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| 1 | Plant abiotic stress response and nutrient use efficiency显示文摘Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies. | Zhizhong Gong Liming Xiong Huazhong Shi Shuhua Yang Luis R.Herrera-Estrella Guohua Xu Dai-Yin Chao Jingrui Li Peng-Yun Wang Feng Qin Jigang Li Yanglin Ding Yiting Shi Yu Wang Yongqing Yang Yan Guo Jian-Kang Zhu | 2020 | Science China(Life Sciences)2020,63,5: | 94 |
| 2 | PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy显示文摘Mitophagy 是为损坏线粒体的特定的消除的选择 autophagy 的一种重要类型。(PINK1 )导致 PTEN 的通常认为的 kinase 蛋白质 1 催化 ubiquitin (Ub ) 的 phosphorylation 在 PINK1-Parkin-mediated mitophagy 的发作起一个关键作用。(PTEN-L ) 磷酸酶和 tensin 相当或相同的事物(PTEN ) 长是 PTEN 的最新识别的 isoform,与到它的 N 终点的 173 氨基酸的增加。这里,我们报导 PTEN-L 是经由它对 phosphorylated ubiquitin 的蛋白质磷酸酶活动的 mitophagy 的一个新奇否定管理者。我们发现 PTEN-L 在外部 mitochondrial 膜(OMM ) 本地化,而 PTEN-L 的删除支持, PTEN-L 的 overexpression 禁止, mitophagy 由各种各样的损坏线粒体的代理人导致了。机械学地, PTEN-L 能够有效地阻止 Parkin mitochondrial translocation,减少 Parkin phosphorylation,维持它的关上的不活跃的符合构造,并且禁止它的 E3 ligase 活动。更重要地, PTEN-L 在 vivo 减少 phosphorylated ubiquitin (pSer65-Ub ) 的水平,并且在 vitro,磷酸酶试金经由它的蛋白质磷酸酶活动证实那 PTEN-L dephosphorylates pSer65-Ub,独立于它的类脂化合物磷酸酶功能。一起拿,我们的调查结果为 ubiquitin 作为蛋白质磷酸酶表明 PTEN-L 的新奇功能,它抵抗在 mitophagy 正式就职和 mitophagy 的最终的抑制导致前馈控制机制的阻塞的调停 PINK1 的 ubiquitin phosphorylation。因此,理解 PTEN-L 的这新奇功能在控制 mitophagy 的分子的难题提供一关键错过片,在包括象 Parkinsons 那样的 neurodegenerative 混乱的许多重要人的疾病的一个批评过程疾病。 | Liming Wang Yik-Lam Cho Yancheng Tang Jigang Wang Jung-Eun Park Yajun Wu Chunxin Wang Yan Tong Ritu Chawla Jianbin Zhang Yin Shi Shuo Deng Guang Lu Yihua Wu Hayden Weng-Siong Tan Pornteera Pawijit Grace Gui-Yin Lim Hui-Ying Chan Jingzi Zhang Lei Fang Hanry Yu Yih-Cherng Liou Mallilankaraman Karthik Boon-Huat Bay Kah-Leong Lim Siu-Kwan Sze Celestial T. Yap Han-Ming Shen | 2018 | Cell Research2018,28,8: | 25 |
| 3 | The discovery of Palaeoproterozoic volcanic rocks in the Bulunkuoler Group from the Tianshuihai Massif in Xinjiang of Northwest China and its geological significance显示文摘In the Dabudaer region of the Tianshuihai Massif (Xinjiang, Northwest China), metavolcanic rocks within the mainly meta-sedimentary Bulunkuoler Group are basalt, basaltic andesite, and rhyolite. In situ zircon U-Pb LA-ICP-MS dating on rhyolite magmatic zircons yielded an age of 2481±14 Ma, interpreted as the eruption age of the Bulunkuoler Group volcanic rocks. The basalt and basaltic andesite are low-Al tholeiite series and the rhyolite is low-Al calc-alkaline series. All of rocks are charac-terized by enrichment of LREE and LILE (Rb, Th and Ba), depletion of P, Nb, Ta and Ti, and absence of Eu anomalies. The εNd(t) of basalts ranges from 3.14 to 4.88 indicating a depleted mantle source. The trace element signatures show that these magmas experienced intense crustal contamination during their ascent. Direct evidence for crustal contamination is the xenocrystic zircons in the ryholite, with ages back to ca. 3300 Ma. The primitive-mantle normalized and Zr/Y-Zr diagrams for the basic volcanic rocks show that they formed in an intra-continental tectonic setting. Combined with the previous studies and compared with North China Craton Neoarchean basic volcanic rocks, it is supposed that the Bulunkuoler Group volcanic rocks reflect the Palaeoproterozoic mantle magma underplating and interaction with felsic crust. | JI WenHua LI RongShe CHEN ShouJian HE ShiPing ZHAO ZhenMing BIAN XiaoWei ZHU HaiPing CUI JiGang REN JuanGang | 2011 | Science China Earth Sciences2011,54,1: | 22 |
