ENVIRONMENTAL GEOCHEMISTRY AND HEALTH
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2024
·Vol. 46
·期 9
·1-11
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IF 3.2
Yang Yu,Li Jing,Xu Jie
The levels of three phenolic endocrine-disrupting compounds (EDCs), NP, BPA and 4-t-OP were determined in water and sediment collected from sites along the Xiangjiang River, Zunyi, China. The NP, BPA and 4-t-OP concentrations ranged from 18.02 to 311.79 ng/L in the surface water, 16.04–408.12 ng/L in the submerged water, and 21.13–892.37 μg/kg dw in the sediment. NP contamination was most severe in both the river water and sediment. The ranges of the three phenolic EDCs were slightly greater in the submerged water than in the surface water ( p > 0.05). The concentrations in the middle reaches were greater than those in the upstream and downstream reaches in both the water and sediment, and significant differences in content were detected in some reaches. The levels of three phenolic EDCs in the water and sediment had a positive correlation. In addition, the distribution coefficient (K d ) indicated that NP was more likely to adsorb to the sediment, and BPA and 4-t-OP were more likely to adsorb to river water. Moreover, the risk quotient (RQ) and hazard quotients (HQ) were used to reveal the environmental and health risks caused by coexposure to the three phenolic pollutants. The results showed that the current pollution is a threat to the environment of the study area and not a threat to the health of the local population.
研究领域:
环境科学
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毒理学
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PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 9
·e70416
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IF 4.2
Xiliang Zhu,Qi Liu,Zhaoyun Cheng,Yi Luo
Bisphenol A (BPA) is a widely used industrial chemical with potential endocrine-disrupting effects on metabolic processes. This study investigates the impact of BPA on hepatic function and transcriptional regulation in mouse livers and AML12 cells. Male mice were exposed to low (5 g/kg) and high (50 g/kg) doses of BPA for six weeks. Transcriptomic analysis was performed on liver tissues, and histological examinations were conducted. AML12 cells were treated with varying BPA concentrations, and PPARG transcriptional activity was assessed using a luciferase reporter assay. Additionally, molecular docking, molecular dynamics (MD) simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), MM-PBSA calculations, and multi-species protein structure comparative analysis were employed to analyse the interaction between BPA and PPARG. Transcriptomic analysis revealed a decrease in differentially expressed genes with higher BPA doses, with low-dose exposure significantly downregulating hepatic Cpt1a mRNA levels. Histological examination indicated lipid vacuole formation at high doses without collagen deposition. BPA consistently inhibited PPARG activity in both MCF7 cells and mouse livers. BPA exposure disrupts hepatic lipid metabolism and PPARG activity, highlighting its role as an endocrine disruptor. Further research is needed to elucidate the long-term effects of BPA on liver health.
研究领域:
毒理学
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分子生物学
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代谢研究
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DOI
PubMed
高影响因子
Environmental Science-Processes & Impacts
·
2024
·
IF 4.3
Weike Zhao,Peilin Li,Bo Yang
This study evaluated the pollution characteristics, spatiotemporal distribution, and ecological risks of eight endocrine-disrupting chemicals (EDCs) in the Minjiang and Tuojiang rivers. Utilizing 3S technology (ArcGIS, remote sensing, GPS) and Fragstats, the research calculated eight landscape pattern indices related to land use types along the Minjiang river and established correlations between landscape factors and EDC distribution through stepwise multiple regression. The results indicated that bisphenol A (BPA) and nonylphenol (NP) were the most concerning EDCs, with detection frequencies of 97–100% and peak concentrations up to 63.35 ng L−1, primarily located in the middle and lower reaches of the Minjiang river and the upper reaches of the Tuojiang river. There was a significant correlation between the spatial distribution of pollutants and landscape patterns, where increased fragmentation, a higher number of patches, and complex patch shapes within a 10-kilometer buffer zone were associated with elevated levels of river pollution. By integrating four classical mathematical models to fit curves for acute and chronic toxicity data of BPA and NP, the findings suggested that BPA posed a higher ecological risk. This interdisciplinary research provided essential theoretical insights for investigating river pollution and its influencing factors, offering a new perspective on simultaneous river pollution control, urban functional zoning, and adjustment of watershed landscape spatial patterns from an urban planning standpoint.
