O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is notably decreased in Alzheimer’s disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered O-GlcNAcylation, β-amyloid (Aβ) accumulation, and necroptosis are unclear. Here, we found that O-GlcNAcylation plays a protective role in AD by inhibiting necroptosis. Necroptosis was increased in AD patients and AD mouse model compared with controls; however, decreased necroptosis due to O-GlcNAcylation of RIPK3 (receptor-interacting serine/threonine protein kinase 3) was observed in 5xFAD mice with insufficient O-linked β-N-acetylglucosaminase. O-GlcNAcylation of RIPK3 suppresses phosphorylation of RIPK3 and its interaction with RIPK1. Moreover, increased O-GlcNAcylation ameliorated AD pathology, including Aβ burden, neuronal loss, neuroinflammation, and damaged mitochondria and recovered the M2 phenotype and phagocytic activity of microglia. Thus, our data establish the influence of O-GlcNAcylation on Aβ accumulation and neurodegeneration, suggesting O-GlcNAcylation–based treatments as potential interventions for AD.

The solid-state electrochemical principle has been a selective and accurate way of sensing chemical components in various environments, including liquid metal, for an extended period of time. Since after Carl Wagner's interpretation of zirconia, there appeared many advances in chemical sensor applications. The electrochemical techniques for the chemical measurements have, in general, several major advantages compared to other methods. The information of interest is directly converted into electrical signal which may be employed in electronic circuits. Electrochemical measurements are always selective for the quantities that undergo the electrochemical redox reaction. In most cases, reactions at equilibrium are considered, but techniques have also been developed to be able to use kinetic limit. Furthermore, the signal is independent of materials properties, such as the ionic conductivity or impurity as long as it is a predominant ionic conductor. Depending on the type of application, voltage or current measurements are employed. While potentiometric method commonly allows measuring chemical species over a wide range of concentration, amperometric sensors generally cover a quite limited range but have a much higher resolution. In this paper, various principles of electrochemical techniques to measure the chemical quantities are introduced. And there are many examples of the status of researches on electrochemical sensors, such as oxygen sensor, carbon dioxide sensor, NO x sensor, SO x sensor, and hydrogen sensor.

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin‐converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID‐19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly studied as nanoscale protein carriers. In order to exploit the potential of sEVs, we design truncated CD9 scaffolds to display sACE2 on the sEV surface as a decoy receptor for the S protein of SARS‐CoV‐2. Moreover, to enhance the sACE2‐S binding interaction, we employ sACE2 variants. sACE2‐loaded sEVs exhibit typical sEVs characteristics and bind to the S protein. Furthermore, engineered sEVs inhibit the entry of wild‐type (WT), the globally dominant D614G variant, Beta (K417N‐E484K‐N501Y) variant, and Delta (L452R‐T478K‐D614G) variant SARS‐CoV‐2 pseudovirus, and protect against authentic SARS‐CoV‐2 and Delta variant infection. Of note, sACE2 variants harbouring sEVs show superior antiviral efficacy than WT sACE2 loaded sEVs. Therapeutic efficacy of the engineered sEVs against SARS‐CoV‐2 challenge was confirmed using K18‐hACE2 mice. The current findings provide opportunities for the development of new sEVs‐based antiviral therapeutics.

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