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PURPOSE: Aging is a major societal concern due to age-related functional losses. Synapses are crucial components of neural circuits, and synaptic density could be a sensitive biomarker to evaluate brain function. [11C]UCB-J is a positron emission tomography (PET) ligand targeting synaptic vesicle glycoprotein 2A (SV2A), which can be used to evaluate brain synaptic density in vivo. METHODS: We evaluated age-related changes in gray matter synaptic density, volume, and blood flow using [11C]UCB-J PET and magnetic resonance imaging (MRI) in a wide age range of 80 cognitive normal subjects (21-83 years old). Partial volume correction was applied to the PET data. RESULTS: Significant age-related decreases were found in 13, two, and nine brain regions for volume, synaptic density, and blood flow, respectively. The prefrontal cortex showed the largest volume decline (4.9% reduction per decade: RPD), while the synaptic density loss was largest in the caudate (3.6% RPD) and medial occipital cortex (3.4% RPD). The reductions in caudate are consistent with previous SV2A PET studies and likely reflect that caudate is the site of nerve terminals for multiple major tracts that undergo substantial age-related neurodegeneration. There was a non-significant negative relationship between volume and synaptic density reductions in 16 gray matter regions. CONCLUSION: MRI and [11]C-UCB-J PET showed age-related decreases of gray matter volume, synaptic density, and blood flow; however, the regional patterns of the reductions in volume and SV2A binding were different. Those patterns suggest that MR-based measures of GM volume may not be directly representative of synaptic density.
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Sustancia Gris , Glicoproteínas de Membrana , Humanos , Anciano de 80 o más Años , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/metabolismo , Glicoproteínas de Membrana/metabolismo , Tomografía de Emisión de Positrones/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Sinapsis/metabolismoRESUMEN
OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.
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Aprendizaje Profundo , Neoplasias de Cabeza y Cuello , Nomogramas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Anciano , Imagenología Tridimensional/métodos , Adulto , Estudios Retrospectivos , RadiómicaRESUMEN
BACKGROUND: This study investigated whether the Combat compensation method can remove the variability of radiomic features extracted from different scanners, while also examining its impact on the subsequent predictive performance of machine learning models. MATERIALS AND METHODS: 135 CT images of Credence Cartridge Radiomic phantoms were collected and screened from three scanners manufactured by Siemens, Philips, and GE. 100 radiomic features were extracted and 20 radiomic features were screened according to the Lasso regression method. The radiomic features extracted from the rubber and resin-filled regions in the cartridges were labeled into different categories for evaluating the performance of the machine learning model. Radiomics features were divided into three groups based on the different scanner manufacturers. The radiomic features were randomly divided into training and test sets with a ratio of 8:2. Five machine learning models (lasso, logistic regression, random forest, support vector machine, neural network) were employed to evaluate the impact of Combat on radiomic features. The variability among radiomic features were assessed using analysis of variance (ANOVA) and principal component analysis (PCA). Accuracy, precision, recall, and area under the receiver curve (AUC) were used as evaluation metrics for model classification. RESULTS: The principal component and ANOVA analysis results show that the variability of different scanner manufacturers in radiomic features was removed (PË0.05). After harmonization with the Combat algorithm, the distributions of radiomic features were aligned in terms of location and scale. The performance of machine learning models for classification improved, with the Random Forest model showing the most significant enhancement. The AUC value increased from 0.88 to 0.92. CONCLUSIONS: The Combat algorithm has reduced variability in radiomic features from different scanners. In the phantom CT dataset, it appears that the machine learning model's classification performance may have improved after Combat harmonization. However, further investigation and validation are required to fully comprehend Combat's impact on radiomic features in medical imaging.
