Exploring the Potential Mechanism of Action of Ursolic Acid against Gastric Cancer and COVID-19 using Network Pharmacology and Bioinformatics Analysis.

BACKGROUND: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis is worse. It is urgent to find effective treatment methods. OBJECTIVE: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and COVID-19 by network pharmacology and bioinformatics analysis. METHODS: The online public database and weighted co-expression gene network analysis (WGCNA) were used to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases. Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets were performed to verify the accuracy of the prediction results. RESULTS: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14) associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1, HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of PARP1, MAPK14, and ACE2. CONCLUSION: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory, anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.

Complete Genome Sequence of a Bovine Coronavirus Isolated from a Goat in Pennsylvania, USA.

We report a complete genome sequence of bovine coronavirus (BCoV) isolated from a goat in the state of Pennsylvania in 2022. BCoV often causes calf scours and winter dysentery in cattle.

The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis.

BACKGROUND: Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities. PURPOSE: To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. METHODS: Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. RESULTS: In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. CONCLUSION: Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.

The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis

Background Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities. Purpose To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. Methods Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. Results In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. Conclusion Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases. Graphical abstract Image, graphical abstract

Transmission history of SARS-CoV-2 in humans and white-tailed deer.

The emergence of a novel pathogen in a susceptible population can cause rapid spread of infection. High prevalence of SARS-CoV-2 infection in white-tailed deer (Odocoileus virginianus) has been reported in multiple locations, likely resulting from several human-to-deer spillover events followed by deer-to-deer transmission. Knowledge of the risk and direction of SARS-CoV-2 transmission between humans and potential reservoir hosts is essential for effective disease control and prioritisation of interventions. Using genomic data, we reconstruct the transmission history of SARS-CoV-2 in humans and deer, estimate the case finding rate and attempt to infer relative rates of transmission between species. We found no evidence of direct or indirect transmission from deer to human. However, with an estimated case finding rate of only 4.2%, spillback to humans cannot be ruled out. The extensive transmission of SARS-CoV-2 within deer populations and the large number of unsampled cases highlights the need for active surveillance at the human-animal interface.

Spatial-temporal Evolution Characteristics and Decoupling Analysis of Influencing Factors of China's Aviation Carbon Emissions

The aviation industry has become one of the top ten greenhouse gas emission industries in the world. China's aviation carbon emissions continue to increase, but the analysis of its influencing factors at the provincial level is still incomplete. This paper firstly uses Stochastic Impacts by Regression on Population, Affluence and Technology model (STIRPAT) model to analyze the time series evolution of China's aviation carbon emissions from 2000 to 2019. Secondly, it uses the Logarithmic Mean Divisia Index (LDMI) model to analyze the influencing characteristics and degree of four factors on China's aviation carbon emissions, which are air transportation revenue, aviation route structure, air transportation intensity and aviation energy intensity. Thirdly, it determines the various factors' influencing direction and evolution trend of 31 provinces' aviation carbon emissions in China (not including Hong Kong, Macao, Taiwan of China due to incomplete data). Finally, it derives the decoupling effort model and analyzes the decoupling relationship and decoupling effort degree between air carbon emissions and air transportation revenue in different provinces. The study found that from 2000 to 2019, China's total aviation carbon emissions continued to grow, while the growth rate of aviation carbon emissions showed a fluctuating downward trend. Air transportation revenue and aviation route structure promote the growth of total aviation carbon emissions, and air transportation intensity and aviation energy intensity have a restraining effect on the growth of total aviation carbon emissions. The scope of negative driving effect of air transportation revenue and air transportation intensity on total aviation carbon emissions in various provinces has increased. While the scope of positive driving influence of aviation route structure on total aviation carbon emissions of various provinces has increased, aviation energy intensity mainly has negative driving influence on total aviation carbon emissions of each province. Overall, the emission reduction trend in the areas to the west and north of the Qinling-Huaihe River Line is obvious. The decoupling mode between air carbon emissions and air transportation revenue in 31 provinces is mainly expansion negative decoupling. The air transportation intensity effect shows strong decoupling efforts in most provinces, the decoupling effort of aviation route structure effect and aviation energy intensity effect is not prominent. [ FROM AUTHOR] Copyright of Chinese Geographical Science is the property of Springer Nature 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.)

Multiple spillovers from humans and onward transmission of SARS-CoV-2 in white-tailed deer.

