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Identification of neuron selective androgen receptor inhibitors

World Journal of Biological Chemistry 2017年第2期8卷 138-150页

作者： Maya Otto-Duessel ben yi tew Steven Vonderfecht Roger Moore Jeremy O Jones Department of Cancer Biology Beckman Research Institute City of Hope National Medical Center Division of Comparative Medicine Beck-man Research Institute City of Hope National Medical Center Department of Molecular Immunology Beckman Research Institute City of Hope National Medical Center

AIM To identify neuron-selective androgen receptor(AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy(SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHODS Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell typeselective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuronselective AR inhibitor was examined in vitro using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-q PCR of AR-regulated genes and *** We identified the thiazole class of antibiotics as com-pounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. One of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FOXM1 activity and accordingly, a novel FOXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FOXM1 expression correlates with cell-type selectivity, FOXM1 co-localizes with AR in the nucleus, and that sh RNA-mediated knock down of FOXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FOXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FOXM1 and AR, and reduces the associa

关键词： Androgen receptor Selective androgen receptor modulator Spinal and bulbar muscular atrophy Kennedy’s disease

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Effects of thermally pretreated temperature on bio-hydrogen production from sewage sludge

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Journal of Environmental Sciences 2006年第1期18卷 6-12页

作者： XIAO ben-yi LIU Jun-xin Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China

Hydrogen can be obtained by anaerobic fermentation of sewage sludge. Therefore, in this paper the effects of thermally pretreated temperatures on hydrogen production from sewage sludge were investigated under different pre-treatment conditions. In the thermal pretreatment, some microbial matters of sludge were converted into soluble matters from insoluble ones. As a result, the suspended solid（SS） and volatile suspended solid（VSS） of sludge decreased and the concentration of soluble COD（SCOD） increased, including soluble carbohydrates and proteins. The experimental results showed that all of those pretreated sludge could produce hydrogen by anaerobic fermentation and the hydrogen yields under the temperatures of 121℃ and 50℃ were 12.23 ml/g VS（most） and 1.17 ml/g VS （least）, respectively. It illuminated that the hydrogen yield of sludge was affected by the thermally pretreated temperatures. Additionally, the endurance of high hydrogen yield depended on the translation of microbial matters and inhibition of methanogens in the sludge. The temperatures of 100℃ and 121℃ （treated time, 30 min） could kill or inhibit completely the methanogens while the others could not. To produce hydrogen and save energy, 100℃ was chosen as the optimal temperature for thermal pretrcatment. The composition changes in liquid phase in the fermentation process were also discussed. The SCOD of sludge increased, which was affected by the pretreatment temperature. The production of volatile fatty acids in the anaerobic fermentation increased with the pretreatment temperature.

关键词： anaerobic fermentation hydrogen production sewage sludge thermally pretreated temperature

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非静水压环境对U_(3)O_(8)高压拉曼声子行为的影响

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光谱学与光谱分析 2025年第1期45卷 59-65页

作者：王艺佳吴彬彬刘静仪房雷鸣刘本琼雷力四川大学原子与分子物理研究所四川成都610065 中国工程物理研究院核物理与化学研究所四川绵阳621022

八氧化三铀(U_(3)O_(8))是动力学和热力学最稳定的铀氧化物。研究U_(3)O_(8)的高压相稳定性和高压声子行为对其在核工业、催化剂等领域的应用具有重要参考价值。由于铀原子([Rn]5f^(3)6d^(1)7s^(2))和氧原子([He]2s^(2)2p^(4))核外电子... 详细信息

