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1.
Mod Pathol ; 37(1): 100354, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37844870

RESUMEN

Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Hemangioma Esclerosante Pulmonar , Humanos , Fosfatidilinositol 3-Quinasas/genética , Hemangioma Esclerosante Pulmonar/genética , Hemangioma Esclerosante Pulmonar/patología , Genómica , Perfilación de la Expresión Génica , ARN
2.
J Exp Bot ; 75(1): 152-167, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37769205

RESUMEN

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3-5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution.


Asunto(s)
Proteínas de Plantas , Plantas , Secuencia de Aminoácidos , Plantas/metabolismo , Proteínas de Plantas/metabolismo , Glicoproteínas/metabolismo , Pared Celular/metabolismo , Prolina/metabolismo
3.
Methods ; 213: 26-32, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36924866

RESUMEN

Amblyopia is an abnormal visual processing-induced developmental disorder of the central nervous system that affects static and dynamic vision, as well as binocular visual function. Currently, changes in static vision in one eye are the gold standard for amblyopia diagnosis. However, there have been few comprehensive analyses of changes in dynamic vision, especially eye movement, among children with amblyopia. Here, we proposed an optimization scheme involving a video eye tracker combined with an "artificial eye" for comprehensive examination of eye movement in children with amblyopia; we sought to improve the diagnostic criteria for amblyopia and provide theoretical support for practical treatment. The resulting eye movement data were used to construct a deep learning approach for diagnostic and predictive applications. Through efforts to manage the uncooperativeness of children with strabismus who could not complete the eye movement assessment, this study quantitatively and objectively assessed the clinical implications of eye movement characteristics in children with amblyopia. Our results indicated that an amblyopic eye is always in a state of adjustment, and thus is not "lazy." Additionally, we found that the eye movement parameters of amblyopic eyes and eyes with normal vision are significantly different. Finally, we identified eye movement parameters that can be used to supplement and optimize the diagnostic criteria for amblyopia, providing a diagnostic basis for evaluation of binocular visual function.


Asunto(s)
Ambliopía , Estrabismo , Niño , Humanos , Ambliopía/diagnóstico , Ambliopía/terapia , Movimientos Oculares , Estrabismo/diagnóstico , Visión Binocular/fisiología , Sistema Nervioso Central
4.
Cancer Sci ; 114(7): 2860-2870, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37094904

RESUMEN

High-risk neuroblastoma (HR-NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5-year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR-NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR-NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box-binding protein-associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR-NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN-amplified, high-risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN-amplified NB cells compared with MYCN-non-amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN-amplified NB. RNA-seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell-cycle regulator, cell-cycle-dependent kinase 1 (CDK1), resulting in cell-cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN-amplified HR-NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR-NB patients by blocking cell-cycle progression and the proliferation of tumor cells.


Asunto(s)
Neuroblastoma , Humanos , Animales , Ratones , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/patología , Proliferación Celular/genética , División Celular , Fase G2 , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica
5.
Biol Proced Online ; 25(1): 11, 2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170211

RESUMEN

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. METHODS: The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. RESULTS: Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. CONCLUSIONS: A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

6.
Mod Pathol ; 36(2): 100008, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36853782

RESUMEN

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.


Asunto(s)
Timoma , Neoplasias del Timo , Factores de Transcripción TFIII , Factores de Transcripción TFII , Humanos , Timoma/genética , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias del Timo/genética , Mutación , Factores de Transcripción TFII/genética
7.
Mod Pathol ; 36(3): 100047, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36788096

RESUMEN

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/genética , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento
8.
Sensors (Basel) ; 23(23)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38067836

RESUMEN

With the development of 5G communication systems, it is a hot topic to embed integrated sensing and communication (ISAC) based on the existing 5G base station by sharing the hardware and the same frequency spectrum. In this paper, we propose a dual pulse repeated frequency (dual-PRF) waveform design of time-division ISAC (TD-ISAC) based on a 5G new radio (NR) communication system using downlink communication slots. We choose time-division mode to design waveform to avoid the interference between sensing and communication. Embedding sensing functions in a 5G NR system, we design a dual-PRF sensing slot to satisfy the constraints of common channel and uplink communication. Considering two uplink modes, namely flexible and fixed, we design two dual-PRF waveforms and illustrate the sensing theory performance of the designed waveform by the ambiguity function. Then, we exploit the designed waveform to the vehicle parameter estimation. To verify that the designed waveform has good adaptability to different signal processing methods, we realize the parameter estimation by two types of methods: the discrete Fourier transformation-based method and the compressed sensing-based method. At last, we verify the effectiveness of the designed waveform system by simulation experiments and real traffic scenarios.

