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Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity,recapitulating key features of FUS proteinopathy

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Protein & Cell 2011年第2期2卷 141-149页

作者： Kazuo Fushimi Charles Long neha Jayaram Xiaoping Chen Liming Li Jane Y.wu Department of neurology Center for Genetic MedicineLurie Comprehensive Cancer CenterNorthwestern University Feinberg School of Medicine303 E.SuperiorChicagoIL 60611USA Department of Molecular Pharmacology and Biological Chemistry Northwestern University Feinberg School of Medicine303 E.SuperiorChicagoIL 60611USA

Mutations in the fused in sarcoma/translocated in liposarcoma(FUS/TLS)gene have been associated with amyotrophic lateral sclerosis(ALS).FUS-positive neuropathology is reported in a range of neurodegenerative diseases,including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology(FTLDU).To examine protein aggregation and cytotoxicity,we expressed human FUS protein in *** of either wild type or ALS-associated R524S or P525L mutant FUS in yeast cells led to formation of aggregates and cytotoxicity,with the two ALS mutants showing increased ***,yeast cells expressing human FUS protein recapitulate key features of FUSpositive neurodegenerative ***,a significant fraction of FUS expressing yeast cells stained by propidium iodide were without detectable protein aggregates,suggesting that membrane impairment and cellular damage caused by FUS expression may occur before protein aggregates become microscopically detectable and that aggregate formation might protect cells from FUS-mediated *** n-terminus of FUS,containing the QGSY and G rich regions,is sufficient for the formation of aggregates but not *** C-terminal domain,which contains a cluster of mutations,did not show aggregation or *** to TDP-43 when expressed in yeast,FUS protein has the intrinsic property of forming aggregates in the absence of other human *** the other hand,the aggregates formed by FUS are thioflavin T-positive and resistant to 0.5%sarkosyl,unlike TDP-43 when expressed in yeast ***,TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.

关键词： FUS/TLS protein aggregation cytotoxicity

二甲双胍介导nF-κB信号通路对糖尿病肾病细胞损伤的保护作用

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激光生物学报 2024年第3期33卷 275-283页

作者：刘丹阳吴振永孙亚茹崔玉秀保定市第二中心医院检验科保定072750

为探究二甲双胍介导核因子-κB(nF-κB)信号通路对糖尿病肾病细胞损伤的保护作用,体外培养人肾小球足细胞(HGPC),利用10、20、30和40 mmol/L D-葡萄糖进行干预,筛选构建HGPC高糖炎症损伤模型的D-葡萄糖最适浓度;再利用20、40、80、160 m... 详细信息

为探究二甲双胍介导核因子-κB(nF-κB)信号通路对糖尿病肾病细胞损伤的保护作用,体外培养人肾小球足细胞(HGPC),利用10、20、30和40 mmol/L D-葡萄糖进行干预,筛选构建HGPC高糖炎症损伤模型的D-葡萄糖最适浓度;再利用20、40、80、160 mmol/L二甲双胍进行干预,筛选最适二甲双胍浓度;随后将细胞分为对照组(Con组)、高糖组(HG组)、二甲双胍组(Met组,30 mmol/L D-葡萄糖+80 mmol/L二甲双胍)、抑制剂组(Y组,30 mmol/L D-葡萄糖+1μmol/L nF-κB通路抑制剂BAY 11-7082)、二甲双胍+抑制剂组(Met+Y组,30 mmol/L D-葡萄糖+80 mmol/L二甲双胍+1μmol/L BAY 11-7082)和二甲双胍+激动剂组(Met+A组,30 mmol/L D-葡萄糖+80 mmol/L二甲双胍+1μmol/L nF-κB通路激动剂Prostratin),干预24 h。利用细胞计数试剂盒-8(CCK-8)检测细胞活力;酶联免疫吸附试验(ELISA)法检测炎症因子水平;Transwell小室法测定细胞侵袭和迁移能力;蛋白免疫印迹(WB)法检测E-钙黏蛋白(E-cadherin)、n-钙黏蛋白(n-cadherin)、波形蛋白(vimentin)、纤连蛋白(Fn)、nF-κB p65和p-nF-κB p65蛋白的表达水平。结果显示:选择30 mmol/L D-葡萄糖干预HGPC细胞24 h以构建HGPC高糖炎症模型,80 mmol/L为二甲双胍最适浓度;HG组细胞炎症因子肿瘤坏死因子(TnF-α)、白细胞介素-1β(IL-1β)水平、细胞侵袭、迁移能力以及n-cadherin、vimentin、Fn和p-nF-κB p65蛋白水平高于Con组,E-cadherin蛋白表达水平低于Con组(PnF-α、IL-1β水平、细胞侵袭能力、迁移能力、n-cadherin、vimentin、Fn和p-nF-κB p65蛋白表达水平显著降低,E-cadherin蛋白表达水平升高(PnF-κB通路激活抑制D-葡萄糖诱导的HGPC炎症反应、侵袭、迁移和上皮间质转化进程,保护高糖诱导的足细胞损伤。

