Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference

AbstractThe severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV

Red Wine Polyphenols for Cancer Prevention

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin

Drift-off warning limits for deepwater drilling platform/riser coupling system

The drift-off dynamic model of deepwater drilling platform and riser coupling system was established. An analysis method on drift-off warning limits of deepwater drilling platform and riser coupling system was proposed, and a deepwater drilling platform/riser system was taken for case study. The analysis model of deepwater riser, wellhead and conductor coupling system and the drift-off dynamic model of platform were established respectively. The drift-off dynamic solver of deepwater platform was developed. The coupling dynamic characteristics and coupling effect of the deepwater drilling platform and riser system were analyzed in combination with example, and the analysis method for drift-off warning limits was described. The results show that: the riser load acting on platform plays a driving role in the platform drift-off in the initial drift-off stage, and begins to inhibit the platform drift-off gradually as the drift-off displacement increases; During the platform drift-off, the transient response speed of upper riser parameters is high, while the transient response of lower riser parameters presents an obvious hysteresis effect; As the current speed increases or water depth decreases, the drift-off warning limits of deepwater drilling platform/riser coupling system decrease and the deepwater drilling riser should be disconnected earlier. Key words: deepwater drilling, drilling platform, riser, drift-off dynamic model, drift-off warning limit

Imine Resveratrol Analogues: Molecular Design, Nrf2 Activation and SAR Analysis

<div><p>Resveratrol is a natural phenol with protective effects against cancer and inflammation-related diseases. Its mechanism of action involves the activation of nuclear factor E2 p45-related factor 2 (Nrf2), which plays a key role in regulation of genes driven by antioxidant response element (ARE). Inspired by the effect of resveratrol, here we synthesized a series of imine resveratrol analogs (IRAs), evaluated their abilities to activate Nrf2 by using cell based ARE-reporter assay. After the first-round screening, preliminary and quantitative structure-activity relationship (SAR) was analyzed, and the structural features determining Nrf2 activation ability were proposed. Two novel IRAs were designed and subsequently synthesized, namely 2-methoxyl-3,6-dihydroxyl-IRA and 2,3,6-trihydroxyl-IRA. They were proved to be the most potent Nrf2 activators among the IRAs.</p></div

Envelopes for connected operation of the deepwater drilling riser

The common critical criterion and nonlinear search method were adopted for the study of connected operation envelopes of deepwater drilling riser and a riser-wellhead-conductor integral finite element model was established. The combination parameters of drilling platform offset, current speed and slip joint stroke were used to determine the riser operability envelopes. The results show that the drilling envelope has an upconing shape and is limited by lower flex joint angle when the surface current speed is low (less than 1.0 m/s). In downstream direction, when the current speed increases, the rotation angle of the lower flex joint increases and the allowable maximum offset of the platform reduces, but in upstream direction, the conditions will be opposite. When surface current speed exceeds 1.0 m/s, the drilling envelope is limited by upper flex joint angle. When it is in upstream direction, the increase of current flow will increase the rotor angle of the upper flexible joint and reduce the drilling envelope rapidly. The non-drilling envelope and emergency disconnect sequence (EDS) actuation envelope are mainly subject to the maximal equivalent stress of the conductor and they will drift towards the upstream direction with the increase of current speed. In addition, through the analysis on influence factors of connection window operation of riser, the tensile force at the top could be increased and drilling fluid density could be reduced properly, so that the drilling envelope could be expanded. Key words: deepwater drilling, riser, drilling envelope, non-drilling envelope, EDS actuation envelop

Analyses and countermeasures of deepwater drilling riser grounding accidents under typhoon conditions

For deepwater drilling riser system facing grounding risk in the South China Sea, a mechanical analysis model of deepwater drilling riser grounding accident was established. Focusing on drilling riser grounding accidents of a deepwater floating drilling platform in the South China Sea, mechanical characteristics and grounding accidents of riser were analyzed. And the riser retrieving window was determined. The results showed that the shape of the riser system after riser grounding is catenary. The maximums of bending moment and von Mises stress are located at lower flex joint. Platform moon pool, tensioner and lower flex joint are damaged due to severe bending deformation in the upper and lower drilling riser system after riser grounding accidents. The riser may fracture if drilling platform continues to move toward shallow water. Drilling platform displacement and riser lift height must be within the riser operation window during riser retrieving, or else the riser may fracture and the LMRP may suffer further damage. Residual riser and LMRP can be retrieved in a fixed position when the drilling riser system is separated from seabed. Key words: typhoon, deepwater, drilling, riser, grounding accident, accident analysi

SAR results from initial screening of IRAs.

<p>SAR results from initial screening of IRAs.</p

Structures (A) and ARE-luciferase activities (B) of 33, 34 and resveratrol.

<p>ARE reporter cells were exposed to <b>33</b>, <b>34</b> and resveratrol (7.5 µM, 15 µM and 30 µM) for 24 h. The value for cells treated with vehicle DMSO (0.1% v/v) was set at 1. Results are from three separate experiments. Values shown are mean ± SD.</p