Analysis of the potential biological value of pyruvate dehydrogenase E1 subunitβin human cancer

BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.

回归秘索思:E.E.卡明斯诗学嬗变之迹

卡明斯作为一位现代派诗人,深受美国意象派诗歌的影响,在20世纪初的新诗运动中,卡明斯诗歌融合了现代主义实验性语言和绘画技巧,形成其独有的视觉化具象诗风格。卡明斯后期诗学呈现出对早期现代主义诗歌与古典文艺的反思与回归,以秘索思为创作的根基和主线,从诗歌语言到艺术风格循着古希腊秘索思的踪迹,从而在现代派与古希腊传统之间建立关联,以回归秘索思对抗理性与逻格斯。在以秘索思为内核的诗学体系中,卡明斯积极吸收欧洲文艺精髓与东方哲思,形成内外一体的对话关系,建构出一套不同于现代派旗手的诗学话语体系,在20世纪现代派诗歌与古典传统的互动中形成了独特的艺术风格。

基于电子商务环境的农机管理系统设计

介绍了电子商务环境的背景和现状,详细描述了农机管理系统的实际需求和业务流程,并根据系统设计原则设计了系统总体架构,最后从人机管理、作业管理及综合信息等3个方面实现了农机管理系统。系统在测试过程中取得了较好的应用效果,是一种具有广泛应用前景的高效农机管理系统。

创伤性脊髓损伤急性期前列腺素E1对血管相关因子的调节和微循环功能的保护

背景:前列腺素E1被证明在血管扩张、炎症、白细胞迁移和黏附中发挥调节作用,但其对创伤性脊髓损伤后脊髓微循环的作用尚缺乏深入的研究。目的:探讨在大鼠创伤性脊髓损伤急性期给予前列腺素E1对血管相关因子的调节和微循环功能的保护作用机制。方法:将72只雌性SD大鼠随机分为3组(n=24),即假手术组、脊髓损伤组、前列腺素E1组。后两组用Allen’s打击法建立脊髓损伤的体内模型,前列腺素E1组大鼠在脊髓损伤后15 min内立即尾静脉注射脂质前列腺素E110μg/kg。分别在损伤后2,24 h测定脊髓微循环血流量和血氧饱和度、脊髓微血管直径和面积、脊髓含水量、血管功能调节因子(血浆血管性血友病因子、血栓素A2、前列环素、内皮素1)和炎症因子(肿瘤坏死因子α、白细胞介素1β)的表达。结果与结论:①脊髓损伤后2 h,前列腺素E1组大鼠的脊髓微血管直径及面积、脊髓微循环血流量和血氧饱和度均高于脊髓损伤组(P<0.05),脊髓含水量低于脊髓损伤组(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素及内皮素1质量浓度均低于脊髓损伤组(P<0.05);②脊髓损伤后24 h,前列腺素E1组大鼠的脊髓微血管面积、血流量和血氧饱和度均高于脊髓损伤组(P<0.05),脊髓含水量低于脊髓损伤组(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素及内皮素1、肿瘤坏死因子α、白细胞介素1β的质量浓度均低于脊髓损伤组(P<0.05);③脊髓损伤组大鼠损伤后24 h的脊髓微血管直径及面积、脊髓微循环血流量和血氧饱和度均高于损伤后2 h(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素、肿瘤坏死因子α、白细胞介素1β的质量浓度均高于损伤后2 h(P<0.05),但是脊髓组织内皮素1质量浓度低于损伤后2 h(P<0.05);④前列腺素E1组大鼠损伤后24 h的脊髓微循环血流量和血氧饱和度低于损伤后2 h(P<0.05),脊髓微血管直径及面积、脊髓含水量高于损伤后2 h(P<0.05);⑤以上结果表明,脊髓损伤大鼠伤后即刻静脉给予前列腺素E1,可调节血管功能调节因子、炎症因子并改善脊髓损伤后脊髓微循环,这为寻找治疗急性脊髓损伤的药物提供了潜在的基础。

基于E^3-Value的服务供应链运作管理流程和方法

目前尽管存在较多以产品为中心的供应链运作管理流程和方法,但在服务供应链领域,由于服务不同于产品的诸多特性局限了其进一步的应用。因此,采用结构化分析思想和方法,提出了基于E3-value的服务供应链运作管理逻辑流程和方法,该方法以价值为导向,不但可以解决现有供应链运作管理模式的一些适应性问题,而且能够解决"供应链运作管理模式为什么是这样,潜在盈利性如何量化"问题。

