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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. It severely affects the quality of life of victims. The prevalence of AD has been increasing in recent years. Therefore, it is of great importance to elucidate the pathogenic mechanism of AD and search for effective therapeutic approaches. Gut microbiota dysbiosis, an altered state of gut microbiota, has been well known for its involvement in the pathogenesis of AD. Much effort has been made in searching for approaches capable of modulating the composition of gut microbiota in recent years. Herbal medicines have attracted extensive attention in recent decades for the prevention and treatment of AD. Here, we gave an overview of the recent research progress on the modulatory effects of herbal medicines and herbal formulae on gut microbiota as well as the possible beneficial effects on AD, which may provide new insights into the discovery of anti-AD agents and their therapeutic potential for AD through modulating the composition of gut microbiota.
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The development of unstable carotid atherosclerotic plaques is associated with the induction of neutrophil extracellular traps (NETs) via the activation of diverse inflammatory mediators in the circulating bloodstream. However, the underlying mechanisms through which NETs influence the microenvironment of atherosclerotic plaques and contribute to the development of unstable carotid plaques remain largely elusive. The objective of this study was to elucidate the role of myeloid differentiation protein 1 (MD-1, LY86)-induced NETs underlying the crosstalk between unstable plaque formation and the plaque microenvironment. We employed bioinformatics analysis to identify key genes associated with carotid-unstable plaque, followed by comprehensive validation using various experimental approaches on tissue specimens and plasma samples classified based on pathological characteristics. Patients with carotid-unstable plaques exhibited elevated plasma concentrations of MD-1 (LY86), while patients with stable plaques demonstrated comparatively lower levels. Furthermore, soluble MD-1 was found to induce the formation of NETs through activation of Toll-like receptor signaling pathway. The proliferative and immature vascularization effects of NETs on endothelial cells, as well as their inhibitory impact on cell migration, are directly correlated with the concentration of NETs. Additionally, NETs were found to activate the NF-κB signaling pathway, thereby upregulating ICAM1, VCAM1, MMP14, VEGFA, and IL6 expression in both Human umbilical vein endothelial cells (HUVECs) and HAECs. Subsequently, a significant increase in intraplaque neovascularization by NETs results in poor carotid plaque stability, and NETs in turn stimulate macrophages to produce more MD-1, generating a harmful positive feedback loop. Our findings suggest that soluble MD-1 in the bloodstream triggers the production of NETs through activation of the Toll-like receptor signaling pathway and further indicate NETs mediate a crosstalk between the microenvironment of the carotid plaque and the neovascularization of the intraplaque region. Inhibiting NETs formation or MD-1 secretion may represent a promising strategy to effectively suppress the development of unstable carotid plaques.
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Objective: Pneumonia is a common and serious infectious disease that affects the older adult population. Severe pneumonia can lead to high mortality and morbidity in this group. Therefore, it is important to identify the risk factors and develop a prediction model for severe pneumonia in older adult patients. Method: In this study, we collected data from 1,000 older adult patients who were diagnosed with pneumonia and admitted to the intensive care unit (ICU) in a tertiary hospital. We used logistic regression and machine learning methods to analyze the risk factors and construct a prediction model for severe pneumonia in older adult patients. We evaluated the performance of the model using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and calibration plot. Result: We found that age, comorbidities, vital signs, laboratory tests, and radiological findings were associated with severe pneumonia in older adult patients. The prediction model had an accuracy of 0.85, a sensitivity of 0.80, a specificity of 0.88, and an AUC of 0.90. The calibration plot showed good agreement between the predicted and observed probabilities of severe pneumonia. Conclusion: The prediction model can help clinicians to stratify the risk of severe pneumonia in older adult patients and provide timely and appropriate interventions.
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Unidades de Terapia Intensiva , Pneumonia , Humanos , Idoso , Feminino , Fatores de Risco , Masculino , Idoso de 80 Anos ou mais , Modelos Logísticos , Curva ROC , Índice de Gravidade de Doença , Aprendizado de Máquina , Medição de Risco/métodos , Comorbidade , Fatores Etários , Centros de Atenção TerciáriaRESUMO
The plant homeodomain finger (PHD finger) protein, a type of zinc finger protein extensively distributed in eukaryotes, plays diverse roles in regulating plant growth and development. While PHD finger proteins have been identified in various species, their functions remain largely unexplored in pea (Pisum sativum). In this study, we identified 84 members of the PHD finger gene family in pea, which displayed an uneven distribution across seven chromosomes. Through a comprehensive analysis using data from Arabidopsis thaliana and Medicago truncatula, we categorized the PHD finger proteins into 20 subfamilies via phylogenetic tree analysis. Each subfamily exhibited distinct variations in terms of quantity, genetic structure, conserved domains, and physical and chemical properties. Collinearity analysis revealed conserved evolutionary relationships among the PHD finger genes across the three different species. Furthermore, we identified the conserved and important roles of the subfamily M members in anther development. RT-qPCR and in situ hybridization revealed high expression of the pea subfamily M members PsPHD11 and PsPHD16 in microspores and the tapetum layer. In conclusion, this analysis of the PHD finger family in pea provides valuable guidance for future research on the biological roles of PHD finger proteins in pea and other leguminous plants.
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Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor; GBM's inevitable recurrence suggests that glioblastoma stem cells (GSC) allow these tumors to persist. Our previous work showed that FOSL1, transactivated by the STAT3 gene, functions as a tumorigenic gene in glioma pathogenesis and acts as a diagnostic marker and potential drug target in glioma patients. Accumulating evidence shows that STAT3 and NF-κB cooperate to promote the development and progression of various cancers. The link between STAT3 and NF-κB suggests that NF-κB can also transcriptionally regulate FOSL1 and contribute to gliomagenesis. To investigate downstream molecules of FOSL1, we analyzed the transcriptome after overexpressing FOSL1 in a PDX-L14 line characterized by deficient FOSL1 expression. We then conducted immunohistochemical staining for FOSL1 and NF-κB p65 using rabbit polyclonal anti-FOSL1 and NF-κB p65 in glioma tissue microarrays (TMA) derived from 141 glioma patients and 15 healthy individuals. Next, mutants of the human FOSL1 promoter, featuring mutations in essential binding sites for NF-κB were generated using a Q5 site-directed mutagenesis kit. Subsequently, we examined luciferase activity in glioma cells and compared it to the wild-type FOSL1 promoter. Then, we explored the mutual regulation between NF-κB signaling and FOSL1 by modulating the expression of NF-κB or FOSL1. Subsequently, we assessed the activity of FOSL1 and NF-κB. To understand the role of FOSL1 in cell growth and stemness, we conducted a CCK-8 assay and cell cycle analysis, assessing apoptosis and GSC markers, ALDH1, and CD133 under varying FOSL1 expression conditions. Transcriptome analyses of downstream molecules of FOSL1 show that NF-κB signaling pathway is regulated by FOSL1. NF-κB p65 protein expression correlates to the expression of FOSL1 in glioma patients, and both are associated with glioma grades. NF-κB is a crucial transcription factor activating the FOSL1 promoter in glioma cells. Mutual regulation between NF-κB and FOSL1 contributes to glioma tumorigenesis and stemness through promoting G1/S transition and inhibiting apoptosis. Therefore, the FOSL1 molecular pathway is functionally connected to NF-κB activation, enhances stemness, and is indicative that FOSL1 may potentially be a novel GBM drug target.
