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Electrocatalytic hydrodechlorination (EHDC) is a promising approach to safely remove halogenated emerging contaminants (HECs) pollutants. However, sluggish production dynamics of adsorbed atomic H (H*ads) limit the applicability of this green process. In this study, bimetallic Pd-Cu@MXene catalysts were synthesized to achieve highly efficient removal of HECs. The alloy electrode (Pd-Cu@MX/CC) exhibited better EHDC performance in comparison to Pd@MX/CC electrode, resulting in diclofenac degradation efficiency of 93.3 ± 0.1%. The characterization analysis revealed that the Pd0/PdII ratio decreased by forming bimetallic Pd-Cu alloy. Density functional theory calculations further demonstrated the electronic configuration modulation of the Pd-Cu@MXene catalysts, optimizing binging energies for H* and thereby facilitating H*ads production and tuning the reduction capability of H*ads. Noteably, the amounts and reduction potential of H*ads for Pd-Cu@MXene catalysts were 1.5 times higher and 0.37 eV lower than those observed for the mono Pd electrode. Hence, the introduction of Cu into the Pd catalyst optimized the dynamics of H*ads production, thereby conferring significant advantages to EHDC reactions. This augmentation was underscored by the successful application of the alloy catalysts supported by MXene in EHDC experiments involving other HECs, which represented a new paradigm for EHDC for efficient recalcitrant pollutant removal by H*ads.
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Cobre , Paládio , Catálise , Cobre/química , Paládio/química , Poluentes Químicos da Água/química , Adsorção , Halogenação , Técnicas Eletroquímicas/métodos , Eletrodos , Diclofenaco/químicaRESUMO
OBJECTIVE: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice. METHODS: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered. RESULTS: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway. CONCLUSIONS: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage.
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Proteínas Hedgehog , MicroRNAs , Transdução de Sinais , Transcriptoma , Animais , Hemorragia Cerebral/genética , Modelos Animais de Doenças , Glucose/toxicidade , Proteínas Hedgehog/metabolismo , Hiperglicemia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma/genéticaRESUMO
Brain extraction (a.k.a. skull stripping) is a fundamental step in the neuroimaging pipeline as it can affect the accuracy of downstream preprocess such as image registration, tissue classification, etc. Most brain extraction tools have been designed for and applied to human data and are often challenged by non-human primates (NHP) data. Amongst recent attempts to improve performance on NHP data, deep learning models appear to outperform the traditional tools. However, given the minimal sample size of most NHP studies and notable variations in data quality, the deep learning models are very rarely applied to multi-site samples in NHP imaging. To overcome this challenge, we used a transfer-learning framework that leverages a large human imaging dataset to pretrain a convolutional neural network (i.e. U-Net Model), and then transferred this to NHP data using a small NHP training sample. The resulting transfer-learning model converged faster and achieved more accurate performance than a similar U-Net Model trained exclusively on NHP samples. We improved the generalizability of the model by upgrading the transfer-learned model using additional training datasets from multiple research sites in the Primate Data-Exchange (PRIME-DE) consortium. Our final model outperformed brain extraction routines from popular MRI packages (AFNI, FSL, and FreeSurfer) across a heterogeneous sample from multiple sites in the PRIME-DE with less computational cost (20 s~10 min). We also demonstrated the transfer-learning process enables the macaque model to be updated for use with scans from chimpanzees, marmosets, and other mammals (e.g. pig). Our model, code, and the skull-stripped mask repository of 136 macaque monkeys are publicly available for unrestricted use by the neuroimaging community at https://github.com/HumanBrainED/NHP-BrainExtraction.
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Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Modelos Teóricos , Redes Neurais de Computação , Neuroimagem/métodos , Adulto , Animais , Conjuntos de Dados como Assunto , Estudos de Viabilidade , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Macaca , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). METHODS: We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. RESULTS: A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. CONCLUSIONS: Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making.
