GPCR-MAPK signaling pathways underpin fitness trade-offs in whitefly.

Trade-offs between evolutionary gain and loss are prevalent in nature, yet their genetic basis is not well resolved. The evolution of insect resistance to insecticide is often associated with strong fitness costs; however, how the fitness trade-offs operates remains poorly understood. Here, we show that the mitogen-activated protein kinase (MAPK) pathway and its upstream and downstream actors underlie the fitness trade-offs associated with insecticide resistance in the whitefly Bemisia tabaci. Specifically, we find a key cytochrome P450 gene CYP6CM1, that confers neonicotinoids resistance to in B. tabaci, is regulated by the MAPKs p38 and ERK through their activation of the transcription factor cAMP-response element binding protein. However, phosphorylation of p38 and ERK also leads to the activation of the transcription repressor Cap "n" collar isoform C (CncC) that negatively regulates exuperantia (Ex), vasa (Va), and benign gonial cell neoplasm (Bg), key genes involved in oogenesis, leading to abnormal ovary growth and a reduction in female fecundity. We further demonstrate that the transmembrane G protein-coupled receptor (GPCR) neuropeptide FF receptor 2 (NPFF2) triggers the p38 and ERK pathways via phosphorylation. Additionally, a positive feedback loop between p38 and NPFF2 leads to the continuous activation of the MAPK pathways, thereby constitutively promoting neonicotinoids resistance but with a significant reproductive cost. Collectively, these findings provide fundamental insights into the role of cis-trans regulatory networks incurred by GPCR-MAPK signaling pathways in evolutionary trade-offs and applied knowledge that can inform the development of strategies for the sustainable pest control.

Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Identification and structural modification of ent-rosane diterpenoids from Euphorbia milii inhibiting RANKL-induced osteoclastogenesis.

Phytochemical study on Euphorbia milii, a common ornamental plant, resulted in the identification of thirteen new ent-rosane diterpenoids (1-13), three new ent-atisane diterpenoids (14-16), and a known ent-rosane (17). Their structures were delineated using spectroscopic data, quantum chemical calculations, and X-ray diffraction experiments. Euphomilone F (1) represented a rare ent-rosane-type diterpenoid with a 5/7/6 skeleton. Euphoainoid G (8) was a rare rosane diterpenic acid. Compounds 9 and 10 carried infrequent tetrahydrofuran rings, and compounds 11-13 was 18-nor-ent-rosane diterpenoids. All isolates were evaluated for their inhibitory effects on RANKL-induced osteoclasts. Notably, compounds with aromatic ester groups (2-7) showed promising activities (IC50 < 10 µM), underscoring the significance of acylated A-ring moieties in the ent-rosane skeleton for anti-osteoclastogenesis. Thirteen synthetic derivatives were obtained through esterification of 17. Of these, compound 27 exhibited remarkable improvement, with an IC50 of 0.8 µM, more than a 12-fold increase in potency compared to the parent compound 17 (IC50 > 10 µM). This work presents a series of new ent-rosane diterpenoids with potential antiosteoporosis agents.

Molecular and Structural Basis for Cγ-C Bond Formation by PLP-Dependent Enzyme Fub7.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes that catalyze γ-replacement reactions are prevalent, yet their utilization of carbon nucleophile substrates is rare. The recent discovery of two PLP-dependent enzymes, CndF and Fub7, has unveiled unique C-C bond forming capabilities, enabling the biocatalytic synthesis of alkyl- substituted pipecolic acids from O-acetyl-L-homoserine and ß-keto acid or aldehyde derived enolates. This breakthrough presents fresh avenues for the biosynthesis of pipecolic acid derivatives. However, the catalytic mechanisms of these enzymes remain elusive, and a dearth of structural information hampers their extensive application. Here, we have broadened the catalytic scope of Fub7 by employing ketone-derived enolates as carbon nucleophiles, revealing Fub7's capacity for substrate-dependent regioselective α-alkylation of unsymmetrical ketones. Through an integrated approach combining X-ray crystallography, spectroscopy, mutagenesis, and computational docking studies, we offer a detailed mechanistic insight into Fub7 catalysis. Our findings elucidate the structural basis for its substrate specificity, stereoselectivity, and regioselectivity. Our work sets the stage ready for subsequent protein engineering effort aimed at expanding the synthetic utility of Fub7, potentially unlocking novel methods to access a broader array of noncanonical amino acids.

