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Reducing building energy consumption, improving aesthetics, and improving occupant privacy as well as comfort by dynamically adjusting solar radiation are important application areas for electrochromic (EC) smart windows. However, the current transition metal oxides still cannot meet the requirements of neutral coloration and large optical modulation. We report NiMoO4 nanosheet films directly grown on fluorine-doped tin oxide glasses. The as-grown NiMoO4 film not only achieves neutral coloration from transparent to dark brown but also shows an ultralarge optical modulation (86.8% at 480 nm) and excellent cycling stability (99.4% retention of maximum optical modulation after 1500 cycles). Meanwhile, an EC device demonstrating good EC performance was constructed. These results will greatly promote the research and development of binary transition metal oxides for both EC and energy-storage applications, and NiMoO4 films may be an excellent candidate to replace NiO films as ion-storage layers in complementary EC devices with WO3 films as EC layers.
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A multi-longitudinal mode (MLM) laser beat-frequency optical fiber vibration sensor using a frequency modulation (FM) radio integrated circuit module as the FM demodulation scheme is presented and demonstrated. To the best of our knowledge, this is the first case where a fiber-optic sensing system is combined with an FM radio module, and dynamic sensing is well achieved. As the carrier of the vibration source, the beat-frequency signal (BFS) generated by the MLM laser is transmitted to the FM radio module for FM and demodulation. The experimental results show that the system can successfully detect the vibration signal in the frequency range of 20 Hz to 18 kHz and accurately demodulate the waveform and amplitude of the vibration signal source. The minimum shape variable detected by the system is 20.67 nm, based on the performance of the commercial FM radio module itself, which can effectively solve the problem of detecting tiny vibration. The idea of the optical fiber vibration sensing system is extremely innovative, with high sensitivity, high signal-to-noise ratio (SNR), good stability, and strong resistance to electromagnetic interference.
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In this study, we developed a flexible and transparent silver/polystyrene/polydimethylsiloxane (Ag/PS/PDMS) substrate with both high density of hot spots and satisfactory uniformity using a cost-effective approach. Via template-guided self-assembly, PS beads were arranged regularly in nanobowls of a square array on PDMS, whose surface structure was transferred from a commercial complementary metal oxide semiconductor chip. Roughness was introduced onto the PS bead surface by nitrogen plasma treatment, followed by sputtering of Ag which generated many hot spots. Differential roughness on the PS bead surface greatly influenced the morphology of the Ag/PS/PDMS substrate. A meat-ball like surface structure was formed with a plasma etching time of 5 min, whose growth mechanism was proposed based on the scanning electron microscope analysis. The high sensitivity and desirable uniformity of the meat-ball like Ag/PS/PDMS substrate were demonstrated by using crystal violet as a Raman reporter, exhibiting an enhancement factor of 2.7 × 107and a relative standard deviation of 5.04%. Thiram of a lower concentration than the maximum residue limit on the cucumber surface could easily be detectedin situby the proposed substrate, demonstrating its great potential forin-situfood safety analysis.
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Hydrazine often receives publicity because it has a wide range of applications but high toxicity at the same time. Here, we invented a novel aldehyde spiropyran fluorescent probe (SP-CHO) for fluorescence determination of hydrazine. The probe was synthesized through a hydrolysis reaction and a condensation reaction. It exhibits a specific response to hydrazine. The influence factors and anti-interference ability of SP-CHO identifying hydrazine were studied. HRMS, 1 H NMR, and density functional theory (DFT) calculations were used to reveal the recognition mechanism. Results showed that SP-CHO can be used for fluorescence determination of hydrazine with high selectivity and sensitivity. An SP-CHO-based fluorescence method was established for quantitation of hydrazine. The detection limit was 1.26 µmol/l, and the linear range was 5-100 µmol/l. The determination of hydrazine in water samples can be completed within 10 min, which shows good application prospects in real-time detection and process monitoring.
