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1.
JMIR Med Inform ; 2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1834197

ABSTRACT

BACKGROUND: Internet-based online virtual health services were originally an important way for the Chinese government to resolve unmet medical service needs due to inadequate medical institutions. Its initial development was not well received. Then, the unexpected COVID-19 pandemic produced a tremendous demand for telehealth in a short time, which stimulated the explosive development of internet hospitals. The Second Affiliated Hospital of Zhejiang University (SAHZU) has taken a leading role in the construction of internet hospitals in China. The pandemic triggered the hospital to develop unique research on health service capacity under strict quarantine policies and to predict long-term trends. OBJECTIVE: To provide policy enlightenment for the construction of internet-based health services to better fight against COVID-19 and to elucidate future directions through an in-depth analysis of two years of online health service data gleaned from SAHZU's experiences and lessons learned. METHODS: We collected data from SAHZU Internet Hospital from Nov 1st, 2019 to Sep 16th, 2021. Over 900,000 users' data were analysed with respect to the demographic characteristics, demands placed on departments by user needs, new registrations, and consultation behaviours. Interrupted time series (ITS) analysis was adopted to evaluate the impact of this momentous emergency event and its long-term trends. With theme analysis and a defined 2D model, three investigations were conducted synchronously to determine users' authentic demands on online hospitals. RESULTS: The general profile of internet hospital users is young or middle-aged women who live in Zhejiang and surrounding provinces. The ITS model indicated that after the intervention (the strict quarantine policies) was implemented during the outbreak, the number of internet hospital users significantly increased (ß_2=105.736, P<0.001). Further, long-term waves of COVID-19 led to an increasing number of users following the outbreak (ß_3=0.167, P<0.001). In theme analysis, we summarized eight major demands of users from SAHZU internet hospital during the national shutdown period and afterwards. online consultation and information service were persistent and universal demands, followed by concerns about medical safety and quality, time, and cost. Users' medical behaviour patterns changed from onsite to online as internet hospital demands increased. CONCLUSIONS: The pandemic has spawned the explosive growth of telehealth, as a public tertiary internet hospital, SAHZU internet hospital is partially and irreversibly integrated into the traditional medical system.As we shared the practical examples of one public internet hospital in China, we put forward suggestions about the future direction of telehealth. Vital experience in the construction of internet hospitals was provided in the normalization of COVID-19 prevention and control, which can be demonstrated as a model of internet hospital management practice for other medical institutions.

2.
Front Psychol ; 13: 789844, 2022.
Article in English | MEDLINE | ID: covidwho-1818009

ABSTRACT

Purpose: College students in the pandemic area are experiencing the problems caused by COVID-19 by themselves or people around them, how to cope with the sudden changes and adjust the psychological stress response, and get experience and grow in the fight against the pandemic is a question worth in-depth discussion. The researchers constructed a mediated regulation model to examine the effects of intrusive rumination on the creativity of college students during the COVID-19 pandemic, as well as the mediating effect of post-traumatic growth and the moderating role of psychological resilience. Methods: A sample of 475 university students from Guangdong Province, China, were surveyed with the Runco Ideational Behavior Scale, the Event Related Rumination Inventory, the Posttraumatic Growth Inventory, and the Psychological Resilience Scale. SPSS (version 23) and PROCESS (version 3.3) were used for correlation analysis, mediation analysis, and mediated moderation analysis. Results: (1) Intrusive rumination was positively correlated with post-traumatic growth and creativity but negatively correlated with psychological resilience. Psychological resilience was positively correlated with post-traumatic growth and creativity. Post-traumatic growth and creativity were positively correlated. (2) Post-traumatic growth played a mediating role in the relationship between intrusive rumination and creativity. (3) Psychological resilience moderated the first half of the pathway "intrusive rumination → post-traumatic growth → creativity." Conclusion: Intrusive rumination affected creativity directly and also indirectly through post-traumatic growth. At the same time, psychological resilience played a moderating role between intrusive rumination and creativity. The correlation between intrusive rumination and post-traumatic growth was stronger when levels of psychological resilience levels were higher.

