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Mitochondria targeting drugs for neurodegenerative diseases——Design, mechanism and application

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2778-2789页

作者： jiajia xu Wei Du Yunhe Zhao Kahleong Lim Li Lu Chengwu Zhang Lin Li Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)Nanjing Tech University(NanjingTech)Nanjing 211816China Department of Anatomy Shanxi Medical UniversityTaiyuan 030001China Lee Kang Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore School of Basic Medical Sciences Shanxi Medical UniversityTaiyuan 030001China The Institute of Flexible Electronics(IFE Future Technologies)Xiamen UniversityXiamen 361005China

Neurodegenerative diseases(NDDs) such as Alzheimer’s disease(AD) and Parkinson ’s disease(PD) are a heterogeneous group of disorders characterized by progressive degeneration of *** threaten the lives of millions of people worldwide and regretfully remain *** is well accepted that dysfunction of mitochondria underlies the pathogenesis of *** of mitochondria results in energy depletion,oxidative stress,calcium overloading,caspases activation,which dominates the neuronal death of ***,mitochondria are the preferred target for intervention of *** far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome,though there are still some obstacles such as targeting specificity,delivery capacity hindering the drugs *** present review,we will elaborately address 1) the strategy to design mitochondria targeting drugs,2) the rescue mechanism of respective mitochondria targeting drugs,3) how to evaluate the therapeutic *** this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs.

关键词： Neurodegenerative diseases Mitochondria Targeting drug Apoptosis Reactive oxygen species Adenosine triphosphate Mitochondrial membrane potential Evaluation

Genistein and daidzein reduced chlorpyrifos induced damage in PC12 cell

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Oil Crop Science 2020年第1期5卷 1-5页

作者： Yu Gao jiajia xu Menglei xu Sunsen Shi Jinfeng Xiong College of Plant Protection Jilin Agricultural UniversityChangchunChina College of Food Science and Engineering/State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchunChina Changchun Institute of Biological Products ChangchunChina

The present study preliminarily evaluated neurotoxicity injuries induced by chlorpyrifos in PC12 cell,which were used as a model for nervous cell *** cultured PC12 cell,application of soy isoflavones(genistein,daidzein,monomer and mixture)significantly reduced chlorpyrifos induced toxicity,a widely used pesticide,and resulted in a better cell survival *** with isoflavones reduced malondialdehyde content,reactive oxygengeneration and acetylcholine level in medium,and maintained mitochondrial membrane potential *** enhanced endogenous antioxidant system in PC12 cell with an increasing in superoxide dismutase perunit *** reduced acetylcholine content in the *** and genistein showed different effects,and their combined effect were greater than *** conclusion,soy isoflavones as an antioxidant and neuroprotectant,enhanced choline metabolism,which effectively mitigated disadvantageous influence of PC12 cell caused by chlorpyrifos.

关键词： Chlorpyrifos Soy isoflavone Genistein Daidzein PC12 cell Cytotoxicity

Modeling and Rectification of Rolling Shutter Effect in CMOS Aerial Cameras

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Journal of Harbin Institute of Technology(New Series) 2017年第4期24卷 71-77页

作者： Lei Wan Ye Zhang Ping Jia jiajia xu Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of Science Graduate School of the Chinese Academy of Science Key Laboratory of Airborne Optical Imaging and Measurement Chinese Academy of Science

Due to the electronic rolling shutter, high-speed Complementary Metal-Oxide Semiconductor( CMOS) aerial cameras are generally subject to geometric distortions,which cannot be perfectly corrected by conventional vision-based algorithms. In this paper we propose a novel approach to address the problem of rolling shutter distortion in aerial imaging. A mathematical model is established by the coordinate transformation method. It can directly calculate the pixel distortion when an aerial camera is imaging at arbitrary gesture *** all pixel distortions form a distortion map over the whole CMOS array and the map is exploited in the image rectification process incorporating reverse projection. The error analysis indicates that within the margin of measuring errors,the final calculation error of our model is less than 1/2 pixel. The experimental results show that our approach yields good rectification performance in a series of images with different distortions. We demonstrate that our method outperforms other vision-based algorithms in terms of the computational complexity,which makes it more suitable for aerial real-time imaging.

