The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate thi...The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.展开更多
Herein,we fabricated a flexible semidry electrode with excellent mechanical performance,satisfactory self-adhesiveness,and low-contact impedance using physical/chemical crosslinked polyvinyl alcohol/polyacrylamide dua...Herein,we fabricated a flexible semidry electrode with excellent mechanical performance,satisfactory self-adhesiveness,and low-contact impedance using physical/chemical crosslinked polyvinyl alcohol/polyacrylamide dual-network hydrogels(PVA/PAM DNHs)as an efficient saline reservoir.The resultant PVA/PAM DNHs showed admirable adhesive and compliance to the hairy scalp,facilitating the establishment of a robust electrode/skin interface for biopotential signal transmission.Moreover,the PVA/PAM DNHs steadily released trace saline onto the scalp to achieve the minimized potential drift(1.47±0.39 mV/min)and low electrode–scalp impedance(18.2±8.9 kΩ@10 Hz).More importantly,the application feasibility of real-world brain−computer interfaces(BCIs)was preliminarily validated by 10 participants using two classic BCI paradigms.The mean temporal cross-correlation coefficients between the semidry and wet electrodes in the eyes open/closed and the N200 speller paradigms are 0.919±0.054 and 0.912±0.050,respectively.Both electrodes demonstrate anticipated neuroelectrophysiological responses with similar patterns.This semidry electrode could also effectively capture robust P-QRS-T peaks during electrocardiogram recording.Considering their outstanding advantages of fast setup,user-friendliness,and robust signals,the proposed PVA/PAM DNH-based electrode is a promising alternative to wet electrodes in biopotential signal acquisition.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.31770184)
文摘The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.
基金supported by the National Natural Science Foundation of China (Nos.62176089,61703152)the Hunan Provincial Natural Science Foundation (Nos.2021JJ30226,2018JJ3134)+1 种基金Scientific Research Foundation of Hunan Provincial Education Department (No.21B0532)Science and Technology Planning Project of Zhuzhou (No.2020015).
文摘Herein,we fabricated a flexible semidry electrode with excellent mechanical performance,satisfactory self-adhesiveness,and low-contact impedance using physical/chemical crosslinked polyvinyl alcohol/polyacrylamide dual-network hydrogels(PVA/PAM DNHs)as an efficient saline reservoir.The resultant PVA/PAM DNHs showed admirable adhesive and compliance to the hairy scalp,facilitating the establishment of a robust electrode/skin interface for biopotential signal transmission.Moreover,the PVA/PAM DNHs steadily released trace saline onto the scalp to achieve the minimized potential drift(1.47±0.39 mV/min)and low electrode–scalp impedance(18.2±8.9 kΩ@10 Hz).More importantly,the application feasibility of real-world brain−computer interfaces(BCIs)was preliminarily validated by 10 participants using two classic BCI paradigms.The mean temporal cross-correlation coefficients between the semidry and wet electrodes in the eyes open/closed and the N200 speller paradigms are 0.919±0.054 and 0.912±0.050,respectively.Both electrodes demonstrate anticipated neuroelectrophysiological responses with similar patterns.This semidry electrode could also effectively capture robust P-QRS-T peaks during electrocardiogram recording.Considering their outstanding advantages of fast setup,user-friendliness,and robust signals,the proposed PVA/PAM DNH-based electrode is a promising alternative to wet electrodes in biopotential signal acquisition.