3.
Metals ; 12(4):533, 2022.
Article in English | ProQuest Central | ID: covidwho-1810022

ABSTRACT

The spent automobile catalysts (SAC) is the major secondary source of palladium and the production of SAC is increasing rapidly over years. The price of palladium keeps rising over the years, which demonstrates its preciousness and urgent industrial demand. Recovering palladium from the spent automobile catalysts benefits a lot from economic and environmental protection aspects. This review aims to provide some new considerations of recovering palladium from the spent automotive catalysts by summarizing and discussing both hydrometallurgical and pyrometallurgical methods. The processes of pretreatment, leaching/extraction, and separation/recovery of palladium from the spent catalysts are introduced, and related reaction mechanisms and process flows are given, especially detailed for hydrometallurgical methods. Hydrometallurgical methods such as chloride leaching with oxidants possess a high selectivity of palladium and low consumption of energy, and are cost-effective and flexible for different volume feeds compared with pyrometallurgical methods. The recovery ratios of palladium and other platinum-group metals should be the focus of competition since their prices have been rapidly increased over the years, and hence more efficient extractants with high selectivity of palladium even in the complexed leachate should be proposed in the future.

4.
J Virol ; 96(9): e0003822, 2022 May 11.
Article in English | MEDLINE | ID: covidwho-1788914

ABSTRACT

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.


Subject(s)
COVID-19 , Lung , Neutrophils , Animals , COVID-19/immunology , Disease Models, Animal , Humans , Lung/pathology , Lung/virology , Lymphopenia/virology , Mice , Neutrophils/immunology , SARS-CoV-2 , Spleen/pathology , Spleen/virology
5.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1787455

ABSTRACT

Influenza shares the same putative transmission pathway with coronavirus disease 2019 (COVID-19), and causes tremendous morbidity and mortality annually globally. Since the transmission of COVID-19 in China, a series of non-pharmaceutical interventions (NPIs) against to the disease have been implemented to contain its transmission. Based on the surveillance data of influenza, Search Engine Index, and meteorological factors from 2011 to 2021 in Xi'an, and the different level of emergence responses for COVID-19 from 2020 to 2021, Bayesian Structural Time Series model and interrupted time series analysis were applied to quantitatively assess the impact of NPIs in sequent phases with different intensities, and to estimate the reduction of influenza infections. From 2011 to 2021, a total of 197,528 confirmed cases of influenza were reported in Xi'an, and the incidence of influenza continuously increased from 2011 to 2019, especially, in 2019–2020, when the incidence was up to 975.90 per 100,000 persons;however, it showed a sharp reduction of 97.68% in 2020–2021, and of 87.22% in 2021, comparing with 2019–2020. The highest impact on reduction of influenza was observed in the phase of strict implementation of NPIs with an inclusion probability of 0.54. The weekly influenza incidence was reduced by 95.45%, and an approximate reduction of 210,100 (95% CI: 125,100–329,500) influenza infections was found during the post-COVID-19 period. The reduction exhibited significant variations in the geographical, population, and temporal distribution. Our findings demonstrated that NPIs against COVID-19 had a long-term impact on the reduction of influenza transmission.

6.
Front Psychiatry ; 13: 812929, 2022.
Article in English | MEDLINE | ID: covidwho-1775797

ABSTRACT

Objective: Nurses are at high risk of psychological distress including stress, depression, and anxiety due to low personnel density and high work demand. Despite mounting evidence showing that role stress is a risk factor for nurses' psychological distress, the mediating and moderating mechanisms underlying this relationship are less known. This study tests the mediation effect of burnout in the association between role stress and psychological distress, and whether this mediation is moderated by social support. Methods: A sample of 623 Chinese nurses were recruited from all hepatological surgery departments in Hunan Province and filled out an online questionnaire to collect data on socio-demographics, role stress, burnout, psychological distress, and social support. Mediation and moderation analyses were carried out in SPSS macro-PROCESS. Results: Burnout partially mediated the positive association between role stress and psychological distress. Social support moderated the indirect effect of role stress on psychological distress via burnout, with the effect being stronger for nurses with low social support than those with high social support. Conclusions: These findings demonstrated how role stress contributed to nurses' psychological distress both directly and indirectly through burnout, and how this indirect effect was moderated by social support. The results provide important practical implications for future prevention and intervention programs to improve nurses' mental health from multiple aspects such as decreasing role stress and burnout while increasing social support.

