A detoxification pathway initiated by a nuclear receptor TcHR96h in Tetranychus cinnabarinus (Boisduval).

Understanding the mechanism of detoxification initiation in arthropods after pesticide exposure is crucial. Although the identity of transcription factors that induce and regulate the expression of detoxification genes in response to pesticides is beginning to emerge, whether transcription factors directly interact with xenobiotics is unclear. The findings of this study revealed that a nuclear hormone receptor, Tetranychus cinnabarinus hormone receptor (HR) TcHR96h, regulates the overexpression of the detoxification gene TcGSTm02, which is involved in cyflumetofen resistance. The nuclear translocation of TcHR96h increased after cyflumetofen exposure, suggesting direct binding with cyflumetofen. The direct binding of TcHR96h and cyflumetofen was supported by several independent proteomic assays that quantify interactions with small molecules. Together, this study proposes a model for the initiation of xenobiotic detoxification in a polyphagous agricultural pest. These insights not only provide a better understanding of the mechanisms of xenobiotic detoxification and metabolism in arthropods, but also are crucial in understanding adaptation in polyphagous herbivores.

Cross resistance, inheritance and fitness advantage of cyetpyrafen resistance in two-spotted spider mite, Tetranychus urticae.

Cyetpyrafen belonging to mitochondrial electron transport inhibitors of complex II (METI II) has been widely applied to manage pest mites in China. To investigate the adaption of Tetranychus urticae in the evolution of cyetpyrafen resistance, a study of cross resistance, mode of inheritance and fitness comparison of resistance using indoor cyetpyrafen resistant strain (resistance ratio, RR > 2, 000-fold) was executed. Cyet-R showed serious cross resistance to cyenopyrafen (>2500-fold) and cyflumetofen (~190-fold). The number of resistant genes was evaluated via chi-square (χ2) test and the concentration-response curve regarding goodness-of-fit between observed and the expected mortality. The LC50s of F1RS (Cyet-R♀ × Tu-YN♂) and F1SR (Tu-YN♀ × Cyet-R♂) were 3126.30 mg/L and 2743.97 mg/L, respectively, without significance, suggesting autosomal inheritance. The degree of dominance (D) values of F1RS and F1SR ranged between 0 and 1, revealing an incompletely dominant inheritance in the tested population of Tetranychus urticae. Plots of concentration-response data for the orthogonal backcross and reverse backcross progenies showed a significant deviation from the expected lines, pointing out a polygenic inheritance. Besides, lifetable analysis showed a fitness advantage of Cyet-R with a significantly decreased adult preadult period and significantly increased total fecundity. This study suggested that cyetpyrafen resistance against T. urticae was inherited as autosomal, incompletely dominant and multigenetic and characterized with serious cross resistance and fitness advantage. Therefore, rational application and preventive strategy should be considered to sustain the efficacy of cyetpyrafen against T. urticae.

Olfactory outcomes after endonasal skull base surgery: a systematic review.

For the last two decades, endonasal approach has been regularly applied to treat skull base lesions. However, postoperative olfactory dysfunction remains an unsolved problem. This systematic review aimed to identify factors that might affect postoperative olfactory prognosis of patients undergoing endonasal surgery for resection of sellar/parasellar lesions. The literature search was conducted comprehensively to exhaust studies which focused on patients' olfaction with objective olfactory assessments after endonasal skull base surgery. We sought to characterize the potential factors that might affect postoperative olfactory outcomes. Nineteen articles met inclusion criteria. We found that (1) endoscopic surgery was beneficial to patients' olfactory prognosis than microscopic surgery (incidence of postoperative decreased olfactory function: 18.48% (39/211) for the endoscopic group and 36.88% (52/141) for the microscopic group, P < 0.01); meta-analysis for single rate, 20% (95% CI 9-30%) for the endoscopic group and 35% (95% CI 0-72%) for the microscopic group); (2) harvesting septal flaps was an unfavorable factor for olfactory recovery and the rescue flap technique should be preferred compared with the HB flap; (3) no evidence showed that resection of the middle turbinate was detrimental to recovery of olfaction. Patients undergoing endoscopic endonasal surgery may have better olfactory outcomes than those undergoing microscopic endonasal surgery for resection of sellar/parasellar lesions. Special attention should be paid when using septal flaps is planned and the rescue flap technique should be the preferred choice. After resecting the middle turbinate, patients' olfaction still has a great chance of returning to the baseline. More homogeneous and high-quality studies are needed for further assessment.

