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LncRNAWiki Two.2: any knowledgebase of human prolonged non-coding RNAs with enhanced curation design along with database system.
A novel aptamer-modified Copper @ Gold nanoclusters (apt-Cu@Au NCs) based ratiometric fluorescent probe was developed for mercury ions (Hg2+) determination in Porphyra. The apt-Cu@Au NCs were well dispersed in solution without Hg2+ but combined together for the formation of thymidine-Hg-thymidine structure with the addition of Hg2+, which further caused the changes in their fluorescence intensities owing to fluorescence resonance energy transfer. Along with that, the changes in fluorescent colors are visible to the naked eye. Accordingly, Hg2+ were determined ranging from 0.1 to 9.0 μM by fluorescence analysis with the detection limit of 4.92 nM. Moreover, a homemade device utilizing smartphone and microfluidic chip was designed for colorimetric determination of Hg2+ ranging from 0.5 to 7.0 μM with good portability and usefulness. The proposed methods were used for Hg2+ detection in Porphyra with the recoveries of 101.83-114.00%, suggesting the considerable potential for evaluating Hg2+ levels in aquatic products.The effect of micronization of granulometrically fractionated olive pomace (OP) on the bioaccessibility of polyphenols and the antioxidant capacity was investigated during sequential in vitro static digestion. Crude OP was fractionated in a 2-mm sieve (F1 > 2 mm; F2 less then 2 mm) and then micronized (300 r min-1, 5 h) generating F1AG (17.8 μm) and F2AG (15.6 μm). Micronization increased the release of hydroxytyrosol, oleuropein, caffeic acid, and decarboxymethyl oleuropein aglycone (3,4-DHPEA-EDA) in the salivary and gastric phase, beyond luteolin in the gastric phase. Micronization also increased the intestinal bioaccessibility of hydroxytyrosol, 3,4-DHPEA-EDA, oleuropein, luteolin, and apigenin; it was more effective for F2AG than F1AG. Micronized samples increased antioxidant capacity in the gastric phase. F2AG exhibited the highest antioxidant capacity in the insoluble intestinal fraction. Thus, micronization can be further exploited to improve the nutraceutical properties of OP by increasing the bioaccessibility and antioxidant capacity of phenolic compounds.FGF21 (Fibroblast Growth Factor 21), which is expressed in the liver, adipose tissue, and pancreas, has been widely known as a therapeutic candidate for metabolic diseases. Though FGF21 is crucial to glucose, lipid, and energy homeostasis, it is not straightforward to develop a new drug with FGF21 due to its short half-life in serum. Here, we derived a novel long-acting FGF21 (LAPS-FGF21), which is chemically conjugated to the human IgG4 Fc fragment for longer half-life in serum. The recombinant human IgG4 Fc fragment and FGF21 were prepared by the refolding of inclusion body and periplasmic expression in Escherichia coli overexpression systems, respectively. The efficacy study of LAPS-FGF21 in a Diet-Induced Obesity (DIO) mouse model revealed that LAPS-FGF21 reduced body weight effectively accompanied by improved glucose tolerance in a dose-dependent manner. The administration of LAPS-FGF21 also improved the blood profiles with a significant reduction in cholesterol and triglyceride levels. Additionally, the pharmacokinetic (PK) studies of LAPS-FGF21 using normal ICR mice demonstrated that the half-life of LAPS-FGF21 was approximately 64-fold longer than FGF21. Taken together, the LAPS-FGF21 could be a feasible drug candidate with excellent bodyweight loss efficacy and longer dosing interval by half-life increase in serum.Relative Response Factors (RRFs) can be used for quantitation of one compound against another and it is widely used for Impurity analysis of pharmaceutical products; however, the application in potency assay is limited. Through an extensive study shown in this paper, it can be concluded that using the "RRF methodology" for potency assay is much more challenging compared to impurity analysis, due to the much tighter criteria required for potency analysis. The effects of instrument settings, which are rarely discussed or recognized in current HPLC analytical method development and quality release testing, are discussed. These factors impact the RRF just as much as other commonly recognized HPLC parameters. The effects of UV detector settings, i.e. Slit Width, Step Width, Band Width, and Data Collection Module, have been explored. This phenomenon has been demonstrated using three compounds to observe the impact of their quantitation due to the significant RRF variations. Finally, principles to reduce RRF variations have been discussed, and practical considerations of RRF application to method development and method transfer are provided.Speciociliatine is a minor indole alkaloid found in kratom, a southeast Asian medicinal plant, used for centuries to increase energy, enhance mood, and mitigate pain and opioid dependence. An ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated to quantify speciociliatine in rat plasma. The quantitation range was 3-600 ng/mL. The validated method was applied to a preclinical pharmacokinetic study in male Sprague-Dawley rats after 2.5 mg/kg intravenous (I.V.) and 20 mg/kg oral (P.O.) dosing. The plasma was analyzed to obtain concentration-time profiles and results were subjected to non-compartmental analysis to determine pharmacokinetic parameters including volume of distribution (6.2 ± 2.3 L/kg I.V.), clearance (0.7 ± 0.2 L/hr/kg), and absolute oral bioavailability (20.7 %). find more Speciociliatine had higher systemic exposure and lower clearance compared to the other kratom alkaloids mitragynine and corynantheidine. The speciociliatine pharmacokinetic parameters described here will help to better understand the overall effects reported with kratom product use.Tissue-based ex-vivo studies on the oromucosal permeability of drugs are often insufficiently adapted to physiological and clinical conditions, which limits their predictivity. Moreover, the scientific community demands for the standardization of ex-vivo studies, since conceptual limitations (e.g. low sensitivity of analytical methods, insufficient monitoring, different designs) restrict the wide implementation in preclinical drug development. Therefore, an innovative ex-vivo permeation process consisting of novel Kerski diffusion cell coupled to fully automated sampling and sample preparation with LC-MS/MS quantification was developed and standardized. Novel assays for routine examination of tissue integrity and viability were developed and embedded in a comprehensive analytical control system. The high level of standardization and automation reduced the differences of between-run to within-run precision to ≤ 0.27 % CV. Successful validation proved a broad calibration range of 0.93-952.38 ng/mL of the model drug cyclobenzaprine with guideline-compliant relative errors from -7.
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