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. Here, we construct a graph convolutional network (GCN)-enhanced model with feature fusion of a molecular graph and molecular descriptors to effectively utilize the significant correlation between critical descriptors and PMT/vPvM substances. The model is built with 213,084 substances following the latest PMT classification criteria. The application domains of the GCN-enhanced model assessed by kernel density estimation demonstrate the high suitability for high-throughput screening PMT/vPvM substances with both a high accuracy rate (86.6%) and a low false-negative rate (6.8%). An online server named PMT/vPvM profiler is further developed with a user-friendly web interface (http://www.pmt.zj.cn/). Our study facilitates a more efficient evaluation of PMT/vPvM substances with a globally accessible screening platform.

Renaissance of elemental phosphorus materials: properties, synthesis, and applications in sustainable energy and environment.

The polymorphism of phosphorus-based materials has garnered much research interest, and the variable chemical bonding structures give rise to a variety of micro and nanostructures. Among the different types of materials containing phosphorus, elemental phosphorus materials (EPMs) constitute the foundation for the synthesis of related compounds. EPMs are experiencing a renaissance in the post-graphene era, thanks to recent advancements in the scaling-down of black phosphorus, amorphous red phosphorus, violet phosphorus, and fibrous phosphorus and consequently, diverse classes of low-dimensional sheets, ribbons, and dots of EPMs with intriguing properties have been produced. The nanostructured EPMs featuring tunable bandgaps, moderate carrier mobility, and excellent optical absorption have shown great potential in energy conversion, energy storage, and environmental remediation. It is thus important to have a good understanding of the differences and interrelationships among diverse EPMs, their intrinsic physical and chemical properties, the synthesis of specific structures, and the selection of suitable nanostructures of EPMs for particular applications. In this comprehensive review, we aim to provide an in-depth analysis and discussion of the fundamental physicochemical properties, synthesis, and applications of EPMs in the areas of energy conversion, energy storage, and environmental remediation. Our evaluations are based on recent literature on well-established phosphorus allotropes and theoretical predictions of new EPMs. The objective of this review is to enhance our comprehension of the characteristics of EPMs, keep abreast of recent advances, and provide guidance for future research of EPMs in the fields of chemistry and materials science.

Embryonic Exposure to UV-328 Impairs the Cell Cycle in Zebrafish (Danio rerio) 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 (Danio rerio) larvae and evaluated the cell cycle arrests and associated developmental alternations. Exposure to UV-328 at 0.25, 0.50, 1.00, 2.00, and 4.00 µg/L downregulated gene expression associated with oxidative stress (cat, gpx, gst, and sod) and apoptosis (caspase-3, caspase-6, caspase-8, and caspase-9) at 3 days postfertilization (dpf). The transcriptome aberration in zebrafish with disrupted p38 mitogen-activated protein kinase (MAPK) cascades was validated based on decreased mRNA expressions of p38 MAPK (0.36-fold), p53 (0.33-fold), and growth arrest and DNA damage-inducible protein 45 α (Gadd45a) (0.52-fold) after a 3- and 14-day exposure alongside a correspondingly decreased protein expression. The percentage of cells in the Gap 1 (G1) phase increased from 69.60% to a maximum of 77.07% (p < 0.05) in the 3 dpf embryos. UV-328 inhibited the p38 MAPK/p53/Gadd45a regulatory circuit but promoted G1 phase cell cycle arrest, abnormally accelerating the embryo hatching and heart rate. This study provided mechanistic insights that enrich the risk profiles of UV-328.

