Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Oxidation-reduction process of Arabidopsis thaliana roots induced by bisphenol compounds based on RNA-seq analysis.

Bisphenol compounds (BPs) have various industrial uses and can enter the environment through various sources. To evaluate the ecotoxicity of BPs and identify potential gene candidates involved in the plant toxicity, Arabidopsis thaliana was exposed to bisphenol A (BPA), BPB, BPE, BPF, and BPS at 1, 3, 10 mg/L for a duration of 14 days, and their growth status were monitored. At day 14, roots and leaves were collected for internal BPs exposure concentration detection, RNA-seq (only roots), and morphological observations. As shown in the results, exposure to BPs significantly disturbed root elongation, exhibiting a trend of stimulation at low concentration and inhibition at high concentration. Additionally, BPs exhibited pronounced generation of reactive oxygen species, while none of the pollutants caused significant changes in root morphology. Internal exposure concentration analysis indicated that BPs tended to accumulate in the roots, with BPS exhibiting the highest level of accumulation. The results of RNA-seq indicated that the shared 211 differently expressed genes (DEGs) of these 5 exposure groups were enriched in defense response, generation of precursor metabolites, response to organic substance, response to oxygen-containing, response to hormone, oxidation-reduction process and so on. Regarding unique DEGs in each group, BPS was mainly associated with the redox pathway, BPB primarily influenced seed germination, and BPA, BPE and BPF were primarily involved in metabolic signaling pathways. Our results provide new insights for BPs induced adverse effects on Arabidopsis thaliana and suggest that the ecological risks associated with BPA alternatives cannot be ignored.

Immobilization of laccase on magnetic PEGDA-CS inverse opal hydrogel for enhancement of bisphenol A degradation in aqueous solution.

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.

Degradation of bisphenol F by peroxymonosulfate activated with palladium-based catalysts.

In this study, supported Pd catalysts were prepared and used as heterogeneous catalysts for the activation of peroxymonosulfate (PMS) which successfully degrade bisphenol F (BPF). Among the supported catalysts (i.e., Pd/SiO2, Pd/CeO2, Pd/TiO2 and Pd/Al2O3), Pd/TiO2 exhibited the highest catalytic activity due to the high isoelectric point and high Pd0 content. Pd/TiO2 prepared by the deposition method leads to high Pd dispersion, which are the key factors for efficient BPF degradation. The influencing factors were investigated during the reaction process and two possible degradation pathways were proposed. Density functional theory (DFT) calculations demonstrate that stronger BPF adsorption and BPF degradation with lower reaction barrier occurs on smaller Pd particles. The catalytic activities are strongly dependent on the structural features of the catalysts. Both experiments and theoretical calculations prove that the reaction is actuated by electron transfer rather than radicals.

Bisphenol S decreased lifespan and healthspan via insulin/IGF-1-like signaling-against mitochondrial stress in Caenorhabditis elegans.

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 µg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.

Bisphenol A induces lipid metabolism disorder and impairs hepatopancreas of Sesarmops sinensis.

Bisphenol A (BPA) is a chemical that disrupts the endocrine system and may have negative implications on the lipid metabolism of organisms. To ascertain BPA implications on lipid metabolism in the hepatopancreas of Sesarmops sinensis, we exposed S. sinensis to different concentrations of BPA for 14 days. The outcomes manifested that BPA may stimulate hepatopancreas injury and lipid deposition in the hepatopancreas of S. sinensis and lead to the increase of hepatosomatic index (HSI). Transcriptome analysis showed that lipid metabolism-related pathways were significantly enriched in KEGG pathways. BPA exposure also caused disorders in lipid metabolism by altering fatty acid composition and lipid metabolites. The up-regulation of lipid synthesis genes and the alteration of lipid transport genes may be important reasons for the disorder of lipid metabolism. Furthermore, these outcomes provide a fresh point of reference for comprehending the ecotoxicological impacts of BPA on aquatic organisms.

Bisphenol AP inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes.

