Energy Metabolism Pattern in Cotton Aphid, Aphis gossypii Glover （Hem.： Aphididae） Exposure to Neonicotinoids

This study was mainly made on the role of energy revisers in cotton aphid, Aphis gossypii Glover （Hemiptera： Aphididae） countered with imidacloprid and thiametoxam. We measured used energy, available energy and the content of total energy in three strains of cotton aphid which were from very resistant to neonicotinoid, sup to semi-sensitive and sensitive speccies, respectively. It was observed changes in energy resources rate in all of the aphid strains at which each substrate was metabolized under stress. Our findings indicated among energy sources, total lipid in susceptible strain was increased in counter of spraying and it was decreased in resistance and semi sensitive strains. Whereas, total protein was decreased in all of the strains encountering with neonicotiniod stress. Total glycogen was increased significantly in different aphid strains and sugar was decreased in countered of spraying.

Energy Intensity and Fitness Cost of Cotton aphid Exposure to Neonicotinoids

Three populations of Aphis gossypii of distinct susceptibility to neonicotinoids show differences in the accumulation and mobilization of energy reserves, what may allow the production of their defensive tools against two neonicotinoid insecticides without impairing their reproductive performance. Bioassays were also carried out for these aphid populations. According to the results obtained, the Ag-R population showed resistant rate significantly higher than the other two populations. Levels of some biochemical characteristics were determined in the resistant, susceptible and semi susceptible populations of cotton aphid. The results obtained in the assays with biochemical parameters indicated significant differences in activity among the populations, with higher activity in using glycogen in the Ag-R population. The inverse activity trends oft （generation time） and DT （doubling time） in both resistant and susceptible populations, one showing fitness disadvantage without insecticide exposure and the other not showing it, may underlay the mitigation of insecticide resistance physiological costs observed in the Ag-R population.

Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell-and metabolism-based fast-screening model

In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.

Degradation of neonicotinoids with different molecular structures in heterogeneous peroxymonosulfate activation system through different oxidation pathways

The elimination of neonicotinoids(NEOs)from water has been a research priority due to their threats to human health and ecosystems.In this study,we established the heterogeneous peroxymonosulfate(PMS)activation system using manganese catalyst(Mn NC)and cobalt catalyst(Co NC)to trigger the nonradical oxidation and synergistic oxidation pathway,respectively to remove NEOs.The results showed that the nonradical oxidation system exhibited superior NEOs degradation capability.The composition of organic pollutants in wastewater significantly impacted subsequent degradation processes.The charge distribution and reaction sites of various NEOs were analyzed using density functional theory(DFT)calculations,and it demonstrated the electron distribution and activity of NEOs were significantly influenced by the type and number of substituents.Nitro group(–NO_(2))and cyanide group(–C≡N)were identified as strong electron-withdrawing groups and prone to be attacked by negatively charged radicals.The transformation of NEOs was analyzed,and result showed that the C and N sites adjacent to the nitro group and cyanide group were more susceptible to oxidation attacks.S and N atoms,which possess strong electronegativity and high electron cloud density,were identified as key active sites in the degradation pathway.The outcomes of this study provide valuable guidance for the oriented regulation of oxidation pathways towards efficient removal of NEOs in water.

Water bridges are essential to neonicotinoids: Insights from synthesis,bioassay and molecular modelling studies

Water-bridged H-bonds have been observed in many cases of ligand-receptor recognitions. To explore the roles of water bridges in the binding of neonicotinoids with receptors, twenty-four neonicotinoid compounds with nine fragments, including 1 H-1,2,3-triazole, CN, COOMe, CONHNH_2, CONHMe, NO_2,NH_2, NHCOMe and NHCSNH_2 were synthesized and evaluated, of which, compounds with cyano group showed the best activities against Aphis craccivora. Accordingly, the cyano group is the optimal fragment mimicking the water bridge. Two cyano-substituted cis-nitromethylene compounds display good insecticidal activities, whereas the LC_(50) values are lower than those of their corresponding prototypes.Docking study showed that the cyano group acts only as H-bond acceptor, while the water bridge can act as both donor and acceptor. It revealed that the water bridge might be stable in the active site and was not suitable to be replaced by other groups. The findings illustrated that the water bridge is necessary for high insecticidal activities of neonicotinoids, which should be also helpful in better understanding the binding mode of neonicotinoids.

