Antimicrobial and Antiviral Nanofibers Halt Co-Infection Spread via Nuclease-Mimicry and Photocatalysis.

The escalating spread of drug-resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug-resistance and transmission of pathogenic microbes. Here, imidazolium-type poly(ionic liquid)/porphyrin (PIL-P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL-P-Ce) are developed. The obtained PIL-P-Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease-mimetic and photocatalytic mechanisms of the PIL-P-Ce are elucidated. Co-infection wound models in mice with methicillin-resistant S. aureus and hepatitis B virus demonstrate that PIL-P-Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease-mimetic activities. As revealed by proteomic analysis, PIL-P-Ce shows minimal phototoxicity to normal tissues. Hence, PIL-P-Ce has potential as a "green" wound dressing to curb the spread of drug-resistant bacteria and viruses in clinical settings.

LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage.

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.

ADAM17 Aggravates the Inflammatory Response by Modulating Microglia Polarization Through the TGF-ß1/Smad Pathway Following Experimental Traumatic Brain Injury.

Microglia-mediated neuroinflammatory responses play important roles in secondary neurological injury after traumatic brain injury (TBI). The TGF-ß pathway participates in the regulation of M1/M2 phenotype transformation of microglia. TGF-ß can activate the Smad pathway by binding to TGF-ßRs, which is regulated by the cleavage function of A disintegrin and metalloproteinase 17 (ADAM17). However, the role of ADAM17 and the associated signaling pathways in the pathological process after TBI remain unclear. Herein, we assessed the transformation of microglia M1/M2 phenotype polarization and the neuroinflammatory response after the inhibition of ADAM17. The formation of TGF-ßRs and TGF-ß1/TGF-ßRII complexes on microglia were detected to evaluate the effect of ADAM17 inhibition on the TGF-ß1/Smad pathway. ADAM17 was highly expressed after TBI and mainly located in the microglia. the inhibition of ADAM17 improved neurological function after TBI. The neuroprotective effect of ADAM17 inhibition was related to a shift from the M1 microglial phenotype to the M2 microglial phenotype, thus reducing TBI-induced neuroinflammation. ADAM17 inhibition increased expression of TGF-ßRs on the microglia membrane, promoted formation of TGF-ß1/TGF-ßRII complexes, and induced intranuclear translocation of Smads, which activated the TGF-ß/Smad pathway. In conclusion, our study suggested that ADAM17 inhibition regulated microglia M1/M2 phenotype polarization through the TGF-ß1/Smad pathway and influenced the neuroinflammatory response after TBI.

A dual aperture (mesoporous and macroporous) system loaded with cell-free fat extract to optimize bone regeneration microenvironment.

Injured bone regeneration requires a systemically and carefully orchestrated series of events involving inflammation, angiogenesis, and osteogenesis. Thus, we designed a multifunctional cell-supporting and drug-retarding dual-pore system: cell-free fat extract (Ceffe)-mesoporous silica nanoparticle (MSN)@poly(lactic-co-glycolic acid) (PLGA) (Ceffe-MSN@PLGA) to mimic the developmental spatial structure, the microenvironment of bone regeneration and integration during injured bone regeneration. In this system, a macroporous scaffold (pore size 200-250 µm) of PLGA is combined with mesoporous MSN (pore size 2-50 nm), aiming at realizing the slow release of Ceffe. Besides, PLGA and MSN are used to recruit the temporary support of cells that are able to degrade simultaneously with bone regeneration and provide space for bone tissue regeneration. And the Ceffe isolated from fresh human adipose tissue has a therapeutic effect in regulating the important functions of early inflammatory cell transformation, neovascularization and eventual osteogenic differentiation. Our results suggest that the mesoporous and macroporous Ceffe-MSN@PLGA system represents a promising strategy to better fit the regeneration of injured bone tissue.

Antimicrobial poly(ionic liquid)-induced bacterial nanotube formation and drug-resistance spread.

Bacterial nanotubes are tubular membranous structures bulging from the cell surface that can connect neighboring bacteria for the exchange of intercellular substances. However, little is known about the formation and function of bacterial nanotubes under the stress of antimicrobial materials. Herein, an imidazolium-type cationic poly(ionic liquid) (PIL) and corresponding PIL membranes with antimicrobial properties were synthesized. The effects of these cationic polymers on the formation of bacterial nanotubes between Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) or Vibrio fischeri (V. fischeri), followed by intraspecies and interspecies exchange of antibiotic resistance genes (ARGs) were investigated. The results showed that bacteria tend to produce more nanotubes accompanied by drug-resistance trade, which can even make the ARGs of pathogens spread to the environmental microbes of V. fischeri. Given the unique antimicrobial sustainability toward bacteria after they acquire ARGs via bacterial nanotubes, antimicrobial PILs demonstrate bright prospects in the battle against resistant bacteria.