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Extreme temperature variations are a problem that must be faced in the practical application of microbial fuel cells (MFCs), but MFCs are not extensively described for low and even freezing temperatures. This study assessed the effect of low-temperature shock on the power generation performance and microbial community structure of MFCs. Two scales of MFCs, the small (mL-MFC) and the large (L-MFC), were constructed in the laboratory and their performance was evaluated before and after freezing at -18 °C. The experimental results demonstrate that both MFCs were capable of rapidly restoring their voltage to the previous level after thawing. For the mL-MFC (rGO/Ag), the power density recovered from 194.30 ± 10.84 mW/m2 to 195.57 ± 4.02 mW/m2 after thawing. For L-MFC (carbon felt electrodes), the power density increased significantly from the initial 1.79 mW/m2 to 173.90 mW/m2 after thawing, but the performance degradation problem after reactor amplification still needs to be solved. The sediment microbial fuel cell (SMFC) was successfully constructed and operated in a natural outdoor environment to maintain high voltage output after the period of frost. Microbial analysis indicated after the frost period, psychrotolerant microorganisms enriched on the anode, such as Flavobacterium and Psychrobacter, while the relative abundance of anaerobic methanogenic bacterium decreased. Overall, freeze-thaw operations had a non-negative impact on the performance of MFCs and provided some references for their practical applications.
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Fontes de Energia Bioelétrica , Congelamento , Reatores Biológicos , Eletricidade , EletrodosRESUMO
Lung cancer is currently the second most common type of cancer with the second incidence rate and the first mortality rate worldwide. Nonsmall cell lung cancer (NSCLC) accounts for ~85% of the total number of cases of lung cancers. Concerning the treatment of NSCLC, targeted therapy has become a research hotspot in recent years because of its favorable efficacy, high selectivity and minimal adverse reactions. Among the drugs used in targeted therapy, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the most common and are categorized into four generations. The use of first and secondgeneration drugs leads to drug resistance within 814 months. This resistance is primarily caused by the T790M mutation, which is the most observed mechanism. A thirdgeneration drug has been developed to address this issue and a fourthgeneration drug is expected to overcome multiple resistance mechanisms, including thirdgeneration drug resistance. However, the fourthgeneration drug has not been launched yet. At present, multiple thirdgeneration targeted drugs have been launched globally, with three being launched in China and several being at research and clinical trial stages. The present article provides a review of the development process, mechanism of action and clinical trials of the thirdgeneration EGFRTKIs, aiming to provide some reference and suggestions for the clinical treatment of NSCLC and scientific research on thirdgeneration targeted drugs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , /uso terapêuticoRESUMO
Microbial fuel cells (MFCs) based biosensors are widely studied to environmental monitoring. The suitable responsive signal is important for microbial electrochemical sensors. However, the responsive signals of toxins have not been investigated in detail. Using sodium selenite as a toxic substance, the different response signals are analyzed over a concentration range from 0 to 150 mg/L in the double chambered. The output voltage and power density had the opposite trend between 0 and 2.5 mg/L and 2.5-150 mg/L. To analyze the reasonable signal of Se(IV) monitoring sensor, correlation analysis of concentrations and responsive signal data (maximum voltage, maximum power density, coulombic recovery, coulombic efficiency, and normalized energy recovery, etc.) has been accomplished. The high concentration of exogenous selenite (2.5-100 mg/L) is negatively correlated with maximum voltage (r = -0.901, p < 0.01) and max power density (r = -0.910, p < 0.01). The low concentration of exogenous selenite is positively correlated with average voltage, max power density, coulombic yield (r = 0.973, 0.999 and 0.975, respectively. p < 0.05). Furthermore, Illumina sequencing results indicate that the addition of sodium selenite solution changes the anode community structure, thereby affecting the removal efficiency of organic matter, which may be the reason why coulombic efficiency and normalized energy recovery are not suitable as sensing signal. Overall, based on the analysis of experimental data, the maximum power density is the best response signal, which provides a reference for the selection of sensor response signal based on microbial fuel cells.
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Fontes de Energia Bioelétrica , Eletricidade , Ácido Selenioso , Selenito de Sódio , EletrodosRESUMO
Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted.
