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1.
Appl Opt ; 63(12): 3123-3129, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38856456

RESUMEN

A highly sensitive optical fiber Fabry-Perot interferometer (FPI) for strain measurement with temperature compensation is proposed. Instead of using another actual reference interferometer, a virtual FPI is constructed to superpose with the sensing FPI to form the Vernier effect. The fundamental and the first-order harmonic Vernier effect are generated to increase the sensitivity by adjusting the parameter of the virtual FPI. In order to separate the strain from the environment temperature, an FBG is cascaded to distinguish the applied temperature. Experimental results demonstrate that, with the help of the fundamental Vernier effect, the sensitivity and temperature of the FPI increases from 1.05 pm/°C to 10.63 pm/°C in the temperature range of 40-120°C, and the sensitivity of strain increases from 2.635 pm/µÎµ to 33.11 pm/µÎµ in the strain range of 0-400 µÎµ. In order to access the tracking points more easily and further enhance the sensitivities, the first-order harmonic Vernier effect is generated by modifying the virtual FPI. Results show that the temperature and strain sensitivities are 21.25 pm/°C and 62.25 pm/µÎµ, respectively. In addition, with the help of the FBG, the strain can be separated from the temperature by solving the cross-sensitivity matrix.

2.
Sensors (Basel) ; 24(2)2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38276375

RESUMEN

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.


Asunto(s)
Técnicas Biosensibles , Glucemia , Humanos , Glucosa Oxidasa/química , Técnicas Biosensibles/métodos , Glucosa/química , Fibras Ópticas
3.
J Environ Manage ; 353: 120202, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38308984

RESUMEN

Surface water plays a crucial role in the ecological environment and societal development. Remote sensing detection serves as a significant approach to understand the temporal and spatial change in surface water series (SWS) and to directly construct long-term SWS. Limited by various factors such as cloud, cloud shadow, and problematic satellite sensor monitoring, the existent surface water mapping datasets might be short and incomplete due to losing raw information on certain dates. Improved algorithms are desired to increase the completeness and quality of SWS datasets. The present study proposes an automated framework to detect SWS, based on the Google Earth Engine and Landsat satellite imagery. This framework incorporates implementing a raw image filtering algorithm to increase available images, thereby expanding the completeness. It improves OTSU thresholding by replacing anomaly thresholds with the median value, thus enhancing the accuracy of SWS datasets. Gaps caused by Landsat7 ETM + SLC-off are respired with the random forest algorithm and morphological operations. The results show that this novel framework effectively expands the long-term series of SWS for three surface water bodies with distinct geomorphological patterns. The evaluation of confusion matrices suggests the good performance of extracting surface water, with the overall accuracy ranging from 0.96 to 0.97, and user's accuracy between 0.96 and 0.98, producer's accuracy ranging from 0.83 to 0.89, and Matthews correlation coefficient ranging from 0.87 to 0.9 for several spectral water indices (NDWI, MNDWI, ANNDWI, and AWEI). Compared with the Global Reservoirs Surface Area Dynamics (GRSAD) dataset, our constructed datasets promote greater completeness of SWS datasets by 27.01%-91.89% for the selected water bodies. The proposed framework for detecting SWS shows good potential in enlarging and completing long-term global-scale SWS datasets, capable of supporting assessments of surface-water-related environmental management and disaster prevention.


Asunto(s)
Monitoreo del Ambiente , Agua , Monitoreo del Ambiente/métodos , Imágenes Satelitales , Ambiente , Algoritmos
4.
Water Sci Technol ; 89(1): 199-211, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38214995

