Effects of low-frequency ultrasound combined with anti-MRSA agents on the mouse model of pulmonary infection.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia with antibiotics alone poses considerable challenges. To address these challenges, low-frequency ultrasound (LFU) emerges as a promising approach. In this study, a mouse pneumonia model was established through intratracheal injection of MRSA to investigate the therapeutic efficacy of LFU in combination with antibiotics. Minimal inhibitory concentration was assessed, and the distribution of antibiotics in the lung and plasma was determined using liquid chromatography coupled with mass spectrometry. Various parameters, including the survival rate, histopathology, lung bacterial clearance, and the expressions of cytokines and inflammation-related genes, were evaluated before and after treatment. Compared with the infection group, both the antibiotic-alone groups [vancomycin (VCM), linezolid, and contezolid (CZD)] and the groups in combination with LFU demonstrated an improvement in the survival status of mice. The average colony-forming units of lung tissue in the LFU combination groups were lower compared with the antibiotic-alone groups. While no significant changes in C-reactive protein and procalcitonin in plasma and bronchoalveolar lavage fluid were observed, histopathological results revealed reduced inflammatory damage in LFU combination groups. The secretion of interleukin-6 and tumor necrosis factor-alpha was decreased by the combination treatment, particularly in the VCM + LFU group. Furthermore, the expressions of MRSA virulence factors (hla and agrA) and inflammation-related genes (Saa3, Cxcl9, and Orm1) were further reduced by the combinations of LFU and antibiotics. Additionally, LFU treatment facilitated the distribution of VCM and CZD in mouse lung tissue at 30 and 45 min, respectively, after dosage.IMPORTANCETreating pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) with antibiotics alone poses significant challenges. In this in vivo study, we present compelling evidence supporting the efficacy of low-frequency ultrasound (LFU) as a promising approach to overcome these obstacles. Our findings demonstrated that LFU enhanced the effectiveness of vancomycin, linezolid, and contezolid in an MRSA pneumonia model. The combination of LFU with anti-MRSA agents markedly improved the survival rate of mice, accelerated the clearance of pulmonary bacteria, reduced inflammatory injury, inhibited the production of MRSA endotoxin, and enhanced the distribution of antibiotics in lung tissue. The application of LFU in the treatment of pulmonary infections held substantial significance. We believe that readers of your journal will find this topic of considerable interest.

The complete mitochondrial genome of the tropical sea urchin Tripneustes gratilla (Linnaeus, 1758) with two spine colors.

The complete mitochondrial genomes of two spine-color individuals, red and white, of the tropical sea urchin species Tripneustes gratilla (Linnaeus, 1758) were sequenced on Illumina system platform. The red-spined species had a genome size of 15,774 bp, while the white-spined species had a genome size of 15,723 bp. Both genomes contained 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. The GC composition in both species was above 40%. In order to investigate the phylogenetic relationships of two different spine-color individuals, a comprehensive analysis was conducted using eight complete mitochondrial genomic sequences of the genus Tripneustes on the software MEGA X. It was observed that the two spine color types of T. gratilla species showed a high similarity of 98.91%. However, different color-spined species of T. gratilla were found in separate branches of the phylogenetic tree of the same sea urchin species.

Design, Synthesis, Antibacterial Activity, and Mechanisms of Novel Benzofuran Derivatives Containing Disulfide Moieties.

The unsatisfactory effects of conventional bactericides and antimicrobial resistance have increased the challenges in managing plant diseases caused by bacterial pests. Here, we report the successful design and synthesis of benzofuran derivatives using benzofuran as the core skeleton and splicing the disulfide moieties commonly seen in natural substances with antibacterial properties. Most of our developed benzofurans displayed remarkable antibacterial activities to frequently encountered pathogens, including Xanthomonas oryzae pv oryzae (Xoo), Xanthomonas oryzae pv oryzicola (Xoc), and Xanthomonas axonopodis pv citri (Xac). With the assistance of the three-dimensional quantitative constitutive relationship (3D-QSAR) model, the optimal compound V40 was obtained, which has better in vitro antibacterial activity with EC50 values of 0.28, 0.56, and 10.43 µg/mL against Xoo, Xoc, and Xac, respectively, than those of positive control, TC (66.41, 78.49, and 120.36 µg/mL) and allicin (8.40, 28.22, and 88.04 µg/mL). Combining the results of proteomic analysis and enzyme activity assay allows the antibacterial mechanism of V40 to be preliminarily revealed, suggesting its potential as a versatile bactericide in combating bacterial pests in the future.

Exosomal proteomics and cytokine analysis distinguish silicosis cases from controls.

Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.