Comprehensive analysis of phospholipid in milk and their biological roles as nutrients and biomarkers.

Phospholipids (PL) have garnered significant attention due to their physiological activities. Milk and other dairy products are important dietary sources for humans and have been extensively used to analyze the presence of PL by various analytical techniques. In this paper, the analysis techniques of PL were reviewed with the eight trigrams of phospholipidomics and a comprehensive fingerprint of 1295 PLs covering 8 subclasses in milk and other dairy products, especially. Technology is the primary productive force. Based on phospholipidomics technology, we further review the relationship between the composition of PL and factors that may be involved in processing and experimental operation, and emphasized the significance of the biological role played by PL in dietary supplements and biomarkers (production, processing and clinical research), and providing the future research directions.

Monitoring Changes in Biochemical and Metabolite Profiles in Garlic Cloves during Storage.

Storage is important for the garlic cloves industry because it is critical to enabling a year-round supply. This study aimed to investigate the changes in biochemical and metabolic profiles in garlic cloves in terms of different temperatures and cultivars during storage using nontargeted and targeted metabolomics. The results showed that the storage temperatures and times were important factors affecting the composition and metabolite content of garlic cloves. In detail, the metabolic profiling of garlic cloves changed significantly at 22 °C, which was mainly related to sprouting. Furthermore, γ-glutamyl peptide was converted into the corresponding flavor precursors or free amino acids, leading to the fluctuation in the amount of nutrients in garlic cloves. In contrast, the quality of garlic cloves remained stable for 290 days at 0 °C though metabolism still occurred, which indicated that the slight chemical changes did not impact the quality significantly and low temperature could prolong their dormancy.

Synergistic developmental effects of zebrafish exposed to combined perfluorooctanoic acid and atrazine.

Perfluorooctanoic acid (PFOA) and atrazine are two endocrine disruptors that are widely found in waters. Negative effects of PFOA and atrazine have been studied individually, but few data have focused on their combined effects. Here, zebrafish embryos were used as model to investigate the combined toxicity of PFOA and atrazine. The acute toxicity of atrazine (11.9 mg/L) to zebrafish embryos was much higher than that of perfluorooctanoic acid (224.6 mg/L) as shown by the 120h-LC50 value. Developmental effects, including delayed yolk sac absorption, spinal curvature, and liver abnormalities, were observed in both one- and two-component exposures. Notably, the rate of embryonic malformations in the co-exposure group was more than twice as high as that of single component exposure in the concentration range of 1/8-1/2 EC50, which indicated a synergistic effect of the binary mixture. The synergistic effect of PFOA-atrazine was further validated by combinatorial index (CI) modeling. In addition, changes of amino acid metabolites, reactive oxygen species and superoxide dismutase indicated that oxidative stress might be the main pathway for enhanced toxicity under co-exposure condition. Overall, co-exposure of PFOA and atrazine resulted in stronger developmental effects and more complicated amino acid metabolic response toward zebrafish, compared with single component exposure.

Levels, Toxic Effects, and Risk Assessment of Pyrrolizidine Alkaloids in Foods: A Review.

Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. To date, more than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health. Here, we summarize the chemical structure, toxic effects, levels, and regulation of PAs in different countries to provide a better understanding of their toxicity and risk assessment. With recent research on the risk assessment of PAs, this review also discusses the challenges facing this field, aiming to provide a scientific basis for PA toxicity research and safety assessment.

Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets.

Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.

AFB1 Triggers Lipid Metabolism Disorders through the PI3K/Akt Pathway and Mediates Apoptosis Leading to Hepatotoxicity.

As the most prevalent mycotoxin in agricultural products, aflatoxin B1 not only causes significant economic losses but also poses a substantial threat to human and animal health. AFB1 has been shown to increase the risk of hepatocellular carcinoma (HCC) but the underlying mechanism is not thoroughly researched. Here, we explored the toxicity mechanism of AFB1 on human hepatocytes following low-dose exposure based on transcriptomics and lipidomics. Apoptosis-related pathways were significantly upregulated after AFB1 exposure in all three hES-Hep, HepaRG, and HepG2 hepatogenic cell lines. By conducting a comparative analysis with the TCGA-LIHC database, four biomarkers (MTCH1, PPM1D, TP53I3, and UBC) shared by AFB1 and HCC were identified (hazard ratio > 1), which can be used to monitor the degree of AFB1-induced hepatotoxicity. Simultaneously, AFB1 induced abnormal metabolism of glycerolipids, sphingolipids, and glycerophospholipids in HepG2 cells (FDR < 0.05, impact > 0.1). Furthermore, combined analysis revealed strong regulatory effects between PIK3R1 and sphingolipids (correlation coefficient > 0.9), suggesting potential mediation by the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (AKT) signaling pathway within mitochondria. This study revealed the dysregulation of lipid metabolism induced by AFB1 and found novel target genes associated with AFB-induced HCC development, providing reliable evidence for elucidating the hepatotoxicity of AFB as well as assessing food safety risks.

