Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene Bmal1 inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion in vitro, and tumor growth in mouse xenograft models of TSCC. After exposure to paclitaxel, Bmal1-overexpressing cells displayed a relative increase in apoptosis and were more susceptible to paclitaxel treatment in vivo Mechanistic investigations suggested a regulatory connection between Bmal1, TERT, and the oncogenic transcriptional repressor EZH2 (enhancer of zeste homolog 2), the recruitment of which to the TERT promoter increased paclitaxel-induced apoptosis and cell growth inhibition. Clinically, paclitaxel efficacy correlated positively with Bmal1 expression levels in TSCC. Overall, our results identified Bmal1 as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in TSCC. Cancer Res; 77(2); 532-44. ©2016 AACR.

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Ni-Co-Y2O3 composite coating was prepared by electrodeposition from an electroplating bath containing a suspension of Y2O3. The morphology and microstructure in view of their possible application as electrocatalytic materials for the hydrogen evolution reaction were characterized by SEM and XRD, respectively. The electrocatalytic efficiency was evaluated on the basis of steady-state polarization, Tafel curves and electrochemical impedance spectroscopy measurements carried out in 0.50 M Na2SO4 + 0.10 M H2SO4 solution. It was found that hydrogen evolution reaction proceeded better in the presence of Y2O3. The hydrogen evolution potential of Ni-Co-Y2O3 composite electrode moved positively about 100 mV at 13 mA cm-2 compared with that of Ni-Co alloy electrode.

The interaction of methyl caffeate with herring sperm DNA was investigated by cyclic voltammetry, differential pulse voltammetry and ultraviolet absorption spectrometry. Methyl caffeate had a well-defined electrochemical signal in 0.50 M acetate buffer (pH 4.6) involving two electrons and two protons. The binding of methyl caffeate to herring sperm DNA resulted in a series of changes in the electrochemical behavior, giving a considerable decrease in the peak currents and a negative shifts in the peak potential of methyl caffeate, suggesting the interaction of methyl caffeate and herring sperm DNA by an electrostatic mode. Furthermore, the data from the electrochemical investigation showed that a non-electroactive supramolecular compound was formed between methyl caffeate and herring sperm DNA. The conclusion was reinforced by ultraviolet absorption spectrometry.

<div>Abstract<p>Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene <i>Bmal1</i> inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion <i>in vitro</i>, and tumor growth in mouse xenograft models of TSCC. After exposure to paclitaxel, Bmal1-overexpressing cells displayed a relative increase in apoptosis and were more susceptible to paclitaxel treatment <i>in vivo</i>. Mechanistic investigations suggested a regulatory connection between Bmal1, TERT, and the oncogenic transcriptional repressor EZH2 (enhancer of zeste homolog 2), the recruitment of which to the <i>TERT</i> promoter increased paclitaxel-induced apoptosis and cell growth inhibition. Clinically, paclitaxel efficacy correlated positively with Bmal1 expression levels in TSCC. Overall, our results identified <i>Bmal1</i> as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in TSCC. <i>Cancer Res; 77(2); 532–44. ©2016 AACR</i>.</p></div>

La 2 O 3 was successfully doped into nickel-cobalt alloy coating on Ti substrate by electrodeposition technology.The surface morphology and microstructure were examined by SEM and XRD, respectively, and the hydrogen evolution property was evaluated by electrochemical techniques, including steady-state polarization, Tafel plot and electrochemical impedance spectroscopy. It was found that the incorporated La 2 O 3 particles resulted in the improvement of roughness and surface area of the composite coating electrode, and hydrogen evolution potential of nickelcobalt-La 2 O 3 composite coating electrode moved positively around 178 mV at 15 mA cm -2 compared with that of nickel-cobalt alloy deposited coating electrode. It was assumed that the enhanced electrocatalytic activity to hydrogen evolution was attributed to the improved surface area and the decreased apparent activation energy, which was verified by hydrogen evolution kinetics parameters calculated from Tafel plots and electrochemical impedance spectroscopy.

<p>Supplementary Material and Methods</p>

<p>The clinical characteristics subjects in patient tissue samples</p>