RESUMEN

Improving the nitrogen and phosphorus removal rates and efficiently controlling membrane fouling are the keys to fully exploiting the applicability of anaerobic membrane bioreactor (AnMBR) process in high-concentration wastewater treatment. To that purpose, an integrated reactor composed of an anaerobic ceramic membrane bioreactor and N anaerobic fluidized bed (AnCMBR-AFB) was built and pollutant removal efficiency, nitrogen and phosphorus recovery characteristics, and membrane pollution features of this integrated reactor were investigated. The results revealed that the integrated reactor had good pollutant removal efficiency, with turbidity, chromaticity, and UV254 average values of the effluent being 0.470 NTU, 0.011 A, and 0.057 cm-1, respectively, and the average CODCr removal rate was 80%. The nitrogen and phosphorus recoveries were significantly higher than the nitrogen and phosphorus removal rates of conventional AnMBR at 23.20 ± 1.17% and 43.34 ± 1.54%, respectively. Microscopic analysis revealed the formation of magnesium ammonium phosphate (MAP) crystals on the carrier's surface, and friction between the carrier and the membrane surface could delay membrane fouling while allowing the contaminated membrane surface to retain significant roughness. Membrane fouling was mostly brought on by amides and saturated hydrocarbons, and inorganic metal ions also played a role to some extent.


Asunto(s)
Contaminantes Ambientales , Aguas Residuales , Eliminación de Residuos Líquidos/métodos , Nitrógeno , Fósforo , Anaerobiosis , Reactores Biológicos , Membranas Artificiales , Aguas del Alcantarillado
5.
Apoptosis ; 28(9-10): 1452-1468, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37410216

RESUMEN

Mitochondrial dysfunction and necroptosis are closely associated, and play vital roles in the medical strategy of multiple cardiovascular diseases. However, their implications in intracranial aneurysms (IAs) remain unclear. In this study, we aimed to explore whether mitochondrial dysfunction and necroptosis could be identified as valuable starting points for predictive, preventive, and personalized medicine for IAs. The transcriptional profiles of 75 IAs and 37 control samples were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene co-expression network analysis, and least absolute shrinkage and selection operator (LASSO) regression were used to screen key genes. The ssGSEA algorithm was performed to establish phenotype scores. The correlation between mitochondrial dysfunction and necroptosis was evaluated using functional enrichment crossover, phenotype score correlation, immune infiltration, and interaction network construction. The IA diagnostic values of key genes were identified using machine learning. Finally, we performed the single-cell sequencing (scRNA-seq) analysis to explore mitochondrial dysfunction and necroptosis at the cellular level. In total, 42 IA-mitochondrial DEGs and 15 IA-necroptosis DEGs were identified. Screening revealed seven  key genes invovled in mitochondrial dysfunction (KMO, HADH, BAX, AADAT, SDSL, PYCR1, and MAOA) and five genes involved in necroptosis (IL1B, CAMK2G, STAT1, NLRP3, and BAX). Machine learning confirmed the high diagnostic value of these key genes for IA. The IA samples showed  higher expression of mitochondrial dysfunction and necroptosis. Mitochondrial dysfunction and necroptosis exhibited a close association. Furthermore, scRNA-seq indicated that mitochondrial dysfunction and necroptosis were preferentially up-regulated in monocytes/macrophages and vascular smooth muscle cells (VSMCs) within IA lesions. In conclusion, mitochondria-induced necroptosis was involved in IA formation, and was mainly up-regulated in monocytes/macrophages and VSMCs within IA lesions. Mitochondria-induced necroptosis may be a novel potential target for diagnosis, prevention, and treatment of IA.


Asunto(s)
Aneurisma Intracraneal , Medicina de Precisión , Humanos , Aneurisma Intracraneal/genética , Necroptosis/genética , Proteína X Asociada a bcl-2 , Apoptosis/genética
6.
Brief Bioinform ; 22(3)2021 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-32591779

RESUMEN

Genome-wide association studies (GWAS) have been widely used for identifying potential risk variants in various diseases. A statistically meaningful GWAS typically requires a large sample size to detect disease-associated single nucleotide polymorphisms (SNPs). However, a single institution usually only possesses a limited number of samples. Therefore, cross-institutional partnerships are required to increase sample size and statistical power. However, cross-institutional partnerships offer significant challenges, a major one being data privacy. For example, the privacy awareness of people, the impact of data privacy leakages and the privacy-related risks are becoming increasingly important, while there is no de-identification standard available to safeguard genomic data sharing. In this paper, we introduce a novel privacy-preserving federated GWAS framework (iPRIVATES). Equipped with privacy-preserving federated analysis, iPRIVATES enables multiple institutions to jointly perform GWAS analysis without leaking patient-level genotyping data. Only aggregated local statistics are exchanged within the study network. In addition, we evaluate the performance of iPRIVATES through both simulated data and a real-world application for identifying potential risk variants in ankylosing spondylitis (AS). The experimental results showed that the strongest signal of AS-associated SNPs reside mostly around the human leukocyte antigen (HLA) regions. The proposed iPRIVATES framework achieved equivalent results as traditional centralized implementation, demonstrating its great potential in driving collaborative genomic research for different diseases while preserving data privacy.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Privacidad , Espondilitis Anquilosante/genética , Genotipo , Humanos
7.
Opt Express ; 31(16): 25372-25384, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710426

