Expressions of miR-21 TGF-beta/Smad signaling pathway in peripheral blood of bronchial asthma patients complicated with respiratory virus infection

OBJECTIVE: To investigate the expressions of peripheral blood microRNA-21(miR-21) and transforming growth factor-beta(TNF-beta)/Smad signaling transduction pathway in patients with bronchial asthma complicated with respiratory virus infection. METHODS: Totally 109 patients with asthma complicated with respiratory virus infection(study group) and 104 patients without virus infection(control group) in the Third People's Hospital of Gansu Province between Feb.2019 and Feb.2021 were selected for the cross-sectional study. The basic data of the two groups were collected, and parameters including vital signs, lung function, peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins were measured. According to the guidelines, the patients of the two groups were divided into acute exacerbation phase and stable phase. The examination results of each group were compared and the levels of peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins expression of patients with asthma complicated with respiratory virus infection were analyzed. RESULTS: In study group, the proportion of respiratory virus infection among 109 patients was 33.94% for influenza virus, 23.85% for human rhinovirus, 19.27% for respiratory syncytial virus, 10.09% for parainfluenza virus, 6.42% for adenovirus, 4.59% for human coronavirus and 1.83% for human metapneumovirus respectively. The proportion of patients with acute exacerbation phase in the study group was higher than that in the control group, and the levels of peripheral blood miR-21, TGF-beta1, Smad7, pSmad2 and pSmad3 were higher than those in control group(P<0.05). The levels of miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 in peripheral blood of patients with acute exacerbation phase of asthma were higher than those of patients with stable phase of asthma(P<0.05). There were no statistical differences in peripheral blood miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 levels in asthma patients with different virus infections. CONCLUSION: Early respiratory virus infections might lead to increased expression of peripheral blood miR-21 and increased activation of TGF-beta/Smad signaling pathway in patients with asthma, which played an important role in acute attack of asthma.

Structural and computational design of a SARS-CoV-2 spike antigen with improved expression and immunogenicity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern challenge the efficacy of approved vaccines, emphasizing the need for updated spike antigens. Here, we use an evolutionary-based design aimed at boosting protein expression levels of S-2P and improving immunogenic outcomes in mice. Thirty-six prototype antigens were generated in silico and 15 were produced for biochemical analysis. S2D14, which contains 20 computationally designed mutations within the S2 domain and a rationally engineered D614G mutation in the SD2 domain, has an ~11-fold increase in protein yield and retains RBD antigenicity. Cryo-electron microscopy structures reveal a mixture of populations in various RBD conformational states. Vaccination of mice with adjuvanted S2D14 elicited higher cross-neutralizing antibody titers than adjuvanted S-2P against the SARS-CoV-2 Wuhan strain and four variants of concern. S2D14 may be a useful scaffold or tool for the design of future coronavirus vaccines, and the approaches used for the design of S2D14 may be broadly applicable to streamline vaccine discovery.

Validation of online mindfulness-enhanced course for stress reduction in teachers.

Background: Mindfulness-based interventions have gained popularity as a means of reducing stress and increasing resilience among the preclinical population. The present study aimed to investigate the effects of an online mindfulness-enhanced course on stress reduction in teachers, especially since online learning and teaching have been frequently applied to respond to emergencies such as COVID-19-relevant school suspension. Methods: The study consisted of two phases. Phase 1 aimed to explore the relationship between teachers' perceived stress and mindfulness traits. In total of 6,252 teachers completed assessments of stress symptoms using the Chinese Perceived Stress Scale (CPSS) and occupational stress sources, as well as mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ). Phase 2 aimed to examine the effectiveness of the online mindfulness-enhanced course. In total of 132 teachers were randomly assigned to either receive a 3-week online mindfulness course specifically designed for stress reduction and emotion regulation (N = 66) or a matched active control group (N = 66) and their pre-training and post-training self-reported states (e.g., perceived stress, mindfulness level, practice time) were measured. Results: The detection rate of Health Risk Stress (≥26 scores) was as high as 61.72%, and a negative association between the score of FFMQ and perceived stress level was found. Importantly, compared to the control group, the mindfulness training group showed a significant decrease in perceived stress and negative emotion, as well as an increase in understanding of the core mechanisms of mindfulness after training. Additionally, individual improvement in FFMQ scores was predicted by practice time. Conclusions: The study showed a high percentage of teachers experiencing stress, and the data supported the reliability and validity of the brief online mindfulness-enhanced course designed to reduce stress and regulate emotion for frontline teachers.

Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients.

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: "asymptomatic", "COVID-19", "[18F]FDG PET/CT", and "nuclear medicine" were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

Profiling Humoral Immunity After Mixing and Matching COVID-19 Vaccines Using SARS-CoV-2 Variant Protein Microarrays.

In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130-0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.

Comparing and combining data from immune assays based on left-censored multivariate normal model assuming common assay differences across settings.

In vaccine research towards the prevention of infectious diseases, immune response biomarkers serve as an important tool for comparing and ranking vaccine candidates based on their immunogenicity and predicted protective effect. However, analyses of immune response outcomes can be complicated by differences across assays when immune response data are acquired from multiple groups/laboratories. Motivated by a real-world problem to accommodate the use of two different neutralization assays in COVID-19 vaccine trials, we propose methods based on left-censored multivariate normal model assuming common assay differences across settings, to adjust for differences between assays with respect to measurement error and the lower limit of detection. Our proposed methods integrate external paired-sample data with bridging assumptions to achieve two objectives, both using pooled data acquired from different assays: (i) comparing immunogenicity between vaccine regimens, and (ii) evaluating correlates of risk. In simulation studies, for the first objective, our method leads to unbiased calibrated assay mean with good coverage of bootstrap confidence interval, as well as valid test for immunogenicity comparison, while the alternative method assuming constant calibration model between assays leads to biased estimate of assay mean with undercoverage problem and invalid test with inflated type-I error; for the second objective, in the presence of noticeable left-censoring rate, our proposed method can drastically outperform the existing method that ignores left-censoring, in terms of reduced bias and improved precision. We apply the proposed methods to SARS-CoV-2 spike-pseudotyped virus neutralization assay data generated in vaccine and convalescent samples by two different laboratories.

The Impact and Mechanism of the COVID-19 Pandemic on Corporate Financing: Evidence from Listed Companies in China

The unexpected emergence of COVID-19 has placed businesses throughout the globe under considerable financial hardship, and financial constraints are a significant barrier to business expansion, particularly in developing countries with insufficient credit markets. Using yearly data for Chinese listed businesses from 367 cities, we examine the impact of COVID-19 on financial restrictions and the corresponding mechanisms of action by using a difference-in-differences (DID) methodology. We discover that COVID-19 leads to a significant increase of 0.117 in the KZ index of listed firms, i.e., an increase in financing constraints, and this result is consistent with various robustness tests. We also show that COVID-19 considerably lowers a company's capacity to obtain external financing by increasing debt costs and deterring commercial credit. The pandemic significantly reduced the company's commercial credit by 0.008 and increased debt costs by 0.2%. Moreover, the data demonstrate variation across industries, business ownership, and firm scale. Our findings indicate that decreasing information asymmetries facilitate successful adaptation to and recovery from external shocks. Our analysis suggests that governments should promulgate policies that are conducive to corporate financing to help companies maintain development during the outbreak of the epidemic and ensure economic sustainability.

Obstructive Sleep Apnea with COVID-19.

