Glycometabolic disorder induced by chronic exposure to low-concentration imidacloprid in zebrafish.

The health risks induced by chronic exposure to low concentrations of imidacloprid (IMI) to zebrafish were investigated in this study. The results indicated that the growth of zebrafish was inhibited after being exposed to 10, 100, and 500 µg/L of IMI for 90 days. Moreover, the blood glucose levels in the IMI-exposed groups were significantly higher compared to the control group. Investigation into the development of zebrafish larvae revealed that IMI exposure hindered the development of the liver and pancreatic islets, organs crucial for glucose metabolism. In addition, the IMI-exposed groups exhibited reduced liver glycogen and plasma insulin levels, along with changes in the activity of enzymes and the transcription levels of genes associated with liver glucose metabolism. These findings suggest that IMI induces glycometabolic disorders in zebrafish. The analysis of intestinal flora revealed that several key bacteria associated with an elevated risk of diabetes were significantly altered in IMI-exposed fish. Specifically, a remarkable decrease was found in the abundance of the genera Aeromonas and Shewanella, which have been found closely related to the development of pancreatic islets. This implies that the alteration of key bacteria in the fish gut by IMI, which in turn affects the development of organs such as the pancreatic islets, may be the initial trigger for abnormalities in glucose metabolism. Our results revealed that chronic exposure to low concentrations of IMI led to glycometabolic disorder in fish. Therefore, considering the pervasive existence of IMI residues in the environment, the health hazards posed by low-concentration IMI to fish cannot be overlooked.

Enhancing harmonic brightness near the cutoff region by using laser pulses with a small positive chirp.

Efficient enhancement of harmonic brightness near the cutoff region is achieved by employing laser pulses with a small positive chirp in theory, where the laser intensity and frequency near the peak of the laser pulse are almost unchanged relative to the chirp-free field. The improvement of harmonic brightness is achieved under the condition that the ionization probability is almost unchanged. Through the analysis of the harmonics contributed by the rising and falling parts of the laser pulse, we have uncovered a "frequency compensation" mechanism that leads to an enhanced harmonic brightness near the cutoff region. Under appropriate chirp parameters, the harmonics contributed by the rising and falling parts can be constructively interfered in a smaller frequency range with greater intensity, thereby obtaining harmonics with good monochromaticity and high brightness. This study explains the mechanism of harmonic brightness enhancement from a new perspective, and provides a new idea for harmonic regulation without changing the ionization.

Dissipation behavior and dietary risk assessment of cyclaniliprole and its metabolite in cabbage under field conditions.

Cyclaniliprole, a novel diamide insecticide, can successfully control Spodoptera litura (Fabricius, 1775) in cabbage. Understanding the residual level of cyclaniliprole in crops and the risk related to its dietary intake is imperative for safe application. Here, we established a simplified, sensitive method for simultaneous analysis of cyclaniliprole and its metabolite NK-1375 (3-bromo-2-((2-bromo-4H-pyrazolo[1,5-d]pyrido[3,2-b]-[1,4]oxazin-4-ylidene)amino)-5-chloro-N-(1-cyclopropylethyl)benzamide) in cabbage by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate their dissipation behavior and residual characteristics. Cyclaniliprole showed rapid dissipation in cabbage and had a half-life of 1.8-2.7 days. The highest residue of total cyclaniliprole (sum of cyclaniliprole and NK-1375) in cabbage from different pre-harvest intervals (3 and 5 days) was 0.25 mg/kg. Our results confirmed the generally low dietary risk quotient of cyclaniliprole (0.243-1.036%) among different age and gender groups in China. Therefore, cyclaniliprole did not pose an unacceptable risk to consumers. This study contributes to setting cyclaniliprole maximum residue limit in cabbage by assessing its dissipation fate and food safety risks.

A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.

Dissipation and dietary exposure risk assessment of pyraclostrobin, fluxapyroxad, difenoconazole, and azoxystrobin in the Fritillaria field ecosystem.

