Organophosphates (OPs) are highly hazardous chemicals with broad-spectrum toxicity. Traditional in vivo methods for determining OP toxicity are time-consuming and labor-intensive. In this study, we developed a quantitative structure-activity relationship (QSAR) model to predict acute rat toxicity of OPs using two-dimensional molecular and quantum chemical descriptors, optimized through genetic algorithm-based multiple linear regression (GA-MLR). The optimal model demonstrated robust performance with the following statistical parameters: coefficient of determination (R2) of 0.7451, leave-one-out cross-validation (LOOCV) coefficient (Q2Loo) of 0.6208, external test set coefficient of determination (R2ext) of 0.7360. These metrics indicate excellent generalization and predictive capabilities of the model. Interpretative analysis of the model revealed that NumHDonors and PEOE_VSA were the most significant descriptors influencing OP toxicity. An increase in hydrogen bond donors within OP molecules reduces toxicity, as these donors enhance hydrophilicity, diminishing membrane permeability. Moreover, the PEOE_VSA descriptor characterizes the partial charge properties of OP molecules, reflecting their electrostatic interactions with acetylcholinesterase (AChE) during binding, which influences toxicity. This study presents an optimized modeling strategy designed for small datasets, enabling stable feature selection and accurate assessment of their contributions to toxicity prediction. This research provides a reliable QSAR approach for OP toxicity prediction while offering new insights into toxicity mechanisms.

Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.

Organophosphate pesticides (OPPs) are widely used environmental chemicals with potential health impacts, but their relationship with atopic dermatitis (AD) remains unclear.

Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2007, we investigated associations between urinary OPP metabolites and AD in 4,258 adults. Six dialkyl phosphate (DAP) metabolites were measured, and weighted quantile sum (WQS) regression was used to assess mixture effects.

Both DMP (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.05-1.31) and DMDTP (OR = 2.23, 95%CI: 1.08-4.60) showed significant positive associations with AD in fully adjusted models. WQS regression revealed significant associations between mixed OPP exposure and AD (OR = 1.25, 95%CI: 1.04-1.50), with DMP contributing most (45.8%) to the mixture effect. Stratified analyses indicated stronger associations in males, younger adults (<60 years), and smokers.

Our findings suggest that OPP exposure, particularly DMP, may be associated with increased AD risk in adults. These results provide new insights into environmental risk factors for AD.

Recent studies link pesticide exposures to cardiovascular disease risk factors. However, research on the combined effects of multiple pesticides on atherosclerotic cardiovascular disease (ASCVD) is limited, particularly in rural areas. Despite advances in toxicogenomics, the mechanisms underlying these effects remain unclear. This study aims to investigate the combined effects and mechanisms of pesticide exposures on ASCVD.

In the cross-sectional study section, 2291 participants were included. Variables were filtered using machine learning models, and associations between mixed exposure to multiple pesticides and ASCVD were explored using environmental mixed exposure models (weighted quartile sum (WQS) regression and quantile-based g-computation (QGC)). In the bioinformatics analysis section, the GEO, CTD, Malacards, and GeneCards databases were used to retrieve target genes for pesticide exposure and atherosclerotic diseases. Enrichment analysis was then performed to identify the biological pathways associated with these genes.

Three machine models screened 34 pesticides. Single pesticide exposures, such as atrazine, oxadiazon, p,p'-DDE, α-BHC, β-BHC, fenitrothion, malathion, fenitrothion, cypermethrin, cypermethrin, and cypermethrin might increase the 10-year ASCVD risk (all P < 0.05). Total mixed pesticide exposure was positively associated with 10-year ASCVD risk in both the QGC (3.223(2.196, 4.730)) and WQS models (4.642(3.070, 7.020)). Notably, there was a linear relationship between totalQGC (P_overal < 0.001; P_nonlinearity = 0.864) and high 10-year ASCVD risk. In toxicogenomic bioinformatics analysis, we identified 112 potential atherosclerosis target genes affected by pesticide exposure. Pathway enrichment analysis suggests pesticide-induced atherosclerosis is linked to pathways such as metabolic pathways, lipid metabolism, MAPK, AMPK, FoxO signaling, apoptosis, fluid shear stress, endocrine resistance, TNF, and PI3K-Akt. Key genes were identified based on maximal clique centrality, including AKT1, TP53, IL6, BCL2, TNF, JUN, PTGS2, CASP3, MAPK3, and CASP9.

Individual and combined exposure to pesticides increased the 10-year ASCVD risk, especially in patients with T2DM. Mixed levels of pesticide exposure were linearly and positively associated with high 10-year ASCVD risk. The mechanism of atherogenesis by mixed pesticide exposure may involve pathways such as lipid metabolism, MAPK, AMPK, FoxO signaling, apoptosis, fluid shear stress, endocrine resistance, TNF, and PI3K-Akt.

Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes (T2D); however, the underlying mechanisms remain unknown. DNA methylation may play a role in this process.

To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.

We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation, and studies on DNA methylation and T2D through January 15, 2024.

We identified six genes (Alu, CABLES1, CDH1, PDX1, PTEN, PTPRN2) related to pesticide exposure and T2D. We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.

DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.

We conducted a systematic review and meta-analysis of observational studies that assessed the relationship between pesticides exposure and type 2 diabetes. We also examined the presence of heterogeneity and biases across the available studies.