7.
Disease Surveillance ; 36(12):1291-1294, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1760875

ABSTRACT

Objective: To understand the pathogen spectrum in the lower respiratory tracts of 100 suspected cases infected with SARS-CoV-2 in Chaoyang district of Beijing from January to March, 2020.

8.
Signal Transduct Target Ther ; 7(1): 83, 2022 03 11.
Article in English | MEDLINE | ID: covidwho-1740428

ABSTRACT

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , T-Lymphocytes/metabolism , Animals , Caco-2 Cells , Chlorocebus aethiops , Humans , Vero Cells
9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329268

ABSTRACT

Introduction: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. Methods: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher exact tests, Spearman correlations and linear regression models. Results: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. Discussion: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323547

ABSTRACT

Computed tomography (CT) reconstruction from X-ray projections acquired within a limited angle range is challenging, especially when the angle range is extremely small. Both analytical and iterative models need more projections for effective modeling. Deep learning methods have gained prevalence due to their excellent reconstruction performances, but such success is mainly limited within the same dataset and does not generalize across datasets with different distributions. Hereby we propose ExtraPolationNetwork for limited-angle CT reconstruction via the introduction of a sinogram extrapolation module, which is theoretically justified. The module complements extra sinogram information and boots model generalizability. Extensive experimental results show that our reconstruction model achieves state-of-the-art performance on NIH-AAPM dataset, similar to existing approaches. More importantly, we show that using such a sinogram extrapolation module significantly improves the generalization capability of the model on unseen datasets (e.g., COVID-19 and LIDC datasets) when compared to existing approaches.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322498

ABSTRACT

Background: Mass immunization is a potentially effective approach to finally control the local outbreak and global spread of COVID-19 pandemic. However, it can also lead to undesirable outcomes if mass vaccination results in increased transmission effective contacts and relaxation of other public health interventions due to the perceived immunity from the vaccine. Methods: : We designed a mathematical model of COVID-19 transmission dynamics that takes into consideration the epidemiological status, public health intervention status (quarantined/isolated), immunity status of the population, and the strain variations. Comparing the control reproduction numbers and the final epidemic sizes (attack rate) in the cases with and without vaccination, we quantified some key factors determining when vaccination in the population is beneficial for preventing and controlling future outbreaks. Results: : Our analyses predicted that there is a critical (minimal) vaccine efficacy rate (or a critical quarantine rate) below which the control reproduction number with vaccination is higher than that without vaccination, and the final attack rate in the population is also higher with the vaccination. We also predicted the worst case scenario occurs when a high vaccine coverage is achieved for a vaccine with lower efficacy rate and when the vaccines increase the transmission efficient contacts. Conclusions: : The analyses show that an immunization program with a vaccine efficacy rate below the predicted critical values will not be as effective as simply investing in the contact tracing/quarantine/isolation implementation. We reached similar conclusions by considering the final epidemic size (or attack rates). This research then highlights the importance of monitoring the impact on transmissibility and vaccine efficacy of emerging strains.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321367

ABSTRACT

Objectives: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results: : 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15±16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type , 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case , and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster , involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316060

ABSTRACT

The COVID-19 pandemic has seen a surge of health misinformation, which has had serious consequences including direct harm and opportunity costs. We investigated (N = 678) the impact of such misinformation on hypothetical demand (i.e., willingness-to-pay) for an unproven treatment, and propensity to promote (i.e., like or share) misinformation online. This is a novel approach, as previous research has used mainly questionnaire-based measures of reasoning. We also tested two interventions to counteract the misinformation, contrasting a tentative refutation based on materials used by health authorities with an enhanced refutation based on best-practice recommendations. We found prior exposure to misinformation increased misinformation promotion (by 18%). Both tentative and enhanced refutations reduced demand (by 18% and 25%, respectively) as well as misinformation promotion (by 29% and 55%). The fact that enhanced refutations were more effective at curbing promotion of misinformation highlights the need for debunking interventions to follow current best-practice guidelines.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315279

