Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia-reperfusion injury in diabetes mellitus rats.

Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia-reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was - 5.44, and the MM-GBSA result of - 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.

Exposure characteristics and cumulative risk assessment of bisphenol A and its substitutes: the Taiwan environmental survey for toxicants 2013.

Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.

Analysis and removal of bisphenols in recycled plastics using polyethylene glycol.

This study examines the presence of bisphenol A (BPA), S (BPS), F (BPF), and M (BPM) in various recycled plastics readily available on the market (LDPE, HDPE, PET, and PP), in light of European Food Safety Authority (EFSA) limits. Twenty samples of different origin are analyzed, cleaning treatments are applied, and the migration potential of these bisphenols into food is studied. BPM is absent in all samples, but a post-consumer recycled LDPE sample reveals high bisphenol concentrations, raising concerns, reaching 8540 ng/g, 370 ng/g, and 29 ng/g of BPA, BPS, and BPF, respectively. Migration tests show substantial migration of these contaminants into food simulants. Using a cleaning treatment with polyethylene glycol (PEG 400) reduces BPA in LDPE, HDPE, PP, and PET samples by 95%, 99%, 97% and 28%, respectively, highlighting the importance of cleaning treatments across various polymers in plastic recycling. These findings not only protect food safety but addressing environmental challenges associated with plastic recycling.

Ultrastructural changes, pigment responses and bioaccumulation in the microalga Phaeodactylum tricornutum Bohlin exposed to BPA analogues.

As well-known, microalgae have a pivotal role in aquatic environments, being the primary producer. In this study, we investigated the effects of Bisphenol A (BPA) analogues on cell ultrastructure, reactive oxygen species (ROS) production and photosynthetic pigment responses in the diatom Phaeodactylum tricornutum. Microalgae were exposed during both exponential and stationary growth phases to an environmental relevant concentration (300 ng/L) of three differing BPA analogues (BPAF, BPF, and BPS) and their mixture (100 ng/L of each compound). Bioaccumulation of such compounds in microalgae was also analysed. During the stationary growth phase, a significant increase in the percentage of cells with hydrogen peroxide production was recorded after exposure to both BPS and MIX. Conversely, no significant effects on total chlorophylls and carotenoids were observed. During exponential growth phase we observed that control cultures had chloroplasts with well-organized thylakoid membranes and a central pyrenoid. On the contrary, the culture cells treated with BPA analogues and MIX showed chloroplasts characterized by evident dilation of thylakoid membranes. The presence of degeneration areas in the cytoplasm was also recorded. During the stationary growth phase, control and culture cells were characterized by chloroplasts with a regular thylakoid system, whereas BPA analogues-exposed cells were characterized by a deep degradation of the cytoplasm but showed chloroplasts without evident alterations of the thylakoid system. Lipid bodies were visible in treated microalgae. Lastly, microalgae bioaccumulated mainly BPS and BPF, alone or in the MIX. Overall, results obtained revealed that BPA analogues can affect some important biochemical and ultrastructure features of microalgae, promoting ROS production. Lastly, the capability of microalgae to bioaccumulate bisphenols suggest a potential ecotoxicological risk for filter-feeders organisms.

Effects of empagliflozin on reproductive system in men without diabetes.

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.

Estrogen-related receptor, a molecular target against lepidoptera pests.

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.

Empagliflozin alleviates neuroinflammation by inhibiting astrocyte activation in the brain and regulating gut microbiota of high-fat diet mice.

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.

Development of novel bisphenol derivatives with a membrane-targeting mechanism as potent gram-positive antibacterial agents.

Antibiotic resistance is becoming increasingly severe. The development of small molecular antimicrobial peptides is regarded as a promising design strategy for antibiotics. Here, a series of bisphenol derivatives with amphiphilic structures were designed and synthesized as antibacterial agents by imitating the design strategy of antimicrobial peptides. After a series of structural optimizations, lead compound 43 was identified, which exhibited excellent antibacterial activity against Gram-positive bacterial strains (MICs = 0.78-1.56 µg/mL), poor hemolytic activity (HC50 > 200 µg/mL), and low cytotoxicity (CC50 > 100 µg/mL). Further biological evaluation results indicated that 43 exerted antibacterial effects by directly destroying bacterial cell membranes and displayed rapid bactericidal properties (within 0.5-1 h), leading to a very low probability of drug resistance. Moreover, in a murine model of corneal infection, 43 exhibited a strong in vivo antibacterial efficacy. These findings indicate that 43 is a promising candidate compound for the treatment of bacterial infections.