| 4 | Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine显示文摘Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts. | Jigang Wang Chengchao Xu Yin Kwan Wong Yujie Li Fulong Liao Tingliang Jiang Youyou Tu | 2019 | Engineering2019,5,1: | 16 |
| 5 | Traditional Chinese medicine in COVID-19显示文摘COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2)has spread across the globe,posing an enormous threat to public health and safety.Traditional Chinese medicine(TCM),in combination with Western medicine(WM),has made important and lasting contributions in the battle against COVID-19.In this review,updated clinical effects and potential mechanisms of TCM,presented in newly recognized three distinct phases of the disease,are summarized and discussed.By integrating the available clinical and preclinical evidence,the efficacies and underlying mechanisms of TCM on COVID-19,including the highly recommended three Chinese patent medicines and three Chinese medicine formulas,are described in a panorama.We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19,but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM. | Ming Lyu Guanwei Fan Guangxu Xiao Taiyi Wang Dong Xu Jie Gao Shaoqin Ge Qingling Li Yuling Ma Han Zhang Jigang Wang Yuanlu Cui Junhua Zhang Yan Zhu Boli Zhang | 2021 | Acta Pharmaceutica Sinica B2021,11,11: | 14 |
| 6 | Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1显示文摘Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis. | Piao Luo Dandan Liu Qian Zhang Fan Yang Yin-Kwan Wong Fei Xia Junzhe Zhang Jiayun Chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang | 2022 | Acta Pharmaceutica Sinica B2022,12,5: | 14 |
| 7 | Effects of chronic exposure to nonylphenol on locomotor activity and social behavior in zebrafish(Danio rerio)显示文摘Nonylphenol(NP),a xenoestrogen ubiquitously found in aquatic ecosystems,is of high environmental concern.The present work assessed the effects of exposure to NP on locomotor activity and social behavior in male and female zebrafish(Danio rerio),to evaluate the possible hazard of NP to fish behavior and to pursue a potential biomarker of NP contamination.Fish were randomly divided into six groups.Five groups were receiving 0.1,1,10,50 and 100 μg/L nominal concentrations of NP for 60 days,respectively.A sixth control group was given the same treatment as the other five groups,but no NP.Locomotor activity,aggressive behavior,group preference and leaving shoal were examined.NP exposure showed marked influence on locomotor activity of the male zebrafish,whereas that of the female was not significantly affected by NP.Aggressive behavior and group preference were significantly affected by NP exposure in both male and female groups.Locomotor activity and aggressive behavior of the male and group preference of both male and female zebrafish were clearly inhibited at 100 μg/L NP.No significant alteration in leaving shoal was observed under NP exposure.The results suggested that changes in locomotor activity and aggressive behavior of the male and group preference of both male and female may be used as an ecologically relevant integrative biomarker of NP contamination. | Jigang Xia,Cuijuan Niu ,Xuejiao Pei Ministry of Education Key Laboratory of Biodiversity Science and Ecological Engineering,College of Life Sciences,Beijing Normal University,100875 Beijing,China. | 2010 | Journal of Environmental Sciences2010,22,9: | 13 |