We conducted a comprehensive literature search of peer-reviewed studies published from 2011 to 2023, without language limitations. A random-effects model was employed to calculate the overall odds ratio (OR) and its corresponding 95% confidence interval (CI).

We included 19 studies (n = 12 case-control and n = 7 cross-sectional) for a total of 45,813 participants in our analysis. Our findings revealed a notable correlation between pesticide exposure and type 2 diabetes (non-specific definition) when not limiting pesticide types (OR: 1.19, 95% CI: 1.11-1.28). Subgroup analysis identified associations between pyrethroid (OR: 1.17, 95% CI: 1.05-1.30) and type 2 diabetes, as well as between organochlorine (OR: 1.26, 95% CI: 1.11-1.43) and type 2 diabetes. However, no statistically significant association was observed between herbicide exposure and the onset of type 2 diabetes (OR: 1.26, 95% CI: 0.91-1.75). In the elderly group, pesticide exposure significantly heightened the risk of type 2 diabetes (OR: 1.25, 95% CI: 1.14-1.38), with no statistically significant heterogeneity among studies (I2 = 14.2%, p = 0.323).

Pesticide (organochlorine and pyrethroid) exposure constitutes a risk factor for type 2 diabetes.

Endocrine disruptors (EDs) can mimic or interfere with hormones in the body, leading to non-communicable diseases, such as obesity, diabetes, and metabolic syndrome. Susceptibility to EDs increases during prenatal and postnatal life, a critical time window. This review aims to summarize the latest evidence on the relation of early life exposure to some EDs with obesity and the other metabolic disorders.  RECENT FINDINGS: There is increasing evidence that early life exposure to EDs may impair adipogenesis by increasing the number and size of adipocytes, thereby increasing susceptibility to obesity in childhood. It is stated that exposure to EDs during the prenatal and postnatal period may raise the risk of type 2 diabetes in adulthood by disrupting glucose, lipid, and insulin homeostasis in the offspring. They can also accelerate the development of type 1 diabetes through various mechanisms, like immunomodulation, gut microbiota, and vitamin D pathways. There is a growing understanding that ED exposure during critical stages of life could play an important role in the development of obesity and metabolic disorders. We suggest setting national goals, global standards, and policies to reduce environmental exposure to pregnant and lactating women, and babies, considered sensitive populations.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 μg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 μg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 μg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 μg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 μg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

The global use of pesticides steadily increased until the early 2010s. Pesticides play a significant role in agriculture in Korea. Metabolic syndrome is more prevalent in rural areas than in urban areas. This study explored the potential association between organophosphate and pyrethroid pesticide exposure and metabolic syndrome.

This study enrolled 1,317 individuals who participated in the Pesticide Exposure and Intoxication Study conducted by the Dankook University Hospital Center for Farmers' Safety and Health from 2014 to 2019. Urinary levels of dimethylphosphate, dimethylthiophosphat, diethylphosphate, and diethylthiophosphate were measured to assess organophosphate pesticide exposure and urinary levels cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, and 3-phenoxybenzoic acid were measured to assess pyrethroid pesticide exposure.

The odds ratio for the 4th quartile group of organophosphate metabolites concentration was 1.48 (95% confidence interval: 1.06-2.09) compared to the 1st quartile group after adjustment for general factors. In addition, a positive trend was observed across the quartile groups of organophosphate metabolites concentration. A positive trend was noted across the quartile groups of organophosphate metabolites in males, while no significant association was observed in females. Furthermore, no significant associations were observed between metabolic syndrome and pyrethroid metabolites concentration.

A positive correlation was observed between the prevalence of metabolic syndrome and the concentrations of urinary organophosphate metabolites, consistent with previous research finding. This association may be attributed to the action of organophosphates as acetylcholinesterase inhibitors, stimulating beta cells in the islets of Langerhans. This can lead to alterations in lipid metabolism and insulin resistance, ultimately leading to metabolic syndrome development. Metabolic syndrome is a major contributor to cardiovascular disease; therefore, it is necessary to identify the risk factors unique to rural areas, such as pesticide exposure.

Fenitrothion (FNT) is a common organophosphorus pesticide that is widely used in both agricultural and domestic pest control. FNT has been frequently detected in various environmental media, including the human body, and is a notable contaminant. Epidemiological investigations have recently shown the implications of exposure to FNT in the incidence of various metabolic diseases, such as diabetes mellitus in humans, indicating that FNT may be a potential endocrine disruptor. However, the effects of FNT exposure on glucose homeostasis and their underlying mechanisms in model organisms remain largely unknown, which may limit our understanding of the health risks of FNT. In this study, FNT (4 5, 90, 180, and 4 50 μM) exposure model of rat hepatocytes (Buffalo Rat Liver, BRL cells) was established to investigate the effects and potential mechanisms of its toxicity on glucose metabolism. Several key processes of glucose metabolism were detected in this study. The results showed significantly increased glucose levels in the culture medium and decreased glycogen content in the FNT-exposed BRL cells. The results of quantitative real-time PCR and enzymology showed the abnormal expression of genes and activity/content of glucose metabolic enzymes involved in glucose metabolism, which might promote gluconeogenesis and inhibit glucose uptake, glycolysis, and glycogenesis. Furthermore, gluconeogenesis and glycolytic were carried out in the mitochondrial membrane. The abnormal of mitochondrial membrane potential may be a potential mechanism underlying FNT-induced glucose metabolism disorder. In addition, the mRNA and protein expression implicated that FNT may disrupt glucose metabolism by inhibiting the AMPKα and IRS1/PI3K/AKT signaling pathways. In conclusion, results provide in vitro evidence that FNT can cause glucose metabolism disorder, which emphasizes the potential health risks of exposure to FNT in inducing diabetes mellitus.

Organophosphorus pesticides (OPPs) are a group of pesticides that are most widely used in the agricultural sector, and farmers are exposed to these chemicals more than other members of society. In this work, an environmentally friendly, simple, and safe ultrasound-assisted dispersive liquid-liquid microextraction (USA-DLLME) method using alcohol-based hydrophobic deep eutectic solvents (HDESs) followed by gas chromatography-mass spectroscopy (GC-MS) was developed for the extraction and determination of OPPs in the blood of farmers studied in Ravansar cohort. DESs synthesized from thymol as hydrogen bond donor (HBD) and aliphatic alcohols as hydrogen bond acceptor (HBA) have been used as extractants. Under optimal experimental conditions, the reproducibility of the method based on 7 replicate measurements of 10 µg L-1 of OPPs in blood samples was in the range of 1.4-3.8%. The method showed a linearity in the range of 0.01-150 µg L-1. The limits of detection and limits of quantification were between 0.003 and 0.02 µg L-1 and 0.01-0.05 µg L-1, respectively. The matrix effect and accuracy of the method were confirmed by spiking different amounts of OPPs in real blood samples and obtaining relative recoveries in the range of 91-112%. The results showed that the concentration of OPPs in the case group was significantly higher than in the control group, which is because the case group was exposed to OPPs during the spraying of agricultural products.

Diabetes and its complications significantly affect individuals' quality of life. The etiology of diabetes mellitus and its associated complications is complex and not yet fully understood. There is an increasing emphasis on investigating the effects of endocrine disruptors on diabetes, as these substances can impact cellular processes, energy production, and utilization, ultimately leading to disturbances in energy homeostasis. Mitochondria play a crucial role in cellular energy generation, and any impairment in these organelles can increase susceptibility to diabetes. This review examines the most recent epidemiological and pathogenic evidence concerning the link between endocrine disruptors and diabetes, including its complications. The analysis suggests that endocrine disruptor-induced mitochondrial dysfunction-characterized by disruptions in the mitochondrial electron transport chain, dysregulation of calcium ions (Ca2+), overproduction of reactive oxygen species (ROS), and initiation of signaling pathways related to mitochondrial apoptosis-may be key mechanisms connecting endocrine disruptors to the development of diabetes and its complications.

A subgroup of endocrine-disrupting chemicals have the ability to disrupt metabolism. These metabolism-disrupting chemicals (MDCs) can end up in aquatic environments and lead to adverse outcomes in fish. Although molecular and physiological effects of MDCs have been studied in adult fish, few studies have investigated the consequences of metabolic disruption in fish during the earliest life stages. To investigate the processes affected by metabolic disruption, zebrafish embryos were exposed to peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone, the PPARγ antagonist T0070907, and the well-known environmentally relevant MDC bisphenol A. Decreased apolipoprotein Ea transcript levels indicated disrupted lipid transport, which was likely related to the observed dose-dependent increases in yolk size across all compounds. Increased yolk size and decreased swimming activity indicate decreased energy usage, which could lead to adverse outcomes because the availability of energy reserves is essential for embryo survival and growth. Exposure to T0070907 resulted in a darkened yolk. This was likely related to reduced transcript levels of genes involved in lipid transport and fatty acid oxidation, a combination of responses that was specific to exposure to this compound, possibly leading to lipid accumulation and cell death in the yolk. Paraoxonase 1 (Pon1) transcript levels were increased by rosiglitazone and T0070907, but this was not reflected in PON1 enzyme activities. The present study shows how exposure to MDCs can influence biochemical and molecular processes involved in early lipid metabolism and may lead to adverse outcomes in the earliest life stages of fish. Environ Toxicol Chem 2024;43:1880-1893. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

To investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures.

In this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression.

In this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89-0.98]), DEP (OR = 0.94 [95% CI: 0.90-0.99]), DMTP (OR = 0.91 [95% CI: 0.86-0.95]), and DETP (OR = 0.85 [95% CI: 0.80-0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects.

Together, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity.

Brown adipose tissue (BAT) activation is an emerging target for obesity treatments due to its thermogenic properties stemming from its ability to shuttle energy through uncoupling protein 1 (Ucp1). Recent rodent studies show how BAT and white adipose tissue (WAT) activity can be modulated to increase the expression of thermogenic proteins. Consequently, these alterations enable organisms to endure cold-temperatures and elevate energy expenditure, thereby promoting weight loss. In humans, BAT is less abundant in obese subjects and impacts of thermogenesis are less pronounced, bringing into question whether energy expending properties of BAT seen in rodents can be translated to human models. Our review will discuss pharmacological, hormonal, bioactive, sex-specific and environmental activators and inhibitors of BAT to determine the potential for BAT to act as a therapeutic strategy. We aim to address the feasibility of utilizing BAT modulators for weight reduction in obese individuals, as recent studies suggest that BAT's contributions to energy expenditure along with Ucp1-dependent and -independent pathways may or may not rectify energy imbalance characteristic of obesity.

