How Does the Degree of Competition in an Industry Affect a Company's Environmental Management and Performance?

Environmental management, which was recognized as a functional part of corporate management, has recently been recognized as a strategic element of all business activities. It can be defined as a series of management activities to improve environmental performance throughout the business process and simultaneously achieve profitability and sustainability. Accordingly, businesses are now abandoning the existing management philosophy that economic and environmental feasibility are inevitably in conflict and establishing strategies and methods to achieve both. Meanwhile, industry affects the business performance of individual companies. Since the performance of a company tends to be influenced by the intensity of competition in an industry, it is necessary to analyze the structural factors that determine the intensity of competition in an industry in order to predict the future performance of a company. Therefore, we studied how environmental management affects corporate performance given the level of industry competition. The results are as follows. First, environmental management positively impacts corporate performance. Second, a high level of competition within an industry moderates the relationship between environmental management and corporate performance. By verifying the influence of the industry to which a company belongs, that is, the level of competition within the industry, we confirm that a company's environmental management can be used strategically to gain a competitive advantage. With the finding that the impact of a company's environmental practices differs by industry in line with the degree of competition, we expect this study to be helpful for future research into strategic ESG activities.

Energetic vs. entropic stabilization between a Remdesivir analogue and cognate ATP upon binding and insertion into the active site of SARS-CoV-2 RNA dependent RNA polymerase.

SARS-CoV-2 RNA dependent RNA polymerase (RdRp) serves as a highly promising antiviral drug target such as for a Remdesivir nucleotide analogue (RDV-TP or RTP). In this work, we mainly used alchemical all-atom simulations to characterize relative binding free energetics between the nucleotide analogue RTP and natural cognate substrate ATP upon initial binding and pre-catalytic insertion into the active site of SARS-CoV-2 RdRp. Natural non-cognate substrate dATP and mismatched GTP were also examined for computation control. We first identified significant differences in dynamical responses between nucleotide initial binding and subsequent insertion configurations to the open and closed active sites of the RdRp, respectively, though the RdRp protein conformational changes between the active site's open and closed states are subtle. Our alchemical simulations indicated that upon initial binding (active site open), RTP and ATP show similar binding free energies to the active sites while in the insertion state (active site closed), ATP is more stabilized (∼-2.4 kcal mol-1) than RTP in free energetics. Additional analyses show, however, that RTP is more stabilized in binding energetics than ATP, in both the insertion and initial binding states, with RTP more stabilized due to the electrostatic energy in the insertion state and due to vdW energy in the initial binding state. Hence, it appears that natural cognate ATP still excels at association stability with the RdRp active site due to that ATP maintains sufficient flexibilities e.g., in base pairing with the template, which exemplifies an entropic contribution to the cognate substrate stabilization. These findings highlight the importance of substrate flexibilities in addition to energetic stabilization in antiviral nucleotide analogue design.

Murine Coronavirus Disease 2019 Lethality Is Characterized by Lymphoid Depletion Associated with Suppressed Antigen-Presenting Cell Functionality.

The disease severity of coronavirus disease 2019 (COVID-19) varies considerably from asymptomatic to serious, with fatal complications associated with dysregulation of innate and adaptive immunity. Lymphoid depletion in lymphoid tissues and lymphocytopenia have both been associated with poor disease outcomes in patients with COVID-19, but the mechanisms involved remain elusive. In this study, human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were used to investigate the characteristics and determinants of lethality associated with the lymphoid depletion observed in SARS-CoV-2 infection. The lethality of Wuhan SARS-CoV-2 infection in K18-hACE2 mice was characterized by severe lymphoid depletion and apoptosis in lymphoid tissues related to fatal neuroinvasion. The lymphoid depletion was associated with a decreased number of antigen-presenting cells (APCs) and their suppressed functionality below basal levels. Lymphoid depletion with reduced APC function was a specific feature observed in SARS-CoV-2 infection but not in influenza A infection and had the greatest prognostic value for disease severity in murine COVID-19. Comparison of transgenic mouse models resistant and susceptible to SARS-CoV-2 infection revealed that suppressed APC function could be determined by the hACE2 expression pattern and interferon-related signaling. Thus, we demonstrated that lymphoid depletion associated with suppressed APC function characterizes the lethality of COVID-19 mouse models. Our data also suggest a potential therapeutic approach to prevent the severe progression of COVID-19 by enhancing APC functionality.

