{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:07:47Z","timestamp":1789128467213,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["QG26017"],"award-info":[{"award-number":["QG26017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004761","name":"Hainan Natural Science Foundation","doi-asserted-by":"publisher","award":["323MS065"],"award-info":[{"award-number":["323MS065"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Teaching Team Program of China Agricultural University"},{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}]},{"name":"2115 Talent Development Program of China Agricultural University"},{"id":[{"id":"https:\/\/ror.org\/04v3ywz14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>Bactrocera dorsalis (Hendel) is a globally significant quarantine pest, and broflanilide represents a new insecticide with potential for its management. However, the molecular responses of B. dorsalis to broflanilide, particularly the involvement of cytochrome P450 genes, remain poorly understood. To address this gap, we compared the midgut and fat body transcriptomes of adults that survived 24 h of exposure to the median lethal concentration (LC50) of broflanilide with those of corresponding controls. Candidate P450 genes were further examined by quantitative real-time PCR (qRT-PCR), RNA interference (RNAi), and molecular docking. RNA-seq identified strong upregulation of CYP6G8 (log2FC = 11.84 and 6.32) and CYP6GX5 (log2FC = 6.48 and 7.83) in the broflanilide-exposed surviving group. qRT-PCR showed that CYP6G8 was significantly upregulated in both tissues, whereas CYP6GX5 was significantly upregulated in the fat body but showed a nonsignificant upward trend in the midgut. Silencing CYP6G8 increased mortality from 43.21% to 64.14%, and CYP6GX5 silencing increased mortality from 31.11% to 87.07% following broflanilide exposure. Docking analyses predicted possible interactions between both proteins and desmethyl-broflanilide (DM-8007), the active metabolite of broflanilide. These results identify CYP6G8 and CYP6GX5 as candidate P450 genes associated with broflanilide tolerance under the tested conditions, although their direct biochemical roles remain to be determined.<\/jats:p>","DOI":"10.3390\/insects17090950","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:51:37Z","timestamp":1789123897000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Upregulation of Two CYP6 Genes Is Associated with the Response to Broflanilide in Bactrocera dorsalis (Hendel, 1912) (Diptera: Tephritidae)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8191-4598","authenticated-orcid":false,"given":"Bo","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MARA Key Lab of Surveillance and Management for Plant Quarantine Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China"},{"name":"Sanya Institute, China Agricultural University, Sanya 572025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Si-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MARA Key Lab of Surveillance and Management for Plant Quarantine Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China"},{"name":"Sanya Institute, China Agricultural University, Sanya 572025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zhi-Hong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MARA Key Lab of Surveillance and Management for Plant Quarantine Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China"},{"name":"Sanya Institute, China Agricultural University, Sanya 572025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-9750","authenticated-orcid":false,"given":"Shao-Kun","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural and Forestry Biosecurity, MARA Key Lab of Surveillance and Management for Plant Quarantine Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China"},{"name":"Sanya Institute, China Agricultural University, Sanya 572025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","unstructured":"CABI Compendium (2020). Bactrocera dorsalis (Oriental Fruit Fly), CABI Compendium."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jaffar, S., Rizvi, S.A.H., and Lu, Y. (2023). Understanding the invasion, ecological adaptations, and management strategies of Bactrocera dorsalis in China: A review. Horticulturae, 9.","DOI":"10.3390\/horticulturae9091004"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1146\/annurev.en.32.010187.000555","article-title":"The biology of dacine fruit flies","volume":"32","author":"Fletcher","year":"1987","journal-title":"Annu. Rev. Entomol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"White, I.M., and Elson-Harris, M.M. (1992). Fruit Flies of Economic Significance: Their Identification and Bionomics, CAB International.","DOI":"10.1079\/9780851987903.0000"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"He, Y., Xu, Y., and Chen, X. (2023). Biology, ecology and management of tephritid fruit flies in China: A review. Insects, 14.","DOI":"10.3390\/insects14020196"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3390\/insects6020297","article-title":"An overview of pest species of Bactrocera fruit flies (Diptera: Tephritidae) and the integration of biopesticides with other biological approaches for their management with a focus on the pacific region","volume":"6","author":"Vargas","year":"2015","journal-title":"Insects"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1127\/entomologia\/2024\/2654","article-title":"A novel potential nAChR variation and the upregulation of CYP304A1 contribute to resistance against lambda-cyhalothrin and spinosad in Bactrocera dorsalis","volume":"44","author":"Liu","year":"2024","journal-title":"Entomol. Gen."