Staphylococcus aureus poses a serious public health threat because of its multidrug resistance and biofilm formation ability. Hence, developing novel anti-biofilm agents and finding targets are needed to mitigate the proliferation of drug-resistant pathogens. In our previous study, we showed that the pyrancoumarin derivative 2-amino-4-(2,6-dichlorophenyl)-3-cyano-5-oxo-4H, 5H- pyrano [3,2c] chromene (LP4C) can destroy the biofilm of methicillin-resistant S. aureus (MRSA) in vitro and in vivo. Here, we further explored the possible mechanism of LP4C as a potential anti-biofilm drug. We found that LP4C inhibits the expression of enzymes involved in the de novo pyrimidine pathway and attenuates the virulence of MRSA USA300 strain without affecting the agr or luxS quorum sensing system. The molecular docking results indicated that LP4C forms interactions with the key amino acid residues of pyrR protein, which functions as the important regulator of bacterial pyrimidine synthesis. These findings reveal that pyrancoumarin derivative LP4C inhibits MRSA biofilm formation and targeting pyrimidine de novo synthesis pathway.

Objective To analyze the impact of sporadic cases of COVID-19 on the work of Transfusion Department, so as to explore the countermeasures. Methods The admission of inpatient departments, the reception of outpatient(including emergency) departments, the workload of transfusion department(including blood typing, unexpected antibody screening and cross matching), and the consumption of blood components in the Xijing Hospital between October and November in 2021, during COVID-19 outbreak, were collected. All the above data was statistically compared to the data in same period in 2018, before the COVID-19 outbreak. Results Due to the COVID-19 epidemic, there was a significant decrease in number of inpatients(280±157.1 vs 340.4±110.2), outpatient(including emergency)(8 359±3 615 vs 10 151±3 225), the workload of blood typing(272.0±132.4 vs 341.6±110.4), unexpected antibody screening(78.26±42.22 vs 98.51±43.53) and crossmatch(237.2±99 vs 475.7±155.6), as well as the consumption(U) of all blood components(457.9±50.32 vs 579.4±62.51) in the Xijing Hospital(P<0.05). In detail, the epidemic had the most direct impact on the number of inpatients and outpatients, which shrank continuously on the 2nd day after official announcement of the new COVID-1 cases. While the workload of blood typing, unexpected antibody screening and crossmatch decreased slightly, with a lag, usually on the 2nd, 3rd and 5th day after official announcement. The decrease of the usage of red blood cells and plasma began from the 7th day after the new epidemic to the 6th day after the end of the epidemic. However, the usage platelets and cryoprecipitate coagulation factors decreased from the 8th and 10th day after the new epidemic to the 2nd and 6th day after the end of the epidemic, respectively. Conclusion The daily work of Blood Transfusion Department has been seriously affected by sporadic COVID-19 epidemic. The working mode, staff structure and inventory ratio of blood components should be adjusted and optimized instantly to maintain the normal conduct of medical treatments in hospitals and ensure the safety of patients.

目的 分析产科RhD阴性孕妇住院期间备血及用血情况,评价产科RhD阴性血液管理的安全性和有效性.方法 选取产科住院期间的24 938例孕妇作为研究对象,通过“采供血机构信息管理系统”软件,对申请以及输注红细胞的病例进行收集.结果 24 938例产科住院备血者中RhD阴性备血者2098例,RhD阴性孕妇备血者占产科备血者的8.41％ (2098/24 938).产科用血率4.70％(1171/24 938),RhD阴性孕妇用血率3.29％ (69/2098),平均输注红细胞3.06U(211U/69,只进不舍).阴性去甘油红细胞解冻率1.86％(39/20 98),解冻去甘油红细胞报废率逐年下降.结论 库存阴性悬浮红细胞每天各型保持2U或者0型4U即可满足产科临床的常规需求.产科RhD阴性血液管理安全、有效,保障了稀有血液的合理利用.

Staphylococcus aureus infection is difficult to eradicate because of biofilm formation and antibiotic resistance. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection necessitates the development of a new agent against bacterial biofilms. We report a new coumarin compound, termed DCH, that effectively combats MRSA in vitro and in vivo and exhibits potent antibiofilm activity without detectable resistance. Cellular proteome analysis suggests that the molecular mechanism of action of DCH involves the arginine catabolic pathway. Using molecular docking and binding affinity assays of DCH, and comparison of the properties of wild-type and ArgR-deficient MRSA strains, we demonstrate that the arginine repressor ArgR, an essential regulator of the arginine catabolic pathway, is the target of DCH. These findings indicate that DCH is a promising lead compound and validate bacterial ArgR as a potential target in the development of new drugs against MRSA biofilms.

Proadrenomedullin N-terminal 20 peptide (PAMP) is elevated in sepsis, but the function and possible mechanism of PAMP in bacterial infection is elusive. This study is aim to evaluate the role of PAMP in the interaction between the Enterohemorrhagic E. coli (EHEC) and the host barrier. Our results showed that PAMP alleviated the EHEC-induced disruption of goblet cells and mucosal damage in the intestine, increased the expression of occludin in the colon of EHEC-infected mice, and reduced the proinflammatory cytokines level in serum significantly compared with the control group. Meanwhile, lipopolysaccharide (LPS) stimulation could dose-dependently induce the expression of preproADM, the precursor of PAMP, in human intestinal epithelial cell (HIEC) and human umbilical vein endothelial cell (HUVEC). In addition, PAMP inhibited the growth of EHEC O157:H7 and destroyed the inner and outer membrane. At low concentration, PAMP attenuated the EHEC virulence genes including hlyA and eaeA, which was also confirmed from reduced hemolysis to red cells and adhesion to HIEC. These results indicated that EHEC infection would modulate the expression of PAMP in intestinal epithelium or vascular endothelium, and in turn exerted a protective effect in EHEC induced infection by rupturing the bacterial cell membrane and attenuating the bacterial virulence.

Background: The development of bacterial biofilm can cause severe chronic infections and antibiotic resistance. Therefore, it poses a significant threat to public health. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) are two major pathogens that can cause biofilm-associated infections, which leads to the urgent necessity of developing new agents with biofilm-forming inhibitory ability. Methods: A series of pyran derivatives were synthesized and characterized, and their in vitro anti-biofilm activity against S. aureus and P. aeruginosa were measured by minimal biofilm inhibitory concentration assay and FITC dye staining. The in vivo antibiofilm therapeutical effects were evaluated in S. aureus induced tissue cage infection mice model and P. aeruginosa induced urinary tract catheter infection rat model. Results: Several pyran derivatives showed the in vitro anti-biofilm activity against S. aureus and P. aeruginosa, and the activity of these compounds was not mediated through the accessory gene regulator (agr) quorum sensing system of S. aureus. One of these pyran derivatives, namely 2-amino-4-(2,6-dichlorophenyl)-3-cyano-5-oxo-4H,5H-pyrano[3,2c]chromene, exhibited significant inhibitory biofilm-formation activity in S. aureus tissue cage infection mice model and in the P. aeruginosa-infected urinary tract catheters of experimental rats. Conclusions: The data indicated that this pyran derivative is a possible lead compound that can be used for the development of novel anti-biofilm agents against S. aureus and P. aeruginosa infection. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences.