Fast detection of cellular thiols in aqueous medium was achieved using a newly developed fluorescence probe (see picture). Based on this probe, a high-throughput fluorescence assay for glutathione reductase was developed.

As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light–responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs). The UCNPs served as “nanotransducers” that can convert NIR light (980 nm) into local ultraviolet light for the cleavage of photosensitive molecules, thereby resulting in on-demand release of CRISPR-Cas9. In addition, by preparing a single guide RNA targeting a tumor gene (polo-like kinase-1), our strategies have successfully inhibited the proliferation of tumor cell via NIR light–activated gene editing both in vitro and in vivo. Overall, this exogenously controlled method presents enormous potential for targeted gene editing in deep tissues and treatment of a myriad of diseases.

No abstract

We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection. We found that HBV-miR-3 expression gradually increased in a dose- and time-dependent manner in HBV-infected HepG2-NTCP cells. HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes, thereby enhancing the IFN-induced anti-HBV effect. In addition, HBV-miR-3 in exosomes facilitated the M1 polarization of macrophages. Furthermore, exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR. In short, these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways, which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.

No abstract

No abstract

Die schnelle Detektion zellulärer Thiole in wässrigem Medium gelingt mithilfe einer neuen Fluoreszenzsonde (siehe Bild). Ein Hochdurchsatz‐Fluoreszenzassay für Glutathion‐Reduktase auf Basis dieser Sonde wurde entwickelt.

Polymer topology exerts a significant effect on its properties and performance for potential applications. Cyclic topology and its derived structures have been recently shown to outperform conventional linear analogues for drug delivery applications. However, an amphiphilic tadpole-shaped copolymer consisting of a cylic hydrophobic moiety has rarely been explored. For this purpose, a tadpole-shaped amphiphilic diblock copolymer of poly­(ethylene oxide)-b-(cyclic poly­(ε-caprolactone)) (mPEG-b-cPCL) was synthesized successfully via ring-opening polymerization (ROP) of ε-CL using a mPEG-based macroinitiator with both a hydroxyl and an azide termini and subsequent intrachain Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAc) click cyclization. A comparison study on the self-assembly behaviors, in vitro drug loading and drug release profiles, and degradation properties of the resulting mPEG-b-cPCL (C) with those of the linear counterpart (mPEG-b-PCL, L) revealed that mPEG-b-cPCL micelles are a better formulation than the micelles formed by the linear counterparts in terms of micelle stability, drug loading capacity, and the degradation property. Interestingly, compared to the single degradation of L, C exhibited a slower two-stage degradation process including the topological change from tadpole shape to linear conformation and the subsequent degradation of a linear polymer. This study therefore uncovered the topological effect of a hydrophobic moiety on the properties of the self-assembled micelles and developed a complementary alternative to enhance the micelle stability by introducing a cyclic hydrophobic segment.