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BACKGROUND: Expanding the number of biomarkers is imperative for studying the etiology and improving venous thromboembolism prediction. In this study, we aimed to identify promising biomarkers or targeted therapies to improve the detection accuracy of early-stage deep vein thrombosis (DVT) or reduce complications. METHODS: Quantibody Human Cytokine Antibody Array 440 (QAH-CAA-440) was used to screen novel serum-based biomarkers for DVT/non-lower extremity DVT (NDVT). Differentially expressed proteins in DVT were analyzed using bioinformatics methods and validated using a customized array. Diagnostic accuracy was calculated using receiver operating characteristics, and machine learning was applied to establish a biomarker model for evaluating the identified targets. Twelve targets were selected for validation. RESULTS: Cytokine profiling was conducted using a QAH-CAA-440 (RayBiotech, USA) quantimeter array. Cross-tabulation analysis with Venn diagrams identified common differential factors, leading to the selection of 12 cytokines for validation based on their clinical significance. These 12 biomarkers were consistent with the results of previous array analysis: FGF-6 (AUC = 0.956), Galectin-3 (AUC = 0.942), EDA-A2 (AUC = 0.933), CHI3L1 (AUC = 0.911), IL-1 F9 (AUC = 0.898), Dkk-4 (AUC = 0.88), IG-H3 (AUC = 0.876), IGFBP (AUC = 0.858), Gas-1 (AUC = 0.858), Layilin (AUC = 0.849), ULBP-2 (AUC = 0.813)and FGF-9 (AUC = 0.773). These cytokines are expected to serve as biomarkers, targets, or therapeutic targets to differentiate DVT from NDVT. CONCLUSIONS: EDA-A2, FGF-6, Dkk-4, IL-1 F9, Galentin-3, Layilin, Big-h3, CHI3L1, ULBP-2, Gas-1, IGFBP-5, and FGF-9 are promising targets for DVT diagnosis and treatment.
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Biomarcadores , Citocinas , Valor Preditivo dos Testes , Análise Serial de Proteínas , Trombose Venosa , Humanos , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Biomarcadores/sangue , Citocinas/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Reprodutibilidade dos Testes , Idoso , Aprendizado de Máquina , Estudos de Casos e Controles , Proteômica , AdultoRESUMO
Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.
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Biomarcadores , Calgranulina A , Molécula 1 de Adesão Intercelular , Molécula 1 de Adesão de Célula Vascular , Trombose Venosa , Trombose Venosa/diagnóstico , Trombose Venosa/metabolismo , Trombose Venosa/sangue , Humanos , Calgranulina A/sangue , Calgranulina A/metabolismo , Biomarcadores/sangue , Animais , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Ratos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Pessoa de Meia-Idade , Feminino , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais , Modelos Animais de Doenças , Adulto , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.
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The LD oilfield is one of the representative offshore oilfields. After weak gel flooding, the recovery rate is significantly improved. However, the oilfield is then in a medium- to high-water content stage, presenting a complex distribution of the remaining oil. The measures for further enhanced oil recovery (EOR) are uncertain. As a result, it is necessary to clarify the distribution pattern and development potential of the remaining oil during the high-water content period after weak gel flooding. In this study, an online nuclear magnetic resonance (NMR) oil displacement experiment and microscopic oil displacement experiment were conducted, and the mechanisms of weak gel flooding and the distribution pattern of the remaining oil were clarified in the LD oilfield. Additionally, high-multiple water flooding and numerical simulation experiments were conducted to analyze the development potential after weak gel flooding. The results show that the effect of weak gel flooding was more significant in the core of 1500 mD, with an increase in oil recovery of 9% compared to 500 mD. At a permeability of 500 mD, the degree of crude oil mobilization in micropores and small pores caused by weak gel flooding was improved by 29.64% and 23.48%, respectively, compared with water flooding. At 1500 mD, the degree of crude oil mobilization in small pores caused by weak gel flooding was increased by 37.79% compared to water flooding. After weak gel flooding, the remaining oil was primarily distributed in medium and large pores. Microscopically, the remaining oil was dominated by cluster residual oil, accounting for 16.49%, followed by columnar, membranous, and blind-end residual oil. High multiple water flooding experiments demonstrated that weak gel flooding could significantly reduce development time. The ultimate oil recovery efficiency of 500 mD and 1500 mD reached 71.85% and 80.69%, respectively. Numerical simulation results show that the ultimate oil recovery efficiency increased from 62.04% to 71.3% after weak gel flooding. This indicated that the LD oilfield still had certain development potential after weak gel flooding. The subsequent direction for enhanced oil recovery focuses mainly on mobilizing oil in medium pores or clustered remaining oil. This will play a crucial role in further exploring methods for utilizing the remaining oil and increasing the recovery rate.