Total Synthesis of Four Classes of Daphniphyllum Alkaloids.

The macrodaphniphyllamine-type, calyciphylline A-type, daphnilongeranin A-type, and daphnicyclidin D-type alkaloids are four structurally related classes of Daphniphyllum alkaloids. On the basis of a systematic analysis of the biogenetic network of these classes, we developed synthetic strategies centered on the C4-N and C1-C8 bonds of calyciphylline A, which took full advantage of the suitable substrates, reactions, and pathways that are altered from their counterparts in the postulated biogenetic network. Through this generalized biomimetic approach, we achieved the first synthesis of 14 Daphniphyllum alkaloids from the four subfamilies.

Cytochrome P450 CYP6DB3 was involved in thiamethoxam and imidacloprid resistance in Bemisia tabaci Q (Hemiptera: Aleyrodidae).

High level resistance for a variety of insecticides has emerged in Bemisia tabaci, a globally notorious insect. Neonicotinoid insecticides have been applied widely to control B. tabaci. Whether a differentially expressed gene CYP6DB3 discovered from transcriptome data of B. tabaci is involved in the resistance to neonicotinoid insecticides remains unclear. In the study, CYP6DB3 expression was significantly up-regulated in both thiamethoxam- and imidacloprid-resistant strains relative to the susceptive strains. We also found that CYP6DB3 expression was up-regulated after B. tabaci adults were exposed to thiamethoxam and imidacloprid. Moreover, knocking down CYP6DB3 expression via feeding corresponding dsRNA significantly reduced CYP6DB3 mRNA levels by 34.1%. Silencing CYP6DB3 expression increased the sensitivity of B. tabaci Q adults against both thiamethoxam and imidacloprid. Overexpression of CYP6DB3 gene reduced the toxicity of imidacloprid and thiamethoxam to transgenic D. melanogaster. In addition, metabolic studies showed that CYP6DB3 can metabolize 24.41% imidacloprid in vitro. Collectively, these results strongly support that CYP6DB3 plays an important role in the resistance of B. tabaci Q to imidacloprid and thiamethoxam. This work will facilitate a deeper insight into the part of cytochrome P450s in the evolution of insecticide resistance and provide a theoretical basis for the development of new integrated pest resistance management.

Novel_miR-1517 mediates CYP6CM1 to regulate imidacloprid resistance in Bemisia tabaci (Hemiptera: Gennadius).

Bemisia tabaci (Hemiptera: Gennadius) is a notorious pest that is capable of feeding on >600 kinds of agricultural crops. Imidacloprid is critical in managing pest with sucking mouthparts, such as B. tabaci. However, the field population of B. tabaci has evolved resistance because of insecticide overuse. The overexpression of the detoxification enzyme cytochrome P450 monooxygenase is considered the main mechanism of imidacloprid resistance, but the mechanism underlying gene regulation remains unclear. MicroRNAs are a type of endogenous small molecule compounds that is fundamental in regulating gene expression at the post-transcriptional level. Whether miRNAs are related to the imidacloprid resistance of B. tabaci remains unknown. To gain deep insight into imidacloprid resistance, we conducted on miRNAs expression profiling of two B. tabaci Mediterranean (MED) strains with 19-fold resistance through deep sequencing of small RNAs. A total of 8 known and 1591 novel miRNAs were identified. In addition, 16 miRNAs showed significant difference in expression levels between the two strains, as verified by quantitative reverse transcription PCR. Among these, novel_miR-376, 1517, and 1136 significantly expressed at low levels in resistant samples, decreasing by 36.9%, 60.2%, and 15.6%, respectively. Moreover, modulating novel_miR-1517 expression by feeding with 1517 inhibitor and 1517 mimic significantly affected B. tabaci imidacloprid susceptibility by regulating CYP6CM1 expression. In this article, miRNAs related to imidacloprid resistance of B. tabaci were systematically screened and identified, providing important information for the miRNA-based technological innovation for this pest management.

Over-expression of UDP-glycosyltransferase UGT353G2 confers resistance to neonicotinoids in whitefly (Bemisia tabaci).

