Effects of Kiwifruit Dietary Fibers on Pasting Properties and In Vitro Starch Digestibility of Wheat Starch.

In this study, the roles of kiwifruit soluble/insoluble dietary fiber (SDF/IDF, respectively) in the pasting characteristics and in vitro digestibility of wheat starch were explored. According to RVA and rheological tests, the IDF enhanced the wheat starch viscosity, decreased the gelatinization degree of the starch granules, and exacerbated starch retrogradation. The addition of SDF in high quantities could reduce the starch gelatinization level, lower the system viscosity, and exacerbate starch retrogradation. Through determining the leached amylose content and conducing scanning electron microscopy, the IDF and SDF added in high quantities was combined with the leached amylose wrapped around the starch granules, which reduced the leached amylose content and decreased the gelatinization degree of the starch granules. The Fourier transform infrared results showed that the addition of both the IDF and SDF resulted in an enhancement in hydrogen bonding formed by the hydroxyl groups of the system. The in vitro digestion results strongly suggested that both the IDF and SDF reduced the wheat starch digestibility. The above findings are instructive for the application of both IDF and SDF in starchy functional foods.

Comparison of the effectiveness of probiotic supplementation in glucose metabolism, lipid profile, inflammation and oxidative stress in pregnant women.

Objective: The optimal probiotic supplementation in pregnant women has not been thoroughly evaluated. By employing a network meta-analysis (NMA) approach, we compared the effectiveness of different probiotic supplementation strategies for pregnant women. Methods: A comprehensive search across multiple databases was performed to identify studies comparing the efficacy of probiotic supplements with each other or the control (placebo) among pregnant women. Results: This NMA, including 32 studies, systematically evaluated 6 probiotic supplement strategies: Lactobacillus, Lacticaseibacillus rhamnosus and Bifidobacterium (LRB), Lactobacillus acidophilus and Bifidobacterium (LABB), Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum (LLB), multi-combination of four probiotics (MP1), and multi-combination of six or more probiotics (MP2). Among these strategies, LLB, MP1, and MP2 all contain LABB. The NMA findings showed that MP1 was the most effective in reducing fasting blood sugar (FBS) (surface under the cumulative ranking curve [SUCRA]: 80.5%). In addition, MP2 was the most efficacious in lowering the homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA: 89.1%). LABB was ranked as the most effective in decreasing low-density lipoprotein cholesterol (LDLC) (SUCRA: 95.5%), total cholesterol (TC) (SUCRA: 95.5%), and high-sensitivity C-reactive protein (hs-CRP) (SUCRA: 94.8%). Moreover, LLB was ranked as the most effective in raising total antioxidant capacity (TAC) (SUCRA: 98.5%). Conclusion: Multi-combination of probiotic strains, especially those strategies containing LABB, may be more effective than a single probiotic strain in glycolipid metabolism, inflammation, and oxidative stress of pregnant women.

Blood Group Antigen A Carriers Exhibit an Extended Progression-Free Survival with no more Immune-Related Adverse Events.

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression-free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98). The association results from the SNP-derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non-antigen A carriers (HR = 0.61, 95% CI = 0.40-0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44-0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune-related adverse events (irAEs) or organ-specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy.

A magnetic resonance imaging-based decision-making tool for predicting complex anal fistulas healing in the early postoperative period.

BACKGROUND: Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period. METHODS: Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated. RESULTS: In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18-65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing. CONCLUSIONS: We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.

Mesenteric creeping fat index defined by CT enterography is associated with early postoperative recurrence in patients with Crohn's disease.

OBJECTIVES: To investigate the value of mesenteric creeping fat index (MCFI) defined by computed-tomography enterography (CTE) in patients with Crohn's Disease (CD) for predicting early postoperative recurrence. METHODS: A total of 110 patients with CD who underwent CTE and I-stage intestinal resection surgery from December 2013 to December 2018 were enrolled. Two radiologists independently assessed CTE parameters, including MCFI, with scores ranging from 1 to 8; bowel-wall thickening, with a scale of 1 to 3; mural hyperenhancement, mural stratification, submucosal fat deposition, mesenteric fibrofatty proliferation, mesenteric hypervascularity, mesenteric fat stranding, with a scale of 0 to 2; abscess/fistula, enlarged mesenteric lymph node, abdominal and pelvic effusion, with a scale of 0 to 1. Imaging findings associated with early recurrence were assessed using logistic regression analysis. RESULTS: Within one year follow-up, early postoperative recurrence occurred in 56.4 % (62/110) patients with CD. In univariate analysis, MCFI, bowel-wall thickening, mesenteric hypervascularity, mesenteric fat stranding, abscess/fistula and mesenteric lymphadenopathy were associated with early postoperative recurrence. Among all variables, MCFI (score ≥ 4) contributes the optimal AUC (0.838 [0.758-0.919]), specificity (89.6 %), positive predictive value (90.7 %), accuracy (83.6 %), and risk ratio (OR = 32.42 [10.69-98.33], p < 0.001). In multivariate analysis, only MCFI was an independent predictor of early postoperative recurrence (OR = 25.71 [7.65-86.35], p < 0.001). CONCLUSION: CTE features are useful in predicting early postoperative recurrence in patients with CD, MCFI may be a valuable tool for clinical monitoring and follow-up.