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Hemorragia Cerebral , Hidrocefalia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hematoma , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/epidemiologia , Prevalência , Tomografia Computadorizada por Raios XRESUMO
The present study was aimed to observe the characteristics of sublingual microcirculation and the changes of humoral factors in healthy people of three different high altitude populations. Three groups of healthy subjects in Guoluo area of Qinghai province (4 100 m) were included: Tibetan group: 30 Tibetans, (45.62 ± 10.15) years old; Han group: 22 two-generation of Han immigrants, (46.23 ± 8.59) years old; migrant group: 23 migrants living at high altitude for 2-5 years, (43.45 ± 8.31) years old. Blood routine test was performed to determine white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), platelet (PLT) count, and neutrophil (NEUT) count. The changes of serum humoral factors including endothelin-1 (ET-1), CD31, CD34, CD105, vascular endothelial growth factor (VEGF), nitric oxide (NO) and noradrenaline (NE) were detected by ELISA. Continuous noninvasive hemodynamics monitor was used to continuously measure the changes of systemic circulation indexes: cardiac output (CO), cardiac index (CI), heart rate (HR), stroke volume (SV), pulse pressure variation (PPV), systemic vascular resistance index (SVRI), and mean arterial pressure (MAP). Blood oxygen was measured by pulse oximeter. Sublingual microcirculation indexes including total vascular density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI) were determined by sidestream dark field imaging. The results showed that there were no difference in systemic circulation among the 3 groups. Compared with Tibetan group, TVD and PVD of microcirculation in Han group and migrant group were significantly increased (P < 0.05). Compared with Tibetan group and Han group, WBC, RBC, HGB and HCT of migrant group were significantly increased (P < 0.05). Compared with Han group and Migrant group, PLT of Tibetan group was significantly increased (P < 0.05). Compared with the Tibetan group, the levels of serum humoral factors CD105 and VEGF were significantly higher in the migrant group (P < 0.05), while compared with Han and migration groups, NO in Tibetan group was significantly increased (P < 0.05). It is suggested that there were significant differences in microcirculation (TVD, PVD), blood routine (WBC, RBC, HGB, HCT) and humoral factors (CD105, VEGF) among different populations in high altitude area. Importantly, the increased microcirculation, erythrocytosis and increased pro-angiogenic factors due to hypoxic environment were observed in long-term residents and migrants, except for permanent residents. These physiological changes have clinical significance in the treatment of septic shock and chronic altitude sickness for different plateau populations.
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Altitude , Microcirculação , Fator A de Crescimento do Endotélio Vascular , Adulto , China , Hemoglobinas , Humanos , Hipóxia , Pessoa de Meia-Idade , TibetRESUMO
Nucleosomes are the basic unit of the three-dimensional structure of chromatin. It is now widely accepted that the positioning and occupancy of nucleosomes play important roles in fundamental genomic processes such as DNA transcription, replication and repair. Among the methods used to provide genome-wide nucleosomal positions and occupancy levels, MNase-seq has proven to be highly effective. Indeed, with this method, the nucleosomal landscapes of a variety of organisms have now been investigated, revealing both commonalities and differences. In this review, we first introduce the technical principles underlying MNase-seq, focusing on details essential to precisely resolve nucleosome positioning and occupancy. We then describe recent advances with this method, as well as future perspectives of its role in chromatin biology, with a particular focus of uncovering mechanistic insights of many disease process.
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Cromatina , N-Glicosil Hidrolases , Nucleossomos , Cromatina/genética , Montagem e Desmontagem da Cromatina , DNA , N-Glicosil Hidrolases/metabolismo , Nucleossomos/genéticaRESUMO
To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down-regulation is involved in human bronchial epithelial carcinogenesis.
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Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Neoplasias Pulmonares/metabolismo , Neoplasias de Células Escamosas/metabolismo , Sequência de Aminoácidos , Biomarcadores Tumorais/química , Biomarcadores Tumorais/genética , Brônquios/patologia , Linhagem Celular , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Análise por Conglomerados , Creatina Quinase Forma BB/química , Creatina Quinase Forma BB/genética , Creatina Quinase Forma BB/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Glutationa S-Transferase pi/química , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Proteínas de Choque Térmico HSP27/química , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Microdissecção e Captura a Laser , Neoplasias Pulmonares/diagnóstico , Chaperonas Moleculares , Dados de Sequência Molecular , Neoplasias de Células Escamosas/diagnóstico , Proteômica , Curva ROC , Estatísticas não Paramétricas , Espectrometria de Massas em TandemRESUMO
Campylotropis xinfeniae, a new species from the dry-hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3-foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.
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Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.
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OBJECTIVE: To investigate the significance of Tp-Te interval for risk stratification of ventricular premature contractions (VPC) in children. METHODS: A total of 120 children with VPC were divided into benign VPC (n=40), organic disease (n=40) and ventricular parasystole groups (n=40) according to the etiology of VPC; another 40 children who underwent physical examination were selected as the normal control group. The four groups were compared in terms of Tp-Te intervals and Tp-Te/QT ratios in leads V3, V4 and V5. RESULTS: The Tp-Te interval in lead V3 was significantly longer in the organic disease group than in the other groups (P<0.05), the benign VPC group had a significantly shorter Tp-Te interval in lead V4 than the normal control and organic disease groups (P<0.05), and the organic disease group had a significantly longer Tp-Te interval in lead V5 than the benign VPC group (P<0.05). The Tp-Te/QT ratios in leads V3-V5 were significantly higher in the organic disease group than in the other groups (P<0.05). The Tp-Te/QT ratios in leads V4 and V5 showed significant differences between the ventricular parasystole and benign VPC groups (P<0.05). CONCLUSIONS: Tp-Te interval is susceptible to changes in heart rate, and it is of little value for the risk stratification of VPC in children. Tp-Te/QT ratio, however, may be used as an important non-invasive index for clinical risk stratification of VPC in children and is worthy of further study.
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Eletrocardiografia , Complexos Ventriculares Prematuros/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Frequência Cardíaca , Humanos , Lactente , Masculino , Risco , Complexos Ventriculares Prematuros/fisiopatologiaRESUMO
OBJECTIVE: To identify the risk factors for accelerated junctional escape rhythm (AJER) in children early after percutaneous ventricular septal defect (VSD) closure. METHODS: A retrospective controlled study was conducted on 42 children who had AJER within one week after percutaneous VSD closure between January 2008 and October 2012. These subjects were compared with controls without AJER after VSD closure in terms of age, sex, diameter of VSD, occluder size, difference between occluder size and diameter of VSD, and distance between VSD and aortic valve ring. Risk factors for AJER were identified by logistic regression analysis. RESULTS: Compared with the control group, the AJER group had a longer distance betweenVSD and aortic valve ring, a larger diameter of VSD (basal diameter), a larger occluder size (waist diameter) , and a bigger difference between the waist diameter of occluder and diameter of VSD (P<0.05). Logistic regression analysis showed that distance between VSD and aortic valve ring (OR=1.813, P<0.05) and occluder size (OR=1.671, P<0.05) are primary risk factors for AJER. CONCLUSIONS: AJER early after percutaneous VSD closure is related to diameter of VSD, occluder size, difference between the waist diameter of occluder and diameter of VSD, and distance between VSD and aortic valve ring. The distance between VSD and aortic valve ring and occluder size are primary risk factors for AJER.
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Arritmias Cardíacas/etiologia , Comunicação Interventricular/cirurgia , Complicações Pós-Operatórias/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores de RiscoRESUMO
Secondary trunk Ginkgo biloba is one of the specific germplasms of G. biloba. In this study, paraffin sectioning, high-performance liquid chromatography and transcriptome sequencing technology were used to study the development of the secondary trunk of G. biloba from the morphological, physiological and molecular levels. The results showed that the secondary trunk of G. biloba originated from the latent buds in the stem cortex at the junction of the root and stem of the main trunk. The development process of secondary trunk was divided into 4 periods: the dormancy period of the secondary trunk buds, the differentiation period, the formation period of transport tissue, and the budding period. Transcriptome sequencing was performed by comparing the germination period and elongation growth period of the secondary trunk with the normal parts of the same period where no secondary trunks occurred. Differential genes involved in phytohormone signal transduction, phenylpropane biosynthesis, phenylalanine metabolism, glycolysis and other pathways can regulate not only the inhibition of early dormant buds but also the later development of the secondary trunk. Genes related to IAA synthesis are upregulated and indole-3-acetic acid content is increased, leading to the up-regulated expression of IAA intracellular vector genes. The IAA response gene (SAUR) receives and responds to IAA signals to promote the development of the secondary trunk. Through the enrichment of differential genes and functional annotations, a key regulatory pathway map for the occurrence of the secondary trunk of G. biloba was sorted out.
