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BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.
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Sistema Cardiovascular , Hipertensão , Adulto , Humanos , Neutrófilos , Inquéritos Nutricionais , Linfócitos , Hipertensão/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Radiotherapy is one of the mainstays of cancer therapy and has been used for treating 65-75% of patients with solid tumors. However, radiotherapy of tumors has two limitations: high-dose X-rays damage adjacent normal tissue and tumor metastases cannot be prevented. RESULTS: Therefore, to overcome the two limitations of radiotherapy, a multifunctional core-shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer were fabricated by assembling Au8NCs on the surface of a bifunctional nanoimmunomodulator R837/BMS nanocore using nanoprecipitation followed by electrostatic assembly. Formed R837/BMS@Au8 NP composed of R837, BMS-1, and Au8 clusters. Au8NC can enhance X-ray absorption at the tumor site to reduce X-ray dose and releases a large number of tumor-associated antigens under X-ray irradiation. With the help of immune adjuvant R837, dendritic cells can effectively process and present tumor-associated antigens to activate effector T cells, meanwhile, a small-molecule PD-L1 inhibitor BMS-1 can block PD-1/PD-L1 pathway to reactivate cytotoxic T lymphocyte, resulting in a strong systemic antitumor immune response that is beneficial for limiting tumor metastasis. According to in vivo and in vitro experiments, radioimmunotherapy based on R837/BMS@Au8 nanoparticles can increase calreticulin expression on of cancer cells, reactive oxygen species generation, and DNA breakage and decrease colony formation. The results revealed that distant tumors were 78.2% inhibited depending on radioimmunotherapy of primary tumors. Therefore, the use of a novel radiosensitizer R837/BMS@Au8 NPs realizes low-dose radiotherapy combined with immunotherapy against advanced cancer. CONCLUSION: In conclusion, the multifunctional core-shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer effectively limiting tumor metastasis and decrease X-ray dose to 1 Gy, providing an efective strategy for the construction of nanosystems with radiosensitizing function.
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Neoplasias , Radiossensibilizantes , Humanos , Adjuvantes Imunológicos , Imiquimode , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Radioimunoterapia , Ouro/químicaRESUMO
Adenosine triphosphate (ATP) is the major energy carrier in organisms, and there are many cellular proteins that can bind to ATP. Among these proteins, kinases are key regulators in several cell signaling processes, and aberrant kinase signaling contributes to the development of many human diseases, including cancer. Hence, small-molecule kinase inhibitors have been successfully used for the treatment of various diseases. Since the ATP-binding pockets are similar for many kinases, it is very important to evaluate the selectivity of different kinase inhibitors. We report here a clickable ATP photoaffinity probe for the global profiling of ATP-binding proteins. After incubating the protein lysate with the ATP probe followed by ultraviolet (UV) irradiation, ATP-binding proteins were labeled with an alkyne handle for subsequent biotin conjugation through click chemistry. Labeled proteins were enriched with streptavidin beads, digested with trypsin, and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). More than 400 ATP-binding proteins, including approximately 200 kinases, could be identified in a single LC-MS/MS run in the data-dependent acquisition mode. We then applied this method to the analysis of targets of three selected ATP-competitive kinase inhibitors. We were able to successfully identify some of their reported target proteins from label-free quantification results and validated the results using Western blot analyses. Together, we developed a clickable ATP photoaffinity probe for proteome-wide profiling of ATP-binding proteins and demonstrated that this chemoproteomic method is amenable to high-throughput target identification of kinase inhibitors.
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Trifosfato de Adenosina , Proteínas de Transporte , Humanos , Trifosfato de Adenosina/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteínas/metabolismo , Fosfotransferases/metabolismoRESUMO
BACKGROUND: This meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD). METHODS: PubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity. RESULTS: A total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, - 2.50 p = < 0.001; PVR: SMD -1.27 95% CI -1.53, - 1.02 p = < 0.001; 6MWD: SMD 1.88 95% CI 1.49, 2.27 p = < 0.001; SpO2: SMD 3.72 95% CI 3.13, 4.32 p = < 0.001). Subgroup analysis showed that younger patients had better efficacy, and the change in SpO2 was an indication for patient selection. The combined mortality rate was 5% at follow-up. CONCLUSIONS: In this meta-analysis, we demonstrated that the TRT strategy may have positive effects on haemodynamics and cardiac function in patients with severe PAH-CHD at short-term follow-up. Our analysis suggests that changes in age and SpO2 may be related to patient prognosis. TRIAL REGISTRATION: The protocol was registered on the PROSPERO website with the registration number CRD42022366552. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced .
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Cardiopatias Congênitas , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/complicações , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar Primária Familiar , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , ArtériasRESUMO
OBJECTIVE: Clostridium perfringens is one of most important bacterial pathogens in the poultry industry and mainly causes necrotizing enteritis (NE). This pathogen and its toxins can cause foodborne diseases in humans through the food chain. In China, with the rise of antibiotic resistance and the banning of antibiotic growth promoters (AGPs) in poultry farming, food contamination and NE are becoming more prevalent. Bacteriophages are a viable technique to control C. perfringens as an alternative to antibiotics. We isolated Clostridium phage from the environment, providing a new method for the prevention of NE and C. perfringens contamination in meat. METHODS: In this study, we selected C. perfringens strains from various regions and animal sources in China for phage isolation. The biological characteristics of Clostridium phage were studied in terms of host range, MOI, one-step curve, temperature and pH stability. We sequenced and annotated the genome of the Clostridium phage and performed phylogenetic and pangenomic analyses. Finally, we studied its antibacterial activity against bacterial culture and its disinfection effect against C. perfringens in meat. RESULTS: A Clostridium phage, named ZWPH-P21 (P21), was isolated from chicken farm sewage in Jiangsu, China. P21 has been shown to specifically lyse C. perfringens type G. Further analysis of basic biological characteristics showed that P21 was stable under the conditions of pH 4-11 and temperature 4-60 °C, and the optimal multiple severity of infection (MOI) was 0.1. In addition, P21 could form a "halo" on agar plates, suggesting that the phage may encode depolymerase. Genome sequence analysis showed that P21 was the most closely related to Clostridium phage CPAS-15 belonging to the Myoviridae family, with a recognition rate of 97.24% and a query coverage rate of 98%. No virulence factors or drug resistance genes were found in P21. P21 showed promising antibacterial activity in vitro and in chicken disinfection experiments. In conclusion, P21 has the potential to be used for preventing and controlling C. perfringens in chicken food production.
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Bacteriófagos , Infecções por Clostridium , Enterite , Doenças das Aves Domésticas , Animais , Humanos , Clostridium perfringens/genética , Bacteriófagos/genética , Galinhas , Desinfecção , Filogenia , Antibacterianos/farmacologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , CarneRESUMO
White matter maturation has been characterized by diffusion tensor (DT) metrics. However, maturational processes and degrees are not fully investigated due to limitations of univariate approaches and limited specificity/sensitivity. Diffusion kurtosis imaging (DKI) provides kurtosis tensor (KT) and white matter tract integrity (WMTI) metrics, besides DT metrics. Therefore, we tried to investigate performances of DKI with the multiparametric analysis in characterizing white matter maturation. Developmental changes in metrics were investigated by using tract-based spatial statistics and the region of interest analysis on 50 neonates with postmenstrual age (PMA) from 37.43 to 43.57 weeks. Changes in metrics were combined into various patterns to reveal different maturational processes. Mahalanobis distance based on DT metrics (DM,DT ) and that combing DT and KT metrics (DM,DT-KT ) were computed, separately. Performances of DM,DT-KT and DM,DT were compared in revealing correlations with PMA and the neurobehavioral score. Compared with DT metrics, WMTI metrics demonstrated additional changing patterns. Furthermore, variations of DM,DT-KT across regions were in agreement with the maturational sequence. Additionally, DM,DT-KT demonstrated stronger negative correlations with PMA and the neurobehavioral score in more regions than DM,DT . Results suggest that DKI with the multiparametric analysis benefits the understanding of white matter maturational processes and degrees on neonates.
