Ca2+ homeostasis imbalance induced by Pparg: A key factor in di (2-ethylhexyl) phthalate (DEHP)-induced cardiac dysfunction in zebrafish larvae.

Widespread application of the typical phthalate plasticizers, di (2-ethylhexyl) phthalate (DEHP), poses a serious potential threat to the health of animals and even humans. Previous studies have confirmed the mechanism of DEHP-induced cardiac developmental defects in zebrafish larvae. However, the mechanism of cardiac dysfunction is still unclear. Thus, this work aimed to comprehensively investigate the mechanisms involved in DEHP-induced cardiac dysfunction through computational simulations, in vivo assays in zebrafish, and in vitro assays in cardiomyocytes. Firstly, molecular docking and western blot initially investigated the activating effect of DEHP on Pparg in zebrafish. Although GW9662 (PPARG antagonist) effectively alleviated DEHP-induced cardiac dysfunction and lipid metabolism disorders, it did not restore significant decreases in mitochondrial membrane potential and ATP levels. In vitro assays in cardiomyocytes, DEHP caused overexpression of PPARG and proteins involved in the regulation of Ca2+ homeostasis, and the above abnormalities were effectively alleviated by GW9662, suggesting that the Ca2+ homeostatic imbalance caused by activation of PPARG by DEHP seems to be the main cause of DEHP-induced cardiac dysfunction. To sum up, this work not only refines the mechanism of toxic effects of cardiotoxicity induced by DEHP, but provides an important theoretical basis for enriching the toxicological effects of DEHP.

Novel insights into DEHP-induced zebrafish spleen damage: Cellular apoptosis, mitochondrial dysfunction, and innate immunity.

DEHP (Di(2-ethylhexyl) phthalate) is the most abundant phthalate component detected in environmental samples as it is widely used in the manufacturing of children's toys, medical devices and furniture. Due to its wide prevalence and propensity to accumulate in the food chain, significant concerns have risen about the safety profile of DEHP. Here, we used a zebrafish model to investigate the toxicity mechanisms of DEHP. Our results indicated that exposure to DEHP altered the ROS content in zebrafish spleen and inhibited the activities of antioxidant enzymes SOD and CAT, detoxification enzyme GSH-Px and induced histopathological damage. In addition, elucidated the mechanism of DEHP significantly promoted apoptosis and caused damage in spleen cells through the bax/bcl-2 pathway. Further genetic testing demonstrated significant alterations in mitochondrial biogenesis, fission, and fusion-related genes and suggested potential mechanistic pathways, including GM10532/m6A/FIS1 axis, the STAT3/POA1 axis, and the NFR1/TFAM axis. Serological and genomic analysis indicated that DEHP exposure activated the C3 complement cascade immune pathway and interfered with innate immune function. IBRv2 analysis proposes that innate immunity may serve as a signal indicator of early toxic responses to DEHP pollutants. This study provided comprehensive cellular and genetic data for DEHP toxicity studies and emphasized the need for future management and remediation of DEHP contamination. It also provides data to specifically support the health risk assessments of DEHP, as well as contributing to broader health and environmental research.

Tissue-specific accumulation of DEHP and involvement of endogenous arachidonic acid in DEHP-induced spleen information and injury.

The plasticizer Diethylhexyl phthalate (DEHP), one of the most common contaminants, is widely detected in environmental and biological samples. However, the accumulation of DEHP in tissue and the molecular mechanisms underlying its physiological damage in the spleen of aquatic organisms have not yet been reported. In this study, gas chromatography-mass spectrometry (GC-MS), histology and multi-omics analysis were used to investigate DEHP exposure-induced alterations in transcriptomic profiles and metabolic network of zebrafish model. After exposure to DEHP, higher concentrations of DEHP were found in the intestine, liver and spleen. Anatomical and histological analyses showed that the zebrafish spleen index was significantly increased and inflammatory damage was observed. Increased splenic neutrophil counts indicate inflammation and tissue damage. Transcriptomic filtering showed that 3579 genes were significantly altered. Metabolomic analysis detected 543 differential metabolites. Multi-omics annotation results indicated that arachidonic acid and 12-Hydroperoxyicosatetraenoic acid (HPETE) are involved in the key inflammatory pathway "Inflammatory mediator regulation of TRP channels". This study demonstrated the accumulation characteristics of DEHP in aquatic zebrafish and the mechanisms of inflammation and tissue damage in the spleen which involve endogenous arachidonic acid. This will provide theoretical basis and data support for health risk assessments and tissue damage of DEHP.

How can urban administrative boundary expansion affect air pollution? Mechanism analysis and empirical test.

As a momentous policy tool for spatial management, urban administrative boundary expansion (UABE) significantly impacts resource reorganization and development modes. However, the environmental effects of UABE are easily ignored. Whether UABE can also impove the environmental quality in addition to its economic effects remains to be answered. To fill this gap, we took the city-county merger policy (CCMP) in China as quasi-experimental evidence and empirically investigated the impacts of CCMP on air pollution based on the difference-in-difference method. The impact mechanisms were also analyzed from a whole-process perspective. The results demonstrate that, apart from expanding the urban scale, UABE can improve urban air quality as well. Further analysis shows that the positive effect is mainly realized by source control and process management, rather than end-of-pipe treatment. Besides, the impacts of UABE on air pollution exhibit obvious spatial heterogeneous characteristics. We also reported that the environmental effects of UABE are largely dependent on governmental control, rather than market factors. According to the results above, flexible administrative boundary adjustment, strict government regulations, and effective market systems are required to realize the dual goals of environmental improvement and space optimization.

Metabolism of diethyl phthalate (DEP) and identification of degradation intermediates by Pseudomonas sp. DNE-S1.

A Pseudomonas sp. DNE-S1 (GenBank accession number MF803832), able to degrade DEP in a wide range of acid-base conditions, was isolated from landfill soil. The growth kinetics of DNE-S1 on DEP followed the inhibition model. Fe3+ could promote the degradation ability of DNE-S1 to DEP probably by over-expression of the gene phthalate dihydrodiol dehydrogenase (ophB) and phthalate dioxygenase ferredoxin reductase (ophA4). The degradation rate of DEP (500 mg L-1 at 12 h) increased by 14.5% in the presence of Fe3+. Cu2+, Zn2+, and Mn2+ showed an inhibiting effect on the degradation performance of the strain and could alter the cellular morphology, surface area and volume of DNE-S1. Three degradation intermediates, namely ethyl methyl phthalate (EMP), dimethyl phthalate (DMP), and phthalic acid (PA), were detected in the biodegradation of DEP, and the biochemical pathway of DEP degradation was proposed. This study provides new information on the biochemical pathways and the responsible genes involved in DEP degradation.