Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17β-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17β-HSD family plays an important role in lipid metabolism, 17β-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17β-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirusmediated hepatic overexpression of human 17β-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17β-HSD13 as a pathogenic protein in the development of NAFLD.lipogenesis | SCDR9 | HSDI7β13
Sigma receptor (R) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in selfadministration procedures. However, the R antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]carbazole hydrobromide (SH 3-28), dosedependently decreased the maximal rates of cocaine selfadministration without affecting comparable responding maintained by food reinforcement. In contrast, a variety of (BD 1063), and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100)] had no effect on cocaine self-administration across the range of doses that decreased rates of food-maintained responding. Rimcazole analogs differed from selective R antagonists in their dual affinities for Rs and the dopamine transporter (DAT) assessed with radioligand binding. Selective DAT inhibitors and R antagonists were studied alone and in combination on cocaine self-administration to determine whether actions at both Rs and the DAT were sufficient to reproduce the effects of rimcazole analogs. Typical DAT inhibitors [2-carbomethoxy-3-(4-fluorophenyl)tropane (WIN 35,428), methylphenidate, and nomifensine] dose-dependently shifted the cocaine dose-effect curve leftward. Combinations of DAT inhibitor and R antagonist doses that were behaviorally inactive alone decreased cocaine self-administration without effects on food-maintained responding. In addition, whereas the DAT inhibitors were self-administered at rates similar to those of cocaine, neither rimcazole analogs nor typical R antagonists (NE-100 and AC927) maintained responding above control levels across a wide range of doses. These findings suggest that the unique effects of rimcazole analogs are due to dual actions at the DAT and Rs and that a combined target approach may have utility in development of medical treatments for cocaine abuse.
Lithium–sulfur batteries possess the merits of low cost and high theoretical energy density but suffer from the shuttle effect of lithium polysulfides and slow redox kinetics of sulfur. Herein, novel Co0.85Se nanoparticles embedded in nitrogen-doped carbon nanosheet arrays (Co0.85Se/NC) were constructed on carbon cloth as the self-supported host for a sulfur cathode using a facile fabrication strategy. The interconnected porous carbon-based structure of the Co0.85Se/NC could facilitate the rapid electron and ion transfer kinetics. The embedded Co0.85Se nanoparticles can effectively capture and catalyze lithium polysulfides, thus accelerating the redox kinetics and stabilizing sulfur cathodes. Therefore, the Co0.85Se/NC-S cathode could maintain a stable cycle performance for 400 cycles at 1C and deliver a high discharge specific capacity of 1361, 1001, and 810 mAh g–1 at current densities of 0.1, 1, and 3C, respectively. This work provides an efficient design strategy for high-performance lithium–sulfur batteries with high energy densities.
Lithium (Li) has garnered considerable attention as an alternative anodes of next‐generation high‐performance batteries owing to its prominent theoretical specific capacity. However, the commercialization of Li metal anodes (LMAs) is significantly compromised by non‐uniform Li deposition and inferior electrolyte–anode interfaces, particularly at high currents and capacities. Herein, a hierarchical three‐dimentional structure with CoSe2‐nanoparticle‐anchored nitrogen‐doped carbon nanoflake arrays is developed on a carbon fiber cloth (CoSe2–NC@CFC) to regulate the Li nucleation/plating process and stabilize the electrolyte–anode interface. Owing to the enhanced lithiophilicity endowed by CoSe2–NC, in situ‐formed Li2Se and Co nanoparticles during initial Li nucleation, and large void space, CoSe2–NC@CFC can induce homogeneous Li nucleation/plating, optimize the solid electrolyte interface, and mitigate volume change. Consequently, the CoSe2–NC@CFC can accommodate Li with a high areal capacity of up to 40 mAh cm–2. Moreover, the Li/CoSe2–NC@CFC anodes possess outstanding cycling stability and lifespan in symmetric cells, particularly under ultrahigh currents and capacities (1600 h at 10 mA cm−2/10 mAh cm−2 and 5 mA cm−2/20 mAh cm−2). The Li/CoSe2–NC@CFC//LiFePO4 full cell delivers impressive long‐term performance and favorable flexibility. The developed CoSe2–NC@CFC provides insights into the development of advanced Li hosts for flexible and stable LMAs.
Lithium is deemed as the anticipated anode for the next-generation energy storage system. Nevertheless, its commercial application is greatly hindered by the uneven deposition and volume expansion in the process of lithium plating and stripping. Here, a three-dimensional lithiophilic current collector with in situ grown CuO nanowire arrays on Cu foam has been demonstrated to effectively ameliorate the above problems. Beneficial from the large specific surface area and lithiophilicity properties, CuO nanowire arrays prominently diminish the local current density and nucleation overpotential, resulting in uniform lithium deposition. Moreover, the optimized anode exhibits a prolonged lifespan for more than 280 cycles at 0.5 mA cm–2 and a high coulombic efficiency of 95.5% for over 150 cycles at 3 mA cm–2 in an assembled half cell, which is maintained steadily for 540 h in a symmetric cell with good capacity retention capabilities in a full cell. This facile approach provides a feasible strategy to realize stable lithium deposition and a high-performance lithium metal anode.
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