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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678387

RESUMEN

In the growth and development of multicellular organisms, the immune processes of the immune system and the maintenance of the organism's internal environment, cell communication plays a crucial role. It exerts a significant influence on regulating internal cellular states such as gene expression and cell functionality. Currently, the mainstream methods for studying intercellular communication are focused on exploring the ligand-receptor-transcription factor and ligand-receptor-subunit scales. However, there is relatively limited research on the association between intercellular communication and highly variable genes (HVGs). As some HVGs are closely related to cell communication, accurately identifying these HVGs can enhance the accuracy of constructing cell communication networks. The rapid development of single-cell sequencing (scRNA-seq) and spatial transcriptomics technologies provides a data foundation for exploring the relationship between intercellular communication and HVGs. Therefore, we propose CPPLS-MLP, which can identify HVGs closely related to intercellular communication and further analyze the impact of Multiple Input Multiple Output cellular communication on the differential expression of these HVGs. By comparing with the commonly used method CCPLS for constructing intercellular communication networks, we validated the superior performance of our method in identifying cell-type-specific HVGs and effectively analyzing the influence of neighboring cell types on HVG expression regulation. Source codes for the CPPLS_MLP R, python packages and the related scripts are available at 'CPPLS_MLP Github [https://github.com/wuzhenao/CPPLS-MLP]'.


Asunto(s)
Comunicación Celular , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Transcriptoma , Perfilación de la Expresión Génica/métodos , Humanos , Biología Computacional/métodos , Redes Reguladoras de Genes , Animales , Programas Informáticos , Algoritmos
2.
Circ Res ; 134(2): 165-185, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38166463

RESUMEN

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , Eferocitosis , Factor 6 Asociado a Receptor de TNF/metabolismo , Aterosclerosis/metabolismo , Inflamación/genética , Ratones Noqueados , Fenotipo , Apolipoproteínas E , Factores Reguladores del Interferón/genética , Ratones Endogámicos C57BL
3.
Brief Bioinform ; 24(5)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37643374

RESUMEN

Silencers are noncoding DNA sequence fragments located on the genome that suppress gene expression. The variation of silencers in specific cells is closely related to gene expression and cancer development. Computational approaches that exclusively rely on DNA sequence information for silencer identification fail to account for the cell specificity of silencers, resulting in diminished accuracy. Despite the discovery of several transcription factors and epigenetic modifications associated with silencers on the genome, there is still no definitive biological signal or combination thereof to fully characterize silencers, posing challenges in selecting suitable biological signals for their identification. Therefore, we propose a sophisticated deep learning framework called DeepICSH, which is based on multiple biological data sources. Specifically, DeepICSH leverages a deep convolutional neural network to automatically capture biologically relevant signal combinations strongly associated with silencers, originating from a diverse array of biological signals. Furthermore, the utilization of attention mechanisms facilitates the scoring and visualization of these signal combinations, whereas the employment of skip connections facilitates the fusion of multilevel sequence features and signal combinations, thereby empowering the accurate identification of silencers within specific cells. Extensive experiments on HepG2 and K562 cell line data sets demonstrate that DeepICSH outperforms state-of-the-art methods in silencer identification. Notably, we introduce for the first time a deep learning framework based on multi-omics data for classifying strong and weak silencers, achieving favorable performance. In conclusion, DeepICSH shows great promise for advancing the study and analysis of silencers in complex diseases. The source code is available at https://github.com/lyli1013/DeepICSH.


