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| 1 | Cancer prevention and control: alarming challenges in China显示文摘China is geographically the third largest country in the world and the most populated low-to-middle-income country. Cancer incidence and mortality rates for some cancers in the USA and European countries have steadily decreased over the last decades, whereas the incidence and mortality of certain cancers in China have been increasing at an alarming speed. Rapid industrialization and urbanization in China have been accompanied by incredible changes in lifestyle and environment combined with an aging population. Mortality caused by lung, colorectal and breast cancers has been steadily increasing, whereas cancer mortality from gastric, esophageal and cervical tumors has tended to decrease. Similar to what has occurred in the United States, unhealthy lifestyles in China, including heavy smoking and poor diet combined with pollution, have contributed to increased cancer risk. China is facing many challenges in cancer treatment and prevention for the general population. The major areas that need to be addressed in the control of cancer in China include cancers associated with environmental pollution,tobacco use, occupational carcinogens, infection, excessive alcohol consumption, dietary deficiencies and obesity. In this perspective, we review the problems in each area and suggest ideas for future directions in cancer research and strategies and actions to reduce the incidence of cancer in China. | Ann M.Bode Zigang Dong Hongyang Wang | 2016 | National Science Review2016，3，1： | 22 |
| 2 | Parallel Control for Continuous-Time Linear Systems:A Case Study显示文摘In this paper,a new parallel controller is developed for continuous-time linear systems.The main contribution of the method is to establish a new parallel control law,where both state and control are considered as the input.The structure of the parallel control is provided,and the relationship between the parallel control and traditional feedback controls is presented.Considering the situations that the systems are controllable and incompletely controllable,the properties of the parallel control law are analyzed.The parallel controller design algorithms are given under the conditions that the systems are controllable and incompletely controllable.Finally,numerical simulations are carried out to demonstrate the effectiveness and applicability of the present method.Index Terms-Continuous-time linear systems,digital twin,parallel controller,parallel intelligence,parallel systems. | Qinglai Wei Hongyang Li Fei-Yue Wang | 2020 | IEEE/CAA Journal of Automatica Sinica2020，7，4： | 18 |
| 3 | Discovery of the Plagiogranites in the Diyanmiao Ophiolite,Southeastern Central Asian Orogenic Belt,Inner Mongolia,China and Its Tectonic Significance显示文摘In this study, plagiogranites in the Diyanmiao ophiolite of the southeastern Central Asian Orogenic Belt(Altaids) were investigated for the first time. The plagiogranites are composed predominantly of albite and quartz, and occur as irregular intrusive veins in pillow basalts. The plagiogranites have high SiO_2(74.37–76.68 wt%) and low Al_2O_3(11.99–13.30 wt%), and intensively high Na_2O(4.52–5.49 wt%) and low K_2O(0.03–0.40 wt%) resulting in high Na_2O/K_2O ratios(11.3–183). These rocks are classified as part of the low-K tholeiitic series. The plagiogranites have low total rare earth element contents(∑REE)(23.62–39.77 ppm), small negative Eu anomalies(δEu=0.44–0.62), and flat to slightly LREE-depleted chondrite-normalized REE patterns((La/Yb)N=0.68–0.76), similar to N-MORB. The plagiogranites are also characterized by Th, U, Zr, and Hf enrichment, and Nb, P, and Ti depletion, have overall flat primitivemantle-normalized trace element patterns. Field and petrological observations and geochemical data suggest that the plagiogranites in the Diyanmiao ophiolite are similar to fractionation-type