Division Chiba UniversityJapan

A measurement technique that can measure the concentration of the solid particles in liquid flow was *** measurement system consists of a color camera and three LCD *** solid particles were put at the bottom of a cylindrical mixing tank in which JetA1 oil was *** mixing of the solid particles was performed by rotating a propeller type agitator with three different rotation speed(500,600,700 r/min).Mixing state was visualized by the LCD displays and a color *** color intensity of the glass particles changes with their *** color information was decoded into three principle colors R,g,and B so that,the calibration curve of color-to-concentration was performed using these information.A neural network was used for this *** transient concentration field of the solid particles was quantitatively visualized.

关键词：测量技术固液混合神经网络浓度场液晶显示器彩色摄像机固体颗粒颜色信息

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Optimization and Application of Liquid Chromatography Determination of Dispersive Liquid-liquid Microextraction Purified Astaxanthin in Shrimp Waste

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Chemical Research in Chinese Universities 2013年第3期29卷 429-433页

作者： ZHU Tao ROW Kyung-ho School of Chemistry and Chemical Engineering Tianjin University of Technology Tianjin 300384 P. R. China Department of Chemical Engineering Inha University Incheon 402-751 Korea

A new molecularly imprinted solid-phase extraction（MISPE） monolithic cartridge was synthesized, and MISPE-DLLME（DLLME=dispersive liquid-liquid microextraction） was developed for purification of astaxanthin in shrimp waste. The eluent（methanol） from MISPE was used as the dispersive solvent in subsequent DLLME for further purifying and enriching the analyte prior to high-performance liquid chromatography（HPLC） analysis. The mobile phase was methanol-acetonitrile-water-dichloromethane（85：5：5：5, volume ratio）, flow rate was 0.7 mL/min and UV wavelength was 476 nm. Under optimal conditions, good linearity was obtained in a range of 0.2--200.0 lug/mL（r2=0.9998） with a limit of detection（LOD） of 0.08 Hg/mL, and the extraction recoveries at three spiked levels ranged from 88.3%--92.5% with a relative standard deviation（RSD） less than 4.3%. Moreover, the mean contents of astaxanthin in the three batches of shrimp waste were 95.9, 85.4 and 77.2 μg/g, respectively. This method combining the advantages of MISPE and DLLME results in high selectivity and low cost, which was applied to determining the astaxanthin level in shrimp waste samples.

关键词： Molecularly imprinted solid-phase extraction Dispersive liquid-liquid microextraction Astaxanthin Shrimp waste

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Aerosol-assisted rapid synthesis of SnS-C composite microspheres as anode material for Na-ion batteries

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Nano Research 2015年第5期8卷 1595-1603页

作者： Seung ho Choi Yun Chan Kang Department of Materials Science and Engineering Korea University Anam-Dong Seongbuk-Gu Seou1136-713 Republic of Korea

SnS-C 合成粉末为 Na 离子电池用作阳极材料通过一个壶水花热分解作好准备。有一致地依附的象立方一样 SnS nanocrystals 的 C microspheres，有非结晶的 C 涂层层，在 900 的准备温度被形成 ????????????????????

关键词：钠离子电池复合材料负极材料快速合成微球气溶胶复合粉末制备温度

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Circulant Double Coverings of a Circulant graph of Valency Five

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Acta Mathematica Sinica,English Series 2007年第1期23卷 23-28页

作者： Rong Quan FENg Jin ho KWAK LMAM School of Mathematical Sciences Peking University Beijing 100871 P. R. China Mathematics Pohang University of Science and Technology Pohang 790-784 Korea

Enumerating the isomorphism classes of several types of graph covering projections is one of the central research topics in enumerative topological graph theory. A covering of g is called circulant if its covering graph is circulant. Recently, the authors [Discrete Math., 277, 73-85 （2004）1 enumerated the isomorphism classes of circulant double coverings of a certain type, called a typical covering, and showed that no double covering of a circulant graph of valency three is circulant. Also, in [graphs and Combinatorics, 21,386 400 （2005）], the isomorphism classes of circulant double coverings of a circulant graph of valency four are enumerated. In this paper, the isomorphism classes of circulant double coverings of a circulant graph of valency five are enumerated.

关键词： graph covering voltage assignment Cayley circulant graph

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2D spinel ZnCo_(2)O_(4) microsheet-coated functional separator for promoted redox kinetics and inhibited polysulfide dissolution

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Journal of Energy Chemistry 2021年第4期30卷 468-475页

作者： Jeong Seok Yeon Tae ho Park Young Hun Ko Periyasamy Sivakumar Jun Su Kim Youngkywon Kim ho Seok Park School of Chemical Engineering Sungkyunkwan UniversitySuwon 16419Gyeonggi-doRepublic of Korea Advanced Batteries Research Center Korea Electronics Technology InstituteSeongnam 13509Gyeonggi-doRepublic of Korea Department of health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology(SAIHST)Sungkyunkwan UniversitySuwon 16419Gyeonggi-doRepublic of Korea Department of Chemistry Dongguk University-Seoul CampusJung-gu 04620 SeoulRepublic of Korea

Lithium-sulfur(Li-S)batteries are receiving increasing attention as one of the potential next-generation batteries,owing to their high energy densities and low ***,practical Li-S batteries with high energy densities are extremely hindered by the sulfur loss,low Coulombic efficiency,and short cycling life originating from the polysulfide(LiPS)*** this study,two-dimensional(2D)ZnCo_(2)O_(4) microsheets fabricated by a facile hydrothermal process are employed to modify the separator,for improving the electrochemical performances of Li-S *** resulting 2D Zn Co_(2)O_(4)-coated separator features a coating thickness of approximately 10 lm,high ionic conductivity of 1.8 m S/cm,and low mass loading of 0.2 mg/cm^(2).This 2D ZnCo_(2)O_(4)-coated separator effectively inhibits Li PS shuttle by a strong chemical interaction with Li PS as well as promotes the redox kinetics by Zn CO2O4-coated layers,as determined by X-ray photoelectron spectroscopy analysis,self-discharge,time-dependent permeation test,Li symmetric cell test,and Li2S nucleation ***,the Li-S batteries based on the 2D Zn Co_(2)O_(4)-coated separator exhibit a high initial discharge capacity of 1292.2 m Ah/g at 0.1 ***,they exhibit excellent long cycle stability at 1 and 2 C with capacity retention of 84%and 86%even after800 cycles,corresponding to a capacity fading rate of 0.020%and 0.016%per cycle,***,these Li-S cells with a high sulfur loading at 5.3 mg/cm^(2) and low electrolyte concentration of 9 l L/mg deliver a high discharge capacity of 4.99 m Ah/cm^(2) after 200 cycles at 0.1 C.

关键词： Lithium sulfur batteries Functional separator 2D microsheet Polysulfide Redox kinetics

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