Hai-Qun Cao

Insecticidal Activity of Melaleuca alternifolia Essential Oil and RNA-Seq Analysis of Sitophilus zeamais Transcriptome in Response to Oil Fumigation.

Background The cereal weevil, Sitophilus zeamais is one of the most destructive pests of stored cereals worldwide. Frequent use of fumigants for managing stored-product insects has led to the development of resistance in insects. Essential oils from aromatic plants including the tea oil plant, Melaleuca alternifolia may provide environmentally friendly alternatives to currently used pest control agents. However, little is known about molecular events involved in stored-product insects in response to plant essential oil fumigation. Results M. alternifolia essential oil was shown to possess the fumigant toxicity against S. zeamais. The constituent, terpinen-4-ol was the most effective compound for fumigant toxicity. M. alternifolia essential oil significantly inhibited the activity of three enzymes in S. zeamais, including two detoxifying enzymes, glutathione S-transferase (GST), and carboxylesterase (CarE), as well as a nerve conduction enzyme, acetylcholinesterase (AChE). Comparative transcriptome analysis of S. zeamais through RNA-Seq identified a total of 3,562 differentially expressed genes (DEGs), of which 2,836 and 726 were up-regulated and down-regulated in response to M. alternifolia essential oil fumigation, respectively. Based on gene ontology (GO) analysis, the majority of DEGs were involved in insecticide detoxification and mitochondrial function. Furthermore, an abundance of DEGs mapped into the metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were associated with respiration and metabolism of xenobiotics, including cytochrome P450s, CarEs, GSTs, and ATP-binding cassette transporters (ABC transporters). Some DEGs mapped into the proteasome and phagosome pathway were found to be significantly enriched. These results led us to propose a model of insecticide action that M. alternifolia essential oil likely directly affects the hydrogen carrier to block the electron flow and interfere energy synthesis in mitochondrial respiratory chain. Conclusion This is the first study to perform a comparative transcriptome analysis of S. zeamais in response to M. alternifolia essential oil fumigation. Our results provide new insights into the insecticidal mechanism of M. alternifolia essential oil fumigation against S. zeamais and eventually contribute to the management of this important agricultural pest.

Design, synthesis and insecticidal activities of N-(4-cyano-1-phenyl-1H-pyrazol-5-yl)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives

Insect ryanodine receptor is one of the promising targets for the development of novel insecticides. In order to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel diphenyl-1H-pyrazole derivatives with cyano substituent were designed and synthesized. Their insecticidal activities against diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the four concentrations. Among these compounds, N-(4-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl)-1-(4-fluorophenyl)-3-phenyl-1H-pyrazole-4-carboxamide (5g) showed 84% larvicidal activity against Plutella xylostella at the concentration of 0.1 mg L−1. Molecular docking showed the predicted binding mode between 5g and protein receptor, which could suggest that the title compounds were the possible activators of insect RyR.

Design, Synthesis and Anti-Tobacco Mosaic Virus (TMV) Activity of 5-Chloro-N-(4-cyano-1-aryl-1H-pyrazol-5-yl)-1-aryl-3-methyl-1H-pyrazole-4-carboxamide Derivatives

A series of novel pyrazole amide derivatives 3a–3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV) with different in vivo and in vitro modes at 500 μg/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV) compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3).

Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS.

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health.

Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK

Mitogen activated protein kinase (MAPK) signal transduction pathway has been proved to play an important role in tumorigenesis and cancer development. MEK inhibitor has been demonstrated significant clinical benefit for blocking MAPK pathway activation and possibly could block reactivation of the MAPK pathway at the time of BRAF inhibitor resistance. Twenty N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives have been designed and synthesized as MEK inhibitors, and their biological activities were evaluated. Among these compounds, compound 7b showed the most potent inhibitory activity with IC50 of 91nM for MEK1 and GI50 value of 0.26μM for A549 cells. The SAR analysis and docking simulation were performed to provide crucial pharmacophore clues that could be used in further structure optimization.

Enhanced degradation of prometryn and other s-triazine herbicides in pure cultures and wastewater by polyvinyl alcohol-sodium alginate immobilized Leucobacter sp. JW-1

The s-triazine herbicides, such as prometryn, have been widely used in agriculture and have raised much public concern over their contamination of water and soil. Leucobacter sp. JW-1 cells were immobilized in polyvinyl alcohol‑sodium alginate (PVA-SA) beads and then used to degrade prometryn. Orthogonal array experiments showed that the optimal immobilization conditions of PVA-SA immobilized Leucobacter sp. JW-1 beads (PSLBs) were 3% JW-1 cells (w/v, wet weight), 10-12% (w/v) PVA, 2-3% (w/v) calcium chloride, and an immobilization time of 24-36h. The PSLBs were more tolerance to pH, temperature and salinity changes than free JW-1 cells and were stable and effective for degrading prometryn through six reuse cycles without losing their degradation capacity. The half-life of prometryn degradation by PSLBs at 100mgL-1 in pesticide plant wastewaters were 1.1-6.9h. The rate constants of prometryn degradation by PSLBs in wastewaters ranged from 304 to 576mgL-1day-1, which were approximately 1.25-118 times those of degradation by free JW-1 cells. The PSLBs degraded 99.9% of atrazine, 99.9% of ametryn, 97.8% of propazine, 100.0% of simetryn, 77.9% of simazine, 98.9% of terbuthylazine, 95.2% of prometon, 98.9% of atraton, and 31.6% of terbumeton at an initial concentration of 50mgL-1 of each herbicide in 2days. This study indicates that PSLBs persistently biodegrade s-triazine herbicides better than JW-1 free cells, and can be an efficient, safe and reusable biomaterial for the removal of s-triazine herbicides from contaminated sites.