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Desenvolvimento Infantil/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Neuroimagem/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
Developing highly active, durable, and cost-effective electrocatalysts for the oxygen evolution reaction (OER) is of prime importance in proton exchange membrane (PEM) water electrolysis techniques. Ru-based catalysts have high activities but always suffer from severe fading and dissolution issues, which cannot satisfy the stability demand of PEM. Herein, a series of iridium-doped yttrium ruthenates pyrochlore catalysts is developed, which exhibit better activity and much higher durability than commercial RuO2 , IrO2 , and most of the reported Ru or Ir-based OER electrocatalysts. Typically, the representative Y2 Ru1.2 Ir0.8 O7 OER catalyst demands a low overpotential of 220 mV to achieve 10 mA cm-2 , which is much lower than that of RuO2 (300 mV) and IrO2 (350 mV). In addition, the catalyst does not show obvious performance decay or structural degradation over a 2000 h stability test. EXAFS and XPS co-prove the reduced valence state of ruthenium and iridium in pyrochlore contributes to the improved activity and stability. Density functional theory reveals that the potential-determining steps barrier of OOH* formation is greatly depressed through the synergy effect of Ir and Ru sites by balancing the d band center and oxygen intermediates binding ability.
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Several studies have demonstrated that B7-H4 is highly expressed in a variety of cancers and often affects tumor development. However, its role in cancer stemness and epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) has not been reported. Here, we investigated the relationship between B7-H4 expression and cancer stemness and EMT by immunohistochemistry in 106 NSCLC tissues obtained from patients. The results confirmed that B7-H4 is highly expressed in NSCLC tissues and closely correlated with the expression of EMT-related proteins (Snail, Vimentin) and cancer stemness-related proteins (SOX2, SOX9, and CD44). Immunofluorescence assay indicated that B7-H4 colocalized with SOX2 and SOX9 in the nuclei of NSCLC cells. Additionally, upon knocking down B7-H4, the expression of SOX2, SOX9, and CD44, as well as of Snail and Vimentin was inhibited, whereas E-cadherin expression was enhanced in NSCLC cells. Meanwhile, inhibiting the expression of B7-H4 resulted in reduced invasion and migration ability of NSCLC cells. Mechanistically, silencing B7-H4 activated the adenosine monophosphate-activated protein kinase /mammalian target of rapamycin signaling, which in turn, negatively regulated cell proliferation, stemness, and migration. In conclusion, our results suggest that B7-H4 expression is high in NSCLC tissues, and it has an effect on EMT and cancer stemness. This further suggests that B7-H4 has a potential role in promoting the progression of NSCLC and thereby could be a potential therapeutic target in NSCLC treatment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidor 1 da Ativação de Células T com Domínio V-Set , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Vimentina/genéticaRESUMO
Signal processing is important in the balancing of the motor armature, where the balancing accuracy depends on the extraction of the signal amplitude and phase from the raw vibration signal. In this study, a motor armature dynamic balancing method based on the long short-term memory network (LSTM) and zero-phase filter (ZPF) is proposed. This method mainly focuses on the extraction accuracy of amplitude and phase from unbalanced signals of the motor armature. The ZPF is used to accurately extract the phase, while the LSTM network is trained to extract the amplitude. The proposed method combines the advantages of both methods, whereby the problems of phase shift and amplitude loss when used alone are solved, and the motor armature unbalance signal is accurately obtained. The unbalanced mass and phase are calculated using the influence coefficient method. The effectiveness of the proposed method is proven using the simulated motor armature vibration signal, and an experimental investigation is undertaken to verify the dynamic balancing method. Two amplitude evaluation metrics and three phase evaluation metrics are proposed to judge the extraction accuracy of the amplitude and phase, whereas amplitude and frequency spectrum analysis are used to judge the dynamic balancing results. The results illustrate that the proposed method has higher dynamic balancing accuracy. Moreover, it has better extraction accuracy for the amplitude and phase of unbalanced signals compared with other methods, and it has good anti-noise performance. The determination coefficient of the amplitude is 0.9999, and the average absolute error of the phase is 2.4°. The proposed method considers both fidelity and denoising, which ensuring the accuracy of armature dynamic balancing.
