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Special Issue:Questions&Data for Better Science and Innovation Call for submissions
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《Journal of Data and Information Science》 CSCD 2024年第3期I0002-I0002,共1页
Editors Yang Wang,Xi'an Jiaotong University Dongbo Shi,Shanghai Jiaotong University Ye Sun,University College London Zhesi Shen,National Science Library,CAS Topic of the Special Issue What are the top questions to... Editors Yang Wang,Xi'an Jiaotong University Dongbo Shi,Shanghai Jiaotong University Ye Sun,University College London Zhesi Shen,National Science Library,CAS Topic of the Special Issue What are the top questions towards better science and innovation and the required data to answer these questions? 展开更多
关键词 COLLEGE questions ISSUE
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姜黄素调控Yes相关蛋白1对子宫内膜癌Warburg效应及生物学行为的影响
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作者 胡颜霞 宋晓霞 张喜红 《新中医》 CAS 2024年第5期207-215,共9页
目的:观察姜黄素调控Yes相关蛋白1 (YAP1)对子宫内膜癌糖酵解Warburg效应及生物学行为的影响。方法:将HEC-1B细胞分为对照组、NC-YAP1组、si-YAP1组及低、中、高剂量组。对照组不做任何处理,NC-YAP1组转染NC-YAP1质粒,si-YAP1组转染si-Y... 目的:观察姜黄素调控Yes相关蛋白1 (YAP1)对子宫内膜癌糖酵解Warburg效应及生物学行为的影响。方法:将HEC-1B细胞分为对照组、NC-YAP1组、si-YAP1组及低、中、高剂量组。对照组不做任何处理,NC-YAP1组转染NC-YAP1质粒,si-YAP1组转染si-YAP1质粒,低、中、高剂量组细胞分别用20、40、80μmol/L的姜黄素处理。试剂盒检测各组细胞葡萄糖消耗量及乳酸含量;CCK-8法检测各组细胞增殖能力;流式细胞术检测各组细胞周期与凋亡;划痕法检测各组细胞迁移能力;Transwell法检测各组细胞侵袭能力。蛋白质印迹(Western blot)法检测YAP1、乳酸脱氢酶-A (LDH-A)、己糖激酶2 (HK2)、丙酮酸激酶2 (PKM2)蛋白表达。结果:与对照组比较,NC-YAP1组YAP1蛋白相对表达水平、乳酸含量及葡萄糖消耗量、LDH-A、HK2、PKM2蛋白水平、细胞增殖抑制率、G0/G1期比例及S期比例、细胞凋亡率、划痕愈合率、细胞侵袭抑制率差异均无统计学意义(P>0.05),si-YAP1组及低、中、高剂量组YAP1蛋白相对表达水平、葡萄糖消耗量及乳酸含量、LDH-A、HK2、PKM2蛋白水平、S期比例、划痕愈合率均降低(P<0.05),细胞增殖抑制率、G0/G1期比例、细胞凋亡率、细胞侵袭抑制率均升高(P<0.05)。与NC-YAP1组比较,siYAP1组及低、中、高剂量组细胞YAP1蛋白相对表达水平、葡萄糖消耗量及乳酸含量、LDH-A、HK2、PKM2蛋白水平、S期比例、划痕愈合率均降低(P<0.05),细胞增殖抑制率、G0/G1期比例、细胞凋亡率细胞侵袭抑制率均升高(P<0.05),且低、中、高剂量组上述指标均呈剂量依赖性(P<0.05)。与si-YAP1组比较,低、中剂量组细胞中YAP1蛋白相对表达水平均增加(P<0.05),而高剂量组差异无统计学意义(P>0.05);低剂量组葡萄糖消耗量及乳酸分泌量、LDH-A、HK2、PKM2蛋白水平、S期比例、划痕愈合率均增加(P<0.05),细胞增殖抑制率、G0/G1期比例、细胞凋亡率、细胞侵袭抑制率均降低(P<0.05),高剂量组葡萄糖消耗量及乳酸分泌量、LDH-A、HK2、PKM2蛋白水平、S期比例、划痕愈合率均降低(P<0.05),细胞增殖抑制率、G0/G1期比例、细胞凋亡率、细胞侵袭抑制率增加(P<0.05),而中剂量组乳酸含量及葡萄糖消耗量、LDH-A、HK2、PKM2蛋白水平、细胞增殖抑制率、G0/G1期比例及S期比例、细胞凋亡率、划痕愈合率、细胞侵袭抑制率差异均无统计学意义(P>0.05)。结论:姜黄素可能通过抑制YAP1表达抑制子宫内膜癌细胞的Warburg效应、增殖、迁移及侵袭等恶性行为。 展开更多
关键词 子宫内膜癌 姜黄素 yes相关蛋白1 Warburg效应
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Yes相关蛋白(YAP)通过激活PI3K/AKT通路促进皮肤鳞状细胞癌细胞侵袭和迁移
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作者 李珍玲 杨凡 +3 位作者 金雪梅 王雪妍 陈胎琴 权春姬 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2024年第3期244-251,共8页
目的探讨Yes相关蛋白(YAP)在皮肤鳞状细胞癌(cSCC)中表达及与cSCC侵袭和迁移中的作用。方法通过免疫组织化学染色法检测cSCC、鲍温病(BD)、癌旁正常皮肤组织中YAP的表达水平,并分析与临床病理参数之间的关系;利用慢病毒转染构建YAP基因... 目的探讨Yes相关蛋白(YAP)在皮肤鳞状细胞癌(cSCC)中表达及与cSCC侵袭和迁移中的作用。方法通过免疫组织化学染色法检测cSCC、鲍温病(BD)、癌旁正常皮肤组织中YAP的表达水平,并分析与临床病理参数之间的关系;利用慢病毒转染构建YAP基因敲低的A431稳定细胞株,利用四甲基罗丹明标记的鬼笔环肽检测A431细胞微丝分布和数量,Transwell TM实验检测细胞侵袭能力,划痕实验检测A431细胞的迁移能力;免疫荧光细胞化学染色法观察敲低YAP后上皮间质转化(EMT)相关标志物上皮钙黏素(E-cadherin)、锌指转录因子Snail的表达;Western blot法检测E-cadherin、Snail、β-catenin、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、磷酸化的蛋白激酶B(p-AKT)、核糖体蛋白S6(S6)、磷酸化S6(p-S6)、4E结合蛋白1(4EBP1)、磷酸化的4EBP1(p-4EBP1)的表达。结果YAP在cSCC和BD中表达显著高于癌旁正常皮肤组织;cSCC中YAP高表达与肿瘤大小、分化程度、侵袭程度密切相关,与患者的性别、年龄、发病部位、形态类型、是否神经脉管侵犯不相关;敲低A431细胞中YAP后,肿瘤细胞的侵袭、迁移能力降低,细胞微丝变细、伪足变少;E-cadherin表达增加,Snail和β-catenin蛋白表达降低,p-AKT、p-S6及p-4EBP1蛋白表达降低。结论YAP在cSCC中高表达,YAP激活PI3K/AKT信号通路促进cSCC的侵袭、迁移及EMT过程。 展开更多
