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1.
CNS Spectrums ; 28(S1):S33, 2023.
Article in English | ProQuest Central | ID: covidwho-2286208

ABSTRACT

BackgroundWith the spread of COVID-19, in application-oriented undergraduate colleges, the difficulty of teaching work for "double-qualified” teachers has greatly increased, resulting in enormous work pressure for some teachers, which is not conducive to the development of teaching work and the physical and mental health of teachers.Subjects and MethodsTwenty "double qualified” teachers from a domestic finance and economics college were selected and divided into an experience group and a control group. The evaluation index system of college teachers' competency and anti-pressure ability is constructed by using hesitant fuzzy language. Teachers in the experience group were trained in positive psychology, and their competency and anti-pressure ability were evaluated before and after the experiment using the evaluation model. The evaluation grade is divided into poor, general, relatively good, good and excellent, and is assigned with integers 1-5 respectively. The measurement type data is displayed in the form of mean ± standard deviation, and the t difference significance test is conducted. The difference significance level is 0.05.ResultsAfter completing the experiment, the statistics are shown in Table 1. Observation Table 1 shows that before the experiment, the P value of the t-test for the competency and compression resistance scores of the two groups of teachers is far greater than 0.05, with no significant difference. However, after the completion of the experiment, the average scores of teachers' competency and compressive capacity in the experience group were 4.52 and 4.63, respectively, higher than those in the control group, and the P value of the t-test was 0.001, which was considered significant.Table 1.Comparison of competence and compressive ability scores of two groups of "double qualified” financial teachersCompetencyCompressive capacity-Experience groupControl grouptPExperience groupControl grouptPBefore experiment3.15±0.143.15±0.170.4851.5263.88±0.203.86±0.240.5711.639After experiment4.52±0.273.16±0.192.8620.0024.63±0.313.85±0.223.3760.001t3.2150.448--3.8940.472--P0.0011.569--0.0011.738--ConclusionsThis research carried out experiments to verify the effect of positive psychological intervention on improving the competency and psychological pressure resistance of "double qualified” teachers. The experimental results showed that the post-competence and anti-pressure ability of the financial "double qualified” teachers in the experience group after positive psychological intervention were higher than those in the control group, and the difference was significant. The experimental results show that positive psychology training is conducive to improving the negative psychological pressure resistance of the "double qualified” teachers in China, so as to enhance their post competency.

2.
Biomed Signal Process Control ; 83: 104724, 2023 May.
Article in English | MEDLINE | ID: covidwho-2246224

ABSTRACT

COVID-19 has put all of humanity in a health dilemma as it spreads rapidly. For many infectious diseases, the delay of detection results leads to the spread of infection and an increase in healthcare costs. COVID-19 diagnostic methods rely on a large number of redundant labeled data and time-consuming data training processes to obtain satisfactory results. However, as a new epidemic, obtaining large clinical datasets is still challenging, which will inhibit the training of deep models. And a model that can really rapidly diagnose COVID-19 at all stages of the model has still not been proposed. To address these limitations, we combine feature attention and broad learning to propose a diagnostic system (FA-BLS) for COVID-19 pulmonary infection, which introduces a broad learning structure to address the slow diagnosis speed of existing deep learning methods. In our network, transfer learning is performed with ResNet50 convolutional modules with fixed weights to extract image features, and the attention mechanism is used to enhance feature representation. After that, feature nodes and enhancement nodes are generated by broad learning with random weights to adaptly select features for diagnosis. Finally, three publicly accessible datasets were used to evaluate our optimization model. It was determined that the FA-BLS model had a 26-130 times faster training speed than deep learning with a similar level of accuracy, which can achieve a fast and accurate diagnosis, achieve effective isolation from COVID-19 and the proposed method also opens up a new method for other types of chest CT image recognition problems.

