Life cycle assessment of hepatotoxicity induced by cyhalofop-butyl in environmental concentrations on zebrafish in light of gut-liver axis.

Cyhalofop-butyl (CB) poses a significant threat to aquatic organisms, but there is a discrepancy in evidence about hepatotoxicity after prolonged exposure to environmental levels. The aim of this study was to investigate long-term hepatotoxicity and its effects on the gut-liver axis through the exposure of zebrafish to environmental concentrations of CB (0.1,1,10 µg/L) throughout their life cycle. Zebrafish experienced abnormal obesity symptoms and organ index after a prolonged exposure of 120 days. The gut-liver axis was found to be damaged both morphologically and functionally through an analysis of histology, electron microscopy subcellular structure, and liver function. The disruption of the gut-liver axis inflammatory process by CB is suggested by the rise in inflammatory factors and the alteration of inflammatory genes. Furthermore, there was a noticeable alteration in the blood and gut-liver axis biochemical parameters as well as gene expression linked to lipid metabolism, which may led to an imbalance in the gut flora. In conclusion, the connection between the gut-liver axis, intestinal microbiota, and liver leads to the metabolic dysfunction of zebrafish exposed to long-term ambient concentrations of CB, and damaged immune system and liver lipid metabolism. This study gives another knowledge into the hepatotoxicity component of long haul openness to ecological centralization of CB, and might be useful to assess the potential natural and wellbeing dangers of aryloxyphenoxypropionate herbicides.

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 µg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 µg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

Neural System Impairment and Involved Microglia-Neuron Regulation of Broflanilide in Zebrafish Larvae.

Broflanilide is widely used to control pests and has attracted attention due to its adverse effects on aquatic organisms. Our previous study showed that broflanilide has a negative impact on the central nervous system (CNS) at lethal dosages; however, its neural effects under practical situations and the underlying mechanisms remain unknown. To elucidate how broflanilide affects the CNS, we exposed zebrafish larvae to broflanilide at 16.9 and 88.0 µg/L (the environmentally relevant concentrations) for 120 h. Zebrafish locomotion was significantly disturbed at 88.0 µg/L, with a decreased moving distance and velocity accompanied by an inhibited neurotransmitter level. In vivo neuroimaging analysis indicated that the nerves of zebrafish larvae, including the axons, myelin sheaths, and neurons, were impaired. The number of neurons was significantly reduced after exposure, with an impaired morphological structure. These changes were accompanied by the abnormal transcription of genes involved in early CNS development. In addition, an increased total number of microglia and an elevated proportion of amoeboid microglia were observed after 88.0 µg/L broflanilide exposure, pointing out to an upstream role of microglia activation in mediating broflanilide neurotoxicity. Meanwhile, increased inflammatory cytokine levels and brain neutrophil numbers were observed, implicating significant inflammatory response and immune toxicity. Our findings indicate that broflanilide interferes with microglia-neuron regulation and induces neurodevelopmental disorders.

Bisphenol analogues induced social defects and neural impairment in zebrafish.

There is evidence in humans that endocrine disrupting chemicals exposure, such as bisphenol A (BPA), is tied to social behavior impacts when evaluated in early life stage. However, the potential social impact of BPA alternatives and its association with central nervous system (CNS) is poorly understood. Here, we performed behavioral test for zebrafish that are continuously exposed to environmental relevant concentrations (5 and 500 ng/L) of BPA, BPF, and BPAF since embryonic stage. Surprisingly, significant social behavior defects, including increased social distance and decreased contact time, were identified in zebrafish treated by 500 ng/L BPAF and BPA. These behavioral changes were accompanied by apparent histological injury, microglia activation, enhanced apoptosis and neuron loss in brain. The gut-brain transcriptional profile showed that genes involved in neuronal development pathways were up-regulated in all bisphenol analogs treatments, indicating a protective phenotype of CNS; however, these pathways were inhibited in gut. Besides, a variety of key regulators in the gut-brain regulation were identified based on protein interaction prediction, such as rac1-limk1, insrb1 and fosab. These findings implicated that the existence of bisphenol analogues in water would influence the social life of fish, and revealed a potential role of gut-brain transcriptional alteration in mediating this effect.

