Yalan Zhang

Synergistic therapeutic strategies for bacterial infection have attracted extensive attentions owing to their enhanced therapeutic effects and less adverse effects compared with monotherapy. Herein, we report a novel synergistic antibacterial platform that integrates the nanocatalytic antibacterial therapy and photothermal therapy (PTT) by hemoglobin-functionalized copper ferrite nanoparticles (Hb-CFNPs). In the presence of a low concentration of hydrogen peroxide (H2O2), the excellent Fenton and Fenton-like reaction activity of Hb-CFNPs can effectively catalyze the decomposition of H2O2 to produce hydroxyl radicals (·OH), rendering an increase in the permeability of the bacterial cell membrane and the sensitivity to heat. With the assistance of NIR irradiation, hyperthermia generated by Hb-CFNPs can induce the death of the damaged bacteria. Additionally, owing to the outstanding magnetic property of Hb-CFNPs, it can improve the photothermal efficiency by about 20 times via magnetic enrichment, which facilitates to realize excellent bactericidal efficacy at a very low experimental dose (20 μg/mL). In vitro antibacterial experiment shows that this synergistic antibacterial strategy has a broad-spectrum antibacterial property against Gram-negative Escherichia coli (E. coli, 100%) and Gram-positive Staphylococcus aureus (S. aureus, 96.4%). More importantly, in vivo S. aureus-infected abscess treatment studies indicate that Hb-CFNPs can serve as an antibacterial candidate with negligible toxicity to realize synergistic treatment of bacterial infections through catalytic and photothermal effects. Accordingly, this study proposes a novel, high-efficiency, and multifunctional therapeutic system for the treatment of bacterial infection, which will open up a new avenue for the design of synergistic antibacterial systems in the future.

Loss of the RNA-binding protein fragile X mental retardation protein (FMRP) represents the most common form of inherited intellectual disability. Studies with heterologous expression systems indicate that FMRP interacts directly with Slack Na(+)-activated K(+) channels (K(Na)), producing an enhancement of channel activity. We have now used Aplysia bag cell (BC) neurons, which regulate reproductive behaviors, to examine the effects of Slack and FMRP on excitability. FMRP and Slack immunoreactivity were colocalized at the periphery of isolated BC neurons, and the two proteins could be reciprocally coimmunoprecipitated. Intracellular injection of FMRP lacking its mRNA binding domain rapidly induced a biphasic outward current, with an early transient tetrodotoxin-sensitive component followed by a slowly activating sustained component. The properties of this current matched that of the native Slack potassium current, which was identified using an siRNA approach. Addition of FMRP to inside-out patches containing native Aplysia Slack channels increased channel opening and, in current-clamp recordings, produced narrowing of action potentials. Suppression of Slack expression did not alter the ability of BC neurons to undergo a characteristic prolonged discharge in response to synaptic stimulation, but prevented recovery from a prolonged inhibitory period that normally follows the discharge. Recovery from the inhibited period was also inhibited by the protein synthesis inhibitor anisomycin. Our studies indicate that, in BC neurons, Slack channels are required for prolonged changes in neuronal excitability that require new protein synthesis, and raise the possibility that channel-FMRP interactions may link changes in neuronal firing to changes in protein translation.