Transcriptome analysis revealed that multiple genes were related to the cyflumetofen resistance of Tetranychus cinnabarinus (Boisduval).

Metabolic resistance is one of the main causes of acaricide resistance. Many previous studies focused on the function of specific genes in insecticides/acaricides resistance. However, during the development of resistance, the overall dynamic of expression levels of detoxification enzyme genes in mites is still unclear. Tetranychus cinnabarinus, a major agricultural pest, which is notorious for developing resistance to acaricides rapidly. In this study, a field susceptible strain (YS) was continuously selected for 16, 25 and 32 generations, and developed to low resistance (7.83-fold, L), medium resistance (17.23-fold, M) and high resistance (86.05-fold, H), respectively. Transcriptome sequencing was performed in YS, L, M and H strains. Overall, compared with YS strain, the number of differential expression genes increased slightly with the development of cyflumetofen-resistance. As for detoxification genes, the median of fold change of up-regulated P450、CCE and GST genes was higher than those of all up-regulated genes in three resistance level, but only the number and the median of fold change of up-regulated P450 genes was increased slightly with the development of resistance. In addition, synergism experiments also proved that P450 and GST genes were the major contributors to the metabolic resistance of cyflumetofen of T. cinnabarinus. These results showed that the resistance of T. cinnabarinus to cyflumetofen was related to many resistant genes, among which P450 genes could play crucial roles in cyflumefen resistance.

Amidase, a novel detoxifying enzyme, is involved in cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval).

Amidase is an important hydrolytic enzyme in detoxification metabolism. Amidase hydrolyzes a wide variety of nonpeptide carbon­nitrogen bonds by attacking a cyano group or carbonyl carbon. However, little is known about the relationship between amidase and insecticides. In this study, the amidase activity was significantly higher in cyflumetofen-resistant strain (CyR) than in the susceptible strain (SS) of Tetranychus cinnabarinus, and diethyl-phosphoramidate (an amidase inhibitor) significantly decreased cyflumetofen resistance in T. cinnabarinus. More importantly, an amidase gene, TcAmidase01, was identified in T. cinnabarinus, and the TcAmidase01 overexpression was detected in both two cyflumetofen-resistant strains (CyR and YN-CyR), indicating that it is involved in cyflumetofen resistance in mites. A phylogenetic analysis showed that TcAmidase01 was clustered with deaminated glutathione amidases, which possess hydrolytic activity. The recombinant TcAmidase01 protein showed amidase activity toward succinamate, and the activity could be inhibited by cyflumetofen. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis provided evidence that recombinant TcAmidase01 could decompose cyflumetofen by hydrolysis, and the potential metabolites (2-(4-(tert-butyl) phenyl)-2-cyanoacetate and 2-(trifluoromethyl) benzoic acid) were identified. These results show that TcAmidase01 contribute to cyflumetofen-resistance in T. cinnabarinus by hydrolyzing cyflumetofen, and this is the first study to suggest that amidase has a role in insecticides resistance in arthropods.

Diffusion Tensor MRI of White Matter of Healthy Full-term Newborns: Relationship to Neurodevelopmental Outcomes.

Background It is well known that white matter injuries observed at birth are associated with adverse neurodevelopmental outcomes later in life. Whether white matter developmental variations in healthy newborns are also associated with changes in later neurodevelopment remains to be established. Purpose To evaluate whether developmental variations of white matter microstructures identified by MRI correlate with neurodevelopmental outcomes in healthy full-term infants. Materials and Methods In this prospective study, pregnant women were recruited and their healthy full-term newborns underwent a brain MRI including diffusion tensor imaging at approximately 2 weeks of age. These infants were tested at approximately 2 years of age with the Bayley Scales of Infant Development (BSID). Voxel-wise correlation analyses of fractional anisotropy (FA), measured with diffusion tensor MRI, and neurodevelopmental test scores, measured by using BSID, were performed by using tract-based spatial statistics (TBSS), followed by region-of-interest (ROI) analyses of correlations between mean FA in selected white matter ROIs and each BSID subscale score. Results Thirty-eight full-term infants (20 boys, 18 girls) underwent MRI examination at 2 weeks of age (14.3 days ± 1.6) and BSID measurement at 2 years of age (732 days ± 6). TBSS analyses showed widespread clusters in major white matter tracts, with positive correlations (P ≤ .05, corrected for the voxel-wise multiple comparisons) between FA values and multiple BSID subscale scores. These correlations were largely independent of several demographic parameters as well as family environment. Gestational age at birth appeared to be a confounding factor as TBSS-observed correlations weakened when it was included as a covariate; however, after controlling for gestational age at birth, ROI analyses still showed positive correlations (P ≤ .05, R = 0.35 to 0.48) between mean FA in many white matter ROIs and BSID cognitive, language, and motor scores. Conclusion There were significant associations between white matter microstructure developmental variations in healthy full-term newborns and their neurodevelopmental outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hu and McAllister in this issue.

Resistant inheritance and cross-resistance of cyflumetofen in Tetranychus cinnabarinus (Boisduval).

As a new acaricide, cyflumetofen can effectively control Tetranychus, Panonychus, as well as other phytophagous mites. But its risk and the way of genetic and resistant inheritance in mites are not clear. In this study, two cyflumetofen-resistant strains (CyR and YN-CyR) were selected for 104 and 12 generations, and developed 104.7-fold and 25.6-fold resistance, respectively. Three crossing groups (CyR_80 × SS, CyR_104 × SS, YN-CyR × SS) were conducted to explore the resistant inheritance of cyflumetofen in T. cinnabarinus changed along with resistant level or not. The results of reciprocal crosses and backcrosses revealed that the incomplete recessive and multiple genes trait involved in two resistant strains. The different stage of resistance also has a same genetic trait. A cross-resistance study revealed that there was no cross-resistance between cyflumetofen and other four acaricides including avermectin, fenpropathrin, propargite and bifenazate respectively, but the cross-resistance to pyridaben reached a high level with 63.8-fold, which indicates an underlying mechanism that can both mediate cyflumetofen- and pyridaben-resistance in T. cinnabarinus.

UGT201H1 overexpression confers cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval).

BACKGROUND: Tetranychus cinnabarinus is one of the most common polyphagous arthropod herbivores, and is primarily controlled by the application of acaricides. The heavy use of acaricides has led to high levels of resistance to acaricides such as cyflumetofen, which poses a threat to global resistance management programs. Cyflumetofen resistance is caused by an increase in metabolic detoxification; however, the role of uridine diphosphate (UDP)-glycosyltransferase (UGT) genes in cyflumetofen resistance remains to be determined. RESULTS: Synergist 5-nitrouracil (5-Nul) significantly enhanced cyflumetofen toxicity in T. cinnabarinus, which indicated that UGTs are involved in the development of cyflumetofen resistance. Transcriptomic analysis and quantitative (q)PCR assays demonstrated that the UGT genes, especially UGT201H1, were highly expressed in the YN-CyR strain, compared to those of the YN-S strain. The RNA interference (RNAi)-mediated knockdown of UGT201H1 expression diminished the levels of cyflumetofen resistance in YN-CyR mites. The findings additionally revealed that the recombinant UGT201H1 protein plays a role in metabolizing cyflumetofen. Our results also suggested that the aromatic hydrocarbon receptor (AhR) probably regulates the overexpression of the UGT201H1 detoxification gene. CONCLUSION: UGT201H1 is involved in cyflumetofen resistance, and AhR may regulates the overexpression of UGT201H1. These findings provide deeper insights into the molecular mechanisms underlying UGT-mediated metabolic resistance to chemical insecticides. © 2024 Society of Chemical Industry.

Improving the efficiency and environmental safety of emamectin benzoate through a pH-responsive metal-organic framework microencapsulation strategy.

Herein, we developed a technique for loading nanopesticides onto Metal-Organic Frameworks (MOFs) to control Spodoptera litura. The average short-axis length of the synthesized carrier emamectin benzoate@PCN-222 @hyaluronic acid (EB@PCN-222 @HA) was ∼40 nm, with an average long-axis length of ∼80 nm. This enabled the manipulation of its size, contact angle, and surface tension on the surface of leaves. Pesticide-loading capacity, determined via thermogravimetric analysis, was measured at ∼16 %. To ensure accurate pesticide release in the alkaline intestine of Spodoptera litura, EB@PCN-222 @HA was engineered to decompose under alkaline conditions. In addition, the carrier delayed the degradation rate of EB, enhancing EB's stability. Loading Nile red onto PCN-222 @HA revealed potential entry into the insect body through feeding, which was supported by bioassay experiments. Results demonstrated the sustained-release performance of EB@PCN-222 @HA, extending its effective duration. The impact of different carrier concentrations on root length, stem length, fresh weight, and germination rate of pakchoi and tomato were assessed. Promisingly, the carrier exhibited a growth-promoting effect on the fresh weight of both the crops. Furthermore, cytotoxicity experiments confirmed its safety for humans. In cytotoxicity assays, PCN-222 @HA showed minimal toxicity at concentrations up to 100 mg/L, with cell survival rates above 80 %. Notably, the EB@PCN-222 @HA complex demonstrated reduced cytotoxicity compared to EB alone, supporting its safety for human applications. This study presents a safe and effective approach for pest control using controlled-release pesticides with extended effective durations.

The dynamic changes of genes revealed that persistently overexpressed genes drive the evolution of cyflumetofen resistance in Tetranychus cinnabarinus.

Changes in gene expression are associated with the evolution of pesticide resistance in arthropods. In this study, transcriptome sequencing was performed in 3 different resistance levels (low, L; medium, M; and high, H) of cyflumetofen-resistant strain (YN-CyR). A total of 1 685 genes, including 97 detoxification enzyme genes, were upregulated in all 3 stages, of which 192 genes, including 11 detoxification enzyme genes, showed a continuous increase in expression level with resistance development (L to H). RNA interference experiments showed that overexpression of 7 genes (CYP392A1, TcGSTd05, CCE06, CYP389A1, TcGSTz01, CCE59, and CYP389C2) is involved in the development of cyflumetofen resistance in Tetranychus cinnabarinus. The recombinant CYP392A1 can effectively metabolize cyflumetofen, while CCE06 can bind and sequester cyflumetofen in vitro. We compared 2 methods for rapid screening of resistance molecular markers, including short-term induction and 1-time high-dose selection. Two detoxification enzyme genes were upregulated in the field susceptible strain (YN-S) by induction with 20% lethal concentration (LC20 ) of cyflumetofen. However, 16 detoxification enzyme genes were upregulated by 1-time selection with LC80 of cyflumetofen. Interestingly, the 16 genes were overexpressed in all 3 resistance stages. These results indicated that 1 685 genes that were upregulated at the L stage constituted the basis of cyflumetofen resistance, of which 192 genes in which upregulation continued to increase were the main driving force for the development of resistance. Moreover, the 1-time high-dose selection is an efficient way to rapidly obtain the resistance-related genes that can aid in the development of resistance markers and resistance management in mites.

Uridine Diphosphate Glycosyltransferases (UGTs) Involved in the Carotenoid-Based Body Color Difference between Tetranychus cinnabarinus (Red) and Tetranychus urticae (Green).

It has long been disputed whether Tetranychus cinnabarinus and Tetranychus urticae belong to the same genus, with T. cinnabarinus regarded as a red form of T. urticae. However, it is unclear why T. urticae and T. cinnabarinus have different body colors. Since carotenoids are responsible for the color of many organisms, the carotenoid profiles of T. cinnabarinus and T. urticae were compared by HPLC. There was no difference in carotenoid type, but T. cinnabarinus contained significantly more neoxanthin, astaxanthin, α-carotene, ß-carotene, and γ-carotene, which may contribute to the deep red color. The transcriptome sequencing of both species identified 4079 differentially expressed genes (DEGs), of which 12 were related to carotenoid metabolism. RNA interference (RNAi) experiments demonstrated that silencing seven of these DEGs resulted in the different accumulation of carotenoid compounds in T. cinnabarinus and T. urticae. In addition, the body of T. urticae turned yellow after two days of feeding with UGT double-stranded RNAs and ß-UGT small interfering RNAs. In conclusion, differences in the carotenoid profiles of T. urticae and T. cinnabarinus may be responsible for the different body colors.

Molecular Basis for the Selectivity of the Succinate Dehydrogenase Inhibitor Cyflumetofen between Pest and Predatory Mites.

Acaricides that act as inhibitors of the mitochondrial succinate dehydrogenase (SDHIs) provide excellent control of phytophagous mites but display limited toxicity to predatory mites and other beneficial organisms. However, the molecular mechanism of selectivity is not fully understood. Here, we first confirm that SDHI acaricides are over 10,000-fold more toxic to spider mites than predatory mites. Next, we show that differential penetration, pro-acaricide activation, or metabolism are most likely not the main reason for this selectivity. In contrast, the inhibition of AB-1 on the SDH target is approximately 200-fold more potent in spider mites compared to predatory mites, revealing strong target-site selectivity. Strikingly, a key motif associated with differential binding was identified and validated by gene editing in Drosophila. Our findings contribute to understanding the selectivity of SDHIs, which can be used for the rational design of selective acaricides in support of an integrated pest management.

