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1.
Atmospheric Pollution Research ; : 101785, 2023.
Article in English | ScienceDirect | ID: covidwho-2308604

ABSTRACT

Hypertension is a common chronic disease, and air pollution is strongly associated with hypertension hospitalization. However, the association between nitrogen dioxide (NO2)1 concentration and hypertension hospitalization has rarely been studied. We collected daily data on hypertension hospitalizations, air pollutants, and meteorology from January 1, 2016 to October 31, 2021. After controlling for the effects of seasonal and long-term trends, weather conditions, weekdays, holidays, and during the novel coronavirus crown epidemic, a generalized additive model with over discrete Poisson regression was used to simulate the association between NO2 concentration and hypertension hospitalizations while quantifying hypertension hospitalizations, hospital stays, and hospital costs attributable to NO2. The results showed that each 10 μg/m3 increase in NO2 concentration was significantly associated with the relative risk (RR) of hypertension admission in Xinxiang, with the greatest effect at lag04 (RR = 1.107;95% confidence interval, 1.046–1.172). Hypertension hospitalizations attributed to NO2 during the study period accounted for 9.70% (484) of the total hypertension hospitalizations, equivalent to 4202 hospital days and 338.55 thousand United States dollars (USD). Increased NO2 concentration increases the risk of hypertension hospitalization in Xinxiang, which poses a significant health and economic burden to society and patients. The findings of this study provide a basis for developing stricter environmental pollutant standards.

2.
J Clin Endocrinol Metab ; 2023 Mar 23.
Article in English | MEDLINE | ID: covidwho-2286235

ABSTRACT

Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet beta-cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the coronavirus disease 2019(COVID-19) pandemic, cases of hyperglycemia, diabetic ketoacidosis (DKA), and new diabetes increased, suggesting that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may be a trigger for or unmask T1D. Possible mechanisms of beta-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic beta-cells, and damage to beta-cells due to infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet beta-cells in the above three aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.

4.
Front Microbiol ; 13: 959433, 2022.
Article in English | MEDLINE | ID: covidwho-2259957

ABSTRACT

The high morbidity of patients with coronavirus disease 2019 (COVID-19) brings on a panic around the world. COVID-19 is associated with sex bias, immune system, and preexisting chronic diseases. We analyzed the gene expression in patients with COVID-19 and in their microbiota in order to identify potential biomarkers to aid in disease management. A total of 129 RNA samples from nasopharyngeal, oropharyngeal, and anal swabs were collected and sequenced in a high-throughput manner. Several microbial strains differed in abundance between patients with mild or severe COVID-19. Microbial genera were more abundant in oropharyngeal swabs than in nasopharyngeal or anal swabs. Oropharyngeal swabs allowed more sensitive detection of the causative SARS-CoV-2. Microbial and human transcriptomes in swabs from patients with mild disease showed enrichment of genes involved in amino acid metabolism, or protein modification via small protein removal, and antibacterial defense responses, respectively, whereas swabs from patients with severe disease showed enrichment of genes involved in drug metabolism, or negative regulation of apoptosis execution, spermatogenesis, and immune system, respectively. Microbial abundance and diversity did not differ significantly between males and females. The expression of several host genes on the X chromosome correlated negatively with disease severity. In this way, our analyses identify host genes whose differential expression could aid in the diagnosis of COVID-19 and prediction of its severity via non-invasive assay.

5.
BMC Cardiovasc Disord ; 22(1): 473, 2022 11 08.
Article in English | MEDLINE | ID: covidwho-2277245

ABSTRACT

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has emerged as an increasingly diagnosed cause of ST-segment elevation myocardial infarction (STEMI), which is easily missed or delayed. The effective use of coronary angiography (CAG) and advanced intracoronary imaging examinations in STEMI patients has led to increased detection of SCAD. CASE PRESENTATION: A 59-year-old woman with acute angina pectoris was diagnosed with STEMI detected by electrocardiography combined with measurement of myocardial enzymes. Due to the ongoing pandemic of coronavirus disease 2019 (COVID-19) in Wuhan, she was first given thrombolytic therapy after excluding contraindications according to the requirements of the current consensus statement; however, subsequently, both the symptoms of ongoing chest pain and the electrocardiographic results indicated the failure of thrombolytic therapy, so the intervention team administered rescue percutaneous coronary intervention treatment under third-grade protection. CAG confirmed total occlusion in the distal left anterior descending (LAD) artery, with thrombolysis in myocardial infarction (TIMI) 0 flow, whereas the left circumflex and right coronary arteries appeared normal, with TIMI 3 flow. Intravenous ultrasound (IVUS) was further performed to investigate the causes of occlusion, which verified the absence of atherosclerosis but detected SCAD with intramural haematoma. During the operation, the guidewire reached the distal end of the LAD artery smoothly, the balloon was dilated slightly, and the reflow of TIMI blood could be seen by repeated CAG. During the follow-up period of one and a half years, the patient complained of occasional, slight chest tightness. The repeated CAG showed that the spontaneous dissection in the LAD artery had healed well, with TIMI 3 flow. The repeated IVUS confirmed that the SCAD and intramural haematoma had been mostly resorbed and repaired. CONCLUSION: This was a case of failed STEMI thrombolysis in our hospital during the outbreak of COVID-19. This case indicates that doctors need to consider the cause of the disease when treating STEMI patients, especially patients without traditional cardiovascular risk factors. Moreover, CAG and intracoronary imaging examinations should be actively performed to identify the aetiology and improve the treatment success rate.