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Regulação Neoplásica da Expressão Gênica , NF-kappa B , Células-Tronco Neoplásicas , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-fos , Animais , Humanos , Camundongos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , NF-kappa B/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genéticaRESUMO
This review specifically examines the important function of the oncoprotein FOSL1 in the dimeric AP-1 transcription factor, which consists of FOS-related components. FOSL1 is identified as a crucial controller of invasion and metastatic dissemination, making it a potential target for therapeutic treatment in cancer patients. The review offers a thorough examination of the regulatory systems that govern the influence exerted on FOSL1. These include a range of changes that occur throughout the process of transcription and after the translation of proteins. We have discovered that several non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a significant role in regulating FOSL1 expression by directly interacting with its mRNA transcripts. Moreover, an investigation into the functional aspects of FOSL1 reveals its involvement in apoptosis, proliferation, and migration. This work involves a comprehensive analysis of the complex signaling pathways that support these diverse activities. Furthermore, particular importance is given to the function of FOSL1 in coordinating the activation of several cytokines, such as TGF-beta, and the commencement of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that migrate into the tumor microenvironment. There is a specific emphasis on evaluating the predictive consequences linked to FOSL1. Insights are now emerging on the developing roles of FOSL1 in relation to the processes that drive resistance and reliance on specific treatment methods. Targeting FOSL1 has a strong inhibitory effect on the formation and spread of specific types of cancers. Despite extensive endeavors, no drugs targeting AP-1 or FOSL1 for cancer treatment have been approved for clinical use. Hence, it is imperative to implement innovative approaches and conduct additional verifications.
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Glioma , Células-Tronco Neoplásicas , Proteínas Proto-Oncogênicas c-fos , Humanos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Carcinogênese/genética , Microambiente Tumoral/genética , Transdução de Sinais , Oncogenes , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Semi-leafless represents an advantageous plant architecture in pea breeding due to its ability to enhance resistance to lodging and potentially to powdery mildew. The introduction of semi-leafless pea varieties is considered a seminal advancement in pea breeding over the past half-century. The afila (af) mutation leads to the replacement of lateral leaflets by highly branched tendrils; combined with the semi-dwarfing le mutation, it forms the semi-leafless cultivated variety. In this study, we identified that mutations in two tandemly-arrayed genes encoding Cys(2)His(2) zinc finger transcription factors, PsPALM1a and PsPALM1b, were closely associated with the afila phenotype. These two genes may be deleted in the af mutant. In situ hybridization showed that both genes exhibit specific expression in early leaflet primordia. Furthermore, suppression of PsPALM1a/PsPALM1b resulted in a high frequency of conversion of lateral leaflets into tendrils. In conclusion, our study provides genetic evidence demonstrating that mutations in PsPALM1a and PsPALM1b are responsible for the af locus, contributing to a better understanding of compound leaf formation in peas and offering new insights for breeding applications related to afila.
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Mutação , Fenótipo , Pisum sativum , Folhas de Planta , Proteínas de Plantas , Fatores de Transcrição , Pisum sativum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Folhas de Planta/genética , Regulação da Expressão Gênica de PlantasRESUMO
The expansion of large-scale aquaculture has exacerbated the challenge of aquatic diseases, resulting in substantial economic losses annually. Currently, traditional laboratory-based diagnostic methods are time-consuming and costly, hindering on-site testing for individual farmers. We address this issue by developing a state-of-the-art handheld isothermal nucleic acid amplification device (WeD-1) capable of fluorescence tracking of reactions and integrating it with an enhanced one-pot Prokaryotic Argonaute based nucleic acid detection method, enabling duplex visual detection of aquatic pathogens. WeD-1 is portable, reusable, user-friendly, and cost-effective, offering real-time smartphone interaction and enabling real-time fluorescence observation during the reaction. The enhanced one-pot Loop-Mediated Isothermal Amplification (LAMP)-PfAgo method, incorporating paraffin-encapsulated lyophilized PfAgo protein, achieves precise target-specific cleavage, significantly enhancing multiplex nucleic acid detection. This innovation streamlines on-site testing, negating the need for specialized laboratory conditions while ensuring an aerosol-free system. With newly developed and highly sensitive LAMP primer sets, our compact WeD-1/LAMP-PfAgo nucleic acid rapid testing system exhibits remarkable sensitivity, readily detecting aquatic pathogens with naked eyes from rapidly prepared fish and shrimp samples within 40 min, even when the Ct values are as high as 34.
