These results directly demonstrate that MITF-M not only influences melanogenesis, but also determines the progression of melanosomal protein in mouse melanocytes.

Liquid biopsy is becoming a promising method for non-invasive cancer detection. In several proof-of-concept studies, long non-coding RNAs (lncRNAs) were found to be potential biomarkers for bladder cancer detection. The objective of this study was to discover a panel of cell-free, urinary lncRNAs as liquid biopsy biomarkers to non-invasively differentiate bladder cancer from chronic urocystitis. To this end, we collected urine samples from both bladder cancer patients and urocystitis patients. These samples were divided into discovery group and validation group. In the discovery group, the expression levels of 16 cell-free urinary lncRNAs were measured by qPCR to discover candidate biomarkers. The diagnostic performance of the candidate lncRNA biomarkers was then evaluated, which led to a panel of lncRNA biomarkers for bladder cancer detection. The performance of this panel of biomarkers was further evaluated in the validation group to see if these lncRNA biomarkers could discriminate the bladder cancer patients from urocystitis patients. We found that all of the 16 lncRNAs evaluated in this study demonstrated significant difference (p<0.05) of expression between bladder cancer patients and urocystitis patients. Nine lncRNAs provided decent diagnostic performance with area under the receiver operating characteristic (ROC) curve (AUC) reaching 0.70 or higher. We then selected the top four lncRNAs, namely UCA1-201, HOTAIR, HYMA1 and MALAT1, to form a panel of urinary biomarkers. Using this panel, bladder cancer patients could be discriminated from urocystitis patients, with sensitivity and specificity reaching 95.7% and 94.3%, respectively. Finally, we confirmed the applicability of the four-lncRNA panel in an independent validation study that included 60 bladder cancer patients and 60 urocystitis patients. Our study paves the way for further studies aimed at large-scale clinical tests of developing lncRNA biomarkers in urine for bladder cancer diagnostics.

BackgroundThe aim of the current experimental study was to scrutinize the neuroprotective effect of ketamine on the isoflurane (iso)-induced cognitive dysfunction in rats via phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) pathway.Materials and methodsSprague-Dawley rats were used for the current experimental study. The rats were divided into six groups and rats were treated with ketamine and memantine. For the estimation of cognitive function study, we used the Morris water test. Pro-inflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-α (TNF-α), and caspase-6; the antioxidant parameters malondialdehyde, glutathione, superoxide dismutase, catalase, and protein carbonyl; acetylcholinesterase, amyloid β, and brain-derived neurotrophic factor were estimated, respectively. The protein expression of AKT, GSK-3β, p21WAF1/CIP1, and p53 was also estimated, respectively.ResultsKetamine significantly enhanced cognitive function and showed anti-inflammatory and antioxidant effects, and exhibited the neuroprotective effect of ketamine against the isoflurane-induced cognitive impairment. Additionally, ketamine significantly (P<0.005) suppressed IL-1β, TNF-α, IL-6, caspase-6 and p21WAF1/CIP1, p53 expression and up-regulated the PI3K/AKT/GSK-3β expression in the group of iso-induced rats.ConclusionWe can conclude that ketamine prevented the cognitive impairment induced by isoflurane anesthesia through anti-apoptotic, anti-inflammatory, and antioxidant effects via the PI3K/AKT/GSK-3β pathway.

A new kind of inorganic−organic hybrid zirconium phosphonate material (NTAZP) with mesoporous structure was synthesized using nitrilotris(methylene)-triphosphonic acid (ATMP) and zirconium dichloride oxide octahydrate. The sample possesses a spherical morphology, and the spheres are composed of lobular lamellae. The lobular lamellae have the structure of a worm-like mesoporous (about 2.7 nm) framework and a high surface area (about 160.4 m 2 /g), which were characterized by SEM, TEM, N 2 sorption, XRD, TG-DTA, elemental analysis, TOC (total organic carbon), XPS, and FT-IR spectroscopy techniques. The as-prepared NTAZP was used as adsorbent for the efficient removal of heavy metal ions (e.g., Pb 2+ , Cu 2+ , and Cd 2+ ). Our results indicate that the material has good prospects for application as an adsorbent in wastewater processing.

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Ad-hoc constraints (also called generic constraints) are important for modelling Constraint Satisfaction Problems (CSPs). Many representations have been proposed to define ad-hoc constraints, such as tables, decision diagrams, binary constraint trees, automata and context-free grammars. However, prior works mainly focus on efficient Generalized Arc Consistency (GAC) propagators of ad-hoc constraints using the representations. In this paper, we ask a more fundamental question which bears on modelling constraints in a CSP as ad-hoc constraints, how the choice of constraints and operations affect tractability. Rather than ad-hoc constraints and their GAC propagators, our focus is on their expressive power in terms of succinctness (polysize) and cost of operations/queries (polytime). We use a large set of constraint families to investigate the expressive power of 14 existing ad-hoc constraints. We show a complete map of the succinctness of the ad-hoc constraints. We also present results on the tractability of applying various operations and queries on the ad-hoc constraints. Finally, we give case studies illustrating how our results can be useful for questions in the modelling of CSPs.

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Fibroblast growth factor 21 (FGF21) is known as a metabolic regulator to regulate the metabolism of glucose and lipids. However, the underlying mechanism of FGF21 on melanin synthesis remains unknown. Therefore, the current study investigates the effect of FGF21 on melanogenesis in alpaca melanocytes. We transfected the FGF21 into alpaca melanocytes, then detected the melanin contents, protein and mRNA levels of pigmentation-related genes in order to determine the melanogenesis-regulating pathway of FGF21. The results showed that FGF21 overexpression suppressed melanogenesis and decreased the expression of the major target genes termed microphthalmia-associated transcription factor (MITF) and its downstream genes, including tyrosinase (TYR) and tyrosinase-related protein 2 (TRP2). However FGF21 increased the expression of phospho-extracellular signal-regulated kinase (p-Erk1/2). In contrast, FGF21-siRNA, a small interference RNA mediating FGF21 silencing, abolished the inhibition of melanogenesis. Altogether, FGF21 may decrease melanogenesis in alpaca melanocytes via ERK activation and subsequent MITF downregulation, which is then followed by the suppression of melanogenic enzymes and melanin production.