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蛋白Z、蛋白Z依赖蛋白酶抑制剂及其他凝血指标与妊娠期高血压疾病的相关性分析 认领
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作者 罗晓华 郭晓珮 +3 位作者 黄玉莲 史娜 谷存华 魏心怡 《国际妇产科学杂志》 CAS 2020年第2期186-189,共4页
目的:研究蛋白Z(PZ)、蛋白Z依赖蛋白酶抑制剂(ZPI)及其他凝血指标[蛋白C(PC)、蛋白S(PS)]与妊娠期高血压疾病(HDP)的相关性。方法:收集2017年6月2018年12月在郑州大学第三附属医院产科收治的HDP患者60例作为研究对象(HDP组),其中妊娠期... 目的:研究蛋白Z(PZ)、蛋白Z依赖蛋白酶抑制剂(ZPI)及其他凝血指标[蛋白C(PC)、蛋白S(PS)]与妊娠期高血压疾病(HDP)的相关性。方法:收集2017年6月2018年12月在郑州大学第三附属医院产科收治的HDP患者60例作为研究对象(HDP组),其中妊娠期高血压组(25例)、子痫前期组(PE组,35例),另外选取健康孕妇50例作为正常妊娠组,未孕妇女30例作为正常未孕组。比较各组血清PZ、ZPI及血浆PS、PC水平,研究其与HDP的相关性,并采用受试者工作特征(ROC)曲线分析其对HDP的诊断价值。结果:①HDP组的血清PZ、ZPI水平均低于正常妊娠组(P<0.05),正常妊娠组高于正常未孕组(P<0.05),血清PZ、ZPI水平与HDP呈负相关(r分别为-0.687和-0.444,P<0.05),ROC曲线下面积分别为0.901(95%CI:0.853~0.948)、0.759(95%CI:0.676~0.841),最佳诊断截断值分别为31.52 ng/mL和14.54 ng/mL。②血浆PS、PC在HDP组低于正常妊娠组和正常未孕组(P<0.05),正常妊娠组与正常未孕组相比差异无统计学意义(P>0.05),血浆PC水平与HDP呈负相关(r为-0.304,P=0.000),PC对HDP诊断的最佳截断值为108.08%,AUC为0.677(95%CI:0.586~0.769)。血浆PS水平与HDP无相关性(P>0.05)。③HDP组2个亚组相比,PE组血清PZ、ZPI水平均低于妊娠期高血压组(P<0.05),而2组血浆PS、PC水平比较差异无统计学意义(P>0.05)。结论:检测妊娠期高血压疾病患者血清中PZ、ZPI及血浆中PS、PC水平,可以及早地发现凝血指标的异常,进行早期干预治疗,最大程度减少HDP的并发症。 展开更多
关键词 高血压 妊娠性 妊娠并发症 心血管 蛋白Z 蛋白Z依赖蛋白酶抑制剂 蛋白S 蛋白C 蛋白酶抑制药
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Protein microarray analysis of cytokine expression changes in distal stumps after sciatic nerve transection 认领
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作者 Xiao-Qing Cheng Xue-Zhen Liang +9 位作者 Shuai Wei Xiao Ding Gong-Hai Han Ping Liu Xun Sun Qi Quan He Tang Qing Zhao Ai-Jia Shang Jiang Peng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期503-511,共9页
A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors... A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a bas 展开更多
关键词 cytokines DISTAL stump gene ontology KYOTO ENCYCLOPEDIA of Genes and Genomes pathway peripheral nerve injury protein microarray PROTEIN-PROTEIN interaction network Wallerian degeneration
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Role of oxysterol-binding protein-related proteins in malignant human tumours 认领
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作者 Hao Liu Shuai Huang 《世界临床病例杂志》 SCIE 2020年第1期1-10,共10页
The oxysterol-binding protein-related protein(ORP)family is a group of proteins that mediate oxysterol metabolism and bioactivity in cells.ORPs constitute a large family of lipid transfer proteins.Much of the current ... The oxysterol-binding protein-related protein(ORP)family is a group of proteins that mediate oxysterol metabolism and bioactivity in cells.ORPs constitute a large family of lipid transfer proteins.Much of the current evidence indicates that certain members of the family of oxysterol-binding proteins(OSBPs)can lead to cancer.Many studies have revealed the putative roles of OSBPs in various cancer types.However,the exact effects and mechanisms of action of members of the OSBP/ORP family in cancer initiation and progression are currently unclear.This review focuses on ORP family members that can accelerate human tumour cell proliferation,migration,and invasion.The mechanisms and functions of various ORPs are introduced in detail.We also attempt to identify the roles of these proteins in malignant tumours with the ultimate aim of determining the exact role of the OSBP/ORP family in human tumour cells. 展开更多
关键词 Oxysterol-binding PROTEIN family Oxysterol-binding protein-related PROTEIN MALIGNANT TUMOUR ROLE Human TUMOUR TUMOUR proliferation migration and invasion
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A Plant SMALL RNA-BINDING PROTEIN 1 Family Mediates Cell-to-Cell Trafficking of RNAi Signals 认领
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作者 Yan Yan Byung-Kook Ham +2 位作者 Yee Hang Chong Shyi-Dong Yeh William J.Lucas 《分子植物:英文版》 SCIE CAS CSCD 2020年第2期321-335,共15页
