Cardioprotective potentials of myricetin on doxorubicin-induced cardiotoxicity based on biochemical and transcriptomic analysis.

Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.

Exploring the dynamic behaviors of five pesticides in lettuce: Implications for consumer health through field and modeling experiments.

Lettuce, a globally consumed nutritious vegetable, is often linked to concerns regarding pesticide residues. To address this issue, we conducted field trials and utilized dynamiCROP modeling to examine the uptake, distribution, translocation, and dissipation of five pesticides (λ-cyhalothrin, difenoconazole, acetamiprid, dimethomorph, and ß-cypermethrin) commonly detected in lettuce. At harvest, pesticides residues were below the maximum residue limits (MRLs) at 0.05, 0.39, 0.047, 0.72, and 0.072 mg kg-1, respectively. Simulation results elucidated distinct behaviors of the pesticides following application to lettuce foliage across various compartments. However, all pesticides exhibited a common dissipation trend, initially stabilizing or increasing before gradually declining. For all five pesticides, the largest contribution of residues on lettuce leaves came from the leaf surface during the early period after application, and from the soil in the long term. Health risk assessments indicated negligible risks associated with consuming lettuce containing these pesticides, both in the short and long term.

Biochemical and molecular-level effects of co-exposure to chlorpyrifos and lambda-cyhalothrin on the earthworm (Eisenia fetida).

Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.

Therapeutic application and potential mechanism of plant-derived extracellular vesicles in inflammatory bowel disease.

BACKGROUND: Plant-derived extracellular vesicles (PDEVs) are membrane vesicles characterized by a phospholipid bilayer as the basic skeleton that is wrapped by various functional components of proteins and nucleic acids. An increasing number of studies have confirmed that PDEVs can be a potential treatment of inflammatory bowel disease (IBD) and can, to some extent, compensate for the limitations of existing therapies. AIM OF REVIEW: This review summarizes the recent advances and potential mechanisms underlying PDEVs obtained from different sources to alleviate IBD. In addition, the review discusses the possible applications and challenges of PDEVs, providing a theoretical basis for exploring novel and practical therapeutic strategies for IBD. KEY SCIENTIFIC CONCEPTS OF REVIEW: In IBD, the crosstalk mechanism of PDEVs may regulate the intestinal microenvironment homeostasis, especially immune responses, the intestinal barrier, and the gut microbiota. In addition, drug loading enhances the therapeutic potential of PDEVs, particularly regarding improved tissue targeting and stability. In the future, not only immunotherapy based on PDEVs may be an effective treatment for IBD, but also the intestinal barrier and intestinal microbiota will be a new direction for the treatment of IBD.

Antibiotic resistance gene distribution in Shine Muscat grapes and health risk assessment of streptomycin residues in mice.

Antibiotic residues and antibiotic resistance genes (ARGs) in fruits and vegetables pose public health risks via the food chain, attracting increased attention. Antibiotics such as streptomycin, used directly on seedless grapes or introduced into vineyard soil through organic fertilizers. However, extensive data supporting the risk assessment of antibiotic residues and resistance in these produce remains lacking. Utilizing metagenomic sequencing, we characterized Shine Muscat grape antibiotic resistome and mobile genetic elements (MGEs). Abundant MGEs and ARGs were found in grapes, with 174 ARGs on the grape surface and 32 in the fruit. Furthermore, our data indicated that soil is not the primary source of these MGEs and ARGs. Escherichia was identified as an essential carrier and potential transmitter of ARGs. In our previous study, streptomycin residue was identified in grapes. Further short-term exposure experiments in mice revealed no severe physiological or histological damage at several environment-related concentrations. However, with increased exposure, some ARGs levels in mouse gut microbes increased, indicating a potential threat to animal health. Overall, this study provides comprehensive insights into the resistance genome and potential hosts in grapes, supporting the risk assessment of antibiotic resistance in fruits and vegetables.

Discovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery.

Formic acid (FA) has emerged as a promising one-carbon feedstock for biorefinery. However, developing efficient microbial hosts for economically competitive FA utilization remains a grand challenge. Here, we discover that the bacterium Vibrio natriegens has exceptional FA tolerance and metabolic capacity natively. This bacterium is remodeled by rewiring the serine cycle and the TCA cycle, resulting in a non-native closed loop (S-TCA) which as a powerful metabolic sink, in combination with laboratory evolution, enables rapid emergence of synthetic strains with significantly improved FA-utilizing ability. Further introduction of a foreign indigoidine-forming pathway into the synthetic V. natriegens strain leads to the production of 29.0 g · L-1 indigoidine and consumption of 165.3 g · L-1 formate within 72 h, achieving a formate consumption rate of 2.3 g · L-1 · h-1. This work provides an important microbial chassis as well as design rules to develop industrially viable microorganisms for FA biorefinery.