},{"key":"ref_8","unstructured":"(2026, February 14). China Pesticide Information Network. Available online: https:\/\/www.icama.cn\/BasicdataSystem\/pesticideRegistration\/tagview.do?pdno=PD20200660."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s12936-020-03466-4","article-title":"Tenebenal: A meta-diamide with potential for use as a novel mode of action insecticide for public health","volume":"19","author":"Lees","year":"2020","journal-title":"Malar. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.bmc.2015.08.008","article-title":"Broflanilide: A meta-diamide insecticide with a novel mode of action","volume":"24","author":"Nakao","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1111\/1744-7917.13142","article-title":"Baseline susceptibility of Helicoverpa armigera, Plutella xylostella, and Spodoptera frugiperda to the meta-diamide insecticide broflanilide","volume":"30","author":"Wang","year":"2023","journal-title":"Insect Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105641","DOI":"10.1016\/j.cropro.2021.105641","article-title":"Global crop impacts, yield losses and action thresholds for fall armyworm (Spodoptera frugiperda): A review","volume":"145","author":"Overton","year":"2021","journal-title":"Crop Prot."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cropro.2005.02.005","article-title":"Assessing the potential impact of biological control of Plutella xylostella (diamondback moth) in cabbage production in Kenya","volume":"24","author":"Macharia","year":"2005","journal-title":"Crop Prot."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1002\/ps.7463","article-title":"Lethal and sublethal effects of broflanilide on four tephritid pests (Diptera: Tephritidae)","volume":"79","author":"Li","year":"2023","journal-title":"Pest Manag. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev.ento.51.110104.151104","article-title":"Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics","volume":"52","author":"Li","year":"2007","journal-title":"Annu. Rev. Entomol."},{"key":"ref_16","first-page":"1386","article-title":"Insecticide resistance and glutathione S-transferases in mosquitoes: A review","volume":"8","author":"Penilla","year":"2009","journal-title":"Afr. J. Biotechnol."},{"key":"ref_17","first-page":"1","article-title":"ABC transporters and their role in protecting insects from pesticides and their metabolites","volume":"Volume 46","author":"Cohen","year":"2014","journal-title":"Advances in Insect Physiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-ento-070621-061328","article-title":"The role of cytochrome P450s in insect toxicology and resistance","volume":"67","author":"Nauen","year":"2022","journal-title":"Annu. Rev. Entomol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1126\/science.1074170","article-title":"A single P450 allele associated with insecticide resistance in Drosophila","volume":"297","author":"Daborn","year":"2002","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1365-2583.2008.00777.x","article-title":"Characterization of two novel cytochrome P450 genes in insecticide-resistant house-flies","volume":"17","author":"Zhu","year":"2008","journal-title":"Insect Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"863","DOI":"10.7150\/ijbs.6744","article-title":"Permethrin induction of multiple cytochrome P450 genes in insecticide resistant mosquitoes, Culex quinquefasciatus","volume":"9","author":"Gong","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pestbp.2013.03.001","article-title":"Multiple P450 genes: Identification, tissue-specific expression and their responses to insecticide treatments in the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae)","volume":"106","author":"Huang","year":"2013","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, X., Li, P., Li, D., Cai, X., Gu, S., Zeng, L., Cheng, D., and Lu, Y. (2024). Dynamics of Bactrocera dorsalis resistance to seven insecticides in south China. Insects, 15.","DOI":"10.3390\/insects15090679"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11223","DOI":"10.1038\/s41598-018-29622-0","article-title":"Trichlorfon and spinosad resistance survey and preliminary determination of the resistance mechanism in Pakistani field strains of Bactrocera dorsalis","volume":"8","author":"Khan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12657","DOI":"10.1073\/pnas.1109535108","article-title":"CYP9Q-mediated detoxification of acaricides in the honey bee (Apis mellifera)","volume":"108","author":"Mao","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1146\/annurev-ento-011118-112007","article-title":"Fat body biology in the last decade","volume":"64","author":"Li","year":"2019","journal-title":"Annu. Rev. Entomol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Schroeder, A., Mueller, O., Stocker, S., Salowsky, R., Leiber, M., Gassmann, M., Lightfoot, S., Menzel, W., Granzow, M., and Ragg, T. (2006). The RIN: An RNA integrity number for assigning integrity values to RNA measurements. BMC Mol. Biol., 7.","DOI":"10.1186\/1471-2199-7-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jare.2022.12.012","article-title":"Genomes of the cosmopolitan fruit pest Bactrocera dorsalis (Diptera: Tephritidae) reveal its global invasion history and thermal adaptation","volume":"53","author":"Zhang","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nmeth.3176","article-title":"Fast and sensitive protein alignment using DIAMOND","volume":"12","author":"Buchfink","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W317","DOI":"10.1093\/nar\/gkab447","article-title":"KOBAS-i: Intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis","volume":"49","author":"Bu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1021\/acssuschemeng.9b00004","article-title":"A facile-synthesized star polycation constructed as a highly efficient gene vector in pest management","volume":"7","author":"Li","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_38","unstructured":"(2026, February 15). UCLA-DOE LAB\u2014SAVES v6.1. Available online: https:\/\/saves.mbi.ucla.edu\/."},{"key":"ref_39","unstructured":"(2026, February 15). PubChem, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W478","DOI":"10.1093\/nar\/gkaf377","article-title":"ProteinsPlus: A publicly available resource for protein structure mining","volume":"53","author":"Ehrt","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W463","DOI":"10.1093\/nar\/gkaf361","article-title":"PLIP 2025: Introducing protein-protein interactions to the protein-ligand interaction profiler","volume":"53","author":"Schake","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ishaaya, I. (2001). Insect midgut as a site for insecticide detoxification and resistance. Biochemical Sites of Insecticide Action and Resistance, Springer.","DOI":"10.1007\/978-3-642-59549-3"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/eesa.1996.1504","article-title":"Changes in protein metabolism in hemolymph and fat body of the silkworm, Bombyx mori (Lepidoptera: Bombycidae) in response to organophosphorus insecticides toxicity","volume":"36","author":"Nath","year":"1997","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ullah, F., Ullah, Z., Gul, H., Li, X., Pan, Y., Zhang, H., Zhang, Z., Huang, J., Emmanouil, R., and Guedes, R.N.C. (2025). Proactive resistance management studies highlight the role of cytochrome P450 genes in the resistance of Tuta absoluta against tetraniliprole. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115180"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shu, H., Lin, Y., Zhang, Z., Qiu, L., Ding, W., Gao, Q., Xue, J., Li, Y., and He, H. (2023). The transcriptomic profile of Spodoptera frugiperda differs in response to a novel insecticide, cyproflanilide, compared to chlorantraniliprole and avermectin. BMC Genom., 24.","DOI":"10.1186\/s12864-022-09095-2"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143623","DOI":"10.1016\/j.chemosphere.2024.143623","article-title":"Genome-wide analysis of detoxification genes conferring diamide insecticide resistance in Spodoptera exigua identifies CYP9A40","volume":"367","author":"Han","year":"2024","journal-title":"Chemosphere"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1002\/ps.5891","article-title":"Genome-wide and expression-profiling analyses of the cytochrome P450 genes in Bactrocera dorsalis (Hendel) and screening of candidate P450 genes associated with malathion resistance","volume":"76","author":"Jing","year":"2020","journal-title":"Pest Manag. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e21416","DOI":"10.1002\/csc2.21416","article-title":"Surfactant toxicity and synergistic activity with pyrethroids in managing resistant Listronotus maculicollis Kirby populations","volume":"65","author":"Price","year":"2025","journal-title":"Crop Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106432","DOI":"10.1016\/j.pestbp.2025.106432","article-title":"Carrier solvent effects on the toxicity and penetration rate of fluralaner in the house fly, Musca domestica L. (Diptera: Muscidae)","volume":"212","author":"Weston","year":"2025","journal-title":"Pestic. Biochem. Physiol."}],"container-title":["Insects"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/9\/950\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:07:01Z","timestamp":1789124821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/9\/950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["insects17090950"],"URL":"https:\/\/doi.org\/10.3390\/insects17090950","relation":{},"ISSN":["2075-4450"],"issn-type":[{"value":"2075-4450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}