Subject(s)
COVID-19 , Myocardial Infarction , ST Elevation Myocardial Infarction , Female , Humans , Middle Aged , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/therapy , COVID-19/complications , Myocardial Infarction/therapy , Coronary Angiography/adverse effects , Thrombolytic Therapy/adverse effects , Hematoma/complications
6.
Adv Sci (Weinh) ; : e2203088, 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2148251

ABSTRACT

Splicing of influenza A virus (IAV) RNA is an essential process in the viral life cycle that involves the co-opting of host factors. Here, it is demonstrated that induction of host serine and arginine-rich splicing factor 5 (SRSF5) by IAV facilitated viral replication by enhancing viral M mRNA splicing. Mechanistically, SRSF5 with its RRM2 domain directly bounds M mRNA at conserved sites (M mRNA position 163, 709, and 712), and interacts with U1 small nuclear ribonucleoprotein (snRNP) to promote M mRNA splicing and M2 production. Mutations introduced to the three binding sites, without changing amino acid code, significantly attenuates virus replication and pathogenesis in vivo. Likewise, SRSF5 conditional knockout in the lung protects mice against lethal IAV challenge. Furthermore, anidulafungin, an approved antifungal drug, is identified as an inhibitor of SRSF5 that effectively blocks IAV replication in vitro and in vivo. In conclusion, SRSF5 as an activator of M mRNA splicing promotes IAV replication and is a host-derived antiviral target.

7.
Frontiers in psychology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2045640

ABSTRACT

The psychological impact of the COVID-19 epidemic on college students is an important topic. With the entry of the post-epidemic era, how universities can better improve students’ psychological resilience in teaching is the research topic of this article. In the form of a questionnaire survey, some entrepreneurial college students investigated the loneliness and psychological resilience of college students after the outbreak of the epidemic and explored the role of self-efficacy in it. The data is collected online through cooperation with an entrepreneurial event, and the participating students are asked for background information such as colleges, grade, and majors. After collecting this information, they answered a series of simplified scale questions about loneliness, self-efficacy, and psychological resilience. In the end, a total of 200 questionnaires from different universities were collected, and the structural equation model was used to explore the role of self-efficacy. The results show that: loneliness has a significant negative effect on Self-efficacy, β = -0.292, p < 0.001;Self-efficacy has a significant positive effect on psychological resilience, β = 0.556, p < 0.0 01;loneliness has a significant negative effect on psychological resilience, β = -0.244, p < 0.01. Self-Efficacy has a significant intermediate effect in loneliness and psychological resilience, with an effective value of -0.111 and p < 0.01. The results show that this exploratory survey finds it important to provide targeted personal self-efficacy improvement activities for college students with a strong sense of loneliness and to combine school and family education organically to help college students form a healthy and upward mentality to better cope with the unknown and troubles caused by the epidemic, which will help improve the psychological resilience of college students in the epidemic.

8.
Frontiers in microbiology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2033958

ABSTRACT

The high morbidity of patients with coronavirus disease 2019 (COVID-19) brings on a panic around the world. COVID-19 is associated with sex bias, immune system, and preexisting chronic diseases. We analyzed the gene expression in patients with COVID-19 and in their microbiota in order to identify potential biomarkers to aid in disease management. A total of 129 RNA samples from nasopharyngeal, oropharyngeal, and anal swabs were collected and sequenced in a high-throughput manner. Several microbial strains differed in abundance between patients with mild or severe COVID-19. Microbial genera were more abundant in oropharyngeal swabs than in nasopharyngeal or anal swabs. Oropharyngeal swabs allowed more sensitive detection of the causative SARS-CoV-2. Microbial and human transcriptomes in swabs from patients with mild disease showed enrichment of genes involved in amino acid metabolism, or protein modification via small protein removal, and antibacterial defense responses, respectively, whereas swabs from patients with severe disease showed enrichment of genes involved in drug metabolism, or negative regulation of apoptosis execution, spermatogenesis, and immune system, respectively. Microbial abundance and diversity did not differ significantly between males and females. The expression of several host genes on the X chromosome correlated negatively with disease severity. In this way, our analyses identify host genes whose differential expression could aid in the diagnosis of COVID-19 and prediction of its severity via non-invasive assay.

