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Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA-binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.
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Estrogênios , Camundongos Endogâmicos mdx , Músculo Esquelético , Proteínas de Ligação a RNA , Animais , Feminino , Camundongos , Estrogênios/metabolismo , Estrogênios/farmacologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/genética , Camundongos Endogâmicos C57BL , Ovariectomia , Mitocôndrias/metabolismo , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/efeitos dos fármacosRESUMO
High-sensitivity and fast-response photodetectors (PDs) are vital part of optical wireless communication (OWC) system. In this work, we develop an organic-inorganic hybrid perovskite material (MAPbI3) based p-i-n structured PD. By optimizing the precursor solution concertation, the PD showed a high responsivity of 0.98 A W-1, a fast response timetrise/tfallof 12/12.5 µs, a specific detectivity of 2.62 × 1013Jones, and the f-3dBof 24 kHz under the 532 nm laser and -0.2 V bias voltage. Furthermore, we designed an OWC system based on the prepared PD. With the baud rate of 19200 bps, the system exhibits a bit error rate less than 10-6, and it can realize 9.63 m long-distance communication and quick transmission applications such as strings, texts, photos, and audios. Our work demonstrates the great application potential of perovskite PDs in the field of optical communication.
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Phosphoproteomics is nowadays the method of choice to comprehensively identify and quantify thousands of phosphorylated peptides and their associated proteins with the goal of interrogating changes in signal transduction pathways and other cellular processes. One of the most popular software suites to analyze phosphoproteomic data sets is MaxQuant, which converts mass spectrometric raw data into quantitative information on phosphopeptides and proteins. However, despite the increased utilization of phosphoproteomics in biomedical research, simple and user-friendly tools supporting downstream statistical analysis and interpretation of these highly complex outputs are still lacking. We have therefore developed Phospho-Analyst, whichâsimilar to its sibling LFQ-Analystâis an easy-to-use, interactive web application specifically designed to reproducibly perform differential expression analyses with "one click" and to visualize phosphoproteomic results in a meaningful and practical manner. Furthermore, if quantitative total proteomic information is available for the same samples, Phospho-Analyst automatically normalizes all phosphoproteomic results to underlying protein abundance levels, thereby ensuring that only genuine changes in phosphorylation events are considered. As such, Phospho-Analyst can not only be used by experienced proteomic veterans but also by researchers without any prior knowledge in (phospho)proteomics, statistics, or bioinformatics. Phospho-Analyst, including a detailed manual, is freely available at https://analyst-suites.org/apps/phospho-analyst/.
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Proteínas , Proteômica , Proteômica/métodos , Software , Espectrometria de Massas/métodos , FosforilaçãoRESUMO
Extrachromosomal circular DNA (eccDNA) is considered a circular DNA molecule that exists widely in nature and is independent of conventional chromosomes. eccDNA can be divided into small polydispersed circular DNA (spcDNA), telomeric circles (t-circles), microDNA, and extrachromosomal DNA (ecDNA) according to its size and sequence. Multiple studies have shown that eccDNA is the product of genomic instability, has rich and important biological functions, and is involved in the occurrence of many diseases, including cancer. In this review, we focus on the discovery history, formation process, characteristics, and physiological functions of eccDNAs; the potential functions of various eccDNAs in human cancer; and the research methods employed to study eccDNA.
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DNA , Neoplasias , Citoplasma , DNA/genética , DNA Circular/genética , Humanos , Neoplasias/genética , Telômero/genéticaRESUMO
BACKGROUND: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky. METHODS: The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model. RESULT: Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094). CONCLUSION: Our study provides a robust signature for predicting patients' prognosis, which might be helpful for therapeutic strategies discovery of LUAD.