关键词： aerial camera CMOS sensor rolling shutter effect coordinate transformation image rectification

A near-infrared multifunctional fluorescent probe for hypoxia monitoring and tumor-targeted therapy

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Chinese Chemical Letters 2022年第3期33卷 1589-1594页

作者： Yuxun Lu jiajia xu Zongyun Jia Siyu Kong Yimu Qiao Lin Li Qiong Wu Ying Zhou College of Chemical Science and Technology Yunnan UniversityKunming 650091China Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)Nanjing Tech University(NanjingTech)Nanjing 211816China

Hypoxia is one of the key characteristics of solid tumors. The over-expression of azoreductase resulting from hypoxia can be used as a target to visualize hypoxic levels and a trigger of the drug release system in tumor treatment. In this work, we developed a near-infrared fluorescent probe YLOD, composed of a near-infrared fluorophore, an azo bond, and an analogue of the anti-tumor drug melphalan. In the presence of azoreductase, YLOD displayed a red emission at 620 nm and released the anti-tumor drug concomitantly, thus achieving the integrated effects of hypoxic imaging and tumor treatment. Furthermore, YLOD successfully inhibited the growth of solid tumors during the tumor suppression experiments in nude mice. Considering all the results, YLOD emerges as a new fluorescence tool that can quickly determine the location and the edges of a tumor, showing concrete potential in clinical cancer treatment.

关键词： Azoreductase Hypoxia Theranostic Tumor

A Review of the Stirring Twenty Years of the China Cosmetics Industry

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China Detergent & Cosmetics 2021年第2期6卷 5-13页

作者： xu jiajia xu Wenjun Jinhua Jumei Network Technology Co. LtdChina

jiajiaIn January 1999,Pu Shu released his debut album,I Go to Year 2000,whose leading track“new boy”wrote,“put on new clothes and new hairstyles,relax with WINDOWS 98,no suffering in the road to come,what a cool future we will have.”While looking back to the past twenty years at the beginning of 2021,people in the cosmetics industry see the“cool future”they have created.

关键词： looking suffering WINDOWS

Overexpression of mechanical sensitive miR-337-3p alleviates ectopic ossification in rat tendinopathy model via targeting IRS1 and Nox4 of tendon-derived stem cells

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Journal of Molecular Cell Biology 2020年第4期12卷 305-317页

作者： Yiyun Geng Xiaoying Zhao jiajia xu xudong Zhang Guoli Hu Sai-Chuen Fu Kerong Dai Xiaodong Chen Yung shu-huang Patrick Xiaoling Zhang Department of Orthopedic Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Shenzhen Key Laboratory of Tissue Engineering Shenzhen Second People's Hospital(The First Hospital Affiliated to Shenzhen University)Shenzhen 518035China The Key Laboratory of Stem Cell Biology Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Department of Orthopaedics and Traumatology Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina

Tendinopathy,which is characterized by the ectopic ossification of tendon,is a common disease occurring in certain population,such as athletes that suffer from repetitive tendon ***,the molecular mechanism underlying the pathogenesis of tendinopathy caused by the overuse of tendon is still ***,we found that the mechanosensitive miRNA,miR-337-3p,had lower expression under uniaxial cyclical mechanical loading in tendon-derived stem cells(TDSCs)and negatively controlled chondro-osteogenic differentiation of ***,downregulation of miR-337-3p expression was also observed in both rat and human calcified tendons,and overexpressing miR-337-3p in patellar tendons of rat tendinopathy model displayed a robust therapeutic ***,we found that the proinflammatory cytokine interleukin-1^was the upstream factor of miR-337-3p that bridges the mechanical loading with its ***,the target genes of miR-337-3p,NADPH oxidase 4,and insulin receptor substrate 1,activated chondro-osteogenic differentiation of TDSCs through JNK and ERK signaling,***,these findings not only provide novel insight into the molecular mechanisms underlying ectopic ossification in tendinopathy but also highlight the significance of miR-337-3p as a putative therapeutic target for clinic treatment of tendinopathy.