Effects of Broflanilide on Oxidative Stress and Expression of Apoptotic Genes in Zebrafish (Danio rerio) Gill.

Broflanilide exerted negative impacts on the gill of zebrafish. Thus, in this study, zebrafish gill was used to assess the apoptosis toxicity of broflanilide by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and apoptosis-related genes. The results found that the minimum threshold for the content and time of broflanilide affecting enzyme content and gene expression was 0.26 mg/L after 24 h exposure. After 96 h exposure, broflanilide could cause apoptosis and exerted significantly increased contents of ROS and MDA, while inhibiting the activities of SOD, CAT, and GPx at 0.26 and 0.57 mg/L. Broflanilide also had adverse effects on apoptosis-related genes, such as tumor protein p53 (p53), associated × (Bax), B-cell lymphama-2 (Bcl-2), caspase-3, caspase-9, and apoptotic protease activating factor-1(apaf-1), at 0.26 mg/L and 0.57 mg/L after 96 h exposure, respectively. These results provide new insight into the potential toxicity mechanisms of broflanilide in zebrafish gills.

Research into the correlation between positional skull deformation and motor performance of infants aged under 4 months.

OBJECTIVE: To investigate the correlation between positional skull deformation (PD) and motor performance of infants under 4 months of age. METHODS: Infants aged under 4 months were enrolled in the children's healthcare and the premature infants follow-up Clinic of the Second Affiliated Hospital of Army Military Medical University. The cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants, and the infant motor performance test (TIMP) was used to evaluate the infant motor performance. The motor performances of infants with different types and degrees of PD were compared, so were the incidences of PD in infants with different motor performance levels. RESULTS: Overall, 2118 infants were recruited and divided according to the types of PD and TIMP scores. The comparison of TIMP scores within different types of PD at different months of age showed that, regardless of the types of PD, TIMP scores of infants with PD were lower than those of normal infants. In particular, the difference in TIMP scores was statistically significant (P < 0.05) in infants with dolichocephaly, plagiocephaly,dolicho-plagiocephaly and brachy-plagiocephy. In addition, the comparison of CVA values of infants with different TIMP score levels at different months of age showed that the CVA values of the extremely low-level group were significantly higher than those of the medium-level and high-level group, especially in the 3-month-old and 4-month-old groups, which showed significant statistical differences (P < 0.05). CONCLUSIONS: PD and motor performance of infants aged under 4 months seem to interact and influenc each other. The more serious the severity of PD were,the worse the motor performance of infants. Conversely, the incidence of PD increased in infants with poor motor performance.

Effects of virtual reality on preoperative anxiety in children: A systematic review and meta-analysis of randomised controlled trials.

AIMS: To synthesise and evaluate the effectiveness of virtual reality interventions in preoperative children. BACKGROUND: Children consider operations as a predictable threat and stressful event. Children's anxiety before an operation increases as the time draws closer. Children could understand the operating room environment and process before the operation using virtual reality, which may reduce their anxiety before an operation. DESIGN: A systematic review and meta-analysis of randomised controlled trials following the Cochrane method were conducted. METHOD: CINAHL, Cochrane Library, Embase, Joanna Briggs Institute, MEDLINE and PubMed databases were searched for randomised controlled trials published before February 2021. A random-effects model meta-analysis to calculate pooled prevalence and 95% confidence intervals was performed. Conduction of the review adheres to the PRISMA checklist. RESULTS: Of 257 articles screened, six interventions involving 529 participants aged 4-12 years were included in the analysis. All study evidence levels were B2/Level 2, the quality was medium to high on the modified Jadad scale, with a low risk of bias. The results revealed that virtual reality significantly reduced preoperative anxiety in children (SMD: -0.91, 95% CI: -1.43 to -0.39, p = .0006). Furthermore, virtual reality significantly improved children's compliance with anaesthesia (SMD: 3.49, 95% CI: 1.32 to 9.21, p = .01). CONCLUSION: Children who used virtual reality before an operation felt more familiar with the operating room environment and understood the preoperative preparation procedures. Virtual reality effectively reduced children's anxiety and improved their compliance with anaesthesia. RELEVANCE TO CLINICAL PRACTICE: This systematic review and meta-analysis investigated the effect of virtual reality on preoperative anxiety in children and the findings supported its positive effects. The results could provide a reference for incorporating virtual reality into preoperative preparation guidelines.