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Teosinte branched 1/Cycloidea/Proliferating cell factor (TCP) transcription factors function in abiotic stress responses. However, how TCPs confer salt tolerance is unclear. Here, we characterized a TCP transcription factor, BpTCP20, that responds to salt stress in birch (Betula platyphylla Suk). Plants overexpressing BpTCP20 displayed increased salt tolerance, and Bptcp20 knockout mutants displayed reduced salt tolerance relative to the wild-type (WT) birch. BpTCP20 conferred salt tolerance by mediating stomatal closure and reducing reactive oxygen species (ROS) accumulation. Chromatin immunoprecipitation sequencing showed that BpTCP20 binds to NeuroD1, T-box, and two unknown elements (termed TBS1 and TBS2) to regulate target genes. In birch, salt stress led to acetylation of BpTCP20 acetylation at lysine 259. A mutated BpTCP20 variant (abolished for acetylation, termed BpTCP20259) was overexpressed in birch, which led to decreased salt tolerance compared with plants overexpressing BpTCP20. However, BpTCP20259-overexpressing plants still displayed increased salt tolerance relative to untransformed WT plants. BpTCP20259 showed reduced binding to the promoters of target genes and decreased target gene activation, leading to decreased salt tolerance. In addition, we identified dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (BpPDCE23), an acetyltransferase that interacts with and acetylates BpTCP20 to enhance its binding to DNA motifs. Together, these results suggest that BpTCP20 is a transcriptional regulator of salt tolerance, whose activity is modulated by BpPDCE23-mediated acetylation.
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Betula , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Tolerância ao Sal , Fatores de Transcrição , Tolerância ao Sal/genética , Acetilação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Betula/genética , Betula/metabolismo , Betula/fisiologia , Acetiltransferases/metabolismo , Acetiltransferases/genética , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio/metabolismoRESUMO
Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.
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Actinidia , Genoma de Planta , Tetraploidia , Actinidia/genética , Evolução Molecular , Adaptação Fisiológica/genética , Evolução BiológicaRESUMO
Environmental awareness is receiving increasing attention in the petroleum industry, especially when associated with chemical agents applied in enhanced oil recovery (EOR) technology. The bio-based surfactant sodium cocoyl alaninate (SCA) is environmentally friendly and can be easily biodegraded, which makes it a promising alternative to traditional surfactants. Herein, the SCA surfactant is proposed as a foaming agent for enhanced oil recovery. Laboratory investigations on the surfactant concentration, foaming performance, microbubble characterization, interfacial tension, and foam-flooding of the traditional surfactants SDS and OP-10 have been conducted. In particular, the anti-salt abilities of these three surfactants have been studied, taking into consideration the reservoir conditions at Bohai Bay Basin, China. The results show that concentrations of 0.20 wt%, 0.20 wt% and 0.50 wt% for SCA, SDS and OP-10, respectively, can achieve optimum foaming ability and foaming stability under formation salinity conditions, and 0.20 wt% SCA achieved the best foaming ability and stability compared to 0.20 wt% SDS and 0.50 wt% OP-10. Sodium fatty acid groups and amino acid groups present in the SCA molecular structure have high surface activities under different salinity conditions, making SCA an excellent anti-salt surfactant for enhanced oil recovery. The microstructure analysis results showed that most of the SCA bubbles were smaller in size, with an average diameter of about 150 µm, and the distribution of SCA bubbles was more uniform, which can reduce the risk of foam coalescence and breakdown. The IFT value of the SCA/oil system was measured to be 0.157 mN m-1 at 101.5 °C, which was the lowest. A lower IFT can make liquid molecules more evenly distributed on the surface, and enhance the elasticity of the foam film. Core-flooding experimental results showed that a 0.30 PV SCA foam and secondary waterflooding can enhance oil recovery by more than 15% after primary waterflooding, which can reduce the mobility ratio from 3.7711 to 1.0211. The more viscous SCA foam caused a greater flow resistance, and effectively reduced the successive water fingering, leading to a more stable driving process to fully displace the remaining oil within the porous media. The bio-based surfactant SCA proposed in this paper has the potential for application in enhanced oil recovery in similar high-salt oil reservoirs.
