Han Peiyu,Shen Li,Nan Nan,Zhou Renwu,Li Tianci,Dai Xiaofeng
Objectives: Vaccination still remains as the most effective approach for preventing infectious diseases such as those caused by virus infection, with cell-based vaccine manufacturing being one flexible solution regarding the spectrum of infectious disorders it can prevent. Rapid cell-based virus propagation can enable high yield of vaccines against viral diseases that may offer critical values in the industry when handling emergent situations such as the ongoing viral disease pandemic.Methods: Through investigating the phenomenon and biological mechanism underlying redox-triggered cell survival towards enhanced viral particle production, this study explores novel strategies for improved yield of viral particles at a reduced cost to meet the increasing demand on cell-based vaccine manufacturing against viral diseases.Results: We found in this study that cold atmospheric plasma (CAP), composed of multiple reactive oxygen and nitrogen species including H2O2, could effectively enhance virus replication via triggering cell mitophagy that was dynamically modulated by the p-EGFR(Tyr1068)/p-Drp1(Ser616) axis using IBRV and MDBK as the virus and cell models, respectively; and removing H2O2 can further enhance virus yield via releasing cells from excessive G0/G1 cell cycle arrest. The observed efficacy of CAP was extended to other viruses such as CDV and CPV.Conclusion: This study provides experimental evidences supporting the use of CAP as a modulator of cell survival including mitophagy and mitochondria dynamics, and makes CAP an interesting and promising tool for enhancing the yield of viral vaccines if translated into the industry.
Despite advances in immunotherapy for the treatment of cancers, not all patients can benefit from programmed cell death ligand 1 (PD-L1) immune checkpoint blockade therapy. Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level; hence, accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects. Therefore, based on the high affinity antibody Nb109, a new site-specifically radiolabeled tracer, 68 Ga-NODA-cysteine, aspartic acid, and valine (CDV)-Nb109, was designed and synthesized to accurately monitor PD-L1 expression. The tracer 68 Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95% and radiochemical purity of 97%. It showed high affinity for PD-L1 with a dissociation constant of 12.34 ± 1.65 nM. Both the cell uptake assay and positron emission tomography (PET) imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells. Meanwhile, dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression, allowing timely interventional immunotherapy. In conclusion, this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
The effects of 7 spice extracts on lipid radical formation were first collectively studied in situ in roasted beef by electron spin resonance (ESR). And the correlations among the ESR and conventional indexes including 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity, reducing power, oxygen radical absorption capacity (ORAC), conjugated diene value (CDV) and thiobarbituric acid-reactive substances (TBARS) were also analysed. Clove was observed the highest scavenging lipid radical and DPPH radical capacity, and rosemary showed the highest peroxyl radical scavenging capacity, while tert-butylhydroquinone (TBHQ) significantly increased lipid radicals in roasted beef ( p < 0.05). ESR showed significant correlations with the DPPH and CDV assays ( p < 0.05) but no correlation with the ORAC and TBARS assays ( p > 0.05), indicating that with the addition of spice extracts, the lipid radical formation in roasted beef could be predicted by the DPPH assay but not be appropriate to evaluate the oxidation stability in roasted beef.
危险品化学品经营许可证（带存储）