Transcriptome analysis reveals hepatotoxicity in zebrafish induced by cyhalofop­butyl.

Cyhalofop­butyl is a highly effective aryloxyphenoxypropionate herbicide and widely used for weed control in paddy fields. With the increasing residue of cyhalofop­butyl, it poses a threat to the survival of aquatic organisms. Here, we investigated the effect of cyhalofop­butyl on zebrafish to explore its potential hepatotoxic mechanism. The results showed that cyhalofop­butyl induced hepatocyte degeneration, vacuolation and necrosis of larvae after embryonic exposure for 4 days and caused liver atrophy after 5 days. Meanwhile, the activities of enzymes related to liver function were significantly increased by 0.2 mg/L cyhalofop­butyl and higher, such as alanine transaminase (ALT) and aspartate transaminase (AST). And the contents of triglyceride (TG) involved in lipid metabolism were significantly decreased by 0.4 mg/L cyhalofop-buty. The expression of genes related to liver development was also significantly down-regulated. Furthermore, transcriptome results showed that the pathways involved in metabolism, immune system and endocrine system were significantly impacted, which may be related to hepatoxicity. To sum up, the present study demonstrated the hepatoxicity caused by cyhalofop-buty and its underlying mechanism. The results may provide new insights for the risk of cyhalofop­butyl to aquatic organisms and new horizons for the pathogenesis of hepatotoxicity.

Monocyte-to-lymphocyte ratio affects prognosis in LAA-type stroke patients.

Nowadays, the prognostic prediction of acute ischemic stroke (AIS) patients is still challenging because of the limited predictive properties of existing models. Blood-based biomarkers may provide additional information to the established prognostic factors. Markers of atherosclerosis have been identified as one of the most promising biomarkers for predicting prognosis, and inflammation, in turn, affects atherosclerosis. According to previous studies, the ratio of monocytes to lymphocytes (MLR) has been reported as a novel indicator of inflammation. Thus, our study was the first to conduct more in-depth research on the relationship between MLR and the prognosis of large artery atherosclerosis (LAA)-type AIS patients. A total of 296 patients with LAA-type stroke were recruited. Of these, 202 patients were assigned to the development cohort, and 94 patients were assigned to the validation cohort. In the development cohort, 202 patients were divided into groups A, B, C, and D according to the quartile method of MLR levels. The one-year prognosis of patients was tracked, and the modified Rankin scale (MRS, with a score ranging from 0 to 6) was mainly selected as the measurement result of the function. The relationship between MLR and prognosis was analyzed by building logistics regression models. The models showed that MLR made significant predictions in poor outcomes of LAA-type stroke patients (odds ratio: 4.037; p = 0.048). At the same time, receiver operating characteristics (ROC) curves were used to compare the predictive values between MLR and clinical prediction score (Barthel Index). This study demonstrated that patients with LAA-type stroke and high MLR had a poor prognosis. MLR might be a reliable, inexpensive, and novel predictor of LAA-type stroke prognosis.

Life Cycle Exposure to Cyhalofop-Butyl Induced Reproductive Toxicity in Zebrafish.

