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Aims. The purpose of the present research is to investigate the effects of the VHL protein antagonist, VH298, on functional activities of fibroblasts and vascular endothelial cells and the effects on the wound healing process in a streptozotocin-induced hyperglycaemic rat model. Methods. HIF-1α and hydroxy-HIF-1α protein levels in VH298-treated rat fibroblasts (rFb) were measured by immunoblotting, rFb proliferation was detected by the CCK-8 assay, and mRNA levels of related genes were measured by quantitative RT-PCR. In vitro wound healing was simulated by the scratch test; angiogenesis was measured by the human umbilical vein endothelial cell (hUVEC) tube formation assay. VH298 or PBS was locally injected into wounds in rat models with streptozotocin- (STZ-) induced hyperglycaemia, the wound tissues were harvested, and haematoxylin-eosin (HE) and Masson trichrome staining and immunohistochemical processes were conducted. Results. HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb, in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signalling, and vascularization. Conclusions. Taken together, VH298 activated the HIF-1 signalling pathway by stabilizing both HIF-1α and hydroxy-HIF-1α. VH298 enhanced rFb functions, promoted hUVEC angiogenesis, and accelerated wound healing in the rat model mimicking diabetes mellitus.

Numerous applications driven by pulsed voltage require pulses to be with high amplitude, high repetitive frequency, and narrow width, which could be satisfied by utilizing avalanche transistors. The output improvement is severely limited by power capacities of transistors. Pulse combining is an effective approach to increase the output amplitude while still adopting conventional pulse generating modules. However, there are drawbacks in traditional topologies including the saturation tendency of combining efficiency and waveform oscillation. In this paper, a hybrid pulse combining topology was adopted utilizing the combination of modularized avalanche transistor Marx circuits, direct pulse adding, and transmission line transformer. The factors affecting the combining efficiency were determined including the output time synchronization of Marx circuits, and the quantity and position of magnetic cores. The numbers of the parallel modules and the stages were determined by the output characteristics of each combining method. Experimental results illustrated the ability of generating pulses with 2-14 kV amplitude, 7-11 ns width, and a maximum 10 kHz repetitive rate on a matched 50-300 Ω resistive load. The hybrid topology would be a convinced pulse combining method for similar nanosecond pulse generators based on the solid-state switches.

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