关键词 yes相关蛋白(YAP) 皮肤鳞状细胞癌 上皮间质转化(EMT) 磷脂酰肌醇3激酶(PI3K) 蛋白激酶B(AKT)
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Structure of the Quarks and a New Model of Protons and Neutrons: Answer to Some Open Questions
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作者 Ágnes Cziráki 《Natural Science》 CAS 2023年第1期11-18,共8页
The described structural model tries to answer some open questions such as: Why do quarks not exist in the open state? Where are the antiparticles from the Big Bang?
关键词 Structure of Quarks New Model PROTON Neutron Open questions
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咪达唑仑调节河马/Yes相关蛋白信号通路缓解心肌缺血再灌注损伤
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作者 陈璐 同晨洁 +1 位作者 姜乐乐 杜晓宣 《心脑血管病防治》 2024年第9期15-20,F0003,共7页
目的探讨咪达唑仑(MDZ)通过调节河马(Hippo)/Yes相关蛋白(YAP)信号通路对大鼠心肌缺血再灌注损伤(MIRI)的影响。方法48只大鼠按随机数字表法分为4组,其中3组用结扎左冠状动脉前降支的方法构建MIRI大鼠模型,并随机分别给予生理盐水(10 mL... 目的探讨咪达唑仑(MDZ)通过调节河马(Hippo)/Yes相关蛋白(YAP)信号通路对大鼠心肌缺血再灌注损伤(MIRI)的影响。方法48只大鼠按随机数字表法分为4组,其中3组用结扎左冠状动脉前降支的方法构建MIRI大鼠模型,并随机分别给予生理盐水(10 mL/kg)、MDZ(0.1 mg/kg)、盐酸法舒地尔(10 mg/kg),为MIRI组、MDZ组、盐酸法舒地尔组,另外1组手术不结扎给予生理盐水(10 mL/kg)为sham组,每组12只。酶联免疫吸附测定法检测血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平;氯化三苯基四氮唑、苏木精伊红、末端尿苷核苷酸末端标记染色检查心肌梗死面积、心肌组织病理变化及心肌细胞凋亡情况;qPCR检测结缔组织生长因子(CTGF)、富含半胱氨酸蛋白61(CYR61)mRNA的表达;免疫印迹法检测切割型半胱氨酸天冬氨酸蛋白酶1(cleaved Caspase-1)及磷酸化(p)-大肿瘤抑制激酶1(LATS1)/LATS1、p-YAP/YAP、p-哺乳动物不育系20样激酶1(MST1)/MST1的表达。结果与sham组比较,MIRI组CK-MB、cTnI、LDH、MDA、TNF-α、IL-1β、心肌梗死面积、心肌细胞凋亡率、cleaved Caspase-1、p-LATS1/LATS1、p-YAP/YAP均升高,CTGF、CYR61 mRNA表达、p-MST1/MST1、SOD水平降低(P<0.05);与MIRI组比较,MDZ组、盐酸法舒地尔组CK-MB、cTnI、LDH、MDA、TNF-α、IL-1β、心肌梗死面积、心肌细胞凋亡率、cleaved Caspase-1、p-LATS1/LATS1、p-YAP/YAP均降低,CTGF、CYR61 mRNA表达、p-MST1/MST1、SOD水平升高(P<0.05)。结论MDZ可能通过激活Hippo/YAP信号通路,抑制氧化应激与炎症反应,降低心肌细胞凋亡,改善MIRI大鼠的心肌损伤。 展开更多
关键词 咪达唑仑 河马/yes相关蛋白信号通路 心肌缺血再灌注
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MKEAH:Multimodal knowledge extraction and accumulation based on hyperplane embedding for knowledge-based visual question answering
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作者 Heng ZHANG Zhihua WEI +6 位作者 Guanming LIU Rui WANG Ruibin MU Chuanbao LIU Aiquan YUAN Guodong CAO Ning HU 《虚拟现实与智能硬件(中英文)》 EI 2024年第4期280-291,共12页
Background External knowledge representations play an essential role in knowledge-based visual question and answering to better understand complex scenarios in the open world.Recent entity-relationship embedding appro... Background External knowledge representations play an essential role in knowledge-based visual question and answering to better understand complex scenarios in the open world.Recent entity-relationship embedding approaches are deficient in representing some complex relations,resulting in a lack of topic-related knowledge and redundancy in topic-irrelevant information.Methods To this end,we propose MKEAH:Multimodal Knowledge Extraction and Accumulation on Hyperplanes.To ensure that the lengths of the feature vectors projected onto the hyperplane compare equally and to filter out sufficient topic-irrelevant information,two losses are proposed to learn the triplet representations from the complementary views:range loss and orthogonal loss.To interpret the capability of extracting topic-related knowledge,we present the Topic Similarity(TS)between topic and entity-relations.Results Experimental results demonstrate the effectiveness of hyperplane embedding for knowledge representation in knowledge-based visual question answering.Our model outperformed state-of-the-art methods by 2.12%and 3.24%on two challenging knowledge-request datasets:OK-VQA and KRVQA,respectively.Conclusions The obvious advantages of our model in TS show that using hyperplane embedding to represent multimodal knowledge can improve its ability to extract topic-related knowledge. 展开更多
关键词 Knowledge-based visual question answering HYPERPLANE Topic-related
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那可丁对肺癌细胞血管生成、Yes相关蛋白及敏感性的作用机制
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作者 汤顾航 杜先凤 姜力豪 《中国老年学杂志》 北大核心 2024年第2期377-382,共6页
目的探讨那可丁对肺癌细胞血管生成、Yes相关蛋白(YAP)及敏感性的作用机制。方法A549按照1.5×106/ml接种于96孔板中,分为肺癌组(无干预的A549细胞)、低浓度那可丁组(A549细胞与20μmol/L的那可丁共培养)、中浓度那可丁组(A549细胞... 目的探讨那可丁对肺癌细胞血管生成、Yes相关蛋白(YAP)及敏感性的作用机制。方法A549按照1.5×106/ml接种于96孔板中,分为肺癌组(无干预的A549细胞)、低浓度那可丁组(A549细胞与20μmol/L的那可丁共培养)、中浓度那可丁组(A549细胞与40μmol/L的那可丁共培养)、高浓度那可丁组(A549细胞与80μmol/L的那可丁共培养),顺铂(DDP)组(A549细胞与20μmg/L的DDP共培养),采用Transwell法检测各组A549细胞侵袭数目;划痕实验检测划痕愈合率;观察各组A549细胞体外管腔形成数目;CCK-8检测DDP+那可丁对A549细胞抑制率;免疫印迹分别检测各组A549细胞碱性成纤维细胞生长因子(bFGF)2、血管内皮细胞生长因子(VEGF)、基质金属蛋白酶(MMP)-9、YAP及磷酸化(p)-YAP。结果与肺癌组相比,不同浓度的那可丁组及DDP组的侵袭数目、划痕愈合率及管腔形成数目均显著降低(P<0.05),低、中及高浓度的那可丁组相互比较存在显著差异(P<0.05),高浓度那可丁组与DDP组相比无统计学意义(P>0.05);DDP组及DDP+那可丁组在DDP浓度为0 mg/L时无统计学意义(P>0.05),在DDP浓度为2.5、5.0、10.0、20.0、40.0、80.0 mg/L时DDP+那可丁组的肺癌A549细胞抑制率均显著高于DDP组(P<0.05);与肺癌组相比,不同浓度的那可丁组及DDP组bFGF2、VEGF、MMP-9、YAP及p-YAP均显著降低,低、中及高浓度的那可丁组相互比较存在差异(P<0.05),高浓度那可丁组与DDP组相比无意义(P>0.05)。结论不同浓度的那可丁均可发挥抗肺癌侵袭、转移及血管管腔形成作用,高浓度效果最佳,研究机制可能与抑制YAP表达而降低bFGF2、VEGF、MMP-9水平相关。 展开更多
关键词 肺癌 那可丁 血管管腔 yes相关蛋白 顺铂
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PAL-BERT:An Improved Question Answering Model
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作者 Wenfeng Zheng Siyu Lu +3 位作者 Zhuohang Cai Ruiyang Wang Lei Wang Lirong Yin 《Computer Modeling in Engineering & Sciences》 SCIE EI 2024年第6期2729-2745,共17页
In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and comput... In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and computing power advance,the issue of increasingly larger models and a growing number of parameters has surfaced.Consequently,model training has become more costly and less efficient.To enhance the efficiency and accuracy of the training process while reducing themodel volume,this paper proposes a first-order pruningmodel PAL-BERT based on the ALBERT model according to the characteristics of question-answering(QA)system and language model.Firstly,a first-order network pruning method based on the ALBERT model is designed,and the PAL-BERT model is formed.Then,the parameter optimization strategy of the PAL-BERT model is formulated,and the Mish function was used as an activation function instead of ReLU to improve the performance.Finally,after comparison experiments with traditional deep learning models TextCNN and BiLSTM,it is confirmed that PALBERT is a pruning model compression method that can significantly reduce training time and optimize training efficiency.Compared with traditional models,PAL-BERT significantly improves the NLP task’s performance. 展开更多
关键词 PAL-BERT question answering model pretraining language models ALBERT pruning model network pruning TextCNN BiLSTM
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抑制Yes相关蛋白通过抑制上皮间质转化减轻CCl_(4)诱导的小鼠肝纤维化
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作者 赵文 阮何静 +4 位作者 汪思远 程羽哲 雷淼 赵久法 刘传苗 《南方医科大学学报》 CAS CSCD 北大核心 2024年第10期1839-1849,共11页
目的探索Yes相关蛋白(YAP)可否通过调控上皮间质转化影响肝纤维化的发生发展。方法将8周龄C57BL/6小鼠18只随机分为对照组、肝纤维化模型组和YAP抑制剂维替泊芬干预组,6只/组。肝纤维化模型采用四氯化碳(CCl_(4))溶液腹腔注射8周造模;... 目的探索Yes相关蛋白(YAP)可否通过调控上皮间质转化影响肝纤维化的发生发展。方法将8周龄C57BL/6小鼠18只随机分为对照组、肝纤维化模型组和YAP抑制剂维替泊芬干预组,6只/组。肝纤维化模型采用四氯化碳(CCl_(4))溶液腹腔注射8周造模;维替泊芬干预组在CCl_(4)基础上第7~9周采用维替泊芬腹腔注射干预。HE染色、Masson染色、肝脏生化学检测观察小鼠肝脏纤维化程度;转录组、蛋白组学测序及联合生信分析探明肝纤维化过程中上皮间质转化通路是否受YAP调控;免疫组化染色和Western blotting检测YAP及上皮间质转化关键基因E-cadherin、N-cadherin、Twist等表达变化。采集健康体检、慢性乙型肝炎、乙肝肝硬化患者血清各60例,酶联免疫吸附法检测其中YAP、N-cadherin、Vimentin、Twist血清表达水平。C57BL/6小鼠24只随机分为对照组、肝纤维化模型组、Twist抑制剂干预组和Twist抑制剂与YAP激动剂共同干预组,6只/组。HE染色、Masson染色、网状纤维染色观察小鼠肝脏纤维化程度,Western blotting检测各组α-SMA、YAP和Twist表达变化。结果小鼠肝组织病理学结果提示肝纤维化小鼠与对照组相比肝小叶结构破坏、假小叶形成,维替泊芬干预组纤维间隔变性,部分小叶结构恢复。随肝纤维化发生,血浆ALT、AST水平显著升高(P<0.01),维替泊芬干预组肝功能改善(P<0.01)。采用肝组织转录组、蛋白组测序及联合分析找到在肝纤维化形成和维替泊芬干预过程中同时在mRNA和蛋白水平差异表达的基因,发现了N-cadherin和Twist在3组间差异具有统计学意义(P<0.05),并进行PPI分析显示YAP与E-cadherin、N-cadherin存在关联。免疫组化和Western blotting结果提示N-cadherin、Twist、Vimentin随肝纤维化形成升高,E-cadherin在肝纤维化组织中表达下降(P<0.01)。抑制YAP可下调肝组织N-cadherin、Twist蛋白表达(P<0.01)。慢性乙型肝炎患者血清YAP、N-cadherin、Vimentin和Twist水平均随肝炎及肝硬化发生升高,在APRI>0.5或FIB-4>1.45患者中显著升高(P<0.01)。血清YAP在健康对照、肝炎、肝硬化患者中平均水平分别为4.09、5.69和5.36 ng/mL(P<0.01),其与N-cadherin、Vimentin、Twist水平均呈显著正相关,相关系数分别为0.626、0.435、0.526。采用Harmine抑制小鼠肝组织Twist表达,并在Harmine基础上予以YAP激动剂XMU-MP-1干预,肝组织病理学结果提示抑制Twist使肝纤维化小鼠肝组织炎症及纤维化程度减轻,同时激活YAP表达可再次加重胶原纤维沉积。Western blotting检测结果提示Harmine下调肝纤维化小鼠肝组织中α-SMA、YAP及Twist蛋白表达,同时激活YAP使肝组织α-SMA和YAP表达升高(P=0.079,P<0.05)。结论上皮间质转化是肝纤维化发生的重要机制之一,抑制YAP可通过减少上皮间质转化发生减轻肝纤维化。 展开更多
关键词 肝纤维化 yes相关蛋白 上皮间质转化 血清标志物
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Yes相关蛋白在电离辐射后表皮干细胞分化中的作用
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作者 王丽彬 陈俊飞 +4 位作者 袁方 王景泽 刘鹿 王学武 袁增强 《中国药理学与毒理学杂志》 CAS 北大核心 2024年第7期511-516,共6页
