Omics Analysis of Odorant-Binding Proteins and Cuticle-Enriched SfruOBP18 Confers Multi-Insecticide Tolerance in Spodoptera frugiperda.

Spodoptera frugiperda is a notorious pest that develops a high resistance to many insecticides. Recently, insect odorant-binding proteins (OBPs) have been proven to participate in insecticide resistance. However, the functional evidence supporting the cross-link between OBPs and insecticide resistance remains unexplored. Here, we identified 50 SfruOBPs from the larval transcriptome and genome. Notably, SfruOBP18 was highly expressed in the larval cuticle and could be induced to upregulate its expression by multi-insecticides. Ligand-binding assays revealed that SfruOBP18 bound strongly with four insecticides; RNAi and insecticide bioassay demonstrated that the knockdown of SfruOBP18 did not affect larval survival and development. However, it can significantly increase the larval susceptibility to multi-insecticides, suggesting an uncommon role of SfruOBP18 in multi-insecticide susceptibility. Our study provides a comprehensive understanding of SfruOBPs and furthermore proves that a larval cuticle-enriched OBP can bind with and confer larval tolerance to multi-insecticides. SfruOBP18 could be a new insecticidal target for controlling Lepidoptera pests.

Overexpression of Two Odorant Binding Proteins Confers Chlorpyrifos Resistance in the Green Peach Aphid Myzus persicae.

The green peach aphid, Myzus persicae, is a worldwide agricultural pest. Chlorpyrifos has been widely used to control M. persicae for decades, thus leading to a high resistance to chlorpyrifos. Recent studies have found that insect odorant binding proteins (OBPs) play essential roles in insecticide resistance. However, the potential resistance mechanism underlying the cross-link between aphid OBPs and chlorpyrifos remains unclear. In this study, two OBPs (MperOBP3 and MperOBP7) were found overexpressed in M. persicae chlorpyrifos-resistant strains (CRR) compared to chlorpyrifos-sensitive strains (CSS); furthermore, chlorpyrifos can significantly induce the expression of both OBPs. An in vitro binding assay indicated that both OBPs strongly bind with chlorpyrifos; an in vivo RNAi and toxicity bioassay confirmed silencing either of the two OBPs can increase the susceptibility of aphids to chlorpyrifos, suggesting that overexpression of MperOBP3 and MperOBP7 contributes to the development of resistance of M. persicae to chlorpyrifos. Our findings provide novel insights into insect OBPs-mediated resistance mechanisms.

Therapeutic drug monitoring of free perampanel concentrations in practice: A practical analytical technique based on centrifugal ultrafiltration sample separation.

Objectives: The centrifugal ultrafiltration-high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.

Lévy Walks and Path Chaos in the Dispersal of Elongated Structures Moving across Cellular Vortical Flows.

In cellular vortical flows, namely arrays of counterrotating vortices, short but flexible filaments can show simple random walks through their stretch-coil interactions with flow stagnation points. Here, we study the dynamics of semirigid filaments long enough to broadly sample the vortical field. Using simulation, we find a surprising variety of long-time transport behavior-random walks, ballistic transport, and trapping-depending upon the filament's relative length and effective flexibility. Moreover, we find that filaments execute Lévy walks whose diffusion exponents generally decrease with increasing filament length, until transitioning to Brownian walks. Lyapunov exponents likewise increase with length. Even completely rigid filaments, whose dynamics is finite dimensional, show a surprising variety of transport states and chaos. Fast filament dispersal is related to an underlying geometry of "conveyor belts." Evidence for these various transport states is found in experiments using arrays of counterrotating rollers, immersed in a fluid and transporting a flexible ribbon.

Discovery, stereospecific characterization and peripheral modification of 1-(pyrrolidin-1-ylmethyl)-2-[(6-chloro-3-oxo-indan)-formyl]-1,2,3,4-tetrahydroisoquinolines as novel selective κ opioid receptor agonists.

A novel series of 1-(pyrrolidin-1-ylmethyl)-2-[(3-oxo-indan)-formyl]-1,2,3,4-tetrahydroisoquinoline derivatives maj-3a-maj-3u were synthesized and evaluated in vitro for their binding affinity at κ-opioid receptors. Maj-3c displayed the highest affinity for κ-opioid receptors (Ki = 0.033 nM) among all the compounds evaluated. Furthermore, all four stereoisomers of compound 3c were prepared, and (1S,18S)-3c was identified as the most potent (Ki = 0.0059 nM) κ-opioid receptor agonist among the four stereoisomers. Maj-3c produced significant antinociception (ED50 = 0.000406 mg kg(-1)) compared to U-50,488H and original BRL 52580 in the acetic acid writhing assay, but its strong sedative effect (ED50 = 0.000568 mg kg(-1)) observed in the mouse rotation test reduced its druggability. To minimize the central nervous system side effects, a series of hydroxyl-containing analogs of maj-3c were synthesized, and maj-11a was found to be a potent κ-opioid receptor agonist (Ki = 35.13 nM). More importantly, the dose for the sedative effect (ED50 = 9.29 mg kg(-1)) of maj-11a was significantly higher than its analgesic dose (ED50 = 0.392 mg kg(-1)), which made it a promising peripheral analgesic candidate compound with weak sedative side effects.

Study to determine the presence of progenitor cells in the degenerated human cartilage endplates.

INTRODUCTION: Cartilage endplate (CEP) degeneration is usually accompanied by loss of cellularity, and this loss may be a crucial key factor in initiation and development of degenerative disc disease. The study of cell types in degenerated CEP could help in understanding CEP etiopathogenesis, and may help in devising new treatments, especially if the presence of progenitor cells could be demonstrated. The aim of this study was to determine if progenitor cells existed in degenerated human CEP. MATERIALS AND METHODS: Cells isolated from CEP were cultured in a three-dimensional agarose suspension to screen for proliferative cell clusters. Cell clusters were then expanded in vitro and the populations were analyzed for colony forming unit, immunophenotype, multilineage induction, and expression of stem cell-related genes. RESULTS: The presence of progenitor cells in degenerated human CEP is indicated by the results of CFU, immunophenotype, multilineage induction, and expression of stem cell-related genes. CONCLUSIONS: We believe that this is the first study which has conclusively shown the presence of progenitor cells in degenerated CEP. The finding of this study may influence the clinical management of degenerative disc disorder.