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, 0.02, 2, and 20 mg/kg BW/day for 5 weeks. Bisphenol A (BPA) and bisphenol S (BPS) at a 1 nM level significantly increased tube formation by 45.1 and 30.2% and induced the microvessel sprouting, while tube length and microvessel sprouting were significantly inhibited by 37.2 and 55.7% after exposure to tetrabromobisphenol S (TBBPS) at 1 µM, respectively. Mechanistically, TBBPA and TBBPS significantly inhibited the interaction between phosphatidylinositol 3-kinase (PI3K) and thyroid receptor (TR), while BPA and BPS favored the interaction between PI3K and estrogen receptor (ER), resulting in abnormal PI3K signaling with consequent distinct angiogenic activity. BPA- and BPS-induced pro-angiogenic effects and TBBPS showed anti-angiogenic effects due to their distinct disruption on the TR/ER-PI3K pathway. Our work provided new evidence and mechanistic insight on the angiogenic activity of bisphenols and expanded the scope of endocrine disruptors with interference in vascular homeostasis.

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. MBT alters conformational changes of AhR ligand binding domain (LBD) as revealed by 500 ns molecular dynamics simulations and activates AhR transcription with upregulation of AhR-target genes CYP1A1 and CYP1B1 to approximately 1.5-fold. MBT upregulates the expression of MMP1, the cancer cell metastasis biomarker, to 3.2-fold and promotes BC cell invasion through an AhR-mediated manner. MBT is further revealed to induce differentially expressed genes (DEGs) most enriched in cancer pathways by transcriptome profiling. The exposure of MBT at environmentally relevant concentrations induces BC risk via AhR signaling disruption, transcriptome aberration, and malignant cell metastasis. A machine learning-based model with an AUC value of 0.881 is constructed to successfully predict 31 MBT analogues. Overall, we provide molecular insight into the BC risk of MBT and develop an effective tool for rapid screening of AhR agonists.

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. The models are constructed with 44 971 substances by conventional learning, deep learning, and ensemble learning algorithms, among which, LightGBM and XGBoost outperform other algorithms with metrics exceeding 0.900. Good model interpretability is achieved through the number of free halogen atoms (fr_halogen) and the logarithm of partition coefficient (MolLogP) as the two most critical molecular descriptors representing the persistence and mobility of substances, respectively. Our screening system exhibits a great generalization capability with area under the receiver operating characteristic curve (AUROC) above 0.951 and is successfully applied to the persistent organic pollutants (POPs), prioritized PMT/vPvM substances, and pesticides. The screening system constructed in this study can serve as an efficient and reliable tool for high-throughput risk assessment and the prioritization of managing emerging contaminants.

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARß: In Vivo, In Vitro, and In Silico 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). Herein, we attempted the use of AOP to decipher the toxic effects of 2,6-di-tert-butylphenol (2,6-DTBP) and its para-quinone metabolite 2,6-di-tert-butyl-1,4-benzoquinone (2,6-DTBQ) based on integrated transcriptomics, molecular modeling, and cell-based assays. Through transcriptomics and quantitative real-time PCR validation, we identified retinoic acid receptor ß (RARß) as the key target biomacromolecule. The epigenetic analysis and molecular modeling revealed RARß interference as one MIE, including DNA methylation and conformational changes. In vitro assays extended subsequent KEs, including altered protein expression of p-Erk1/2 and COX-2, and promoted cancer cell H4IIE proliferation and metastasis. These toxic effects altogether led to carcinogenic risk as the AO of 2,6-DTBP and 2,6-DTBQ, in line with chemical carcinogenesis identified from transcriptome profiling. Overall, our simplified AOP network of 2,6-DTBP and 2,6-DTBQ facilitates relevant health risk assessment.

Thyroid Dysfunction of Zebrafish (Danio rerio) after Early-Life Exposure and Discontinued Exposure to Tetrabromobiphenyl (BB-80) and OH-BB-80.