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

Blending a sweet pill to swallow with TRIZ and industry talks for enhanced learning during the COVID-19 pandemic

BACKGROUND: While studies have investigated relationships among learning motivation, social presence, and cognitive presence, there appear to be no studies on the inclusion of industry talks and the theory of inventive problem-solving (TRIZ) in strengthening engineering students' learning motivation, social presence, and cognitive presence within a blended learning setting. OBJECTIVE: This study investigated the influence of industry talks and TRIZ on learning motivation, social presence, and cognitive presence in a blended learning environment. METHODS: Data samples were obtained from 98 engineering students in a blended learning course and analysed using Spearman's correlation test, regression, ANOVA, and t-test. RESULTS: Findings suggested that TRIZ and industry talks strongly, positively, and significantly correlated with learning motivation, social presence, and cognitive presence. A well-rounded learning experience compounded of TRIZ and industry talks significantly affected learning motivation, social presence, and cognitive presence, thereby enhancing students' programme outcome (PO) achievement. CONCLUSIONS: These findings can be attributed to the students' independent learning capabilities with TRIZ and industry talks. Analogically, embracing TRIZ and industry talks helps turn blended learning into a "sweet instead of bitter pill to swallow" for engineering students in the face of the COVID-19 pandemic.

Trends in Depressive Symptoms and Suicidality of South Korean Adolescents: Comparison of Expected and Observed Prevalence During the COVID-19 Pandemic.

PURPOSE: Depressive symptoms and suicidality of adolescents during the COVID-19 pandemic are emerging public health issues. However, there is a lack of representative studies on adolescents' mental health that considers the preceding secular trends. METHODS: This descriptive study used nationally representative cross-sectional data of Korean adolescents from the Korea Youth Risk Behavior Survey from 2005 to 2020 (N = 1,035,382). We utilized joinpoint regression analysis to explore the temporal prevalence trends of depressive symptoms, suicidal ideation, and suicide attempts. Based on the annual percentage change until 2019, the expected and actual prevalence in 2020 (N = 54,948) was compared to describe departures of prevalence from the trend line. These trends between sex, school level, ethnic status, and socioeconomic status were also compared. RESULTS: Considering the recent increase in secular trends until 2019, the actual observed values in 2020 were lower than expected by 13% in depressive symptoms, 20% in suicidal ideation, and 40% in suicide attempts. The gap between sexes, school levels, ethnic status, and socioeconomic groups was similar or narrowed in 2020 compared to previous trends. DISCUSSION: We observed a lower prevalence of depressive symptoms and suicidality among Korean adolescents than expected about 9 months from the beginning of the COVID-19 pandemic despite the recent increase in secular trends.

Genesis, evolution and effectiveness of Singapore's national sorting logic and home recovery policies in handling the COVID-19 Delta and Omicron waves