Design, synthesis and biological evaluation of novel nicotinamide derivatives bearing a substituted pyrazole moiety as potential SDH inhibitors

BACKGROUND Succinate dehydrogenase (SDH) plays an important role in the Krebs cycle, which is considered as an attractive target for development of succinate dehydrogenase inhibitors (SDHIs) based on antifungal agents. Thus, in order to discover novel molecules with high antifungal activities, SDH as the target for a series of novel nicotinamide derivatives bearing substituted pyrazole moieties were designed and synthesised via a one-pot reaction. RESULTS The biological assay data showed that compound 3 l displayed the most potent antifungal activity with EC50 values of 33.5 and 21.4 µm against Helminthosporium maydis and Rhizoctonia cerealis, respectively. Moreover, 3 l exhibited the best inhibitory ability against SDH enzymes. The results of docking simulation showed that 3 l was deeply embedded into the SDH binding pocket, and the binding model was stabilised by a cation-π interaction with Arg 43, Tyr 58 and an H-bond with Trp 173. CONCLUSION The study suggests that the pyrazole nicotinamide derivative 3 l may serve as a potential SDHI that can be used as a novel antifungal agent, and provides valuable clues for the further design and optimisation of SDH inhibitors.

Degradation Dynamics and Dietary Risk Assessments of Two Neonicotinoid Insecticides during Lonicera japonica Planting, Drying, and Tea Brewing Processes

The degradation dynamics and dietary risk assessments of thiamethoxam and thiacloprid during Lonicera japonica planting, drying, and tea brewing processes were systematically investigated using high-performance liquid chromatography. The half-lives of thiamethoxam and thiacloprid were 1.0-4.1 d in the honeysuckle flowers and leaves, with degradation rate constants k ranging from -0.169 to -0.696. The safety interval time was 7 d. The sun- and oven-drying (70 °C) percent digestions were 59.4-81.0% for the residues, which were higher than the shade- and oven-drying percentages at lower temperatures (30, 40, 50, and 60 °C, which ranged from 37.7% to 57.0%). The percent transfers of thiamethoxam and thiacloprid were 0-48.4% and 0-25.2%, respectively, for the different tea brewing conditions. On the basis of the results of this study, abiding by the safety interval time is important, and using reasonable drying methods and tea brewing conditions can reduce the transfer of thiamethoxam and thiacloprid to humans.

Factors Affecting Transfer of Pyrethroid Residues from Herbal Teas to Infusion and Influence of Physicochemical Properties of Pesticides

The transfer of pesticide residues from herbal teas to their infusion is a subject of particular interest. In this study, a multi-residue analytical method for the determination of pyrethroids (fenpropathrin, beta-cypermethrin, lambda-cyhalothrin, and fenvalerate) in honeysuckle, chrysanthemum, wolfberry, and licorice and their infusion samples was validated. The transfer of pyrethroid residues from tea to infusion was investigated at different water temperatures, tea/water ratios, and infusion intervals/times. The results show that low amounts (0–6.70%) of pyrethroids were transferred under the different tea brewing conditions examined, indicating that the infusion process reduced the pyrethroid content in the extracted liquid by over 90%. Similar results were obtained for the different tea varieties, and pesticides with high water solubility and low octanol–water partition coefficients (log Kow) exhibited high transfer rates. Moreover, the estimated values of the exposure risk to the pyrethroids were in the range of 0.0022–0.33, indicating that the daily intake of the four pyrethroid residues from herbal tea can be regarded as safe. The present results can support the identification of suitable tea brewing conditions for significantly reducing the pesticide residue levels in the infusion.

Promoting photosensitized reductive dechlorination of chlorothalonil using epigallocatechin gallate in water.

Chlorothalonil (CTL) is a broad-spectrum fungicide. Photodegradation is a main degradation pathway of CTL in water. Because of the high aquatic toxicity of CTL and its metabolite 4-hydroxy CTL (CTL-OH), it is significant to develop an effective method to degrade CTL but without formation of CTL-OH. Epigallocatechin gallate (EGCG) is an abundant tea byproduct and has more than 100-fold reducing power than vitamin C. The present study reports photosensitization effects of EGCG on CTL photodegradation in water under sunlight and artificial lights. The results indicated that EGCG significantly photosensitizes CTL photodegradation. Under high-pressure mercury light illumination, CTL underwent primarily reductive dechlorination. CTL-OH, a main CTL photolytic product, was not detected when EGCG was added in the water. We concluded that EGCG not only significantly enhances CTL photodegradation rate but also alters the photodegradation pathways, avoiding the production of the highly toxic CTL-OH. The results indicated high potential of using EGCG to minimize CTL aquatic toxicity and pollution.