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Although the potent antibacterial ability of radezolid against Staphylococcus aureus has been widely reported worldwide, its antibacterial and anti-biofilm activity against the S. aureus clinical isolates from China remains elusive. In this study, the minimum inhibitory concentration (MIC) of radezolid was determined in S. aureus clinical isolates from China using the agar dilution method, and the relationship between radezolid susceptibility and ST distribution was also investigated. The anti-biofilm activity of radezolid against S. aureus was determined by a crystal violet assay and compared with that of linezolid and contezolid. The quantitative proteomics of S. aureus treated with radezolid was analyzed, and the genetic mutations in radezolid-induced resistant S. aureus were determined by whole-genome sequencing. The dynamic changes in transcriptional expression levels of several biofilm-related genes were analyzed by quantitative RT-PCR. Our data showed that radezolid MIC ranged from ≤0.125 to 0.5 mg/L, which was almost 1/4 × MIC of linezolid against S. aureus, indicating the greater antibacterial activity of radezolid than linezolid. The S. aureus clinical isolates with radezolid MICs of 0.5 mg/L were most widely distributed in ST239 of MRSA and ST7 of MSSA. Moreover, the more robust anti-biofilm activity of radezolid with subinhibitory concentrations (1/8 × MIC and 1/16 × MIC) was demonstrated against S. aureus when compared with that of contezolid and linezolid. Genetic mutations were found in glmS, 23S rRNA, and DUF1542 domain-containing protein in radezolid-induced resistant S. aureus selected by in vitro induction of drug exposure. Quantitative proteomic analysis of S. aureus indicated that the global expression of some biofilm-related and virulence-related proteins was downregulated. Quantitative RT-PCR further confirmed that the expressions of some downregulated biofilm-related proteins, including sdrD, carA, sraP, hlgC, sasG, spa, sspP, fnbA, and oatA, were decreased after 12 h and 24 h of exposure to radezolid. Conclusively, radezolid shows robust antibacterial and anti-biofilm activity against S. aureus clinical isolates from China when compared with contezolid and linezolid.

Additional file 1: Figure S1. Changes of microglial polarization phenotypes in the peri-infarct region after MCAO reperfusion. Representative immunofluorescent staining of CD206 (a) and iNOS (b) in Iba-1+ cells on the brain sections obtained from ischemic rats at 1, 3,5,7, and 14 days after middle cerebral artery occlusion (MCAO)reperfusion or from sham-operated animals. Scale bar: 10μm.

Additional file 2.

Additional file 2: Figure S2. Unedited blots for Figure 2c, Figure 5c and Figure 6c.

Additional file 4: Table S2. The differential expressed miRNAs in the peri-infarct region at 7 days post-modeling.

Additional file 1. Additional figures and tables.

Additional file 3: Table S1. Sequences of the primers used for detecting miRNAs by qRT-PCR.

Additional file 1.

Additional file 1 : Table S1. MIC values of YycG inhibitors, ampicillin vancomycin linezolid and daptomycin against E. faecium EF16M64. Table S2. Sequence analysis of Enterococcus faecium DO YycG with other homologues. Table S3. MICs and MDR phenotypes of two thiazolidione derivatives and clinical relevant agents against 102 clinical E faecium strains. Table S4. The RLU values of the kinase activities with different concentration of H2-60 and H2-81.

Additional file 5: Table S3. Mature sequencesof the top six miRNAsincreased by rTMS treatment.

More and more companies are turning their attention to business socialization. Literary sources were analyzed in the article and it was determined that all theoretical approaches to the formation of a corporate social responsibility strategy can be combined into the following concepts: instrumental concept, political concept, integrative concept, ethical concept. In the context of the economic crisis, it is necessary to focus on combining the instrumental approach with the integrative one. It should be achieved by introducing corporate social responsibility into the activities of enterprises in a such way as to ensure improving the image of the enterprise, which will lead to an increase in financial and other performance indicators, and the opportunity of socially significant actions, contribute to the development of society while integrating the principles of corporate social responsibility into all areas of the enterprise activity.

The article is devoted to defining the concept of corporate social responsibility in modern economic conditions that are characterized, on the one hand, by increasing humanistic values in society, public consciousness, the desire for sustainable economic systems, and on the other hand, by limited resources due to the crisis caused by the global pandemic. The article analyses scientific approaches to defining the concept of corporate social responsibility. The authors propose their own definition, according to which the main purpose of introducing corporate social responsibility into the company’s strategy is to achieve the target level of key performance indicators by improving the image of the organization because of socially significant actions and effective interaction with all stakeholders. According to this, the object, subject and principles of corporate social responsibility are defined in the article. The obtained results can be the basis for the development of a modern concept of corporate social responsibility, scientific and methodological approaches for its implementation in the company’s strategy.

PhoU homologs are one of the determinant factors in the regulation of persister formation and phosphate metabolism in many bacterial species; however, the functions of PhoU homologs exhibit species-specific characteristics. The pathogenesis of Staphylococcus aureus is closely correlated with persister formation and virulence factors. The functions of two PhoU homologs, PhoU1 and PhoU2, in S. aureus are unclear yet. In this study, single- and double-deletion mutants of phoU1 and phoU2 were generated in strain USA500 2395. The ΔphoU1 or ΔphoU2 mutants displayed a change in persister formation and virulence compared to the parent strain; the persisters to vancomycin and levofloxacin were decreased at least 1,000-fold, and the number of intracellular bacteria surviving in the A549 cells for 24 h decreased to 82 or 85%. The α-hemolysin expression and activity were increased in the ΔphoU2 mutants. Transcriptome analysis revealed that 573 or 285 genes were differentially expressed by at least 2.0-fold in the ΔphoU1 or ΔphoU2 mutant vs. the wild type. Genes involved in carbon and pyruvate metabolism were up-regulated, and virulence genes and virulence regulatory genes were down-regulated, including type VII secretion system, serine protease, leukocidin, global regulator (sarA, rot), and the two-component signal transduction system (saeS). Correspondingly, the deletion of the phoU1 or phoU2 resulted in increased levels of intracellular pyruvate and ATP. Deletion of the phoU2, but not the phoU1, resulted in the up-regulation of inorganic phosphate transport genes and increased levels of intracellular inorganic polyphosphate. In conclusion, both PhoU1 and PhoU2 in S. aureus regulate virulence by the down-regulation of multiple virulence factors (type VII secretion system, serine protease, and leucocidin) and the persister generation by hyperactive carbon metabolism accompanied by increasing intracellular ATP. The results in S. aureus are different from what we have previously found in Staphylococcus epidermis, where only PhoU2 regulates biofilm and persister formation. The different functions of PhoU homologs between the two species of Staphylococcus warrant further investigation.

Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases.