A bibliometric analysis of autophagy in lung diseases from 2012 to 2021.

Background: Autophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis. Methods: Publications were retrieved from the 2012-2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease. Results: A total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that "autophagy" and "apoptosis" were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases. Conclusion: The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19-related lung diseases.

A bibliometric analysis of NLRP3 inflammasome in acute lung injury/acute respiratory distress syndrome from 2010 to 2021.

Background: Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is essential in the pathogenesis of acute respiratory distress syndrome (ARDS), a fatal clinical syndrome that deteriorated from acute lung injury (ALI). This bibliometric study aims to offer a thorough insight into the scientific output about NLRP3 inflammasome in ALI/ARDS and explore the intellectual base, developing trajectory and emerging trends. Methods: We retrieved the literature from 2010 to 2021 from Science Citation Index Expanded (SCIE) database. Bibliometrix (3.1.4) R package and CiteSpace (5.8.R3) were used for further analysis and visualization. Results: A total of 508 English articles and reviews published from 2010 to 2021 were identified. The annual number of publications presented a rapidly developing trend especially in recent years. Among all the 42 countries, China was the most productive and most cited country, while the USA had the greatest impact. Peter A. Ward from the USA was the most productive corresponding author, and 4 of these top 10 corresponding authors were from China. The most cited reference was written by Ahmed (2017) of Zhejiang University in China. The Journal of Immunology had highest citation count and G-index. Furthermore, the major disciplines of research front have drifted from "Medicine, Medical, Clinical" to "Molecular, Biology, Immunology" over the past 12 years. In the co-occurring network, the terms "acute lung injury," "NLRP3 inflammasome," "interleukin-1ß," "NF-κB," and "NLRP3 activation" occurred most frequently, while in burst detection, "oxidative stress" had the highest burst strength. Co-citation network revealed that Cluster 2 "virus infection" was the most active area, including the most citation bursts. Cluster 0 "severe COVID-19" and Cluster 1 "dual inhibitor PTUPB" were emerging themes in recent years, and they involved the largest number of publications. Conclusions: This bibliometric analysis revealed a rapid growth trend of the relatively novel topic: NLRP3 inflammasome in ALI/ARDS. China was the largest contributor, while the USA offered the most landmark papers. The major disciplines of research front drifted from "Medicine, Medical, Clinical" to "Molecular, Biology, Immunology." In recent years, studies about the role of NLRP3 in COVID-19-associated ALI/ARDS and oxidative stress became hot spots.

The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases.

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle is disrupted. Itaconate is derived from cis-aconitate decarboxylation by cis-aconitate decarboxylase (ACOD1) in the mitochondrial matrix and is also known as immune-responsive gene 1 (IRG1). Studies have demonstrated that itaconate plays an important role in regulating signal transduction and posttranslational modification through its immunoregulatory activities. Itaconate is also an important bridge among metabolism, inflammation, oxidative stress, and the immune response. This review summarizes the structural characteristics and classical pathways of itaconate, its derivatives, and the compounds that release itaconate. Here, the mechanisms of itaconate action, including its transcriptional regulation of ATF3/IκBζ axis and type I IFN, its protein modification regulation of KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, and TFEB, and succinate dehydrogenase and glycolytic enzyme metabolic action, are presented. Moreover, the roles of itaconate in diseases related to inflammation and oxidative stress induced by autoimmune responses, viruses, sepsis and IRI are discussed in this review. We hope that the information provided in this review will help increase the understanding of cellular immune metabolism and improve the clinical treatment of diseases related to inflammation and oxidative stress.

Bibliometric analysis of global research trends on pyroptosis in lung disease.

Background: Pyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease. Methods: On February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results. Result: 1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: "NOD-like receptor3 (NLRP3) inflammasome", "inflammation", "oxidative stress", and "acute lung injury (ALI)". Conclusion: The research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.

Bibliometric analysis of global research trends on pyroptosis in lung disease

Background Pyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease. Methods On February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results. Result 1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: “NOD-like receptor3 (NLRP3) inflammasome”, “inflammation”, “oxidative stress”, and “acute lung injury (ALI)”. Conclusion The research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.

Magnesium Hydride Ameliorates Endotoxin-Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell Apoptosis

Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1β, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1β pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1β pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.