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Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , BenchmarkingRESUMO
Bolted connections have been widely applied in engineering structures, loosening will happen when bolted connections are subjected to continuous cyclic load, and a significant rotation between the nut and the bolt can be observed. Combining deep learning with machine vision, a bolt loosening detection method based on the fifth version of You Only Look Once (YOLOv5) is proposed, and the rotation of the nut is identified to detect the bolt loosening. Two different circular markers are added to the bolt and the nut separately, and then YOLOv5 is used to identify the circular markers, and the rotation angle of the nut against the bolt is calculated according to the center coordinate of each predicted box. A bolted connection structure is adopted to illustrate the effectiveness of the method. First, 200 images containing bolts and circular markers are collected to make the dataset, which is divided into a training set, verification set and test set. Second, YOLOv5 is used to train the model; the precision rate and recall rate are respectively 99.8% and 100%. Finally, the robustness of the proposed method in different shooting environments is verified by changing the shooting distance, shooting angle and light condition. When using this method to detect the bolt loosening angle, the minimum identifiable angle is 1°, and the maximum detection error is 5.91% when the camera is tilted 45°. The experimental results show that the proposed method can detect the loosening angle of the bolted connection with high accuracy; especially, the tiny angle of bolt loosening can be identified. Even under some difficult shooting conditions, the method still works. The early stage of bolt loosening can be detected by measuring the rotation angle of the nut against the bolt.
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In mammals, female fertility is determined by the outcome of follicular development (ovulation or atresia). The TGF-ß/SMAD signaling pathway is an important regulator of this outcome. However, the molecular mechanism by which the TGF-ß/SMAD signaling pathway regulates porcine follicular atresia has not been fully elucidated. Microrchidia family CW-type zinc finger 2 (MORC2) is anovel epigenetic regulatory protein widely expressed in plants, nematodes, and mammals. Our previous studies showed that MORC2 is a potential downstream target gene of the TGF-ß/SMAD signaling pathway. However, the role of MORC2 in porcine follicular atresia is unknown. To investigate this, qRT-PCR, western blotting, and TdT-mediated dUTP nick-end labeling were performed. Additionally, the luciferase activity assay was conductedto confirm that the TGF-ß/SMAD signaling pathway regulates MORC2. Our results demonstrate that MORC2 is animportant anti-apoptotic molecule that prevents porcine follicular atresia via a pathway involving mitochondrial apoptosis, not DNA repair. Notably, this studyrevealsthat the TGF-ß/SMAD signaling pathway inhibits porcine granulosa cell apoptosis by up-regulating MORC2. The transcription factor SMAD4 regulated the expression of MORC2 by binding to its promoter. Our results will help to reveal the mechanism underlying porcine follicular atresia and improve the reproductive efficiency of sows.
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Atresia Folicular , Células da Granulosa , Animais , Feminino , Atresia Folicular/genética , Células da Granulosa/metabolismo , Luciferases/metabolismo , Mamíferos/metabolismo , Transdução de Sinais , Suínos , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein that is highly expressed in various cancers. Although LETM1 is known to be associated with poor prognosis in colorectal cancer (CRC), its roles in autophagic cell death in CRC have not been explored. In this study, we examined the mechanisms through which LETM1 mediates autophagy in CRC. Our results showed that LETM1 was highly expressed in CRC tissues and that down-regulation of LETM1 inhibited cell proliferation and induced S-phase arrest. LETM1 silencing also suppressed cancer stem cell-like properties and induced autophagy in CRC cells. Additionally, the autophagy inhibitor 3-methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness, whereas the autophagy activator rapamycin had the opposite effects. Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS-mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.
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Autofagia , Proteínas de Ligação ao Cálcio/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Células-Tronco Neoplásicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Inativação Gênica , Humanos , Imunofenotipagem , Proteínas de Membrana/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Biológicos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. Although HBXIP is known to be associated with a poor prognosis for bladder cancer (BC), its effects on glycolysis and angiogenesis in BC have not been investigated. BC prognosis and relative gene expression of HBXIP were analyzed using the GEPIA, UALCAN, and STRING databases. BC cell angiogenesis and glycolysis were assessed by vasculogenic mimicry and glycolysis assay. Human umbilical vein endothelial cell (HUVEC) viability, migration, and angiogenesis were assessed by CCK8, transwell, wound healing, and tube formation assays. The results showed that HBXIP was highly expressed in BC tissues and cells. Knockdown of HBXIP expression decreased the levels of glucose uptake, lactate production, and glycolytic enzyme expression in BC cells, and decreased cell viability and migration of HUVECs. Additionally, silencing HBXIP reduced the total length of tubes and number of intersections, and EPO and VEGF protein expression in BC cells and HUVECs. Furthermore, knockdown of HBXIP expression reversed cell viability, migration, tube formation, and vasculogenic mimicry under high glucose and lactate conditions. Mechanistically, silencing of HBXIP reduced the protein expression levels of pAKT-ser473 and pmTOR, and inhibition of HBXIP, AKT, and mTOR expression decreased glycolytic enzyme protein expression. Our findings suggest that HBXIP reduces glycolysis in BC cells via regulation of AKT/mTOR signaling, thereby blocking BC angiogenesis. Collectively, this study provides a potential strategy to target HBXIP and AKT/mTOR for regulating glycolysis progression concurrently with anti-angiogenesis effects, and thereby develop novel therapeutics for the treatment of BC.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Glicólise , Neovascularização Patológica/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/irrigação sanguínea , Proteínas Adaptadoras de Transdução de Sinal/genética , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
SETD8 is a lysine methyltransferase containing an SET domain, which is involved in the carcinogenesis of many cancer types through monomethylation of the histone H4 lysine 20. However, its prognostic value and underlying mechanisms in gastric adenocarcinoma (GA) have not been extensively studied. Here, we assessed SETD8 expression and its relationship with clinicopathological parameters, cancer stemness-related proteins, cell cycle-related proteins, and PI3K/Akt pathway proteins in GA. SETD8 expression in GA tissues was correlated with the primary tumor stage, lymph node metastasis, tumor size, gross type, and clinical stage. SETD8 was an independent predictor of poor overall survival of patients with GA. Cox regression analysis showed that SETD8 is a potential biomarker of unfavorable clinical outcomes in patients with GA. Moreover, SETD8 overexpression was associated with cancer stemness-related genes, cell cycle-related genes, and PI3K/Akt/NF-κB pathway genes in clinical GA tissue samples. SETD8 silencing downregulated the expression of cancer stemness-associated genes (LSD1 and SOX2) and inhibited GA cell proliferation, spheroid formation, invasion, and migration. Additionally, LY294002 significantly reduced the expression of SETD8, pAkt-Ser473, pPI3K-p85, and NFκB-p65 in MKN74 and MKN28 cells. SETD8 may be a novel cancer stemness-associated protein and potential prognostic biomarker in GA.
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Adenocarcinoma/genética , Histona Desmetilases/genética , Histona-Lisina N-Metiltransferase/genética , Fatores de Transcrição SOXB1/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromonas/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteína Oncogênica v-akt/genética , Prognóstico , Neoplasias Gástricas/patologiaRESUMO
This paper proposes a method based on a planar array of electrostatic induction electrodes, which uses human body electrostatics to measure the height of hand movements. The human body is electrostatically charged for a variety of reasons. In the process of a hand movement, the change of a human body's electric field is captured through the electrostatic sensors connected to the electrode array. A measurement algorithm for the height of hand movements is used to measure the height of hand movements after the direction of it has been obtained. Compared with the tridimensional array, the planar array has the advantages of less space and easy deployment; therefore, it is more widely used. In this paper, a human hand movement sensing system based on human body electrostatics was established to perform verification experiments. The results show that this method can measure the height of hand movements with good accuracy to meet the requirements of non-contact human-computer interactions.
