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As a newly emergent type-II Dirac semimetal, platinum telluride (PtTe_{2}) stands out from other two dimensional noble-transition-metal dichalcogenides for the unique band structure and novel physical properties, and has been studied extensively. However, the ultrafast response of low energy quasiparticle excitation in terahertz frequency remains nearly unexplored yet. Herein, we employ optical pump-terahertz probe (OPTP) spectroscopy to systematically study the photocarrier dynamics of PtTe_{2} thin films with varying pump fluence, temperature, and film thickness. Upon photoexcitation the terahertz photoconductivity (PC) of PtTe_{2} films shows abrupt increase initially, while the terahertz PC changes into negative value in a subpicosecond timescale, followed by a prolonged recovery process that lasted a few nanoseconds. The magnitude of both positive and negative terahertz PC response shows strongly pump fluence dependence. We assign the unusual negative terahertz PC to the formation of small polaron due to the strong electron-phonon (e-ph) coupling, which is further substantiated by temperature and film thickness dependent measurements. Moreover, our investigations give a subpicosecond timescale of simultaneous carrier cooling and polaron formation. The present study provides deep insights into the underlying dynamics evolution mechanisms of photocarrier in type-II Dirac semimetal upon photoexcitation, which is of crucial importance for designing PtTe_{2}-based optoelectronic devices.
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Semiconducting nanowires offer many opportunities for electronic and optoelectronic device applications due to their unique geometries and physical properties. However, it is challenging to synthesize semiconducting nanowires directly on a SiO2 /Si substrate due to lattice mismatch. Here, a catalysis-free approach is developed to achieve direct synthesis of long and straight InSe nanowires on SiO2 /Si substrates through edge-homoepitaxial growth. Parallel InSe nanowires are achieved further on SiO2 /Si substrates through controlling growth conditions. The underlying growth mechanism is attributed to a selenium self-driven vapor-liquid-solid process, which is distinct from the conventional metal-catalytic vapor-liquid-solid method widely used for growing Si and III-V nanowires. Furthermore, it is demonstrated that the as-grown InSe nanowire-based visible light photodetector simultaneously possesses an extraordinary photoresponsivity of 271 A W-1 , ultrahigh detectivity of 1.57 × 1014 Jones, and a fast response speed of microsecond scale. The excellent performance of the photodetector indicates that as-grown InSe nanowires are promising in future optoelectronic applications. More importantly, the proposed edge-homoepitaxial approach may open up a novel avenue for direct synthesis of semiconducting nanowire arrays on SiO2 /Si substrates.
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BACKGROUND: Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. However, the role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer. METHODS: In this study, pathological features and clinical data of 232 cervical cancer patients were retrospectively reviewed. Semaphorin 5A protein and mRNA expression was detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction, respectively. In vitro, we determined the role and mechanistic pathways of semaphorin 5A in tumor progression in cervical carcinoma cell lines. RESULTS: Semaphorin 5A expression was significantly higher in stage IIb tumors than in stage Ia, Ib, and IIa tumors. High semaphorin 5A expression was significantly associated with pelvic lymph node metastasis, lymphovascular permeation, and poor survival. Semaphorin 5A induced lymphangiogenesis through a plexin-B/Met/vascular endothelial growth factor-C pathway. Semaphorin 5A also increased cervical cancer cell invasion by stimulating the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 via PI3K/AKT and plexin-B3. CONCLUSION: Our findings indicate that semaphorin 5A may represent a poor prognostic biomarker and anti-metastasis therapeutic target in cervical cancer.
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BACKGROUND: The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. METHODS: The once daily injections of hPTH(1-34) and GR (1-34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. RESULTS: After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1-34), GR(1-34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1-34) on fracture healing showed no difference to those of GR(1-34). Consistently, GR(1-34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1-34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1-34) treatment. CONCLUSION: These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1-34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.
