简介:摘要目的探讨外源性硫化氢(H2S)减轻大鼠局灶性脑缺血再灌注时神经元凋亡与PINK1/Parkin通路介导的线粒体自噬的关系。方法健康雄性SD大鼠216只,6~8周龄,体重250~270 g,采用随机数字表法分为4组(n=54):对照组(C组)、脑缺血再灌注组(I/R组)、H2S组、H2S+3-甲基腺嘌呤(H2S+3-MA组)。采用大脑中动脉栓塞法制备局灶性脑缺血再灌注损伤模型。H2S+3-MA组于再灌注前15 min时腹腔注射3-MA 10 mg/kg,余组腹腔注射等容量生理盐水。H2S组和H2S+3-MA组于再灌注即刻腹腔注射外源性H2S供体0.25% NaSH 10 mg/kg,余组腹腔注射等容量生理盐水。于再灌注1、3和7 d时行神经功能评分和corner实验(计算左侧转身百分比);取脑组织,确定脑梗死体积百分比、Bax、Bcl-2和caspase-3阳性细胞率、神经元凋亡率,Western blot法检测线粒体微管相关蛋白1轻链3(LC3)、PINK1和Parkin的表达,计算LC3-Ⅱ与LC3-Ⅰ表达的比值(LC3-Ⅱ/LC3-Ⅰ)。结果与C组比较,I/R组再灌注各时点神经功能评分降低,左侧转身百分比、脑梗死体积百分比、脑组织Bax、Bcl-2和caspase-3阳性细胞率、神经元凋亡率及LC3-Ⅱ/LC3-Ⅰ升高,PINK1和Parkin表达上调(P<0.05);与I/R组比较,H2S组再灌注各时点神经功能评分和Bcl-2阳性细胞率升高,左侧转身百分比、脑梗死体积百分比、脑组织Bax和caspase-3阳性细胞率、神经元凋亡率降低,PINK1和Parkin表达上调,LC3-Ⅱ/LC3-Ⅰ升高(P<0.05),H2S+3-MA组上述指标差异无统计学意义(P>0.05);与H2S组比较,H2S+3-MA组再灌注各时点神经功能评分和Bcl-2阳性细胞率降低,左侧转身百分比、脑梗死体积百分比、脑组织Bax和caspase-3阳性细胞率、神经元凋亡率升高,PINK1和Parkin表达下调,LC3-Ⅱ/LC3-Ⅰ降低(P<0.05)。结论外源性H2S抑制大鼠局灶性脑缺血再灌注时神经元凋亡的机制与增强PINK1/Parkin通路介导的线粒体自噬有关。
简介:摘要:通过调查发现,现阶段,我国小规模学校乘着义务教育均衡发展的东风,学生的学习环境,教师的办公与生活条件都有了很好的改善,但是小规模学校普遍存在教师人数少,很多教研活动无法有效开展的状况,虽然很多学校也都陆续开展教研活动,但是往往实际效果并不理想,这也使得很多教师的专业素质始终停滞不前,势必会对学校的整体发展产生一定影响,同时也会影响到我国教育事业的整体发展。随着我国网络信息技术水平不断提升,其在我国教育事业中的应用越来越深入,并且在实际应用的过程中发挥出了较为理想的效果。基于此,本文也尝试对小规模学校网络教研一体化有效实施策略进行分析。
简介:摘要:公共艺术手段能以较低的成本有效改善矿区空间环境,挖掘地域文化,延续场所精神,是废弃矿区再生的有效有段。本文从公共艺术的特征和构成入手,提出了以题材主导价值输出和以形式主导空间关系两种景观再生设计方法,探索了废弃矿区再生的有效途径。 关键词:废弃矿区;公共艺术;再生设计;可持续发展
简介:摘要:所谓“1+1+1”人才培养模式是实现一年专业基础教育和文化教育、一年校企联合见习教学、一年固定岗位顶岗实习。而在现代人才培养理念下,需要形成专业学习、技术学习、职业学习的“1+1+1”综合模式,其在三年时间里保证中职学生拥有丰富的理论知识、实践能力以及良好的职业道德。本文对中职烹饪教育的创新“1+1+1”人才培养模式展开分析,希望对此类教学能够具有借鉴价值。
简介:摘要:随着改革的逐步落实,由于高中生面临着来自高考的巨大压力,学校在课程改革上也相应面临着较多困难,学生仍处于被动接受的状态,其中“1+1”数学教学模式可以打破常规的教学模式,也是当前高中数学教师必走之路。教师应当采用新的教学模式,从而增加学生与学生之间,以及教师和学生之间的交流次数,让学生和教师共同进步,使学生可以主动探索学习数学的乐趣。本文针对“1+1”高中数学教学模式进行分析,提出相应的策略。
简介:AbstractBackground:Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.
简介:摘要帕金森病(PD)是世界上第二常见的神经退行性疾病,它的发病机制与线粒体功能障碍、氧化应激反应以及钙稳态失衡有关。近年来,PD与Ca2+的关系成为研究热点,钙稳态失衡可通过不同的途径导致PD。细胞内Ca2+水平取决于钙库操纵性钙内流(SOCE),而SOCE由钙释放激活钙通道调节分子1(Orai1)、基质相互作用分子1(STIM1)及瞬时受体电位通道1(TRPC1)相互作用组成的功能复合体调节。常见的PD神经毒素可通过降低Orai1-STIM1-TRPC1复合体功能,损伤SOCE及其下游的信号通路选择性损伤多巴胺能神经元,并且Orai1-STIM1-TRPC1复合体可能通过作用于小胶质细胞以及内质网调控神经炎症、自噬现象以影响PD的发生发展。因此恢复Orai1-STIM1-TRPC1复合体表达及功能,维持钙稳态可能成为PD的有效治疗靶点。
简介:摘要:本课例借助信息技术制造的课件来进行课堂辅助教学, 从而达到实现学生在一堂阅读课里的听说读写四会能力得到全面提升的教学目标。