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Saturation attack based route planning and threat avoidance algorithm for cruise missiles 被引量:12
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作者 guanghui wang Xuefeng Sun +1 位作者 Liping Zhang Chao Lv 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2011年第6期948-953,共6页
According to the characteristic of cruise missiles,navigation point setting is simplified,and the principle of route planning for saturation attack and a concept of reference route are put forward.With the help of the... According to the characteristic of cruise missiles,navigation point setting is simplified,and the principle of route planning for saturation attack and a concept of reference route are put forward.With the help of the shortest-tangent idea in route-planning and the algorithm of back reasoning from targets,a reference route algorithm is built on the shortest range and threat avoidance.Then a route-flight-time algorithm is built on navigation points.Based on the conditions of multi-direction saturation attack,a route planning algorithm of multi-direction saturation attack is built on reference route,route-flight-time,and impact azimuth.Simulation results show that the algorithm can realize missiles fired in a salvo launch reaching the target simultaneously from different directions while avoiding threat. 展开更多
关键词 aerospace system engineering control and navigation technology of aero-craft mission planning route planning cruise missile saturation attack threat avoidance.
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Intrinsic apoptotic pathway and G2/M cell cycle arrest involved in tubeimoside I-induced EC109 cell death 被引量:14
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作者 Yang Xu guanghui wang +5 位作者 Quancheng Chen Ting Lin Zhiping Zeng Qiang Luo Jie Liu Cuiling Sun 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2013年第3期312-321,共10页
Objective: Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (E... Objective: Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (ESCC) for a long term. tubeimoside I (TBMS1) is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells. Methods: Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins' expression and location. Results: Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMSl-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B 1/cdc2 complex-related G2/M cell cycle arrest. Conclusions: Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC. 展开更多
关键词 Anticancer drug G2/M cell cycle arrest intrinsic apoptosis subcellular proteomics and tubeimoside I(TBMS 1)
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Fixed-length roof cutting with vertical hydraulic fracture based on the stress shadow effect:A case study 被引量:5
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作者 Feiteng Zhang Xiangyu wang +3 位作者 Jianbiao Bai Wenda Wu Bowen Wu guanghui wang 《International Journal of Mining Science and Technology》 SCIE EI CAS CSCD 2022年第2期295-308,共14页
Pre-driven longwall retracement roadway(PLRR)is commonly used in large mine shaft.The support crushing disasters occur frequently during the retracement,and roof management is necessary.Taking the 31107 panel as resea... Pre-driven longwall retracement roadway(PLRR)is commonly used in large mine shaft.The support crushing disasters occur frequently during the retracement,and roof management is necessary.Taking the 31107 panel as research background,the roof breaking structure of PLRR is analyzed.It is concluded that the roof cutting with vertical hydraulic fracture(HF)at a specified position,that is,fixed-length roof cutting,can reduce support load and keep immediate roof intact.The extended finite element method(XFEM)is applied to simulate hydraulic fracturing.The results show that both the axial and transverse hydraulic fracturing cannot effectively create vertical HFs.Therefore,a novel construction method of vertical HF based on the stress shadow effect(SSE)is proposed.The stress reversal region and HF orientation caused by the prefabricated hydraulic fracture(PF)are verified in simulation.The sub-vertical HFs are obtained between two PFs,the vertical extension range of which is much larger than that of directional hydraulic fracturing.The new construction method was used to determine the field plan for fixed-length roof cutting.The roof formed a stable suspended structure and deformation of the main PLRR was improved after hydraulic fracturing. 展开更多
关键词 Roof cutting Hydraulic fracture Stress shadow effect Retracement roadway Extended finite element method
