One of the major causes of chemotherapy failure in cancer treatment is multidrug resistance (MDR) which is mediated by the ABCB1/P-glycoprotein. Previously, through the use of an extensive screening process, we found that vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor significantly reverses MDR in ABCB1 overexpressing cancer cells, and its efficacy was greater than that of tadalafil, another PDE-5 inhibitor. The present study was designed to determine the reversal mechanisms of vardenafil and tadalafil on ABC transporters-mediated MDR. Vardenafil or tadalafil alone, at concentrations up to 20 µM, had no significant toxic effects on any of the cell lines used in this study, regardless of their membrane transporter status. However, vardenafil when used in combination with anticancer substrates of ABCB1, significantly potentiated their cytotoxicity in ABCB1 overexpressing cells in a concentration-dependent manner, and this effect was greater than that of tadalafil. The sensitivity of the parenteral cell lines to cytotoxic anticancer drugs was not significantly altered by vardenafil. The differential effects of vardenafil and tadalafil appear to be specific for the ABCB1 transporter as both vardenafil and tadalafil had no significant effect on the reversal of drug resistance conferred by ABCC1 (MRP1) and ABCG2 (BCRP) transporters. Vardenafil significantly increased the intracellular accumulation of [3H]-paclitaxel in the ABCB1 overexpressing KB-C2 cells. In addition, vardenafil significantly stimulated the ATPase activity of ABCB1 and inhibited the photolabeling of ABCB1 with [125I]-IAAP. Furthermore, Western blot analysis indicated the incubation of cells with either vardenafil or tadalafil for 72 h did not alter ABCB1 protein expression. Overall, our results suggest that vardenafil reverses ABCB1-mediated MDR by directly blocking the drug efflux function of ABCB1.
The air bearing motorized spindle (ABMS) is the key component of the ultra-precision machine tool, which plays an important role in the ultra-precision machining process and directly influences machining accuracy. The influence of unbalanced magnetic force (UMF) on the nonlinear dynamic behavior of the ABMS is not understood clearly. To reveal the potential influence of the UMF, a mathematical model of the ABMS considering multiphysics fields is established. The variation trend of the UMF is simulated, and the nonlinear dynamic behavior of the ABMS is analyzed which emphasizes on the stability of the rotating shaft. It is shown that the UMF varies linearly at large rotor eccentricity which meets well with previous research, but it is noteworthy the UMF varies nearly to a quadratic function at small rotor eccentricity. The result of rotor dynamics shows that the UMF can change the converge position of the rotor center and the converge speed. Moreover, when at certain rotor mass and external load, the UMF can enlarge the stability boundary of the rotor. This research provides an example of analyzing the nonlinear dynamic behavior of the ABMS considering multiphysics fields which may help to the further investigation.
To obviate the use of radioactive materials, a simple unipolar electrical neutralizer based on a corona discharge was developed to neutralize electrospray aerosols used when coupling capillary liquid chromatography (CLC) and capillary electrophoresis (CE) to condensation nucleation light-scattering detection (CNLSD). The electrical neutralizer could be operated with either a positive or negative corona to generate ions to neutralize oppositely charged aerosols generated by electrospray and allow sensitive detection with CNLSD. The device could further be operated with organic solvents as well as aqueous buffer. The parameters affecting the corona discharge and neutralization process were studied and optimized. Compared to a CNLSD system using a radioactive neutralizer, the system with the electrical neutralizer showed higher signal and signal-to-noise ratio for test compounds, which indicated better neutralization efficiency of the charged aerosol. Highly reproducible results were obtained with the robust and durable electrical neutralizer with both CLC- and CE-electrospray-CNLSD systems.
CVD synthetic diamond plays an important role in the jewelry market due to its excellent performance and low cost. In this paper, colorless CVD synthetic diamonds produced by a Chinese company were investigated in detail with their gemological, spectroscopic, and luminescent properties compared with natural colorless diamonds. Compared with natural diamonds, CVD synthetic diamonds have high-order interference color and more apparent abnormal birefringence. The results of infrared spectra indicate that all the CVD samples are classified as type IIa, while the natural samples belong to type Ia. The CVD samples show lamellar growth and mottled luminescence pattern and have blue, orange red, purple red, and blue fluorescence, respectively, while most of the natural samples show blue fluorescence. CVD diamonds show lamellar growth structure, and natural diamonds show irregular ring-like growth structure. Thus, multiple methods combined with analysis are required to distinguish synthetic diamonds from natural diamonds. This work provides an experimental basis for the identification of CVD synthetic diamonds.
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