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Adenocarcinoma de Pulmão/patologia , Adenosina/análogos & derivados , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Processamento Pós-Transcricional do RNA , Microambiente Tumoral/imunologia , Adenocarcinoma de Pulmão/classificação , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenosina/química , Epigênese Genética , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Metilação , Prognóstico , Taxa de Sobrevida , TranscriptomaRESUMO
BACKGROUND: This study is to examine the feasibility of shear wave elastography (SWE) anisotropy in assessing the prognosis of breast cancer. METHODS: We enrolled 119 breast cancer patients from January 2017 to October 2019. SWE was performed before operation. Emax (maximum elasticity value), Emean (average elasticity value), Esd (standard deviation of the lesion elasticity value), Eratio (elasticity value of adipose tissue), anisotropy coefficient and difference were recorded. After operation, we collected clinical pathological data, and performed immunohistochemistry and real-time PCR tests on CD44, CD24, E-cadherin, ß-catenin, vimentin and N-cadherin. Finally, we analyzed the correlation among parameters of SWE, anisotropy and clinicopathology, and markers of CSCs (cancer stem cells) and EMT (epithelial-mesenchymal transition). RESULTS: Emax, Emean and Esd of the cross section were higher than those of the longitudinal section. Breast cancer with a higher elastic modulus was often accompanied by a hyperechoic halo, which was manifested as mixed echo and post-echo attenuation, and was accompanied by a higher BI-RADS (breast imaging reporting and data system) classification. When breast cancer had hyperechoic halo and weakened posterior echo, SWE of the lesion showed more obvious anisotropy. In addition, larger diameter of the longitudinal section indicated higher stiffness of the cross section. Correlation analysis showed that E-cadherin was negatively correlated with SWE in longitudinal section. CD44, N-cadherin, ß-catenin were positively correlated with SWE in longitudinal and cross sections. Vimentin and CD24 had no correlation with SWE parameters. CONCLUSION: SWE of breast cancer is anisotropic. The cross-sectional SWE is better than the longitudinal SWE, Emax is better than Emean, the anisotropy of SWE is better than SWE, and the anisotropy factor is better than the anisotropy difference.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Técnicas de Imagem por Elasticidade/métodos , Transição Epitelial-Mesenquimal , Células-Tronco Neoplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Biomarcadores Tumorais/metabolismo , Módulo de Elasticidade , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , PrognósticoRESUMO
Ear rot is one of the most prevalent and destructive diseases of maize. During field surveys, it was found that a Penicillium ear rot broke out in some areas of Shanxi, Shaanxi, Hebei, and Tianjin in China, with an incidence of 3 to 90%. A Penicillium sp. was isolated from diseased kernels covered with greyish green mold, and three isolates were identified by morphologic and molecular characteristics. The pathogenicity of isolate ZBS205 to maize ears was further determined by artificial inoculation in a field. Furthermore, the sensitivity of isolate ZBS205 against six commonly used fungicides was also evaluated. According to macro- and micromorphologic characteristics, isolate ZBS205 was generally identical to Talaromyces funiculosus (teleomorph of Penicillium funiculosum). The partial gene sequences of the nuclear ribosomal ITS1-5.8S-ITS2 (ITS) region, ß-tubulin, putative ribosome biogenesis protein (Tsr1), and the second largest subunit of the RNA polymerase II (RPB2) from isolates ZBS205, D49-1, and S73-1 showed the highest nucleotide identity to T. funiculosus strain X33, and the phylogenetic analysis conducted by the neighbor-joining method with the combined data of the four genes demonstrated that these three isolates clustered with T. funiculosus strain X33. These results suggested that the fungus isolated from diseased maize kernels was T. funiculosus. Pathogenicity testing showed that the T. funiculosus isolate ZBS205 was pathogenic to maize ears, which showed symptoms of rotted cob and deteriorated kernels. This is the first report of T. funiculosus as the definitive pathogen causing maize ear rot. The result of fungal sensitivity against fungicides showed that pyraclostrobin exhibited the highest toxicity to mycelial growth and could be used as a candidate agent for the prevention and control of T. funiculosus ear rot. The results of the present study provide a basis for understanding ear rot caused by T. funiculosus, and they should play an important role in disease management.
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Fungicidas Industriais , Talaromyces , Fungicidas Industriais/farmacologia , Filogenia , Doenças das Plantas , Talaromyces/genética , Zea maysRESUMO
Deregulated expression of N-acetylgalactosaminyltransferases (GALNTs), which is responsible for the initial step of mucin-type O-glycosylation, could produce abnormal truncated O-glycans and thereby exert pivotal functions during malignant transformation. GALNT4 is one of the few isoforms preferring to catalyze partial GalNAc-glycosylated substrates and modify the sites not utilized by other known GALNTs. This study aims to evaluate the impact of GALNT4 expression on malignant transformation of hepatocellular carcinoma (HCC). Immunohistochemistry and in situ hybridization analysis were performed to assess GALNT4 and miR-9 level in clinical specimens, respectively. GALNT4 expression is markedly repressed in primary HCC tissues, and reduced expression of GALNT4 is significantly associated with adverse survival of patients with HCC. Functional investigations demonstrate that repressed GALNT4 could promote migration, invasion, anoikis resistance, and stemness of HCC cells in vitro as well as tumor growth in vivo The wild-type GALNT4 could modify O-linked glycosylation on EGFR and thus modulate the activity of EGFR. A luciferase activity assay further identified microRNA-9 (miR-9) as the crucial specific arbitrator for GALNT4 expression in HCC cells. Furthermore, restoring GALNT4 expression attenuates miR-9-mediated oncogenic functions. Kaplan-Meier survival analysis indicates that the miR-9/GALNT4 expression signature yields promising prognostic significance to refine the risk stratification of patients with HCC. In conclusion, this study establishes the miR-9/GALNT4 axis as a potential adverse prognostic factor and therapeutic target for HCC patients.
