MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3

miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3′-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3′-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke.     

一种内燃机试验数字直接点火系的研制

数字直接点火系是由传感器组、电控单元及执行器等部分组成的高能点火系统，是目前汽油发动机中最先进的电子点火系。设计并实现了一种基于L497点火控制器的数字直接点火系，并给出了该点火系的工作过程及性能参数。样机试验结果表明所研制的数字直接点火系的方案可行、性能可靠。     

生物可降解镁植入物——骨肿瘤患者的潜在支架

骨癌患者切除术后可能发生复发和转移.传统的金属支架可以对骨缺损部位提供力学支撑,但无法有效清除复发的肿瘤细胞.本文中,我们介绍了一种可以抑制骨肉瘤生长的生物可降解镁丝植入物.简而言之,镁丝释放镁离子激活锌指蛋白Snail1从胞浆到细胞核的转运,通过下游的miRNA-181d-5p/TIMP3和miRNA-181c-5p/NLK两条平行的抗肿瘤信号通路诱导骨肉瘤细胞凋亡,抑制骨肉瘤细胞增殖.同时,镁丝释放出的氢气消除了细胞内过多的活性氧,从而抑制了骨肿瘤细胞的生长.裸鼠骨肉瘤细胞皮下荷瘤实验进一步证实镁丝能有效抑制肿瘤生长,延长荷瘤小鼠生存期.此外,镁丝对正常细胞和组织无毒性,揭示了镁植入物是骨肉瘤患者潜在的抗肿瘤支架材料.     

K497与FGH741合金的热等静压扩散连接

采用热等静压（ＨＩＰ）固－固扩散连接工艺,研究了Ｋ４９７与ＦＧＨ７４１合金ＨＩＰ连接及热处理后的组织变化、结合界面的组织、力学性能及界面区元素的扩散规律。结果表明,在ＨＩＰ和热处理阶段,ＦＧＨ７４１合金未发生再结晶,其晶粒度与母材基本相同,均为ＡＳＴＭ５～６级,Ｋ４９７合金的粗大枝晶组织和共晶相经热处理后基本消除。结合界面冶金结合良好,形成了一个由亚晶和再结晶晶粒组成的界面区且无有害相析出。结合试     

Overexpression of microRNAs miR-25-3p,miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction,Validation of Results and Study of the Biochemical Pathways Involved

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.     

用于宫颈癌标志物检测的新型电化学传感器设计

为了提高宫颈癌标志物检测的准确率,提出并设计了一种基于生物共轭探针与DSN酶双向信号放大的比率型电化学生物传感器。利用捕获探针在传感器中植入DSN酶,通过循环释放miRNA,实现核酸标志物信号的放大;利用MB-DNA-AuNp生物共轭探针实现了MB信号的增强。实验结果表明,随着miRNA-21浓度的升高,Fc的电化学峰值电流降低,MB的电化学峰值电流显著增加,该型传感器对于核酸和蛋白质两种典型宫颈癌标志物的检测具有很高的灵敏度和精确度。     

初诊2型糖尿病患者循环miRNA-101的表达变化及临床意义

目的:测定初诊2型糖尿病（type 2 diabetes mellitus,T2DM）患者血清miRNA-101的表达水平,分析其变化的临床意义。方法: 采用qRT-PCR法检测30例初诊T2DM患者及正常受试者血清中miRNA-101表达水平,并测定相关临床指标。两因素间关系采用Pearson相关分析。评估miRNA-101和其他参数的关联应用多元逐步回归分析。结果: 初诊T2DM患者血清中miRNA-101表达水平显著高于正常对照组（P<0.05）。血清miRNA-101表达水平与空腹血糖（fasting plasma glucose,FPG）和糖化血红蛋白A1c（glycosylated hemoglobin A1c,HbA1c）呈正相关（P<0.05）。在校正性别、年龄、体质量后,多元逐步回归分析表明miRNA-101水平与HbA1c呈显著正相关（P<0.05）。结论:初诊T2DM患者血清miRNA-101表达水平增高,可能与HbA1c升高有关。     

点火控制器L497在汽油辛烷值测定机中的应用

L497是一种霍尔信号触发的高性能点火控制器,它广泛应用于汽车的点火系。分析了L497在低转速发动机下存在的两大问题:功耗大;闭合角控制的不稳定性。提出通过改变L497集成块的外围电路和外围元件参数解决了上述问题,并将它很好地应用于汽油辛烷值测定机的点火系。