FeNi (oxy)hydroxides embedded with high-valence Mo atoms: A efficient and robust water oxidation electrocatalyst.

The incorporation of high-valence transition metal atoms into FeNi (oxy)hydroxides may be a promising strategy to regulate the intrinsic electronic states, thereby reducing the thermodynamic barrier and accelerating oxygen evolution reaction (OER). Here, a high-valence Mo atoms doping route is proposed by an efficient self-reconstruction strategy to prepare MoFeNi (oxy)hydroxides for efficient alkaline OER. By using borides (MoNiB) as sacrificial template and Mo source, FeNi (oxy)hydroxides nanoflakes embedded with high-valence Mo atoms (MoFeNi) is successfully synthesized, which can modulate the electron coordination to improve the intrinsic catalytic activity. Remarkably, the obtained MoFeNi exhibits extremely low overpotential (η100 = 252 mV and η500 = 288 mV) and small Tafel slope (18.35 mV dec-1). The robust catalyst can run stably for hours at 500 mA cm-2. Characterization results and theoretical calculations confirmed that the addition of high-valence Mo effectively modulated the intrinsic electronic structure of metal sites and optimized the adsorption/desorption energy of the intermediates, accelerating OER reactions kinetics. By coupling MoFeNi anode with Pt/C cathode, anion exchange membrane (AEM) electrolyser can operate stably at 500 mA cm-2 with about less than 2.2 V. This research introduces a novel approach to develop ideal electrocatalysts through the incorporation of high-valence molybdenum species.

Bimetallic metal-organic framework-derived bamboo-like N-doped carbon nanotube-encapsulated Ni-doped MoC nanoparticles for water oxidation.

Molybdenum carbide materials with unique electronic structures have received special attention as water-splitting catalysts, but their structural stability in the alkaline water electrolysis process is not satisfactory. This study reports an in situ pyrolysis method for preparing NiMo-based metal-organic framework (MOF)-derived chain-mail oxygen evolution reaction (OER) electrocatalysts and bamboo-like N-doped carbon nanotube (NCNT)-encapsulated Ni-doped MoC nanoparticles (NiMoC-NCNTs). The NCNTs can provide chain mail shells to protect the inner highly reactive Ni-doped MoC cores from electrochemical corrosion by the alkaline electrolyte and regulate their catalytic properties through charge redistribution. Benefiting from high N-doping with abundant pyridinic moieties and abundant active sites of the periodic bamboo-like nodes, the as-prepared NiMoC-NCNTs display an outstanding activity for the OER with an overpotential of 310 mV at 10 mA cm-2 and a superior long-term stability of 50 h. Density functional theory calculations reveal that the excellent electrocatalytic activity of NiMoC-NCNTs comes from the electron transfer from NiMoC nanoparticles to NCNTs, resulting in a decrease in the local work function at the carbon surface and optimized free efficiencies of OER intermediates on C sites. This work provides an effective approach to improve the structural stability of fragile catalysts by equipping them with carbon-based chain.

Optimized Electronic Modification of S-Doped CuO Induced by Oxidative Reconstruction for Coupling Glycerol Electrooxidation with Hydrogen Evolution.

Glycerol (electrochemical) oxidation reaction (GOR) producing organic small molecule acid and coupling with hydrogen evolution reaction is a critical aspect of ensuring balanced glycerol capacity and promoting hydrogen generation on a large scale. However, the development of highly efficient and selective non-noble metal-based GOR electrocatalysts is still a key problem. Here, an S-doped CuO nanorod array catalyst (S-CuO/CF) constructed by sulfur leaching and oxidative remodeling is used to drive GOR at low potentials: It requires potentials of only 1.23 and 1.33 V versus RHE to provide currents of 100 and 500 mA cm-2, respectively. Moreover, it shows satisfactory comprehensive performance (at 100 mA cm-2, Vcell = 1.37 V) when assembled as the anode in asymmetric coupled electrolytic cell. Furthermore, we propose a detailed cycle reaction pathway (in alkaline environment) of S-doped CuO surface promoting GOR to produce formic acid and glycolic acid. Among them, the C-C bond breaking and lattice oxygen deintercalation steps frequently involved in the reaction pathway are the key factors to determine the catalytic performance and product selectivity. This research provides valuable guidance for the development of transition metal-based electrocatalysts for GOR and valuable insights into the glycerol oxidation cycle reaction pathway.

HBsAg spontaneous seroclearance in a cohort of HBeAg-seronegative patients with chronic hepatitis B virus infection.

Loss of hepatitis B surface antigen (HBsAg) is considered to reflect the resolution of a hepatitis B virus (HBV) infection. Patient characteristics and various seromarkers were evaluated to characterize factors predicting spontaneous HBsAg loss in a cohort of HBeAg-seronegative patients with presumed chronic HBV infection. Relationships between seromarkers and HBsAg loss were assessed annually and after 6 years using binary logistic regression. Among the 634 participants, 117 (18.45%) cleared HBsAg after 6 years, with a 3.08% annual seroclearance rate. Baseline HBsAg levels and platelet (PLT) counts were predictors of HBsAg seroclearance. The HBsAg level predicted HBsAg seroclearance better than the PLT count (area under the receiver operating characteristic curve (AUROC): HBsAg, 0.965 (95%CI, 0.947-0.980) versus PLT count, 0.617 (95%CI, 0.561-0.669); P < 0.001). A cutoff HBsAg level of 10 IU/ml at baseline predicted spontaneous HBsAg seroclearance at 6 years with a diagnostic accuracy of 93.4%, a sensitivity of 87.2%, a specificity of 94.8%, a positive predictive value of 79.1%, and a negative predictive value of 97.0%. HBsAg seroclearance may occur more commonly than expected. A serum HBsAg level <10 IU/ml and PLT count were accurate predictors of clearance.

