NRF2-HIF2α Signaling Attenuates Endothelial Cell Senescence and Maintains Intercellular Junctions in Diabetes.

In the context of diabetes, endothelial cells frequently exhibit compromised intercellular junctions and accelerated cellular senescence simultaneously. The precise mechanisms underlying these issues and the identification of effective treatments remain largely undefined. Our findings reveal that human umbilical vein endothelial cells (HUVECs) can counteract senescence and uphold the integrity of intercellular junctions under mildly to moderately elevated glucose levels (10 mM and 15 mM) via two primary mechanisms: i) The acetylation of NRF2 at lysine residues K56, K68, and K52 prevents its ubiquitination, enhancing the transcription of antioxidant genes GST, SOD1, and GPX1. This activity diminishes cytoplasmic oxidative stress, thereby mitigating endothelial cell senescence. ii) The interaction between the Neh2 domain of NRF2 and the PAS-B domain of HIF-2α within the nucleus curtails the attachment of HIF-2α to the NOX4/p22phox promoter. This action lessens oxidative stress near the cell membrane, maintaining intercellular junctions by safeguarding the disulfide bonds in occludin and E-cadherin from disruption. However, these protective strategies prove insufficient under severe hyperglycemic conditions (25 mM). Further investigation has identified Oltipraz, an activator of NRF2, as also promoting the degradation of HIF-2α. Through its simultaneous modulation of NRF2 and HIF-2α, Oltipraz significantly reduces cellular senescence and prevents the deterioration of intercellular junctions in HUVECs subjected to high glucose concentrations (25 mM). Our research positions Oltipraz as a promising therapeutic candidate for mitigating diabetes-induced vascular endothelial damage, potentially offering benefits against diabetes-related atherosclerosis and valvular calcification.

The impact of digital transformation of infrastructure on carbon emissions: Based on a "local-neighborhood" perspective.

In light of the recent worldwide scientific and technological revolution, it is imperative that urban infrastructure undergo a digital transformation in order to lower carbon emissions and support sustainable urban growth. However, to date, there is a lack of empirical research on carbon emissions based on the digital transformation of urban infrastructure. This paper uses data from 178 prefecture-level cities in China from 2005 to 2020 to study the impact of digital transformation of urban infrastructure on carbon emissions based on the "local-neighbourhood" perspective using a spatial difference-in-differences model. The results show that the digital transformation of urban infrastructure reduces the intensity of local carbon emissions while also reducing the carbon emissions of neighbouring cities, with a spatial spillover effect, and the boundary of this spatial spillover is 600 km. Mechanistic analyses suggest that digital transformation of urban infrastructure can reduce carbon emissions locally as well as in nearby areas by promoting green technological innovations. In light of this, this study has important policy implications for maximising the contribution of digital transformation of infrastructure to reducing carbon emissions.

Microelectronic printed chitosan/chondroitin sulfate/ZnO flexible and environmentally friendly triboelectric nanogenerator.

The triboelectric nanogenerator (TENG) of natural biomaterials is a new type of energy harvesting device and can be used as a self-powered sensor, which has received extensive research and attention. In this paper, based on the biocompatibility of chitosan and chondroitin sulfate, ZnO-modified chitosan/chondroitin sulfate/ZnO TENG was prepared for research on wearable devices and sustainable power supply devices. This study employs molecular dynamics to compute the interaction energy between chitosan and ZnO molecules. Theoretical calculations have unequivocally substantiated the occurrence of a binding interaction between these two molecular entities. The effect of ZnO on chitosan/chondroitin sulfate morphology was investigated by atomic force microscopy. The chitosan/chondroitin sulfate/ZnO TENG has high flexibility and electrical output performance. It can reach 105 V and 3.3 µA of open-circuit voltage and short-circuit current. Chitosan/chondroitin Sulfate/ZnO TENG successfully converts the mechanical energy of human motion into electrical energy. Strong electrical signals are exhibited when making fists and waving fingers and wrists. The TENG is a self-powered source and lights up 70 blue light-emitting diodes (LEDs). The chitosan/chondroitin sulfate/ZnO TENG has demonstrated its capabilities in energy harvesting and wearable self-powered sensors.