卵形鲳鲹促性腺激素β亚基的克隆鉴定及其受雌二醇的调控

促性腺激素(GtH,gonadotropin hormone)是垂体合成和分泌的一类重要糖蛋白激素,包括促卵泡生成素(Fsh,follicle stimulating hormone)和促黄体生成素(Lh,luteinizing hormone),在促进性腺发育和成熟过程中发挥重要作用。本研究成功克隆了卵形鲳鲹(Trachinotus ovatus)fshβ和lhβ基因的开放阅读框(ORF,open reading frame)序列,fshβORF长度为363 bp,lhβORF长度为447 bp。通过荧光定量PCR技术(qPCR,quantitative realtime PCR)检测,发现fshβ和lhβ基因在卵形鲳鲹的下丘脑-垂体-性腺轴(HPG,hypothalamus-pituitary-gonadal axis)显著表达,在垂体中的表达水平最高,其次是下丘脑和性腺。此外,通过体外实验评估17β-雌二醇(E2,17β-estradiol)对卵形鲳鲹垂体组织中fshβ和lhβ基因表达的影响。结果显示,10μmol/L E2处理6 h后,GtHβ亚基基因的表达被极显著抑制。最后,使用雌激素受体(ER,estrogen receptor)拮抗剂体外孵育卵形鲳鲹垂体组织,发现广谱性拮抗剂Fulvestrant、ERβ拮抗剂Cyclofenil和ERα拮抗剂MPP(MPP dihydrochloride)均能够消除E2对GtHβ亚基基因表达的抑制作用。综上所述,研究结果表明E2对卵形鲳鲹GtH的分泌具有负反馈调节作用,为卵形鲳鲹生殖调控机制提供了有价值的见解。

基于e^3-value的电子商务模式的结构化分析——以数据库服务提供商为例

在对电子商务模式的描述方法研究进行综述的基础上,介绍了e3-value的主要概念及分析步骤,并以数据库服务提供商的电子商务模式为例,说明了利用e3-value进行结构化分析的基本过程,最后对该分析方法进行了评价。

通脉开窍丸治疗血管性痴呆模型大鼠海马区神经元的铁死亡变化

背景:研究表明铁死亡与血管性痴呆存在密切联系,通脉开窍丸对于改善血管性痴呆患者的认知功能有一定疗效,但其作用机制不明确。目的:基于核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)/血红素氧合酶1(heme oxygenase-1,HO-1)/谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)信号通路调控铁死亡探讨通脉开窍丸对血管性痴呆干预作用以及分子机制。方法:84只雄性SD大鼠,其中12只大鼠用作假手术组,其余大鼠用改良2-VO法制备成血管性痴呆的模型,成模后随机分为模型组、通脉开窍丸高、中、低剂量(27.6,13.8,6.9 g/kg)组、联合组[通脉开窍丸高剂量+ML385(20 mg/kg)]、盐酸多奈哌齐组(0.45 mg/kg),灌胃给药1次/d,联合组同时腹腔注射Nrf2抑制剂ML385,1次/d,连续4周。采用Morris水迷宫检测大鼠的学习记忆能力;苏木精-伊红染色观察各组大鼠海马组织中神经元病理学变化;比色法试剂盒检测大鼠血清中还原型谷胱甘肽、Fe^(2+)、丙二醛的浓度;普鲁士蓝染色法检测大鼠海马组织中铁沉积情况;透射电镜观察大鼠海马组织中神经元线粒体超微结构变化;蛋白免疫印迹法检测大鼠海马神经元Nrf2、HO-1、GPX4、XCT、铁蛋白重链1(ferritin heavy chain 1,FTH1)蛋白的表达。结果与结论:(1)与假手术相比,模型组大鼠逃避潜伏期时间明显延长(P<0.05),穿越平台次数明显减少(P<0.05);海马组织松散,神经元细胞核深染,染色质固缩甚至裂解;CA1区铁离子聚集;线粒体萎缩变小,线粒体嵴溶解消失,线粒体膜密度增厚;血清中Fe^(2+)、丙二醛水平上升,还原型谷胱甘肽水平下降(P<0.05);海马组织GPX4、HO-1、XCT、Nrf2、FTH1蛋白表达显著降低(P<0.05)。(2)与模型组相比,通脉开窍丸各剂量组和盐酸多奈哌齐组大鼠平均逃避潜伏期均明显缩短(P<0.05),穿越平台次数增加(P<0.05);海马神经元恢复明显,CA1区神经元铁离子聚集明显减少,线粒体结构和功能好转;血清Fe^(2+)、丙二醛水平显著降低(P<0.05),血清还原型谷胱甘肽浓度及海马组织中GPX4,HO-1,XCT,Nrf2,FTH1蛋白表达显著升高(P<0.05)。(3)与通脉开窍丸高剂量组相比,盐酸多奈哌齐组治疗效果差异无显著性意义(P>0.05),联合组大鼠水迷宫逃避潜伏期时间延长(P<0.05),穿越平台次数减少(P<0.05),大鼠CA1区神经元病理改变情况不明显,铁沉淀增加,血清中丙二醛、Fe^(2+)浓度增加(P<0.05),还原型谷胱甘肽浓度减少(P<0.05),海马组织神经元线粒体萎缩变小,且Nrf2、XCT、HO-1、GPX4、FTH1蛋白的表达减少(P<0.05)。在一定范围内,通脉开窍丸剂量越高效果越好,且高剂量治疗效果不亚于盐酸多奈哌齐。(4)结果说明,通脉开窍丸可以减轻大鼠海马组织神经元病理改变,改善血管性痴呆大鼠的认知功能,其作用机制可能与Nrf2/HO-1/GPX4信号通路的激活抑制铁死亡有关。