Glucocorticoid Receptor ß Acts as a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation.

We previously reported that glucocorticoid receptor ß (GRß) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ß-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GRß and ß-catenin/TCF in the progression of glioma. Here, we reported that GRß knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GRß knockdown decreased TCF/LEF transcriptional activity without affecting ß-catenin/TCF complex. Both GRα and GRß directly interact with TCF-4, while only GRß is required for sustaining TCF/LEF activity under hormone-free condition. GRß bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GRß and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of ß-catenin stabilization. Taken together, these results suggest a novel cross-talk between GRß and TCF-4 which regulates Wnt signaling and the proliferation in gliomas.

[Study on the correlation of GCS and MDR1 genes in inducing multidrug resistance in human K562/A02 cell line].

OBJECTIVE: To investigate the correlation of glucosylceramide synthase (GCS) gene and multidrug resistance 1 (MDR1) gene in inducing multidrug resistance in human multidrug-resistant K562/A02 cell line, and search for a novel strategy for reversing multidrug resistance of leukemia cells. METHODS: The expression levels of GCS and MDR1 mRNA in K562 and K562/A02 cells were assayed by RT-PCR. siRNAs targeting the GCS and MDR1 gene were transfected into K562/A02 cells with liposome, respectively. The differential expression of GCS and MDR1 mRNAs, as well as their correlation, were detected by RT-PCR and real time quantitative-PCR(QPCR). RESULTS: The expression level of GCS and MDR1 mRNA was dramatically lower in drug-sensitive K562 cells compared with the K562/A02 cells. The GCS mRNA was inhibited by 73%(59%-82%) and MDR1 mRNA expression was down regulated by 67% (38%-82%) in K562/A02 cells after being transfected with GCS siRNA. The expression level of MDR1 mRNA was inhibited by 81%(63%-91%) and GCS mRNA expression had no apparent change in K562/A02 cells treated with MDR1 small interference RNA(siRNA). CONCLUSION: Positive correlation was detected between the expression of GCS and MDR1 mRNA in K562/A02 cells and MDR1 mRNA expression was down regulated after silencing the GCS gene expression.

GCS induces multidrug resistance by regulating apoptosis-related genes in K562/AO2 cell line.

We have previously shown that the expression of glucosylceramide synthase (GCS) gene in drug-resistant K562/AO2 human leukemia cell was higher than that in drug-sensitive K562 cell, and the sensitivity to adriamycin of K562/AO2 cell was enhanced by inhibiting GCS. It is concluded that the overexpression of GCS gene is one of the reasons which lead to multidrug resistance (MDR) of leukemia cell. Meanwhile, we also found that higher expression of Bcl-2 gene and protein were exhibited in K562/AO2 cell compared with K562 cell. Basing on this, we hypothesized that the high expression of GCS gene which results in MDR of leukemia cell is correlated with Bcl-2 signal transduction. In order to validate the hypothesis, the inhibition of GCS gene in K562/AO2 cell was observed by using chemical suppressor PPMP and siRNA targeted at GCS, and applying RT-PCR and flow cytometry, the expression levels of apoptosis-related gene Bcl-2 and Bax were analyzed before and after inhibiting GCS gene in K562/AO2 cell. The results demonstrated that the gene and protein of Bcl-2 in K562/AO2 cell were both down-regulated significantly after GCS gene being inhibited; however, the Bax mRNA expression had no apparent change in different groups. This suggested that GCS gene may contributed to MDR of human leukemia cell K562/AO2 by Bcl-2 signal transduction.

Overexpression of glucosylceramide synthase in associated with multidrug resistance of leukemia cells.

Ceramide, as a second messenger, initiates one of the major signal transduction pathways in tumor apoptosis. Glucosylceramide synthase (GCS) catalyzes glycosylation of ceramide and produces glucosylceramide. Through GCS, ceramide glycosylation allows cellular escape from ceramide-induced programmed cell death. Here we investigated the expression of GCS in human leukemia cells and an association between GCS and multidrug resistance of leukemia cells. Using RT-PCR technique the level of GCS gene was detected in 65 clinical multidrug resistance/non-resistance cases with leukemia, and in K562 and K562/A02 cell lines. AlamarBlue Assay was applied to confirm the multidrug resistant of K562/A02 cells. PPMP, which is a chemical inhibitor for GCS, was used to determine the relationship between GCS and drug-resistance in K562/A02 cells. In addition, multidrug resistance gene (mdr1), Bcl-2 and Bax mRNA was also analyzed by RT-PCR. The expression of GCS and mdr1 mRNA in clinic multidrug resistance samples exhibited significantly increased compared with clinic drug sensitive group (P<0.05). There was the positive correlation both the expression of GCS and mdr1 genes in leukemia samples (P<0.01, gamma=0.7). AlamarBlue Assay showed that the K562/A02 cell line was 115-fold more resistant to adriamycin and 36-fold more resistant to vincristine compared with drug-sensitive K562 cell line. There also was significant expression difference of GCS and mdr1 genes between K562 and K562/A02 cells. Bcl-2 gene exhibited higher expressions whatever in clinic drug-resistance samples or K562/A02 cells, whereas the expressions of Bax gene were higher in drug-sensitive samples and K562 cells. PPMP increased sensitivity to adriamycin toxicity by inhibiting GCS in K562/A02 cells. Therefore, it is suggested that a high level of GCS in leukemia is possible contributed to multidrug resistance of leukemia cells. Abnormally expressions of the genes in associated with cell apoptosis might be one of the main molecular pathology mechanisms of multidrug resistance caused by GCS gene.