Organic phosphorus insecticides (OPPs) are a class of environmental pollutants widely used worldwide with potential human health risks. We aimed to assess the association between exposure to OPPs and osteoarthritis (OA) particularly in participants with atherosclerotic cardiovascular disease (ASCVD).

Participants' information was obtained from data in the National Health and Nutrition Examination (NHANES). Weighted logistic regression models were utilized to detect associations between OPPs metabolites and OA. Restricted cubic spline plots (RCS) were drawn to visualize the dose-response relationship between each metabolite and OA prevalence. Weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR), were applied to investigate the joint effect of mixtures of OPPs on OA.

A total of 6871 samples were included in our study, no significant associations between OPPs exposure and OA incidence were found in whole population. However, in a subset of 475 individuals with ASCVD, significant associations between DMP (odds ratio [OR] as a continuous variable = 1.22, 95% confidence interval [CI]: 1.07,1.28), DEP ((odds ratio [OR] of the highest tertile compared to the lowest = 2.43, 95% confidence interval [CI]: 1.21,4.86), and OA were observed. DMP and DEP showed an increasing dose-response relationship to the prevalence of OA, while DMTP, DETP, DMDTP and DEDTP showed a nonlinear relationship. Multi-contamination modeling revealed a 1.34-fold (95% confidence intervals:0.80, 2.26) higher prevalence of OA in participants with high co-exposure to OPPs compared to those with low co-exposure, with a preponderant weighting (0.87) for the dimethyl dialkyl phosphate metabolites (DMAPs). The BKMR also showed that co-exposure of mixed OPPs was associated with an increased prevalence of OA, with DMP showing a significant dose-response relationship.

High levels of urine dialkyl phosphate metabolites (DAP) of multiple OPPs are associated with an increased prevalence of OA in patients with ASCVD, suggesting the need to prevent exposure to OPPs in ASCVD patients to avoid triggering OA and further avoid the occurrence of cardiovascular events caused by OA.

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides. Some reports have shown that diazinon causes immunotoxic effects; diazoxon, the oxon metabolite of diazinon, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of diazoxon on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that diazoxon leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, diazoxon does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, diazoxon inhibits leukocyte responsiveness to phorbol myristate acetate and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that diazoxon significantly affects key molecular parameters related to cell signaling.

Organophosphate pesticides (OPs) are widely utilized in agricultural production, and the residues threaten public health and environmental safety due to their toxicity. Herein, a novel and simple DNA aptamer-based sensor has been fabricated for the rapid, visual, and quantitative detection of profenofos and isocarbophos. The proposed DNA aptamers with a G-quadruplex spatial structure could be recognized by SYBR Green I (SG-I), resulting in strong green fluorescence emitted by SG-I. The DNA aptamers exhibit a higher specific binding ability to target OP molecules through aromatic ring stacking, disrupting the interaction between SG-I and DNA aptamers to induce green fluorescence quenching. Meanwhile, the fluorescence wavelength of G-quadruplex fluorescence emission peaks changes, accompanied by an obvious fluorescence variation from green to blue. SG-I-modified aptasensor without any additive reference fluorescence units for use in multicolor fluorescence assay for selective monitoring of OPs was first developed. The developed aptasensor provides a favorable linear range from 0 to 200 nM, with a low detection limit of 2.48 and 3.01 nM for profenofos and isocarbophos, respectively. Moreover, it offers high selectivity and stability in real sample detection with high recoveries. Then, a self-designed portable smartphone sensing platform was successfully used for quantitative result outputs, demonstrating experience in designing a neotype sensing strategy for point-of-care pesticide monitoring.

Nanozymes, as innovative materials, have demonstrated remarkable potential in the field of electrochemical biosensors. This article provides an overview of the mechanisms and extensive practical applications of nanozymes in electrochemical biosensors. First, the definition and characteristics of nanozymes are introduced, emphasizing their significant role in constructing efficient sensors. Subsequently, several common categories of nanozyme materials are delved into, including metal-based, carbon-based, metal-organic framework, and layered double hydroxide nanostructures, discussing their applications in electrochemical biosensors. Regarding their mechanisms, two key roles of nanozymes are particularly focused in electrochemical biosensors: selective enhancement and signal amplification, which crucially support the enhancement of sensor performance. In terms of practical applications, the widespread use of nanozyme-based electrochemical biosensors are showcased in various domains. From detecting biomolecules, pollutants, nucleic acids, proteins, to cells, providing robust means for high-sensitivity detection. Furthermore, insights into the future development of nanozyme-based electrochemical biosensors is provided, encompassing improvements and optimizations of nanozyme materials, innovative sensor design and integration, and the expansion of application fields through interdisciplinary collaboration. In conclusion, this article systematically presents the mechanisms and applications of nanozymes in electrochemical biosensors, offering valuable references and prospects for research and development in this field.

Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N = 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N = 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes.

