ention paradigm markedly increased expression of phosphorylated PI3K, AKT and GSK-3, but reduced phosphorylated β-catenin. Moreover, the axon guidance proteins expression level was significant higher in EE group. In parallel to these findings, EE significantly enhanced recovery of lost spatial learning memory function in MCAO rats without affecting infarct size. Together, MRI findings along with histological results strongly supported that the three-phase EE paradigm benefited neurovascular reorganization and thereby improved poststroke cognitive function. Moreover, our findings suggest that this type of EE paradigm induced neurogenesis and angiogenesis, at least in part, via regulating PI3K/AKT/GSK-3/β-catenin signaling pathway and activation of the intrinsic axonal guidance molecules in animal models of ischemic stroke.Though the pathogenesis of hyperuricemia-induced renal complications is not precisely known, hyperuricemia has been recognized as an independent risk factor for renal disease. While the clinical implication of hyperuricemia in renal disease has been a contemporary topic of debate, growing body of bench and clinical evidences certainly suggest a causative role of high uric acid in renal abnormalities by implicating diverse pathologic and molecular mechanisms. Urate crystals after having deposited in the kidney could cause hyperuricemia nephropathy leading to glomerular hypertrophy and tubulointerstitial fibrosis, while high serum uric acid might predict progressive renal damage and dysfunction. Hyperuricemia could be associated with manifestation of tubular injury and macrophage infiltration as well as an increased expression of inflammatory mediators. This review sheds light on the mechanistic aspects pertaining to hyperuricemia-associated renal abnormalities. Besides, the renal detrimental actions of high uric acid possibly mediated through its potential role on oxidative stress, renal inflammation, endothelial dysfunction, glycocalyx shedding, endothelial-to-mesenchymal transition and more specifically on the renal epithelial-to-mesenchymal transition have been addressed. Moreover, this review discusses a number of potential targets such as endothelin-1, TLR4/NF-kB, PI3K/p-Akt, Wnt5a/Ror2, NLRP3 inflammasome, NADPH oxidase, ERK1/2, enhancer of zeste homolog 2, serum response factor and Smad3/TGF-β signalling pathways, among others, implicated in hyperuricemia-associated renal abnormalities. This review finally apprises a number of bench and clinical studies which supporting a notion that the pharmacologic reduction of high uric acid might have a therapeutic value in the management of renal abnormalities, with an emphasis on febuxostat and its renal pleiotropic actions.Our gut microbiota is a complex and dynamic ecosystem with a paramount role in shaping our metabolic and immunological functions. Recent research suggests that aging may negatively affect the composition, diversity, and function of our microbiota mainly due to alterations in diet and immunologic reactivity (i.e. immunosenescence), and increased incidence of certain diseases and, therefore, increased exposure to certain medication (e.g. antibiotics, proton pump inhibitors). Taletrectinib research buy In turn, this aging-related gut dysbiosis may contribute to the initiation and/or progress of other metabolic diseases, and consequently, to a decrease in healthy longevity. On the positive side, promising therapeutic interventions, such as diet supplementation with prebiotics, probiotics and synbiotics, or fecal microbiota transplantation, aimed to counteract these aging-related deleterious consequences, could improve our health, and extend our healthy lifespan. In this context, the current review aims to assess the latest progress in identifying the key elements affecting the gut microbiota of the older adults and their mechanism of action, and the effectiveness of the therapeutic interventions aimed at restoring the diversity and healthy functions of the gut microbiota in older individuals.Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on GnRH and steroidogenesis pathways is still limited. In this study, we first identified two gonadotropin receptor like genes (LGR and LGR5L) and four steroidogenesis-related genes (CYP17A, HSD17B12, HSD3B1 and HSD3B2) in the scallop Patinopecten yessoensis. By examining the expression of 11 genes in the ganglia and/or gonad as well as the concentration of progesterone, testosterone and estradiol in the gonad, we postulate that a potential GnRH signaling pathway (GnRH-GnRHR-GPB5-LGR/LGR5L) in the cerebral and pedal ganglia (CPG) and steroidogenesis pathway (CYP17A, HSD17B12 and HSD3B1) in the gonad are involved in regulating sex steroid hormones. E2/T index that indicates aromatase activity is higher in the ovary than testis and is positively correlated with the expression of FOXL2 in the gonad, implying the presence of aromatase in the scallop. In addition, we confirmed that expression of most of the downstream genes in the two pathways was significantly elevated after injection of mature py-GnRH peptide. This study would contribute to a new understanding of the molecular basis underlying reproduction regulation by GnRH in mollusks.We propose a new analytical method for determining the response threshold in electroretinogram (ERG) in which the wave shows a biphasic slow dc-potential shift. This method uses the recorded wave to the highest intensity stimuli in each wavelength tested as a template wave f(t), and it was compared with other recorded waves obtained under lower intensities g(t). Our test recordings in medaka Oryzias latipes were analogous between the template and the compared waveforms, although there were differences in amplitude and time lag (τ, peak time difference) which occurred as a result of the difference in stimulus intensity. Cross-correlation analysis was applied. Based on the obtained cross-correlation function Cfg(τ) in each comparison, τ was determined as the time lag at which the cross-correlation coefficient Rfg(τ) showed the maximum value. Determined thresholds that were based on both the experimenter’s visual inspection and this new method agreed well when the adoption condition was set to satisfy R(τ) ≥ 0.7 and τ ≤ 150 ms in scotopic or τ ≤ 120 ms in photopic conditions.