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.

Pesticide residues in animal-derived food: Current state and perspectives.

Pesticides are widely used in the cultivation and breeding of agricultural products all over the world. However, their direct use or indirect pollution in animal breeding may lead to residual accumulation, migration, and metabolism in animal-derived foods, posing potential health risks to humans through the food chain. Therefore, it is necessary to detect pesticide residues in animal-derived food using simple, reliable, and sensitive methods. This review summarizes sample extraction and clean-up methods, as well as the instrumental determination technologies such as chromatography and chromatography-mass spectrometry for residual analysis in animal-derived foods, including meat, eggs and milk. Additionally, we perspectives on the future of this field. This information aims to assist relevant researchers in this area, contribute to the development of ideas and novel technical methods for residual detection, metabolic research and risk assessment of pesticides in animal-derived food.

The neurobehavioral impacts of typical antibiotics toward zebrafish larvae.

Due to the widely usage in livestock, aquaculture and clinics, antibiotic residues are existed in aqueous environments and their potential toxicity to aquatic organisms is concerning. Here, we used zebrafish as the model to investigate the neurotoxicity and involved mechanism of seven antibiotics that were frequently detected in surface waters. The results revealed that the short-term exposure to clarithromycin (CLA), chlortetracycline (CTC) and roxithromycin (ROX) induced behavioral effects, with effective concentration of 1 µg/L (CTC and ROX) and 100 µg/L (CLA, CTC and ROX) respectively. A significant decrease in the travel distance and velocity as well as an increase in turn angle was measured. TUNEL assay identified increased cell apoptosis in brain sections of larvae exposed to three neurotoxic antibiotics, which raised the possibility that the behavioral symptoms were associated with neural damage. Transcriptome sequencing showed that the three antibiotics could affect the nervous system of zebrafish including the alteration of synaptogenesis and neurotransmission. Additionally, ROX and CTC affected pathways involved in mitochondrial stress response and endocrine system in zebrafish larvae. Besides, BDNF, ASCL1, and CREBBP are potential upstream regulatory factors that mediated these impacts. These findings indicated that exposure of CTC, ROX and CLA may cause abnormal behavior toward zebrafish larvae under environmental relevant concentration and revealed the potential role of neural cell apoptosis and synaptogenesis signaling in mediating this effect.

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.

Multiomics reveals new biomarkers and mechanistic insights into the combined toxicity effects of 2,2',4,4',5,5'-hexachlorobiphenyl and atrazine exposures in MCF-7 cells.

Humans are constantly exposed to complicated chemical mixtures from the environment and food rather than being exposed to a single pollutant. The underlying mechanisms of the complicated combined toxicity of endocrine disrupting chemicals (EDCs) are still mainly unexplored. In this study, two representative EDCs, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and atrazine (ATZ), were selected to explore their combined effects on MCF-7 cell proliferation at environmental exposure concentrations by an integrated analysis of metabolomics and transcriptomics. The results showed that 1 µM ATZ and PCB153 combined exposure significantly accelerated MCF-7 cell growth by 18.2%. More than 400 metabolites detected by UHPLC-QTOF/MS were used to observe metabolism differences induced by binary mixtures. Metabolomics analysis verified that ATZ and PCB153 exposure alone or in combination could have an additive effect on metabolism and induce significant disruption to glycolysis, purine metabolism and the TCA cycle, which provide energy demand and biosynthetic substrates for cell proliferation. Compared to PCB153 and ATZ exposure alone, a combined effect was observed in purine and pyrimidine metabolic pathways. Hexokinase 3 (HK3) and cytochrome P450 19 subfamily A1 (CYP19A1) were identified as differentially expressed genes based on transcriptomic analysis. By integrating metabolome and transcriptome analysis, the proliferation effects of ATZ and PCB153 were induced at low doses in MCF-7 cells through potential interference with the downstream transcription signaling of CYP19A1. Furthermore, molecular docking indicated that PCB153 and ATZ directly affected CYP19A1. Altogether, the regulation of pivotal metabolites and differentially expressed genes could provide helpful information to reveal the mechanism by which PCB153 and ATZ affect MCF-7 cell proliferation.