9.
J Med Virol ; 94(10): 5051-5055, 2022 10.
Article in English | MEDLINE | ID: covidwho-1981861

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.


Subject(s)
COVID-19 Drug Treatment , Antiviral Agents/therapeutic use , Humans , Pandemics/prevention & control , SARS-CoV-2
10.
Front Med (Lausanne) ; 8: 823346, 2021.
Article in English | MEDLINE | ID: covidwho-1979041

ABSTRACT

The vaccine is still the best clinical measure for effective prevention and control of coronavirus disease 2019 (COVID-19). The vaccine-associated ocular adverse reactions should be noted in detail among the medical community. We reported twelve eyes of 9 patients presented at the Department of Ophthalmology, Qilu Hospital of Shandong University from March to August 2021 with ocular complaints following COVID-19 vaccination. The main inclusion criterion was the development of ocular symptoms within 14 days after receiving a dose of an inactivated COVID-19 vaccine. The mean (SD) age was 44.7 ± 16.5 years (range, 19-78 years), among which seven (77.8%) cases were women. The mean time of ocular adverse events was 7.1 days (range, 1-14 days) after receiving the inactivated COVID-19 vaccine. One patient was diagnosed with choroiditis, 1 with uveitis, 4 with keratitis, 1 with scleritis, 1 with acute retinal necrosis, and 1 with iridocyclitis. Although the causal relationship between vaccines and ocular adverse events cannot be established from this case series report, physicians should pay attention to the ocular adverse reactions following the COVID-19 vaccine administration.

11.
ACS Infect Dis ; 8(6): 1191-1203, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1873405

ABSTRACT

SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allows for rapid movement of the existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells when the receptor-binding domain of the spike protein on the surface of SARS-CoV-2 binds to ACE2 followed by cleavage at two cut sites by TMPRSS2. Therefore, a molecule capable of inhibiting the protease activity of TMPRSS2 could be a valuable antiviral therapy. Initially, we used a fluorogenic high-throughput screening assay for the biochemical screening of 6030 compounds in NCATS annotated libraries. Then, we developed an orthogonal biochemical assay that uses mass spectrometry detection of product formation to ensure that hits from the primary screen are not assay artifacts from the fluorescent detection of product formation. Finally, we assessed the hits from the biochemical screening in a cell-based SARS-CoV-2 pseudotyped particle entry assay. Of the six molecules advanced for further studies, two are approved drugs in Japan (camostat and nafamostat), two have entered clinical trials (PCI-27483 and otamixaban), while the other two molecules are peptidomimetic inhibitors of TMPRSS2 taken from the literature that have not advanced into clinical trials (compounds 92 and 114). This work demonstrates a suite of assays for the discovery and development of new inhibitors of TMPRSS2.


Subject(s)
COVID-19 Drug Treatment , Percutaneous Coronary Intervention , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Drug Repositioning/methods , Humans , Pandemics , SARS-CoV-2 , Serine Endopeptidases
12.
J Clin Virol Plus ; 2(2): 100074, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1867341

ABSTRACT

Large scale screening of health care workers and the general population for asymptomatic COVID-19 infection requires modalities that are amenable to testing at scale while retaining acceptable levels of sensitivity and specificity. This study evaluated a novel COVID-19 Direct-RT LAMP assay using saliva samples in asymptomatic individuals by comparison to RT-PCR. Additional studies were performed using VTM collected from routine diagnostic testing. Analytical sensitivity was determined for Direct RT-LAMP assay using the WHO International Standard. Finally, quantified results from RT-PCR testing of 9177 nose and throat swabs obtained from routine diagnostic testing were used to estimate the sensitivity of Direct RT-LAMP using the limit of detection curve obtained from the analytical sensitivity data. Results from saliva testing demonstrated a sensitivity of 40.91% and a specificity of 100% for Direct RT-LAMP. The sensitivity and specificity for nose and throat swabs were 44.85% and 100% respectively. The 95% limit of detection (LOD) for Direct RT-LAMP was log 7.13 IU/ml (95% 6.9-7.5). The estimated sensitivity for Direct-RT LAMP based on the results of 9117 nose and throat swabs was 34% and 45% for saliva and VTM respectively. The overall diagnostic sensitivity of Direct RT-LAMP was low compared to RT-PCR. Testing of nose and throat swabs and estimating the sensitivity based on a large cohort of clinical samples demonstrated similar results. This study highlights the importance of utilising the prospective collection of samples from the intended target population in the assessment of diagnostic sensitivity.