Synthesis,insecticidal activity and stability study of novel nitromethylene neonicotinoids with five-membered aromatic heterocycles

Twenty-four novel neonicotinoid analogues with nitromethylene and five-membered aromatic heterocycles were designed and synthesized.All target molecular structures have been confirmed by analytical and spectral data.Some compounds exhibited notable insecticidal activities against aphid(Aphis medicaginis)and brown planthopper(Nilaparvata lugens).The aqueous stability test confirmed that the stabilities of those compounds were superior to the leading compound,and the photostability was even better than that of imidacloprid.

Computational Investigations about the Effects of Heteromolecular Aggregation on Bioactivities:a Case of Neonicotinoids and Water

Molecular aggregation state of bioactive compounds plays a key role in bio-interactive procedure.Diverse ag-gregation states of bioactive compounds contribute to different biological or chemical properties.Water-bridge,as the simple hetero-molecular aggregation,has been found bridging the binding between many bioactive compounds and their targets through hydrogen bonding network,e.g.in the recognition of neonicotinoids with insect nAChRs.To better understanding the roles of water-bridge on bioactivities of compounds,an approach of hetero-dimeric ag-gregation with water was proposed.Quantitative structure-activity relationship(QSAR)and pharmacophore mod-eling investigations were applied on 19 neonicotinoids,as well as their aggregates with water.The aggregate-based CoMSIA,PHASE and linear QSAR models presented better statistical significance and predictabilities than the monomer ones,which indicated that the bioactivities correlated with the aggregate properties and water bridged hy-drogen bond of the active site.All results revealed the essential roles of water-bridge in ligand recognition,which should be considered in future ligand design and optimization.

Association between new onset type 1 diabetes and real-world antibiotics and neonicotinoids’exposure-related gut microbiota perturbation

Background The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes(T1D)children and their associations as environmental triggers through gut microbiota shifts remained unknown.We thus investigated the antibiotics and neonicotinoids’exposure levels and their associations with gut microbiota in pediatric T1D.Methods Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited.Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry.Children were grouped according to the kinds of antibiotics’and neonicotinoids’exposures,respectively.The 16S rRNA of fecal gut microbiota was sequenced,and the correlation with urine antibiotics and neonicotinoids’concentrations was analyzed.Results The overall detection rates of antibiotics were 72.5%and 61.2%among T1D and healthy children,whereas the neonicotinoids detection rates were 70.6%and 52.2%(P=0.044).Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D,with the odd ratios of 2.579 and 3.911.Furthermore,co-exposure to antibiotics and neonicotinoids was associated with T1D,with the odd ratio of 4.924.Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota.However,children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together.Conclusion High antibiotics and neonicotinoids exposures were found in T1D children,and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera,which might increase the risk of T1D.

Incorporation of N-doped biochar into zero-valent iron for efficient reductive degradation of neonicotinoids:mechanism and performance

The extensive use of neonicotinoids on food crops for pest management has resulted in substantial environmental contamination.It is imperative to develop an effective remediation material and technique as well as to determine the evolution pathways of products.Here,novel ball-milled nitrogen-doped biochar(NBC)-modified zero-valent iron(ZVI)composites(named MNBC-ZVI)were fabricated and applied to degrading neonicotinoids.Based on the characterization results,NBC incorporation introduced N-doped sites and new allying heterojunctions and achieved surface charge redistribution,rapid electron transfer,and higher hydrophobicity of ZVI particles.As a result,the interaction between ZVI particles and thiamethoxam(a typical neonicotinoid)was improved,and the adsorption-desorption and reductive degradation of thiamethoxam and·H generation steps were optimized.MNBC-ZVI could rapidly degrade 100%of 10 mg·L^(−1) thiamethoxam within 360 min,its reduction rate constant was 12.1-fold greater than that of pristine ZVI,and the electron efficiency increased from 29.7%to 57.8%.This improved reactivity and selectivity resulted from increased electron transfer,enhanced hydrophobicity,and reduced accumulation of iron mud.Moreover,the degradation of neonicotinoids occurred mainly via nitrate reduction and dichlorination,and toxicity tests with degradation intermediates revealed that neonicotinoids undergo rapid detoxification.Remarkably,MNBCZVI also presented favorable tolerance to various anions,humic acid,wastewater and contaminated soil,as well as high reusability.This work offers an efficient and economic biochar-ZVI remediation technology for the rapid degradation and detoxification of neonicotinoids,significantly contributes to knowledge on the relevant removal mechanism and further advances the synthesis of highly reactive and environmentally friendly materials.

Synthesis and insecticidal activities of novel bridged-neonicotinoids

A series of novel bridged-neonicotinoid analogues were designed and synthesized, which were constructed by starting material 8 with cyclopentenone or cyclohexenone in the presence of catalyst aluminium chloride. All of the compounds were characterized and confirmed by^1H NMR,^（13）C NMR, HRMS and IR. The bioassay tests showed that compounds 5 and 6a showed higher bioactivities than imidacloprid against Aphis craccivora.