目的探讨Yes相关蛋白(YAP)在电离辐射(IR)后表皮干细胞(EPSC)分化中的作用。方法①利用打孔器建立小鼠背部皮肤损伤,随后分为IR组(给予^(60)Coγ射线局部照射),对照组(不照射);照射后0,1,3,6,9和12 d收集创面皮肤组织提取RNA和蛋白,West... 目的探讨Yes相关蛋白(YAP)在电离辐射(IR)后表皮干细胞(EPSC)分化中的作用。方法①利用打孔器建立小鼠背部皮肤损伤,随后分为IR组(给予^(60)Coγ射线局部照射),对照组(不照射);照射后0,1,3,6,9和12 d收集创面皮肤组织提取RNA和蛋白,Western印迹法检测创面愈合过程中YAP蛋白变化;实时荧光定量PCR(RT-qPCR)检测创面愈合过程中Yap及其下游靶基因结缔组织生长因子(Ctgf)和富含半胱氨酸蛋白61(Cyr61)的mRNA变化。②将EPSC给予60Coγ射线照射,细胞对照组不照射;4或8 Gy剂量照射后4,12,24和36 h收集细胞提取RNA,RT-qPCR检测YAP mRNA变化。4或8 Gy剂量照射36 h收集细胞提取蛋白,Western印迹法检测YAP蛋白水平;③短发夹RNA(shRNA)构建稳定的YAP基因敲低细胞,Western印迹法验证shYAP的敲低效率;RT-qPCR检测IR后YAP敲低对K1和K10 mRNA的影响。结果①与对照组相比,IR组小鼠在创面愈合过程中YAP蛋白水平显著降低(P<0.05,P<0.01),Yap及其下游靶基因Ctgf和Cyr61的mRNA水平显著降低(P<0.05,P<0.01)。②与细胞对照组相比,IR组细胞YAP mRNA和蛋白水平显著降低(P<0.01)。③在shYAP稳转细胞中,YAP蛋白水平显著降低(P<0.01);shYAP在IR后EPSC分化标志物K1和K10的mRNA水平明显降低(P<0.01)。结论YAP调控IR后创面愈合过程中EPSC的分化。 展开更多
关键词 yes相关蛋白 电离辐射 表皮干细胞 细胞分化
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Operational requirements analysis method based on question answering of WEKG
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作者 ZHANG Zhiwei DOU Yajie +3 位作者 XU Xiangqian MA Yufeng JIANG Jiang TAN Yuejin 《Journal of Systems Engineering and Electronics》 SCIE CSCD 2024年第2期386-395,共10页
The weapon and equipment operational requirement analysis(WEORA) is a necessary condition to win a future war,among which the acquisition of knowledge about weapons and equipment is a great challenge. The main challen... The weapon and equipment operational requirement analysis(WEORA) is a necessary condition to win a future war,among which the acquisition of knowledge about weapons and equipment is a great challenge. The main challenge is that the existing weapons and equipment data fails to carry out structured knowledge representation, and knowledge navigation based on natural language cannot efficiently support the WEORA. To solve above problem, this research proposes a method based on question answering(QA) of weapons and equipment knowledge graph(WEKG) to construct and navigate the knowledge related to weapons and equipment in the WEORA. This method firstly constructs the WEKG, and builds a neutral network-based QA system over the WEKG by means of semantic parsing for knowledge navigation. Finally, the method is evaluated and a chatbot on the QA system is developed for the WEORA. Our proposed method has good performance in the accuracy and efficiency of searching target knowledge, and can well assist the WEORA. 展开更多
关键词 operational requirement analysis weapons and equipment knowledge graph(WEKG) question answering(QA) neutral network
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基于非靶向代谢组学技术探讨Yes相关蛋白1改善马兜铃酸I诱导小鼠肝损伤的机制
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作者 薛玉 李彩格 +5 位作者 刘一玮 杨佳丽 张智琴 纪敬敏 于琨 石新丽 《中药新药与临床药理》 CAS CSCD 北大核心 2024年第1期46-55,共10页
目的基于非靶向代谢组学技术探讨Yes相关蛋白1(YAP1)改善马兜铃酸I(Aristolochic acid I,AAI)诱导小鼠肝损伤的机制。方法随机选取8只3周龄雄性肝细胞特异性Yap1基因敲除(基因型为Yap1^(Flox/Flox),Albumin-Cre,简称Yap1^(LKO))小鼠作为... 目的基于非靶向代谢组学技术探讨Yes相关蛋白1(YAP1)改善马兜铃酸I(Aristolochic acid I,AAI)诱导小鼠肝损伤的机制。方法随机选取8只3周龄雄性肝细胞特异性Yap1基因敲除(基因型为Yap1^(Flox/Flox),Albumin-Cre,简称Yap1^(LKO))小鼠作为Yap1^(LKO)+AAI组,8只Yap1Flox对照小鼠作为Yap1^(Flox)+AAI组。2组小鼠均按照2.5 mg·kg^(-1)·d^(-1)剂量腹腔注射AAI,连续14 d。采用鼠尾PCR法鉴定基因型;微板法测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性;HE染色法观察肝脏组织病理变化;免疫组织化学法测定肝组织中YAP1蛋白表达情况。采用非靶向代谢组学方法分析肝脏组织差异代谢物,利用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用技术分析样品,通过主成分分析(PCA)、偏最小二乘法判别分析(PLS-DA)和正交偏最小二乘法判别分析(OPLS-DA)筛选差异代谢物,利用HMDB数据库、METLIN数据库对代谢物进行鉴定,通过KEGG数据库对差异代谢物进行通路富集分析。