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1.
Circulation ; 148(7): 589-606, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37203562

RESUMO

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.


Assuntos
Dissecção Aórtica , Músculo Liso Vascular , Animais , Humanos , Camundongos , Dissecção Aórtica/genética , Sistema de Sinalização das MAP Quinases , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosforilação
2.
Opt Lett ; 48(12): 3183-3186, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37319057

RESUMO

In this Letter, we present a scheme for detecting fiber-bending eavesdropping based on feature extraction and machine learning (ML). First, 5-dimensional features from the time-domain signal are extracted from the optical signal, and then a long short-term memory (LSTM) network is applied for eavesdropping and normal event classification. Experimental data are collected from a 60 km single-mode fiber transmission link with eavesdropping implemented by a clip-on coupler. Results show that the proposed scheme achieves a 95.83% detection accuracy. Furthermore, since the scheme focuses on the time-domain waveform of the received optical signal, additional devices and a special link design are not required.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação
3.
Am J Nephrol ; 54(3-4): 106-116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37245508

RESUMO

INTRODUCTION: This observational cohort study evaluated the prognostic value of mast cells in the pathogenesis and progression of IgA nephropathy. METHODS: A total of 76 adult IgAN patients were enrolled into this study from Jan 2007 and June 2010. Immunohistochemistry and immunofluorescence were used to identify tryptase-positive mast cells in renal biopsy samples. Patients were classified into Tryptasehigh and Tryptaselow groups. Depending on an average of 96-month follow-up, the predictive value of tryptase-positive mast cells in IgAN progression was analyzed. RESULTS: Tryptase-positive mast cells were found frequently in IgAN kidneys while rarely observed in normal kidneys. We also found IgAN patients in Tryptasehigh group presented both severe clinical and pathological renal manifestations. Furthermore, Tryptasehigh group contained more interstitial macrophages and lymphocytes infiltration than Tryptaselow group. Higher tryptase-positive cells density is associated with poor prognosis in patients with IgAN. CONCLUSIONS: High renal mast cells density is associated with severe renal lesions and poor prognosis in patients with Immunoglobulin A nephropathy. High renal mast cells density might be used as a predictor of poor prognosis in patients with IgAN.


Assuntos
Glomerulonefrite por IGA , Mastócitos , Adulto , Humanos , Contagem de Células , Glomerulonefrite por IGA/patologia , Rim/patologia , Mastócitos/patologia , Prognóstico , Triptases
4.
Appl Intell (Dordr) ; 53(9): 10053-10067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35991679

RESUMO

Most existing action quality assessment (AQA) methods provide only an overall quality score for the input video and lack an evaluation of each substage of the movement process; thus, these methods cannot provide detailed feedback for users. Moreover, the existing datasets do not provide labels for substage quality assessment. To address these problems, in this work, a new label-reconstruction-based pseudo-subscore learning (PSL) method is proposed for AQA in sporting events. In the proposed method, the overall score of an action is not only regarded as a quality label but also used as a feature of the training set. A label-reconstruction-based learning algorithm is built to generate pseudo-subscore labels for the training set. Moreover, based on the pseudo-subscore labels and overall score labels, a multi-substage AQA model is fine-tuned from the PSL model to predict the action quality score of each substage and the overall score for an athlete. Several ablation experiments are performed to verify the effectiveness of each module. The experimental results show that our approach achieves state-of-the-art performance.

5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(11): 1703-1710, 2023 Nov 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38432861

