Legacy per- and polyfluoroalkyl substances (PFASs) have elicited much concern because of their ubiquitous distribution in the environment and the potential hazards they pose to wildlife and human health. Although an increasing number of effective PFAS alternatives are available in the market, these alternatives bring new challenges. This paper comprehensively reviews how PFASs bind to transport proteins (e.g., serum albumin, liver fatty acid transport proteins and organic acid transporters), nuclear receptors (e.g., peroxisome proliferator activated receptors, thyroid hormone receptors and reproductive hormone receptors) and membranes (e.g., cell membrane and mitochondrial membrane). Briefly, the hydrophobic fluorinated carbon chains of PFASs occupy the binding cavities of the target proteins, and the acid groups of PFASs form hydrogen bonds with amino acid residues. Various structural features of PFAS alternatives such as chlorine atom substitution, oxygen atom insertion and a branched structure, introduce variations in their chain length and hydrophobicity, which potentially change the affinity of PFAS alternatives for endogenous proteins. The toxic effects and mechanisms of action of legacy PFASs can be demonstrated and compared with their alternatives using binding models. In future studies, in vitro experiments and in silico quantitative structure-activity relationship modeling should be better integrated to allow more reliable toxicity predictions for both legacy and alternative PFASs.

Environmental health and toxicology research on polystyrene nanoplastics has attracted considerable attention. However, from the perspective of ecotoxicity, the definition of polystyrene nanoplastic size has been insufficient. In this paper, we systematically described the adverse effects of nanoplastics of different sizes (i.e., 0–1000 nm) penetrating biological barriers, including the blood–brain barrier, blood–air barrier, intestinal barrier, placental barrier, blood–testis barrier, and skin barrier. Negative impacts strongly associated with polystyrene nanoplastics including neurotoxicity, enterotoxicity, reproductive and pulmonary toxicity. Defining nanoplastics based on their ability to bypass various environmental and biological barriers, rather than simply applying the size definition of engineered nanomaterials directly to nanoplastics, can contribute to a better understanding of these ubiquitous environmental pollutants, supporting the assessment of their ecological health risks, and allowing the development of more effective control measures.

In this study, zebrafish (Danio rerio) were exposed to polystyrene nanoplastics (PS-NPs, 80 nm) at 0, 15, or 150 μg/L for 21 days and supplied with a low or high vitamin D (VD) diet (280 or 2800 IU/kg, respectively, indicated by - or +) to determine whether and how VD can regulate lipid metabolism disorder induced by PS-NPs. Six groups were created according to the PS-NP concentration and VD diet status: 0-, 0+, 15-, 15+,150-, and 150 +. Transmission electron microscopy showed that PS-NPs accumulated in the livers of zebrafish, which led to large numbers of vacuoles and lipid droplets in liver cell matrices; this accumulation was most prominent in the 150- group, wherein the number of lipid droplets increased significantly by 136.36%. However, the number of lipid droplets decreased significantly by 76.92% in the 150+ group compared with the 150- group. An examination of additional biochemical indicators showed that the high VD diet partially reversed the increases in the triglyceride and total cholesterol contents induced by PS-NPs (e.g., triglycerides decreased by 58.52% in the 150+ group, and total cholesterol decreased by 44.64% in the 15+ group), and regulated lipid metabolism disorder mainly by inhibiting lipid biosynthesis. Untargeted lipidomics analysis showed that exposure to PS-NPs was associated mainly with changes in the lipid molecular content related to cell membrane function and lipid biosynthesis and that the high VD diet reduced the content of lipid molecules related to lipid biosynthesis, effectively alleviating cell membrane damage and lipid accumulation. These findings highlight the potential of VD to alleviate lipid metabolism disorder caused by PS-NP exposure, thereby providing new insights into how the toxic effects of NPs on aquatic organisms could be reduced.