BACKGROUND: Previous studies found that C57BL/6 mouse was susceptible to atherosclerosis, while BALB/c mouse was resistant to atherosclerosis. The stenosis of the culprit vessel and the severity of myocardial infarction were correlated to the levels of OX40L expression. Whether OX40L has differential expression between C57BL/6 and BALB/c mouse was not identified.OBJECTIVE: To observe the differential expression of OX40L mRNA and protein in C57BL/6 and BALB/c mouse.METHODS: Total RNA and protein were extracted by Trizol and RIPA Buffer from heart, brain, kidney, skeletal muscle and spleen tissues of C57BL/6 and BALB/c mice. RT-PCR and Western Blot were used to detect OX40L mRNA and protein expression in heart, brain, kidney, spleen and skeletal muscle of two kinds of mice. The differential expression of OX40L mRNA and protein between C57BL/6 and BALB/c mice was observed.RESULTS AND CONCLUSION: RT-PCR results showed that the mRNA expression level of OX40L in heart of C57BL/6 mice mouse was significantly higher than BALB/c mice (P ＜ 0.05); the mRNA expression level of OX40L in spleen of BALB/c mice was significantly higher than C57BL/6 mice (P ＜ 0.05). There were no significant differences in the brain, kidney and skeletal muscle between these two strains. The results of Western Blot showed that the protein expression level of OX40L in heart, brain and kidney of C57BL/6 mice were significantly higher than BALB/c mice (P ＜ 0.05). There were no significant differences in skeletal muscle and spleen between these two strains. The OX40L mRNA transcription level in heart was higher in C57BL/6 mouse than BALB/c mouse, while the expression in spleen was lower than the latter. The OX40L protein levels in C57BL/6 mouse heart, brainand kidney were higher than BALB/c mouse. The differences of OX40L expression between the two strains of mice indicated that OX40L may promote to C57BL/6 mouse susceptible to atherosclerosis.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.