Graph Convolutional Network-Enhanced Model for Screening Persistent, Mobile, and Toxic and Very Persistent and Very Mobile Substances.

The global management for persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances has been further strengthened with the rapid increase of emerging contaminants. The development of a ready-to-use and publicly available tool for the high-throughput screening of PMT/vPvM substances is thus urgently needed. However, the current model building with the coupling of conventional algorithms, small-scale data set, and simplistic features hinders the development of a robust model for screening PMT/vPvM with wide application domains.

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect.

Increased epidemiological evidence indicates the association of bisphenol exposure with human vascular disorders, while the underlying mechanism has not been clarified. Here, we sought to unveil the potential angiogenic effect and the underlying mechanism of bisphenols with different structural features using endothelial cells treated with an environmentally relevant concentration of bisphenols (range: 1 nM to 10 μM) and a C57BL/6 mouse model fed with doses of 0.002, 0.

Bisphenol analogues induce thyroid dysfunction via the disruption of the thyroid hormone synthesis pathway.

Bisphenol analogues are widely used in industrial and daily-use consumer products having imperfect thyroid hormones (THs) structures. Widespread exposure interferes with thyroid-related health outcomes in human. The mechanisms of disruption on TH synthesis and subsequent thyroid dysfunction by different bisphenol analogues remain unclear.

Embryonic Exposure to UV-328 Impairs the Cell Cycle in Zebrafish () by Inhibiting the p38 MAPK/p53/Gadd45a Signaling Pathway.

The benzotriazole UV stabilizer UV-328 is well known for its potent antioxidative properties; however, there are concerns about how it may affect signaling nodes and lead to negative consequences. This study identified the key signaling cascades involved in oxidative stress in zebrafish () larvae and evaluated the cell cycle arrests and associated developmental alternations. Exposure to UV-328 at 0.

Machine Learning-Based Models with High Accuracy and Broad Applicability Domains for Screening PMT/vPvM Substances.

Persistent, mobile, and toxic (PMT) substances and very persistent and very mobile (vPvM) substances can transport over long distances from various sources, increasing the public health risk. A rapid and high-throughput screening of PMT/vPvM substances is thus warranted to the risk prevention and mitigation measures. Herein, we construct a machine learning-based screening system integrated with five models for high-throughput classification of PMT/vPvM substances.

Impaired barrier integrity of endothelial cells induced by PEGylated black phosphorus nanosheets.

PEGylated black phosphorus nanosheets (PEG-BPNSs) have shown promising applications in biomedicine and potentially interact with the vasculature following iatrogenic exposures. Whether the exposure to PEG-BPNSs could induce toxic effects on endothelial cells that line the blood vessels remains largely unknown. Herein, we investigate the cellular response and transcriptional profiling of human umbilical vein endothelial cells (HUVECs) after the exposure to BPNSs and PEG-BPNSs.

Promotion of Bladder Cancer Cell Metastasis by 2-Mercaptobenzothiazole via Its Activation of Aryl Hydrocarbon Receptor Transcription: Molecular Dynamics Simulations, Cell-Based Assays, and Machine Learning-Driven Prediction.

2-Mercaptobenzothiazole (MBT) is an industrial chemical widely used for rubber products, corrosion inhibitors, and polymer materials with multiple environmental and exposure pathways. A growing body of evidence suggests its potential bladder cancer (BC) risk as a public health concern; however, the molecular mechanism remains poorly understood. Herein, we demonstrate the activation of the aryl hydrocarbon receptor (AhR) by MBT and reveal key events in carcinogenesis associated with BC.

Carcinogenic Risk of 2,6-Di--Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: , , and Investigations.

Thousands of contaminants are used worldwide and eventually released into the environment, presenting a challenge of health risk assessment. The identification of key toxic pathways and characterization of interactions with target biomacromolecules are essential for health risk assessments. The adverse outcome pathway (AOP) incorporates toxic mechanisms into health risk assessment by emphasizing the relationship among molecular initiating events (MIEs), key events (KEs), and adverse outcome (AO).

Benzophenone-1 induced aberrant proliferation and metastasis of ovarian cancer cells via activated ERα and Wnt/β-catenin signaling pathways.

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10-10 M) on estrogen receptor (ER) α-associated signaling pathways.

Endothelial barrier dysfunction induced by anthracene and its nitrated or oxygenated derivatives at environmentally relevant levels.

