Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice

Background Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex;however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding This study was supported by grants from the 10.13039/501100005150Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the 10.13039/501100001809National Natural Science Foundation of China, and the 10.13039/501100004826Natural Science Foundation of Beijing.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Global Climate Resources for Camping and Nature-Based Tourism

Climate change is impacting the distribution of climate resources upon which nature-based tourism and recreation depends. Accordingly, we examine the global distribution of climate resources from 1948 to 2016 using the Camping Climate Index (CCI), a composite index previously validated for camping and national parks visitation for 80% of the world’s major climate types found in the United States. Calculating the CCI globally, spatial and temporal analysis indicates that climate suitability differs greatly for nature-based tourism and that changes have occurred over the last 50 years in many destinations. Locations with higher latitudes and altitudes have primarily experienced shifts towards more favorable climate conditions. Conditions have worsened in tropical and subtropical regions such as central Africa, central Australia, and Southern Asia. Results demonstrate that the redistribution of global climate resources for nature-based tourism and recreation is primarily driven by warming temperatures and the increased frequency of extreme weather events in some regions. Study findings are of particular interest to destination managers and planners of outdoor locations susceptible to weather and climate change.

Hybrid Cryptography with a One–Time Stamp to Secure Contact Tracing for COVID–19 Infection

The COVID-19 pandemic changed the lives of millions of citizens worldwide in the manner they live and work to the so-called new norm in social standards. In addition to the extraordinary effects on society, the pandemic created a range of unique circumstances associated with cybercrime that also affected society and business. The anxiety due to the pandemic increased the probability of successful cyberattacks and as well as their number and range. For public health officials and communities, location tracking is an essential component in the efforts to combat the disease. The governments provide a lot of mobile apps to help health officials to trace the infected persons and contact them to aid and follow up on the health status, which requires an exchange of data in different forms. This paper presents the one-time stamp model as a new cryptography technique to secure different contact forms and protect the privacy of the infected person. The one-time stamp hybrid model consists of a combination of symmetric, asymmetric, and hashing cryptography in an entirely new way that is different from conventional and similar existing algorithms. Several experiments have been carried out to analyze and examine the proposed technique. Also, a comparison study has been made between our proposed technique and other state-of-the-art alternatives. Results show that the proposed one-time stamp model provides a high level of security for the encryption of sensitive data relative to other similar techniques with no extra computational cost besides faster processing time.

The Perceptions and Views of Rural Residents Towards COVID-19 Recovered Patients in China: A Descriptive Qualitative Study.

INTRODUCTION: With the effective treatments of novel coronavirus disease 2019 (COVID-19), thousands of patients have recovered from COVID-19 globally. The public perceptions and views are vital to facilitate recovered COVID-19 patients reintegrate into society. In China, the rural population accounts for nearly 70% of the total population. Therefore, we chose to evaluate perceptions and views of rural residents towards COVID-19 recovered patients in China. METHODS: Fifteen participants were sampled from a village with the severe COVID-19 epidemic in Zibo city, Shandong Province. The fifteen participants who lived in the village with COVID-19 recovered patients were included. They were over 18 years of age and were voluntary to participant in the study. A descriptive qualitative design using semi-structured telephone interviews was undertaken. Thematic analysis was undertaken. RESULTS: Five main themes emerged from the data: (1) Perceived personal characteristics of COVID-19 recovered patients; (2) Perceived difficulties faced by COVID-19 recovered patients; (3) Perceptions on the social relationship with COVID-19 recovered patients; (4) Views on COVID-19 recovered patients going to public venues; (5) Views on helping COVID-19 recovered patients. Each theme was supported by several subthemes. CONCLUSION: Our study showed that discrimination and reduced social intimacy exist among rural residents. To improve their views or the situation, relevant departments could lead health educational programs and encourage supportive social connections. Through these strategic messaging, rural residents are expected to recognize that COVID-19 recovered patients need more social support, rather than discrimination and resistance, which helps recovered patients better return to society.

Quarantine experience of close contacts of COVID-19 patients in China: A qualitative descriptive study.

OBJECTIVE: Close contacts of novel coronavirus disease 2019 (COVID-19) patients may suffer from physical and psychological problems. Few studies have investigated the quarantine experiences of close contacts of COVID-19 patients. The objective of this study was to best capture participants' quarantine experiences during the COVID-19 outbreak in China. METHODS: A descriptive, qualitative design was used. All interviews were recorded and coded using thematic analysis. RESULTS: Fifteen participants took part in this study. The following five themes emerged: (1) experience in the early stage of quarantine; (2) experience in the middle stage of quarantine; (3) experience in the late stage of quarantine; (4) self-coping persisted throughout the quarantine period; and (5) external support was evident throughout the quarantine period. CONCLUSION: Our study highlights the need to assess the psychological state of close contacts in the early stage of quarantine and to provide psychological support for them, especially for the older and the less educated. Although close contacts had physical symptoms and psychological issues, they adopted positive coping strategies, which indicated that they were vulnerable but strong. Furthermore, external support from the Chinese government helped them cope with the quarantine effectively. Learning from the quarantine experience is expected to help the Chinese government and institutions from other parts of the world to better care for close contacts.