The novel coronavirus disease-2019 (COVID-19) and the ensuing pandemic have greatly impacted the global healthcare system due to its high infectiousness, associated high mortality, and a complete lack of immunity in the population. Globally, the COVID-19 pandemic has unleashed a health crisis that has not only seriously disrupted people's lives but also affected their normal sleep, along with physical and mental health; this situation is especially exacerbated in people suffering from pre-existing conditions, such as sleep apnea. A recent meta-analysis of 18 studies by Miller et al. (September 2020) showed that obstructive sleep apnea (OSA) is related to higher mortality and morbidity in patients with COVID-19 and is most likely independent of other risk factors. A recent meta-analysis indicated that COVID-19 patients with OSA are more severely affected than those without OSA, thereby providing further evidence that concurrent OSA may elevate the severity of COVID-19 infection, along with the risk of mortality. The COVID-19 pandemic has significantly impacted the diagnosis and therapeutic management of patients with OSA. Thus, it is necessary to identify and develop new diagnostic and therapeutic avenues in the future. In this context, the current study summarizes known associations between COVID-19 and OSA and the regular diagnostic and therapeutic strategies for OSA in the light of COVID-19 pandemic prevention and control.

Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19.

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.

Analysis of the correlations between insomnia and mental health during the COVID-19 pandemic in Germany.

Objective: This study evaluates correlations between insomnia and mental health during the COVID-19 pandemic in Germany. Methods: The internet-based International COVID-19 Sleep Study (ICOSS) questionnaire including sociodemographic questions as well as sleep- and emotion-related scales was distributed in Germany during the COVID-19 pandemic from May 1 to September 30, 2020. Insomnia and mental state were assessed using the Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ), Generalized Anxiety Disorder (GAD-2), and visual analogue scale. Qualitative analyses of demographic characteristics were performed and correlation analyses of the variables calculated. Results: A total of 1103 individuals participated and 858 valid questionnaires (70.61% females) were obtained. Mean age and body mass index were 41.97 ± 12.9 years and 26 ± 5.9 kg/m2, respectively. Most participants were married (n = 486, 56.6%), living in the city (n = 646, 75.3%), and white (n = 442, 51.5%). The prevalence of insomnia, anxiety, and depression was 19.5% (ISI > 7), 6.6% (GAD-2 > 3), and 4.8% (PHQ-2 > 3), respectively. Compared to the insomnia group, the mean and median ISI, PHQ­4, PHQ­2, and GAD­2 scores of the non-insomnia group were lower, while their mean and median quality of life and quality of health scores were significantly higher (P < 0.05). Pearson correlation analysis showed a positive correlation between the ISI and PHQ­2 (r = 0.521, P < 0.001), GAD­2 (r = 0.483, P < 0.001), and PHQ­4 scores (r = 0.562, P < 0.001); however, the ISI score negatively correlated with the quality of life (r = -0.490, P < 0.001) and quality of health scores (r = -0.437, P < 0.001). Conclusion: Insomnia, anxiety, and depression were very prevalent during the pandemic. Anxiety and depression were more severe in the insomnia than in the non-insomnia group, and insomnia and mental health are closely related.

"Big data" driven tech mining and ST&I management: an introduction.

Since the first Global Tech Mining (GTM) conference was held in Atlanta in 2011, the GTM conference has created a platform to connect tech mining researchers, exchange ideas and research progress, and promote collaborations. When it came to its 10th anniversary in 2020, COVID-19 forced the GTM conference into an online format. In tumultuous times for ST&I research activity, the GTM conference sought to focus on several issues: How to better collect and combine multiple "large data" sources? How to analyze these data effectively? And how to utilize these results more powerfully in ST&I management? In this collection, 15 papers are selected after evaluating by the science advisory committee, the guest editor team, and our peer review experts to address the following aspects regarding "tech mining": (1) DATA: Maximizing the potential of traditional and novel data; (2) METHODS: Advancing and integrating methods; (3) APPLICATIONS: Innovative analyses translating to usefulintelligence.

Glycyrrhetinic acid: A potential drug for the treatment of COVID-19 cytokine storm.