Asunto(s)
Aprendizaje Profundo , Genoma Humano , Humanos , Línea Celular , Epigénesis Genética , Multiómica
4.
Brief Bioinform ; 25(1)2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-38127088

RESUMEN

With the emergence of spatial transcriptome sequencing (ST-seq), research now heavily relies on the joint analysis of ST-seq and single-cell RNA sequencing (scRNA-seq) data to precisely identify cell spatial composition in tissues. However, common methods for combining these datasets often merge data from multiple cells to generate pseudo-ST data, overlooking topological relationships and failing to represent spatial arrangements accurately. We introduce GTAD, a method utilizing the Graph Attention Network for deconvolution of integrated scRNA-seq and ST-seq data. GTAD effectively captures cell spatial relationships and topological structures within tissues using a graph-based approach, enhancing cell-type identification and our understanding of complex tissue cellular landscapes. By integrating scRNA-seq and ST data into a unified graph structure, GTAD outperforms traditional 'pseudo-ST' methods, providing robust and information-rich results. GTAD performs exceptionally well with synthesized spatial data and accurately identifies cell spatial composition in tissues like the mouse cerebral cortex, cerebellum, developing human heart and pancreatic ductal carcinoma. GTAD holds the potential to enhance our understanding of tissue microenvironments and cellular diversity in complex bio-logical systems. The source code is available at https://github.com/zzhjs/GTAD.


Asunto(s)
Análisis de Expresión Génica de una Sola Célula , Programas Informáticos , Humanos , Animales , Ratones
5.
Hepatology ; 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38231043

RESUMEN

BACKGROUND AND AIMS: Acute liver failure (ALF) is a rare but life-threatening condition, and DILI, particularly acetaminophen toxicity, is the leading cause of ALF. Innate immune mechanisms further perpetuate liver injury, while the role of the adaptive immune system in DILI-related ALF is unclear. APPROACH AND RESULTS: We analyzed liver tissue from 2 independent patient cohorts with ALF and identified hepatic T cell infiltration as a prominent feature in human ALF. CD8 + T cells were characterized by zonation toward necrotic regions and an activated gene expression signature. In murine acetaminophen-induced liver injury, intravital microscopy revealed zonation of CD8 + but not CD4 + T cells at necrotic areas. Gene expression analysis exposed upregulated C-C chemokine receptor 7 (CCR7) and its ligand CCL21 in the liver as well as a broadly activated phenotype of hepatic CD8 + T cells. In 2 mouse models of ALF, Ccr7-/- mice had significantly aggravated early-phase liver damage. Functionally, CCR7 was not involved in the recruitment of CD8 + T cells, but regulated their activation profile potentially through egress to lymphatics. Ccr7-/- CD8 + T cells were characterized by elevated expression of activation, effector, and exhaustion profiles. Adoptive transfer revealed preferential homing of CCR7-deficient CD8 + T cells to the liver, and depletion of CD8 + T cells attenuated liver damage in mice. CONCLUSIONS: Our study demonstrates the involvement of the adaptive immune system in ALF in humans and mice. We identify the CCR7-CCL21 axis as an important regulatory pathway, providing downstream protection against T cell-mediated liver injury.

6.
Brief Bioinform ; 23(4)2022 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-35667080

RESUMEN

PIWI-interacting RNAs (piRNAs) are short 21-35 nucleotide molecules that comprise the largest class of non-coding RNAs and found in a large diversity of species including yeast, worms, flies, plants and mammals including humans. The most well-understood function of piRNAs is to monitor and protect the genome from transposons particularly in germline cells. Recent data suggest that piRNAs may have additional functions in somatic cells although they are expressed there in far lower abundance. Compared with microRNAs (miRNAs), piRNAs have more limited bioinformatics resources available. This review collates 39 piRNA specific and non-specific databases and bioinformatics resources, describes and compares their utility and attributes and provides an overview of their place in the field. In addition, we review 33 computational models based upon function: piRNA prediction, transposon element and mRNA-related piRNA prediction, cluster prediction, signature detection, target prediction and disease association. Based on the collection of databases and computational models, we identify trends and potential gaps in tool development. We further analyze the breadth and depth of piRNA data available in public sources, their contribution to specific human diseases, particularly in cancer and neurodegenerative conditions, and highlight a few specific piRNAs that appear to be associated with these diseases. This briefing presents the most recent and comprehensive mapping of piRNA bioinformatics resources including databases, models and tools for disease associations to date. Such a mapping should facilitate and stimulate further research on piRNAs.