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Aprendizaje Automático , Fantasmas de Imagen , Humanos , Tomografía Computarizada por Rayos X , Tomógrafos Computarizados por Rayos X , Análisis de Componente Principal , Redes Neurales de la Computación , Algoritmos , RadiómicaRESUMEN
Few studies have reported on the continuous evolution of dual-linker zeolitic imidazolate frameworks' (ZIFs) structure and morphology during the crystal growth process. Herein, we report the synthesis of a novel ZIF material with CHA topology (ZIF-301-eIm) via the combination of a small-sized 2-ethylimidazole (eIm) with the large-sized 5-chlorobenzimidazole ligand. A series of derivative materials with distinct structures and morphologies were obtained via two pathways: (1) insufficient amount of eIm with prolonged crystallization time (pathway A) and (2) sufficient amount of eIm with prolonged crystallization time (pathway B). Various characterization techniques revealed the continuous evolution of structure and morphology during the crystal growth process. Insufficient amount of eIm and crystallization time (crystallization pathway A) led to ZIF-301-eIm derivatives with defective and open structures alongside an aggregated morphology of nanoparticles. Prolonging the crystallization time allowed small-sized eIm ligands to gradually fill into the framework, resulting in the formation of ZIF-301-eIm-A5 characterized by complete but dense structures with a perfect polyhedral morphology. Remarkably, a sufficient amount of eIm during synthesis (crystallization pathway B) formed ZIF-301-eIm-B1 with a similar structure and morphology to ZIF-301-eIm-A5 in just 1 day. ZIF-301-eIm-B3, with intact, dense structures, exhibits superior acetone/butanol separation performance compared to ZIF-301-eIm-A3 due to small pore windows and large cages facilitating selective adsorption of acetone through exclusion separation.
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The coronavirus disease 2019 (COVID-19) pandemic has led to a fundamental number of morbidity and mortality worldwide. Glucosamine was indicated to help prevent and control RNA virus infection preclinically, while its potential therapeutic effects on COVID-19-related outcomes are largely unknown. To assess the association of habitual glucosamine use with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, and mortality with COVID-19 in a large population based cohort. Participants from UK Biobank were reinvited between June and September 2021 to have SARS-CoV-2 antibody testing. The associations between glucosamine use and the risk of SARS-CoV-2 infection were estimated by logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for COVID-19-related outcomes were calculated using COX proportional hazards model. Furthermore, we carried out propensity-score matching (PSM) and stratified analyses. At baseline, 42 673 (20.7%) of the 205 704 participants reported as habitual glucosamine users. During median follow-up of 1.67 years, there were 15 299 cases of SARS-CoV-2 infection, 4214 cases of COVID-19 hospital admission, and 1141 cases of COVID-19 mortality. The fully adjusted odds ratio of SARS-CoV-2 infection with glucosamine use was 0.96 (95% CI: 0.92-1.01). The fully adjusted HR were 0.80 (95% CI: 0.74-0.87) for hospital admission, and 0.81 (95% CI: 0.69-0.95) for mortality. The logistic regression and Cox proportional hazard analyses after PSM yielded consistent results. Our study demonstrated that habitual glucosamine use is associated with reduced risks of hospital admission and death with COVID-19, but not the incidence of SARS-CoV-2 infection.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios de Cohortes , Hospitalización , HospitalesRESUMEN
OBJECTIVE: This study aims to observe and analyze the clinical characteristics and prognosis of adenovirus (ADV) infection diagnosed by metagenomic next-generation sequencing (mNGS) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), which was performed following Beijing Protocol. METHODS: The clinical data of patients who developed ADV infection diagnosed by mNGS after Haplo-HSCT between January 2019 and March 2021, recorded in three transplantation centers, were retrospectively analyzed. Potential risk factors for infection and the clinical manifestations of ADV involvement in different end-organs were also studied. Additionally, the patient prognosis regarding the available treatment was observed. RESULTS: A total of seven patients were diagnosed with ADV infection by the mNGS technique after Haplo-HSCT of 976 patients enrolled. The risk factors for infection included antithymocyte globulin steroid-refractory graft-versus-host disease (GVHD) history, CD25 monoclonal antibody or ruxolitinib treatment history and <300 cells/µL of CD3+ T cells count in peripheral blood. The clinical manifestations of ADV infection included encephalitis, hepatitis, cystitis, and pneumonia. Six patients were treated with cidofovir (CDV) and intravenous immunoglobulin (IVIg), and one with CDV, ribavirin, IVIg, thymosin Alpha-1 for injection and low-dose donor lymphocyte infusion. One case showed negative ADV DNA results with improved conditions; however, the patient died of the relapse of the primary disease in the later stage. The remaining six died of ADV infection. CONCLUSION: mNGS can provide screening for ADV and information on ADV subtypes, helpful to understand tissue tropism. This technique could be useful in diagnosing patients at high risk for ADV infection. ADV infection can involve multiple organs, has difficulty in early diagnosis, and has a poor prognosis. Currently, effective treatments are inadequate.