八氧化三铀(U_(3)O_(8))是动力学和热力学最稳定的铀氧化物。研究U_(3)O_(8)的高压相稳定性和高压声子行为对其在核工业、催化剂等领域的应用具有重要参考价值。由于铀原子([Rn]5f^(3)6d^(1)7s^(2))和氧原子([He]2s^(2)2p^(4))核外电子结构存在显著差异,因此很难通过同步辐射X射线衍射技术探测高压下铀氧化合物中U-O键合的细微变化。然而拉曼光谱对高压下U-O键合变化非常敏感,它能揭示物质在高压下包括键合或者化学计量等方面的重要信息。目前对U_(3)O_(8)高压结构相变的研究通常聚焦于静水压环境,而非静水压环境对U_(3)O_(8)高压相变的影响尚未得到深入研究。该研究基于金刚石对顶砧的高压拉曼散射技术探究了静水压和非静水压环境对正交α-U_(3)O_(8)高压相变与声子行为的影响。研究表明,静水压(8.1 GPa)和非静水压(8.2 GPa)条件下α-U_(3)O_(8)高压相变起始压力很接近。但由于非静水压环境中样品内的微区偏应力较大,因此非静水压环境中U_(3)O_(8)高压相变结束压力(16.4 GPa)比静水压环境中相应压力(18.5 GPa)约低2~3个GPa。同时本文给出了两对比实验中主拉曼模的一阶压力系数与Mode-Grüneisen参数γ。对比分析可知,高压相变前静水压条件下各主模零压下的一阶压力系数绝对值|dω/d P|几乎均大于非静水压条件下的相应值,这表明相变前非静水压环境中各拉曼模对压力响应不明显;一旦高压相变开始,由于较大微区偏应力的存在极大程度增强了铀氧原子外层电子的耦合作用,故相变后非静水压下压力系数绝对值显著增大。零压下B(6)2模的γ值最小,因此对外部扰动有更积极的响应。此外室温加压时A(3)2和A(4)2模(代表沿a轴氧原子的振动)的一阶压力系数通常小于B(4)2和B(6)2模(代表bc面内氧原子的位移),这表明α-U_(3)O_(8)高压相变前a轴比b、c轴更难被压缩。该工作深入探究了静水压和非静水压环境对α-U_(3)O_(8)高压相变的影响,为了解α-U_(3)O_(8)高压相稳定性和晶格动力学行为提供了重要参考。

关键词： U_(3)O_(8) 高压拉曼光谱高压相变非静水压

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Capacity and failure mechanism of laterally loaded jet-grouting reinforced piles: Field and numerical investigation

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Science China(Technological Sciences) 2016年第5期59卷 763-776页

作者： HE ben WANG Li Zhong HONG yi College of Civil Engineering and Architecture Zhejiang University

This study presents the results of field and numerical investigations of lateral stiffness, capacity, and failure mechanisms for plain piles and reinforced concrete piles in soft clay. A plastic-damage model is used to simulate concrete piles and jet-grouting in the numerical analyses. The field study and numerical investigations show that by applying jet-grouting sur- rounding the upper 7.5D （D = pile diameter） of a pile, lateral stiffness and beating capacity of the pile are increased by about 110% and 100%, respectively. This is partially because the jet-grouting increases the apparent diameter of the pile, so as to en- large the extent of failure wedge and hence passive resistance in front of the reinforced pile. Moreover, the jet-grouting pro- vides a circumferential confinement to the concrete pile, which suppresses development of tensile stress in the pile. Corre- spondingly, tension-induced plastic damage in the concrete pile is reduced, causing less degradation of stiffness and strength of the pile than that of a plain pile. Effectiveness of the circumferential confinement provided by the jet-grouting, however, diminishes once the grouting cracks because of the significant vertical and circumferential tensile stress near its mid-depth. The lateral capacity of the jet-grouting reinforced pile is, therefore, governed by mobilized passive resistance of soil and plastic damage of jet-grouting.

关键词： jet-grouting reinforced cast-in-place piles field test finite element analysis lateral bearing capacity lateral stiffness plastic damage failure mechanism

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敌草快对鸡输卵管膨大部组织结构、细胞凋亡及繁殖性能相关基因表达的影响

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农业生物技术学报 2025年第1期33卷 146-156页

作者：戴逸园丁香胡威刘犇肖佩怡杨雪郑文亚樊庆灿宜春学院生命科学与资源环境学院江西省高等学校硒农业工程技术研究中心江西绿科农牧科技有限公司

联吡啶类除草剂敌草快(Diquat)作为现代农业生产中常用的农药，极易引起禽类发生氧化应激，为探究敌草快诱导的氧化应激对鸡输卵管膨大部的影响，本研究选取45只健康且体重相近的180日龄康乐黄母鸡(Gallus gallus)，随机分成3组，每组1... 详细信息

联吡啶类除草剂敌草快(Diquat)作为现代农业生产中常用的农药，极易引起禽类发生氧化应激，为探究敌草快诱导的氧化应激对鸡输卵管膨大部的影响，本研究选取45只健康且体重相近的180日龄康乐黄母鸡(Gallus gallus)，随机分成3组，每组15只。各组鸡均饲喂基础饲粮且自由饮水，经1周适应性饲养后，实验组分别一次性腹腔注射10和20 mg/kg BW(body weight,体重)的敌草快，对照组腹腔注射等剂量的生理盐水，21 d后采集输卵管膨大部组织，利用抗氧化功能检测试剂盒检测抗氧化指标，利用苏木素-伊红(hematoxylin-eosin, HE)染色技术观察病理损伤，利用免疫组织化学(immunohistochemistry, IHC)技术检测相关蛋白的分布，利用qPCR和Western blot技术检测细胞凋亡和繁殖性能相关基因及蛋白的表达。结果显示，敌草快组的输卵管膨大部中过氧化氢酶(catalase, CAT)、总超氧化物歧化酶(total superoxide dismutase, T-SOD)活性显著降低(P<0.05)，丙二醛(malondialdehyde, MDA)浓度显著升高(P<0.05)。HE染色结果显示，敌草快组的输卵管膨大部管径减小，固有层细胞分布稀疏，黏膜上皮游离面纤毛受损，敌草快20 mg/kg组的黏膜上皮细胞出现空泡化。IHC结果显示，敌草快组的输卵管膨大部黏膜上皮和固有层中增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)的染色强度降低，无翅型鼠乳腺癌病毒整合位点4(Wingless-related murine mammary tumor virus integration site 4, Wnt4)在黏膜上皮游离面的染色强度也降低。qPCR结果显示，敌草快20 mg/kg组的输卵管膨大部中抗凋亡相关基因B-细胞淋巴瘤-2(B-cell lymphoma-2, Bcl-2)表达水平显著下调(P<0.05)，敌草快组促凋亡相关基因Bcl-2相关X蛋白(Bcl-2 associated X protein, Bax)和半胱氨酸蛋白酶3(Caspase3)的基因表达水平及Bax/Bcl-2均显著上调(P<0.05)；繁殖性能相关基因透明带精子结合蛋白2(zona pellucida sperm-binding protein 2, ZP2)和Wnt4的基因表达水平显著下调(P<0.05)。Western blot结果显示，Bcl-2、Bax、Caspase3、ZP2和Wnt4的蛋白表达水平与基因表达的变化趋势基本一致。上述研究结果表明，敌草快能够诱导鸡输卵管膨大部发生氧化应激和细胞凋亡，进而损伤膨大部组织结构及抑制繁殖性能相关基因的表达。本研究为缓解联吡啶类农药对禽类输卵管的损伤及保护繁殖性能提供理论参考。

关键词：敌草快氧化应激母鸡输卵管膨大部细胞凋亡繁殖性能相关基因

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Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation through NF-κB and AKT Signaling Pathway

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Chinese Journal of Integrative Medicine 2022年第5期28卷 419-424页

作者： XU ben PENG yi-ji ZHU Wei-jie Department of Urology Peking University First Hospital and Institute of UrologyPeking UniversityNational Urological Cancer CenterBeijing(100034)China

Objective:To investigate the effect of curcumin on viability of clear cell renal cell carcinoma(cc RCC)and analyze its possible ***:In cell lines of A498 and 786-O,the effects of curcumin(1.25,2.5,5 and 10μmol/L)on the viability of cc RCC were analyzed at 24,48 and 72 h by MTT *** protein expression levels of ADAMTS18 gene,p65,phosphorylation p65(pp65),AKT,phosphorylation AKT(p AKT)and matrix metallopeptidase 2(MMP-2)before and after curcumin(10μmol/L)treatment were examined by Western ***-time PCR and methylation specific PCR(MSP)were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment(10μmol/L).Results:Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose-and time-dependent manner(P<0.01).Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment,accompanied by down-regulation of nuclear factorκB(NF-κk B)related protein(p65 and pp65),AKT related protein(AKT and p AKT),and NF-κB/AKT common related protein *** ADAMTS18 gene overexpressed,the expression levels of p65,AKT and MMP2 were downregulated,of which were conversely up-regulated in silenced ADAMTS18(sh-ADAMTS18).The expression of pp65,p AKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC(NF-κB inhibitor)and LY294002(AKT inhibitor).Conclusion:Curcumin could inhibit the viability of cc RCC by down-regulating ADAMTS18 gene methylation though NF-κB and AKT signaling pathway.