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Vírus da Influenza A Subtipo H1N1 , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Animais , Anticorpos Neutralizantes , Cães , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Hemaglutininas , Humanos , Influenza Humana/prevenção & controle , Células Madin Darby de Rim Canino , CamundongosRESUMO
The study investigates the diagnostic efficacy of ultrasound combined with the molybdenum target mode in breast cancer staging and the relationship between blood flow parameters and the expression of insulin-like growth factor 1 (IGF-1) and factor 2 (IGF-2) and prognosis. A total of 96 patients admitted to hospital from January 2020 to January 2021 are included in the breast cancer group, and 58 patients admitted to our hospital during the same period are included in the control group, who are diagnosed with benign breast lesions. All patients receive clinicopathological diagnosis, ultrasound detection, and X-ray molybdenum detection. Ultrasound detection, molybdenum target detection, ultrasound combined with the molybdenum target detection mode, and clinicopathological diagnosis results are compared. B-ultrasound combined with the molybdenum target detection mode has high efficiency in diagnosing breast cancer and differentiating pathological stages. Besides, blood flow parameters of patients are closely related to IGF-1 and IGF-2, and IGF-1 and IGF-2 expressions are closely related to the prognosis of patients. Subsequent diagnosis of the disease degree of breast cancer patients can be carried out by ultrasound combined with the molybdenum target detection mode. In addition, the expression of IGF-1 and IGF-2 in patients can be monitored to improve the clinical diagnosis and treatment plan to improve the prognosis of patients, which has a high clinical application value and is worth promoting.
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Neoplasias da Mama , Fator de Crescimento Insulin-Like I , Neoplasias da Mama/patologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Fator de Crescimento Insulin-Like II/uso terapêutico , Molibdênio/uso terapêutico , Estadiamento de Neoplasias , PrognósticoRESUMO
Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.
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COVID-19 , SARS-CoV-2 , Linfócitos T CD8-Positivos , Humanos , Fenótipo , Receptores de Antígenos de Linfócitos T/genética , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas , Vacinas de mRNARESUMO
Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.
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Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Autoimunidade , Epitopos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Humanos , CamundongosRESUMO
SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants.
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Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , COVID-19/imunologia , Resfriado Comum/imunologia , Imunidade Humoral/imunologia , SARS-CoV-2/imunologia , Animais , Infecções Assintomáticas , COVID-19/virologia , Estudos de Casos e Controles , Linhagem Celular , Resfriado Comum/virologia , Reações Cruzadas/imunologia , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the ex vivo profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection. We found that the order of exposure determined the relative distribution between spike- and non-spike-specific responses, with vaccination after infection leading to further expansion of spike-specific T cells and differentiation to a CCR7-CD45RA+ effector phenotype. In contrast, individuals experiencing a breakthrough infection mount vigorous non-spike-specific responses. In-depth analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all types of exposures elicit diverse repertoires characterized by shared, dominant TCR motifs, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and that current vaccination protocols continue to expand and differentiate spike-specific memory responses.
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BACKGROUND: Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection. Yet, it remains unclear if IAV NS1 can exploit a common mechanism to counteract these RNA sensing pathways to type I IFN production at once, then promoting viral propagation in the host. METHODS: Luciferase reporter assays were conducted to determine the effect of NS1 and its mutants on the RIG-I and TLR3 pathways to the activation of the IFN-ß and NF-κB promoters. Coimmunoprecipitation and confocal microscopic analyses were used to the interaction and colocalization between NS1 and TRAF3. Ubiquitination assays were performed to study the effect of NS1 and its mutants on TRAF3 ubiquitination. A recombinant mutant virus carrying NS1 E152A/E153A mutations was generated by reverse genetics for biochemical, ex vivo, and in vivo analyses to explore the importance of NS1 E152/E153 residues in targeting the RNA sensing-TRAF3-type I IFN axis and IAV pathogenicity. RESULTS: Here we report that NS1 subverts the RIG-I, TLR3, and TLR7 pathways to type I IFN production through targeting TRAF3 E3 ubiquitin ligase. NS1 harbors a conserved FTEE motif (a.a. 150-153), in which the E152/E153 residues are critical for binding TRAF3 to block TRAF3 ubiquitination and type I IFN production by these RNA sensing pathways. A recombinant mutant virus carrying NS1 E152A/E153A mutations induces higher type I IFN production ex vivo and in vivo, and exhibits the attenuated phenotype in infected mice, indicating the importance of E152/E153 residues in IAV pathogenicity. CONCLUSIONS: Together our work uncovers a novel mechanism of IAV NS1-mediated immune evasion to promote viral infection through targeting the RNA sensing-TRAF3-type I IFN axis.
