An optical strategy for detecting hypochlorite in vitro and cells with high selectivity and stability based on a lanthanide-doped upconversion probe† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2ra05414k

The excessive use of sodium hypochlorite disinfectant for preventing COVID-19 can be harmful to the water environment and humans. More importantly, owing to hypochlorite being a biomarker of immune responses in living organisms, its abnormal production can damage nucleic acids and protein molecules, eventually causing many diseases (even cancer). Exploring a reliable, rapid, and non-invasive method to monitor the hypochlorite level in vitro and in cells can be significant. Herein, we report a novel ratiometric fluorescence sensing strategy based on Astrazon Brilliant Red 4G dye-sensitized NaGdF4:Yb3+, Er3+@NaYF4 core–shell upconversion nanoparticles (UCNPs@ABR 4G). Based on the combination mechanism of the fluorescent resonant energy transfer effect (FRET) and redox, a linear model of fluorescence intensity ratio and hypochlorite concentration was constructed for a fast response and high selectivity monitoring of hypochlorite in vitro and in vivo. The detection limit was calculated to be 0.39 μM. In addition, this sensing strategy possessed good stability and circularity, making it valuable both for the quantitative detection of hypochlorite in water and for the visualization of intracellular hypochlorite. The proposed optical probe is promising for the efficient and stable non-invasive detection of hypochlorite. The excessive use of sodium hypochlorite disinfectant for preventing COVID-19 can be harmful to the water environment and humans.

An optical strategy for detecting hypochlorite in vitro and cells with high selectivity and stability based on a lanthanide-doped upconversion probe.

The excessive use of sodium hypochlorite disinfectant for preventing COVID-19 can be harmful to the water environment and humans. More importantly, owing to hypochlorite being a biomarker of immune responses in living organisms, its abnormal production can damage nucleic acids and protein molecules, eventually causing many diseases (even cancer). Exploring a reliable, rapid, and non-invasive method to monitor the hypochlorite level in vitro and in cells can be significant. Herein, we report a novel ratiometric fluorescence sensing strategy based on Astrazon Brilliant Red 4G dye-sensitized NaGdF4:Yb3+, Er3+@NaYF4 core-shell upconversion nanoparticles (UCNPs@ABR 4G). Based on the combination mechanism of the fluorescent resonant energy transfer effect (FRET) and redox, a linear model of fluorescence intensity ratio and hypochlorite concentration was constructed for a fast response and high selectivity monitoring of hypochlorite in vitro and in vivo. The detection limit was calculated to be 0.39 µM. In addition, this sensing strategy possessed good stability and circularity, making it valuable both for the quantitative detection of hypochlorite in water and for the visualization of intracellular hypochlorite. The proposed optical probe is promising for the efficient and stable non-invasive detection of hypochlorite.

Adaptive Evolution of the Fox Coronavirus Based on Genome-Wide Sequence Analysis.

Purpose: To report the first complete fox coronavirus (CoV) genome sequence obtained through genome-wide amplifications and to understand the adaptive evolution of fox CoV. Methods: Anal swab samples were collected from 35 foxes to detect the presence of CoV and obtain the virus sequence. Phylogenetic analysis was conducted using MrBayes. The possibility of recombination within these sequences was assessed using GARD. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Data Monkey platforms. Results: Of the 35 samples, two were positive, and complete genome sequences for the viruses were obtained. Phylogenetic analysis, using Bayesian methods, of these sequences, together with other CoV sequences, revealed that the fox CoV sequences clustered with canine coronavirus (CCoV) sequences, with sequences from other carnivores more distantly related. In contrast to the feline, ferret and mink CoV sequences that clustered into species-specific clades, the fox CoV fell within the CCoV clade. Minimal evidence for recombination was found among the sequences. A total of 7, 3, 14, and 2 positively selected sites were identified in the M, N, S, and 7B genes, respectively, with 99, 111, and 581 negatively selected sites identified in M, N, and S genes, respectively. Conclusion: The complete genome sequence of fox CoV has been obtained for the first time. The results suggest that the genome sequence of fox CoV may have experienced adaptive evolution in the genes replication, entry, and virulence. The number of sites in each gene that experienced negative selection is far greater than the number that underwent positive selection, suggesting that most of the sequence is highly conserved and important for viral survive. However, positive selection at a few sites likely aided these viruses to adapt to new environments.

NK cell receptor and ligand composition influences the clearance of SARS-CoV-2.

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.

Synthesis and pharmacological evaluation of choroquine derivatives bearing long aminated side chains as antivirus and anti-inflammatory agents.

Starting from the antimalarial drugs chloroquine and hydroxychloroquine, we conducted a structural optimization on the side chain of chloroquine by introducing amino substituted longer chains thus leading to a series of novel aminochloroquine derivatives. Anti-infectious effects against SARS-Cov2 spike glycoprotein as well as immunosuppressive and anti-inflammatory activities of the new compounds were evaluated. Distinguished immunosuppressive activities on the responses of T cell, B cell and macrophages upon mitogen and pathogenic signaling were manifested. Compounds 9-11 displayed the most promising inhibitory effects both on cellular proliferation and on the production of multiple pro-inflammatory cytokines, including IL-17, IFN-γ, IL-6, IL-1ß and TNF-α, which might be insightful in the pursuit of treatment for immune disorders and inflammatory diseases.

The psychological impact of COVID-19 pandemic on medical staff in Guangdong, China: a cross-sectional study.

BACKGROUND: During previous pandemic outbreaks, medical staff have reported high levels of psychological distress. The aim of the current study was to report a snapshot of the psychological impact of the coronavirus disease 2019 (COVID-19) pandemic and its correlated factors on medical staff in Guangdong, China. METHODS: On the 2nd and 3rd February 2020, soon after the start of the COVID-19 pandemic, we surveyed medical staff at four hospitals in Guangdong, China, to collect demographic characteristics, Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS-14), and Insomnia Severity Index (ISI) scores. RESULTS: Complete responses were received from 1045 medical staff. Respondents were divided into high- and low-risk groups according to their working environment of contacting with potential or confirmed COVID-19 cases. The proportion of staff with anxiety (55.4% v. 43.0%, p < 0.001) or depression (43.6% v. 36.8%, p = 0.028) was significantly higher in the high-risk group than the low-risk group. The percentage of staff with severe anxiety was similar in the two groups. Doctors were more susceptible to moderate-to-severe depressive symptoms. The high-risk group had higher levels of clinical insomnia (13.5% v. 8.5%, p = 0.011) and were more likely to be in the upper quartile for stress symptoms (24.7% v. 19.3%, p = 0.037) than the low-risk group. Additionally, work experience negatively correlated with insomnia symptoms. CONCLUSIONS: It is important for hospitals and authorities to protect both the physical and psychological health of medical staff during times of pandemic, even those with a low exposure risk.