Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole\'s potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals.

Bacteria equipped with virulence systems based on highly bioactive small molecules can circumvent their host\'s defense mechanisms. Pathogens employing this strategy are currently threatening global rice production. In the present study, variations in the virulence of the highly destructive Burkholderia plantarii were observed in different rice-producing regions. The environment-linked variation was not attributable to any known host-related or external factors. Co-occurrence analyses indicated a connection between reduced virulence and 5-Amino-1,3,4-thiadiazole-2-thiol (ATT), a non-bactericidal organic compound. ATT, which accumulates in rice plants during metabolization of specific agrochemicals, was found to reduce virulence factor secretion by B. plantarii up to 88.8% and inhibit pathogen virulence by hijacking an upstream signaling cascade. Detailed assessment of the newly discovered virulence inhibitor resulted in mechanistic insights into positive effects of ATT accumulation in plant tissues. Mechanisms of virulence alleviation were deciphered by integrating high-throughput data, gene knockout mutants, and molecular interaction assays. TroK, a histidine protein kinase in a two-component system that regulates virulence factor secretion, is likely the molecular target antagonized by ATT. Our findings provide novel insights into virulence modulation in an important plant-pathogen system that relies on the host\'s metabolic activity and subsequent signaling interference.

The primary factors that restrict agricultural productivity and jeopardize human and food safety are heavy metals (HMs), including arsenic, cadmium, lead, and aluminum, which adversely impact crop yields and quality. Plants, in their adaptability, proactively engage in a multitude of intricate processes to counteract the impacts of HM toxicity. These processes orchestrate profound transformations at biomolecular levels, showing the plant\'s ability to adapt and thrive in adversity. In the past few decades, HM stress tolerance in crops has been successfully addressed through a combination of traditional breeding techniques, cutting-edge genetic engineering methods, and the strategic implementation of marker-dependent breeding approaches. Given the remarkable progress achieved in this domain, it has become imperative to adopt integrated methods that mitigate potential risks and impacts arising from environmental contamination on yields, which is crucial as we endeavor to forge ahead with the establishment of enduring agricultural systems. In this manner, nanotechnology has emerged as a viable field in agricultural sciences. The potential applications are extensive, encompassing the regulation of environmental stressors like toxic metals, improving the efficiency of nutrient consumption and alleviating climate change effects. Integrating nanotechnology and nanomaterials in agrochemicals has successfully mitigated the drawbacks associated with traditional agrochemicals, including challenges like organic solvent pollution, susceptibility to photolysis, and restricted bioavailability. Numerous studies clearly show the immense potential of nanomaterials and nanofertilizers in tackling the acute crisis of HM toxicity in crop production. This review seeks to delve into using NPs as agrochemicals to effectively mitigate HM toxicity and enhance crop resilience, thereby fostering an environmentally friendly and economically viable approach toward sustainable agricultural advancement in the foreseeable future.

Regulatory agencies worldwide set pesticide environmental quality standards, which are proposed independently in each dependent environmental media rather than across the complete fate route. Thus, lacking the fate-pathway perspective in defining pesticide environmental quality standards might cause undesirable pesticide residue from the upper compartment (e.g., soil) to the lower compartment (e.g., water). This study aimed to harmonize the self-consistency of pesticide environmental quality standards across environmental media via the fate-pathway analysis. The introduced qualitative and quantitative rules defined environmental quality standards of pesticides in six major environmental scenarios in the soil and water system based on related regulatory objectives. Fate factors simulated via USEtox were used to create a preliminary quantitative link between theoretical maximum legal masses of pesticides across environmental compartments. Using chlorpyrifos and 2,4-D as examples, their standard values were comparatively assessed in selected environmental media in China and the United States. According to the investigative findings, missing the respective environmental quality standards of pesticides in the agricultural soil could significantly influence the implementation of those in freshwater. Taking a fate-pathway perspective, the self-consistency test highlighted that defining pesticide environmental quality standards for freshwater was the most challenging task, as the freshwater compartment typically comprises multiple lower environmental compartments with diverse regulatory objectives. Overall, this theoretical study has the potential to illuminate the harmonization of pesticide environmental quality standards throughout the entire environmental fate pathway, ultimately leading to improved regulatory efficiency and communication. Future research should focus on risk-based model implementation, regulatory response evaluation, and legal limit interpretation to better integrate environmental pesticide management under a variety of regulatory goals.