RESUMO

OBJECTIVES: The effect of three-dimensional (3D) printed bone-attached guide plate assisted cannulated screw fixation of pelvic fracture is reliable, but extensive soft tissue dissection is still required when installing the guide plate. This study aims to compare the efficacy of posterior pelvic ring fracture fixation with iliosacral screw insertion between the assistance of modified percutaneous patient specific 3D printed guide template and conventional fluoroscopy. METHODS: From May, 2019 and September 2021, 28 patients sustained posterior pelvic ring fractures were randomized into 2 groups: A guide template group, in which the iliosacral screw was inserted for fixation of the posterior pelvic ring fracture with the assistance of modified percutaneous patient specific 3D printed guide template, and a fluoroscopy group, in which the iliosacral screw was inserted under the guidance of conventional fluoroscopy. The operation time, fluoroscopic frequency, intraoperative blood loss, and incision length were recorded for each screw insertion. Fracture reduction was evaluated according to the Matta criteria. The screw position was evaluated according to the modified Gras classification, and the functional outcome was evaluated according to Majeed score. The parameters of both groups were compared, and statistical analysis was performed. RESULTS: All the 28 patients were followed up for 12-24 months. Of them, 15 iliosacral screws were inserted in 14 patients in the guide template group, and 14 iliosacral screws were inserted in 14 patients in the fluoroscopy group. The operation time, fluoroscopic frequency, screw deviation, incision length, and blood loss in the guide template group were 20-30(25.8±2.8) min, 9-15(12.2±1.9), 2-4(2.6±0.7) mm, 4-5(4.6±0.5) cm, and 5-10 (7.8±1.7) mL, respectively, whereas those in the fluoroscopy group were 30-60(48.1±7.5) min, 40-96(64.7±16.3), 3-6(4.2±0.9) mm, 0.8-1.2(1.0±0.1) cm, and 2-5(3.1±1.3) mL, respectively, and there were statistical significance (all P<0.001). Fracture reduction was evaluated according to the Matta criteria, and all the patients reached excellence and good (P=0.584) in the 2 groups. According to modified Gras classification, there were 12 Grade I screws, 3 Grade II screws, and 0 Grade III screws in the guide template group, and 10 Grade I screws, 3 Grade II screws, and 1 Grade III screw in the fluoroscopy group, with no statistical significance (P=0.334). The functional outcome was evaluated according to Majeed score at the last follow-up, without significant difference between the guide template group and the fluoroscopy group (P=0.908). CONCLUSIONS: Compared with the conventional fluoroscopy, it would cost less operation time, less fluoroscopic frequency and increase more accurate screw insertion to fixate the posterior pelvic ring fracture with the assistance of modified percutaneous patient specific 3D printed guide template.


Assuntos
Fraturas Ósseas , Hiperaldosteronismo , Ferida Cirúrgica , Humanos , Fraturas Ósseas/cirurgia , Dissecação , Fluoroscopia , Impressão Tridimensional , Parafusos Ósseos
6.
Allergy ; 77(2): 619-632, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34706102

RESUMO

BACKGROUND: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent M. bovis strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy. METHODS: Three genes, BCG_3174, BCG_1782, and BCG_2432c, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of M. bovis and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo. RESULTS: Of the three identified genes, only the disruption of BCG_2432c, namely ΔBCG_2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. ΔBCG_2432c showed a stronger ability to trigger intracellular ROS-mediated complete autophagic flux in infected THP-1 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN-γ+ CD4+ TEM and IL-2+ CD4+ TCM cells in the spleens and lungs of ΔBCG_2432c-vaccinated mice. CONCLUSIONS: The insufficient efficacy of the BCG vaccine is attributable to the important autophagy-inhibition gene BCG_2432c that blocks the autophagosome-lysosome pathway of antigen presentation. ΔBCG_2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB.


Assuntos
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose , Animais , Autofagia , Vacina BCG , Humanos , Camundongos , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose/prevenção & controle
7.
Acta Biochim Biophys Sin (Shanghai) ; 54(4): 556-564, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35607955

RESUMO

Age has been found to be one of the main risk factors for the severity and outcome of COVID-19. However, differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown. In this study, we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups. By antibody response landscape maps, we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age. The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence, disease severity and age of the COVID-19 patients. Furthermore, the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged <50 and high S1 IgG responses are enriched in mild COVID-19 patients aged >60. In addition, high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged >70. These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age, which may facilitate a deeper understanding of the immune responses in COVID-19 patients.


Assuntos
Fatores Etários , Formação de Anticorpos , COVID-19 , Idoso , Anticorpos Antivirais/sangue , COVID-19/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Peptídeos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
8.
Sensors (Basel) ; 22(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36365901

RESUMO

The growth models of total bacterial count in freshly squeezed strawberry juice were established by gas and taste sensors in this paper. By selecting the optimal sensors and fusing the response values, the Modified Gompertz, Logistic, Huang and Baranyi models were used to predict and simulate the growth of bacteria. The results showed that the R2 values for fitting the growth model of total bacterial count of the sensor S7 (an electronic nose sensor), of sweetness and of the principal components scores were 0.890-0.944, 0.861-0.885 and 0.954-0.964, respectively. The correlation coefficients, or R-values, between models fitted by the response values and total bacterial count ranged from 0.815 to 0.999. A single system of electronic nose (E-nose) or electronic tongue (E-tongue) sensors could be used to predict the total bacterial count in freshly squeezed strawberry juice during cold storage, while the higher rate was gained by the combination of these two systems. The fusion of E-nose and E-tongue had the best fitting-precision in predicting the total bacterial count in freshly squeezed strawberry juice during cold storage. This study proved that it was feasible to predict the growth of bacteria in freshly squeezed strawberry juice using E-nose and E-tongue sensors.