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Corantes Fluorescentes , Água , Corantes Fluorescentes/química , Espectrometria de Fluorescência , Água/química , Aldeídos , Hidrazinas/químicaRESUMO
Recently, robotic sensor systems have gained more attention annually in complex system sense strategies. The robotic sensors sense the information from itself and the environment, and fuse information for the use of perception, decision, planning, and control. As an important supplement to traditional industrial robots, co-bots (short for co-working robots) play an increasingly vital role in helping small and medium-sized enterprises realize intelligent manufacturing. They have high flexibility and safety so that they can assist humans to complete highly repetitive and high-precision work. In order to maintain robot safe operation in the increasing complex working environment and human-computer intelligent interactive control, this paper is concerned with the problem of applicant accuracy analysis and singularity avoidance for co-bots. Based on the dynamic model with load and torque sensors, which is used to detect the external force at the end of the robot, this paper systematically analyzes the causes of singularity phenomenon in the robot motion control. The inverse solution is obtained by analytical method and numerical method, respectively. In order to ensure the smooth and safe operation in the whole workspace, it is necessary for a robot to avoid singularity. Singularity avoidance schemes are utilized for different control tasks, including point-to-point control and continuous path control. Corresponding simulation experiments are designed to verify the effectiveness of different evasion schemes, in which the advantages and disadvantages are compared and analyzed.
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Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Movimento (Física) , Software , TorqueRESUMO
A spray dressing based on lyotropic liquid crystalline (LLC) with adjustable crystalline lattices was investigated in this study. It possesses water-triggering phase transition property and ease of spraying on wound, as well as stable drug encapsulation and controllable drug release. When it comes to wound with exudate, adequate water absorption and sustainable mechanical strength after water absorption was important for a good dressing, while most of the normal LLC dressings were still unable to meet such standards. Herein, a type of hyaluronic acid (HA)-incorporated LLC-based spray dressing (HLCSD) was developed to overcome the above limitations. After comparing HAs with different molecular weights (MWs) and concentrations, 3% HA with MW of 800~1000 kD was chosen as an ideal amount of excipients to add into the HLCSD. The water absorption of HLCSD precursor increased by 150% with the appearance of enlarged water channels. The complex modulus of HLCSD gel also increased from 1 to 100 kPa, which suggested lasting wound coverage and good patient compliance when used clinically. The spraying and phase transition properties of HLCSD was studied and showed acceptable changes. Moreover, good safety comparable with the commercial product Purilon® was also demonstrated in an in vivo acute skin irritation test. Thus, the improved HLCSD was a promising dressing for exudation wound treatment.
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Cristais Líquidos , Água , Bandagens , Humanos , Ácido Hialurônico , CicatrizaçãoRESUMO
Escherichia coli O157:H7, Cronobacter spp., and Salmonella spp. are common food-borne pathogens in milk that may cause serious diseases. In the present study, we established a simple, rapid, and specific method to simultaneously detect viable E. coli O157:H7, Cronobacter spp., and Salmonella spp. in milk. Three specific genes, fliC from E. coli O157:H7, cgcA from Cronobacter spp., and invA from Salmonella spp., were selected and used to design primers and probes. False-positive results were eliminated with the use of a combined sodium deoxycholate (SD) and propidium monoazide (PMA) treatment. Using the optimized parameters, this SD-PMA treatment combined with multiplex real-time PCR (SD-PMA-mRT-PCR) detected E. coli O157:H7, Cronobacter spp. and Salmonella spp. respectively, at 102 cfu/mL in pure culture or artificially spiked skim milk samples. A reasonable recovery rate (from 100 to 107%) for detection of viable bacteria using the SD-PMA-mRT-PCR assay was obtained in the presence of dead bacteria at 107 cfu/mL. The SD-PMA-mRT-PCR method developed in this study can accurately detect and monitor combined contamination with E. coli O157:H7, Cronobacter spp., and Salmonella spp. in milk and milk products.
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Cronobacter/isolamento & purificação , Escherichia coli O157/isolamento & purificação , Leite/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Salmonella/isolamento & purificação , Animais , Azidas , Ácido Desoxicólico , Microbiologia de Alimentos , Propídio/análogos & derivados , Sensibilidade e EspecificidadeRESUMO
Mutations that cause increased and/or inappropriate activation of FGFR3 are responsible for a collection of short-limbed chondrodysplasias. These mutations can alter receptor trafficking and enhance receptor stability, leading to increased receptor accumulation and activity. Here, we show that wildtype and mutant activated forms of FGFR3 increase expression of the cytoplasmic deacetylase HDAC6 (Histone Deacetylase 6) and that FGFR3 accumulation is compromised in cells lacking HDAC6 or following treatment of fibroblasts or chondrocytes with small molecule inhibitors of HDAC6. The reduced accumulation of FGFR3 was linked to increased FGFR3 degradation that occurred through a lysosome-dependent mechanism. Using a mouse model of Thanatophoric Dysplasia Type II (TDII) we show that both HDAC6 deletion and treatment with the small molecule HDAC6 inhibitor tubacin reduced FGFR3 accumulation in the growth plate and improved endochondral bone growth. Defective endochondral growth in TDII is associated with reduced proliferation and poor hypertrophic differentiation and the improved bone growth was associated with increased chondrocyte proliferation and expansion of the differentiation compartment within the growth plate. These findings further define the mechanisms that control FGFR3 accumulation and contribute to skeletal pathology caused by mutations in FGFR3.
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Acondroplasia/genética , Histona Desacetilases/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Crânio/anormalidades , Displasia Tanatofórica/genética , Acondroplasia/tratamento farmacológico , Acondroplasia/metabolismo , Acondroplasia/patologia , Anilidas/administração & dosagem , Animais , Desenvolvimento Ósseo/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Camundongos , Mutação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Crânio/metabolismo , Crânio/patologia , Displasia Tanatofórica/metabolismo , Displasia Tanatofórica/patologiaRESUMO
Fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the control of endochondral ossification, and bone growth and mutations that cause hyperactivation of FGFR3 are responsible for a collection of developmental disorders that feature poor endochondral bone growth. FGFR3 is expressed in proliferating chondrocytes of the cartilaginous growth plate but also in chondrocytes that have exited the cell cycle and entered the prehypertrophic phase of chondrocyte differentiation. Achondroplasia disorders feature defects in chondrocyte proliferation and differentiation, and the defects in differentiation have generally been considered to be a secondary manifestation of altered proliferation. By initiating a mutant activated knockin allele of FGFR3 (FGFR3K650E) that causes Thanatophoric Dysplasia Type II (TDII) specifically in prehypertrophic chondrocytes, we show that mutant FGFR3 induces a differentiation block at this stage independent of any changes in proliferation. The differentiation block coincided with persistent expression of SOX9, the master regulator of chondrogenesis, and reducing SOX9 dosage allowed chondrocyte differentiation to proceed and significantly improved endochondral bone growth in TDII. These findings suggest that a proliferation-independent and SOX9-dependent differentiation block is a key driving mechanism responsible for poor endochondral bone growth in achondroplasia disorders caused by mutations in FGFR3.
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Condrogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Mutação de Sentido Incorreto , Osteogênese/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Fatores de Transcrição SOX9/genética , Crânio/anormalidades , Displasia Tanatofórica/genética , Animais , Condrócitos/patologia , Regulação para Baixo , Camundongos , Displasia Tanatofórica/etiologiaRESUMO
Mnt (Max's next tango) is a Max-interacting transcriptional repressor that can antagonize both the proproliferative and proapoptotic functions of Myc in vitro. To ascertain the physiologically relevant functions of Mnt and to help define the relationship between Mnt and Myc in vivo, we generated a series of mouse strains in which Mnt was deleted in T cells in the absence of endogenous c-Myc or in the presence of ectopic c-Myc. We found that apoptosis caused by loss of Mnt did not require Myc but that ectopic Myc expression dramatically decreased the survival of both Mnt-deficient T cells in vivo and Mnt-deficient MEFs in vitro. Consequently, Myc-driven proliferative expansion of T cells in vitro and thymoma formation in vivo were prevented by the absence of Mnt. Consistent with T-cell models, mouse embryo fibroblasts (MEFs) lacking Mnt were refractory to oncogenic transformation by Myc. Tumor suppression caused by loss of Mnt was linked to increased apoptosis mediated by reactive oxygen species (ROS). Thus, although theoretically and experimentally a Myc antagonist, the dominant physiological role of Mnt appears to be suppression of apoptosis. Our results redefine the physiological relationship between Mnt and Myc and requirements for Myc-driven oncogenesis.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/fisiologia , Proliferação de Células , Transformação Celular Neoplásica , Proteínas Proto-Oncogênicas c-myc/fisiologia , Proteínas Repressoras/fisiologia , Linfócitos T/citologia , Animais , Apoptose , Camundongos , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: To develop a novel injectable strontium-containing calcium phosphate cement with collagen. METHODS: A novel calcium phosphate bone cement (CPC) was prepared with the addition of strontium element, collagenl, and modified starch; the injectability, solidification time, microstructure, phase composition, compressive strength, anti-collapsibility and histological properties of material were evaluated. RESULTS: The results showed that the material could be injected with an excellent performance; the modified starch significantly improved the anti-washout property of cement; with the liquid to solid ratio of 0.3, the largest compressive strength of cement was obtained (48.0 MPa ± 2.3 MPa); histological examination of repair tissue showed that the bone was repaired after 16 weeks; the degradation of cement was consistent with the new bone growth. CONCLUSION: A novel injectable collagen-strontium-containing CPC with excellent compressive strength and suitable setting time was prepared, with addition of modified starch. The CPC showed a good anti-washout property and the degradation time of the cement met with the new bone growing. This material is supposed to be used in orthopedic and maxillofacial surgery for bone defects.
