{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:42:44Z","timestamp":1789386164925,"version":"build-2803163510"},"reference-count":58,"publisher":"The Royal Society","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["National Basic Research Program of China (No. 2012"],"award-info":[{"award-number":["National Basic Research Program of China (No. 2012"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 31272365"],"award-info":[{"award-number":["No. 31272365"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["XDB14040203"],"award-info":[{"award-number":["XDB14040203"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>\n                    With the widespread use of avermectins (AVMs) for managing parasitic and agricultural pests, the resistance of worms and insects to AVMs has emerged as a serious threat to human health and agriculture worldwide. The reduced penetration of AVMs is one of the main reasons for the development of the resistance to the chemicals. However, the detailed molecular mechanisms remain elusive. Here, we use the larvae of\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    as the model organism to explore the molecular mechanisms underlying the development of penetration resistance to AVMs. We clearly show that the chitin layer is thickened and the efflux transporter P-glycoprotein (P-gp) is overexpressed in the AVM-resistant larvae epidermis. We reveal that the activation of the transcription factor Relish by the over-activated epidermal growth factor receptor (EGFR)\/AKT\/ERK pathway induces the overexpression of the chitin synthases\n                    <jats:italic>DmeCHS1\/2<\/jats:italic>\n                    and P-gp in the resistant larvae. Interestingly, we discover for the first time, to the best of our knowledge, that AVM directly interacts with EGFR and leads to the activation of the EGFR\/AKT\/ERK pathway, which activates the transcription factor Relish and induces the overexpression of\n                    <jats:italic>DmeCHS1\/2<\/jats:italic>\n                    and P-gp. These findings provide new insights into the molecular mechanisms underlying the development of penetration resistance to drugs.\n                  <\/jats:p>","DOI":"10.1098\/rsob.150231","type":"journal-article","created":{"date-parts":[[2016,4,13]],"date-time":"2016-04-13T05:13:19Z","timestamp":1460524399000},"page":"150231","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Direct interaction of avermectin with epidermal growth factor receptor mediates the penetration resistance in\n                    <i>Drosophila<\/i>\n                    larvae"],"prefix":"10.1098","volume":"6","author":[{"given":"Li-Ping","family":"Chen","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China"},{"name":"Department of Veterinary Medicine and Animal Science, Beijing Agriculture College, Beijing 102206, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2016,4]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.15.3.361"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00184a014"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.en.36.010191.000515"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2006.09.032"},{"key":"e_1_3_4_6_2","first-page":"64","article-title":"Avermectin resistance of the cattle tick Boophilus microplus in Brazil","volume":"149","author":"Martins JR","year":"2001","journal-title":"Vet. 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