结果(1)AAI诱导14 d,Yap1^(LKO)小鼠的体质量增长低于Yap1^(Flox)小鼠,但差异无统计学意义(P>0.05)。在第14天,与Yap1^(Flox)+AAI组比较,Yap1^(LKO)+AAI组小鼠血清中的ALT、AST酶活性明显升高(P<0.05),肝脏组织病理损伤明显加重。Yap1^(Flox)小鼠肝脏有YAP1蛋白阳性表达,而Yap1^(LKO)小鼠无YAP1蛋白阳性表达。(2)通过代谢组学分析共筛选出139种显著变化(VIP>1且P<0.05)的差异代谢物,与Yap1^(LKO)+AAI组小鼠相比,Yap1Flox+AAI组小鼠的62种肝脏代谢物上调,包括胆碱、牛磺酸、亚牛磺酸、α-亚麻酸、桐油酸、鹅去氧胆酸等;77种代谢物下调,包括甘油磷酸胆碱、L-磷脂酰胆碱、L-谷氨酰胺、L-丝氨酸、L-谷胱甘肽、5-甲硫腺、苯丙氨酸、6-磷酸葡萄糖、乳酸、尿酸苷等。KEGG富集通路主要有胆碱代谢、甘油磷脂代谢、胰岛素抵抗、谷胱甘肽代谢等。结论肝细胞特异性Yap1基因敲除加重了AAI诱导的小鼠肝脏损伤,YAP1通过上调胆碱、牛磺酸等不饱和脂肪酸,参与调控胆碱代谢、甘油磷脂代谢等,从而改善AAI诱导的小鼠肝损伤。 展开更多
关键词 yes相关蛋白1 马兜铃酸I 药物性肝损伤 代谢组学 胆碱代谢 小鼠
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Yes关联蛋白1在食管鳞状细胞癌中的临床意义
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作者 刘坤 管瑛瑛 +3 位作者 蒋冬先 许惠娟 侯英勇 侯君 《中国临床医学》 2024年第5期772-777,共6页
目的探讨Yes关联蛋白1(Yes-associated protein 1,YAP1)在食管鳞状细胞癌组织中的表达情况及临床意义。方法采用免疫组化技术检测439例食管鳞状细胞癌患者癌组织中YAP1的表达,分析YAP1阳性组与阴性组患者的临床病理参数差异。采用Kaplan... 目的探讨Yes关联蛋白1(Yes-associated protein 1,YAP1)在食管鳞状细胞癌组织中的表达情况及临床意义。方法采用免疫组化技术检测439例食管鳞状细胞癌患者癌组织中YAP1的表达,分析YAP1阳性组与阴性组患者的临床病理参数差异。采用Kaplan-Meier生存曲线分析YAP1对患者生存的影响。结果食管鳞状细胞癌中,YAP1的阳性率为30.52%(134/439)。YAP1阳性组患者肿瘤浸润更深(P<0.001)。Kaplan-Meier生存曲线分析显示,在生存期长于30个月的患者中,YAP1阳性者无瘤生存期(disease-free survival,DFS)和总生存期(overall survival,OS)更长(P<0.05)。Cox多因素回归分析显示,浸润深度是影响患者DFS(HR=1.371,95%CI 0.993~1.894,P=0.035)和OS(HR=1.489,95%CI 1.066~2.080,P=0.020)的独立因素。结论YAP1在部分食管鳞状细胞癌中表达;对于生存期大于30个月的患者,YAP1表达阳性提示预后更好。 展开更多
关键词 食管鳞状细胞癌 yes关联蛋白1 预后
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DPAL-BERT:A Faster and Lighter Question Answering Model
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作者 Lirong Yin Lei Wang +8 位作者 Zhuohang Cai Siyu Lu Ruiyang Wang Ahmed AlSanad Salman A.AlQahtani Xiaobing Chen Zhengtong Yin Xiaolu Li Wenfeng Zheng 《Computer Modeling in Engineering & Sciences》 SCIE EI 2024年第10期771-786,共16页
Recent advancements in natural language processing have given rise to numerous pre-training language models in question-answering systems.However,with the constant evolution of algorithms,data,and computing power,the ... Recent advancements in natural language processing have given rise to numerous pre-training language models in question-answering systems.However,with the constant evolution of algorithms,data,and computing power,the increasing size and complexity of these models have led to increased training costs and reduced efficiency.This study aims to minimize the inference time of such models while maintaining computational performance.It also proposes a novel Distillation model for PAL-BERT(DPAL-BERT),specifically,employs knowledge distillation,using the PAL-BERT model as the teacher model to train two student models:DPAL-BERT-Bi and DPAL-BERTC.This research enhances the dataset through techniques such as masking,replacement,and n-gram sampling to optimize knowledge transfer.The experimental results showed that the distilled models greatly outperform models trained from scratch.In addition,although the distilled models exhibit a slight decrease in performance compared to PAL-BERT,they significantly reduce inference time to just 0.25%of the original.This demonstrates the effectiveness of the proposed approach in balancing model performance and efficiency. 展开更多