Asunto(s)
Proteínas Argonautas , Células Germinativas , Animales , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Simulación por Computador , Elementos Transponibles de ADN , Células Germinativas/metabolismo , Humanos , Mamíferos/genética , Mamíferos/metabolismo , ARN Interferente Pequeño/genética
7.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-35998924

RESUMEN

CRISPR-Cas system is an adaptive immune system widely found in most bacteria and archaea to defend against exogenous gene invasion. One of the most critical steps in the study of exploring and classifying novel CRISPR-Cas systems and their functional diversity is the identification of Cas proteins in CRISPR-Cas systems. The discovery of novel Cas proteins has also laid the foundation for technologies such as CRISPR-Cas-based gene editing and gene therapy. Currently, accurate and efficient screening of Cas proteins from metagenomic sequences and proteomic sequences remains a challenge. For Cas proteins with low sequence conservation, existing tools for Cas protein identification based on homology cannot guarantee identification accuracy and efficiency. In this paper, we have developed a novel stacking-based ensemble learning framework for Cas protein identification, called CRISPRCasStack. In particular, we applied the SHAP (SHapley Additive exPlanations) method to analyze the features used in CRISPRCasStack. Sufficient experimental validation and independent testing have demonstrated that CRISPRCasStack can address the accuracy deficiencies and inefficiencies of the existing state-of-the-art tools. We also provide a toolkit to accurately identify and analyze potential Cas proteins, Cas operons, CRISPR arrays and CRISPR-Cas locus in prokaryotic sequences. The CRISPRCasStack toolkit is available at https://github.com/yrjia1015/CRISPRCasStack.


Asunto(s)
Archaea , Proteómica , Archaea/genética , Sistemas CRISPR-Cas , Edición Génica/métodos , Aprendizaje Automático
8.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-35940845

RESUMEN

High-quality genome chromosome-scale sequences provide an important basis for genomics downstream analysis, especially the construction of haplotype-resolved and complete genomes, which plays a key role in genome annotation, mutation detection, evolutionary analysis, gene function research, comparative genomics and other aspects. However, genome-wide short-read sequencing is difficult to produce a complete genome in the face of a complex genome with high duplication and multiple heterozygosity. The emergence of long-read sequencing technology has greatly improved the integrity of complex genome assembly. We review a variety of computational methods for complex genome assembly and describe in detail the theories, innovations and shortcomings of collapsed, semi-collapsed and uncollapsed assemblers based on long reads. Among the three methods, uncollapsed assembly is the most correct and complete way to represent genomes. In addition, genome assembly is closely related to haplotype reconstruction, that is uncollapsed assembly realizes haplotype reconstruction, and haplotype reconstruction promotes uncollapsed assembly. We hope that gapless, telomere-to-telomere and accurate assembly of complex genomes can be truly routinely achieved using only a simple process or a single tool in the future.


Asunto(s)
Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Mapeo Cromosómico , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos
9.
Bioinformatics ; 39(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37294799

RESUMEN

MOTIVATION: Enhancers are vital cis-regulatory elements that regulate gene expression. Enhancer RNAs (eRNAs), a type of long noncoding RNAs, are transcribed from enhancer regions in the genome. The tissue-specific expression of eRNAs is crucial in the regulation of gene expression and cancer development. The methods that identify eRNAs based solely on genomic sequence data have high error rates because they do not account for tissue specificity. Specific histone modifications associated with eRNAs offer valuable information for their identification. However, identification of eRNAs using histone modification data requires the use of both RNA-seq and histone modification data. Unfortunately, many public datasets contain only one of these components, which impedes the accurate identification of eRNAs. RESULTS: We introduce DeepITEH, a deep learning framework that leverages RNA-seq data and histone modification data from multiple samples of the same tissue to enhance the accuracy of identifying eRNAs. Specifically, deepITEH initially categorizes eRNAs into two classes, namely, regularly expressed eRNAs and accidental eRNAs, using histone modification data from multiple samples of the same tissue. Thereafter, it integrates both sequence and histone modification features to identify eRNAs in specific tissues. To evaluate the performance of DeepITEH, we compared it with four existing state-of-the-art enhancer prediction methods, SeqPose, iEnhancer-RD, LSTMAtt, and FRL, on four normal tissues and four cancer tissues. Remarkably, seven of these tissues demonstrated a substantially improved specific eRNA prediction performance with DeepITEH, when compared with other methods. Our findings suggest that DeepITEH can effectively predict potential eRNAs on the human genome, providing insights for studying the eRNA function in cancer. AVAILABILITY AND IMPLEMENTATION: The source code and dataset of DeepITEH have been uploaded to https://github.com/lyli1013/DeepITEH.