关键词：糖尿病肾病二甲双胍核因子-κB信号通路 D-葡萄糖诱导人肾小球足细胞炎症

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中链甘油三酯的生酮饮食在化疗3个月以上乳腺癌患者中的随机对照研究

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肿瘤代谢与营养电子杂志 2024年第2期11卷 195-200页

作者：刘柳张园园何珍吴贝徐洋曹蔚武汉市第三医院/武汉大学附属同仁医院肿瘤科湖北武汉430061

目的分析基于中链甘油三酯(MCT)的生酮饮食在接受化疗3个月以上的乳腺癌患者中的应用价值。方法选取武汉市第三医院2021年3月至2023年3月期间入院的乳腺癌患者(接受化疗干预3个月以上)120例,简单随机将其分为对照组(60例)、干预组(60例... 详细信息

目的分析基于中链甘油三酯(MCT)的生酮饮食在接受化疗3个月以上的乳腺癌患者中的应用价值。方法选取武汉市第三医院2021年3月至2023年3月期间入院的乳腺癌患者(接受化疗干预3个月以上)120例,简单随机将其分为对照组(60例)、干预组(60例)。其中,对照组接受传统化疗饮食干预,干预组接受基于MCT的生酮饮食干预,两组患者均实施为期5周的临床观察。比较两组患者干预前、干预1周、2周、3周、5周血酮、血糖及体重情况。同时,比较两组患者炎症指标[C反应蛋白(CRP)、肿瘤坏死因子(TnF)-α、白介素-1β(IL-1β)]、免疫指标(CD3^(+)、CD4^(+)、CD8^(+)T细胞)、肠道门水平优势菌群(厚壁菌门、拟杆菌门、变型菌门)、不良反应(恶心、呕吐、腹泻、便秘)、低血糖发生率差异。结果干预1周至5周,干预组血酮水平较干预前升高,且干预组血酮水平高于对照组[(1.84±0.12)mmol/L比(0.41±0.10)mmol/L]、[(2.10±0.11)mmol/L比(0.42±0.09)mmol/L]、[(2.01±0.15)mmol/L比(0.44±0.10)mmol/L]、[(2.00±0.19)mmol/L比(0.43±0.08)mmol/L](P<0.05)。干预1周至5周,干预组血糖水平较干预前升高,且干预组血糖水平低于对照组(P<0.05)。干预5周,与干预前相比,两组患者体重均下降(P<0.05)。干预后,干预组CD3^(+)、CD4^(+)T细胞占比高于对照组[(70.15±6.07)%比(57.62±5.09)%]、[(54.02±5.62)%比(43.06±4.98)%],CD8^(+)T细胞占比[(30.62±3.45)%比(35.62±3.11)%]、炎症指标低于对照组(P<0.05)。干预后,两组患者厚壁菌门、变型菌门丰度均较干预前下降,拟杆菌门较干预前上升,且干预组拟杆菌门丰度高于对照组,厚壁菌门、变型菌门丰度低于对照组(P<0.05)。干预组不良反应总发生率(13.33%,8/60)显著低于对照组(31.67%,19/60)(P<0.05)。结论对接受化疗3个月以上的乳腺癌患者而言,基于MCT的生酮饮食干预可改善患者的整体健康状况、减少化疗的不良反应等,生酮饮食治疗乳腺癌过程安全、可行,可为临床乳腺癌化疗及不良反应改善提供参考。