plagiogranites. Furthermore, the REE patterns of the plagiogranites are similar to those of the gabbros and pillow basalts in the ophiolite. In plots of SREE–SiO_2, La–SiO_2, and Yb–SiO_2, the plagiogranites, pillow basalts, and gabbros show trends typical of crystal fractionation. As such, the plagiogranites are oceanic in origin, formed by crystal fractionation from basaltic magmas derived from depleted mantle, and are part of the Diyanmiao ophiolite. LA–ICP–MS U–Pb dating of zircons from the plagiogranites yielded ages of 328.6±2.1 and 327.1±2.1 Ma, indicating an early Carboniferous age for the Diyanmiao ophiolite. These results provide petrological and geochronological evidence for the identification of the Erenhot–Hegenshan oceanic basin and Hegenshan suture of the Paleo-Asian Ocean. | LI Yingjie WANG Jinfang WANG Genhou DONG Peipei LI Hongyang HU Xiaojia | 2018 | Acta Geologica Sinica(English Edition)2018，92，2： | 12 |
| 4 | Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment显示文摘A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis(PGD), noninvasive prenatal testing(NIPT), and noninvasive prenatal diagnosis(NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2 c.235del C heterozygous embryo resulted in a singleton pregnancy. At the 13 th week of gestation, genomic DNA(g DNA) from the trio family and cell-free DNA(cf DNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders. | XIONG WenPing WANG DaYong GAO Yuan GAO Ya WANG HongYang GUAN Jing LAN Lan YAN JunHao ZONG Liang YUAN Yuan DONG Wei HUANG SeXin WU KeLiang WANG YaoShen WANG ZhiLi PENG HongMei LU YanPing XIE LinYi ZHAO Cui WANG Li ZHANG QiuJing GAO Yun LI Na YANG Ju YIN ZiFang HAN Bing WANG Wei CHEN Zi-Jiang WANG QiuJu | 2015 | Science China(Life Sciences)2015，58，9： | 12 |
| 5 | Zircon LA-ICP-MS U-Pb Age and Island-Arc Origin of the Bayanhua Gabbro in the Hegenshan Suture Zone, Inner Mongolia显示文摘Objective The Bayanhua Nb-enriched gabbro is newly discovered in the Diyanmiao-Meilaotewula SSZ-type ophiolitic mélange belt of the Hegenshan suture zone,Inner Mongolia.Nb-enriched arc gabbros are usually believed to result from partial melting of the mantle wedge peridotites metasomatized by slab melts derived from the subducting oceanic slab,which represent arc magmatic markers of | WANG Jinfang LI Yingjie LI Hongyang | 2017 | Acta Geologica Sinica(English Edition)2017，91，6： | 10 |
| 6 | A human circulating immune cell landscape in aging and COVID-19显示文摘Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly. | Yingfeng Zheng Xiuxing Liu Wenqing Le Lihui Xie He Li Wen Wen Si Wang Shuai Ma Zhaohao Huang Jinguo Ye Wen Shi Yanxia Ye Zunpeng Liu Moshi Song Weiqi Zhang Jing-Dong J.Han Juan Carlos lzpisua Belmonte Chuanle Xiao Jing Qu Hongyang Wang Guang-Hui Liu Wenru Su | 2020 | Protein & Cell2020，11，10： | 10 |
| 7 | Assessment of the Ecological Security in the Three Gorges Reservoir Area by Using the Ecological Footprint Method显示文摘The ecological footprint concept and its calculation models are useful for the measurement of the sustainable level of social and economic development.The ecological security situation of the Three Gorges Reservoir Area(TGRA) was evaluated using this concept in this study.The construction of the Three Gorges Reservoir has led to the change in the ecology and immigration status of TGRA.The ecological footprint method is an important means to study the regional ecological security.Our results suggested that,by excluding the areas for biodiversity conservation(12% of the total land),the ecological footprint per capita was 0.57895 ha,which exceeded the ecological carrying capacity in TGRA.The total ecological deficit was found to be 11,522,193.34 ha,accounting for 95.02% of the ecological carrying capacity.These findings suggested that the ecological security of TGRA was not good.In order to compensate for the ecological deficit,it was essential to introduce natural resources from other regions. | WANG Haiming WANG Hai'e SUN Hongyang WANG Xiaolan LIAO Xiaoyong CHEN Zhijian LI Xianwei | 2012 | Journal of Mountain Science2012，9，6： | 9 |
| 8 | Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis显示文摘Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine(DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium(DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine,the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota. | Chenjie Qin Huilu Zhang Linghao Zhao Min Zeng Weijian Huang Gongbo Fu Weiping Zhou Hongyang Wang Hexin Yan | 2018 | Science China(Life Sciences)2018，61，12： | 8 |
| 9 | Optical sensors for power transformer monitoring:A review显示文摘Power transformers play a vital role in power transmission systems from the energy source to the consumption center.In situ diagnostics of the performance of power transformers provides a variety of benefits to ensure reliable electricity transmission.Immunity to electromagnetic interference,high sensitivity,high insulation as well as small dimensions of optical sensing make it very attractive for applications in power transformer monitoring.This paper presents a critical review of various diagnostic methods for power transformers such as partial discharge,dissolved gases,temperature and other important sensing,and optical detection.The advantages and disadvantages of different monitoring methods are carefully discussed and assessed.Finally,the existing technical barriers and future prospects of optical monitoring methods for power transformers are presented. | Guoming Ma Yuan Wang Weiqi Qin Hongyang Zhou Chao Yan Jun Jiang Yiguang Ju | 2021 | High Voltage2021，6，3： | 7 |
| 10 | 听神经病和梅尼埃病患者耳蜗电图振幅比与面积比差异分析显示文摘目的分析听神经病(Auditory Neuropathy/Auditory Neuropathy Spectrum Disorder, AN/ANSD)与梅尼埃病(Meniere’s disease,MD)患者交替短声诱发的耳蜗电图各项参数差异与特征。方法对正常听力对照组10人(20耳)及听神经病19人(38耳)、梅尼埃病16人(单侧14例,双侧2例)行耳蜗电图检查,刺激声为交替短声100dBnH。对照组较AN和MD多做2组强度分别为80、90dBnHL。统计分析应用SPSS(版本25.0),MD组症状耳与非症状耳采取配对t检验;正常对照组、MD组、AN三组对比采取方差分析。数据非正态分布或方差不齐时行非参数检验。结果 MD症状耳与非症状耳、正常对照组与AN、MD的平均听阈均存在统计学差异;正常对照组不同强度100dBnHL与80dBnHL在SP和AP振幅与潜伏期之间有显著性差异;正常对照组、梅尼埃症状耳组、AN三组SP、AP同时引出率分别为100%、100%、87%。MD组14耳症状耳与非症状耳仅SP振幅与SP/AP振幅比有显著性差异;正常对照组、AN组、MD三组比较,除外SP振幅,其余参数均有显著统计学差异(P <0.05)。以正常对照组SP/AP振幅比95%置信区间上限0.31,SP/AP面积比上限1.47,MD症状耳阳性率振幅比、面积比均为83.33%,非症状耳振幅比及面积比阳性率分别为35.71%及57.14%;AN振幅比及面积比阳性率均为100%。结论 AN与MD患者振幅比和面积比的比值均增高,其差异源于AN患者AP振幅异常降低或消失;MD患者在高强度刺激时AP振幅随听力损失降低但SP振幅不变或增高。ECochG辅助诊断单侧MD自身对照更有意义;SP/AP振幅比、面积比是辅助诊断梅尼埃病和听神经病的有效手段。 | 兰兰 汪明敏 韩冰 李兴启 谢林怡 熊芬 于黎明 王秋菊 WANG Hongyang | 2019 | 中华耳科学杂志2019，17，6： | 6 |
| 11 | Low frequency oscillation characteristics of East China Power Grid after commissioning of Huai-Hu ultra-high voltage alternating current project显示文摘The low frequency oscillation characteristics of East China Power Grid after commissioning of the first ultra-high voltage alternating current(UHVAC)project-the Huai-Hu UHVAC project are studied.Several low frequency oscillation cases occurred in East China Power Grid in the past few years are reviewed and summarized.Based on the analysis of the different typical operation modes,the main low frequency oscillation modes in East China Power Grid in the early stages of development of ultra-high voltage(UHV)are summarized,and the impacts of the significant power grid maintenance on low frequency oscillation characteristics are analyzed.Besides,the oscillation mode of UHV generators to East China Power Grid is researched,and the importance of the power system stabilizator(PSS)is emphasized.Furthermore,the comparative analysis between the time domain and the frequency domain is carried out,and the influences of the governing system on low frequency oscillation characteristics are revealed.Finally,both the focus and the direction of low frequency oscillation research are presented. | Chao WANG Yang LV Hongyang HUANG Jing ZHANG Jihong LI Yingyi LI Weizhen SUN Yong CHANG | 2015 | Journal of Modern Power Systems and Clean Energy2015，3，3： | 6 |