Nano- and micro-polystyrene plastics interfered the gut barrier function mediated by exosomal miRNAs in rats.

Microplastics (MPs) are widely distributed in the global environment, entering and accumulating in organisms in various ways and posing health threats. MPs can damage intestine; however, the mechanism by which MPs cause intestinal damage in rats is unclear. Here, rats were exposed to 50 nm PS-NPs or 5 µm PS-MPs for 4 weeks to evaluate the possible effects on intestinal barrier function and exosomal miRNAs expressions. The results showed that PS-NPs or PS-MPs disrupted the gut microbiota and affected gut barrier function at the biological level. In addition, PS-NPs and PS-MPs altered the composition of exosomal miRNAs in the intestinal and serum. Both PS-NPs and PS-MPs decreased the expression of miR-126a-3p in the intestinal and serum exosomes, which is an important signalling molecule involved in MPs induced gut barrier function disorder. More importantly, both in vitro and in vivo experiments indicated that miR-126a-3p was closely related to oxidative damage of intestinal cells through the PI3K-Akt pathway and eventually promote cell apoptosis by regulating the target gene of PIK3R2. Our study suggested that PS-NPs and PS-MPs could affect rat intestinal barrier function through an exosomal miRNA mediated pathway.

The Dissipation Behavior and Risk Assessment of Carbendazim Under Individual and Joint Applications on Peach (Amygdalus persica L.).

Dissipation, residue levels, and ingestion risks of carbendazim in peach (Amygdalus persica L.) were investigated with individual and joint applications in the present study. The dissipation kinetics of carbendazim, chlorpyrifos, prochloraz, and imidacloprid were evaluated by the first-order kinetics. When carbendazim was individually applied, the final residual concentration was 2.97 mg kg-1 and the half-life was 17.4 d. In the joint application of carbendazim with chlorpyrifos, prochloraz, and imidacloprid, the residual concentrations at 35 d after spraying were 7.16, 7.50, and 4.26 mg kg-1 and the half-lives were 30.8, 23.7, and 23.2 d, respectively, which showed an increase of 1.3-1.8 times compared with the single application of carbendazim. In addition, the effects of household processing of rinsing and peeling were investigated, and a high removal rate of 54.6% and 76.5% were found. Furthermore, the carbendazim ingestion risk assessment was conducted, which indicated that the acute health risk (aHI) and hazard quotient (HQ) of carbendazim were all within acceptable levels ranging from 21.7% to 40.9%. However, a higher ingestion risk of carbendazim was found under the joint application. This study provides some preliminary guidance for the joint application and risk assessment of carbendazim in peach, which is worth further investigation.

[Ecological Risk and Health Risk of Heavy Metal Pollution in Vegetable Production System of Zhejiang Province].

In order to understand the heavy metal contamination of soil and vegetables in the vegetable production system of Zhejiang Province and the health risks of vegetables consumed by residents, typical vegetable production bases in Zhejiang Province were selected as the study areas; 102 pairs of vegetable and soil samples were collected; the distribution characteristics of heavy metals Cd, Cu, Pb, Cr, As, Ni, and Hg in the vegetable production system of Zhejiang Province were analyzed, and the ecological health risks of the vegetable production system were systematically evaluated using the Nemerow composite pollution index, potential ecological risk index, and dietary exposure assessment model. The results showed that Cd in the soil seriously exceeded the standard, with an exceedance rate of 97.2%. The main risk of soil pollution was moderate and mild, and the highest risk was Cd, followed by Pb, Cu, and As. Among vegetables, only a small amount of bean and fruit vegetables exceeded the Cd content, with the exceedance rates of 12.5% and 8.7%, respectively. The BCF of different types of vegetables differed significantly and could be ranked accordingly:leafy vegetables>bean vegetables>melon vegetables>root vegetables. The non-carcinogenic and carcinogenic risks of Zhejiang residents consuming local vegetables were within acceptable limits, with children being more at risk than adults (P<0.01), and Cd and Pb contributing the most to health risks. The overall vegetables produced by the vegetable production system in Zhejiang Province were at a safe level, but there is a need to strengthen the control of Cd and Pb pollution sources.