In plants,RNA interference(RNAi)plays a pivotal role in growth and development,and responses to environmental inputs,including pathogen attack.The intercellular and systemic trafficking of small interfering RNA(siRNA)... In plants,RNA interference(RNAi)plays a pivotal role in growth and development,and responses to environmental inputs,including pathogen attack.The intercellular and systemic trafficking of small interfering RNA(siRNA)/microRNA(miRNA)is a central component in this regulatory pathway.Currently,little is known with regards to the molecular agents involved in the movement of these si/miRNAs.To address this situation,we employed a biochemical approach to identify and characterize a conserved SMALL RNA-BINDING PROTEIN 1(SRBP1)family that mediates non-cell-autonomous small RNA(sRNA)trafficking.In Arabidopsis,AtSRBP1 is a glycine-rich(GR)RNA-binding protein,also known as AtGRP7,which we show binds single-stranded siRNA.A viral vector,Zucchini yellow mosaic virus(ZYMV),was employed to functionally characterized the AtSRBP1-4(AtGRP7/2/4/8)RNA recognition motif and GR domains.Cellular-based studies revealed the GR domain as being necessary and sufficient for SRBP1 cell-to-cell movement.Taken together,our findings provide a foundation for future research into the mechanism and function of mobile sRNA signaling agents in plants. 展开更多
关键词 RNAI small RNA-binding protein family small RNA movement non-cell-autonomous protein glycinerich protein
Navigating the dynamic landscape of alpha-synuclein morphology:a review of the physiologically relevant tetrameric conformation 认领
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作者 Heather RLucas Ricardo DFernández 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期407-415,共9页
N-acetylatedα-synuclein(αSyn)has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson’s disease.In recent years,a physiologically relevant,higher order conf... N-acetylatedα-synuclein(αSyn)has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson’s disease.In recent years,a physiologically relevant,higher order conformation has been identified as a helical tetramer that is tailored by buried hydrophobic interactions and is distinctively aggregation resistant.The canonical mechanism by which the tetramer assembles remains elusive.As novel biochemical approaches,computational methods,pioneering purification platforms,and powerful imaging techniques continue to develop,puzzling information that once sparked debate as to the veracity of the tetramer has now shed light upon this new counterpart inαSyn neurobiology.Nuclear magnetic resonance and computational studies on multimericαSyn structure have revealed that the protein folding propensity is controlled by small energy barriers that enable large scale reconfiguration.Alternatively,familial mutations ablate tetramerization and reconfigure polymorphic fibrillization.In this review,we will discuss the dynamic landscape ofαSyn quaternary structure with a focus on the tetrameric conformation. 展开更多
关键词 ALPHA-SYNUCLEIN amyloid FIBRILS intrinsically disordered PROTEIN MULTIMER N-ACETYLATION oligomer Parkinson’s disease PROTEIN folding PROTEIN structure TETRAMER
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Interactive association between processing induced molecular structure changes and nutrient delivery on a molecular basis,revealed by cutting-edge vibrational biomolecular spectroscopy 认领
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作者 Aya Ismael Victor Hugo Guevara-Oquendo +1 位作者 Basim Refat Peiqiang Yu 《畜牧与生物技术杂志:英文版》 SCIE CAS CSCD 2020年第1期211-226,共16页