RESUMEN

In this article, highly sensitive voltage, thermal and magnetic field fiber sensors were obtained in magnetic nanoparticles-doped E7 liquid crystals filled into photonic crystal fibers (PLCF). The voltage and temperature sensitivity reached at 12.598 nm/V and -3.874 nm/°C, respectively. The minimum voltage response time is 48.2 ms. The phase transition temperature Tc of liquid crystal with magnetic dopant was reduced from 60 °C to 46 °C. The magnetic field sensor based on magnetic nanoparticles-doped PLCF were obtained with sensitivity of 118.2 pm/mT from 400 to 460 mT.

8.
Inorg Chem ; 62(30): 12001-12008, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37452746

RESUMEN

A europium(III) metal-organic framework (MOF), namely, {[[(CH3)2NH2]3Eu2(DTTP-2OH)2(HCOO)(H2O)]·4H2O}n (Eu-MOF, H4DTTP-2OH = 2',5'-dihydroxy-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid) has been assembled through solvothermal method. The Eu-MOF is a three-dimensional (3D) (4,4,8)-connected topological framework with binuclear Eu(III) clusters as secondary building units, in which a richly ordered hydrogen bonding network formed among the free H2O molecules, dimethylamine cations, and phenolic hydroxyl groups provides a potential pathway for proton conduction. The proton conductivity reaches the category of superionic conductors (σ > 10-4 S cm-1) at room temperature with a maximum conductivity of 1.91 × 10-3 S cm-1 at 60 °C and 98% RH. Moreover, it also can be used as a fluorescence sensor in aqueous solution with detection limits of 0.14 µM for tetracycline, 0.13 µM for oxytetracycline and 0.11 µM for doxycycline. These results pave new methods for constructing MOFs with high proton conductivity and responsive fluorescence.

9.
J Transl Med ; 20(1): 80, 2022 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-35123484

RESUMEN

BACKGROUND: Long noncoding RNA NEAT1 has been implicated in glioma progression. However, the effect of NEAT1 on glycolysis of glioma cell and the potential mechanism remain unclear. METHODS: In vitro experiments, including CCK-8, colony formation, ECAR, and lactate detection assays were performed to evaluate the effect of NEAT1 on proliferation and glycolysis of glioma cell. RNA pulldown and RIP assays were performed to identify the interaction between NEAT1 and PGK1. Truncated mutation of NEAT1 and PGK1 was used to confirm the specific interactive domains between NEAT1 and PGK1. Animal studies were performed to analyze the effect of NEAT1/PGK1 on glioma progression. RESULTS: NEAT1 knockdown significantly suppressed the proliferation and glycolysis of glioma cells. NEAT1 could specifically interact with PGK1, which promotes PGK1 stability. Hairpin A of NEAT1 is essential for interaction with M1 domain of PGK1. Depletion of NEAT1 markedly inhibited tumor growth in mice, while PGK1 could reverse this effect. Higher expression of NEAT1 was associated with poor overall survival of GBM patients. CONCLUSIONS: NEAT1 over expression promotes glioma progression through stabilizing PGK1. NEAT1/PGK1 axis is a candidate therapeutic target for glioma treatment.


Asunto(s)
Glioma , ARN Largo no Codificante , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , Ratones , Fosfoglicerato Quinasa/genética , Fosfoglicerato Quinasa/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
10.
J Opt Soc Am A Opt Image Sci Vis ; 39(3): 431-439, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35297426

RESUMEN

A type of Christiansen filter that takes the form of a smooth cylindrical lens of even symmetry is proposed. By varying the shape of the lens, the filter can be made to realize many common filtering responses, including the polynomial function response, the Gaussian function response, and the sinc function response. A systematic design technique based on inverse scattering is established, and a desired, prescribed response can be tailored by properly shaping the lens of the filter. Three prototypical Christiansen filters, namely, a second-order all-real-roots filter, a second-order sinc filter, and a Gaussian filter, are synthesized using the proposed method. A prescribed response at 545 nm with a FWHM of 2 nm is achieved systematically by all of the three Christiansen filters.

