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It remains unclear whether phthalates are associated with gallstones and whether the associations of phthalate alternatives with gallstones are different from traditional phthalates. In this study, 1735 participants from the NHANES 2017–2018 were included and their urine was used to detect phthalate metabolites. We used logistic and restricted cubic spline regressions to assess individual associations and dose–response relationships between phthalate metabolites and gallstones, quantile g-computation and Bayesian kernel machine regression to assess mixed associations of phthalate metabolites with gallstones, and subgroup analyses to explore potential effect modifiers. We observed that individual associations of cyclohexane-1,2-dicarboxylic acid-mono(carboxyoctyl) ester phthalate (MCOCHP) (OR: 1.423, 95% CI: 1.098–1.844) and cyclohexane 1,2-dicarboxylic acid monohydroxy isononyl ester (MHNCH) (OR: 1.380, 95% CI: 1.080–1.763) with gallstones were linearly positive, mixed association of phthalate metabolites (OR: 2.453, 95% CI: 1.054–5.708) with gallstones was also positive, and MCOCHP and MHNCH had positive weights. The associations of phthalate metabolites with gallstones were higher in the males and participants with age ≥ 60 years, BMI ≥ 30 kg/m2, hypertension, and diabetes. MCOCHP and MHNCH had the highest groupPIP (groupPIP: 0.941), mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP) had the highest condPIP (condPIP: 0.721), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), MCOCHP, and mono-isobutyl phthalate (MiBP) also had high condPIPs (condPIP > 0.5). The trend in mixed associations of phthalate metabolites with gallstones was positive. Our study suggests that traditional phthalates and phthalate alternatives are associated with gallstones, especially in the elderly, men, obese, hypertensive populations, and diabetic populations, and phthalate alternatives are associated with a higher risk of gallstones. [ABSTRACT FROM AUTHOR]

In our investigation, we probed the ramifications of low selenium diets and HT-2 mycotoxin exposure on spinal development and structural fidelity in murine models. A cohort of 48 male mice was segregated into six groups: a control set, a singular low selenium diet group, two cohorts exposed to distinct concentrations of HT-2 toxin (1.6 and 3.2 mg/kg·bw·d), and two assemblies subjected to a confluence of low selenium intake and each designated HT-2 dosage. Across an 8-week investigative period, parameters such as body mass, markers of bone metabolism, and cellular vigor were assiduously monitored. Analytical techniques encompassed biomechanical assessments, X-ray scrutiny, and micro-computed tomography (micro-CT) evaluations. Our results unveiled a dose-dependent diminution in the body mass of mice exclusively exposed to HT-2 toxin, whereas concurrent exposure to both low selenium and HT-2 toxins elicited a synergistic effect. Pertinent shifts were observed in calcium, phosphorus, and vitamin D concentrations, as well as in the operational dynamics of osteoblasts and osteoclasts, aligning with toxin dosage and combined exposure. Variations in biomechanical attributes were also discerned, mirroring the levels of toxin exposure. Micro-CT and X-ray examinations further corroborated the extensive detrimental impact on the cortical and trabecular architecture of the mice's spinal columns. This inquiry elucidates the complex synergistic interactions between low selenium and HT-2 mycotoxin on murine spinal development and integrity under co-exposure conditions. These findings accentuate the exigency of comprehensively understanding the solitary and joint effects of these toxins on osseous health, providing pivotal insights for future toxicological research and public health strategies. [ABSTRACT FROM AUTHOR]

