The prevalence of antimicrobial-resistant pathogens significantly limited the number of effective antibiotics available clinically, which urgently requires new drug targets to screen, design, and develop novel antibacterial drugs. Two-component system (TCS), which is comprised of a histidine kinase (HK) and a response regulator (RR), is a common mechanism whereby bacteria can sense a range of stimuli and make an appropriate adaptive response. HKs as the sensor part of the bacterial TCS can regulate various processes such as growth, vitality, antibiotic resistance, and virulence, and have been considered as a promising target for antibacterial drugs. In the current review, we highlighted the structural basis and functional importance of bacterial TCS especially HKs as a target in the discovery of new antimicrobials, and summarize the latest research progress of small-molecule HK-inhibitors as potential novel antimicrobial drugs reported in the past decade.
With the continuous spread of drug-resistant tuberculosis, there is an urgent need for new antituberculosis drugs with new mechanisms. The ability of
Mtb
to resist oxidative stress is extremely important for maintaining redox homeostasis and survival in the host.
Background: Although various surgical techniques have been reported for aortic arch reconstruction for proximal and distal transverse arch (PDTA) hypoplasia, no consensus has been reached on a surgical option for initial arch reconstruction. This study was undertaken to review various arch reconstruction options for PDTA hypoplasia in Chinese infants. Methods: A retrospective review of 121 infants who underwent initial arch reconstruction of the proximal and distal aortic arches between 2010 and 2020 was performed. Freedom from recoarctation was analyzed using Kaplan-Meier analysis. Univariate and multivariable Cox regression analyses were performed to determine perioperative data associated with an increased risk of recoarctation after surgery. Results: Aortic arch reconstruction was performed by end-to-side anastomosis (ESA) (n=37) or patch repair [autologous pericardial patch (APP), n=53; bovine pericardial patch (BPP), n=20; autologous pulmonary artery patch (APAP), n=11]. The relative diameter of the proximal arch was 0.51±0.07, and the relative diameter of the distal arch was 0.43±0.07. The median follow-up time was 679 (range, 388-1,362) days. Recoarctation was observed in 44 (36.4%) patients. ESA was an independent risk factor for further development of recoarctation after the initial aortic arch reconstruction [hazard ratio (HR) =2.13; P=0.020].Conclusions: Aortic arch reconstruction via ESA was an independent risk factor for late recoarctation of the proximal and distal aortic arches in patients who underwent the initial surgery in infancy.
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