Triclosan (TCS) is an eminent antibacterial agent. However, extensive usage causes potential health risks like hepatotoxicity, intestinal damage, kidney injury, etc. Existing studies suggested that TCS would disrupt bile acid (BA) enterohepatic circulation, but its toxic mechanism remains unclear. Hence, the current study established an 8-week TCS exposure model to explore its potential toxic mechanism. The results discovered 8 weeks consecutive administration of TCS induced distinct programmed cell death, inflammatory cell activation and recruitment, and excessive BA accumulation in liver. Furthermore, the expression of BA synthesis and transport associated genes were significantly dysregulated upon TCS treatment. Additional mechanism exploration revealed that Fxr inhibition induced by TCS would be the leading cause for unusual BA biosynthesis and transport. Subsequent Fxr up-stream investigation uncovered TCS exposure caused pyroptosis and its associated IL-1β would be the reason for Fxr reduction mediated by NF-κB. NF-κB blocking by dimethylaminoparthenolide ameliorated TCS induced BA disorder which confirmed the contribution of NF-κB in Fxr repression. To sum up, our findings conclud TCS-caused BA disorder is attributed to Fxr inhibition, which is regulated by the IL-1β-NF-κB signaling pathway. Hence, we suggest Fxr would be a potential target for abnormal BA stimulated by TCS and its analogs.
Our investigation seeks to uncover the intricate nature of mercury dynamics in the free troposphere through analysis of the isotopic composition of total gaseous elemental mercury (TGM) at the high altitude Mauna Loa Observatory (MLO, 3397 m) in Hawaii, USA. By focusing on this unique site, we aim to provide essential insights into the behavior and cycling of mercury, contributing valuable data to a deeper understanding of its global distribution and environmental impacts. Forty-eight hours of TGM sampling from January to September 2022 revealed significant variations in δ202Hg (−1.86 % to −0.32 %; mean = −1.17 ± 0.65 %, 2 SD, n = 34) and small variations in Δ199Hg (−0.27 % to 0.04 %; mean = −0.13 ± 0.14 %, 2 SD, n = 34) and Δ200Hg (−0.20 % to 0.06 %; mean = −0.05 ± 0.13 %, 2 SD, n = 34). During the sampling period, GEM was negatively correlated with gaseous oxidized mercury (GOM). However, the GOM/GEM ratio was not −1, suggesting that GEM oxidation and subsequent scavenging occurred previously. The δ202Hg isotopic compositions of TGM at MLO were different from those of reported values of high-altitude mountains; the δ202Hg of TGM at MLO was lower than the isotopic ratios that were obtained from other mountain regions. The unique atmospheric conditions at Mauna Loa, with (upslope winds during the day and downslope winds at night, likely result in the) possibly mixing of GEMs from terrestrial (and possibly oceanic GEM emission) sources with and tropospheric sources, influencing and affect the isotopic composition. During the late summer to early fall (September 14–28), negative correlations were found between relative humidity and GOM and between particle number concentrations and Δ199Hg, indicating the gas-to-particle partitioning of the atmospheric mercury during this period. This study will improve our understanding on mercury dynamics of marine origin and high altitudes and shed light on its complex interactions with environmental factors.
Weeds cause economic losses in cropping systems, leading to the use of 1.7 million tons of herbicides worldwide for weed control annually. Once in the environment, herbicides can reach non-target organisms, causing negative impacts on the ecosystem. Herbicide retention, transport, and degradation processes determine their environmental fate and are essential to assure the safety of these molecules. Radiometric strategies using carbon-14 herbicides (14C) are suitable approaches for determining herbicide absorption, translocation, degradation, retention, and transport in soil, plants, and water. In this work, we demonstrate how 14C-herbicides can be used from different perspectives. Our work focused on herbicide-plant-environment interactions when the herbicide is applied (a) through the leaf, (b) in the soil, and (c) in the water. We also quantified the mass balance in each experiment. 14C-mesotrione foliar absorption increased with oil and adjuvant addition (5–6 % to 25–46 %), and translocation increased only with adjuvant. More than 80 % of 14C-quinclorac and 14C-indaziflam remained in the soil and cover crops species absorbed less than 20 % of the total herbicides applied. In water systems, Salvinia spp. plants removed 10–18 % of atrazine from the water. Atrazine metabolism was not influenced by the presence of the plants. The radiometric strategies used were able to quantify the fate of the herbicide in different plant systems and the mass balance varied from 70 % to 130 %. Importantly, we highlight a critical and practical view of tracking herbicides in different matrices. This technique can aid scientists to explore other pesticides as environmental contaminants.
Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 μg/L and 10.7 μg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI1.5) and the phenotypic endpoint (LD50) with rp=-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.