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Consolidação da Fratura/fisiologia , Orquiectomia/efeitos adversos , Osteogênese/fisiologia , Hormônio Paratireóideo/farmacologia , Transdução de Sinais/fisiologia , Fosfolipases Tipo C/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/tratamento farmacológico , Fraturas do Colo Femoral/enzimologia , Consolidação da Fratura/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orquiectomia/tendências , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed. RESULTS The FRET analysis found that PTH(1-34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-ß. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1-28) or GR(1-34), and the difference was blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1-28); the other was PKA-independent and associated with PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Hormônio Paratireóideo/metabolismo , Proteína Quinase C/metabolismo , Células 3T3 , Animais , Apoptose , Proteínas de Transporte/metabolismo , Diferenciação Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Células HEK293/metabolismo , Humanos , Camundongos , Osteoblastos/metabolismo , Fosfoinositídeo Fosfolipase C/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fosfolipases Tipo C/metabolismoRESUMO
The presence of grain boundaries is inevitable for chemical vapor deposition (CVD)-grown MoS2 domains owing to various merging behaviors, which greatly limits its potential applications in novel electronic and optoelectronic devices. It is therefore of great significance to unravel the merging behaviors of the synthesized polygon shape MoS2 domains. Here we provide systematic investigations of merging behaviors and electrostatic properties of CVD-grown polycrystalline MoS2 crystals by multiple means. Morphological results exhibit various polygon shape features, ascribed to polycrystalline crystals merged with triangle shape MoS2 single crystals. The thickness of triangle and polygon shape MoS2 crystals is identical manifested by Raman intensity and peak position mappings. Three merging behaviors are proposed to illustrate the formation mechanisms of observed various polygon shaped MoS2 crystals. The combined photoemission electron microscopy and kelvin probe force microscopy results reveal that the surface potential of perfect merged crystals is identical, which has an important implication for fabricating MoS2-based devices.
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To enhance the quality of human life in a rapidly urbanized world plagued with high transportation, the masterful contribution of improved urban and local air quality cannot be overemphasized. In order to reduce human exposure to near-road air pollution, several approaches including the installation of roadside structural barriers especially in open street areas, such as city entrances are being applied. In the present study, the air quality around real world and idealized green infrastructures was investigated by means of numerical simulation and a short field measurement campaign. Fair agreement was found between ENVI-met modelled and measured particulate matter's concentration data around a realistic vegetation barrier indicating a fair representation of reality in the model. Several numerical experiments were conducted to investigate the influence of barrier type (vegetation/hedge and green wall) and dimensions on near-road air quality. The results show different horizontal/vertical patterns and magnitudes of upwind and downwind relative concentration (with and without a barrier) depending on wind condition, barrier type and dimension. Furthermore, an integrated dispersion-deposition approach was employed to assess the impact on air quality of near-road vegetation barrier. At last, recommendations to city and urban planners on the implementation of roadside structural barriers were made.
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Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Emissões de Veículos/análise , Cidades , Simulação por Computador , Recuperação e Remediação Ambiental , Hidrodinâmica , Modelos Teóricos , Material Particulado/análise , Urbanização , VentoAssuntos
Anetodermia/diagnóstico por imagem , Doenças do Cabelo/diagnóstico por imagem , Pilomatrixoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adolescente , Anetodermia/complicações , Anetodermia/patologia , Dermoscopia , Doenças do Cabelo/patologia , Humanos , Imuno-Histoquímica , Masculino , Pilomatrixoma/complicações , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologiaRESUMO
UNLABELLED: Based on Savitzky-Golay (SG) smoothing screening, principal component analysis (PCA) combined with separately supervised linear discriminant analysis (LDA) and unsupervised hierarchical clustering analysis (HCA) were used for non-destructive visible and near-infrared (Vis-NIR) detection for breed screening of transgenic sugarcane. A random and stability-dependent framework of calibration, prediction, and validation was proposed. A total of 456 samples of sugarcane leaves planting in the elongating stage were collected from the field, which was composed of 306 transgenic (positive) samples containing Bt and Bar gene and 150 non-transgenic (negative) samples. A total of 156 samples (negative 50 and positive 106) were randomly selected as the validation set; the remaining samples (negative 100 and positive 200, a total of 300 samples) were used as the modeling set, and then the modeling set was subdivided into calibration (negative 50 and positive 100, a total of 150 samples) and prediction sets (negative 50 and positive 100, a total of 150 samples) for 50 times. The number of SG smoothing points was ex- panded, while some modes of higher derivative were removed because of small absolute value, and a total of 264 smoothing modes were used for screening. The pairwise combinations of first three principal components were used, and then the optimal combination of principal components was selected according to the model effect. Based on all divisions of calibration and prediction sets and all SG smoothing modes, the SG-PCA-LDA and SG-PCA-HCA models were established, the model parameters were optimized based on the average prediction effect for all divisions to produce modeling stability. Finally, the model validation was performed by validation set. With SG smoothing, the modeling accuracy and stability of PCA-LDA, PCA-HCA were signif- icantly improved. For the optimal SG-PCA-LDA model, the recognition rate of positive and negative validation samples were 94.3%, 96.0%; and were 92.5%, 98.0% for the optimal SG-PCA-LDA model, respectively. CONCLUSION: Vis-NIR spectro- scopic pattern recognition combined with SG smoothing could be used for accurate recognition of transgenic sugarcane leaves, and provided a convenient screening method for transgenic sugarcane breeding.
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Plantas Geneticamente Modificadas/classificação , Saccharum/genética , Espectroscopia de Luz Próxima ao Infravermelho , Cruzamento , Análise por Conglomerados , Análise Discriminante , Folhas de Planta , Análise de Componente Principal , Saccharum/classificaçãoRESUMO
Neurological or neurodevelopmental disorders, such as Parkinson's disease and dyslexia, can impair rhythm perception and production. Deficits in rhythm are associated with poor performance in language, attention, and working memory tasks. Research indicates that retraining rhythmic skills may enhance these related cognitive functions. In this context, using tactile aids for rhythm training emerges as a promising approach for children who do not fully benefit from conventional audiovisual rhythm games. This is because tactile aids can compensate for sensory deficiencies and facilitate more extensive brain activation. In our study, we employed functional near-infrared spectroscopy (fNIRS) to assess the impact of tactile aids on brain cortical activation during rhythmic training in children aged 6-12 years (N = 25). We also measured the participants' spontaneous motor rhythms. The findings indicate that tactile stimulation significantly improves performance in synchronized rhythm tasks compared to audiovisual stimulation alone, particularly enhancing activation in brain regions associated with speech training such as the prefrontal cortex, motor cortex, and temporal areas. These results not only support the application of rhythm training in speech rehabilitation, but also highlight the potential of tactile aids as an effective multisensory learning strategy.
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Espectroscopia de Luz Próxima ao Infravermelho , Jogos de Vídeo , Humanos , Criança , Masculino , Feminino , Tato/fisiologia , Desempenho Psicomotor/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Auxiliares Sensoriais , PeriodicidadeRESUMO
Singing plays a critical role in enhancing musicality, sound discrimination, and attention, and proves advantageous for speech rehabilitation in children with hearing impairments. Computer-based training games are well-suited to the learning behaviors of children, with substantial evidence suggesting that music training augments speech training capabilities in this demographic. Despite this, there is a lack of detailed exploration into the design of interactive online music training interfaces tailored for these needs. This study investigates brain activation changes using two visual feedback singing games, analyzed through functional near-infrared spectroscopy: a serious game (SG) and an entertainment game (EG) with visually enhanced feedback. It also assesses the efficacy of home-based music training software for speech rehabilitation. Methods involved recording oxygenated hemoglobin concentration (Delta [HbO]) signals from the prefrontal cortex, motor cortex, occipital lobe, and temporal lobe in 21 children (average age: 9.3 ± 1.9 years) during two singing interface experiments. Subjects also completed the Intrinsic Motivation Inventory (IMI) questionnaire post-experiment. Main results showed that brain regions, particularly the temporal lobe, exhibited stronger and more pronounced activation signals with the SG interface compared to the EG, suggesting that SG is more effective for speech system rehabilitation. The Intrinsic Motivation Scale results revealed higher acceptability for SG than for EG. This study provides insights into designing online speech rehabilitation products for children with hearing impairment, advocating for better interactive training methods from a neuroscience perspective.