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Imunidade Inata , Vírus da Influenza A/genética , Proteínas não Estruturais Virais/genética , Proteínas Associadas aos Microtúbulos/genética , RNA Viral/genética , Fator 3 Associado a Receptor de TNF/genéticaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The "gold standard" assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.
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Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Testes de Neutralização/métodos , SARS-CoV-2/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos/imunologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Vírus da Estomatite Vesicular New Jersey/imunologiaRESUMO
The efficacy of coronavirus disease 2019 (COVID-19) vaccines administered after COVID-19-specific monoclonal antibody is unknown, and "antibody interference" might hinder immune responses leading to vaccine failure. In an institutional review board-approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar postvaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD) for 4 important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351, and P.1) as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting. TRIAL REGISTRATION: The St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995.
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Outbreaks of infection by novel avian influenza virus strains in humans cause public health issues worldwide, and the development of vaccines against such novel strains is the most effective method for the prevention of these virus outbreaks. All types of vaccines must be tested for potency before use; thus, quantitative potency assays are needed for influenza vaccines. The single radial immunodiffusion (SRID) assay is considered the gold standard for quantification of influenza virus antigens, and the SRID reference reagents are essential for the determination of vaccine potency. However, it remains debatable whether reference reagents derived from egg-based vaccine platforms can be used to precisely quantify non-egg-derived vaccines; thus, influenza vaccine production using cell-based platforms has attracted increasing attention. To evaluate the utility of reference reagents derived from a cell-based influenza vaccine platform, we prepared cell-based reference reagents from MDCK cell-grown viruses and compared them with egg-derived reference reagents. A primary liquid standard (PLS) was purified from cell-derived candidate influenza vaccine viruses, and hemagglutinin (HA) antigen content was determined by a densitometric method. The produced PLS could be stored at 4°C for more than 10 months. We also established a simple HA protein purification method for goat antiserum preparation, and the performance of the resulting antiserum was compared to that of standard reagents obtained using different production platforms. The results of this study indicate that these reference reagents can be used for both cell-based and egg-based production platforms and that the differences between these two types of platforms are negligible.
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Vacinas contra Influenza , Influenza Humana , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Indicadores e Reagentes , Potência de VacinaRESUMO
Novel low-pathogenic avian influenza (LPAI) H5N2 viruses hit poultry farms in Taiwan in 2003, and evolved into highly pathogenic avian influenza (HPAI) viruses in 2010. These viruses are reassortant viruses containing HA and NA genes from American-lineage H5N2 and six internal genes from local H6N1 viruses. According to a serological survey, the Taiwan H5N2 viruses can cause asymptomatic infections in poultry workers. Therefore, a development of influenza H5N2 vaccines is desirable for pandemic preparation. In this study, we employed reverse genetics to generate a vaccine virus having HA and NA genes from A/Chicken/CY/A2628/2012 (E7, LPAI) and six internal genes from a Vero cell-adapted high-growth H5N1 vaccine virus (Vero-15). The reassortant H5N2 vaccine virus, E7-V15, presented high-growth efficiency in Vero cells (512 HAU, 107.6 TCID50/mL), and passed all tests for qualification of candidate vaccine viruses. In ferret immunization, two doses of inactivated whole virus antigens (3 µg of HA protein) adjuvanted with alum could induce robust antibody response (HI titre 113.14). In conclusion, we have established reverse genetics to generate a qualified reassortant H5N2 vaccine virus for further development.