The aquaculture sector is facing environmental issues because of rising chemical pollution of aquatic systems, which may be caused by man-made or natural causes. The combined action of these mixtures can produce an effect that is either severalfold higher or severalfold lower than the overall toxicity of the individual components. The objective of this study is to evaluate the impact of three individual toxicants: lead (Pb 0.088 mg L−1), mercury (Hg 0.084 mg L−1), and pendimethalin (PM 0.355 mg L−1) and their combinations on the behavior, oxidative stress, immunology, biochemistry, and histopathological changes in Nile tilapia. The results show that mortality was evident across all treatment groups and was highest in the mixture (MIX) group, at 33.4%. Some of these behavioral changes included increased mucus secretion, fin rot, and dark skin coloration of the fish, all of which were evidently exacerbated in the MIX group. The erythrocyte and hemoglobin indices presented marked reductions in the MIX and PM groups in comparison to the control group. The MIX group had higher levels of serum creatinine and urea, as well as the liver enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. They also had higher levels of malondialdehyde and lower levels of total antioxidant capacity, which showed oxidative stress. The stress biomarkers, cortisol and glucose, showed greater impact on the MIX and PM groups. The neurobehavioral assessment demonstrated noticeable decreased acetylcholinesterase levels in PM and MIX-exposed groups. In the serum immunological parameters, levels of nitric oxide and lysozyme were lower, especially in the MIX and PM groups. In all experimental groups, especially the MIX group, the levels of spleen pro-inflammatory cytokine genes were higher. The histopathological examination revealed marked lesions in the gills, liver, and brains in the form of inflammation, necrosis, and circulatory alterations. Among the exposed groups, the MIX group exhibited the highest histopathological changes. Collectively, our findings demonstrated significant toxic effects of heavy metals and herbicides on Nile tilapia, revealing a synergistic impact on both physiological and histopathological responses resulting from combined exposures. The data evidently indicate the ecological hazards associated with heavy metals and herbicides in aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Chemical pollution is an increasing worldwide concern, with children being especially vulnerable to the harmful effects of air pollution. This study aimed to characterize the mixture of volatile organic compounds (VOCs) present in indoor air across residential, educational, and recreational settings. It analyzed data on VOC concentrations from previous sampling campaigns conducted in households with children, primary schools, and indoor swimming pools (70 buildings, 151 indoor spaces) in northern Portugal. The findings reveal the co-occurrence of 16 VOCs (1,2,4-trimethylbenzene, benzene, ethylbenzene, m/o/p-xylenes, styrene, toluene, tetrachloroethylene, 2-ethylhexanol, butanol, acetophenone, ethyl acetate, benzaldehyde, decanal, nonanal, 1-methoxy-2-propanol and limonene) across all three settings, primarily associated to emissions from building materials and detergents. However, distinct patterns were also observed in the VOCs detected across the three indoor environments: in homes, the predominant VOCs were primarily released from cleaning and fragranced products; in schools, from ammonia-based cleaners and occupant activities; and in swimming pools, the predominant airborne chemicals were disinfection by-products resulting from the chemical dynamics associated with water disinfection. Overall, the findings highlight the need for additional research to deepen our understanding of the risks posed by combined exposure to multiple indoor air chemicals for children. These results also underscore the importance of developing and enforcing regulations to monitor VOC levels in environments frequented by children and implementing preventive measures to minimize their exposure to harmful chemicals. [ABSTRACT FROM AUTHOR]

Copyright of Asian Journals of Ecotoxicology is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The aquaculture sector is facing environmental issues because of rising chemical pollution of aquatic systems, which may be caused by man-made or natural causes. The combined action of these mixtures can produce an effect that is either severalfold higher or severalfold lower than the overall toxicity of the individual components. The objective of this study is to evaluate the impact of three individual toxicants: lead (Pb 0.088 mg L−1), mercury (Hg 0.084 mg L−1), and pendimethalin (PM 0.355 mg L−1) and their combinations on the behavior, oxidative stress, immunology, biochemistry, and histopathological changes in Nile tilapia. The results show that mortality was evident across all treatment groups and was highest in the mixture (MIX) group, at 33.4%. Some of these behavioral changes included increased mucus secretion, fin rot, and dark skin coloration of the fish, all of which were evidently exacerbated in the MIX group. The erythrocyte and hemoglobin indices presented marked reductions in the MIX and PM groups in comparison to the control group. The MIX group had higher levels of serum creatinine and urea, as well as the liver enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. They also had higher levels of malondialdehyde and lower levels of total antioxidant capacity, which showed oxidative stress. The stress biomarkers, cortisol and glucose, showed greater impact on the MIX and PM groups. The neurobehavioral assessment demonstrated noticeable decreased acetylcholinesterase levels in PM and MIX-exposed groups. In the serum immunological parameters, levels of nitric oxide and lysozyme were lower, especially in the MIX and PM groups. In all experimental groups, especially the MIX group, the levels of spleen pro-inflammatory cytokine genes were higher. The histopathological examination revealed marked lesions in the gills, liver, and brains in the form of inflammation, necrosis, and circulatory alterations. Among the exposed groups, the MIX group exhibited the highest histopathological changes. Collectively, our findings demonstrated significant toxic effects of heavy metals and herbicides on Nile tilapia, revealing a synergistic impact on both physiological and histopathological responses resulting from combined exposures. The data evidently indicate the ecological hazards associated with heavy metals and herbicides in aquatic ecosystems.

Objective·To analyze the relationship between prenatal mixed heavy metal/metalloid exposure and the cognitive and temperament development of the offspring.Methods·A prospective birth cohort study was conducted in Shanghai from 2010 to 2012. Maternal venous blood samples were collected at 28‒36 weeks of gestation to measure prenatal maternal blood heavy metal/metalloid concentrations. At 24‒36 months of age, the cognitive and temperament development of the offspring were assessed by using Gesell Developmental Scale and Toddler Temperament Scale, respectively. Demographic and clinical information of mothers and children was collected via questionnaires and hospital medical records. Bayesian kernel machine regression (BKMR) models were employed to assess the effects of prenatal mixed heavy metal/metalloid exposure on toddlers' cognitive and temperament development.Results·A total of 139 mother-child pairs with complete data were included in the study. At enrollment, the mean maternal age was (29.39±3.41) years, and the mean birth weight of the infants was (3.47±0.42) kg, with 59.71% female infants. At follow-up, the average age of the toddlers was (32.91±2.69) months. Based on prior research and multivariable linear regression models, four heavy metals/metalloid—chromium (Cr), manganese (Mn), arsenic (As), and lead (Pb)—were identified as potentially associated with cognitive and temperament development in children. The median concentrations of Mn, Pb, As, and Cr in the maternal venous blood during pregnancy were 3.32, 3.60, 2.03, and 1.78 μg/dL, respectively. After adjusting for related confounders, the BKMR analyses found that when the overall concentrations of the four heavy metals/metalloid (Cr, Mn, As, and Pb) were higher than the 50th percentile, children's fine motor development quotients showed a decreasing trend as the overall concentrations of the four heavy metals/metalloid increased. Scores for adaptability, persistence, and threshold of response on the temperament scale showed a decreasing trend as well. Prenatal Mn exposure levels made the greatest contribution to the effects on children's fine motor development [PIP (posterior inclusion probability)=0.617], prenatal As exposure levels made the greatest contribution to the effects on children's persistence trait (PIP=0.656), and prenatal Cr exposure levels made the greatest contribution to the effects on children's reaction threshold trait (PIP=0.447). The contribution of all four heavy metals/metalloid to the effects on children's adaptive dimension was similar.Conclusion·Children's fine motor development and the adaptability, persistence, and threshold traits of temperament may be related to prenatal mixed exposure to heavy metals/metalloid (Mn, As, Pb, and Cr). Particular attention should be paid to the relationship between prenatal Mn exposure and children's fine motor development, and between prenatal As and Cr exposure and children's temperament development.

