HNF4A as a potential target of PFOA and PFOS leading to hepatic steatosis: Integrated molecular docking, molecular dynamic and transcriptomic analyses.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are indeed among the most well known and extensively studied Per- and polyfluoroalkyl substances (PFASs), and increasing evidence confirm their effects on human health, especially liver steatosis. Nonetheless, the molecular mechanisms of their initiation of hepatic steatosis is still elusive. Therefore, potential targets of PFOA/PFOS must be explored to ameliorate its adverse consequences. This research aims to investigate the molecular mechanisms of PFOA and PFOS-induced liver steatosis, with emphasis on identifying a potential target that links these PFASs to liver steatosis. The potential target that causes PFOA and PFOS-induced liver steatosis have been explored and determined based on molecular docking, molecular dynamics (MD) simulation, and transcriptomics analysis. In silico results show that PFOA/PFOS can form a stable binding conformation with HNF4A, and PFOA/PFOS may interact with HNF4A to affect the downstream conduction mechanism. Transcriptome data from PFOA/PFOS-induced human stem cell spheres showed that HNF4A was inhibited, suggesting that PFOA/PFOS may constrain its function. PFOS mainly down-regulated genes related to cholesterol synthesis while PFOA mainly up-regulated genes related to fatty acid ß-oxidation. This study explored the toxicological mechanism of liver steatosis caused by PFOA/PFOS. These compounds might inhibit and down-regulate HNF4A, which is the molecular initiation events (MIE) that induces liver steatosis.

Plant pathogen resistance is mediated by recruitment of specific rhizosphere fungi.

Beneficial interactions between plants and rhizosphere microorganisms are key determinants of plant health with the potential to enhance the sustainability of agricultural practices. However, pinpointing the mechanisms that determine plant disease protection is often difficult due to the complexity of microbial and plant-microbe interactions and their links with the plant's own defense systems. Here, we found that the resistance level of different banana varieties was correlated with the plant's ability to stimulate specific fungal taxa in the rhizosphere that are able to inhibit the Foc TR4 pathogen. These fungal taxa included members of the genera Trichoderma and Penicillium, and their growth was stimulated by plant exudates such as shikimic acid, D-(-)-ribofuranose, and propylene glycol. Furthermore, amending soils with these metabolites enhanced the resistance of a susceptible variety to Foc TR4, with no effect observed for the resistant variety. In total, our findings suggest that the ability to recruit pathogen-suppressive fungal taxa may be an important component in determining the level of pathogen resistance exhibited by plant varieties. This perspective opens up new avenues for improving plant health, in which both plant and associated microbial properties are considered.