New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.
Human monkeypox is a viral zoonotic smallpox-like disease caused by the monkeypox virus (MPXV) and has become the greatest public health threat in the genus Orthopoxvirus after smallpox was eradicated. The host immune response to MPXV plays an essential role in disease pathogenesis and clinical manifestations. MPXV infection leads to skin lesions with the genital area as the main feature in the current outbreak and triggers a strong immune response that results in sepsis, deep tissue abscess, severe respiratory disease, and injuries to multiple immune organs. Emerging evidence shows that the immunopathogenesis of MPXV infection is closely associated with impaired NK-cell function, lymphopenia, immune evasion, increased antibodies, increased blood monocytes and granulocytes, cytokine storm, inhibition of the host complement system, and antibody-dependent enhancement. In this overview, we discuss the immunopathology and immunopathogenesis of monkeypox to aid the development of novel immunotherapeutic strategies against monkeypox.