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Improvement potential analysis for integrated fractionating and heat exchange processes in delayed coking units 被引量:2
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作者 Yang Lei Danlin Zeng guanghui wang 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2016年第8期1047-1055,共9页
A novel diagram-based representation approach is developed to analyze the thermodynamic efficiency and identify quickly the promising energy-use improvement for integrated fractionating and heat exchange processes in ... A novel diagram-based representation approach is developed to analyze the thermodynamic efficiency and identify quickly the promising energy-use improvement for integrated fractionating and heat exchange processes in delayed coking units. For considering temperature dependence of heat capacity and integrating fractionating and heat exchange processes, an advanced energy level composite curve is constructed by using the simulation results and a stepwise procedure. More accurate results of exergy analysis are obtained and the interaction between different components of the integrated system can be properly revealed in an integrated figure. Then the exergy calculation is performed to validate the performance of processes and to define the targets for improvement. The avoidable exergy destruction is also analyzed by applying the concepts of avoidable and unavoidable exergy destructions for the integrated system. In a case study for a Chinese refinery, the results reveal that the heat exchange between gas oil and deethanization gasoline is the most inefficient process with the highest retrofitting potential, and the lowest exergy efficiency of component in the integration system is only29.4%. The improvement potential and exergy efficiency for the fractionator are 38.1% and 97.3%, respectively.It is obvious that the fractionator is not the most promising component for improvement. 展开更多
关键词 Energy LEVEL EXERGY Avoidable EXERGY DESTRUCTION INTEGRATED system DISTILLATION
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Alisol B 23-acetate-induced HepG2 hepatoma cell death through mTOR signaling-initiated G_1 cell cycle arrest and apoptosis: A quantitative proteomic study 被引量:2
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作者 Ji Xia Qiang Luo +6 位作者 Shengbin Huang Fuquan Jiang Lin wang guanghui wang Jingjing Xie Jie Liu Yang Xu 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2019年第2期375-388,共14页
Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach bas... Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics predictions.Results: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were confirmed.Conclusions: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis. 展开更多
关键词 Alisol B 23-acetate APOPTOSIS cell cycle MTOR RIBOSOME proteins
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Controlled synthesis of cobalt nanocrystals on the carbon spheres for enhancing Fischer–Tropsch synthesis performance 被引量:2
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作者 Ting Kuang Shuai Lyu +4 位作者 Sixu Liu Yuhua Zhang Jinlin Li guanghui wang Li wang 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2019年第6期67-73,共7页
Non-porous carbon sphere was used as support to synthesize supported cobalt Fischer-Tropsch catalysts with high activity and durability. Strong metal-support interaction was avoided and intrinsic activity of pristine ... Non-porous carbon sphere was used as support to synthesize supported cobalt Fischer-Tropsch catalysts with high activity and durability. Strong metal-support interaction was avoided and intrinsic activity of pristine cobalt nano-particles was studied. Thermal decomposition synthesis method was applied to obtain cobalt catalysts with high dispersion and narrow particle size distribution. Furthermore the cobalt size can be controlled by the molar ratio of o-dichlorobenzene/benzylamine. Compared with supported cobalt catalysts prepared by incipient wetness impregnation method and ultrasonic impregnation method,the catalyst prepared by thermal decomposition method showed higher catalytic activity, higher long chain hydrocarbons selectivity and lower methane selectivity. 展开更多
关键词 FISCHER-TROPSCH SYNTHESIS Cobalt-based CATALYSTS DISPERSION Thermal decomposition
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Fabrication of functional hollow carbon spheres with large hollow interior as active colloidal catalysts 被引量:2
