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1.
PLoS Pathog ; 18(2): e1009986, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35139135

RESUMO

The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection.


Assuntos
Antivirais/farmacologia , Produtos do Gene rev/metabolismo , Vírus da Anemia Infecciosa Equina/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antioxidantes/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
Viral Immunol ; 35(4): 291-302, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35196150

RESUMO

In this study, B and T lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM) expression on the surface of circulating CD4+ T and CD8+ T cells of patients with chronic hepatitis B (CHB) was investigated to explore their relationship with hepatitis B virus (HBV) clinical parameters. Both BTLA and HVEM were significantly upregulated on CD4+ T and CD8+ T cells of CHB patients compared with healthy controls (p < 0.01). Intriguingly, in CHB patients, the percentage of BTLA expression was positively correlated with that of HVEM (CD4+ T cells: r = 0.5461, p < 0.001 and CD8+ T cells: r = 0.4206, p < 0.01). Moreover, the percentage of BTLA expression was positively correlated with the levels of aspartate aminotransferase (AST) (CD4+ T cells: r = 0.3136, p < 0.05 and CD8+ T cells: r = 0.3159, p < 0.05) and alanine aminotransaminase (ALT) (CD4+ T cells: r = 0.3177, p < 0.05 and CD8+ T cells: r = 0.3311, p < 0.05). At the same time, the percentage of HVEM expression was also positively correlated with AST levels (CD4+ T cells: r = 0.3721, p < 0.05 and CD8+ T cells: r = 0.3325, p < 0.05) and ALT (CD4+ T cells: r = 0.3689, p < 0.05 and CD8+ T cells: r = 0.3476, p < 0.05). However, the percentage of BTLA and HVEM expression did not show significant relevance to HBV viral load. Further study demonstrated that BTLA inhibitory signaling could significantly inhibit T cell proliferation, activation, and cytokine production under optimal T cell receptor signaling (p < 0.05). Thereby, our findings indicate that the increased BTLA and HVEM expression on the surface of CD4+ and CD8+ T cells might represent a certain clinical significance and be involved in CHB progression during T cell exhaustion.

3.
Front Cardiovasc Med ; 9: 857019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369289

RESUMO

Electrocardiogram (ECG), as a product that can most directly reflect the electrical activity of the heart, has become the most common clinical technique used for the analysis of cardiac abnormalities. However, it is a heavy and tedious burden for doctors to analyze a large amount of ECG data from the long-term monitoring system. The realization of automatic ECG analysis is of great significance. This work proposes a beat-level interpretation method based on the automatic annotation algorithm and object detector, which abandons the previous mode of separate R peak detection and heartbeat classification. The ground truth of the QRS complex is automatically annotated and also regarded as the object the model can learn like category information. The object detector unifies the localization and classification tasks, achieving an end-to-end optimization as well as decoupling the high dependence on the R peak. Compared with most advanced methods, this work shows superior performance. For the interpretation of 12 heartbeat types in the MIT-BIH dataset, the average accuracy is 99.60%, the average sensitivity is 97.56%, and the average specificity is 99.78%. This method can be used as a clinical auxiliary tool to help doctors diagnose arrhythmia after receiving large-scale database training.

4.
J Virol ; 95(23): e0108721, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34495693

RESUMO

Envelope glycoproteins (Envs) of lentiviruses harbor unusually long cytoplasmic tails (CTs). Natural CT truncations always occur in vitro and are accompanied by attenuated virulence, but their effects on viral replication have not been fully elucidated. The Env in equine infectious anemia virus (EIAV) harbors the longest CT in the lentiviral family, and a truncated CT was observed in a live attenuated vaccine. This study demonstrates that CT truncation significantly increased EIAV production, as determined by comparing the virion yields from EIAV infectious clones in the presence and absence of the CT. A significant increase in a cleaved product from the CT-truncated Env precursor, but not the full-length Env, was observed. We further confirmed that the presence of the CT inhibited the cleavage of the Env precursor and found that a functional domain located at the C terminus was responsible for this function. Moreover, CT-truncated Env was mainly localized at the plasma membrane (PM), while full-length Env was mainly localized in the cytoplasm. The CT truncation caused a dramatic reduction in the endocytosis of Env. These results suggest that the CT can modulate the processing and trafficking of EIAV Env and thus regulate EIAV replication. IMPORTANCE The mature lentivirus envelope glycoprotein (Env) is composed of a surface unit (SU) and a transmembrane unit (TM), which are cleaved products of the Env precursor. After mature Env is heterodimerically formed from the cleavage of the Env precursor, it is trafficked to the plasma membrane (PM) for incorporation and virion assembly. Env harbors a long cytoplasmic tail (CT), which has been increasingly found to play multiple roles in the Env biological cycle. Here, we revealed for the first time that the CT of equine infectious anemia virus (EIAV) Env inhibits cleavage of the Env precursor. Simultaneously, the CT promoted Env endocytosis, resulting in weakened Env localization at the PM. We also validated that the CT could significantly decrease EIAV production. These findings suggest that the CT regulates the processing and trafficking of EIAV Env to balance virion production.