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Técnicas Biossensoriais , Ácidos Nucleicos , Animais , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In lower vertebrates like fish, the inner ear and lateral line hair cells (HCs) can regenerate after being damaged by proliferation/differentiation of supporting cells (SCs). However, the HCs of mouse cochlear could only regenerate within one to two weeks after birth but not for adults. METHODS AND RESULTS: To better understand the molecular foundations, we collected several public single-cell RNA sequencing (scRNAseq) data of mouse cochleae from E14 to P33 and extracted the prosensory and supporting cells specifically. Gene Set Enrichment Analysis (GSEA) results revealed a down-regulation of genes in Notch signaling pathway during postnatal stages (P7 and P33). We also identified 107 time-course co-expression genes correlated with developmental stage and predicated that EZH2 and KLF15 may be the key transcriptional regulators for these genes. Expressions of candidate target genes of EZH2 and KLF15 were also found in supporting cells of the auditory epithelia in chick and the neuromasts in zebrafish. Furthermore, inhibiting EZH2 suppressed regeneration of hair cells in zebrafish neuromasts and altered expressions of some developmental stage correlated genes. CONCLUSIONS: Our results extended the understanding for molecular basis of hair cell regeneration ability and revealed the potential role of Ezh2 in it.
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Análise da Expressão Gênica de Célula Única , Animais , Camundongos , Proliferação de Células/genética , Células Ciliadas Auditivas/metabolismo , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: Although neck pain has become a serious economic and social problem worldwide, the etiology remains poorly understood. The aim of current study is to explore the possible pathogenesis of discogenic neck pain by analyzing the relationship between inflammatory cytokines and discogenic neck pain and provide a valuable reference for the prevention and treatment of discogenic neck pain. METHODS: A total of 111 cervical disc samples were collected between October 1, 2021, and October 1, 2022: 38 samples from the discogenic neck pain group, 41 samples from the symptomatic control group, and 32 samples from the normal control group. The concentration of nitric oxide (NO), interleukin (IL)-1, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was determined using the enzyme-linked immunosorbent assay in each sample, and the degeneration degree of the target discs were evaluated using T2-weighted sagittal magnetic resonance imaging (MRI) according to the Miyazaki disc degeneration grading system. Whether the differences among the three groups were statistically significant was tested using one-way analysis of variance and an unpaired t-test, respectively. RESULTS: The differences of the baseline characteristics were not statistically significant between the discogenic neck pain group and the symptomatic control group (p > 0.05). The expression of inflammatory cytokines in disc samples from the discogenic neck pain group (NO: 9.89 ± 1.75, IL-1ß: 10.74 ± 1.92, IL-6:31.65 ± 2.46, and TNF-α: 5.96 ± 1.91) was increased in comparison with the disc samples from both the symptomatic control group (NO: 7.15 ± 2.78, IL-1ß: 8.03 ± 1.87, IL-6: 25.79 ± 2.12, and TNF-α: 4.18 ± 2.87) and the normal control group (NO: 6.11 ± 1.37, IL-1ß: 5.84 ± 2.25, IL-6: 20.65 ± 1.26, and TNF-α: 2.05 ± 0.58). The differences were statistically significant (p < 0.001). Further, there were no statistical differences in the degree of degeneration between discogenic neck pain group and symptomatic control group. CONCLUSIONS: The increased expression of inflammatory cytokines in diseased cervical intervertebral discs might play a key role in the pathogenesis of discogenic neck pain. Although inflammation is involved in intervertebral disc degeneration, there is no linear positive correlation between the concentration of inflammatory cytokines and the degree of disc degeneration.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Citocinas/metabolismo , Degeneração do Disco Intervertebral/patologia , Cervicalgia/etiologia , Fator de Necrose Tumoral alfa , Interleucina-6 , Disco Intervertebral/metabolismo , Óxido Nítrico/metabolismoRESUMO
Plant lateral organs are often elaborated through repetitive formation of developmental units, which progress robustly in predetermined patterns along their axes. Leaflets in compound leaves provide an example of such units that are generated sequentially along the longitudinal axis, in species-specific patterns. In this context, we explored the molecular mechanisms underlying an acropetal mode of leaflet initiation in chickpea pinnate compound leaf patterning. By analyzing naturally occurring mutants multi-pinnate leaf1 (mpl1) that develop higher-ordered pinnate leaves with more than forty leaflets, we show that MPL1 encoding a C2H2-zinc finger protein sculpts a morphogenetic gradient along the proximodistal axis of the early leaf primordium, thereby conferring the acropetal leaflet formation. This is achieved by defining the spatiotemporal expression pattern of CaLEAFY, a key regulator of leaflet initiation, and also perhaps by modulating the auxin signaling pathway. Our work provides novel molecular insights into the sequential progression of leaflet formation.