11.
BMC Pulm Med ; 22(1): 389, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36303179

RESUMEN

BACKGROUND: Patients with obstructive sleep apnoea (OSA), male sex, obesity, older age or hypertension are prone to hypoxemia during flexible bronchoscopy. This study investigated whether using a high-flow nasal cannula (HFNC) could reduce the incidence of oxygen desaturation during bronchoscopy under deep sedation in patients at risk of hypoxemia. METHODS: A total of 176 patients at risk of hypoxemia who underwent flexible bronchoscopy under deep sedation were randomly assigned to two groups: the HFNC group (humidified oxygen was supplied via a high-flow nasal cannula at a rate of 60 L/min and a concentration of 100%, n = 87) and the facemask group (oxygen was supplied via a tight-fitting facemask at a rate of 6 L/min and a concentration of 100%, n = 89). RESULTS: Oxygen desaturation occurred in 4 (4.6%) patients in the HFNC group and 26 (29.2%) patients in the facemask group (P < 0.001). The facemask group required more jaw thrust manoeuvres than the HFNC group (43[48.3%] vs. 5[5.7%], P < 0.001). 8 patients (9.0%) in the facemask group and none in the HFNC group required bag-mask ventilation (P = 0.012). CONCLUSION: The use of an HFNC can reduce the incidence of oxygen desaturation and the requirement for airway intervention in patients at risk of hypoxemia during flexible bronchoscopy under deep sedation. TRIAL REGISTRATION: www.chiCTR.org.cn Identifier: ChiCTR2100044105. Registered 11/03/2021.


Asunto(s)
Cánula , Ventilación no Invasiva , Humanos , Masculino , Cánula/efectos adversos , Ventilación no Invasiva/efectos adversos , Máscaras/efectos adversos , Broncoscopía/efectos adversos , Incidencia , Hipoxia/etiología , Hipoxia/prevención & control , Oxígeno , Terapia por Inhalación de Oxígeno/efectos adversos
12.
Molecules ; 27(12)2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35745074

RESUMEN

Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 ß-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and ß types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for ß-thalassemia screening.


Asunto(s)
Espectrometría de Masa por Ionización de Electrospray , Talasemia beta , Hemoglobinas , Humanos , Iones , Proyectos Piloto , Espectrometría de Masa por Ionización de Electrospray/métodos , Talasemia beta/diagnóstico
13.
Rev Endocr Metab Disord ; 22(2): 407-420, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33245468

RESUMEN

Gestational diabetes mellitus (GDM) characterized by hyperglycemia during pregnancy is a risk factor for various maternal and fetal complications. The key pathophysiological mechanisms underlying its development have not been elucidated, largely due to the lack of a model that accurately simulates the major clinical and pathological features of human GDM. In this review, we discuss the refined criteria for an ideal animal model of GDM, focusing on the key clinical and pathophysiological characteristics of human GDM. We provide a comprehensive overview of different models and currently used species for GDM research. In general, insulin insufficiency consequent to pancreatic ß-cell death represents the current leading strategy to mimic human GDM-like hyperglycemia in animals. Nonetheless, these models have a limited capacity to mimic the natural history of GDM, the marked alteration in circulating estrogen/ progestogen, obesity and its related metabolic complications. We discuss emerging evidence of the increased susceptibility to GDM in rodents and large animals with genetic modifications in pregnancy-related hormones. An appraisal of current GDM models suggests that a combination strategy involving dietary stress, pregnancy-related hormones, insulin resistance and metabolic disorders might enable the development of better GDM models and expedite the translation of basic research findings to GDM treatment.