3.
Front Vet Sci ; 9: 978453, 2022.
Article in English | MEDLINE | ID: covidwho-2023030

ABSTRACT

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging swine enteropathogenic coronavirus that causes severe diarrhea in neonatal piglets, leading to serious economic losses to the pig industries. At present, there are no effective control measures for SADS, making an urgent need to exploit effective antiviral therapies. Here, we confirmed that Aloe extract (Ae) can strongly inhibit SADS-CoV in Vero and IPI-FX cells in vitro. Furthermore, we detected that Emodin from Ae had anti-SADS-CoV activity in cells but did not impair SADS-CoV infectivity directly. The time-of-addition assay showed that Emodin inhibits SADS-CoV infection at the whole stages of the viral replication cycle. Notably, we found that Emodin can significantly reduce virus particles attaching to the cell surface and induce TLR3 (p < 0.001), IFN-λ3 (p < 0.01), and ISG15 (p < 0.01) expressions in IPI-FX cells, indicating that the anti-SADS-CoV activity of Emodin might be due to blocking viral attachment and the activation of TLR3-IFN-λ3-ISG15 signaling axis. These results suggest that Emodin has the potential value for the development of anti-SADS-CoV drugs.

4.
J Virol ; 96(17): e0090722, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2001774

ABSTRACT

The rapid global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused serious health problems, highlighting the urgent need for antiviral drugs. The viral main protease (Mpro) plays an important role in viral replication and thus remains the target of choice for the prevention or treatment of several viral diseases due to high sequence and structural conservation. Prolonged use of viral protease inhibitors can lead to the development of mutants resistant to those inhibitors and to many of the available antiviral drugs. Here, we used feline infectious peritonitis virus (FIPV) as a model to investigate its development of resistance under pressure from the Mpro inhibitor GC376. Passage of wild-type (WT) FIPV in the presence of GC376 selected for a mutation in the nsp12 region where Mpro cleaves the substrate between nsp12 and nsp13. This mutation confers up to 3-fold resistance to GC376 and nirmatrelvir, as determined by EC50 assay. In vitro biochemical and cellular experiments confirmed that FIPV adapts to the stress of GC376 by mutating the nsp12 and nsp13 hydrolysis site to facilitate cleavage by Mpro and release to mediate replication and transcription. Finally, we demonstrate that GC376 cannot treat FIP-resistant mutants that cause FIP in animals. Taken together, these results suggest that Mpro affects the replication of coronaviruses (CoVs) and the drug resistance to GC376 by regulating the amount of RdRp from a distant site. These findings provide further support for the use of an antiviral drug combination as a broad-spectrum therapy to protect against contemporary and emerging CoVs. IMPORTANCE CoVs cause serious human infections, and antiviral drugs are currently approved to treat these infections. The development of protease-targeting therapeutics for CoV infection is hindered by resistance mutations. Therefore, we should pay attention to its resistance to antiviral drugs. Here, we identified possible mutations that lead to relapse after clinical treatment of FIP. One amino acid substitution in the nsp12 polymerase at the Mpro cleavage site provided low-level resistance to GC376 after selection exposure to the GC376 parental nucleoside. Resistance mutations enhanced FIPV viral fitness in vitro and attenuated the therapeutic effect of GC376 in an animal model of FIPV infection. Our research explains the evolutionary characteristics of coronaviruses under antiviral drugs, which is helpful for a more comprehensive understanding of the molecular basis of virus resistance and provides important basic data for the effective prevention and control of CoVs.


Subject(s)
Antiviral Agents , Coronavirus 3C Proteases , Coronavirus, Feline , Drug Resistance, Viral , Mutation , Protease Inhibitors , Animals , Antiviral Agents/pharmacology , Cats/virology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Coronavirus, Feline/drug effects , Coronavirus, Feline/enzymology , Coronavirus, Feline/genetics , Drug Resistance, Viral/genetics , Protease Inhibitors/pharmacology
5.
J Phys Chem Lett ; 13(31): 7197-7205, 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-1972509

ABSTRACT

Remdesivir is one nucleotide analogue prodrug capable to terminate RNA synthesis in SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) by two distinct mechanisms. Although the "delayed chain termination" mechanism has been extensively investigated, the "template-dependent" inhibitory mechanism remains elusive. In this study, we have demonstrated that remdesivir embedded in the template strand seldom directly disrupted the complementary NTP incorporation at the active site. Instead, the translocation of remdesivir from the +2 to the +1 site was hindered due to the steric clash with V557. Moreover, we have elucidated the molecular mechanism characterizing the drug resistance upon V557L mutation. Overall, our studies have provided valuable insight into the "template-dependent" inhibitory mechanism exerted by remdesivir on SARS-CoV-2 RdRp and paved venues for an alternative antiviral strategy for the COVID-19 pandemic. As the "template-dependent" inhibition occurs across diverse viral RdRps, our findings may also shed light on a common acting mechanism of inhibitors.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/chemistry , Humans , Pandemics , RNA, Viral/chemistry , RNA-Dependent RNA Polymerase , Viral Transcription
6.
J Phys Chem Lett ; 13(18): 4111-4118, 2022 May 12.
Article in English | MEDLINE | ID: covidwho-1829965