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In order to detect the effect of EZH2 genes on proliferation, migration, invasion, and apoptosis of colon carcinoma cell strains HCT116 and HT29 by the Wnt/ß-catenin signaling pathway, qRT-PCR was applied to measure relative expressions of EZH2, RUNX3, CEA, CA199, MMP-9, VEGF, ß-catenin, and CyclinD1 in each group; Western-blot was employed with the intention of exploring relative expressions of these proteins in vivo and in vitro; monoclonal proliferation experiments and CCK-8 assay was adopted so as to check cell proliferation; the effect on cell migration was investigated via Transwell assay and cell scratch wound assay; flow cytometry was applied with a view to determining the effect on cell apoptosis. Transfected HCT116 cells are injected subcutaneously into nude mice. In colon cell strains HCT-116 and HT29, contrasted to the si-NC group, the RUNX3 expression was prominently up-regulated in the si-EZH2 group. Besides, expressions of CEA, CA199, MMP-9, and VEGF were significantly reduced; down-regulation of EZH2 genes remarkably inhibited cell proliferation, invasion and migration when facilitating apoptosis; down-regulation of EZH2 genes also significantly reduced expressions of essential proteins ß-catenin and CyclinD1 on the Wnt pathway. The subcutaneous tumor body of nude mice was reduced. EZH2-OE is the opposite trend to si-EZH2; The EZH2 gene may target regulatory RUNX3 regulation via that Wnt/ß-catenin signaling pathway, hence affecting colon carcinoma cell proliferation, invasion, migration, and apoptosis. Therefore, EZH2 may become a promising target for the clinical therapy of colon carcinoma.
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Carcinoma , Neoplasias do Colo , MicroRNAs , Animais , Humanos , Camundongos , beta Catenina/genética , beta Catenina/metabolismo , Carcinoma/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt/genéticaRESUMO
How liquids transport in the shale system has been the focus because of fracturing fluid loss. In this study, a single-nanopore model is established for liquid transport in shale while considering the slip effect and effective viscosity of confined fluids. Then, the fractal Monte Carlo (FMC) model is proposed to upscale the single-pore model into shale porous media. The effects of different transport mechanisms, shale wettability, and pore characteristic parameters on confined liquid flow in shale rock are investigated. Results show that FMC permeabilities are 2-3 orders of magnitude larger than intrinsic and slip-corrected permeabilities in organic matter. However, the slip effect and effective viscosity have little influence on water flow in inorganic matter. With the contact angle of organic pore (θom) increasing and contact angle of inorganic pore (θin) decreasing, the effective permeability of the whole shale matrix grows in number. The enhancement factor in the situation of θom = 170° and θin = 20° is 4 orders of magnitude larger than the case of θom = 130° and θin = 40°, although the close effective macroscopic contact angle (θeff = 80°) occurs in these two cases, which indicates that shale microscopic wettability has a significant impact on the confined liquid transport. Moreover, with the increase of porosity and maximum pore diameters, shale permeability increases rapidly, but the enhancement factor has the opposite trend. Compared with the tiny impact of the variance of minimum inorganic pore diameters, minimum organic pore diameters have more significant impacts on liquid flow in shale systems, and the enhancement factor also rapidly increases up to 30 times for the case of 0.5 nm because of the strong slip effect.
