Inhibiting Receptor of Advanced Glycation End Products Attenuates Pressure Overload-Induced Cardiac Dysfunction by Preventing Excessive Autophagy

The receptor for advanced glycation end products (RAGE) is involved in heart failure (HF) by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, the role of RAGE in pressure overload-induced HF is not well understood. We found that stimulation of RAGE triggered the death of neonatal rat ventricular myocytes (NRVMs), while cell death was alleviated by ATG5 knockdown. Using transverse aortic constriction (TAC) in mice as a model of pressure overload-induced HF, we demonstrated that RAGE knockout or RAGE blockade attenuated cardiac hypertrophy and fibrosis as well as cardiac dysfunction at 8 weeks after TAC. Importantly, RAGE knockout reversed upregulation of autophagy related proteins (LC3BII/I and Beclin 1) and reduced cardiomyocyte death, indicating that excessive autophagy after TAC was inhibited. Moreover, RAGE knockout or blockade reduced the upregulation of pp65-NFκB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of HF by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure

Assessing the effect of urban digital infrastructure on green innovation: mechanism identification and spatial-temporal characteristics

Abstract Under the background of digitization and greening in China, digital infrastructure offers new opportunities for developing green innovation. This paper investigates the effect of digital infrastructure on urban green innovation using panel data from 285 Chinese prefecture-level cities between 2011 and 2020, and explains the mechanism and its spatial-temporal dynamic effect. The results demonstrate that digital infrastructure promotes urban green innovation. Talent agglomeration, R&D investment increase, and industrial structure upgrading are crucial channels. Furthermore, depending on a city’s size, human capital, environmental regulations, and financial subsidies, digital infrastructure contributes to urban green innovation differently. Also, there is not only a positive spatial spillover effect of digital infrastructure but a threshold effect that presents a nonlinear trend of rising marginal effect. This study provides a new perspective for promoting digital infrastructure and urban green innovation, which makes a difference in facilitating its high-level development collaboratively

Optimization of Work Environment and Community Labor Health Based on Digital Model—Empirical Evidence from Developing Countries

As far as we know, for large manufacturing enterprises, there is often a community of labor gathered around such enterprises, which is especially used as a place for the enterprise to place the labor force. This paper aimed to update the industry model of Chinese Manufacturing Enterprises (CMEs) to improve workers’ health management. This work first discusses the value, mode, and process of Enterprise Digital Transformation (EDT) and Worker Health and Safety Management (WHSM). Then, it proposes the CMEs-oriented EDT model and WHSM system based on Big Data Technology (BDT) and the Internet of Things (IoT). The proposed model and system are verified through a case study on the Shanghai BYD manufacturing enterprise (short for BYD) using the Fuzzy Comprehensive Evaluation Method (CFEM). The EDT model verification considers the adaptation and performance of enterprises after EDT. The WHSM system considers workers’ oxygen inhalation status to evaluate their heart and cardiovascular health. The results show that EDT improves the enterprise’s revenue and reshuffles the revenue structure. The EDT model has absolute adaptability to BYD. It has greatly improved BYD’s indexes, especially financial performance, market capability, and technical capability

Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice’s body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5′-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol’s upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders