Virus-like structures for combination antigen protein mRNA vaccination.

Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

Satisfactory degradation of tetracycline by a pH-universal CoFe-LDH/MoS2 heterojunction catalyst in Fenton process.

Fenton or Fenton-like reactions have been widely used in various fields, including solar energy conversion to generate hydroxyl radicals, environmental remediation, biology, and life science. However, the slow Fe3+/Fe2+ cycle and narrow applicable pH range still present significant challenges. Here, a heterostructured CoFe-layered double hydroxide/MoS2 nanocomposite (CoFe-LDH/MoS2) was prepared via simple electrostatic interactions. The heterostructure establishes a robust interfacial contact, leading to an abundance of exposed Mo6+ sites. Consequently, the developed CoFe-LDH/MoS2+H2O2 system exhibited superior performance in the degradation of tetracycline (>85%) within 60 min across a wide pH range from acidic to basic. Moreover, the CoFe-LDH/MoS2 heterojunction catalysts exhibited exceptional resistance to common anions and efficiently degraded various organic pollutants. The mechanism study verified that the CoFe-LDH/MoS2 had high efficiency in producing 1O2 and ‧OH to degrade various organic pollutants. The present study will serve as a foundation for creating efficient catalyst systems for related environmental remediation.

Combinatorial Virtual Screening Revealed a Novel Scaffold for TNKS Inhibition to Combat Colorectal Cancer.

The abnormal Wnt signaling pathway leads to a high expression of ß-catenin, which causes several types of cancer, particularly colorectal cancer (CRC). The inhibition of tankyrase (TNKS) activity can reduce cancer cell growth, invasion, and resistance to treatment by blocking the Wnt signaling pathway. A pharmacophore search and pharmacophore docking were performed to identify potential TNKS inhibitors in the training databases. The weighted MM/PBSA binding free energy of the docking model was calculated to rank the databases. The reranked results indicated that 26.98% of TNKS inhibitors that were present in the top 5% of compounds in the database and near an ideal value ranked 28.57%. The National Cancer Institute database was selected for formal virtual screening, and 11 potential TNKS inhibitors were identified. An enzyme-based experiment was performed to demonstrate that of the 11 potential TNKS inhibitors, NSC295092 and NSC319963 had the most potential. Finally, Wnt pathway analysis was performed through a cell-based assay, which indicated that NSC319963 is the most likely TNKS inhibitor (pIC50 = 5.59). The antiproliferation assay demonstrated that NSC319963 can decrease colorectal cancer cell growth; therefore, the proposed method successfully identified a novel TNKS inhibitor that can alleviate CRC.