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Eletrodos , Mãos , Movimento , Eletricidade Estática , Algoritmos , HumanosRESUMO
In this work, an artificial electrode/electrolyte (E/E) interface, made by coating the electrode surface with a quaternary ammonium cation (R4 N+ ) surfactant, was successfully developed, leading to a change in the CO2 reduction reaction (CO2 RR) pathway. This artificial E/E interface, with high CO2 permeability, promotes CO2 transportation and hydrogenation, as well as suppresses the hydrogen evolution reaction (HER). Linear and branched surfactants facilitated formic acid and CO production, respectively. Molecular dynamics simulations show that the artificial interface provided a facile CO2 diffusion pathway. Moreover, density-functional theory (DFT) calculations revealed the stabilization of the key intermediate, OCHO*, through interactions with R4 N+ . This strategy might also be applicable to other electrocatalytic reactions where gas consumption is involved.
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BACKGROUND: Quantitative susceptibility mapping (QSM) is emerging as a technique that quantifies the paramagnetic nonheme iron in brain tissue. Brain iron quantification during early development provides insights into the underlying mechanism of brain maturation. PURPOSE: To quantify the spatiotemporal variations of brain iron-related magnetic susceptibility in deep gray matter nuclei during early development by using QSM. STUDY TYPE: Retrospective. SUBJECTS: Eighty-seven infants and children aged 1 month to 6 years. FIELD STRENGTH/SEQUENCE: Enhanced T2 *-weighted angiography using a 3D gradient-echo sequence at 3.0T. ASSESSMENT: QSM was calculated by modified sophisticated harmonic artifact reduction for phase data and sparse linear equations and sparse least squares-based algorithm. Means of susceptibility in deep gray matter nuclei (caudate nucleus, putamen, globus pallidus, thalamus) relative to that in splenium of corpus callosum were measured. STATISTICAL TESTS: Relationships of mean susceptibility with age and referenced iron concentration were tested by Pearson correlation. Differences of mean susceptibility between the selected nuclei in each age group were compared by one-way analysis of variance (ANOVA) and Fisher's Linear Significant Difference (LSD) test. RESULTS: Positive correlations of susceptibility with both referenced iron concentration and age were found (P < 0.0001); particularly, globus pallidus showed the highest correlation with age (correlation coefficient, 0.882; slope, 1.203; P < 0.001) and greatest susceptibility (P < 0.05) among the selected nuclei. DATA CONCLUSION: QSM allows the feasible quantification of iron deposition in deep gray matter nuclei in infants and young children, which exhibited gradual accumulation at different speeds. The fastest and highest iron accumulation was observed in the globus pallidus with increasing age during early development. LEVEL OF EVIDENCE: 4 Technical Efficacy:Stage 2 J. Magn. Reson. Imaging 2018.