研究领域:
环境科学
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生态学
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地理信息系统
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DOI
PubMed
高影响因子
PNAS Nexus
·
2025
·Vol. 4
·期 5
·
IF 3.8
Sun Kai,Shi Zeyu,Dai Lingzhi,Si Youbin,Ma Junchao,Lin Hui,Yu Han-Qing
Endocrine-disrupting chemicals (EDCs), such as 17β-estradiol (E2) and bisphenol A (BPA), can induce DNA damage, leading to genomic instability and cell death. Laccase, an enzyme secreted by diverse organisms, plays a critical role in mitigating the cytotoxicity of these contaminants. Despite its importance, the dynamic evolution and interaction mechanisms of EDCs and DNA in laccase catalysis remain poorly understood. This study investigates the interactions between EDCs and DNA during laccase-induced polymerization transfer at a molecular level. As the DNA concentration was increased from 0 to 7.575 nM, the pseudo-first-order kinetic constants for E2 and BPA decreased by 2.03 and 2.10 times, respectively. DNA-bound EDCs disrupted the catalytic activity and stability of laccase, thereby delaying the polymerization transfer rate of EDCs. E2 and BPA bound to DNA base pairs via groove and intercalative modes, respectively. Laccase-induced polymerization reduced damage to the DNA helix and base stacking caused by EDC binding. Moreover, the resulting DNA–EDC-precipitated polymers, formed through continuous laccase polymerization, exhibited denser and more complex structures compared with spherical EDC-precipitated polymers, confirming DNA encapsulation and/or binding. This work underscores the intramolecular mechanisms of EDC interaction with DNA in vitro during the laccase-induced polymerization, offering efficient ways to mitigate the genotoxicity of EDCs.Endocrine-disrupting chemicals (EDCs) are often described as “a ticking time bomb threatening human survival” (1). Globally, the widespread presence of both natural and synthetic EDCs, such as 17β-estradiol (E2) and bisphenol A (BPA), has raised significant concerns about their detrimental effects on wildlife and human health (2, 3). Due to their persistent and bioaccumulative nature, EDCs represent a latent crisis for both environmental and human health. Moreover, these chemicals undergo transformations in the environment to form secondary pollutants, which are often more toxic than their precursors (4). These compounds, entering organisms directly or indirectly, have been linked to reproductive disorders, deformities in sexual organs, sex reversal, and feminization in wildlife species (5). Recent studies also correlate the exposure to EDCs with increasing rates of large-bowel, breast, cervical, and ovarian cancers in women and declining sperm count and motility in men (6, 7).The hazardous effects of EDCs are attributed to their interactions with DNA, disrupting DNA repair, replication, and transcription processes, and thereby causing enhanced DNA damage and cell death (8, 9). Understanding the dynamic processes and intermolecular interactions of EDCs with DNA is crucial for elucidating their mechanisms of genotoxicity.DNA, the carrier and transmitter of hereditary information in nearly all living systems, plays a central role in vital biogenetic processes, such as gene expression, transcription, mutation, and carcinogenesis (10). Composed of pentose sugar, phosphoric acid, and nitrogenous bases, DNA's genetic information is encoded by specific sequences of these bases. The stability of the DNA helix is significantly maintained by the stacking and hydrogen-bonding interactions between nucleobases (11). Thus, the interaction of EDCs with DNA could directly impact its structure and function, leading to DNA damage in exposed cells and altering its existing functions (1). Organic pollutants of biological importance are known to interact with DNA through noncovalent interactions, including electrostatic interactions, groove binding, and intercalative binding (12–14).Laccase (EC 1.10.3.2, oxygen oxidoreductase), a member of the multicopper oxidase superfamily, is naturally secreted by a variety of organisms such as bacteria, fungi, plants, and insects. It has garnered attention for its high activity, low energy requirements, and nontoxicity in degrading harmful phenolic substances (15, 16). Laccase catalyzes the oxidation of EDCs, facilitating the formation of phenoxy radicals, which subsequently polymerize into dimers, trimers, tetramers, oligomers, and polymers (17, 18). Despite its potential, the detailed understanding of the dynamic evolution and molecular mechanisms of interaction between EDCs and DNA during laccase-induced polymerization remains scant.This work aims to elucidate, at the molecular level, the dynamic processes and interaction mechanisms between EDCs and DNA during the laccase-induced polymerization transfer. We explored the reaction kinetics of EDCs under varying