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Infecciones por Adenoviridae , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Retrospectivos , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/tratamiento farmacológico , Cidofovir , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Lead (Pb) is a pervasive toxic metal contaminant associated with a high risk of myocardial injury. However, the precise mechanism underlying Pb-induced myocardial injury has yet to be fully elucidated. In this study, a murine model of Pb exposure (0, 1, 5, and 10 mg/kg) was employed to investigate the involvement of neutrophil degranulation in the induction of myocardial injury. Notably, serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) increased significantly in Pb-exposed mice, whereas cTnI levels in cardiomyocytes decreased, suggesting that Pb exposure may cause early myocardial injury. Moreover, Pb exposure was found to promote neutrophil degranulation, as evidenced by elevated myeloperoxidase (MPO) and neutrophil elastase (NE) concentrations in both the serum of Pb-exposed workers and Pb-exposed mice, as well as the extracellular supernatant of neutrophils following exposure. However, we found that serum level of cTnI enhanced by Pb exposure is associated with increased NE levels in the serum, but not with MPO levels. Upon treatment with NE inhibitor (sivelestat), the serum level of cTnI markedly reduced in Pb-exposed mice, we found that early myocardial injury is associated with NE levels in the serum. At the molecular level, western blotting analysis revealed an upregulation of ERK1/2 expression in vitro following Pb exposure, suggesting that the activation of the ERK1/2 signaling pathway may underlie the participation of neutrophil degranulation in Pb-induced myocardial injury. In summary, our findings demonstrate that Pb exposure can initiate early myocardial injury by promoting the neutrophil degranulation process, thereby highlighting the potential role of this process in the pathogenesis of Pb-associated myocardial injury.
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Plomo , Neutrófilos , Ratones , Animales , Neutrófilos/metabolismo , Plomo/toxicidad , Miocitos Cardíacos/metabolismo , Elastasa de Leucocito/metabolismoRESUMEN
Background: The impact of the dietary B vitamins intakes on the development of depression has been scarcely investigated. Thus, this study aimed to examine the associations of dietary B vitamins intakes with the risk of depression in American adults. Methods: The data we used in this study were from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. We used the Logistic regression models to analyze the associations of the dietary intakes of B vitamins with the risk of depression. Results: 17,732 individuals (8,623 males and 9,109 females) were enrolled in the study and they were all 18 or older. Compared to the lowest quartile of dietary intake, the ORs (95%CIs) of the highest quartile were 0.64 (0.50-0.82), 0.78 (0.62-0.97), 0.60 (0.47-0.78), 0.65 (0.50-0.84), and 0.71 (0.54-0.95) for vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12, respectively. Compared to the people whose dietary intakes below the RDA in the model 2, those with intake meeting the RDA of vitamin B1 (OR: 0.68; 95%CI: 0.56-0.84), niacin (OR: 0.65; 95%CI: 0.51-0.81), B6 (OR: 0.65; 95%CI: 0.52-0.81), or B12 (OR: 0.65; 95%CI: 0.48-0.88) had a lower risk of depression, severally. We also found a nonlinear negative association between dietary vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12 intakes and the risk of depression in the dose-response analyses, severally. Conclusions: Our results suggested that dietary vitamin B1, vitamin B2, niacin, vitamin B6, and vitamin B12 intakes may be inversely associated with the risk of depression.