基于e^3-value的移动商务商业模式仿真分析

本文运用e3-value结构化仿真分析方法构建基于价值链的移动商务商业模式的价值模型。通过相关参数输入模型,对其进行模拟试算,得到该商业模式的盈利性和合理性评价。通过e3-value模型创新关键因素价值活动、价值界面及价值端口的解构,调整价值模型及其变量,得到移动商务价值网商业模式价值模型。通过模型试算结果对比,分析讨论移动商务价值网商业模式的合理性及模型创新发展策略。

舒婷与E.E.肯明斯之诗作思想的比较研究

从诗歌思想与诗歌张力方面比较了朦胧派诗人舒婷、美国后现代主义诗人E.E.肯明斯诗歌创作的相似点。两位诗人引领时代潮流,肩负时代重任,圆满展现了诗歌的独特价值,完成了诗人的历史使命。

行断意连:论E.E.卡明斯视觉诗的语篇衔接特征

卡明斯视觉诗在词汇、结构、语义、语音、社会符号等五个层面上的语篇衔接特征说明,视觉诗特殊的建行形式,在看似断裂的形式下,隐藏着丰富的篇内衔接和篇外衔接。这种表面上的断裂并没有影响语篇意义的连贯,相反,它起到了语篇衔接的作用,促成了语篇的连贯,反映了诗体及作者的风格,并不影响诗歌意义及结构的衔接与连贯。

现代派诗歌偏离的限度——由美国现代派激进诗人E.E.肯明斯引发的思考

针对美国现代派诗人肯明斯诗歌中的偏离现象,探讨现代派诗歌偏离的限度,提出了三条限度:交流限度、审美限度和思想限度。

基于深度学习的5E教学模式实践与反思——以“探究平抛运动的特点”为例

随着新课程标准和学科核心素养的进一步实施,深度学习逐渐成为教学实践的主流.深度学习帮助学生建构系统化知识框架,旨在注重建构知识的过程,促进学生知识迁移.5E教学模式的五个环节“引入、探究、解释、拓展、评估”在物理教学中层层递进,与深度学习完美契合,能够促进学生高阶思维的发展以及核心素养的培养.

Correlations of the expression of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in colon cancer tissues

BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.