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Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Fígado/patologia , MicroRNAs/genética , N-Acetilgalactosaminiltransferases/genética , Adulto , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Feminino , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/genética , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Accumulating evidence indicates that the neural precursor cell-expressed, developmentally downregulated 4-like (Nedd4L) related with some tumor progression pathways and was found abnormally expressed in several kinds of solid cancers. However, the role and mechanism of Nedd4L in HCC remain unknown. This study was to assess the role of Nedd4L in HCC tumorigenesis and prognosis. The real-time quantitative RT-PCR and immunohistochemistry results revealed that Nedd4L was downregulated in HCC tissues compared to corresponding peri-noncancerous tissue, and HCC patients with low expression of Nedd4L exhibited poor prognosis assessed by Kaplan-Meier and Cox regression analysis in 78 HCC patients. Furthermore, knockdown of Nedd4L could significantly promote proliferation of HCC cells by CCK-8 and colony formation assays in vitro; whereas ectopic expression of Nedd4L resulted in attenuating proliferation in vitro and tumor growth in vivc determined by nude mice xenografts model. Mechanically, Nedd4L could phosphorylate ERK1/2 and regulate genes related with apoptosis. Collectively, Nedd4L plays a tumor suppressive role in HCC, possibly through triggering MAPK/ERK-mediated apoptosis, and Nedd4L downregulation may be a potential prognostic biomarker as well as a therapeutic target for HCC.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Proliferação de Células , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , China/epidemiologia , Regulação para Baixo , Feminino , Humanos , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUD: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis. However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In the present study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCC progression and outcome. METHODS: Wnt5a expression and cellular distribution in HCCs and their matched paracancerous tissues from 87 patients were analyzed with tissue microarray and immunohistochemistry and compared with hepatic Wnt3a signaling. Wnt5a expression was categorized into low or high based on immunohistochemistry. Overall survival rate of HCC patients was estimated in correlation with the hepatic Wnt5a level using Kaplan-Meier method; the survival difference between patients with low and those with high Wnt5a was compared with log-rank test; and prognostic analysis was carried out with Cox regression. RESULTS: Total incidence of Wnt5a expression in the HCC tissues was 70.1%, which was significantly lower (χ2â¯=â¯13.585, Pâ¯<â¯0.001) than that in their paracancerous tissues (88.5%). Significant difference of Wnt5a intensity was found between HCC and their paracancerous tissues (Zâ¯=â¯8.463, Pâ¯<â¯0.001). Wnt5a intensity was inversely correlated with Wnt3a signaling (râ¯=â¯-0.402, Pâ¯<â¯0.001) in HCC tissues. A decrease of Wnt5a expression in relation to the clinical staging from stage I to IV and low or no staining at advanced HCC were observed. Wnt5a level was related to periportal embolus (χ2â¯=â¯11.069, Pâ¯<â¯0.001), TNM staging (χ2â¯=â¯8.852, Pâ¯<â¯0.05), 5-year survival (χ2â¯=â¯4.961, Pâ¯<â¯0.05), and confirmed as an independent prognosis factor of HCC patients (hazard ratio: 1.957; 95% confidence interval: 1.109-3.456; Pâ¯<â¯0.05). CONCLUSIONS: The decrease of hepatic Wnt5a signaling is associated with HCC progression and poor prognosis.
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Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Neoplasias Hepáticas/química , Proteína Wnt-5a/análise , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Proliferação de Células , Distribuição de Qui-Quadrado , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Tempo , Resultado do Tratamento , Via de Sinalização Wnt , Proteína Wnt3A/análise , Adulto JovemRESUMO
Recently, a comment paper on "A New Elliptical Model for Device-Free Localization" (Sensors 2016, 16, 577) has been presented, and the authors have provided a modified model. However, there are still some misunderstandings. In this reply, we further explain the proposed elliptical model in (Sensors 2016, 16, 577) to make it more understandable.
