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1.
iScience ; : 104309, 2022.
Article in English | ScienceDirect | ID: covidwho-1804380

ABSTRACT

SUMMARY MicroRNAs (miRNAs) have been shown to play important roles in viral infections, but their associations with SARS-CoV-2 infection remain poorly understood. Here we detected 85 differentially expressed miRNAs (DE-miRNAs) from 2,336 known and 361 novel miRNAs that were identified in 233 plasma samples from 61 healthy controls and 116 COVID-19 patients using the high throughput sequencing and computational analysis. These DE-miRNAs were associated with SASR-CoV-2 infection, disease severity, and viral persistence in the COVID-19 patients, respectively. Gene ontology and KEGG pathway analyses of the DE-miRNAs revealed their connections to viral infections, immune responses, and lung diseases. Finally, we established a machine learning model using the DE-miRNAs between various groups for classification of COVID-19 cases with different clinical presentations. Our findings may help understand the contribution of miRNAs to the pathogenesis of COVID-19 and identify potential biomarkers and molecular targets for diagnosis and treatment of SARS-CoV-2 infection.

2.
Adv Sci (Weinh) ; : e2104333, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1782562

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

3.
Front Public Health ; 10: 808988, 2022.
Article in English | MEDLINE | ID: covidwho-1776006

ABSTRACT

Objective: This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic subjects with diabetic retinopathy (DR) and those without DR (NDR) in an urban community in Northeast China, as well as their risk factors in subjects with DR and NDR. Methods: A community-based survey involving 1,662 subjects was conducted in Fushun, China, between July 2012 and May 2013. The subjects included diabetics with DR (n = 783) and those NDR (n = 879), and questionnaires were completed to collect information about their sociodemographic and healthcare characteristics. A Chi-square test and multiple logistic analyses were performed to analyze the data. Results: Among the DR group, 21.88% had a good knowledge of DR, 94.15% had a positive attitude, and 68.07% followed good practice, whereas 20.98% of the NDR group had a good knowledge of DR, 94.18% had a positive attitude, and 66.92% followed good practice. There was no significant difference in the KAP of the two groups of subjects. In the NDR group, a good level of knowledge was associated with a high-level of education (OR = 0.1, 0.2; p < 0.05), a good attitude was associated with retirement (OR = 0.2; p < 0.05), and good practice was associated with being female, having a high-level of education, and the type of treatment (OR = 0.5, 0.4, 2.3, 3.1; p < 0.05). In the DR group, good practice was associated with older age and retirement (OR = 0.6, 0.4; p < 0.05). Conclusions: There was no significant difference between the DR and NDR subjects in the overall levels of KAP, but both groups showed a poor level of knowledge. Age, gender, education, occupation, and type of treatment were the main factors associated with the KAP scores, more risk factors in the NDR group than in the DR group. There is an urgent need for coordinated educational campaigns with a prioritized focus on the northeast region of China, especially NDR group.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Health Knowledge, Attitudes, Practice , China , Cross-Sectional Studies , Female , Humans , Urban Population
4.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1733448

ABSTRACT

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

5.
Sci Total Environ ; 825: 153964, 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1689055

ABSTRACT

Fine particulate matter (PM2.5) pollution poses significant health concerns worldwide and can cause respiratory diseases. However, how it causes health problems is still poorly understood. Angiotensin-converting enzyme (ACE)2 is a terminal carboxypeptidase implicated in the functions of renin-angiotensin system (RAS) and plays a crucial role in the control of lung inflammation. To investigate whether ACE2 functions in PM2.5-induced lung inflammation, wild-type (WT) C57BL/6J mice and ACE2 knock-out (KO) mice were intratracheally instilled with PBS or PM2.5 suspension for 3 consecutive days, respectively. The concentrations of cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. The expression of ACE2 and ACE and activation of inflammatory signaling pathways in lung tissues were evaluated by immunofluorescence staining and Western blotting. We found that PM2.5 exposure increased ACE2 expression. Loss of ACE2 significantly elevated the levels of total proteins, total cells, and the concentrations of MCP-1, IL-1ß in BALF after PM2.5 challenge. Additionally, loss of ACE2 enhanced lung pathologies, airway resistance, and inflammatory signaling activation. Collectively, loss of ACE2 exacerbates PM2.5-induced acute lung injury in mice.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325222

ABSTRACT

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001;Approval Number: P20001/PJ01.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325150