Fritillaria (Beimu in Chinese) is a well-known traditional Chinese medicinal herbal and valuable health food, which has attracted more and more attention. In this study, an efficient method was developed to determine pyraclostrobin, fluxapyroxad, difenoconazole, and azoxystrobin in plants, fresh Fritillaria, dry Fritillaria, and soil via liquid chromatography-tandem mass spectrometry. The average recoveries of the method were 78.9-109.7% with relative standard deviations of 0.94-11.1%. The dissipation half-lives of the four fungicides were 4.4-7.7 days in the Fritillaria plant and 11.6-18.2 days in the soil. The terminal residues of four fungicides were 0.033-0.13 mg/kg in fresh Fritillaria, 0.096-0.42 mg/kg in dry Fritillaria, and 0.12-0.74 mg/kg in soil. In the risk assessment of dietary exposure, all the chronic hazard quotient and acute hazard quotient index values were far below 100%, which were both acceptable to consumers. Accordingly, 7 days was recommended as the pre-harvest interval for the four fungicides in Fritillaria. This work could guide the safe use of these fungicides in Fritillaria and also give a reference for the Chinese government to establish the maximum residue limits (MRLs).

Influence of Different Heater Structures on the Temperature Field of AlN Crystal Growth by Resistance Heating.

Based on the actual hot zone structure of an AlN crystal growth resistance furnace, the global numerical simulation on the heat transfer process in the AlN crystal growth was performed. The influence of different heater structures on the growth of AlN crystals was investigated. It was found that the top heater can effectively reduce the axial temperature gradient, and the side heater 2 has a similar effect on the axial gradient, but the effect feedback is slightly weaker. The axial temperature gradient tends to increase when the bottom heater is added to the furnace, and the adjustable range of the axial temperature gradient of the side 1 heater + bottom heater mode is the largest. Our work will provide important reference values for AlN crystal growth by the resistance method.

Guadipyr, a new insecticide, induces microbiota dysbiosis and immune disorders in the midgut of silkworms (Bombyx mori).

Guadipyr, which combines neonicotinoid and semicarbazone functional groups in one molecule, exhibits good activity on several pests and high acute and chronic toxicity to silkworms (Bombyx mori). In this report, the effects of low-dose guadipyr on the midgut microbiota and immune system of silkworms were studied. Results showed that the structure and richness of the midgut microbiota of silkworms were altered after being treated with 5.25 mg/L (1/10 of LC50) of guadipyr. The abundance of Pseudomonas was evidently increased, whereas Curvibacter was substantially reduced, which might be related to the growth and immunity of silkworms. The expression of key genes in the Toll, IMD, and JAK/STAT pathways, which ultimately led to the downregulation of antimicrobial peptide genes (AMPs), such as CecA, Defensin1, Leb, and glv2, was reduced upon guadipyr exposure. Simultaneously, the suppression of steroid hormone 20-hydroxyecdysone receptor and response genes, such as BR-C Z4, was detected in the exposed groups. The decreased expression of these immune regulatory pathway-related and 20-hydroxyecdysone signal pathway-related genes indicated that the immune system of silkworms was affected by low-dose guadipyr. Our results revealed the negative effects of guadipyr on silkworms and highlighted the unneglectable toxicity of low-dose guadipyr to this economic insect. Given the risk, it is necessary to control the application of guadipyr in or around the mulberry fields.

Residue behavior and risk assessment of validamycin a in grape under field conditions.

The dissipation and residue of validamycin A in grapes were investigated under field conditions. An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of validamycin A in grapes was established and validated. Methanol and water (90/10, v/v) were used for validamycin A extraction and purification used MCX solid-phase extraction cartridges. The average recoveries of validamycin A in grapes at 0.01, 0.50, and 5.0 mg/kg levels were between 83.8 and 91.4%, with relative standard deviations of 2.3-3.0%. The half-lives of validamycin A in grape were 4.4-6.1 days. The terminal residues in grapes over a range of harvest times (7, 14, and 21 days) were no more than 0.73 mg/kg. According to Chinese consumption data, the risk quotient (RQ) of validamycin A was 3.22%, demonstrating a low risk to consumers. The current study may offer guidance for validamycin A use and could aid the government in determining the maximum residue level (MRL) values for validamycin A in grapes.