| 12 | MoS2 nanorods with inner caves through synchronous encapsulation of sulfur for high performance Li–S cathodes显示文摘Lithium–sulfur(Li–S)batteries have become one of the most promising candidates for next-generation batteries owing to their high specific capacity,low cost,and environment-friendliness.Many efforts have been made to mitigate the'shuttle effect'through physical adsorption and chemical bonding.MoS2 has been proposed as a cathode material to provide effective anchoring sites for lithium polysulfides(Li PSs),but is still limited by its layer structure.Herein,we designed novel MoS2 nanorods with inner caves based on our previous work,and performed synchronous encapsulation of sulfur during the synthesis process.The outer MoS2 tubular shells physically inhibit the outward diffusion of polysulfide species while the inner particles chemically anchor the polysulfides to prevent shuttling.As the cathode matrix in Li–S batteries,the electrochemical results deliver a high initial discharge capacity of 1213 mAhg^-1 for sulfur at 0.1 C.After cycling at 1 C for 300 cycles,the cells exhibit a capacity decay of only 0.076%per cycle and high average coulombic efficiency over 95%.The tubular MoS2 structure is an innovative and appealing design,which could be regarded as a prospective substrate for the improved performance of Li–S batteries. | Yikun Yi Zechen Liu Pu Yang Tao Wang Xuewen Zhao Hongyang Huang Yonghong Cheng Jinying Zhang Mingtao Li | 2020 | Journal of Energy Chemistry2020，29，6： | 5 |
| 13 | The Gut Microbiota, Tumorigenesis, and Liver Diseases显示文摘一个多世纪以前,科学家们就首次发现了肿瘤区域中细菌的存在。但是,微生物在肿瘤发生中的作用近年来才被认识到。近几十年来,与肠道菌群失调相关的疾病代表了全世界最严重的一些公共卫生问题。大量的流行病学研究表明,肠道菌群与某些常见肿瘤密切相关。然而,肠道菌群与肿瘤相关联的具体分子机制仍不明确。研究表明,肠道菌群的改变有助于确定肝癌、酒精相关肝病、非酒精性脂肪肝和肝硬化的发生和发展。鉴于益生菌是一种可通过调节免疫系统促进人类健康的药物,其可能会为肝细胞癌(HCC)和非酒精性脂肪肝的治疗提供新方向。本文总结了肠道菌群在肿瘤及肝病中的研究进展,综述了肠道菌群与肿瘤和肝病之间的关系。此外,考虑到细菌内稳态的重要性,我们也对益生菌进行了概述,旨在为相关疾病的治疗提供指导。 | Guishuai Lv Ningtao Cheng Hongyang Wang | 2017 | Engineering2017，3，1： | 5 |
| 14 | Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study显示文摘 | Qiujin Shen Jia Fan Xin-Rong Yang Yexiong Tan Weifeng Zhao Yang Xu Ning Wang Yongdong Niu Zheng Wu Jian Zhou Shuang-Jian Qiu Ying-Hong Shi Bin Yu Ning Tang Wei Chu Min Wang Jinhua Wu Zhigang Zhang Shengli Yang Jianren Gu Hongyang Wang Wenxin Qin | 2012 | Lancet Oncology2012，，8： | 4 |
| 15 | Carbonyl polymeric electrode materials for metal-ion batteries显示文摘Benefiting from the diversity and subjective design feasibility of molecular structure, flexibility,lightweight, molecular level controllability, resource renewability and relatively low cost, polymeric electrode materials are promising candidates for the next generation of sustainable energy resources and have attracted extensive attention for the foreseeable large scale applications. The conductive polymers have been utilized as electrode materials in the pioneer reports, which, however, have the disadvantages of low stability, low reversibility and slope voltage due to the delocalization of charges in the whole conjugated systems. The discovery of carbonyl materials aroused the interest of organic and polymeric materials for batteries again. This review presents the recent progress in carbonyl polymeric electrode materials for lithium-ion batteries, sodium-ion batteries and magnesium-ion batteries. This comprehensive review is expected to be helpful forarousing more interest of organic materials for metal-ion batteries and designing novel battery materials with high performance. | Mi Tang Hongyang Li Erjing Wang Chengliang Wang | 2018 | Chinese Chemical Letters2018，29，2： | 4 |