Bisphenol A (BPA) is among the extensively researched environmental endocrine-disrupting chemicals (EDCs), and its utilization is restricted owing to the detrimental impacts it has on human health. Bisphenol AP (BPAP) is one of the alternatives to BPA, but the influence of BPAP on human health has not been elucidated. The objective of the current research was to determine the influence of BPAP exposure on the in vitro maturation of mouse oocytes and to explore its potential reproductive toxicity. BPAP exposure was found to inhibit polar body extrusion during mouse oocyte maturation, resulting in an arrest at the metaphase I stage of meiosis. Exposure to BPAP led to sustained activation of BubR1, preventing the degradation of both Securin and Cyclin B1. Mechanistically, BPAP exposure disrupts spindle assembly and chromosome alignment. Levels of acetylated α-tubulin were significantly elevated in BPAP-treated oocytes, reflecting decreased spindle stability. Exposure to BPAP also induced DNA damage and impaired DNA damage repair. In addition, BPAP exposure altered histone modification levels. In summary, this investigation suggests that exposure to BPAP can influence cytoskeletal assembly, interfere with cell cycle progression, induce DNA damage, alter histone modifications, and ultimately impede oocyte meiotic maturation. This investigation enhances understanding of the impact of bisphenol analogs on female gametes, underscoring that BPAP cannot be considered a reliable replacement for BPA.

Detecting Bisphenol A Leaching from Four Different Commercially Available Clear Aligner Sheets: An Ex Vivo Study.

AIM: The study aimed to detect and quantify bisphenol A (BPA) leaching in salivary samples of patients undergoing clear aligner therapy (CAT) using four different commercially available sheets. MATERIALS AND METHODOLOGY: Four different commercially available clear aligners namely Monoflex®, Erkodur®, Leone®, and Duran® were delivered to 20 volunteers who were grouped into (n = 5) group A, group B, group C, and group D, respectively. Salivary samples were collected immediately before aligner insertion (day 0) and at day 1, day 5, and day 7 after aligner wear. Comparisons were made between baseline (day 0) BPA levels and subsequent time points to assess the leaching kinetics of BPA from the clear aligners by liquid chromatography/mass spectrometry. RESULTS: The overall mean leaching of 0.74 ± 0.33 ppm at T1 (day 1) was observed among four groups of aligners, while no leaching was detected at T5 (day 5) and T7 (day 7). Among the four groups, the highest leaching of 1.24 ppm was detected from Duran at T1 followed by Monoflex (0.76 ppm), Erkodur (0.56 ppm), and Leone (0.43 ppm). CONCLUSION: It can be concluded that leaching only during the first 24 hours of aligner usage was dominant compared to other time intervals. Among the aligners considered, Duran was found to be the least safe followed by Monoflex, Erkodur, and Leone. CLINICAL SIGNIFICANCE: Since aligners are expanding in usage it is important to consider their biocompatibility. Even though the results indicate minimal leaching of BPA, it has a cumulative negative effect when patients undergo prolonged treatment with aligners. How to cite this article: Azhagudurai N, Rajendran R, Aishwarya K, et al. Detecting Bisphenol A Leaching from Four Different Commercially Available Clear Aligner Sheets: An Ex Vivo Study. J Contemp Dent Pract 2024;25(6):535-539.

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort.

BACKGROUND: Exposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC). METHODS: During the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed. RESULTS: Bisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols. CONCLUSION: Higher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.

GC-MS metabolomics of French lettuce (Lactuca Sativa L. var capitata) leaves exposed to bisphenol A via the hydroponic media.

INTRODUCTION: Bisphenol A (BPA), an organic compound used to produce polycarbonate plastics and epoxy resins, has become a ubiquitous contaminant due to its high-volume production and constant release to the environment. Plant metabolomics can trace the stress effects induced by environmental contaminants to the variation of specific metabolites, making it an alternative way to study pollutants toxicity to plants. Nevertheless, there is an important knowledge gap in metabolomics applications in this area. OBJECTIVE: Evaluate the influence of BPA in French lettuce (Lactuca Sativa L. var capitata) leaves metabolic profile by gas chromatography coupled to mass spectrometry (GC-MS) using a hydroponic system. METHODS: Lettuces were cultivated in the laboratory to minimize biological variation and were analyzed 55 days after sowing (considered the plant's adult stage). Hexanoic and methanolic extracts with and without derivatization were prepared for each sample and analyzed by GC-MS. RESULTS: The highest number of metabolites was obtained from the hexanoic extract, followed by the derivatized methanolic extract. Although no physical differences were observed between control and contaminated lettuce leaves, the multivariate analysis determined a statistically significant difference between their metabolic profiles. Pathway analysis of the most affected metabolites showed that galactose metabolism, starch and fructose metabolism and steroid biosynthesis were significantly affected by BPA exposure. CONCLUSIONS: The preparation of different extracts from the same sample permitted the determination of metabolites with different physicochemical properties. BPA alters the leaves energy and membrane metabolism, plant growth could be affected at higher concentrations and exposition times.

Sub-acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice.

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.

A novel visible light-driven oxygen doped C3N4/Bi12O17Cl2/ferrate(VI) system for Bisphenol A degradation: Radical and nonradical pathways.

In this study, visible light-activated photocatalyst oxygen-doped C3N4@Bi12O17Cl2 (OCN@BOC) and Fe(VI) coupling system was proposed for the efficient degradation of bisphenol A (BPA). The comprehensive characterization of the OCN@BOC photocatalyst revealed its excellent photogenerated carrier separation rate in heterogeneous structures. The OCN@BOC/Fe(VI)/Vis system exhibited a remarkable BPA removal efficiency of over 84% within 5 min. Comparatively, only 37% and 59% of BPA were degraded by single OCN@BOC and Fe(VI) in 5 min, respectively. Reactive species scavenging experiments, phenyl sulfoxide transformation experiments, and electron paramagnetic resonance experiments confirmed the involvement of superoxide radicals (⋅O2-), singlet oxygen (1O2), as well as iron(V)/iron(IV) (Fe(V)/Fe(IV)) species in the degradation process of BPA. Furthermore, density functional theoretical calculations and identification of intermediates provided insights into the potential degradation mechanism of BPA during these reactions. Additionally, simulation evaluations using an ecological structure activity relationship model demonstrated that the toxicity of BPA to the ecological environment was mitigated during its degradation process. This study presented a novel strategy for removing BPA utilizing visible light photocatalysts, highlighting promising applications for practical water environment remediation with the OCN@BOC/Fe(VI)/Vis system.

Sustainable hydrochar as an efficient persulfate activator for cost-effective degradation of bisphenol A.

This study explored Mason pine-derived hydrochar (MPHC) as an effective adsorbent and persulfate (PS) activator for degrading bisphenol A (BPA). Increasing MPHC dosage from 0.25 to 2.0 g L-1 raised BPA removal from 42% to 87%. Similarly, at the same MPHC dosage range and fixed PS concentration (8 mM), BPA removal by MPHC/PS increased from 66% to 91%. Additionally, at a fixed MPHC dosage (1.0 g L-1), higher PS concentrations (2-32 mM) resulted in an overall BPA removal increase from 78% to 99%. The optimal pH for BPA removal by MPHC was at pH 3, while for MPHC/PS was at pH 9. BPA degradation by MPHC was optimal at pH 3, whereas MPHC/PS was at pH 3 and pH 9. Additionally, pH 7 favored BPA adsorption for both MPHC and MPHC/PS. The study also considered the influence of coexisting anions and humic acid (HA). PO43- and NO3- influence adsorption on MPHC, but these anions' effect on MPHC/PS is limited. Furthermore, the existence of HA had minimal influence on BPA removal by MPHC/PS. The contributions of different reactive species by MPHC for BPA degradation are as follows: electron-hole (h+) 2%, singlet oxygen (1O2) 7%, superoxide radicals (O2•-) 13%, electron (e-) 2%, hydroxyl radical (•OH) 3%, whereas the remaining 48% removal was the contribution of adsorption. For MPHC/PS, adsorption accounted for 39 %, more reactive species were involved in degradation, and the donations are (h+) 3%, sulfate radicals (SO4•-) 3%, (1O2) 19%, (O2•-) 15%, (e-) 2%, and (•OH) 2%. Additionally, the performance of MPHC remains stable after three operational cycles. The preparation cost of MPHC is 3.01 € kg-1. These results highlight the potential of MPHC as an environmentally friendly material for activating PS and removing organic pollutants, suggesting its promising application in future environmental remediation efforts.

Subchronic toxic effects of bisphenol A on the gut-liver-hormone axis in rats via intestinal flora and metabolism.

Background: Bisphenol A (BPA), a characteristic endocrine disruptor, is a substance that seriously interferes with the human endocrine system and causes reproductive disorders and developmental abnormalities. However, its toxic effects on the gut-liver-hormone axis are still unclear. Method: Male and female rats were exposed to BPA (300 mg/kg) by oral gavage for 60 consecutive days. H&E staining was used for histopathological evaluation, and the serum biochemical indexes were determined using an automatic analyzer. The 16S rRNA gene sequencing was used to detect the intestinal microbial diversity, and the GC-MS was used to analyze the contents of short-chain fatty acids (SCFAs) in colon contents. UPLC-QTOF MS was used to analyze the related metabolites. The ELISA method was used to assess the levels of serum inflammatory factors. Results: Histopathological analysis indicated that the liver, heart, and testis were affected by BPA. There was a significant effect on alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the male-BPA group (P < 0.05), and globulin (GLB), indirect bilirubin (IBIL), alkaline phosphatase (ALP), ALT, TG, TC, high-density lipoprotein (HDL), and creatinine (Cr) in the female-BPA group (P < 0.05). Metagenomics (16S rRNA gene sequencing) analysis indicated that BPA reduced the diversity and changed the composition of gut microbiota in rats significantly. Compared with the control and blank groups, the contents of caproic acid, isobutyric acid, isovaleric acid, and propanoic acid in the colon contents decreased in the male-BPA group (P < 0.05), and caproic acid, isobutyric acid, isovaleric acid, and valeric acid in the colon contents decreased in the female-BPA group (P < 0.05). Metabolomic analysis of the serum indicated that BPA could regulate bile acid levels, especially ursodeoxycholic acid (UDCA) and its conjugated forms. The contents of amino acids, hormones, and lipids were also significantly affected after exposure to BPA. The increase in interleukin-6 (IL-6), interleukin-23 (IL-23), and transforming growth factor-ß (TGF-ß) in the serum of the male-BPA group suggests that BPA exposure affects the immune system. Conclusion: BPA exposure will cause toxicity to rats via disrupting the gut-liver-hormone axis.

Enhanced chemiluminescence by carbon dots for rapid detection of bisphenol A and nitrite.

Herein, a novel chemiluminescence (CL) sensor was successfully developed based on chlorine doped carbon dots (Cl/CDs) for the rapid determination of bisphenol A (BPA) and nitrite. The Cl/CDs were synthesized through a hydrothermal method, using ascorbic acid as the precursor and hydrochloric acid as the dopant. It was found that Cl/CDs significantly enhanced the CL intensity of the acid-KMnO4 system, while BPA and nitrite quenched the CL intensity of the Cl/CDs-sensitized acid-KMnO4 system. Under optimal conditions, BPA exhibited a linear detection range of 0.05-10 µM, with limits of detection (LOD) and quantification (LOQ) of 0.86 nM and 2.8 nM, respectively. Nitrite showed a linear detection range of 0.7-100 µM, with LOD and LOQ of 22.5 nM and 75 nM, respectively. The CL sensor was successfully use to determine BPA in water samples and nitrite in pickles, ham and celery, with spike recovery rates of 96.3 %-104.8 % and 96.0 %-104.9 %, respectively.

Highly efficient activation of peroxymonosulfate via KOH-activated Fe@NC for the degradation of bisphenol A.

In this study, the KOH-modified Fe-ZIF-derived carbon materials (Fe@NC-KOH-x) were designed for Fenton-like systems to enhance bisphenol A (BPA) removal from wastewater. Compared with the Fe@NC without KOH activation, the pore structure, BET (Brunner-Emmet-Teller) surface area, and oxygen-containing functional group of KOH-activated Fe@NC-KOH-x are dramatically improved, which increases the adsorption and catalytic performance. The Fe@NC-KOH-900/PMS system showed significant BPA removal reactivity across wide pH ranges and low doses of Fe@NC-KOH-900. Interestingly, our findings indicated that the removal effectiveness of BPA improved when PMS was introduced following the saturation adsorption of Fe@NC-KOH-x, as compared to the simultaneous introduction of Fe@NC-KOH-x and PMS. More particularly, through regression analysis, we found that the proportion of reactive species in the Fe@NC-KOH-x/PMS system changes with the increase of pyrolysis temperature, and there was a certain relationship between structure-function and active species in the Fe@NC-KOH-x/PMS system. O-C = O, Fe-N4, C-O, and pyrrolic N in Fe@NC-KOH-x lead to the generation of •OH, and SO4-•, C = O, Fe-N4, and defect are closely related to FeIV = O, and the formation of 1O2 is affected by Fe-N4, graphite N, C = O, and defect. Also, the density functional theory (DFT) calculation and the potential correlation between catalyst active centers and reactive oxygen species indicate that Fe-N4 is the main active site of Fe@NC-KOH-x. These outcomes of the study offer an innovation for enhanced elimination of BPA in wastewater treatment and provide a dynamic understanding of the mechanism of BPA degradation.

Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation.

Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system.

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure.

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

Exposure and potential risks of thirteen endocrine- disrupting chemicals in pharmaceuticals and personal care products for breastfed infants in China.

Ingestion of breast milk represents the primary exposure pathway for endocrine-disrupting chemicals (EDCs) in newborns. To elucidate the associated risks, it is essential to quantify EDC levels in both breast milk and infant urine. This study measured the concentrations of 13 EDCs, including parabens (methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), iso-propyl paraben, butyl paraben, and iso-butyl paraben), bisphenols (bisphenol A (BPA), bisphenol F, bisphenol S, bisphenol AF, and bisphenol Z), triclosan (TCS), and triclocarban, in breast milk and infant urine to assess their potential health effects and endocrine disruption risks. In total, 1 014 breast milk samples were collected from 20 cities across China, along with 144 breast milk samples and 134 urine samples from a mother-infant cohort in Hangzhou. The EDCs were detected using ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry. Endocrine-disrupting potency was evaluated using a predictive method based on EDC affinity for 15 hormone receptor proteins. The toxicological priority index (ToxPi), incorporating population exposure data, was employed to assess health risks associated with exposure to multiple EDCs. Among the 13 EDCs, MP, EP, PP, BPA, and TCS were detected in over 50 % of breast milk samples, with the highest median concentrations observed for MP (0.37 ng/mL), EP (0.29 ng/mL), and BPA (0.17 ng/mL). Across the 20 cities, 0 %-40 % of infants had a hazard index (HI) exceeding 1. Based on affinity prediction analysis and estimated exposure, cumulative endocrine disruption risk intensity was ranked as MP > TCS > BPA > EP > PP. This research highlights the extensive exposure of Chinese infants to EDCs, offering a detailed analysis of their varying endocrine disruption potencies and underscoring the significant health risks associated with EDCs in breast milk.

Safe concentration, unsafe effects: Impact of BPA on antioxidant function in the hepatopancreas and ovarian gene expression in oriental river prawns (Macrobrachium nipponense).

This study investigated the effects of Bisphenol A (BPA), a common endocrine-disrupting chemical, on the antioxidant enzyme activities in the hepatopancreas and the expression of genes related to ovarian development in oriental river prawns (Macrobrachium nipponense). The 24hLC50 and 48hLC50 values for BPA were 80.59 mg/L and 63.90 mg/L, respectively, with a safe concentration of 12.06 mg/L. Prawns were exposed to low (4.85 mg/L), safe (12.06 mg/L), and high (30.00 mg/L) concentrations of BPA for 10 days to measure enzyme activities, and for 20 days followed by 7 days in BPA-free water to measure gene expression. Short-term exposure (12 h, 1d, 3d) to low concentration BPA did not significantly affect superoxide dismutase (SOD) activity in the hepatopancreas (P > 0.05), but long-term exposure (6d, 10d) significantly reduced SOD activity (P < 0.05). Catalase (CAT) activity showed no significant changes throughout the low concentration exposure period (P > 0.05). At safe and high concentrations, SOD and CAT activities significantly decreased after 12 h of exposure (P < 0.05). BPA affected heat shock protein 90 (HSP90) expression in the ovary, with low concentration BPA significantly upregulating HSP90 after 1 day (P < 0.05), but returning to normal levels after 10 and 20 days. At the safe concentration, HSP90 was significantly upregulated at all three sampling points (1d, 10d, 20d) (P < 0.05), while high concentration exposure led to significant upregulation only on day 10 (P < 0.05). Low concentration BPA had no significant effect on Cathepsin B (CB) and Cathepsin L (CL) gene expression in the ovaries (P > 0.05). However, safe concentration exposure promoted CB expression on days 1, 10, and 20 (P < 0.05), while high concentration exposure significantly increased CB expression on day 1 (P < 0.05), with levels returning to normal on days 10 and 20. CL expression significantly increased after 20 days of exposure to both safe and high concentrations (P < 0.05). Gene expression levels in the ovaries returned to normal after transfer to BPA-free water, with HSP90 and CB normalizing by day 1, and CL by day 7. These results indicate that even safe concentrations of BPA impose stress on the hepatopancreas and increase the expression of HSP90, CB, and CL genes in the ovaries, affecting ovarian development. And, these effects are reversible within a certain period after the removal of BPA.