Cyhalofop-butyl (CyB) is a herbicide widely used in paddy fields that may transfer to aquatic ecosystems and cause harm to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to CyB at environmental concentrations (0.1, 1 and 10 µg/L) throughout their adult life cycle, from embryo to sexual maturity. The effects of CyB on zebrafish growth and reproduction were studied. It was found that female spawning was inhibited, and adult male fertility decreased. In addition, we examined the expression of sex steroid hormones and genes related to the hypothalamus-pituitary-gonad-liver (HPGL) axis. After 150 days of exposure, the hormone balance in zebrafish was disturbed, and the concentrations of 17ß-estradiol (E2) and vitellogenin (VTG) were decreased. Changes in sex hormone were regulated by the expression of genes related to the HPGL axis. These results confirmed that long-term exposure to CyB at environmental concentrations can damage the reproductive capacity of zebrafish by disrupting the transcription of genes related to the HPGL axis. Overall, these data may provide a new understanding of the reproductive toxicity of long-term exposure to CyB in zebrafish parents and offspring.

Integrated toxicity assessment of DEHP and DBP toward aquatic ecosystem based on multiple trophic model assays.

To comprehensively understand the toxic risks of phthalates to aquatic ecosystems, we examined the acute toxicity of di-(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) on multiple trophic models, including algae (Chlorella vulgaris), Daphnia magna and fish (Danio rerio, Pseudorasbora parva). Thus, a 15-day zebrafish exposure was conducted to trace the dynamic changes of phthalate-induced toxic effects. Among the four species, D. magna exhibited the strongest sensitivity to both DEHP and DBP, followed by D. rerio and P. parva. C. vulgaris exhibited the lowest sensitivity to phthalates. The sub-chronic zebrafish assay demonstrated that 1000 µg/L DBP induced significant mortality at 15 days post-exposure (dpe), and DEHP exhibited no lethality at the tested concentrations (10-5000 µg/L). Zebrafish hepatic SOD activity and sod transcription levels were inhibited by DBP from 3 dpe, which was accompanied by increased malondialdehyde level, while zebrafish exposed to DEHP exhibited less oxidative damage. Both DEHP and DBP induced time-dependent alterations on Ache activity in zebrafish brains, thus indicating the potential neurotoxicity toward aquatic organisms. Additionally, 1000 µg/L and higher concentration of DBP caused hepatic DNA damage in zebrafish from 7 dpe. These results provide a better understanding of the health risks of phthalate to water environment.

Parental exposure to propiconazole at environmentally relevant concentrations induces thyroid and metabolism disruption in zebrafish (Danio rerio) offspring: An in vivo, in silico and in vitro study.

Propiconazole is used against fungal growth in agriculture and is released into the environment, but is a potential health threat to aquatic organisms. Propiconazole induces a generational effect on zebrafish, although the toxic mechanisms involved have not been described. The aim of this study was to investigate the potential mechanisms of abnormal offspring development after propiconazole exposure in zebrafish parents. Zebrafish were exposed to propiconazole at environmentally realistic concentrations (0.1, 5, and 250 µg/L) for 100 days and their offspring were grown in control solution for further study. Heart rate, hatching rate, and body length of hatched offspring were reduced. An increase in triiodothyronine (T3) content and the T3/T4 (tetraiodothyronine) ratio was observed, indicating disruption of thyroid hormones. Increased protein level of transthyretin (TTR) in vivo was consistent with the in silico molecular docking results and T4 competitive binding in vitro assay, suggests higher binding affinity between propiconazole and TTR, more than with T4. Increased expression of genes related to the hypothalamus-pituitary-thyroid (HPT) axis and altered metabolite levels may have affected offspring development. These findings emphasizes that propiconazole, even on indirect exposure, represents health and environmental risk that should not be ignored.

A Systematic Review of Associations between Energy Use, Fuel Poverty, Energy Efficiency Improvements and Health.

Energy use in buildings can influence the indoor environment. Studies on green buildings, energy saving measures, energy use, fuel poverty, and ventilation have been reviewed, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The database PubMed was searched for articles published up to 1 October 2020. In total, 68 relevant peer-reviewed epidemiological or exposure studies on radon, biological agents, and chemicals were included. The main aim was to assess current knowledge on how energy saving measures and energy use can influence health. The included studies concluded that buildings classified as green buildings can improve health. More efficient heating and increased thermal insulation can improve health in homes experiencing fuel poverty. However, energy-saving measures in airtight buildings and thermal insulation without installation of mechanical ventilation can impair health. Energy efficiency retrofits can increase indoor radon which can cause lung cancer. Installation of a mechanical ventilation systems can solve many of the negative effects linked to airtight buildings and energy efficiency retrofits. However, higher ventilation flow can increase the indoor exposure to outdoor air pollutants in areas with high levels of outdoor air pollution. Finally, future research needs concerning energy aspects of buildings and health were identified.