Polycyclic aromatic hydrocarbons (PAHs) are epidemiologically associated with cardiovascular diseases characterized by early key events involving in the disruption of endothelial barrier function. Whether PAHs can induce adverse cardiovascular outcome by directly destabilizing endothelial barrier function remains elusive. Herein, we investigated the effect of anthracene (ANT), 9-nitroanthracene (9-NANT), and 9,10-anthraquinone (9,10-AQ) on vascular endothelial barrier functions in human umbilical vein endothelial cells (HUVECs).

Transcriptome aberration in mice uterus associated with steroid hormone response and inflammation induced by dioxybenzone and its metabolites.

Benzophenone-type UV filters have been implicated in multiple adverse reproductive outcomes, yet the underlying processes and molecular targets on the female reproductive tract remain largely unknown. Herein, we investigated the effect of dioxybenzone, one of the widely used congeners, and its demethylated (M1) and hydroxylated (M2) metabolites on transcriptome profiles of ICR mice uterus and identified potential cellular targets in human endometrial stromal cells (HESCs) separated from normal endometrium tissues. Dioxybenzone, M1 and M2 (20 mg/kg bw/d) significantly induced transcriptome aberration with the induction of 683, 802, and 878 differentially expressed genes mainly involved in cancer, reproductive system disease and inflammatory disease.

2,6-Di-tert-butylphenol and its quinone metabolite trigger aberrant transcriptional responses in C57BL/6 mice liver.

2,6-Di-tert-butylphenol (2,6-DTBP) is used as an antioxidant with wide commercial applications and its residues have been detected in various environmental matrices. 2,6-DTBP may enter human body via ingestion, inhalation or other exposure pathways. However, its susceptibility to biotransformation and potential of the metabolic products to trigger aberrant transcriptional responses remain unclear.

Enhanced Disrupting Effect of Benzophenone-1 Chlorination Byproducts to the Androgen Receptor: Cell-Based Assays and Gaussian Accelerated Molecular Dynamics Simulations.

Benzophenone-1 (BP-1), one of the commonly used ultraviolet filters, has caused increasing public concern due to frequently detected residues in environmental and recreational waters. Its susceptibility to residual chlorine and the potential to subsequently trigger endocrine disruption remain unknown. We herein investigated the chlorination of BP-1 in swimming pool water and evaluated the endocrine disruption toward the human androgen receptor (AR).

Dioxybenzone triggers enhanced estrogenic effect via metabolic activation: in silico, in vitro and in vivo investigation.

Dioxybenzone is widely used in cosmetics and personal care products and frequently detected in multiple environmental media and human samples. However, the current understanding of the metabolic susceptibility of dioxybenzone and the potential endocrine disruption through its metabolites in mimicking human estrogens remains largely unclear. Here we investigated the in vitro metabolism of dioxybenzone, detected the residue of metabolites in rats, and determined the estrogenic disrupting effects of these metabolites toward estrogen receptor α (ERα).

Pentabromoethylbenzene Exposure Induces Transcriptome Aberration and Thyroid Dysfunction: , and Investigations.

Pentabromoethylbenzene (PBEB), as one of the novel brominated flame retardants (NFBRs), has caused increasing public concern for health risks. Till now, information regarding potential effects of PBEB on thyroid function remains unclear. Herein, we investigated thyroid disruption of PBEB and and evaluated thyroid dysfunction induced by PBEB using Sprague-Dawley rats.

The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor β.

Polybrominated biphenyls (PBBs) were widely used as additive brominated flame retardants. Their hydroxylated products (OH-PBBs) have been detected frequently in various marine mammals, causing an increased health risk. Till now, there lacks information on the potential disruption of OH-PBBs toward thyroid hormone receptor (TR) and the molecular characteristics of their interactions remain largely unknown.

Natural sunlight-driven aquatic toxicity enhancement of 2,6-di-tert-butylphenol toward Photobacterium phosphoreum.

The tert-butylphenols (TBPs) are one group of alkylated phenolic compounds with wide applications in UV absorbers and antioxidants. They are becoming contaminants of emerging concern with residues frequently detected in natural surface water or drinking water. The direct sunlight may photolyze TBPs in waters and affect their aquatic toxicities; however, such data are very limited.

Metabolic Susceptibility of 2-Chlorothioxanthone and Its Toxic Effects on mRNA and Protein Expression and Activities of Human CYP1A2 and CYP3A4 Enzymes.

Thioxanthones (TXs) are photoinitiators widely used in UV curable resins and food packaging, and their residues have been frequently detected in human bodies. Our current understanding of the susceptibility of residual TXs to metabolism and their effects on human health is very limited. The in vitro metabolism of TXs and its toxic effects on cytochrome P450 (CYP) (the key xenobiotic metabolizing enzymes) were examined in this study.