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PEST MANAGEMENT SCIENCE · 2022 ·Vol. 78 ·期 10 ·4407-4416 · IF 4.462

Preparation and characterization of emamectin benzoate nanocapsules based on the dual role of polydopamine

Liyin Shi,Weiyao Yan,Li Sun,Chaoqun Hou,Nuo Wei,Zhiyang Chen,Jianguo Feng

Background Developing pesticide-controlled release formulations with foliage adhesion has become the focus of current research in the field of crop protection. In this study, an excellent adhesive nanocapsule loaded with emamectin benzoate (Eb@PDA) was prepared via emulsion interfacial polymerization based on the self-polymerization ability and adhesion properties of polydopamine (PDA). Results The physicochemical properties of the Eb@PDA were characterized by scanning electron microscopy, transmission electron microscopy, particle size statistics, Fourier transform infrared spectroscopy and X-ray diffraction. The Eb@PDA presented a regular spherical shape, with an average particle size of 163.8 nm. Compared with conventional formulations, it had higher pesticide-loading content (34%) and excellent adhesion onto corn leaf. In addition, Eb@PDA showed sustained-release characteristics, facilitating the release of Eb at low pH and high temperature. Eb@PDA could effectively protect Eb against photodegradation and had a longer effective period for controlling Spodoptera frugiperda and Spodoptera exigua . Furthermore, acute toxicity tests showed that the 50% lethal concentration (LC 50 ) was 80.91 and 57.91 mg kg −1 at 7 and 14 days, respectively, indicating a lower toxicity of the Eb@PDA to earthworms. The cells (L02) treated with Eb@PDA showed a higher cell viability but a lower apoptosis rate (only 5.75%), demonstrating the lower cytotoxicity of the Eb@PDA. Conclusion The self-prepared Eb@PDA could be used as a formulation with the advantages of slow release, UV shielding, strong leaf adhesion, superior insecticidal properties, sustained effectiveness and biosafety. It will also facilitate the development of an efficient and safe pesticide delivery system. © 2022 Society of Chemical Industry.

研究领域: 农药科学 · 材料科学 · 植物保护
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PEST MANAGEMENT SCIENCE · 2024 · IF 3.8

Discovery of novel piperidine-containing thymol derivatives as potent antifungal agents for crop protection

Xiaoqun Yang,Shichun Jiang,Meng Zhang,Tingting Li,Zhichao Jin,Xingxing Wu,Yonggui Robin Chi

BACKGROUND Plant fungal diseases pose a significant threat to crop production. The extensive use of chemical pesticides has led to growing environmental safety risks and pesticide resistance of various plant pathogens. Therefore, it is an urgent task to explore novel eco-friendly fungicidal agents with high efficacy to combat fungal infection. RESULTS In this study, we rationally designed a series of novel thymol derivatives by incorporation of the sulfonamide moiety and evaluated their biological activities against plant pathogenic fungi. The bioassay results underscored the remarkable in vitro antifungal activity of compounds 5m and 5t against Phytophthora capsici ( P. capsici ), with EC 50 values of 8.420 and 8.414 μ g/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649 μ g/mL) and cabendazim (CAB, 251.625 μ g/mL). Furthermore, compound 5v exhibited excellent in vitro antifungal activity against Sclerotinia sclerotiorum ( S. sclerotiorum ), with an EC 50 value of 12.829 μ g/mL, significantly outperforming AZO (63.629 μ g/mL). In vivo bioassays demonstrated the impactful activity of compound 5v against S. sclerotiorum , achieving over 98% curative and protective efficacies at the concentration of 200 μ g/mL. Further mechanistic investigations unveiled that compound 5v induced mycelial shrinkage and collapse in S. sclerotiorum , resulting in organelle damage and the accumulation of antioxidant enzyme activity. CONCLUSION The significant antifungal efficacy of the prepared thymol derivatives shall encourage further exploration of compound 5v as a promising candidate to develop novel fungicides for crop protection. © 2024 Society of Chemical Industry.