| 16 | Synergistic effects in Mn-Co mixed oxide supported on cordierite honeycomb for catalytic deep oxidation of VOCs显示文摘A series of Co-Mn mixed oxide catalyst supported on a cordierite monolith was facilely synthesized by ultrasonic impregnation.Its catalytic performance was evaluated in the combustion of toluene,ethyl acetate and its mixture.It was observed that with incorporating Mn into Co_(3)O_(4),the formation of solid solution with spinel structure could significantly improve the catalytic activity of pure phase Co_(3)O_(4).And the monolithic Co_(0.67)Mn_(0.33)O_(x) catalyst showed the best catalytic performance in the catalytic oxidation of toluene and ethyl acetate which could be completely oxidized at 220 and 180℃ respectively under the reaction velocity(WHSV)about 45,000 m L/(g·hr)and pollutant concentration of 500 ppm V.The total conversion temperature of the VOCs mixture was at 230℃(500 ppm V toluene and 500 ppm V ethyl acetate)and determined by the temperature at which the most difficult molecule was oxidized.The excellent catalytic performance of monolithic Co_(0.67)Mn_(0.33)O_(x) was attributed to the higher content of Mn^(3+),Co^(3+),surface adsorbed oxygen and better redox ability.The prepared catalyst showed the good mechanical stability,reaction stability,and good adaptability to different reaction conditions. | Hongyang Zhao Hui Wang Zhenping Qu | 2022 | Journal of Environmental Sciences2022，34，2： | 4 |
| 17 | Construction of Pd-M (M = Ni, Ag, Cu) alloy surfaces for catalytic applications显示文摘合金作为异构的催化剂轰炸增加利用效率并且提高金属原子的催化活动的 ultrathin 的制造为有效金属 nanocatalysts 的构造作为一个有效方法被认出了,特别地高贵金属的 nanocatalysts。在这研究,我们表明 Pd-M 的成功的形成(M = Ni, Ag, Cu ) 有 preformed nanoscale Pd 种子上的悦耳的厚度的合金壳。这合成的成功主要依靠 M 离子和 M 广告原子的随后的散开的慢减小的联合进 Pd 种子的表面格子。Pd-M 合金壳的作文被改变增加的先锋的类型和数量容易调节,并且壳厚度根据反应时间被操作。更显著地,这些合金壳的表面结构在反应以后被维持,暗示 Pd-M 合金壳的任何需要的表面结构能被使用适当开始材料准备。这些合金表面显著地展出的 chloronitrobenzenes 表演的加氢的进一步催化的评估与 Pd 种子相比改进了选择。Pd-Ni 合金表面展出更好催化的选择(象一样高 >99%) 比 Pd 催化剂。 | Xiang Li Xixi Wang Maochang Liu Hongyang Liu Qiang Chen Yadong Yin Mingshang Jin | 2018 | Nano Research2018，11，2： | 4 |
| 18 | α-Synuclein aggregation and transmission in Parkinson’s disease: a link to mitochondria and lysosome显示文摘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. | Rui Wang Hongyang Sun Haigang Ren Guanghui Wang | 2020 | Science China(Life Sciences)2020，63，12： | 4 |
| 19 | Prognostic significance of combining high mobility group Box-1 and OV-6 expression in hepatocellular carcinoma显示文摘The inflammatory environment and existence of cancer stem cells are critical for progression and intrahepatic recurrence of hepatocellular carcinoma(HCC) after curative resections. Here, we investigated the prognostic significance of combining high mobility group box 1(HMGB1) expression and hepatic progenitor marker OV6 in hepatocellular carcinoma. Expression of HMGB1 and OV6 was evaluated using immunohistochemistry profiling in tissue microarrays containing samples from 208 HCC patients. Invasive clinical or pathological factors were found in patients with high expression of HMGB1 or OV6. Higher HMGB1 was associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence(85.5% vs. 62.4%, P<0.001). We also found that more OV6 positive staining was correlated with poor prognosis of HCC patients(P<0.001). Notably, expression of HMGB1 was positively correlated with OV6 in density(R2=0.032, P<0.001) and reversely related to HCC outcomes. Abnormal expression of HMGB1 in combination with positive staining of OV6 displayed poorer prognostic performance than single biomarker alone(area under curve(AUC) survival=0.696). Therefore, HMGB1 and OV6 positive staining are promising prognostic parameters for HCC, and we propose that HMGB1 and OV6 may cooperate with each other and predict poor prognosis of HCC. | Jihui Zhu Han Yu Shuzhen Chen Pinghua Yang Zihui Dong Yan Ling Hao Tang Shilei Bai Wen Yang Liang Tang Feng Shen Hongyang Wang Wen Wen | 2018 | Science China(Life Sciences)2018，61，8： | 4 |
| 20 | Poly-PR in C9ORF72-Related Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis显示文摘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. | Rui Wang Xingyun Xu Zongbing Hao Shun Zhang Dan Wu Hongyang Sun Chenchen Mu Haigang Ren Guanghui Wang | 2019 | Neuroscience Bulletin2019，35，5： | 4 |
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