BACKGROUND: The cytokine storm (CS) triggered by coronavirus disease 2019 (COVID-19) has caused serious harm to health of humanity and huge economic burden to the world, and there is a lack of effective methods to treat this complication. PURPOSE: In this research, we used network pharmacology and molecular docking to reveal the interaction mechanism in the glycyrrhetinic acid (GA) for the treatment of CS, and validated the effect of GA intervention CS by experiments. STUDY DESIGN: First, we screened corresponding target of GA and CS from online databases, and obtained the action target genes through the Venn diagram. Then, protein-protein interaction (PPI) network, Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the action target genes were acquired by R language to predict its mechanism. Next, molecular docking was performed on core targets. Finally, experiments in which GA intervened in lipopolysaccharide (LPS)-induced CS were implemented. RESULTS: 84 action target genes were obtained from online database. The PPI network of target genes showed that TNF, IL6, MAPK3, PTGS2, ESR1 and PPARG were considered as the core genes. The results of GO and KEGG showed that action target genes were closely related to inflammatory and immune related signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, Human cytomegalovirus infection, PPAR signaling pathway and so on. Molecule docking results prompted that GA had fine affinity with IL6 and TNF proteins. Finally, in vivo and in vitro experimental results showed that GA could significantly inhibit LPS-induced CS. CONCLUSION: GA has a potential inhibitory effect on CS, which is worthy of further exploration.

A Rare Adverse Effect of the COVID-19 Vaccine on Autoimmune Encephalitis.

Since countries commenced COVID-19 vaccination around the world, many vaccine-related adverse effects have been reported. Among them, short-term memory loss with autoimmune encephalitis (AE) was reported as a rare adverse effect. Since case numbers are limited, this brief report may draw the attention of the medical community to this uncommon adverse effect and serve as a reference for future vaccine improvement. However, given the high risk of adverse outcomes when infected with SARS-CoV-2 and the clearly favorable safety/tolerability profile of existing vaccines, vaccination is still recommended.

Erratum to: Analysis of the correlations between insomnia and mental health during the COVID-19 pandemic in Germany.

[This corrects the article DOI: 10.1007/s11818-022-00347-7.].

Investigation of the Mechanism of Periploca forrestii against Rheumatoid Arthritis with Network Pharmacology-Based Analysis.

Periploca forrestii Schltr (P. forrestii) is an edible medicinal herb with various health benefits such as treating antirheumatoid arthritis (RA), reducing inflammation, and preventing tumor growth. The active ingredients in P. forrestii responsible for its protective effect against RA, however, remain unknown. In this study, the active ingredient of P. forrestii and its potential mechanism of action against RA were investigated by network pharmacology and enrichment analysis. The methods included predicting target genes of P. forrestii, constructing a protein interaction network, and performing gene-ontology (GO) and Kyoto-encyclopedia of genes and genomes (KEGG) enrichment analysis. We discovered targets of RA through retrieval of OMIM and GeneCards public databases. Cardiac glycosides (CGs) are considered the primarily active ingredients of P. forrestii, and the target genes of GCs were discovered to be overlapped with relevant targets of RA using the Venn diagram. After that, prediction of relevant targets of P. forrestii was accomplished with a network pharmacology-based approach. Through the Venn diagram, we discovered 99 genes shared in the target genes of P. forrestii and RA. Gene enrichment analysis showed that the mechanisms of CGs against RA are associated with 55 signaling pathways, including endocrine resistance, Epstein-Barr virus infection, bladder cancer, prostate cancer, and coronavirus disease (COVID-19) signaling pathways. Coexpression analysis indicated ADSL, ATIC, AR, CCND1, MDM2, and HSP90AA1 as the hub genes between putative targets of P. forrestii-derived CGs and known therapeutic targets of RA. In conclusion, we clarified the mechanism of action of P. forrestii against RA, which would provide a basis for further understanding the clinical application of P. forrestii.

How scientific research reacts to international public health emergencies: a global analysis of response patterns.

As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.