Epidemiological and toxicological studies on neonicotinoids and obesity have been relevant to adults and young children, but data are limited in adolescents. This study aimed to examine the association between urinary neonicotinoid concentrations and obesity measures among Chinese adolescent. A total of 524 urine samples from 300 boys (11.3-16.1 years) and 224 girls (12.1-15.8 years) were collected to detect the concentrations of eleven neonicotinoids. Generalized linear regression, weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR) were used to estimate covariate-adjusted associations between detectable neonicotinoids and ten indicators of obesity. Nitenpyram concentration was associated with increased body mass index z-score (β = 0.170, 95% CI: 0.041, 0.299) and greater odds of being general obesity (OR = 2.46, 95% CI: 1.11, 5.46). N-desmethyl- acetamiprid concentration was associated with an increase in waist-to-height ratio (β = 0.102, 95% CI: 0.029, 0.176) and waist-to-hip ratio (β = 0.083, 95% CI: 0.011, 0.155). The concentrations of clothianidin (OR = 2.06, 95% CI: 1.10, 3.88) and flonicamid (OR = 2.39, 95% CI: 1.07, 5.32) were associated with greater odds of being abdominal obesity. In contrast, the concentrations of imidacloprid (OR = 0.35, 95% CI: 0.14, 0.88) and thiacloprid (OR = 0.28, 95% CI: 0.08, 0.99) were associated with lower odds of being general obesity. The estimates of general obesity and abdominal obesity increased significantly when concentrations of neonicotinoids mixture were at or above the 55th and 65th percentiles, respectively, compared to the 50th percentile concentration. Sex modified the association between nitenpyram and clothianidin and the risk of obesity with a positive association among boys, and a nonsignificant inverse association among girls. The findings suggest that these associations may be mixed and sex-specific.

Epidemiological studies have related exposure to pesticides to increased risk of diabetes. However, few studies have evaluated the health effects of mixed pesticides exposure, especially in an elderly population. Here, we utilized gas chromatography-tandem mass spectrometry to quantify the levels of 39 pesticides in 4 categories in a Chinese elderly population. Then we used general linear models to explore the association between individual pesticide exposure and type 2 diabetes mellitus (T2DM). Restricted cubic spline (RCS) models were fitted to identify potential non-linearities between those associations. Furthermore, stratified analysis by gender was conducted to explore the gender-specific associations. Finally, we used weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the effects of mixed exposure to 39 pesticides. The results showed that exposure to pesticides was associated with high risk of T2DM, with β-Hexachlorocyclohexane (β-BHC) and oxadiazon being the most significant independent contributors, which was pronounced among elderly women. Moreover, the association of β-BHC and oxadiazon with T2DM was linear. These indicated that it is an urgent need to take practical measures to control these harmful pesticides.

Pomelo (Citrus grandis) is a highly popular and juicy member of the citrus family. However, little is known regarding the occurrence and distribution of pesticides in pomelo. In this study, we determined the levels of legacy (n = 25) and current-use pesticides (n = 2) in all parts of pomelo (i.e., epicarp, mesocarp, endocarp, pulp, and seed) and paired soil and leaf samples collected from two pomelo orchards in South China. At least one target pesticide was detected in the pomelo fruit, soil, and leaf samples, indicating that these pesticides were ubiquitous. The spatial distribution of the total concentration of pesticides in the pomelo parts was in the order of epicarp (216 ng/g) > mesocarp (9.50 ng/g) > endocarp (4.40 ng/g) > seed (3.80 ng/g) > pulp (1.10 ng/g), revealing different spatial distributions in pomelo. Principal component analysis was performed based on the concentrations of the target pesticides in the pulp and paired samples of epicarp, leaf, topsoil, and deep soil to examine the translocation pathway of the pesticides in pomelo. Close correlations were found among the target pesticides, and the pesticides in the pulp were mainly transferred from the epicarp, topsoil, or deep soil. We also explored the factors that affected such transport and found that the main translocation pathway of the non-systemic pesticide (i.e., buprofezin) into the pulp was the epicarp, whereas the systemic pesticide (i.e., pyriproxyfen) was mainly derived from the soil. The cumulative chronic dietary risks of all the pesticides resulting from pomelo consumption were much lower than the acceptable daily intake values for the general population. However, the prolonged risk of exposure to these pesticides should not be underestimated. The potential health risks posed by legacy and current-use pesticides, which are widely and frequently utilized, should be given increased attention.

Obesity, diabetes, hypertension and dyslipidemia are well-established risk factors for cardiovascular diseases (CVDs), and have been associated with exposure to persistent organic pollutants. However, studies have been lacking as regards effects of non-persistent pesticides on CVD risk factors. Here, we investigated whether background chronic exposure to polychlorinated biphenyls (PCBs) and multiclass pesticides were associated with the prevalence of these CVD risk factors in 502 Belgian and 487 Luxembourgish adults aged 18-69 years from the Nutrition, environment and cardiovascular health (NESCAV) study 2007-2013. We used hair analysis to evaluate the chronic internal exposure to three PCBs, seven organochlorine pesticides (OCs) and 18 non-persistent pesticides. We found positive associations of obesity with hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH) and chlorpyrifos, diabetes with pentachlorophenol (PCP), fipronil and fipronil sulfone, hypertension with PCB180 and chlorpyrifos, and dyslipidemia with diflufenican and oxadiazon, among others. However, we also found some inverse associations, such as obesity with PCP, diabetes with γ-HCH, hypertension with diflufenican, and dyslipidemia with chlorpyrifos. These results add to the existing evidence that OC exposure may contribute to the development of CVDs. Additionally, the present study revealed associations between CVD risk factors and chronic environmental exposure to currently used pesticides such as organophosphorus and pyrethroid pesticides.

Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and the risk of diabetes mellitus (DM) is scarce. This study used 4 years of NHANES data (2013-2016) to further investigate the association. A total of 2535 participants were enrolled in this cross-sectional study. The baseline information and urinary glyphosate levels in diabetic and non-diabetic groups were compared. Using multivariable logistic regression mode, we explored the association between both the continuous and categorical forms of urinary glyphosate and DM risk. Further subgroup analyses based on categorical covariates were also conducted. Urinary glyphosate levels were 0.42 ng/ml in participants with diabetes and 0.34 ng/ml in participants without diabetes (P < 0.05). As a continuous variable, ln-transformed urinary glyphosate was significantly associated with an increased risk of DM in the most adjusted model (OR 1.28, 95% CI 1.03-1.57). However, the association was not significant in the most adjusted categorical model (P > 0.05).In further subgroup analyses, the associations remained significant in several subgroups. This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.

Paraoxonase 1 (PON1) is an antioxidant enzyme linked to metabolic disorders by genome-wide association studies in humans. Exposure to metabolic disrupting chemicals (MDCs) such as bisphenol A (BPA), together with genetic and dietary factors, can increase the risk of metabolic disorders. The objective of this study was to investigate how PON1 responds to the metabolic changes and oxidative stress caused by a western diet, and whether exposure to BPA alters the metabolic and PON1 responses. Zebrafish larvae at 14 days post fertilization were fed a custom-made western diet with and without aquatic exposure to two concentrations of BPA for 5 days. A combination of western diet and 150 μg/L BPA exposure resulted in a stepwise increase in weight, length and oxidative stress, suggesting that BPA amplifies the western diet-induced metabolic shift. PON1 arylesterase activity was increased in all western diet and BPA exposure groups and PON1 lactonase activity was increased when western diet was combined with exposure to 1800 μg/L BPA. Both PON1 activities were positively correlated to oxidative stress. Based on our observations we hypothesize that a western diet caused a shift towards fatty acid-based metabolism, which was increased by BPA exposure. This shift resulted in increased oxidative stress, which in turn was associated with a PON1 activity increase as an antioxidant response. This is the first exploration of PON1 responses to metabolic challenges in zebrafish, and the first study of PON1 in the context of MDC exposure in vertebrates.

Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research.

Population and food requirements are increasing daily throughout the world. To fulfil these requirements application of pesticides is also increasing. Organophosphorous (OP) and Organocarbamate (OC) compounds are widely used pesticides. These pesticides are used for suicidal purposes too. Both inhibit Acetylcholinesterase (AChE) and cholinergic symptoms are mainly used for the diagnosis of pesticide poisoning. Although the symptoms of the intoxication of OP and OC are similar, recent research has described different targets for OP and OC pesticides. Researchers believe the distinction of OP/OC poisoning will be beneficial for the management of pesticide exposure. OP compounds produce adducts with several proteins. There is a new generation of OP compounds like glyphosate that do not inhibit AChE. Therefore, it's high time to develop biomarkers that can distinguish OP poisoning from OC poisoning.

The human exposure to anticholinergic pesticides has been associated with the development of various diseases. Therefore, several biomarkers have been proposed for biomonitoring human exposure to anticholinergic pesticides.

This work evaluated the effect of human exposure to anticholinergic pesticides on β-glucuronidase (GUSB) levels.

A systematic review was performed using PubMed, Web of Science, Scopus, and EBSCO databases up to December 2021. The statistical analysis employed standardized mean differences and meta-regression. And the trial sequential analysis was performed.

Nine studies were included. A monotonic relationship was observed between poisoning severity and GUSB. Furthermore, BuChE levels were correlated with GUSB levels.

The results indicated that GUSB levels could be used as a possible diagnosis biomarker in poisoning related to anticholinergic pesticide exposure. However, the use of GUSB to assess the chronic exposure to anticholinergic pesticides could be only performed in recent exposure (≈ 7 days after last exposure).

The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure.

Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (ORs) or β with 95% confidence intervals (CIs), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM.

High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM.

Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM.

A fast, eco-friendly and accurate ratiometric fluorescent strategy is presented for the determination of organophosphorus pesticides (OPs) using intrinsic dual-emission silica nanoparticles modified with Rhodamine 6G (SiNPs-Rho6G). SiNPs-Rho6G had intrinsic dual-emission at 410 and 550 nm. The substrate acetylcholine was catalyzed by acetylcholinesterase (AChE) to produce thiocholine (TCh). TCh triggered the specific reaction of Ellman's reagent 5, 5-dithiobis (2-nitrobenzoic acid) to obtain 5-thio-2-nitrobenzoic acid, which caused the decrease in fluorescence intensity of SiNPs-Rho6G at 410 nm by the inner filter effect, while the fluorescence intensity of SiNPs-Rho6G at 550 nm was not significantly changed. OPs caused the recovery of the fluorescence at 410 nm by inhibiting the activity of AChE. Thus, the quantitative detection of OPs could be achieved through utilizing the catalytic characteristic of AChE. The linear curve from 0.010 to 0.250 μg mL^-1 with a detection limit of 7 ng mL^-1 was obtained for the determination of chlorpyrifos (Cpf). The ratiometric probe was used to detect the spiked Cpf in environmental and food samples with good recoveries. Therefore, combined with the dual emission characteristics of SiNPs-Rho6G and the specificity of the enzyme, the ratio fluorescence sensing platform has potential application prospects in OPs determinations.