The associations of ambient air pollution exposure and low-grade inflammation with lung function remain uncertain. In this study, 276,289 subjects were enrolled in the UK Biobank. Individual exposure to ambient air pollution (including nitrogen dioxide [NO2], nitrogen oxides [NOx]), and particulate matter [PM2.5, PM10, PMcoarse]) were estimated by using the land-use regression model. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were tested, and low-grade inflammation score (INFLA score) was calculated for each subject. In this cross-sectional study, the median concentrations of air pollution were 9.89 µg/m3 for PM2.5, 15.98 µg/m3 for PM10, 6.09 µg/m3 for PMcoarse, 25.60 µg/m3 for NO2, and 41.46 µg/m3 for NOx, respectively. We observed that PM2.5, PM10, PMcoarse, NO2, NOx was negatively associated with lung function. Besides, significant positive associations between PM exposure and low-grade inflammation were noted. Per interquartile range (IQR) increase in PM2.5, PM10, and PMcoarse was related to higher INFLA score, and the β (95 % CI) was 0.06 (0.03, 0.08), 0.03 (0.02, 0.05), and 0.03 (0.01, 0.04), respectively. Additionally, we found significant negative associations between INFLA scores and lung function. One-unit increase in INFLA score was linked with 12.41- and 11.31-ml decreases in FVC and FEV1, respectively. Compared with individuals with low air pollution exposure and low INFLA scores, participants with high air pollution and high INFLA scores had the lowest FVC and FEV1. Additionally, we observed that INFLA scores could modify the relationships of PM2.5, NO2, and NOx with FVC and FEV1 (P interaction <0.05). The negative impact of air pollutants on lung function was more pronounced in subjects with high INFLA scores in comparison to those with low INFLA scores. In conclusion, we demonstrated negative associations between ambient air pollution and lung function, and the observed associations were strengthened and modified by low-grade inflammation.
Epidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood.
Bronchial epithelial BEAS-2B cells were either pre-treated with 2 µM nicotine during 16 h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses.
Less γH2AX foci were detected at 1 h after alpha radiation exposure (1–2 Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1 h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27 h after irradiation. Although nicotine did not alter G2 arrest at 24 h, it assisted in cell cycle progression at 48 h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1β (4 Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci.
This study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.
Background: Exposure to fine or respirable particulate matter has been linked to an elevated risk of gestational diabetes mellitus (GDM). However, the association between exposure to particulate matter with an aerodynamic diameter ≤ 1 μm (PM1) and GDM has not been explored.
Methods: We conducted a cohort study involving 60,173 pregnant women from nine hospitals in Beijing, China, from February 2015 to April 2021. Daily concentrations of PM1 and ozone were obtained from a validated spatiotemporal artificial intelligence model. We used a modified Poisson regression combined with distributed lag models to estimate the association between weekly-specific PM1 exposure and the risk of GDM after adjusting for individual-level covariates.
Results: Among the 51,299 pregnant women included in the final analysis, 4008 were diagnosed with GDM. Maternal exposure to PM1 during preconception and gestational periods was generally associated with an increased risk of GDM. The most pronounced associations were identified during the 12th week before pregnancy, the 5th-8th weeks of the first trimester, and the 23rd-24th weeks of the second trimester. Each 10 μg/m3 increase in PM1 was associated with a relative risk of GDM of 1.65 (95 % CI: 1.59, 1.72) during the preconception period, 1.67 (95 % CI: 1.61, 1.73) in the first trimester, 1.52 (95 % CI: 1.47, 1.58) in the second trimester, and 2.54 (95 % CI: 2.45, 2.63) when considering the first and second trimester combined.
Conclusions: Exposure to PM1 before and during pregnancy was associated with an increased risk of GDM, particularly during the 12 weeks before pregnancy and gestational weeks 5-8 and 23-24.
Copper (Cu) is recognized as an essential trace elements for the body; However, excessive levels of Cu can lead to toxic effects. We investigated the effects of Cu2+(75 μg/L, 150 μg/L, and 300 μg/L) on the rainbow trout liver. Combination of transcriptome and metabolome analyses, the regulatory mechanisms of the liver under Cu stress were elucidated. The results showed that Cu affected the antioxidant levels, leading to disruptions in the normal tissue structure of the liver. Combined transcriptome and metabolome analyses revealed significant enrichment of the insulin signaling pathway and the adipocytokine signaling pathway. Additionally, Cu2+ stress altered the amino acid metabolism in rainbow trout by reducing serine and arginine levels while increasing proline content. Apoptosis is inhibited and autophagy and lipid metabolism are suppressed; In summary, Cu2+ stress affects energy and lipid metabolism, and the reduction of serine and arginine represents a decrease in the antioxidant capacity, whereas the increase in proline and the promotion of apoptosis potentially serving as crucial strategies for Cu2+ resistance in rainbow trout. These findings provided insights into the regulatory mechanisms of rainbow trout under Cu2+ stress and informed the prevention of heavy metal pollution and the selection of biomarkers under Cu pollution.
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