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Cicer , Cicer/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/genética , Folhas de Planta/metabolismo , Morfogênese , Ácidos Indolacéticos/metabolismoRESUMO
Purpose: To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP. Patients and Methods: We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery. Relevant occupational and demographic data from all patients were statistically analyzed, and all variables were made categorical. Forward stepwise logistic regression models were constructed for preoperative chronic neck pain to explore the possible risk factors associated with chronic neck pain. Results: The differences in smoking, being an office worker, BMI, and disease types between NP and no-NP groups were statistically significant. In contrast, there were no statistically significant in age, sex, academic level, duration, and degeneration grade between the two groups. Moreover, further logistic regression analysis indicated that smoking, being an office worker, having an abnormal BMI, and cervical spondylotic radiculopathy (CSR) were related to chronic neck pain. Conclusion: The present study indicated that smoking, being an office worker, having an abnormal BMI, and CSR were predisposing risk factors for NP associated with cervical degenerative disease. Although intervertebral disc degeneration is the pathology basis of NP, the degeneration grade was not related to the occurrence of NP in our current study. Therefore, quitting smoking, avoiding sedentariness, and maintaining a normal BMI may prevent NP to some extent.
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In order to overcome the defects of fast-growing poplar wood, such as low strength and poor toughness, this paper introduces a method of modifying poplar wood via impregnation with silica sol/melamine-glyoxal (silica sol/MG) resin and explores its effects on the physical, mechanical, and thermal properties of poplar wood. It was found via scanning electron microscopy that the composite modifier covered and filled the cell lumen, cell interstitial space, and cell wall pores of poplar wood. Further, infrared spectroscopy and X-ray photoelectron spectroscopy analyses confirmed that chemical cross-linking occurred between the silica sol/MG resin composite modifier and the internal groups of poplar wood and that the Si-O-Si flexible long chains introduced in the composite modifier formed a cross-linking network with poplar wood such as Si-O-Si and Si-O-C, which led to the improvement of the physical and mechanical properties and the enhancement of the thermal stability of poplar wood. The method provides a theoretical basis for the high-value utilization of fast-growing poplar wood.
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Plant organ size is an important agronomic trait tightly related to crop yield. However, the molecular mechanisms underlying organ size regulation remain largely unexplored in legumes. We previously characterized a key regulator F-box protein MINI ORGAN1 (MIO1)/SMALL LEAF AND BUSHY1 (SLB1), which controls plant organ size in the model legume Medicago truncatula. In order to further dissect the molecular mechanism, MIO1 was used as the bait to screen its interacting proteins from a yeast library. Subsequently, a KIX protein, designated MtKIX8, was identified from the candidate list. The interaction between MIO1 and MtKIX8 was confirmed further by Y2H, BiFC, split-luciferase complementation and pull-down assays. Phylogenetic analyses indicated that MtKIX8 is highly homologous to Arabidopsis KIX8, which negatively regulates organ size. Moreover, loss-of-function of MtKIX8 led to enlarged leaves and seeds, while ectopic expression of MtKIX8 in Arabidopsis resulted in decreased cotyledon area and seed weight. Quantitative reverse-transcription PCR and in situ hybridization showed that MtKIX8 is expressed in most developing organs. We also found that MtKIX8 serves as a crucial molecular adaptor, facilitating interactions with BIG SEEDS1 (BS1) and MtTOPLESS (MtTPL) proteins in M. truncatula. Overall, our results suggest that the MIO1-MtKIX8 module plays a significant and conserved role in the regulation of plant organ size. This module could be a good target for molecular breeding in legume crops and forages.