关键词： curcumin clear cell renal cell carcinoma ADAMTS18 gene methylation signaling pathway

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An effective way to treat the iron-rich acid mine drainage from coal mining in Guizhou’s mountainous areas

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Journal of Mountain Science 2020年第6期17卷 1345-1359页

作者： LIU Lei LIU ben-hong LI Wei ZHANG yi College of Architecture and Environment Sichuan UniversityChengdu 610065China

Acid Mine Drainage(AMD)from coal mining is a serious environmental issue which affects water quality,ecology,and the overall landscape of the basin.A large number of coal mine tailings in the mountainous regions of Guizhou Province,China were unattended and iron-rich AMD was directly discharged to the *** discharge leaves the river―yellow‖and heavily *** study tries to find an efficient and economical method for treating iron-rich *** sampled AMD water in two sites:Yangliujie town of Duyun city(hereafter,called Yangliujie),and Xinglong Coal Mine,Duliu town of Guiding county(hereafter,called Xinglong).We performed iron removal laboratory experiment with Cement-bentonite Agent(CBA,80%cement and 20%bentonite)in 500 mL AMD water from Yangliujie,scale-up experiment in 15 L AMD water from both Yangliujie and Xinglong,and engineering application in Xinglong *** experiment results showed the iron removal rate can reach 99.8%and the removal rate depends on the CBA dosage and the treatment *** the scale-up experiment,we found that Fe concentration could be reduced from 587.0 to 0.2 mg/L when adding 20 g/L CBA to the AMD water and aerating for 3 *** sampled water in Xinglong has a very high Fe concentration(Fe 1019.8 mg/L)and the concentration varies with seasons,it is not economical to add the CBA directly to the AMD *** the abundant and cheap limestone resources in Guizhou,we used a twostep treatment method,first we added CaCO3 to raise the pH,and then we took the supernatant liquor and added CBA to the *** was shown that 15 g/L of CBA was a good dosage for iron removal with Fe concentration being reduced from 1019.8 to 0.3 mg/L when CaCO3 was used to raise the *** best treatment realized over 99.9%iron removal,99.2%NH3-N removal,98.9%CODMn removal,and heavy metals in the treated water were reduced to under the limit stipulated in the―Environmental Quality Standards of Surface Water in China‖.Thus in th

关键词： Iron(Fe) pH Acid mine drainage Cement bentonite Mountainous area

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TLR3 gene polymorphisms in cancer:a systematic review and meta-analysis

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Chinese Journal of Cancer 2015年第6期34卷 8-20页

作者： ben-Gang Wang De-Hui yi Yong-Feng Liu Department 1 of General Surgery the First Affiliated Hospital of China Medical University

Introduction:Recent studies examining the association of Toll-like receptor 3(TLR3)gene polymorphisms with the risk of developing various types of cancer have reported conflicting *** this association could advance our knowledge of the influence of TLR3 single nucleotide polymorphisms(SNPs)on cancer ***:We systematically reviewed studies that focused on a collection of 12 SNPs located in the TLR3 gene and the details by which these SNPs influenced cancer ***,14 case-control studies comprising a total of7997 cases of cancer and 8699 controls were included in a meta-analysis of 4 highly studied SNPs(rs3775290,rs3775291,rs3775292,and rs5743312).Results:The variant TLR3 genotype rs5743312(C9948T,intron 3,C>T)was significantly associated with an increased cancer risk as compared with the wild-type allele(odds ratio[OR]=1.11,95%confidence interval[CI]=1.00–1.24,P=0.047).No such association was observed with other TLR3 *** the stratified analysis,the rs3775290(C13766T,C>T)variant genotype was found to be significantly associated with an increased cancer risk in Asian ***,the rs3775291(G13909A,G>A)variant genotype was significantly associated with an increased cancer risk in Asians,subgroup with hospital-based controls,and subgroup with a small sample ***:After data integration,our findings suggest that the TLR3 rs5743312 polymorphism may contribute to an increased cancer risk.

