Search

Drug repurposing is considered a promising strategy to fight antimicrobial resistance (AMR). Methotrexate (Mtx), a classical anticancer drug, could strongly inhibit bacterial dihydrofolate reductase (DHFR). However, its poor permeability into bacteria and potent human cytotoxicity make it unsuitable as an antibacterial. Herein, we reported the conjugation of Mtx with a siderophore to construct "Trojan horse" antibacterials. The most potent conjugate 8 with nanomolar minimum inhibitory concentration (MIC) values exhibited over 1.00×10 3 -fold improved activity against Gram-positive Streptococcus pneumoniae (S. pneumoniae) and Gram-negative Yersinia enterocolitica (Y. enterocolitica) compared with Mtx, while possessing 2.31×10 3 -fold reduced human cytotoxicity, resulting in 2.08×10 6 -fold improvements in the therapeutic index. This proof-of-principle study verifies that siderophore conjugation is an effective strategy for developing new antibacterials from anticancer drugs., (© 2022 Wiley-VCH GmbH.)

Objective: To investigate the prevalence of throat disease in secondary school teachers of Urumqi., Method: Use Stage-Two random sampling at 11689 teachers from 109 secondary schools in Urumqi; Draw 3 217 from 11689 teachers in 109 secondary schools to accept voice self-assessment questionnaire survey and routine examination of throat, and the one who were confirmed abnormal in routine inspection would be underway stroboscopic laryngoscopy., Result: The total illness prevalence rate of throat disease in secondary school teachers of Urumqi is 28.23%; there is no statistic difference of illness prevalence rate between male and female teachers (P > 0.05). However, results showed statistical significance of illness prevalence rate in teachers of different racial-groups with different years of teaching experience (P < 0.05). Teachers who have 5 to 15 years of teaching experience suffer a high incidence of throat diseases. Among eight racial groups involved in investigation, Kazak teachers are in the highest illness prevalence rate. The results of assessment for voice disorder index between teachers with and without throat diseases showed statistical difference in total score TVH (P < 0.05), which is shown significant in the physical and emotional areas (P < 0.05), while there is no statistical difference in function. Diseases of pharyngeal portion are mainly chronic pharyngitis and hyperplastic tonsil in tongue root; Diseases of laryngeal portion are mainly chronic laryngitis and vocal nodule for female, while mainly chronic laryngitis and vocal polypus for male., Conclusion: There is no significant difference in illness prevalence rate of throat disease for secondary school teachers in Urumqi between genders; the highest prevalence rate is in teachers who have 5 to 15 years teaching experience; among different racial groups, Kazak teachers are of the highest illness prevalence rate; the illness prevalence of throat diseases is related with voice disorder index.