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Cimentos Ósseos/química , Fosfatos de Cálcio/química , Colágeno/química , Estrôncio/química , Animais , Cimentos Ósseos/uso terapêutico , Força Compressiva , Teste de Histocompatibilidade , Injeções , CoelhosRESUMO
Mutations in fibroblast growth factor (FGF) receptors are responsible for a variety of skeletal birth defects, but the underlying mechanisms responsible remain unclear. Using a mouse model of thanatophoric dysplasia type II in which FGFR3(K650E) expression was directed to the appendicular skeleton, we show that the mutant receptor caused a block in chondrocyte differentiation specifically at the prehypertrophic stage. The differentiation block led to a severe reduction in hypertrophic chondrocytes that normally produce vascular endothelial growth factor, which in turn was associated with poor vascularization of primary ossification centers and disrupted endochondral ossification. We show that the differentiation block and defects in joint formation are associated with persistent expression of the chondrogenic factor Sox9 and down-regulation of ß-catenin levels and activity in growth plate chondrocytes. Consistent with these in vivo results, FGFR3(K650E) expression was found to increase Sox9 and decrease ß-catenin levels and transcriptional activity in cultured mesenchymal cells. Coexpression of Fgfr3(K650E) and Sox9 in cells resulted in very high levels of Sox9 and cooperative suppression of ß-catenin-dependent transcription. Fgfr3(K650E) had opposing effects on Sox9 and ß-catenin protein stability with it promoting Sox9 stabilization and ß-catenin degradation. Since both Sox9 overexpression and ß-catenin deletion independently blocks hypertrophic differentiation of chondrocytes and cause chondrodysplasias similar to those caused by mutations in FGFR3, our results suggest that dysregulation of Sox9 and ß-catenin levels and activity in growth plate chondrocytes is an important underlying mechanism in skeletal diseases caused by mutations in FGFR3.
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Articulações , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Fatores de Transcrição SOX9 , Displasia Tanatofórica , beta Catenina , Animais , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Regulação da Expressão Gênica , Lâmina de Crescimento/citologia , Lâmina de Crescimento/metabolismo , Humanos , Articulações/crescimento & desenvolvimento , Articulações/metabolismo , Camundongos , Mutação , Osteogênese/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais , Crânio/anormalidades , Crânio/metabolismo , Crânio/fisiopatologia , Displasia Tanatofórica/genética , Displasia Tanatofórica/metabolismo , Displasia Tanatofórica/fisiopatologia , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Soil erosion leads to soil degradation and depletion of land resources, posing a significant threat to industrial production and ecological sustainability. In high-altitude regions, rill erosion is the main form of soil erosion in mining areas, however, our understanding of morphology and developmental characteristics of rills and the mechanisms influencing them remains limited. In this study, data were collected from 96 rill plots across two gold mines in the eastern Tibetan Plateau according to vegetation restoration modes (natural restoration (CK) and planted with Elymus dahuricus (ED), Medicago sativa (MS), and multi-plant mixed (Avena fatua L. + Elymus dahuricus + Medicago sativa + Oxytropis coerulea, MM)) and restoration periods (1 year, 3 years, 4 years, and 6 years). We investigated the variations of 7 indicators that can reveal rill morphological and developmental characteristics across different restoration modes and restoration periods, and utilized a partial least squares structural equation model (PLS-SEM) to analyze the effects of 15 indicators from topography, soil, and vegetation on rill erosion modulus (REM). The results indicated that artificial vegetation restoration effectively restrained rill development, notably by decreasing the frequency of wider (>15 cm) and deeper (>10 cm) rills when compared to CK plots. Planting MM and ED exhibited greater efficacy in controlling rill erosion than planting MS. However, the effectiveness of planting ED in controlling rill erosion gradually weakened with time, while MM consistently maintained a strong inhibitory effect. Topographic features, soil texture, and vegetation significantly influenced the REM through direct or indirect effects. Plant root functional traits were the main driving factors in reducing REM, affecting not only REM directly but also influencing vegetation-induced soil properties to indirectly effect REM.