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OBJECTIVES: The purpose of this study was to investigate the correlation between multi-slice computed tomographic perfusion imaging (CTPI) parameters and immunohistologic markers of angiogenesis in esophageal squamous cell carcinoma (ESCC). METHODS: Fifty patients with histologically proven esophageal squamous cell carcinoma were enrolled in this study. All subjects underwent multi-slice CT perfusion scan. The hemodynamic parameters of vascular tumor, including blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were generated. All the ESCC specimens were stained immunohistochemically to identify CD31 for quantification of microvessel density (MVD). CTPI parameters were correlated with MVD by using Pearson correlation analysis. RESULTS: The value of CT perfusion parameters of ESCC were as follows: BF 116.71 ± 47.59 ml/100 g/min, BV 6.74 ± 2.70 ml/100 g, MTT 6.42 ± 2.84 s, PS 13.82 ± 6.25 ml/100 g/min. The mean MVD of all 50 tumor specimens was 34.44 ± 19.75. The PS values were significantly higher in ESCC patients with involvement of lymph node than those without involvement of lymph node (p < 0.01). Blood volume and permeability surface were positively correlated with MVD (p < 0.01), whereas no significant correlation was observed between MVD and BF or between MVD and MTT. CONCLUSIONS: Blood volume and permeability surface were positively correlated with MVD. CTPI could reflect the angiogenesis in ESCC.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Meios de Contraste , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Ácidos Tri-IodobenzoicosRESUMO
[This corrects the article DOI: 10.3389/fneur.2021.655800.].
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EGFR is a potent stimulator of invasion and metastasis in head and neck squamous cell carcinomas (HNSCC). However, the mechanism by which EGFR may stimulate tumor cell invasion and metastasis still need to be elucidated. In this study, we showed that activation of EGFR by EGF in HNSCC cell line SCC10A enhanced cell migration and invasion, and induced loss of epitheloid phenotype in parallel with downregulation of E-cadherin and upregulation of N-cadherin and vimentin, indicating that EGFR promoted SCC10A cell migration and invasion possibly by an epithelial to mesenchymal transition (EMT)-like phenotype change. Interestingly, activation of EGFR by EGF induced production of matrix metalloproteinase-9 (MMP-9) and soluble E-cadherin (sE-cad), and knockdown of MMP-9 by siRNA inhibited sE-cad production induced by EGF in SCC10A. Moreover, both MMP-9 knockdown and E-cadherin overexpression inhibited cell migration and invasion induced by EGF in SCC10A. The results indicate that EGFR activation promoted cell migration and invasion through inducing MMP-9-mediated degradation of E-cadherin into sE-cad. Pharmacologic inhibition of EGFR, MEK, and PI3K kinase activity in SCC10A reduced phosphorylated levels of ERK-1/2 and AKT, production of MMP-9 and sE-cad, cell migration and invasion, and expressional changes of EMT markers (E-cadherin and N-cadherin) induced by EGF, indicating that EGFR activation promotes cell migration and invasion via ERK-1/2 and PI3K-regulated MMP-9/E-cadherin signaling pathways. Taken together, the data suggest that EGFR activation promotes HNSCC SCC10A cell migration and invasion by inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin into sE-cad related to activation of ERK-1/2 and PI3K signaling pathways.
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Caderinas/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , Receptores ErbB/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteólise , Carcinoma de Células Escamosas , Adesão Celular , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/fisiologia , Receptores ErbB/agonistas , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
BACKGROUND: The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells. RESULTS: We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins. CONCLUSION: The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.