Singapore developed several novel strategies to transition towards "living with COVID-19", while protecting hospital capacity. The Home Recovery Programme (HRP) was a national, centrally-administered programme that leveraged technology and telemedicine to allow low-risk individuals to safely recover at home. The HRP was subsequently expanded by partnering primary care doctors in caring for more cases in the community. A key enabler was the National Sorting Logic (NSL), a multi-step triage algorithm allowing risk-stratification of large numbers of COVID-19 patients at a national-level. At the core of the NSL was a risk assessment criterion, comprising of Comorbidities-of-concern, Age, Vaccination status, Examination/clinical findings and Symptoms (CAVES). The NSL sorted all COVID-19 cases into the various levels of care – Primary Care, HRP, COVID-19 Treatment Facility and Hospital. By adopting a national approach towards managing healthcare capacities and triaging COVID-19 patients, Singapore was able to prioritize healthcare resources for high-risk individuals and prevent hospital capacities from being overwhelmed. As part of the national response strategy to tackle COVID-19, Singapore set up and integrated key national databases to enable responsive data analysis and support evidence-based policy decisions. Using data collected between 30 August 2021 to 8 June 2022, we conducted a retrospective cohort study to evaluate the outcomes and effectiveness of vaccination policies, NSL and home-based recovery. A total of 1,240,183 COVID-19 cases were diagnosed during this period, spanning both Delta and Omicron waves, Overall, Singapore experienced very low severity (0.51%) and mortality (0.11%) rates. Vaccinations significantly lowered severity and mortality risks across all age groups. The NSL was effective in predicting risk of severe outcomes and was able to right-site >93% of cases into home-based recovery. By leveraging high vaccination rates, technology and telemedicine, Singapore was able to safely navigate through two COVID-19 waves without impacting severity/mortality rates nor overwhelming hospital capacities.

Dissecting nucleotide selectivity in viral RNA polymerases.

Designing antiviral therapeutics is of great concern per current pandemics caused by novel coronavirus or SARS-CoV-2. The core polymerase enzyme in the viral replication/transcription machinery is generally conserved and serves well for drug target. In this work we briefly review structural biology and computational clues on representative single-subunit viral polymerases that are more or less connected with SARS-CoV-2 RNA dependent RNA polymerase (RdRp), in particular, to elucidate how nucleotide substrates and potential drug analogs are selected in the viral genome synthesis. To do that, we first survey two well studied RdRps from Polio virus and hepatitis C virus in regard to structural motifs and key residues that have been identified for the nucleotide selectivity. Then we focus on related structural and biochemical characteristics discovered for the SARS-CoV-2 RdRp. To further compare, we summarize what we have learned computationally from phage T7 RNA polymerase (RNAP) on its stepwise nucleotide selectivity, and extend discussion to a structurally similar human mitochondria RNAP, which deserves special attention as it cannot be adversely affected by antiviral treatments. We also include viral phi29 DNA polymerase for comparison, which has both helicase and proofreading activities on top of nucleotide selectivity for replication fidelity control. The helicase and proofreading functions are achieved by protein components in addition to RdRp in the coronavirus replication-transcription machine, with the proofreading strategy important for the fidelity control in synthesizing a comparatively large viral genome.

Effects of Virtual Reality Exercise Program on Blood Glucose, Body Composition, and Exercise Immersion in Patients with Type 2 Diabetes.

BACKGROUND: This study is a preliminary study to examine the effect of a virtual reality exercise program (VREP) on type 2 diabetes patients. METHOD: This is a randomized controlled trial for patients with type 2 diabetes (glycated hemoglobin ≥ 6.5%), diagnosed by a specialist. The virtual reality environment was set up by attaching an IoT sensor to an indoor bicycle and linking it with a smartphone, enabling exercise in an immersive virtual reality through a head-mounted display. The VREP was implemented three times a week, for two weeks. The blood glucose, body composition, and exercise immersion were analyzed at baseline, and two weeks before and after the experimental intervention. RESULT: After VREP application, the mean blood glucose (F = 12.001 p < 0.001) and serum fructosamine (F = 3.274, p = 0.016) were significantly lower in the virtual reality therapy (VRT) and indoor bicycle exercise (IBE) groups than in the control group. There was no significant difference in the body mass index between the three groups; however, the muscle mass of participants in the VRT and IBE groups significantly increased compared with that of the control (F = 4.445, p = 0.003). Additionally, exercise immersion was significantly increased in the VRT group compared with that in the IBE and control groups. CONCLUSION: A two week VREP had a positive effect on blood glucose, muscle mass, and exercise immersion in patients with type 2 diabetes, and is highly recommended as an effective intervention for blood glucose control in type 2 diabetes.