DNA concentrations using a pseudo-first-order kinetic model and utilized high-resolution mass spectrometry (HRMS) to identify key oxidation products. Advanced spectroscopic techniques, such as UV-Vis spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and circular dichroism (CD) spectroscopy, were employed to reveal the dynamic interactions of DNA with EDCs during polymerization. Atomic force microscopy (AFM) was used to unmask the dynamic variations in DNA morphology on interaction with EDCs and their oligomers from the molecular perspective. Further, the precipitated polymers were characterized using scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS), FTIR, and 13C-nuclear magnetic resonance spectroscopy (13C-NMR). Molecular dynamics simulation (MDS) was conducted to verify the intermolecular interactions between DNA and the oligomers of EDCs. The cytotoxicity of DNA–EDC solutions treated by laccase-induced polymerization was evaluated over time. By uncovering the dynamic evolution and intermolecular interactions of EDCs and DNA in vitro during the laccase-induced polymerization, this study offers insights into molecular strategies for mitigating the genotoxicity of EDCs.Increasing DNA concentrations significantly impeded the laccase-induced single-electron oxidation transfer of EDCs. Figure S1 illustrates that the oxidation rates of E2 and BPA decreased from 97.25 to 80.37% and 71.64 to 54.18%, respectively, after a 3-h reaction, as the DNA concentration was increased from 0 to 7.575 nM. The laccase-mediated oxidation of EDCs adhered to a pseudo-first-order kinetics model within 1 h, with k1 values for E2 and BPA decreasing by factors of 2.03 and 2.10, respectively, as the DNA concentration was increased (R2 = 0.96–0.99). This suggests that laccase activity was inversely related to the DNA concentration during the enzyme-catalyzed oxidation of EDCs (Fig. S2). Linear regression analysis further elucidated the dependency of the k1 value on low DNA concentration (0–0.7575 nM), revealing a linear relationship (R2 ≥ 0.98) and calculated pseudo-second-order rate coefficients (k2) for E2 and BPA of 1.52 and 0.33 nM−1·h−1, respectively (Fig. 1a and b).High levels of phenoxy radicals, produced by the laccase-induced oxidation of EDCs, facilitated the polymerization transfer. HRMS identified the polymerization products, revealing their molecular architectures through computational analysis (Table S1 and Fig. 1c). Notably, three major E2 oligomers—dimer (m/z = 541.3310), trimer (m/z = 811.4930), and tetramer (m/z = 1,081.6555)—suggested the pattern of n × M − 2(n − 1) for EDC polymerization products, where n is the number of polymerized EDC monomers and M is the molecular mass of the monomer. Additionally, a peak at m/z = 269.1548 indicated the formation of estrone (E1) by deprotonation, accounting for <2.4% of the initial E2 after 1 h of reaction. This pattern was consistent with the laccase-induced polymerization of BPA, suggesting that polymerization transfer is the predominant pathway in EDC oxidation by laccase, regardless of the presence of DNA.UV-Vis absorption spectroscopy confirmed the interaction modes between DNA and EDCs. The UV-Vis absorption spectra of DNA displayed two peaks at 234 and 260 nm (Fig. S3). The addition of E2 resulted in a hyperchromic effect at 260 nm, indicating damage to the DNA helix through a nonintercalative interaction mode. The degree of E2 polymerization transfer correlated negatively with the intensities of the characteristic DNA peaks (Fig. 2a). In contrast, the interaction with BPA showed a hypochromic effect, suggesting an intercalative binding that involves strong π–π aromatic stacking interactions between BPA and the phosphate backbone of the DNA helix (19). The degree of BPA polymerization transfer correlated positively with DNA peak intensities (Fig. 2b). Clearly, laccase-induced polymerization effectively reduced the concentration of EDCs and mitigated their interaction with DNA.The molecular fingerprint of DNA is located in the spectral region of 1,800–700 cm−1 due to nitrogenous bases, phosphate, and deoxyribose stretching vibrations. Binding of EDCs to DNA bases was investigated by analyzing spectral changes at 1,691, 1,648, 1,605, and 1,485 cm−1 that were attributed to guanine, thymine, adenine, and cytosine base vibrations, respectively. FTIR spectra explored the binding sites of DNA and EDCs, with characteristic DNA peaks indicating interactions at thymine and adenine bases, which appeared to be primary binding sites for EDCs (Fig. 2c and d). CD spectroscopy further revealed conformational changes in DNA induced by EDCs, highlighting the distinct interaction modes of E2 and BPA with DNA. The upward shift in the positive peak suggested enhanced base stacking due to groove binding by E2, while the downward shift in the negative peak for BPA indicated intercalative binding (Fig. 2e and f).AFM does not require any additional sample pretreatment to observe samples in liquids, making it exceptionally suitable for DNA imaging and therefore plays an important role in probing the intermolecular interactions of EDCs and DNA during the laccase-induced polymerization. AFM offered direct evidence of DNA binding with EDCs at the molecular level (Fig. 3). No obvious change in the contour length of DNA was observed in the presence of E2, confirming that E2 bound to DNA by groove mode (Fig. 3a). However, the interaction of intercalating BPA with DNA could lead to an increase in the contour length of DNA by bridging two or more DNA molecules (Fig. 3e). Further, the enhanced degree of EDC polymerization boosted DNA encapsulation and/or binding, forming larger spherical particles (Fig. 3b–d and f–h).SEM analysis showed that compared with the spherical E2-precipitated polymers, DNA–E2-precipitated polymers displayed a denser and thicker morphology, indicative of tighter and more complex structural integration (Fig. 4a and b). EDS confirmed a lower carbon-to-oxygen ratio in the DNA–E2-precipitated polymers compared with those without DNA, suggesting more extensive oxygen bonding. A similar phenomenon was also found in the BPA and DNA–BPA-precipitated polymers (Fig. 4e and f). As demonstrated in Fig. 4c and g, the EDC-precipitated polymers displayed the functional characteristics of the aromatic skeleton, phenolic –OH, and ether linkage. By comparison, the intensities and positions of the above functional groups in the DNA–EDC-precipitated polymers changed unmistakably. 13C-NMR spectra of the precipitated polymers revealed a predominance of aromatic and phenolic carbon, indicating that DNA was potentially encapsulated and/or bound to the EDC-precipitated polymers during the laccase-induced polymerization and thus facilitated more complex carbon backbone formations (Fig. 4d and h).The dynamics of polymerization and the molecular interactions were extensively analyzed to elucidate the complex behavior of EDCs in the presence of DNA during laccase catalysis. These insights provide a deeper understanding of the intramolecular mechanisms through which laccase-mediated processes may mitigate the genotoxicity of EDCs, highlighting the potential applications of laccase polymerization for the decontamination and detoxification of EDCs at the molecular level.To support the above experimental results, we further explored the stability and position changes of EDCs and their oligomers binding to DNA by computer-aided MDS. Root-mean-square deviation (rmsd) serves as a measure of the stability and interaction between DNA and substrates. Higher rmsd values suggest more unstable interactions. In this study, the interactions of DNA with EDCs and their oligomers (dimer, trimer, and tetramer) were examined over a 100-ns MDS period. As illustrated in Fig. 5a–e, rmsd values for DNA-bound E2 and its oligomers ranged from 0 to 7.0 Å. The average rmsd for DNA-bound E2 was 1.05 Å, indicating more stable interactions compared with DNA-bound E2 dimer (2.68 Å), trimer (1.73 Å), and tetramer (2.10 Å). Hydrogen bonds, crucial for the affinity and selectivity of the DNA-substrate complex, diminished in number from the monomer to the oligomers, underscoring the enhanced stability of DNA-bound E2. Conversely, for BPA, the mean rmsd values increased with oligomerization; DNA-bound BPA monomer exhibited an rmsd of 3.06 Å, greater than its oligomers—dimer (1.74 Å), trimer (2.45 Å), and tetramer (2.44 Å; Fig. 5f–j), correlating with an increase in hydrogen bonds with higher molecular weights, indicating greater stability in DNA-bound BPA oligomers.As mentioned above, hydroxyl substitution facilitated the binding of EDCs and their oligomers to DNA, but the intermolecular binding was relatively unstable (rmsd > 1). Figure 6 shows the position changes of EDCs and their dimers, trimers, and tetramers relative to DNA at different simulation times. As the MDS time was increased, EDCs and their oligomers gradually deviated from the initial binding sites of DNA. Furthermore, these results also disclosed abnormal DNA structures, which were consistent with the CD spectroscopy. Overall, the MDS results confirm that EDCs and their oligomers unstably bound to their corresponding binding sites during the simulation process.The dynamic interactions and mechanisms of DNA with EDCs during the laccase-induced polymerization remain poorly understood. Laccase facilitates the one-electron oxidation of EDCs, predominantly leading to polymerization products, while DNA hampers this transfer by interacting with functional groups of DNA molecules, such as base pairs and phosphate skeletons. This interaction forms complexes of DNA-bound EDCs, which obstruct laccase's catalytic activity and stability, thereby slowing the polymerization rate of EDCs. In contrast, the polymerization