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Altitude , Elymus , Plantas , Solo , Mineração , ChinaRESUMO
Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR-Cas9 screening using a reporter driven by the L1 5' UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
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Sistemas CRISPR-Cas , Elementos Nucleotídeos Longos e Dispersos , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Animais , Camundongos , Ativação Transcricional , Zigoto/metabolismo , Transcrição Gênica , Regulação da Expressão Gênica , Regiões 5' não TraduzidasRESUMO
OBJECTIVE: The 'no-reflow' phenomenon after a primary percutaneous coronary intervention (pPCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) is a strong predictor of both short- and long-term mortality. We therefore developed and prospectively validated a risk score system in order to identify STEMI patients at high risk in terms of no-reflow after primary PCI. METHODS: The first part of our study used data from 1,615 STEMI patients who underwent primary PCI within 12 h from symptom onset. Using logistic regression, we derived a risk score to predict angiographic no-reflow using baseline clinical variables. From this score, we developed a simplified fast-track screen that can be used before reperfusion. In the second part of our study, we prospectively validated the score system using receiver-operating characteristic (ROC) curves with data from 692 STEMI patients. RESULTS: The model included six clinical items: age, neutrophil count, admission plasma glucose, ß-blocker treatment, time-to-hospital admission and Killip classes. The risk score system demonstrated a good risk prediction with a c-statistic of 0.757 (95% CI 0.732-0.781) based on ROC analysis. CONCLUSION: A simple risk score system based on clinical variables is useful to predict the risk of developing no-reflow after pPCI in patients with STEMI.
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Infarto do Miocárdio/terapia , Fenômeno de não Refluxo/diagnóstico , Intervenção Coronária Percutânea , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Estudos Prospectivos , Curva ROC , Medição de RiscoRESUMO
Topography plays a crucial role in determining the structure of alpine forests, as it restricts the availability of nutrients and water necessary for plant growth. Nevertheless, our information on how variations in forest carbon allocation patterns driven by fine-scale topography are influenced by broader-scale environmental contexts is limited. In the northern Tibetan Plateau, we combined field data from 89 forest plots with a high-resolution (1 m2) digital elevation model (DEM) and utilized a linear mixed-effects model to investigate how microtopography (characterized by slope, aspect, and topographic wetness index (TWI)) and broader-scale environmental context (characterized by elevation) and their interactions affect the carbon allocation patterns of alpine forest. Our results revealed that at low and high elevations with pronounced subsurface resource limitations, plants tend to allocate a higher proportion of carbon to the root system and have lower aboveground carbon stocks (ACS). Microtopographic heterogeneity significantly influenced the carbon allocation patterns of forest, with the intensity and direction of these effects varying across the environmental gradient. At low elevations, topographically wetter and northerly microhabitats had higher ACS and lower ratios of below- and aboveground carbon stocks (RBA); however, at high elevations, topographically drier and southerly microhabitats had higher ACS and lower RBA. TWI and aspect had the weakest effect on ACS and RBA in the mid-elevations. The relationship between slope and ACS and RBA was significantly positive but not evidently related to the broader-scale environmental gradient.
