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Cisplatin is a widely used chemotherapeutic drug that can induce ovarian damage. Icariin (ICA), a natural antioxidant derived from Epimedium brevicornum Maxim., has been found to protect against organ injury. The aim of the present study was to investigate whether ICA can exert an ovarian-protective effect on cisplatin induced premature ovarian failure (POF) and the underlying mechanism involved. The preventive effect of ICA was evaluated using body weight, the oestrous cycle, ovarian histological analysis, and follicle counting. ICA treatment increased body weight, ovarian weight, and the number of follicles and improved the oestrous cycle in POF mice. ICA reduced cisplatin-induced oxidative damage and upregulated the protein expression levels of Nrf2, GPX4 and HO-1. Moreover, ICA reduced the expression levels of Bax and γH2AX and inhibited ovarian apoptosis. In addition, ICA activated the Nrf2 pathway in vitro and reversed changes in the viability of cisplatin-induced KGN cells, reactive oxygen species (ROS) levels, lipid peroxidation, and apoptosis, and these effects were abrogated when Nrf2 was knocked down or inhibited. Molecular docking confirmed that ICA promotes the release of Nrf2 by competing with Nrf2 for binding to Keap1. The inhibitory effects of ICA on cisplatin-induced oxidative stress, ferroptosis, and apoptosis may be mediated by its modulatory effects on the Nrf2 pathway, providing a novel perspective on the potential mechanisms by which ICA prevents POF. [ABSTRACT FROM AUTHOR]

Graphene has a high work function of 4.6 eV, and it can't be directly used as thermionic emission material. The graphene work function shows a decreasing trend in alkali metal/oxygen (AM/O) coadsorption experiments. Anderson–Newns (AN) model is a classical theoretical model for calculating the work function of adsorption surface. The present study, aiming at AM/O adsorption system, modifies and optimizes the AN model by redefining the calculation method of adsorption bond length λ and establishes the relationship between material work function, thermionic emission performance, and surface coverage. Based on the modified model, the influence of work function decline and thermionic emission performance of cesium/oxygen, potassium/oxygen, and sodium/oxygen graphene adsorption systems is studied. The results show that the work function of graphene affected by the three AM/O adsorbents is basically the same with the increase of coverage, and all of them quickly decrease to the lowest value and then increase slightly. The maximum work function declines are 3.51, 3.30, and 2.83 eV, respectively. At 1000 K, the maximum output current densities are 340, 36, and 0.15 A cm−2, respectively. [ABSTRACT FROM AUTHOR]

The cytoskeleton of Trypanosoma brucei, a unicellular eukaryote and a parasitic protozoan, is defined by the subpellicular microtubule corset that is arranged underneath the plasma membrane. We recently identified two orphan kinesins, TbKIN-C and TbKIN-D, that cooperate to regulate the organization of the subpellicular microtubule corset and thereby maintain cell morphology in the procyclic form of T. brucei. In this report, we characterize the function of TbKIN-C and TbKIN-D in the bloodstream form of T. brucei and investigate their functional cooperation in both the bloodstream and procyclic forms. TbKIN-C and TbKIN-D form a tight complex in vivo in the bloodstream form. TbKIN-C is strongly enriched at the posterior tip of the cell, whereas TbKIN-D is distributed throughout the cell body at all cell cycle stages. RNAi of TbKIN-C or TbKIN-D in the bloodstream form inhibits cell proliferation and leads to cell death, due to cytokinesis defects. RNAi of TbKIN-C and TbKIN-D also results in defects in basal body segregation, but does not affect the synthesis and segregation of the flagellum and the flagellum attachment zone (FAZ) filament. Knockdown of TbKIN-C and TbKIN-D does not disrupt the organization of the subpellicular microtubule corset, but produces multinucleated cells with an enlarged flagellar pocket and misplaced flagella. Interestingly, depletion of TbKIN-C results in rapid degradation of TbKIN-D and, similarly, knockdown of TbKIN-C destabilizes TbKIN-D, suggesting that formation of TbKIN-C/TbKIN-D complex stabilizes both kinesins and is required for the two kinesins to execute their essential cellular functions. Altogether, our results demonstrate the essential role of the two kinesins in cell morphogenesis and cytokinesis in the bloodstream form and the requirement of heteromeric complex formation for maintaining the stability of the two kinesins.

Morphogenesis of a vascular network requires dynamic vessel growth and regression. To investigate the cellular mechanism underlying this process, we deleted focal adhesion kinase (FAK), a key signaling mediator, in endothelial cells (ECs) using Tie2-Cre mice. Targeted FAK depletion occurred efficiently early in development, where mutants exhibited a distinctive and irregular vasculature, resulting in hemorrhage and lethality between embryonic day (e) 10.5 and 11.5. Capillaries and intercapillary spaces in yolk sacs were dilated before any other detectable abnormalities at e9.5, and explants demonstrate that the defects resulted from the loss of FAK and not from organ failure. Time-lapse microscopy monitoring EC behavior during vascular formation in explants revealed no apparent decrease in proliferation or migration but revealed increases in cell retraction and death leading to reduced vessel growth and increased vessel regression. Consistent with this phenotype, ECs derived from mutant embryos exhibited aberrant lamellipodial extensions, altered actin cytoskeleton, and nonpolarized cell movement. This study reveals that FAK is crucial for vascular morphogenesis and the regulation of EC survival and morphology.

Considering that many parameters with mutual influence which were difficult to be considered comprehensively were involved in the optimization design of thermoelectric power generation system, a method that can calculate the optimal design scheme quantitatively according to the heat source characteristic was proposed in this work. The optimum working temperature of the thermoelectric module was determined by coupling the measured thermoelectric module performance curve with the temperature relationship of the cold and hot ends under the design condition. Then, based on the iterative method, the influence of various fin radiator structural parameters on heat dissipation performance was quantitatively analyzed by FLUENT software, so as to deliver the best combination of radiator parameters. The results showed that under the condition of constant heat flux density of 36 kw/m2, in order to obtain the best system efficiency, the cold end temperature should be controlled as 50 oC, and the fin radiator base thickness, fin spacing and fin height of the matched radiator should be 8 mm, 3 mm and 90 mm respectively.