The emergence of carbapenem-resistantAcinetobacter baumanniiandPseudomonas aeruginosaraises fears of untreatable infections and poses the greatest health threats. Antimicrobial peptides (AMPs) are regarded as the most ideal solution to this menace. In this study, a set of peptides was designed based on our previously reported peptide cathelicidin-BF-15, and the lead peptide ZY4, a cyclic peptide stabilized by a disulfide bridge with high stability in vivo (the half-life is 1.8 h), showed excellent activity againstP. aeruginosaandA. baumannii, including standard and clinical multidrug-resistant (MDR) strains. ZY4 killed bacteria by permeabilizing the bacterial membrane and showed low propensity to induce resistance, exhibited biofilm inhibition and eradication activities, and also killed persister cells. Notably, administration of ZY4 decreased susceptibility to lung infection byP. aeruginosaand suppressed dissemination ofP. aeruginosaandA. baumanniito target organs in a mouse septicemia infection model. These findings identify ZY4 as an ideal candidate against MDR bacterial infections.
Graphene has an extremely high in-plane strength yet considerable out-of-plane softness. High crystalline order of graphene assemblies is desired to utilize their in-plane properties, however, challenged by the easy formation of chaotic wrinkles for the intrinsic softness. Here, we find an intercalation modulated plasticization phenomenon, present a continuous plasticization stretching method to regulate spontaneous wrinkles of graphene sheets into crystalline orders, and fabricate continuous graphene papers with a high Hermans' order of 0.93. The crystalline graphene paper exhibits superior mechanical (tensile strength of 1.1 GPa, stiffness of 62.8 GPa) and conductive properties (electrical conductivity of 1.1 × 10 5 S m −1 , thermal conductivity of 109.11 W m −1 K −1). We extend the ultrastrong graphene papers to the realistic laminated composites and achieve high strength combining with attractive conductive and electromagnetic shielding performance. The intercalation modulated plasticity is revealed as a vital state of graphene assemblies, contributing to their industrial processing as metals and plastics.
Candida albicansis a human opportunistic pathogen that causes superficial and life-threatening infections. An important reason for the failure of current antifungal drugs is related to biofilm formation, mostly associated with implanted medical devices. The present study investigated the synergistic antifungal efficacy of low-frequency and low-intensity ultrasound combined with amphotericin B (AmB)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (AmB-NPs) againstC. albicansbiofilms. AmB-NPs were prepared by a double-emulsion method and demonstrated lower toxicity than free AmB. We then established biofilms and treated them with ultrasound and AmB-NPs separately or jointlyin vitroandin vivo. The results demonstrated that the activity, biomass, and proteinase and phospholipase activities of biofilms were decreased significantly after the combination treatment of AmB-NPs with 42 kHz of ultrasound irradiation at an intensity of 0.30 W/cm2for 15 min compared with the controls, with AmB alone, or with ultrasound treatment alone (P < 0.01). The morphology of the biofilms was altered remarkably after joint treatment based on confocal laser scanning microscopy (CLSM), especially in regard to reduced thickness and loosened structure. Furthermore, the same synergistic effects were found in a subcutaneous catheter biofilm rat model. The number of CFU from the catheter exhibited a significant reduction after joint treatment with AmB-NP and ultrasound for seven continuous days, and CLSM and scanning electron microscopy (SEM) images revealed that the biofilm on the catheter surface was substantially eliminated. This method may provide a new noninvasive, safe, and effective therapy forC. albicansbiofilm infection.
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