Effects of bisphenol A and tauroursodeoxycholic acid on maturation of porcine oocytes and parthenogenetic development of embryos.

Prolonged exposure of bisphenol A (BPA) has adverse effects on in vitro maturation (IVM) of oocytes, but treatment with tauroursodeoxycholic acid (TUDCA) can improve the IVM and development of embryos. The purpose of this study was to investigate the effects of BPA and both BPA and TUDCA on IVM and parthenogenetic development of embryos. The results showed that BPA treatment adverse effects on the cumulus expansion index, survival rate, polar body rate, mitochondrial distribution of the oocytes after maturation culture, and that it also decreased the cleavage rate and blastocyst rate of embryos after parthenogenetic develpoment. In addition, BPA treatment upregulated expression of genes related to endoplasmic reticulum stress and apoptosis and increased the intracellular reactive oxygen species (ROS) level, while it decreased expression of genes related to cumulus expansion. However, the supplementation of TUDCA relieved these adverse effects of BPA except polar body rate, blastocyst rate, and expression of BCL2 and PTGS1. In conclusion, the supplementation of TUDCA can partly attenuate the negative effects of BPA on IVM and parthenogenetic development of embryos, possibly by modification of the expression of genes related to endoplasmic reticulum stress, apoptosis and cumulus expansion, intracellular ROS level, and mitochondrial distribution.

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations.

In situ construction of Ag/Bi2O3/Bi5O7I heterojunction with Bi-MOF for enhance the photocatalytic efficiency of bisphenol A by facet-coupling and s-scheme structure.

In this study, Ag/Bi2O3/Bi5O7I with s-scheme heterostructures were successfully synthesized in situ by nano-silver modification of CUA-17 and halogenated hydrolysis.The growth rate of Bi2O3 crystals was effectively controlled by adjusting the doping amount of Ag, resulting in the formation of a facet-coupling heterojunctions. Through the investigation of the microstructure and compositional of catalysts, it has been confirmed that an intimate facet coupling between the Bi2O3 (120) facet and the Bi5O7I (312) facet, which provides robust support for charge transfer. Under visible light irradiation, the AgBOI.3 heterojunction photocatalyst exhibited an outstanding degradation rate of 98.2% for Bisphenol A (BPA) with excellent stability. Further characterization using optical, electrochemical, impedance spectroscopy, and electron spin resonance techniques revealed significantly enhanced efficiency in photogenerated charge separation and transfer, and confirming the s-scheme structure of the photocatalyst. Density functional theory calculations was employed to elucidate the mechanism of BPA degradation and the degradation pathway of BPA was investigated by LC-MS. Finally, the toxicity of the degradation intermediates was evaluated using T.E.S.T software.

Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure.

OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. RESEARCH AND DESIGN METHODS: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping. RESULTS: Between the baseline and 12-month time point, plasma IL-1B was reduced (- 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (- 158.9 pmole/min/106 cells, P = 0.0497 vs. - 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups. GOV REGISTRATION: NCT03782259.

Acetylcholinesterase and dopamine inhibition suppress the filtration rate, burrowing behaviours, and immunological responses induced by bisphenol A in the hemocytes and gills of date mussels, Lithophaga lithophaga.

