Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 129
Filter
Add filters

Year range
1.
Applied Energy ; 309:118458, 2022.
Article in English | ScienceDirect | ID: covidwho-1616365

ABSTRACT

The black swan event will usually cause a great impact on the normal operation of society. The scarcity of such events leads to a lack of relevant data and challenges in dealing with related problems. Different situations also make the traditional methods invalid. In this paper, a transfer learning framework and a convolutional neuron network are proposed to deal with the black swan small-sample events (BEST-L). Taking the COVID-19 as a typical black swan event, the BEST-L is utilized to achieve accurate mid-term load forecasting using the relationship between economy and electricity consumption. The experiment results show that the transfer learning model can effectively learn the basic knowledge about the relationship between the adopted input and output data and use a relatively small amount of data during the black swan event to improve the target areas' generalization. The approach and results can provide an effective approach to respond and react to sudden changes quickly and effectively in similar open problems.

2.
Front Cardiovasc Med ; 8: 756790, 2021.
Article in English | MEDLINE | ID: covidwho-1574359

ABSTRACT

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited. Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI). Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.

3.
Preprint in English | EuropePMC | ID: ppcovidwho-295142

ABSTRACT

Background: Information regarding antibody response to COVID-19 vaccines in cancer patients undergoing therapy is needed for vaccine recommendations and timing of additional doses. This longitudinal study evaluates anti-RBD and neutralizing antibody (NAb) response to COVID-19 vaccines in patients on treatment and post stem cell transplant (SCT).Methods: For mRNA vaccines, anti-RBD and NAb were assessed before vaccination (T0), prior to 2nd dose (T1), 1 month after the 2nd dose (T2), and 3 months after the 2nd dose (T3). For J&J, T1 was 1 month, T2, 2 months and T3, 4 months after vaccine. Primary objective was GMTs of anti-RDB and NAb (%) at above timepoints. Other objectives were a) proportion of patients with anti-RBD ≥100 U/mL, b) correlation between anti-RBD and NAb, c) antibody responses of the 2 mRNA vaccines, and d) anti-RBD in breakthrough COVID-19 cases.Findings: Between 3/2/2021 and 7/30/2021, 438 cancer patients were enrolled. 108 (25%) were post-SCT and 330 (75%) on treatment: 176 (40%) on chemotherapy (C), 21 (5%) on chemoimmunotherapy (C+I), 72 (19%) on immunotherapy (I), and 58 (13%) on targeted oral agents (TOA). 60 % received Pfizer, 36 % Moderna, and 4% J&J. 11·82% of patients had anti-RBD ≥100 U/mL at T0, 25·15% at T1, 75·44 % at T2, and 81·38% at T3. At T3, 84·91% of patients on C, 81·89% on C+I, 86·67% on I, 78·18% post-SCT, and 77·50% on TOA had anti-RBD ≥ 100 U/mL. GMTs were 1·59 at T0, 12·91 at T1, 480·8 at T2 and 439·1 at T3. Neutralization (≥30%) was observed in 14·71%, 38·89%, 80·56% and 81·33% of patients at T0, T1, T2, and T3. There was no difference between the mRNA vaccines. Five patients had breakthrough infection. Four with anti-RBD available had pre-infection anti-RBD <100 U/mL. Interpretation: Four months after SARS-CoV-2 vaccination, ~ 80% of patients on cancer therapy or post-SCT have anti-RBD ≥100 U/mL and ≥30% NAb. Anti-RBD ≥100 U/mL predicts virus neutralization with accuracy. In regions with limited vaccine availability/hesitancy, antibody testing can identify 20% of the patients with relatively low titres for booster prioritization..Funding Information: This work was supported in part by the University of Kansas Cancer Centre and the Investigator Initiated Steering Committee, a grant from the NIGMS (P20 GM130423), and The University of Kansas Cancer Centre Support Grant from the NCI (P30 CA168524). A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Endowed. Declaration of Interests: AKG and ZYP are co-founders of Sinochips Diagnostics;PS serves as advisory board member and consultant to Merck, Novartis, Exact Sciences, Seattle Genetics, Immunomedics, Myriad Genetics, AstraZeneca, Puma Biotechnology;JZ served as a scientific advisor/consultant for AstraZeneca, Biodesix, Novocure, Bayer, Daiichi Sankyo, Mirati, Novartis, Cardinal Health, Bristol Myers Squibb, Nexus Health and Sanofi and is on the speakers’ bureau for AstraZeneca and MJH Life Sciences and has received research funding from AstraZeneca, Biodesix, Novartis, Genentech/Roche, Mirati, AbbVie and Hengrui Therapeutics;GCD serves on an advisory board for Novartis;JPM serves as advisory board member and consultant to Novartis, Kite Pharmaceuticals, BMS and Allovir;RAR received institutional support from Bayer, NuCana, Incyte, AstraZeneca, Eureka therapeutics, Merck, Pfizer, and owns stock in Seattle Genetics, Actinium Pharmaceuticals Inc.;MH received consulting fees from Janssen, Pharmacyclics, Novartis Inc., Kite Pharmaceuticals and TG therapeutics. The remaining authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Review Board of the University of Kansas Medical Centre.

