Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10⁻⁵) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.     

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.     

Temperature effects on the enhanced or deteriorated buoyancy-driven heat transfer in differentially heated enclosures filled with nanofluids

ABSTRACT

A two-phase model based on the double-diffusive approach is used to perform a numerical study of natural convection in differentially heated vertical cavities filled with water-based nanofluids, assuming that Brownian diffusion and thermophoresis are the only slip mechanisms by which the solid phase can develop a significant relative velocity with respect to the liquid phase. The system of the governing equations of continuity, momentum, and energy for the nanofluid, and continuity for the nanoparticles, is solved through a computational code, which incorporates three empirical correlations for the evaluation of the effective thermal conductivity, the effective dynamic viscosity, and the thermophoretic diffusion coefficient, all based on the literature experimental data. The pressure–velocity coupling is handled using the SIMPLE-C algorithm. Numerical simulations are executed for three different nanofluids, using the diameter and the average volume fraction of the suspended nanoparticles, as well as the cavity width, the average temperature of the nanofluid, and the temperature difference imposed across the cavity, as independent variables. It is found that the heat transfer performance of the nanofluid relative to that of the base fluid increases notably with increasing the average temperature, showing a peak at an optimal particle loading. Conversely, the other controlling parameters have moderate effects.     

Phenotypic and genotypic characterization of Oenococcus oeni strains isolated from Italian wines

A phenotypic and genotypic characterization of 84 Oenococcus oeni isolates from Italian wines of different oenological areas was carried out. Numerical analysis of fatty acid profiles grouped the isolates into two clusters at low level of similarity (63%), the minor cluster containing seven isolates besides the type and the reference strains. Forthy-eight O. oeni isolates, representative of the two clusters, showed no differences in their metabolic properties (heterolactic fermentation pattern, citrate degradation capability and formation of some secondary metabolites). Moreover, the analysis of species-specific randomly amplified polymorphic DNA and 16S-23S rDNA intergenic spacer region polymorphism as well as the sequence-specific separation of V3 region from 16S rDNA by denaturing gradient gel electrophoresis demonstrated a substantial homogeneity among the isolates. On the basis of ApaI Pulsed Field Gel Electrophoresis (PFGE) restriction patterns, the 84 isolates were grouped into five different clusters at 70% similarity, but no correlation with the phenotypic groups could be demonstrated. However, by combining phenotypic and genotypic data, the 84 O. oeni isolates grouped into eight phenotypic-genotypic combined profiles and a relationship between the origin of the isolates and their combined profile became evident, so that a sort of strain specificity can be envisaged for each wine-producing area.     

Combustion of fine aluminum and magnesium powders in water

Micron-sized metal powders carried by a nitrogen flow were fed along the axis of a cylindrical hydrogen/oxygen diffusion flame. The particles ignited and burned in the water vapor at approximately 2500 K. Experiments were performed at atmospheric pressure. The environment in which particles burned was characterized in detail using computational fluid dynamics. The computations confirmed that the metal powders burned in water while the effect of oxygen and other oxidizing species could be neglected. Combustion was characterized experimentally for micron-sized powders of both aluminum and magnesium. Particle size distributions were measured using low-angle laser light scattering. Optical emission of the burning particles was recorded using filtered photomultiplier tubes. Measured durations of individual particle emission pulses were assumed to represent their burn times; these data were classified into logarithmically spaced time bins. The distribution of the particle burn times was correlated with their size distributions assuming that larger size particles burned longer. It was observed that correlation between the burn times, t, and particle diameters, D, can be approximately described as t ∼ D^0.64 and t ∼ D^0.68 for aluminum and magnesium powders, respectively. The results were compared to previous reports and possible reasons for discrepancies between the present and earlier results were discussed.     

Experimental study of dry reforming of biogas in a tubular anode-supported solid oxide fuel cell

The performance of a tubular Ni/YSZ anode supported SOFC directly fed by an anaerobic digestion simulated biogas, with an extra addition of carbon dioxide to operate in conservative operating conditions to avoid coking on the anode support, was investigated. The fuel cell has been tested at a fixed oven temperature of 800 °C and under biogas/CO₂ mixtures with different volumetric ratios, fuel utilization (FU) and current densities. Polarization curves and performance maps were obtained to better understand the influence of the investigated operational parameters on the cell behavior. Furthermore, since the tubular geometry enables an easy separation of the anode and cathode exhaust gases, the anode off-gas has been collected and monitored through a gas-chromatograph under open circuit voltage to investigate on the catalytic behavior of a Ni-based state-of-the-art anode. For corresponding operative conditions, performances of the cell for biogas/CO₂ 1/1.5 (i.e. CH₄/CO₂ 30/70) and 1/2 (i.e. CH₄/CO₂ 24/76) were at least 2% and 4% lower than the case 1/1 (i.e. CH₄/CO₂ 20/80), respectively. The highest efficiency of 43.4% was reached at 17.5 A and FU = 70%.