Assuntos
Mapeamento Encefálico , Substância Cinzenta/diagnóstico por imagem , Ferro/metabolismo , Imageamento por Ressonância Magnética , Fatores Etários , Algoritmos , Artefatos , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/crescimento & desenvolvimento , Criança , Pré-Escolar , Feminino , Globo Pálido/diagnóstico por imagem , Globo Pálido/crescimento & desenvolvimento , Substância Cinzenta/crescimento & desenvolvimento , Humanos , Processamento de Imagem Assistida por Computador/métodos , Lactente , Masculino , Variações Dependentes do Observador , Putamen/diagnóstico por imagem , Putamen/crescimento & desenvolvimento , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/crescimento & desenvolvimentoRESUMO
BACKGROUNDS: We previously demonstrated the presence of onychodermis below nail matrix and nail bed. Because nail matrix is a producer of nail plate, we hypothesized that onychodermis below nail matrix could be the nail counterpart of follicular dermal papilla. In this study, we sought to further characterize histologic, histochemical, and immunohistochemical features of nail matrix onychodermis. METHODS AND RESULTS: Hematoxylin and eosin slides of 10 polydactyly nail units and 10 nail matrix biopsies from children and adults were reviewed. In polydactyly nail units, the onychodermis beneath nail matrix was characterized by onychofibroblasts showing abundant cytoplasm, and this area was slightly separated from the undersurface of the nail matrix. Nail matrix biopsy specimens also showed similar histology in the nail matrix onychodermis. Alcian blue stain demonstrated mucin deposition in onychofibroblasts within the nail matrix onychodermis. Immunohistochemically, elastin was rarely expressed in the nail matrix onychodermis while it was strongly expressed in the dermis of other areas of polydactyly nail units. Elastin was not expressed in follicular dermal papilla of terminal hair follicles of the scalp. CONCLUSION: Our findings demonstrate the presence and localization of nail matrix onychodermis (onychomatricodermis). Our study also demonstrates similar elastin expression patterns in the onychomatricodermis and follicular dermal papilla.
Assuntos
Derme , Folículo Piloso , Unhas , Polidactilia , Derme/metabolismo , Derme/patologia , Feminino , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Imuno-Histoquímica , Masculino , Unhas/metabolismo , Unhas/patologia , Polidactilia/metabolismo , Polidactilia/patologiaRESUMO
Walking is a basic requirement for participating in daily activities. Neurological diseases such as stroke can significantly affect one's gait and thereby restrict one's activities that are a part of daily living. Previous studies have demonstrated that gait temporal parameters are useful for characterizing post-stroke hemiparetic gait. However, no previous studies have investigated the symmetry, regularity and stability of post-stroke hemiparetic gaits. In this study, the dynamic time warping (DTW) algorithm, sample entropy method and empirical mode decomposition-based stability index were utilized to obtain the three aforementioned types of gait features, respectively. Studies were conducted with 15 healthy control subjects and 15 post-stroke survivors. Experimental results revealed that the proposed features could significantly differentiate hemiparetic patients from healthy control subjects by a Mann-Whitney test (with a p-value of less than 0.05). Finally, four representative classifiers were utilized in order to evaluate the possible capabilities of these features to distinguish patients with hemiparetic gaits from the healthy control subjects. The maximum area under the curve values were shown to be 0.94 by the k-nearest-neighbor (kNN) classifier. These promising results have illustrated that the proposed features have considerable potential to promote the future design of automatic gait analysis systems for clinical practice.
Assuntos
Marcha/fisiologia , Paresia/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Adulto , Algoritmos , Feminino , Análise da Marcha/métodos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/terapia , Estatísticas não Paramétricas , Acidente Vascular Cerebral/terapia , Caminhada/fisiologiaRESUMO
Hemiparesis is one of the common sequelae of neurological diseases such as strokes, which can significantly change the gait behavior of patients and restrict their activities in daily life. The results of gait characteristic analysis can provide a reference for disease diagnosis and rehabilitation; however, gait correlation as a gait characteristic is less utilized currently. In this study, a new non-contact electrostatic field sensing method was used to obtain the electrostatic gait signals of hemiplegic patients and healthy control subjects, and an improved Detrended Cross-Correlation Analysis cross-correlation coefficient method was proposed to analyze the obtained electrostatic gait signals. The results show that the improved method can better obtain the dynamic changes of the scaling index under the multi-scale structure, which makes up for the shortcomings of the traditional Detrended Cross-Correlation Analysis cross-correlation coefficient method when calculating the electrostatic gait signal of the same kind of subjects, such as random and incomplete similarity in the trend of the scaling index spectrum change. At the same time, it can effectively quantify the correlation of electrostatic gait signals in subjects. The proposed method has the potential to be a powerful tool for extracting the gait correlation features and identifying the electrostatic gait of hemiplegic patients.