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Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner. Furthermore, betulin treatment decreases the levels of glucose consumption and lactate production in 786-O cells, while minimal effects were observed in Caki-2 cells. In addition, betulin significantly inhibited the expression of PKM2 and HK2 in 786-O cells. Finally, knockdown of PKM2 or HK2 in 786-O reversed the anti-proliferative effects of betulin, and overexpression of PKM2 or HK2 in Caki-2 cells enhanced the sensitivity to betulin treatment. Taken together, these findings demonstrated the critical role of mTOR activation in RCC cells to betulin treatment, suggesting that betulin might be valuable for targeted therapies in RCC patients with mTOR activation.
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Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Ativação Enzimática/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Betula/química , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Triterpenos/química , Proteínas de Ligação a Hormônio da TireoideRESUMO
Beta-1,4-galactosyltransferase II is found to be associated with the alterations of tumor-related glycosylation. However, the clinical significance of beta-1,4-galactosyltransferase II in non-metastatic clear-cell renal cell carcinoma has not been reported up to now. Herein, our researches suggested that the expression level of beta-1,4-galactosyltransferase II was first found to be positively associated with tumor size, Fuhrman grade, lymphovascular invasion, rhabdoid differentiation, tumor necrosis and poor overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma, both in training set and validation set. Moreover, beta-1,4-galactosyltransferase II expression was identified as an independent adverse prognosticator for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Ultimately, prognostic accuracy of the nomogram integrating beta-1,4-galactosyltransferase II with other independent prognostic parameters was dramatically improved for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Taken together, beta-1,4-galactosyltransferase II is a potential independent adverse prognostic factor for postoperative recurrence and survival, which could be developed as a useful biomarker for non-metastatic clear-cell renal cell carcinoma by a series of further independent and retrospective studies, so as to help the postsurgical management of clear-cell renal cell carcinoma patients.
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Carcinoma de Células Renais/enzimologia , Galactosiltransferases/metabolismo , Neoplasias Renais/enzimologia , Carcinoma de Células Renais/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Prognóstico , Estudos Retrospectivos , Análise Serial de TecidosRESUMO
Device-free localization (DFL) based on wireless sensor networks (WSNs) is expected to detect and locate a person without the need for any wireless devices. Radio tomographic imaging (RTI) has attracted wide attention from researchers as an emerging important technology in WSNs. However, there is much room for improvement in localization estimation accuracy. In this paper, we propose a geometry-based elliptical model and adopt the orthogonal matching pursuit (OMP) algorithm. The new elliptical model uses not only line-of-sight information, but also non-line-of-sight information, which divides one ellipse into several areas with different weights. Meanwhile the OMP, which can eliminate extra bright spots in image reconstruction, is used to derive an image estimator. The experimental results demonstrate that the proposed algorithm could improve the accuracy of positioning by up to 23.8% for one person and 33.3% for two persons over some state-of-the-art RTI methods.
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Based on Time-Frequency (TF) analysis and a-contrario theory, this paper presents a new approach for extraction of linear arranged power transmission tower series in Polarimetric Synthetic Aperture Radar (PolSAR) images. Firstly, the PolSAR multidimensional information is analyzed using a linear TF decomposition approach. The stationarity of each pixel is assessed by testing the maximum likelihood ratio statistics of the coherency matrix. Then, based on the maximum likelihood log-ratio image, a Cell-Averaging Constant False Alarm Rate (CA-CFAR) detector with Weibull clutter background and a post-processing operator is used to detect point-like targets in the image. Finally, a searching approach based on a-contrario theory is applied to extract the linear arranged targets from detected point-like targets. The experimental results on three sets of PolSAR data verify the effectiveness of this approach.
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Hepatic annexin A2 (ANXA2) orchestrates multiple biologic processes and clinical symptoms and plays a key role in development, metastasis, and drug resistance of lethal hepatocellular carcinoma (HCC). However, the prognostic significance of ANXA2 for HCC has not been elucidated up to now. In this study, ANXA2 was frequently found to be up-regulated in HCC tissues compared with benign liver disease (BLD) tissues, which was consistent with the results in serum samples and tissue specimens of patients with HCC. Furthermore, ANXA2 expression was significantly correlated with differentiated degree, intrahepatic metastasis, portal vein thrombus, and tumor node metastasis (TNM) staging. More importantly, increased ANXA2 level was first confirmed to be closely associated with shortened overall survival of HCC (χ (2) = 12.872, P = 0.005) and identified as an independent prognostic factor (hazard ratio 1.338, 95 % confidence interval (CI) 1.013 ~ 1.766, P = 0.040), suggesting that ANXA2 up-regulation might represent an acquired metastasis phenotype of HCC, help to screen out high-risk population for HCC, or more effectively treat a subset of postsurgical HCC patients positive for ANXA2.
