Retinal Degeneration Response to Graphene Quantum Dots: Disruption of the Blood-Retina Barrier Modulated by Surface Modification-Dependent DNA Methylation.

Graphene quantum dots (GQDs) are used in diverse fields from chemistry-related materials to biomedicines, thus causing their substantial release into the environment. Appropriate visual function is crucial for facilitating the decision-making process within the nervous system. Given the direct interaction of eyes with the environment and even nanoparticles, herein, GQDs, sulfonic acid-doped GQDs (S-GQDs), and amino-functionalized GQDs (A-GQDs) were employed to understand the potential optic neurotoxicity disruption mechanism by GQDs. The negatively charged GQDs and S-GQDs disturbed the response to light stimulation and impaired the structure of the retinal nuclear layer of zebrafish larvae, causing vision disorder and retinal degeneration. Albeit with sublethal concentrations, a considerably reduced expression of the retinal vascular sprouting factor sirt1 through increased DNA methylation damaged the blood-retina barrier. Importantly, the regulatory effect on vision function was influenced by negatively charged GQDs and S-GQDs but not positively charged A-GQDs. Moreover, cluster analysis and computational simulation studies indicated that binding affinities between GQDs and the DNMT1-ligand binding might be the dominant determinant of the vision function response. The previously unknown pathway of blood-retinal barrier interference offers opportunities to investigate the biological consequences of GQD-based nanomaterials, guiding innovation in the industry toward environmental sustainability.

Triazole fungicides disrupt embryonic stem cell differentiation: Potential modulatory role of the retinoic acid signaling pathway.

The developmental toxicity and human health risks of triazole fungicides (TFs) have attracted worldwide attention due to the ability to enter the human body in a variety of ways. Nevertheless, the specific mechanism by which TFs exert remains incompletely understood. Given that retinoic acid (RA) signaling pathway are closely related to development, this study aimed to screen and identify developmentally disabled chemicals in commonly used TFs and to reveal the potential effects of TFs on developmental retardation through the RA signaling pathway in mouse embryonic stem cells (mESCs). Specifically, six typical TFs (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole) were exposed through the construction of an embryoid bodies (EBs)-based in vitro global differentiation models. Our results clarified that various TFs disturbed lineage commitment during early embryonic development. Crucially, the activation of RA signaling pathway, which alters the expression of key genes and interferes the transport and metabolism of retinol, may be responsible for this effect. Furthermore, molecular docking, molecular dynamics simulations, and experiments using a retinoic acid receptor α inhibitor provide evidence supporting the potential modulatory role of the retinoic acid signaling pathway in developmental injury. The current study offers new insights into the TFs involved in the RA signaling pathway that interfere with the differentiation process of mESCs, which is crucial for understanding the impact of TFs on pregnancy and early development.

Developmental Toxicity of Fine Particulate Matter: Multifaceted Exploration from Epidemiological and Laboratory Perspectives.

Particulate matter of size ≤ 2.5 µm (PM2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health.

Triazole fungicides exert neural differentiation alteration through H3K27me3 modifications: In vitro and in silico study.

Considering that humans are unavoidably exposed to triazole fungicides through the esophagus, respiratory tract, and skin contact, revealing the developmental toxicity of triazole fungicides is vital for health risk assessment. This study aimed to screen and discriminate neural developmental disorder chemicals in commonly used triazole fungicides, and explore the underlying harmful impacts on neurogenesis associated with histone modification abnormality in mouse embryonic stem cells (mESCs). The triploblastic and neural differentiation models were constructed based on mESCs to expose six typical triazole fungicides (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole). The result demonstrated that although no cytotoxicity was observed, different triazole fungicides exhibited varying degrees of alterations in neural differentiation, including increased ectodermal differentiation, promoted neurogenesis, increased intracellular calcium ion levels, and disturbance of neurotransmitters. Molecular docking, cluster analysis, and multiple linear regressions demonstrated that the binding affinities between triazole fungicides and the Kdm6b-ligand binding domain were the dominant determinants of the neurodevelopmental response. This partially resulted in the reduced enrichment of H3K27me3 at the promoter region of the serotonin receptor 2 C gene, finally leading to disturbed neural differentiation. The data suggested potential adverse outcomes of triazole fungicides on embryonic neurogenesis even under sublethal doses through interfering histone modification, providing substantial evidence on the safety control of fungicides.