| 8 | Cold-Induced CBF–PIF3 Interaction Enhances Freezing Tolerance by Stabilizing the phyB Thermosensor in Arabidopsis显示文摘Growth inhibition and cold-acclimation strategies help plants withstand cold stress,which adversely affects growth and survival.PHYTOCHROME B(phyB)regulates plant growth through perceiving both light and ambient temperature signals.However,the mechanism by which phyB mediates the plant response to cold stress remains elusive.Here,we show that the key transcription factors mediating cold acclimation,C-REPEAT BINDING FACTORs(CBFs),interact with PHYTOCHROME-INTERACTING FACTOR 3(PIF3)under cold stress,thus attenuating the mutually assured destruction of PIF3–phyB.Cold-stabilized phyB acts downstream of CBFs to positively regulate freezing tolerance by modulating the expression of stress-responsive and growth-related genes.Consistent with this,phyB mutants exhibited a freezing-sensitive phenotype,whereas phyB-overexpression transgenic plants displayed enhanced freezing tolerance.Further analysis showed that the PIF1,PIF4,and PIF5 proteins,all of which negatively regulate plant freezing tolerance,were destabilized by cold stress in a phytochrome-dependent manner.Collectively,our study reveals that CBFs–PIF3–phyB serves as an important regulatory module for modulating plant response to cold stress. | Bochen Jiang Yiting Shi Yue Peng Yuxin Jia Yan Yan Xiaojing Dong Hui Li Jie Dong Jigang Li Zhizhong Gong Michael F.Thomashow Shuhua Yang | 2020 | Molecular Plant2020,13,6: | 13 |
| 9 | Deformation mechanism and stability control of roadway along a fault subjected to mining显示文摘It is difficult to maintain the roadway around a fault because of the fractured surroundings,complex stress environment,and large and intense deformation in the mining process.Based on a tailgate of panel S2205 in Tunliu colliery,in Shanxi province,China,we investigated the evolution of stress and displacement of rocks surrounding the roadway during the drivage and mining period using theoretical analysis,numerical simulation and field trial methods.We analyzed the deformation and failure mechanisms of the tailgate near a fault.The deformation of surrounding rock caused by unloading in the drivage period is large and asymmetric,the roadway convergence increases with activation of the fault and secondary fracture develops in the mining period.Therefore,we proposed a specific control technique of the roadway along a fault as follows:(1) High-strength yielding bolt not only supports the shallow rock to loadbearing structures,but also releases primary deformation energy by use of a pressure release device in order to achieve high resistance to the pressure retained;(2) Grouting of near-fault ribside after initial stabilization of the rock deformation is used to reinforce the broken rock,and to improve the integral load-bearing capacity of the roadway.The research results were successfully applied to a field trial. | Yan Shuai Bai Jianbiao Li Wenfeng Chen Jigang Li Lei | 2012 | International Journal of Mining Science and Technology2012,22,4: | 11 |
| 10 | Finite element simulation and experimental test of the wear behavior for self-lubricating spherical plain bearings显示文摘In this study, based on the classical Archard adhesion wear theory, a three-dimensional finite element model was established, with the aim of simulating the failure process of self-lubricating spherical plain bearings in the swinging wear condition. The results show that the self-lubricating spherical plain bearings go through two different stages during the wear process, namely, initial wear stage and stable wear stage. Because the large contact points wear out during the initial wear stage, the maximum contact pressure decreases as the test period increases. The relatively larger wear depth region shows elliptical distribution, and the maximum distribution appears in the central contact area. The wear depth reaches 0.974 mm after swinging 25,000 