The occurrence of typical psychotropic drugs in the aquatic environments and their potential toxicity to aquatic organisms - A review.

Psychotropic drugs (PDs) and their bioactive metabolites often persist in aquatic environments due to their typical physical properties, which made them resistant to removal by traditional wastewater treatment plants (WWTPs). Consequently, such drugs and/or their metabolites are frequently detected in both aquatic environments and organisms. Even at low concentrations, these drugs can exhibit toxic effects on non-target organisms including bony fish (zebrafish (Danio rerio) and fathead minnows) and bivalves (freshwater mussels and clams). This narrative review focuses on the quintessential representatives of three different categories of PDs-antiepileptics, antidepressants, and antipsychotics. The data regarding their concentrations occurring in the environment, patterns of distribution, the degree of enrichment in various tissues of aquatic organisms, and the toxicological effects on them are summarized. The toxicological assessments of these drugs included the evaluation of their effects on the reproductive, embryonic development, oxidative stress-related, neurobehavioral, and genetic functions in various experimental models. However, the mechanisms underlying the toxicity of PDs to aquatic organisms and their potential health risks to humans remain unclear. Most studies have focused on the effects caused by acute short-term exposure due to limitations in the experimental conditions, thus making it necessary to investigate the chronic toxic effects at concentrations that are in coherence with those occurring in the environment. Additionally, this review aims to raise awareness and stimulate further research efforts by highlighting the gaps in the understanding of the mechanisms behind PD-induced toxicity and potential health risks. Ultimately, the study underscores the importance of developing advanced remediation methods for the removal of PDs in WWTPs and encourages a broader discussion on mitigating their environmental impacts.

Antimicrobial and the Resistances in the Environment: Ecological and Health Risks, Influencing Factors, and Mitigation Strategies.

Antimicrobial contamination and antimicrobial resistance have become global environmental and health problems. A large number of antimicrobials are used in medical and animal husbandry, leading to the continuous release of residual antimicrobials into the environment. It not only causes ecological harm, but also promotes the occurrence and spread of antimicrobial resistance. The role of environmental factors in antimicrobial contamination and the spread of antimicrobial resistance is often overlooked. There are a large number of antimicrobial-resistant bacteria and antimicrobial resistance genes in human beings, which increases the likelihood that pathogenic bacteria acquire resistance, and also adds opportunities for human contact with antimicrobial-resistant pathogens. In this paper, we review the fate of antimicrobials and antimicrobial resistance in the environment, including the occurrence, spread, and impact on ecological and human health. More importantly, this review emphasizes a number of environmental factors that can exacerbate antimicrobial contamination and the spread of antimicrobial resistance. In the future, the timely removal of antimicrobials and antimicrobial resistance genes in the environment will be more effective in alleviating antimicrobial contamination and antimicrobial resistance.

Joint toxic effects of thiamethoxam and flusilazole on the adult worker honey bees (Apis mellifera L.).

Insect pollinators are routinely exposed to a complex mixture of many pesticides. However, traditional environmental risk assessment is only carried out based on ecotoxicological data of single substances. In this context, we aimed to explore the potential effects when worker honey bees (Apis mellifera L.) were simultaneously challenged by thiamethoxam (TMX) and flusilazole (FSZ). Results displayed that TMX possessed higher toxicity to A. mellifera (96-h LC50 value of 0.11 mg a. i. L-1) than FSZ (96-h LC50 value of 738 mg a. i. L-1). Furthermore, the mixture of TMX and FSZ exhibited an acute synergistic impact on the pollinators. Meanwhile, the activities of SOD, caspase 3, caspase 9, and PPO, as well as the expressions of six genes (abaecin, dorsal-2, defensin-2, vtg, caspase-1, and CYP6AS14) associated with oxidative stress, immune response, lifespan, cell apoptosis, and detoxification metabolism were noteworthily varied in the individual and mixture challenges than at the baseline level. These data revealed that it is imminently essential to investigate the combined toxicity of pesticides since the toxicity evaluation from individual compounds toward honey bees may underestimate the toxicity in realistic conditions. Overall, the present results could help understand the potential contribution of pesticide mixtures to the decline of bee populations.

