Background This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. Methods This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10 11 viral particles per mL or 5 × 10 10 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov , NCT04341389 . Findings 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 10 11 viral particles n=253; 5 × 10 10 viral particles n=129) or placebo (n=126). In the 1 × 10 11 and 5 × 10 10 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 10 11 and 5 × 10 10 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (7...
Finding efficient electrocatalysts for oxygen evolution reaction (OER) that can be effectively integrated with semiconductors is significantly challenging for solar‐driven photo‐electrochemical (PEC) water splitting. Herein, amorphous cobalt–iron hydroxide (CoFeH) nanosheets are synthesized by facile electrodeposition as an efficient catalyst for both electrochemical and PEC water oxidation. As a result of the high electrochemically active surface area and the amorphous nature, the optimized amorphous CoFeH nanosheets exhibit superior OER catalytic activity in alkaline environment with a small overpotential (280 mV) to achieve significant oxygen evolution (j = 10 mA cm−2) and a low Tafel slope (28 mV dec−1). Furthermore, CoFeH nanosheets are simply integrated with BiVO4 semiconductor to construct CoFeH/BiVO4 photoanodes that exhibit a significantly enhanced photocurrent density of 2.48 mA cm−2 (at 1.23 V vs reversible hydrogen electrode (RHE)) and a much lower onset potential of 0.23 V (vs RHE) for PEC‐OER. Careful electrochemical and optical studies reveal that the improved OER kinetics and high‐quality interface at the CoFeH/BiVO4 junction, as well as the excellent optical transparency of CoFeH nanosheets, contribute to the high PEC performance. This study establishes amorphous CoFeH nanosheets as a highly competitive candidate for electrochemical and PEC water oxidation and provides general guidelines for designing efficient PEC systems.
Background: Recently, we reported that some dairy cows could produce high amounts of milk with high amounts of protein (defined as milk protein yield [MPY]) when a population was raised under the same nutritional and management condition, a potential new trait that can be used to increase high-quality milk production. It is unknown to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to MPY. Here, analysis of rumen metagenomics and metabolomics, together with serum metabolomics was performed to identify potential regulatory mechanisms of MPY at both the rumen microbiome and host levels. Results: Metagenomics analysis revealed that several Prevotella species were significantly more abundant in the rumen of high-MPY cows, contributing to improved functions related to branched-chain amino acid biosynthesis. In addition, the rumen microbiome of high-MPY cows had lower relative abundances of organisms with methanogen and methanogenesis functions, suggesting that these cows may produce less methane. Metabolomics analysis revealed that the relative concentrations of rumen microbial metabolites (mainly amino acids, carboxylic acids, and fatty acids) and the absolute concentrations of volatile fatty acids were higher in the high-MPY cows. By associating the rumen microbiome with the rumen metabolome, we found that specific microbial taxa (mainly Prevotella species) were positively correlated with ruminal microbial metabolites, including the amino acids and carbohydrates involved in glutathione, phenylalanine, starch, sucrose, and galactose metabolism. To detect the interactions between the rumen microbiome and host metabolism, we associated the rumen microbiome with the host serum metabolome and found that Prevotella species may affect the host's metabolism of amino acids (including glycine, serine, threonine, alanine, aspartate, glutamate, cysteine, and methionine). Further analysis using the linear mixed effect model estimated contributions to the variation in MPY based on different omics and revealed that the rumen microbial composition, functions, and metabolites, and the serum metabolites contributed 17.81, 21.56, 29.76, and 26.78%, respectively, to the host MPY.
Currently, knowledge on the extent to which rumen microbiota differ in a large population of cattle fed the same diet and whether such differences are associated with animal performance is limited. This study was conducted to characterize the rumen microbiota of a large cohort of lactating Holstein dairy cows (n = 334) that were fed the same diet and raised under the same environment, aiming to uncover linkages between core and pan rumen microbiomes and host phenotypes. Amplicon sequencing of the partial 16S rRNA gene identified 391 bacterial genera as the pan bacteriome and 33 genera as the core bacteriome. Inter-animal variation existed in both pan and core bacteriomes, with the effect of lactation stage being more prominent than those of parity (the number of pregnancies, ranging from 2 to 7) and sire. Spearman correlation network analysis revealed significant correlations among bacteria, rumen short chain fatty acids, and lactation performance, with the core and non-core genera accounting for 53.9 and 46.2% of the network, respectively. These suggest that the pan rumen bacteriome together with the core bacteriome potentially contributes to variations of milk production traits. Our findings provide understanding of the potential functions of non-core rumen microbes, suggesting the possibility of enhancing bacterial fermentation using strategies to manipulate core and non-core bacteriome for improved cattle performance. This study revealed rumen bacteriome from a large dairy cattle cohort (n=334) raised under the same management and showed the linkages among the rumen core and pan bacteriome, rumen short chain fatty acids, and milk production phenotypes. The findings from the current study suggest that the pan rumen bacteriome together with the core bacteriome potentially contributes to variations of host milk production traits. Fundamental knowledge on the rumen core and pan microbiome and their roles in contributing to lactation performance provides novel insights into future manipulation strategies of rumen microbiota to enhance milk production.
We report polymorphic CoSe2 (p-CoSe2) with mixed orthorhombic and cubic phases as a highly active electrocatalyst toward hydrogen evolution reaction (HER). The p-CoSe2 is obtained by calcining CoSex via electrodeposition at 300 °C. The results of X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) demonstrated the crystal structure of p-CoSe2. The p-CoSe2 exhibits excellent electrocatalytic activity for HER with a low onset overpotential of -70 mV and a small Tafel slope of ∼30 mV/decade, which are basically state-of-the-art performance of earth-abundant electrocatalysts. The HER performance of p-CoSe2 was much higher than that of amorphous CoSex, cubic CoSe2, and CoSe. This study offers a competitive electrocatalyst for HER and opens up a new strategy to the synthesis of catalysts for energy conversion.
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