Genesis, evolution and effectiveness of Singapore's national sorting logic and home recovery policies in handling the COVID-19 Delta and Omicron waves.

Singapore developed several novel strategies to transition towards "living with COVID-19", while protecting hospital capacity. The Home Recovery Programme (HRP) was a national, centrally-administered programme that leveraged technology and telemedicine to allow low-risk individuals to safely recover at home. The HRP was subsequently expanded by partnering primary care doctors in caring for more cases in the community. A key enabler was the National Sorting Logic (NSL), a multi-step triage algorithm allowing risk-stratification of large numbers of COVID-19 patients at a national-level. At the core of the NSL was a risk assessment criterion, comprising of Comorbidities-of-concern, Age, Vaccination status, Examination/clinical findings and Symptoms (CAVES). The NSL sorted all COVID-19 cases into the various levels of care - Primary Care, HRP, COVID-19 Treatment Facility and Hospital. By adopting a national approach towards managing healthcare capacities and triaging COVID-19 patients, Singapore was able to prioritize healthcare resources for high-risk individuals and prevent hospital capacities from being overwhelmed. As part of the national response strategy to tackle COVID-19, Singapore set up and integrated key national databases to enable responsive data analysis and support evidence-based policy decisions. Using data collected between 30 August 2021 to 8 June 2022, we conducted a retrospective cohort study to evaluate the outcomes and effectiveness of vaccination policies, NSL and home-based recovery. A total of 1,240,183 COVID-19 cases were diagnosed during this period, spanning both Delta and Omicron waves, Overall, Singapore experienced very low severity (0.51%) and mortality (0.11%) rates. Vaccinations significantly lowered severity and mortality risks across all age groups. The NSL was effective in predicting risk of severe outcomes and was able to right-site >93% of cases into home-based recovery. By leveraging high vaccination rates, technology and telemedicine, Singapore was able to safely navigate through two COVID-19 waves without impacting severity/mortality rates nor overwhelming hospital capacities.

Prevalence and prognosis of acute pancreatitis in critically ill patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU). METHODS: This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality. RESULTS: A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection. CONCLUSIONS: Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.

Distinct Molecular Mechanisms Characterizing Pathogenesis of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has continued for over 2 years, following the outbreak of coronavirus-19 (COVID-19) in 2019. It has resulted in enormous casualties and severe economic crises. The rapid development of vaccines and therapeutics against SARS-CoV-2 has helped slow the spread. In the meantime, various mutations in the SARS-CoV-2 have emerged to evade current vaccines and therapeutics. A better understanding of SARS-CoV-2 pathogenesis is a prerequisite for developing efficient, advanced vaccines and therapeutics. Since the outbreak of COVID-19, a tremendous amount of research has been conducted to unveil SARSCoV-2 pathogenesis, from clinical observations to biochemical analysis at the molecular level upon viral infection. In this review, we discuss the molecular mechanisms of SARS-CoV-2 propagation and pathogenesis, with an update on recent advances.

Comparison of the pathogenesis of SARS-CoV-2 infection in K18-hACE2 mouse and Syrian golden hamster models.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, causes life-threatening disease. This novel coronavirus enters host cells via the respiratory tract, promoting the formation of severe pulmonary lesions and systemic disease. Few animal models can simulate the clinical signs and pathology of COVID-19 patients. Diverse preclinical studies using K18-hACE2 mice and Syrian golden hamsters, which are highly permissive to SARS-CoV-2 in the respiratory tract, are emerging; however, the systemic pathogenesis and cellular tropism of these models remain obscure. We intranasally infected K18-hACE2 mice and Syrian golden hamsters with SARS-CoV-2, and compared the clinical features, pathogenesis, cellular tropism and infiltrated immune-cell subsets. In K18-hACE2 mice, SARS-CoV-2 persistently replicated in alveolar cells and caused pulmonary and extrapulmonary disease, resulting in fatal outcomes. Conversely, in Syrian golden hamsters, transient SARS-CoV-2 infection in bronchial cells caused reversible pulmonary disease, without mortality. Our findings provide comprehensive insights into the pathogenic spectrum of COVID-19 using preclinical models.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