Asunto(s)
Aprendizaje Profundo , ARN Largo no Codificante , Humanos , Transcripción Genética , Genoma Humano , Histonas/genética , Elementos de Facilitación Genéticos , ARN Largo no Codificante/genética
10.
Clin Chem Lab Med ; 62(6): 1092-1100, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38253403

RESUMEN

OBJECTIVES: The standardization of cystatin C (CysC) measurement has received increasing attention in recent years due to its importance in estimating glomerular filtration rate (GFR). Mass spectrometry-based assays have the potential to provide an accuracy base for CysC measurement. However, a precise, accurate and sustainable LC-MS/MS method for CysC is still lacking. METHODS: The developed LC-MS/MS method quantified CysC by detecting signature peptide (T3) obtained from tryptic digestion. Stable isotope labeled T3 peptide (SIL-T3) was spiked to control matrix effects and errors caused by liquid handling. The protein denaturation, reduction and alkylation procedures were combined into a single step with incubation time of 1 h, and the digestion lasted for 3.5 h. In the method validation, digestion time-course, imprecision, accuracy, matrix effect, interference, limit of quantification (LOQ), carryover, linearity, and the comparability to two routine immunoassays were evaluated. RESULTS: No significant matrix effect or interference was observed with the CysC measurement. The LOQ was 0.21 mg/L; the within-run and total imprecision were 1.33-2.05 % and 2.18-3.90 % for three serum pools (1.18-5.34 mg/L). The LC-MS/MS method was calibrated by ERM-DA471/IFCC and showed good correlation with two immunoassays traceable to ERM-DA471/IFCC. However, significant bias was observed for immunoassays against the LC-MS/MS method. CONCLUSIONS: The developed LC-MS/MS method is robust and simpler and holds the promise to provide an accuracy base for routine immunoassays, which will promote the standardization of CysC measurement.


Asunto(s)
Cistatina C , Espectrometría de Masas en Tándem , Cistatina C/sangre , Humanos , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masas en Tándem/normas , Inmunoensayo/métodos , Inmunoensayo/normas , Cromatografía Liquida/métodos , Límite de Detección , Cromatografía Líquida con Espectrometría de Masas
11.
BMC Public Health ; 24(1): 998, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600464

RESUMEN

BACKGROUND: This study aimed to investigate the utilization rate and equity of health examination service among the middle-aged and elderly population in China from 2011 to 2018. The contribution of various determinants to the inequity in health examination service utilization was also examined. METHODS: Data from the China Health and Retirement Longitudinal Survey (CHARLS) were analyzed to assess the health examination service utilization rate among the middle-aged and elderly population. A concentration curve and concentration index were employed to measure the equity of health examination service utilization and decomposed into its determining factors. Horizontal inequity index was applied to evaluate the trends in equity of health examination service. RESULTS: The health examination service utilization rates among the middle-aged and elderly population were 29.45%, 20.69%, 25.40%, and 32.05% in 2011, 2013, 2015, and 2018, respectively. The concentration indexes for health examination service utilization were 0.0080 (95% CI: - 0.0084, 0.0244), 0.0155 (95% CI: - 0.0054, 0.0363), 0.0095 (95% CI: - 0.0088, 0.0277), and - 0.0100 (95% CI: - 0.0254, 0.0054) from 2011 to 2018, respectively. The horizontal inequity index was positive from 2011 to 2018, evidencing a pro-rich inequity trend. Age, residence, education, region, and economic status were the major identified contributors influencing the equity of health examination service utilization. CONCLUSIONS: A pro-rich inequity existed in health examination service utilization among the middle-aged and elderly population in China. Reducing the wealth and regional gap, providing equal educational opportunities, and strengthening the capacity for chronic disease prevention and control are crucial for reducing the inequity in health examination service utilization.