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Anexina A2/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anexina A2/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/sangue , Neoplasias/genética , Prognóstico , Ativação TranscricionalRESUMO
OBJECTIVE: To investigate the effects of Annexin A2 (ANXA2) deficiency on the malignant biological behaviour of hepatoma cells. METHODS: The human hepatocellular carcinoma (HCC) cells lines MHCC97-H, HepG2, SMMC-7721, SMMC-7402 and L02 were evaluated. The expression and distribution of ANXA2 were analysed by western blotting, real-time PCR, immunofluorescence and immunohistochemistry.Cell cycle was assessed by flow cytometry and propidium iodide staining. Effects of ANXA2 silencing on invasion and migration potential were assessed by transwell assay and wound healing assay, respectively. Proliferative potential was assessed by CCK-8 kit in vitro and xenograft tumour-growth assay in vivo. The t-test, chi square test, rank sum test, q-test and F-test were used for statistical analyses. RESULTS: The expression level of ANXA2 was markedly higher in the MHCC97-H cells with high metastasis potential than in the HepG2, SMMC-7721, SMMC-7402 and L02 cells. The efficiency of shRNA-mediated ANXA2 deficiency was more than 80%. Immunofluorescence analysis of the MHCC97-H cells indicated that ANXA2 expression was mainly localized to the cellular membrane and cytoplasm, with some nuclear localization. Down-regulation of ANXA2 led to S-phase arrest of HCC cells (q =8.001, P =0.002) and an inhibition of proliferation (q =17.140, P less than 0.01), migration (q =12.808, P less than 0.01) and invasion potential (q =9.069, P =0.002). Xenograft tumour-growth assay indicated that shRNA targeting of ANXA2 led to lower tumour weight (q =11.968, P < 0.001) and down-regulated ANXA2 expression (Z =2.530, P =0.011). CONCLUSION: Down-regulation of Annexin A2 gene transcription effectively changes the biological behaviours of hepatoma cells, and may represent a potential target of HCC molecular therapies.
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Anexina A2/genética , RNA Interferente Pequeno , Transcrição Gênica , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/patologia , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
Most artificial lights exhibit subtle fluctuations in intensity and frequency in response to the influence of the grid's alternating current, providing the potential to estimate the Electric Network Frequency (ENF) from conventional frame-based videos. Nevertheless, the performance of Video-based ENF (V-ENF) estimation largely relies on the imaging quality and thus may suffer from significant interference caused by non-ideal sampling, scene diversity, motion interference, and extreme lighting conditions. In this paper, we show that the ENF can be extracted without the above limitations from a new modality provided by the so-called event camera, a neuromorphic sensor that encodes the light intensity variations and asynchronously emits events with extremely high temporal resolution and high dynamic range. Specifically, we formulate and validate the physical mechanism for the ENF captured in events and then propose a simple yet robust Event-based ENF (E-ENF) estimation method through mode filtering and harmonic enhancement. To validate the effectiveness, we build the first Event-Video ENF Dataset (EV-ENFD) and its extension EV-ENFD+ with diverse scenarios, including static, dynamic, and extreme lighting scenes. Comprehensive experiments have been conducted on our proposed datasets, showcasing that our proposed E-ENF significantly outperforms the V-ENF in extracting accurate ENF traces, especially in challenging environments.
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Introduction: We aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features. Methods: Ultrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve. Results: We found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value. Discussion: The Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.
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The FragPipe computational proteomics platform is gaining widespread popularity among the proteomics research community because of its fast processing speed and user-friendly graphical interface. Although FragPipe produces well-formatted output tables that are ready for analysis, there is still a need for an easy-to-use and user-friendly downstream statistical analysis and visualization tool. FragPipe-Analyst addresses this need by providing an R shiny web server to assist FragPipe users in conducting downstream analyses of the resulting quantitative proteomics data. It supports major quantification workflows including label-free quantification, tandem mass tags, and data-independent acquisition. FragPipe-Analyst offers a range of useful functionalities, such as various missing value imputation options, data quality control, unsupervised clustering, differential expression (DE) analysis using Limma, and gene ontology and pathway enrichment analysis using Enrichr. To support advanced analysis and customized visualizations, we also developed FragPipeAnalystR, an R package encompassing all FragPipe-Analyst functionalities that is extended to support site-specific analysis of post-translational modifications (PTMs). FragPipe-Analyst and FragPipeAnalystR are both open-source and freely available.