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Vírus da Influenza A Subtipo H5N2/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/isolamento & purificação , Influenza Humana/prevenção & controle , Vírus Reordenados/imunologia , Animais , Anticorpos Antivirais/sangue , Chlorocebus aethiops , Furões , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H5N2/genética , Vírus da Influenza A Subtipo H5N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Neuraminidase/genética , Neuraminidase/imunologia , Vírus Reordenados/genética , Vírus Reordenados/crescimento & desenvolvimento , Vírus Reordenados/isolamento & purificação , Genética Reversa , Taiwan , Resultado do Tratamento , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Células Vero , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
Human infections of novel avian influenza A virus (H7N9) emerged in early 2013 and caused about 40% case-fatality through 2017. Therefore, development of influenza H7N9 vaccines is critical for pandemic preparedness. Currently, there are three means of production of commercial influenza vaccines: egg-based, mammalian cell-based, and insect cell-based platforms. The insect cell-based platform has the advantage of high speed in producing recombinant protein. In this study, we evaluate the stability and immunogenicity of two different influenza H7 HA expression constructs generated using the baculovirus system, including membrane-based full-length HA (mH7) and secreted ectodomain-based H7 (sH7). The mH7 construct could form an oligomer-rosette structure and had a high hemagglutinin (HA) titer 8192. In contrast to mH7, the sH7 construct could not form an oligomer-rosette structure and did not have HA titer before cross-linking with anti-His antibody. Thermal stability tests showed that the sH7 and mH7 constructs were unstable at 43⯰C and 52⯰C, respectively. In a mice immunization study, the mH7 construct but not the sH7 construct could induce robust HI and neutralizing antibody titers. In conclusion, further development of the mH7 vaccine candidate is desirable.
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Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunogenicidade da Vacina , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Proteínas Recombinantes/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Feminino , Expressão Gênica , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vacinas contra Influenza/administração & dosagem , Camundongos , Proteínas Recombinantes/genéticaRESUMO
During December 2003 and March 2004, large scale epidemics of low-pathogenic avian influenza (LPAI) H5N2 occurred in poultry farms in central and southern Taiwan. Based on genomic analysis, these H5N2 viruses contain HA and NA genes of American-lineage H5N2 viruses and six internal genes from avian influenza A/H6N1 viruses endemic in poultry in Taiwan. After disappearing for several years, these novel influenza H5N2 viruses caused outbreaks in poultry farms again in 2008, 2010 and 2012, and have evolved into high pathogenic AI (HPAI) since 2010. Moreover, asymptomatic infections of influenza H5N2 were detected serologically in poultry workers in 2012. Therefore, we evaluated antigenicity and pathogenicity of the novel H5N2 viruses in ferrets. We found that no significant antigenic difference was detected among the novel H5N2 viruses isolated from 2003 to 2014 and the novel H5N2 viruses could cause mild infections in ferrets. Monitoring zoonotic transmission of the novel H5N2 viruses is necessary.
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Vírus da Influenza A Subtipo H5N2/imunologia , Vírus da Influenza A Subtipo H5N2/patogenicidade , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Animais , Anticorpos Antivirais/sangue , Galinhas , Feminino , Furões , Vírus da Influenza A Subtipo H5N2/genética , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Influenza Aviária/sangue , Influenza Aviária/epidemiologia , Influenza Aviária/patologia , Masculino , Filogenia , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/patologia , Taiwan/epidemiologia , Estados Unidos/epidemiologia , VirulênciaRESUMO
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key RNA viral sensors for triggering antiviral immunity. The underlying mechanisms for RLRs to trigger antiviral immunity have yet to be explored. Here we report the identification of TAPE (TBK1-associated protein in endolysosomes) as a novel regulator of the RLR pathways. TAPE functionally and physically interacts with RIG-I, MDA5, and IPS-1 to activate the IFN-ß promoter. TAPE knockdown impairs IFN-ß activation induced by RLRs but not IPS-1. TAPE-deficient cells are defective in cytokine production upon RLR ligand stimulation. During RNA virus infection, TAPE knockdown or deficiency diminishes cytokine production and antiviral responses. Our data demonstrate a critical role for TAPE in linking RLRs to antiviral immunity.