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Niacina , Complejo Vitamínico B , Masculino , Femenino , Adulto , Humanos , Encuestas Nutricionales , Depresión/epidemiología , Vitamina B 12 , Riboflavina , Vitamina B 6 , Vitamina A , Vitamina K , Ingestión de Alimentos , Tiamina , Ácido FólicoRESUMEN
The combination of new noble metal nanomaterials and surface enhanced Raman scattering (SERS) technology has become a new strategy to solve the problem of low sensitivity in the detection of traditional Chinese medicine. In this work, taking natural cicada wing (C.w.) as a template, by optimizing the magnetron sputtering experimental parameters for the growth of Ag nanoparticles (NPs) on vanadium-titanium (V-Ti) nanorods, the nanogaps between the nanorods were effectively regulated and the Raman signal intensity of the Ag15/V-Ti20/C.w. substrate was improved. The proposed homogeneous nanostructure exhibited high SERS activity through the synergistic effect of the electromagnetic enhancement mechanism at the nanogaps between the Ag NPs modified V-Ti nanorods. The analytical enhancement factor (AEF) value was as high as 1.819 × 108, and the limit of detection (LOD) was 1 × 10-11 M for R6G. The large-scale distribution of regular electromagnetic enhancement "hot spots" ensured the good reproducibility with the relative standard deviation (RSD) value less than 7.31%. More importantly, the active compound of Artemisinin corresponded the pharmacological effect of Artemisia annua was screened out by SERS technology, and achieved a LOD of 0.01â mg/l. This reliable preparation technology was practically applicable to produce SERS-active substrates in detection of pharmacodynamic substance in traditional Chinese medicine.
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Artemisininas , Nanopartículas del Metal , Nanotubos , Animales , Espectrometría Raman , Titanio/química , Nanopartículas del Metal/química , Plata/química , Vanadio , Reproducibilidad de los Resultados , Nanotubos/químicaRESUMEN
BACKGROUND: Streptozotocin is a classic drug used to induce diabetes in animal models. OBJECTIVE: The aim of this study is to investigate the liver transcriptome of Kunming mice with diabetes induced by either streptozotocin (STZ) or Non-STZ. METHODS: Forty male mice were randomly assigned into four groups: Control (Ctr, standard diet), mHH (high fat and high carbohydrate diet), mHS (high fat and high carbohydrate diet for 4 weeks followed by 60 mg/kg STZ for 3 consecutive days) and mSH (60 mg/kg STZ for 3 consecutive days followed by a high fat and high carbohydrate diet for 12 weeks). All mice injected with STZ were identified as diabetic despite the sequential feeding of high fat and high carbohydrate diets. RESULTS: Only 7 of 13 mice in the mHH group met the diagnostic criteria for diabetes. The asting blood glucose (FBG) of the mHH, mHS, mSH and Ctrl groups was 13.27 ± 1.14, 15.01 ± 2.59, 15.95 ± 4.38 and 6.28 ± 0.33 mmol/L at the 12th week, respectively. Compared with the mHH group, transcription was elevated in 85 genes in the livers of mHS mice, while 21 genes were downregulated and 97 genes were upregulated in the mSH group while 35 genes were decreased. A total of 43 co-expressed genes were identified in the mHS vs mHH and mSH vs mHH groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses showed that two corporate GO terms and two KEGG pathways were significantly annotated in the STZ-treated groups. Both the GO term and pathway were related to the metabolism mediated by p53. CONCLUSION: A high fat and high carbohydrate diet combined with a low dose of STZ can effectively induce diabetes in Kunming mice despite the abnormal expressions of genes in the liver. The differentially expressed genes were related to metabolism mediated by p53.