ABSTRACT

The special epistemic characteristics of the COVID-19, such as the long incubation period and the infection through asymptomatic cases, put severe challenge to the containment of its outbreak. By the end of March 2020, China has successfully controlled the within-spreading of COVID-19 at a high cost of locking down most of its major cities, including the epicenter, Wuhan. Since the low accuracy of outbreak data before the mid of Feb. 2020 forms a major technical concern on those studies based on statistic inference from the early outbreak. We apply the supervised learning techniques to identify and train NP-Net-SIR model which turns out robust under poor data quality condition. By the trained model parameters, we analyze the connection between population flow and the cross-regional infection connection strength, based on which a set of counterfactual analysis is carried out to study the necessity of lock-down and substitutability between lock-down and the other containment measures. Our findings support the existence of non-lock-down-typed measures that can reach the same containment consequence as the lock-down, and provide useful guideline for the design of a more flexible containment strategy.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323881

ABSTRACT

Discharged COVID-19 patients have been found to be retested positive for SARS-CoV-2 (re-positive), which has widely raised concern among the public. We investigated the prevalence and transmission risk of re-positive cases in discharged COVID-19 patients and their SARS-CoV-2-specific antibody levels in Wuhan, China. Of 1065 discharged COVID-19 patients investigated, 518 (48.64%) patients were males;the mean age was 53.29 ± 14.91 years, with a median duration of 40 (IQR: 31–47) days since discharge. 63 patients were tested re-positive for SARS-CoV-2, with the re-positive prevalence to be 5.92% (95%CI: 4.50%-7.33%). The re-positive prevalence was higher in females (7.86%, 95%CI: 5.61%-10.12%) than that in males (3.86%, 95%CI: 2.20%-5.52%, P  = 0.006). Re-positive prevalence was similar in patients tested positive and negative for IgG (6.01% vs 5.56%, P  = 0.821) or IgM (6.38% vs 5.07%, P  = 0.394). Illness severity and duration from illness onset to retest were not associated with the risk of positive results for SARS-CoV-2 after discharge. All 196 environmental samples collected from 49 re-positive patients were tested negative for SAR-CoV-2. Only one close contact to the re-positive patient had been tested positive for SARS-CoV-2;however, he might be a previous COVID-19 case but had not been detected before. Viral culture of 6 nasopharyngeal specimens presented no cytopathic effect of Vero E6 cells. Virus sequencing of 11 nasopharyngeal specimens indicated genomic fragments of SARS-CoV-2. 898 (84.72%) patients and 705 (66.51%) patients were tested positive for SARS-CoV-2-specific IgG and IgM, respectively. Self-report symptoms at the survey were similar, regardless of the level of antibody. All the re-positive patients and their matched non-re-positive patients were tested negative for SARS-CoV-2 four months later. These findings indicate that Testing re-positive of SARS-CoV-2 is common in discharged COVID-19 patients, but no evidence showed the transmission risk of these re-positive cases. Further isolation of recovered COVID-19 patients is unnecessary. However, only 85% recovered COVID-19 patients had SARS-CoV-2-specific antibody, which suggested discharged COVID-19 patients still had potential re-infection risk.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323745

ABSTRACT

Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients. Methods: : From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed. Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points. Conclusions: : Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323708

ABSTRACT

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely unknown. Here, we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. Notable cell subsets include (NCAM1hiCD160+)NK and (TRAV1-2+CD8+)MAIT cells increased in the asymptomatic subjects, (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients, (CD68-CSF1R-IL1BhiCD14+)classical monocytes associated with age and disease severity, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC associated with the viral persistence, neutrophils and (CD68-CSF1R-IL1BhiCD14+ )classical monocytes dramatically increased in a fatal patient, whereas (LAG3+CD160+CD8+)NKT and (FOXP3+IL2RA+IL7R+CD4+)Treg cells markedly increased in a patient with humoral immunodeficiency. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, apoptosis and other processes. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.Funding Information: This study is supported in part by the Department of Science and Technology of Shaanxi Province (Grant No. 2020ZDXM2-SF-02) (CZ and BS) and the operational funds from The First Affiliated Hospital of Xi’an Jiaotong University (CZ and BS).Declaration of Interests: The authors declare that they have no competing financial interests.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315169

ABSTRACT

During a pandemic, it is essential to secure a broad allocation of life-saving goods, such as medical and protective products, to save lives. However, these goods are often in short supply, due to consumer hoarding, insufficient manufacturing capacity and price gouging. Herein, we develop a game-theoretic supply chain model to evaluate the impact of government regulations on the shortage of life-saving goods and profit within the supply chain. Our model considers three types of regulation: (i) price regulation in the form of a price cap, (ii) purchase regulation or demand rationing and (iii) a combination thereof. The most distinguishing feature of our model is that it captures consumer panic buying, insufficient capacity, price surges and controls on the supply and demand side of the supply chain that are widely observed during a pandemic. The results establish reasonably simple prescriptions for policymakers to design effective and easy-to-implement regulations to mitigate shortages of critical supplies in the face of a pandemic.