Assuntos
Membrana Celular/metabolismo , Anemia Infecciosa Equina/virologia , Genes env/genética , Vírus da Anemia Infecciosa Equina/metabolismo , Vírion/metabolismo , Animais , Endocitose , Genoma Viral , Células HEK293 , HIV-1 , Cavalos , Humanos , Vírus da Anemia Infecciosa Equina/genética , Vacinas Atenuadas , Proteínas do Envelope Viral/genética , Vírion/genética , Replicação Viral
5.
J Phys Condens Matter ; 33(33)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34107462

RESUMO

We have studied the valence effects on the stability of Stone-Wales (SW) defect in some typical two-dimensional honeycomb crystals containing group-IV, V, and VI elements employing density functional theory. The energetics involved in an in-plane formation process of SW defects in pristine and substitutionally doped materials is simulated. The SW defects are stable and have a rotation angle about 90 degree in the group-IV materials. They may become less stable with a smaller rotation angle in the group-V materials and seem difficult to exist in the group-VI materials. Group-VI doping may help eliminate SW defects while group-IV and V doping might introduce SW defects in some group-VI compounds.

6.
Medicine (Baltimore) ; 100(15): e25427, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847642

RESUMO

ABSTRACT: This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722-0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients' survival and prognosis on an individual basis.


Assuntos
Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/terapia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/terapia , Nomogramas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER , Fatores Sexuais , Taxa de Sobrevida
7.
J Clin Lab Anal ; 35(5): e23757, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33734488

RESUMO

BACKGROUND: Chronic inflammation is a hallmark of colorectal mucinous adenocarcinoma (CMA). Albumin-to-fibrinogen ratio (AFR) and fibrinogen-to-pre-albumin ratio (FPR) were independent prognostic factors for many kinds of solid malignancies. However, the association between the inflammatory scores and progression of metastatic CMA remains unknown. METHODS: Peripheral blood neutrophil count and circulating fibrinogen, albumin, and pre-albumin levels were detected, and neutrophil-to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio(NPAR), AFR, and FPR were calculated in 42 metastatic MCA patients. Kaplan-Meier curve, Cox regression, time-dependent receiver operating characteristic curve (tdROC) were selected to investigate the prognostic utility of them in the patients. RESULTS: Metastatic CMA patients commonly occurred in middle-younger patients (80.95%). NPAR (adjusted hazard ratio (HR)=2.405, 95% confidence interval (CI)=1.195-4.842) and FPR (plog-rank =0.007, adjusted HR=2.364, 95% CI=1.203-4.645) were significantly associated with poor progression-free survival in these patients. The prognostic prediction area under tdROC (AUROC) of FPR was significantly higher than that of NPAR(0.703 versus 0.537). Moreover, the patients with a high CA19-9-FPR score showed worse outcomes than those with the low score (plog-rank <0.001, adjusted HR=7.273, 95% CI=2.721-19.435 for the score 1 versus 0). The prediction AUROC, sensitivity, and specificity of the score were 0.892 (0.788-0.996), 76.32%, and 100.00%, respectively, and its predicted efficacy was better than that of the single biomarkers. CONCLUSION: The combined CA19-9-FPR score is an economical, simple, effective, and independent prognostic factor for metastatic MCA.


Assuntos
Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/patologia , Antígeno CA-19-9/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Progressão da Doença , Fibrinogênio/metabolismo , Pré-Albumina/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais
8.
Nat Commun ; 12(1): 897, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563974

RESUMO

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/fisiologia , Linfócitos T/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Memória Imunológica , Interferon gama/metabolismo , Cinética , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CCR7/metabolismo
9.
Clin Exp Pharmacol Physiol ; 48(6): 902-910, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33527445