products of EDCs, also bound to DNA via hydrogen bonds, form denser and thicker structures compared with those without DNA, suggesting potential encapsulation and/or binding within the DNA–EDC polymers. Understanding these dynamic processes and interactions provides insights into mitigating the genotoxicity and cancer risks associated with EDCs.The EDC polymers precipitated through laccase-induced polymerization play a crucial role in reducing the cytotoxic effects of EDCs (20). The phytotoxicity assessments of DNA–EDC solutions treated through laccase-induced polymerization, illustrated in Fig. S4, demonstrate significant reductions in EDC-induced inhibitory effects on seed germination and root elongation. For instance, the germination index (GI) of wheat seeds treated with E2 increased from 12.85% (severe inhibition) to 87.48% (no inhibition) over a 9-h laccase polymerization period. The addition of DNA maintained a GI of 57.69%, even after 9 h. Furthermore, the cytotoxicity of polymerization products diminished over time, showcasing the potential of laccase-induced polymerization in alleviating the genotoxic effects of EDCs. Significantly, microbial enzymes may degrade DNA, resulting in the release of DNA-bound EDCs. Future studies are required to explore the stability of DNA-bound EDCs and their oligomers, as well as the long-term effects of the complexes in the environment. Furthermore, the in vivo interactions of DNA with EDCs should also be explored to uncover the self-detoxification mechanisms of laccase-producing organisms at a genomic level.In summary, this work provides comprehensive insights into the complex interactions between EDCs and DNA in the context of laccase-mediated reactions. The findings reveal that DNA significantly alters the kinetics and mechanisms of EDC polymerization, potentially offering a novel approach to mitigate the environmental impact and genotoxicity of these harmful compounds. By elucidating the specific binding interactions and the resulting structural changes in DNA and EDC polymers, this research contributes to a deeper understanding of the intramolecular mechanisms of EDC interaction with DNA in vitro during the laccase-induced polymerization and opens new avenues for the development of more effective decontamination and detoxification strategies in vivo.E2 (C18H24O2, ≥98%), BPA (C15H16O2, ≥99%), double-stranded salmon testes DNA (%G-C content: 41.2%; molecular mass: 1.3 × 106 Da; DNA fragment lengths: ∼2,000 bp), and Trametes versicolor laccase (light brown, ≥0.5 U·mg−1) were sourced from Sigma-Aldrich Co., China. Methanol (CH3OH, suitable for high-performance liquid chromatography [HPLC], ≥99.9%) and acetonitrile (CH3CN, suitable for HPLC, ≥99.9%) were procured from Thermo Fisher Scientific Inc., USA. Tris-HCl buffer solution (10 mM, pH 7), citrate-phosphate buffer solution (CPBS, 10 mM), and Murashige and Skoog (MS) medium were obtained from Aladdin Chemistry Co., China. Stock solutions of E2 and BPA were prepared in methanol at 1 mM. Laccase stock solution (100 U·mL−1) and DNA stock solution (dissolving 75.75 nmol of DNA in 100 mL Tris-HCl buffer) were prepared in Milli-Q water. UV absorption at 260 nm with a molar extinction coefficient (ε260) of 6,600 L·mol−1·cm−1 was used to determine the DNA concentration in the solution. The DNA purity, indicated by an absorbance ratio at 260 and 280 nm (A260/A280) of >1.83, confirmed high purity. Wheat seeds (Triticum aestivum L.) were supplied by the Anhui Academy of Agriculture Sciences, China. All solutions were prepared using Milli-Q water (18.25 MΩ·cm) and stored at 4 °C prior to use.The reaction kinetics of EDCs catalyzed by laccase in the presence of DNA were conducted in 20 mL of CPBS at 25 ± 0.5 °C and pH 5 under dark conditions. A concentration of 0.5 U·mL−1 laccase was added to solutions containing 5 μM of either E2 or BPA and varying concentrations of DNA (0–7.575 nM). Periodically, 0.5 mL samples were extracted from the reaction mixture, quenched immediately with an equivalent volume of methanol, and filtered through a 0.22-μm membrane for analysis. Experiments were replicated in triplicate, and the oxidation kinetics of EDCs were modeled by pseudo-first-order kinetics:where k1 is the pseudo-first-order rate constant and [EDCs] is the residual concentration of free EDCs in the reaction system at a given time.Details on the determination of laccase activity are provided in the Supporting Information.Quantitative and qualitative analyses, including HPLC and HRMS, are described in the Supporting Information.The interaction mode between DNA and EDCs during enzymatic catalysis was examined using a UV-Vis spectrophotometer (UV-2550, Shimadzu Co., Japan) equipped with 1 cm quartz cuvettes. Samples were analyzed at preset intervals (0, 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 min) for UV absorption spectrum (220–300 