Bisphenol A (BPA), a common industrial chemical with estrogenic activity, has recently gained attention due to its well-documented negative effects on humans and other organisms in the environment. The potential immunotoxicity and neurotoxicity of BPA remain poorly understood in marine invertebrate species. Therefore, the impacts of exposure to BPA on a series of behaviours, immune responses, oxidative stress, neural biomarkers, histology, and the ultrastructure of gills were investigated in the date mussel, Lithophaga lithophaga. After 28 days of exposure to 0.25, 1, 2, and 5 µg/L BPA, hemolymphs from controls and exposed date mussels were collected, and the effects of BPA on immunological parameters were evaluated. Moreover, oxidative stress and neurochemical levels were measured in the gills of L. lithophaga. BPA reduced filtration rates and burrowing behaviour, whereas a 2 µg/L BPA resulted in an insignificant increase after 24 h. The exposure of date mussels to BPA significantly increased total hemocyte counts, a significant reduction in the diameter and phagocytosis of hemocytes, as well as gill lysozyme level. BPA increased lipid peroxidation levels and SOD activity in gills exposed to 2 and 5 µg/L BPA, but decreased GSH levels and SOD activity in 0.25 and 1 µg/L BPA-treated date mussels. Dose-dependent dynamics were observed in the inhibition of acetylcholinesterase activity and dopamine levels. Histological and scanning electron microscope examination revealed cilia erosion, necrosis, inflammation, and hyperplasia formation in the gills. Overall, our findings suggest a relationship between BPA exposure and changes in the measured immune parameters, oxidative stress, and neurochemical disturbances, which may be factored into the mechanisms underlying BPA toxicity in marine molluscs, providing a scientific foundation for marine BPA risk assessment and indicating immunosuppression in BPA-exposed date mussels.

[Effects of Dapagliflozin on contrast-induced acute kidney injury in patients with type 2 diabetes mellitus underwent percutaneous coronary intervention].

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

[Determination of six bisphenols in human urine by ultra-high performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To develop and validate a solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of six bisphenols(bisphenol S, bisphenol F, bisphenol A, 2, 2'-methylenediphenol, bisphenol AF, bisphenol AP) in urine. METHODS: After enzymolysis of urine sample, the target substances were quickly purified and extracted by WAX solid phase extraction column. On ACQUITY BEH C_(18) column(2.1 mm×100 mm, 1.7 µm), the mobile phase of water and methanol was used to separate. Finally, multi-reaction detection was carried out under electrospray negative ion scanning, and quantification was carried out by internal standard method. RESULTS: The correlation coefficients(r) of the target compounds were all more than 0.998 in the range of 0.1-50.0 ng/mL, the linearity was good, and the detection limits were all lower than 0.1 ng/mL. The recoveries of the three standard concentrations(0.5, 5.0 and 50.0 ng/mL) were all between 80% and 120%, and the relative standard deviation was less than 20%(n=5). The standard reference material was detected and the concentration was within the reference range. CONCLUSION: This method can be used to detect six bisphenols in urine quickly and accurately, is suitable for the trace analysis of bisphenol compounds in human urine.

Simultaneous removal of calcium, phosphorus, and bisphenol A from industrial wastewater by Stutzerimonas sp. ZW5 via microbially induced calcium precipitation (MICP): Kinetics, mechanism, and stress response.

The biological treatment of complex industrial wastewater has always been a research hotspot. In this experiment, a salt-tolerant strain Stutzerimonas sp. ZW5 with aerobic denitrification and biomineralization ability was screened, and the optimum conditions of ZW5 were explored by kinetics. The removal efficiencies of nitrate (NO3--N), bisphenol A (BPA), phosphorus (PO43--P), and calcium (Ca2+) were 94.47 %, 100 %, 98.87 %, and 83.04 %, respectively. The removal mechanism of BPA was the adsorption of microbial induced calcium precipitation (MICP) and extracellular polymeric substances (EPS). Moreover, BPA could weaken the electron transfer ability and growth metabolism of microorganisms and affect the structure of biominerals. At the same time, the stress response of microorganisms would increase the secretion of EPS to promote the process of biomineralization. Through nitrogen balance experiments, it was found that the addition of BPA would lead to a decrease in the proportion of gaseous nitrogen. This experiment offers novel perspectives on the treatment of industrial effluents and microbial stress response.

Assessing health risks in bottled water: chemical compounds and their impact on human health.