Assuntos
Nariz Eletrônico , Fragaria , Carga Bacteriana , Paladar , Língua
9.
Respir Res ; 22(1): 146, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980216

RESUMO

BACKGROUND: Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been used as first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, during treatment, cancer cells often develop resistance to gefitinib, the mechanisms of which are not fully understood. This study was designed to elucidate the expression and role of long non-coding RNA (lncRNA)-PCAT-1, a potential biomarker for drug resistance and a therapeutic target for NSCLC, in gefitinib resistance in NSCLC cells. METHODS: In this study, we verified differential PCAT-1 expression in NSCLC gefitinib-resistant tissues or cells. PCAT-1 knockdown, clone formation, Transwell, flow cytometry, and immunofluorescence assays were used to verify the correlation between PCAT-1 and gefitinib sensitivity. A nude mouse tumor-bearing model verified that PCAT-1 can reverse gefitinib resistance in vivo. Then, a PI3K/Akt agonist was used to verify the possible mechanism of PCAT-1 action. RESULTS: PCAT-1 is highly expressed in gefitinib-resistant NSCLC tissues and cells. PCAT-1 knockdown enhanced gefitinib sensitivity and gefitinib-induced apoptosis in H1299/GR cells. PCAT-1 knockdown reduced tumor volume and weight, and reversed acquired gefitinib resistance in vivo. PCAT-1 knockdown inhibited AKT and GSK3 phosphorylation in H1299/GR cells. A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. PCAT-1 is as potential target for improving the clinical efficacy of gefitinib.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , RNA Longo não Codificante/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Nus , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Allergy ; 76(2): 551-561, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33040337

RESUMO

BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Portador Sadio/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/diagnóstico , Teste para COVID-19/métodos , Portador Sadio/sangue , Portador Sadio/diagnóstico , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade
11.
Helicobacter ; 26(1): e12758, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33259676

RESUMO

BACKGROUND: Helicobacter pylori is a gram-negative bacterium involved in many gastric pathologies such as ulcers and cancers. Although the treatment for this infection has existed for several years, the development of a vaccine is nevertheless necessary to reduce the severe forms of the disease. For more than three decades, many advances have been made particularly in the understanding of virulence factors as well as the pathogenesis of gastric diseases caused by H. pylori. Among these key virulence factors, specific antigens have been identified: Urease, Vacuolating cytotoxin A (VacA), Cytotoxin-associated gene A (CagA), Blood group antigen-binding adhesin (BabA), H. pylori adhesin A (HpaA), and others. OBJECTIVES: This review will focus on H. pylori adhesins, in particular, on HpaA and on the current knowledge of H. pylori vaccines. METHODS: All of the information included in this review was retrieved from published studies on H. pylori adhesins in H. pylori infections. RESULTS: These proteins, used in their native or recombinant forms, induce protection against H. pylori in experimental animal models. CONCLUSION: H. pylori adhesins are known to be promising candidate vaccines against H. pylori. Future research should be carried out on adhesins, in particular, on HpaA.


Assuntos
Adesinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Infecções por Helicobacter , Helicobacter pylori , Animais , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/imunologia , Urease/imunologia , Fatores de Virulência/imunologia
12.
Clin Gastroenterol Hepatol ; 18(11): 2564-2572.e1, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32109631

RESUMO

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.


Assuntos
Varizes Esofágicas e Gástricas , Trombose Venosa , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/patologia , Hemorragia Gastrointestinal/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Veia Porta/patologia , Prevalência , Estudos Retrospectivos , Trombose Venosa/complicações , Trombose Venosa/epidemiologia , Trombose Venosa/patologia
13.
FASEB J ; 33(6): 7721-7733, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30893562

RESUMO

Calcium is an important messenger in the neuronal system, but its specific role in axonal regeneration has not been fully investigated. To clarify it, we constructed a noninvasive in vivo calcium-imaging model of zebrafish Mauthner cells and monitored subcellular calcium dynamics during axonal regeneration. Using the calcium indicator GCamp6f, we observed that the regenerative length correlated with the peak amplitude of the evoked calcium response before axotomy, which suggested that the evoked calcium response might serve as a useful indicator of evoked neuronal activity and axonal regenerative capacity. To investigate this possibility, we overexpressed an inward rectifying potassium channel protein, Kir2.1a, to decrease the Mauthner neuronal activity and found that the inhibition of the calcium response correlated with decreased axonal regeneration. In contrast, treatment of pentylenetetrazol and knockout of the sodium voltage-gated channel α subunit 1 gene increased the calcium response and thus enhanced axonal regeneration. Our results therefore increased the understanding of the correlation between the neural activity and the vertebrate axonal regeneration.-Chen, M., Huang, R.-C., Yang, L.-Q., Ren, D.-L., Hu, B. In vivo imaging of evoked calcium responses indicates the intrinsic axonal regenerative capacity of zebrafish.


