A Vaccine with Multiple Receptor-Binding Domain Subunit Mutations Induces Broad-Spectrum Immune Response against SARS-CoV-2 Variants of Concern.

With the emergence of more variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune evasion of these variants from existing vaccines, the development of broad-spectrum vaccines is urgently needed. In this study, we designed a novel SARS-CoV-2 receptor-binding domain (RBD) subunit (RBD5m) by integrating five important mutations from SARS-CoV-2 variants of concern (VOCs). The neutralization activities of antibodies induced by the RBD5m candidate vaccine are more balanced and effective for neutralizing different SARS-CoV-2 VOCs in comparison with those induced by the SARS-CoV-2 prototype strain RBD. Our results suggest that the RBD5m vaccine is a good broad-spectrum vaccine candidate able to prevent disease from several different SARS-CoV-2 VOCs.

[Distribution of Micro-plastics in the Soil Covered by Different Vegetation in Yellow River Delta Wetland].

Micro-plastics (MPs) pollution has been a hotspot in soil environment. To explore the correlation of the vegetation cover and the distribution of MPs in Yellow River Delta wetland, the characters of MPs in the soil sampled at 16 sites where reed (Phragmites communis, a low-salt dominant species) and Suaeda salsa (a high-salt dominant species) covered were investigated. The abundance of MPs here ranged to 80-4640 n·kg-1, and the particle size ranged to 13 µm-5 mm. The main components of MPs with large size were polyethylene (PE), polyethylene terephthalate (PET) and polystyrene (PS), and the content of PET ranged to 0.22-1.16 µg·kg-1. The barrier effect of reed on MPs was higher than that of Suaeda salsa. The average abundance of MPs and PET contents at the sites where reed covered were 1423 n·kg-1 and 0.62 µg·kg-1, and they mainly consisted of small particles with a size less than 50 µm. The average abundance of MPs and PET contents at the site Suaeda salsa covered were 584 n·kg-1 and 0.33 µg·kg-1, and they mainly consisted of fragments and fibers with a size ranged to 100-1000 µm. The abundance of MPs in the soil was significantly correlated with the growth statues of the vegetations (P=0.001). Therefore, the distribution of MPs in the soil in the same area covered by different vegetation might be spatial different.

Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

Characterization of PM2.5-bound phthalic acid esters (PAEs) at regional background site in northern China: Long-range transport and risk assessment.

Eleven major phthalic acid esters (PAEs) congeners were analyzed for PM2.5 samples collected at Mount Tai, a high elevation mountain site in northern China from June to August 2015. The results showed that the average concentration of PAEs in PM2.5 was 19.48ngm-3, and bis(2-Ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) were the predominant species in particle-phase, whereas diethyl phthalate (DEP) and dimethyl phthalate (DMP) were the prevailing PAEs in gas-phase. PAE concentrations decreased at the beginning of cloud/fog events, while they increased after the cloud/fog events since the liquid-phase PAEs could be absorbed by solid-phase PAEs. Potential source contribution function (PSCF) analysis and principal component analysis (PCA) revealed that the highest PSCF value of air masses were mainly sourced from southwest of Mount Tai and multiple sources contributed to PAEs. A Monte Carlo simulation was applied to estimate the incremental lifetime cancer risks (ILCR) from inhalation exposure on the basis of DEHP concentrations. The estimated values of ILCR for the general population were lower than the U.S. Environmental Protection Agency threshold, which is 10-6. However, since the local population was exposed to various local emission sources, the actual health risk is undervalued.

Analysis on the interaction domain of VirG and apyrase by pull-down assay.

VirG is outer membrane protein of Shigella and affects the spread of Shigella. Recently it has been reported that apyrase influences the location of VirG, although the underlying mechanism remains poorly understood. The site of interaction between apyrase and VirG is the focus of our research. First we constructed recombinant plasmid pHIS-phoN2 and pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) by denaturation-renaturation, the phoN2:kan mutant of Shigella flexneri 5a M90T by a modified version of the lambda red recombination protocol originally described by Datsenko and Wanner and the complemented strain M90TΔphoN2/pET24a(PhisphoN2). Second, the recombinant plasmid pHIS-phoN2 and the pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) were transformed into E. coli BL21 (DE3) and induced to express the fusion proteins. Third, the fusion proteins were purified and the interaction of VirG and apyrase was identified by pull-down. Fourth, VirG was divided and the interaction site of apyrase and VirG was determined. Finally, how apyrase affects the function of VirG was analyzed by immunofluorescence. Accordingly, the results provided the data supporting the fact that apyrase combines with the α-domain of VirG to influence the function of VirG.

Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents.

A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 µM for AChE and 0.82-11.45 µM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aß aggregation inhibitory activity at 20 µM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.

Plasma degradation of Cationic Blue dye with contact glow discharge electrolysis.

Contact glow discharge electrolysis (CGDE) of Cationic Blue SD-GTL (CB) was investigated by determining degradation rates and rate constants under different voltages, pH, temperature and initial concentrations. The results indicated that 500 V was the optimum voltage for CGDE of CB under experimental conditions. The effect of pH was not appreciable. Fe²(+) and Fe³(+) had a remarkable catalytic effect on the degradation of CB. The degradation rate was up to 99.7% after 3 minutes CGDE treatment when the concentration of Fe²(+) was 20.0 mg/L. And when the concentration of Fe³ (+) was 5.0 mg/L, the degradation rate was only 68.6% after 10 minutes CGDE treatment. The reaction mechanisms were also well illustrated by relative reactions and their rate constants. It had been demonstrated that CB underwent oxidative degradation in CGDE.

[Progress in type III secretion system].

Many Gram-negative bacteria use the type III secretion system (TTSS) to inject toxin proteins into host cells, then cause the plague disease, typhoid fever, diarrhea disease etc. Chaperone proteins is one of four components of MTSS and play an important role in helping the secretion of toxin proteins. Although these proteins had been found for almost ten years, the detailed function of chaperones is enigmatic. In this review, a brief introduction is given about the progress of classification, function of chaperones and characteristics of the interactions between chaperones and substrates.