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作者 Qiang Sun guanghui wang +2 位作者 Wencui Li Xiangqian Zhang Anhui Lu 《Journal of Natural Gas Chemistry》 EI CAS CSCD 2012年第3期251-256,共6页
In this study, we have established a facile method to synthesize functional hollow carbon spheres with large hollow interior, which can act as active colloidal catalysts. The method includes the following steps: firs... In this study, we have established a facile method to synthesize functional hollow carbon spheres with large hollow interior, which can act as active colloidal catalysts. The method includes the following steps: first, hollow polymer spheres with large hollow interior were prepared using sodium oleate as the hollow core generator, and 2,4-dihydroxybenzoic acid and hexamethylene tetramine (HMT) as the polymer precursors under hydrothermal conditions; Fe3+ or Ag+ cations were then introduced into the as-prepared hollow polymer spheres through the carboxyl groups; finally, the hollow polymer spheres can be pseudomorphically converted to hollow carbon spheres during pyrolysis process, meanwhile iron or silver nanoparticles can also be formed in the carbon shell simultaneously. The structures of the obtained functional hollow carbon spheres were characterized by TEM, XRD, and TG. As an example, Ag-doped hollow carbon spheres were used as colloid catalysts which showed high catalytic activity in 4-nitrophenol reduction reaction. 展开更多
关键词 hollow carbon spheres hydrothermal synthesis ion-exchange colloidal catalysts
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Reconstruction of anterior skull base defects using frontalis muscle galea aponeurotica skull pedicle flaps
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作者 Kun Liu guanghui wang +6 位作者 Hong Zhang Yuping Wu Yangcheng Lv Jingsong Liu Jieke Ma Cheng Li Jiang Zhu 《The Chinese-German Journal of Clinical Oncology》 CAS 2013年第6期257-260,共4页
Objective: The aim of our study was to reconstruct soft and hard tissue perforating defects of the anterior skull base in a 1-stage surgical procedure with a combined craniofacial approach. Methods: Soft and hard ti... Objective: The aim of our study was to reconstruct soft and hard tissue perforating defects of the anterior skull base in a 1-stage surgical procedure with a combined craniofacial approach. Methods: Soft and hard tissue defects of the anterior skull base were successfully reconstructed in 43 patients during a 1-stage surgery through the use of frontalis muscle galea aponeuretica skull flaps with 1 or 2 vascularized pedicles. The skull flap areas were up approximately 7 cmx 14 cm. Results: Intracranial infection and cerebrospinal fluid leakage were not observed in the 43 patients, and all incisions healed. Of 33 malignant tumor patients, 25 patients received follow-up examinations for longer than 2 years, and 18 patients survived for 2 years. Conclusion: Frontalis muscle galea aponeurotica skull pedicle flaps provided a constant blood supply and re- suited in soft and thin tissue. The pedicle flaps, together with the external cranial bone plate, strengthened the support, but still allowed for bending and shaping. In addition, the flap harvesting approach was consistent with surgery approach, without aesthetic compromises. 展开更多
关键词 skull base reconstructive surgery bone reconstruction classification
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Rainbow Matchings in Properly Colored Bipartite Graphs
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作者 guanghui wang Guizhen Liu 《Open Journal of Discrete Mathematics》 2012年第2期62-64,共3页
Let G be a properly colored bipartite graph. A rainbow matching of G is such a matching in which no two edges have the same color. Let G be a properly colored bipartite graph with bipartition (X,Y) and . We show that ... Let G be a properly colored bipartite graph. A rainbow matching of G is such a matching in which no two edges have the same color. Let G be a properly colored bipartite graph with bipartition (X,Y) and . We show that if , then G has a rainbow coloring of size at least . 展开更多
关键词 RAINBOW Matching BIPARTITE GRAPHS
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Identification of propranolol and derivatives that are chemical inhibitors of phosphatidate phosphatase as potential broad-spectrum fungicides 被引量:1
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作者 Juan Zhao Yu Chen +16 位作者 Zhifen Ding Yaru Zhou Ruiqing Bi Ziting Qin Lei Yang Peng Sun Qiping Sun Guang Chen Daiyuan Sun Xianya Jiang Lu Zheng Xiao-Lin Chen Hu Wan guanghui wang Qiang Li Huailong Teng Guotian Li 《Plant Communications》 SCIE CSCD 2024年第1期215-230,共16页
Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechani... Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives.Here,we show that propranolol,a phosphatidate phosphatase(Pah)inhibitor,effectively suppresses fungal growth,sporulation,sexual reproduction,and infection of diverse plants.The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol.Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M.oryzae.Propranolol inhibits a broad spectrum of 12 plant pathogens,effectively inhibiting infection of barley,wheat,maize,tomato,and pear.To improve antifungal capacity,we synthesized a series of propranolol derivatives,one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1.Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in thefield.Taken together,our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism.Propranolol and its derivatives may therefore be promising candidates for fungicide development. 展开更多
关键词 PROPRANOLOL molecular design chemical modification VIRULENCE lipid metabolism Pyricularia oryzae
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Size-dependent activity of Fe-N-doped mesoporous carbon nanoparticles towards oxygen reduction reaction 被引量:1
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作者 Yilun Zhao Zhengbin Tian +3 位作者 Wenquan wang Xiaohui Deng Jo-Chi Tseng guanghui wang 《Green Carbon》 2024年第2期221-230,共10页
The rational design of Fe–N–C catalysts that possess easily accessible active sites and favorable mass transfer,which are usually determined by the structure of catalyst supports,is crucial for the oxygen reduction ... The rational design of Fe–N–C catalysts that possess easily accessible active sites and favorable mass transfer,which are usually determined by the structure of catalyst supports,is crucial for the oxygen reduction reaction(ORR).In this study,an oleic acid-assisted soft-templating approach is developed to synthesize size-controlled nitrogen-doped carbon nanoparticles(ranging from 130 nm to 60 nm and 35 nm,respectively)that feature spiral mesopores on their surface(SMCs).Next,atomically dispersed Fe–Nx sites are fabricated on the size-tunable SMCs(Fe1/SMC-x,where x represents the SMC size)and the size-dependent activity toward ORR is investigated.It is found that the catalytic performance of Fe1/SMCs is significantly influenced by the size of SMCs,where the Fe1/SMC-60 catalyst shows the highest ORR activity with a half-wave potential of 0.90 V vs.RHE in KOH electrolyte,indicating that the gas-liquid-solid three-phase interface on the Fe1/SMC-60 enhances the accessibility of Fe–Nx sites.In addition,when using Fe1/SMC-60 as the cathode catalyst in aqueous zinc-air batteries(ZABs),it delivers a higher open-circuit voltage(1.514 V),a greater power density(223 mW cm^(−2)),and a larger specific capacity/energy than Pt/C-based counterparts.These results further highlight the potential of Fe1/SMC60 for practical energy devices associated with ORR and the importance of size-controlled synthesis of SMCs. 展开更多
关键词 Soft-templating approach Size-dependent activity Fe-N-C catalyst Oxygen reduction reaction Zinc-air battery
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Quantifying trapping stability of optical tweezers with an external flow
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作者 FENG XU YARONG YU +9 位作者 YANG LIU YAO CHANG WENXIANG JIAO LIN wang HOPUI HO BEI WU FEI XU YANQING LU YUANJIE PANG guanghui wang 《Photonics Research》 SCIE EI CAS CSCD 2024年第8期1741-1749,共9页
Optical tweezers(OTs)can immobilize and manipulate objects with sizes that span between nano-and micrometer scales.The manipulating ability of OTs is traditionally characterized by stability factor(S),which can only i... Optical tweezers(OTs)can immobilize and manipulate objects with sizes that span between nano-and micrometer scales.The manipulating ability of OTs is traditionally characterized by stability factor(S),which can only indicate an empirical“hit-or-miss”process.Additionally,the current quantitative models for trapping stability rarely consider the influence of external flow.In this paper,a comprehensive analysis to quantify the optical trapping stability in a perturbed asymmetric potential well is presented from the perspective of statistics,especially for weak trapping scenarios.Our analytical formulation takes experimentally measurable parameters including particle size,optical power,and spot width as inputs and precisely outputs a statistically relevant mean trapping time.Importantly,this formulation takes into account general and realistic cases including fluidic flow velocity and other perturbations.To verify the model,a back-focal-plane-interferometer-monitored trapping experiment in a flow is set up and the statistical characteristics of trapping time demonstrate good agreement with theoretical predictions.In total,the model quantitatively reveals the effects of external disturbance on trapping time,which will find applications where optical trapping stability is challenged by external perturbations in weak trapping conditions. 展开更多
