查找使用阿拉丁产品的科研文献

Repurposing 4-Hydroxyphenylpyruvate dioxygenase inhibitors as novel agents for mosquito control: A structure-based design approach

Jin Dong,Yi-Xuan Fu,Bai-Feng Zheng,Meng-Xi Chen,Qiong Chen,Kandegama Wishwajith,Jiangqing Dong,Hong-Yan Lin,Guang-Fu Yang

Mosquito-borne diseases remain a significant global health burden, necessitating innovative vector control strategies. 4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors, widely used as herbicides, have been recently explored for their potential to disrupt mosquito tyrosine metabolic pathways, offering a novel approach to mosquito control. This study utilized a structure-based rational design strategy to repurpose existing HPPD inhibitors, such as pyrazole-benzene 2,2-dioxothiadiazole and pyrazole-1,3-isoindolinone hybrids, targeting Aedes aegypti HPPD ( Aa HPPD). Biochemical assays demonstrated that a series of synthesized hybrid compounds exhibited superior inhibitory activity against mosquito-derived HPPD compared to traditional inhibitors, the IC 50 values of compound a9 and compound c14 are 7.70 nM and 53.80 nM, respectively. Crystallographic analysis showed stable inhibitor binding mediated by chelation with metal ions in the active site and π-π interactions with Phe336 and Phe364. C6/36 cell assays further confirmed elevated tyrosine accumulation and significantly affected energy metabolism in the tricarboxylic acid cycle following treatment with the newly designed inhibitors. These findings highlight the potential of repurposed HPPD inhibitors as safe and effective mosquito control agents with novel mechanisms of action.

Multi-omics analysis reveals AaaaNAT1 as a critical regulator of physiological homeostasis in Aedes aegypti

Xue Gong,Zhinan Lin,Yanjiao Zhou,Dingfeng Duan,Qian Han,Chenghong Liao

Physiological homeostasis is fundamental to vector competence in Aedes aegypti . Using RNA interference coupled with integrated multi-omics analysis (transcriptome, proteome, and metabolome), we elucidated the critical role of Arylalkylamine N-acetyltransferase-1 of Aedes aegypti (AaaaNAT) in maintaining salivary gland homeostasis and systemic physiological integrity. AaaaNAT1 knockdown precipitated genome-wide transcriptomic repression in salivary glands, concurrent suppression of energy metabolism, activation of compensatory protein synthesis, and extensive metabolic reprogramming. These molecular perturbations manifested as severely compromised immune defense, evidenced by rapid mortality upon bacterial challenge, and dramatically enhanced insecticide susceptibility. Notably, the LC50 of chlorpyrifos decreased from 7.90 μg/mL to 0.93 μg/mL, representing an ∼8-fold sensitivity increase. Multi-omics integration further revealed that AaaaNAT1 dysfunction disrupts sphingolipid signaling and impairs detoxification pathways, ultimately driving physiological collapse. Our findings establish AaaaNAT1 as a pivotal orchestrator of physiological homeostasis and stress adaptation, positioning it as a high-value molecular target for innovative vector control strategies. This work provides a robust framework for identifying critical gene targets and lays a solid foundation for translational applications in mosquito-borne disease prevention.

Larvicidal activity of Illicium difengpi BN Chang (Schisandraceae) Stem Bark and its Constituent Compounds against Aedes aegypti L

Y Liu,XC Liu,QY Liu,C Niu,ZL Liu

Functional Characterization of an Antenna-Biased Odorant Receptor AaOr96 Involved in Tea Tree Oil Repellency Against Aedes aegypti

Mengli Chen,Zhanyi Xu,Guoxing Chen,Peitong Chen,Chunxia Tian,Jiali Qian,Tiefeng Song,Yongfeng Jin,Guonian Zhu,Ru Yan

Numerous essential oils have been well acknowledged as eco-friendly alternatives to combat insect pests due to synthetic insecticide-induced pest resistance and environment pollution. As a highly commercial essential oil, tea tree oil exhibits excellent insecticidal and repellent activities. However, the molecular mechanism of the olfactory system mediating the tea tree oil-induced repellency against insect pests remains unknown. In our study, mosquito was used as a suitable model to examine the molecular mechanism of tea tree oil-induced repellency against insect pests. The results showed that tea tree oil exhibited excellent spatial and oviposition repellency against Aedes aegypti adults and outstanding repellency against larvae, which were conferred by the main constituent terpinen-4-ol. The reduced repellency in the Orco–/– mutant strain revealed that tea tree oil-induced repellency against mosquitoes was dependent on odorant receptor(s). Moreover, we identified one antenna-biased odorant receptor, AaOr96, that was involved in detecting constituents of tea tree oil to elicit repellency, and the predicted protein–ligand complex indicated that AaOr96 interacted with terpinen-4-ol via van der Waals forces from five key residues. Finally, knocking out AaOr96 resulted in a reduced spatial repellency against A. aegypti by tea tree oil and terpinen-4-ol, and a reduced oviposition repellency by terpinen-4-ol, but not by tea tree oil. Our study not only reveals that tea tree oil has great potential in pest management but also provides more insights into the molecular basis of repellency of essential oils.

Effect of proteolytic and detoxification enzyme inhibitors on Bacillus thuringiensis var. israelensis tolerance in the mosquito Aedes aegypti

Xiaohua Hu,Yajie Guo,Songqing Wu,Zhaoxia Liu,Tao Fu,Ensi Shao,Carballar-Lejarazú Rebeca,Guohui Zhao,Zhipeng Huang,Ivan Gelbič,Xiong Guan,Shuangquan Zou,Lei Xu,Lingling Zhang

Bacillus thuringiensis var. israelensis (Bti) is highly pathogenic to mosquito larvae and is widely used for mosquito control. Its mosquitocidal activity however is relatively low compared to many chemical insecticides. The detoxification mechanisms in the mosquito, among other things, might neutralize the Bti activity, resulting in resistance or tolerance. We tested whether or not the detoxification mechanisms against chemical insecticides might also operate against Bti, rendering it less effective. We targeted four enzymes in Aedes aegypti larvae involved in detoxification with inhibitors that have been used in resistance studies in chemical insecticides and assayed their effects on Bti toxicity. Results revealed that phenylmethanesulphonyl fluoride (PMSF), diethyl maleate, phenobarbital (PB), and piperonyl butoxide (PBO) altered Bti toxicity to various degrees. PMSF is a serine protease inhibitor that prevents Bti digestion and improves Bti activity. PB that induces several detoxifying enzymes had two different effects depending on the method of treatment. Mortality was higher when treatment with PB was discontinuous (149%) whereas with continuous treatment it was lower (101%). PBO, a typical cytochrome P450 inhibitor, increased Bti effect (159%). The combination of discontinuous pretreatment of larvae with PB followed by PBO had a synergistic effect and showed increased activity (146%). It appears that the mechanism for Bti resistance in mosquitoes is similar to that of chemical insecticides. Our studies indicate that we may be able to increase Bti activity by inhibiting some of the detoxification systems as active as broad spectrum chemical insecticides.

Photoactivated 9-methylacridine destroys midgut tissues of Aedes aegypti larvae by targeting ROS-mediated apoptosis in the mitochondrial pathway of midgut cells

Xian Xiao,Qiang Gao,Lan-Ying Wang,Yun-Fei Zhang,Yan-Ping Luo

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc , AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.

Chemical composition of Dipsacus asper Wallich ex Candolle (Dipsacaceae) essential oil and its activity against mosquito larvae of Aedes aegypti and Culex pipiens pallens

Hong Yu Lu,Xin Chao Liu,Qi Zhi Liu,Zhi Long Liu

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.

Evaluation of the Intergenerational Effects of Arecoline on Aedes aegypti via Acute Exposure and Its Role in Inducing the Leg Deformities Involved in Chitin Synthesis Inhibition

Yuejie Wu,Fei Wang,Longxiang Gao,Yunfei Zhang,Lanying Wang,Yanping Luo

Arecoline is a major active alkaloid in Areca catechu L. Currently, its biological toxicity has been extensively explored using multiple models, such as cell lines, animal embryos and representatives of rodent and non-rodent species. However, the intergenerational impacts of this compound on aquatic invertebrate species remain still unclear. Thus, in this study, using Aedes aegypti as the model insect, we evaluated the toxicity of arecoline to the larvae and its subsequent effects on the developmental parameters of the parental ( F 0 ) and offspring ( F 1 ) generations. Arecoline exhibited a high toxicity to A. aegypti larvae with the LC 50 value of 72.68 μg/mL via acute exposure for 48 h. As a result, the cumulative pupation rate of F 0 decreased significantly by ranging from 12.96% to 38.50% with the increase of arecoline concentration from 51.63 to 63.27 μg/mL as compared with that of the blank control. Similarly, the F 0 cumulative emergence rate and the average egg number per female exhibited reductions of 15.30%–43.88% and 26.32%–45.10%, respectively. Meanwhile, leg deformities of F 0 adults were observed as the main visible morphological defects with a maximum rate value of 11.89% at 63.27 μg/mL of arecoline. In contrast, the lifecycle parameters for F 0 mentioned above were not significantly affected in the F 1 generation. In addition, Gene Ontology (GO) analysis of the transcriptome data demonstrated that arecoline-induced leg deformities were associated with extracellular chitin-related biological processes. Furthermore, five chitin synthesis pathway genes ( G6PI , GFAT , GNPNA , UAP and CHS ) of F 0 adults were significantly down-regulated with ranging from 1.62 to 7.80 folds of the control adults. Correspondingly, the activity of chitin synthetase was significantly inhibited by 72.88% after arecoline exposure. As expected, the chitin contents of leg-deformed adults and their legs were also evidently reduced by 61.13% and 65.44%, respectively. These results imply that acute exposure of arecoline is of high toxicity to A. aegypti larvae and affected the subsequent intergenerational growth and development of F 0 rather than F 1 , and that a decrease in chitin synthesis was involved in arecoline-induced leg deformities of A. aegypti .