Abstract We estimated the association between combined exposure to air pollutants and the development of cardiometabolic multimorbidity (CM) and all-cause mortality. An air pollution score was calculated to determine the combined exposure to five air pollutants. CM was defined as the instance of at least two types of diseases. A genetic risk score (GRS) was calculated for each individual. A multistate regression model was used to investigate the effect of the combined associations of air pollutants on each stage of CM progression. After multivariable adjustment, the air pollution score was related with greater susceptibility of CM and all-cause mortality, and those with a high GRS for cardiovascular disease (CVD) or coronary heart disease (CHD) and a high air pollution score had a greater susceptibility of incident CM and all-cause mortality. The multistate model revealed that the greater air pollution score was connected with the susceptibility of progressing from disease-free baseline to having one cardiometabolic disease, and next to CM, and eventually to death. Combined exposure to five air pollutants were related with greater susceptibility of CM and all-cause mortality in a dose-dependent style and is related with the progression of CM and with all-cause mortality.

We estimated the association between combined exposure to air pollutants and the development of cardiometabolic multimorbidity (CM) and all-cause mortality. An air pollution score was calculated to determine the combined exposure to five air pollutants. CM was defined as the instance of at least two types of diseases. A genetic risk score (GRS) was calculated for each individual. A multistate regression model was used to investigate the effect of the combined associations of air pollutants on each stage of CM progression. After multivariable adjustment, the air pollution score was related with greater susceptibility of CM and all-cause mortality, and those with a high GRS for cardiovascular disease (CVD) or coronary heart disease (CHD) and a high air pollution score had a greater susceptibility of incident CM and all-cause mortality. The multistate model revealed that the greater air pollution score was connected with the susceptibility of progressing from disease-free baseline to having one cardiometabolic disease, and next to CM, and eventually to death. Combined exposure to five air pollutants were related with greater susceptibility of CM and all-cause mortality in a dose-dependent style and is related with the progression of CM and with all-cause mortality. [ABSTRACT FROM AUTHOR]

The escalating release of multi-walled carbon nanotubes (MWCNTs) into the environment has raised concerns due to their potential ecotoxicological impacts. However, their combined phytotoxicity with heavy metals such as copper (Cu) is still unclear. This study investigated the individual and combined toxic effects of MWCNTs (MWCNT, MWCNT-OH, and MWCNT-COOH) and Cu2+ on ryegrass (Lolium multiflorum), uniquely considering different addition orders. The results show that Cu severely inhibited the growth of ryegrass while MWCNTs exhibited a hormesis effect on ryegrass. When MWCNT and Cu were combined, the malondialdehyde (MDA) content in ryegrass showed a 32.39% increase at 20 mg/L MWCNT exposure, suggesting reduced oxidative stress. However, at the higher concentration of 1000 mg/L, it led to a significant 75.22% reduction in ryegrass biomass. MWCNT-COOH had the most pronounced effect, reducing the total chlorophyll content by 39.76% compared to unmodified MWCNT and by 10.67% compared to MWCNT-OH (500 mg/L). Additionally, pre-induced MWCNTs might alleviate the Cu in the plant by 23.08–35.38% through adsorption in the nutrient solution. Small molecule organic acids and amino acids primarily mediated the response to environmental stress in ryegrass. This research provides crucial insights into understanding the complex interactions of MWCNT and Cu2+ and their combined effects on plant ecosystems. [ABSTRACT FROM AUTHOR]

Combined proton—neutron therapy can be the best opportunity for neutron radiation therapy due to highly conformal proton irradiation and high relative biological effectiveness of neutrons. The study compares 4 schemes of sequential in vitro exposure of Chinese hamster fibrosarcoma cells B14-150 to 14.5 MeV neutrons and a scanning beam of protons. Treatment efficiency increased with increasing the contribution of the neutron component to the total dose from 30 to 40% and the delivery of the neutron dose as the first fraction in the two-fraction proton—neutron exposure. [ABSTRACT FROM AUTHOR]