关键词 PROCESS FLOW TRAPPING
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图神经网络 被引量:26
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作者 白铂 刘玉婷 +5 位作者 马驰骋 王光辉 闫桂英 闫凯 张明 周志恒 《中国科学:数学》 CSCD 北大核心 2020年第3期367-384,共18页
近年来,随着海量数据的涌现,可以表示对象之间复杂关系的图结构数据越来越受到重视并给已有的算法带来了极大的挑战.图神经网络作为可以揭示深层拓扑信息的模型,已开始广泛应用于诸多领域,如通信、生命科学和经济金融等.本文对近几年来... 近年来,随着海量数据的涌现,可以表示对象之间复杂关系的图结构数据越来越受到重视并给已有的算法带来了极大的挑战.图神经网络作为可以揭示深层拓扑信息的模型,已开始广泛应用于诸多领域,如通信、生命科学和经济金融等.本文对近几年来提出的图神经网络模型和应用进行综述,主要分为以下几类:基于空间方法的图神经网络模型、基于谱方法的图神经网络模型和基于生成方法的图神经网络模型等,并提出可供未来进一步研究的问题. 展开更多
关键词 图结构数据 图神经网络 空间方法 谱方法 图自编码器 图对抗生成网络 图循环神经网络
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基于五大价值导向的“破四唯”和“立新标” 被引量:6
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作者 潘教峰 王光辉 鲁晓 《科学通报》 EI CAS CSCD 北大核心 2022年第3期236-241,共6页
评价制度是整个科技体制的一项基础制度.其中,科技人才评价是人才发展的"指挥棒",影响科技人才事业发展的价值取向、领域方向、资源配置等关键要素.2021年5月,习近平总书记在"两院"院士大会、中国科学技术协会第十... 评价制度是整个科技体制的一项基础制度.其中,科技人才评价是人才发展的"指挥棒",影响科技人才事业发展的价值取向、领域方向、资源配置等关键要素.2021年5月,习近平总书记在"两院"院士大会、中国科学技术协会第十次代表大会上强调,要重点抓好完善评价制度等基础改革;要"破四唯"和"立新标"并举(http://www.gov.cn/xinwen/2021-05/28/content;613702.htm). 展开更多
关键词 科技体制 科技人才 资源配置 人才评价 价值导向 指挥棒 完善评价 价值取向
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Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner 被引量:7
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作者 Dan Wu Zongbing Hao +1 位作者 Haigang Ren guanghui wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2018年第6期1037-1046,共10页
Autophagy is an evolutionarily-conserved selfdegradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles.Recently, vesicle-associated membrane protein-associated pr... Autophagy is an evolutionarily-conserved selfdegradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles.Recently, vesicle-associated membrane protein-associated protein B(VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3(microtubuleassociated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin1 by VAPB was at the transcriptional level. Moreover,knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1. 展开更多
关键词 VAPB AUTOPHAGY Beclin 1 ALS Autophagic flux LC3
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α-Synuclein aggregation and transmission in Parkinson’s disease: a link to mitochondria and lysosome 被引量:5
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作者 Rui wang Hongyang Sun +1 位作者 Haigang Ren guanghui wang 《Science China(Life Sciences)》 SCIE CAS CSCD 2020年第12期1850-1859,共10页
The presence of intraneuronal Lewy bodies(LBs) and Lewy neurites(LNs) in the substantia nigra(SN) composed of aggregatedα-synuclein(α-syn) has been recognized as a hallmark of pathological changes in Parkinson’s di... The presence of intraneuronal Lewy bodies(LBs) and Lewy neurites(LNs) in the substantia nigra(SN) composed of aggregatedα-synuclein(α-syn) has been recognized as a hallmark of pathological changes in Parkinson’s disease(PD). Numerous studies have shown that aggregated α-syn is necessary for neurotoxicity. Meanwhile, the mitochondrial and lysosomal dysfunctions are associated with α-syn pathogenicity. The hypothesis that α-syn transmission in the human brain contributes to the instigation and progression of PD has provided insights into PD pathology. This review will provide a brief overview of increasing researches that shed light on the relationship of α-syn aggregation with mitochondrial and lysosomal dysfunctions, and highlight recent understanding of α-syn transmission in PD pathology. 展开更多
关键词 Α-SYNUCLEIN Lewy pathology MITOCHONDRIA LYSOSOME AGGREGATION transmission
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Poly-PR in C9ORF72-Related Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis 被引量:4
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作者 Rui wang Xingyun Xu +6 位作者 Zongbing Hao Shun Zhang Dan Wu Hongyang Sun Chenchen Mu Haigang Ren guanghui wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2019年第5期889-900,共12页
GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 ... GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 produce five dipeptide repeat(DPR) proteins by an unconventional repeat-associated non-ATG(RAN)translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs(poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5 Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase(JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PRinduced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependentendocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides. 展开更多
关键词 Amyotrophic lateral SCLEROSIS C9ORF72 Poly-PR CLATHRIN ER stress
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Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease 被引量:5
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作者 Rui wang Haigang Ren +2 位作者 Elena Kaznacheyeva Xiaojun Lu guanghui wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2023年第3期479-490,共12页
The accumulation of pathological α-synuclein(α-syn)in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson... The accumulation of pathological α-synuclein(α-syn)in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease(PD).Recently,the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution ofα-syn in PD patients.Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells,which contributes to the clearance of α-syn.However,the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons,which promotes the spread of α-syn pathology.In this article,we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis,highlighting the relationships between glial responses and the spread ofα-syn pathology. 展开更多
关键词 Parkinson's disease α-synuclein pathology Microglial activation Astrocyte activation Neuroinfammation
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Regulation of autophagic flux by CHIP 被引量:2
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作者 Dongkai Guo Zheng Ying +4 位作者 Hongfeng wang Dong Chen Feng Gao Haigang Ren guanghui wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2015年第4期469-479,共11页
Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many ... Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an important role in neurodegeneration. In this study, we identified the regulation of autophagic flux by CHIP (carboxy-terminus of HscT0-interacting protein). Knockdown of CHIP induced autophagosome formation through increasing the PTEN protein level and decreasing the AKT/mTOR activity as well as decreasing phosphorylation of ULK1 on Ser757. However, degradation of the autophagic substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of cells to autophagic cell death induced by bafilomycin AI. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux. 展开更多
关键词 CHIP/STUB1 autophagic flux neuro-degeneration MTOR AKT
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NSC-640358 acts as RXRa ligand to promote TNFa-mediated apoptosis of cancer cell 被引量:2
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作者 Fan Chen Jiebo Chen +15 位作者 Jiacheng Lin Anton V. Cheltsov Lin Xu Ya Chen Zhiping Zeng Liqun Chen Mingfeng Huang Mengjie Hu Xiaohong Ye YuqiZhou guanghui wang Ying su Long Zhang Fangfang Zhou Xiao-kun Zhang HU Zhou 《Protein & Cell》 SCIE CAS CSCD 2015年第9期654-666,共13页
Retinoid X receptor a (RXRα) and its N-terminally trun- cated version tRXRα play important roles in tumorige. nesis, while some RXRg ligands possess potent anti- cancer activities by targeting and modulating the t... Retinoid X receptor a (RXRα) and its N-terminally trun- cated version tRXRα play important roles in tumorige. nesis, while some RXRg ligands possess potent anti- cancer activities by targeting and modulating the tumorigenic effects of RXRo and tRXRa. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRa and inhibits the transactivation of RXRα homod- imer and RXRa/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRa, essential for 9-cis-retinoic acid binding and activating RXRg transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra w-w stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRa-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor a (TNFα)-induced AKT activation and stimulates TNFa-mediated apoptosis in cancer cells in an RXRa/tRXRo dependent manner.The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRa to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRa ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFa-mediated cancer cell apoptosis by targeting RXRα/tRXRα. 展开更多
关键词 NSC-640358 ligand RXRa tRXRα TNFα apoptosis
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