The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders.     

轮胎胶应力诱导脱硫化及PE-HD动态交联热塑性弹性体制备

采用在废旧轮胎胶粉(GTR)与高密度聚乙烯(PE-HD)的熔融挤出过程中提高双螺杆挤出机螺杆转速的高剪切应力诱导方法,研究了双螺杆挤出机的螺杆转速、挤出反应温度及脱硫促进剂仲丁醇、烷基酚多硫化物(420或450)和正丁胺对轮胎胶脱硫共混物的凝胶含量、熔体流动速率、溶胶红外吸收光谱及轮胎胶脱硫共混物/三元乙丙橡胶(EPDM)动态交联热塑性弹性体力学性能的影响。结果表明:高转速同向双螺杆挤出机的高剪切作用可诱发废旧轮胎胶共混物中交联网络的断链和解交联反应,引起脱硫共混物凝胶含量的下降、未熔融凝胶颗粒尺寸的减小及熔体流动速率的增加;4种促进剂均具有明显促进脱硫反应的作用,其中450或正丁胺的促进脱硫效果较好,并引起脱硫共混物凝胶含量下降、熔体流动速率上升及动态交联热塑性弹性体力学性能的明显改善;当以正丁胺为脱硫促进剂时,最佳脱硫反应条件(240℃和1000r/min)下,脱硫共混物/EPDM动态交联热塑性弹性体的拉伸强度和断裂伸长率分别达到12.5MPa和440.6%。     

应变速率对Fe-Mn-Si-Cr-Ni合金组织和力学性能的影响

目前的TRIP钢由于Mn、Si含量较低,室温条件下仅保留约10%的残余奥氏体,结果使变形过程中材料产生的相变诱发塑性量有限,不能满足一些要求产生更大相变诱发塑性场合的需要。研究表明：提高钢中Mn、Si含量并辅以适量其它合金元素（如铬和镍）是提高材料相变诱发塑性的有效途径。研究了Fe-17Mn-5Si-10Cr-4Ni合...     

Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction

Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16^INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.     

涤纶HOY结构形成的计算机模拟

在基本纺丝动力学方程的基础上,引入显著的应力诱导结晶作用,运用改进的Euler方法和牛顿二分法,通过计算机求解动力学方程组,模拟涤纶HOY结构的形成过程,获得了纤维结构形成与卷绕速度、质量流量和侧吹风温度的关系。结果表明,增大卷绕速度或减小质量流量,有利于增大纤维的结晶度及双折射,侧吹风温度降低使结晶位置移向喷丝孔方向。计算机模拟的结果与相关文献给出的实验结果吻合良好。     

压痕过程中非晶Cu形变诱导晶化行为的原子模拟

采用Mishin镶嵌原子势,通过分子动力学方法模拟了非晶Cu在压痕作用下的形变诱导晶化行为,考察了压痕过程中能量、应力与微观结构演化的关系.局部塑性变形区域出现微小晶核,随着变形的增加,晶核不断生长与合并,局部塑性变形是导致非晶晶化的根本原因最终生成的晶粒具有面心立方结构,其(111)密排面平行于剪切面.非晶相中的纳米晶粒能提高非晶材料的刚度.     

Fe-17Mn-10Cr-5Si-4Ni合金低温应力诱发相变特点及其形状记忆效应研究

用x射线衍射分析、显微组织观察等研究了Fe-17Mn-10Cr-5Si-4Ni合金在低温(低于室温)下应力诱发相变的特点及其形状记忆效应。合金在室温拉伸变形时,当应变量超过5％由于应力诱发E马氏体的相变作用而形成α＇马氏体;当变形温度低于室温时应力优先诱发γ→α＇马氏体转变。正是这种应力诱发相变特征的转变使合金的形状记忆效应在室温以下出现奇特低谷。     

Exogenous dsRNA Induces RNA Interference of a Chalcone Synthase Gene in Arabidopsis thaliana

Recent investigations have shown the possibility of artificial induction of RNA interference (RNAi) via plant foliar treatments with naked double-stranded RNA (dsRNA) to silence essential genes in plant fungal pathogens or to target viral RNAs. Furthermore, several studies have documented the downregulation of plant endogenous genes via external application of naked gene-specific dsRNAs and siRNAs to the plant surfaces. However, there are limited studies on the dsRNA processing and gene silencing mechanisms after external dsRNA application. Such studies would assist in the development of innovative tools for crop improvement and plant functional studies. In this study, we used exogenous gene-specific dsRNA to downregulate the gene of chalcone synthase (CHS), the key enzyme in the flavonoid/anthocyanin biosynthesis pathway, in Arabidopsis. The nonspecific NPTII-dsRNA encoding the nonrelated neomycin phosphotransferase II bacterial gene was used to treat plants in order to verify that any observed effects and processing of AtCHS mRNA were sequence specific. Using high-throughput small RNA (sRNA) sequencing, we obtained six sRNA-seq libraries for plants treated with water, AtCHS-dsRNA, or NPTII-dsRNA. After plant foliar treatments, we detected the emergence of a large number of AtCHS- and NPTII-encoding sRNAs, while there were no such sRNAs after control water treatment. Thus, the exogenous AtCHS-dsRNAs were processed into siRNAs and induced RNAi-mediated AtCHS gene silencing. The analysis showed that gene-specific sRNAs mapped to the AtCHS and NPTII genes unevenly with peak read counts at particular positions, involving primarily the sense strand, and documented a gradual decrease in read counts from 17-nt to 30-nt sRNAs. Results of the present study highlight a significant potential of exogenous dsRNAs as a promising strategy to induce RNAi-based downregulation of plant gene targets for plant management and gene functional studies.     

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.