研究领域: 农业科学 · 植物病理学 · 化学生物学
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PEST MANAGEMENT SCIENCE · 2024 · IF 3.8

Design, synthesis, antimicrobial activity, and mechanism of novel 3-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives

Yuguo Zheng,Mei Chen,Renfeng Zhang,Wei Xue

BACKGROUND Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting. RESULTS The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro . In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae ( Xoo ), with an EC 50 value of 27.47 μg mL −1 , surpassing conventional control agents such as thiazole zinc (41.55 μg mL −1 ) and thiodiazole copper (53.39 μg mL −1 ). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo , which in turn affected the reproduction and growth of bacteria. CONCLUSION This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry.

研究领域: 农业化学 · 植物病理学 · 药物科学
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2023 ·Vol. 79 ·期 7 ·2527-2538 · IF 4.1

Development of axially chiral urazole scaffolds for antiplant virus applications against potato virus Y

Jiamiao Jin,Chengli Mou,Juan Zou,Xin Xie,Chen Wang,Tingwei Shen,Youlin Deng,Benpeng Li,Zhichao Jin,Xiangyang Li,Yonggui Robin Chi

BACKGROUND Potato virus Y (PVY) was first discovered by Smith in 1931 and is currently ranked as the fifth most significant plant virus. It can cause severe damage to plants from the family Solanaceae , which results in billions of dollars of economic loss worldwide every year. To discover new antiviral drugs, a class of multifunctional urazole derivatives bearing a stereogenic C  N axis were synthesized with excellent optical purities for antiviral evaluations against PVY. RESULTS The absolute configurations of the axially chiral compounds exhibited obvious distinctions in antiviral bioactivities, with several of these enantio-enriched axially chiral molecules showing excellent anti-PVY activities. In particular, compound ( R )- 9f exhibited remarkable curative activities against PVY with a 50% maximal effective concentration (EC 50 ) of 224.9 μg mL −1 , which was better than that of ningnanmycin (NNM), which had an EC 50 of 234.0 μg mL −1 . And the EC 50 value of the protective activities of compound ( R )- 9f was 462.2 μg mL −1 , which was comparable to that of NNM (442.0 μg mL −1 ). The mechanisms of two enantiomer of the axially chiral compounds 9f were studied by both molecule docking and defensive enzyme activity tests. CONCLUSION Mechanistic studies demonstrated that the axially chiral configurations of the compounds played significant roles in the molecule PVY-CP (PVY Coat Protein) interactions and could enhance the activities of the defense enzymes. The (S)-9f showed only one carbon–hydrogen bond and one π–cation interaction between the chiral molecule and the PVY-CP amino acid sites. In contrast, the (R)-enantiomer of 9f exhibited three hydrogen bonding interactions between the carbonyl groups and the PVY-CP active sites of ARG157 and GLN158. The current study provides significant information on the roles that axial chiralities play in plant protection against viruses, which will facilitate the development of novel green pesticides bearing axial chiralities with excellent optical purities. © 2023 Society of Chemical Industry.

研究领域: 植物病理学 · 有机化学 · 药学
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2021 ·Vol. 78 ·期 4 ·1500-1507 · IF 4.845

V101I and R81T mutations in the nicotinic acetylcholine receptor β1 subunit are associated with neonicotinoid resistance in Myzus persicae