关键词：基因多态性癌症系统单核苷酸多态性 Toll样受体 SNPs 基因变异等位基因

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Simultaneously enhanced electrochemical performance and air stability of Ni-rich cathode with a modified washing process

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Rare Metals 2024年第1期43卷 87-97页

作者： ben-Rui Hu ying-yi Yuan Yu-Cheng Wang Xun-Hui Xiong School of Environment and Energy Guangdong Provincial Key Laboratory of Advanced Energy Storage MaterialsSouth China University of TechnologyGuangzhou 510640China

Water washing has been regarded as one of the most effective strategies to remove surface residual lithium of nickel-rich layered oxides for lithium-ion batteries(LIBs).However,the loss of lattice lithium during the water washing process deteriorates the electrochemical performances and air ***,washing the LiNi_(0.90)Co_(0.05)Al_(0.02)O_(2)(NCA) with ammonium dihydrogen phosphate(NH_(4)H_(2)PO_(4)) solution has been proposed to simultaneously enhance electrochemical performances and air stability,in which in-situ generated Li_(3)PO_(4) coating layer on surface of NCA can suppress the loss of lattice ***,as a fast ionic conductor,Li_(3)PO_(4) coating layer on NCA can prevent the direct contact with electrolyte/*** a result,the NH_(4)H_(2)PO_(4) solution washed NCA cathode can deliver a high capacity of131.9 mAh·g^(-1) at 10.0C rate as well as impressive cycle stability with a capacity retention of 83.1% after 100 cycles at 1.0C,much higher than those of water washed NCA(WS-NCA) *** exposed in air for 7 days,the NH_(4)H_(2)PO_(4) solution washed NCA electrode can more effectively maintain the structural integrity as well as the electrochemical performances than water-washed *** work provides a simple and effective approach to enhance the cycle stability and air stability of Nickel-rich cathode materials.

关键词： Layered Ni-rich cathode Residual lithium Li_(3)PO_(4)coating Rate performance Air stability

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Spin-dependent transport properties and Seebeck effects for a crossed graphene superlattice p-n junction with armchair edge

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Frontiers of physics 2018年第4期13卷 145-157页

作者： ben-Hu Zhou ben-Liang Zhou Yang-Su Zeng Man-yi Duan Guang-Hui Zhou Department of Physics Shaoyang University Shaoyang 422001 China Department of Physics and Key Laboratory for Low-Dimensional Structures and Quantum Manipulation (Ministry of Education) Hunan Normal University Changsha 410081 China College of Physics and Electronic Engineering Sichuan Normal University Chengdu 610068 China

Using the nonequilibrium Green＇s function method combined with the tight-binding Hamiltonian, we theoretically investigate the spin-dependent transmission probability and spin Seebeck coefficient of a crossed armchair-edge graphene nanoribbon （AGNR） superl＇attice p-n junction under a perpendicular magnetic field with a ferromagnetic insulator, where junction widths Wi of 40 and 41 are considered to exemplify the effect of semiconducting and metallic AGNRs, respectively. A pristine AGNR system is metallic when the transverse layer m = 3j ＋ 2 with a positive integer j and an insulator otherwise. When stubs are present, a semiconducting AGNR junction with width W1= 40 always shows metallic behavior regardless of the potential drop magnitude, magnetization strength, stub length, and per- pendicular magnetic field strength. However, metallic or semiconducting behavior can be obtained from a metallic AGNR junction with Wi = 41 by adjusting these physical parameters. Furthermore, a metal-to-semiconductor transition can be obtained for both superlattice p-n junctions by adjust- ing the number of periods of the superlattice. In addition, the spin-dependent Seebeck coefficient and spin Seebeck coefficient of the two systems are of the same order of magnitude owing to the appearance of a transmission gap, and the maximum absolute value of the spin Seebeck coefficient reaches 370 μV/K when the optimized parameters are used. The calculated results offer new possi- bilities for designing electronic or heat-spintronic nanodevices based on the graphene superlattice p-n junction.

关键词： crossed graphene superlattice p-n junction spin-dependent transport properties Seebeck coefficient nonequilibrium Green's function

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