ABSTRACT

Along with the accelerated process of urbanization, the contradiction between social development and environment become increasingly conspicuous. Herein, we access the transport and fate of polycyclic aromatic hydrocarbons (PAHs) by a newly proposed multiple land-use fugacity (MLUF) model to provide comprehensive understanding of PAHs distribution in an urban and suburban areas. PAHs behave differently towards distinct soil types and land covers within the soil phase. We suggest and implement the MLUF model to estimate the PAHs distribution in diverse land types. Moreover, we introduce a multivariate interpretation and systematic model calibration framework to validate the MLUF model adaptability in different land-use area. Accordingly, the organic film on impervious surfaces holds the highest PAHs concentration than other compartments, also soil and sediment phases keep most of PAHs. The potential cancer risk of PAHs in different land-usecompartments follow the order of urban green space > agricultural area > forest and semi-nature area. Besides, the dynamic MLUF model is developed and implemented to the period of COVID-19 pandemic for quantitively estimating the dynamic variations of the PAHs concentration. Finally, we can realize the better scientific understanding of the typical PAHs environmental pollutants transfer phenomena and distribution fates in urban and suburban areas.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306299

ABSTRACT

The COVID-19 is sweeping the world with deadly consequences. Its contagious nature and clinical similarity to other pneumonias make separating subjects contracted with COVID-19 and non-COVID-19 viral pneumonia a priority and a challenge. However, COVID-19 testing has been greatly limited by the availability and cost of existing methods, even in developed countries like the US. Intrigued by the wide availability of routine blood tests, we propose to leverage them for COVID-19 testing using the power of machine learning. Two proven-robust machine learning model families, random forests (RFs) and support vector machines (SVMs), are employed to tackle the challenge. Trained on blood data from 208 moderate COVID-19 subjects and 86 subjects with non-COVID-19 moderate viral pneumonia, the best result is obtained in an SVM-based classifier with an accuracy of 84%, a sensitivity of 88%, a specificity of 80%, and a precision of 92%. The results are found explainable from both machine learning and medical perspectives. A privacy-protected web portal is set up to help medical personnel in their practice and the trained models are released for developers to further build other applications. We hope our results can help the world fight this pandemic and welcome clinical verification of our approach on larger populations.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312737

ABSTRACT

The SARS-CoV-2 virus has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs among regions, and this variation may affect the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 S protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y.The mutant pseudoviruses were used to infect four susceptible cell lines (i.e., Huh7, hACE2-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity was evaluated using the newly constructed pseudoviruses, mouse serum, and 11 monoclonal antibodies. The neutralizing activity in immunized mouse serum was not significantly reduced for the mutant strains. Additionally, mutant strains in Portugal showed escape from 9 of 11 monoclonal antibodies. Neutralization resistance was mainly caused by the S477N, N439K, and N501Y mutations in the Spike receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.

17.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326486

ABSTRACT

While Computed Tomography (CT) reconstruction from X-ray sinograms is necessary for clinical diagnosis, iodine radiation in the imaging process induces irreversible injury, thereby driving researchers to study sparse-view CT reconstruction, that is, recovering a high-quality CT image from a sparse set of sinogram views. Iterative models are proposed to alleviate the appeared artifacts in sparse-view CT images, but the computation cost is too expensive. Then deep-learning-based methods have gained prevalence due to the excellent performances and lower computation. However, these methods ignore the mismatch between the CNN's \textbf{local} feature extraction capability and the sinogram's \textbf{global} characteristics. To overcome the problem, we propose \textbf{Du}al-\textbf{Do}main \textbf{Trans}former (\textbf{DuDoTrans}) to simultaneously restore informative sinograms via the long-range dependency modeling capability of Transformer and reconstruct CT image with both the enhanced and raw sinograms. With such a novel design, reconstruction performance on the NIH-AAPM dataset and COVID-19 dataset experimentally confirms the effectiveness and generalizability of DuDoTrans with fewer involved parameters. Extensive experiments also demonstrate its robustness with different noise-level scenarios for sparse-view CT reconstruction. The code and models are publicly available at https://github.com/DuDoTrans/CODE