Humans are at risk of exogenous exposure to exogenous chemicals. Challenges exist for the comprehensive monitoring of residues with different physical and chemical properties in serum. Here, an on-line two-dimensional liquid chromatography (2D-LC) - high resolution mass spectrometry system (HRMS) was developed, expanding the range of the partition coefficient in octanol/water of the residue analysis from -8 to 12. A high-coverage serum residue screening strategy was further designed by integrating 2D-LC system with HRMS full MS/data independent acquisition and automatic spectral library searching. This strategy enables to simultaneously screen 1210 pesticides, veterinary/human drugs, other chemical pollutants and their metabolites in serum with a single analysis. Method validation showed 92% and 81% of 1022 residues spiked in serum could be detected at 50 ng/mL and 5 ng/mL, respectively. The developed method was applied to the analysis of 24 separately pooled serum samples, 58 suspect residues were found, some of them were detected at high frequencies over than 50%. Among them, 4,6-Dinitro-O-cresol and probable carcinogenic folpet are highly toxic, and cimaterol is banned in China. Collectively, this study developed a 2D-LC-HRMS -based screening strategy for screening pesticides, veterinary/human drugs, and other chemical pollutants in serum, it is helpful for studying the effect of exogenous exposures on human health.

Exposure to pesticides has been associated with obesity and diabetes in humans and experimental models mainly due to endocrine disruptor effects. First contact with environmental pesticides occurs during critical phases of life, such as gestation and lactation, which can lead to damage in central and peripheral tissues and subsequently programming disorders early and later in life.

We reviewed epidemiological and experimental studies that associated pesticide exposure during gestation and lactation with programming obesity and diabetes in progeny.

Maternal exposure to organochlorine, organophosphate and neonicotinoids, which represent important pesticide groups, is related to reproductive and behavioral dysfunctions in offspring; however, few studies have focused on glucose metabolism and obesity as outcomes.

We provide an update regarding the use and metabolic impact of early pesticide exposure. Considering their bioaccumulation in soil, water, and food and through the food chain, pesticides should be considered a great risk factor for several diseases. Thus, it is urgent to reformulate regulatory actions to reduce the impact of pesticides on the health of future generations.

A regional-scale survey was conducted to assess the occurrence, distribution, and risk of two extensively used pesticides (organophosphate pesticides and pyrethroids) in agricultural soils from the Pearl River Delta (PRD), South China. All target organophosphate pesticides (OPPs) and pyrethroids (PYs) were detected in the soil samples and both with a detection rate of 100%. The residues of the sum of six OPPs and the sum of four PYs were in the range of LOD-991 ng/g and 8.76-2810 ng/g, respectively. Dimethoate was the dominant OPPs, and fenpropathrin was the predominant PYs in the soils of the PRD region. With intensive agricultural activities, higher residues of OPPs and PYs in soils were detected closer to the seaside, among which Zhuhai city and Huizhou city suffered more serious combined pesticide pollution. The vertical compositional profiles showed that dimethoate could be detected through each soil layer in the PRD region's nine cities. The human exposure estimation of OPPs showed insignificant risks to the local population. In contrast, cypermethrin and fenpropathrin showed a potential ecological risk of 2.5% and 3.75% of the sampling sites, respectively. These results can facilitate those commonly used pesticide controls and promote sustainable soil management.

Significant risks to human health have been associated with chronic exposure to low doses of pesticides, a situation which may be frequent among agricultural workers. In this context, and regarding the agricultural-based economy of central Chile, we aimed to explore the genotoxic damage in agricultural workers and reproductive risk among women in rural and urban areas of Curicó, a traditional agricultural district in Chile. Hence, we sampled a group of rural agricultural workers associated with pesticide management (n = 30) and an urban unexposed group (n = 30). Our results showed that the agricultural workers had higher micronuclei frequencies (MN: β = 13.27; 95% CI _low = 11.08, CI _high = 15.47) and women had a 40-fold higher risk of reproductive problems (OR = 40.32; 95% CI _low = 2.60, CI _high = 624.31) than the unexposed group. The factor analysis of mixed data (FAMD) showed that neither the sex nor smoking habits appear to define the ordination of the data. Nevertheless, the exposure level did segregate them in the multidimensional space (explained variance: 35.38% dim-1; 18.63% dim-2). This pilot study highlights the higher risks of biological conditions negatively associated with the health of agricultural workers.

Evidence showed organophosphorus (OPs) insecticide exposure is common in general population with endocrine-disrupting effects. However, the association between OPs metabolites and sex hormones remains unclear.

To investigate the association between OPs metabolites and sex hormones.

Data of 1438 participants from NHANES 2015-2016 was applied. Urinary OPs metabolites, dialkyl phosphates (DAPs), and serum sex hormones (total testosterone (TT), estradiol (E₂), and sex hormone-binding globulin (SHBG)) were measured. Free androgen index (FAI) and TT/E₂ ratio were also calculated. The generalized linear regression model and restricted cubic spline (RCS) model were employed to evaluate the association and exposure-response curve of DAPs and sex hormones in males and females. The modulation effect of age on their associations in female participants was also explored.

After adjusting for confounding factors, DETP was negatively associated with E₂ (β = -0.03; 95% CI: -0.05, -0.01) and FAI (β = -0.03; 95% CI: -0.06, -0.001) in males. In females, all the four DAP metabolites (DMP, DEP, DMTP, and DETP) were negatively associated with FAI (DMP: β = -0.06, 95% CI: -0.11, -0.01; DEP: β = -0.06, 95% CI: -0.12, -0.01; DMTP: -0.05, 95% CI: -0.09, -0.02; DETP: -0.09, 95% CI: -0.14, -0.04). DETP was also found negatively associated with TT and TT/E₂ ratio in females. The associations between DETP and TT, FAI, and TT/E₂ ratio were modified by gender (P_interaction<0.05). RCS analysis found these associations were in linear decreased exposure-response curves. For females of different age groups, the inverse associations of DETP with TT and FAI remained stable. Decreased FAI with DMP and DMTP was also found in females ≤50 years old.

Our study indicates OPs metabolites had negative associations with androgen indicators, which was characterized as decreased FAI and E₂ in males and decreased TT, FAI, and TT/E₂ ratio in females, particularly among females ≤50 years old. Further studies are warranted in larger-scale populations.

Pancreatic adenocarcinoma (PA) incidence is rising worldwide, especially in France. The evolution of known risk factors such as tobacco smoking, obesity, type 2 diabetes, chronic pancreatitis, or constitutional mutations is not sufficient to explain this trend. Pesticides are known risk factors in other malignancies. Previous studies have outlined pesticides' influence in PA, such as dichlorodiphenyltrichloroethane as plausible risk factors. The general population is directly or indirectly exposed to pesticides through air, food or water. Some of these chemicals may accumulate in the body all along lifetime and may harm carriers. The toxic mixing effects of these chemicals are not well documented. Several hypotheses have been put forward to explain how pesticides can induce indirect (fatty pancreas, induced diabetes) or direct (oxidative stress, cell damage) carcinogenesis in pancreatic cells through inflammation. A strong corpus exists acknowledging pesticides as a PA risk factor. However, published studies do not provide a sufficient level of evidence to prove causality and current prospective case-control studies are still ongoing.

The association of chronic exposure to pesticides with overweight and abdominal obesity in adult farmers was investigated. This cross-sectional study included a random sample of 122 farmers and their family members of both sexes (61% were male), living in the municipality of Farroupilha, southern Brazil. Pesticide groups and their individual compounds were self-reported and classified according to major functional and chemical classes (never used, 1-20 years, or > 20 years of use). Abdominal obesity and overweight were the outcomes of interest. A multivariate Poisson regression model was analyzed. After confounding factors were controlled, chronic use (>20 years) of insecticides (PR: 1.45; 95% CI: 1.00-2.10) and organophosphorus pesticides (PR: 1.48, 95% CI: 1.02-2.12) was associated with a higher prevalence of overweight but not abdominal obesity. Additional studies are needed to confirm our findings and clarify the specific mechanisms of these pollutants in the etiology of obesity.

Florfenicol (FF), a widely used veterinary antibiotic, has been frequently detected in both aquatic environments and human body fluids. As a result, there is a growing concern on its health risks. Previous studies have revealed various toxicities of FF on animals, while there are relatively limited researches on its metabolic toxicity. Herein, by employing zebrafish as an in vivo model, endpoints at multiple levels of biological organization were measured to investigate the metabolic toxicity, especially disturbances on lipid metabolism, of this emerging pollutant. Our results indicated that early-life exposure (from 2 h past fertilization (hpf) to 15 days past fertilization (dpf)) to FF significantly increased body mass index (BMI) values, staining areas of visceral lipids, and triacylglycerol (TAG) and total cholesterol (TC) contents of larvae. Further, by analyzing expression patterns of genes encoding key proteins regulating lipid metabolism, our data suggested that promoted intestinal absorption and hepatic de novo synthesis of lipids, suppressed TAG decomposition, and inhibited FFA oxidation all contributed to TAG accumulation in larvae. Following whole-life exposure (from 2 hpf to 120 dpf), BMI values, TAG and TC contents all increased significantly in males, and significant increases of hepatic TAG levels were also observed in females. Moreover, FF exposure interfered with lipid homeostasis of males and females in a gender-specific pattern. Our study revealed the obesogenic effects of FF at environmentally relevant concentrations (1, 10, and 100 μg/L) and therefore will benefit assessment of its health risks. Additionally, our results showed that FF exposure caused a more pronounced obesogenic effect in zebrafish larvae than adults, as suggested by significant increases of all endpoints at individual, tissular, and molecular levels in larvae. Therefore, our study also advances the application of zebrafish larval model in assessing metabolic toxicity of chemicals, due to the higher susceptibility of larvae than adults.