Environmental concerns have consistently been a focal point for the scientific community. Pollution is a critical ecological issue that poses significant threats to human health and agricultural production. Contamination with heavy metals and pesticides is a considerable concern, a threat to the environment, and warrants special attention. In this study, we investigated the significant issues arising from sub-chronic exposure to imidacloprid (IMI), mercury (Hg), and cadmium (Cd), either alone or in combination, using zebrafish (Danio rerio) as an animal model. Additionally, we assessed the potential protective effects of polyfloral honey enriched with natural ingredients, also called honey formulation (HF), against the combined sub-chronic toxic effects of the three contaminants. The effects of IMI (0.5 mg·L−1), Hg (15 μg·L−1), and Cd (5 μg·L−1), both individually and in combination with HF (500 mg·L−1), on zebrafish were evaluated by quantifying acetylcholinesterase (AChE) activity, lipid peroxidation (MDA), various antioxidant enzyme activities like superoxide dismutase and glutathione peroxidase (SOD and GPx), 2D locomotor activity, social behavior, histological and immunohistochemical factors, and changes in body element concentrations. Our findings revealed that all concentrations of pollutants may disrupt social behavior, diminish swimming performances (measured by total distance traveled, inactivity, and swimming speed), and elevate oxidative stress (OS) biomarkers of SOD, GPx, and MDA in zebrafish over the 21-day administration period. Fish exposed to IMI and Hg + Cd + IMI displayed severe lesions and increased GFAP (Glial fibrillary acidic protein) and S100B (S100 calcium-binding protein B) protein expression in the optic tectum and cerebellum, conclusively indicating astrocyte activation and neurotoxic effects. Furthermore, PCNA (Proliferating cell nuclear antigen) staining revealed reduced cell proliferation in the IMI-exposed group, contrasting with intensified proliferation in the Hg + Cd group. The nervous system exhibited significant damage across all studied concentrations, confirming the observed behavioral changes. Moreover, HF supplementation significantly mitigated the toxicity induced by contaminants and reduced OS. Therefore, the exposure to chemical mixtures offers a more complete picture of adverse impacts on aquatic ecosystems and the supplementation with bioactive compounds can help to reduce the toxicity induced by exposure to environmental pollutants. [ABSTRACT FROM AUTHOR]

Occupational exposure to carcinogenic respirable crystalline silica and noise requires a deeper understanding and an assessment of the possible health risks caused by their combined action. Data on individual exposure to respirable crystalline silica (RCS) and occupational noise (ON) was collected among 44 open-pit miners. The study group was divided into two groups according to the job tasks performed. The individual exposure, exceeding of maximum admissible concentration/intensity, and predicted hearing thresholds (HTs) (according to ISO 1999:2013) were compared between the groups directly participating in the technological process (group 1; N = 23) and performing auxiliary, supervising, or laboratory activities (group 2; N = 21). All the analysed indices were significantly higher for group 1; therefore, the job category may predict ON and RCS exposure among open-pit miners. A statistically significant relationship (rs = 0.66, p < 0.05) was found between the time-weighted average (TWA) 8 h RCS and individual daily noise exposure levels. Exposure to noise in the course of employment causes the risk of hearing impairment (mean HTs for 2, 3, and 4 kHz > 25 dB) up to 74% and 4.4% (in the case of groups 1 and 2, respectively). Further studies are needed before conclusions concerning the effects of co-exposure to ON and RCS on open-pit miners can be made. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have indicated that exposure to heavy metals related to bone health is primarily limited to some common harmful metals, and the impact of lead has not been fully understood. This study aims to explore the relationship between urine lead exposure and bone density. Methods: 1,310 adults were included from the NHANES database (2015-2018), and through generalized linear regression analysis and constrained cubic spline models, the association between lead levels and total bone density as well as lumbar spine bone density was explored. The study also examined the impact of combined exposure to lead and cadmium on bone density. Results and conclusions: Urinary lead levels were significantly negatively correlated with total bone mineral density (b: -0.015; 95%CI: -0.024, -0.007) and lumbar spine bone mineral density (b: -0.019; 95%CI: -0.031, -0.006). Compared to the lowest three quartiles of lead levels, the adjusted odds ratios for T3 changes in total bone mineral density and lumbar spine bone mineral density were 0.974 (95%CI: 0.959, 0.990) and 0.967 (95%CI: 0.943, 0.991), indicating a significant negative trend. Further analysis with constrained cubic spline models revealed a non-linear decreasing relationship between urinary lead and total bone mineral density as well as lumbar spine bone mineral density. Stratified analyses suggested that the relationship between urinary lead levels and bone mineral density might be significantly influenced by age, while gender showed no significant impact on the relationship. Moreover, combined exposure to lead and cadmium was found to be associated with decreased bone mineral density, emphasizing the potential synergistic effects between lead and cadmium on bone health. However, the specific mechanisms of lead and its effects on different populations require further comprehensive research. This study provides valuable insights for further exploration and development of relevant public health policies. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Guangdong University of Technology is the property of Journal of Guangdong University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundPrevious research has demonstrated that exposure to individual heavy metals elevates the incidence rate of congenital heart defects (CHDs). However, there is a paucity of data concerning the relationship between combined exposure to multiple heavy metals and the occurrence of CHDs. This study seeks to investigate the association between combined heavy metal exposure in pregnant women and the incidence of CHDs in their offspring in Lanzhou, China.MethodsWe conducted a comprehensive review of the birth cohort study undertaken at our hospital from 2010 to 2012, with the objective of investigating the association between combined heavy metal exposure in pregnant women and the incidence of CHDs in their offspring. This analysis was performed utilizing a multifactorial conditional logistic regression model.ResultA nested case-control study was conducted involving 97 case groups and 194 control groups. The median concentrations of nickel (Ni), barium (Ba), lead (Pb), and titanium (Ti) in the blood of pregnant women were measured at 25.58 μg/L, 84.38 μg/L, 69.67 μg/L, and 304.65 μg/L, respectively. The research identified a significant correlation between the concentrations of Ni, Pb, and Ti in the blood of pregnant women and the risk of CHDs (P