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Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
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Hiperuricemia , Óxido Nítrico , Humanos , Ácido Úrico , Disponibilidade Biológica , CitocinasRESUMO
SARS-CoV-2-positive patients exhibit gut and oral microbiome dysbiosis, which is associated with various aspects of COVID-19 disease (1-4). Here, we aim to identify gut and oral microbiome markers that predict COVID-19 severity in hospitalized patients, specifically severely ill patients compared to moderately ill ones. Moreover, we investigate whether hospital feeding (solid versus enteral), an important cofounder, influences the microbial composition of hospitalized COVID-19 patients. We used random forest classification machine learning models with interpretable secondary analyses. The gut, but not the oral microbiota, was a robust predictor of both COVID-19-related fatality and severity of hospitalized patients, with a higher predictive value than most clinical variables. In addition, perturbations of the gut microbiota due to enteral feeding did not associate with species that were predictive of COVID-19 severity. IMPORTANCE SARS-CoV-2 infection leads to wide-ranging, systemic symptoms with sometimes unpredictable morbidity and mortality. It is increasingly clear that the human microbiome plays an important role in how individuals respond to viral infections. Our study adds to important literature about the associations of gut microbiota and severe COVID-19 illness during the early phase of the pandemic before the availability of vaccines. Increased understanding of the interplay between microbiota and SARS-CoV-2 may lead to innovations in diagnostics, therapies, and clinical predictions.
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COVID-19 , Microbioma Gastrointestinal , Humanos , SARS-CoV-2 , Métodos de Alimentação , HospitaisRESUMO
The expansion of power development industry is facing enormous pressure to reduce carbon emissions in the context of global decarbonization. Using solar energy instead of traditional fossil energy to adjust energy structure is one of the important means for reducing carbon emissions. Existing research focuses on the evaluation of the generation potential of centralized or distributed photovoltaic power plants, rather than the comprehensive evaluation of multi-type power plants. Based on multi-source remote sensing data for information extraction and suitability evaluation, this paper develops a method to comprehensively evaluate the construction potential of multi-type photovoltaic power stations and determine the potential of photovoltaic power generation and carbon emission reduction on the Qinghai-Tibet Plateau (QTP). The results showed that estimating the power generation potential of only single-type photovoltaic power stations cannot accurately reflect the photovoltaic power generation potential of QTP. It is also demonstrated that the emission reduction effect of the photovoltaic power generation in all prefecture-level cities of QTP can meet national emission reduction targets, showing high annual power generation potential, of which 86.59% is concentrated in Qinghai province's Guoluo, Yushu, and Haixi. An accurate estimation of the photovoltaic power generation potential in QTP can provide a useful theoretical basis for developing carbon-saving and emission reduction strategies for clean energy in China.
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Carbono , Energia Solar , Tibet , Carbono/análise , Monitoramento Ambiental/métodos , ChinaRESUMO
BACKGROUND: Trajectories of pulse oxygen saturation (SpO2) within the first few days after birth are important to inform the strategy for identifying asymptomatic hypoxemic disease but remain poorly substantiated at higher altitudes. METHODS: We performed a longitudinal cohort study with consecutive neonates at a local hospital in Luchun County, China, at an altitude of 1650 m between January and July 2020. We repeatedly measured the pre- and post-ductal SpO2 values at 6, 12, 18, 24, 36, 48, and 72 hours after birth for neonates without oxygen supplements. All neonates underwent echocardiography and were followed up to 42 days after discharge. We included neonates without hypoxemic diseases to characterize the trajectories of SpO2 over time using a linear mixed model. We considered the 2.5th percentile as the reference value to define hypoxemic conditions. RESULTS: A total of 1061 neonates were enrolled. Twenty-five had non-cardiac hypoxemic diseases, with 84% (21/25) presenting with abnormal SpO2 within 24 hours. One had tetralogy of Fallot identified by echocardiography. Among the 1035 asymptomatic neonates, SpO2 values declined from 6 hours after birth, reached a nadir at 48 hours, and tended to level off thereafter, with identical patterns for both pre- and post-ductal SpO2. The reference percentile was 92% for both pre- and post-ductal SpO2 and was time independent. CONCLUSIONS: A decline within 48 hours features SpO2 trajectories within the first 72 hours at moderate altitude. Our findings suggest that earlier screening may favorably achieve a benefit-risk balance in identifying asymptomatic hypoxemic diseases in this population.