Circular RNA, circ1-3p, is Involved in Cyflumetofen Resistance by Acting as a Competitive RNA against miR-1-3p in Tetranychus cinnabarinus.

As a newly recognized type of noncoding RNA, circular RNA can mediate a variety of physiological changes in mammals by regulating the post-transcriptional expression level of genes. However, the function of circRNA in the evolution of pesticide resistance in arthropods is still unknown. In this study, 2546 circRNAs were identified in Tetranychus cinnabarinus by transcriptome sequencing. The differentially expressed gene analysis indicated that 44 circRNAs were overexpressed in a cyflumetofen-resistant strain, of which a circRNA (named circ1-3p) was found to contain the response elements of miR-1-3p, an miRNA that is involved in cyflumetofen resistance by targeting TcGSTm04. The circular structure of circ1-3p was further determined using a divergent primer. The results of different molecular assays in vitro and in vivo showed that circ1-3p can compete with TcGSTm04 in miR-1-3p binding. The colocalization of circ1-3p and miR-1-3p was found using fluorescence in situ hybridization, suggesting that circ1-3p can directly sponge miR-1-3p in T. cinnabarinus. In addition, silencing the expression of circ1-3p resulted in the upregulation of miR-1-3p and the downregulation of TcGSTm04 as well as a significant increase in the sensitivity of T. cinnabarinus to cyflumetofen. All these pieces of evidence indicates that overexpressed circ1-3p promotes the expression of TcGSTm04 through sponging miR-1-3p, thereby involving in the evolution of cyflumetofen resistance in T. cinnabarinus.

Transcription factors CncC and Maf connect the molecular network between pesticide resistance and resurgence of pest mites.

Pesticide resistance and resurgence are serious problems often occurring simultaneously in the field. In our long-term study of a fenpropathrin-resistant strain of Tetranychus cinnabaribus, enhancement of detoxification and modified fecundity mechanisms were both observed. Here we investigate the network across these two mechanisms and find a key node between resistance and resurgence. We show that the ecdysone pathway is involved in regulating the fecundity of T. cinnabaribus. The concentration change of ecdysone is consistent with the fecundity curve; the concentration of ecdysone is higher in the fenpropathrin-resistant strain which has stronger fecundity. The enhancement of ecdysone is due to overexpression of two P450 genes (CYP314A1 and CYP315A1) in the ecdysone synthesis pathway. Silencing expression of these CYP genes resulted in lower concentration of ecdysone, reduced expression of vitellogenin, and reduced fecundity of T. cinnabaribus. The expression of CYP315A1 is regulated by transcription factors Cap-n-collar isoform C (CncC) and Musculoaponeurotic fibrosarcoma protein (Maf), which are involved in regulating other P450 genes functioning in detoxification of fenpropathrin in T. cinnabaribus. A similar regulation is established in citrus pest mite Panonychus citri showing that the CncC pathway regulates expression of PcCYP315A1, which affects mite fecundity. Transcription factors are activated to upregulate detoxification genes facilitating pesticide resistance, while the "one to multiple" regulation mode of transcription factors simultaneously increases expression of metabolic enzyme genes in hormone pathways and alters the physiology of pests. This is an important response of arthropods to pesticides which leads to resistance and population resurgence.

Selenium mediated host plant-mite conflict: defense and adaptation.

BACKGROUND: Selenium has shown effectiveness in protecting plants from herbivores. However, some insects have evolved adaptability to selenium. RESULTS: Selenium accumulation in host plants protected them against spider mite feeding. Selenium showed toxic effects on spider mites by reducing growth and interfering with reproduction. After 40 generations on selenium-rich plants, a Tetranychus cinnabarinus strain (Tc-Se) developed adaptability to selenium, with an increased rate of population growth and enhanced ability for selenium metabolism. The high expression of two genes (GSTd07 and SPS1) in the selenium metabolism pathway might be involved in selenium metabolism in spider mites. After GSTd07 and SPS1 were silenced, the selenium adaptability decreased. Recombinant GSTd07 protein promoted the reaction between sodium selenite and glutathione (GSH) and increased the production of sodium selenite metabolites. The results indicated that GSTd07 was involved in the first step of selenium metabolism. CONCLUSION: Plants can resist spider mite feeding by accumulating selenium. Spider mites subjected to long-term selenium exposure can adapt to selenium by increasing the expression of key genes involved in selenium metabolism. These results elucidate the mechanism of the interaction between mites and host plants mediated by selenium. This study of the interaction between selenium-mediated host plants and spider mites may lead to the development of new and less toxic methods for the prevention and control of spider mites. © 2021 Society of Chemical Industry.

Successful Treatment of Spontaneous Cerebrospinal Fluid Rhinorrhea With Endoscopic Third Ventriculostomy and Lumboperitoneal Shunt: A Case Report.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea represents an important clinical entity that is being observed with increasing prevalence, ranging from 14 to 55%. Spontaneous CSF rhinorrhea is associated with elevated intracranial pressure (ICP), which is rarely stopped without surgical intervention. Endoscopic endonasal repair is typically warranted for CSF rhinorrhea. However, the recurrence rate of CSF leaks after the endoscopic endonasal repair of skull base defects due to ICP is usually high. We describe a 25-year-old man without a history of head injury, tumor, or obesity. The onset of his symptoms occurred in 1 week in the form of a persistent clear left nostril rhinorrhea. Computed tomography (CT) and magnetic resonance images (MRI) showed signs of CSF in the left sphenoidal sinus, meningocele in the left frontal sinus, empty sella, hydrocephalus, and Chiari I malformation (CIM). Cine-MRI revealed the flow of CSF was obstructed at the aqueduct and the outlet of the fourth ventricle. Endoscopic third ventriculostomy (ETV) was performed for the patient with obstructive hydrocephalus. Post-operative CSF pressure measurement demonstrated elevated ICP. The patient still had case of CSF rhinorrhea, and subsequently underwent lumboperitoneal shunt (LPS) for treatment of ICP. The patient showed a prompt resolution of CSF leak. Ten months later, the patient showed a significant improvement in terms of his herniated tonsil and cessation of CSF rhinorrhea.

lincRNA_Tc13743.2-miR-133-5p-TcGSTm02 regulation pathway mediates cyflumetofen resistance in Tetranychus cinnabarinus.

Differential expression of metabolic detoxification enzymes is an important mechanism involved in pesticide/acaricide resistance of mite pests. The competing endogenous RNA hypothesis offers a new opportunity to investigate post-transcriptional regulation of those genes. In this study, 4454 long non-coding RNAs were identified in the carmine spider mite Tetranychus cinnabarinus by transcriptome sequencing. Software-based predictions indicated that a long intergenic non-coding RNA, (lincRNA)_Tc13743.2 and a detoxification enzyme gene, TcGSTm02, both contained a microRNA (miR-133-5p) response element. Over-expression of lincRNA_Tc13743.2 and TcGSTm02 were detected in a cyflumetofen-resistant T. cinnabarinus strain (CyR), whereas down-regulation of miR-133-5p was observed in this strain. Conversely, up-regulation of miR-133-5p could inhibit TcGSTm02 expression levels, and both lincRNA_Tc13743.2 and TcGSTm02 were significantly enriched in miR-133-5p biotin-avidin pull-down assays. RNA-binding protein immunoprecipitation assay showed that lincRNA_Tc13743.2 and TcGSTm02 bound to a silencing complex containing miR-133-5p. Moreover, a luciferase reporter assay based on a human cell line revealed that over-expression of lincRNA_Tc13743.2 could significantly reduce the inhibition exerted by miR-133-5p through the TcGSTm02 3'UTR. In addition, co-localization of lincRNA_Tc13743.2 and miR-133-5p was detected using fluorescence in situ hybridization, suggesting that lincRNA_Tc13743.2 interacts directly with miR-133-5p in spider mites. More importantly, silencing the expression of lincRNA_Tc13743.2 significantly reduced the expression levels of TcGSTm02 and increased the sensitivity of spider mites to cyflumetofen. Our data show that lincRNA_Tc13743.2 up-regulates TcGSTm02 expression by competing for miR-133-5p binding, demonstrating that a lincRNA_Tc13743.2-miR-133-5p-TcGSTm02 pathway mediates cyflumetofen resistance in mites.

The cytochrome P450 CYP389C16 contributes to the cross-resistance between cyflumetofen and pyridaben in Tetranychus cinnabarinus (Boisduval).

BACKGROUND: Acaricide resistance is a serious problem in spider mites. Cyflumetofen is a new complex II inhibitor, whereas pyridaben acts at complex I and has been used for decades. Although cross-resistance between cyflumetofen and pyridaben has been observed in Tetranychus cinnabarinus, the specific mechanisms at play have not yet been investigated. RESULTS: Investigation into the cross-resistance mechanisms identified five P450s, among which CYP389C16 was evaluated as the most likely candidate conferring cross-resistance. Knockdown of CYP389C16 expression via RNA interference diminished the level of cross-resistance in the cyflumetofen-resistant strain. In addition, recombinant CYP389C16 (40 pmol) effectively metabolized 25.0 ± 0.7% of cyflumetofen, 39.7 ± 1.0% of pyridaben, and 69.3 ± 3.3% of AB-1 (active de-esterified metabolite of cyflumetofen) within 2 h. In addition, hydroxylation metabolite of AB-1 was identified by HPLC-MS/MS. CONCLUSIONS: The study reveals that overexpressed CYP389C16 is involved in the cross-resistance between cyflumetofen and pyridaben in T. cinnabarinus. © 2019 Society of Chemical Industry.

Downregulation of carboxylesterase contributes to cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval).

BACKGROUND: Increased expression or point mutations of carboxyl/cholinesterases (CCEs) have been involved in many cases of insecticide and acaricide resistance. However, it has been only rarely documented that downregulation of CCE genes is associated with resistance, although many insecticides and acaricides need hydrolytic activation in vivo. Previously, expression analysis of a laboratory-selected cyflumetofen-resistant strain of Tetranychus cinnabarinus indicated that resistance was associated with increased expression of a CCE gene of TcCCE04, but also the downregulation of two CCE genes, TcCCE12 and TcCCE23. RESULTS: Synergism experiments revealed the importance of ester hydrolysis in cyflumetofen toxicity, because treatment with S,S,S-tributylphosphorotrithioate (DEF) caused strong inhibition of cyflumetofen hydrolysis, in both the susceptible and resistant strains. Moreover, silencing expression of TcCCE12 and TcCCE23 via RNAi further decreased the susceptibility of mites to cyflumetofen significantly, suggesting that downregulated CCE genes could be involved in cyflumetofen resistance. In addition, it was shown that recombinant TcCCE12 protein could hydrolyze cyflumetofen effectively. CONCLUSION: Decreased esterase activity via downregulation of specific CCE genes most likely contributes to cyflumetofen resistance by decreased activation of cyflumetofen to its active metabolite. Mixtures of cyflumetofen and esterase-inhibition acaricides (e.g. organophosphates or carbamates) should be avoided in field applications. © 2019 Society of Chemical Industry.

White Matter Microstructure Correlates with Memory Performance in Healthy Children: A Diffusion Tensor Imaging Study.

BACKGROUND AND PURPOSE: The complex function of memory has been linked to both brain gray and white matter (WM). WM abnormalities are associated with memory impairment in pathological conditions. We investigated whether variation in WM microstructure in healthy children also correlates with memory performance. METHODS: Sixty-five 7.5 to 8.5-year-old healthy children had a brain MRI scan using diffusion tensor imaging (DTI). They were also assessed for memory performance using the Children's Memory Scale (CMS). Eight indices that evaluate verbal and visual memory (immediate and delayed) were measured. DTI parameters reflecting WM microstructure, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were calculated and correlated with memory indices. RESULTS: Tract-based spatial statistics analysis showed multiple WM tracts in which DTI parameters correlated with CMS indices. Specifically, FA (a reflection of WM integrity) and RD values (a reflection of myelination) in multiple projecting, association, and commissural WM tracts correlated with verbal delayed index (P < .05, corrected for voxel-wise multiple comparisons). Also, FA values in several WM tracts, including superior longitudinal fasciculus and posterior corona radiata, positively correlated with delayed recognition index (P < .05, corrected). Region of interest analyses showed similar correlations between FA/RD and CMS scores in WM regions involving these tracts and additionally in the cingulum, and detected additional MD-CMS correlations in several regions. CONCLUSIONS: Significant correlations between DTI parameter values and CMS indices in multiple WM tracts in healthy children indicate that neuroimaging can sensitively detect brain WM changes associated with variations of memory function, even for that in the normal range.