An eicosanoid-centric view of atherothrombotic risk factors

Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world. Atherosclerosis followed by thrombosis (atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events. Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and proteins directly involved in these processes, traditional cardiovascular risk factors (hyperlipidemia, hypertension, smoking, diabetes mellitus, sex, and age) remain the most useful predictor of disease. Eicosanoids (20 carbon polyunsaturated fatty acid derivatives of arachidonic acid and other essential fatty acids) are emerging as important regulators of cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing eicosanoid signaling, have contributed to the lack of therapies directed at the eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between eicosanoids and cardiovascular risk factors.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.     

海子抒情诗中“秋”意象解析

海子诗歌意象丰富，意蕴深厚，极具艺术张力，例如“秋”意象。本文从三方面论述海子抒情诗中“秋”意象。首先，“秋”象征丰收而荒凉的人世；其次，论述“秋”的感伤；最后，“秋”是幻象丛生的国度。     

浅析电力变压器的事故处理

电力变压器是电力系统中很重要的设备,一旦发生事故,将造成很大的经济损失.分析各种电力变压器事故,找出原因,总结出处理事故的办法,把事故损失控制在最小范围内,尽量减少对系统的损害.     

Comparison study of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin microspheres

To compare two microspheres of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin loaded theophylline as pulmonary sustained drug delivery carriers, the characteristics and ciliotoxicity were studied. The drug loadings of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin microspheres were 21.09% and 21.42%, and the encapsulation efficiencies were 91.40% and 92.80%. The distributions of 50% (d _0.5) of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin microspheres were 4.89 and 5.83 μm, respectively. Both microspheres showed spherical shape with smooth or wrinkled surfaces. FT-IR of chitosan/β-cyclodextrin microspheres demonstrated that theophylline had formed hydrogen bonds with chitosan and β-cyclodextrin, while for the carboxymethyl chitosan/β-cyclodextrin microspheres theophylline had interaction with carboxymethyl chitosan. The moisture absorption showed that an equilibrium was reached within 24 h. The two microspheres possessed better adaptability. In vitro release of theophylline from chitosan/β-cyclodextrin microspheres was slower than that from carboxymethyl chitosan/β-cyclodextrin microspheres at pH 6.8. Biography: LI Ruobao(1968–), male, Associate professor, research direction: foundation research of respiratory system.     

Inferring requirement goals from model implemented in UML

UML is used widely in many software development processes. However, it does not make explicit requirement goals. Here is a method tending to establish the semantic relationship between requirements goals and UML models. Before the method is introduced, some relevant concepts are described.     

浅析电力变压器的事故处理

电力变压器是电力系统中很重要的设备,一旦发生事故,将造成很大的经济损失。分析各种电力变压器事故,找出原因,总结出处理事故的办法,把事故损失控制在最小范围内,尽量减少对系统的损害。     

TiC掺杂对MCMB烧结体组织和性能的影响

以Tween 80为分散剂,分别以丙烯酰胺和N,N'-亚甲基双丙烯酰胺为单体和交联剂,采用凝胶注模工艺制备中间相碳微球(mesocarbon microbead,MCMB)片状素坯,再经过1 600 ℃的烧结,制备MCMB素坯烧结体试样.试验研究了粒度大小对粉体分散性、MCMB碳材料催化石墨化效果、烧结后MCMB碳材料层板物理性能的影响,并分析了产生这些影响的原因.研究结果表明:50 nm的TiC在MCMB烧结体中的分散效果好于15 μm的TiC;随着Ti质量分数的增加,掺杂50 nm 的TiC层板性能优于掺杂15 μm的层板;50 nm的TiC比15 μm的TiC更适合做MCMB的掺杂物.     

汉代西北疆域的经济开发

西北边疆问题是研究汉代疆域史的一个重要问题,西北边疆的开发,促进了民族的融合和地区的发展.本文着力于从汉代对西北连续经济开发的主要工程、经济开发的意义及影响两个方面进行论述,从而为当今西部大开发提供一些历史借鉴.