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Altitude , Oximetria , Recém-Nascido , Humanos , Estudos Prospectivos , Estudos Longitudinais , Saturação de Oxigênio , Oxigênio , Estudos de CoortesRESUMO
The purpose of this study is to obtain the reference range of peripheral perfusion index (PPI) of asymptomatic well newborns at 6 to 72 h of life at different altitudes. A population-based prospective cohort study was conducted in cities at different altitudes in China. Asymptomatic well newborns were enrolled consecutively from six hospitals with an altitude of 4 to 4200 m between February 1, 2020, and April 15, 2021. PPI was measured at 6, 12, 24, 48, and 72 h after birth on the right hand (pre-ductal) and either foot (post-ductal) using a Masimo SET Radical-7 oximeter. Fiftieth percentile reference curves of the pre- and post-ductal PPI values at 6-72 h after birth were generated using the Lambda Mu Sigma method. Linear mixed-effects regression was performed to determine the influence of different altitude levels on PPI values over different measurement time points. A total of 4257 asymptomatic well newborns were recruited for analysis. The median and quartile pre- and post-ductal PPI values at 6-72 h of life at different altitudes were 1.70 (1.20, 2.60) and 1.70 (1.10, 2.70) for all infants, 1.30 (1.10, 1.90) and 1.10 (0.88, 1.80) for infants at low altitude, 1.40 (1.00, 2.00) and 1.30 (0.99, 2.00) at mild altitudes, 1.90 (1.30, 2.50) and 1.80 (1.20, 2.70) at moderate altitudes, 1.80 (1.40, 3.50) and 2.20 (1.60, 4.30) for high altitudes, 3.20 (2.70, 3.70), and 3.10 (2.10, 3.30) for higher altitudes, respectively. Overall, both pre- and post-ductal PPI increased with altitude. The 50th percentile curves of pre- and post-ductal PPI values in well newborns at mild, low, moderate, and high altitudes were relatively similar, while the difference between the PPI curves of infants at higher altitudes and other altitudes was significantly different. Conclusions: With the increase of altitude, pre- and post-ductal PPI of newborns increases. Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. What is Known: ⢠Monitoring hemodynamics is very important to neonates. As an accurate and reliable hemodynamic monitoring index, PPI can detect irreversible damage caused by insufficient tissue perfusion and oxygenation early, directly, noninvasively, and continuously. What is New: ⢠Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. With the increase of altitude, pre- and post-ductal PPI of newborns increase with statistical significance. Therefore, the values and disease thresholds of PPI for asymptomatic neonates should be modified according to altitudes.
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Altitude , Índice de Perfusão , Lactente , Humanos , Recém-Nascido , Estudos Prospectivos , Oximetria , ChinaRESUMO
DNA-protein interaction is one of the most crucial interactions in biological processes. However, the technologies available to study DNA-protein interactions are all based on DNA hybridization; however, DNA hybridization is not highly specific and is relatively low in efficiency. RNA-guided DNA recognition is highly specific and efficient. To overcome the limitations of technologies based on DNA hybridization, we built a DNA-binding protein capture technology based on the clustered regularly interspaced palindromic repeats (CRISPR)-dead Cas9 (dCas9) system and transient genetic transformation, termed reverse chromatin immunoprecipitation based on CRISPR-dCas9 system (R-ChIP-dCas9). In this system, dCas9 was fused with Strep-Tag II to form a fusion protein for StrepTactin affinity purification. Transient transformation was performed for the expression of dCas9 and guide RNA (gRNA) to form the dCas9-gRNA complex in birch (Betula platyphylla) plants, which binds to the target genomic DNA region. The dCas9-gRNA-DNA complex was crosslinked, then the chromatin was sonicated into fragments, and purified using StrepTactin beads. The proteins binding to the target genomic DNA region were identified using mass spectrometry. Using this method, we determined the upstream regulators of a NAM, ATAF, and CUC (NAC) transcription factor (TF), BpNAC090, and 32 TFs potentially regulating BpNAC090 were identified. The reliability of R-ChIP-dCas9 was further confirmed by chromatin immunoprecipitation, electrophoretic mobility shift assays, and yeast one-hybrid. This technology can be adapted to various plant species and does not depend on the availability of a stable transformation system; therefore, it has wide application in identifying proteins bound to genomic DNA.