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Proteínas de Arabidopsis , Arabidopsis , Medicago truncatula , Medicago truncatula/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Tamanho do Órgão , Filogenia , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
Layered narrow bandgap quasi-two-dimensional (2D) transition metal dichalcogenides (TMDs) demonstrated excellent performance in long-wave infrared (LWIR) detection. However, the low light on/off ratio and specific detectivity (D*) due to the high dark current of the device fabricated using a single narrow bandgap material hindered its wide application. Herein, we report a type-III broken-gap band-alignment WSe2/PdSe2 van der Waals (vdW) heterostructure. The heterodiode device has a prominently low dark current and exhibits a high photoresponsivity (R) of 55.3 A W-1 and a high light on/off ratio >105 in the visible range. Notably, the WSe2/PdSe2 heterodiode shows an excellent uncooled LWIR response, with an R of â¼0.3 A W-1, a low noise equivalence power (NEP) of 4.5 × 10-11 W Hz-1/2, and a high D* of 1.8 × 108 cm Hz1/2 W-1. This work provides a new approach for designing high-performance room-temperature operational LWIR photodetectors.
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Children with ADHD are frequently reported to demonstrate a positive illusory bias in multiple domains. Less is known about such a bias in college students. This study examined academic positive illusory bias in college students and whether cultural factors play a role in its expression. A total of 633 college students from China and the United States completed measures designed to assess biased self-perception of academics. Among other measures, the nonclinical sample completed a math task and then estimated their own achievement and completed measures of intellectual and scholastic self-competence. Symptoms of ADHD were unrelated to overconfidence on the math task and were negatively related to reports of self-competence. However, individualism and collectivism were related to overconfidence and self-competence. In contrast to results from research in other domains, academic positive illusory bias among those with more symptoms of ADHD does not appear to persist into college.
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Transtorno do Deficit de Atenção com Hiperatividade , Ilusões , Criança , Estados Unidos , Humanos , China , Autoimagem , EstudantesRESUMO
The present study explores the potentials of bioinformatics analysis to identify hub genes linked to intervertebral disc degeneration (IDD) and explored the potential molecular mechanism of transcription factor-microRNA regulatory network. Furthermore, the hub genes were identified through quantitative reverse transcriptase PCR (qRT-PCR). GEO database expression profile datasets for candidate genes (GSE124272) were downloaded. Genes that were differentially expressed (DEGs) were detected utilizing limma technique in the R programming language. Search Tool for the Retrieval of Interacting Genes/Proteins and NetworkAnalyst software identified hub genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis as well as Gene Ontology annotation of the DEGs were performed using Metascape. Using Bioinformatics data from the TRRUST, StarBase, and TransmiR databases, a TF-miRNA-hub genes network was constructed. qRT-PCR was utilized to confirm the result. As compared to healthy persons, 521 DEGs, comprising 203 down-regulated and 318 up-regulated genes, as well as 7 core genes, were found in people with IDD. Analysis revealed that all seven essential genes were under-expressed. qRT-PCR further confirmed the low expression of these seven important genes. Based on the TRRUST database, 16 TFs that could target five junction genes were then predicted. According to the StarBase database, four miRNAs were linked to crucial genes, while the TransmiR database predicted regulatory connections between four miRNAs and five TFs. The expression of the TP53-(hsa-miR-183-5p)-CCNB1 TF-miRNA-mRNA interaction network was discovered to be correlated with IDD. Throughout this investigation, a network of TF-miRNA-mRNA connections was built for investigation of the probable molecular mechanisms responsible for IDD. The identification of hub genes associated with IDD may reveal promising IDD treatment strategies.
