Highly Diastereoselective Synthesis of a HCV NS5B Nucleoside Polymerase Inhibitor.

An asymmetric synthesis of HCV NS5B nucleoside polymerase inhibitor (1) is described. This novel route features several remarkably diastereoselective and high-yielding transformations, including construction of the all-carbon quaternary stereogenic center at C-2 via a thermodynamic aldol reaction. A subsequent glycosylation reaction with activated uracil via C-1 phosphate and installation of the cyclic phosphate group using an achiral phosphorus(III) reagent followed by oxidation provides 1.

Leaching kinetics of cobalt from the scraps of spent aerospace magnetic materials.

Based on physicochemical properties of the scraps of spent aerospace magnetic materials, a roasting - magnetic separation followed by sulfuric acid leaching process was proposed to extract cobalt. Roasting was performed at 500 °C to remove organic impurity. Non-magnetic impurities were reduced by magnetic separation and then the raw material was sieved into desired particle sizes. Acid leaching was carried out to extract cobalt from the scraps and experimental parameters included agitation speed, particle size, initial concentration of sulfuric acid and temperature. Agitation speed higher than 300 r/min had a relatively small impact on the cobalt extraction. As the particle size reduced, the content of cobalt in the raw material decreases and the extraction of cobalt by acid leaching increased at first and decreased afterwards. Raising the initial concentration of sulfuric acid and temperature contributed to improve the cobalt extraction and the influence of temperature was more remarkable. SEM image revealed that the spent aerospace magnetic materials mainly existed in the sliced strip flake with a loose surface and porous structure. Under the experimental condition, the leaching rate of cobalt from the scraps in sulfuric acid solution could be expressed as ln(-ln(1 - α)) = lnk + nlnt. The apparent activation energy was found to be 38.33 kJ/mol and it was mainly controlled by the surface chemical reaction.

GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activation of ERK1/2.

Estrogen receptors, including classic nuclear receptors ERα, ERß, and membrane receptor GPR30, are expressed in vascular tissues and exert protective actions in vascular diseases. But the expression pattern and functional roles of GPR30 in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we found that ERα, ERß, and GPR30 were decreased with VSMCs passaging in vitro or growing in vivo and activation of GPR30 promoted ERα expression. Then, we validated that activation of GPR30 significantly decreased migratory capability of VSMCs and suppressed ERα, whereas PDGF-BB (20 ng/mL) treatment caused increase of migration. And activation of GPR30 led to reduction of osteopontin and cellular retinol binding protein 1, enhancement of calponin and 3F8, and upregulation of total and phosphorylated ERK1/2 expression in VSMCs knocked down by GPR30, ERα, and ERß or treated with PDGF-BB. These data suggest that GPR30 promotes VSMCs reducing migration and maintaining differentiated phenotype via activation of ERK1/2 pathway. Our findings provide novel mechanisms of GPR30 protection of VSMCs as well as a new target for prevention of vascular aging.

EGCG attenuates atherosclerosis through the Jagged-1/Notch pathway.

Atherosclerosis is the most common cause of cardiovascular diseases worldwide. Oxidized low-density lipoprotein (ox-LDL) is a particularly important risk factor in the pathogenesis of atherosclerosis. Accumulating evidence has indicated that epigallocatechin-3-gallate (EGCG; a catechin found in the popular beverage, greent tea) protects against ox-LDL-induced atherosclerosis. However, the underlying mechanisms remain unclear. In the present study, ox-LDL (100 mg/l) induced damage to, and the apoptosis of human umbilical vein endothelial cells (HUVECs) by reducing endothelial nitric oxide synthase (eNOS) expression and promoting inducible nitric oxide synthase (iNOS) expression; these effects were abrogated by the addition of 50 µM EGCG. Furthermore, ox-LDL rapidly activated the membrane translocation of p22phox, and altered the protein expression of Jagged-1 and Notch pathway-related proteins [Math1, hairy and enhancer of split (HES)1 and HES5]; these effects were also prevented by pre-treatment with 50 µM EGCG. In addition, Jagged-1 played a significant role in the EGCG-mediated protection against ox-LDL-induced apoptosis and ox-LDL­diminished cell adhesion in the HUVECs. Finally, EGCG inhibited high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E (ApoE) knockout (ApoE-KO) mice through the Jagged-1/Notch pathway. Taken together, these findings demonstrate that 50 µM EGCG protects against ox-LDL-induced endothelial dysfunction through the Jagged-1/Notch signaling pathway. Moreover, our data provide insight into the possible molecular mechanisms through which EGCG attenuates ox-LDL­induced vascular endothelial dysfunction.

[Correlation of CKP and VEGF expression and microvessel density to spiral CT manifestations of thymoma].

OBJECTIVE: To investigate the correlation of cytokeratin pan (CKP), vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) to spiral CT manifestations of thymoma. METHODS: Eighty-four thymoma patients were underwent spiral CT examination, and 40 of the patients also had enhanced CT examination. All the CT findings were carefully reviewed to analyze their correlation to the expressions of CKP, VEGF and MVD. RESULTS: The enhancement on spiral CT images increased with the levels of VEGF expression and MVD counting (P<0.01). Significant correlations were observed between VEGF expression, MVD counting and such spiral CT findings as lobular contours, cusp-like or sawtooth-like margins and tumor invasions of the pleural membrane, pericardium and great vessels (P<0.05). CKP expression showed no obvious correlation to these findings by spiral CT. CONCLUSION: Spiral CT can reflect the pathological characteristics of thymoma, and may serve as a noninvasive modality for preoperative evaluation of thymoma.