3,3',5,5'-Tetrabromobiphenyl (BB-80) was once used as additive flame retardants. Whether its early exposure and discontinued exposure alter thyroid function remains unknown. We investigate adverse effects after early-life exposure and discontinued exposure to BB-80 and hydroxylated BB-80 (OH-BB-80) on thyroid hormone (TH) levels, thyroid tissue, and transcriptome profiles in zebrafish larvae. BB-80 at 10 µg/L induces pathological changes of thyroid with reduced thyroid follicles in larvae (P < 0.05), whereas OH-BB-80 significantly increases T4 and T3 contents (1.8 and 2.5 times of the control, P < 0.05) at 14 days postfertilization (dpf) without morphological thyroid alterations. BB-80 and OH-BB-80 cause transcriptome aberrations with key differentially expressed genes involved in the disruption of TH synthesis and signal transduction (BB-80 at 14 dpf) or TH pathway activation (OH-BB-80 at 21 dpf). After 7 days of discontinued exposure, thyroglobulin (tg) and thyroid peroxidase (tpo) genes are downregulated (P < 0.05) by 52 and 48% for BB-80 and by 49 and 39% for OH-BB-80, respectively; however, the whole-body TH levels fail to fully recover, and the locomotor activity is impaired more by BB-80. Our results indicate significant adverse impacts of BB-80 and OH-BB-80 on TH homeostasis and thyroid function of zebrafish.

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). The structures of monochlorinated (P1) and dichlorinated (P2) products were separated and characterized by mass spectrometry and 1H-1H NMR correlation spectroscopy. P1 and P2 exhibited significantly higher antiandrogenic activity in yeast two-hybrid assays (EC50, 6.13 µM and 9.30 µM) than did BP-1 (12.89 µM). Our 350 ns Gaussian accelerated molecular dynamics simulations showed the protein dynamics in a long-time scale equilibrium, and further energy calculations revealed that although increased hydrophobic interactions are primarily responsible for enhanced binding affinities between chlorinated products and the AR ligand binding domain, the second chloride in P2 still hinders the complex motion because of the solvation penalty. The mixture of BP-1-P1-P2 elicited additive antiandrogenic activity, well fitted by the concentration addition model. P1 and P2 at 1 µM consequently downregulated the mRNA expression of AR-regulated genes, NKX3.1 and KLK3, by 1.7-9.1-fold in androgen-activated LNCaP cells. Because chlorination of BP-1 occurs naturally by residual chlorine in aquatic environments, our results regarding enhanced antiandrogenic activity and disturbed AR signaling provided evidence linking the use of personal care products with potential health risks.

Inhibited Nitric Oxide Production of Human Endothelial Nitric Oxide Synthase by Nitrated and Oxygenated Polycyclic Aromatic Hydrocarbons.

Nitrated and oxygenated polycyclic aromatic hydrocarbons (NPAHs and OPAHs) from the direct atmospheric emission or the degradation of parent PAHs are increasingly recognized because of their potential health risks. Herein, we investigated the effects of four NPAHs/OPAHs (1-NNAP, 9-NANT, 9,10-AQ, and 9-FLU) and their parent PAHs (NAP, ANT, and FLU) on endothelium function with regard to endothelial nitric oxide synthase (eNOS) and endothelium-derived nitric oxide (NO) production in human umbilical vein endothelial cells. The eNOS enzymatic activity and NO production were promoted by NAP, ANT, and FLU; however, eNOS activity was dropped by 52.8, 52.1, 52.5, and 44.5%, and NO production was decreased by 31.1, 50.3, 65.0, and 35.0% after 24 h exposure to 0.01 µM 1-NNAP, 9-NANT, 9,10-AQ, and 9-FLU, respectively. The mRNA expression of eNOS and protein expression of phosphorylated eNOS (Ser1177) were increased by three PAHs but decreased by four NPAHs/OPAHs. The 100 ns molecular dynamics simulations reveal the conformational alteration in the key propionate of heme upon the binding of NPAHs/OPAHs. Our findings provide the first in silico and in vitro evidence for the potential endothelial dysfunction of nitrated and oxygenated PAHs. The health risk implications of NPAHs/OPAHs and corresponding parent PAHs warrant further research.