Dissipation behavior, residue distribution, and risk assessment of triflumizole and FM-6-1 in greenhouse strawberries and soil.

This study aimed to develop a reliable method for the simultaneous analysis of triflumizole (TRIF) and its primary metabolite FM-6-1 (N-4-chloro-2-trifluoromethylphenyl-2-propoxy-acetamidine) in the soil and treated strawberries using solid phase extraction (SPE) coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS). Using this method, TRIF and FM-6-1 degradation in strawberries and the soil under greenhouse conditions were investigated. The field trials showed that t1/2 of TRIF and total residues (the sum of TRIF and FM-6-1) were 1.6-2.2 days and 2.4-2.9 days in strawberry and 4.3-6.1 days and 5.5-6.9 days in soil, respectively. Terminal total residues were ≤ 0.39 mg/kg in strawberry and ≤ 0.42 mg/kg in soil from 5 to 10 days of harvest. The risk quotient (RQ) of TRIF was below 1.89%, showing that the dietary risk of TRIF in strawberry was low. These findings provide guidance for the use of TRIF on crops and provide reference to establish the maximum residue level (MRL) of TRIF in strawberry.

Combined toxic effects of fludioxonil and triadimefon on embryonic development of zebrafish (Danio rerio).

Pesticides scarcely exist as individual compounds in the water ecosystem, but rather as mixtures of multiple chemicals at relatively low concentrations. In this study, we aimed to explore the mixture toxic effects of fludioxonil (FLU) and triadimefon (TRI) on zebrafish (Danio rerio) by employing different toxicological endpoints. Results revealed that the 96-h LC50 values of FLU to D. rerio at multiple developmental stages ranged from 0.055 (0.039-0.086) to 0.61 (0.33-0.83) mg L-1, which were less than those of TRI ranging from 3.08 (1.84-5.96) to 9.75 (5.99-14.78) mg L-1. Mixtures of FLU and TRI exerted synergistic effects on embryonic zebrafish. Activities of total superoxide dismutase (T-SOD) and catalase (CAT) were markedly altered in most of the individual and pesticide mixture treatments compared with the control. The expressions of 16 genes involved in oxidative stress, cellular apoptosis, immune system and endocrine system displayed that embryonic zebrafish were affected by the individual pesticides and their mixtures, and greater variations of four genes (ERɑ, Tnf, IL and bax) were found when exposed to pesticide mixtures compared with their individual compounds. Therefore, more studies on mixture toxicities among different pesticides should be taken as a priority when evaluating their ecological risk.

Lethal toxicity and gene expression changes in embryonic zebrafish upon exposure to individual and mixture of malathion, chlorpyrifos and lambda-cyhalothrin.

Pesticides are usually present as mixtures in water environments. Evaluating the toxic effects of individual pesticide may not be enough for protecting ecological environment due to interactions among substances. In this study, we aimed to examine the lethal doses and gene expression changes in zebrafish (Danio rerio) upon exposure to individual and mixture pesticides [malathion (MAL), chlorpyrifos (CHL) and lambda-cyhalothrin (LCY)]. Individual pesticide toxicity evaluation manifested that the toxicity of the three pesticides to D. rerio at various developmental stages (embryonic, larval, juvenile and adult stages) followed the order of LCY > CHL > MAL. On the contrary, the least toxicity to the animals was discovered from MAL. Most of the tested pesticides displayed lower toxicities to the embryonic stage compared with other life stages of zebrafish. Synergistic effects were monitored from two binary mixtures of LCY in combination with MAL or CHL and ternary mixture of MAL + CHL + LCY. The expressions of 16 genes involved in oxidative stress, immunity system, cell apoptosis and endocrine disruption at the mRNA level revealed that embryonic zebrafish were influenced by the individual or mixture pesticides. The expressions of Tnf, P53, TRα, Crh and Cyp19a exerted greater variations upon exposure to pesticide mixtures compared with their individual compounds. Collectively, the transcriptional responses of these genes might afford early warning biomarkers for identifying pollutant exposure, and the data acquired from this study provided valuable insights into the comprehensive toxicity of pesticide mixtures to zebrafish.

Biological response of zebrafish after short-term exposure to azoxystrobin.

Azoxystrobin (AZ) is a broad-spectrum systemic fungicide that widely used in the world. The present study investigated the toxicity effects on zebrafish after short-term exposure of AZ. Results demonstrated that the larval stage was most susceptible to AZ in the multiple life stages of zebrafish, with 96 h-LC50 value of 0.777 mg/L. Zebrafish larvae were exposed to different AZ concentrations (0, 0.1, 1, 10, 100 µg/L) and examined on 24, 48 and 72 h. It was found that AZ induced ROS accumulation, increased GST, GPX and POD activity and the transcriptions of antioxidant and stress response related genes, while the opposite trend occurred for SOD and CAT activity in 24-h or 48-h exposure period. The increased E2 and VTG levels in zebrafish larvae, and altered transcription levels of regulatory and steroidogenic genes in the hypothalamus-pituitary-gonad (HPG) axis indicated the endocrine disruption capacity of AZ. The transcripts of mdm2, p53, ogg1, bcl2, bbc3, cas8 and cas9 involved in cell apoptosis, and the mRNA levels of cytokines and chemokines such as cxcl-c1c, ccl, il-1ß, il-8, ifn, and tnfα were in accordance with the trends of the examined genes involved in oxidative stress and endocrine system. The results suggested that short-term exposure to AZ might impose ecotoxicological effects on zebrafish larvae, and the information presented here also provide molecular strategies and increase mechanistic understanding of AZ-induced toxic response, and help elucidate the environmental risks of AZ.

Residue behavior and risk assessment of imidacloprid applied on greenhouse-cultivated strawberries under different application conditions.

A risk assessment for imidacloprid applied on strawberries under different conditions was performed after residue determination using the quick, cheap, effective, rugged, and safe (QuEChERS) method. The application conditions were varied according to the applied dosage, addition of a plant oil or organosilicon surfactant, water volume, and sprayer type. The degradation dynamics of imidacloprid on strawberries followed first-order kinetics. At applied doses of 30-60 g a.i. ha-1, the half-lives of imidacloprid were 2.89-3.46, 1.98-3.65, and 2.57-2.77 days after application without a surfactant or with a plant oil or organosilicon surfactant, respectively. For water volumes of 112.5, 225, 450, 675, and 900 L ha-1, the half-lives of imidacloprid applied in the presence of the plant oil surfactant were 3.30, 7.70, 5.33, 7.70, and 6.30 days, respectively. The half-lives after application with a knapsack mist duster, electric sprayer, and manual sprayer were 2.16, 5.77, and 7.70 days, respectively. The health risk assessment revealed risk quotients less than 1 in all cases, indicating that the application of imidacloprid poses a low health risk to humans after a pre-harvest interval of 10 days under our application conditions. The risk assessment results can provide reference data for setting a reasonable maximum residue limit for imidacloprid on strawberries in China.

Joint acute toxicity of the herbicide butachlor and three insecticides to the terrestrial earthworm, Eisenia fetida.

The herbicide butachlor and three insecticides phoxim, chlorpyrifos, and lambda-cyhalotrhin are widely used pesticides with different modes of action. As most previous laboratory bioassays for these pesticides have been conducted solely based on acute tests with a single compound, only limited information is available on the possible combined toxicity of these common chemicals to soil organisms. In this study, we evaluated their mixture toxicity on the terrestrial earthworm, Eisenia fetida, with binary, ternary, and quaternary mixtures. Two different types of bioassays were employed in our work, including a contact filter paper toxicity test and a soil toxicity test. Mixture toxicity effects were assessed using the additive index method. For all of the tested binary mixtures (butachlor-phoxim, butachlor-chlorpyrifos, and butachlor-lambda-cyhalothrin), significant synergistic interactions were observed after 14 days in the soil toxicity assay. However, greater additive toxicity was found after 48 h in the contact toxicity bioassay. Most of the ternary and quaternary mixtures exhibited significant synergistic effects on the worms in both bioassay systems. Our findings would be helpful in assessing the ecological risk of these pesticide mixtures to soil invertebrates. The observed synergistic interactions underline the necessity to review soil quality guidelines, which are likely underestimating the adverse combined effects of these compounds.

Pretilachlor has the potential to induce endocrine disruption, oxidative stress, apoptosis and immunotoxicity during zebrafish embryo development.

The objectives of the present study were to investigate the toxic effects of pretilachlor on zebrafish during its embryo development. The results demonstrated that the transcription of genes involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis was increased after exposure to 50, 100, 200 µg/L pretilachlor for 96 h, the aromatase activity, vitellogenin (VTG) and thyroid hormones T3 and T4 levels in zebrafish were also up-regulated simultaneously. Pretilachlor exposure induced a noticeable increase in ROS level, increased the transcription and level of antioxidant proteins (e.g., CAT, SOD and GPX). Moreover, the up-regulation of P53, Mdm2, Bbc3 expression and Caspase3 and Caspase9 activities in the apoptosis pathway suggested pretilachlor might trigger cell apoptosis in zebrafish. In addition, the transcription of CXCL-C1C, IL-1ß and IL-8 related to the innate immunity was down-regulated after pretilachlor exposure. These data suggested that pretilachlor could simultaneously induce endocrine disruption, apoptosis, oxidative stress and immunotoxicity during zebrafish embryo development.

Degradation of three fungicides following application on strawberry and a risk assessment of their toxicity under greenhouse conditions.

The health risk to humans of pesticide application on minor crops, such as strawberry, requires quantification. Here, the dissipation and residual levels of three fungicides (pyraclostrobin, myclobutanil, and difenoconazole) were studied for strawberry under greenhouse conditions using high-performance liquid chromatography (HPLC)-tandem mass spectrometry after Quick, Easy, Cheap, Effective, Rugged, and Safe extraction. This method was validated using blank samples, with all mean recoveries of these three fungicides exceeding 80%. The residues of all three fungicides dissipated following first-order kinetics. The half-lives of pyraclostrobin, myclobutanil, and difenoconazole were 1.69, 3.30, and 3.65 days following one time application and 1.73, 5.78, and 6.30 days following two times applications, respectively. Fungicide residue was determined by comparing the estimated daily intake of the three fungicides against the acceptable daily intake. The results indicate that the potential health risk of the three fungicides was not significant in strawberry when following good agricultural practices (GAP) under greenhouse conditions.

Risk assessment of applicators to chlorpyrifos through dermal contact and inhalation at different maize plant heights in China.