Background:This study was conducted to determine protein molecular structure profiles and quantify the relationship between protein structural features and protein metabolism and bioavailability of blend pel eted prod... Background:This study was conducted to determine protein molecular structure profiles and quantify the relationship between protein structural features and protein metabolism and bioavailability of blend pel eted products(BPP)based on co-products(canola or carinata)from processing with different proportions of pulse pea screenings and lignosulfonate chemical compound.Method:The protein molecular structures were determined using the non-invasive advanced vibrational molecular spectroscopy(ATR-FT/IR)in terms of chemical structure and biofunctional groups of amides(ⅠandⅡ),α-helix andβ-sheet.Results:The results showed that increasing the level of the co-products in BPP significantly increased the spectral intensity of the amide area and amide height.The products exhibited similar protein secondaryα-helix toβ-sheet ratio.The protein molecular structure profiles(amidesⅠandⅡ,α-helix toβ-sheet)were highly associated with protein degradation kinetics and intestinal digestion.In conclusion,the non-invasive vibrational molecular spectroscopy(ATR-FT/IR)could be used to detect inherent structural make-up characteristics in BPP.Conclusion:The molecular structural features related to protein biopolymer were highly associated with protein utilization and metabolism. 展开更多
关键词 ALPHA-HELIX and BETA-SHEET Amides(ⅠandⅡ) Biofunctional groups Chemical STRUCTURE PROTEIN metabolism and bioavailability PROTEIN molecular STRUCTURE
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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain 认领
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作者 Xiao-He Gu Heng Li +4 位作者 Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期270-276,共7页
Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neu... Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016. 展开更多
关键词 Δ78 locus BRAIN region dopaminergic neurons glial cell line-derived NEUROTROPHIC factor mouse BRAIN precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-TYPE REPEATS splice variants
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Peptide asparaginyl ligases——renegade peptide bond makers 认领
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作者 James P.Tam Ning-Yu Chan +2 位作者 Heng Tai Liew Shaun J.Tan Yu Chen 《中国科学:化学英文版》 SCIE EI CAS CSCD 2020年第3期296-307,共12页
Making peptide bonds is tightly controlled by genetic code and machinery which includes cofactors,ATP,and RNAs.In this regard,the stand-alone and genetic-code-independent peptide ligases constitute a new family of ren... Making peptide bonds is tightly controlled by genetic code and machinery which includes cofactors,ATP,and RNAs.In this regard,the stand-alone and genetic-code-independent peptide ligases constitute a new family of renegade peptide-bond makers.A prime example is butelase-1,an Asn/Asp(Asx)-specific ligase that structurally belongs to the asparaginyl endopeptidase family.Butelase-1 specifically recognizes a C-terminal Asx-containing tripeptide motif,Asn/Asp-Xaa-Yaa(Xaa and Yaa are any amino acids),to form a site-specific Asn-Xaa peptide bond either intramolecularly as cyclic proteins or intermolecularly as modified proteins.Our work in the past five years has validated that butelase-1 is a potent and versatile ligase.Here we review the advances in ligases,with a focus on butelase-1,and their applications in engineering bioactive peptides and precision protein modifications,antibody-drug conjugates,and live-cell labeling. 展开更多
关键词 asparaginyl ENDOPEPTIDASE Asn-specific LIGATION bioorthogonal LIGATION butelase CHEMOENZYMATIC LIGATION live-cell LABELING PROTEIN engineering PROTEIN modification site-specific LABELING tandem LIGATION
Shenfu injection attenuates lipopolysaccharide-induced myocardial inflammation and apoptosis in rats 认领
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作者 CHEN Rui-Juan RUI Qing-Lin +3 位作者 WANG Qiong TIAN Fang WU Jian KONG Xiang-Qing 《中国天然药物:英文版》 SCIE CAS CSCD 2020年第3期226-233,共8页