13.
Front Psychol ; 13: 868692, 2022.
Article in English | MEDLINE | ID: covidwho-1862677

ABSTRACT

The outbreak of Coronavirus disease 2019 (COVID-19) has caused enterprises to face more challenges, such as operational management, production and sales management, and human resource management, among other issues. In the context of the global knowledge economy, employees with high knowledge and skills have become an important source of corporate growth and breakthroughs. However, employees may intend to transfer to other companies due to the pressure of the external and internal environments, so the main topic explored by this paper will be the change of employees' turnover intention. The purpose of this study was to explore the influence mechanism that propels the employees' self-efficacy, job stress, and turnover intention, and the moderating effect of transformational leadership. A total of 553 valid responses from several information service companies in China are collected via purposive sampling and used in the data analysis. This study conducts partial least squares structural equation modeling partial least squares structural equation modeling (PLS-SEM) to analyze collected data. The results of the path analysis with structural equation modeling show that employees' psychological contracts have a positive impact on the self-efficacy and a negative impact on the job stress. Employees' self-efficacy has a negative impact on job stress and turnover intention; transformational leadership plays a significant moderator in the research framework. Based on research findings, the theoretical and managerial implications are presented.

14.
Discrete Dynamics in Nature & Society ; : 1-6, 2022.
Article in English | Academic Search Complete | ID: covidwho-1840659

ABSTRACT

This paper employs data envelopment analysis (DEA) to determine crop production efficiency in 15 major provinces of China during 2019-2020. The total power of agricultural machinery, the application amount of chemical fertilizer, the irrigation area of cultivated land, the area of grain sowing, and the total capacity of reservoirs in each province are defined as the input items. The production of food, production of oil plants, and production of fruits are considered output items. According to the findings from the DEA, the most efficient crop production is observed in Shandong and Xinjiang provinces. We also discuss the role of farmers' uncertainty perceptions in COVID-19. By cluster analysis, the provinces with large grain sown area and high grain yield are Henan and Heilongjiang, the provinces with moderate grain production in the grain sown area are Hunan, Hubei, Jiangxi, Guizhou, and Yunnan, and Xinjiang, Shandong, Hebei, Anhui, Sichuan, Jiangsu, Inner Mongolia, and Jilin are the provinces with low grain production. [ FROM AUTHOR] Copyright of Discrete Dynamics in Nature & Society is the property of Hindawi Limited 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.)

15.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202204.0185.v3

ABSTRACT

There are two contrary opinions regarding the risk if mainland China (MC) moves away from its zero-COVID policy. Some experts think the risk shall be much lower than influenza as per MC’s own COVID-19 case fatality rate (CFR), while some other experts think the risk shall be much higher than influenza as per the COVID-19 CFRs of other regions. We elucidate here that this and multiple other striking differences in the CFR between various scenarios all support and substantially resulted from the view that good IDM is highly powerful to mitigate COVID-19, where IDM (isolation-disinfection-maintenance) means isolation of COVID-19 cases from other people, disinfection of their living environments, and health maintenance (e.g., rest, nutrition, breathing). The high effect of good IDM is also supported by the theoretic functions of IDM in minimizing co-infections and maintaining body functions, and the fact that all the 505 COVID-19 deaths reported in MC in 2022 before May 5 died directly of severe underlying diseases with COVID-19. Although it is tough for people in poverty to obtain good IDM, good IDM can be feasible at home for the most mild cases and in hospitals for the most severe cases. Therefore, good IDM can be crucial to mitigating COVID-19 worldwide. It also suggests that the risk for China to end its zero-COVID policy depends on China’s control policies or measures. Based on the effect of IDM, the cautious co-existence policy was proposed for COVID-19 control. This policy could reduce the whole death toll in MC because good IDM is non-specific and can reduce deaths of various other diseases. The cautious co-existence policy (non-specific) and the vaccination policy (specific) aid each other to mitigate COVID-19, and they cannot replace each other. Those who are qualified in health for vaccination should be vaccinated against COVID-19 timely.


Subject(s)
COVID-19
16.
J Chem Inf Model ; 62(8): 1988-1997, 2022 04 25.
Article in English | MEDLINE | ID: covidwho-1783923

ABSTRACT

The cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time consuming, and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in ∼2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets.