New insights into the DPSIR model: Revealing the dynamic feedback mechanism and efficiency of ecological civilization construction in China

Managing ecosystems is considered a "wicked problem" without clear solutions due to the limited understanding of complex ecosystems and social dynamics. In this study, a method based on the Driving forces–Pressures–State–Impacts–Responses (DPSIR) framework was developed to reveal the Ecological Civilization Construction (ECC) together with structural equation modeling (SEM), panel data model (PDM), coupling and coordination degree (CCD) model, and data envelopment analysis (DEA). The SEM reveals that component Responses as exogenous variables can better explain the DPSIR framework nexuses than Driving forces, indicating that environmental protection measures taken by Chinese government played a dominant role in ECC. ECC indexes (ECCI) of 30 Chinese provinces were 18–87% higher in 2019 than 2012, and the PDM demonstrates that temperature, precipitation, and GDP can explain about 87.2% of ECCI variation among 30 provinces. About 12–40% increase in CCD within the DPSIR framework were detected in 30 Chinese provinces in 2019 compared to 2012. The DEA suggests that China's ECC's average comprehensive and technical efficiencies were only 0.62 and 0.77 in 2019, respectively. Meanwhile, these results show that ECC remains to be strengthened and coordinated. Implications on ECC were proposed for some provinces. Overall, this study proposes a Response-driven pathway named RDPSI can explain the achievements and limitation factors in China's ECC. Also, our results emphasize the importance of integrating science and technology, policy formulation, and precise implementation to achieve sustainable development. • A new method for studying the dynamic relationship of the SES is developed. • A sustainable development pathway named RDPSI is proposed. • China has formed a SES of positive feedback cycle, but the system is unstable. • There are increasingly significant spatial correlation issues in 30 Chinese provinces. [ FROM AUTHOR] Copyright of Journal of Cleaner Production is the property of Elsevier B.V. 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.)

Protective Effect of Fluorofenidone Against Acute Lung Injury Through Suppressing the MAPK/NF-κB Pathway

Acute lung injury (ALI) is a severe disease that presents serious damage and excessive inflammation in lungs with high mortality without effective pharmacological therapy. Fluorofenidone (AKFPD) is a novel pyridone agent that has anti-fibrosis, anti-inflammation, and other pharmacological activities, while the effect of fluorofenidone on ALI is unclarified. Here, we elucidated the protective effects and underlying mechanism of fluorofenidone on lipopolysaccharide (LPS)-induced ALI. In this study, fluorofenidone alleviated lung tissue structure injury and reduced mortality, decreased the pulmonary inflammatory cell accumulation and level of inflammatory cytokines IL-1β, IL-6, and TNF-α in the bronchoalveolar lavage fluid, and attenuated pulmonary apoptosis in LPS-induced ALI mice. Moreover, fluorofenidone could block LPS-activated phosphorylation of ERK, JNK, and P38 and further inhibited the phosphorylation of IκB and P65. These results suggested that fluorofenidone can significantly contrast LPS-induced ALI through suppressing the activation of the MAPK/NF-κB signaling pathway, which indicates that fluorofenidone could be considered as a novel therapeutic candidate for ALI.

Specific Interleukin-1 Inhibitors, Specific Interleukin-6 Inhibitors, and GM-CSF Blockades for COVID-19 (at the Edge of Sepsis): A Systematic Review.

Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically ill COVID-19 patients with multiple organ dysfunction developed characteristics typical of sepsis and met the diagnostic criteria for sepsis. Timely detection of cytokine storm and appropriate regulation of inflammatory response may be significant in the prevention and treatment of sepsis. This study evaluated the efficacy and safety of specific interleukin (IL)-1 inhibitors, specific IL-6 inhibitors, and GM-CSF blockades in the treatment of COVID-19 (at the edge of sepsis) patients through systematic review and meta-analysis. METHODOLOGY: A literature search was conducted on PubMed, EMBASE, Clinical Key, Cochrane Library, CNKI, and Wanfang Database using proper keywords such as "SARS-CoV-2," "Corona Virus Disease 2019," "COVID-19," "anakinra," "tocilizumab," "siltuximab," "sarilumab," "mavrilimumab," "lenzilumab," and related words for publications released until August 22, 2021. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. RESULTS: Based on the inclusion and exclusion criteria, 43 articles were included in the final review. The meta-analysis results showed that tocilizumab could reduce the mortality of patients with COVID-19 (at the edge of sepsis) [randomized controlled trials, RCTs: odds ratio (OR) 0.71, 95%CI: 0.52-0.97, low-certainty evidence; non-RCTs: risk ratio (RR) 0.68, 95%CI: 0.55-0.84, very low-certainty evidence) as was anakinra (non-RCTs: RR 0.47, 95%CI: 0.34-0.66, very low-certainty evidence). Sarilumab might reduce the mortality of patients with COVID-19 (at the edge of sepsis), but there was no statistical significance (OR 0.65, 95%CI: 0.36-1.2, low-certainty evidence). For safety outcomes, whether tocilizumab had an impact on serious adverse events (SAEs) was very uncertain (RCTs: OR 0.87, 95%CI: 0.38-2.0, low-certainty evidence; non-RCTs 1.18, 95%CI: 0.83-1.68, very low-certainty evidence) as was on secondary infections (RCTs: OR 0.71, 95%CI: 0.06-8.75, low-certainty evidence; non-RCTs: RR 1.15, 95%CI: 0.89-1.49, very low-certainty evidence). CONCLUSIONS: This systematic review showed that tocilizumab, sarilumab, and anakinra could reduce the mortality of people with COVID-19 (at the edge of sepsis), and tocilizumab did not significantly affect SAEs and secondary infections. The current evidence of the studies on patients treated with siltuximab, mavrilimumab, and lenzilumab is insufficient. In order to establish evidence with stronger quality, high-quality studies are needed. Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020226545.