Analysis on the technical results of tuberculosis laboratory testing in Liaoning Province from 2016 to 2022 / 中国热带医学

@#Abstract: Objective To evaluate the application of TB laboratory detection technology in Liaoning Province from 2016 to 2022, and to provide scientific basis for further improving the detection rate of Mycobacterium tuberculosis in the province. Methods The medical records of registered tuberculosis patients in Liaoning Province from 2016 to 2022 were collected from the "Tuberculosis Information Management System" in the "China Disease Prevention and Control Information System" subsystem. Statistical analysis was performed for sputum coating, sputum culture, and molecular biology testing. Results From 2016 to 2022, a total of 152 778 patients with pulmonary tuberculosis were registered in Liaoning Province. The detection rate of sputum smear microscopy was 98.03% (149 775/152 778), the detection rate of sputum culture was 20.72% (31 661/152 778), and the detection rate of molecular biology testing was 20.21% (30 737/152 778). From 2018 to 2022, the rate of molecular biological detection showed an increasing trend (χ2trend=7 104.466, P<0.01), while from 2016 to 2021, the detection rate of sputum culture showed an increasing trend, with statistical significance (χ2trend=3,068.701, P<0.01). The sputum smear detection rate showed a downward trend（χ2trend=689.913, P<0.01). . There were significant differences in the results of sputum smear microscopy, sputum culture, and molecular biology testing, as confirmed by the McNemar test (P<0.01). The positive rate of pathogenic academics increased from 26.27% in 2016 to 51.55% in 2022, showing a yearly upward trend (χ2trend=5 262.863, P<0.01), with significant differences between each year (χ2=5 686.935, P<0.01). Among pulmonary tuberculosis patients with positive pathogenic microorganisms, the proportion of sputum smear-positive cases decreased from 94.32% to 52.36%, showing a downward trend (χ2trend=5 010.104, P<0.01). The proportion of culture-positive cases increased from 5.68% in 2016 to 12.83% in 2022, showing an upward trend (χ2trend=122.501, P<0.01). In Liaoning Province, molecular biology testing has been carried out since 2018, and the proportion of molecular biology-positive cases increased from 11.51% to 34.81%, showing an increasing trend (χ2trend=1 969.326, P<0.01). The number of positive patients in molecular biological tests in municipal hospitals accounted for 18.69% (8 386/44 778) of etiological positive patients, while the number of positive patients in county-level hospitals accounted for 13.61% (2 439/17 924) of etiological positive patients, with significant differences (χ2=231.594, P<0.01). Conclusions The implementation of molecular biology testing for tuberculosis in Liaoning Province is one of the main measures to improve the positive rate of etiology, and it helps to diagnose tuberculosis patients timely and accurately

Bromuconazole exposure induces cardiotoxicity and lipid transport disorder in larval zebrafish.

Bromuconazole (BRO), as one of the typical triazole fungicides, has not been reported on its effects on aquatic organisms. In this study, zebrafish embryos were used as experimental objects to evaluate the toxicity of BRO. In the acute embryo toxicity test, it was observed that the heart rate and growing development were affected by BRO in a concentration-dependent manner, and the half-lethal concentration (LC50) of BRO at 96 h post-fertilization (hpf) was about 11.83 mg/L. Then, low concentrations of BRO (50 ng/L, 0.075 mg/L, 0.3 mg/L, 1.2 mg/L), which were set according to the LC50 and environmental related concentrations, were used to analyze the toxic effects on the different endpoints in larval zebrafish. Interestingly, the transcriptomic analysis found that most different expressed genes (DEGs) could be focused on the pathways of lipid metabolism, myocardial function, glycometabolism, indicating that heart function and lipid metabolism in larval zebrafish were disrupted by BRO. For supporting this idea, we re-exposed the transgenic zebrafish and WT zebrafish embryos, proved that BRO caused damage to heart development and lipid transport on morphological and genetic level, which was consistent with transcriptomic results. In addition, BRO exposure caused oxidative damage in the larvae. Taken together, BRO exposure could affect the myocardial contraction function and lipid transport in larval zebrafish, accompanied by disturbances in the level of oxidative stress, which was of great significance for improving the biotoxicological information of BRO.

Transgenerational effects of co-exposure to cadmium and carbofuran on zebrafish based on biochemical and transcriptomic analyses.