Asunto(s)
Diabetes Gestacional , Hiperglucemia , Resistencia a la Insulina , Células Secretoras de Insulina , Animales , Femenino , Humanos , Insulina , Embarazo
14.
Clin Genet ; 97(1): 25-38, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31432497

RESUMEN

DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II-III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease-free survival [DFS]) in 28 331 CRC patients at stage II-III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68-0.82; P < .001), as well as DFS (HR = 0.67, 95% CI: 0.59-0.75, P < .001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine-based treatment for either OS (HR = 0.84, 95%CI: 0.60-1.17; P = .31) or DFS (HR = 0.83, 95%CI: 0.60-1.15; P = .27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43-0.71; P < .001) and DFS (HR = 0.60, 95% CI: 0.50-0.73; P < .001). Our analysis indicate that dMMR CRC patients at stage II-III had higher OS and DFS than pMMR ones, and fluoropyrimidine-based chemotherapy could improve survival in pMMR patients rather than dMMR ones.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Reparación de la Incompatibilidad de ADN/genética , Pronóstico , Pirimidinas/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Humanos , Estadificación de Neoplasias
15.
Opt Express ; 28(2): 1076-1083, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32121824

RESUMEN

We report on the detailed analyses of mode coupling from fiber core to cladding in excessively tilted fiber gratings (ETFGs). Cladding modes responsible for the typical dual peak pairs in the transmission spectrum of ETFGs are identified with phase matching condition, which suggests two set of dual peak pairs generated from coupling to cladding modes with even and odd azimuthal order. The polarization dependence of those dual peak pairs are also investigated by calculating the coupling coefficients of cladding modes for two orthogonal polarizations. With the calculated coupling coefficients, the measured polarization dependent spectra can be reproduced numerically.

16.
Opt Express ; 28(4): 5179-5188, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32121743

RESUMEN

In this paper, pure silk protein was extracted from Bombyx mori silks and fabricated into a new kind of disordered bio-microfiber structure using electrospinning technology. Coherent random lasing emission with low threshold was achieved in the silk fibroin fibers. The random lasing emission wavelength can be tuned in the range of 33 nm by controlling the pump location with different scattering strengths. Therefore, the bio-microfiber random lasers can be a wide spectral light source when the system is doped with a gain or energy transfer medium with a large fluorescence emission band. Application of the random lasers of the bio-microfibers as a low-coherence light source in speckle-free imaging had also been studied.


Asunto(s)
Fibroínas/química , Rayos Láser , Luz , Animales , Bombyx , Fibroínas/ultraestructura , Procesamiento de Imagen Asistido por Computador , Dispositivos Ópticos
17.
Insect Mol Biol ; 29(1): 19-37, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31265751

RESUMEN

Wolbachia and Spiroplasma are both maternally inherited endosymbionts in arthropods, and they can co-infect the same species. However, how they interact with each other in the same host is not clear. Here we investigate a co-infected Tetranychus truncatus spider mite strain that shares the same genetic background with singly infected and uninfected strains to detect the impacts of the two symbionts on their host. We found that Wolbachia-infected and Spiroplasma-infected mites can suffer significant fitness costs involving decreased fecundity, although with no effect on lifespan or development. Wolbachia induced incomplete cytoplasmic incompatibility in T. truncatus both in singly infected and doubly infected strains, resulting in female killing. In both females and males of the co-infected spider mite strain, Wolbachia density was higher than Spiroplasma density. Transcriptome analysis of female adults showed that the most differentially expressed genes were found between the co-infected strain and both the singly infected Spiroplasma strain and uninfected strain. The Wolbachia strain had the fewest differentially expressed genes compared with the co-infected strain, consistent with the higher density of Wolbachia in the co-infected strain. Wolbachia, therefore, appears to have a competitive advantage in host mites over Spiroplasma and is likely maintained in populations by cytoplasmic incompatibility despite having deleterious fitness effects.