4.
Front Pharmacol ; 11: 614024, 2020.
Article in English | MEDLINE | ID: covidwho-1542362

ABSTRACT

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1ß, and CXCL2.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-292884

ABSTRACT

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

6.
Journal of Cleaner Production ; : 129838, 2021.
Article in English | ScienceDirect | ID: covidwho-1531542

ABSTRACT

The stock of disposable face masks has climbed steadily due to COVID-19, which results in an urgent worldwide environmental problem. This investigation aims to assess the potential of using waste mask chips (MC) as reinforcement in granular soil. To evaluate the mechanical properties of the mask chips - granular soil mixture (MSM), a series of monotonic and cyclic triaxial tests with different confining pressures and MC contents are conducted. Then, the shear behavior of MSM is quantified from both static (strength, stiffness, dilatancy) and dynamic (energy absorption capacity, resilient modulus, deformation) perspectives. Furthermore, based on the static and dynamic indexes, the effects of adding MC into granular soil are comprehensively analyzed. All experimental results indicate that the MSMs exbibit an increase of shear strength and a reduction of shear-induced volumetric dilation, but a decrease in stiffness. The addition of MC also leads to an increase in energy absorption but will not affect the cumulative strain of MSMs. Thus, MC has great potential to be used in the embankment construction of road and railway, backfill or reclamation construction, and so on. In addition, the influence of mask chip content on mechanical behaviors of MSM can be considered in current constitutive models for further engineering calculation and design relating to of MSMs. This experimental study provides a new perspective and thought on the recycling of waste face masks in civil engineering.

7.
Lancet Infect Dis ; 21(12): 1654-1664, 2021 12.
Article in English | MEDLINE | ID: covidwho-1531911

ABSTRACT

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.

8.
World J Clin Cases ; 9(30): 9050-9058, 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1524638

ABSTRACT

BACKGROUND: Since December 2019, there have been many new cases of coronavirus pneumonia in Wuhan, Hubei Province, which has gradually spread throughout the country. AIM: To explore our hospital's innovative management system to ensure the efficient operation of fever clinics during the epidemic, since controlling the spread of disease is an important way to prevent and control the epidemic. METHODS: In total, 200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups. RESULTS: The fever clinic in our hospital operated smoothly, and infection with the novel coronavirus disease (COVID-19) has not been reported in our hospital. Additionally, we did not have any cases of missed diagnosis. The awareness regarding COVID-19 infection sources, transmission routes, early symptoms, and preventive measures was significantly higher in our fever clinic than in those of the pre-management group. CONCLUSION: "An integrated system, three separate responsibilities" ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases, which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital, ultimately achieving the maximum effect of epidemic prevention and control.

9.
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.

11.
Emerg Microbes Infect ; 10(1): 365-375, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1490458

ABSTRACT

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.


Subject(s)
Hepatitis E/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Papillomavirus Infections/immunology , Papillomavirus Vaccines/immunology , Vaccines, Synthetic/immunology , Viral Hepatitis Vaccines/immunology , Adolescent , Adult , Aged , Antibodies, Viral/immunology , Female , Hepatitis E/prevention & control , Hepatitis E/virology , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Immunity , Immunoglobulin G/immunology , Male , Middle Aged , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/genetics , Vaccination/adverse effects , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Viral Hepatitis Vaccines/administration & dosage , Viral Hepatitis Vaccines/adverse effects , Viral Hepatitis Vaccines/genetics , Young Adult
12.
J Am Soc Nephrol ; 2021 Feb 17.
Article in English | MEDLINE | ID: covidwho-1496670

ABSTRACT

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

15.
PLoS One ; 16(10): e0258274, 2021.
Article in English | MEDLINE | ID: covidwho-1470665

ABSTRACT

OBJECTIVE: We aim to estimate the total factor productivity and analyze factors related to the Chinese government's health care expenditure in each of its provinces after its implementation of new health care reform in the period after 2009. MATERIALS AND METHODS: We use the Malmquist DEA model to measure efficiency and apply the Tobit regression to explore factors that influence the efficiency of government health care expenditure. Data are taken from the China statistics yearbook (2004-2020). RESULTS: We find that the average TFP of China's 31 provincial health care expenditure was lower than 1 in the period 2009-2019. We note that the average TFP was much higher after new health care reform was implemented, and note this in the eastern, central and western regions. But per capita GDP, population density and new health care reform implementation are found to have a statistically significant impact on the technical efficiency of the provincial government's health care expenditure (P<0.05); meanwhile, region, education, urbanization and per capita provincial government health care expenditure are not found to have a statistically significant impact. CONCLUSION: Although the implementation of the new medical reform has improved the efficiency of the government's health expenditure, it is remains low in 31 provinces in China. In addition, the government should consider per capita GDP, population density and other factors when coordinating the allocation of health care input. SIGNIFICANCE: This study systematically analyzes the efficiency and influencing factors of the Chinese government's health expenditure after it introduced new health care reforms. The results show that China's new medical reform will help to improve the government's health expenditure. The Chinese government can continue to adhere to the new medical reform policy, and should pay attention to demographic and economic factors when implementing the policy.


Subject(s)
Government , Health Care Reform/economics , Health Expenditures , China , Regression Analysis
16.
Preprint in English | EuropePMC | ID: ppcovidwho-291394

ABSTRACT

Objectives: To analyze the operation status and data over the last 8 years of operation of the first human milk bank (HMB) in East China.MethodsData related to the costs, donors, donation, pasteurization, and recipients were extracted from the web-based electronic monitoring system of the HMB for the period August 1, 2013 to July 31, 2021. ResultsOver the 8 years of operation, 1,555 qualified donors donated 7,396.5 L of qualified milk at a cost of ¥1.94 million, with the average cost per liter of donor human milk being ¥262.3. The donors were between 25 and 30 years of age, and the majority (80.1%) were primipara. All the donated milk was pasteurized and subjected to bacteriological tests before and after pasteurization: 95.4% passed the pre-pasteurization tests, and 96.3% passed the post-pasteurization tests. A total of 9,207 newborns received 5,775.2 L of pasteurized donor milk. The main reason for the prescription of donor human milk was preterm birth. As a result of continuous quality improvements, January 2016 witnessed a significant increase in the volume of qualified DHM and the number of qualified donors. However, in 2020, as a result of the restrictions related to the COVID-19 pandemic, the volume of qualified DHM and the number of qualified donors decreased. Conclusions

17.
Nat Commun ; 12(1): 5652, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440473

ABSTRACT

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/therapy , Immunization, Passive/methods , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Monoclonal/metabolism , Antibodies, Viral/administration & dosage , Antibodies, Viral/isolation & purification , Antibodies, Viral/metabolism , Binding Sites/genetics , Binding Sites/immunology , Broadly Neutralizing Antibodies/administration & dosage , Broadly Neutralizing Antibodies/isolation & purification , Broadly Neutralizing Antibodies/metabolism , CHO Cells , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Cricetulus , Epitopes/immunology , HEK293 Cells , Humans , Mice , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Neutralization Tests , Pandemics/prevention & control , Protein Multimerization , Receptors, Virus/metabolism , SARS-CoV-2/genetics , Sf9 Cells , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
18.
Electron Commer Res Appl ; 49: 101093, 2021.
Article in English | MEDLINE | ID: covidwho-1440000

ABSTRACT

Food selling platforms are facing both challenges and opportunities during the COVID-19 outbreak as the enforcement of social distancing protocols has pushed consumers with serious health and safety concerns to shop online. Observing that platforms and their suppliers have adopted blockchain technologies and linked selected information nodes separately to foster consumers' trust, we establish a game-theoretic model to study the operations decisions and blockchain adoption strategies for a food supply chain consisting of one platform and one supplier. We explore the values and impacts of blockchain on the retailing platform, supplier, and consumers, respectively. An all-win situation is achieved when both members of the supply chain adopt blockchain. We further propose that not all prevalent supply chain contracts can achieve supply chain coordination in the presence of blockchain. In extended studies, we examine the incentives of the supply chain members' blockchain implementation with consideration of the fixed cost of such adoption, product infection, and tampered information.

19.
Signal Transduct Target Ther ; 6(1): 347, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1437669

ABSTRACT

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Basigin/antagonists & inhibitors , Basigin/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , COVID-19/genetics , Chlorocebus aethiops , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
SELECTION OF CITATIONS
SEARCH DETAIL
...