RESUMO

Inflammatory bowel disease (IBD) is a chronic progressive disorder characterized by complicated gastrointestinal inflammation. Research on therapeutic agents is still urgent due to the lack of satisfactory treatments. Gut macrophages are considered to be predominant in excessive inflammatory responses. Thus, we aimed to investigate whether depletion of macrophages would have a beneficial effect on IBD and could be a potential therapeutic strategy. In this study, we established a 12-day Dextran sodium sulphate (DSS)-induced colitis mouse model and determined the effect of the macrophage depletion agent Clophosome (neutral clodronate liposomes; CNC). The results showed that CNC significantly alleviated the symptoms of colitis, as demonstrated by greater weight gain, decreased disease activity index (DAI) scores, and lower histopathological damage scores, as well was reduced levels of the proinflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α. To investigate T cell subsets, cells were isolated from the lamina propria and cultured to analyse the expression of IL-17A, interferon (IFN)-γ and Foxp3 in CD4+ cells by flow cytometry. The data showed that during the process of colitis, the frequencies of CD4+ IL-17A+ T cells were significantly increased. Notably, CNC treatment markedly reduced the population of CD4+ IL-17A+ T cells, especially CD4+ IL-17A+ IFN-γ+ T cells. Furthermore, intestinal barrier integrity, as assessed by immunostaining of mucin and tight junction proteins, was severely disrupted in colitis. CNC improved the intestinal barrier by enhancing the expression of muc-2 and occludin. In summary, our findings demonstrated that CNC successfully ameliorated DSS-induced colitis and that its effect may be associated with inhibiting inflammatory responses and maintaining intestinal integrity.


Assuntos
Colite , Sulfato de Dextrana , Animais , Colo , Imunidade , Interleucina-17/metabolismo , Mucosa Intestinal , Camundongos , Proteínas de Junções Íntimas
10.
Int J Biol Sci ; 17(2): 498-513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613108

RESUMO

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/ß-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , MicroRNAs/metabolismo , Fator de Transcrição PAX5/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , RNA Longo não Codificante/genética
11.
Autophagy ; 17(10): 2800-2817, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172327

RESUMO

The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully establishes infection in macrophages with functional SAMHD1 remains unclear. Here, we demonstrate that while equine SAMDH1 can limit EIAV replication in equine macrophages at the reverse transcription stage, the antiviral effect is counteracted by the well-known transcriptional regulator Rev, which downregulates equine SAMHD1 through the lysosomal pathway. Remarkably, Rev hijacks BECN1 (beclin 1) and PIK3C3 to mediate SAMHD1 degradation in a canonical macroautophagy/autophagy-independent pathway. Our study illustrates that equine lentiviral Rev possesses important functions in evading cellular innate immunity in addition to its RNA regulatory function, and may provide new insights into the co-evolutionary arms race between SAMHD1 and lentiviruses.Abbreviations:3-MA: 3-methyladenine; AA: amino acid; ACTB: actin beta; AD: activation domain; ATG: autophagy related; Baf A1: bafilomycin A1; BD: binding domain; BECN1: beclin 1; BH3: BCL2-homology-3 domain; BiFC: bimolecular fluorescence complementation; CCD: coiled-coil domain; class III PtdIns3K: class III phosphatidylinositol 3-kinase; CQ: chloroquine; Co-IP: co-immunoprecipitation; dNTPase: dGTP-stimulated deoxynucleoside triphosphate triphosphohydrolase; ECD: evolutionarily conserved domain; EIAV: equine infectious anemia virus; eMDMs: equine monocyte-derived macrophages; GFP: green fluorescent protein; HD: histidine-aspartic; HIV-1: human immunodeficiency virus-1; hpi: hours post infection; hpt: hours post transfection; KO: knockout; LAMP2: lysosomal associated membrane protein 2; LMB: leptomycin B; PMA: phorbol 12-myristate 13-acetate; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ND: unknown non-essential domain; NES: nuclear export signal; NLS: localization signal; NS: statistically non-significant; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RBD: RNA binding domain; RT: reverse transcriptase; siRNAs: small interfering RNAs; SAMHD1: SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1; SIV: simian immunodeficiency virus; VN: C-terminal residues of Venus 174 to 238; VC: N-terminal residues 2 to 173 of Venus.


