Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy

Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient’s selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.     

An Autophagy-Disrupting Small Molecule Promotes Cancer Cell Death via Caspase Activation

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.     

NUMERICAL ANALYSES OF DESIGN AND ASSEMBLY FOR MAIN COMPONENTS OF BESIII

The design and manufacture of the main drift chamber(MDC) and the electro-magnetic calorimeter are most important issues in Beijing electron-positron collider upgraded projects. The whole mass of electro-magnetic calorimeter (EMC) in BESIII is 40t, thus high stiffness, strength and dynamical properties are required for the design of entire structural of electro-magnetic calorimeter. Based on numerical technique, the strength and the dynamical properties of EMC are analyzed, which provide theoretical reference for the design of entire structural of EMC. The MDC is composed of the elements with 28680 pre-stressed high-sensitive wires and during the assembly the wires are stringed layer by layer. The stretching forces of the wires vary continuously and couple with each other in the whole process. The modeling technique with high precision (especially "element birth and death") is carefully used to study the stress state during the process of assembly. So the variations of the stretching force of the wire are investigated, and several design schemes are evaluated and optimized. The research results have been adopted in the Beijing electron-positron collider's new project directly.     

Alisertib Induces Cell Cycle Arrest,Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G₂/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5′ AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.     

杂化纠缠系统的纠缠猝死研究

研究了一类杂化纠缠态在两种不同类型退相干信道下的纠缠动力学行为,以及退相干过程中出现的纠缠猝死现象.计算了相位阻尼信道和退极化信道下的纠缠度,并分析了纠缠度随时间的变化.结果表明在相位阻尼信道下不会出现纠缠猝死现象;在退极化信道下杂化纠缠态会经历纠缠猝死,纠缠度在某一特定的时间内衰减为零.     

稀疏颗粒增强镍基复合材料的应力场及损伤分析

陶瓷颗粒增强镍基合金复合材料是一种性能优良的复合材料,它能够将增强相和基体的性能相结合。应用细观力学和有限元理论将复合材料简化为含两个陶瓷颗粒的单胞,对材料单向拉伸下的应力场进行模拟,分析其应力的分布情况和复合材料的性能特征。结果表明,单胞中的应力是不均匀的,高刚度颗粒的界面附近应力最大并将首先破坏。最后利用单元消去技术模拟材料开裂情况下的应力场变化及裂纹扩展路径。研究对于理论分析和实验具有一定的参考和指导作用。     

Fantasies of women confronting death.

These 2 studies explore the unconscious significance of death. 5 psychoanalytically oriented theories are discussed and used as the basis for scoring fantasy material. In the first study, 25 cancer patients and matched controls hospitalized for minor illnesses were given the TAT. Major findings for the dying patients point to (a) no increase in the use of denial, (b) an increase in themes of punishment, and (c) a rise in fantasies of illicit sexuality. The possibility is raised that death itself is sexualized and that this sexualization may at times increase, at other times decrease, death anxiety. In the second study, 25 women with a variety of serious illnesses and their controls were given selected TAT cards and new pictures. Results generally supported the prior findings. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

γ射线诱发细胞程序性死亡的时间及剂量效应研究

通过对辐射所致程序性细胞死亡（ＰＣＤ）的研究，揭示了射线诱发小鼠胸腺细胞ＰＣＤ生成的时间及剂量效应规律，采用不同的检测ＰＣＤ方法（ＤＮＡ片段分析法及流式细胞术），比较了不同组织的辐射敏感性差异，结果表明，照射后４～６ｈ诱发胸腺细胞ＰＣＤ生成最多。不同剂量照射，照后６ｈ取胸腺，发现２０Ｇｙ时胸腺细胞ＰＣＤ生成最多，脾，胸腺对辐射影响，小剂量（１Ｇｙ）即可检测ＰＣＤ形成；而心脏，大脑，肾对射线不敏感，