Ecotoxicology and Environmental Safety最新文献

Background

PM_2.5 is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH₄⁺, SO₄²⁻, and NO₃⁻, constituting major components. Early-life PM_2.5 exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies.

Methods

Four groups of C57BL/6 J mice were assigned to four exposure conditions: PM_2.5 NO₃⁻, PM_2.5 SO₄²⁻, PM_2.5 NH₄⁺ and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F₁ mice (offspring) were kept in clean air without exposure to PM_2.5. Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation.

Results

F₁ mice in PM_2.5 NH₄⁺, SO₄^2- and NO₃⁻ groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM_2.5 WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation.

Conclusions

PM_2.5 WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring’s respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1–101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

Background

There is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive.

Methods

A meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate.

Results

A total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18–2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00–1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01–1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma.

Conclusion

Our results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

In an acute contact test with bees the compound of interest is dissolved in a carrier solvent (frequently acetone) and then a droplet of the solution is placed on the dorsal thorax of the bee. The volume of the droplet is standardised to 1 µL for honeybees and to 2 µL for bumblebees. In practice the same droplet volume is used for bees with very different sizes. In this research the effect of the droplet volume was evaluated with acute contact tests with dimethoate for the alfalfa leafcutter bee, the red mason bee, the honeybee and the bumblebee. The results were analysed with a ToxicoKinetic ToxicoDynamic (TKTD) model to separate kinetic from dynamic effects. This allows to compare the sensitivity of the bee based on the effect threshold and not on the time, species and test dependent LD₅₀s. The analysis of the test results indicates that the magnitude of the response of the bees increased with increasing droplet size. The results also showed that the manifestation of effects over time is slower for the red mason bee and the bumblebee compared to the honeybee and the alfalfa leafcutter bee. This implies that the result of a 2 day test with a fixed dosing volume results in different response for a bumblebee compared to the alfalfa leafcutter bee, not because of different sensitivities of the bees involved but due to the difference of relative dosed surface ratio. So comparing the sensitivity of bee species, based on standardised tests is biased and amplifies the sensitivity for the smaller bee species.

Metamifop (MET) is a widely used pesticides in paddy field and it has good weed control effect. As a chiral pesticide that may be hazardous to human health through food chain transmission, there could be selective differences in the metabolism and toxicity of its enantiomers, so the study of chiral MET may offer an assessment of MET toxicity and stereoselectivity at the enantiomeric level. A total of 39, 43 and 31 differential metabolites were screened from the data sets of Rac-, R-(-)- and S-(+)-MET, respectively. Metabolic pathway analysis revealed that MET and its enantiomers primarily affected sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, α-linolenic acid metabolism and arachidonic acid metabolism. Rac- and S-(+)-MET affected the synthesis of glycosylphosphatidylinositol (GPI)-anchored biomolecules. R-(-)- and S-(+)-MET affected glutathione metabolism. R-(-)-MET affected vitamin B6 metabolism, selenium compound metabolism, and steroid biosynthesis. Pyrimidine metabolism was only affected by Rac-MET. The experimental results indicated that MET and its enantiomers may affect the nervous and immune systems in rats. Further inter-group difference analysis also demonstrated stereoselectivity of MET and its enantiomers on rat serum metabolism. These findings may provide more detailed information on the toxicity of Rac-, S-(+)- and R-(-)-MET in rat, as well as some context for assessing the environmental risk of the three agents to organisms.

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

In recent years, the environmental impact of microplastics (MPs) and antibiotics (ATs) as pollutants cannot be ignored. In order to evaluate the carrier effect of MPs in the aqueous environment, three MPs, polyamide (PA), polyethylene (PE) and polyethylene terephthalate (PET), were selected in this study, and their structures were analyzed by means of characterization. A preliminary description of their interactions with sulfamonomethoxine was carried out by adsorption kinetics and isotherm fitting. The dominance of non-bonding capacity (van der Waals and electrostatic interaction forces) in the adsorption process was demonstrated using molecular dynamics (MD) simulations and density functional theory (DFT), with the interaction strengths ranked as PA > PE > PET, respectively. PA is less adsorbent stable at the molecular level but exhibits the largest adsorption capacity influenced by the characterized structure and multiple interaction forces. PET possesses a stronger stability and is not easily replaced by other substances. This will help to further understand the complex effect mechanism between MPs and organic pollutants, and provide an important reference for the prevention and control of environmental pollution.

Di (2-ethylhexyl) phthalate (DEHP), an artificially synthetic plasticizer, is a widespread environmental endocrine disruptor, which has raised substantial concern among the public about its potential reproductive toxicity effects. Taking large amounts of DEHP disrupts the normal functioning of the ovaries, however, the toxicological effects and the mechanisms by which DEHP impairs fetal folliculogenesis remain poorly understood. Our research aims to elucidate the associations between utero exposure to DEHP and fetal folliculogenesis in offspring. In this research, we monitored the spatiotemporal and expression levels of GDF9-Hedgehog (Hh) pathway-related genes during postnatal days 3–14, confirming initially the potential associations between defects in theca cell development and the downregulation of GDF9-Hh signaling. Moreover, utilizing an ovarian organ in vitro culture model, rescue validation experiments demonstrated that the addition of recombinant GDF9 protein effectively alleviate the theca cell damage caused by DEHP, thus supporting the aforementioned associations. In conclusion, our findings validate the significant role of the GDF9-Hh pathway in the enduring reproductive toxicity resulting from prenatal exposure to DEHP.

Background

Expiratory airflow limitation (EAL) is closely associated with respiratory health in youth and adulthood. Owing to limited evidence, we aim to estimate the association between air pollutants, both individually and in combination, along with their chemical compositions, and the risk of EAL in youth based on data obtained from Northeast China Biobank.

Methods

Pulmonary function was evaluated using a medical-grade pulmonary function analyzer, with EAL defined as a forced expiratory flow in 1 s/ forced vital capacity ratio of < 0.8. Land use regression models were used to predict exposure to six air pollutants. Air pollution score (APS) for each participant was constructed as combined exposure. The chemical composition of particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM_2.5) was determined using a validated machine-learning algorithm. Logistic regression models were employed to estimate effect sizes, and odds ratio (OR) and 95 % confidence intervals (CI) were calculated.

Results

In total, 905 EAL cases were identified among the 4301 participants, with a prevalence of 21.04 %. Each inter-quartile range increase in APS was associated with a 25 % higher risk of EAL (OR = 1.25, 95 % CI: 1.12, 1.39). Among the pollutants analyzed, PM_2.5 exposure had the strongest association with the risk of EAL (OR = 1.33, 95 % CI: 1.18, 1.52). Out of the five chemical components, sulfate (SO^2-₄) (OR = 1.39, 95 % CI: 1.24, 1.57) and ammonium (NH⁺₄) (OR = 1.39, 95 % CI: 1.23, 1.57) exhibited the strongest associations with the risk of EAL.

Conclusions

Overall, combined effects of air pollution increased the risk of EAL in youth, with SO^2-₄ and NH⁺₄ emerging as the predominant contributing chemical components in Northeast China.