SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

The spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but the functions of its glycosylation are unknown. Here we demonstrate that S is recognized in a glycan-dependent manner by multiple innate immune receptors including the mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate that such receptors are highly expressed in innate immune cells in tissues susceptible to SARS-CoV-2 infection. Binding of the above receptors to S is characterized by affinities in the picomolar range and consistent with S glycosylation analysis demonstrating a variety of N- and O-glycans as receptor ligands. These results indicate multiple routes for SARS-CoV-2 to interact with human cells and suggest alternative strategies for therapeutic intervention.

An investigation and analysis on job burnout of medical staffs in minority border areas / 中华医学教育探索杂志

Objective To explore the status of job burnout of medical staffs in minority border areas. Methods A total of 906 medical personnel from Pu'er hospitals in Yunnan Province were as-sessed with Maslach Burnout Inventory General Survey (MBI-GS) by t test, descriptive statistics, chi-square test, ANOVA and LSD-t pairwise comparison. Results ①The emotional exhaustion, cynicism and reduced personal accomplishment of medical staffs in minority border areas (1.55±1.40, 0.99± 1.29, 2.47±1.98) are significantly lower than general areas (P=0.000, 0.010, 0.000); ②emotional ex-haustion, cynicism and Maslach Burnout Inventory (MBI) total points of different levels of hospital medi-cal staff, the score of which in descending order are:municipal, county and township (town) levels (P=0.000, 0.000, 0.000); ③Female medical personnel's emotional exhaustion and cynicism are scored significantly higher than males medical staff (P=0.000, 0.025); ④The scores of emotional exhaustion, cynicism, reduced personal accomplishment and MBI total points of Bachelor medical staff are signifi-cantly higher than those of colleges as well as secondary schools and below (P=0.000, 0.000, 0.000, 0.012); ⑤The scores of reduced personal achievement of Lahu medical staff are higher than those of other ethnic groups (P=0.009). Conclusion In medical staffs in minority border areas there exists a certain extent of job burnout, which presents differences among genders, educational background, hos-pitals and ethnic groups.

Rapid inhibition of ATP-induced currents by dexamethasone in rat dorsal root ganglion neurons / 解放军医学杂志

Objective Glucocorticoid hormone may nongenomically affect cell functions in addition to its classic effects on gene expression. The purpose of present study was to explore whether dexamethasone, a synthetical glucocorticoid hormone, has a rapid nongenomic effect on ATP-induced currents in rat dorsal root ganglion (DRG) neurons and the related signal transduction pathway. Methods The effects of dexamethasone on ATP-induced currents were studied on cultured DRG neurons using patch clamp technique. Results Three types of currents (transient, sustained and biphasic) were evoked by ATP (100 ?mol/L) in cultured DRG neurons. When DRG neurons were pretreated with dexamethasone (0.01-10?mol/L) for 30s, inhibition of the transient current and the transient component of the biphasic current evoked by ATP in DRG neurons was observed. The inhibitory effect of dexamethasone was dose-dependent. However, dexamethasone did not seem to affect the sustained current and the sustained component of the biphasic current induced by ATP. The inhibitory effect of dexamethasone on ATP-induced currents was blocked by glucocorticoid receptor antagonist RU38486 (10?mol/L) and protein kinase A inhibitor H-89 (10?mol/L), but not by G protein inhibitor GDP-?-S (0.2mmol/L) and protein kinase C inhibitor chelerythrine chloride (10?mol/L). Conclusions Dexamethasone can selectively inhibit the transient current mediated by P2X3 receptors in DRG neurons. The inhibitory effect of dexamethasone might be mediated by glucocorticoid receptor through activating PKA signal pathway. These results suggest that glucocorticoid hormone might participate in the control of pain by modulating the actions of extracellular ATP in sensory neurons.

Dorsal root ganglion P2X_3 receptor expression and electrophysiological characteristics in rats with neuropathic pain / 第三军医大学学报

Objective To investigate the P2X3 receptor expression and electrophysiological characteristics in dorsal root ganglion (DRG) in rat with neuropathic pain caused by chronic constriction injury of sciatic nerve (CCI) Methods P2X3 receptor expressions in L4,L5 and L6 DRG following CCI were observed by using a polyclonal antibody to label the P2X3 receptor ATP-activated currents in corresponding DRG neurons following CCI were observed by using electrophysiological technique Results A significant increase in P2X3 immunoreactivity was observed in the ipsilateral (injured) L4,L5 and L6 DRG and spinal cord on 7,14 d after CCI In small diameter neurons,a significant increase in the number of cells exhibiting a transient current to ATP was observed on 7,14 d after CCI Moreover,amplitude of these currents was increased Conclusion After CCI,the expression and function of P2X3 receptor in corresponding DRG are increased