关键词 DPAL-BERT question answering systems knowledge distillation model compression BERT Bi-directional long short-term memory(BiLSTM) knowledge information transfer PAL-BERT training efficiency natural language processing
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情志应激激素受体调控Yes相关蛋白1影响乳腺癌细胞上皮间充质转化进程研究
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作者 曾伟 孙文娜 +2 位作者 廖女珠 罗丽珊 李耀泉 《中医药导报》 2024年第5期13-17,共5页
目的:探究情志应激激素受体(GR)与Yes相关蛋白1(YAP1)对乳腺癌MCF-7细胞转移的调控机制,以期为乳腺癌的治疗提供新思路。方法:通过免疫组化实验分析乳腺癌组织和癌旁组织GR和YAP1的表达;将MCF-7细胞分为:si NC组、si GR组和si YAP1组,... 目的:探究情志应激激素受体(GR)与Yes相关蛋白1(YAP1)对乳腺癌MCF-7细胞转移的调控机制,以期为乳腺癌的治疗提供新思路。方法:通过免疫组化实验分析乳腺癌组织和癌旁组织GR和YAP1的表达;将MCF-7细胞分为:si NC组、si GR组和si YAP1组,分别通过MTT实验、Transwell实验、细胞划痕实验和流式细胞术分析MCF-7细胞的增殖、侵袭、迁移能力及凋亡率,通过蛋白免疫印迹实验分析细胞GR和YAP1的表达水平。结果:与癌旁正常组织比较,乳腺癌组织YAP1与GR的表达水平升高。与si NC组比较,si GR组和si YAP1组的MCF-7细胞增殖能力、侵袭能力、迁移能力显著降低,凋亡率增加(P<0.05)。与si NC组比较,si GR组的MCF-7细胞的YAP1和GR表达水平降低(P<0.05),si YAP1组的MCF-7细胞的YAP1表达水平降低(P<0.05)。结论:乳腺癌患者的癌组织中YAP1与GR的表达水平升高。GR被激活后,通过调控细胞内的YAP1通路影响MCF-7细胞的增殖、迁移和侵袭能力以及凋亡率,进而导致乳腺癌MCF-7细胞转移,靶向调节YAP1抑制乳腺癌上皮间充质转化(EMT)发生可为乳腺癌患者提供新的治疗策略。 展开更多
关键词 情志应激 情志应激激素受体 yes相关蛋白1 乳腺癌 上皮间充质转化 转移 MCF-7细胞
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益肾化湿颗粒对糖尿病肾病小鼠中Yes相关蛋白的调控作用 被引量:2
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作者 蔡小凡 黄洁波 +4 位作者 邢玥 符欣漪 邓跃毅 钟逸斐 吴慧娟 《中国药理学通报》 CAS CSCD 北大核心 2023年第10期1944-1949,共6页
目的探讨益肾化湿颗粒(Yishen Huashi Granule,YSHS)对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)小鼠的保护作用及可能的相关机制。方法建立STZ诱导DN小鼠模型,随机分为模型组、YSHS组及YAP抑制剂维替泊芬组,同时设立对照组。造模成功后8周... 目的探讨益肾化湿颗粒(Yishen Huashi Granule,YSHS)对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)小鼠的保护作用及可能的相关机制。方法建立STZ诱导DN小鼠模型,随机分为模型组、YSHS组及YAP抑制剂维替泊芬组,同时设立对照组。造模成功后8周开始干预,疗程4周。分别检测各组干预前后尿蛋白及干预后血肌酐、尿素氮水平。疗程结束后处死小鼠,行光镜HE染色观察肾小球病理变化,Western blot检测YAP、p-YAP S127及CTGF的蛋白表达,RT-PCR检测YAP、CTGF及足细胞蛋白nephrin、podocalyxin、WT1的mRNA表达。结果YSHS组在生化指标上较模型组均有好转,HE染色显示肾小球病理损伤有所改善。模型组YAP、p-YAP S127及CTGF的蛋白表达增多,YAP和CTGF的mRNA表达亦增多,而3种足细胞蛋白的mRNA表达减少。经YSHS治疗后,YAP、p-YAP S127及CTGF的蛋白表达与YAP、CTGF的mRNA表达量均有所下降,而nephrin、podocalyxin、WT1的mRNA表达量升高。结论YSHS可降低DN小鼠尿蛋白、保护肾功能并减轻肾小球病理损伤,其机制可能与下调肾组织中YAP,减少CTGF表达水平并上调足细胞蛋白的mRNA表达有关。 展开更多
关键词 糖尿病肾病 益肾化湿颗粒 yes相关蛋白 Hippo信号通路 结缔组织生长因子 足细胞
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Design of Questions in the Teaching of English Reading
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作者 金力 《内蒙古师范大学学报(哲学社会科学版)》 1999年第S3期96-100,共5页
Questions which were conventionally designed to check reading comprehension can also be used to enhance understanding. Different types of questions can be designed to achieve different purposes in reading. While desig... Questions which were conventionally designed to check reading comprehension can also be used to enhance understanding. Different types of questions can be designed to achieve different purposes in reading. While designing questions, teachers should take into consideration such points as the language used, manner of presentation and types of questions etc. Moreover, once