Rapid and Portable Detection of Hg and Cd in Grain Samples Based on Novel Catalytic Pyrolysis Composite Trap Coupled with Miniature Atomic Absorption Spectrometry.

As toxic metals, Hg and Cd are a concern for food safety and human health; their rapid and portable analysis is still a challenge. A portable and rapid Hg-Cd analyzer constructed from a metal-ceramic heater (MCH)-based electrothermal vaporizer (ETV), an on-line catalytic pyrolysis furnace (CPF), a composite Pt/Ni trap, and a homemade miniature atomic absorption spectrometer (AAS) was proposed for grain analysis in this work. To enhance sensitivity, a new folded light path was designed for simultaneous Hg and Cd analysis using charge coupled device (CCD) in AAS. To eliminate the grain matrix interference, a catalytic pyrolysis furnace with aluminum oxide fillers was utilized to couple with a composite Pt/Ni trap. The method limits of detection (LODs) were 1.1 µg/kg and 0.3 µg/kg for Hg and Cd using a 20 mg grain sample, fulfilling the real sample analysis to monitor the grain contamination quickly; linearity R2 > 0.995 was reached only using standard solution calibration, indicating the sample was free of grain matrix interference. The favorable analytical accuracy and precision were validated by analyzing real and certified reference material (CRM) grains with recoveries of 97-103% and 96-111% for Hg and Cd, respectively. The total analysis time was less than 5 min without sample digestion or use of any chemicals, and the instrumental size and power consumption were <14 kg and 270 W, respectively. Compared with other rapid methods, this newly designed Hg-Cd analyzer is proven to be simple, portable, and robust and is, thus, suitable to quickly monitor Hg and Cd contamination in the field to protect grain and food safety.

Multi-omics analysis of a drug-induced model of bipolar disorder in zebrafish.

Emerging studies demonstrate that inflammation plays a crucial role in the pathogenesis of bipolar disorder (BD), but the underlying mechanism remains largely unclear. Given the complexity of BD pathogenesis, we performed high-throughput multi-omic profiling (metabolomics, lipidomics, and transcriptomics) of the BD zebrafish brain to comprehensively unravel the molecular mechanism. Our research proved that in BD zebrafish, JNK-mediated neuroinflammation altered metabolic pathways involved in neurotransmission. On one hand, disturbed metabolism of tryptophan and tyrosine limited the participation of the monoamine neurotransmitters serotonin and dopamine in synaptic vesicle recycling. On the other hand, dysregulated metabolism of the membrane lipids sphingomyelin and glycerophospholipids altered the synaptic membrane structure and neurotransmitter receptors (chrnα7, htr1b, drd5b, and gabra1) activity. Our findings revealed that disturbance of serotonergic and dopaminergic synaptic transmission mediated by the JNK inflammatory cascade was the key pathogenic mechanism in a zebrafish model of BD, provides critical biological insights into the pathogenesis of BD.

Rapid detection of ultratrace urinary arsenic by direct sampling microplasma vaporization based on silicon nitride.

At present, immediate monitoring urinary arsenic is still a challenge for treating arsenic poisoning patients. Thus, a fast, reliable and accurate analytical approach is indispensable to monitor ultratrace arsenic in urine sample for health warning. In this work, a silicon nitride (SN) rod was first integrally utilized as a sample carrier for ≤50 µL urinary aliquot, an electric heater for removing water and ashing sample as well as a high voltage electrode for dielectric barrier discharge vaporization (DBDV). The direct analytical method of arsenic in urine without sample digestion was thus developed using atomic fluorescence spectrometer (AFS) as a model detector. After 4 V electrically heating the SN rod for 60 s, urine sample was dehydrated and ashed outside; then, DBD was exerted under 0.8 A with 0.8 L/min H2 + Ar (1:9, v:v) for 20 s to vaporize arsenic analyte from the SN rod. After optimization, 0.014 µg/L arsenic detection limit (LOD) was reached with favorable analytical precision (RSD <5%) and accuracy (91-110% recoveries) for real sample analysis. As a result, the whole analysis process only consumes <3 min to exclude complicated sample preparation; furthermore, the designed DBDV system only occupies 25 W and <2 kg, which renders a miniature sampling component to hyphenate with a miniature detector to detect arsenic. Thus, this direct sampling DBDV method extremely fulfills the fast, sensitive and precise detection of ultratrace arsenic in urine sample.

