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Jiazhen Wang

Publications and source records attributed to Jiazhen Wang.

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Perfluorodecanoic acid (PFDA) disrupts immune regulation via the toll-like receptor signaling pathway in zebrafish

As there are a growing number of per- and polyfluoroalkyl substances (PFAS) alternative substitutes applied globally, it remains paramount to characterize their potential health risks. Perfluorodecanoic acid (PFDA) is the most common alternative PFAS detected in the environment; however, its toxic effects and underlying mechanism of action to aquatic biota remains unclear. In this study, we present in vitro evidence of PFDA-induced immunotoxicity and gain insight into underlying molecular mechanisms. PFDA induced immune dysfunction in zebrafish primarily through immunosuppression, apoptosis, and inflammatory response which further cascaded to suppress innate and adaptive immunities, ultimately weaking the ability of larvae to defend against pathogenic infection. PFDA-induced immunotoxicity was driven by a dysregulation in the toll-like receptor (TLR) signaling pathway, which was validated through a cotreatment of PFDA with either a morpholino knockdown or inhibitor of myeloid differentiation factor 88. Comparative toxicity studies were carried out with a subset of other alternative PFAS (PFBA, PFOA, PFNA) and it was found that PFDA posed a greater immunotoxic response than other commonly identified PFAS in the environment. This work identified a major target of PFDA, disrupting immune function through the TLR signaling pathway, while inducing a greater toxic response among other tested PFAS, which provides novel insights into understanding the potential environmental risks of PFAS substitutes.

Environmental Science & Technology

Perfluorodecanesulfonate (PFDS) induces innate immune toxicity through the NF-κB pathway in early life stage zebrafish

Perfluorodecanesulfonate (PFDS), a long-chain polyfluoroalkyl substance (PFAS), is widely detected in aquatic environments and increasingly recognized for its environmental persistence and bioaccumulative potential; however, its immunotoxicity remains poorly understood in aquatic biota. In this study, early life stage zebrafish ( Danio rerio ) were exposed to environmentally relevant concentrations of PFDS and PFOS for 120 h to better characterize the adverse effects of PFDS on aquatic organisms. Additionally, the toxicological differences between PFDS and PFOS at the same exposure concentrations were compared, as PFDS is a known substitute for PFOS. PFDS bioaccumulated in zebrafish larvae at environmentally relevant concentrations, which disrupted immune function by altering the number of macrophages and neutrophils, inducing oxidative stress, and dysregulating immune markers such as interleukins and immunoglobulins. Mechanistically, PFDS activated the nuclear factor kappa B (NF-κB) signaling pathway, driving pro-inflammatory cytokine expression and immune dysfunction. Furthermore, the use of a NF-κB morpholino knockdown confirmed the role of the NF-κB pathway in mediating PFDS-induced immunotoxicity. These findings provide the first comprehensive evidence of PFDS-induced immunotoxicity being mediated through NF-κB activation, offering novel insights into the ecological risks of long-chain perfluorosulfonic acids. Notably, PFDS exhibited a stronger immunotoxic response relative to PFOS, indicating that its adverse effects may be more severe. Overall, these findings provide valuable insights for the ecological risk assessment of PFDS and the toxic potential that unregulated PFAS can have to aquatic systems.

Environment International

High-throughput screening identifies bisphenol P as a potent cardiotoxin, inducing cardiotoxicity through apoptosis and NF-κB Pathway

The increasing use of plastic additives, particularly bisphenols (BPs), has raised significant concerns about their potential risks to human health, especially during critical developmental stages. In this study, we developed a novel high-throughput toxicity screening platform using zebrafish ( Danio rerio ) to identify and prioritize chemicals with cardiotoxic potential, which is based on multidimensional exposure pathways ranging from environmental to human levels. The platform quantitatively assesses heart rate changes based on multilevel exposure pathways (environmental, ecological, and human), effectively prioritizing the most relevant cardiotoxic compounds with potential health risks. Using this platform, we identified bisphenol P (BPP), a widely used substitute for bisphenol A, as a potent cardiotoxic compound. BPP exposure significantly inhibited heart development and function in zebrafish, inducing abnormal heart morphology, reduced heart rate, cardiac output, and hemodynamic disturbances. Additionally, NF-κB signaling pathway analysis, including morpholino knock-down and inhibitor experiments, confirmed that BPP mediates cardiac toxicity by inducing cardiomyocyte apoptosis. Our findings underscore the toxicity that BP substitutes can have, while highlighting the potential of this multidimensional screening platform in evaluating cardiovascular toxicity and guiding future toxicological assessments during critical developmental windows.

Environmental Science & Technology

Hepatotoxic response of perfluorooctane sulfonamide (PFOSA) in early life stage zebrafish (Danio rerio) is greater than perfluorooctane sulfonate (PFOS)

Perfluorooctane sulfonamide (PFOSA), a typical perfluorooctane sulfonate precursor (PreFOS), has been detected in the aquatic environment globally. However, the effects of PFOSA at levels measured in the environment have not been well characterized in aquatic organisms. In this study, we evaluated the transcriptional, biochemical, histopathological, and morphological effects of PFOSA to characterize the underlying mechanisms of toxicity by using a universal model in aquatic ecotoxicology, zebrafish ( Danio rerio ). Transcriptional changes in PFOSA-exposed zebrafish predicted hepatic fibrosis and associated immune function. Subsequent, sublethal impacts were observed, which included significant alterations in liver-specific protein levels, increased immune cell numbers, and liver pathological structural damage. In addition, we compared the effects caused by PFOSA and perfluorooctane sulfonate (PFOS) at the same exposure concentration and found a greater hepatotoxic effect of PFOSA relative to PFOS, indicating that the adverse impacts of PFOSA may be more severe. This was the first study to comparatively explore the hepatotoxic response of PFOSA and PFOS in aquatic organisms, which can be used for ecological risk assessments of PreFOS compounds.

Journal of Hazardous Materials

Immunotoxic response of bio-based plastic on early life stage zebrafish (Danio rerio): A safe alternative to petroleum-based plastics?

Bio-based plastics are marketed as environmentally friendly alternatives to petroleum-based plastics, although they require specific composting conditions for degradation, which leads to their accumulation in the environment and potential risks to aquatic organisms. We hypothesized that the accumulation of bio-based plastics may induce immunotoxic responses in fish. Our research focused on the accumulation and immunotoxicity of 80 nm polylactic acid (PLA) and polystyrene (PS) (0.1–10 mg/L) on early life stage zebrafish ( Danio rerio ) exposed for 7 days. Compared to PS, there was a higher accumulation of PLA in larvae. Exposure to PLA resulted in a significant increase in neutrophils and macrophages, while immune protein levels such as Complement 3 (C3), Immunoglobulin M (IgM), and C-reactive protein (CRP) were significantly reduced. Furthermore, the mRNA expression of pro-inflammatory cytokines, including tnf-α and il-6 , were significantly elevated in PLA treatments. Additionally, PLA-exposed zebrafish were more susceptible to infection by Vibrio parahaemolyticus . Interestingly, at the same concentration, exposures to PS did not induce significant changes in macrophages or immune protein levels, C3 and IgM. This suggests that PLA has a greater immunotoxic response relative to PS. Our research findings contradict the popular belief that bio-based plastics are non-toxic and harmless, which may have potential risk to aquatic organisms.

Journal of Hazardous Materials