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Peripheral artery disease (PAD), primarily caused by atherosclerosis, leads to the narrowing or blockage of arteries that supply blood to the limbs. This study explores the pro-angiogenic effects of L-theanine and its underlying mechanisms in a mouse model of hindlimb ischemia (HLI). To evaluate L-theanine's pro-angiogenic effects, human umbilical vein endothelial cells (HUVECs) were subjected to tube formation, migration, sprouting, and proliferation assays. In vivo, C57BL/6 mice with induced HLI were treated with L-theanine. Blood flow recovery was measured via Doppler ultrasound, and vascular density was analyzed using immunofluorescence staining. RNA sequencing identified neuropilin-1 (NRP1) as a key regulator, and the expression levels of NRP1 and VEGFR2 were examined through qPCR and Western blotting. L-theanine significantly enhanced angiogenesis in HUVECs, as demonstrated by improved tube formation, migration, sprouting, and proliferation. In mice, L-theanine treatment resulted in increased vessel density and improved blood flow recovery. Furthermore, L-theanine was found to activate the NRP1/VEGFR2 signaling pathway in both HUVECs and the HLI mouse model. These findings indicate that L-theanine can promote angiogenesis and activate key pathways involved in vascular repair, suggesting its potential as a therapeutic agent for treating vascular defects associated with PAD.

Abstract Advanced nanomaterials are at the core of innovation for the microelectronics industry. Designing, characterizing, and testing two-terminal devices, such as metal-insulator-metal structures, is key to improving material stack design and integration. Electrical biasing within in situ transmission electron microscopy using MEMS-based platforms is a promising technique for nano-characterization under operando conditions. However, conventional focused ion beam sample preparation can introduce parasitic current paths, limiting device performance and leading to overestimated electrical responses. Here we demonstrate connectivity of TEM lamella devices obtained from a novel electrical contacting method based solely on van der Waals forces. This method reduces parasitic leakage currents by at least five orders of magnitude relative to reported preparation approaches. Our methodology enables operation of stack devices inside a microscope with device currents as low as 10 pA. We apply this approach to observe in situ biasing-induced defect formation, providing valuable insights into the behavior of an SrTiO3-based memristor.