18.
J Pharm Biomed Anal ; 211: 114632, 2022 Mar 20.
Article in English | MEDLINE | ID: covidwho-1665218

ABSTRACT

The incidence of depression has increased significantly during the COVID-19 pandemic. This disease is closely associated with serotonin 1A (5-HT1A) receptor and often treated by complex prescription containing Curcuma wenyujin Y. H. Chen et C. Ling. Therefore, we hypothesized that this herb contains bioactive compounds specially binding to the receptor. However, the rapid discovery of new ligands of 5-HT1A receptor is still challenging due to the lack of efficient screening methods. To address this problem, we developed and characterized a novel approach for the rapid screening of ligands by using immobilized 5-HT1A receptor as the chromatographic stationary phase. Briefly, haloalkane dehalogenase was fused at the C-terminal of 5-HT1A receptor, and the modified 5-HT1A receptor was immobilized on amino-microspheres by the reaction between haloalkane dehalogenase and 6-chlorohexanoic acid linker. Scanning electron microscope and X-ray photo-electron were used to characterize the morphology and element of the immobilized receptor. The binding of three specific ligands to 5-HT1A receptor was investigated by two different methods. Moreover, we examined the feasibility of 5-HT1A receptor colume in high throughput screening of new ligands from complex systems as exemplified by Curcuma wenyujin Y. H. Chen et C. Ling. Gweicurculactone, 2-hydroxy-1-(3,4-dihydroxybenzene)-7-(4'-hydroxybezene)-heptane and curcuminol F were identified as the ligands of 5-HT1A receptor with the binding energies of -7.06 kcal/mol, -7.77 kcal/mol and -5.26 kcal/mol, respectively. Collectively, these results indicated that the immobilized 5-HT1A receptor was capable of screening bioactive compound from complex system, providing an effective methodology for high throughput screening.


Subject(s)
Drugs, Chinese Herbal , Curcuma/chemistry , Drugs, Chinese Herbal/chemistry , High-Throughput Screening Assays , Ligands , Receptor, Serotonin, 5-HT1A
19.
Arch Virol ; 167(2): 459-470, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1653515

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Humans , Mice , Mutation , Portugal/epidemiology , Spike Glycoprotein, Coronavirus/genetics
20.
Biosens Bioelectron ; 200: 113922, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1588209

ABSTRACT

Fast, affordable, portable, and sensitive technology to detect COVID-19 is critical to address the current outbreak. Here, we present a CRISPR/Cas12a-derived electrochemical aptasensor for cost-effective, fast, and ultrasensitive COVID-19 nucleocapsid protein (Np) detection. First, an electrochemical sensing interface was fabricated by immobilizing methylene blue labeled poly adenines DNA sequence (polyA-MB electrochemical reporter) on a gold electrode surface. Second, an arched probe was prepared via hybridization of Np aptamer and an activator strand. In the presence of COVID-19 Np, the activator strand could be released from the arched probe due to the specific interaction between the target and the aptamer, which then activated the trans-cleavage activity of the CRISPR/Cas12a system. Subsequently, the polyA-MB reporters were cleaved from the electrode surface, decreasing the current of differential pulse voltammetry (DPV) at a potential of -0.27 V(vs. Ag/AgCl). The CRISPR/Cas12a-derived electrochemical aptasensor shows a highly efficient performance for COVID-19 Np detection in 50 pg mL-1 to 100 ng mL-1 with a limit of detection (LOD) low to 16.5 pg mL-1. Notably, the whole process of one test can be completed within 30 min. Simultaneously, the aptasensor displays a high selectivity to other proteins. The further measurements demonstrate that the aptasensor is robust in a natural system for point-of-care testing, such as in tap water, milk, or serum. The aptasensor is universal and expandable and holds great potential in the COVID-19 early diagnosis, environmental surveillance, food security, and other aspects.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , COVID-19 , CRISPR-Cas Systems , Electrochemical Techniques , Electrodes , Gold , Humans , Limit of Detection , Nucleocapsid Proteins , SARS-CoV-2
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