Comparative Metabolomic Analysis of the Nutritional Aspects from Ten Cultivars of the Strawberry Fruit.

Strawberry (Fragaria × ananassa) is among the most widely cultivated fruits with good taste and rich nutrients. Many strawberry species, including white strawberries, are planted all over the world. The metabolic profiles of strawberry and distinctions among different cultivars are not fully understood. In this study, non-targeted metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to analysis the metabolites in 10 strawberry species. A total of 142 compounds were identified and were divided into six categories. Tochiotome may differ most from the white strawberry (Baiyu) by screening 72 differential metabolites. Histidine, apigenin, cyanidin 3-glucoside and peonidin 3-glucoside had potential as biomarkers for distinguishing Baiyu and another 11 strawberry groups. Amino acid metabolisms, anthocyanin biosynthesis and flavonoid biosynthesis pathways were mainly involved in the determination of the nutrition distinctions. This research contributes to the determination of the nutrition and health benefits of different strawberry species.

Maternal transfer of florfenicol impacts development and disrupts metabolic pathways in F1 offspring zebrafish by destroying mitochondria.

Maternal exposure to antibiotics existing in the environment is a predisposing factor for developmental malformation with metabolic disorders in offspring. In this study, female zebrafish (3 months) were exposed to 0.05 mg/L and 0.5 mg/L florfenicol (FF) for 28 days. After pairing and spawning with healthy male fish, F1 embryos were collected and developed to 5 d post-fertilization (dpf) in clear water. And the adverse effects on the F1 generation were examined thoroughly. The fecundity of F0 female fish and the hatchability, mortality, and body length of F1 larvae significantly decreased in the treatment group. Meanwhile, multi-malformation types were found in the exposure group, including delayed yolk sac absorption, lack of swim bladder, and spinal curvature. Metabolomic and transcriptomic results revealed alterations in metabolism with dysregulation in tricarboxylase acid cycle, amino acid metabolism, and disordered lipid metabolism with elevated levels of glycerophospholipid and sphingolipid. Accompanying these metabolic derangements, decreased levels of ATP and disordered oxidative-redox state were observed. These results were consistent with the damaged mitochondrial membrane potential and respiratory chain function, suggesting that the developmental toxicity and perturbed metabolic signaling in the F1 generation were related to the mitochondrial injury after exposing F0 female zebrafish to FF. Our findings highlighted the potential toxicity of FF to offspring generations even though they were not directly exposed to environmental contaminants.

Novel Platinum-Nickel Composite Trap for Simultaneous and Direct Determination of Mercury and Cadmium in Soil and Its Mechanism Study.

In this work, following a metal-ceramic heater (MCH) as an electrothermal vaporizer (ETV), a novel composite Pt/Ni trap based on platinizing the foamed nickel was first fabricated to trap Hg and Cd simultaneously. So, a solid sampling Hg-Cd analyzer was developed to simultaneously detect trace Hg and Cd in soil samples, mainly consisting of an MCH, a composite Pt/Ni trap, and an atomic fluorescence spectrometer (AFS). This small-size MCH-ETV system only consumes 100 W for the complete vaporization of Hg and Cd in soil matrices. The Pt/Ni trap fulfills the complete trapping of Hg and Cd following the solid sampling MCH-ETV system and then fast releases them by heating. It was proved that trapped and released Hg and Cd by the Pt/Ni trap are atomic species using X-ray photoelectron spectroscopy (XPS) and other approaches; specially, the effective cotrapping of Hg and Cd might be due to forming alloys of Hg + Pt and Cd + Ni on the Pt/Ni trap. Under the optimized conditions, the method detection limits (LODs) of Hg and Cd reached 0.4 µg/kg and 0.04 µg/kg for a 20 mg sample size, the relative standard deviations (RSDs) were within 12% and 8% for soil samples, respectively, and the recoveries ranged from 96% to 105%, indicating favorable analytical sensitivity, precision, and accuracy. The whole analysis time can be controlled within 5 min without the soil digestion process. The proposed Hg-Cd analyzer is thus suitable for rapid detection of Hg and Cd in soil samples with advantages such as simplicity, green, and safety. Further, the proposed solid sampling ETV-composite trap method has a promising application potential in the field and rapid detection for multielements.

A national-scale distribution of organochlorine pesticides (OCPs) in cropland soils and major types of food crops in China: Co-occurrence and associated risks.

