Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.
Patterned nanostructures with ultrasmall features endow functional devices with unique nanoconfinement and performance enhancements. The increasing demand for miniaturization has stimulated the development of sub-100 nm nanopatterning techniques. Beyond conventional lithography-which is limited by unavoidable factors-advanced patterning techniques have been reported to produce nanoscale features down to molecular or even atomic scale. In this review, unconventional techniques for sub-100 nm nanopatterning are discussed, in particular the principles by which to achieve the desired patterns (among other important issues). Such techniques can be classified into three categories: template-replica, template-induced, and template-free techniques. Moreover, multi-dimensional nanostructures consist of various building materials, the unique properties of which are summarized. Finally, the remaining challenges and opportunities for large-scale patterning, the improvement of device performance, the multi-dimensional nanostructures of biocompatible materials, molecular-scale patterning, and the carbon footprint requirements for future nanofabrication processes are discussed.
Constructing precisely oriented assemblies and exploring their orientation-dependent properties remain a challenge for Janus nanoparticles (JNPs) due to their asymmetric characteristics. Herein, we propose a bubble-driven instant quasi-1D interfacial strategy for the oriented assembly of JNP chains in a highly controllable manner. It is found that the rapid formation of templated bubbles can promote the interfacial orientation of JNPs kinetically, while the confined quasi-1D interface in the curved liquid bridge can constrain the disordered rotation of the particles, yielding well-oriented JNP chains in a long range. During the evaporation process, the interfacial orientation of the JNPs can be transferred to the assembled chains. By regulating the amphiphilicity of the JNPs, both heteraxial and coaxial JNP assemblies are obtained, which show different polarization dependences on light scattering, and the related colorimetric logic behaviors are demonstrated. This work demonstrates the great potential of patterned interfacial assembly with a manageable orientation and shows the broad prospect of asymmetric JNP assembly in constructing novel optoelectronic devices.
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