questions have been designed, it’s essential for teachers to think about the techniques for the use of these questions. If appro- priately used, questions contribute greatly to students’ understanding of what they’ re reading by helping to explore the meaning that language conveys, in addition to developing proper reading skills. Therefore, teachers should be able to teach reading with well-designed questions so that the ultimate goal of understanding the text is likely to be achieved. 展开更多
关键词 question DESIGN READING UNDERSTANDING
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Gender Differences In Using Questions——An Investigation of the Questions Used by Mr. Rochester and Jane in Jane Eyre
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作者 李清辉 楼捷 《海外英语》 2015年第21期198-199,共2页
In literature,differences in the description of female and male characters have been noticeable for a long time.In this study,the novel Jane Eyre is uses as a material to investigate whether there are in fact any sign... In literature,differences in the description of female and male characters have been noticeable for a long time.In this study,the novel Jane Eyre is uses as a material to investigate whether there are in fact any significant differences in the questions Mr.Rochester and Jane use and how the questions function to portray these two main characters. 展开更多
关键词 questions Functions of the questions CONTEXT
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Questions to Be Asked in the Fast Reading Classroom and Principles
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作者 郝瑞英 《科技信息》 2009年第30期I0113-I0114,共2页
In the fast reading classroom the main work for the teacher isto ask questionsfor the sake of checking students'comprehension of the text in question. Questions could be classified according to different criteria.... In the fast reading classroom the main work for the teacher isto ask questionsfor the sake of checking students'comprehension of the text in question. Questions could be classified according to different criteria. This paper classifies the questions according to the teaching procedures,and suggests a few principles to ask questions. 展开更多
关键词 英语学习 学习方法 外语学习 学习兴趣
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Chinese Culture in ELT Classroom—The Influence of Chinese Culture on Students' Answering Questions
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作者 鲁玲萍 《山东师范大学外国语学院学报(基础英语教育)》 2005年第3期21-24,57,共5页
Based on personal observation and students’ self-reports, this article studies the characteristics presented by students in answering questions. It is found that Chinese culture plays an important part in explaining ... Based on personal observation and students’ self-reports, this article studies the characteristics presented by students in answering questions. It is found that Chinese culture plays an important part in explaining their specific behaviors. Hence, in order to lessen the negative effect of it, the author offers her own suggestions. 展开更多
关键词 中小学 英语教学 跨文化交际 问题意识
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