A characteristic feature of COVID‐19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is the dysregulated immune response with impaired type I and III interferon (IFN) expression and an overwhelming inflammatory cytokine storm. RIG‐I‐like receptors (RLRs) and cGAS–STING signaling pathways are responsible for sensing viral infection and inducing IFN production to combat invading viruses. Multiple proteins of SARS‐CoV‐2 have been reported to modulate the RLR signaling pathways to achieve immune evasion. Although SARS‐CoV‐2 infection also activates the cGAS–STING signaling by stimulating micronuclei formation during the process of syncytia, whether SARS‐CoV‐2 modulates the cGAS–STING pathway requires further investigation. Here, we screened 29 SARS‐CoV‐2‐encoded viral proteins to explore the viral proteins that affect the cGAS–STING signaling pathway and found that SARS‐CoV‐2 open reading frame 10 (ORF10) targets STING to antagonize IFN activation. Overexpression of ORF10 inhibits cGAS–STING‐induced interferon regulatory factor 3 phosphorylation, translocation, and subsequent IFN induction. Mechanistically, ORF10 interacts with STING, attenuates the STING–TBK1 association, and impairs STING oligomerization and aggregation and STING‐mediated autophagy; ORF10 also prevents the endoplasmic reticulum (ER)‐to‐Golgi trafficking of STING by anchoring STING in the ER. Taken together, these findings suggest that SARS‐CoV‐2 ORF10 impairs the cGAS–STING signaling by blocking the translocation of STING and the interaction between STING and TBK1 to antagonize innate antiviral immunity.

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Ferroelectric nanowires have attracted great attention due to their excellent physical properties. We report the domain structure, ferroelectric, piezoelectric, and conductive properties of bismuth ferrite (BFO, short for BiFeO3) nanowires characterized by scanning probe microscopy (SPM). The X-ray diffraction (XRD) pattern presents single phase BFO without other obvious impurities. The piezoresponse force microscopy (PFM) results indicate that the nanowires possess a multidomain configuration, and the maximum piezoelectric coefficient (d33) of single BFO nanowire is 22.21 pm/V. Poling experiments and local switching spectroscopy piezoresponse force microscopy (SS-PFM) demonstrate that there is sufficient polarization switching behavior and obvious piezoelectric properties in BFO nanowires. The conducting atomic force microscopy (C-AFM) results show that the current is just hundreds of pA at 8 V. These lay the foundation for the application of BFO nanowires in nanodevices.

Despite the vital role miRNA-27a plays in driving the development and progress of liver cancer, miRNA-based inhibition therapy is hampered due to its undesired degradation and off-target effects. Herein, a multifunctional nanoparticle for noninvasive tracking of targeted delivery of anti-miR-27a oligonucleotides against liver cancer was constructed.Methods: Dual-fluorescent conjugates (QD-HA-PEI) were first fabricated through crosslinking hyaluronic acid (HA), polyethyleneimine (PEI) and near-infrared (NIR) fluorescent quantum dots (QDs) via a facile one-pot approach. Antisense oligonucleotide was then encapsulated by QD-HA-PEI to form anti-miR-27a/QD-HA-PEI via electrostatic interactions. Targeting, biodistribution, bioimaging, in vitro cytotoxicity and in vivo anti-tumor effects were evaluated and the underlying mechanism was studied.Results: The NIR fluorescence of anti-miR-27a/QD-HA-PEI could be employed to monitor CD44 receptor-targeted cellular uptake and tumor accumulation. Importantly, the intrinsic fluorescence of anti-miR-27a/QD-HA-PEI remained in the “ON” state in extracellular or blood environment, but switched to the “OFF” state in the intracellular environment, indicating pH-responsive oligonucleotide release. Furthermore, anti-miR-27a/QD-HA-PEI exhibited effective and selective anti-cancer effects in vitro and in vivo with fewer side effects via the direct down-regulation of oncogenic transcription factors FOXO1 and PPAR-γ.Conclusion: Our findings validate the dual-fluorescent nanoparticles as delivery vectors of therapeutic miRNA, capable of simultaneous tumor imaging and tracking of miRNA-based modulation therapy, thereby providing an efficient and safe approach for liver cancer theranostics.