Dermal and respiratory exposure assessments and risk assessment for applicators were performed with 48% chlorpyrifos EC. The chlorpyrifos was applied with lever-operated knapsacks under three spraying environments, namely, average maize field heights of 62 cm (A1), 108 cm (A2), and 212 cm (A3). The whole body dosimetry technique was applied to collect dermal exposure samples including cotton protective garments, gloves, socks, and hats. A personal air monitor equipped with an XAD-2 resin was used for respiratory exposure assessment. Without personal protective equipment (PPE) the total potential dermal exposure (PDE) was 27.8, 90.6, and 462.1 mL h(-1) under A1, A2, and A3 spraying environments, respectively. In addition, with the change in the maize plant height, the major exposure parts on the applicators were also different. Under single-layer garment and glove protection circumstances, internal dermal exposure (IDE) was 3.37 mL h(-1) for A1, 4.28 mL h(-1) for A2, and 18.32 mL h(-1) for A3. Potential inhalation exposure (PIE) was detected in A3, but it was not detected in A1 and A2. For risk assessment, the margin of safety (MOS) was calculated from the PDE or IDE and PIE. The MOS values for the three spraying environments were <1 under no PPE and single-layer garment and glove protection circumstances, indicating high possibility of health risk. However, with double protective garments, the MOS values for A1 and A2 cases were all >1, but the MOS was <1 in the A3 case.

Insecticide toxic effects on Trichogramma ostriniae (Hymenoptera: Trichogrammatidae).

BACKGROUND: The parasitoid Trichogramma ostriniae (Pang and Chen) is a major natural enemy of many lepidopterans, but only a few studies have been conducted on the compatibility of biological and chemical controls. In this study, the selectivity of 30 insecticides to T. ostriniae adults was evaluated. RESULTS: Among the seven classes of chemicals tested, organophosphates and carbamates had the highest intrinsic toxicity to the wasp, with LC(50) values ranging from 0.032 (0.029-0.038) to 2.38 (1.91-3.15) mg AI L(-1). They are followed by phenylpyrazoles, avermectins, neonicotinoids and pyrethroids, which induce variable toxicity responses, with LC(50) values ranging from 0.14 (0.11-0.21) to 56.67 (48.94-67.24) mg AI L(-1), from 2.57 (1.85-4.28) to 4.48 (3.34-6.83) mg AI L(-1), from 2.48 (1.80-4.03) to 503.6 (457.6-557.5) mg AI L(-1) and from 5.44 (3.95-8.84) to 104.2 (92.48-119.7) mg AI L(-1) respectively. The insect growth regulators (IGRs) exhibited least toxicity to the parasitoid. CONCLUSION: Risk quotient analysis classifies neonicotinoids, avermectins, pyrethroids, IGRs and phenylpyrazoles (with the exception of butane-fipronil and fipronil) as safe agents to the parasitoid, but categorises organophosphates and carbamates as slightly to moderately toxic or dangerous to T. ostriniae.

Toxicity assessment of 45 pesticides to the epigeic earthworm Eisenia fetida.

This study was conducted to investigate comparative toxicity of 45 pesticides, including insecticides, acaricides, fungicides, and herbicides, toward the epigeic earthworm Eisenia fetida. Results from a 48-h filter paper contact test indicated that clothianidin, fenpyroximate, and pyridaben were supertoxic to E. fetida with LC(50) values ranging from 0.28 (0.24-0.35) to 0.72 (0.60-0.94) µg cm(-2), followed by carbaryl, pyridaphenthion, azoxystrobin, cyproconazole, and picoxystrobin with LC(50) values ranging from 2.72 (2.22-0.3.19) to 8.48 (7.38-10.21) µg cm(-2), while the other pesticides ranged from being relatively nontoxic to very toxic to the worms. When tested in artificial soil for 14 d, clothianidin and picoxystrobin showed the highest intrinsic toxicity against E. fetida, and their LC(50) values were 6.06 (5.60-6.77) and 7.22 (5.29-8.68) mg kg(-1), respectively, followed by fenpyroximate with an LC(50) of 75.52 (68.21-86.57) mgkg(-1). However, the herbicides fluoroglycofen, paraquat, and pyraflufen-ethyl exhibited the lowest toxicities with LC(50) values>1000 mg kg(-1). In contrast, the other pesticides exhibited relatively low toxicities with LC(50) values ranging from 133.5 (124.5-150.5) to 895.2 (754.2-1198.0) mg kg(-1). The data presented in this paper provided useful information for evaluating the potential risk of these chemicals to soil invertebrates.