From Environmental Toxicants to Antibacterial Agents:BPA Analogues Selectively Inhibit the Growth of Gram-Positive Bacteria by Disturbing Biosynthesis of the Cell Wall

Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.

Plantain-based diet modulates atrazine-induced testicular toxicities in rats

Objective:To assess the potential of plantain-based diet in modulating testicular toxicities in rats exposed to atrazine.Methods:The plantain-based diet at 50%,25% and 12.5% were prepared from the basal diet by substituting the corn starch with plantain fruit pulp flour at different percentages.Wistar rats were fed plantain-based diet in varying concentrations ranging from 12.5% to 50% of the basal diet for 21 days before or after atrazine treatment in a two-phase experiment:preventive and therapeutic phases.The therapeutic model(n=35)had seven groups with 5 rats each,including the control,atrazine,atrazine recovery,atrazine plus plantain-based diet 50%,25%,12.5%,and atrazine plus quercetin groups.The preventive model(n=30)had six groups of 5 rats,consisting of the control,atrazine,50%,25%,12.5% plantain-based diet plus atrazine,and quercetin plus atrazine groups.Gonadal hormones(testosterone,luteinizing hormone and follicle-stimulating hormone),sperm parameters(sperm motility,viability,morphology and concentration),and testicular function indices(protein,cholesterol,glycogen,acid phosphatase,alkaline phosphatase and lactate dehydrogenase)were measured.Results:The gonadal hormones,sperm characteristics,and testicular function indices of the rat testis decreased significantly in the atrazine group alongside degeneration of the histoarchitecture.However,plantain-based diet restored the gonadal hormone concentrations,semen parameters,and testicular function indices in both the preventive and therapeutic models.Conclusions:Treatment with plantain-based diet protects against rat testicular toxicity caused by atrazine via the modulation of gonadal hormones,sperm quality,testicular function index as well as histoarchitecture of rat testes.

Endocrine-Disrupting Chemicals: Possible Genesis of Ovarian Tumors

Background: Prolonged exposure to environmental toxicants like endocrine-disrupting chemicals has been linked to several ovarian pathologies. Exposure to endocrine-disrupting chemicals may start at any time of life from the fetal stage to adulthood resulting in various health complications The purpose of our study is to compare the concentration levels and association of benzopyrene, bisphenol A and genistein in patients with ovarian tumors and normal control group. We also sort to evaluate the predictive performance of benzopyrene, bisphenol A and genistein in patients with ovarian tumors. Methods: A case-control study was conducted for randomly selected participants involving 30 patients and 30 controls. 30 patients with radiologically diagnosed and histopathological confirmed ovarian tumors were included in the study between January 2022 and December 2022. Urine samples from each group were analyzed using liquid chromatography-mass spectrometry. Descriptive analysis for normally distributed continuous variables was done accordingly. Concentration levels of endocrine-disrupting chemicals were assessed using the Mann-Whitney test. The association of endocrine-disrupting chemicals with pathological ovarian tumors was analyzed using binary logistic regression. Evaluation of the diagnostic performance of endocrine-disrupting chemicals was analyzed using the ROC curve. Results: Overall, patients were significantly (P = 0.000) older than the healthy controls. Mean years (SD) were 36.7 (7.90) and 28.8 years (4.89) for patients and normal women respectively. Endometriomas had the highest incidence of 50%. The level of benzopyrene and bisphenol A in patients was significantly higher than those in the control group, while the level of genistein was significantly higher in normal controls. Benzopyrene and bisphenol A were significantly associated with ovarian cysts, and the incidence of pathological ovarian cysts was positively correlated to these EDCs, with OR value 64.79 (P = 0.005) for benzopyrene and 9.609 (P = 0.001) for bisphenol A. Genistein was significantly negatively correlated with the incidence of pathological ovarian tumors, with OR value of 0.153 (P = 0.007). Diagnostic performance on the AUC for benzopyrene, bisphenol A and genistein&l.

Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice

This study evaluated toxic efficacy of Eupatorium adenophorum extracts,against the Kunming mice.In acute study,we firstly tested median lethal dose(LD50)in mice of three cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone(DAOA),9-oxo-agerophorone(OA)and 9-oxo-10,11-dehydro-agerophorone(ODA)from Eupatorium adenophorum(Ea).DAOA(215–4640 mg/kg BW,given orally)showed lowest LD50 at 926 mg/kg BW for male mice in contrast with OA(1470 mg/kg BW)and ODA(1470 mg/kg BW).In sub-acute study,repeated doses(75–300 mg/kg BW,for 7 days)of DAOA/OA increased blood parameters,liver and spleen index in dose dependent relationship,along with decrease in thymus index.The blood biochemical and histopathological examination showed that DAOA/OA dose 300 mg/kg BW significantly causes pathological changes of hepatic lobules and hepatocytes,which are consistent with cholestasis and hepatic injury.75 mg/kg dose of DAOA/OA was found to be approximately/totally safe over the span of 7 days treatment showing no change in all above described parameters.Cadinene sesquiterpenes guarantee low risk to environment as a type of low toxic botanical components,which may find potential application in biopesticides development field.

Interactions between engineered nanoparticles and dissolved organic matter: A review on mechanisms and environmental effects

Dissolved organic matter（DOM） is ubiquitous in the environment and has high reactivity.Once engineered nanoparticles（ENPs） are released into natural systems, interactions of DOM with ENPs may significantly affect the fate and transport of ENPs, as well as the bioavailability and toxicity of ENPs to organisms. However, because of the complexity of DOM and the shortage of useful characterization methods, large knowledge gaps exist in our understanding of the interactions between DOM and ENPs. In this article, we systematically reviewed the interactions between DOM and ENPs, discussed the effects of DOM on the environmental behavior of ENPs, and described the changes in bioavailability and toxicity of ENPs caused by DOM. Critical evaluations of published references suggest further need for assessing and predicting the influences of DOM on the transport,transformation, bioavailability, and toxicity of ENPs in the environment.

Reproductive toxicity of enrofloxacin in Caenorhabditis elegans involves oxidative stress-induced cell apoptosis

Fluoroquinolone antibiotics(FQs)that persist and bioaccumulate in the environment have aroused people’s great concern.Here,we studied the adverse effects of FQs in soil animals of Caenorhabditis elegans via food-chronically exposure.The result shows C.elegans exposed to FQs exhibited reproductive toxicity with small-brood size and low-egg hatchability.To study the underlying mechanism,we conduct a deep investigation of enrofloxacin(ENR),one of the most frequently detected FQs,on nematodes which is one of commonly used animal indicator of soil sustainability.The concentration-effect curves simulated by the Hill model showed that the half effect concentrations(EC50)of ENR were(494.3±272.9)μmol/kg and(107.4±30.9)μmol/kg for the brood size and the hatchability,respectively.Differential gene expression between the control and the ENR-exposure group enriched with the oxidative stress and cell apoptosis pathways.The results together with the enzyme activity in oxidative stress and the cell corpses suggested that ENR-induced reproductive toxicity was related to germ cell apoptosis under oxidative stress.The risk quotients of some soil and livestock samples were calculated based on the threshold value of EC10 for the egg hatchability(2.65μmol/kg).The results indicated that there was possible reproductive toxicity on the nematodes in certain agricultural soils for the FQs.This study suggested that chronic exposure to FQs at certain levels in environment would induce reproductive toxicity to the nematodes and might reduce the soil sustainability,alarming the environment risks of antibiotics abuse.

Effects of lead pollution on soil microbial community diversity and biomass and on invertase activity

Lead(Pb)pollution is one of the most widespread and harmful environmental problems worldwide.Determination of changes in soil properties and microbial functional diversity due to land use is needed to establish a basis for remediation of soil pollution.This study aimed to investigate soils contaminated by Pb from different sources and to analyze the functional diversity and metabolism of soil microbial communities using Biolog technology.Pb pollution(>300 mg kg-1)significantly influenced the diversity and metabolic functions of soil microbial communities.Specifically,Pb contamination significantly reduced soil microbial biomass carbon(C)and nitrogen(N)levels and catalase activity while increasing invertase activity.Furthermore,Biolog EcoPlate assays revealed that Pb pollution reduced the general activities of soil microorganisms,suppressing their ability to utilize C sources.In Pb-contaminated areas lacking vegetation cover,Shannon,Simpson,and McIntosh diversity indices of soil microorganisms were significantly reduced.The microbial diversity and biomass C and N levels were affected by land use and soil properties,respectively,whereas soil enzyme activity was primarily affected by the interaction between land use and soil properties.Our results provide a reference and a theoretical basis for developing soil quality evaluation and remediation strategies.

Studying developmental neurotoxic effects of bisphenol A(BPA) using embryonic stem cells

There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development（Betts,2010;US EPA,2015）.