Acute toxicity of broflanilide on neurosecretory system and locomotory behavior of zebrafish (Danio rerio).

Broflanilide, a novel meta-diamide insecticide, possesses moderate acute toxicity to zebrafish, with a 96-h median lethal concentration (96-LC50) of 0.76 mg/L. However, its effect on fish behavior and the underlying mechanisms are still unclear. The present study evaluated the effects of broflanilide on the zebrafish brain over a 96-h exposure by comparing the histopathological changes and relative expression of targeted genes with the behavioral metrics. The results of the toxicity test showed that broflanilide could cause deformities, such as deformation of the operculum and spinal curvature, at 0.6, 0.82 and 1.15 mg/L. Results also showed tissue damage and apoptosis in the cerebellum under 0.27 and 0.6 mg/L exposure. Additionally, broflanilide affected the neurotransmitters, metabolites and transcripts of genes associated with dopamine, gamma-aminobutyric acid expression. and the signaling pathways in zebrafish brains at 0.60 mg/L after 1 h and 96 h of exposure, while the levels of glutamate, glutamate decarboxylase, GABA transaminase, nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP) were also inhibited at 0.27 mg/L after 96 h of exposure. The accumulated swimming distance was significantly longer and the average speed was significantly faster than the control at 0.27 and 0.6 mg/L after 1-h of exposure, while these metrics were lowered at 0.6 mg/L after 96 h of exposure. The study results demonstrates that broflanilide affects the zebrafish brain, neurotransmitters and associated fish behaviors. This study also provides deeper insight into the mechanistic understanding of the effects of broflanilide on the zebrafish brain.

Bisphenol F Impaired Zebrafish Cognitive Ability through Inducing Neural Cell Heterogeneous Responses.

The central nervous system (CNS) is a sensitive target for endocrine-disrupting chemicals, such as bisphenol analogues. Bisphenol A (BPA) usage is associated with the occurrence of many neurological diseases. With the restricted use of BPA, bisphenol F (BPF) has been greatly introduced for industrial manufacture and brings new hazards to public CNS health. To understand how BPF affects the neural system, we performed a cognitive test for zebrafish that are continuously exposed to environmentally relevant concentrations (0.5 and 5.0 µg/L) of BPF since embryonic stage and identified suppressed cognitive ability in adulthood. Single-cell RNA sequencing of neural cells revealed a cell composition shift in zebrafish brain post BPF exposure, including increase in microglia and decrease in neurons; these changes were further validated by immune staining. At the same time, a significant inflammatory response and increased phagocytic activity were detected in zebrafish brain post BPF exposure, which were consistent with the activation of microglia. Cell-specific transcriptomic profiles showed that abnormal phagocytosis, activated brain cell death, and apoptosis occurred in microglia post BPF exposure, which are responsible for the neuron loss. In addition, certain neurological diseases were affected by BPF in both excitatory and inhibitory neurons, such as the movement disorder and neural muscular disease, however, with distinctly involved genes. These findings indicate that BPF exposure could lead to an abnormal cognitive behavior of zebrafish through inducing heterogeneous changes of neural cells in brain and revealed the dominating role of microglia in mediating this effect.

Polystyrene Nanoplastics Toxicity to Zebrafish: Dysregulation of the Brain-Intestine-Microbiota Axis.

