The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8
Polymyxin is a cationic polypeptide antibiotic that can disrupt bacterial cell membrane by interacting with its lipopolysaccharide molecules and is used as a last resort drug against lethal infections by the carbapenem-resistant superbugs (like NDM-1). However, global discovery of the MCR-1 colistin resistance dramatically challenges the newly renewed interest in colistin for clinical use.The mcr-1-harboring plasmids were acquired from swine and human Escherichia coli isolated in China, from 2015 to 2016, and subjected to Illumina PacBio RSII and Hi-Seq2000 for full genome sequencing. PCR was applied to close the gap of the assembled contigs. Ori-Finder was employed to predict the replication origin (oriC) in plasmids. The phenotype of MCR-1-producing isolates was evaluated on the LBA plates with various level of colistin. Genetic deletion was used to test the requirement of the initial "ATG" codon for the MCR-1 function.Here, we report full genomes of over 10 mcr-1-harboring plasmids with diversified replication incompatibilities. A novel hybrid IncI2/IncFIB plasmid pGD17-2 was discovered and characterized from a swine isolate with colistin resistance. Intriguingly, co-occurrence of two unique mcr-1-bearing plasmids (pGD65-3, IncI2, and pGD65-5, IncX4) was detected in a single isolate GD65, which might accelerate dissemination of the mcr-1 under environmental selection pressure. Genetic analyses of these plasmids mapped mobile elements in the context of antibiotic resistance and determined two insertion sequences (ISEcp1 and ISApl1) that are responsible for the mobilization of mcr-1. Gene deletion also proved that the first ATG codon is redundant in the mcr-1 gene.Collectively, our results extend landscapes of the diversified mcr-1-bearing plasmid reservoirs.
Abstract Understanding how groundwater storage (GWS) responds to climate change is essential for water resources management and future water availability in the Tibetan Plateau (TP). However, the dominant factor controlling long‐term GWS changes remains unclear and its responses to climate change are not well understood. Here we combined multi‐source datasets including in‐situ measurements, satellite observations, global models, and reanalysis products to reveal that GWS increased at 5.59 ± 1.44 Gt/yr during 2003–2016 while showing spatial heterogeneities with increasing trends in northern TP and glacial regions and declining trends in central and southern TP. The accelerated transformation from solid water (glaciers, snow, and permafrost; −17.72 ± 1.53 Gt/yr) into liquid water provide more recharge to groundwater, dominating the total GWS increase. This study contributes to a better understanding of the hydrological cycle under climate change and provides key information for projecting water availability under different future scenarios in the TP.
Abstract Background Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis. N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro. NAC can affect several signaling pathways involving in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and inflammatory response. Therefore, NAC may not only protect against the direct injurious effects of oxidants, but also beneficially alter inflammatory events in colitis. This study was conducted to investigate whether NAC could alleviate the AA-induced colitis in a porcine model. Methods Weaned piglets were used to investigate the effects of NAC on AA-induced colitis. Severity of colitis was evaluated by colon histomorphology measurements, histopathology scores, tissue myeloperoxidase activity, as well as concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon. The protective role of NAC was assessed by measurements of antioxidant status, growth modulator, cell apoptosis, and tight junction proteins. Abundances of caspase-3 and claudin-1 proteins in colonic mucosae were determined by the Western blot method. Epidermal growth factor receptor, amphiregulin, tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4) mRNA levels in colonic mucosae were quantified using the real-time fluorescent quantitative PCR. Results Compared with the control group, AA treatment increased ( P < 0.05) the histopathology scores, intraepithelial lymphocyte (IEL) numbers and density in the colon, myeloperoxidase activity, the concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon, while reducing ( P < 0.05) goblet cell numbers and the protein/DNA ratio in the colonic mucosa. These adverse effects of AA were partially ameliorated ( P < 0.05) by dietary supplementation with NAC. In addition, NAC prevented the AA-induced increase in caspase-3 protein, while stimulating claudin-1 protein expression in the colonic mucosa. Moreover, NAC enhanced mRNA levels for epidermal growth factor and amphiregulin in the colonic mucosa. Conclusion Dietary supplementation with NAC can alleviate AA-induced colitis in a porcine model through regulating anti-oxidative responses, cell apoptosis, and EGF gene expression.
Abstract Biotin protein ligase (BPL) is widespread in the three domains of the life. The paradigm BPL is the Escherichia coli BirA protein, which also functions as a repressor for the biotin biosynthesis pathway. Here we report that Lactococcus lactis possesses two different orthologues of birA ( birA 1 _LL and birA 2 _LL ). Unlike the scenario in E. coli, L. lactis appears to be auxotrophic for biotin in that it lacks a full biotin biosynthesis pathway. In contrast, it retains two biotin transporter-encoding genes ( bioY 1 _LL and bioY 2 _LL ), suggesting the use of a scavenging strategy to obtain biotin from the environment. The in vivo function of the two L. lactis birA genes was judged by their abilities to complement the conditional lethal E. coli birA mutant. Thin-layer chromatography and mass spectroscopy assays demonstrated that these two recombinant BirA proteins catalyze the biotinylation reaction of the acceptor biotin carboxyl carrier protein (BCCP), through the expected biotinoyl-AMP intermediate. Gel shift assays were used to characterize bioY 1 _LL and BirA1 _LL . We also determined the ability to uptake 3 H-biotin by L. lactis. Taken together, our results deciphered a unique biotin scavenging pathway with redundant genes present in the probiotic bacterium L. lactis .
Aquatic submerged vegetation is widespread in rivers. The transverse distribution of flow velocity in rivers is altered because of the vegetation. Based on the vegetation coverage, the cross-section of the ecological channels can be divided into the non-vegetated area and the vegetated area. In the vegetated area, we defined two depth-averaged velocities, which included the water depth-averaged velocity, and the vegetation height-averaged velocity. In this study, we optimized the ratio of these two depth-averaged velocities, and used this velocity ratio in the Navier–Stokes equation to predict the lateral distribution of longitudinal velocity in the open channel that was partially covered by submerged vegetation. Based on the Navier–Stokes equations, the term “vegetation resistance” was introduced in the vegetated area. The equations for the transverse eddy viscosity coefficient ξ, friction coefficient f, drag force coefficient Cd, and porosity α were used for both the non-vegetated area and the vegetated area, and the range of the depth-averaged secondary flow coefficient was investigated. An analytical solution for predicting the transverse distribution of the water depth-averaged streamwise velocity was obtained in channels that were partially covered by submerged vegetation, which was experimentally verified in previous studies. Additionally, the improved ratio proposed here was compared to previous ratios from other studies. Our findings showed that the ratio in this study could perform velocity prediction more effectively in the partially covered vegetated channel, with a maximum average relative error of 4.77%. The improved ratio model reduced the number of parameters, which introduced the diameter of the vegetation, the amount of vegetation per unit area, and the flow depth. This theoretical ratio lays the foundation for analyzing the flow structure of submerged vegetation.
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