关键词：乳腺癌化疗饮食中链甘油三酯生酮饮食

Synthesis,Crystal Structure and Anti-ischemic Activity of(E)-1-(4-(Bis(4-methoxyphenyl)methyl)piperazin-1-yl)-3-(4-acetoxy-3-methoxyphenyl)prop-2-en-1-one

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Chinese Journal of Structural Chemistry 2015年第5期34卷 681-687页

作者： ZHOnG Yan LIU Ya-Lin XU Zhao-Ying XU Yi LI Ping wu Bin School of Chemistry and Chemical Engineering Southeast University School of Pharmacy Nanjing Medical University School of Basic Medical Sciences Nanjing Medical University

A new cinnamide derivative,（E）-1-（4-（bis（4-methoxyphenyl）methyl）piperazin-1-yl）-3-（4-acetoxy-3-methoxyphenyl）prop-2-en-1-one（C31H34n2O6,Mr = 530.60）,has been synthesized by the condensation of 1-（bis（4-methoxyphenyl）methyl）piperazine and（E）-3-（4-acetoxy-3-methoxyphenyl）acrylic *** compound was characterized by 1H nMR,13 C nMR,H RMS and single-crystal X-ray *** crystal belongs to the orthorhombic system,space group P212121 with a = 24.946（5）,b = 7.6380（15）,c = 14.555（3） A,V = 2773.3（10） A^3,Z = 4,Dc = 1.271 g/cm^3,F（000） = 1128,μ = 0.088 mm-1,Mo Kα radiation（λ = 0.71073 A）,the final R = 0.0641 and w R = 0.1170.A total of 3009 unique reflections were collected,of which 1760 with I 〉 2σ（I） were *** C（17）–H（17B）···O（3） and C（22）–H（22A）···O（3） interactions as well as intermolecular C（27）–H（27A）···O（3） hydrogen bonds help to stabilize the crystal *** title compound was evaluated for the anti-ischemic activity in vitro and in *** bioassay results indicated that the title compound displayed efficient activities against glutamine-induced neurotoxicity in PC12 cells and significantly prolonged the survival time of mice subjected to acute cerebral ischemia.

关键词： cinnamide crystal structure synthesis anti-ischemic activity

Design and simulation of self-powered radio frequency identification (RFID) tags for mobile temperature monitoring

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Science China(Technological Sciences) 2013年第1期56卷 1-7页

作者： CHU HeQun.wu GuangMin CHEn JianMing FEI Fei MAI John D LI Wen J MEMS Laboratory Department of Physics Faculty of Science Kunming University of Science and Technology Department of Mechanical and Biomedical Engineering City University of Hong Kong

This paper presents a design for a self-powered radio frequency identification (RFID) tag with a thin film bulk acoustic reso- nating piezoelectric power supply (PPS), which can be used for portable remote temperature monitoring. We call this system a PPS-RFID for short. The RFID systems have been found to have many applications in the internet of things (IOT) in the past decade. But semi-active RFID tags require an onboard battery which limits their applications in many fields. For these reasons, our research focuses on power sources for the RFID tags. This paper emphasizes the circuit design and simulation of PPS. In our tests, 0.283 mW was generated by PPS at 1 Hz vibration by a 650 n impact force. The results showed that the integrated PPS could supply sufficient power for the designed PPS-RFID tag. The PPS-RFID tag can be widely used for temperature monitoring during mobile transport of perishable items such as medicines or food.

关键词： self-powered radio frequency identification (RFID) piezoelectric temperature monitoring energy harvesting internet of things

A new Disease of Cherry Plum Tree with Yellow Leaf Symptoms Associated with a novel Phytoplasma in the Aster Yellows Group

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Journal of Integrative Agriculture 2014年第8期13卷 1707-1718页

作者： LI Zheng-nan ZHAnG Lei TAO Ye CHI Ming XIAnG Yu wu Yun-feng State Key Laboratory of Crop Stress Biology for Arid Areas College of Plant Protection Northwest A&F University Agriculture and Agri-Food Canada Pacifi c Agri-Food Research Center SummerlandBritish Columbia V0H 1Z0 Canada College of Forestry Northwest A&F University