The combined exposure to environmental pollutants can result in unanticipated adverse effects on human health, and how to compare and assess these effects has always been a matter of great concern for the international community. Currently, several prevalent methods for assessing combined exposure risks in the field of human health risk assessment primarily encompass the hazard index (HI) method, the point of departure index (PODI) method, the margin of exposure (MOE) method, and the relative potency factor (RPF) method. The review summarizes the application of these methods to the cumulative risk assessment of combined exposure to the same class of chemicals with the same toxic mechanism, primarily focusing on pesticides such as organophosphorus pesticides, pyrethroids, carbamates, and neonicotinoids, as well as typical compounds intimately related to human production and life, including organophosphorus flame retardants, per- and poly-fluoroalkyl substances, and bisphenols. Furthermore, progress in the application of physiologically based pharmacokinetics models to human health risk assessment has been introduced, which might provide more options for risk assessment of combined exposure to multiple chemicals, and help to provide insights for further exploration and establishment of more systematic and scientific approaches to human health risk assessment.

Na Li,1 Liufu Cui,1 Gary Tse,2,3 Panagiotis Korantzopoulos,4 Konstantinos P Letsas,5 George Bazoukis,6,7 Shuohua Chen,8 Nan Zhang,2 Xuemei Yang,9 Peipei Liu,10 Lili Wu,11 Gan-Xin Yan,12,13 Gregory Yoke Hong Lip,14,15 Shouling Wu,8 Tong Liu2 1Department of Rheumatology and Immunology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; 5Arrhythmia Unit, Laboratory of Cardiac Pacing and Electrophysiology, Onassis Cardiac Surgery Center, Athens, Greece; 6Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus; 7European University Cyprus, Medical School, Nicosia, Cyprus; 8Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 9School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 10School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 11Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 12Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA; 13Department of Cardiology, Fuwai Huazhong Hospital, Zhengzhou, Henan Province, People’s Republic of China; 14Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; 15Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China, Email drwusl@163.comObjective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP.Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB.Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP.Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. Keywords: hyperuricemia, inflammation, cardiac conduction block, combined exposure, risk factors, mediation

Abstract Background Industrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis. Methods Female rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays. Results F rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels. Conclusion Folliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated.

Pesticides and veterinary drugs are widely employed to support food production. Assessing potential risks associated with the dietary consumption of pesticide and veterinary drug residues is, however, essential. Potential risks depend on the toxicity degree of the analyzed residue and population exposure levels. Human populations are exposed to numerous chemical substances through different pathways with varying exposure times, leading to increased health risks when compared to exposure to individual chemicals. Cumulative exposure assessments usually assess combined exposures to multiple chemicals through multiple exposure pathways. In this sense, this comprehensive review aims to provide insights into cumulative dietary pesticide and veterinary drug residue exposures. The main methodologies, strategies, and legislation employed by international agencies to this end are discussed. A review concerning articles that apply existing methodologies and approaches, as well as the challenges in this context faced by Brazil is also presented. As this is a critical issue not only for Brazilian public health but also for the global community, regulatory agencies should prioritize formulating regulations that incorporate exposure assessments regarding the simultaneous presence of residues and contaminants in foodstuffs. [ABSTRACT FROM AUTHOR]

