Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F5a, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including Staphylococcus aureus, a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on S. aureus biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F5a could significantly inhibit S. aureus biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate S. aureus mature biofilms with the minimum biofilm eradication concentration of 32.0 μg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in S. aureus biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F5a could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating S. aureus biofilm.
Both melanoma cells and tissues were allowed to interact with an identical pool of billions of human-safe phage nanofiber clones with each genetically displaying a unique 12-mer peptide at the tips, respectively, resulting in the discovery of bionanofibers displaying a melanoma cell/tissue dual-homing peptide for personalized targeted melanoma therapy.
Objective The pathogenesis of sepsis is still unclear due to its complexity, especially in children. This study aimed to analyse the immune microenvironment and regulatory networks related to sepsis in children at the molecular level and to identify key immune-related genes to provide a new basis for the early diagnosis of sepsis. Methods The GSE145227 and GSE26440 datasets were downloaded from the Gene Expression Omnibus. The analyses included differentially expressed genes (DEGs), functional enrichment, immune cell infiltration, the competing endogenous RNA (ceRNA) interaction network, weighted gene coexpression network analysis (WGCNA), protein–protein interaction (PPI) network, key gene screening, correlation of sepsis molecular subtypes/immune infiltration with key gene expression, the diagnostic capabilities of key genes, and networks describing the interaction of key genes with transcription factors and small-molecule compounds. Finally, real-time quantitative PCR (RT–qPCR) was performed to verify the expression of key genes. Results A total of 236 immune-related DEGs, most of which were enriched in immune-related biological functions, were found. Further analysis of immune cell infiltration showed that M0 macrophages and neutrophils infiltrated more in the sepsis group, while fewer activated memory CD4 + T cells, resting memory CD4 + T cells, and CD8 + T cells did. The interaction network of ceRNA was successfully constructed. Six key genes (FYN, FBL, ATM, WDR75, FOXO1 and ITK) were identified by WGCNA and PPI analysis. We found strong associations between key genes and constructed septic molecular subtypes or immune cell infiltration. Receiver operating characteristic analysis showed that the area under the curve values of the key genes for diagnosis were all greater than 0.84. Subsequently, we successfully constructed an interaction network of key genes and transcription factors/small-molecule compounds. Finally, the key genes in the samples were verified by RT–qPCR. Conclusion Our results offer new insights into the pathogenesis of sepsis in children and provide new potential diagnostic biomarkers for the disease.
Background: To investigate the dynamic changes in high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19) patients with different severities in different disease stages. Methods: We retrospectively collected the clinical and imaging data of 96 patients in Yunnan Province, China, who were diagnosed with COVID-19 between January 22 and March 15, 2020. Based on disease severity, the COVID-19 patients were classified into four types: mild (n=15), moderate (n=59), severe (n=19), and critical (n=3). Based on hospital stay and number of computed tomography (CT) scans, the clinical/ disease course was divided into four stages, including stage 1 (days 0-4), stage 2 (days 5-9), stage 3 (days 10-14), and stage 4 (days 15-19). The HRCT findings, CT value, and lesion volume were analyzed for each stage and compared among the four stages of COVID-19 patients. Results: CT findings were negative over the four stages for all mild COVID-19 patients. More lesions were found in the peripheral lung fields than in peripheral + central fields (P<0.05), and the number of negative patients in stage 4 were more than those in stages 1-3 (P<0.05). The left and right lower lobe were the most frequently affected lobes (P<0.05). In moderate patients, round ground glass opacities (GGOs) decreased from stage 1 to stage 4; partial consolidation peaked in stage 2 and then decreased in stages 3-4; Huang et al. Dynamic changes in chest CT of COVID-19 patients
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