Shenfu injection(SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide(LPS)-induced myocardia... Shenfu injection(SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide(LPS)-induced myocardial inflammation and apoptosis.Experiments were carried out in Sprague-Dawley(SD) rats treated with LPS or LPS + SFI, and in H9 C2 cardiomyocytes. The sepsisassociated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS(20 mg·kg–1). SFI attenuated the increased expression of tumor necrosis factor(TNF)-α and interleukin(IL)-1β induced by LPS both in serum and heart. In LPS group,cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase(p-MEK) and phosphorylated extracellular regulated protein kinases(p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways. 展开更多
关键词 Shenfu injection LIPOPOLYSACCHARIDE INFLAMMATION APOPTOSIS Mitogen-activated protein kinase kinase Extracellular regulated protein kinases
GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice 认领
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作者 Huan Liu Xiang-Dan Gong +3 位作者 Xin Zhao Yue Qian Xiao-Ping Gu Tian-Jiao Xia 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期128-135,共8页
Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment.GLYX-13(rapastinel)acts on the glycine site of N-methyl-D-aspartate receptors(NMDARs)and has been shown t... Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment.GLYX-13(rapastinel)acts on the glycine site of N-methyl-D-aspartate receptors(NMDARs)and has been shown to enhance hippocampus-dependent learning and memory function.However,the mechanisms by which GLYX-13 affects learning and memory function are still unclear.In this study,we investigated these mechanisms in a mouse model of long-term anesthesia exposure.Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure(1.5%for 6 hours).Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test.The mRNA expression and phosphorylated protein levels of NMDAR pathway components,N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca^2+/calmodulin dependent protein kinaseⅡ(CaMKII)-cyclic adenosine monophosphate response element binding protein(CREB),in the hippocampus were evaluated by quantitative RT-PCR and western blot assay.Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B,CaMKII and CREB mRNA and phosphorylated protein levels.Intracerebroventricular injection of KN93,a selective CaMKII inhibitor,significantly diminished the effect of GLYX-13 on cognitive function and NR2B,CaMKII and CREB levels in the hippocampus.Taken together,our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus.Therefore,GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction.This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November 20,2017. 展开更多
关键词 Ca^2+/calmodulin-dependent PROTEIN kinaseⅡ cognitive impairment contextual FEAR conditioning cyclic adenosine MONOPHOSPHATE response element binding PROTEIN GLYX-13 ISOFLURANE N-METHYL-D-ASPARTATE receptor novel object recognition rapastinel
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蛋白质的摄入量及来源对骨密度的影响 认领
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作者 刘蕾 范鹰 《中国骨质疏松杂志》 CAS CSCD 北大核心 2020年第5期777-780,共4页
中国人口老龄化日趋明显,骨质疏松症及其相关的骨折等并发症患病率急剧上升。蛋白质是除钙和维生素D外,维持骨骼生长发育、力学性能和骨折愈合的重要营养素。研究发现,蛋白质摄入量过多或过少都对骨代谢有不利影响。适当增加蛋白质摄入... 中国人口老龄化日趋明显,骨质疏松症及其相关的骨折等并发症患病率急剧上升。蛋白质是除钙和维生素D外,维持骨骼生长发育、力学性能和骨折愈合的重要营养素。研究发现,蛋白质摄入量过多或过少都对骨代谢有不利影响。适当增加蛋白质摄入可以增加全身骨密度,还可预防髋部骨折。素食者和素食主义者股骨颈和腰椎的骨密度低于杂食者,而且素食主义者的骨折率高于杂食者。过多摄入含有酸化氨基酸的动物来源蛋白质(如半胱氨酸和甲硫氨酸)会增加患骨质疏松症的风险。以鱼、橄榄油和低摄入红肉为特征的地中海饮食模式与较高的骨密度有关。因此,适量而均衡的蛋白质摄入有利于骨健康。 展开更多
关键词 蛋白质 素食 动物来源蛋白质 骨代谢 骨密度 骨质疏松 骨质疏松性骨折
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28例IgD型多发性骨髓瘤患者实验室检查特点和临床特征分析 认领
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作者 郑伟 陆捷 +1 位作者 桂清荣 王东云 《检验医学》 CAS 2020年第3期224-228,共5页
目的探讨IgD型多发性骨髓瘤(MM)患者临床表现和实验室检查的特征。方法对28例IgD型MM患者的临床表现和实验室检查结果进行回顾性分析,同时与IgG型MM患者进行比较。结果28例IgD型MM患者中,IgD-κ亚型3例、IgD-λ亚型25例。IgD型MM患者血... 目的探讨IgD型多发性骨髓瘤(MM)患者临床表现和实验室检查的特征。方法对28例IgD型MM患者的临床表现和实验室检查结果进行回顾性分析,同时与IgG型MM患者进行比较。结果28例IgD型MM患者中,IgD-κ亚型3例、IgD-λ亚型25例。IgD型MM患者血常规(血红蛋白、红细胞、白细胞、血小板)和血清钙与IgG型MM患者比较,差异均无统计学意义(P>0.05)。IgD型MM患者的尿素、肌酐和白蛋白均高于IgG型MM患者(P<0.05),总蛋白、IgA、IgG和IgM均低于IgG型MM患者(P<0.05)。IgD型MM患者血清总轻链、游离轻链、游离κ/λ比值及尿液总轻链、总κ/λ比值与IgG型MM比较差异均有统计学意义(P<0.05)。28例IgD型MM患者中,有21例(75%)尿液中检出本-周蛋白。IgD型MM基因型多表现为1q21扩增。结论IgD型MM临床表现缺乏特异性,需要进行全面的实验室检查,包括免疫球蛋白定量检测、免疫固定电泳、骨髓细胞形态学分析、基因检测等,以提高诊断率。 展开更多
