简介:瞄准:到表示人的gastric-cancer-related基因介绍的分析,GCRG123在人的胃的图章戒指房间癌纸巾,并且在GCRG123上执行生物信息学分析。方法:原位杂交被用来在嵌入石蜡的胃的纸巾探索GCRG123表示模式,包括图章戒指房间癌的15个盒子,15肠类型的腺癌,和15正常胃粘膜。北弄污被用来在在胃图章戒指房间癌和肠类型的腺癌纸巾之间的GCRG123表示分析差别。包括强风,Multalin和叫,联机软件被申请生物信息学分析。生物工学信息(NCBI)和加利福尼亚大学圣克鲁斯(UCSC)的国家中心数据库被用于分析。结果:当蓝色猛抛,原位杂交信号出现了限制了为细胞质。十从胃的环状体房间癌,正常胃的粘膜上皮和幽门腺的15个盒子显示出高GCRG123表示。低GCRG123表示在胃的肠类型的腺癌和正常胃腺被观察。北弄污表明GCRG123在图章戒指房间癌组织是起来调整的但是在肠类型的腺癌组织下面调整。强风和Multalin分析表明GCRG123顺序与人的长散布的原子元素retrotransposons的ORF2顺序有92%类似(LINE-1,L1)。叫分析显示了印射到所有染色体的那GCRG123。GCRG123被发现在Rb,IL-2的5'flanking区域和凝固第九因子基因的intron-17和-23集成。结论:GCRG123,L1家庭的一个积极成员,在人的胃的图章戒指是起来调整的房间癌。
简介:有限治疗选择为好攻击的前列腺癌症是可得到的。Gossypol被报导了在癌症的许多类型举办一项有势力anticancer活动。它能增加癌症房间的敏感到alkylating代理人,减少multidrug抵抗和减少转移。它是否能在癌症房间导致autophagy,还没是坚定的。这里,我们在vitro在人的前列腺癌症房间线PC3和LNCaP上调查了apogossypolone(ApoG2)和(?)-gossypol的antiproliferative活动。到ApoG2的PC-3和LNCaP房间的暴露导致了autophagy的几个特定的特征特征,包括在酸的小囊的细胞器的细胞质和形成的膜的液泡的外观。联系autophagy的LC3-II和beclin-1的表示在治疗以后在两根房间线增加了。有3-methyladenine的autophagy的抑制支持了两种房间类型的apoptosis。一起拿,这些数据证明autophagy的那正式就职能在人的前列腺癌症房间对apoptosis代表防卫机制。
简介:AbstractObjective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes. The conventional mutation detection strategy consists of sequencing of individual candidate genes separately, a time consuming and costly approach. In this study, we perform genome-wide single nucleotide polymorphism (SNP) array to identify candidate genes of hereditary hypotrichosis.Methods:A consanguineous family with two patients with hereditary hypotrichosis was enrolled, and autozygosity mapping by genome-wide SNP array was utilized to identify candidate genes.Results:Autozygosity mapping delineated runs of homozygosity, and alignment of the 11 genes identified the hairless (HR) gene as the candidate gene. Nucleotide sequencing revealed a novel homozygous mutation c.381delT, p.Ser127ArgfsTer40.Conclusion:This study illustrates how autozygosity mapping by a high-density SNP array streamlines mutation detection in heritable skin diseases.
简介:AbstractObjective:In contrast to the most commonly reported forms of maturity-onset diabetes of the young (MODY), including MODY2, MODY3 and MODY5, MODY6 is a relatively rare subtype. To investigate whether NEUROD1 is responsible for MODY in Chinese individuals, we screened its mutations in MODY pedigrees and explored the potential pathogenic mechanisms.Methods:Polymerase chain reaction direct sequencing was performed to screen NEUROD1 mutations in 32 Chinese MODY probands who were negative for the GCK/MODY2, HNF1A/MODY3 and HNF1B/MODY5 genes in this observational study. In addition, we enrolled 201 unrelated, non-diabetic control subjects of Han Chinese descent. The functional significance of newly identified mutations was analyzed using clinical phenotype, pathophysiology and three-dimensional structure studies. This study was approved by the Institutional Review Board of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China (approval No. YS-2017-83) on March 3, 2017.Results:E59Q (c.175 G>C, p.Glu59Gln), a heterozygous missense mutation in the NEUROD1 gene, was identified in one family with MODY. The Glu59 residue in NeuroD1 is highly conserved across mammalian species. Four diabetic patients carrying the mutation (a proband and her son, brother and sister) were lean, with a body mass index of 20.9 (20.3-21.2) kg/m2. Compared with their unaffected relatives (n= 4), E59Q carriers (n= 4) had significantly decreased ratios of fasting and 2-hour insulin to plasma glucose (both fasting plasma insulin/fasting plasma glucose and 2-hour postprandial plasma insulin/2-hour postprandial plasma glucose, P < 0.005). The proband’s father had an E59Q mutation and normal glucose tolerance, which suggested non-penetrance. The E59Q mutation was not detected in other probands or in the 201 control subjects with normal glucose tolerance. Two salt-bridge bonds of Glu59 were disrupted at the Q59 mutation site.Conclusion:The NEUROD1-E59Q mutation changed the molecular conformation of the N-terminal in NeuroD1, which may decrease binding of the E59Q mutant to the insulin promoter and insulin gene transcription activity, therefore causing the MODY6 subtype with defective insulin secretion.
简介:新鲜的水息肉水螅属于门Cnidaria,它在bilaterians的外观前从后生动物的系分叉。以便在metazoans理解apoptosis的进化,我们开始阐明了在这个模型有机体的分子的细胞死亡机械。基于EST和整个水螅染色体集会,我们识别了15caspases。我们证明一个人在apoptosis期间被激活,四与N终端DED,卡片或DD领域有开始者caspases的特征,二在vitro经历autoprocessing。另外,我们描述七Bcl-2-like和二象Bak一样蛋白质。为大多数Bcl-2家庭蛋白质,我们观察了mitochondrial本地化。当在哺乳动物的房间表示了时,象HyBak一样1和2强烈导致的apoptosis。禁止的apoptosis与显示出特别强壮的保护的效果的HyBcl-2-like4在哺乳动物的房间由camptothecin劝诱了的六个Bcl-2家庭成员。这蛋白质也与象HyBak一样交往了1在酵母二混血儿的试金。在它的BH3领域的保存白氨酸的变化两个都与象HyBak一样废除了相互作用1并且anti-apoptotic效果。而且,我们BH-3-only描述新奇水螅蛋白质。这些之一与Bcl-2-like4交往了并且在哺乳动物的房间导致了apoptosis。我们的数据显示为房间死亡规定的一个复杂网络的进化在多细胞的组织的最早、最简单的水平产生了,它在此展出了一复杂性实质地高级比在protostome模型有机体Caenorhabditis和果蝇。
简介:【摘要】“单元整体教学”要求教师基于学生的学情,对教学内容进行分析、整合、重组,并以一个完整的教学主题作为一个单元的教学。有利于学生形成逻辑性、结构性的思维方式,促进学生语言综合运用能力的整体发展。本论文主要从单元整体的视角出发,结合PEP教材内容谈论如何进行单元整体设计。
简介:摘要:在英语教学中,有意识地培养学生的文化意识和思维品质,有助于学生形成国际视野,理解并尊重文化差异,能从跨文化视角进行交际。文章围绕PEP《英语》三下Unit 2 My family的教学案例,从主题意义和文化差异两个方面介绍文化意识和思维品质培养的具体方法和途径,提出教师应探究主题意义、设计基于主题意义的教学目标和启发式问题链来推进教学。教师还应当挖掘语篇的文化差异,巧设转换、梯度性活动,训练学生思维,使学生具有相应文化意识的同时,还有积极灵活的思维能力实现跨文化交际,促进小学英语学科核心素养的落地开花。
简介:AbstractBackground:The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.Methods:In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators.Results:No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]Highvs.Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHighvs.Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHighvs.Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHighvs.Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001).Conclusions:In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.