Asunto(s)
Disparidades en Atención de Salud , Jubilación , Persona de Mediana Edad , Humanos , Anciano , Factores Socioeconómicos , China , Estudios Longitudinales
12.
Int J Mol Sci ; 25(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892162

RESUMEN

Single-cell RNA sequencing (scRNA-seq) is widely used to interpret cellular states, detect cell subpopulations, and study disease mechanisms. In scRNA-seq data analysis, cell clustering is a key step that can identify cell types. However, scRNA-seq data are characterized by high dimensionality and significant sparsity, presenting considerable challenges for clustering. In the high-dimensional gene expression space, cells may form complex topological structures. Many conventional scRNA-seq data analysis methods focus on identifying cell subgroups rather than exploring these potential high-dimensional structures in detail. Although some methods have begun to consider the topological structures within the data, many still overlook the continuity and complex topology present in single-cell data. We propose a deep learning framework that begins by employing a zero-inflated negative binomial (ZINB) model to denoise the highly sparse and over-dispersed scRNA-seq data. Next, scZAG uses an adaptive graph contrastive representation learning approach that combines approximate personalized propagation of neural predictions graph convolution (APPNPGCN) with graph contrastive learning methods. By using APPNPGCN as the encoder for graph contrastive learning, we ensure that each cell's representation reflects not only its own features but also its position in the graph and its relationships with other cells. Graph contrastive learning exploits the relationships between nodes to capture the similarity among cells, better representing the data's underlying continuity and complex topology. Finally, the learned low-dimensional latent representations are clustered using Kullback-Leibler divergence. We validated the superior clustering performance of scZAG on 10 common scRNA-seq datasets in comparison to existing state-of-the-art clustering methods.


Asunto(s)
Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Análisis por Conglomerados , Humanos , RNA-Seq/métodos , Análisis de Secuencia de ARN/métodos , Algoritmos , Programas Informáticos , Aprendizaje Profundo , Biología Computacional/métodos , Análisis de Expresión Génica de una Sola Célula
13.
BMC Bioinformatics ; 24(1): 137, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37029385

RESUMEN

Vesicle transport proteins not only play an important role in the transmembrane transport of molecules, but also have a place in the field of biomedicine, so the identification of vesicle transport proteins is particularly important. We propose a method based on ensemble learning and evolutionary information to identify vesicle transport proteins. Firstly, we preprocess the imbalanced dataset by random undersampling. Secondly, we extract position-specific scoring matrix (PSSM) from protein sequences, and then further extract AADP-PSSM and RPSSM features from PSSM, and use the Max-Relevance-Max-Distance (MRMD) algorithm to select the optimal feature subset. Finally, the optimal feature subset is fed into the stacked classifier for vesicle transport proteins identification. The experimental results show that the of accuracy (ACC), sensitivity (SN) and specificity (SP) of our method on the independent testing set are 82.53%, 0.774 and 0.836, respectively. The SN, SP and ACC of our proposed method are 0.013, 0.007 and 0.76% higher than the current state-of-the-art methods.


Asunto(s)
Algoritmos , Posición Específica de Matrices de Puntuación , Proteínas de Transporte Vesicular , Secuencia de Aminoácidos , Proteínas Portadoras , Máquina de Vectores de Soporte , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/aislamiento & purificación
14.
BMC Plant Biol ; 23(1): 609, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38036956

