SARS-Cov-2 Spike-S1 Antigen Test Strip with High Sensitivity Endowed by High-Affinity Antibodies and Brightly Fluorescent QDs/Silica Nanospheres.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

How nursing students' risk perception affected their professional commitment during the COVID-19 pandemic: the mediating effects of negative emotions and moderating effects of psychological capital.

Nurses play a pivotal role in the delivery of medical services. Professional commitment is crucial for nursing professionals' long-term, healthy, and sustainable development. However, nursing students' professional commitment levels are currently unsatisfactory in China, especially given that the COVID-19 pandemic has posed unprecedented challenges to the profession. Therefore, studies investigating the professional commitment levels of nursing students and the underlying influencing factors are urgently required. This study explored how nursing students' risk perceptions, negative emotions, and psychological capital affected their professional commitment during the COVID-19 pandemic. A cross-sectional study was conducted among nursing students using risk perception, professional commitment, negative emotions, and psychological capital scales. An analysis of 1142 Chinese nursing students suggested that nursing students' risk perception positively impacted professional commitment and that negative emotions mediated this association. Importantly, psychological capital moderates the mediating effect of negative emotions and can buffer the negative emotions caused by risk perception. This study demonstrated that effective intervention strategies should be implemented in multiple dimensions such as education, individual, public and society to improve the professional commitment of nursing students.

Spatiotemporal disparities in regional public risk perception of COVID-19 using Bayesian Spatiotemporally Varying Coefficients (STVC) series models across Chinese cities.

Regional public attention has been critical during the COVID-19 pandemic, impacting the effectiveness of sub-national non-pharmaceutical interventions. While studies have focused on public attention at the national level, sub-national public attention has not been well investigated. Understanding sub-national public attention can aid local governments in designing regional scientific guidelines, especially in large countries with substantial spatiotemporal disparities in the spread of infections. Here, we evaluated the online public attention to the COVID-19 pandemic using internet search data and developed a regional public risk perception index (PRPI) that depicts heterogeneous associations between local pandemic risk and public attention across 366 Chinese cities. We used the Bayesian Spatiotemporally Varying Coefficients (STVC) model, a full-map local regression for estimating spatiotemporal heterogeneous relationships of variables, and improved it to the Bayesian Spatiotemporally Interacting Varying Coefficients (STIVC) model to incorporate space-time interaction non-stationarity at spatial or temporal stratified scales. COVID-19 daily cases (median contribution 82.6%) was the most critical factor affecting public attention, followed by urban socioeconomic conditions (16.7%) and daily population mobility (0.7%). After adjusting national and provincial impacts, city-level influence factors accounted for 89.4% and 58.6% in spatiotemporal variations of public attention. Spatiotemporal disparities were substantial among cities and provinces, suggesting that observing national-level public dynamics alone was insufficient. Multi-period PRPI maps revealed clusters and outlier cities with potential public panic and low health literacy. Bayesian STVC series models are systematically proposed and provide a multi-level spatiotemporal heterogeneous analytical framework for understanding collective human responses to major public health emergencies and disasters.

COVID-19 Vaccination Acceptance in China after It Becomes Available: A Cross-Sectional Study.

The outbreak of coronavirus disease 2019 (COVID-19) has led to numerous tragic deaths all over the world. Great efforts have been made by worldwide nations for COVID-19 targeted vaccine development since the disease outbreak. In January 2021, the Chinese government started to provide free vaccination among nationwide communities, which was optional for citizens. As no evidence has been provided so far regarding COVID-19 vaccination acceptance since the initiation of nationwide vaccination, this study aims to investigate COVID-19 vaccination acceptance among Chinese citizens as well as its associated factors as an attempt to bridge such gap embedded in the current literature. An anonymous cross-sectional study was conducted online in March and April 2021 among adults, with the survey questionnaire designed based on the framework of the health belief model (HBM). Information on socio-demographics, risk perception, past pandemic-related experience, awareness of vaccination as well as acceptance of COVID-19 vaccination were collected. Chi-squared test and multi-level regression were performed to distinguish the acceptance between different groups as well as to identify the significant predictors. A total of 3940 participants completed the survey, with 90.6% of the participants reporting strong willingness to get vaccinated. A list of factors were found to be significantly associated with individuals' acceptance of vaccination, including the region of residence, ethnicity, annual income, whether or not they had experienced a major pandemic event in the past, risk perception of the COVID-19 as well as the awareness of receiving vaccination. Safety concerns about the vaccine (27.7%), concerns about receiving vaccination immediately after newly developed vaccines were released into the market (22.4%) as well as concerns about the potential side effects induced by vaccination (22.1%) were identified as the primary reasons of residents' resistance against vaccination. Overall, residents demonstrated strong willingness to receive vaccination against COVID-19 in China. However, the improvement of vaccination-related knowledge among Chinese residents should be highlighted as a critical strategy to facilitate the penetration of nationwide vaccination in order to ultimately achieve the establishment of herd immunity in China.

