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    题名 作者 年代 出处 被引量
1Dynamic mechanism and present situation of rural settlement evolution in China显示文摘这篇论文提供影响农村解决的进化的因素的详细分析,包括自然环境限制,基础结构,地区性的文化继承和集成,都市化和农村工业转变,陆地使用改革和革新,农村家庭行为变换,宏控制政策因素等等。在农村解决进化上基于效果的方法和度之间的差别,这些因素被分类进基本因素,新型的因素和变化因素。基本因素的开车主要集中于农村解决的传统的继承,新型的因素主要影响因素可以引起的农村解决转变,和变化突然的变化。所有这些因素为农村解决的进化组成三车轮的开车机制,并且塑造三条典型司机路径:慢在变化因素下面在基本因素,到在新型的因素下面的快速的开发的新路径,和突然的变化路径下面弄平路径。纸也在解决系统的方面调查农村解决进化的全面状况,解决规模,解决形态学,解决功能,解决文化,解决环境,等等。农村解决进化的一般过程被划分成四个阶段:起始、过渡、发展、成熟的阶段。ZHOU Guohua HE Yanhua TANG Chengli YU Tao XIAO Guozhen ZHONG Ting 2013Journal of Geographical Sciences2013,23,3:65
2Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report显示文摘Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.Zhi He Bo-Ta Cui Ting Zhang Pan Li Chu-Yan Long Guo-Zhong Ji Fa-Ming Zhang 2017World Journal of Gastroenterology2017,23,19:37
3Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen 2021Cancer Communications2021,41,11:29
4A Regional Ocean Reanalysis System for Coastal Waters of China and Adjacent Seas显示文摘A regional ocean reanalysis system for the coastal waters of China and adjacent seas has been developed by the National Marine Data and Information Service(NMDIS).It produces a dataset package called CORA (China ocean reanalysis).The regional ocean model used is based on the Princeton Ocean Model with a generalized coordinate system(POMgcs).The model is parallelized by NMDIS with the addition of the wave breaking and tidal mixing processes into model parameterizations.Data assimilation is a sequential three-dimensional variational(3D-Var) scheme implemented within a multigrid framework.Observations include satellite remote sensing sea surface temperature(SST),altimetry sea level anomaly(SLA),and temperature/salinity profiles.The reanalysis fields of sea surface height,temperature,salinity,and currents begin with January 1986 and are currently updated every year. Error statistics and error distributions of temperature,salinity and currents are presented as a primary evaluation of the reanalysis fields using sea level data from tidal gauges,temperature profiles,as well as the trajectories of Argo floats.Some case studies offer the opportunity to verify the evolution of certain local circulations.These evaluations show that the reanalysis data produced provide a good representation of the ocean processes and phenomena in the coastal waters of China and adjacent seas.Guijun Han Wei Li Xuefeng Zhang Dong Li Zhongjie He Xidong Wang Xinrong Wu Ting Yu Jirui Ma 2011Advances in Atmospheric Sciences2011,28,3:27
5Photoactivated CRY1 and phyB Interact Directly with AUX/IAA Proteins to Inhibit Auxin Signaling in Arabidopsis显示文摘光是在 Arabidopsis 通过蓝色和调停 cryptochrome 的 red/far-red 光光敏电阻器和调停 phytochrome 的小径禁止胚轴房间延伸的关键环境暗示。相反,作为枢轴的内长的植物激素,植物生长素通过 AUX/IAA 蛋白质(AUX/IAAs ) 的植物生长素受体 TIR1/AFBs-mediated 降级支持胚轴延伸。然而,位于发信号的光和植物生长素的对抗相互作用下面的分子的机制仍然保持不清楚。这里,我们报导光禁止由 cryptochrome 的蓝、红的轻依赖者的相互作用通过 AUX/IAAs 的稳定发信号的植物生长素 1 (CRY1 ) 并且有 AUX/IAAs 的 phytochrome B 分别地。有 AUX/IAAs 的 CRY1 的蓝被触发光的相互作用与 AUX/IAAs 禁止 TIR1 的协会,导致这些蛋白质的导致植物生长素的降级的压抑。我们的结果显示光敏电阻器下游地直接作为一样与植物生长素受体分享 AUX/IAAs 表明部件。我们建议由光敏电阻器和植物生长素受体的 AUX/IAA 蛋白质稳定性的那条对抗规定允许植物平衡光和植物生长素信号优化他们的生长。Feng Xu Shengbo He Jingyi Zhang Zhilei Mao Wenxiu Wang Ting Li Jie Hua Shasha Du Pengbo Xu Ling Li Hongli Lian Hong-Quan Yang 2018Molecular Plant2018,11,4:24