Pentabromoethylbenzene Exposure Induces Transcriptome Aberration and Thyroid Dysfunction: In Vitro, in Silico, and in Vivo 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 in vitro and in silico and evaluated thyroid dysfunction induced by PBEB using Sprague-Dawley rats. PBEB showed thyroid receptor (TR) ß antagonistic activity with IC50 of 9.82 × 10-7 M in the dual-luciferase reporter gene assay and induced relative reorientation of helix 11 (H11) and H12 of the TR ligand binding domain as revealed by molecular dynamics simulations. PBEB (0.2, 2, 20 mg/kg BW/d) markedly altered the transcriptome profile of thyroid with induction of 17, 42, and 119 differentially expressed genes (DEGs) involved in thyroid hormone signaling and synthesis pathway, of which transthyretin and albumin are common DEGs. The 28-d exposure to PBEB significantly decreased the triiodothyronine level (from 7.23 to 5.67 ng/mL) and increased the thyrotropin level (from 7.88 to 12.86 mU/L) for female rats. PBEB consequently reduced thyroid weight and altered its morphology with more depleted follicles. Overall, our study provides the first account of evidence on PBEB exerted thyroid disruption, transcriptome aberration, and morphological alteration, facilitating health risk assessment of PBEB and structurally related NBFRs.

Thyroid Disruption by Bisphenol S Analogues via Thyroid Hormone Receptor ß: in Vitro, in Vivo, and Molecular Dynamics Simulation Study.

Bisphenol S (4-hydroxyphenyl sulfone, BPS) is increasingly used as a bisphenol A (BPA) alternative. The global usage of BPS and its analogues (BPSs) resulted in the frequent detection of their residues in multiple environmental media. We investigated their potential endocrine-disrupting effects toward thyroid hormone receptor (TR) ß. The molecular interaction of BPSs toward TRß ligand binding domain (LBD) was probed by fluorescence spectroscopy and molecular dynamics (MD) simulations. BPSs caused the static fluorescence quenching of TRß LBD. The 100 ns MD simulations revealed that the binding of BPSs caused significant changes in the distance between residue His435 at helix 11(H11) and residue Phe459 at H12 in comparison to no ligand-bound TRß LBD, indicating relative repositioning of H12. The recombinant two-hybrid yeast assay showed that tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A (TBBPA) have potent antagonistic activity toward TRß, with an IC10 of 10.1 and 21.1 nM, respectively. BPS and BPA have the antagonistic activity with IC10 of 312 and 884 nM, respectively. BPSs significantly altered the expression level of mRNA of TRß gene in zebrafish embryos. BPS and TBBPS at environmentally relevant concentrations have antagonistic activity toward TRß, implying that BPSs are not safe BPA alternatives in many BPA-free products. Future health risk assessments for TR disruption and other adverse effects should focus more on the structure-activity relationship in the design of environmentally benign BPA alternatives.

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. 2-Chlorothioxanthone (2-Cl-TX) significantly inhibited the enzymatic activities of CYP1A2 and CYP3A4 with IC50 of 8.36 and 0.86 µM, respectively. The exposure to 2-Cl-TX at 2.5 µM up-regulated the mRNA expression of CYP1A2 and CYP3A4 in human hepatocellular carcinoma cells to 3.03-fold and 2.02-fold, respectively. 2-Cl-TX at 2.5 µM caused 2.19-fold and 1.98-fold overexpression of CYP1A2 and CYP3A4, respectively. In vitro studies revealed that 2-Cl-TX was biotransformed into two metabolites through the sulfoxidation of the sulfur atom, or via the hydroxylation of aromatic carbon. Results from this study, including the metabolic susceptibility of residual 2-Cl-TX, the proposed metabolites and the significant toxic effect on the activities, mRNA, and protein expression of CYP1A2 and CYP3A4, are vital to the human health and safety risk assessment from this ubiquitous xenobiotic.