Many animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and could act as reservoirs; however, transmission in free-living animals has not been documented. White-tailed deer, the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 is circulating in deer, 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through January of 2021 were assayed for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 (33.2%) deer samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, following the November 2020 peak of human cases in Iowa, and coinciding with the onset of winter and the peak deer hunting season, SARS-CoV-2 RNA was detected in 80 of 97 (82.5%) RPLN samples collected over a 7-wk period. Whole genome sequencing of all 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%) and B.1.311 (n = 19; 20%) accounting for ∼75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple human-to-deer transmission events followed by subsequent deer-to-deer spread. These discoveries have important implications for the long-term persistence of the SARS-CoV-2 pandemic. Our findings highlight an urgent need for a robust and proactive "One Health" approach to obtain enhanced understanding of the ecology, molecular evolution, and dissemination of SARS-CoV-2.

Do neighborhood food environments matter for eating through online-to-offline food delivery services?

Eating through online-to-offline (O2O) food delivery services has in recent years emerged as an important diet behavior especially amid the COVID-19 pandemic. There is not much understanding of this relatively new diet behavior and its influence factors. In an attempt to answer the research question if the neighborhood food environment matters for eating through O2O food delivery services, this research collects primary data on people's experience of using O2O food delivery services through a sample questionnaire survey and secondary data on foodscapes including the spatial distributions of food sources of various types in Shanghai. Personal sociodemographic characteristics, home and workplace food environments are considered as potential explanatory factors of eating through O2O food delivery services. The study reveals that there are significant differences between home and workplace food environments in Shanghai and that home food environments are more influential on eating through O2O food delivery services than workplace food environments;the healthy food availability and accessibility at residential neighborhoods are found to significantly reduce the probability of eating through O2O food delivery services;lack of healthy food choices and being in the suburb explain O2O food delivery service consumptions at workplace. Findings of this research are relevant for promoting healthy eating through urban planning and urban design practices.

Thymus Degeneration and Regeneration.

The immune system's ability to resist the invasion of foreign pathogens and the tolerance to self-antigens are primarily centered on the efficient functions of the various subsets of T lymphocytes. As the primary organ of thymopoiesis, the thymus performs a crucial role in generating a self-tolerant but diverse repertoire of T cell receptors and peripheral T cell pool, with the capacity to recognize a wide variety of antigens and for the surveillance of malignancies. However, cells in the thymus are fragile and sensitive to changes in the external environment and acute insults such as infections, chemo- and radiation-therapy, resulting in thymic injury and degeneration. Though the thymus has the capacity to self-regenerate, it is often insufficient to reconstitute an intact thymic function. Thymic dysfunction leads to an increased risk of opportunistic infections, tumor relapse, autoimmunity, and adverse clinical outcome. Thus, exploiting the mechanism of thymic regeneration would provide new therapeutic options for these settings. This review summarizes the thymus's development, factors causing thymic injury, and the strategies for improving thymus regeneration.

Response and resilience of Asian agrifood systems to COVID-19: An assessment across twenty-five countries and four regional farming and food systems.

Context: The COVID-19 pandemic has been affecting health and economies across the world, although the nature of direct and indirect effects on Asian agrifood systems and food security has not yet been well understood. Objectives: This paper assesses the initial responses of major farming and food systems to COVID-19 in 25 Asian countries, and considers the implications for resilience, food and nutrition security and recovery policies by the governments. Methods: A conceptual systems model was specified including key pathways linking the direct and indirect effects of COVID-19 to the resilience and performance of the four principal Asian farming and food systems, viz, lowland rice based; irrigated wheat based; hill mixed; and dryland mixed systems. Based on this framework, a systematic survey of 2504 key informants (4% policy makers, 6% researchers or University staff, 6% extension workers, 65% farmers, and 19% others) in 20 Asian countries was conducted and the results assessed and analysed. Results and conclusion: The principal Asian farming and food systems were moderately resilient to COVID-19, reinforced by government policies in many countries that prioritized food availability and affordability. Rural livelihoods and food security were affected primarily because of disruptions to local labour markets (especially for off-farm work), farm produce markets (notably for perishable foods) and input supply chains (i.e., seeds and fertilisers). The overall effects on system performance were most severe in the irrigated wheat based system and least severe in the hill mixed system, associated in the latter case with greater resilience and diversification and less dependence on external inputs and long market chains. Farming and food systems' resilience and sustainability are critical considerations for recovery policies and programmes, especially in relation to economic performance that initially recovered more slowly than productivity, natural resources status and social capital. Overall, the resilience of Asian farming and food systems was strong because of inherent systems characteristics reinforced by public policies that prioritized staple food production and distribution as well as complementary welfare programmes. With the substantial risks to plant- and animal-sourced food supplies from future zoonoses and the institutional vulnerabilities revealed by COVID-19, efforts to improve resilience should be central to recovery programmes. Significance: This study was the first Asia-wide systems assessment of the effects of COVID-19 on agriculture and food systems, differentiating the effects of the pandemic across the four principal regional farming and food systems in the region.