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Carbono , Desenvolvimento Vegetal , Plantas , ÁguaRESUMO
BACKGROUND: Brachial-ankle pulse wave velocity (baPWV), which reflects the stiffness of both central and peripheral muscular arteries, has been frequently used as a simple index for assessing arterial stiffness. The aim of the present study was to investigate the prevalence of arterial stiffness in North China based on baPWV measurements, and explore the associations between increased arterial stiffness and risk factors of cardiovascular diseases (CVD). METHODS: Twenty-three community populations were established in North China. For each participant, parameters for calculating baPWV, including blood pressures and pressure waveforms, were measured using a non-invasive automatic device. All participants were required to respond to an interviewer-led questionnaire including medical histories and demographic data, and to receive blood tests on biochemical indictors. RESULTS: A total of 2,852 participants were finally investigated. Among them, 1,201 people with low burden of CVD risk factors were chosen to be the healthy reference sample. The cut-off point of high baPWV was defined as age-specific 90th percentile of the reference sample. Thus, the prevalence of high baPWV was found to be 22.3% and 26.4% in men and women respectively. After adjusted for age, heart rate (HR), systolic blood pressure (SBP), fasting glucose level, and smoking were significantly associated with high baPWV in men; while level of serum total cholesterol (TC), HR, SBP, and diabetes were significantly associated with high baPWV in women. CONCLUSIONS: Based on the age-specific cut-off points, the middle-aged population has a higher prevalence of high baPWV in North China. There exists a difference between men and women in terms of the potential risk factors associated with arterial stiffness.
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Doenças Cardiovasculares/etiologia , Rigidez Vascular , Adulto , Idoso , Tornozelo/irrigação sanguínea , Velocidade do Fluxo Sanguíneo , Artéria Braquial/fisiopatologia , China/epidemiologia , Colesterol/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fluxo Pulsátil , Fatores de RiscoRESUMO
Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality worldwide. Regulatory T cells (Tregs) are a key constituent of immune cells in the tumor microenvironment (TME) and are significantly associated with patient outcomes. Our study aimed to construct a Treg-associated signature to predict the prognosis of CRC patients. The genes' expression values and patients' clinicopathological features were downloaded from TCGA and gene expression omnibus (GEO) databases. The single-cell RNA (scRNA) sequencing data of CRC were analyzed through the Deeply Integrated human Single-Cell Omics database. WGCNA analysis was used to select Tregs-associated genes (TrAGs). The infiltrated levels of immune and stromal cells were accessed through the ESTIMATE algorithm. Cox regression analysis and the LASSO algorithm were implemented to construct prognostic models. Gene set enrichment analysis (GSEA) was performed to annotate enriched gene sets. Based on scRNA sequencing data, our study uncovered that more Tregs were significantly enriched in the TME of CRC. Then we identified 123 differentially expressed TrAGs which mainly participated in immune regulation. Given that CRC patients were reclassified into 2 subgroups with distinct overall survival based on 26 differentially expressed TrAGs with prognostic values, we subsequently constructed a signature for CRC. After training and validating in independent cohorts, we proved that this prognostic model can be well applied to predict the prognosis of CRC patients. Further analysis exhibited that more tumor-suppressing immune cells and higher immune checkpoint genes were enriched in CRC patients with high-risk scores. Moreover, immunohistochemistry analysis validated that the genes in the prognostic model were significantly elevated in CRC tissues. We were the first to construct a prognostic signature for CRC based on TrAGs and further revealed that the poor prognosis of patients was mainly attributed to the tumor-suppressing microenvironment and upregulated immune checkpoint genes in tumor tissues.
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Neoplasias Colorretais , Cooperação do Paciente , Humanos , Estudos Retrospectivos , Prognóstico , Fatores de Risco , Neoplasias Colorretais/genética , Microambiente Tumoral/genéticaRESUMO
Purpose: A new approach to monitor drug release and image inflammatory reactions in vitro and in vivo based on FRET mechanism was reported. Methods: In this study, mixed micelles containing a synthesized fluorescent donor DAN-PPS-mPEG and its quencher DAB-PPS-mPEG were prepared. Their stabilities, self-assembling and oxidation-responsiveness towards oxidants were tested in vitro and in vivo. Results: The conjugated polymers were synthesized and the morphological change and the fluorescent spectra of the prepared micellar system were measured. After incubating the DAN/DAB-PPS-mPEG mixed micelles with stimulated L929 fibroblast cells, the result of confocal laser microscopy showed fluorescence restoration of the micelles. Furthermore, an acute inflammatory injury mouse model was used to test the micelles in vivo. The micelles showed its ability to visualize the inflammatory site in the abdomen of the mice. Conclusion: The results confirmed that DAN/DAB-PPS-mPEG mixed micelles can respond to oxidants and release encapsulated cargos with corresponding fluorescence restoration, and visualize the inflammatory cells in vitro and inflammatory reactions in vivo.