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Brominated flame retardants (BFRs), commonly found in consumer products, have been identified as potential hazards to liver function. While the individual effects of specific BFRs are somewhat understood, there is limited evidence on how mixtures of these chemicals, especially when influenced by demographic factors, interact to affect liver function. This study utilized data from 10,828 participants aged 12 and above from the National Health and Nutrition Examination Survey (2005–2016) to investigate the associations between BFRs (both individually and in combinations) and biomarkers of liver injury. The study focused on how age, gender, and body mass index (BMI) modify modulate these effects. Multivariate linear regression, restricted cubic spline function, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp) models were used to analyze the linear, non-linear, and joint associations between BFR levels and liver function parameters. We found positive associations between the mixed BFRs index and AST, ALT, GGT, ALP, and TBIL levels and a negative association with ALB levels. PBDE28, PBDE47, and PBB153 consistently contributed to the top weight in both the WQS and qgcomp models. Most critically, the study demonstrated that the relationship between co-exposure to BFRs and liver function parameters was modified by age, gender, and BMI. Therefore, our study highlights the importance of considering demographic diversity in assessing the risk of BFR-induced liver damage and supports the implementation of tailored preventive and intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Industrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known target of endocrine-disrupting chemicals. This function holds biological processes that are decisive for the fertility of women themselves and for the health of future generations. However, insufficient research has evaluated the risk of combined mixtures on this function. This study aimed to assess the direct impacts of a realistic exposure to eight combined environmental toxicants on the critical process of folliculogenesis. Methods: Female rabbits were exposed daily and orally to either a mixture of eight environmental toxicants (F group) or the solvent mixture (NE group, control) from 2 to 19 weeks of age. The doses were computed from previous toxicokinetic data to reproduce steady-state serum concentrations in rabbits in the range of those encountered in pregnant women. Ovarian function was evaluated through macroscopic and histological analysis of the ovaries, serum hormonal assays and analysis of the expression of steroidogenic enzymes. Cellular dynamics in the ovary were further investigated with Ki67 staining and TUNEL assays. Results: F rabbits grew similarly as NE rabbits but exhibited higher total and high-density lipoprotein (HDL) cholesterol levels in adulthood. They also presented a significantly elevated serum testosterone concentrations, while estradiol, progesterone, AMH and DHEA levels remained unaffected. The measurement of gonadotropins, androstenedione, pregnenolone and estrone levels yielded values below the limit of quantification. Among the 7 steroidogenic enzymes tested, an isolated higher expression of Cyp19a1 was measured in F rabbits ovaries. Those ovaries presented a significantly greater density/number of antral and atretic follicles and larger antral follicles without any changes in cellular proliferation or DNA fragmentation. No difference was found regarding the count of other follicle stages notably the primordial stage, the corpora lutea or AMH serum levels. Conclusion: Folliculogenesis and steroidogenesis seem to be subtly altered by exposure to a human-like mixture of environmental toxicants. The antral follicle growth appears promoted by the mixture of chemicals both in their number and size, potentially explaining the increase in atretic antral follicles. Reassuringly, the ovarian reserve estimated through primordial follicles number/density and AMH is spared from any alteration. The consequences of these changes on fertility and progeny health have yet to be investigated. [ABSTRACT FROM AUTHOR]

Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10–1.27), 1.27(1.21–1.33) and 1.50 (1.33–1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification. • The primary finding of this study was that the combination of high UA and high CRP was associated with increased risks of CVD, which was age-dependent. • The association between UA and CVD was mediated by CRP, suggesting proper control of CRP can be effective to reduce the effects of UA on CVD. • Compared to incorporating either UA or CRP alone, incorporating both UA and CRP into the traditional China-PAR model showed the best incremental value. • The effects of combined exposure to high UA and high CRP on different outcome events had site differences, with a higher risk of CHD and HF than stroke. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are usually co-exposed with a variety of plastic-related products. This co-exposed is harmful to human health. Mono-2-ethylhexyl phthalate (MEHP) is a primary metabolite of di-2-ethylhexyl phthalate (DEHP), a common plasticizer. Once entering into the body, MPs and MEHP accumulate in the liver. Therefore, it is important to study the toxic effects of the co-exposed of MPs and MEHP on the liver and explore the potential mechanisms. In this study, HepG2 cells were treated with polystyrene microplastics (PS-MPs), MEHP, or PS-MPs combined with MEHP. The cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expression of COXI, COXIII, SIRT3 and SOD2 were measured. The results showed that PS-MPs or MEHP exposure increased ROS generation and decreased MMP. PS-MPs exposure alone reduced protein expression of COXI and COXIII. These harmful effects were more pronounced when combined exposure, indicated a synergistic effect. Further molecular mechanism study exhibited that PS-MPs treatment down-regulated the protein expression of SIRT3 and SOD2. MEHP treatment down-regulated the protein expression of SIRT3. The combined exposure of PS-MPs and MEHP synergistically down-regulated the protein expression of SIRT3 and SOD2. In summary, the combined exposure of PS-MPs and MEHP resulted in oxidative stress and mitochondrial damage in HepG2 cells, and the underlying molecular mechanism is related to the inhibition of the SIRT3/SOD2 signaling pathway. [ABSTRACT FROM AUTHOR]

Cognitive impairment (CI) is a prodrome of many neurodegenerative diseases with complex and unclear pathogenesis. Metal exposure has been found to be associated with CI, but existing population studies are scarce and have the limitations of single outcome and ignoring mixed exposures. This cross-sectional study was conducted in Shanghai, China, enrolling 836 seniors aged over 60 years to investigate the relationship between combined metal exposure (Lead (Pb), cadmium (Cd), and mercury (Hg)) and CI in the elderly and the mediating effect of oxidative stress. It was found that there were significant differences in urinary Pb, Cd, Hg and blood Pb levels between the CI and normal groups. Urinary Pb and Cd levels were significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score, amyloid β42 (Aβ42), and Aβ42/40, while urinary Cd, Hg and blood Hg were significantly positively correlated with phosphorylated tau protein (P-tau). Weighted quantile sum (WQS) regression indicated that combined metal exposure had a more significant effect on CI than individual exposure. Mediation modeling revealed that plasma superoxide dismutase (SOD) was involved in the effects of urinary Cd on Aβ42/40 and P-tau, with mediation effects accounting for 20 % of the total effect. This study emphasized the combined exposure to metals, and the results can help to properly understand the association between mixed metals exposure and CI in the elderly, as well as provide population data and theoretical basis for identifying early environmental risk factors and discovering potential mechanisms of CI.