关键词 多发性骨髓瘤 IgD型 免疫固定电泳 M蛋白 本-周蛋白
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Inhibitory Effects of Cypermethrin on Interactions of the Androgen Receptor with Coactivators ARA70 and ARA55 认领
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作者 DING Zhen SHEN Jun Yu +6 位作者 HONG Jia Wei ZHANG Rui LI Zheng WANG Qi ZHANG Jin Peng ZHANG Mei Rong XU Li Chun 《生物医学与环境科学:英文版》 SCIE CAS CSCD 2020年第3期158-164,共7页
Objective The purpose of this study was to investigate the anti-androgenic mechanism of cypermethrin involving coactivators.Methods Mammalian two-hybrid assays were performed to study the effects of cypermethrin on in... Objective The purpose of this study was to investigate the anti-androgenic mechanism of cypermethrin involving coactivators.Methods Mammalian two-hybrid assays were performed to study the effects of cypermethrin on interactions of the androgen receptor(AR)with the coactivators androgen receptor-associated protein70(ARA70)and androgen receptor-associated protein 55(ARA55).Results The results showed that AR–ARA70 and AR–ARA55 interactions were remarkably enhanced by dihydrotestosterone(DHT,P≤0.05).Cypermethrin inhibited DHT-induced AR–ARA70 and AR–ARA55 interactions significantly(P≤0.05).Conclusion The study indicates that cypermethrin exhibits inhibitory effects on AR transcription associated with repression of AR–ARA70 and AR–ARA55 interactions in a ligand-dependent manner.The data show novel anti-androgenic mechanisms of cypermethrin that contribute to male reproductive toxicology. 展开更多
关键词 CYPERMETHRIN ANDROGEN receptor signaling ANDROGEN receptor-associated PROTEIN 70 ANDROGEN receptor-associated PROTEIN 55
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Crystal structure of Cas1 in complex with branched DNA 认领
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作者 Jing Yang Jiazhi Li +5 位作者 Jiuyu Wang Gang Sheng Min Wang Hongtu Zhao Yanhua Yang Yanli Wang 《中国科学:生命科学英文版》 SCIE CAS CSCD 2020年第4期516-528,共13页
Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new spacers.We have determined crystal structures of Thermus ther... Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new spacers.We have determined crystal structures of Thermus thermophilus Cas1 involved in new spacer acquisition both in complex with branched DNA and in the free state.Cas1 forms an asymmetric dimer without DNA.Conversely,two asymmetrical dimers bound to two branched DNAs result in the formation of a DNA-mediated tetramer,dimer of structurally asymmetrical dimers,in which the two subunits markedly present different conformations.In the DNA binding complex,the N-terminal domain adopts different orientations with respect to the C-terminal domain in the two monomers that form the dimer.Substrate binding triggers a conformational change in the loop 164–177 segment.This loop is also involved in the 3′fork arm and 5′fork arm strand recognition in monomer A and B,respectively.This study provides important insights into the molecular mechanism of new spacer adaptation. 展开更多
关键词 CRISPR CAS protein Cas1 ADAPTATION DNA integration structure PROTEIN-DNA COMPLEX
Breast cancer immunology and immunotherapy:targeting the programmed cell death protein-1/programmed cell death protein ligand-1 认领
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作者 Jing Zhao Jian Huang 《中华医学杂志:英文版》 SCIE CAS CSCD 2020年第7期853-862,共10页
Historically,breast cancer has been regarded as an immunogenic"cold"tumor.However,the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast c... Historically,breast cancer has been regarded as an immunogenic"cold"tumor.However,the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer.This review discusses the immune system,immune features of breast cancer,and the programmed cell death protein-1/programmed cell death protein ligand-1(PD-1/PD-L1)inhibitors used in the treatment of breast cancer.High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer.Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy.Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy,which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy,molecularly targeted therapies,and other immunotherapies to maximize the clinical efficacy.Collectively,the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going. 展开更多
关键词 Breast cancer Immune microenvironment IMMUNOTHERAPY Programmed CELL DEATH protein ligand-1 INHIBITORS Programmed CELL DEATH protein-1 INHIBITORS
Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery 认领
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作者 WANG Ruijue SHENG Kai +2 位作者 HOU Yingqin SUN Jialing LU Hua 《高等学校化学研究:英文版》 SCIE CAS CSCD 2020年第1期134-138,共5页
Protein delivery is of central importance for both diagnostic and therapeutic applications.However,protein delivery faces challenges including poor endosomal escape and thus limited efficiency.Here,we report the facil... Protein delivery is of central importance for both diagnostic and therapeutic applications.However,protein delivery faces challenges including poor endosomal escape and thus limited efficiency.Here,we report the facile construction and screening of a small library of cationic helical polypeptides for cytosolic protein delivery.The library is based on a random copolymer poly(γ-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}esteryl-L-glutamate)-randompoly(γ-6-chlorohexyl-L-glutamate)[P(EG3-r-ClC6)Glu],which is then modified with various pyridine derivatives and alkyl thiols.Flow Cytometry,confocal laser scanning microscopy,and viability assay collaboratively identify two leading polymers,showing efficient delivery of enhanced green fluorescent protein(eGFP)and low cytoto-xicity.This finding is further validated by the cytosolic delivery of RNase A and cytochrome C(Cyt C)to HeLa cells in the viability assay.Together,this work demonstrates that high-throughput screening is an effective and viable approach to the selection of cationic helical polypeptides for the cytosolic delivery of functional proteins. 展开更多
关键词 CATIONIC HELICAL polypeptide PROTEIN delivery CYTOSOLIC PROTEIN
Attenuation of inflammation in streptozotocin-induced diabetic rabbits by Matricaria chamomilla oil: A focus on targeting NF-κB and NLRP3 signaling pathways 认领
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作者 Saeid Saghahazrati Seyed Abdulmajid Ayatollahi +1 位作者 Farzad Kobarfard Bagher Minaii Zang 《中草药:英文版》 CAS 2020年第1期73-78,共6页
Objectives:The present study was conducted to investigate the protective effects of chamomile oil from Matricaria chamomilla against type 1 diabetes mellitus(T1 DM)and its potential mechanisms.Methods:T1 DM was establ... Objectives:The present study was conducted to investigate the protective effects of chamomile oil from Matricaria chamomilla against type 1 diabetes mellitus(T1 DM)and its potential mechanisms.Methods:T1 DM was established in male New Zealand white rabbits via a single intraperitoneal infusion of streptozotocin(STZ)(80 mg/kg body weight-1,dissolved in 0.2 m L of normal saline).Different doses of chamomile oil(25,50 and 100 mg/kg)were orally administrated to STZ induced diabetic rabbits for 21 consecutive days.The expression of pro-inflammatory cytokines was determined using ELISA assay.The expression of NF-κB and NLRP3 was measured using Western blot assay.Results:Compared with normal rabbits,STZ-induced diabetic rabbits exhibited significant increased levels of blood glucose and decreased levels of serum insulin that were reversed using middle and high tested dose of chamomile oil.Likewise,STZ-induced diabetic rabbits showed a significant increased expression of NF-κB and NLRP3 proteins in the pancreas tissue that was reversed by high tested dose of chamomile oil.Conclusion:Collectively,our findings demonstrated that chamomile oil possesses anti-hyperglycemic,and anti-inflammatory activities in STZ-induced diabetic rabbits by targeting inflammatory cytokines and NF-κB and NLRP3 signaling pathways. 展开更多
