Integrating data-dependent acquisition (DDA) and data-independent acquisition (DIA) approaches can enable highly sensitive mass spectrometry, especially for imunnopeptidomics applications. Here we report a streamlined platform for both DDA and DIA data analysis. The platform integrates deep learning-based solutions of spectral library search, database search, and de novo sequencing under a unified framework, which not only boosts the sensitivity but also accurately controls the specificity of peptide identification. Our platform identifies 5-30% more peptide precursors than other state-of-the-art systems on multiple benchmark datasets. When evaluated on immunopeptidomics datasets, we identify 1.7-4.1 and 1.4-2.2 times more peptides from DDA and DIA data, respectively, than previously reported results. We also discover six T-cell epitopes from SARS-CoV-2 immunopeptidome that might represent potential targets for COVID-19 vaccine development. The platform supports data formats from all major instruments and is implemented with the distributed high-performance computing technology, allowing analysis of tera-scale datasets of thousands of samples for clinical applications.
An innovative method of combustion–calcination of a nitrate–ethanol solution to produce magnetic Co0.5Ni0.5Fe2O4 nanoparticles was developed. The calcination temperature and the volume of ethanol were two pivotal elements that determine the properties of the Co0.5Ni0.5Fe2O4 nanoparticles in this study. When the volume of ethanol used was increased from 20 ml to 40 ml, the crystallinity of the Co0.5Ni0.5Fe2O4 nanoparticles increased; further increase of the volume of ethanol decreased the crystallinity. The smallest nanoparticle was obtained using 20 ml ethanol. As the calcination temperature increased from 400 °C to 700 °C, the saturation magnetization of the Co0.5Ni0.5Fe2O4 nanoparticles increased from 12.8 emu g−1 to 30.8 emu g−1. Co0.5Ni0.5Fe2O4 nanoparticles fabricated using 20 ml ethanol at 400 °C were used to study the removal of methyl blue (MB) by adsorption. Experimental data revealed that the adsorption was best described by pseudo-second kinetics. The adsorption isotherm applied the Temkin model, which indicated the presence of a single and multilayer associative mechanism in the adsorption of MB on the Co0.5Ni0.5Fe2O4 nanoparticles. The effect of pH and recycling on the adsorption was measured. At pH values ≥5, the adsorption was high. After eight cycles of use and recycling, the relative removal rate of MB by the Co0.5Ni0.5Fe2O4 nanoparticles was 75% of the initial adsorption value.
β-hydroxybutyrate, a ketone body metabolite, has been shown to suppress depression-like behavior in rodents. In this study, we examined its antidepressive property in acute and chronic administration modes in mice by using forced swim test and tail suspension test. Results showed that the decrease effect of β-hydroxybutyrate (300 mg/kg) on immobility time in the tail suspension test and forced swim test in stress-naive mice began to be significant at day 11. In a dose-dependent experiment, β-hydroxybutyrate treatment (11 days) showed significant antidepressant activities at the dose of 200 and 300 mg/kg. Unlike fluoxetine, β-hydroxybutyrate treatment (300 mg/kg) showed no antidepressant activities in the acute (1 hour before the test) and three times administration mode within 24 hours (1, 5, and 24 hours before the test). But in a co-administration mode, β-hydroxybutyrate (100 mg/kg) -fluoxetine (2.5 mg/kg) co-administration exhibited an obvious antidepressant activity in the tail suspension test and forced swim test. Further analysis showed that the antidepressant effects of β-hydroxybutyrate and fluoxetine were not associated with the change in mouse locomotor activity. Furthermore, both chronic β-hydroxybutyrate treatment and β-hydroxybutyrate-fluoxetine co-treatment suppressed chronic unpredictable stress-induced increase in immobility time in the tail suspension test and forced swim test as well as chronic unpredictable stress-induced decrease in mouse body weight. Taken together, these results indicate that β-hydroxybutyrate (1) needs a relatively long time to show comparable behavioral activity to that of fluoxetine in assays that are sensitive to the behavioral effects of established antidepressant compounds and (2) can augment the antidepressant action of a sub-therapeutic dose of fluoxetine.
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