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Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Animales , Animales no Consanguíneos/genética , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Insulina/metabolismo , Hígado/patología , Masculino , Ratones/genética , Especificidad de Órganos/genética , Estreptozocina/farmacología , Transcriptoma/genéticaRESUMEN
Inflammation is an essential mechanism of various diseases. The development and resolution of inflammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in inflammation. SPMs are involved in the pathophysiology of different diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the inflammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of inflammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases.
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Inmunidad Innata/fisiología , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Metabolismo de los Lípidos/fisiología , Neumonía/inmunología , Neumonía/metabolismo , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/metabolismo , Neumonía/diagnósticoRESUMEN
Achieving self-assembled nanostructures with ultra-small feature sizes (e. g., below 5â nm) is an important prerequisite for the development of block copolymer lithography. In this work, the preparation and self-assembly of a series of giant molecules composed of vinyl polyhedral oligomeric silsesquioxane (VPOSS) tethered with monodispersed oligo(L-lactide) chains are presented. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) results demonstrate that ultra-small domain sizes (down to 3â nm) of phase separated lamellar morphology are achieved in bulk, driven by the strong tendency and fast kinetics for crystallization of VPOSS moieties. Moreover, upon gamma ray radiation, VPOSS cages in the lamellar structure can be crosslinked via polymerization of the vinyl groups. After pyrolysis at high temperature, ultra-thin two-dimensional nano-silica sheets can be obtained.
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Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis.
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Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Becaplermina/metabolismo , Fibroblastos/metabolismo , Homeostasis/genética , Obesidad/genética , Proteína de Unión al Calcio S100A4/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adipocitos/citología , Tejido Adiposo/citología , Animales , Becaplermina/genética , Proteínas de Ciclo Celular , Diferenciación Celular , Dieta Alta en Grasa/efectos adversos , Matriz Extracelular , Fibroblastos/citología , Regulación de la Expresión Génica , Masculino , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Transgénicos , Obesidad/etiología , Obesidad/metabolismo , Obesidad/patología , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteína de Unión al Calcio S100A4/metabolismo , Células Madre/citología , Células Madre/metabolismo , Vía de Señalización Wnt , Proteínas Señalizadoras YAPRESUMEN
Aleutian mink disease (AMD), caused by Aleutian mink disease virus (AMDV), is a very important infectious disease of mink. Currently, elimination of antibody- or antigen-positive animals is the most successful strategy for eradicating AMD, but the claw-cutting method of blood sampling is difficult to perform and painful for the animal. In this study, we aimed to establish an antigen capture enzyme-linked immunosorbent assay (AC-ELISA) method for the efficient detection of AMDV antigens using fecal samples. A purified mouse monoclonal antibody (mAb) was used as the capture antibody, and a rabbit polyclonal antibody (pAb) was used as the detection antibody. The assay was optimized by adjusting a series of parameters. Using a cutoff value of 0.205, the limit of detection of the AC-ELISA for strain AMDV-G antigen was 2 µg/mL, and there was no cross-reaction with other mink viruses. The intra- and inter-assay standard deviations were below 0.046, and the correlation of variance (CV) values were 1.24-7.12% when testing fecal samples. Compared with conventional PCR results, the specificity and sensitivity were 91.5% and 90.6%, respectively, and the concordance rate between the two methods was 91.1%.
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Virus de la Enfermedad Aleutiana del Visón/inmunología , Enfermedad Aleutiana del Visón/diagnóstico , Antígenos/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Visón/virología , Enfermedad Aleutiana del Visón/inmunología , Animales , Anticuerpos Antivirales/inmunología , Proteínas de la Cápside/inmunología , Ratones , Ratones Endogámicos BALB C , Visón/inmunología , ConejosRESUMEN
The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation.
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Lactancia/genética , Glándulas Mamarias Animales/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Transcripción/fisiología , Animales , Diferenciación Celular/genética , Células Epiteliales/fisiología , Femenino , Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Embarazo , Transducción de Señal/genéticaRESUMEN
Chronic fatigue syndrome (CFS) is characterized by extreme fatigue and disabling symptoms. Women with CFS often have a high risk of gynaecological problems such as irregular menstruation, endometriosis and pelvic pain and sexual dysfunction. Our previous results have shown that, in pregnant mice, CFS significantly decreased the progestational hormone level in serum, as well as learning and memory, and the function of the hypothalamus-pituitary-gonadal axis. In addition, the F1 generation also suffered from congenital hypothyroidism. At present, there has been no report about placenta formation and embryonic development in pregnant mice with CFS. The aim of the present study was to investigate the influence of CFS on the morphology, oxidative stress and Wnt/ß-catenin signalling pathway during placenta formation. In this study, we found that CFS decreased the number of implantation sites for blastocysts, and increased the number of absorbed, stillborn and malformed fetuses. The morphology and structure of the placenta were abnormal in pregnant mice with CFS. Further study found that the oxidative stress in serum, uterus and placenta was increased in pregnant mice with CFS, while the levels of antioxidase were decreased. CFS also inhibited the Wnt/ß-catenin signalling pathway in the placenta. These results suggested that inhibition of the Wnt/ß-catenin signalling pathway and enhanced oxidative stress play an important role in abnormal placentation in pregnant mice with CFS.
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Síndrome de Fatiga Crónica , beta Catenina , Animales , Femenino , Ratones , Estrés Oxidativo , Placenta , Embarazo , Vía de Señalización Wnt , beta Catenina/metabolismoRESUMEN
The human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways mounted against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages (M1), interferon gamma (IFNγ) CD4 T cells, innate lymphoid cells 1 (NKp44+ ILC1), CD8 T cells (Effector-Memory4, EM4), invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For intracellular protozoa, the tolerable host immunological pathway is TH1-like immunity involving macrophages (M2), interferon gamma (IFNγ)/TGFß CD4 T cells, innate lymphoid cells 1 (NKp44- ILC1), CD8 T cells (EM3), invariant natural killer T 1 (iNKT1) cells, and immunoglobulin A1 (IgA1) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils (N1), interleukin-22 CD4 T cells, innate lymphoid cells 3 (NCR+ ILC3), iNKT17 cells, and IgG2 B cells. For free-living extracellular protozoa, the tolerable host immunological pathway is TH17 immunity involving neutrophils (N2), interleukin-17 CD4 T cells, innate lymphoid cells 3 (NCR- ILC3), iNKT17 cells, and IgA2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), interleukin-5/interleukin-4 CD4 T cells, interleukin-25 induced inflammatory innate lymphoid cells 2 (iILC2), tryptase-positive mast cells (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, chymase- and tryptase-positive mast cells (MCct), interleukin-3/interleukin-4 CD4 T cells, interleukin-33 induced nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, interleukin-9 mast cells (MMC9), thymic stromal lymphopoietin induced innate lymphoid cells 2, interleukin-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. In addition, specific transcription factors important for specific immune responses were listed. This JAK/STAT signaling is key to controlling or inducing different immunological pathways. In sum, Tfh is related to STAT5ß, and BCL6 expression. Treg is related to STAT5α, STAT5ß, and FOXP3. TH1 immunity is related to STAT1α, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1α, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3α and AHR. THαß immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, and ISGF. TH1-like immunity is related to STAT1α, STAT4, STAT5α, and STAT5ß. TH9 immunity is related to STAT6, STAT5α, STAT5ß, and PU.1. TH17 immunity is related to STAT3α, STAT5α, STAT5ß, and RORG. TH3 immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, STAT5α, STAT5ß, and ISGF. This categorization provides a complete framework of immunological pathways against four types of parasitic infections. This framework as well as relevant JAK/STAT signaling can provide useful knowledge to control allergic hypersensitivities and parasitic infections via development of vaccines or drugs in the near future.
