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Diabetic retinopathy is the most common microvascular complication caused by chronic hyperglycemia and is a leading cause of blindness; however, the underlying molecular mechanism has not been clearly elucidated. Therefore, we investigated whether regulation of AMPK and GAPDH by transglutaminase 2 (TGase2) is important for hyperglycemia-induced microvascular leakage in the diabetic retina. In human retinal endothelial cells (HRECs) and diabetic mouse retinas, we found that TGase2, activated by sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels, played an essential role in hyperglycemia-induced vascular leakage. ROS generation and TGsae2 activation were involved in hyperglycemia-induced AMPK dephosphorylation, which resulted in vascular endothelial–cadherin (VE-cadherin) disassembly and increased fluorescein isothiocyanate-dextran extravasation. Furthermore, high glucose–induced TGase2 activation suppressed GAPDH activity, determined by an on-chip activity assay, through inhibition of AMPK, which induced VE-cadherin disassembly and endothelial permeability in HRECs. Overall, our findings suggest that inhibition of AMPK and GAPDH by TGase2 plays a pivotal role in hyperglycemia-induced microvascular leakage in the retinas of diabetic mice. Article Highlights: Reactive oxygen species–mediated activation of transglutaminase 2 (TGase2) inhibited AMPK in the diabetic retina. AMPK inhibition resulted in vascular endothelial–cadherin disassembly and microvascular leakage. TGase2 suppressed GAPDH activity and induced endothelial permeability through AMPK inhibition. Inhibition of AMPK and GAPDH by TGase2 is important for microvascular leakage in the diabetic retina. [ABSTRACT FROM AUTHOR]

Real‐world applications of graphene require reliable routes for synthesizing large‐area graphene and methods to tune its structural and electrical properties. A viable and facile route is presented for synthesizing 3D porous graphene (3PG) on PI films with tunable patterns and locations via the photon‐pen writing technique and subsequent oxygen plasma treatment. The laser power and scan speed are optimized for 3PG synthesis. The electrical properties and surface hydrophilicity are controlled via surface customization of 3PG with optimal oxygen plasma treatment duration and laser inter‐spacing. The capability of humidity sensors based on surface‐customized 3PG with hydrophobic surface is demonstrated. [ABSTRACT FROM AUTHOR]

2D van der Waals (vdW) hetero integration, which features exotic interplanar interactions derived from mixed‐dimensional heterostructures, is an emergent platform for implementing high‐performance electronics and broadband/wavelength‐tunable photodetectors. However, the production of large‐area 2D spatially homogeneous transition‐metal dichalcogenides (TMDs) and elucidation of the electrostatic dynamics governing the interlayer interactions are two paramount prerequisites for realizing practical 2D‐TMD‐heterostructure‐based photodetectors. Here, a wafer‐scale synthesis of mixed‐dimensional Pt–MoS2‐based vdW heterostructures is unprecedentedly demonstrated by manipulating the platinization conditions. The rationally designed platinization yields dimensionality‐tailored Pt, including Pt nanofilm, Pt nanoparticles, and Pt atoms, with MoS2 as host platform. From density functional theory calculations, this study insights that Mo vacancy sites on the MoS2 surface are thermo‐dynamically favorable sites for Pt with an adsorption energy of −2.25 eV, then Pt clusters are sequentially formed neighboring the specific Pt‐substituted position with a formation energy of 1.30 eV. Intensive microscopic and spectroscopic analyses reveal the structural, chemical, and electrical features, validating the proposed dynamics‐related mechanism. The dimensionality‐tailored vdW heterostructures exhibit outstanding optoelectrical properties with excellent photoresponsivity (2.04 mA W−1) and highly sensitive detectivity (9.82 × 106 cm Hz1/2 W−1). [ABSTRACT FROM AUTHOR]

C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. We investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells (HPMVECs) and streptozotocin-induced diabetic mice. VEGF, which is elevated in the lungs of diabetic mice, activated transglutaminase 2 (TGase2) in HPMVECs by sequential elevation of intracellular Ca 2+ and reactive oxygen species (ROS) levels. VEGF also induced vascular endothelial (VE)-cadherin disruption and increased the permeability of endothelial cells, both of which were prevented by the TGase inhibitors monodansylcadaverine and cystamine or TGM2-specific small interfering RNA. C-peptide prevented VEGF-induced VE-cadherin disruption and endothelial cell permeability through inhibiting ROS-mediated activation of TGase2. C-peptide supplementation inhibited hyperglycemia-induced ROS generation and TGase2 activation and prevented vascular leakage and metastasis in the lungs of diabetic mice. The role of TGase2 in hyperglycemia-induced pulmonary vascular leakage and metastasis was further demonstrated in diabetic Tgm2 -/- mice. These findings demonstrate that hyperglycemia induces metastasis, and C-peptide prevents the hyperglycemia-induced metastasis in the lungs of diabetic mice by inhibiting VEGF-induced TGase2 activation and subsequent vascular leakage.-Jeon, H.-Y., Lee, Y.-J., Kim, Y.-S., Kim, S.-Y., Han, E.-T., Park, W. S., Hong, S.-H., Kim, Y.-M., Ha, K.-S. Proinsulin C-peptide prevents hyperglycemia-induced vascular leakage and metastasis of melanoma cells in the lungs of diabetic mice.