BackgroundThe global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic.MethodsWe collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2.ResultTransmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins.ConclusionsThese results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs.

Immunotherapy showed remarkable efficacy in several cancer types. However, the majority of patients do not benefit from immunotherapy. Evaluating tumor heterogeneity and immune status before treatment is key to identifying patients that are more likely to respond to immunotherapy. Demographic characteristics (such as sex, age, and race), immune status, and specific biomarkers all contribute to response to immunotherapy. A comprehensive immunodiagnostic model integrating all these three dimensions by artificial intelligence would provide valuable information for predicting treatment response. Here, we coined the term “immunodiagnosis” to describe the blueprint of the immunodiagnostic model. We illustrated the features that should be included in immunodiagnostic model and the strategy of constructing the immunodiagnostic model. Lastly, we discussed the incorporation of this immunodiagnosis model in clinical practice in hopes of improving the prognosis of tumor immunotherapy.

ObjectivesOlder populations have a relatively high prevalence of unmet healthcare needs, which can result in poor health status. Moreover, in the coming century, frailty is expected to become one of the most serious global public health challenges. However, there is a lack of clear evidence proving an association between unmet healthcare needs and frailty. This study aimed to assess whether unmet healthcare needs predict the onset of frailty in China.MethodsThe association between frailty and unmet healthcare needs was explored by analyzing data from the China Health and Retirement Longitudinal Study (CHARLS) using random-effects logistic regression and Cox regression with time-varying exposure.ResultsAt baseline, 7,719 respondents were included in the analysis. Random-effects logistic regression shows that unmet outpatient healthcare needs were associated with increased risk of both contemporaneous (adjusted OR [aOR], 1.17; 95% CI, 1.02–1.35) and lagged (aOR, 1.24; 95% CI, 1.05–1.45) frailty, as were unmet inpatient needs (contemporaneous: aOR, 1.28; 95% CI, 1.00–1.64; lagged: aOR, 1.55; 95% CI, 1.17–2.06). For respondents not classified as frail at baseline (n = 5,392), Cox regression with time-varying exposure shows significant associations of both unmet outpatient needs (adjusted HR, 1.23; 95% CI, 1.05–1.44) and unmet inpatient needs (adjusted HR, 1.48; 95% CI, 1.11–1.99) with increased risk of developing frailty.ConclusionsReducing unmet healthcare needs would be a valuable intervention to decrease frailty risk and promote healthy aging in middle-aged and older populations. It is urgent and essential that the equity and accessibility of the medical insurance and health delivery systems be strengthened.

Military personnel encountered multiple stressful events during the COVID-19 lockdown. Reducing non-combat attrition due to mental disorders is crucial for military morale and combat effectiveness. Grounded in stress theory and regulatory focus theory, this study investigates the influence of resilience on military personnel’s mental health; coping style and regulatory focus are considered potential mediators and moderators, respectively. We conducted a routine psychological assessment on 1,110 military personnel in China. The results indicate that: (1) resilience has a negative impact on the psychological symptoms of military groups; (2) mature and mixed coping styles in military personnel mediate the association between resilience and psychological symptoms; and (3) regulatory focus predominance has a negative moderating effect on mature coping styles’ effects on psychological symptoms. Furthermore, this study supports previous findings that resilience and mental health are interrelated; it demonstrates that military personnel can effectively reduce negative psychological symptoms by improving their resilience level and adopting mature coping styles under stressful situations. The current study presents interventional insights regarding coping styles and mental health from a self-regulatory perspective during the COVID-19 pandemic.

Net community production (NCP) is defined as the difference between gross primary production (GPP) and total community respiration (R). NCP indicates the balance between the production and consumption of community organic carbon, therefore making it a key parameter for evaluating the efficiency of carbon sequestration using the biological pump (BP). It is difficult to quantify NCP directly via satellite, because there are complex processes in community production and respiration. We reviewed previous research on satellite-based NCP and classified the methods into two primary categories: empirical methods and semi-analytical methods. The former category was established based on numerical relationships between NCP and satellite-based proxies, while the latter was developed by utilizing mechanistic analysis to establish quantitative expressions linking NCP to such proxies. Although satellite-based calculations of NCP have been attempted, they still suffer from significant uncertainties. Future research should focus on the precise calculation of satellite-based NCP by investigating the underlying processes and mechanisms that regulate NCP, developing regional models, and increasing the resolution of satellite sensors, as well as applying satellite lidar and coordinated multi-sensor observation technology.

Approximately 5% of advanced colorectal carcinomas (CRCs) and 12–15% of early CRCs are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Nowadays, PD-L1 inhibitors or combined CTLA4 inhibitors are the major strategies for advanced or metastatic MSI-H colorectal cancer, but some people still show drug resistance or progression. Combined immunotherapy has been shown to expand the benefit population in non-small-cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), and other tumors while reducing the incidence of hyper-progression disease (HPD). Nevertheless, advanced CRC with MSI-H remains rare. In this article, we describe a case of an elder patient with MSI-H advanced CRC carrying MDM4 amplification and DNMT3A co-mutation who responded to sintilimab plus bevacizumab and chemotherapy as the first-line treatment without obvious immune-related toxicity. Our case provides a new treatment option for MSI-H CRC with multiple risk factors of HPD and highlights the importance of predictive biomarkers in personalized immunotherapy.