Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans (preprint)

The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (xpEHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are less vulnerable to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.

Using Adamic-Adar Index Algorithm to Predict Volunteer Collaboration: Less is More (preprint)

Social networks exhibit a complex graph-like structure due to the uncertainty surrounding potential collaborations among participants. Machine learning algorithms possess generic outstanding performance in multiple real-world prediction tasks. However, whether machine learning algorithms outperform specific algorithms designed for graph link prediction remains unknown to us. To address this issue, the Adamic-Adar Index (AAI), Jaccard Coefficient (JC) and common neighbour centrality (CNC) as representatives of graph-specific algorithms were applied to predict potential collaborations, utilizing data from volunteer activities during the Covid-19 pandemic in Shenzhen city, along with the classical machine learning algorithms such as random forest, support vector machine, and gradient boosting as single predictors and components of ensemble learning. This paper introduces that the AAI algorithm outperformed the traditional JC and CNC, and other machine learning algorithms in analyzing graph node attributes for this task.

Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro.

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment.

Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. A novel oral noncovalent inhibitor of 3C-like protease, named WU-04, was developed as a promising drug candidate for COVID-19 treatment.

Breakthrough infection with Omicron subvariant BF.7 induces broadly neutralizing antibodies to SARS-CoV-2 variants including XBB lineage (preprint)

Since China eased its COVID-19 response strategies in late 2022, we have been witnessing a rapid and wide spread of SARS-CoV-2 infection across the major cities, including capital Beijing, where Omicron subvariant BF.7 has been dominating the infection. Here, we show that such expansion is unlikely due to a higher binding affinity of BF.7 to human receptor angiotensin-converting enzyme 2 (ACE2) as the similar binding activities were found for other Omicron subvariants tested such as BA.1, BA.5.2, BQ.1, BQ.1.1, XBB, and XBB.1. Additionally, through study of antibody response among six different clinical cohorts, we found that primary infection with BF.7 among the unvaccinated individuals only elicited type-specific neutralizing antibodies to the infecting virus and its close related strains. By a distinct contrast, breakthrough infection with BF.7 among the vaccinated individuals, particularly those severe cases, induced strong and broadly neutralizing antibodies to a diverse panel of SARS-CoV-2 variants and Omicron subvariants including the XBB lineage. A deeper understanding of how these broadly neutralizing antibodies were generated or boosted by BF.7 breakthrough infection will hold the key for augmenting antibody immunity against diverse SARS-CoV-2 variants.

Atomically Dispersed d10 s-block Au Boosts Photocatalytic 1e- Water Oxidation for Self-Cleaning, Sanitation and Safe Drinkable Water­­ (preprint)

Providing affordable safe drinking water and universal sanitation poses a grand challenge especially after the global COVID-19 pandemic. In this work, we developed atomically dispersed Au on potassium-incorporated polymeric carbon nitride (AuKPCN) that could simultaneously boost photocatalytic generation of ·OH and H2O2 with an apparent quantum efficiency over 90% at 400–420 nm. The introduction of potassium into the poly(heptazine imide) matrix formed strong K-N bonds, preventing Au from forming strong interactions with N. Instead, Au formed a bond with C, only having weak interactions with N on KPCN, which rendered Au with an oxidation number close to 0. The results of in-situ vibrational spectroscopy, isotopic experiments, transient absorption spectroscopy and time-dependent density functional theory (TDDFT) simulations revealed that the low-valent Au could append its 6s orbital into the band diagram of AuKPCN that formed a trapping level for generating highly localized holes under photoexcitation. These highly localized holes could boost the 1e− water oxidation reaction to form highly oxidative ·OH and simultaneously unbind the hydrogen atom in H2O molecule, which greatly promoted the hydrogenation process during the 2e− oxygen reduction reaction (ORR) to produce H2O2. The photogenerated ·OH on AuKPCN led to a more than 120-fold efficiency enhancement for visible-light-response superhydrophilicity as compared to that of the commercial TiO2. The onsite fixed-bed reactor under photo-illumination achieved a remarkable 132.5 LH2O m− 2 day− 1 water disinfection rate (lg6), which is about 30 times superior than the TiO2 photocatalytic advanced oxidation process in the most ideal case (< 4 LH2O m− 2 day− 1; lg4).

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools.