Assuntos
Axônios/metabolismo , Cálcio/metabolismo , Regeneração Nervosa , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados , Axotomia
14.
Biol Proced Online ; 21: 17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496923

RESUMO

BACKGROUND: The presence of residual DNA carried by biological products in the body may lead to an increased oncogenicity, infectivity, and immunomodulatory risk. Therefore, current agencies including WHO, EU, and the FDA limited the accepted amounts of residual DNA (less than 10 ng or 100 pg/dose). Among the methods of detecting residual DNA, qPCR is considered to be the most practical for residual DNA quantitation due to its sensitivity, accuracy, precision, and time-saving. RESULTS: In this study, the detection capacity of this method was determined by comparing the detected concentration of the commercial kit and the self-designed primer/probe set after the same treatment of the extraction method. Then, a universal sample pretreatment method based on a co-precipitant was optimized. The validation results demonstrated that the method has appropriate specificity, sensitivity, accuracy, and precision according to ICH guidelines. The limit of detection and quantitation reached 3 fg/ul and 0.3 pg/reaction respectively, which satisfies the requirement of limit of residual DNA detection in biologics. Spike recovery (82.3-105.7%) showed that the proposed qPCR assay was accurate and has good extraction efficiency. Moreover, the precision of the method based on intra- and inter-assay was 0.065-0.452% and 0.471-1.312%, respectively. CONCLUSIONS: These results all indicated that the method for determination of residual DNA in biological products expressed from CHO cells is sensitive, accurate and robust.

15.
BMC Neurol ; 19(1): 54, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953462

RESUMO

BACKGROUND: Serum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke. METHODS: This was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. RESULTS: A total of 768 patients were finally included in the study and divided into two age groups: a younger group (age < 65 years) and an older group (age ≥ 65 years). On univariate analysis, four factors-lower total T3, free T3 concentrations, higher scores on the National Institute of Health Stroke Scale (NIHSS) and the presence of atrial fibrillation-were associated with poor functional outcomes in both groups. In addition, older age, female gender, higher free T4, and lower TSH levels were also associated with poor function in the older group. On multiple logistic regression analysis, higher NIHSS scores (odds ratio [OR] =1.95; 95% confidence interval [CI], 1.66-2.30; P ≤ .001) and lower total T3 concentrations (OR = 0.06; 95% CI, 0.01-0.68; P = .024) remained independently associated with poor functional outcome in the older group. However, the independent association with poor function of lower total T3 was not confirmed in the younger group. CONCLUSIONS: The prognostic value of low total T3 is age-associated and more meaningful in an older population.


Assuntos
Biomarcadores/sangue , Isquemia Encefálica/sangue , Acidente Vascular Cerebral/sangue , Tri-Iodotironina/sangue , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Tireotropina/sangue , Tiroxina/sangue
16.
BMC Pediatr ; 19(1): 62, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777044

RESUMO

BACKGROUND: Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. CASE PRESENTATION: The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2-3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 µmol/L, IBIL24 µmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. CONCLUSIONS: Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation.


Assuntos
Anquirinas/genética , Mutação , Esferocitose Hereditária/genética , Transfusão de Sangue , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Esferocitose Hereditária/terapia
17.
Sensors (Basel) ; 19(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554229

RESUMO

The fields of human activity analysis have recently begun to diversify. Many researchers have taken much interest in developing action recognition or action prediction methods. The research on human action evaluation differs by aiming to design computation models and evaluation approaches for automatically assessing the quality of human actions. This line of study has become popular because of its explosively emerging real-world applications, such as physical rehabilitation, assistive living for elderly people, skill training on self-learning platforms, and sports activity scoring. This paper presents a comprehensive survey of approaches and techniques in action evaluation research, including motion detection and preprocessing using skeleton data, handcrafted feature representation methods, and deep learning-based feature representation methods. The benchmark datasets from this research field and some evaluation criteria employed to validate the algorithms' performance are introduced. Finally, the authors present several promising future directions for further studies.