In animal species, the brain-gut axis is a complex bidirectional network between the gastrointestinal (GI) tract and the central nervous system (CNS) consisting of numerous microbial, immune, neuronal, and hormonal pathways that profoundly impact organism development and health. Although nanoplastics (NPs) have been shown to cause intestinal and neural toxicity in fish, the role of the neurotransmitter and intestinal microbiota interactions in the underlying mechanism of toxicity, particularly at environmentally relevant contaminant concentrations, remains unknown. Here, the effect of 44 nm polystyrene nanoplastics (PS-NPs) on the brain-intestine-microbe axis and embryo-larval development in zebrafish (Danio rerio) was investigated. Exposure to 1, 10, and 100 µg/L PS-NPs for 30 days inhibited growth and adversely affected inflammatory responses and intestinal permeability. Targeted metabolomics analysis revealed an alteration of 42 metabolites involved in neurotransmission. The content of 3,4-dihydroxyphenylacetic acid (DOPAC; dopamine metabolite formed by monoamine oxidase activity) was significantly decreased in a dose-dependent manner after PS-NP exposure. Changes in the 14 metabolites correlated with changes to 3 microbial groups, including Proteobacteria, Firmicutes, and Bacteroidetes, as compared to the control group. A significant relationship between Firmicutes and homovanillic acid (0.466, Pearson correlation coefficient) was evident. Eight altered metabolites (l-glutamine (Gln), 5-hydroxyindoleacetic acid (5-HIAA), serotonin, 5-hydroxytryptophan (5-HTP), l-cysteine (Cys), l-glutamic acid (Glu), norepinephrine (NE), and l-tryptophan (l-Trp)) had a negative relationship with Proteobacteria although histamine (His) and acetylcholine chloride (ACh chloride) levels were positively correlated with Proteobacteria. An Associated Network analysis showed that Firmicutes and Bacteroidetes were highly correlated (0.969). Furthermore, PS-NPs accumulated in the gastrointestinal tract of offspring and impaired development of F1 (2 h post-fertilization) embryos, including reduced spontaneous movements, hatching rate, and length. This demonstration of transgenerational deficits is of particular concern. These findings suggest that PS-NPs cause intestinal inflammation, growth inhibition, and restricted development of zebrafish, which are strongly linked to the disrupted regulation within the brain-intestine-microbiota axis. Our study provides insights into how xenobiotics can disrupt the regulation of brain-intestine-microbiota and suggests that these end points should be taken into account when assessing environmental health risks of PS-NPs to aquatic organisms.

Quizalofop-P-ethyl induced developmental toxicity and cardiotoxicity in early life stage of zebrafish (Danio rerio).

Quizalofop-P-ethyl (QpE), a highly efficient selective herbicide, has good control effect on annual and perennial weeds. However, its excessive use will pose a threat to the ecological environment. QpE has been proven harmful to aquatic organisms, but there is little evidence on the adverse effects of QpE in the early life of aquatic organisms. In this work, zebrafish (Danio rerio) embryos were treated with 0.10, 0.20, 0.30, 0.40, and 0.50 mg/L of QpE for 120 h. The findings revealed that the LC50 value of QpE to zebrafish embryos was 0.23 mg/L at 96 hpf. QpE exposure significantly increased the mortality rate, decreased the hatching rate and caused morphological defects during zebrafish embryonic development, with a concentration dependent manner. QpE also caused severe morphological changes in the cardiovascular system, as well as resulted in a dysfunction in cardiovascular performance. Meanwhile, both histopathological examination and neutrophil observations showed inflammatory response occurred in the heart. Furthermore, several genes associated with heart development and inflammation were significantly altered following QpE exposure. A protein-protein interaction (PPI) network analysis proved that there was a connection between the changed heart development-relevant and inflammation-related genes. Taken together, our findings suggest that QpE causes cardiotoxicity in zebrafish embryos by altering the expression of genes in the regulatory network of cardiac development, which might be aggravated by inflammatory reactions, thereby affecting embryo development. These findings generated here are useful for in-depth assessment of the effects of QpE on early development of aquatic organisms and providing theoretical foundation for risk management measures.

Exposure to difenoconazole induces reproductive toxicity in zebrafish by interfering with gamete maturation and reproductive behavior.