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Setting up a three-stage pre-endoscopy triage during the coronavirus disease 2019 pandemic: A multicenter observational study

Objectives Between May and July 2021, the coronavirus disease 2019 (COVID-19) pandemic led to a sharp surge in community transmission in Taiwan. We present a three-stage restructuring process of pre-endoscopy triage at the beginning of the pandemic, which can support urgent endoscopic procedures while protecting endoscopy staff. Methods The pre-endoscopy triage framework was set up with three checkpoints at the hospital entrance, outpatient department, and endoscopy unit, with a specific target patient population and screening methods. Relevant data included the number of endoscopic procedures performed, outpatient department visits, and performing screening methods such as temperature measurement, travel, occupation, contact, and clustering history checking, polymerase chain reaction assay, and rapid antigen test. Results Forehead temperature measurement and verification of travel, occupation, contact, and clustering history provided rapid, easy, and early mass screening of symptomatic patients at the hospital entrance. During the pandemic, outpatient department visits and endoscopic procedures decreased by 37% and 64%, respectively. The pre-endoscopy screening methods used displayed regional variations in COVID-19 prevalence. Among 16 endoscopy units with a community prevalence of ≥ 31.04 cases per 100,000 residents, 12 (75%) used polymerase chain reaction assay and four (25%) used rapid antigen test to identify asymptomatic patients before endoscopy. Of 6540 pre-endoscopy screening patients, 15 (0.23%) tested positive by laboratory testing. No endoscopy-related nosocomial COVID-19 infections were reported during the pandemic. Conclusions We present a three-stage pre-endoscopy triage based on the local laboratory capacity, medical resources, and community prevalence. These measures could be useful during the COVID-19 pandemic.

The Impact of Consumers' Loneliness and Boredom on Purchase Intention in Live Commerce During COVID-19: Telepresence as a Mediator.

This paper examines the relationship between consumer loneliness, boredom, telepresence, influencer-brand image congruence and purchase intention by investigating consumers of live commerce during the COVID-19 period. With the help of an online survey website, survey data was gathered on 550 Chinese customers who experienced live commerce shopping in China. Although previous studies have shown that consumer boredom and loneliness have an impact on purchase intention, the mechanism of influence remains unclear. As a result, additional research is needed to study the link between boredom and loneliness and customer purchase intention. Consumers' purchase intention was influenced by their feelings of loneliness and boredom. Telepresence played a mediating role in the impact of loneliness and boredom on purchase intention. Influencer-brand image congruence played a moderating role in the impact of consumers' boredom on purchase intention. The study results contribute to the research of factors impacting consumers' purchase intention. In addition, this study can help live commerce merchants better understand the impact factors of consumers' purchase intention and contribute to the development of live commerce.

BRET-Based Self-Cleaving Biosensors for SARS-CoV-2 3CLpro Inhibitor Discovery.

The 3C-like protease (3CLpro) of SARS-CoV-2 is an attractive drug target for developing antivirals against SARS-CoV-2. A few small molecule inhibitors of 3CLpro are in clinical trials for COVID-19 treatments, and more inhibitors are under development. One limiting factor for 3CLpro inhibitors development is that the cellular activities of such inhibitors should be evaluated in Biosafety Level 3 (BSL-3) laboratories. Here, we design DNA-coded biosensors that can be used in BSL-2 laboratories to set up cell-based assays for 3CLpro inhibitor discovery. The biosensors were constructed by linking a green fluorescent protein (GFP2) to the N-terminus and a Renilla luciferase (RLuc8) to the C-terminus of SARS-CoV-2 3CLpro, with the linkers derived from the cleavage sequences of 3CLpro. After overexpression of the biosensors in human embryonic kidney (HEK) 293T cells, 3CLpro can be released from GFP2 and RLuc by self-cleavage, resulting in a decrease of the bioluminescence resonance energy transfer (BRET) signal. Using one of these biosensors, pBRET-10, we evaluated the cellular activities of several 3CLpro inhibitors. These inhibitors restored the BRET signal by blocking the proteolysis of pBRET-10, and their relative activities measured using pBRET-10 were consistent with their previously reported anti-SARS-CoV-2 activities. We conclude that the biosensor pBRET-10 is a useful tool for SARS-CoV-2 3CLpro inhibitor discovery. IMPORTANCE The virus proteases 3CLpro are validated drug targets for developing antivirals to treat coronavirus diseases, such as COVID-19. However, the development of 3CLpro inhibitors relies heavily on BSL-3 laboratories. Here, we report a series of BRET-based self-cleaving biosensors that can be used to set up cell-based assays to evaluate the cell permeability and cellular activity of SARS-CoV-2 3CLpro inhibitors in BSL-2 laboratories. The cell-based assay is suitable for high-throughput screening for 3CLpro inhibitors because of the simplicity and good reproducibility of our biosensors. The design strategy can also be used to design biosensors for other viral proteases for which the activation processes involve the self-cleavage of polyproteins.

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

Intraseasonal variation of the northeast Asian anomalous anticyclone and its impacts on PM2.5 pollution in the North China Plain in early winter