6Cap-assisted endoscopic sclerotherapy for hemorrhoids: Methods, feasibility and efficacy显示文摘AIM: To evaluate the methodology, feasibility, safety and efficacy of a novel method called cap-assisted endoscopic sclerotherapy(CAES) for internal hemorrhoids.METHODS: A pilot study on CAES for grade Ⅰ to Ⅲ internal hemorrhoids was performed. Colon and terminal ileum examination by colonoscopy was performed for all patients before starting CAES. Polypectomy and excision of anal papilla fibroma were performed if polyps or anal papilla fibroma were found and assessed to be suitable for resection under endoscopy. CAES was performed based on the requirement of the cap, endoscope, disposable endoscopic long injection needle, enough insufflated air and sclerosing agent.RESULTS: A total of 30 patients with grade Ⅰ to Ⅲ internal hemorrhoids was included. The follow-up was more than four weeks. No bleeding was observed after CAES. One(3.33%) patient claimed mild tenesmus within four days after CAES in that an endoscopist performed this procedure for the first time. One hundred percent of patients were satisfied with this novel procedure, especially for those patients who underwent CAES in conjunction with polypectomy or excision of anal papilla fibroma.CONCLUSION: CAES as a novel endoscopic sclerotherapy should be a convenient, safe and effective flexible endoscopic therapy for internal hemorrhoids.Ting Zhang Li-Juan Xu Jie Xiang Zhi He Zhao-Yuan Peng Guang-Ming Huang Guo-Zhong Ji Fa-Ming Zhang 2015World Journal of Gastrointestinal Endoscopy2015,7,19:22
7Vector-based RNA interference against vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of colorectal cancer in vivo in mice显示文摘背景:RNA 干扰(RNAi ) 技术是正在出现一很有势力产生的工具一细胞需要的基因击倒。这研究的目的是探索指向生长 factor-C (VEGF-C ) 能禁止的脉管的内皮的 RNAi 是否渲染表面的肿瘤 lymphangiogenesis 和肿瘤生长。方法:我们使用了基于向量的 RNAi 在结肠癌在试管内和在活体内禁止 VEGF-C 表示。VEGF-C 表示被即时聚合酶链反应并且 Westen 弄污确定。在老鼠建立 LoVo 房间肿瘤异种皮移植,我们皮下地接种 1.0 x 10 (6 ) 在裸体老鼠的 LoVo 房间;在注射以后,肿瘤被允许成长 4 个星期直到到达的体积(75.8+/-55.8 ) 公里(3 ) 。老鼠然后随机被划分成二个组:(1 ) VEGF-C-siRNA 组(n=10 ) 收到了 LoVo-VEGF-C-siRNA 的“治疗学”的原生质标志 50 microg 的直接注射进肿瘤团;(2 ) 控制组(n=10 ) 在 20 microl 与 LoVo 控制被注射无菌进肿瘤的 0.9% NaCl 答案集中。肿瘤生长,微 lymphatics 和微容器被比较因为鼠标超过 4 个星期管理了全身的 VEGF-C-siRNA 或控制。结果:在冒号肿瘤房间的 VEGF-C 的 mRNA 和蛋白质表示排队, LoVo,稳定地有 VEGF-C-siRNA 向量的 transfected,显著地击倒分别地调整了 45.3% 和 35.3% 。在活体内,在注射以后的四个星期,肿瘤体积比在 LoVo 控制组在 VEGF-C-siRNA 组是显著地更小的((314.8+/-54.8 ) 公里(3 ) 对(553.9+/-90.1 ) 公里(3 )) ;在 VEGF-C-siRNA 的淋巴节点转移(30%) 的发生显著地与 LoVo 控制组(70%) 相比被禁止;在 VEGF-C-siRNA 组,微 lymphatics 的数字每显微镜的地是(5.3+/-0.7 ) 并且(24.2+/-6.5 ) 微容器的数字与 LoVo 控制组(12.5+/-6.9 ) 并且(相比每显微镜的地被减少 42.1+/-7.4 )( 所有 P<0.001 ) 。结论:用调停 siRNA 的基因 silencing 向量的 VEGF-C 表示的抑制减少了 lymphangiogenesis 和淋巴节点转移并且提高了幸存。HE Xiao-wen YU Xiao LIU Ting YU Shi-yi CHEN Dao-jin 2008Chinese Medical Journal2008,,5:21
8Novel radar dwell scheduling algorithm based on pulse interleaving显示文摘The problem of scheduling radar dwells in multifunction phased array radar systems is addressed. A novel dwell scheduling algorithm is proposed. The whole scheduling process is based on an online pulse interleaving technique. It takes the system timing and energy constraints into account. In order to adapt the dynamic task load, the algorithm considers both the priorities and deadlines of tasks. The simulation results demonstrate that compared with the conventional adaptive dwell scheduling algorithm, the proposed one can improve the task drop rate and system resource utility effectively.Cheng Ting He Zishu Tang Ting 2009Journal of Systems Engineering and Electronics2009,20,2:20
9Serum uric acid levels correlate with atrial fibrillation in patients with chronic systolic heart failure显示文摘ZHAO Qing-yan YU Sheng-bo HUANG He CUI Hong-ying QIN Mu HUANG Ting HUANG Cong-xin 2012Chinese Medical Journal2012,,10:20
10Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs.3 doses in young women显示文摘A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women.A randomized,immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China.Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301)or 3 doses at months 0,1 and 6(n=304).Girls aged 15–17 years(n=149)and women aged 18–26 years(n=225)received 3 doses.The objectives included noninferiority analysis of the IgG geometric mean concentration(GMC)ratio(95%CI,lower bound>0.5)to HPV-16 and HPV-18 at month 7 in girls compared with women.In the per-protocol set,the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95%CI,1.56,1.99)for HPV-16 and 1.93(95%CI,1.69,2.21)for HPV-18)and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95%CI,1.25,1.62)for HPV-16 and 1.17(95%CI,1.02,1.33)for HPV-18).Noninferiority was also demonstrated for neutralizing antibodies.The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.Yue-Mei Hu Meng Guo Chang-Gui Li Kai Chu Wen-Gang He Jing Zhang Jian-Xiang Gu Juan Li Hui Zhao Xiang-Hong Wu Bi-Zhen Lin Zhi-Jie Lin Xing-Mei Yao Ya-Fei Li Fei-Xue Wei Yue Huang Ying-Ying Su Feng-Cai Zhu Shou-Jie Huang Hui-Rong Pan Ting Wu Jun Zhang Ning-Shao Xia 2020Science China(Life Sciences)2020,63,4:19
11p53 upregulated by HIF-la promotes hypoxiainduced G2/M arrest and renal fibrosis in vitro and in vivo显示文摘Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis.Limin Liu Peng Zhang Ming Bai Lijie He Lei Zhang Ting Liu Zhen Yang Menglu Duan Minna Liu Baojian Liu Rui Du Qi Qian Shiren Sun 2019Journal of Molecular Cell Biology2019,11,5:18
12Dwell scheduling algorithm for multifunction phased array radars based on the scheduling gain显示文摘A real-time dwell scheduling model, which takes the time and energy constraints into account is founded from the viewpoint of scheduling gain. Scheduling design is turned into a nonlinear programming procedure. The real-time dwell scheduling algorithm based on the scheduling gain is presented with the help of two heuristic rules. The simulation results demonstrate that compared with the conventional adaptive scheduling method, the algorithm proposed not only increases the scheduling gain and the time utility but also decreases the task drop rate.Cheng Ting He Zishu Tang Ting 2008Journal of Systems Engineering and Electronics2008,19,3:18
13A DC Grid Benchmark Model for Studies of Interconnection of Power Systems显示文摘Reducing carbon emissions in the power sector is critical for transitioning to a sustainable and low-carbon future.Estimating carbon efficiency of demand side response(DSR)in the power system is an important step towards realizing potential environmental benefits.Marginal emission factor(MEF)is an effective tool for estimating incremental changes in carbon emissions as a result of a change in demand.However,estimation methods currently used for evaluating MEF can be improved upon,specifically,by factoring in the ramp-rate constraint of generators in the fuel cost based merit order dispatch.In this paper is described a new method for MEF assessment under ramp-rate constraints;the method is then compared with two conventional estimations in a British power system.Three fuel price scenarios are used to conduct a sensitivity analysis of MEFs to fuel prices.Conclusions are drawn that can pave the way for future improvements in estimating MEF in power systems.Ting An Xiaoxin Zhou Congda Han Yanan Wu Zhiyuan He Hui Pang Guangfu Tang 2015CSEE Journal of Power and Energy Systems2015,1,4:17
14Adaptive Dwell Scheduling for Digital Array Radar Based on Online Pulse Interleaving显示文摘CHENG Ting HE Zishu LI Huiyong 2009Chinese Journal of Electronics2009,18,3:15