Side Chains of Parabens Modulate Antiandrogenic Activity: In Vitro and Molecular Docking Studies.

Parabens have been widely used in packaged foods, pharmaceuticals, and personal-care products. Considering their potential hydrolysis, we herein investigated structural features leading to the disruption of human androgen receptor (AR) and whether hydrolysis could alleviate such effects using the recombinant yeast two-hybrid assay. Parabens with an aryloxy side chain such as benzyl paraben and phenyl paraben have the strongest antiandrogenic activity. The antiandrogenic activity of parabens with alkyloxyl side chains decreases as the side chain length increases from 1 to 4, and no antiandrogenic effect occurred for heptyl, octyl, and dodecyl parabens with the number of alkoxyl carbon atoms longer than 7. The antiandrogenic activity of parabens correlates significantly with their binding energies (R2 = 0.84, p = 0.01) and were completely diminished after the hydrolysis, particularly for parabens with aryloxy side chains. The Km for the hydrolysis of parabens with aromatic moiety side chain is 1 order of magnitude higher than that of the parabens with alkyl side chains. Both in vitro and in silico data, for the first time, suggest parabens with aromatic side chains are less prone to hydrolysis. Our results provide an insight into risk of various paraben and considerations for design of new paraben-related substitutes.

Enantioselective determination of acaricide etoxazole in orange pulp, peel, and whole orange by chiral liquid chromatography with tandem mass spectrometry.

An efficient enantioselective method for the determination of etoxazole in orange pulp, peel, and whole orange was developed using liquid chromatography with tandem mass spectrometry. The enantioseparation was performed on a Chiralpak AD-3R column at 30ºC using acetonitrile with 0.1% formic acid solution (80:20, v/v) as the mobile phase in less than 5 min. Quantification was achieved using matrix-matched standard calibration curves. The overall mean recoveries for two enantiomers from orange pulp and whole orange were 91.0-99.6% and the orange peel was 92.6-103.1%, with relative standard deviations of 0.8-5.4% intraday and 2.0-4.8% interday at 1, 10, and 100 µg/kg levels, and 1.3-5.2% intraday and 3.5-4.3% interday at 5, 50, and 500 µg/kg levels, respectively. The limits of quantification for all enantiomers in three matrices did not exceed 5 µg/kg. Moreover, the absolute configuration of etoxazole enantiomers had been determined by the combination of experimental and predicted electronic circular dichroism spectra, and the first eluted enantiomer was confirmed as (S)-etoxazole on a Chiralpak AD-3R column while (R)-etoxazole was first on three cellulose chiral columns. The application of the proposed method to real sample analysis suggests its potential use in enantioselective determination of etoxazole enantiomers in citrus.

Atomic insights into distinct hormonal activities of Bisphenol A analogues toward PPARγ and ERα receptors.

Bisphenol A analogues (BPAs) belong to a wide variety of large volume chemicals with diverse applications yet emerging environmental concerns. Limited experimental data have demonstrated that BPAs with different halogenation patterns distinctly affect the agonistic activities toward proliferator-activated receptor (PPAR)γ and estrogen receptors (ER)α. Understanding the modes of action of BPAs toward different receptors is essential, however, the underlying molecular mechanism is still poorly understood. Here we probed the molecular recognition process of halogenated BPAs including TBBPA, TCBPA, BPAF, BPC, triBBPA, diBBPA, and monoBBPA toward PPARγ and ERα by molecular modeling, especially the impact of different halogen patterns. Increasing bromination at phenolic rings of BPAs was found highly correlated with electrostatic interactions (R(2) = 0.978 and 0.865 toward PPARγ and ERα, respectively) and van der Waals interactions (R(2) = 0.995 and 0.994 toward PPARγ and ERα, respectively). More halogenated phenolic rings at 3,5-positions of BPAs increase the shielding of the hormonally active phenolic OH and markedly decrease electrostatic interactions favorable for agonistic activities toward PPARγ, but unfavorable for agonistic activities toward ERα. The halogenation at the phenolic rings of BPAs exerts more impact on molecular electrostatic potential distribution than halogenation at the bridging alkyl moiety. Different halogenations further alter hydrogen bond interactions of BPAs and induce conformational changes of PPARγ ligand binding domain (LBD) and ERα LBD, specifically affecting the stabilization of helix H12 attributable to the different agonistic activities. Our results indicate that structural variations in halogenation patterns result in different interactions of BPAs with PPARγ LBD and ERα LBD, potentially causing distinct agonistic/antagonistic toxic effects. The various halogenation patterns should be fully considered for the design of future environmentally benign chemicals with reduced toxicities and desired properties.