Subject(s)
Antiviral Agents , SARS-CoV-2 , Virus Internalization , Actins , Antiviral Agents/chemistry , Heparan Sulfate Proteoglycans , Humans , SARS-CoV-2/drug effects , Virus Internalization/drug effects , COVID-19 Drug Treatment
17.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
18.
Front Neurol ; 12: 769511, 2021.
Article in English | MEDLINE | ID: covidwho-1606848

ABSTRACT

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem medical condition with heterogeneous symptom expression. Currently, there is no effective cure or treatment for the standard care of patients. A variety of ME/CFS symptoms can be linked to the vital life functions of the brainstem, the lower extension of the brain best known as the hub relaying information back and forth between the cerebral cortex and various parts of the body. Objective/Methods: Over the past decade, Magnetic Resonance Imaging (MRI) studies have emerged to understand ME/CFS with interesting findings, but there has lacked a synthesized evaluation of what has been found thus far regarding the involvement of the brainstem. We conducted this study to review and evaluate the recent MRI findings via a literature search of the MEDLINE database, from which 11 studies met the eligibility criteria. Findings: Data showed that MRI studies frequently reported structural changes in the white and gray matter. Abnormalities of the functional connectivity within the brainstem and with other brain regions have also been found. The studies have suggested possible mechanisms including astrocyte dysfunction, cerebral perfusion impairment, impaired nerve conduction, and neuroinflammation involving the brainstem, which may at least partially explain a substantial portion of the ME/CFS symptoms and their heterogeneous presentations in individual patients. Conclusions: This review draws research attention to the role of the brainstem in ME/CFS, helping enlighten future work to uncover the pathologies and mechanisms of this complex medical condition, for improved management and patient care.

19.
SLAS Discov ; 27(2): 86-94, 2022 03.
Article in English | MEDLINE | ID: covidwho-1586501

ABSTRACT

Effective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay. Here, the pseudotyped particles (PP) contain SARS-CoV-2 spike in a membrane enveloping both the murine leukemia virus (MLV) gag-pol polyprotein and luciferase reporter RNA. Upon addition of PP to HEK293-ACE2 cells, the SARS-CoV-2 spike protein binds to the ACE2 receptor on the cell surface, resulting in priming by host proteases to trigger endocytosis of these particles, and membrane fusion between the particle envelope and the cell membrane. The internalized luciferase reporter gene is then expressed in cells, resulting in a luminescent readout as a surrogate for spike-mediated entry into cells. This SARS-CoV-2 PP entry assay can be executed in a biosafety level 2 containment lab for high throughput screening. From a collection of 5,158 approved drugs and drug candidates, our screening efforts identified 7 active compounds that inhibited the SARS-CoV-2-S PP entry. Of these seven, six compounds were active against live replicating SARS-CoV-2 virus in a cytopathic effect assay. Our results demonstrated the utility of this assay in the discovery and development of SARS-CoV-2 entry inhibitors as well as the mechanistic study of anti-SARS-CoV-2 compounds. Additionally, particles pseudotyped with spike proteins from SARS-CoV-2 B.1.1.7 and B.1.351 variants were prepared and used to evaluate the therapeutic effects of viral entry inhibitors.


Subject(s)
Antiviral Agents/pharmacology , High-Throughput Screening Assays/methods , SARS-CoV-2/drug effects , Virus Internalization/drug effects , HEK293 Cells , Humans
20.
Chemical Engineering Journal ; : 133635, 2021.
Article in English | ScienceDirect | ID: covidwho-1517081

ABSTRACT

The chloroxylenol (PCMX) has shown well virucidal efficacy against COVID-19, but the large-scale utilization of which will undoubtedly pose extra environmental threaten. In the present study, the recycled industrial phenylenediamine residue was used and an integrated strategy of “carbonization-casting-activation” using super low-dose of activator and templates was established to achieve in-situ N/O co-doping and facile synthesis of a kind of hierarchical hyperporous carbons (HHPC). The sample of HHPC-1.25-0.5 obtained with activator and template to residue of 1.25 and 0.5 respectively shows super-high specific surface area of 3602 m2/g and volume of 2.81 cm3/g and demonstrates remarkable adsorption capacity of 1475 mg/g for PCMX in batch and of 1148 mg/g in dynamic column adsorption test. In addition, the HHPC-1.25-0.5 exhibits excellent reusability and tolerance for PCMX adsorption under various ionic backgrounds and real water matrix conditions. The combined physio-chemistry characterization, kinetic study and DFT calculation reveal that the enhanced high performances originate from the hierarchical pore structure and strong electrostatic interaction between PCMX and surface rich pyridinic-N and carbonyl groups.

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