15Uric formaldehyde levels are negatively correlated with cognitive abilities in healthy older adults显示文摘Recent studies have shown that the abnormal accumulation of endogenous formaldehyde could be a critical factor in age-related cognitive decline. The aim of this study was to estimate the correlation between uric formaldehyde and general cognitive abilities in a community-based elderly population, and to measure the extent and direction in which the correlation varied with demographic characteristics. Using a double-blind design, formaldehyde in human urine was analyzed by high-performance liquid chromatography(n = 604), and general cognitive abilities were measured using the Montreal Cognitive Assessment(MoCA). Demographic characteristics, in terms of age, gender, residential region, and education were taken into consideration. We found that uric formaldehyde levels were inversely correlated with the MoCA score, and the concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated and those living in old urban or rural areas. In cytological experiments, the level of cellular formaldehyde released into the medium increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in excess impairedthe processes of N2a cells and neurites of primary cultured rat hippocampal cells. However, removal of formaldehyde markedly rescued and regenerated the processes of N2a cells. These results demonstrated a negative correlation between the endogenous formaldehyde and general cognitive abilities. High formaldehyde levels could be a risk factor for cognitive impairment in older adults, and could be developed as a non-invasive marker for detection and monitoring of age-related cognitive impairment.Jing Yu Tao Su Ting Zhou Yingge He Jing Lu Juan Li Rongqiao He 2014Neuroscience Bulletin2014,30,2:14
16Structure and photocatalytic properties of TiO_2-Graphene Oxide intercalated composite显示文摘TiO2-Graphene Oxide intercalated composite (TiO2-Graphene Oxide) has been successfully prepared at low temperature (80°C) with graphite oxide (GO) and titanium sulfate (Ti(SO4)2) as initial reactants.GO was firstly exfoliated by NaOH and formed single and multi-layered graphite oxide mixture which can be defined as graphene oxide,[TiO]2+ induced by the hydrolysis of Ti(SO4)2 diffused into graphene oxide interlayer by electrostatic attraction.The nucleation and growth of TiO2 crystallites took place at low temperature and TiO2-Graphene Oxide composite was successfully synthesized.Furthermore,the photocatalytic properties of TiO2-Graphene Oxide under the irradiation of UV light were also studied.The results show that the degradation rate of methyl orange is 1.16 mg min-1 g-1(refer to the efficiency of the initial 15 min).Compared with P25 powder,this kind of intercalation composite owns much better efficiency.On the other hand,the reusable properties and stable properties of TiO2-Graphene Oxide intercalated composite are also discussed in this paper.At last,crystalline structure,interface status,thermal properties and microscopic structure of TiO2-Graphene Oxide were characterized by X-ray diffraction (XRD),X-ray photoelectron spectroscopy (XPS),thermogravimetric analysis (TGA),field emission scanning electron microscopy (FESEM) and high-resolution Transmission Electron Microscopy (HRTEM).Also,we have analyzed major influencing factors and mechanism of the composite structures which evidently improve the photocatalytic properties.ZHANG Qiong HE YunQiu CHEN XiaoGang HU DongHu LI LinJiang YIN Ting JI LingLi 2011Chinese Science Bulletin2011,56,3:14
17Diagnosis and endovascular treatment of spontaneous direct carotid-cavernous fistula显示文摘背景自发的直接颈动脉多孔的管( CCF )是相对稀罕的,很少报告在纸是报导临床的特征的这的 literature.The 目的被发现了,成像调查结果和为有自发的直接 CCF 的九个病人的临床的数据在2003年5月和2007年11月和 endovascular treatment.Sudden neuro-ophthalmologic 的结果之间招收的有我们回顾地分析了的自发的直接 CCF.Methods 的病人的 endovascularYU Jia-sheng LEI Ting CHEN Jin-cao HE Yue CHEN Jian LI Ling 2008Chinese Medical Journal2008,,16:12