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To observe longitudinally the expression of Programmed death 1(PD-1) on peripheral blood T cells in chronic hepatitis B patients underwent antiviral treatment with entecavir (ETV) and to explore the relationship between PD-1 expression and HBeAg seroconversion. Twenty HBeAg positive patients underwent antiviral treatment with ETV were followed up for 51 weeks. 14 patients remained HBeAg positive and 6 patients achieved HBeAg seroconversion. Peripheral blood was collected at six time points: T0: baseline, T1: 2-4week; T2: 5-10week; T3: 11-20week; T4: 21-30week: T5: 31-51week. PD-1 expressions on T cells were assessed by flow cytometry. Serum HBV DNA loads were determined by real-time fluorescent quantitative polymerase chain reaction (PCR) and serum ALT levels were examined at the same time. At baseline, serum HBV DNA load of patients without HBeAg seroconversion and with HBeAg seroconversion were (7.54+/-0.67) log10 copies/ml and (7.30+/-0.79) log10 copies/ml (P more than 0.05), the ALT levels were (187.26+/-184.15) U/L and (272.17+/-215.07) U/L (P more than 0.05), PD-1 exprissions on CD4+ T cells were 6.04%+/-3.71% and 6.77%+/-2.88% (P more than 0.05), PD-1 exprissions on CD8+ T cells were 6.39%+/-3.33% and 8.88%+/-2.84% (P more than 0.05). After ETV treatment, serum HBV DNA loads and ALT levels both decreased gradually, which was positively correlated with PD-1 expressions on CD4+ and CD8+ T cells (r=0.212, P = 0.05; r=0.377, P less than 0.01; r=0.279, P less than 0.05; r=0.347, P less than 0.01). During the same monitoring period, the HBV DNA loads, ALT levels and PD-1 expressions on T cells of the patients with HBeAg seroconversion decreased significantly as compared with the patients without HBeAg seroconversion. Besides, the decrease of HBV DNA loads during period deltaT0-T1 and deltaT0-T2 and PD-1 expressions on CD8+ T cells during period deltaT0-T2 and deltaT0-T3 were significantly different between these two kinds of patients (49.9% vs 37.3%, P less than 0.05; 56.7% vs 47.4%, P less than 0.05; 70.1% vs -4.2%, P less than 0.05; 66.9% vs 24.5%, P less than 0.05). The rapid decrease of PD-1 expression on peripheral CD8+ T cells after antiviral treatment with ETV is positvely correlated with the decrease of serum HBV DNA loads and may be used as a predictive index for HBeAg seroconversion in HBeAg positive patients.
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Objective: To observe the circulation and microcirculation characteristics of healthy han people in Qinghai at different Guoluo (4 100 m) and Huzhu (2 600 m) and in Shanghai in plain area (4 m). Methods: The 28 healthy han people aged (45.62±10.15) from Guoluo in Qinghai, 27 healthy han people aged (47.25±8.43) from Huzhu in Qinghai and 20 healthy han people aged (43.12±8.28) from Shanghai were divided into three groups: Guoluo group (GL), Huzhu group (HZ) and Shanghai group (SH); Venous blood was collected for routine blood test: red blood cells count(RBC), hemoglobin(HGB), hematocrit(HCT), platelet(PLT); and coagulation index: prothrombin time(PT), interntionl normlized ratio(INR), fibrin(Fib), activated partial thromboplastin time (APTT), thrombin time(TT), continuous non - invasive hemodynamic monitor (CNAP) was used for continuous measurement: cardiac output (CO), heart rate (HR), stroke volume (SV), pulse pressure variation rate (PPV), systemic vascular resistance index (SVRI), mean arterial pressure (MAP); pulse oxygen monitoring instrument is used for monitoring SPO2 (pulse oxygen); the total vascular density (TVD), perfusion vascular density (PVD), proportion of perfused vascular(PPV), and microvascular flow index (MFI) of sublingual microcirculation were observed by using peripheral dark field imaging (SDF) monitoring technique. Results: Compared with the Shanghai group, the RBC and HGB levels in the Huzhu group and the Guoluo group were significantly increased (Pï¼0.05), while PLT levels were significantly decreased (Pï¼0.05); The levels of PT, Fib, APTT, TT, CO, HR, SV, MAP and SPO2 in the Huzhu group were significantly decreased (Pï¼0.05), while the levels of TVD, PVD, PPV and MFI were significantly increased (Pï¼0.05). In Guoluo group, the levels of HCT, Fib, CO, SV, PPV, MAP, TVD and PVD were significantly increased (Pï¼0.05), while the levels of PT, INR, TT and SPO2 were significantly decreased (Pï¼0.05). Compared with the Huzhu group, the levels of RBC, HGB, HCT, Fib and APTT of Guoluo group were significantly increased (Pï¼0.05); while the levels of SPO2, TVD, PVD, INR and TT were significantly decreased (Pï¼0.05). Conclusion: The microcirculation of healthy people in different altitude areas is significantly different, and the microcirculation density of healthy people in high altitude areas is significantly higher than that in plain areas, especially in moderate altitude areas. Its special physiological significance is of guiding significance for the treatment of infectious shock and chronic altitude disease in plateau areas.
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Altitude , Etnicidade , China , Hemoglobinas , Humanos , MicrocirculaçãoRESUMO
Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer-assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion-prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion-prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.
Assuntos
Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hematoma/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Hemorragia Cerebral/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Hematoma/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. RESULTS: In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70-10.60; p = 0.002). CONCLUSIONS: The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.