In the present study, we hypothesized that hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy plays a protective role in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Mitophagy was evaluated by measuring the changes of mitophagy flux, mitochondria DNA copy number, and the changes of mitophagy-related proteins including translocase of outer mitochondrial membrane 20 (TOMM20), cytochrome c oxidase IV (COX IV), microtubule-associated protein 1 light chain 3B (LC3B), and mitochondria adaptor nucleoporin p62 in HK2 cells, a human tubular cell line. Results show that HIF-1α knockout significantly attenuated hypoxia/reoxygenation (H/R)-induced mitophagy, aggravated H/R-induced apoptosis, and increased the production of reactive oxygen species (ROS). Similarly, H/R induced significantly increase in Bcl-2 19-kDa interacting protein 3 (BNIP3), a downstream regulator of HIF-1α. Notably, BNIP3 overexpression reversed the inhibitory effect of HIF-1α knockout on H/R-induced mitophagy, and prevented the enhancing effect of HIF-1α knockout on H/R-induced apoptosis and ROS production. For in vivo study, we established HIF-1α flox/flox ; cadherin-16-cre mice in which tubular HIF-1α was specifically knockout. It was found that tubular HIF-1α knockout significantly inhibited I/R-induced mitophagy, and aggravated I/R-induced tubular apoptosis and kidney damage. In contrast, adenovirus-mediated BNIP3 overexpression significantly reversed the decreased mitophagy, and prevented enhanced kidney damage in tubular HIF-1α knockout mice with I/R injury. In summary, our study demonstrated that HIF-1α-BNIP3-mediated mitophagy in tubular cells plays a protective role through inhibition of apoptosis and ROS production in acute kidney damage.

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Solid-state lithium metal batteries with solid electrolytes are promising for next-generation energy-storage devices. However, it remains challenging to develop solid electrolytes that are both mechanically robust and strong against external mechanical load, due to the brittleness of ceramic electrolytes and the softness of polymer electrolytes. Herein, we propose a nacre-inspired design of ceramic/polymer solid composite electrolytes with the "brick-and-mortar" microstructure. The nacre-like ceramic/polymer electrolyte (NCPE) simultaneously possesses a much higher fracture strain (1.1%) than pure ceramic electrolytes (0.13%) and a much larger ultimate flexural strength (7.8 GPa) than pure polymer electrolytes (20 MPa). The electrochemical performance of NCPE is also much better than pure ceramic or polymer electrolytes, especially under mechanical load. A 5 × 5 cm 2 pouch cell with LAGP/poly(ether−acrylate) (PEA) NCPE exhibits stable cycling with a capacity retention of 95.6% over 100 cycles at room temperature, even undergoes a large This article is protected by copyright. All rights reserved. point load of 10 N. In contrast, cells based on pure ceramic and pure polymer electrolyte show poor cycle life. The NCPE provides a new design for solid composite electrolyte and opens up new possibilities for future solid-state lithium metal batteries and structural energy storage. The rapid-growing demands for portable electronics and electric vehicles have bolstered needs for next-generation lithium batteries with high energy density [1-4]. However, lithium batteries become more thermally vulnerable as energy density increases. Thermal runaway and explosion are prone to be triggered by failures such as mechanical damage and lithium dendrite growth inside batteries [5, 6]. Nonflammable solid-state ceramic electrolytes (SSEs) provide alternatives to conventional flammable liquid electrolytes [7-9]. Various ceramic electrolytes with attractive ionic conductivities have been developed in the past two decades, including NASICON-type Li 1.5 Al 0.5 Ge 1.5 (PO 4) 3 (LAGP) [10] , Li 1.3 Al 0.3 Ti 1.7 (PO 4) 3 (LATP) [11, 12] , garnet Li 7 La 3 Zr 2 O 12 (LLZO) [13, 14] , and sulfides, such as This article is protected by copyright. All rights reserved. NCPEs, polymer electrolytes and ceramic electrolytes were cut with a thickness of 500 μm and a size of 1.5 cm. A loading rate of 0.5 mm min-1 and a support span of 1.5 cm were used in all tests. The results were averaged from those in five similar specimens. The flexural stress is and The flexural strain is , where F, L, w, h, and D are the applied point force, span length, sample width, thickness, and flexural deflection, respectively. Vickers indentation was carried out on SANS-UTM 6000 using a Vickers indenter. Finite Element Mechanical Simulation: 2D nonlinear finite element simulations were conducted using the software ABAQUS v6.14. In these simulations, the stress/strain distributions and crack propagation in a regular brick-mortar structure and a ceramic film are calculate...

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The different ways of allowing time window violations lead to different types of the vehicle routing problems with soft time windows (VRPSTW). In this paper, different types of VRPSTW are analysed. A unified penalty function and a unified tabu search algorithm for the main types of VRPSTW are presented, with which different types of VRPSTW can be solved by simply changing the values of corresponding parameters in the penalty function. Computational results on benchmark problems are provided and compared with other methods in the literature. Some best known solutions for the benchmark problems in the literature have been improved with the proposed algorithm.

This paper introduces a new class of problem, the disrupted vehicle routing problem (VRP), which deals with the disruptions that occur at the execution stage of a VRP plan. The paper then focuses on one type of such problem, in which a vehicle breaks down during the delivery and a new routing solution needs to be quickly generated to minimise the costs. Two Tabu Search algorithms are developed to solve the problem and are assessed in relation to an exact algorithm. A set of test problems has been generated and computational results from experiments using the heuristic algorithms are presented.

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