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BCI games have been widely employed as non-invasive therapeutic interventions for conditions, but their efficacy remains a subject of debate. This study explores the efficacy of two prevalent forms of Brain-Computer Interface (BCI)-based attention training games: video games (VG) and physical games (PG). The effectiveness of these games has been examined through the lens of neuroscience, using functional Near-Infrared Spectroscopy (fNIRS) to monitor cortical activation. After the fNIRS test, subjects completed an Intrinsic Motivation Inventory (IMI) questionnaire. PG tasks activated six channels (L-PFC, R-PFC and R-TL), while VG tasks activated only one (R-PFC). Furthermore, females exhibited stronger activation during PG tasks, while males had none in either. Our findings suggest that under equivalent game rules and themes, PG may prove more effective for cognitive rehabilitation than VG, with stronger intrinsic motivation. We also found this result may exhibit gender differences. Finally, this research offers valuable insights for the future design of BCI-based games from a neuroscience perspective.
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Interfaces Cérebro-Computador , Masculino , Feminino , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Encéfalo , Motivação , AtençãoRESUMO
BACKGROUND: Traffic-related air pollution (TRAP) is a major contributor to urban pollution and varies sharply at the street level, posing a challenge for air quality modeling. Traditional land use regression models combined with data from fixed monitoring stations may be unable to predict and characterize fine-scale TRAP, especially in complex urban environments influenced by various features. This study aims to estimate fine-scale (50 m) concentrations of nitrogen oxides (NO and NO2) in Hong Kong using a deep learning (DL) structured model. METHODS: We collected data from mobile air quality sensors on buses and crowd-sourced Google real-time traffic status as a proxy for real-time traffic emissions. Our DL model was compared with existing machine learning models to assess performance improvements. Using an interpretable machine learning method, we hierarchically evaluated the global, local, and interaction effects for different features. RESULTS: Our DL model outperformed existing machine learning models, achieving R2 values of 0.72 for NO and 0.69 for NO2. The incorporation of traffic status as a key predictor improved model performance by 9% to 17%. The interpretable machine learning method revealed the importance of traffic-related features and their pairwise interactions. CONCLUSION: The results indicate that traffic-related features significantly contribute to TRAP and provide insights and guidance for urban planning. By incorporating crowd-sourced Google traffic information, we assessed traffic abatement scenarios that could inform targeted strategies for improving urban air quality.
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Poluentes Atmosféricos , Poluição do Ar , Aprendizado Profundo , Monitoramento Ambiental , Emissões de Veículos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Monitoramento Ambiental/métodos , Hong Kong , Poluição do Ar/estatística & dados numéricos , Cidades , Óxidos de Nitrogênio/análise , Poluição Relacionada com o Tráfego/análiseRESUMO
Extrovert-introvert personality can take an active role in affecting people's attitudes, tastes, and behaviors in education. However, little research has been conducted to study whether and how extrovert-introvert personality may influence children's interaction with the attention training system. In this manuscript, we present the results of a user study that not only measured the influence of children's extrovert-introvert personality on their preference for two typical types of attention training systems (i.e., cognitive-based and neurofeedback-based) but also employed functional near-infrared spectroscopy (fNIRS) to investigate how the personality may influence cortical activation in children. Our results show that, for extroverted children, the neurofeedback attention training system elicited significantly greater activation in the prefrontal cortex and posterior parietal cortex, and was more likely to be preferred. The findings could be useful for developing more effective attention training systems based on user personality.