nm) in 1-nm increments at 25 ± 0.5 °C. ATR-FTIR spectroscopy (NEXUS-870, Thermo Nicolet Co., USA) and CD spectroscopy (Chirascan, APL, UK) were also employed to further explore the binding mechanism between DNA and EDCs.The morphological changes of DNA binding to EDCs and their oligomers were directly observed by AFM. DNA (7.575 nM) and EDCs (5 μM) were incubated at 25 ± 0.5 ° C and pH 5.0 to ensure that EDCs were adequately bound to DNA. Next, the enzymatic reaction was initiated by adding 0.5 U·mL−1 laccase to the mixture. By adjusting the pH of the mixture to 1.5, the enzymatic reaction was periodically terminated. To prepare the sample for AFM, 50 μL of the mixed solution was pipetted onto freshly cracked mica sheets, gently washed with ultrapure water and air-dried, and then imaged by AFM (Dimension Icon, Bruker Co., USA). AFM images were recorded at a resolution of 500 × 500 pixels and a scanning line speed of 0.600–0.998 Hz.Precipitated polymers collected from the laccase-induced polymerization transfer of EDCs were freeze-dried, ground, and sieved. Their microstructures, functional groups, and chemical compositions were characterized using SEM (Regulus 8100, Hitachi, Japan) equipped with an EDS (Bruker Co., Germany), FTIR, and 13C-NMR (Avance III, Bruker Co., Germany).MDS was performed to model the interaction of DNA with EDCs and their oligomers (dimer, trimer, and tetramer). The 3D structure of B-DNA dodecamer d(CGCGAATTCGCG)2 was sourced from the Protein Data Bank (PDB ID: 2B0 K). The structures of EDCs and their oligomers were built using ChemBioDraw Ultra 14.0, optimized with ChemBio3D Ultra 14.0, with nonpolar hydrogen atoms merged and Kollman charges added using MGLTools 1.5.6. Simulations were conducted using GROMACS 2016.4 with the AMBER99SB force field. Rmsd was calculated to assess the stability of each complex:where Natm is the number of atoms, rA is the position of atom A, and rAref is the reference position of atom A.The phytotoxicity of DNA and EDC solutions treated by laccase-induced polymerization was evaluated using a GI. Wheat seeds were monitored over a 3-day cultivation period in MS medium under controlled conditions. The GI was calculated using the formula:where NCRS and NMW are the number of seeds germinated in the reaction solution and Milli-Q water, respectively, and RCRS and RMW are the root lengths in the reaction solution and Milli-Q water, respectively.Supplementary material is available at PNAS Nexus online.This work was financially supported by the National Natural Science Foundation of China (42277019 and 51821006) and the Natural Science Foundation-Excellent Youth Fund Project of Anhui Province, China (2308085Y28).K.S., Z.S., and J.M. were involved in data curation and formal analysis. L.D. was involved in formal analysis. Y.S. was involved in software, validation, and writing—review and editing. H.L. was involved in software and validation. H.-Q.Y. was involved in conceptualization, resources, supervision, funding acquisition, writing—original draft, project administration, and writing—review and editing.All data are included in the article and Supporting Information.
研究领域:
环境科学
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分子生物学
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2021
·Vol. 29
·期 4
·6360-6374
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IF 4.223
Wu Jiawei,Xie Haijian,Zhang Chunhua,Bouazza Abdelmalek,Sun Zhilin,Qiu Zhanhong
The leakage of chemical compounds in landfill leachate led to serious environment pollution, especially, the compounds termed endocrine disruptors such as bisphenol A (BPA). It is very important to study the adsorption behavior of endocrine disruptors in modified soil for predicting and evaluating the potential harm of endocrine disruptors to the soil. Bentonite-amended Chinese loess mixtures, with various proportions of bentonite, were used for the removal of BPA from an aqueous solution. A batch test was used to investigate the adsorption properties of bisphenol A on bentonite and Chinese loess mixtures. The influences of bentonite proportion, temperature, reaction time, pH, and soil-water ratios on the adsorption process were considered. The Fourier transform infrared spectra (FTIR) was used to clarify the change of functional groups before and after the adsorption of BPA on soil. The adsorption mechanism of BPA on soil was discussed preliminary. The results show that the addition of bentonite to the loess can improve the adsorption rate of BPA. The adsorption of BPA was mainly a spontaneous, exothermic, entropy decreasing physical adsorption process. The interaction between bentonite content and reaction concentration had a beneficial effect on BPA adsorption. The linear relationship between bentonite content and adsorption capacity was obtained. The results indicate that bentonite amended loess can provide a good liner for BPA.
研究领域:
环境科学
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土壤学
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PubMed
高影响因子
CANCER LETTERS
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2024
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IF 9.1
Chunyu Liu,Jiawei Chen,Yukun Cong,Kang Chen,Haoran Li,Qingliu He,Liang Chen,Yarong Song,Yifei Xing
With the widespread use of anti-androgen therapy, such as abiraterone and enzalutamide, the incidence of neuroendocrine prostate cancer (NEPC) is increasing. NEPC is a lethal form of prostate cancer (PCa), with a median overall survival of less than one year after diagnosis. In addition to the common bone metastases seen in PCa, NEPC exhibits characteristics of visceral metastases, notably liver metastasis, which serves as an indicator of a poor prognosis clinically. Key factors driving the neuroendocrine plasticity of PCa have been identified, yet the underlying mechanism behind liver metastasis remains unclear. In this study, we identified PROX1 as a driver of neuroendocrine plasticity in PCa, responsible for promoting liver metastases. Mechanistically, anti-androgen therapy alleviates transcriptional inhibition of PROX1. Subsequently, elevated PROX1 levels drive both neuroendocrine plasticity and liver-specific transcriptional reprogramming, promoting liver metastases. Moreover, liver metastases in PCa induced by PROX1 depend on reprogrammed lipid metabolism, a disruption that effectively reduces the formation of liver metastases.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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PubMed
高影响因子
CHEMOSPHERE
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2025
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IF 8.1
Siyu Liu,Xinyue Zhao,Yaobin Ding,Lina Wang,Yiyang Li,Jun He,Chengjun Wang
Water microdroplets are ubiquitous in atmospheric environment, where photo-irradiation and O 3 are available, while photo-decomposition of trace organic pollutants in microdroplets and the impact of atmospheric environmental factors on the photo-chemistry remain unclear. In this study, photochemical generation of reactive oxygen species and degradation of typical endocrine disturbing compounds (EDCs) in microdroplets were investigated under various atmospheric conditions (O 3 , inorganic anions and fulvic acid). The experimental results demonstrate that EDCs can be degraded in microdroplets, and the degradation efficiency is further improved under the stimulated solar irradiation. The degradation efficiency of estrone (E1), estradiol (E2), ethinyl estradiol (EE2), testosterone (T) exposing to sunlight irradiation is 55.45 %, 64.11 %, 89.72 %, and 24.72 %, respectively. The degradation of EDCs is attributed to the generation of hydroxyl and superoxide radicals at or near the microdroplets interface. In addition, with O 3 , the degradation efficiency of EDCs in microdroplets increased to 100 %, 100 %, 100 %, and 83.87 %, respectively. Common inorganic ions (Cl − , NO 3 − , SO 4 2− , and HCO 3 − ) and fulvic acid exhibit positive effects for degradation of EDCs at varying extents. Overall, these findings shed light on the generation of reactive oxygen species and degradation patthways of trace EDCs in microdroplets and improve the understanding of the effect associated with relevant environmental factors in atmospheric microdroplets.
研究领域:
环境科学
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生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Chenhuan Wang,Qianqian Wang,Junmin Wang,Kaiyuan Si,Huajie Zhu,Qiuhua Wu
There is an immediate need for meticulous design of easily accessible, cost-effective, chemically stable and eco-friendly materials for effectively removal of water contaminant. Herein, targeting typical water contaminants, endocrine disrupting chemicals (EDCs), three cationic hyper-cross-linked porous polymers (ciHCP-1, ciHCP-2, ciHCP-3) with multiple adsorption sites were designed with 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as precursor. The ciHCP-3 with large surface area (806 m 2 g −1 ) exhibited high sorption capacity (137–366 mg g −1 ), and fast adsorption kinetics (5 min) for the EDCs, which is superior to the reported sorbents. The adsorption mechanisms can be attributed to the synergistic effect of physisorption and chemisorption. The high preparation reproducibility, physicochemical stability, and reuse capability of ciHCP highlights its great potential in practical water remediation applications.
研究领域:
环境科学
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材料科学
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化学工程
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PubMed
高影响因子
CHEMOSPHERE
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2019
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IF 5.108
Shuying Li,Hongbing Jiang,Kun Qiao,Wenjun Gui,Guonian Zhu
Silkworm ( Bombyx mori ) is one of the most important economic insects in the world, while pesticides impact its economic benefits. Tebuconazole is a fungicide that has been frequently detected in agriculture systems at concentrations that affect endocrine function in organisms. In the present study, silkworm larvae at different instar stages were exposed to tebuconazole, respectively. Cocoon weight, cocoon shell weight and cocoon shell rate were significantly decreased by 6.8%, 11.8% and 4.4% respectively, after exposure to 0.40 mg/L tebuconazole at 2nd -3rd instar stage. Vacuolization was found in the exposure silkworm under histopathological study at all stages exposures, indicating potential damage to silk gland. Downregulation of genes transcription ( Fibh , Fibl , P25 , Ser2 , Ser3 ) involved with protein synthesis in the silk gland were further observed, and the results showed significant decreasing in mRNA expression among the tebuconazole treatments. Ecdysteroid levels in silkworm were changed with pronounced decreases after exposed to tebuconazole. In contrast, exposure to tebuconazole significantly increased juvenile hormone 1 concentrations and the maximum increasing fold of juvenile hormone 1 was up to 3.73 which was observed at stage I exposure. In addition, co-exposure to 2 and 10 mg/L forskolin able to mitigate tebuconazole-induced downregulate of mRNA expression of Sgf1 in the present study, indicating the potential mechanism of tebuconazole-induced chronic toxicity in silkworm may relative to PI3K/AKT/TORC1/Sgf1 pathway.