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INTRODUCTION: We previously reported that TRPM7 regulates glioma cells' stemness through STAT3. In addition, we demonstrated that FOSL1 is a response gene for TRPM7, and the FOSL1 gene serves as an oncogene to promote glioma proliferation and invasion. METHODS: In the present study, we determined the effects of FOSL1 on glioma stem cell (GSC) markers CD133 and ALDH1 by flow cytometry, and the maintenance of stem cell activity by extreme limiting dilution assays (ELDA). To further gain insight into the mechanism by which TRPM7 activates transcription of the FOSL1 gene to contribute to glioma stemness, we constructed a FOSL1 promoter and its GAS mutants followed by luciferase reporter assays and ChIP-qPCR in a glioma cell line and glioma patient-derived xenoline. We further examined GSC markers ALDH1 and TRPM7 as well as FOSL1 by immunohistochemistry staining (IHC) in brain tissue microarray (TMA) of glioma patients. RESULTS: We revealed that FOSL1 knockdown reduces the expression of GSC markers CD133 and ALDH1, and FOSL1 is required to maintain stem cell activity in glioma cells. The experiments also showed that mutations of - 328 to - 336 and - 378 to - 386 GAS elements markedly reduced FOSL1 promoter activity. Constitutively active STAT3 increased while dominant-negative STAT3 decreased FOSL1 promoter activity. Furthermore, overexpression of TRPM7 enhanced while silencing of TRPM7 reduced FOSL1 promoter activity. ChIP-qPCR assays revealed that STAT3, present in nuclear lysates of glioma cells stimulated by constitutively activated STAT3, can bind to two GAS elements, respectively. We demonstrated that deacetylation of FOSL1 at the Lys-116 residue located within its DNA binding domain led to an increase in FOSL1 transcriptional activity. We found that the expression of TRPM7, ALDH1, and FOSL1 protein is associated with grades of malignant glioma, and TRPM7 protein expression correlates to the expression of ALDH1 and FOSL1 in glioma patients. CONCLUSIONS: These combined results demonstrated that TRPM7 induced FOSL1 transcriptional activation, which is mediated by the action of STAT3, a mechanism shown to be important in glioma stemness. These results indicated that FOSL1, similar to GSC markers ALDH1 and TRPM7, is a diagnostic marker and potential drug target for glioma patients.
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Glioma , Canais de Cátion TRPM , Humanos , Canais de Cátion TRPM/genética , Oncogenes , Bioensaio , Encéfalo , Glioma/genética , Proteínas Serina-Treonina Quinases , Fator de Transcrição STAT3/genéticaRESUMO
BACKGROUND: Nurse engagement and retention are critical issues affecting the quality of healthcare. Although the work environment is known to affect nursing performance and patient outcomes, little is known regarding the impact of this environment on nurse burnout and future work intention, especially in non-Western settings. PURPOSE: This study explored the extent to which Taiwanese nurses' perceptions of their practice environment mediates burnout levels and intention-to-stay. METHODS: This descriptive, correlational study, conducted between September and December 2020, recruited nurses employed at a regional teaching hospital located in a relatively rural region in Taiwan. The participants completed standardized questionnaires, including a demographic information form, the 31-item Practice Environment Scale of the Nursing Work Index (PES-NWI), the 22-item Maslach Burnout Inventory (MBI-HSS), and the 6-item Intention-to-stay (ITS) scale. The mediating effect among the variables related to intention-to-stay was examined using Model 4 of the PROCESS macro and tested using the bootstrapping method (repeated 5,000 times) with a p value < .05. RESULTS: The mean age of the 376 participants was 34.3 years (SD = 8.1). Nearly one-third (30.3%) scored > 27 on the emotional exhaustion subscale of the MBI-HSS, indicating they were "highly burned-out". Also, nearly one-third (30.6%) were uncertain about their intention to stay with their current employer. Burnout was associated with intention-to-stay (ß = -.088, p < .001), and holding a positive perception toward their practice environment was shown to mediate the relationship between burnout and intention-to-stay (ß = -.015; p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Targeted interventions and technical support that promote a collaborative climate and psychological empowerment in clinical practice may alleviate burnout and intention-to-leave in nurses and improve workplace quality.