Molecular Ferroelectric Crystals with Superior Pyroelectricity, Plasticity, and Recyclability.

The pyroelectric effect is used in a wide range of applications such as infrared (IR) detection and thermal energy harvesting, which require the pyroelectric materials to simultaneously have a high pyroelectric coefficient and a low dielectric constant for high figures of merit. However, in conventional proper ferroelectrics, the positive correlation between the pyroelectric coefficient and the dielectric constant imposes an insurmountable challenge in upgrading the figures of merit. Here, we explored superior pyroelectricity in [(CH3)4N][FeCl4] (TMA-FC) and [(CH3)4N][FeCl3Br] (TMA-FCB) molecular ferroelectric plastic crystals, which could decouple this positive correlation due to the nature of improper polarization behavior. Therefore, TMA-FC and TMA-FCB derive a high pyroelectric coefficient and a low dielectric constant simultaneously, yielding record-high figures of merit around room temperature. Furthermore, the favorable plasticity enables ferroelectric crystals to attach surfaces with different shapes for device design and integration. More interestingly, the molecular ferroelectrics could be softened and reshaped at elevated temperatures without decay in pyroelectricity, making them recyclable for cost savings and e-waste reduction. Combined with the facile fabrication process, the findings of this work would open avenues for employing molecular ferroelectric plastic crystals in the manufacture of high-performance pyroelectric devices.

Nutrient condition modulates the antibiotic tolerance of Pseudomonas aeruginosa.

The variation in nutrient content across diverse environments has a significant impact on the survival and metabolism of microorganisms. In this study, we examined the influence of nutrients on the antibiotic tolerance of the PAO1 strain of Pseudomonas aeruginosa. Our findings indicate that under nutrient-rich conditions, this strain exhibited relatively high tolerance to ceftazidime, chloramphenicol, and tetracycline, but not aminoglycosides and fluoroquinolones. Transcriptome analysis revealed that genes associated with antibiotic tolerance were expressed more efficiently in nutrient-rich media, including ribosomal protein genes and multidrug efflux pump genes, which conferred higher tetracycline tolerance to the strain. Furthermore, the genes responsible for translation, biosynthesis, and oxidative phosphorylation were suppressed when nutrients were limited, resulting in decreased metabolic activity and lower sensitivity to ciprofloxacin. Artificial interference with ATP synthesis utilizing arsenate confirmed that the curtailment of energy provision bolstered the observed tolerance to ciprofloxacin. In general, our results indicate that this strain of P. aeruginosa tends to activate its intrinsic resistance mechanisms in nutrient-rich environments, thereby enhancing resistance to certain antibiotics. Conversely, in nutrient-limited environments, the strain is more likely to enter a dormant state, which enables it to tolerate antibiotics to which it would otherwise be sensitive. These findings further suggest that antibiotics released in environments with varying eutrophication levels may have divergent effects on the development of bacterial antibiotic resistance.

Geraniol attenuates virulence factors by inhibiting quorum sensing of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that can cause severe respiratory tract infections. Geraniol, a chemical component of essential oils, has antimicrobial and anti-inflammatory activities, along with low toxicity. However, the effect and mechanism of geraniol against P. aeruginosa virulence factors are rarely studied. In this study, we investigated the quorum sensing (QS) inhibitory effects and mechanisms of geraniol against P. aeruginosa PAO1, using physiological and biochemical techniques, quantitative reverse transcription polymerase chain reaction, and transcriptomics. Geraniol slightly affected P. aeruginosa PAO1 growth, prolonged the lag phase, and delayed growth periods in a concentration-dependent manner. Geraniol inhibited three QS systems of P. aeruginosa, las, rhl, and pqs by suppressing the expression level of their key genes, including the three signal synthetase encoding genes of lasI, rhlI, and pqsABCDEH, and the corresponding signal receptor encoding genes of lasR, rhlR, and pqsR. Geraniol also suppressed certain virulence genes regulated by these three QS systems, including rhlABC, lasAB, lecAB, phzABMS, and pelABG, resulting in the attenuation of the related virulence factors, rhamnolipids, exoprotease LasA, elastase, lectin, pyocyanin, and biofilm. In conclusion, geraniol can suppress the virulence factors of P. aeruginosa PAO1 by inhibiting the three QS systems of las, rhl, and pqs. This study is significant for improving the treatment of bacterial infections caused by P. aeruginosa.

Multidimensional evaluation of teaching strategies for pharmacology based on a comprehensive analysis involving 21,269 students.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education. Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined. Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students' theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%). Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

Epigallocatechin-3-gallate alleviates type 2 diabetes mellitus via ß-cell function improvement and insulin resistance reduction.

Objectives: Epigallocatechin-3-gallate (EGCG) has a good therapeutic effect on type 2 diabetes mellitus (T2DM). This work was designed to explore EGCG's effectiveness in insulin resistance (IR) and pancreas islet ß-cell function in a rat model of T2DM. Materials and Methods: Eight-week-old male Sprague Dawley rats were randomly divided into 6 groups, including the Control (normal diet), Diabetes (high-sucrose high-fat [HSHF] diet combined with tail vein injection of streptozotocin [STZ] for T2DM induction) and Treatment Diabetic rats which were treated with metformin [500 mg/kg/d] or EGCG [25, 50 or 100 mg/kg/d] intragastric administration for 10 weeks. With the exception of control animals, the other groups were fed the HSHF diet. EGCG's effects on IR and insulin secretion were assessed by measuring body weights, and fasting blood glucose (FBG), postprandial blood glucose (PBG) and insulin levels. The morphological and molecular changes of pancreas islet ß-cells were examined by hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM) and immunofluorescence. Results: Rats fed the HSHF diet combined with STZ treatment had increased body weights and blood glucose amounts, accompanied by IR and impaired ß-cell function, induced T2DM, and EGCG dose-dependently restored the above indicators. Additionally, EGCG upregulated the pancreatic transcription factors pancreatic duodenal homeobox protein-1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). Conclusion: These results suggest that EGCG reduces blood glucose amounts, and improve IR and islet ß-cell disorder in T2DM.

Response to Comment on "Improper molecular ferroelectrics with simultaneous ultrahigh pyroelectricity and figures of merit".

Szafranski and Katrusiak stated that [Hdabco]ClO4 and [Hdabco]BF4 are proper ferroelectrics and exhibit much smaller pyroelectric coefficients than our results. We disagree with the arguments and provide a detailed answer highlighting misunderstandings in their interpretation.

A Biodegradable and Recyclable Piezoelectric Sensor Based on a Molecular Ferroelectric Embedded in a Bacterial Cellulose Hydrogel.

Currently, various electronic devices make our life more and more safe, healthy, and comfortable, but at the same time, they produce a large amount of nondegradable and nonrecyclable electronic waste that threatens our environment. In this work, we explore an environmentally friendly and flexible mechanical sensor that is biodegradable and recyclable. The sensor consists of a bacterial cellulose (BC) hydrogel as the matrix and imidazolium perchlorate (ImClO4) molecular ferroelectric as the functional element, the hybrid of which possesses a high sensitivity of 4 mV kPa-1 and a wide operational range from 0.2 to 31.25 kPa, outperforming those of most devices based on conventional functional biomaterials. Moreover, the BC hydrogel can be fully degraded into glucose and oligosaccharides, while ImClO4 can be recyclable and reused for the same devices, leaving no environmentally hazardous electronic waste.

Constrained least-squares algorithm for active optics correction of a primary mirror.

Active optics technology improves the performance and image quality of large telescopes. To effectively compensate for optical aberrations, the constrained least-squares (CLS) algorithm, which considers the characteristics of the resultant moment, the force budget, and the local force smoothness, is proposed to optimize the force distribution. First, the constraint of the resultant moment is used to decouple the shape control and location control. Then, through the force budget, the surface residual and force amplitude can be balanced. At last, the local smooth constraint is proposed to reduce the mirror's internal stress. Simulations were conducted on a 4 m thin mirror to compare the force distributions obtained by the least-squares, bending modes (BMs), and CLS algorithms. The results show that under equivalent residuals, the proposed algorithm is superior to the BM algorithm and performs better on local force smoothness.

Pseudomonas aeruginosa heteroresistance to levofloxacin caused by upregulated expression of essential genes for DNA replication and repair.

Pseudomonas aeruginosa (P. aeruginosa), a common cause of severe chronic infections, has developed heteroresistance to several antibiotics, thus hindering successful treatment. In this study, we aimed to investigate the characteristics and mechanisms underlying levofloxacin (LVX) heteroresistance in P. aeruginosa PAS71 and PAS81 clinical isolates using a combination of physiological and biochemical methods, bacterial genomics, transcriptomics, and qRT-PCR. The six P. aeruginosa strains, namely PAS71, PAS72, PAS81, PAS82, ATCC27853, and PAO1, were studied. The Kirby-Bauer (K-B), minimum inhibitory concentration (MIC) test, and population analysis profile (PAP) experimental results showed that PAS71, PAS81, ATCC27853, and PAO1 were heteroresistant to LVX, with MIC of 0.25, 1, 0.5, and 2 µg/ml, respectively; PAS72 and PAS82 were susceptible to LVX with a MIC of 0.25 and 0.5 µg/ml, respectively. The resistance of PAS71 and PAS81 heteroresistant subpopulations was unstable and had a growth fitness cost. Genomic and transcriptomic results proved that the unstable heteroresistance of PAS71 and PAS81 was caused by elevated expression of essential genes involved in DNA replication and repair, and homologous recombination, rather than their genomic single-nucleotide polymorphism (SNP) and insertion-deletion (InDel) mutations. Additionally, PAS71 and PAS81 enhanced virulence and physiological metabolism, including bacterial secretion systems and biosynthesis of siderophore group nonribosomal peptides, in response to LVX stress. Our results suggest that the upregulation of key genes involved in DNA replication and repair, and homologous recombination causes unstable heteroresistance in P. aeruginosa against LVX. This finding provides novel insights into the occurrence and molecular regulation pathway of P. aeruginosa heteroresistant strains.

Activation of the ROS/CncC and 20-Hydroxyecdysone Signaling Pathways Is Associated with Xanthotoxin-Induced Tolerance to λ-Cyhalothrin in Spodoptera litura.

Adaptation to phytochemicals in herbivorous insects can influence tolerance to insecticides. However, it is unclear how insects use phytochemicals as cues to activate their metabolic detoxification systems. In this study, we found that dietary exposure to xanthotoxin enhanced tolerance of Spodoptera litura larvae to λ-cyhalothrin. Xanthotoxin ingestion significantly elevated the mRNA levels of 35 detoxification genes as well as the transcription factors Cap 'n' collar isoform-C (CncC) and its binding factor small muscle aponeurosis fibromatosis isoform-K (MafK). Additionally, xanthotoxin exposure increased the levels of reactive oxygen species (ROS), while ROS inhibitor N-acetylcysteine (NAC) treatment blocked xanthotoxin-induced expression of CncC, MafK, and detoxification genes and also prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. The 20-hydroxyecdysone (20E) signaling pathway was effectively activated by xanthotoxin, while blocking of 20E signaling transduction prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. Application of 20E induced the expression of multiple xanthotoxin-induced detoxification genes and enhanced λ-cyhalothrin tolerance in S. litura. NAC treatment blocked xanthotoxin-induced 20E synthesis, while the CncC agonist curcumin activated the 20E signaling pathway. These results indicate that the ROS/CncC pathway controls the induction of metabolic detoxification upon exposure to xanthotoxin, at least in part, through its regulation of the 20E signaling pathway.

Molecular Ferroelectric-Based Flexible Sensors Exhibiting Supersensitivity and Multimodal Capability for Detection.

Although excellent dielectric, piezoelectric, and pyroelectric properties matched with or even surpassing those of ferroelectric ceramics have been recently discovered in molecular ferroelectrics, their successful applications in devices are scarce. The fracture proneness of molecular ferroelectrics under mechanical loading precludes their applications as flexible sensors in bulk crystalline form. Here, self-powered flexible mechanical sensors prepared from the facile deposition of molecular ferroelectric [C(NH2 )3 ]ClO4 onto a porous polyurethane (PU) matrix are reported. [C(NH2 )3 ]ClO4 -PU is capable of detecting pressure of 3 Pa and strain of 1% that are hardly accessible by the state-of-the-art piezoelectric, triboelectric, and piezoresistive sensors, and presents the ability of sensing multimodal mechanical forces including compression, stretching, bending, shearing, and twisting with high cyclic stability. This scaling analysis corroborated with computational modeling provides detailed insights into the electro-mechanical coupling and establishes rules of engineering design and optimization for the hybrid sponges. Demonstrative applications of the [C(NH2 )3 ]ClO4 -PU array suggest potential uses in interactive electronics and robotic systems.

Copper niobate nanowires boosted by a N, S co-doped carbon coating for superior lithium storage.

With the development of electric vehicles, more and more attention has been paid to the kinetic performance of batteries, which is related to rapid charge/discharge and safety issues. To improve this aspect, Cu2Nb34O87 nanowires covered by nitrogen and sulfur co-doped carbon (Cu2Nb34O87/NSC nanowires) are prepared by electrospinning combined with surface coating. As-prepared Cu2Nb34O87/NSC nanowires present a high ion diffusion coefficient and electronic conductivity, showing good a kinetic performance. Specifically, they deliver a splendid capacity of 311.2 mA h g-1 at 1 C and a superior cycling stability with a capacity fading of 0.031% per cycle upon 1000 cycles. At the same time, the electrochemical and structural reversibility is fully discussed and demonstrated by ex situ XRD, ex situ SEM and ex situ XPS based on the redox couples of Cu2+/Cu+, Nb5+/Nb4+, and Nb4+/Nb3+. Contributing to peculiar physico-chemical properties, Cu2Nb34O87/NSC nanowires are expected to be a candidate material for the anode in lithium-ion batteries.

Phytochemical Flavone Confers Broad-Spectrum Tolerance to Insecticides in Spodoptera litura by Activating ROS/CncC-Mediated Xenobiotic Detoxification Pathways.

Tolerance to chemical insecticides can be driven by the necessity of herbivorous insects to defend against host plant-produced phytochemicals. However, how the phytochemicals are sensed and further transduced into a defense response associated with insecticide tolerance is poorly understood. Herein, we show that pre-exposure to flavone, a flavonoid phytochemical, effectively enhanced larval tolerance to multiple synthetic insecticides and elevated detoxification enzyme activities in Spodoptera litura. RNA-Seq analysis revealed that flavone induced a spectrum of genes spanning phase I and II detoxification enzyme families, as well as two transcription factors Cap "n" collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis (MafK). Knocking down of CncC by RNA interference suppressed flavone-induced detoxification gene expression and rendered the larvae more sensitive to the insecticides. Flavone exposure elicited a reactive oxygen species (ROS) burst, while scavenging of ROS inhibited CncC-mediated detoxification gene expression and suppressed flavone-induced detoxification enzyme activation. Metabolome analysis showed that the ingested flavone was mainly converted into three flavonoid metabolites, and only 3-hydroxyflavone was found to affect the ROS/CncC pathway-mediated metabolic detoxification. These results indicate that the ROS/CncC pathway is an important route driving detoxification gene expression responsible for insecticide tolerance after exposure to the phytochemical flavone.

Activation of the NR2E nuclear receptor HR83 leads to metabolic detoxification-mediated chlorpyrifos resistance in Nilaparvata lugens.

Increased production of detoxification enzymes appears to be the primary route for insecticide resistance in many crop pests. However, the mechanisms employed by resistant insects for overexpression of detoxification genes involved in insecticide resistance remain obscure. We report here that the NR2E nuclear receptor HR83 plays a critical role in chlorpyrifos resistance by regulating the expression of detoxification genes in the brown planthopper (BPH), Nilaparvata lugens. HR83 was highly expressed in the fat body and ovary of adult females in chlorpyrifos-resistant BPHs. Knockdown of HR83 by RNA interference showed no effect on female fecundity, whereas caused a decrease of resistance to chlorpyrifos. This treatment also led to a dramatic reduction in the expression of multiple detoxification genes, including four UDP-glycosyltransferases (UGTs), three cytochrome P450 monooxygenases (P450s) and four carboxylesterases (CarEs). Among these HR83-regulated genes, UGT-1-3, UGT-2B10, CYP6CW1, CYP4CE1, CarE and Esterase E4-1 were over-expressed both in the fat body and ovary of the resistant BPHs. Functional analyses revealed that UGT-2B10, CYP4CE1, CarE and Esterase E4-1 are essential for the resistance of BPH to chlorpyrifos. Generally, this study implicates HR83 in the metabolic detoxification-mediated chlorpyrifos resistance and suggests that the regulation of detoxification genes may be an ancestral function of the NR2E nuclear receptor subfamily.