The combined toxicity of heavy metals and pesticides to aquatic organisms is still largely unexplored. In this study, we investigated the combined impacts of cadmium (Cd) and carbofuran (CAR) on female zebrafish (F0 generation) and their following F1 generation. Results showed that mixtures of Cd and CAR induced acute synergistic effects on both zebrafish adults of the F0 generation and embryos of the F1 generation. Combined exposure to Cd and CAR could obviously alter the hepatic VTG level of females, and the individual exposures increased the relative mRNA levels of vtg1 and vtg2. Through maternal transmission, co-exposure of Cd and CAR caused toxicity to 4-day-old larvae of the F1 generation, evidenced by the significant changes in T4 and VTG levels, CYP450 activity, and the relative transcriptional levels of genes related to the hormone, oxidative stress, and apoptosis. These effects were also reflected by the global gene expression pattern to 7-day-old larvae of F1 generation using the transcriptomic analysis, and they could also affect energy metabolism. Our results provided a more comprehensive insight into the transgenerational toxic impacts of heavy metal and pesticide mixtures. These findings highlighted that it was highly necessary to consider transgenerational exposures in the ecological risk assessment of chemical mixtures.

Unraveling the Mechanism of Purple Leaf Formation in Brassica napus by Integrated Metabolome and Transcriptome Analyses.

Brassica napus as both oilseed and vegetable, is widely cultivated in China. The purple leaf of B. napus is rich in anthocyanins and can provide valuable nutrients. Although several high-anthocyanin cultivars have been reported, the molecular mechanism underlying anthocyanin biosynthesis in B. napus remains lesser-known. Therefore, in this study, we conducted integrative metabolome and transcriptome analyses in three B. napus cultivars with different leaf colors. Overall, 39 flavonoids were identified (including 35 anthocyanins), and 22 anthocyanins were differentially accumulated in the leaves, contributing to the different leaf colors. Cyanidin-3,5,3'-O-triglucoside was confirmed as the main contributor of the purple leaf phenotype. Meanwhile, other anthocyanins may play important roles in deepening the color of B. napus leaves. A total of 5,069 differentially expressed genes (DEGs) and 32 overlapping DEGs were identified by RNA-sequencing; hence, the correlation between anthocyanin content and DEG expression levels was explored. Two structural genes (DFR and ANS), three GSTs (homologous to TT19), and 68 differentially expressed transcription factors (TFs), especially MYB-related TFs and WRKY44, were identified in three B. napus varieties characterized by different leaf color, thereby indicating that these genes may contribute to anthocyanin biosynthesis, transport, or accumulation in B. napus leaves. The findings of study provide important insights that may contribute to gaining a better understanding of the transcriptional regulation of anthocyanin metabolism in B. napus.

Polystyrene microplastics exacerbate experimental colitis in mice tightly associated with the occurrence of hepatic inflammation.

The potential health effects of microplastics (MPs) have become a public concern due to their ubiquitousness in the environment and life. Numerous studies have demonstrated that a high dose of MPs can adversely affect gastrointestinal health. However, few studies have focused on the impact of microplastics on patients' health with respect to gastrointestinal diseases. Inflammatory bowel disease (IBD) has emerged as a global disease with a rapidly increasing incidence. IBD, a specific gastrointestinal illness characterized by acute, chronic inflammation and intestinal barrier dysfunction, might increase sensitivity to MPs exposure. Herein, we investigated the impact and mechanism of PS-MPs on dextran sodium sulfate (DSS)-induced colitis. The results demonstrated that gavage with PS-MPs alone caused minimal effects on the intestinal barrier and liver status of mice. For mice with colitis, additional PS-MPs exposure caused a shorter colon length, aggravated histopathological damage and inflammation, reduced mucus secretion, and increased the colon permeability. Furthermore, PS-MPs exposure also increased the risk of secondary liver injury associated with inflammatory cell infiltration. These findings provide more histopathological evidence and suggest a need for more research on the health risk of MPs for sensitive individuals.

Catechin from green tea had the potential to decrease the chlorpyrifos induced oxidative stress in larval zebrafish (Danio rerio).