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DNA , Plantas , Reprodutibilidade dos Testes , Imunoprecipitação da Cromatina/métodos , RNA , Sistemas CRISPR-Cas/genéticaRESUMO
BACKGROUND: Glioblastoma is the most common and most aggressive type of primary brain tumor. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of intranasal granulocyte-macrophage colony stimulating factor (GM-CSF) administration combined with chemoradiotherapy in patients with glioblastoma who underwent surgery. METHODS: Ninety-two patients were randomly divided into two groups: a control group (n= 46), who received radiotherapy with adjuvant local delivery of nimustine hydrochloride (ACNU) and systemic administration of temozolomide, and an intervention group (n= 46), who received intranasal GM-CSF prior to each cycle of adjuvant chemotherapy in addition to the treatment of the control group. Karnofsky performance status (KPS) scores, progression-free survival (PFS), overall survival (OS), and adverse effects were calculated and compared between the two groups. RESULTS: Compared with the control group, the intervention group had longer PFS (7.8 vs. 6.9 months, P= 0.016) and OS (19.2 vs. 17.1 months, P= 0.045, without adjustment for interim analyses). The KPS scores were also higher in the intervention group than in the control group after 6 months (84.35 ± 8.86 vs. 80.65 ± 7.72; t= 4.552, P= 0.036). Furthermore, the patients in the intervention group had lower incidence of neutropenia and thrombocytopenia (8.7% vs. 29.5%, P= 0.012; 8.7% vs. 18.2%, P= 0.186). Other adverse events were similar in both groups, and most adverse events were grade I/II and resolved spontaneously. CONCLUSION: Intranasal GM-CSF enhances the efficacy of the local ACNU administration combined with oral temozolomide chemotherapy. The survival and performance status were significantly improved in patients with glioblastoma after surgery. Additionally, the GM-CSF therapy was able to reduce the occurrence of chemotherapy-related neutropenia and thrombocytopenia.
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Neoplasias Encefálicas , Glioblastoma , Neutropenia , Trombocitopenia , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Nimustina/uso terapêutico , Fator Estimulador de Colônias de Macrófagos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neutropenia/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Granulócitos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapiaRESUMO
The basilar artery has the most perioperative complications in stenting compared to the other intracranial arteries. We aim to study whether the procedural safety in stenting for basilar stenosis has improved. This study was a single-arm, non-randomized trial that included historically controlled patients for comparison. Between January 2012 and March 2019, 147 consecutive patients with symptomatic basilar stenoses receiving elective stenting treatment were included in current basilar artery stenting (BAS) group. The prospectively collected and registered 120 patients by the same interventional team from September 2001 to November 2011 were set as historical BAS group for control. A total of 267 individuals were included in this study, with a mean age of 59.5â ±â 8.1 years. The proportion of patients with lesion length >15 mm was 26.5% (39/147) in the current BAS group versus 4.2% (5/120) in the historical BAS group. We found significant differences between these 2 groups in Mori A (17.7% vs 42.5%) and Mori C patients (42.9% vs 13.3%). The proportion of patients receiving preoperative high-resolution magnetic resonance (HRMRI) evaluation was 83.0% (122/147) in the current BAS group versus 20.8% (25/120) in the historical group (Pâ <â .05). Balloon-expendable stent (BES) (nâ =â 1), Wingspan (nâ =â 34), and Enterprise (nâ =â 112) stents were placed in the current BAS group. In contrast, only balloon-expendable stent (BES) (nâ =â 48) and Wingspan (nâ =â 72) were deployed in the historical BAS group. The incidence of the safety endpoint (SE) was 4.1% (involving 6 patients) in the current BAS group versus 11.7% (involving 14 patients) in the historical BAS group (Pâ <â .05). In multivariate analysis, no risk factor was associated with the occurrence of the safety endpoint (SE). When BAS cases operated by the surgical team accumulated to 120 to 150, the incidence of complications decreased significantly. This is the largest sample size study to discuss the safety of BAS. The significantly decreased incidence of complications indicates that the improving technical measures and the accumulation of operation experience are necessary.
