Aflatoxin B1 exposure triggers hepatic lipotoxicity via p53 and perilipin 2 interaction-mediated mitochondria-lipid droplet contacts: An in vitro and in vivo assessment.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins widely found in food contaminants, and its target organ is the liver. It poses a major food security and public health threat worldwide. However, the lipotoxicity mechanism of AFB1 exposure-induced liver injury remains unclear and requires further elucidation. Herein, we investigated the potential hepatic lipotoxicity of AFB1 exposure using in vitro and in vivo models to assess the public health hazards of high dietary AFB1 exposure. We demonstrated that low-dose of AFB1 (1.25 µM for 48 h, about one-fifth of the IC50 in HepG2 and HepaRG cells, IC50 are 5.995 µM and 5.266 µM, respectively) exposure significantly induced hepatic lipotoxicity, including abnormal lipid droplets (LDs) growth, mitochondria-LDs contacts increase, lipophagy disruption, and lipid accumulation. Mechanistically, we showed that AFB1 exposure promoted the mitochondrial p53 (mito-p53) and LDs-associated protein perilipin 2 (PLIN2) interaction-mediated mitochondria-LDs contacts, resulting in lipid accumulation in hepatocytes. Mito-p53-targeted inhibition, knockdown of PLIN2, and rapamycin application efficiently promoted the lysosome-dependent lipophagy and alleviated the hepatic lipotoxicity and liver injury induced by AFB1 exposure. Overall, our study found that mito-p53 and PLIN2 interaction mediates three organelles-mitochondria, LDs, and lysosomal networks to regulate lipid homeostasis in AFB1 exposure-induced hepatotoxicity, revealing how this unique trio of organelles works together and provides a novel insight into the targeted intervention in inter-organelle lipid sensing and trafficking for alleviating hazardous materials-induced hepatic lipotoxicity.

Temporal and spatial characteristics of green total factor productivity in energy-intensive industry in China.

China's energy-intensive industry (EII) is characterized by high pollution, high energy consumption, and high emissions. It is essential to boost this sector's green total factor productivity (GTFP) in order to support the sustainable development of the China's economy and help to achieve the objective of carbon neutrality. This work measures the evolution of GTFP in EII and its subsectors at provincial and regional level from 2001 to 2019, identifies the causes of these changes, and finally analyzes the particular spatial aggregation effect of GTFP in EII. It is discovered that the GTFP of China's EII has significantly improved throughout the sample period and exhibits a spatial structure of "high in the coastal areas and low in the west and center." The main driver of GTFP growth for China's EII and its subsectors was technological advance. Smelting and pressing of ferrous metals (SPFM) and smelting and pressing of non-ferrous metals (SPNM) were the industries with the most significant technological progress. Remarkable spatial correlations existed among the GTFP of EII at provincial level. The GTFP values of EII in coastal regions were relatively high and tend to benefit the adjacent provinces but there was a polarization effect in the Middle Reaches of Yellow River (YR). Finally, policy implications are provided for the sustainable development of China's EII.