关键词 CHAMOMILE OIL INFLAMMATION NF-ΚB PROTEIN NLRP3 PROTEIN type 1 diabetes mellitus
RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃ 认领
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作者 Li-Min Guo Zhen Wang +8 位作者 Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期865-874,共10页
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under... Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017. 展开更多
关键词 GSK'872 human brain tissue hyperpyrexia METHAMPHETAMINE mixed LINEAGE kinase domain-like protein necrostatin-1 NECROPTOSIS nerve REGENERATION neural REGENERATION rat CORTICAL neurons receptor-interacting protein-3 synergistic effect
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Relationship between β-amyloid protein 1-42, thyroid hormone levels and the risk of cognitive impairment after ischemic stroke 认领
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作者 Lei Mao Xiao-Han Chen +6 位作者 Jian-Hua Zhuang Peng Li Yi-Xin Xu Yu-Chen Zhao Yue-Jin Ma Bin He You Yin 《世界临床病例杂志》 SCIE 2020年第1期76-87,共12页
BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure... BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure are affected by many factors,and the ability of evaluating the progress of patients with PSCI is insufficient.Therefore,it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI.Recent studies have shown thatβ-amyloid protein 1-42(Aβ1-42)and thyroid hormone levels are closely related to PSCI,which may be the influencing factors of PSCI,but there are few related studies.AIM To investigate the relationship between serum levels of Aβand thyroid hormones in acute stage and PSCI and its predicted value.METHODS A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study.Baseline data and serological indicators were recorded to assess cognitive function of patients.All patients were followed up for 1 year.Their cognitive functions were evaluated within 1 wk,3 mo,6 mo and 1 yr after stroke.At the end of follow-up,the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score,and the relationship between biochemical indexes and the progression of PSCI was explored.RESULTS Compared with patients with non-PSCI,the levels of Aβ1-42,triiodothyronine(T3)and free thyroxin were lower in the patients with PSCI.Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T3 in PSCI was also lower than that of the non-PSCI patients.Further analysis revealed that Aβ1-42(r=0.348),T3(r=0.273)and free thyroxin(r=0.214)were positively correlated with disease progression(P<0.05),suggesting that these indicators have the potential to predict disease progression and outcome.Cox regression analysis showed that Aβ1-42 and T3 were important factors of PSCI.Then stratified analysis showed that the lower the Aβ1-42 and T3,the higher risk of PSCI in patients who 展开更多
关键词 POST-STROKE COGNITIVE impairment TRIIODOTHYRONINE Β-AMYLOID PROTEIN Prognosis Montreal COGNITIVE assessment Free THYROXIN
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利用近红外技术预测向日葵籽仁品质性状 认领
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作者 汪磊 谭美莲 +4 位作者 傅春玲 汪魏 王力军 尹紫艳 严兴初 《中国油料作物学报》 CAS CSCD 北大核心 2020年第1期147-153,共7页
为实现向日葵育种材料品质性状的快速预测,选取154份向日葵籽仁样品,结合化学测定值和近红外光谱,利用化学计量学手段建立向日葵籽仁品质指标的近红外模型,评估其在籽仁粗蛋白、粗脂肪、油酸、亚油酸等重要品质性状测定中的可行性。结... 为实现向日葵育种材料品质性状的快速预测,选取154份向日葵籽仁样品,结合化学测定值和近红外光谱,利用化学计量学手段建立向日葵籽仁品质指标的近红外模型,评估其在籽仁粗蛋白、粗脂肪、油酸、亚油酸等重要品质性状测定中的可行性。结果表明,改进偏最小二乘法建模效果最佳,其粗脂肪、粗蛋白、油酸、亚油酸、饱和脂肪酸及不饱和脂肪酸的定标相关系数分别为0.975、0.950、0.973、0.951和0.913,交叉验证相关系数分别为0.969、0.939、0.915、0.927和0.711。用检验集对模型进行验证,粗脂肪、蛋白质、油酸、亚油酸、饱和及不饱和脂肪酸的外部检验决定系数(R~2)分别为0.959、0.950、0.937、0.906和0.930。本研究建立的模型质量较高,能够满足向日葵籽仁品质成分的快速测定,可为向日葵品质育种前期大量、快速的筛选提供技术支持。 展开更多
关键词 向日葵 粗脂肪含量 蛋白质 油酸 亚油酸 近红外光谱
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