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This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human cytochrome P450 (CYP) 3A4 (CYP3A4) and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50 mg/kg resveratrol), and group C (150 mg/kg resveratrol). After 30 min administration of resveratrol, a single dose of ticagrelor (18 mg/kg) was administered orally. The in vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated ultra high-performance liquid chromatography--tandem mass spectrometer methods. For the in vivo study, the area under the concentration-time curve and mean peak plasma concentrations of ticagrelor in group B and C appeared to be significantly higher than the control group, while volume of distribution in terminal phase and apparent clearance of ticagrelor in group B and C were significantly decreased. For the in vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The half-maximal inhibitory concentration values of resveratrol were 56.75 [micro]M, 69.07 [micro]M, and 14.22 [micro]M, respectively. Our results indicated that resveratrol had an inhibitory effect on the metabolism of ticagrelor in vitro and in vivo. Further research should focus on the clinical combination of resveratrol with ticagrelor, and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction. Key words: resveratrol, ticagrelor, cytochrome P450, drug metabolism, drug interaction, inhibition effect, pharmacokinetics. La presente etude portait sur l'effet du resveratrol sur les proprietes pharmacocinetiques du ticagrelor chez le rat, de meme que sur la biotransformation du ticagrelor dans le CYP3A4 et les microsomes hepatiques chez l'humain. Nous avons reparti aleatoirement 18 rats Sprague-Dawley dans trois groupes : groupe A (temoin), groupe B (resveratrol a 50 mg/kg) et groupe C (resveratrol a 150 mg/kg). Trente minutes apres l'administration de resveratrol, nous avons administre une dose unique de ticagrelor (18 mg/kg) par voie orale. Nous avons effectue l'experience in vitro en vue d'examiner l'influence du resveratrol sur la biotransformation du ticagrelor par le CYP3A4*1 ainsi que sur les microsomes hepatiques d'humains et de rats lorsqu'administre par voie orale. Nous avons analyse des echantillons biologiques series a l'aide de methodes validees de chromatographie liquide a ultra haute performance en tandem avec la spectrometrie de masse. Dans le cadre de l'etude in vivo, la surface sous la courbe des concentrations dans le temps et la concentration plasmatique maximale moyenne du ticagrelor semblaient etre nettement plus elevees dans les groupes B et C que chez les temoins, tandis que le volume de distribution pendant la phase terminale et la clairance apparente du ticagrelor s'abaissaient de facon marquee dans les groupes B et C. Dans le cadre de l'etude in vitro, le resveratrol presentait un effet inhibiteur sur le CYP3A4*1 ainsi que sur les microsomes hepatiques d'humains et de rats. Les valeurs des concentrations demi-inhibitrices du resveratrol etaient de 56,75 [micro]M, de 69,07 [micro]M et de 14,22 [micro]M, respectivement. Nos resultats ont montre que le resveratrol avait un effet inhibiteur sur la biotransformation du ticagrelor in vitro comme in vivo. On devrait porter plus d'attention a l'association en clinique du resveratrol avec le ticagrelor, et les concentrations plasmatiques de ticagrelor devraient etre surveillees en vue d'eviter la survenue de reactions indesirables. Mots-cles: resveratrol, ticagrelor, ccytochrome P450, biotransformation des medicaments, interaction medicamenteuse, effet inhibiteur, pharmacocinetique., Introduction and background Ticagrelor is a reversible, direct-acting, and peroral P2Y12 receptor antagonist that is used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (Husted [...]

Summary: Soybean is a short‐day plant that typically flowers earlier when exposed to short‐day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome‐wide association studies (GWAS) using two re‐sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13‐3, which encodes a protein homologous to the pseudo‐response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13‐3 in the natural population, with haplotype H4 (qFT13‐3H4) being lost during domestication, while qFT13‐3H1 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13‐3H1 were located in high‐latitude regions. Knockout of qFT13‐3 accelerated flowering and maturity time under long‐day conditions, indicating that qFT13‐3 functions as a flowering inhibitor. Our results also showed that qFT13‐3 directly downregulates the expression of GmELF3b‐2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13‐3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13‐3 can be utilized for the breeding of high‐yield cultivars with a short maturity time suitable for high latitudes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. RESULTS: A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. CONCLUSIONS: Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.

This paper aims to present the exact closed-form solutions for the free vibration of double-beam systems composed of two parallel beams connected by an arbitrary number of discrete elastic supports. The general solutions of the mode shapes of the double-beam system are derived employing the Laplace transform method from a perspective of the entire domain of beams without enforcement of any segmentation. A unified strategy applied to various boundary conditions is proposed to determine the independent constants involved in the general solutions, as well as the frequency equation. Numerical calculations are performed to verify the present solutions by comparing the results from the previous literature and finite element simulation, and to discuss the effects of support parameters (stiffness, location, and number) on the modal characteristics of the double-beam system in detail. Outcomes show that the support location plays a pivotal role in regulating the modal characteristics of the double-beam system; for each-order mode, there are one or more potential optimal positions to maximize the effect of the elastic support. The mode veering phenomenon is detected as the support parameters change. It is highlighted that, by introducing an amplitude similarity index, the proximity degree for the mode shapes of the two beams influenced by the support parameters can be evaluated quantitatively. The present analysis is greatly helpful to the optimal design, health monitoring, and vibration control of the double-beam system. [ABSTRACT FROM AUTHOR]

Advances in plant phenotyping technologies are dramatically reducing the marginal costs of collecting multiple phenotypic measurements across several time points. Yet, most current approaches and best statistical practices implemented to link genetic and phenotypic variation in plants have been developed in an era of single‐time‐point data. Here, we used time‐series phenotypic data collected with an unmanned aircraft system for a large panel of soybean (Glycine max (L.) Merr.) varieties to identify previously uncharacterized loci. Specifically, we focused on the dissection of canopy coverage (CC) variation from this rich data set. We also inferred the speed of canopy closure, an additional dimension of CC, from the time‐series data, as it may represent an important trait for weed control. Genome‐wide association studies (GWASs) identified 35 loci exhibiting dynamic associations with CC across developmental stages. The time‐series data enabled the identification of 10 known flowering time and plant height quantitative trait loci (QTLs) detected in previous studies of adult plants and the identification of novel QTLs influencing CC. These novel QTLs were disproportionately likely to act earlier in development, which may explain why they were missed in previous single‐time‐point studies. Moreover, this time‐series data set contributed to the high accuracy of the GWASs, which we evaluated by permutation tests, as evidenced by the repeated identification of loci across multiple time points. Two novel loci showed evidence of adaptive selection during domestication, with different genotypes/haplotypes favored in different geographic regions. In summary, the time‐series data, with soybean CC as an example, improved the accuracy and statistical power to dissect the genetic basis of traits and offered a promising opportunity for crop breeding with quantitative growth curves. [ABSTRACT FROM AUTHOR]

In this paper, we are concerned with the problem of finding fixed points of nonexpansive mappings on Hadamard manifolds. To solving this kind of problem, a modified Riemannian Halpern algorithm, which is a natural generalization of a modified Halpern algorithm in Euclidean space is proposed. By giving some mild assumptions and necessary lemmas, the global convergence of the proposed algorithm is established. Finally, when the problem is solved in the framework of Hadamard manifolds, the numerical experiments show the effectiveness of the proposed algorithm, especially in computational time and number of iterations. [ABSTRACT FROM AUTHOR]