Asunto(s)
Citocinas/inmunología , Inmunidad Innata , Leucocitos/inmunología , Enfermedades Parasitarias/inmunología , HumanosRESUMEN
BACKGROUND: Current evidence on the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance is inconsistent. Therefore, the aim is to explore the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in the U.S. noninstitutionalized population of older adults. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Intakes of ω-3 and ω-6 fatty acids were obtained through two 24-h dietary recalls and were adjusted by energy. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning sub-test, Animal Fluency test and Digit Symbol Substitution Test (DSST). For each cognitive test, people who scored lower than the lowest quartile in each age group were defined as having low cognitive performance. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance. RESULTS: A total of 2496 participants aged 60 years or older were included. In the full-adjusted model, the odds ratios (ORs) with 95% confidence interval (CI) of CERAD test score, Animal Fluency test score and DSST test score were 0.58 (0.38-0.88), 0.68 (0.47-0.99) and 0.59 (0.37-0.92) for the highest versus lowest tertile of dietary ω-3 fatty acids intake, respectively; the ORs with 95% CI of CERAD test score, Animal Fluency test score and DSST test score were 0.48 (0.31-0.75), 0.60 (0.40-0.92) and 0.50 (0.34-0.75) for the highest versus lowest tertile of dietary ω-6 fatty acids intake, respectively. The association between ω-6: ω-3 ratio and cognitive performance was not statistically significant in three tests. In dose-response relationship analysis, L-shaped associations were apparent for ω-3 and ω-6 fatty acids intake with CERAD test score, Animal Fluency test score and DSST test score. CONCLUSIONS: Dietary ω-3 and ω-6 fatty acids intake might be inversely associated with low cognitive performance.
Asunto(s)
Disfunción Cognitiva/epidemiología , Dieta/métodos , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Encuestas Epidemiológicas/métodos , Anciano , Anciano de 80 o más Años , Cognición , Estudios Transversales , Dieta/efectos adversos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Femenino , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
The study used the data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 to analyse the relationship of dietary vitamin B1, B2, niacin, B6, B12 and dietary folate equivalent (DEF) intakes with metabolic syndrome. In the multivariate-adjusted model 2, compared with the lowest quartile of dietary intake, the odd ratios (ORs;95% confidence intervals (CIs)) were 0.73 (0.59-0.91), 0.76 (0.61-0.95), 0.76 (0.59-0.98) and 0.77 (0.62-0.96) for the highest quartile of vitamin B1, niacin, B6 and DFE, respectively. The ORs (95%CIs) for the third and the highest quartile of vitamin B2 were 0.78 (0.61-0.99) and 0.62 (0.47-0.83). A linear inverse relationship was found between dietary vitamin B1, niacin, B6, DFE and metabolic syndrome, and a non-linear inverse relationship was found between dietary vitamin B2 and metabolic syndrome. Our results suggested that higher intake of vitamin B1, B2, niacin, B6 and DFE were all associated with reduced risk of metabolic syndrome.
Asunto(s)
Ácido Fólico/administración & dosificación , Síndrome Metabólico/prevención & control , Niacina/administración & dosificación , Riboflavina/administración & dosificación , Tiamina/administración & dosificación , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Adulto , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas Nutricionales , Fenómenos Fisiológicos de la Nutrición , Oportunidad Relativa , Riesgo , Adulto JovenRESUMEN
Sensitive and selective detection of harmful gas is an important task in environmental monitoring. In this work, a gas sensor based on cataluminescence (CTL) for detection of acetaldehyde was designed by using nano-NiO as the sensing material. The sensor shows sensitive response to acetaldehyde at a relatively low working temperature of 200 °C. The linear range of CTL intensity versus acetaldehyde concentration is 0.02-2.5 mg/L, with a limit of detection of 0.006 mg/L at a signal-to-noise ratio of three. Mechanism study shows that electronically excited CO2 is the excited intermediate for CTL emission during the catalytic oxidation of acetaldehyde on the NiO surface. The proposed sensor has promising application in monitoring acetaldehyde in residential buildings and in the workplace.