12.
Front Psychol ; 12: 601383, 2021.
Article in English | MEDLINE | ID: covidwho-1608970

ABSTRACT

In the environment of COVID-19, people are faced with mortality salience (MS) and socioeconomic crisis. According to the terror management theory, the MS would lead to particular consumption attitudes and behaviors caused by the self-esteem and cultural worldview defense. The creativity as a potential value of products needs to be examined to explore how the MS changed the creativity evaluation of three types of products categorized into normal, renovative, and innovative products, based on the degree of originality (Zhang et al., 2019). Two experiments were conducted to examine (1) the MS effect on the creativity and purchase intention evaluation and (2) both MS and country-of-origin effect on the evaluations. The results show that usefulness and purchase intention are affected by both effects, and the novelty is mainly affected by MS.

13.
European Journal of Operational Research ; 2021.
Article in English | ScienceDirect | ID: covidwho-1549760

ABSTRACT

During a pandemic, it is essential to secure a broad allocation of life-saving goods, such as medical and protective products, to save lives. However, these goods are often in short supply, due to consumer hoarding, insufficient manufacturing capacity and price gouging. Herein, we develop a game-theoretic supply chain model to evaluate the impact of government regulations on the shortage of life-saving goods and profit within the supply chain. Our model considers three types of regulation: (i) price regulation in the form of a price cap, (ii) purchase regulation or demand rationing and (iii) a combination thereof. The most distinguishing feature of our model is that it captures consumer panic buying, insufficient capacity, price surges and controls on the supply and demand side of the supply chain that are widely observed during a pandemic. The results establish reasonably simple prescriptions for policymakers to design effective and easy-to-implement regulations to mitigate shortages of critical supplies in the face of a pandemic.

14.
Microb Biotechnol ; 14(6): 2356-2368, 2021 11.
Article in English | MEDLINE | ID: covidwho-1522630

ABSTRACT

Salinomycin, an FDA-approved polyketide drug, was recently identified as a promising anti-tumour and anti-viral lead compound. It is produced by Streptomyces albus, and the biosynthetic gene cluster (sal) spans over 100 kb. The genetic manipulation of large polyketide gene clusters is challenging, and approaches delivering reliable efficiency and accuracy are desired. Herein, a delicate strategy to enhance salinomycin production was devised and evaluated. We reconstructed a minimized sal gene cluster (mini-cluster) on pSET152 including key genes responsible for tailoring modification, antibiotic resistance, positive regulation and precursor supply. These genes were overexpressed under the control of constitutive promoter PkasO* or Pneo . The pks operon was not included in the mini-cluster, but it was upregulated by SalJ activation. After the plasmid pSET152::mini-cluster was introduced into the wild-type strain and a chassis host strain obtained by ribosome engineering, salinomycin production was increased to 2.3-fold and 5.1-fold compared with that of the wild-type strain respectively. Intriguingly, mini-cluster introduction resulted in much higher production than overexpression of the whole sal gene cluster. The findings demonstrated that reconstitution of sal mini-cluster combined with ribosome engineering is an efficient novel approach and may be extended to other large polyketide biosynthesis.


Subject(s)
Streptomyces , Multigene Family , Pyrans , Ribosomes/genetics , Streptomyces/genetics
15.
Signal Transduct Target Ther ; 6(1): 389, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1510582

ABSTRACT

SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2. By replacing the VSV glycoprotein with the spikes (S) of SARS-CoV-2 and SARS-CoV, we generated two replication-competent recombinant viruses, rVSV-SARS-CoV-2 and rVSV-SARS-CoV. Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV, no obvious cross-neutralizing activity was observed in the immunized mice sera. In macaques, neutralizing antibody (NAb) titers induced by one i.n. dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m. dose. Thus, our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n. administration instead of the traditional i.m. immunization in human. Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV-2 in a route-independent manner, we generated a chimeric antigen by replacing the receptor binding domain (RBD) of SARS-CoV S with that from the SARS-CoV-2. rVSV expressing the chimera (rVSV-SARS-CoV/2-RBD) induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2, with a safe Th1-biased response. Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV. hACE2 mice receiving a single i.m. dose of either rVSV-SARS-CoV-2 or rVSV-SARS-CoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs. Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Gene Knock-In Techniques , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Neutralization Tests , Recombinant Fusion Proteins/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
16.
Front Cell Infect Microbiol ; 11: 755508, 2021.
Article in English | MEDLINE | ID: covidwho-1497026