RESUMEN

BACKGROUND: Plants show developmental plasticity with variations in environmental nutrients. Considering low-cost rock dust has been identified as a potential alternative to artificial fertilizers for more sustainable agriculture, the growth responses of Arabidopsis seedlings on three rock meals (basalt, granite, and marlstone) were examined for the different foraging behavior, biomass accumulation, and root architecture. RESULTS: Compared to ½ MS medium, basalt and granite meal increased primary root length by 13% and 38%, respectively, but marlstone caused a 66% decrease, and they all drastically reduced initiation and elongation of lateral roots but lengthened root hairs. Simultaneous supply of organic nutrients and trace elements increased fresh weight due to the increased length of primary roots and root hairs. When nitrogen (N), phosphorus (P), and potassium (K) were supplied individually, N proved most effective in improving fresh weight of seedlings growing on basalt and granite, whereas K, followed by P, was most effective for those growing on marlstone. Unexpectedly, the addition of N to marlstone negatively affected seedling growth, which was associated with repressed auxin biosynthesis in roots. CONCLUSIONS: Our data indicate that plants can recognize and adapt to complex mineral deficiency by adjusting hormonal homeostasis to achieve environmental sensitivity and developmental plasticity, which provide a basis for ecologically sound and sustainable strategies to maximize the use of natural resources and reduce the production of artificial fertilizers.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Plantones , Ácidos Indolacéticos , Fertilizantes , Raíces de Plantas , Homeostasis , Nutrientes
15.
Small ; 19(26): e2206791, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37010037

RESUMEN

2D materials with atomic thickness display strong gate controllability and emerge as promising materials to build area-efficient electronic circuits. However, achieving the effective and nondestructive modulation of carrier density/type in 2D materials is still challenging because the introduction of dopants will greatly degrade the carrier transport via Coulomb scattering. Here, a strategy to control the polarity of tungsten diselenide (WSe2 ) field-effect transistors (FETs) via introducing hexagonal boron nitride (h-BN) as the interfacial dielectric layer is devised. By modulating the h-BN thickness, the carrier type of WSe2 FETs has been switched from hole to electron. The ultrathin body of WSe2 , combined with the effective polarity control, together contribute to the versatile single-transistor logic gates, including NOR, AND, and XNOR gates, and the operation of only two transistors as a half adder in logic circuits. Compared with the use of 12 transistors based on static Si CMOS technology, the transistor number of the half adder is reduced by 83.3%. The unique carrier modulation approach has general applicability toward 2D logic gates and circuits for the improvement of area efficiency in logic computation.

16.
J Mol Recognit ; 36(1): e2999, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36225143

RESUMEN

Phage display technology is commonly applied for high-throughput screening of single-domain antibodies (sdAbs), and the problem of non-specific adsorption caused by carrier proteins seriously affects the biopanning of single-domain antibodies specific to haptens. In this paper, enrofloxacin (ENR)-functionalized cryogels were prepared by the ethylenediamine (EDA) and carbodiimide methods for application in the biopanning of ENR-specific phages. To improve the efficiency of biopanning, double blocking, a wash solution flow rate of 1 mL/min, and phage pre-incubation were applied to the biopanning process through single-factor experiments. Results of flat colony counting showed that the phage output of AG-ENR cryogels was 15 times higher than that of AG cryogels for the same input amount. And seven complete sequences of ENR-specific shark sdAbs were obtained by monoclonal phage ELISA and sequence alignment. All these results indicate that functionalized cryogels could be used as a novel and efficient method for phage biopanning for single-domain antibodies to haptens.


Asunto(s)
Criogeles , Anticuerpos de Dominio Único , Criogeles/metabolismo , Haptenos , Adsorción , Ensayos Analíticos de Alto Rendimiento , Biblioteca de Péptidos
17.
BMC Cancer ; 23(1): 608, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37391693

RESUMEN

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Ováricas , Femenino , Humanos , Anciano , Pronóstico , Nomogramas , Carcinoma Epitelial de Ovario , China/epidemiología , Carcinoma Endometrioide/epidemiología , Carcinoma Endometrioide/terapia , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/terapia
18.
Inorg Chem ; 62(16): 6352-6360, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37045789