Effect of antitumor therapy on cancer patients infected by SARS-CoV-2: A systematic review and meta-analysis.

BACKGROUND: Cancer patients are at a high risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and are more likely to develop severe illness and have higher mortality once infected. In the COVID-19 pandemic, it is urgent to understand the effects of antitumor therapy on the prognosis of patients with COVID-19. METHODS: A systematic literature search was conducted in PubMed, Cochrane Library, Embase, MedRxiv, and Chinese National Knowledge Infrastructure (CNKI) until 21 June 2020. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were evaluated using a random effects model to analyze the effects of antitumor therapies on COVID-19 patients. RESULTS: For cancer patients with COVID-19, the death events related to antitumor treatment were higher than those with no antitumor treatment (OR = 1.55; 95% CI 1.07-2.25; p = 0.021). Compared with patients in the survival group, the non-survival group showed no significant differences in patients who received antitumor therapy. Compared with patients in the non-severe group, the severe group was more likely to receive antitumor therapy (OR = 1.50; 95% CI 1.02-2.19; p = 0.037) and there was a significant difference. The incidence of severe events was higher in the subgroup of chemotherapy (OR = 1.73; 95% CI 1.09-2.73). CONCLUSION: The synthesized evidence suggests that cancer patients with COVID-19 who received antitumor treatment shortly before symptom onset are more likely to experience severe symptoms and have high mortality. Receiving chemotherapy is an unfavorable factor for the prognosis of cancer patients with COVID-19.

Maternal Mental Health Status and Approaches for Accessing Antenatal Care Information During the COVID-19 Epidemic in China: Cross-Sectional Study.

BACKGROUND: China was the first country in the world to experience a large-scale COVID-19 outbreak. The rapid spread of the disease and enforcement of public health measures has caused distress among vulnerable populations such as pregnant women. With a limited understanding of the novel, emerging infectious disease, pregnant women have sought ways to access timely and trusted health care information. The mental health status of pregnant women during this public health emergency, as well as how they responded to the situation and where and how they obtained antenatal care information, remain to be understood. OBJECTIVE: This study aimed to evaluate the mental health status of pregnant women during the COVID-19 epidemic in China by measuring their perceived stress, anxiety, and depression levels; explore the approaches used by them to access antenatal health care information; and determine their associations with maternal mental health status. METHODS: We conducted a web-based, cross-sectional survey to assess the mental health status of Chinese pregnant women by using the validated, Chinese version of Perceived Stress Scale, Self-Rating Anxiety Scale, and Edinburgh Depression Scale. We also collected information on the various approaches these women used to access antenatal care information during the early stage of the COVID-19 epidemic, from February 5 to 28, 2020. RESULTS: A total of 1873 pregnant women from 22 provinces or regions of China participated in the survey. The prevalence of perceived stress, anxiety, and depression among these participants was 89.1% (1668/1873; 95% CI 87.6%, 90.4%), 18.1% (339/1873; 95% CI 16.4%, 19.9%), and 45.9% (859/1873; 95% CI 43.6%, 48.1%), respectively. Hospitals' official accounts on the Chinese social media platforms WeChat and Weibo were the most popular channels among these pregnant women to obtain antenatal care information during the COVID-19 outbreak. Access to antenatal care information via the hospitals' official social media accounts was found to be associated with a significantly lower risk of perceived stress (adjusted odds ratio [aOR] 0.46, 95% CI 0.30-0.72; P=.001), anxiety (aOR 0.53, 95% CI 0.41-0.68; P<.001), and depression (aOR 0.73, 95% CI 0.59-0.91; P=.005). Access to health care information via hospital hotlines or SMS was found to be significantly associated with a lower risk of anxiety only (OR 0.77, 95% CI 0.60-0.98; P=.04). CONCLUSIONS: During the COVID-19 outbreak in China, pregnant women experienced high levels of perceived stress, anxiety, and depression. During such public health emergencies, mental health care services should be strengthened to reassure and support pregnant women. Specific information targeted at pregnant women, including information on how to cope in an emergency or major disease outbreak, developed and disseminated by health care institutions via social media platforms could be an effective way to mitigate mental health challenges and ensure epidemic preparedness and response in the future.