ABSTRACT

COVID-19 continues to circulate globally in 2021, while under the precise policy implementation of China's public health system, the epidemic was quickly controlled, and society and the economy have recovered. During the pandemic response, nucleic acid detection of SARS-CoV-2 has played an indispensable role in the first line of defence. In the cases of emergency operations or patients presenting at fever clinics, nucleic acid detection is required to be performed and reported quickly. Therefore, nucleic acid point-of-care testing (POCT) technology for SARS-CoV-2 identification has emerged, and has been widely carried out at all levels of medical institutions. SARS-CoV-2 POCT has served as a complementary test to conventional polymerase chain reaction (PCR) batch tests, thus forming an experimental diagnosis platform that not only guarantees medical safety but also improves quality services. However, in view of the complexity of molecular diagnosis and the biosafety requirements involved, pathogen nucleic acid POCT is different from traditional blood-based physical and chemical index detection. No guidelines currently exist for POCT quality management, and there have been inconsistencies documented in practical operation. Therefore, Shanghai Society of Molecular Diagnostics, Shanghai Society of Laboratory Medicine, Clinical Microbiology Division of Shanghai Society of Microbiology and Shanghai Center for Clinical Laboratory have cooperated with experts in laboratory medicine to generate the present expert consensus. Based on the current spectrum of major infectious diseases in China, the whole-process operation management of pathogen POCT, including its application scenarios, biosafety management, personnel qualification, performance verification, quality control, and result reporting, are described here. This expert consensus will aid in promoting the rational application and robust development of this technology in public health defence and hospital infection management.


Subject(s)
COVID-19 , Nucleic Acids , China , Consensus , Humans , Point-of-Care Testing , SARS-CoV-2
17.
Front Cell Dev Biol ; 9: 766142, 2021.
Article in English | MEDLINE | ID: covidwho-1497022

ABSTRACT

As an evolutionarily conserved cellular process, autophagy plays an essential role in the cellular metabolism of eukaryotes as well as in viral infection and pathogenesis. Under physiological conditions, autophagy is able to meet cellular energy needs and maintain cellular homeostasis through degrading long-lived cellular proteins and recycling damaged organelles. Upon viral infection, host autophagy could degrade invading viruses and initial innate immune response and facilitate viral antigen presentation, all of which contribute to preventing viral infection and pathogenesis. However, viruses have evolved a variety of strategies during a long evolutionary process, by which they can hijack and subvert host autophagy for their own benefits. In this review, we highlight the function of host autophagy in the key regulatory steps during viral infections and pathogenesis and discuss how the viruses hijack the host autophagy for their life cycle and pathogenesis. Further understanding the function of host autophagy in viral infection and pathogenesis contributes to the development of more specific therapeutic strategies to fight various infectious diseases, such as the coronavirus disease 2019 epidemic.

18.
Front Immunol ; 12: 748566, 2021.
Article in English | MEDLINE | ID: covidwho-1463474

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Immunoglobulin G/metabolism , SARS-CoV-2/physiology , Adult , Antibody-Dependent Cell Cytotoxicity , Case-Control Studies , Chromatography, High Pressure Liquid , Complement Pathway, Mannose-Binding Lectin , Female , Glycosylation , Humans , Male , Middle Aged , Phenotype
19.
BMJ Open ; 11(6): e049762, 2021 06 09.
Article in English | MEDLINE | ID: covidwho-1376505

ABSTRACT

INTRODUCTION: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk. METHODS AND ANALYSIS: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention. ETHICS AND DISSEMINATION: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15986016.


Subject(s)
Cell Phone , Dementia , Mobile Applications , Aged , China , Dementia/prevention & control , Humans , London , Middle Aged , Randomized Controlled Trials as Topic
20.
Org Biomol Chem ; 19(30): 6650-6656, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-1343477

ABSTRACT

The exquisite chemodiversity of terpenoids is the product of the large diverse terpene synthase (TPS) superfamily. Here, by using structural and phylogenetic analyses and site-directed mutagenesis, we identified a residue (Cys440 in Nicotiana tabacum 5-epi-aristolochene synthase) proximal to an ion-binding motif common to all TPSs and named the preNSE/DTE residue, which determines the product specificity of sesquiterpene synthases from different plant species. In sesquiterpene synthases catalyzing 1,10-cyclization (1,10-cyclases) of farnesyl diphosphate, mutation of the residue in both specific and promiscuous 1,10-cyclases from different lineages leads to the accumulation of monocyclic germacrene A-11-ol, which is "short-circuited" from complex cyclization cascades, suggesting a key role of this residue in generating the first common intermediate of 1,10-cyclization. Altering this residue in a specific 1,11-cyclase results in alternative 1,10-cyclization products. Moreover, the preNSE/DTE residue can be harnessed to engineer highly specific sesquiterpene synthases for an improved proportion of high-value terpenoids, such as patchoulol, a main constituent of several traditional Chinese medicines that could treat SARS-CoV-2.


Subject(s)
Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/metabolism , Biocatalysis , Alkyl and Aryl Transferases/genetics , Catalytic Domain , Cyclization , Models, Molecular , Mutagenesis, Site-Directed , Phylogeny , Tobacco/enzymology
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