简介:AbstractBackground:Microribose nucleic acids (miRNAs) are implicated in the progression of lung adenocarcinoma. MicroRNA-345-5p (miR-345-5p) is a recently identified anti-oncogene in some human cancers, but its functional role and possible molecular mechanism in lung adenocarcinoma remain unknown. This study aimed to identify the biological function and underlying mechanism of miR-345-5p in lung adenocarcinoma cells.Methods:In this study, lung adenocarcinoma tissues and adjacent tissues were collected in the First Affiliated Hospital of Anhui Medical University between April 2016 and February 2017. The expression of miR-345-5p and ras homolog family member A (RhoA) in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines (A549, H1650, PC-9, and H441) was detected by reverse transcription quantitative polymerase chain reaction analysis. Functional assays including colony formation, flow cytometry analysis, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of lung adenocarcinoma cells. In addition, RNA pulldown and luciferase reporter assays were conducted to evaluate the relationship between miR-345-5p and RhoA. Difference between the two groups was analyzed with Student’s t test, while that among multiple groups was analyzed with one-way analysis of variance.Results:MiR-345-5p expression displayed lower level in lung adenocarcinoma tissues (0.241 ± 0.095 vs.1.000 ± 0.233, t = 19.247, P < 0.001) and cell lines (F = 56.992, P < 0.001) than control tissues and cells. Functional experiments demonstrated that upregulation of miR-345-5p inhibited the malignant phenotypes of lung adenocarcinoma cells via suppressing cell proliferation, migration, invasion, and facilitating cell apoptosis. Additionally, RhoA was verified to be the downstream target of miR-345-5p. Expression of RhoA was downregulated by overexpression of miR-345-5p in PC-9 (0.321 ± 0.047 vs. 1.000 ± 0.127, t = 8.536, P < 0.001) and H1650 (0.398 ± 0.054 vs. 1.000 ± 0.156, t = 4.429, P = 0.011) cells. Rescue assays revealed that overexpression of RhoA rescued the suppressive effects of miR-345-5p upregulation on proliferation, migration, and invasion of lung adenocarcinoma cells. Further, miR-345-5p was found to regulate the Rho/Rho-associated protein kinase (ROCK) signaling pathway by downregulation of RhoA in lung adenocarcinoma cells.Conclusions:MiR-345-5p plays a tumor suppressor role in lung adenocarcinoma cells by downregulating RhoA to inactivate the Rho/ROCK pathway.
简介:AbstractObjective:To investigate the possible regulatory mechanism of corticotropin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) in 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion (IR) model.Methods:Pregnant rats (n=60) were randomly divided into four experimental groups by random number table (Control, EE, IR, and EE-IR groups),and were studied on the 17th, 19th, and 21st gestational days (GD) (n=5 in each group at the indicated time). Growth and development indicators of fetal rats among these four groups were recorded. Enzyme-linked immunosorbent assay was employed to detect CRH, UCN, and WFS1 levels in maternal sera. Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH, UCN, and WFS1. Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons.Results:A significant difference was found in placenta weight (F=8.10, P<0.05), fetal rat weight (F=40.86, P<0.05), fetal rat length (F=61.61, P<0.05), and fetal rat tail length (F=55.63, P<0.05) among four groups on the 17th ,19th , and 21st GD.What’s more, the overall differences of maternal serum UCN levels among Control, EE, IR, and EE-IR groups were significant (F=2.48, P<0.05). Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control (0.46±0.15 vs. 0.24±0.09, P<0.05), EE (0.46±0.15 vs. 0.17±0.04, P>0.05), and IR (0.46±0.15 vs. 0.22±0.15, P>0.05) groups at 19th GD, indicating that endoplasmic reticulum stress may be activated. However, the expression of CRH (0.42±0.05 vs. 0.58±0.12, P<0.05), UCN (0.43±0.01 vs. 0.47±0.16, P>0.05), and WFS1 (0.57±0.07 vs. 0.74±0.12, P>0.05) protein in the EE-IR group was subsided compared to the IR group at 17th GD.Conclusion:Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model. This study revealed that significant changes in the maternal sera level of UCN , placental level of WFS1 mRNA and placental levels of CRH, UCN, and WFS1 protein in chronic versus acute stress in a rat model of pregnancy. This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels, following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.
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简介:摘要:英语作为一门外语学科,是中职学校的重要文化基础课程之一。它不仅支撑着学生的专业知识学习,还关系到学生未来的就业方向。传统的中职英语口语课堂教学模式以教师讲解为主,学生死记硬背的内容较多,而口语练习量太少,这种“灌输式”的教学方式已经过时,不利于激发学生的英语学习兴趣。中职学校以培养社会技能型人才为导向,注重学生的职业素养和综合能力。因此,在中职英语口语教学中,英语教师应该把重点放在培养学生的口语运用能力上,合理创设特定场景进行英语口语模拟训练,让学生在将来的工作岗位上能用英语与外国人进行简单交际。本文基于信息化手段视角及中职英语口语课堂教学现状,在情景教学法的理论基础上探索中职英语口语情景教学的策略,希望能为中职英语口语教学提供一些参考。
简介:【内容摘要】:中共中央办公厅、国务院办公厅印发《关于进一步减轻义务教育阶段学生作业负担和校外培训负担的意见》(以下简称“双减”意见)。其中就提出:全面减压作业总量和时长,合理调控作业结构,减轻学生过重作业负担。学校教育教学质量和服务水平要进一步提升,作业布置需要更加科学合理。因此老师在设计,布置作业中,更需要在2022新版义务教育小学英语课程标准的指导下,在单元主题意义的整体教学建构中,从多方面深入思考,让作业真正的起到学,练,评三位一体,减负增效的作用。