9.
Sensors (Basel) ; 23(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37571638

RESUMEN

The design of an integrated sensing and communication (ISAC) waveform compatible with the 5G new radio (NR) system is crucial in enabling ISAC by utilizing the hardware of existing base stations (BSs). In this paper, we design an inner-frame time division multiplexed sensing waveform in the frame structure of 5G NR to achieve ISAC. The designed waveform is computed by the simulated annealing algorithm on an optimization cost function of a constrained combination of the peak-to-sidelobe ratio (PSLR) and the integrated sidelobe ratio (ISLR) of the velocity ambiguity function. Specifically, the constraints are the 5G communication protocol and 5G NR frame structure. In addition, we conducted corresponding signal detection and estimation methods to illustrate the performance of the sensing waveform. Both theoretical analysis and simulation experiments show that the designed waveform can effectively achieve target detection and parameter estimation under low sensing cost conditions.

10.
Antimicrob Agents Chemother ; 66(12): e0053122, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36448833

RESUMEN

Delamanid (DLM) and pretomanid (PTM) are recent additions to the anti-tuberculosis (TB) drug armamentarium, and they offer more effective options for drug-resistant TB treatment. In particular, DLM is included in Group C, which is recommended for use in longer multidrug-resistant (MDR)-TB regimens. Previous studies have shown that resistance to DLM/PTM is caused by mutations in the ddn, fgd1, fbiA, fbiB, fbiC, and fbiD genes, which are related to the F420-dependent bioactivation pathway. Herein, we conduct in vitro selection of DLM-resistant strains using clinical Mycobacterium tuberculosis (MTB) isolates with various drug resistance profiles. The spontaneous resistance frequency of drug-susceptible (DS) MTB (1.14 × 10-6 to 1.04 × 10-4) to DLM was similar to that of H37Rv (8.88 × 10-6 to 9.96 × 10-6) but higher than those of multidrug-resistant MTB (2.03 × 10-7 to 3.18 × 10-6) and extensively drug-resistant (XDR) MTB (4.67 × 10-8 to 3.60 × 10-6). Of the 100 independently selected DLM-resistant MTB mutants, 65% harbored mutations in genes associated with either DLM prodrug activation (ddn, 39.73%; fgd1, 16.44%) or the F420 biosynthetic pathway (fbiA, 16.44%; fbiB, 5.48%; fbiC, 21.92%). Of the 45 mutations we identified, 38 were not previously reported. A structure analysis revealed that several point mutations affected the ligand binding or structural stability of enzymes related to DLM resistance, which would block the enzyme activity required for prodrug activation. Our results elucidate the in vitro spontaneous DLM-resistance patterns of different clinical strains, which could improve the understanding of the causes of DLM resistance in clinical strains and of the effects on drug resistance of different mutations in genes that are related to the DLM activation pathway.


Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Profármacos , Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Profármacos/farmacología
11.
J Org Chem ; 87(2): 1477-1484, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-35014269

RESUMEN

Reported herein is a photoredox-catalyzed amination of o-hydroxyarylenaminones with tert-butyl ((perfluoropyridin-4-yl)oxy)carbamate, a versatile amidyl-radical precursor developed in our laboratory. This work establishes a new cascade pathway for the assembly of a range of 3-aminochromones under mild conditions. Downstream transformations of the obtained 3-aminochromones to construct diverse amino pyrimidines greatly broaden the applications of this photocatalyzed protocol.


Asunto(s)
Cromonas , Aminación , Catálisis
12.
Neurosurg Rev ; 45(3): 1847-1859, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35015193

RESUMEN

Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the validity of cerebrospinal fluid (CSF) data in predicting shunt-dependent hydrocephalus (SDHC) in patients with hemorrhagic stroke. PubMed, CENTRAL, and Embase databases were searched for relevant studies published through July 31, 2021. The 16 studies with 1505 patient included those in which CSF data predicted risk for SDHC and reports on CSF parameters in patients in whom SDHC or hydrocephalus that was not shunt-dependent developed following hemorrhagic stroke. We appraised the study quality using Newcastle-Ottawa Scale and conducted a meta-analysis of the pooled estimates of the CSF predictors. The meta-analysis revealed three significant CSF predictors for shunt dependency, i.e., higher protein levels (mean difference [MD] = 32.09 mg/dL, 95% confidence interval [CI] = 25.48-38.70, I2 = 0%), higher levels of transforming growth factor ß1 (TGF-ß1; MD = 0.52 ng/mL, 95% CI = 0.42-0.62, I2 = 0%), and higher ferritin levels (MD = 108.87 µg/dL, 95% CI = 56.68-161.16, I2 = 36%). The red blood cell count, lactate level, and glucose level in CSF were not significant in predicting SDHC in patients with hemorrhagic stroke. Therefore, higher protein, TGF-ß1, and ferritin levels in CSF are significant predictors for SDHC in patients with hemorrhagic stroke. Measuring these CSF parameters would help in the early recognition of SDHC risk in clinical care.