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Personalidade , Córtex Pré-Frontal , Humanos , Criança , Escolaridade , Transtornos da Personalidade , AtençãoRESUMO
BACKGROUND: The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different drugs for reducing testosterone levels in women with PCOS. METHODS: We searched studies from inception until January 10, 2023, through PubMed, Embase, and Cochrane Library database. All studies comparing different drugs for reducing testosterone levels in women with polycystic ovary syndrome were included in this network meta-analysis. Outcomes were total testosterone levels, free testosterone levels, and withdraw due to adverse events. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. RESULTS: Finally, a total of 13 studies were finally included in this network meta-analysis. In head-to-head comparison, atorvastatin (WMDâ -3.1, 95% CrI: -3.7 toâ -2.5), metformin (WMDâ -2.6, 95% CrI: -3.5 toâ -1.6), metformin + simvastatin (WMDâ -2.8, 95% CrI: -4.1 toâ -1.5), simvastatin (WMDâ -2.7, 95% CrI: -4.2 toâ -1.3), spironolactone (WMDâ -3.1, 95% CrI: -4.3 toâ -1.9), spironolactone + metformin (WMDâ -3.2, 95% CrI: -4.5 toâ -2.0) were all more effective than the placebo, and the difference was statistically significant (Pâ <â .05). The SUCRA shows that spironolactoneâ +â metformin ranked first (SUCRA, 85.0%), Atorvastatin ranked second (SUCRA, 77.7%), Spironolactone ranked third (SUCRA, 77.2%), and metforminâ +â simvastatin ranked the fourth. The SUCRA of different drugs for free testosterone levels shows that atorvastatin ranked first (SUCRA, 75.0%), spironolactoneâ +â metformin ranked second (SUCRA, 5.3%), metforminâ +â simvastain ranked third (SUCRA, 62.6%), and spironolactone ranked the fourth (SUCRA, 56.4%). No statistically significant differences were found between the 2 treatment groups for withdrawn due to adverse events (Pâ >â .05). CONCLUSIONS: Considering the network meta-analysis and rankings, atorvastatin was recommended to be the optimal drug for treatment PCOS. However, the optimal dose of atorvastatin was unknown and should be verified by more randomized controlled trials.
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Metformina , Síndrome do Ovário Policístico , Humanos , Feminino , Espironolactona/uso terapêutico , Atorvastatina/uso terapêutico , Metanálise em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Metformina/uso terapêutico , Sinvastatina/uso terapêutico , Testosterona/uso terapêuticoRESUMO
Introduction: Immunity is involved in a variety of bone metabolic processes, especially osteoporosis. The aim of this study is to explore new bone immune-related markers by bioinformatics method and evaluate their ability to predict osteoporosis. Methods: The mRNA expression profiles were obtained from GSE7158 in Gene expression Omnibus (GEO), and immune-related genes were obtained from ImmPort database (https://www.immport.org/shared/). immune genes related to bone mineral density(BMD) were screened out for differential analysis. protein-protein interaction (PPIs) networks were used to analyze the interrelationships between different immune-related genes (DIRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DIRGs function were performed. A least absolute shrinkage and selection operation (LASSO) regression model and multiple Support Vector Machine-Recursive Feature Elimination (mSVM-RFE) model were constructed to identify the candidate genes for osteoporosis prediction The receiver operator characteristic (ROC) curves were used to validate the performances of predictive models and candidate genes in GEO database (GSE7158,GSE13850).Through the RT - qPCR verify the key genes differentially expressed in peripheral blood mononuclear cells Finally, we constructed a nomogram model for predicting osteoporosis based on five immune-related genes. CIBERSORT algorithm was used to calculate the relative proportion of 22 immune cells. Results: A total of 1158 DEGs and 66 DIRGs were identified between high-BMD and low-BMD women. These DIRGs were mainly enriched in cytokine-mediated signaling pathway, positive regulation of response to external stimulus and the cellular components of genes are mostly localized to external side of plasma membrane. And the KEGG enrichment analysis were mainly involved in Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction,Natural killer cell mediated cytotoxicity. Then five key genes (CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1) were identified and used as features to construct a predictive prognostic model for osteoporosis using the GSE7158 dataset. Conclusion: Immunity plays an important role in the development of osteoporosis.CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1were play an important role in the occurrences and diagnosis of OP.
