Elevating herbivore-induced JA-Ile enhances potato resistance to the polyphagous beet armyworm but not to the oligophagous potato tuber moth.

BACKGROUND: The oligophagous potato tuber moth (PTM), Phthorimaea operculella, and the polyphagous beet armyworm (BAW), Spodoptera exigua, are two destructive pests of potato, and infestations can lead to serious reduction in potato yield. However, potato plant responses to the two herbivories are only poorly understood. Endogenous jasmonoyl-isoleucine (JA-Ile) is a signal responsible for the induction of plant anti-herbivore defenses. Elevation of JA-Ile by blocking its catabolism is considered to be an effective and sustainable approach to enhance plant resistance to insect pests. However, it is not clear whether this approach can enhance potato resistance to PTM and BAW. RESULTS: We demonstrated that the transcriptional changes induced by simulated PTM and BAW feeding overlap to a large extent, and that 81.5% of the PTM- and 90.5% of the BAW-responsive genes were commonly regulated. We also generated potato transgenic lines, irStCYP94B3s, in which the three JA-Ile hydroxylases were all simultaneously silenced. These lines exhibited enhanced resistance only to BAW, but not to PTM, although levels of JA-Ile and its downstream induced defensive chemicals, including caffeoylputrescine, dicaffeoylspermidine, lyciumoside II, and the nicotianosides I, II, and VII, were all present at higher levels in PTM-infested than in BAW-infested irStCYP94B3s lines. CONCLUSION: Our results provide support for the hypothesis that StCYP94B3 genes are able to act as potential targets for the control of polyphagous insect pests in potato, and reveal that the oligophagous PTM has evolved an effective mechanism to cope with JA-Ile-induced anti-herbivore defenses. © 2022 Society of Chemical Industry.

Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics.

The primary objective of this study was to develop and validate an efficient and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach as a means to detect tropifexor plasma concentrations in beagle dogs and to study its pharmacokinetic profile in beagle dogs. The chromatographic separation of tropifexor and oprozomib (internal standard, ISTD) on the column, with the addition of acetonitrile for rapid precipitation and protein extraction, was achieved with 0.1% formic acid aqueous solution-acetonitrile for the mobile phase. A Xevo TQ-S triple quadrupole tandem mass spectrometer, under the selective reaction monitoring (SRM) mode, for the determination of the concentrations in the positive ion mode. The mass transfer pairs of tropifexor and oprozomib (ISTD) were m/z 604.08 ⟶ 228.03 and m/z 533.18 ⟶ 199.01, respectively. The profile displayed well linearity with calibration curves for tropifexor and oprozomib (ISTD) ranging from 1.0 to 200 ng/mL. In parallel, the lower limit of quantification (LLOQ) value for tropifexor could be measured with the aid of this novel technique at 1.0 ng/mL. In addition, the scope of intraday and interday for analyte accuracy was between -4.86% and 1.16%, with a precision of <7.31%. The recoveries of the analytes were >88.13% and were free of significant matrix effects. The stability met the requirements for the quantification of plasma samples under various conditions. Finally, the pharmacokinetic profile of tropifexor in beagle dog plasma following oral administration of 0.33 mg/kg tropifexor was determined by using the method facilitated in this work.

Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study.

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from -1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The C max of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0-t) and AUC(0-∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.

Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study.

Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography-tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1-5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.

Assessment of a 3D printed simulator of a lateral ventricular puncture in interns' surgical training.

PURPOSE: In this study, a simulator for training lateral ventricular puncture (LVP) was developed using three-dimensional (3D) printing technology, and its function of improving the skills of LVP in young interns was evaluated. METHODS: A virtual 3D craniocerebral simulator of a 51-year-old female patient with hydrocephalus was reconstructed with 3D printing technology. The anatomical and practical validity were assessed by all interns on a 13-item Likert scale. The usefulness of this simulator was evaluated once a week by two neurosurgeons, based on the performance of the interns, using the objective structured assessment of technical skills (OSATS) scale. RESULTS: The Likert scale showed that all participants agreed with the overall appearance of the simulator. Also, the authenticity of the skull was the best, followed by the lateral ventricles, analog generation system of intraventricular pressure, cerebrum, and the scalp. This simulator could help the participants' learning about the anatomy of the lateral ventricle, effective training, and repeating the steps of LVP. During training, the interns' ratio of success in LVP elevated gradually. At each evaluation stage, all mean performance scores for each measure based on the OSATS scale were higher than the previous. CONCLUSIONS: The 3D printed simulator for LVP training provided both anatomical and practical validity, and enabled young doctors to master the LVP procedures and skills.

Event-Triggered Adaptive Fuzzy Tracking Control for Uncertain Nonlinear Systems Preceded by Unknown Prandtl-Ishlinskii Hysteresis.

In this article, the problem of event-triggered tracking control for a class of uncertain nonlinear systems with unknown Prandtl-Ishlinskii (PI) hysteresis is investigated. To solve this problem, two control schemes are proposed via synthesizing the techniques of the event-triggered strategy, fuzzy-logic systems (FLSs), and adaptive backstepping control. The first basic design scheme applies an effective method to keep a balance between communication constraints and system performance under the influence of actuator PI hysteresis, while the Zeno behavior can be avoided. Furthermore, the basic design scheme not only guarantees the tracking error asymptotically converges to zero but also establishes a preserved transient performance. Nevertheless, note that the inclusive sign functions of the basic design scheme will cause possible chattering phenomenon, an alternative event-triggered adaptive control approach is then proposed. Unlike the previous control scheme, the second chattering-avoidance design approach ensures asymptotic convergence of the tracking error within a prescribed boundary δ , and finally the [Formula: see text]-norm transient performance of the tracking error is constructed. Simulations verify the established theoretical results that the proposed schemes successfully overcome the communication constraints and compensate the actuator PI hysteresis, and also present different tracking performances between two control schemes for comparison.

Event-Triggered Adaptive Fuzzy Tracking Control With Guaranteed Transient Performance for MIMO Nonlinear Uncertain Systems.

This paper investigates an event-triggered adaptive tracking control problem of multi-input and multi-output (MIMO) triangular structure nonlinear systems with nonparametric uncertainties. The implementation of this paper can be roughly classified into two steps: 1) solving the existing rate-limited communication constraints and 2) guaranteeing perfect tracking control performance. By using the relative threshold event-triggered strategy, the communication resource constraint is availably resolved, while the Zeno behavior can be avoided. In addition, by constructing a series of novel Lyapunov functions, an effective adaptive fuzzy control method is developed. The proposed fuzzy control scheme contains fewer calculations by the operation of addressing the square of the norm of the fuzzy weight vector for the entire MIMO system. It is proved that all of the closed-loop signals are global bounded, and the proposed method is not only capable of guaranteeing output tracking performance but is also available to ensure preserved transient performance. Simulation studies show the effectiveness of our approach and verify our established theory.

Crowding-induced cooperativity in DNA surface hybridization.

High density DNA brush is not only used to model cellular crowding, but also has a wide application in DNA-functionalized materials. Experiments have shown complicated cooperative hybridization/melting phenomena in these systems, raising the question that how molecular crowding influences DNA hybridization. In this work, a theoretical modeling including all possible inter and intramolecular interactions, as well as molecular details for different species, is proposed. We find that molecular crowding can lead to two distinct cooperative behaviours: negatively cooperative hybridization marked by a broader transition width, and positively cooperative hybridization with a sharper transition, well reconciling the experimental findings. Moreover, a phase transition as a result of positive cooperativity is also found. Our study provides new insights in crowding and compartmentation in cell, and has the potential value in controlling surface morphologies of DNA functionalized nano-particles.