Asunto(s)
Spiroplasma/fisiología , Tetranychidae/microbiología , Wolbachia/fisiología , Animales , Coinfección/microbiología , Femenino , Fertilidad , Perfilación de la Expresión Génica , Masculino , Simbiosis , Tetranychidae/genética , Tetranychidae/metabolismo
18.
BMC Cardiovasc Disord ; 20(1): 27, 2020 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959127

RESUMEN

BACKGROUND: TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD. To date, seven variants within TAB2 were reported associated with CHD, only two of them are nonsense mutations. CASE PRESENTATION: Here we describe a three-generation Chinese family that included five CHD patients with heart valvular defects, such as mitral or tricuspid valves prolapse or regurgitation, and aortic valve stenosis or regurgitation. Our proband was a pregnant woman presenting with mitral, tricuspid, and aortic defects; her first child experienced sudden cardiac death at the age of 2 years. Whole-exome sequencing of the proband revealed a novel nonsense variant in TAB2 (c.C446G, p.S149X), which results in the elimination of the majority of C-terminal amino acids of TAB2, including the critical TAK1-binding domain. The variant was identified in five affected patients but not in the eight unaffected family members using Sanger sequencing and was classified as "pathogenic" according to the latest recommendation on sequence variants laid out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. CONCLUSION: We described a family with CHD caused by a novel TAB2 nonsense mutation. Our study broadens the mutation spectrum of TAB2; to the best of our knowledge, this is the first report of a pathogenic mutation within TAB2 in a Chinese population.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Codón sin Sentido , Genes Dominantes , Cardiopatías Congénitas/genética , Adulto , Pueblo Asiatico/genética , Niño , Preescolar , China , Análisis Mutacional de ADN , Muerte Súbita Cardíaca/etiología , Femenino , Muerte Fetal/etiología , Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/etnología , Herencia , Humanos , Lactante , Masculino , Linaje , Fenotipo , Embarazo , Factores de Riesgo , Secuenciación del Exoma
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(12): 1360-1363, 2020 Dec 10.
Artículo en Zh | MEDLINE | ID: mdl-33306822

RESUMEN

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency. METHODS: Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing. RESULTS: Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality. CONCLUSION: The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.


Asunto(s)
Pruebas Genéticas , Diagnóstico Prenatal , Trastornos Innatos del Ciclo de la Urea , N-Acetiltransferasa de Aminoácidos/genética , China , Femenino , Humanos , Masculino , Mutación/genética , Linaje , Embarazo , Trastornos Innatos del Ciclo de la Urea/diagnóstico , Trastornos Innatos del Ciclo de la Urea/genética , Secuenciación del Exoma
20.
J Cell Physiol ; 234(10): 18653-18665, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31062344

RESUMEN

Acute myocardial infarction (AMI), a severe consequence of coronary atherosclerotic heart disease, is often associated with high mortality and morbidity. Emerging evidence have shown that the inhibition of the extracellular-signal-regulated kinase (ERK) signaling pathway appears to protect against AMI. Epiregulin (EREG) is an autocrine growth factor that is believed to activate the MEK/ERK signaling pathway. Therefore, the aim of the present study was to determine the expression patterns of EREG in AMI and to further study its effects on AMI induced experimentally in rats focusing on angiogenesis and left ventricular remodeling. Microarray-based gene expression profiling of AMI was used to identify differentially expressed genes. To understand the biological significance of EREG and whether it is involved in AMI disease through the ERK1/2 signaling pathway, rats after AMI were treated with small interfering RNA (siRNA) against EREG, an ERK1/2 pathway inhibitor, PD98059, or both of them. The microarray data sets GSE66360 and GSE46395 showed that EREG was robustly induced in AMI. Both siRNA-mediated depletion of EREG and PD98059 treatment were shown to significantly increase infarct size and left ventricular cardiomyocyte loss and enhance left ventricular remodeling. In addition, we also found that the ERK1/2 signaling pathway was inhibited following siRNA-mediated EREG inhibition and PD98059 could enhance the effects of EREG inhibition on AMI. In conclusion, these findings highlight that the silencing of EREG inhibits angiogenesis and promotes left ventricular remodeling by disrupting the ERK1/2 signaling pathway, providing a novel therapeutic target for limiting AMI.


Asunto(s)
Epirregulina/metabolismo , Sistema de Señalización de MAP Quinasas , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica , Remodelación Ventricular , Animales , Diástole/efectos de los fármacos , Electrocardiografía , Flavonoides/farmacología , Pruebas de Función Cardíaca , Hemodinámica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Infarto del Miocardio/patología , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Neovascularización Fisiológica/efectos de los fármacos , ARN Interferente Pequeño/metabolismo , Ratas Wistar , Sístole/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos
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