Disruption of the hormonal network and the enantioselectivity of bifenthrin in trophoblast: maternal-fetal health risk of chiral pesticides.

Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling to increase health risks to the maternal-fetal system, yet few studies have been conducted on the currently used chiral EDCs. This work tested the hypothesis that pyrethroids could enantioselectively interfere with trophoblast cells. Cell viability, hormone secretion, and steroidogenesis gene expression of a widely used pyrethroid, bifenthrin (BF), were evaluated in vitro, and the interactions of BF enantiomers with estrogen receptor (ER) were predicted. At low or noncytotoxic concentrations, both progesterone and human chorionic gonadotropin secretion were induced. The expression levels of progesterone receptor and human leukocyte antigen G genes were significantly stimulated. The key regulators of the hormonal cascade, GnRH type-I and its receptor, were both upregulated. The expression levels of selected steroidogenic genes were also significantly altered. Moreover, a consistent enantioselective interference of hormone signaling was observed, and S-BF had greater effects than R-BF. Using molecular docking, the enantioselective endocrine disruption of BF was predicted to be partially due to enantiospecific ER binding affinity. Thus, BF could act through ER to enantioselectively disturb the hormonal network in trophoblast cells. These converging results suggest that the currently used chiral pesticides are of significant concern with respect to maternal-fetal health.

Enantioselective determination of carboxyl acid amide fungicide mandipropamid in vegetables and fruits by chiral LC coupled with MS/MS.

An efficient enantioselective method for the determination of mandipropamid in vegetables and fruits was presented by LC coupled with MS/MS. The mandipropamid residues in samples (potato, pepper, grape, and watermelon) were extracted with acetonitrile containing 1% acetic acid. An aliquot was cleaned up with primary and secondary amine and C18 sorbent. Complete enantioseparation of mandipropamid enantiomers in <4 min was obtained on a Lux Cellulose-2 column at 25°C using methanol with 0.1% formic acid/0.1% aqueous formic acid solution (85:15, v/v) as mobile phase. Good linearity was obtained over the concentration range of 0.5-250 µg/L for each enantiomer in the standard solution and sample matrix calibration curves. Quantification was achieved using matrix-matched standard calibration curves. The interday mean recoveries, intraday repeatability, and inter-day reproducibility varied from 76.4 to 97.1%, 3.4 to 9.4%, and 3.5 to 11.4%, respectively. The limits of quantification for mandipropamid enantiomers in vegetables and fruits were both 1 µg/kg. Moreover, the absolute configuration of mandipropamid enantiomers was determined by the combination of experimental and predicted electronic circular dichroism spectra, and the first eluted enantiomer was confirmed as (R)-mandipropamid on five chiral columns.

Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro.

Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreventive compounds which are readily obtainable. Sulforaphane (SFN) is isolated from cruciferous vegetables and has the potentials to reduce carcinogenesis through various pathways. In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA damage. Currently, it is difficult to predict whether SFN has the potentials to reduce the risk of TCDD based on the conflicting observations in the study. Therefore, further studies should be urgent to reveal the function and mechanism of SFN in the stress of such POPs on human health.