Assuntos
Aprendizado Profundo , Algoritmos , Humanos , Aprendizado de Máquina
18.
Sensors (Basel) ; 19(5)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818796

RESUMO

Although widely used in many applications, accurate and efficient human action recognition remains a challenging area of research in the field of computer vision. Most recent surveys have focused on narrow problems such as human action recognition methods using depth data, 3D-skeleton data, still image data, spatiotemporal interest point-based methods, and human walking motion recognition. However, there has been no systematic survey of human action recognition. To this end, we present a thorough review of human action recognition methods and provide a comprehensive overview of recent approaches in human action recognition research, including progress in hand-designed action features in RGB and depth data, current deep learning-based action feature representation methods, advances in human⁻object interaction recognition methods, and the current prominent research topic of action detection methods. Finally, we present several analysis recommendations for researchers. This survey paper provides an essential reference for those interested in further research on human action recognition.


Assuntos
Reconhecimento Automatizado de Padrão/métodos , Visão Ocular/fisiologia , Percepção Visual/fisiologia , Algoritmos , Atividades Humanas , Humanos , Movimento (Física) , Esqueleto/fisiologia , Inquéritos e Questionários
19.
J Clin Nurs ; 28(21-22): 3949-3956, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31408559

RESUMO

AIMS AND OBJECTIVES: To assess the self-management activities among rural patients with chronic hepatitis B (CHB), and the influence of psychosocial and demographic factors on their self-management activities. BACKGROUND: Chronic hepatitis B is a serious public health concern. Rural patients may have limited access to healthcare services. Although self-management is important for controlling chronic hepatitis B, few studies focus on the self-management activities among rural patients with chronic hepatitis B. Understanding self-management activities and related factors in this population are important to design and implement appropriate intervention strategies. DESIGN: A cross-sectional study. METHODS: From June-December 2017, totally 236 rural patients with chronic hepatitis B were recruited from hepatology department in two hospitals in Chongqing, China. The questionnaire included demographic characteristics, Chronic Hepatitis B Self-Management Scale, Self-Efficacy for Managing Chronic Disease, and Social Support Rating Scale. The study followed the STROBE checklist. RESULTS: Rural patients with chronic hepatitis B reported poor self-management activities for the score indexes of symptom management (57.36%), lifestyle management (54.89%), psychosocial coping (54.84%) and disease information management (53.11%) were all below 60%. Self-efficacy, objective support, subjective support, gender, education level and marital status showed significant effect on self-management activities. CONCLUSION: Rural patients with chronic hepatitis B were found to perform insufficient self-management activities. Self-efficacy, social support, gender, education level and marital status were identified to influence their self-management activities. RELEVANCE TO CLINICAL PRACTICE: Self-management activities should be promoted among rural patients with chronic hepatitis B. The factors that were identified in this study should be addressed when developing interventions to promote the performance of self-management activities for rural patients with chronic hepatitis B.


Assuntos
Hepatite B Crônica/terapia , População Rural/estatística & dados numéricos , Autogestão/estatística & dados numéricos , Adulto , China , Estudos Transversais , Feminino , Hepatite B Crônica/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Autoeficácia , Autogestão/psicologia , Inquéritos e Questionários
20.
J Proteome Res ; 17(4): 1509-1520, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29533670

RESUMO

Protein post-translational modification by ubiquitin-fold modifier 1, UFM1, regulates many biological processes such as response to endoplasmic reticulum stress and regulation of tumor progression. A recent study has indicated that the UFM1-binding and PCI domain-containing protein 1 (UFBP1) is required for the conjugation of UFM1 to a substrate. However, other biological functions of UFBP1 have not been explored. Here, we use immunoprecipitation and label-free quantitative proteomics to identify UFBP1-interacting proteins in a mammalian cell line. About 80 potential interacting proteins are obtained from MS analyses of three biological replicates. Bioinformatics analyses of these proteins suggest that UFBP1 may participate in the regulation of protein folding, stability, and trafficking. Biochemical experiments discover that UFBP1 expression downregulates the protein level and reduces the stability of several of its interacting proteins, while UFBP1 knockdown increases their protein levels. Protein synthesis inhibition and proteasomal inhibition experiments reveal that UFBP1 promotes their ubiquitination and degradation. Experiments using a model UFBP1-interacting protein ANT3 demonstrate that UFBP1 enhances the interaction between ANT3 and its E3 ligase and thus promotes its ubiquitination and degradation. Our work elucidates a novel molecular mechanism by which UFBP1 regulates protein ubiquitination and degradation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Processamento de Proteína Pós-Traducional , Proteólise , Proteômica , Ubiquitinação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Translocador 3 do Nucleotídeo Adenina/metabolismo , Animais , Linhagem Celular , Regulação para Baixo , Células HEK293 , Humanos , Mamíferos , Ligação Proteica , Ubiquitina-Proteína Ligases/metabolismo
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