Xiao Xu,Qian Ding,Xiu Wang,Ruijie Wang,Farman Ullah,Xiwu Gao,Dunlun Song

BACKGROUND The peach-potato aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), is a major pest worldwide. The intensive use of insecticides has led to the development of resistance against neonicotinoid insecticides. The R81T mutation in the nicotinic acetylcholine receptor (nAChR) beta1 subunit is considered a crucial mechanism adaptation to neonicotinoid resistance in M. persicae and Aphis gossypii . RESULTS Resistance-related mutations (R81T and V101I) were detected in the imidacloprid-resistant M. persicae AH19 population. The V101I mutation is reported for the first time. The V101I and R81T mutations existed separately, indicating that the two mutations evolved independently. Imidacloprid resistance in the AH19 population was stable without insecticide exposure. Four mutant strains were selected from the population with stable resistance. The resistance of the AH19-T, AH19-I, and AH19-TI strains to imidacloprid, thiamethoxam, and dinotefuran was significantly increased compared with the AH19-W strain. Synergism bioassays showed that the inhibition of three detoxification enzymes did not affect imidacloprid resistance in the AH19-T and AH19-I strains. Expression of nAChR β1 subunits in the AH19-W, AH19-T, and AH19-I strains remained unchanged. CONCLUSION The V101I mutation is associated with neonicotinoid resistance in M. persicae . The resistance of the AH19-T and AH19-I strains to neonicotinoids appears to be mainly due to the R81T and V101I mutations, whereas these mutations, together with changes in the cytochrome P450 monooxygenases and nAChR expression may be responsible for the development of neonicotinoid resistance in the AH19-TI strain. © 2021 Society of Chemical Industry.

研究领域: 昆虫学 · 分子生物学 · 害虫管理
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2021 ·Vol. 77 ·期 6 ·2843-2853 · IF 4.845

Discovery of behaviorally active semiochemicals in Aenasius bambawalei using a reverse chemical ecology approach

Chong Xu,Fuxiang Yang,Shuanggang Duan,Dongzhen Li,Lei Li,Manqun Wang,Aiming Zhou

BACKGROUND The invasive mealybug, Phenacoccus solenopsis , has caused serious damage to cotton crops throughout the world. Aenasius bambawalei is a dominant endoparasitoid of P. solenopsis . Exploration of behaviorally active semiochemicals may promote the efficacy of parasitoids used in biological control. Reverse chemical ecology, based on the physiological function of odorant-binding proteins (OBPs), provides an effective approach to screen behaviorally active compounds to target insect pests. Determination of the binding mechanisms and specificity towards different odorants in A. bambawalei may facilitate the development of more-efficient biological control strategies. RESULTS We characterized the expression profile and analyzed the binding affinity of OBP28 in A. bambawalei . AbamOBP28 showed high expression in the wings and antennae of both male and female A. bambawalei . A fluorescence competitive binding assay indicated that AbamOBP28 displayed strong binding affinity to most candidate ligands. Circular dichroism spectra demonstrated that 1-octen-3-one, myrcene, dodecane, 2,4,4-trimethyl-2-pentene, nonanal, and limonene elicited conformational changes in AbamOBP28. Electrophysiological and behavioral bioassays revealed that diethyl sebacate, 2,4,4-trimethyl-2-pentene, and 1-octen-3-one evoked significant electroantennography responses and functioned as attractants in A. bambawalei at specific concentrations. Furthermore, three-dimensional structure modeling and molecular docking showed that hydrogen bonds were formed by Glu1 and Ser75 of AbamOBP28 with diethyl sebacate, respectively. CONCLUSION These results demonstrate that AbamOBP28 is involved in the chemoreception of A. bambawalei . The identified protein provides a potential target for efficient enemy utilization and pest control, and the overall results may help develop protocols for more effective screening of behaviorally active semiochemicals. © 2021 Society of Chemical Industry

研究领域: 昆虫学 · 化学生态学 · 生物控制
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2022 ·Vol. 78 ·期 8 ·3365-3375 · IF 4.462

A pH- and redox-stimulated responsive hollow mesoporous silica for triggered delivery of fungicides to control downy mildew of Luffa cylindrica

Liupeng Yang,Huiya Chen,Wenjuan Yan,Suqing Huang,Dongmei Cheng,HanHong Xu,Zhixiang Zhang