IntroductionThe aim of the study was to investigate the occupational epidemiological characteristics of hearing loss among noise-exposed workers through a cross-sectional study and to explore the impact of combined noise and dust exposure on workers’ hearing loss through a longitudinal study.ResultsThis cross-sectional study revealed that the risk of speech-frequency hearing loss increases with age (OR = 1.096, 95%CI = 1.081–1.111). Independent factors influencing high-frequency hearing loss include sex, age, hazardous factors, industry category, and enterprise size. Scientific research and technical services (OR = 1.607, 95%CI = 1.111–2.324), wholesale and retail (OR = 2.144, 95%CI = 1.479–3.107), manufacturing (OR = 1.907, 95%CI = 1.429–2.545), and other industries (OR = 1.583, 95%CI = 1.002–2.502) are risk factors for high-frequency hearing loss, whereas being female (OR = 0.297, 95%CI = 0.236–0.373) is a protective factor against high-frequency hearing loss. Independent factors influencing occupational noise-induced hearing loss include sex, working age, hazardous factors, industry category, smoking, and drinking, with the risk of occupational noise-induced hearing loss increasing with working age (OR = 1.045, 95%CI = 1.031–1.058). Noise and dust work (OR = 1.271, 95%CI = 1.011–1.597), other work (OR = 0.619, 95%CI = 0.479–0.800), manufacturing (OR = 2.085, 95%CI = 1.336–3.254), other industries (OR = 2.063, 95%CI = 1.060–4.012), occasional smokers (OR = 0.863, 95%CI = 0.652–1.142), regular smokers (OR = 1.216, 95% CI = 0.987–1.497), and excessive drinkers (OR = 2.171, 95%CI = 1.476–3.193) are risk factors for occupational noise-induced hearing loss, whereas being female (OR = 0.496, 95%CI = 0.347–0.709) is a protective factor against occupational noise-induced hearing loss. The longitudinal study revealed differences in pure-tone hearing threshold test results at 500 Hz, 1,000 Hz, 3,000 Hz, 4,000 Hz, and 6,000 Hz in both ears before and after enrollment among noise-exposed workers (p

To evaluate the oral toxicity of nanoparticles (NPs), it is necessary to consider the interactions between NPs and nutrient molecules. Recently, we reported that epigallocatechin gallate (EGCG), a healthy component in green tea, alleviated the toxicity of ZnO NPs to 3D Caco‐2 spheroids in vitro. The present study investigated the combined effects of EGCG and ZnO NPs to mice in vivo. Mice were administrated with 35 or 105 mg/kg bodyweight ZnO NPs with or without the presence of 80 mg/kg bodyweight EGCG via gastric route, once a day, for 21 days, and the influences of EGCG on the toxicity of ZnO NPs to intestine were investigated. We found that EGCG altered the colloidal properties of ZnO NPs both in water and artificial intestine juice. As expected, ZnO NPs induced toxicological effects, such as decreased bodyweight, higher Chiu's scores, and ultrastructural changes in intestine, whereas EGCG alleviated these effects. Combined exposure to EGCG and ZnO NPs also changed trace element levels in mouse intestine. For example, the levels of Ti, Co, and Ni were only significantly elevated after co‐exposure to EGCG and ZnO NPs, and Fe levels were only significantly decreased by ZnO NPs. Western blot analysis suggested that tight junction (TJ) and endoplasmic reticulum (ER) proteins were elevated by ZnO NPs, but EGCG inhibited this trend. Combined, these data suggested that gastric exposure to ZnO NPs induced intestinal damage, trace element imbalance, and TJ/ER protein expression in mouse intestine, whereas EGCG alleviated these effects of ZnO NPs. This study investigated the combined effects of EGCG and ZnO NPs to mouse intestine. EGCG altered hydrodynamic size, zeta potential, and solubility of ZnO NPs. After gastric administration, ZnO NPs induced damages to intestine, impaired trace element balance, and increased TJ and ER proteins, whereas EGCG altered the bio‐effects of ZnO NPs. These data suggested a need to investigate the in vivo oral toxicity of ZnO NPs in the presence of food molecule. [ABSTRACT FROM AUTHOR]