Difenoconazole (DCZ) is a triazole fungicide that negatively affects aquatic organisms and humans. However, data regarding the reproductive toxicity of DCZ are insufficient. In this study, we used zebrafish (from 2 h post-fertilization [hpf] to adulthood) as a model to evaluate whether DCZ at environmentally relevant concentrations (0.1, 1.0, and 10.0 µg/L) induces reproductive toxicity. After exposure to DCZ, egg production and fertilization rates were reduced by 1.0 and 10.0 µg/L. A significant decrease in gamete frequency (late vitellogenic oocytes and spermatozoa) was observed at 10.0 µg/L. The concentrations of 17ß-estradiol (E2), testosterone (T), and vitellogenin (VTG) were disrupted in females and males by 1.0 and 10.0 µg/L. Exposure to 10.0 µg/L DCZ significantly inhibited the contact time between female and male fish, which was mainly achieved by affecting male fish. The transcription of genes involved in the hypothalamus-pituitary-gonad (HPG) axis was significantly changed after treatment with DCZ. Overall, these data show that the endocrine-disrupting effect of DCZ on the zebrafish HPG axis inhibited gamete maturation and disrupted reproductive behavior, reducing fertility.

Bisphenol analogues induced metabolic effects through eliciting intestinal cell heterogeneous response.

The metabolic effects of endocrine-disrupting chemicals, such as bisphenol analogues, have drawn increasing attention. Bisphenol A (BPA) usage is associated with the occurrence of many metabolic diseases. With the restricted use of BPA, alternatives like bisphenol F (BPF) and bisphenol AF (BPAF) have been greatly introduced for industrial manufacture, and brings new hazard to public health. To understand how bisphenol analogues induced metabolic effects, zebrafish are continuous exposed to environmental level (0.5 µg/L) of BPA, BPF and BPAF since embryonic stage, and identified hepatic steatosis and insulin resistance at 60-day post fertilization. Hepatic transcriptional profile indicated that pancreatic disease pathways were activated by BPA, but were inhibited by BPF. At the same time, increased lipid secretion and gluconeogenesis pathways in zebrafish liver was found post BPAF exposure. Significant inflammatory response, histological injury and increased mucus secretion was detected in zebrafish intestine post exposure of three bisphenol analogues. Single-cell RNA sequencing of zebrafish intestinal cells revealed activation of lipid uptake and absorption pathways in enterocyte lineages, which well explained the hepatic steatosis induced by BPA and BPF. Besides, genes related to carbohydrate metabolism, diabetes and insulin resistance were activated in intestinal immune cell types by three bisphenol analogues. These findings indicated that BPA and its alternatives could lead to abnormal lipid and carbohydrate metabolism of zebrafish through inducing cell heterogeneous changes in gut, and revealed both molecular and cellular mechanism in mediating this effect.

Insights into the mechanisms of organic pollutant toxicity to earthworms: Advances and perspectives.

Earthworms play positive ecological roles in soil formation, structure, and fertility, environmental protection, and terrestrial food chains. For this review, we searched the Web of Science database for articles published from 2011 to 2021 using the keywords "toxic" and "earthworm" and retrieved 632 publications. From the perspective of bibliometric analysis, we conducted a co-occurrence network analysis using the keywords "toxic" and "earthworm" to identify the most and least reported topics. "Eisenia fetida," "bioaccumulation," "heavy metals," "oxidative stress," and "pesticides" were the most common terms, and "microbial community," "bacteria," "PFOS," "bioaugmentation," "potentially toxic elements," "celomic fluid," "neurotoxicity," "joint toxicity," "apoptosis," and "nanoparticles" were uncommon terms. Additionally, in this review we highlight the main routes of organic pollutant entry into soil, and discuss the adverse effects on the soil ecosystem. We then systematically review the mechanisms underlying organic pollutant toxicity to earthworms, including oxidative stress, energy and lipid metabolism disturbances, neurological toxicity, intestinal inflammation and injury, gut microbiota dysbiosis, and reproductive toxicity. We conclude by discussing future research perspectives, focusing on environmentally relevant concentrations and conditions, novel data processing approaches, technologies, and detoxification and mitigation methods. This review has implications for soil management in the context of environmental pollution.