Global Trends in Research of Macrophages Associated With Acute Lung Injury Over Past 10 Years: A Bibliometric Analysis.

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords "NLRP3" and "extracellular vesicles" appeared most frequently. Besides, researches on COVID-19-induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19-induced ALI and may be a target for the treatment of COVID-19.

A Retrospective Cohort Study on the Clinical Course of Patients With Moderate-Type COVID-19.

Background: A large number of people contracted moderate-type COVID-19 around the world. However, to our knowledge no studies have covered the clinical course of patients with moderate-type COVID-19. This study describes the clinical course of moderate-type patients with COVID-19 from Wuhan City and Yiyang City, and explores factors relevant to the length of hospitalization and symptoms relief. Methods: The study analyzed the clinical course of 107 moderate-type patients with COVID-19 from the outbreak area (Wuhan) and the imported area (Yiyang), and used automatic linear modeling and multivariate linear regression analysis to explore the factors relevant to the length of hospitalization and symptoms relief. Furthermore, we created a scoring system to value the length of hospitalization and symptoms relief. Results: Lymphopenia, elevated C-reactive protein, increased LDH, bilateral lung GGO (ground glass opacity), and lung consolidation were more likely to appear in ordinary inpatients with moderate-type COVID-19 from Wuhan (P < 0.05), compared to infected medical staff from Wuhan and ordinary inpatients with moderate-type COVID-19 from Yiyang. Meanwhile, the length of hospitalization and symptoms relief was longer in ordinary patients with moderate-type COVID-19 from Wuhan (P < 0.05). Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO were linearly related to the length of hospitalization (P < 0.05); onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation were linearly related to the length of symptoms relief (P < 0.05). By using the scoring system, we found that the time of hospitalization and symptoms relief lengthened as the scores increased. Conclusions: This study described the clinical course of patients with moderate-type COVID-19, and found that ordinary patients with moderate-type COVID-19 in outbreak areas were more serious and needed stronger treatment and longer treatment time. Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO can be effective predictors of the length of hospitalization. And onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation can be effective predictors of the amount of time until symptoms relief. Most importantly, we have created a scoring system, which could contribute to the diagnosis and treatment of COVID-19.

Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients.

High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.

Convalescent plasma may be a possible treatment for COVID-19: A systematic review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has spread globally. Therapeutic options including antivirals, anti-inflammatory compounds, and vaccines are still under study. Convalescent plasma(CP) immunotherapy was an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. In the epidemic of COVID-19, a large number of literatures reported the application of CP. However, there is controversy over the efficacy of CP therapy for COVID-19. This systematic review was designed to evaluate the existing evidence and experience related to CP immunotherapy for COVID-19. METHODS: A literature search was conducted on Pubmed, Cochrane Library, Clinical Key, Wanfang Database; China National Knowledge Infrastructure(CNKI) were used to search for the proper keywords such as SARS-CoV-2, COVID-19, plasma, serum, immunoglobulins, blood transfusion, convalescent, novel coronavirus, immune and the related words for publications published until 15.10.2020. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. Data extraction and risk of bias assessments were performed by two reviewers. RESULTS: Based on the inclusions and exclusions criteria, 45 articles were included in the final review. First, meta-analysis results of RCTs showed that, there were no statistically significant differences between CP transfusion and the control group in terms of reducing mortality(OR 0.79, 95% CI 0.52-1.19, I2 = 28%) and improving clinical symptoms(OR 1.21, 95%CI 0.68-2.16; I2 = 0%). The results of controlled NRSIs showed that CP therapy may reduce mortality in COVID-19 patients(RR 0.59, 95% CI 0.53-0.66, I2 = 0%). Second, limited safety data suggested that CP is a well-tolerated therapy with a low incidence of adverse events. But, due to lack of safety data for the control group, it is really not easy to determine whether CP transfusion has an impact on moderate to serious AEs. Thirdly, for children, pregnant, elderly, tumor and immunocompromised patients, CP may be a well-tolerated therapy, if the disease cannot be controlled and continues to progress. Studies were commonly of low or very low quality. CONCLUSIONS: Although the results of limited RCTs showed that CP cannot significantly reduce mortality, some non-RCTs and case report(series) have found that CP may help patients improve clinical symptoms, clear the virus, and reduce mortality, especially for patients with COVID-19 within ten days of illness. We speculate that CP may be a possible treatment option. High-quality studies are needed for establishing stronger quality of evidence and pharmacists should also be actively involved in the CP treatment process and provide close pharmaceutical care.

Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition.

Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.

COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster.

Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2-14 days, and mostly 3-7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.