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In the protracted \"arms race\" between host and plant pathogenic bacteria, host organisms have evolved powerful weapons known as host defense peptides (HDPs). However, natural HDPs are not suitable for large-scale applications; therefore, researchers have chosen to develop bespoke small-molecule functional mimics. Phenothiazine derivatives were developed as functional HDPs mimics, owing to their broad biological activity and high lipophilicity. The phenothiazine analogues designed in this study exhibited excellent in vitro bioactivity against the three Gram-negative bacteria Xanthomonas oryzae pv oryzae, Xanthomonas axonopodis pv citri, and Pseudomonas syringae pv actinidiae, with optimal EC50 values of 0.80, 0.31, and 1.91 μg/mL, respectively. Preliminary evidence suggests that compound C2 may act on bacterial cell membranes and interact with bacterial Deoxyribonucleic acid in the groove binding mode. In vivo trials showed that compound C2 was highly effective against rice leaf blight (51.97-56.69%), with activity superior to those of bismerthiazol (40.7-43.4%) and thiodiazole copper (30.2-37.1%). Our study provides strong evidence to support the development of phenothiazine derivatives into pesticide candidates.

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Benzoxazole and benzothiazole have a broad spectrum of agricultural biological activities, such as antibacterial, antiviral, and herbicidal activities, which are important fused heterocyclic scaffold structures in agrochemical discovery. In recent years, great progress has been made in the research of benzoxazoles and benzothiazoles, especially in the development of herbicides and insecticides. With the widespread use of benzoxazoles and benzothiazoles, there may be more new products containing benzoxazoles and benzothiazoles in the future. We systematically reviewed the application of benzoxazoles and benzothiazoles in discovering new agrochemicals in the past two decades and summarized the antibacterial, fungicidal, antiviral, herbicidal, and insecticidal activities of the active compounds. We also discussed the structural-activity relationship and mechanism of the active compounds. This work aims to provide inspiration and ideas for the discovery of new agrochemicals based on benzoxazole and benzothiazole.

Organochlorine pesticides show biological toxicity and their degradation typically takes many years. Previous studies of agrochemical-contaminated areas have mainly focused on limited target compounds, and emerging pollutants in soil have been overlooked. In this study, we collected soil samples from an abandoned agrochemical-contaminated area. Target analysis and non-target suspect screening by gas chromatography coupled with time-of-flight mass spectrometry were combined for qualitative and quantitative analysis of organochlorine pollutants. Target analysis showed that dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) were the main pollutants. With concentrations between 3.96 × 106 and 1.38 × 107 ng/g, these compounds posed significant health risks at the contaminated site. Non-target suspect screening identified 126 organochlorine compounds, most of which were chlorinated hydrocarbons and 90% of the compounds contained a benzene ring structure. The possible transformation pathways of DDT were inferred from proven pathways and the compounds identified by non-target suspect screening that had similar structures to DDT. This study will be useful for studies of the degradation mechanism of DDT. Semi-quantitative and hierarchical cluster analysis of compounds in soil showed that the distribution of contaminants in soil was influenced by the types of pollution sources and distance to them. Twenty-two contaminants were found in the soil at relatively high concentrations. The toxicities of 17 of these compounds are currently not known. These results improve our understanding of the environmental behavior of organochlorine contaminants in soil and are useful for further risk assessments of agrochemical-contaminated areas.

The dinitrophenol herbicide dinoseb is an uncoupler of mitochondrial oxidative phosphorylation (OXPHOS). Studies in fish demonstrate impaired OXPHOS is associated with altered immune system responses and locomotor activity in fish. The objective of this study was to determine the effect of dinoseb on zebrafish (Danio rerio) during early stages of development. We measured oxygen consumption rates of embryos, transcripts related to OXPHOS, growth, and the immune system (cytokines and immune-signaling transcripts), and locomotor activity. We hypothesized that OXPHOS of fish would be impaired in vivo, leading to altered basal immune system expression and locomotor activity. Oxidative respiration assessments in embryos revealed that dinoseb decreased both mean basal respiration and oligomycin-induced ATP-linked respiration. Expression levels of cytochrome c oxidase complex IV, 3-hydroxyacyl-COA dehydrogenase and superoxide dismutase 1 were decreased in larvae following exposure to dinoseb while succinate dehydrogenase complex flavoprotein subunit A, insulin growth factor 1 (igf1) and igf2a mRNA were increased in abundance. Immune-related transcripts chemokine (C-X-C motif) ligand 1 and matrix metallopeptidase 9 (MMP-9) were decreased in expression levels while toll-like receptor 5a and 5b were increased in expression. In addition, a visual motor response test was conducted on both 6 and 7 dpf larvae to determine if dinoseb impaired locomotor activity. Dinoseb decreased locomotor activity in 7 dpf larvae but not 6 dpf. This study improves knowledge of toxicity mechanisms for dinoseb in early stages of fish development and demonstrates that mitochondrial toxicants may disrupt immune signaling in zebrafish.