A novel phytoplasma was detected in a cherry plum（Prunus cerasifera Ehrh） tree that mainly showed yellow leaf symptom. The tree was growing in an orchard located in Yangling District, Shaanxi Province, China. The leaves started as chlorotic and yellowing along leaf minor veins and leaf tips. Chlorosis rapidly developed to inter-veinal areas with the whole leaf becoming pale yellow in about 1-4 wk. Large numbers of phytoplasma-like bodies（PLBs） were seen under transmission electron microscopy. The majority of the PLBs was spherical or elliptical vesicles, with diameters in range of 0.1-0.6 μm, and distributed in the phloem cells of the infected tissues. A 1 246-bp 16 S ribosomal RnA（rRnA） gene fragment was amplified from DnA samples extracted from the yellow leaf tissues using two phytoplasma universal primer pairs R16mF2/R16mR1 and R16F2n/R16R2. Phylogenetic analysis using the 16 S rRnA gene sequence suggested that the phytoplasma associated with the yellow leaf symptoms belongs to a novel subclade in the aster yellows（AY） group（16SrI group）. Virtual and actual restriction fragment length polymorphism（RFLP） analysis of the 16 S rRnA gene fragment revealed that the phytoplasma was distinguishable from all existing 19 subgroups in the AY group（16SrI） by four restriction sites, Hinf I, Mse I, Sau3 A I and Taq I. The similarity coefficients of comparing the RFLP pattern of the 16 S rRnA gene fragment of this phytoplasma to each of the 19 reported subgroups ranged from 0.73 to 0.87, which indicates the phytoplasma associated with the cherry plum yellow leaf（CPYL） symptoms is probably a distinct and novel subgroup lineage in the AY group（16SrI）. In addition, the novel phytoplasma was experimentally transmitted to periwinkle（Catharanthus roseus） plants from the tree with CPYL symptoms and then back to a healthy 1-yr-old cherry plum tree via dodder（Cuscuta odorata） connections.

关键词： phytoplasma cherry plum yellow leaf CPYL phytoplasma-like bodies 16S rRnA restriction fragment length polymorphism d odder-bridged transmission

Fatigue Performance of Microalloyed High-strength Rebar and Analysis of Fracture Mechanism

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Journal of Iron and Steel Research International 2015年第12期22卷 1149-1155页

作者： Peng-yan LU Yu LIU Hua-jie wu Gang LIU Xiang MEnG Yang XU Engineering Research Institute University of Science and Technology Beijing School of Metallurgical and Ecological Engineering University of Science and Technology Beijing Collaborative Innovation Center of Steel Technology University of Science and Technology Beijing

Fatigue performance of hot-rolled ribbed-steel bar with the yield strength of 500 MPa （HRB500） was stud- ied with bend-rotating fatigue test at a stress ratio of R = -1. It is determined by staircase method that its fatigue strength for 107 cycles is 451 MPa, which is higher than that of common carbon structural steel. This should be at- tributed to the fine-grain strengthening resulting from the high content of alloy element V and Thermo-Mechanical Control Process （TMCP）. The S-n curve function is also obtained by nonlinear regression with three parameters power function. The fatigue fractures of the specimen were further analyzed with Scanning Electron Microscopy （SEM） and Energy Disperse Spectroscopy （EDS） to study the fracture mechanism. Taking into account microstruc- ture, hardness and cleanliness of the material, it implies that the fatigue fractures of HRB500 rebar all arise from surface substrates in which many brittle inclusions are contained, and that the fatigue crack propagation is principally based on the mechanism of quasi-cleavage fracture, because of the intracrystalline hard spots leading to stress con- centration and thus to the cracks. Moreover, the transient breaking area exhibits microvoid coalescence of ductile fracture due to the existing abundant inclusions.