18Alfalfa-containing diets alter luminal microbiota structure and short chain fatty acid sensing in the caecal mucosa of pigs显示文摘Background: Pork produced by outdoor-reared pigs raised mostly on alfalfa pastures attracts increasing population of consumer from most of the world. In China, pigs were raised with alfalfa-containing diets to seek for good quality pork.However, the influence of dietary alfalfa involving high level of insoluble dietary fiber(IDF) on pig intestinal luminal microbiota composition remains unclear. The objective of this study was to investigate the effects of alfalfa on luminal microbiota and short chain fatty acids(SCFA) production, and gene expressions involved in SCFA sensing, transporting and absorbing in pig caecal mucosa.Results: Twenty-four growing pigs were randomly allotted to four diets containing 0%, 5%, 10% and 15% alfalfa meal for a 28-d experiment. Ingestion of alfalfa meal-contained diets significantly increased the ratio of body weight gain to feed consumption. Illumina MiS eq sequencing of the V3 region of the 16 S r RNA genes showed that alfalfa-containing diet significantly decreased the relative abundance of genera Turicibacter, Acidiphilium, Paracoccus, Propionibacterium,Corynebacterium, Pseudomonas, Acinetobacter, and Staphylococcus, and increased the relative abundance of genera Lachnospira, Marvinbryantia, and Desulfovibrio in the caecal digesta. Butyrate concentration was significantly increased in the hindgut by the supplementation of alfalfa meal in diets. The m RNA gene expressions of FFAR3, SMCT1, MCT1,PYY, and GCG were significantly increased in the caecal mucosa of pigs fed alfalfa meal.Conclusions: Our results suggested that alfalfa-containing diet has exerted significant impacts on caecal microbiota composition, butyrate concentration and significantly upregulated m RNA expression of host caecal mucosal genes involved in SCFA sensing and absorption as well as regulation of satiety.Jiawei Wang Chunfu Qin Ting He Kai Qiu Wenjuan Sun Xin Zhang Ning Jiao Weiyun Zhu Jingdong Yin 2018Journal of Animal Science and Biotechnology2018,9,2:12
19Potentiating CD8^(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling显示文摘Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation remains largely unexplored.Herein,we found that the low-density lipoprotein receptor(LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+T cell antitumor activity.Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+T cells:LDLR interacts with the T-cell receptor(TCR)complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes(CTLs).Furthermore,we found that the tumor microenvironment(TME)downregulates CD8+T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9(PCSK9)which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs.Moreover,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+T cells by alleviating the suppressive effect on CD8+T cells and consequently inhibit tumor progression.While previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.Juanjuan Yuan Ting Cai Xiaojun Zheng Yangzi Ren Jingwen Qi Xiaofei Lu Huihui Chen Huizhen Lin Zijie Chen Mengnan Liu Shangwen He Qijun Chen Siyang Feng Yingjun Wu Zhenhai Zhang Yanqing Ding Wei Yang 2021Protein & Cell2021,12,4:12
20Visualizing the microtubule-associated protein tau in the nucleus显示文摘Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form.LU Jing LI Ting HE RongQiao BARTLETT Perry F GTZ Jürgen 2014Science China(Life Sciences)2014,57,4:11
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