Topoisomerase 2 inhibitor etoposide promotes interleukin-10 production in LPS-induced macrophages via upregulating transcription factor Maf and activating PI3K/Akt pathway.

Topoisomerase (TOP) inhibitors were commonly used as chemotherapeutic agents in the treatment of cancers. In our present study, we found that etoposide (ETO), a topoisomerase 2 (TOP2) inhibitor, upregulated the production of Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-stimulated macrophages. Besides, other TOP2 inhibitors including doxorubicin hydrochloride (DOX) and teniposide (TEN) were also able to augment IL-10 production. Meanwhile, the expression levels of pro-inflammatory factors, for example IL-6 and TNF-α, were also decreased accordingly by the treatment of the TOP2 inhibitors. Of note, ETO facilitated IL-10 secretion, which might be regulated by transcription factor Maf via PI3K/AKT pathway, as pharmaceutic blockage of kinase PI3K or AKT attenuated ETO-induced Maf and IL-10 expression. Further, in LPS-induced mice sepsis model, the enhanced generation of IL-10 was observed in ETO-treated mice, whereas pro-inflammatory cytokines were decreased, which significantly reduced the mortality of mice from LPS-induced lethal cytokine storm. Taken together, these results indicated that ETO may exhibit an anti-inflammatory role by upregulating the alteration of transcription factor Maf and promoting subsequential IL-10 secretion via PI3K/Akt pathway in LPS-induced macrophages. Therefore, ETO may serve as a potential anti-inflammatory agent and employed to severe pro-inflammatory diseases including COVID-19.

Qing-Fei-Pai-Du decoction and wogonoside exert anti-inflammatory action through down-regulating USP14 to promote the degradation of activating transcription factor 2.

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.

Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19.

BACKGROUND: The traditional Chinese medicine (TCM) formula Qing-Fei-Pai-Du decoction (QFPDD) was the most widely used prescription in China's campaign to contain COVID-19, which has exhibited positive effects. However, the underlying mode of action is largely unknown. PURPOSE: A systems pharmacology strategy was proposed to investigate the mechanisms of QFPDD against COVID-19 from molecule, pathway and network levels. STUDY DESIGN AND METHODS: The systems pharmacological approach consisted of text mining, target prediction, data integration, network study, bioinformatics analysis, molecular docking, and pharmacological validation. Especially, we proposed a scoring method to measure the confidence of targets identified by prediction and text mining, while a novel scheme was used to identify important targets from 4 aspects. RESULTS: 623 high-confidence targets of QFPDD's 12 active compounds were identified, 88 of which were overlapped with genes affected by SARS-CoV-2 infection. These targets were found to be involved in biological processes related with the development of COVID-19, such as pattern recognition receptor signaling, interleukin signaling, cell growth and death, hemostasis, and injuries of the nervous, sensory, circulatory, and digestive systems. Comprehensive network and pathway analysis were used to identify 55 important targets, which regulated 5 functional modules corresponding to QFPDD's effects in immune regulation, anti-infection, anti-inflammation, and multi-organ protection, respectively. Four compounds (baicalin, glycyrrhizic acid, hesperidin, and hyperoside) and 7 targets (AKT1, TNF-α, IL6, PTGS2, HMOX1, IL10, and TP53) were key molecules related to QFPDD's effects. Molecular docking verified that QFPDD's compounds may bind to 6 host proteins that interact with SARS-CoV-2 proteins, further supported the anti-virus effect of QFPDD. At last, in intro experiments validated QFPDD's important effects, including the inhibition of IL6, CCL2, TNF-α, NF-κB, PTGS1/2, CYP1A1, CYP3A4 activity, the up-regulation of IL10 expression, and repressing platelet aggregation. CONCLUSION: This work illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation, and multi-organ protection. It may strengthen the understanding of QFPDD and facilitate more application of this formula in the campaign to SARS-CoV-2.