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2′, 7′-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1β and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg), a potent neurotoxin, poses substantial risks to prenatal brain development by crossing the placental barrier. In our daily lives, we are exposed to various environmental metals simultaneously with MeHg. Therefore, the combined exposure effects of these metals and MeHg should be investigated. Hence, this study examined the combined fetal exposure effects of MeHg and copper (Cu), an essential element. Gene expression changes in the fetal brains of mice exposed to MeHg, Cu, or both were examined through RNA-seq analysis. Our results showed that the number of variable genes exposed to combined MeHg and Cu increased compared with that in single exposure. Most of them were gene variations specific to combined exposure. Gene Ontology biological process analysis revealed the amplified effects on GABAergic interneurons in the cerebral cortex under combined exposure. IPA pathway analysis indicated considerable variations in pathways related to oxidative stress, neuronal development, and energy metabolism, including the activation of NRF2-mediated oxidative stress response and the suppression of mitochondrial fatty acid beta-oxidation. These findings highlighted the complexity and enhanced risks of combined MeHg and Cu exposure. Therefore, neurodevelopmental effects were more severe and multifaceted than those caused by individual exposures. This research highlighted the importance of understanding the mechanisms of the combined exposure effects of MeHg. [ABSTRACT FROM AUTHOR]

To investigate the relationship between selenium (Se) based multi-element combined exposure and cognitive function in rural elderly individuals, a cross-sectional study was conducted. The study involved 416 older adults aged 60 and above, residing in four different areas of Enshi county, China, with varying soil Se levels. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to measure the concentrations of Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As), and lead (Pb) in whole blood. Nine standard cognitive tests were applied to assess cognitive function. Analysis of the least absolute shrinkage and selection operator regression (LASSO), covariance (ANCOVA), and generalized linear model (GLM) were utilized to investigate the relationship between element exposure and cognitive function. The results of LASSO revealed that Se, Cu, Fe, Zn, Ca, and Pb were independently identified to be associated with cognition. Both ANCOVA and GLM demonstrated that Se and Ca were correlated with cognitive function. The multi-element model showed higher composite Z scores of 0.32 (95% CI: 0.09 to 0.55) for log-transformed Se (P = 0.007), 0.75 (95% CI: 0.01 to 1.49) for log-transformed Cu (P = 0.048), and a lower score of − 0.67 (95% CI: − 1.26 to − 0.08) for log-transformed Ca (P = 0.025). Furthermore, there was evidence that Se could counteract the negative impact of Ca on cognitive function (P for interaction = 0.031). Our findings suggested that higher levels of Se and Cu were associated with better cognitive function in the elderly and Se can counteract the cognitive damage caused by Ca. [ABSTRACT FROM AUTHOR]

Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100 nm and/or 1 μm) and Cd for 25 days.The results showed that PS at 100 nm caused more severe oxidative damage and cell apoptosis than PS at 1 μm. Combined exposure to PS at both 100 nm and 1 μm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100 nm vs. 1 μm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100 nm PS+1μm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.

Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5μm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.

Occupational exposure to carcinogenic respirable crystalline silica and noise requires a deeper understanding and an assessment of the possible health risks caused by their combined action. Data on individual exposure to respirable crystalline silica (RCS) and occupational noise (ON) was collected among 44 open-pit miners. The study group was divided into two groups according to the job tasks performed. The individual exposure, exceeding of maximum admissible concentration/intensity, and predicted hearing thresholds (HTs) (according to ISO 1999:2013) were compared between the groups directly participating in the technological process (group 1; N = 23) and performing auxiliary, supervising, or laboratory activities (group 2; N = 21). All the analysed indices were significantly higher for group 1; therefore, the job category may predict ON and RCS exposure among open-pit miners. A statistically significant relationship (rs = 0.66, p < 0.05) was found between the time-weighted average (TWA) 8 h RCS and individual daily noise exposure levels. Exposure to noise in the course of employment causes the risk of hearing impairment (mean HTs for 2, 3, and 4 kHz > 25 dB) up to 74% and 4.4% (in the case of groups 1 and 2, respectively). Further studies are needed before conclusions concerning the effects of co-exposure to ON and RCS on open-pit miners can be made.

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

• A time-course progression was noted in PFBS innate toxicity. • Hypoxia was more potent than PFBS to disrupt sex endocrine system. • Hypoxia was the major driver of estrogenic activity in coexposure group. • Hypoxia suspended the egg spawn of marine medaka. • PFBS and hypoxia combination skewed the balance of thyroid hormones. Perfluorobutanesulfonate (PFBS) is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts. However, the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown. In the present study, adult marine medaka were exposed to environmentally realistic concentrations of PFBS (0 and 10 µg/L) under normoxia or hypoxia conditions for 7 days, aiming to explore the interactive behavior between PFBS and hypoxia. In addition, PFBS singular exposure was extended till 21 days under normoxia to elucidate the time-course progression in PFBS toxicity. The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure. With regard to the sex endocrine system, 7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females, which, subsequently, recovered after the 21-day exposure. The potency of hypoxia to disturb the sex hormones was much stronger than PFBS. A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure. Changes in sex endocrinology of coexposed fish were largely determined by hypoxia, which drove the formation of an estrogenic environment. PFBS further enhanced the endocrine disrupting effects of hypoxia. However, the hepatic synthesis of vitellogenin and choriogenin, two commonly used sensitive biomarkers of estrogenic activity, failed to initiate in response to the estrogen stimulus. Compared to sex endocrine system, disturbances in thyroidal axis by PFBS or hypoxia were relatively mild. Overall, the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia. [Display omitted] [ABSTRACT FROM AUTHOR]