Asunto(s)
Accidente Cerebrovascular Hemorrágico , Hidrocefalia , Hemorragia Subaracnoidea , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Ferritinas , Humanos , Hidrocefalia/líquido cefalorraquídeo , Hidrocefalia/etiología , Hidrocefalia/cirugía , Hemorragia Subaracnoidea/complicaciones , Factor de Crecimiento Transformador beta1
13.
Microsc Microanal ; : 1-12, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35466906

RESUMEN

A real-time image reconstruction method for scanning transmission electron microscopy (STEM) is proposed. With an algorithm requiring only the center of mass of the diffraction pattern at one probe position at a time, it is able to update the resulting image each time a new probe position is visited without storing any intermediate diffraction patterns. The results show clear features at high spatial frequency, such as atomic column positions. It is also demonstrated that some common post-processing methods, such as band-pass filtering, can be directly integrated in the real-time processing flow. Compared with other reconstruction methods, the proposed method produces high-quality reconstructions with good noise robustness at extremely low memory and computational requirements. An efficient, interactive open source implementation of the concept is further presented, which is compatible with frame-based, as well as event-based camera/file types. This method provides the attractive feature of immediate feedback that microscope operators have become used to, for example, conventional high-angle annular dark field STEM imaging, allowing for rapid decision-making and fine-tuning to obtain the best possible images for beam-sensitive samples at the lowest possible dose.

14.
Microsc Microanal ; : 1-9, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36117265

RESUMEN

A decade ago, a statistics-based method was introduced to count the number of atoms from annular dark-field scanning transmission electron microscopy (ADF STEM) images. In the past years, this method was successfully applied to nanocrystals of arbitrary shape, size, and composition (and its high accuracy and precision has been demonstrated). However, the counting results obtained from this statistical framework are so far presented without a visualization of the actual uncertainty about this estimate. In this paper, we present three approaches that can be used to represent counting results together with their statistical error, and discuss which approach is most suited for further use based on simulations and an experimental ADF STEM image.

15.
Angew Chem Int Ed Engl ; 61(45): e202211035, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36111983

RESUMEN

An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.


Asunto(s)
Alquenos , Fluorocarburos , Catálisis , Acetona
16.
J Proteome Res ; 20(9): 4303-4317, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34355917

RESUMEN

Alzheimer's disease (AD) is the most common cause of dementia, accounting for an estimated 60-80% of cases, and is the sixth-leading cause of death in the United States. While considerable advancements have been made in the clinical care of AD, it remains a complicated disorder that can be difficult to identify definitively in its earliest stages. Recently, mass spectrometry (MS)-based metabolomics has shown significant potential for elucidation of disease mechanisms and identification of therapeutic targets as well diagnostic and prognostic markers that may be useful in resolving some of the difficulties affecting clinical AD studies, such as effective stratification. In this study, complementary gas chromatography- and liquid chromatography-MS platforms were used to detect and monitor 2080 metabolites and features in 48 postmortem tissue samples harvested from the superior frontal gyrus of male and female subjects. Samples were taken from four groups: 12 normal control (NC) patients, 12 cognitively normal subjects characterized as high pathology controls (HPC), 12 subjects with nonspecific mild cognitive impairment (MCI), and 12 subjects with AD. Multivariate statistics informed the construction and cross-validation (p < 0.01) of partial least squares-discriminant analysis (PLS-DA) models defined by a nine-metabolite panel of disease markers (lauric acid, stearic acid, myristic acid, palmitic acid, palmitoleic acid, and four unidentified mass spectral features). Receiver operating characteristic analysis showed high predictive accuracy of the resulting PLS-DA models for discrimination of NC (97%), HPC (92%), MCI (∼96%), and AD (∼96%) groups. Pathway analysis revealed significant disturbances in lysine degradation, fatty acid metabolism, and the degradation of branched-chain amino acids. Network analysis showed significant enrichment of 11 enzymes, predominantly within the mitochondria. The results expand basic knowledge of the metabolome related to AD and reveal pathways that can be targeted therapeutically. This study also provides a promising basis for the development of larger multisite projects to validate these candidate markers in readily available biospecimens such as blood to enable the effective screening, rapid diagnosis, accurate surveillance, and therapeutic monitoring of AD. All raw mass spectrometry data have been deposited to MassIVE (data set identifier MSV000087165).