The whitefly, Bemisia tabaci, comes up high metabolic resistance to most neonicotinoids in long-term evolution, which is the key problem of pest control. UGT glycosyltransferase, as a secondary detoxification enzyme, plays an indispensable role in detoxification metabolism. In this study, UGT inhibitors, 5-nitrouracil and sulfinpyrazone, dramatically augmented the toxic damage of neonicotinoids to B. tabaci. A UGT named UGT353G2 was identified in whitefly, which was notably up-regulated in resistant strain (3.92 folds), and could be induced by most neonicotinoids. Additionally, the using of RNA interference (RNAi) suppresses UGT353G2 substantially increased sensitivity to neonicotinoids in resistant strain. Our results support that UGT353G2 may be involved in the neonicotinoids resistance of whitefly. These findings will help further verify the functional role of UGTs in neonicotinoid resistance.

Molecular characterization of an NADPH cytochrome P450 reductase from Bemisia tabaci Q: Potential involvement in susceptibility to imidacloprid.

NADPH cytochrome P450 reductase (CPR) is an integral component of cytochrome P450-mediated biological reactions, such as the metabolism of xenobiotics, including insecticides. CPR has been reported to be associated with insecticide tolerance in several insects. However, the biochemical characteristics and biological function of CPR in Bemisia tabaci Q (BtCPR) remain undefined. In this study, BtCPR was cloned, and bioinformatic analysis showed that BtCPR is a transmembrane protein with a molecular weight (MW) of 76.73 kDa and contains conserved binding domains (FMN, FAD, and NADPH). Tissue- and developmental stage-dependent expression indicated that the highest expression levels of BtCPR occurred in head tissue and in male adults. Transcripts of BtCPR in the field B. tabaci Q strain were 1.62-fold higher than those of the laboratory B. tabaci Q strain. In both field and laboratory adults, the susceptibility of BtCPR-knockdown B. tabaci Q to imidacloprid substantially increased compared to that of the B. tabaci Q control group. Furthermore, the heterologous expression of BtCPR in Sf9 cells exhibited catalytic activity for cytochrome c reduction, following Michaelis-Menten kinetics. Sf9 cells overexpressing BtCPR had greater viability than the control cells when treated with imidacloprid. The results suggest that BtCPR could affect the susceptibility of B. tabaci Q to imidacloprid and could also be considered a novel target for pest control.

Molecular characterization and functional analysis of the Halloween genes and CYP18A1 in Bemisia tabaci MED.

The ecdysteroid hormone 20-hydroxyecdysone (20E), a critical hormone in arthropods, plays an essential role in insect growth, molting and reproduction. A previous study showed that 20E is actually regulated by six P450 genes (five P450 genes belonging to the Halloween family and a CYP18A1 gene) in model insects. However, the role of the six P450 genes in Bemisia tabaci Q (also call Mediterranean, MED), an important pest of field crops, remains unclear. Here, six P450 genes were cloned by RT-PCR, and the phylogenetic tree indicated a close orthologous relationship of these P450 genes between MED and other insects. Spatiotemporal expression profiling revealed that five P450 genes (CYP18A1, CYP306A1, CYP307A2, CYP314A1 and CYP315A1) were expressed at significantly higher levels in the head than in the abdomen and thorax. Four P450 genes (CYP302A1, CYP307A2, CYP314A1 and CYP315A1) were expressed at the highest levels in males, and CYP18A1 was expressed at the highest levels in the 4th nymph stage. The molting process was delayed by approximately 1-3 days after knockdown of these genes at the 4th nymph stage, and the mean proportion of shriveled or dead insects reached 8.3% (CYP18A1), 20.8% (CYP302A1), 7.0% (CYP307A2), 31.8% (CYP306A1), 28.6% (CYP314A1) and 24.1% (CYP315A1). In addition, 20E rescued the negative effect of ds-CYP306A1, ds-CYP314A1 and ds-CYP315A1 on the eclosion rate. We concluded that these Halloween genes and CYP18A1 likely participate in the development of MED, and in particular, CYP306A1 could be used as a putative insecticide target for controlling this piercing-sucking insect.