Bottled mineral and spring water constitute one of the main sources of drinking water. Relevant legal acts in each country individually regulate the highest permitted concentrations of harmful substances in these waters. However, current regulations do not take into account newly emerging contaminants such as BPA. Analysis of the chemical composition of 72 bottled waters from the Polish market showed that undesirable elements occur in quantities that do not exceed the maximum permissible concentrations. Special attention should be paid to bottled therapeutic water, which may contain elevated concentrations of some micronutrients, such as Al, B, Ba, Fe, Mn, or Sr contributing to the pattern of health risk with excessive consumption of this type of water. The presence of BPA was confirmed in 25 tested waters. The calculated hazard index values showed that the most exposed group are children up to 12 years of age. The greatest attention should be paid to waters with high mineralisation, for which the calculated risk values are the highest.

A new G3BP1-GFP reporter system for assessing skin toxicity by real-time monitoring of stress granules in vitro.

The skin, the organ with the largest surface area in the body, is the most susceptible to chemical exposure from the external environment. In this study, we aimed to establish an in vitro skin toxicity monitoring system that utilizes the mechanism of stress granule (SG) formation induced by various cellular stresses. In HaCaT cells, a keratinocyte cell line that comprises the human skin, a green fluorescent protein (GFP) was knocked in at the C-terminal genomic locus of Ras GTPase-activating protein-binding protein 1 (G3BP1), a representative component of SGs. The G3BP1-GFP knock-in HaCaT cells and wild-type (WT) HaCaT cells formed SGs containing G3BP1-GFP upon exposure to arsenite and household chemicals, such as bisphenol A (BPA) and benzalkonium chloride (BAC), in real-time. In addition, the exposure of G3BP1-GFP knock-in HaCaT cells to BPA and BAC promoted the phosphorylation of eukaryotic initiation factor 2 alpha and protein kinase R-like endoplasmic reticulum kinase, which are cell signaling factors involved in SG formation, similar to WT HaCaT cells. In conclusion, this novel G3BP1-GFP knock-in human skin cell system can monitor SG formation in real-time and be utilized to assess skin toxicity to various substances.

Bisphenol AF exposure synergistically increases the risk for suicidality among early adolescents with child maltreatment: A prospective cohort study.

BACKGROUND: Child maltreatment (CM) is correlated with suicidality risk among adolescents. Additionally, exposure to bisphenol AF (BPAF) may increase this risk. However, the combined effect of CM and BPAF exposure remains unknown and should be further investigated. METHODS: In this study, 1,475 early adolescents (mean age = 12.48 years) from the Chinese Early Adolescents Cohort were enrolled. Data were collected at three time points with an interval of 12 months between 2019 and 2021. Participants' history of CM and suicidality (including suicidal ideation and suicidal attempts) were evaluated using a self-report questionnaire. Blood samples were obtained from participants to measure serum BPAF concentrations at baseline. Group-based trajectory modeling was employed to identify different developmental trajectories of suicidality across the three waves. After adjusting for potential confounders, the association between CM and BPAF exposure on suicidal ideation and suicidal attempts was assessed using logistic regression and Poisson regression analyses. RESULTS: Participants with CM were associated with a risk of one- and two-year incident suicidality (all ps < 0.05), and BPAF levels were positively associated with two-year incident suicidal ideation (adjusted OR = 1.68, 95% CI: 1.13-2.50). Additionally, middle and high levels of BPAF exposure synergistically increase the risk for one- and two-year incident suicidal ideation among participants with CM (adjusted ORs = 2.00-3.83). Similarly, participants exposed to high-level BPAF as well as CM were at a greater risk of one- and two-year incident suicidal attempts than those with low-level BPAF exposure and no CM (adjusted incidence rate ratio [IRRs] = 2.82-4.34). Moreover, compared with participants with a low developmental trajectory of suicidality across the three waves, high BPAF exposure exhibited a significant synergistic effect on participants with CM in the persistently high suicidal ideation trajectory and the increasing suicidal attempts trajectory (all ps < 0.05). Sex subgroup analysis revealed that females were more susceptible to the synergistic effect of BPAF and CM exposure on suicidality than males. CONCLUSIONS: Environmental factors and the psychological status of individuals may synergistically increase their susceptibility to suicidality. These results offer novel insights into enhancing our understanding of suicidality among adolescents.