RESUMEN

A series of 3DOM cerium-based perovskite catalysts with different B-site elements were prepared by the colloidal crystal template method and excess impregnation method with Cr, Ni, and Mn as the B-site elements. The physical and chemical properties of the catalysts were investigated by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), hydrogen temperature-programmed reduction (H2-TPR), and oxygen temperature-programmed desorption (O2-TPD) characterization techniques. The results showed that the catalyst with Mn as the B-site element had a high-quality macropore structure (pore size 200-250 nm), large specific surface area (45.26 m2/g), and abundant surface adsorbed oxygen content (Oads/Olatt = 0.46). The addition of manganese enhanced the low-temperature reducibility, and the main reduction peak was below 400 °C. The O2-TPD results showed that 3DOM CeMnO3 expressed the highest adsorption oxygen content. The 3DOM CeMnO3 possessed the best catalytic performance with T50% = 102 °C and T90% = 203 °C during the catalytic oxidation of toluene. Intermediate product study hinted that toluene was first converted into benzoic acid and benzaldehyde and then further degraded into small molecules. The catalyst with the best activity also exhibited good stability, and toluene degradation rate remained above 85% at 200°C for more than 20 h of continuous experiments.

19.
Clin Chem Lab Med ; 61(10): 1770-1779, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37053598

RESUMEN

OBJECTIVES: This study aims to investigate and update the consistency and comparability of plasma renin activity (PRA) assays in measuring clinical samples. The contributions of recalibration, blank subtraction, and incubation strategies to interchangeability were also explored. METHODS: Five different laboratories were evaluated using forty-six individual plasma samples, including four liquid chromatography-tandem mass spectrometry (LC‒MS/MS) assays and one chemiluminescence immunoassay (CLIA). Spearman correlation coefficient (R), Passing-Bablok regression, and Bland‒Altman plot analyses were used to evaluate the consistency among assays. Consistency before and after recalibration, blank subtraction, and incubation strategy unification was compared. RESULTS: A good correlation was observed among all assays (R>0.93). None of the samples measured by all assays showed coefficient variation (CV) <10 %, and 37 % of samples showed overall CVs >20 %. The 95 % confidence intervals (CIs) for slopes did not contain 1 for most assay pairs. Large relative biases (-85.1-104.2 %) were found, and 76 % (52-93 %) of samples had unacceptable biases. Recalibration reduced the calibration bias. Ignoring blank subtraction improved the comparability across all assays while unifying incubation did not. CONCLUSIONS: The interchangeability of PRA measurement was unsatisfying. Harmonization on calibrator and ignoring blank were recommended. Unifying incubation strategy was unnecessary.


Asunto(s)
Renina , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Calibración , Mediciones Luminiscentes , Inmunoensayo/métodos
20.
Clin Chem Lab Med ; 61(8): 1455-1462, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-36866730

RESUMEN

OBJECTIVES: Except for the large bias of some measurement systems for serum cystatin C (CysC) measurements, unacceptable imprecision has been observed for the heterogenous system. This study analyzed the external quality assessment (EQA) results in 2018-2021 to provide an insight into the imprecision of CysC assays. METHODS: Five EQA samples were sent to participating laboratories every year. Participants were divided into reagent/calibrator-based peer groups, for which the robust mean of each sample and robust coefficient of variation (CV) were calculated by Algorithm A from ISO 13528. Peers with more than 12 participants per year were selected for further analysis. The limit of CV was determined to be 4.85% based on clinical application requirements. The concentration-related effect on CVs was investigated using logarithmic curve fitting; the difference in medians and robust CVs between instrument-based subgroups was also evaluated. RESULTS: The total number of participating laboratories increased from 845 to 1,695 in four years and heterogeneous systems remained the mainstream (≥85%). Of 18 peers with ≥12 participants, those using homogeneous systems showed relatively steady and small CVs over four years, with the mean four-year CVs ranging from 3.21 to 3.68%. Some peers using heterogenous systems showed reduced CVs over four years, while 7/15 still had unacceptable CVs in 2021 (5.01-8.34%). Six peers showed larger CVs at the low or high concentrations, and some instrument-based subgroups presented greater imprecision than others. CONCLUSIONS: More efforts should be made to improve the imprecision of heterogeneous systems for CysC measurement.


Asunto(s)
Cistatina C , Humanos , Pruebas de Función Renal
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