Pulsed Current Electrodeposition of Silicon Thin Films Anodes for Lithium Ion Battery Applications

Electrodeposition of amorphous silicon thin films on Cu substrate from organic ionic electrolyte using pulsed electrodeposition conditions has been studied. Scanning electron microscopy analysis shows a drastic change in the morphology of these electrodeposited silicon thin films at different frequencies of 0, 500, 1000, and 5000 Hz studied due to the change in nucleation and the growth mechanisms. These electrodeposited films, when tested in a lithium ion battery configuration, showed improvement in stability and performance with an increase in pulse current frequency during deposition. XPS analysis showed variation in the content of Si and oxygen with the change in frequency of deposition and with the change in depth of these thin films. The presence of oxygen largely due to electrolyte decomposition during Si electrodeposition and the structural instability of these films during the first discharge–charge cycle are the primary reasons contributing to the first cycle irreversible (FIR) loss observed in the pulse electrodeposited Si–O–C thin films. Nevertheless, the silicon thin films electrodeposited at a pulse current frequency of 5000 Hz show a stable capacity of ~805 mAh·g−1 with a fade in capacity of ~0.056% capacity loss per cycle (a total loss of capacity ~246 mAh·g−1) at the end of 500 cycles

Inhibition of Endothelin-1-Mediated Contraction of Hepatic Stellate Cells by FXR Ligand

Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands

Coordinated Regulation of Dimethylarginine Dimethylaminohydrolase-1 and Cationic Amino Acid Transporter-1 by Farnesoid X Receptor in Mouse Liver and Kidney and Its Implication in the Control of Blood Levels of Asymmetric Dimethylarginine

Asymmetric dimethylarginine (ADMA) is a potent endogenous inhibitor of endothelial nitric-oxide synthase (eNOS), and increased plasma concentrations of ADMA have been regarded as a risk factor for a number of cardiovascular diseases. Circulating ADMA is largely taken up by liver and kidney via system y+ carriers of the cationic amino acid (CAT) family and subsequently metabolized by dimethylarginine dimethylaminohydrolases (DDAHs). As such, agents targeted at enhancing ADMA metabolism may prove to be useful in the prevention and/or treatment of various types of cardiovascular disease. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and plays an important role in the maintenance of cholesterol and bile acid homeostasis. We report here that treatment of mice with an FXR agonist 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole; GW4064) led to increased expression of DDAH-1 and CAT-1 in both liver and kidney. In cultured human hepatocytes and kidney proximal tubular epithelial cells, GW4064 increased CAT-1 expression, and this was associated with a significant increase in the cellular uptake of ADMA. Promoter analyses suggest that CAT-1 is a likely target of FXR, and a functional FXR response element was found in the promoter region of CAT-1 gene. These data suggest that FXR may play an important role in regulating blood levels of ADMA via coordinated regulation of DDAH-1 and CAT-1 in liver and kidney

Roles of microRNA-29a in the Antifibrotic Effect of Farnesoid X Receptor in Hepatic Stellate CellsS⃞

Liver fibrosis is a chronic disorder that is characterized by an alteration of the balance between fibrogenesis and fibrinolysis, which results in accumulation of excessive amounts of extracellular matrix (ECM) and distortion of the normal liver architecture. The activation and transformation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells constitute a major mechanism for the increased production of ECM in the liver. The nuclear receptor farnesoid X receptor (FXR) shows potent antifibrotic activity in HSCs and protects animals in rodent models of liver fibrosis. However, the detailed mechanism remains incompletely understood. In this study, we report that treatment with 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064), a synthetic FXR ligand, led to up-regulation of microRNA-29a (miR-29a) in HSCs isolated from wild-type mice, rats, and humans but not from FXR(−/−) mice. miR-29a seems to play an inhibitory role in the regulation of ECM production because of the following: 1) transfection of HSCs with miR-29a mimic resulted in drastic down-regulation of the mRNA expression of several genes that encode ECM proteins; and 2) miR-29a significantly inhibited the expression of a reporter expression plasmid that contains the 3′-untranslated region of the corresponding ECM genes. Our results suggest that miR-29a is a FXR target gene because miR-29a promoter activity was significantly increased by pharmacologic or genetic activation of FXR. Functional analysis of human miR-29a promoter identified an imperfect inverted repeat spaced by one nucleotide DNA motif, inverted repeat-1 (5′-AGGTCAcAGACCT-3′), as a likely FXR-responsive element that is involved in miR-29a regulation. Our study uncovers a new mechanism by which FXR negatively regulates the expression of ECM in HSCs

GW4064 treatment inhibited ET-1-induced Rho-kinase activity in activated HSCs.

<p>Activated HSCs were treated with DMSO or 1 µmol/L GW4064 for 18 hours. ET-1 (10 nM) was then added to the medium, and the cells were harvested 10 min later. Phosphorylation of meosin was detected by Western using appropriate phospho-specific antibody. An immunoblot of total meosin present in the cell extracts is shown as a loading control (lower panel). A representative immunoblot from three independent experiments is presented.</p

GW4064 treatment inhibited transdifferentiation of HSCs.

<p>Freshly isolated rat HSCs were cultured for 7 days in 10% FCS alone (control) or 10% FCS medium containing 1 µmol/L GW4064. The expression of α-SMA mRNA (A) and protein (B) was examined by real-time RT-PCR and immunofluorescence staining, respectively. Data are mean ±SE of 6 experiments. *<i>P</i><.001 vs. control cells.</p

GW4064 treatment inhibited ET-1-induced phosphorylation of MLC in activated HSCs.

<p>Activated HSCs were treated with DMSO or 1 µmol/L GW4064 for 18 hours. ET-1 (10 nM) was then added to the medium, and the cells were harvested 10 min later. Phosphorylation of MLC was detected by Western using appropriate phospho-specific antibody. An immunoblot of total MLC present in the cell extracts is shown as a loading control (lower panel). A representative immunoblot from three independent experiments is presented.</p

GW4064 treatment inhibited the upregulation of ET-1 expression during HSC activation.

<p>Freshly isolated rat HSCs were cultured for 7 days in 10% FCS alone (control) or 10% FCS medium containing 1 µmol/L GW4064. The mRNA expression levels of ET-1 (A), ETB (B) and ETA (C) were examined by real-time RT-PCR, respectively. Data are mean ±SE of 6 experiments. *<i>P</i><.001 vs. control cells.</p

GW4064 treatment of HSCs led to reduced contractile response to ET-1.

<p>Freshly isolated rat HSCs were cultured for 7 days in 10% FCS medium alone (control) or 10% FCS medium containing 1 µmol/L GW4064. Collagen gel lattices that contained the control or GW4064-treated HSCs were prepared as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013955#s4" target="_blank"><i>Materials & Methods</i></a>. Hydrated collagen lattices were photographed 6 hours after addition of ET-1 (10 nM). Data are mean ±SE of 6 experiments. *<i>P</i><.001 vs. control cells.</p