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Neocórtex , Enfermedad de Alzheimer/diagnóstico , Biomarcadores , Disfunción Cognitiva/diagnóstico , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metabolómica
17.
Molecules ; 26(19)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34641425

RESUMEN

Edible oils are valuable sources of nutrients, and their classification is necessary to ensure high quality, which is essential to food safety. This study reports the establishment of a rapid and straightforward SALDI-TOF MS platform used to detect triacylglycerol (TAG) in various edible oils. Silver nanoplates (AgNPts) were used to optimize the SALDI samples for high sensitivity and reproducibility of TAG signals. TAG fingerprints were combined with multivariate statistics to identify the critical features of edible oil discrimination. Eleven various edible oils were discriminated using principal component analysis (PCA). The results suggested the creation of a robust platform that can examine food adulteration and food fraud, potentially ensuring high-quality foods and agricultural products.


Asunto(s)
Grano Comestible/química , Nanopartículas del Metal/química , Aceites de Plantas/análisis , Aceites de Plantas/clasificación , Plata/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Triglicéridos/análisis , Análisis de los Alimentos/métodos , Análisis de Componente Principal
18.
Genes Chromosomes Cancer ; 58(11): 809-814, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31334571

RESUMEN

NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis.


Asunto(s)
Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Tumor Rabdoide/genética , Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Carcinoma/genética , Proteínas de Ciclo Celular/genética , Femenino , Fusión Génica/genética , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Mandíbula , Proteínas de Fusión Oncogénica/genética , Sarcoma/genética , Análisis de Secuencia de ARN , Factores de Transcripción/genética , Adulto Joven , Dedos de Zinc/genética
19.
Phys Rev Lett ; 123(24): 247601, 2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-31922871

RESUMEN

Oxygen interstitials and vacancies play a key role in modulating the microstructure and properties of nonstoichiometric oxide systems, such as those used for superconductors and multiferroics. Key to understanding the tuning mechanisms resulting from oxygen doping is a knowledge of the precise positions of these lattice defects, and of the interaction both between these defects and with many order parameters. Here, we report how such information can, for the first time, be obtained from a sample of LuFe_{2}O_{4.22} using a range of techniques including advanced electron microscopy, atomic-resolution spectroscopy, and density functional theory calculations. The results provide quantitative atomic details of the crystal unit cell, together with a description of the ferroelastic, ferroelectric, and ferromagnetic order parameters. We elucidate also the interaction between these order parameters and the positions of the oxygen interstitials in the oxygen-enriched sample. The comprehensive analysis of oxygen interstitial ordering provides insights into understanding the coupling among different degrees of freedom in rare earth ferrites and demonstrates that oxygen content regulation is a powerful tool for tuning the microstructure and properties for this class of quantum material.

20.
J Clin Lab Anal ; 33(3): e22716, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30461054

RESUMEN

BACKGROUND: In this study, we aimed to optimize the condition of propidium monoazide (PMA) treatment for direct detection of Mycobacterium tuberculosis (MTB) from clinical specimens. METHODS: The light exposure time, dark incubation time, bacterial load, and PMA concentration were varied to determine the optimal condition of PMA treatment. RESULTS: Overall, the maximum ΔCq value was observed in the group receiving a light exposure time of 20 minutes, which was significantly higher than the others (P < 0.05). The prolongation of dark incubation time seemed more likely to result in greater ΔCq value, and the ΔCq values were 2.0, 4.1, 6.5, 10.1, and 12.7 cycles under dark incubation time of 10, 20, 40, 60, and 120 minutes, respectively. Alternatively, the 4+ samples exhibited favorable detection results at the application of 104 -fold dilution by PMA assay with Cq values higher than 35 cycles. Further evaluation revealed that the PMA assay showed an accordance rate of 98.0% (98/100) among clinical sputa. CONCLUSIONS: we develop an acceptable method to directly identify the live bacteria from sputum samples. Our data demonstrate that the dark incubation plays a crucial role in the efficacy of PMA treatment for MTB.


Asunto(s)
Técnicas Bacteriológicas/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/fisiología , Esputo/microbiología , Carga Bacteriana , Humanos , Viabilidad Microbiana , Tuberculosis/microbiología
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