ABSTRACT

Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2. Previous works have shown that remdesivir carrying 1'-substitution can act as a "delayed chain terminator", while nucleotide analogues with 2'-methyl group substitution could immediately terminate the chain extension. However, how the inhibition can be established by the 3'-ribose modification as well as other 2'-ribose modifications is not fully understood. Herein, we have evaluated the potential of several adenosine analogues with 2'- and/or 3'-modifications as obligate chain terminators by comprehensive structural analysis based on extensive molecular dynamics simulations. Our results suggest that 2'-modification couples with the protein environment to affect the structural stability, while 3'-hydrogen substitution inherently exerts "immediate termination" without compromising the structural stability in the active site. Our study provides an alternative promising modification scheme to orientate the further optimization of obligate terminators for SARS-CoV-2 RdRp.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/chemistry , Humans , Nucleotides/chemistry , RNA-Dependent RNA Polymerase , Ribose , Virus Replication
7.
Sustain Prod Consum ; 30: 851-869, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1627870

ABSTRACT

Past studies related to embodied pollutant accounting reported that free trade has increased the environmental pollution of developing economies, because the developed countries "outsource" their pollutants to developing nations. The COVID-19 pandemic has stimulated the rise of the most serious protectionism after World War II. This study is aimed to discuss whether protectionism improve the environment in developing countries by developing a comprehensive evaluation model, which integrates multi-regional input-output (MRIO), data envelopment analysis (DEA), and scenario analysis. We revealed the role of protectionism from two perspectives: the single impact on pollutant emissions and the comprehensive impact on environmental efficiency. Specifically, the capital inputs, labor inputs, energy consumption, economic output, carbon dioxide, sulfur dioxide and nitrogen oxides emissions related to global trade activities were simulated based on the MRIO. And then, sector-level trade environmental efficiency was computed by intergrading the MRIO and DEA using a non-radial directional distance function. Finally, the environmental efficiency of both developing and developed countries under two scenarios with and without trade were estimated. The results confirmed that trade has increased the CO2, SO2 and NOX emissions of developing economies by 12.9%, 9.8% and 12.3%, and has reduced that of developed economies by 6.0%, 29.4% and 21.2%, respectively. However, the results also uncovered that the environmental efficiency of developing and developed economies was dropped by 3% and 5%, respectively, under no-trade scenario. We contend that protectionism is not conducive to the sustainable development of developing countries because it lowers their environmental efficiency, although it may reduce their territorial pollutant emissions. For developed countries, the single impact of protectionism on pollutant emission reduction and the comprehensive impact on environmental efficiency are both negative.

8.
EBioMedicine ; 75: 103736, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1568649

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has killed millions of people worldwide. The current crisis has created an unprecedented demand for rapid test of SARS-CoV-2 infection. METHODS: Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a fast and convenient method to amplify and identify the transcripts of a targeted pathogen. However, the sensitivity and specificity of RT-LAMP were generally regarded as inferior when compared with the gold standard RT-qPCR. To address this issue, we combined bioinformatic and experimental analyses to improve the assay performance for COVID-19 diagnosis. FINDINGS: First, by experimental screening as well as high-throughput sequencing studies, we discovered new primer features that impacted LAMP sensitivity and specificity. These features were then used to build an improved bioinformatics algorithm to design LAMP primers targeting SARS-CoV-2. We further rigorously validated these new assays for their efficacy and specificity. We demonstrated that multiplexed RT-LAMP assay could directly detect as low as 1.5 copies/µL of SARS-CoV-2 particles in saliva, without the need of RNA isolation. We further tested this ultra-sensitive and specific RT-LAMP assay using saliva samples from COVID-19 patients. Clinical validation results indicated that the new RT-LAMP assay was comparable to standard RT-qPCR in overall assay sensitivity and specificity. INTERPRETATION: In summary, our new LAMP primer design algorithm along with the validated assays provide a fast and reliable method for the diagnosis of COVID-19 cases. FUNDING: National Institutes of Health.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva/virology , COVID-19/diagnosis , COVID-19/genetics , Humans , Sensitivity and Specificity
9.
Adv Drug Deliv Rev ; 179: 113998, 2021 12.
Article in English | MEDLINE | ID: covidwho-1465980

