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Mitochondrial dysfunction is considered a pathogenic linker in the development of non-alcoholic steatohepatitis (NASH). Inappropriate mitochondrial protein-quality control, possibly induced by insufficiency of the mitochondrial matrix caseinolytic protease P (ClpP), can potentially cause mitochondrial dysfunction. Herein, we aimed to investigate hepatic ClpP levels in a diet-induced model of NASH and determine whether supplementation of ClpP can ameliorate diet-induced NASH.NASH was induced by a high-fat/high-fructose (HF/HFr) diet in C57BL/6J mice. Stress/inflammatory signals were induced in mouse primary hepatocytes (MPHs) by treatment with palmitate/oleate (PA/OA). ClpP levels in hepatocytes were reduced using the RNAi-mediated gene knockdown technique but increased through the viral transduction of ClpP. ClpP activation was induced by administering a chemical activator of ClpP.Hepatic ClpP protein levels in C57BL/6J mice fed a HF/HFr diet were lower than the levels in those fed a normal chow diet. PA/OA treatment also decreased the ClpP protein levels in MPHs. Overexpression or activation of ClpP reversed PA/OA-induced mitochondrial dysfunction and stress/inflammatory signal activation in MPHs, whereas ClpP knockdown induced mitochondrial dysfunction and stress/inflammatory signals in these cells. On the other hand, ClpP overexpression or activation improved HF/HFr-induced NASH characteristics such as hepatic steatosis, inflammation, fibrosis, and injury in the C57BL/6J mice, whereas ClpP knockdown further augmented steatohepatitis in mice fed a HF/HFr diet.Reduced ClpP expression and subsequent mitochondrial dysfunction are key to the development of diet-induced NASH. ClpP supplementation through viral transduction or chemical activation represents a potential therapeutic strategy to prevent diet-induced NASH.Western diets, containing high fat and high fructose, often induce non-alcoholic steatohepatitis (NASH). Mitochondrial dysfunction is considered pathogenically linked to diet-induced NASH. We observed that the mitochondrial protease ClpP decreased in the livers of mice fed a western diet and supplementation of ClpP ameliorated western diet-induced NASH.

This paper aims to demonstrate the importance of the precursor film density during the development of the microstructure and photovoltaic properties of CuInSe2 (CISe) thin films prepared from nanoparticulate precursors and to provide a simple but effective means to improve the density. In order to improve the packing density of a Cu–In alloy nanocrystalline layer deposited by a doctor-blade method, a mild, wet, ball-milling technique is applied to colloidal ink without the use of organic additives or mechanical pressing. The focused ion beam milled cross-sections clearly show that the relative density of the precursor layers increases with an increase in the milling duration. The CISe thin films obtained by annealing the intermetallic layers with a relative density of 0.78 exhibit extremely low porosity on the well-faceted surface, a thicker top layer with large grains in a typical double-layered structure, a uniform and planar surface morphology, and a thinner MoSe2 layer. The transmission electron microscopy analysis also reveals that the nanocrystals in the bottom layer exist in the chalcopyrite CISe phase, forming a well-connected mesoporous network. As a result, the PV performance of low-bandgap (1.0 eV) CISe solar cells is greatly improved, rendering a power conversion efficiency as high as 9.32%. Changes in the PV parameters induced by the increase in the relative density of the precursor layer are discussed in conjunction with the improved crystalline quality and the consequent improvements in diode characteristics, such as the series resistance, shunt conductance, and recombination current.

The olivine Fe2GeS4 compound has attracted much attention as a thermodynamically stable derivative of pyrite FeS2, which has been studied extensively as an earth-abundant light-absorbing candidate material. Nevertheless, reports on nanocrystalline Fe2GeS4 and its optoelectronic properties are limited. Herein, Fe2GeS4 nanocrystals are synthesized via a solvent-free mechanochemical process. This process not only reduces the synthesis time, but also avoids the use of hazardous solvents, thereby mitigating environmental concerns. The crystallinity of the synthesized nanocrystals is significantly enhanced by a post-heat treatment in a sulfur-containing atmosphere, showing no phase decomposition. Lattice-resolved micrographs reveal that the post-annealed nanocrystals have a hexagonal-faceted platelet structure with (002) base planes. The oxide layer near the surface region is removed by the post-annealing process, most likely due to the replacement of oxygen with sulfur in the controlled atmosphere. The post-annealed Fe2GeS4 nanocrystals clearly exhibit an optical band gap of 1.43 eV and near-band-edge photoluminescent emission at 1.41 eV. This is the first experimental demonstration of the Fe2GeS4 nanocrystals having optoelectronic properties that are suitable for solar applications.

Kesterite Cu2ZnSnSe4 (CZTSe) thin films prepared by the selenization of mechanochemically synthe- sized Cu2ZnSnS4 (CZTS) nanocrystal films are systematically investigated as a function of the annealing time in terms of the phase purity, microstructure, composition, and device characteristics. It is shown that selenization for an extended time does not cause a noticeable amount of Sn loss or segregation of Zn-rich layers. Thus, the prolonged annealing leads to improvements (reduction) in the shunt conductance, reverse saturation current, and diode ideality factor. However, it also leads to a deterioration of the series resistance, of which influence turned out to overwhelm all of the aforementioned positive effects on the device performance. As a consequence, the CZTSe solar cell exhibits its highest efficiency (5.43%) at the shortest annealing time (10 min). Impedance spectroscopy is demonstrated to be of good use in detecting the change in the back contact of CZTSe solar cells during annealing. The impedance spectra of the CZTSe solar cells are analyzed in association with the microstructures of the back-contact electrodes, demonstrating that the increase in the series resistance is attributed to the formation of the resistive MoSe2 layer.

Beta cell loss and insulin resistance play roles in the pathogenesis of type 2 diabetes. Elevated levels of free fatty acids in plasma might contribute to the loss of beta cells. The objective of this study was to find a chemical that could protect against palmitate-induced beta cell death and investigate whether such chemical could improve hyperglycemia in mouse model of type 2 diabetes. Sodium fluorocitrate (SFC), an aconitase inhibitor, was found to be strongly and specifically protective against palmitate-induced INS-1 beta cell death. However, the protective effect of SFC on palmitate-induced cell death was not likely to be due to its inhibitory activity for aconitase since inhibition or knockdown of aconitase failed to protect against palmitate-induced cell death. Since SFC inhibited the uptake of palmitate into INS-1 cells, reduced metabolism of fatty acids was thought to be involved in SFC’s protective effect. Ten weeks of treatment with SFC in db/db diabetic mice reduced glucose level but remarkably increased insulin level in the plasma. SFC improved impairment of glucose-stimulated insulin release and also reduced the loss of beta cells in db/db mice. Conclusively, SFC possessed protective effect against palmitate-induced lipotoxicity and improved hyperglycemia in mouse model of type 2 diabetes.

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells.

The synthesis of (±)-Hagen's gland lactone 1 has been completed in three steps in 44% from commercially available starting materials. The work is highlighted by a straightforward preparation of butenolide through an epoxide opening using 2-lithiofuran and a concise and stereoselective synthesis of furano-γ-lactone by a novel DBU-promoted sequential isomerization/intramolecular oxa-Michael addition of a hydroxybutenolide.

Efficient Cu2ZnSnSe4 (CZTSe) solar cells were fabricated with a simple, environmentally friendly, and scalable synthetic method for Cu2ZnSnS4 (CZTS) nanocrystals. CZTS nanoparticles were mechanochemically synthesized from elemental precursors on a relatively large scale (∼20 g), during which no solvents or additives were used, thus alleviating the complex process of particle synthesis. An analysis of the time evolution of the crystalline phase and morphology of precursor powders revealed that the formation of the CZTS compound was completed in 0.5 h once initiated, suggesting that the mechanochemically induced self-propagating reaction prevails. CZTS ink was prepared by dispersing the as-synthesized nanoparticles in an environmentally benign solvent (160 mg mL(-1) in ethanol) without using any additives, after which it was cast onto Mo-coated glass substrates by a doctor-blade method. Subsequent reactive annealing at 560 °C under a Se-containing atmosphere resulted in substantial grain growth along with the nearly complete substitution of Se. The CZTSe solar cells therefrom exhibited power conversion efficiency levels as high as 6.1% (based on the active area, 0.44 cm(2)) with a relatively high open-circuit voltage (0.42 V) in comparison with the bandgap energy of 1.0 eV.

This paper presents a motion planning algorithm for dual redundant manipulators performing a coordinated motion. In particular, the algorithm is developed for a dual-arm, point-to-point motion planning problem of moving from one relative configuration to another relative configuration. The high degrees of redundancy of dual arms usually exceed the number of task constraints, and the extra degrees of freedom are used to satisfy the usual constraints from joint limits and collision avoidance. To handle the case of applying a tool to an object of a complicated shape, a global motion planner is introduced in addition to the local motion planner. The algorithm is tested with a human-like robot having two arms with 9 degrees of freedom each, and its performance is reported.