Catechin is a biological compound in green tea (Camellia sinesis), which has anti-oxidant, anti-cancer, anti-apoptotic, anti-inflammatory, and attenuated effects in different experimental models. Chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide, has resulted in oxidative stress, mitochondrial dysfunction, and apoptosis in zebrafish. The goal of this study is to assess whether catechin can alleviate CPF-induced oxidative damage and apoptosis in the early developmental stage of zebrafish. According to the results, we observed that 200 µg/L CPF exposure could induce oxidative stress, ROS production and changing the antioxidant-related enzymes and genes in larval zebrafish. Interestingly, catechin had the potential to reduce the oxidative damage and cell apoptosis caused by CPF exposure in larval zebrafish at different endpoints. Especially, catechin could promote the contents of GSH and activity of GST in zebrafish larvae injured by CPF, suggesting that catechin could repair oxidative damage at a certain degree by regulating the activities and gene transcription of some key enzymes related to GSH pathway in zebrafish. In addition, at transcriptional levels, a high concentration of catechin exposure reduced the expression genes of Mn-SOD, Cat, gst, and GPX induced by CPF in larval zebrafish. These genes mainly reflected the degree of oxidative damage of zebrafish, which was basically consistent with the enzyme activity. Catechin also could reduce the transcription of p53 and bax, which are tightly related to the apoptosis induced by CPF in zebrafish larvae. The expression of genes was consistent with ROS production, which proved that catechin could alleviate the apoptosis induced by CPF. This study discovered that catechin had some antioxidant effects in aquatic animals to reduce the toxicity caused by pesticides and offered the scientific basis for the utilization and development of catechin.

Transcriptomic and targeted metabolomic analysis revealed the toxic effects of prochloraz on larval zebrafish.

Prochloraz (PCZ), an imidazole fungicide, has been extensively used in horticulture and agriculture to protect against pests and diseases. To investigate the potential toxicity of PCZ on aquatic organisms, larval zebrafish, as a model, were exposed to a series of concentrations (0, 20, 100, and 500 µg/L) of PCZ for 7 days. With transcriptomic analysis, we found that exposure to high dose PCZ could produce 76 downregulated and 345 upregulated differential expression genes (DEGs). Bioinformatics analysis revealed that most of the DEGs were characterized in the pathways of glycolipid metabolism, amino acid metabolism and oxidative stress in larval zebrafish. Targeted metabolomic analysis was conducted to verify the effects of PCZ on the levels of acyl-carnitines and some amino acids in larval zebrafish. In addition, biochemical indicators related to glycolipid metabolism were affected obviously, manifested as elevated triglyceride (TG) levels and decreased glucose (Glu) levels in whole larvae. The expression levels of genes associated with glycolipid metabolism were affected in larvae after exposure to PCZ (PK, GK, PEPckc, SREBP, ACO). Interestingly, we further confirmed that PCZ could induce oxidative stress by the changing enzyme activities (T-GSH, GSSG) and upregulating several related genes levels in larval zebrafish. Generally, our results revealed that the endpoints related to glycolipid metabolism, amino acid metabolism and oxidative stress were influenced by PCZ in larval zebrafish.

Combined lethal toxicity, biochemical responses, and gene expression variations induced by tebuconazole, bifenthrin and their mixture in zebrafish (Danio rerio).

Pesticides commonly occur as mixtures in an aqueous environment, causing deleterious effects on human health and the environment. However, the mechanism underlying the combined effects on aqueous organisms remains largely unknown, especially at low concentrations. In the current study, we inspected the interactive toxicity of tebuconazole (TEB), a triazole fungicide, and bifenthrin (BIF), a pyrethroid insecticide, to zebrafish (Danio rerio) using various toxicological assays. Our data revealed that the 96 h-LC50 (lethal concentration 50) values of BIF to fish at different life periods (embryonic, larval, juvenile, and adult periods) ranged from 0.013 (0.011-0.016) to 0.41 (0.35-0.48) mg a.i. L-1, which were lower than that of TEB ranging from 1.1 (0.88-1.3) to 4.8 (4.1-5.7) mg a.i. L-1. Combination of TEB and BIF induced synergetic acute toxicity to embryonic fish. Activities of T-SOD, POD, and GST were distinctly altered in most individual and joint administrations. Expressions of 16 genes associated with oxidative stress, cellular apoptosis, immune system, and endocrine system at the mRNA level were evaluated, and the information revealed that embryonic zebrafish were impacted by both individual compounds and their combinations. Six genes (cas9, P53, gr, TRα, IL-8, and cxcl-clc) exhibited greater changes when exposed to pesticide mixtures. Therefore, the joint effects induced by the pesticides at low concentrations should be considered in the risk assessment of mixtures and regulated as priorities for mixture risk management in the aqueous ecosystem. More research is needed to identify the threshold concentrations of the realistic pesticide mixtures above which synergistic interactions occur.