Sporadic E responds to the 2022 Tonga volcano eruptions recorded by the Meridian Project

In this study,ionosonde observations over Fuke(19.5°N,109.1°E),Wuhan(30.5°N,114.4°E),and Mohe(53.5°N,122.3°E)were analyzed to demonstrate the responses of the sporadic E()to the severe atmospheric disturbances caused by the Tonga volcanic eruptions on January 15,2022.The most prominent signature was the disappearance of the layer after~10:00 UT over Wuhan and Fuke,which was attributed to the vertical drift caused by the eruptions.The occurred intermittently after 13:00 UT following the arrival of the tropospheric Lamb wave.To examine the causal mechanism for the intermittence,we also included data of horizontal winds in the mesosphere and lower thermosphere region recorded by the meteor radars at Wuhan and Mohe in this study.The wind disturbances with periods of~20 hours contributed to the formation of the layer in the nighttime on January 15.

Effects of mesoscale gravity waves on sporadic E simulated by a one-dimensional dynamic model

In addition to being driven by tidal winds,the sporadic E(Es)layers are modulated by gravity waves(GWs),although the effects are not yet comprehensively understood.In this article,we discuss the effects of mesoscale GWs on the Es layers determined by using a newly developed model,MISE-1D(one-dimensional Model of Ionospheric Sporadic E),with low numerical dissipation and high resolution.Driven by the wind fields resolved by the high-resolution version of the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension(WACCM-X),the MISE-1D simulation revealed that GWs significantly influence the evolution of the Es layer above 100 km but have a very limited effect at lower altitudes.The effects of GWs are diverse and complex,generally including the generation of fluctuating wavelike structures on the Es layer with frequencies similar to those of the GWs.The mesoscale GWs can also cause increases in the density of Es layers,or they can disperse or diffuse the Es layers and increase their thickness.In addition,the presence of GWs is a key factor in sustaining the Es layers in some cases.

咸味猪骨肽部分替代NaCl对低盐香肠品质和风味的影响

本文旨在探讨咸味猪骨肽部分替代NaCl生产低盐香肠的可能性。分析了不同比例咸味猪骨肽替代NaCl对香肠的感官、质构特性、色差、pH、出品率、水分含量、滋味和挥发性成分的影响。结果显示,添加1%NaCl+1%咸味猪骨肽的香肠在色泽、外观、口感和风味方面优于对照组(添加2%NaCl),组织状态和对照组相当,同时,显著改善了香肠的质构特性(P<0.05)。电子舌结果显示,1%NaCl+1%咸味猪骨肽的低盐香肠咸味、鲜味、甜味和丰富度均优于对照组和其他试验组,同时,酸味、苦味和苦的回味显著降低。但是,不同咸味猪骨肽替代NaCl的香肠出品率和水分含量均显著下降(P<0.05)。顶空气相色谱-离子迁移谱(Headspace-Gas Chromatography-Ion Mobility Spectrometry,HS-GC-IMS)分析发现,咸味猪骨肽的添加改变了香肠的挥发性成分,结合感观评分结果,一定量的咸味猪骨肽替代NaCl赋予了低盐香肠更好的风味。综上结果表明,1%NaCl+1%咸味猪骨肽能够有效替代2%NaCl,实现了低盐香肠减盐不减咸的效果。

Comparative analysis of empirical and deep learning models for ionospheric sporadic E layer prediction

Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.

The Prognostic Value of Pathological and Molecular Margins Marked by p53 and eIF4E in Laryngeal Carcinoma

Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.

Q550E高强钢及焊接接头的疲劳裂纹扩展研究

焊接构造是钢桥的薄弱部位,在反复车辆荷载作用下,疲劳损伤正逐步成为影响桥梁服役安全的关键问题之一。以Q550E高强钢为研究对象,开展母材和对接焊缝接头的静力拉伸和疲劳裂纹扩展试验,建立母材及焊接连接件的疲劳裂纹增长模型,揭示了应力比对高强钢焊接节点疲劳裂纹扩展速率的影响规律;开展基于FRANC3D和ABAQUS的联合仿真模拟分析,通过敏感性分析明确关键影响参数。结果表明:随着应力比的增大,疲劳裂纹扩展速率参数m增大、lg C减小,应力强度因子门槛值减小;对接焊缝m值约为母材的2倍,对接焊缝裂纹门槛值大于母材,且对应力比更敏感;联合仿真方法可准确预测高强钢焊接接头疲劳寿命,高应力比下试件厚度和初始裂纹深度对疲劳扩展影响显著。