ABSTRACT

Gene therapy has been widely investigated for the treatment of genetic, acquired, and infectious diseases. Pioneering work utilized viral vectors; however, these are suspected of causing serious adverse events, resulting in the termination of several clinical trials. Non-viral vectors, such as lipid nanoparticles, have attracted significant interest, mainly due to their successful use in vaccines in the current COVID-19 pandemic. Although they allow safe delivery, they come with the disadvantage of off-target delivery. The application of ultrasound to ultrasound-sensitive particles allows for a direct, site-specific transfer of genetic materials into the organ/site of interest. This process, termed ultrasound-targeted gene delivery (UTGD), also increases cell membrane permeability and enhances gene uptake. This review focuses on the advances in ultrasound and the development of ultrasonic particles for UTGD across a range of diseases. Furthermore, we discuss the limitations and future perspectives of UTGD.


Subject(s)
Gene Transfer Techniques , Genetic Therapy/methods , Molecular Targeted Therapy/methods , Ultrasonics , Animals , COVID-19 , Humans , Liposomes , Nanoparticles
10.
Environ Sci Pollut Res Int ; 28(33): 45756-45764, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1193153

ABSTRACT

A more comprehensive understanding of the impact of the COVID-19 pandemic on changes in pollution could serve us to better deal with the environmental challenges caused by the pandemic. Existing studies mainly focused on the linear impact of the pandemic on the pollutants without considering the impact of other factors. To fill the research gap, the nonlinear relationship between pandemic and pollutants with considering the temperature factor was explored by developing panel threshold regression approach. In the proposed approach, the number of confirmed cases was set as explanatory variable, concentrations of NO2 and PM2.5 were set as explained variables, temperature was used as threshold variable, and other air pollution indicators were used as control variables. The results showed that there is a threshold effect between the changes in confirmed COVID-19 cases and the concentrations of PM2.5 and NO2, confirming the impact of the pandemic on pollutions was nonlinear. The results also show that the negative impact of pandemic on pollution increased when the temperature was rising. This work had theoretical and practical significance. The nonlinear research perspective of this article provided a methodological reference for exploring the relationship between epidemic and pollutant-related variables. Furthermore, this study expanded the scope of application of the threshold panel regression model and enriched the quantitative analysis of epidemics and pollutants.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Environmental Pollutants , Air Pollutants/analysis , Air Pollution/analysis , China/epidemiology , Cities , Humans , Pandemics , Particulate Matter/analysis , SARS-CoV-2
11.
Phys Chem Chem Phys ; 23(10): 5852-5863, 2021 Mar 14.
Article in English | MEDLINE | ID: covidwho-1125003

ABSTRACT

COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. Remdesivir is one effective inhibitor for SARS-CoV-2 viral RNA replication. It supersedes other NTP analogues because it not only terminates the polymerization activity of RNA-dependent RNA polymerase (RdRp), but also inhibits the proofreading activity of intrinsic exoribonuclease (ExoN). Even though the static structure of Remdesivir binding to RdRp has been solved and biochemical experiments have suggested it to be a "delayed chain terminator", the underlying molecular mechanisms is not fully understood. Here, we performed all-atom molecular dynamics (MD) simulations with an accumulated simulation time of 24 microseconds to elucidate the inhibitory mechanism of Remdesivir on nucleotide addition and proofreading. We found that when Remdesivir locates at an upstream site in RdRp, the 1'-cyano group experiences electrostatic interactions with a salt bridge (Asp865-Lys593), which subsequently halts translocation. Our findings can supplement the current understanding of the delayed chain termination exerted by Remdesivir and provide an alternative molecular explanation about Remdesivir's inhibitory mechanism. Such inhibition also reduces the likelihood of Remdesivir to be cleaved by ExoN acting on 3'-terminal nucleotides. Furthermore, our study also suggests that Remdesivir's 1'-cyano group can disrupt the cleavage site of ExoN via steric interactions, leading to a further reduction in the cleavage efficiency. Our work provides plausible and novel mechanisms at the molecular level of how Remdesivir inhibits viral RNA replication, and our findings may guide rational design for new treatments of COVID-19 targeting viral replication.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Cyanides/chemistry , Nucleotides/metabolism , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/physiology , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/chemistry , Alanine/metabolism , Alanine/pharmacology , Alanine/therapeutic use , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Humans , Molecular Dynamics Simulation , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Ribose/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Static Electricity , Virus Replication/drug effects , COVID-19 Drug Treatment
12.
Cardiovasc Res ; 116(14): 2197-2206, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-872983

