Science Bulletin最新文献

Hepatic ischemia-reperfusion injury (HIRI) is an important cause of liver injury following liver transplantation and major resections, and neutrophils are the key effector cells in HIRI. Double-negative T regulatory cells (DNT) are increasingly recognized as having critical regulatory functions in the immune system. Whether DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils, as in HIRI, remains largely unknown. In this study, we found that murine and human DNT highly expressed CD39 that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73, to induce high levels of neutrophil apoptosis. Furthermore, extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling pathway. Adoptive transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent manner. Lastly, the adoptive transfer of A2ar^-/- DNT validated the importance of adenosine/A2AR signaling, in promoting DNT survival and immunomodulatory function to protect against HIRI in vivo. In conclusion, purinergic signaling is crucial for DNT homeostasis in HIRI. Augmentation of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders.

Fibers have been of great significance in our daily lives, especially in the industrial production of masks. Research in this area has been focused on developing microfibers with superior functions to enhance the filtration performances of the masks. Herein, inspired by the frog's predation mechanism using its tongues to swiftly grab flying insects, we propose novel porous wettable microfibers from microfluidics to efficiently capture particles in the air for filtration. Upon pre-dispersing LP emulsions into polyurethane (PU), porous microfibers dispersed with oil droplets could be continuously spun from a co-flow microfluidic device based on the quick phase inversion of PU. To design an optimal system with frog-tongue-like interfacial adhesion properties, the wettability performances of the porous microfibers are investigated under full, partial, and no oil coverage conditions. When implemented in a mask, the 3D patterned networks based on the frog-tongue-inspired microfibers have been proven with remarkable particle capture performances while maintaining good air permeability. Based on these features, we believe that frog-tongue-inspired microfibers and their derived masks are of practical significance in multiple applications.

Excess intracellular H₂S induces destructive mitochondrial toxicity, while overload of Zn²⁺ results in cell pyroptosis and potentiates the tumor immunogenicity for immunotherapy. However, the precise delivery of both therapeutics remains a great challenge. Herein, an electrically activable ZnS nanochip for the controlled release of H₂S and Zn²⁺ was developed for enhanced gas-ionic-immunotherapy (GIIT). Under an electric field, a locality with particularly high concentrations of H₂S and Zn²⁺ was established by the voltage-controlled degradation of the ZnS nanoparticles (NPs). Consequently, the ZnS nanochip-mediated gas-ionic therapy (GIT) resulted in mitochondrial membrane potential depolarization, energy generation inhibition, and oxidative stress imbalance in tumor cells. Interestingly, the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway was activated due to the mitochondrial destruction. Moreover, the released Zn²⁺ resulted in the increase of the intracellular Zn levels and cell pyroptosis, which enhanced the immunogenicity via the release of damage-associated molecular patterns (DAMPs). In vitro and in vivo studies revealed that the ZnS nanochip-based GIT effectively eliminated the tumors under an electric field and mobilized the cytotoxic T lymphocytes for immunotherapy. The combination with αCTLA-4 further promoted the adaptive immune response and inhibited tumor metastasis and long-term tumor recurrence. This work presented an electrically activable ZnS nanochip for combined immunotherapy, which might inspire the development of electric stimulation therapy.