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RNA Helicases DEAD-box/metabolismo , Proteínas de Ligação a DNA/química , Proteínas Repressoras/química , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Proteína DEAD-box 58 , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Sistema Imunitário , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Ligação Proteica , Proteínas Serina-Treonina Quinases/química , Interferência de RNA , Receptores Imunológicos , Proteínas Repressoras/metabolismo , Transdução de Sinais , Células VeroRESUMO
OBJECTIVE: To investigate the effectiveness of kyphoplasty in treating osteoporotic vertebral fracture according to comparative study. METHODS: Between March 2006 and August 2007, 60 patients with osteoporotic vertebral fractures were treated. Kyphoplasty was performed in 40 patients (test group) and conservative treatment was performed in 20 patients as control (control group). In test group, there were 6 males and 34 females with an average age of 68.7 years (range, 56-78 years). The disease duration was 10-18 months (mean, 12 months). A total of 73 vertebral bodies fractured. In control group, there were 5 males and 15 females with an average age of 70.1 years (range, 57-80 years). The disease duration was 9-16 months (mean, 13 months). A total of 41 vertebral bodies fractured. There was no significant difference in the general data between 2 groups (P > 0.05). RESULTS: All incisions healed by first intention in test group, and no leakage of bone cement occurred. The patients of 2 groups were followed up 36-38 months. The visual analogue scale (VAS) scores, European Vertebral Osteoporosis Study (EVOS) questionnaire scores, anterior and middle vertebral column heights, and Cobb angles of test group at 1-3 days, 12 and 36 months after treatment were significantly improved when compared with those before operation (P < 0.05); but there was no significant difference between before treatment and after treatment in control group (P > 0.05). After 12 and 36 months, the VAS scores, EVOS scores, anterior and middle vertebral column heights, and Cobb angles of test group were better than those of control group (P < 0.05). The incidence of vertebral re-fractures was higher in control group than in test group after 36 months (chi2 = 16.347, P = 0.015). CONCLUSION: Kyphoplasty can effectively relieve pain and restore the function after the procedure. The risk of vertebral re-fractures after kyphoplasty can be reduced in comparison with conservative treatment.
Assuntos
Fraturas por Compressão/cirurgia , Cifoplastia , Fraturas da Coluna Vertebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas por Compressão/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Fraturas da Coluna Vertebral/etiologiaRESUMO
BACKGROUND: After anterior cruciate ligament (ACL) reconstruction, some patients suffered from sensory disturbance around the surgical incision of the leg. This research was aimed to investigate the relationship between the different skin incisions and the injury of the infrapatellar branch of the saphenous nerve (IPBSN) post ACL reconstruction. METHODS: ACL reconstructions were performed with quadruple hamstring tendon for 60 patients. Sensory disturbance around the skin incision was followed up at an average of 14.5 +/- 4.7 months post operation. Among the 60 patients, vertical incision for 35 patients and oblique incision for 25 patients were used for graft taking during ACL reconstruction. The lengths of the incisions were measured. The patients were asked to mark the sensory disturbance zone at follow up time, and then the marked area was measured. The IPBSN of 15 cadaver knees were anatomized. The distance between the IPBSN and the upper edge of the pes anserinus tendon at the middle point of the incision was measured. Independent-samples t-test, chi-square and Mann-Whitney tests were used for statistical analyses. RESULTS: The patients' age (P = 0.329), the follow-up time (P = 0.681), and the incision length (P = 0.732) between the two groups had no significant difference. Twenty-three patients (65.7%) in the vertical incision group had IPBSN injury compared with 6 patients (24.0%) in oblique incision group (P = 0.002). The average sensory disturbance area in vertical incision group ((48.0 +/- 75.3) cm(2)) was significantly larger (P = 0.004) than that in the oblique group ((8.4 +/- 19.4) cm(2)). The anatomy measurement showed the average distance between IPBSN and the upper edge of the pes anserinus tendon was 0.6 cm at the incision. CONCLUSIONS: Oblique incision with less risk of damage for IPBSN may be better for graft harvesting in ACL reconstruction. As the IPBSN is so near and parallel to the hamstring tendons, damage to the IPBSN is one of the potential complications for graft harvesting, regardless of the incision used. That's why even in the oblique incision group, 24% patients also had sensory disturbance complication.