ABSTRACT

The high mortality rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a critical concern of the coronavirus disease 2019 (COVID-19) pandemic. Strikingly, men account for the majority of COVID-19 deaths, with current figures ranging from 59% to 75% of total mortality. However, despite clear implications in relation to COVID-19 mortality, most research has not considered sex as a critical factor in data analysis. Here, we highlight fundamental biological differences that exist between males and females, and how these may make significant contributions to the male-biased COVID-19 mortality. We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans. In contrast, there is strong evidence, especially in the context of viral infections, that sexual dimorphism plays a central role in the genetic and hormonal regulation of immune responses, both of the innate and the adaptive immune system. We review evidence supporting that ineffective anti-SARS-CoV-2 responses, coupled with a predisposition for inappropriate hyperinflammatory responses, could provide a biological explanation for the male bias in COVID-19 mortality. A prominent finding in COVID-19 is the increased risk of death with pre-existing cardiovascular comorbidities, such as hypertension, obesity, and age. We contextualize how important features of sexual dimorphism and inflammation in COVID-19 may exhibit a reciprocal relationship with comorbidities, and explain their increased mortality risk. Ultimately, we demonstrate that biological sex is a fundamental variable of critical relevance to our mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.


Subject(s)
COVID-19/mortality , Cardiovascular Diseases/mortality , Health Status Disparities , Inflammation/mortality , SARS-CoV-2/immunology , Animals , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/virology , Comorbidity , Female , Host-Pathogen Interactions , Humans , Inflammation/diagnosis , Inflammation/immunology , Inflammation/virology , Male , Prognosis , Risk Assessment , Risk Factors , Sex Characteristics , Sex Factors
13.
Viruses ; 12(2)2020 02 21.
Article in English | MEDLINE | ID: covidwho-833229

ABSTRACT

Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CLpro) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CLpro of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CLpro and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CLpro in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CLpro and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CLpro. Finally, we explored the substrate specificity of PEDV 3CLpro at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CLpro substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.


Subject(s)
Antiviral Agents/pharmacology , Peptide Hydrolases/chemistry , Porcine epidemic diarrhea virus/drug effects , Protease Inhibitors/pharmacology , Pyrrolidines/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Catalytic Domain , Chlorocebus aethiops , Crystallography, X-Ray , Models, Molecular , Peptide Hydrolases/metabolism , Porcine epidemic diarrhea virus/enzymology , Porcine epidemic diarrhea virus/physiology , Protease Inhibitors/chemistry , Protease Inhibitors/metabolism , Pyrrolidines/chemistry , Pyrrolidines/metabolism , Substrate Specificity , Sulfonic Acids , Transmissible gastroenteritis virus/enzymology , Vero Cells , Virus Replication/drug effects
14.
Financ Res Lett ; 38: 101716, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-712300

ABSTRACT

We examine the role of ESG performance during market-wide financial crisis, triggered in response to the COVID-19 global pandemic. The unique circumstances create an inimitable opportunity to question if investors interpret ESG performance as a signal of future stock performance and/or risk mitigation. Using a novel dataset covering China's CSI300 constituents, we show (i) high-ESG portfolios generally outperform low-ESG portfolios (ii) ESG performance mitigates financial risk during financial crisis and (iii) the role of ESG performance is attenuated in 'normal' times, confirming its incremental importance during crisis. We phrase the results in the context of ESG investment practices.

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