关键词： mechanosensitive miRNA tendon-derived stem cells mechanical loading chondro-osteogenesis tendinopathy

PDGFRαreporter activity identifies periosteal progenitor cells critical for bone formation and fracture repair

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Bone Research 2022年第1期10卷 122-136页

作者： jiajia xu Yiyun Wang Zhu Li Ye Tian Zhao Li Amy Lu Ching-Yun Hsu Stefano Negri Cammy Tang Robert J.Tower Carol Morris Aaron W.James Departments of Pathology Johns Hopkins UniversityBaltimoreMD 21205USA Departments of Orthopedics Johns Hopkins UniversityBaltimoreMD 21205USA Department of Oral and Maxillofacial Surgery School of StomatologyChina Medical UniversityShenyangLiaoningPR China

The outer coverings of the skeleton,which is also known as the periosteum,are arranged in concentric layers and act as a reservoir for tissue-specific bone *** cellular heterogeneity within this tissue depot is being increasingly ***,inducible PDGFRαreporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture *** these processes,PDGFRαreporter^(+)progenitors give rise to Nestin+periosteal cells before becoming osteoblasts and *** diphtheria toxin-mediated ablation of PDGFRαreporter^(+)cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture *** ossicle transplantation,both mouse PDGFRαreporter^(+)periosteal cells and human Pdgfrα+periosteal progenitors expand,ossify,and recruit marrow to a greater extent than their counterpart periosteal cells,whereas PDGFRαreporter^(−)periosteal cells exhibit a predisposition to chondrogenesis in *** RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRαreporter^(+)periosteal cells,which partly underlie the osteoblastogenic features of this cell population.

关键词： progenitor fracture reservoir

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时滞振动控制系统部分极点配置问题的多步法

振动与冲击 2018年第7期37卷 38-42,68页

作者：徐佳佳刘皞南京航空航天大学理学院南京211106

对时滞单输入振动控制系统的部分极点配置问题作了分析和探讨。提出了求解时滞多输入振动控制系统部分极点配置问题的多步法,将不"想要"的特征值配置到给定特征值,其余特征对保持不变,这种方法很容易编程实现且不需要利用动柔度矩阵或求... 详细信息

对时滞单输入振动控制系统的部分极点配置问题作了分析和探讨。提出了求解时滞多输入振动控制系统部分极点配置问题的多步法,将不"想要"的特征值配置到给定特征值,其余特征对保持不变,这种方法很容易编程实现且不需要利用动柔度矩阵或求解Sylvester方程。数值试验的结果表明多步法是有效的。

关键词：部分极点配置时滞多步法

The Impacts of Highly Resourced Vocational Schools on Student Outcomes in China

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China & World Economy 2020年第6期28卷 125-150页

作者： Guirong Li jiajia xu Liying Li Zhaolei Shi Hongmei Yi James Chu Elena Kardanova Yanyan Li Prashant Loyalka Scott Rozelle International Center for Action Research on Education School of EducationHenan UniversityChina Henan University of Engineering China Freeman Spogli Institute Stanford UniversityUSA School of Advanced Agricultural Sciences Peking UniversityChina Higher School of Economics National Research UniversityRussia School of Education Henan UniversityChin Graduate School of Education Stanford UniversityUSA

Policymakers in developing countries have prioritized the mass expansion of vocational education and training(VET).This study examines whether the quality of VET in developing countries increases by investing greater resources per *** achieve this goal,we examine the impacts of attending model schools(which have far more resources per student)on a range of student cognitive,non-cognitive,and behavioral *** representative data from a survey of approximately 12,000 VET students from China,multivariate regression and propensity score matching analyses show that attending model vocational high schools do not benefit student outcomes,despite their substantially greater resources.

关键词： non-cognitive skills school expenditure student achievement vocational education and training