Organochlorine pesticides (OCPs) are persistent organic pollutants (POPs) that resist degradation in the environment. OCPs remain detectable in cropland systems in China. However, spatial distribution of OCPs across China and associated ecological and health risks, as well as the relationship between levels of OCPs in cropland soils and crops, remain to be elucidated. To fill these gaps, we conducted a national-scale characterization of 19 individual OCPs in cropland soils and food crops including cereals and legumes in China, which were on-spot sampled simultaneously. Sparse canonical correlation analysis was employed to investigate the co-occurrence of OCPs in cropland soils and corresponding food crops. The ecological soil screening levels and risk quotient method were adopted for ecological and health risk assessment, respectively. Dichlorodiphenyltrichloroethanes (DDTs) were dominant in cropland systems, with its levels ranging up to 337 and 22.8 µg/kg in cropland soils and food crops, respectively. The mean ∑OCP levels in cropland soils varied from below the limit of detection to 337 µg/kg. Peanuts were the most contaminated crop, in which endosulfans and hexachlorobenzene (HCB) were co-occurrent with those in cropland soils (correlation coefficient R = 0.999 and 0.947, respectively). Besides, lindane and ß-endosulfan in rice were co-occurrent with those in cropland soils (R = 0.810 and 0.868, respectively). The componential ratio analysis indicated fresh inputs of technical DDT, lindane, chlordane, endosulfan, HCB and aldrin. Among these pesticides, ecological impacts of DDTs, lindane, aldrin and ß-endosulfan could be expected. Human health risk assessment suggested that daily consumption of the OCP-contaminated food crops raises a health concern especially for male teens. It is concluded that OCPs remain present in cropland systems in China at levels that raise a concern for both environment and human health.

Use of Transcriptomics to Reveal the Joint Immunotoxicity Mechanism Initiated by Difenoconazole and Chlorothalonil in the Human Jurkat T-Cell Line.

It is very important to evaluate the immunotoxicity and molecular mechanisms of pesticides. In this study, difenoconazole and chlorothalonil were evaluated for immunotoxicity by using the human Jurkat T-cell line, and the EC50 were 24.66 and 1.17 mg/L, respectively. The joint exposure of difenoconazole and chlorothalonil showed a synergistic effect at low concentrations (lower than 10.58 mg/L) but an antagonistic effect at high concentrations (higher than 10.58 mg/L). With joint exposure at a concentration of EC10, the proportion of late apoptotic cells was 2.26- and 2.91-fold higher than that with exposure to difenoconazole or chlorothalonil alone, respectively. A transcriptomics analysis indicated that the DEGs for single exposure are associated with immunodeficiency disease. Single exposure to chlorothalonil was mainly involved in cation transportation, extracellular matrix organization, and leukocyte cell adhesion. Single exposure to difenoconazole was mainly involved in nervous system development, muscle contraction, and immune system processes. However, when the joint exposure dose was EC10, the DEGs were mainly involved in the formation of cell structures, but the DEGs were mainly involved in cellular processes and metabolism when the joint exposure dose was EC25. The results indicated that the immunotoxicological mechanisms underlying joint exposure to difenoconazole and chlorothalonil are different under low and high doses.

Comparative Transcriptome Analysis to Investigate the Immunotoxicity Mechanism Triggered by Dimethomorph on Human Jurkat T Cell Lines.

Dimethomorph (DMM) is a broad-spectrum fungicide used globally in agricultural production, but little is known regarding the immunotoxicity of DMM in humans. In this study, the immunotoxicity of DMM on human Jurkat T cells was evaluated in vitro. The results indicated that the half-effective concentration (EC50) of DMM for Jurkat cells was 126.01 mg/L (0.32 mM). To further elucidate the underlying mechanism, transcriptomics based on RNA sequencing for exposure doses of EC25 (M21) and EC10 (L4) was performed. The results indicated that compared to untreated samples (Ctr), 121 genes (81 upregulated, 40 downregulated) and 30 genes (17 upregulated, 13 downregulated) were significantly differentially regulated in the L4 and M21 samples, respectively. A gene ontology analysis indicated that the significantly differentially expressed genes (DEGs) were mostly enriched in the negative regulation of cell activities, and a KEGG pathway analysis indicated that the DEGs were mainly enriched in the immune regulation and signal transduction pathways. A quantitative real-time PCR for the selected genes showed that compared to the high-dose exposure (M21), the effect of the low-dose DMM exposure (L4) on gene expression was more significant. The results indicated that DMM has potential immunotoxicity for humans, and this toxicity cannot be ignored even at low concentrations.