Virtual Reality Exercise Program Effects on Body Mass Index, Depression, Exercise Fun and Exercise Immersion in Overweight Middle-Aged Women: A Randomized Controlled Trial.

Background: This study explored the effects of a virtual reality exercise program on overweight middle-aged women. Methods: This randomized controlled trial included women 40−65 years of age with a body mass index (BMI) of 23 kg/m2 or more living in Daejeon City. The virtual reality environment was set up by attaching an IoT sensor to an indoor bicycle and linking it with a smartphone, enabling exercise in an immersive virtual reality through a head-mounted display. Results: In the virtual reality exercise group, the BMI was significantly decreased after the 8-week intervention compared with the baseline value (F = 59.491, p < 0.001). The depression scores were significantly different among the three groups, with the intervention effect being more significant in the virtual reality exercise group than in the indoor bicycle exercise and control groups (F = 3.462, p < 0.001). Furthermore, the levels of exercise fun (F = 12.373, p < 0.001) and exercise immersion (F = 14.629, p < 0.001) were significantly higher in the virtual reality exercise group than in the indoor bicycle exercise and control groups. Conclusions: The virtual reality exercise program positively affected the BMI and the levels of depression, exercise fun, and exercise immersion in overweight middle-aged women. It is an effective home exercise program for obesity management in this population.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Caudatin attenuates inflammatory reaction by suppressing JNK/AP-1/NF-κB/caspase-1 pathways in activated HMC-1 cells.

One of the interfering factors in Coronavirus disease 2019 (COVID-19) is the cytokine storm, which contributes to hyperinflammation. Mast cells cause COVID-19 hyperinflammation by increasing inflammatory cytokine levels. We investigated whether caudatin, an active compound of Cynanchum auriculatum, could suppress inflammatory response signaling in human mast cell line, HMC-1 cells. Caudatin suppressed activation of c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) in HMC-1 cells. Caudatin suppressed nuclear translocation of catalytic subunit (p65) of nuclear factor (NF)-κB by blocking IκBα phosphorylation and degradation. Caudatin also reduced levels of activated-caspase-1 protein and activation of caspase-1. Non-toxic caudatin doses inhibited the mRNA expression and protein synthesis of pro-inflammatory cytokines. A significant finding was that caudatin inhibited JNK/AP-1/NF-κB/caspase-1 signaling molecules, reducing the secretion of inflammatory cytokines. Consequently, we propose that caudatin might be used as a material in health functional foods to alleviate mast cell-mediated inflammatory conditions like COVID-19.

Corrigendum: Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits.

[This corrects the article DOI: 10.3389/fimmu.2022.1055811.].

Brain organoids for addressing COVID-19 challenge.

COVID-19 is a systemic disease involving multiple organs, and clinically, patients have symptoms of neurological damage to varying degrees. However, we do not have a clear understanding of the relationship between neurological manifestations and viral infection due to the limitations of current in vitro study models. Brain organoids, formed by the differentiation of stem cells under 3D culture conditions, can mimic the structure of tiny cell clusters with neurodevelopmental features in different patients. The paper reviewed the history of brain organoids development, the study of the mechanism of viral infection, the inflammatory response associated with neurological damage, the detection of antiviral drugs, and combined microarray technology to affirm the status of the brain organoid models in the study of COVID-19. In addition, our study continuously improved the model in combination with emerging technologies, to lay a theoretical foundation for clinical application and academic research.

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice;type II pneumocytes in SFTPB-hACE2 mice;and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.