Comparative effectiveness of six Chinese herb formulas for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

BACKGROUND: Six Chinese herb formulas, namely, the Weijing decoction (WJ), the Maxingshigan decoction (MXSG), the Yuebijiabanxia decoction (YBBX), the Qingqihuatan decoction (QQHT), the Dingchuan decoction (DC) and the Sangbaipi decoction (SBP), are commonly used, along with routine pharmacotherapy, to manage the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In this study, we conducted a systematic review to summarize the efficacy of these six formulas, and we also conducted a network meta-analysis (NMA) to rank these formulas. METHODS: We searched five English databases and four Chinese databases, with dates ranging from the starting dates of these databases to December 2016. Randomized controlled trials that evaluated any of the six Chinese herb formulas combined with the use of pharmacotherapy for AECOPD were identified. RESULTS: Fifty-five studies involving 4560 participants were included. The pairwise meta-analyses showed that WJ and QQHT had superior effects on the improvement of lung function (forced expiratory volume in 1 seconds; FEV1) (mean difference (MD): 0.25, 95% confidence interval (CI): 0.19-0.30 and 0.34, 95%CI: 0.10-0.58). MXSG, WJ and QQHT were found to be more effective for improving arterial blood gases (PaO2 and PaCO2). In terms of effective rates, all of these formulas had additional favourable effects compared to routine pharmacotherapy. The results of the NMA analyses indicated that only MXSG showed superior add-on effects for the improvement of FEV1 (MD: 0.37, 95% credible interval (CrI): 0.03-0.72). Most of the formulas combined with routine pharmacotherapy were superior to pharmacotherapy alone for the improvement of arterial blood gases and effective rates. The ranking tests suggested that QQHT and MXSG combined with routine pharmacotherapy might be optimal options for the treatment of AECOPD. CONCLUSIONS: This NMA indicated that QQHT and MXSG might be more effective treatment regimens for AECOPD. Further well-designed studies that specifically examine the direct comparisons of these formulas are needed to support our conclusions.

Changes in the expression of four ABC transporter genes in response to imidacloprid in Bemisia tabaci Q (Hemiptera: Aleyrodidae).

Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), a globally invasive species complex that causes serious damage to field crops, has developed resistance to imidacloprid and many other pesticides. Insect detoxify to pesticides may partially depend on ABC transporters, which contribute to the detoxification of xenobiotics. To determine whether genes in the ABCG subfamily are involved in imidacloprid detoxification in B. tabaci Q, we cloned four ABCG subfamily genes based on the published MED/Q genome and on our previous study of the transcriptional response of ABC transporters in B. tabaci Q adults to imidacloprid. As indicated by the quantification of mRNA levels after a 6-h exposure, the expression level of ABCG3 was 3.3-fold higher in B. tabaci Q adults exposed to 100 µg/mL imidacloprid rather than to the buffer control. The expression level of ABCG3 was higher in females than in males but did not significantly differ among eggs or nymphal stages and did not significantly differ among head, thorax, and abdomen tissues of adults. Knockdown of ABCG3 via RNA interference significantly increased the mortality of imidacloprid-treated laboratory and field-collected adults of B. tabaci Q. These results indicate that the ABCG3 gene may be involved in imidacloprid detoxification by B. tabaci Q.

Electroacupuncture for Poststroke Spasticity: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects and safety of electroacupuncture (EA) for stroke patients with spasticity. DATA SOURCES: Five English databases (PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database) and 4 Chinese databases (Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database, Wanfang Database) were searched from their inception to September 2016. STUDY SELECTION: Randomized controlled trials were included if they measured spasticity with the Modified Ashworth Scale (MAS) in stroke patients and investigated the add-on effects of electroacupuncture to routine pharmacotherapy and rehabilitation therapies. DATA EXTRACTION: Information on patients, study design, treatment details and outcomes assessing spasticity severity, motor function, and activities of daily living was extracted. DATA SYNTHESIS: In total, 22 trials involving 1425 participants met the search criteria and were included. The estimated add-on effects of EA to reduce spasticity in the upper limbs as measured by the MAS (standardized mean difference [SMD]=-.57; 95% confidence interval [CI], -.84 to -.29), and to improve overall motor function as measured by the Fugl-Meyer Assessment of Sensorimotor Recovery (mean difference [MD]=10.60; 95% CI, 8.67-12.53) were significant. Significant add-on effects of EA were also shown for spasticity in the lower limbs, lower-limb motor function, and activities of daily living ([SMD=-.88; 95% CI, -1.42 to -.35;], [MD=4.42; 95% CI, .06-8.78], and [MD=6.85; 95% CI, 3.64-10.05], respectively), although with high heterogeneity. For upper-limb motor function, no significant add-on effects of EA were found. CONCLUSIONS: EA combined with conventional routine care has the potential of reducing spasticity in the upper and lower limbs and improving overall and lower extremity motor function and activities of daily living for patients with spasticity, within 180 days poststroke. Further studies of high methodological and reporting quality are needed to confirm the effects and safety of EA, and to explore the adequate and optimal protocol of EA for poststroke spasticity, incorporating a group of comprehensive outcome measures in different populations.

[Reporting quality and effect size comparison in randomized controlled trials of bo's abdominal acupuncture using CONSORT statement and STRICTA].

OBJECTIVE: To evaluate the reporting quality of randomized controlled trials (RCT) that compared Bo's abdominal acupuncture with conventional body acupuncture, and compare the efficacy and safety between them by performing a Meta-analysis. METHODS: All RCTs comparing Bo's abdominal acupuncture with conventional body acupuncture were included. English and Chinese databases were searched from their respective inceptions to March 2014. The reporting quality was assessed according to the "Consolidated Standards of Reporting Trials" (CONSORT) checklist for parallel RCTs and the revised "Standards for Reporting Interventions in Clinical Trials of Acupuncture" (STRICTA). A Meta-analysis was conducted to synthesize the effect sizes, and publication bias was evaluated by the Egger linear regression test using Stata. RESULTS: Ninety-seven studies were included, of which most lacked adequate reporting information, and 80.4% showed that the efficacy of abdominal acupuncture is superior to conventional body acupuncture, especially for the following diseases: lumbar disc herniation, cervical spondylosis, omarthritis and cervical vertigo, except simple obesity. Effect-sizes were controversial when evaluating different outcomes. CONCLUSION: The international standard CONORT statement and STRICTA guidelines should be strictly applied when reporting acupuncture RCTs in the future. Abdominal acupuncture appears to be more effective compared with conventional body acupuncture for some diseases. However, fur-her high quality blind RCTs using validated out-ome indexes and standard reporting are warranted.

Dang shen [Codonopsis pilosula (Franch.) Nannf] herbal formulae for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the efficacy and safety of Dang shen [Codonopsis pilosula (Franch.) Nannf., root] formulae for the treatment of chronic obstructive pulmonary disease (COPD). English and Chinese databases were searched, and 48 randomized controlled trials were included. Dang shen formulae improved lung function forced expiratory volume in 1 s compared with conventional pharmacotherapy (CP) [mean difference (MD) 0.22 L, 95% confidence interval (CI) 0.13-0.31, p < 0.001, I(2) = 5%] and quality of life (St. Georges Respiratory Questionnaire) compared with placebo (MD -7.19, 95% CI -10.82 to -3.56, p < 0.001, I(2) = 0%) and when combined with CP versus CP (MD -9.05, 95% CI -12.72 to -5.38, p < 0.001, I(2) = 89%). Dang shen formulae also increased distance walked in 6 min when combined with CP versus CP alone (MD 51.43 m, 95% CI 30.06-72.80, p < 0.001, I(2) = 27%) and reduced frequency/days with COPD exacerbations. Risk of bias was evaluated using the Cochrane tool. Methodological shortfalls were identified. Adverse events were low and not different between intervention and control groups. Thirty-three events were reported, including gastrointestinal upset, dry mouth, and insomnia. Dang shen formulae appear to improve some aspects of the included COPD outcomes. However, owing to methodological flaws, the current evidence is inadequate to support the routine use of Dang shen formulae outside of Chinese medicine practice. However, these results justify further investigation.

Current status and implementation strategies of patient education in core outcome set development.

OBJECTIVE: Patient participation is essential for Core Outcome Set (COS) development studies. Patient education during participation may help patients better express their views in COS studies. This study aimed to investigate the current status of patient participation and the specified educational information in COS studies. METHODS: We conducted a systematic review of COS development studies. Information on patient participation in COS research, and especially details of patient education, was analyzed. RESULTS: In total, 146 COS development studies were included in this review. Of these, 125 studies (85.6%) mentioned patient participation. Most studies did not provide explicit information on patient participation. Some studies mentioned recruiting patients, but ultimately, none of them responded. Six studies reported conducting patient education through workshops, creating patient forums, or providing videos and slides. However, these studies did not provide details on education. Twenty-three studies used the plain language to explain patient outcomes. CONCLUSION: COS developers are increasingly focusing on patient participation. However, only a few COS studies have explicitly reported conducting measures related to patient education. Further patient education is necessary when they participate in the development of a new Core Outcome Set. PRACTICE IMPLICATION: This article provides implementation strategies related to patient education for future COS development studies.

High-Frequency Space Diffusion Model for Accelerated MRI.

Diffusion models with continuous stochastic differential equations (SDEs) have shown superior performances in image generation. It can serve as a deep generative prior to solving the inverse problem in magnetic resonance (MR) reconstruction. However, low-frequency regions of k -space data are typically fully sampled in fast MR imaging, while existing diffusion models are performed throughout the entire image or k -space, inevitably introducing uncertainty in the reconstruction of low-frequency regions. Additionally, existing diffusion models often demand substantial iterations to converge, resulting in time-consuming reconstructions. To address these challenges, we propose a novel SDE tailored specifically for MR reconstruction with the diffusion process in high-frequency space (referred to as HFS-SDE). This approach ensures determinism in the fully sampled low-frequency regions and accelerates the sampling procedure of reverse diffusion. Experiments conducted on the publicly available fastMRI dataset demonstrate that the proposed HFS-SDE method outperforms traditional parallel imaging methods, supervised deep learning, and existing diffusion models in terms of reconstruction accuracy and stability. The fast convergence properties are also confirmed through theoretical and experimental validation. Our code and weights are available at https://github.com/Aboriginer/HFS-SDE.

Cytochrome P450 CYP6EM1 Underpins Dinotefuran Resistance in the Whitefly Bemisia tabaci.

Being a destructive pest worldwide, the whitefly Bemisia tabaci has evolved resistance to neonicotinoid insecticides. The third-generation neonicotinoid dinotefuran has commonly been applied to the control of the whitefly, but its underlying mechanism is currently unknown. On the base of our transcriptome data, here we aim to investigate whether the cytochrome P450 CYP6EM1 underlies dinotefuran resistance in the whitefly. Compared to the susceptible strain, the CYP6EM1 gene was found to be highly expressed in both laboratory and field dinotefuran-resistant populations. Upon exposure to dinotefuran, the mRNA levels of CYP6EM1 were increased. These results demonstrate the involvement of this gene in dinotefuran resistance. Loss and gain of functional studies in vivo were conducted through RNAi and transgenic Drosophila melanogaster assays, confirming the role of CYP6EM1 in conferring such resistance. In a metabolism assay in vitro, the CYP6EM1 protein could metabolize 28.11% of dinotefuran with a possible dinotefuran-dm-NNO metabolite via UPLC-QTOF/MS. Docking of dinotefuran to the CYP6EM1 protein showed a good binding affinity, with an energy of less than -6.0 kcal/mol. Overall, these results provide compelling evidence that CYP6EM1 plays a crucial role in the metabolic resistance of B. tabaci to dinotefuran. Our work provides new insights into the mechanism underlying neonicotinoid resistance and applied knowledge that can contribute to sustainable control of a global pest such as whitefly.

Dynamic monitoring of the insecticide resistance status of Bemisia tabaci across China from 2019-2021.

BACKGROUND: Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a major agricultural insect pest that causes severe economic losses worldwide. Several insecticides have been applied to effectively control this key pest. However, owing to the indiscriminate use of chemical insecticides, B. tabaci has developed resistance against these chemical compounds over the past several years. RESULTS: From 2019 to 2021, 23 field samples of B. tabaci were collected across China. Twenty species were identified as the Mediterranean 'Q' type (MED) and three were identified as MED/ Middle East-Asia Minor 1 mixtures. Subsequently, resistance of the selected populations to different insecticides was evaluated. The results showed that 13 populations developed low levels of resistance to abamectin. An overall upward trend in B. tabaci resistance toward spirotetramat, cyantraniliprole and pyriproxyfen was observed. In addition, resistance to thiamethoxam remained low-to-moderate in the 23 field populations. CONCLUSION: These findings suggest that the overall resistance of the field-collected B. tabaci populations has shown an upward trend over the years in China. We believe our study can provide basic data to support integrated pest management and insecticide resistance management of field B. tabaci in China. © 2023 Society of Chemical Industry.