Characterisation of Neonicotinoid and Pymetrozine Resistance in Strains of Bemisia tabaci(Hemiptera:Aleyrodidae)from China

Four strains of the Q biotype and one of the B biotype of the whitefly Bemisia tabaci collected from China were characterised for resistance to four neonicotinoid insecticides and pymetrozine.Q biotype strains showed moderate to strong resistance to imidacloprid,thiamethoxam and acetamiprid,but little or no cross-resistance to dinotefuron.Resistance to neonicotinoids was consistently associated with resistance to pymetrozine,despite the latter having a distinct（though unresolved）mode of action.The single B biotype strain proved largely susceptible to all the insecticides investigated.Resistance in the Q biotype strains was associated with over-expression of a cytochrome P450 monooxygenase gene,CYP6CM1,whose substrate specificity presumably accounts for the observed cross-resistance profiles.

Design and Synthesis of 3-(1-Phenylethyl)thiazolidine-2-thione Derivatives with Potential Biological Activities

A series of novel neonicotinoids derivatives 4a―4p was designed and synthesized by introducing the ethylbenzene group into the thiazole ring, their structures were confirmed by IR, 1H NMR and elemental analysis. The crystal structure of compound 4j has been determined by X-ray diffraction analysis.

Effect of pesticides on phosphorylation of tau protein,and its influence on Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive and neurodegenerative illness which results in alterations in cognitive development.It is characterized by loss/dysfunction of cholinergic neurons,and formation of amyloid plaques,and formation of neurofibrillary tangles,among other changes,due to hyperphosphorylation of tau-protein.Exposure to pesticides in humans occurs frequently due to contact with contaminated food,water,or particles.Organochlorines,organophosphates,carbamates,pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment.The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein,and its cognitive implications in the development of AD.It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198,Ser199,Ser202,Thr205,Ser396 and Ser404.Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta,and protein phosphatase-2A.Moreover,it altered the expression of the microtubule associated protein tau gene,and changed levels of intracellular calcium.These changes affected tau protein phosphorylation and neuroinflammation,and also increased oxidative stress.In addition,the exposed subjects had poor level of performance in tests that involved evaluation of novelty,as test on verbal,non-verbal,spatial memory,attention,and problem-solving skills.

Carbon Paste Electrodes for the Analysis of Some Agricultural Pollutants and Trace Metals

The present work is concerned with the voltammetric application of unmodified tricresyl phosphate carbon paste electrode （TCP-CPE） and in situ bismuth-film modified tricresyl phosphate-based carbon paste electrode （BiF-TCP-CPE）. The TCP-CPE was examined with the main objective of using it for the differential pulse voltammetric analysis of some neonicotinoid insecticides in aqueous Britton-Robinson buffer solution pH 7.0 as supporting electrolyte. After comparing the performance of the TCP-CPE with that of silicone oil carbon paste electrode, quantitative analysis of imidacloprid, thiamethoxam and clothianidin was performed in model solutions and real samples （river water and commercial insecticide formulations）. The in situ prepared BiF-TCP-CPE was tested for a simultaneous detection of selected heavy metal ions （Cd^2＋ and Pb^2＋） at a μg/dm^3 concentration level, using square wave anodic stripping voltammetric technique. The influence of different electrochemical pretreatments of the working electrode on the bismuth deposition and analyte signals were investigated. Film formation was studied at untreated, pre-cathodized and pre-anodized TCP-CPEs in the acetic buffer solution pH 4.6, containing 1 μg/cm^3 Bi （III）.

Pharmacophore model for neonicotinoid insecticides

An effective prediction pharmacophore model （RMS = 0.634, Correl = 0.893, Weight = 1.463, Config = 11.940） was successfully obtained by 3D-QSAR based on a series of nAChR （nicotinic acetylcholine receptors） agonists, which consists of a hydrogen- bonding acceptor, a hydrogen-bond donor, a hydrophobic aliphatic and a hydrophobic aromatic centre. This pharmacophore model may provide theoretical basis for designation and development of higher active insecticides.

S-(+)-(E)-1-(2-furfuryl)-5-substituted-1,3,5-hexahydrotriazine-2-N-nitroimines:Synthesis,Crystal Structure and DFT Calculations

A novel neonicotinoid analogue（C13H19N5O5,3a）had been synthesized,the structure was characterized by elemental analysis,IR and 1H NMR spectra,and the S-（＋）-（E）-configuration was confirmed by single-crystal X-ray diffraction.The crystal belongs to monoclinic,space group P21 with a = 8.7076（17）,b = 8.3211（17）,c = 10.642（2）,β = 92.370（3）o,V = 770.4（3）3,Z = 2,Dc = 1.402 g/cm3,μ = 0.110 mm-1,Mr = 325.33,F（000）= 344,S = 1.027,R = 0.0543 and wR = 0.1229 for 3601 unique reflections with 2919 observed ones（I 2σ（I））.Compound 3a is stabilized by intramolecular hydrogen bonds and intermolecular force.In addition,the structure of compound 3a was optimized by the B3LYP/6-31G（d,p）.DFT/B3LYP optimizations were performed based on X-ray geometries applying 6-31G（d,p）basis set.The optimized structure of compound 3a by the B3LYP/6-31G（d,p）method is more bent than in the crystal.IR spectrum of the solid compound is consistent with the X-ray structure.The HOMO-LUMO gap in 3a（5.3 eV）indicates high kinetic stabilities of compound 3a.The preliminary bioassay test showed that 3a exhibited good activities against Nilaparvata legen,Pseudaletia separate Walker and Aphis medicagini at 500 mg/L.

Synthesis, Crystal Structure and Insecticidal Activities of Novel Neonicotinoid Derivatives

Ten new N-oxalyl derivatives of neonicotinoid compound were designed and synthesized. Their structures were confirmed by ^1H NMR spectra, elemental analysis and X-ray diffraction. The preliminary insecticidal activities of the new compounds were evaluated. The results of bioassays indicate that the title Compounds exhibit moderate insecticidal activities. Surprisingly, the insecticidal activity of compound 7b against bean aphids at 200 mg/kg is 100%, which is comoarable to that of the commercialized imidacloprid.

Synthesis and Crystal Structure of the Optical Activity of (Z)-Nitromethylene Neonicotinoid Analogue

A novel （Z）-nitromethylene neonicotinoid analogue （C23H27Cl2N5O4·2H2O） （II） with optical activity has been synthesized, the structure was characterized by elemental analysis, IR and 1H NMR spectra, and the （Z）-configuration was confirmed by single-crystal X-ray diffraction. The crystal belongs to triclinic, space group P1 with a = 7.4638（3）, b = 12.6232（5）, c = 15.2990（6）, α = 71.907（1）, β = 89.397（2）, γ = 80.314（1）°, V = 1349.28（9）3, Z = 2, Dc = 1.340 g/cm3, μ = 0.286 mm-1, Mr = 544.43, F（000） = 572, S = 1.056, R = 0.0801 and wR = 0.2366 for 4998 unique reflections with 3012 observed ones （I 〉 2σ（I））. In the crystal, the dihedral angle between the pyridine and 4-Cl-phenyl rings is 58.13°. Intermolecular O-H···O, C-H···O and C-H···Cl hydrogen bonds involving water molecules stabilize the crystal structure.

Comparing the Impact of a Neonicotinoid and Biorational Agroneem on Herbivorous and Beneficial Arthropods on Cowpea and Tomato

Cowpea （Vigna unguiculata L. Walp.） and tomato （Lycopersicum esculentum L. Karst） are attacked by a wide range of insect pests worldwide. In many cases, pesticides are used to control the pests. In 2010 and 2011, we conducted field experiments to evaluate and compare the effectiveness of a biorational （Agroneem~） and conventional pesticide （imidacloprid or thiamethoxam） on insect pests of these crops. In the first year, two varieties of cowpea （Mississippi Silver and Pinkeye Purple Hull） and two of tomato （Mariana and German Johnson） were used; in the second year, the better performing of each group （Mississippi Silver and Mariana） were used for the study. A split-plot design with four replications in Year 1, and a randomized complete block design with six treatment combinations in Year 2. In the first year, both pesticide groups were applied following manufacturer＇s recommendation （10-14 d cycles）; and in the second year, the application of the pesticides was driven by economic thresholds level （ETL） of insect pests. The most prevalent species of insects recorded in both crops were in the families： Chrysomelidae, Pentatomidae, Cicadellidae, Vespidae, Sarcophagidae, Thripidae and Sphingidae. In both years, the diversity of insects on cowpea was greater than on tomato and more insects were observed in the second year compared to the first, despite the absence of significant difference （P 〉 0.05） between varieties in the treated plots. The yield of cowpea and tomato was comparable in all sprayed plots.

Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

Chiral pollutants often pose significant differential environmental health risks.In this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically investigated.Firstly,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was revealed.The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of S-configuration.Meanwhile,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine.Thirdly,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.