Assuntos
Angioplastia com Balão , Stents , Humanos , Pessoa de Meia-Idade , Idoso , Constrição Patológica , Resultado do Tratamento , Estudo Historicamente Controlado , Stents/efeitos adversosRESUMO
The existence of so-called blue-green cavities in the luminescence spectrum has been a hindrance to the improvement in the performance of traditional phosphor-converted white light emitting diodes. The commercial phosphors synthesized in reducing atmospheres can also cause problems such as equipment complexity, increased cost, and environmental pollution. Herein, a series of cyan-emitting Lu3GaxAl5-xO12: Ce3+ (x = 0, 1, 2, 3, 4) garnet phosphors were synthesized by a traditional solid-state reaction in a nonreducing atmosphere at different temperatures. The crystal structure, grain morphology, optical properties, and thermal quenching behavior were used to analyze the optical properties of the as-prepared phosphors. The luminescence intensity of samples is affected by the synthesis temperature and energy gap between the conduction band and the lowest energy of the 5d excited state of the host lattice. With the substitution of Al3+ by Ga3+, the regularity of the excitation and emission band movement is determined by the combined effects of crystal field splitting (CFS) and the nephelauxetic effect (NE). The temperature dependence of luminescence was studied. The thermal quenching mechanism was clarified by the thermal ionization model. Finally, by employing Lu2.94Ga2Al3O12: Ce3+0.06 as a cyan component, a w-LED with a high color rendering index of 93.2 and low correlation color temperature of 3880 K based on a blue chip and commercial red phosphors were fabricated in order to explore its possible application in high quality w-LED.
RESUMO
Background: The role of rivaroxaban in patients with heart failure (HF) combined with left ventricular (LV) thrombus remains unknown in current guideline-directed anticoagulant therapy. The aim of this study was to investigate the impact on clinical outcomes of rivaroxaban compared to vitamin K antagonists (VKAs) in patients with HF combined with LV thrombus. Methods: We retrospectively extracted clinical, echocardiographic and follow-up data of HF patients (all classifications) admitted at China-Japan Union Hospital of Jilin University from January 2017 to June 2021. A total of 198 patients with HF were identified with LV thrombus by echocardiography, 78 of them were managed with VKAs, 109 with rivaroxaban. Results: The median follow-up was 17.0 months (interquartile range: 6.0-24.0 months). High rates of major cardiovascular adverse events (MACEs) were observed in both the rivaroxaban and VKAs groups (49.5% vs. 57.7%). However, rivaroxaban versus VKAs observed a decrease in MACEs (adjusted HR:0.636; 95%CI:0.418-0.970; p = 0.035) and systemic embolism (4.6% vs. 12.8%; adjusted HR:0.318; 95%CI:0.108-0.933; p = 0.037; Gray's test p = 0.041) but was not found to have a benefit with regard to LV thrombus resolution (59.6% vs. 70.6%; adjusted HR: 1.303; 95% CI:0.898-1.890; p = 0.163; Gray's test p = 0.073). Additionally, there was no significant between-group difference in the rate of International Society on Thrombosis and Hemostasis (ISTH) bleeding events. Conclusion: Our data found that in populations with HF combined with LV thrombus, the overall prognosis in both the rivaroxaban and VKAs groups was catastrophic. Although rivaroxaban improved the prognosis to some extent, a considerable need remains for new treatments to improve their clinical course.