{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:23:53Z","timestamp":1787286233388,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402415"],"award-info":[{"award-number":["32402415"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Insect Science"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    While G protein\u2010coupled receptors (GPCRs) are recognized as key upstream regulators of insecticide resistance in various agricultural pests, effective strategies to exploit these receptors for practical pest control remain largely undeveloped. In this study, we screened and identified\n                    <jats:italic>TMEM145<\/jats:italic>\n                    as a novel GPCR significantly upregulated in clothianidin resistant Nilaparvata lugens. RNAi\u2010mediated knockdown of\n                    <jats:italic>TMEM145<\/jats:italic>\n                    suppressed the expression of the detoxification gene\n                    <jats:italic>CYP6ER1<\/jats:italic>\n                    and the transcription factor AP\u20101, successfully restoring clothianidin susceptibility with a lethal dose ratio (LCR\n                    <jats:sub>50<\/jats:sub>\n                    ) of 1.78. Through structure\u2010based virtual screening of 4000 bioactive molecules targeting TMEM145, we mined pectolinarin as a potential inhibitor exhibiting a high binding affinity of \u221210.945 kcal\/mol. Its structural scaffold, apigenin, was identified as an alternative with a binding affinity of \u22128.223 kcal\/mol. Experimental validation confirmed that chemical inhibition by these flavonoids significantly downregulated detoxification gene expression. In vivo bioassays demonstrated that pectolinarin markedly increased clothianidin susceptibility, achieving a synergistic effect with an LCR\n                    <jats:sub>50<\/jats:sub>\n                    of 2.87. These results demonstrate that targeting upstream GPCR\u2010mediated regulatory nodes with natural synergists offers a promising and sustainable approach to managing metabolic resistance in agricultural pests.\n                  <\/jats:p>","DOI":"10.1111\/1744-7917.70347","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T03:44:08Z","timestamp":1787283848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural TMEM145 GPCR inhibitors enhancing clothianidin susceptibility in\n                    <i>Nilaparvata lugens<\/i>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-4197","authenticated-orcid":false,"given":"Guijian","family":"Zhang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory for Crop Diseases &amp; Insect Pests &amp; Weeds Control, Key Laboratory of Integrated Pests Management on Crops in Central China of Ministry of Agricultural and Rural Affairs Institute of Plant Protection and Soil Science, Hubei Academy of Agricultural Sciences  Wuhan China"},{"name":"Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqian","family":"Chang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory for Crop Diseases &amp; Insect Pests &amp; Weeds Control, Key Laboratory of Integrated Pests Management on Crops in Central China of Ministry of Agricultural and Rural Affairs Institute of Plant Protection and Soil Science, Hubei Academy of Agricultural Sciences  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"He","sequence":"additional","affiliation":[{"name":"Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology Huazhong Agricultural University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-0653","authenticated-orcid":false,"given":"Liang","family":"Lv","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory for Crop Diseases &amp; Insect Pests &amp; Weeds Control, Key Laboratory of Integrated Pests Management on Crops in Central China of Ministry of Agricultural and Rural Affairs Institute of Plant Protection and Soil Science, Hubei Academy of Agricultural Sciences  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-3759","authenticated-orcid":false,"given":"Hu","family":"Wan","sequence":"additional","affiliation":[{"name":"Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology Huazhong Agricultural University  Wuhan 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