关键词： HRB500 bend-rotating fatigue performance fracture mechanism inclusion

Biomineralization of organic matter in cobalt-rich crusts from the Marcus–Wake Seamounts of the western Pacific Ocean

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Acta Oceanologica Sinica 2014年第12期33卷 67-74页

作者： ZHAO Jun ZHAnG Haisheng wu Guanghai LU Bing PULYAEVA Irina A ZHAnG Haifeng PAnG Xuehui Key Laboratory of Marine Ecosystem and Biogeochemistry Second Institute of Oceanography State Oceanic Administration State Scientific Centre Yuzhmorgeologia Gelendzhik 353461 Russia School of Chemistry and Engineering University of Jinan

Organic matter in cobalt-rich crust （CRC） from the Marcus-Wake Seamounts of the western Pacific Ocean, Sample CM1D03, has been analyzed to understand the source, geochemistry and mineralization of organic matter, and the mineralization environment. Biomarkers, includingn-alkanes, isoprenoids, terpanes and sterols, have been detected in various layers of the CRC sample, using gas chromatography （GC） and gas chromatography-mass spectrometry （GC-MS）. The content of organic carbon （OC） and its stable isotope （δ13C）, and the combined features of the biomarkers show that the mineralized organic matter in CM1D03 CRC was mainly derived from microorganisms and lower plankton （e.g., bacteria and algae, respectively） from marine surface water, with some terrestrial higher plant components. The ratio of chloroform bitu-men ＂A＂： OC was high in the CRC, between 10.51 and 20.66, showing significant migration characteristics of n-alkanes. Four mineralization categories of organic matter were recognized based on GC chromatograms ofn-alkane molecules：（1） primitive type （bacteria and algae）, which is characterized by moderately mature ofn-alkanes preserving the original characteristics of the organic matter from microorganisms and lower plankton; （2） microbial degradation type, which is characterized by low contents ofn-alkanes and rising baseline in the chromatogram, with the ＂bulge＂ being the products of organic matter by biodegradation; （3） organic matter migration type, which is characterized by low carbon number ofn-alkanes withnC18 as the main peak carbon, without odd even predominance, and low concentrations of isoprenoids and hydro-carbons with high carbon number; and （4） organic matter hydrothermal type, which is characterized by relatively low concentration of small molecular weightn-alkanes, pristane, and phytane, accompanied by higher concentration ofn-alkanes with carbon number greater thannC18. This study shows that biomarkers can record controlling factors of mineraliz

关键词： ubiomineralization cobalt-rich crust biomarker Marcus-Wake Seamounts

Purification, Biological Activities, and Molecular Cloning of a novel Mannose-Binding Lectin from Bulbs of Zephyranthes candida Herb （Amaryllidaceae）

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Journal of Integrative Plant Biology 2006年第2期48卷 223-231页

作者： Chuan-Fang wu Jian Li Jie An Li-Qing Chang Fang Chen Jin-Ku Bao College of Life Sciences Sichuan University Chengdu 610064 China

A novel mannose-bindlng aggiutinln was purified from bulbs of Zephyranthes candida Herb by extraction, precipitation with 80% （nH4）2SO4, and ion-exchange chromatography on DEAE-Sepharose followed by gel flitration on Sephscryl S-100. The purified Z. candida agglutlnln （ZCA） migrated as a single band of 12 kDa on sodium dodecyi suifate-poiyecryiamide gel electrophoresis under reducing and non-reducing conditions. The apparent molecular mass of the iectln, as datermlned by gel filtration chromatography, was 48 kDa. The results Indicated that ZCA was composed of four Identical subunlts of 12 kDa each （homotetramerlc nature）. The ZCA agglutlhated rabbit erythrocytes, Escherichla coil and Saccharomyces cerevislae ceils at concentrations of 0.95, 1.90, and 31.30 μg/mL, respectively. Bloassays Indicated that ZCA has a significant effect on wheat aphid survival. Mortality after 7 d was 〉 90% at 0.26%. A degenerate primer was designed In accordance with the n-terminal partial sequence of purified ZCA. The full-length cDnA was cloned by 3＇- and 5＇-rapid amplification of cDnA ends. The full-length cDnA had 661 bp and the sequence encoded an open reading frame of 168 amino acids. The mature protein of ZCA Includes 109 amino acid residues and the molecular weight of the protein was 12.1 kDa. The result show that the zca gene encodes a protein precursor with a signal peptlde, a mature protein, and a C-terminal cleavage amino acids sequence. Molecular modeling of ZCA Indicated that Its three-dimensional atructure strongly resembies that of the snowdrop aggiutinin. Blocks＇ analysis revealed that the deduced amino acid sequence of ZCA has three functional domains specific for agglutination and three carbohydrate binding boxes （QDnY）.

关键词： agglutinating activity insecticidal activity molecular clone sequence analysis Zephyranthes candida agglutinin.