研究领域:
昆虫学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 13
·10898
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IF 5.6
Zhiying Liang,Yafen Guo,Duan Pi,Xiang Li,Bingying Li,Yongsi Huang,Xiaohong Song,Ramji Kumar Bhandari,Xuegeng Wang
Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka (Oryzias sinensis). In the acute toxic exposure, the LC50of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.Keywords:Bisphenol F;Chinese medaka;toxicity;developmental defects;endocrine disruptor
研究领域:
环境科学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
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2024
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IF 4.1
Chunyun Zhang,Luoxin Li,Juan Jose Alava,Zebang Yan,Peng Chen,Yasmeen Gul,Lixin Wang,Dongmei Xiong
Nanoplastics (NPs) have been commonly detected in aquatic ecosystems, and their negative effects on aquatic organisms have raised concerns in the scientific community and general public. The acute toxicity, neurotoxicity, and metabolic toxicity induced by NPs on fishes have been reported by many studies, although less attention has been focused on how mother exposed to NPs affected their offspring in aquatic organisms. Here, female zebrafish (F0) were exposed to 0, 200 and 2000 μg/L polystyrene nanoplastics (PS-NPs) for 42 d, with their offspring (F1) reared in clear water until sexual maturity. The results showed that PS-NPs were detected in various organs of F0 and F1. PS-NPs exposure significantly decreased gonadal 17-estradiol (E2), while increasing testosterone (T) contents. Lower levels of cyp19a1a, lhr and erα expressions in the 2000 μg/L group were consistent with a reduced number of mature oocytes (MO), but an increase in perinucleolar oocytes (PO). Interestingly, the expression of vtg was only up-regulated by 200 μg/L PS-NPs. After exposure, the egg production was dramatically reduced, but the hatching rate and heartbeat of F1 embryos from treated females were significantly higher than those observed in females from the control group. Maternal PS-NPs exposure significantly decreased the E2 and T levels in F1 adults, while PS-NPs exposure significantly up-regulated the sox9a but down-regulated the foxl2a in F1 larvae of 30 days post fertilization (dpf). This study showed that PS-NPs caused reproductive toxicity by changing the hypothalamic-pituitary-gonadal (HPG) axis-related genes, impairing the reproductive capacity of female zebrafish, affecting the development and disrupting the endocrine function of F1. These results suggested that PS-NPs had adverse effects on fish reproductive system both in the directly exposed generation and in their unexposed offspring.
研究领域:
环境科学
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毒理学
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生态学
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鱼类生物学
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DOI
PubMed
高影响因子
Journal of Environmental Sciences
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2024
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IF 5.9
Shike Zhang,Xinyi Su,Jiada Zhang,Tingting He,Lei Tang,Zepei Zhao,Linying Cao
N-phenyl-N′-(1,3-dimethylbutyl)-p-phenylenediamine (6PPD) is a tire rubber antioxidant that can be oxidized to form derivative 6PPD-quinone (6PPD-Q). 6PPD and 6PPD-Q have been detected in human urine with concentrations reaching nanomolar levels. However, their human adverse effects and toxic mechanism are not explicit. This study elucidated their lipid metabolism disruption effects on hepatic cells (HepG2) and revealed a potential molecular mechanism via estrogen-related receptor γ (ERRγ) pathway. The results of fluorescence competitive binding assay showed that 6PPD and 6PPD-Q could bind to ERRγ with an IC 50 (the concentration of a ligand competing 50% probe from ERRγ) of 9 nmol/L and 6 nmol/L, respectively. The reporter gene assay indicated that 6PPD-Q activated ERRγ in a concentration-dependent mode with the lowest observable effective concentration (LOEC) of 100 nmol/L and the maximum induction rate of 320%, while 6PPD displayed weak ERRγ activity. The molecular docking showed that the binding energies of 6PPD/6PPD-Q with agonistic ERRγ were much lower than those with antagonistic ERRγ, implying that 6PPD/6PPD-Q tended to display ERRγ agonistic binding mode. The BODIPY fluorescence staining and triglyceride (TG) assay revealed that 6PPD and 6PPD-Q promoted lipid accumulation and TG production in HepG2 cells with LOEC of 10 nmol/L and 100 nmol/L, respectively. The ERRγ antagonist (GSK5182) co-exposure reversed the lipid induction effects of 6PPD/6PPD-Q, which confirmed the regulatory roles of ERRγ. Overall, our study revealed a novel endocrine disruption mechanism of 6PPD and 6PPD-Q via ERRγ and their hepatic lipid inducing risks, providing novel information for their health hazard evaluation.
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）