Have Previous COVID-19 Vaccinations Shaped the Potential Enhancing Infection of Variant Strains?

OBJECTIVE: This study aimed to investigate the infection status of Omicron in the population and the association between COVID-19 vaccination and infection with Omicron. METHODS: We conducted a cross-sectional study to openly recruit participants for a survey of SARS-CoV-2 infection by convenience sampling from 1 January to 15 January 2023 after a COVID-19 pandemic swept across China. Additionally, the binary logistic regression model was adopted to evaluate the association between COVID-19 vaccination and the infection outcomes or symptom severity, respectively. Meanwhile, the relations between the vaccination and duration of the symptoms were estimated via ordinal logistic analysis. RESULTS: Of the 2007 participants, the prevalence of infection with Omicron was 82.9%. Compared with unvaccinated individuals, inactivated COVID-19 vaccination could increase the risk of Omicron infection (OR = 1.942, 95% CI: 1.093-3.448), and the receipt of at least one dose of non-inactivated COVID-19 vaccines was a protective factor against infection (OR = 0.428, 95% CI: 0.226-0.812). By contrast, no relations were observed in COVID-19 vaccination with the symptoms of infection and duration of symptoms (p > 0.05). CONCLUSIONS: This cross-sectional study concluded that inactivated COVID-19 vaccination might increase the risk of Omicron infection, which should be a concern during COVID-19 vaccination and the treatment of variant infections in the future, and the receipt of at least one dose of non-inactivated COVID-19 vaccine was a protective factor against infection.

Isoflurane preconditioning protects hepatocytes from oxygen glucose deprivation injury by regulating FoxO6.

The forkhead protein (FoxO) family plays a crucial role in regulating oxidative stress, cell proliferation, and apoptosis. FoxO6, a member of the FoxO family, helps regulate oxidative stress in gastric cancer and hepatocellular carcinoma. However, it is unclear whether FoxO6 participates in the protective effect of isoflurane preconditioning in liver injury caused by oxidative stress in ischemia. In this study, we explored the role and mechanism of FoxO6 in the protective effect of isoflurane preconditioning during hepatocyte injury caused by oxygen-glucose deprivation (OGD). Cells from the human fetal hepatocyte (LO2) line were incubated with 0%, 1%, 2%, 2.5%, 3%, 3.5%, 4%, or 5% isoflurane for 3 h and then exposed to OGD. Data showed that 3% isoflurane preconditioning inhibited FoxO6 expression, caspase-3 activity, and reactive oxygen species production and promoted cell viability. FoxO6 overexpression abolished the effects of 3% isoflurane preconditioning on caspase-3 activity, reactive oxygen species production, and cell viability in these cells. Moreover, FoxO6 regulated nuclear factor erythroid 2-related factor (Nrf2) expression via c-Myc after 3% isoflurane preconditioning and OGD exposure. Thus, isoflurane preconditioning prevented OGD-induced injury in LO2 cells by modulating FoxO6, c-Myc, and Nrf2 signaling.

Novel affinity membranes with macrocyclic spacer arms synthesized via click chemistry for lysozyme binding.

Affinity membrane has great potential for applications in bioseparation and purification. Disclosed herein is the design of a novel affinity membrane with macrocyclic spacer arms for lysozyme binding. The clickable azide-cyclodextrin (CD) arms and clickable alkyne ethylene-vinyl alcohol (EVAL) chains are designed and prepared. By the azide-alkyne click reaction, the EVAL-CD-ligands affinity membranes with CD spacer arms in three-dimensional micro channels have been successfully fabricated. The FT-IR, XPS, NMR, SEM and SEM-EDS results give detailed information of structure evolution. The abundant pores in membrane matrix provide efficient working channels, and the introduced CD arms with ligands (affinity sites) provide supramolecular atmosphere. Compared with that of raw EVAL membrane, the adsorption capacity of EVAL-CD-ligands membrane (26.24mg/g) show a triple increase. The study indicates that three effects (inducing effect, arm effect, site effect) from CD arms render the enhanced performance. The click reaction happened in membrane matrix in bulk. The effective lysozyme binding and higher adsorption performance of affinity membranes described herein compared with other reported membranes are markedly related with the proposed strategy involving macrocyclic spacer arms and supramolecular working channels.

Analysis of the complex formation, interaction and electron transfer pathway between the "open" conformation of NADPH-cytochrome P450 reductase and aromatase.

The complex structure of human aromatase (CYP19) and the open form of ΔTGEE mutant NADPH-cytochrome P450 reductase (mCPR) was constructed using template-based protein alignment method. Dynamic simulation of formed complex was performed on NAMD 2.9, in which CHARMm all 27_prot_lipid_na force field and an explicit TIP3P water solvent model were applied. The result showed mCPR in its open conformation could steadily combine with aromatase from the proximal face. Data analysis indicates hydrogen bonds and four salt bridges on the binding surface enhance the interaction between the two protein molecules. Amino acid, Lys108 plays a key role in aromatase activity through the formation of a salt bridge with Asp147 and two hydrogen bonds with Asp147 and Gln150 in mCPR. The optimal pathway for the first electron transfer from CPR to aromatase was revealed and calculated using HARLEM software. The rates for solvent mediated and non-solvent mediated electron transfer from FMNH2 to heme were determined as 1.04×10(6)s(-)(1) and 4.86×10(5)s(-)(1) respectively, which indicates the solvent water can facilitate the electron transfer from FMNH2 to heme. This study presents a novel strategy for the study of the protein-protein interactions based on the template-based protein alignment, which may help new aromtase development targeting the electron transfer between mCPR and aromatase.