times. PTFE fibers, which possess a good friction performance but poor abrasion resistance, abundantly exist on the friction surfaces of the fabric liner. Consequently, the friction torque during the initial wear stage is slightly smaller than the friction torque during the stable wear stage; however, the wear rate during the initial wear stage is high. The reliability and effectiveness of the finite element model are verified by experiment. The developed finite element model can be used for the analysis of the wear mechanisms of bearings and the prediction of the service life of bearings. | Yahong XUE Jigang CHEN Sumin GUO Qingliang MENG Junting LUO | 2018 | Friction2018,6,3: | 11 |
| 11 | Genomic basis for light control of plant development显示文摘Light is one of the key environmental signals regulating plant growth and development.Therefore,understanding the mechanisms by which light controls plant development has long been of great interest to plant biologists.Traditional genetic and molecular approaches have successfully identified key regulatory factors in light signaling,but recent genomic studies have revealed massive reprogramming of plant transcriptomes by light,identified binding sites across the entire genome of several pivotal transcription factors in light signaling,and discovered the involvement of epigenetic regulation in light-regulated gene expression.This review summarizes the key genomic work conducted in the last decade which provides new insights into light control of plant development. | Jigang Li William Terzaghi Xing Wang Deng | 2012 | Protein & Cell2012,3,2: | 11 |
| 12 | Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield显示文摘Artemisia annua is the major natural source of artemisinin,an anti-malarial medicine commonly used worldwide.Here,we present chromosome-level haploid maps for two A.annua strains with different artemisinin contents to explore the relationships between genomic organization and artemisinin production.High-fidelity sequencing,optical mapping,and chromatin conformation capture sequencing were used to assemble the heterogeneous and repetitive genome and resolve the haplotypes of A.annua.Approximately 5o,ooo genes were annotated for each haplotype genome,and a triplication event that occurred approximately 58.12million years ago was examined for the first time in this species.A total of 3,903,467-5,193,414 variants(SNPs,indels,and structural variants)were identified in the 1.5-Gb genome during pairwise comparison between haplotypes,consistent with the high heterozygosity of this species.Genomic analyses revealed a correlation between artemisinin concents and the copy number of amorpha-4,11-dienes ynthasegenes.This correlation was further confirmed by resequencing of 36A.annua samples with varied artemisinin contents.Circular consensus sequencing of transcripts facilitated the detection of paralog expression.Collectively,our study provides chromosome-level allele-aware genome assemblies for two A.annua strains and new insights into the biosynthesis of artemisinin and its regulation,which will contribute to conquering malaria worldwide. | Baosheng Liao Xiaofeng Shen Li Xiang Shuai Guo Shiyu Chen Ying Meng Yu Liang Dandan Ding Junqi Bai Dong Zhang Tomasz Czechowski Yi Li Hui Yao Tingyu Mai Caroline Howard Chao Sun Haitao Liu Jiushi Liu Jin Pei Jihai Gao Jigang Wang Xiaohui Qiu Zhihai Huang Hongyi Li Ling Yuan Jianhe Wei lan Graham Jiang Xu Boli Zhang Shilin Chen | 2022 | Molecular Plant2022,15,8: | 9 |
| 13 | TRANSLUCENT GREEN, an ERF Family Transcription Factor, Controls Water Balance in Arabidopsis by Activating the Expression of Aquaporin Genes显示文摘水是在几乎所有生活有机体的最丰富的分子。Aquaporins 是玩控制房间的水内容的批评 rolesin 的隧道蛋白质。这里,我们报导 AP2/EREBP 家庭抄写 factorin Arabidopsis thaliana 的鉴定,半透明的格林( TG )其在转基因的植物的 overexpression 给了提高的干旱忍耐并且使 leaves.TG 蛋白质成玻璃在原子核是局部性的,在 vitro 绑 DRE 和 GCC 元素,并且在酵母房间充当 transcriptional 使活跃之物。Microarray 分析揭示了 TG,五基因在之中编码 aquaporins 调整的 330 基因的一个总数。短暂表示试金证明 TG 直接绑在 threeaquaporin 基因的倡导者,例如 AtTIP1; 1, AtTIP2; 3,并且 AtPIP2; 2,直接显示那 TG 调整这些基因的表示。而且, AtTIP1 的 overexpression; 1 在转基因的 Arabidopsis 植物导致了使成玻璃的显型,类似于在 TG overexpression 线观察的那些。进野类型的叶子的水注射概括了 vitrifiedleaf 显型,它被从脉管的捆割掉水供应颠倒。一起拿,我们在通过直接激活 aquaporin genes.Key 词的表达式的 Arabidopsis 的数据 supportthat TG 控制水平衡: | Danling Zhu Zhe Wu Guangyu Cao Jigang Li Jia Wei Tomohiko Tsuge Hongya Gua Takashi Aoyama Li-Jia Qu | 2014 | Molecular Plant2014,7,4: | 8 |
| 14 | Spatial Distribution of Integrated Impact Index of Mega-event——A Case Study of Expo '99 Kunming显示文摘Taking the affinity between events and media as a conceptualization base, a total of 1032 related news re-ports of Expo '99 Kunming, gathered from the internet data bank of China INFOBANK from 1992 to 2003, are used as data sources. After classifying them with a communication research method-the content analysis, a data bank for SPSS is set up, and a mathematic model called the Integrated Impact Index of Expo '99 Kunming is constituted. With the model, the spatial distribution of the total integrated impacts of Expo '99 Kunming on the regions or cities with different regional scales is analysed quantitatively. The conclusions are: 1) the Expo '99 Kunming made obvious integrated impacts on the regions or cities of every scale, especially in the venue city and the region-Kunming City and Yunnan Province; 2) it had corresponding impacts on other provinces; 3) the spatial distribution of Integrated Impact Index had a disaggregation with both plane extension and spotted decentralization; and 4) there was a distance decay law in all three scales of regions (Kunming City, Yunnan Province and the whole China), which incarnated the spatial extension law of the integrated impact of a special mega-event. | DAI Guangquan BAO Jigang | 2008 | Chinese Geographical Science2008,18,3: | 7 |
| 15 | COP9 signalosome: Discovery, conservation,activity, and function显示文摘The COP9 signalosome(CSN)is a conserved protein complex,typically composed of eight subunits(designated as CSN1 to CSN8)in higher eukaryotes such as plants and animals,but of fewer subunits in some lower eukaryotes such as yeasts.The CSN complex is originally identified in plants from a genetic screen for mutants that mimic light-induced photomorphogenic development when grown in the dark.The CSN complex regulates the activity of cullin-RING ligase(CRL)families of E3 ubiquitin ligase complexes,and play critical roles in regulating gene expression,cell proliferation,and cell cycle.This review aims to summarize the discovery,composition,structure,and function of CSN in the regulation of plant development in response to external(light and temperature)and internal cues(phytohormones). | Nanxun Qin Dongqing Xu Jigang Li Xing Wang Deng | 2020 | Journal of Integrative Plant Biology2020,62,1: | 6 |
| 16 | Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease显示文摘 | Jingyao Zhang Jie Ma Xiaoyun Du Dapeng Wu Hong Ai Jigang Bai Shunbin Dong Qinling Yang Kai Qu Yi Lyu Robert K Valenzuela Chang Liu | 2015 | Chinese Medical Journal2015,,1: | 6 |
| 17 | Experimental validation of dynamic polarization compensation in ground-satellite quantum key distribution显示文摘Ground-satellite quantum key distribution(QKD)is a feasible way to implement global-scale quantum communication.Herein we propose an approach to dynamically compensate the polarization of the photons when passing through the optical telescope used in ground-satellite QKD.Our results experimentally demonstrate that the fidelity of any polarization state after dynamic compensation can be achieved by more than 99.5%,which fulfills the requirements of ground-satellite QKD. | WANG ChaoZe GUO Hui REN JiGang CAO Yuan PENG ChengZhi LIU WeiYue | 2014 | Science China(Physics,Mechanics & Astronomy)2014,57,7: | 6 |
| 18 | Quantitative Analysis Model and Application of the Hydrocarbon Distribution Threshold显示文摘烃来源岩石显然控制烃水库的形成和分发。基于来源控制理论的地质的概念,烃分发阀值的概念被提出。这为岩石调节在烃盆移居的来源控制的烃意味着最大的范围。三个定量分析模型在这个基础上被建议,也就是烃累积概率,最大的烃规模阀值和储备分发概率,分别地指形成一座烃水库的概率,烃水库和在在烃分发阀值以内的某个区域的储备分发的百分比的可能的最大的规模。539 座烃水库上的统计分析从七沉积的盆在 28 个烃来源厨房里发现了并且最大的水库规模可能在烃盆,烃累积概率和油和煤气的储备分发形成了的东方中国表演下垂概率都被烃来源岩石的特征控制。通常,当从烃的距离采购原料,摇中心和烃分泌物边界变得更长并且来源岩石中心得到的烃的烃分泌物紧张更小,将有烃累积的更低的概率。相应量的模型基于单个因素统计和 multivariate 分析被建立。在 Jiyang 消沉的实际申请证明从为烃分发阀值的定量分析模型的预言与实际探索结果同意很好,显示定量分析模型是可能的是一个可行工具。 | JIANG Fujie PANG Xiongqi GUO Jigang | 2013 | Acta Geologica Sinica(English Edition)2013,87,1: | 6 |
| 19 | Impairment of the autophagy-lysosomal pathway in Alzheimer’s diseases: Pathogenic mechanisms and therapeutic potential显示文摘Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and microtubule associated protein tau(MAPT/tau)in neuronal cells are hallmarks of AD.So far,the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes.Recently,there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis.Interestingly,the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD.Here,we first summarize the recent genetic,pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD.We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins,Aβand MAPT/tau,in AD.Finally,we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials.Overall,this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment. | Wei Zhang Chengchao Xu Jichao Sun Han-Ming Shen Jigang Wang Chuanbin Yang | 2022 | Acta Pharmaceutica Sinica B2022,12,3: | 6 |
| 20 | Probucol decreases homocysteine-stimulated CRP production in rat aortic smooth muscle cells via regulating HO-1/NADPH oxidase/ROS/p38 pathway显示文摘The elevated homocysteine level is an independent risk factor for atherosclerosis, which is characterized as a chronic inflammatory disease associated with oxidative stress. We have confirmed that homocysteine can stimulate the production of C-reactive protein (CRP) in rat aortic smooth muscle cells (RASMCs). In the present study, we investigated the role of probucol in homocysteine-induced CRP expression in cultured RASMCs and high-methionine-diet-induced hyperhomocysteinemic rats. The results showed that probucol decreased homocysteine-induced CRP mRNA and protein expression in RASMCs in a concentration-dependent manner. In addition, the animal experiment showed that probucol not only inhibited CRP expression in the vessel wall but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further investigations revealed that probucol markedly increased heme oxygenase-1 activity, suppressed nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, diminished superoxide anion generation, and decreased p38 phosphorylation in RASMCs and hyperhomocysteinemic rat aorta. These data demonstrate that probucol can inhibit homocysteine-induced CRP generation by interfering with the NADPH oxidase/p38 signal pathway in RASMCs, which will provide new evidence for the anti-inflammatory and anti-atherosclerotic effects of probucol. | Yuxia Li Qun Zhao Yuan Cao Jigang Si Jing Li Kai Cao Xiaoming Pang | 2021 | Acta Biochimica et Biophysica Sinica2021,53,2: | 5 |