The canonical view of the northeast Asian anomalous anticyclone (NAAA) is a crucial factor for determining poor air quality (i.e., higher particulate matter, PM2.5 concentrations) in the North China Plain (NCP) on the interannual timescale. However, there is considerable intraseasonal variability in the NAAA in early winter (November–January), and the corresponding mechanism of its impacts on PM2.5 pollution in the NCP is not well understood. Here, we find that the intraseasonal NAAA usually establishes quickly on day 3 prior to its peak day with a duration of 8 d, and its evolution is closely tied to the Rossby wave from upstream (i.e., the North Atlantic). Moreover, we find that the NAAA with a westward tilt might be mainly related to the wavenumbers 3–4. Further results reveal that against this background, the probability of regional PM2.5 pollution for at least 3 d in the NCP is as high as 69 % (80 % at least 2 d) in the Nov–Jan (NDJ) period 2000–2021. In particular, air quality in the NCP tends to deteriorate on day 2 prior to the peak day and reaches a peak on the next day with a life cycle of 4 d. In the course of PM2.5 pollution, a shallower atmospheric boundary layer and stronger surface southerly wind anomaly associated with the NAAA in the NCP appear 1 d earlier than poor air quality, which provides dynamic and thermal conditions for the accumulation of pollutants and finally occurrence of the PM2.5 pollution on the following day. Furthermore, we show that the stagnant air leading to poor air quality is determined by the special structure of temperature in the vertical direction of the NAAA, while weak ventilation conditions might be related to a rapid build-up of the NAAA. The present results quantify the impact of the NAAA on PM2.5 pollution in the NCP on the intraseasonal timescale.

Optimal Neural Network Approximation of Wasserstein Gradient Direction via Convex Optimization (preprint)

The computation of Wasserstein gradient direction is essential for posterior sampling problems and scientific computing. The approximation of the Wasserstein gradient with finite samples requires solving a variational problem. We study the variational problem in the family of two-layer networks with squared-ReLU activations, towards which we derive a semi-definite programming (SDP) relaxation. This SDP can be viewed as an approximation of the Wasserstein gradient in a broader function family including two-layer networks. By solving the convex SDP, we obtain the optimal approximation of the Wasserstein gradient direction in this class of functions. Numerical experiments including PDE-constrained Bayesian inference and parameter estimation in COVID-19 modeling demonstrate the effectiveness of the proposed method.

Photocatalytic Chemical Crosslinking for Profiling RNA–Protein Interactions in Living Cells

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome‐wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX‐MS) and RNA sequencing (PhotoCAX‐seq) for the study of the composition and dynamics of protein‐RNA interactions. By integrating the blue light‐triggered photocatalyst with a dual‐functional RNA–protein crosslinker (RP‐linker) and the phase separation‐based enrichment strategy, PhotoCAX‐MS revealed a total of 2044 RBPs in human HEK293 cells. We further employed PhotoCAX to investigate the dynamic change of RBPome in macrophage cells upon LPS‐stimulation, as well as the identification of RBPs interacting directly with the 5′ untranslated regions of SARS‐CoV‐2 RNA. [ FROM AUTHOR] Copyright of Angewandte Chemie International Edition is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Evolutionary Game Analysis of Co-Opetition Strategy in Energy Big Data Ecosystem under Government Intervention

This study discusses how to facilitate the barrier-free circulation of energy big data among multiple entities and how to balance the energy big data ecosystem under government supervision using dynamic game theory. First, we define the related concepts and summarize the recent studies and developments of energy big data. Second, evolutionary game theory is applied to examine the interaction mechanism of complex behaviors between power grid enterprises and third-party enterprises in the energy big data ecosystem, with and without the supervision of government. Finally, a sensitivity analysis is conducted on the main factors affecting co-opetition, such as the initial participation willingness, distribution of benefits, free-riding behavior, government funding, and punitive liquidated damages. The results show that both government supervision measures and the participants’ own will have an impact on the stable evolution of the energy big data ecosystem in the dynamic evolution process, and the effect of parameter changes on the evolution is more significant under the state of no government supervision. In addition, the effectiveness of the developed model in this work is verified by simulated analysis. The present model can provide an important reference for overall planning and efficient operation of the energy big data ecosystem.

A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis.

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein-protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K-AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible "dangerous liaison" between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.

The Effect of Post-Graduate Year Training on the Self-Efficacy and Emotional Traits of Physicians Facing the COVID-19 Pandemic.

Background: Taiwan implemented the post-graduate year (PGY) training to reform the medical education system to provide holistic medical care after severe acute respiratory syndrome in 2003. In late 2019, COVID-19 quickly spread across the globe and became a pandemic crisis. This study aimed to investigate whether the establishment of the PGY training had positive effects on the self-efficacy and emotional traits of medical workers. Methods: One hundred and ten physicians, including PGY, residents, and visiting staff, were investigated using the General Self-Efficacy Scale (GSES) and Emotional Trait and State Scale (ETSS), and their feedback and suggestions were collected. An exploratory factor analysis was done to reduce the factor dimensions using the varimax rotation method, which was reduced to four factors: "the ability to cope with ease", "proactive ability", "negative emotion", and "positive emotion". A comparison with and without PGY training when facing the COVID-19 pandemic was conducted. Results: Those who had received PGY training (n = 77) were younger, had a lower grade of seniority, and had less practical experience than those who had not received PGY (n = 33). Those who had received PGY training had significantly higher scores for the factors "ability to cope with ease", "proactive ability", and "positive emotion" than those who had not received PGY training. Conclusion: The study revealed that PGY training may have had positive effects on the personal self-efficacy and emotional traits of physicians coping with the COVID-19 pandemic.