BACKGROUND Downy mildew, a devastating disease of cucurbitaceous crops caused by Pseudoperonospora cubensis . Although a variety of fungicides are used to control downy mildew, choosing an effective product can be challenging. Environmental stimulus-responsive pesticide delivery systems have great potential to improve the effectiveness of disease and pest control and reduce the impact on environmentally beneficial organisms. RESULTS In this work, a disulfide bond (SS)-modified and chitosan oligosaccharide (COS)-capped hollow mesoporous silica (HMS) pesticide delivery system was synthesized using a hard template method for the control of downy mildew in cucurbit crops. The synthesized nanoparticles were loaded with dimethomorph (DMM), denoted as DMM@HMS-SS-COS, and the developmental toxicity of these nanoparticles to zebrafish embryos were evaluated. The results showed that the prepared DMM@HMS-SS-COS exhibited excellent dual response properties to pH and glutathione (GSH), with an encapsulation rate of up to 24.36%. DMM@HMS-SS-COS has good ultraviolet (UV) radiation stability and adhesion properties. Compared with dimethomorph suspension concentrate (SC), DMM@HMS-SS-COS was more effective against downy mildew for up to 21 days. Toxicity tests showed that DMM@HMS-SS-COS significantly reduced the effect of DMM on the hatching rate and survival rate of zebrafish embryos. CONCLUSIONS This work not only demonstrates that DMM@HMS-SS-COS could be used as a nanodelivery system for intelligent control of downy mildew but also emphasizes the necessity of increasing the acute toxicity of nanoformulations to non-target organisms in environmental risk assessment. © 2022 Society of Chemical Industry.

研究领域: 农业科学 · 纳米技术 · 植物病理学 · 环境科学
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2021 ·Vol. 77 ·期 7 ·3224-3232 · IF 4.845

Phenyl imidazolidin-2-ones antagonize a β-adrenergic-like octopamine receptor in diamondback moth (Plutella xylostella)

Xi-le Deng,Lei Guo,Hai-hao Ma,Xue-ping Hu,Xiao-mao Zhou

BACKGROUND The diamondback moth ( Plutella xylostella ) is one of the most destructive lepidopteran pests on cruciferous vegetables. However, resistance has emerged to current chemical and biological insecticides used for P. xylostella control, indicating the necessity of screening new targets on P. xylostella , and finding new insecticides against P. xylostella . In particular, octopamine receptors are representative G protein-coupled receptors found only in invertebrates and are potential targets for identifying novel insecticides. RESULTS A β-adrenergic-like octopamine receptor gene ( PxOA2B1 ) was cloned, and its pharmacological characteristics in P. xylostella were studied. The results demonstrated that octopamine could activate the PxOA2B1 receptor, with a half-maximal effective concentration (EC 50 ) of 49.5 n m . Amitraz, an insecticide and acaricide, and its metabolite ( N -2,4-dimethylphenyl- N ′-methylformamidine; DPMF) were also found to act as PxOAB1R agonists. We synthesized phenyl imidazolidin-2-one derivatives 3a–h using DPMF as the lead compound, and compounds 3a–h showed similar antagonist activities as phentolamine, mianserin and chlorpromazine. In particular, 3d , with an EC 50 of 25.2 n m , showed very similar antagonist activity to mianserin. CONCLUSION This research found that PxOAB1R might be a potential target for P. xylostella control. Phenyl imidazolidin-2-ones could be novel potential antagonists targeted at octopamine receptors and would be useful tools for the design and development of novel insecticides. © 2021 Society of Chemical Industry

研究领域: 昆虫学 · 农药科学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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PEST MANAGEMENT SCIENCE · 2025 ·Vol. 82 ·期 1 ·319-327 · IF 3.8

Optimizing sex pheromone lures for male trapping specificity between Spodoptera frugiperda and Mythimna loreyi

Yu He,Jing-Jing Ye,Si-Ruo Liu,Mo-Yang Chen,Teng-Fei Bai,Jian-Wen Li,Shu-wei Yan,Jian-Rong Huang,Jian-Yu Deng,Ian W. Keesey,Jin Zhang,Qi Yan,Shuang-Lin Dong

BACKGROUND Spodoptera frugiperda and Mythimna loreyi are sympatric pests of corn and other gramineous crops. In addition, the two species share three primary pheromone components Z 9-14:Ac, Z 7-12:Ac and Z 11-16:Ac, resulting in capture of males from both species by commercially available lures, which poses a great challenge for species-specific population monitoring. RESULTS To increase the specificity of the pheromone blend used in lures, we conducted comparative investigations between the two species, with respect of female calling rhythms, components in female pheromone glands, male electrophysiological and sexual excitement responses to pheromone gland components. Based on differences between the two species obtained from these investigations, we further designed and tested a variety of blend formulations for the species-specificity in the field trapping assays, with the reported ternary blend for S. frugiperda ( Z 9-14:Ac/ Z 7-12:Ac/ Z 11-16:Ac = 88/1.0/11) as a positive control. The results showed that the ratio of component Z 7-12:Ac is the major determinant of the male trapping specificity of the blends in lures. Compared to the positive control, increasing the ratio of Z 7-12:Ac to 10 in the ternary blend greatly improved the specificity and captures for M. loreyi males, while reducing its ratio to 0.4 significantly improved the specificity and retained the capture ability for S. frugiperda males. CONCLUSION The optimal blend was determined to be Z 9-14:Ac/ Z 7-12:Ac/ Z 11-16:Ac at a ratio of 88/0.4/11 for S. frugiperda , and 88/10/11 for M. loreyi . These findings offer highly species-specific sex pheromone formulations for population monitoring and male trapping of the two sympatric pests. © 2025 Society of Chemical Industry.

CAS / MDL: 124-19-6
研究领域: 昆虫学 · 害虫管理 · 化学生态学 · 农业科学
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PEST MANAGEMENT SCIENCE · 2025 · IF 3.8

Cytochrome P450 and glutathione S-transferase may confer bensulfuron-methyl resistance in Cyperus iria

Juncheng Wu,Zhengyuan Tao,Jingyi Cao,Wei Hu,Minghao Jiang,Yahui Li,Haiqun Cao,Min Liao,Ning Zhao

BACKGROUND Rice flatsedge ( Cyperus iria L.) is one of the most troublesome weeds infesting rice fields across China. Bensulfuron-methyl, an acetolactate synthase (ALS)-inhibiting herbicide, has been widely used for the control of Cyperaceae weeds in rice production. However, long-term and extensive use of this herbicide has resulted in the evolution of resistant C. iria populations. In this study, a suspected bensulfuron-methyl-resistant (R) population collected from a rice field that survived field-recommended applications was investigated to elucidate its resistance level and underlying mechanism. RESULTS Compared with a susceptible (S) population, the R population exhibited a high level of resistance to bensulfuron-methyl [resistance index (RI) = 12.88] and cross-resistance to metazosulfuron (RI = 11.66), bispyribac-sodium (RI = 9.10) and penoxsulam (RI = 6.35). No mutations were detected in the ALS gene, and ALS expression levels did not differ significantly between the R and S plants. Pretreatment with the cytochrome P450 inhibitor malathion and the glutathione S -transferase inhibitor 4-chloro-7-nitrobenzoxadiazole effectively reversed bensulfuron-methyl resistance in R plants. Liquid chromatography tandem mass spectrometry analysis showed that the R plants metabolized bensulfuron-methyl significantly faster than the S plants. RNA sequenccing analysis revealed remarkable upregulation of CYP97A3 and GSTF1 in the R population, while molecular docking indicated strong binding affinities between both enzymes and bensulfuron-methyl at their active sites. CONCLUSION These results reveal that enhanced expression of CYP97A3 and GSTF1 may contribute to bensulfuron-methyl resistance in C. iria , highlighting the role of metabolic detoxification in the evolution of non-target-site resistance in this species. © 2025 Society of Chemical Industry.

CAS / MDL: 10199-89-0
研究领域: 杂草科学 · 植物生理学 · 分子生物学 · 除草剂抗性 · 农业植物学
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PEST MANAGEMENT SCIENCE · 2025 · IF 3.8

Herbicidal mechanism of Isovanillic acid and computational structure-guided design of high-potency derivatives

He Wang,Yanjing Guo,Yu Ji,Qing Liu,Qizhen Chen,Qianlong Zhang,Mingying Yang,Bernal E. Valverde,Shiguo Chen

BACKGROUND Natural products are a valuable resource for exploring novel pesticides and play a crucial role in weed management. Isovanillic acid (IVA), a bioactive compound produced by plants, exhibits various active functions. However, studies on IVA's herbicidal activity and its mechanism of action remain scarce. This study demonstrates that IVA acts as a natural photosystem II (PSII) inhibitor, providing new insights into its phytotoxicity. RESULTS IVA significantly inhibited photosynthetic activity in Chlamydomonas reinhardtii and induced visible leaf lesions on Ageratina adenophora . Phytotoxicity bioassays confirmed that IVA has a broad-spectrum activity, highlighting its potential as a bioherbicide. Chlorophyll fluorescence studies demonstrated that IVA primarily disrupts PSII electron flow beyond plastoquinone Q A , ultimately inactivating PSII reaction centers. Isothermal titration calorimetry (ITC) experiment confirmed the binding affinity between D1 protein and IVA, while molecular docking analysis further identified histidine 215 of the D1 protein as IVA's key binding residue—a mechanism shared with classical phenolic PSII herbicides. Using the IVA-D1 protein interaction model, 41 IVA derivatives were designed and ranked based on free energy calculations and toxicity predictions. Among these, three optimized compounds (D11, D12 and D13) with higher predict binding affinity but lower mammalian toxicity than IVA were screened and synthesized. Structure–activity relationship analysis revealed that these derivatives achieved approximately twofold stronger PSII inhibition and significantly enhanced herbicidal efficacy compared to the parent compound. CONCLUSION These results identify IVA as a novel natural PSII inhibitor and a strategic scaffold for discovering new high-efficacy herbicidal derivatives. © 2025 Society of Chemical Industry.

CAS / MDL: 1689-84-5 645-08-9
研究领域: 植物科学 · 农药化学 · 计算生物学 · 天然产物化学 · 光合作用研究
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PEST MANAGEMENT SCIENCE · 2024 · IF 3.8

Preparation of a long-lasting tablet of spinosad microspheres and its residual insecticidal efficacy against the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae) larvae

Hongxiao Yu,Yunqi Li,Hong Wang,Lei Zhang,Penghui Suo,Tianyun Su,Qian Han

BACKGROUNDS In order to provide a long-lasting formulation for spinosad (SP) targeting larval stages of Aedes aegypti (Linnaeus) and others alike, a SP tablet was developed based on microspheres, using polylactic acid as inside coating material. The microspheres were encapsulated using polyethylene glycol and 1-hexadecanol to form a sustained-release SP tablet. Micromorphology, active ingredient loading, structure identification, photolysis resistance and biological activity were evaluated in this report. RESULTS (i) The SP microspheres had an average particle size of 6.16 ± 2.28 μm, low adhesion and good dispersion as evaluated by scanning electron microscopy and morphology. (ii) The average active ingredient loading and encapsulation of SP microspheres were 32.80 ± 0.74% and 78.41 ± 2.22%, respectively. (iii) The chemical structure of encapsulated SP was confirmed by Fourier transform infrared and 1 H-nuclear magnetic resonance. (iv) The photostability of the microspheres and the tablets were evaluated. The results showed that DT 50 (time required to dissipate 50% of the mass originally present) of SP was 0.95 days in microspheres and 6.94 days in tablets. (v) The long-term insecticidal activity of SP tablets was investigated, and the tablet had a long-lasting activity against the mosquito larvae, showing 100% larval mortality for 63 days. CONCLUSIONS The study provided a new long-lasting formulation of SP, which displayed good efficacy in the control of Ae. aegypti larvae. © 2024 Society of Chemical Industry.

CAS / MDL: 9002-89-5
研究领域: 药学 · 害虫控制 · 微囊技术 · 公共卫生
✓ 已验证 产品关联 DOI PubMed 高影响因子
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