A microneedle (MN) is a micron-sized needle with a height of 10-2000 μm and a width of 10-50 μm, which can penetrate through the epidermis layer to dermal tissue directly without pain. Microneedles are widely used in transdermal drug delivery systems (TDDS) because they are efficient, safe, convenient and painless. Morphologically, microneedles are divided into four types: solid microneedles, coated microneedles, dissolving microneedles, and hollow microneedles. Different types of microneedles play different roles in different research fields. Microneedles also have different characteristics and applications depending on the materials they are made from. In recent years, microneedles have frequently been used to deliver drugs, genes, proteins, RNA, and vaccines, and have achieved amazing therapeutic effect. Meanwhile, a variety of nano-carriers combined with microneedle delivery systems highlight the application of microneedles. The materials, types, and applications of the microneedles are summarized in this review. Overall, this review aims to serve as a foundational study of microneedles and hopes to promote their clinical application.
Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell–cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.
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