Assuntos
Autofagia , Lentivirus Equinos , Animais , Proteína Beclina-1/metabolismo , Cavalos , Lisossomos/metabolismo , Proteína 1 com Domínio SAM e Domínio HD/genética
12.
Am J Cancer Res ; 10(11): 3622-3643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294258

RESUMO

Estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, was reported to be highly associated with the progression and tumorigenesis of several human malignancies. However, the biological role and underlying molecular mechanisms of ERRα in pancreatic cancer (PC) remain unknown. The present study demonstrated that ERRα was significantly overexpressed in PC tissues and cell lines. Its high expression was correlated with tumor size, distant metastasis, TNM stage, tumor differentiation and poor prognosis of PC. Subsequent functional assays showed that ERRα promoted PC cell proliferation, tumor growth, as well as migration and invasion via activating the epithelial-mesenchymal transition. In addition, knockdown of ERRα induced apoptosis and G0/G1 cell cycle arrest in PC cells. Plasminogen activator inhibitor 1 (PAI1) was identified by RNA sequencing, knockdown of which could suppress the cell proliferation, migration and invasion that promoted by ERRα overexpression. Further mechanistic investigation using chromatin immunoprecipitation and dual-luciferase reporter assays revealed that ERRα could bind to the PAI1 promoter region and transcriptionally enhance PAI1 expression. Moreover, our data indicated that ERRα played its oncogenic role in PC via activating the MEK/ERK pathway. Taken together, our study demonstrates that ERRα promotes PC progression by enhancing the transcription of PAI1 and activation of the MEK/ERK pathway, pointing to ERRα as a novel diagnostic and therapeutic target for PC.

13.
Emerg Microbes Infect ; 9(1): 1309-1320, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32525460

RESUMO

Lentiviruses harbour high genetic variability for efficient evasion from host immunity. An attenuated equine infectious anaemia (EIA) vaccine was developed decades ago in China and presented remarkably robust protection against EIA. The vaccine was recently proven to have high genomic diversity, particular in env. However, how and to what extent the high env diversity relates to immune protection remains unclear. In this study, we compared immune protections and responses of three groups of horses stimulated by the high-diversity vaccine EIAV_HD, a single molecular clone of the vaccine EIAV_LD with low env diversity, as well as a constructed vaccine strain EIAV_MD with moderate env diversity. The disparity of virus-host interactions between three env diversity-varied groups (5 horses in each group) was evaluated using clinical manifestation, pathological scores, and env-specific antibody. We found the highest titres of env antibodies (Abs) or neutralizing Abs (nAbs) in the EIAV_HD group, followed by the EIAV_MD group, and the lowest titres in the EIAV_LD group (P<0.05). The occurrence of disease/death was different between EIAV_HD group (1/0), EIAV_MD (2/2), and EIAV_LD group (4/2). A similar env diversity-related linear relationship was observed in the clinical manifestations and pathological changes. This diversity-dependent disparity in changes between the three groups was more distinct after immunosuppression, suggesting that env diversity plays an important role in protection under low host immunocompetence. In summary, inoculation with vaccines with higher genetic diversity could present broader and more efficient protection. Our findings strongly suggest that an abundance of Env antigens are required for efficient protection against lentiviruses.


Assuntos
Anemia Infecciosa Equina/prevenção & controle , Produtos do Gene env/imunologia , Vírus da Anemia Infecciosa Equina/fisiologia , Polimorfismo de Nucleotídeo Único , Vacinas Virais/administração & dosagem , Animais , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , Anemia Infecciosa Equina/imunologia , Produtos do Gene env/genética , Sequenciamento de Nucleotídeos em Larga Escala , Cavalos , Vacinas Atenuadas , Vacinas Virais/imunologia , Vacinas Virais/farmacologia , Replicação Viral/efeitos dos fármacos
14.
Sci Rep ; 10(1): 9105, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499513

RESUMO

We have studied the charge and spin thermopower systematically in a ferromagnetic junction of graphene-like zigzag nanoribbon modified by two on-site disorders in the tight-binding model. Symmetries of the transmission spectra and geometry configuration of the two disorders are important factors in determining the thermoelectric properties of the system. Conditions to achieve pure charge and pure spin thermopower are discussed from the perspective of symmetry. Symmetry breaking is required sometimes to obtain large figure of merit. The type and strength of the disorders can be used to further manipulate the spin polarization of thermal current. Disorders inside nanoribbon instead of on edge can then be used to finely tune the performance of the junction. The results may have great application value in designing thermoelectric devices.

15.
Stem Cell Res Ther ; 11(1): 188, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434593

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

16.
World J Pediatr ; 16(3): 232-239, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32333248

RESUMO

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.


Assuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Criança , Consenso , Humanos , SARS-CoV-2
17.
Viruses ; 12(2)2020 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079099

RESUMO

Tetherin is an interferon-inducible type II transmembrane glycoprotein which inhibits the release of viruses, including retroviruses, through a "physical tethering" model. However, the role that the glycosylation of tetherin plays in its antiviral activity remains controversial. In this study, we found that mutation of N-glycosylation sites resulted in an attenuation of the antiviral activity of equine tetherin (eqTHN), as well as a reduction in the expression of eqTHN at the plasma membrane (PM). In addition, eqTHN N-glycosylation mutants colocalize obviously with ER, CD63, LAMP1 and endosomes, while WT eqTHN do not. Furthermore, we also found that N-glycosylation impacts the transport of eqTHN in the cell not by affecting the endocytosis, but rather by influencing the anterograde trafficking of the protein. These results suggest that the N-glycosylation of eqTHN is important for the antiviral activity of the protein through regulating its normal subcellular localization. This finding will enhance our understanding of the function of this important restriction factor.


Assuntos
Antígeno 2 do Estroma da Médula Óssea/genética , Antígeno 2 do Estroma da Médula Óssea/metabolismo , Espaço Intracelular/metabolismo , Animais , Endocitose , Glicosilação , Células HEK293 , Cavalos , Humanos , Mutação , Transporte Proteico , Liberação de Vírus
19.
CNS Neurosci Ther ; 26(3): 385-393, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31729196

RESUMO

Epilepsy is a neurological disease, and the main clinical manifestation is recurrent seizures. The exact etiology of epilepsy and the pathogenesis of the disorder are not yet fully understood. Atlastin-1, a dynamin-like GTPase, interacts with microtubules and is responsible for vesicle formation, both of which are highly associated with the development of epilepsy. Here, we reported that the expression level of atlastin-1 protein was reduced in the temporal neocortex of patients with temporal lobe epilepsy and in the hippocampus and adjacent cortex of a pentylenetetrazol-kindled epileptic mouse model. Cells expressing atlastin-1 coexpressed the inhibitory synaptic marker GAD67 in the temporal cortex and hippocampus of patients with epilepsy and an epileptic mouse model. The lentivirus-mediated overexpression of atlastin-1 protein in the hippocampus of mice suppressed seizure activity in behavioral experiments. Patch-clamp recordings in the Mg2+ -free epilepsy cell model showed that atlastin-1 overexpression inhibited neuronal excitability by suppressing the discharge frequency of spontaneous action potentials rather than by changing the passive and active properties of action potentials. Inhibitory synaptic transmission, but not excitatory synaptic currents, increased after atlastin-1 overexpression. These findings suggest that atlastin-1 likely contributes to the occurrence and development of epilepsy through inhibitory synaptic transmission.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Hipocampo/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Convulsões/metabolismo , Lobo Temporal/metabolismo , Adolescente , Adulto , Animais , Criança , Feminino , Hipocampo/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Neurônios/patologia , Convulsões/patologia , Lobo Temporal/patologia , Adulto Jovem
20.
Viruses ; 11(12)2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810278

RESUMO

Interferon-mediated host factors myxovirus (Mx) proteins are key features in regulating influenza A virus (IAV) infections. Viral polymerases are essential for viral replication. The Mx1 protein has been known to interact with viral nucleoprotein (NP) and PB2, resulting in the influence of polymerase activity and providing interspecies restriction. The equine influenza virus has evolved as an independent lineage to influenza viruses from other species. We estimated the differences in antiviral activities between human MxA (huMxA) and equine Mx1 (eqMx1) against a broad range of IAV strains. We found that huMxA has antiviral potential against IAV strains from non-human species, whereas eqMx1 could only inhibit the polymerase activity of non-equine species. Here, we demonstrated that NP is the main target of eqMx1. Subsequently, we found adaptive mutations in the NP of strains A/equine/Jilin/1/1989 (H3N8JL89) and A/chicken/Zhejiang/DTID-ZJU01/2013 (H7N9ZJ13) that confer eqMx1 resistance and sensitivity respectively. A substantial reduction in Mx1 resistance was observed for the two mutations G34S and H52N in H3N8JL89 NP. Thus, eqMx1 is an important dynamic force in IAV nucleoprotein evolution. We, therefore, suggest that the amino acids responsible for Mx1 resistance should be regarded as a robust indicator for the pandemic potential of lately evolving IAVs.


Assuntos
Doenças dos Cavalos/metabolismo , Doenças dos Cavalos/virologia , Interações Hospedeiro-Patógeno , Vírus da Influenza A/fisiologia , Proteínas de Resistência a Myxovirus/metabolismo , Infecções por Orthomyxoviridae/veterinária , Replicação Viral , Animais , Cães , Evolução Molecular , Células HEK293 , Cavalos , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Mutação , Proteínas do Nucleocapsídeo , Filogenia , Ligação Proteica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Especificidade da Espécie , Proteínas do Core Viral/genética , Proteínas do Core Viral/metabolismo
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