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Leucócitos Mononucleares , Osteoporose , Feminino , Humanos , Fosfatidilinositol 3-Quinases , Osteoporose/genética , Aprendizado de Máquina , Biologia Computacional , CitocinasRESUMO
Stroke prognosis is negatively associated with an elevation of serum bilirubin, but how bilirubin worsens outcomes remains mysterious. We report that post-, but not pre-, stroke bilirubin levels among inpatients scale with infarct volume. In mouse models, bilirubin increases neuronal excitability and ischemic infarct, whereas ischemic insults induce the release of endogenous bilirubin, all of which are attenuated by knockout of the TRPM2 channel or its antagonist A23. Independent of canonical TRPM2 intracellular agonists, bilirubin and its metabolic derivatives gate the channel opening, whereas A23 antagonizes it by binding to the same cavity. Knocking in a loss of binding point mutation for bilirubin, TRPM2-D1066A, effectively antagonizes ischemic neurotoxicity in mice. These findings suggest a vicious cycle of stroke injury in which initial ischemic insults trigger the release of endogenous bilirubin from injured cells, which potentially acts as a volume neurotransmitter to activate TRPM2 channels, aggravating Ca2+-dependent brain injury.
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Acidente Vascular Cerebral , Canais de Cátion TRPM , Animais , Camundongos , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Bilirrubina/metabolismo , Camundongos Knockout , Encéfalo/metabolismo , Infarto , Cálcio/metabolismoRESUMO
This paper presents the development of a compact, three-electrode electrochemical device functionalized by a biocompatible layer of hyaluronic acid methacrylate (HAMA) hydrogel for the adsorptive removal of detrimental lead (Pb(II)) ions in aqueous solutions. An adsorption mechanism pertaining to the observed analytical performance of the device is proposed and further experimentally corroborated. It is demonstrated that both the molecular interactions originating from the HAMA hydrogel and electrochemical accumulation originating from the electrode beneath contribute to the adsorption capability of the device. Infrared spectral analysis reveals that the molecular interaction is mainly induced by the amide functional group of the HAMA hydrogel, which is capable of forming the Pb(II)-amide complex. In addition, inductively coupled plasma mass spectrometric (ICP-MS) analysis indicates that the electrochemical accumulation is particularly valuable in facilitating the adsorption rate of the device by maintaining a high ion-concentration gradient between the solution and the hydrogel layer. ICP-MS measurements show that 94.08% of Pb(II) ions present in the test solution can be adsorbed by the device within 30 min. The HAMA hydrogel-modified electrochemical devices exhibit reproducible performance in the aspect of Pb(II) removal from tap water, with a relative standard deviation (RSD) of 1.28% (for n = 8). The experimental results suggest that the HAMA hydrogel-modified electrochemical device can potentially be used for the rapid, on-field remediation of Pb(II) contamination.
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Ácido Hialurônico , Poluentes Químicos da Água , Adsorção , Amidas , Hidrogéis , Concentração de Íons de Hidrogênio , Íons , Cinética , Chumbo , Metacrilatos , Soluções , Água/química , Poluentes Químicos da Água/químicaRESUMO
BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC. METHODS: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility. RESULTS: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of -347 to -358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744. CONCLUSIONS: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer.