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Spatial active noise control (ANC) systems focus on minimizing unwanted acoustic noise over continuous spatial regions by generating anti-noise fields with secondary loudspeakers. Conventionally, error microphones are necessary inside the region to measure the channels from the secondary loudspeakers to the error microphones and record the residual sound field during the noise control. These error microphones highly limit the implementation of spatial ANC systems because of their impractical geometry and obstruction to the users from accessing the region. Recent advances, such as virtual sensing, focus on ANC with microphones placed away from the region. While these techniques relax the usage of error microphones during the noise control, an error microphone array remains necessary during the secondary channel estimation. In this paper, we propose a method to estimate secondary channels without using an error microphone array. Instead, a moving higher order microphone is applied to obtain the secondary channels from the secondary loudspeakers to the region of interest, which includes all desired error microphone locations. By simulation, we show that the proposed method is robust against various measuring errors introduced by the movement of the microphone and is suitable for the secondary channel estimation in spatial ANC systems.
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The successful synthesis of ruthenium oxide/reduced graphene oxide (RuO2/rGO) heterostructures by one-pot hydrothermal method using graphene oxides and RuCl3 as precursors is reported. The heterostructures had high peroxidase-like (POD-like) activities, which catalyzes the oxidation of classical peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to create a blue colored reaction product. The catalytic activity was significantly enhanced by the synergistic effect between RuO2 nanoparticles and rGO. RuO2/rGO had a low Km of 0.068 mM and a high vmax of 1.228 × 10-7 M·s-1 towards TMB in the TMB-H2O2 catalytic oxidation system. In addition, the POD-like activity originating from the electron transfer mechanism was confirmed by cytochrome C (Cyt C) oxidation experiment. A colorimetric method based on RuO2/rGO heterostructures was developed with good sensitivity and selectivity for glucose detection with a limit of detection of 3.34 µM and a linear range of 0-1500 µM. The RuO2/rGO heterostructures have potential applications in the biomedical areas, such as biosensor and diagnostics.
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Colorimetría , Peroxidasas , Colorimetría/métodos , Glucosa , Grafito , Peróxido de Hidrógeno/químicaRESUMEN
Short-chain fatty acids (SCFAs) are the products of the microbial fermentation of dietary fiber in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and play an important role in maintaining host health. This study was aimed at investigating the effects of sodium propionate (NaP) supplementation in the diet with a high proportion of soybean meal (SBM) on the growth, inflammatory status, and anti-infectious ability in juvenile turbot. Four experimental diets were designed: (1) fish meal- (FM-) based diet (control group), (2) SBM protein replacing 45% FM protein in the diet (high SBM group), (3) 0.5% NaP supplementation in the high SBM diet (high SBM+0.5% NaP group), and (4) 1.0% NaP supplementation in the high SBM diet (high SBM+1.0% NaP group). The results confirmed that the fish fed the high SBM diet for 8 weeks showed the decreased growth performance, the typical enteritis symptoms, and the increased mortality responding to Edwardsiella tarda (E. tarda) infection. However, 0.5% NaP supplementation in the high SBM diet promoted the growth performance of turbot and restored the activities of digestive enzymes in the intestine. Moreover, dietary NaP ameliorated the intestinal morphology, enhanced the expression of intestinal tight junction proteins, improved the antioxidant capacity, and suppressed the inflammatory status in turbot. Finally, the expression of antibacterial components and the resistance to bacterial infection were increased in NaP-fed turbot, especially in high SBM+1.0% NaP group. In conclusion, the supplementation of NaP in high SBM diet promotes the growth and health in turbot and provides a theoretical basis for the development of NaP as a functional additive in fish feed.
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Infectious diseases are among the world's principal health problems. It is crucial to develop rapid, accurate and cost-effective methods for the detection of pathogenic microorganisms. Recently, considerable progress has been achieved in the field of inorganic enzyme mimics (nanozymes). Compared with natural enzymes, nanozymes have higher stability and lower cost. More interestingly, their properties can be designed for various demands. Herein, we introduce the latest research progress on the detection of pathogenic microorganisms by using various nanozymes. We also discuss the current challenges of nanozymes in biosensing and provide some strategies to overcome these barriers.
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Bacterias/aislamiento & purificación , Materiales Biomiméticos/química , Nanoestructuras/química , Técnicas Biosensibles , Enfermedades Transmisibles/microbiologíaRESUMEN
The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.
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Ácido Ascórbico/análisis , Grafito/química , Iridio/química , Nanopartículas del Metal/química , Poliaminas/química , Ácido Ascórbico/química , Bencidinas/química , Catálisis , Colorimetría/métodos , Colorantes/química , Peróxido de Hidrógeno/química , Límite de Detección , Nanocompuestos/química , Oxidación-Reducción , Peroxidasa/químicaRESUMEN
Bletilla striata (Thunb.) Reichb. f. (Orchidaceae), also known as Bai-ji, is a traditional Chinese herb that is widely used in Asia to treat hematemesis, hemoptysis, traumatic bleeding and other similar disorders. Most studies have focused on the pharmacological activities of polysaccharide extracts from B. striata. Our previous studies found that the nonpolysaccharide fraction from B. striata extract also has a hemostatic effect; however, the active constituents responsible for this pharmacological action are unclear. Thus, the metabolic profiles of the nonpolysaccharide fraction were investigated in Sprague-Dawley rats and intestinal bacteria models using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Mass data were acquired by the MSE method. Eight components including five prototypes and three metabolites were identified in rat biofluids after oral administration of the nonpolysaccharide fraction. The parent compounds underwent various metabolic processes, including hydrolysis, deglucosylation, glycosylation and sulfate conjugation. The results not only reveal the possible metabolic pathway, but also indicate the potential pharmacological components. Further mechanistic studies using nonpolysaccharide compounds of the B. striata extract are required to obtain potential candidate compounds.
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Bacterias/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/metabolismo , Orchidaceae , Espectrometría de Masa por Ionización de Electrospray/métodos , Succinatos/metabolismo , Animales , Bilis/microbiología , Heces/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Humanos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
New materials for achieving direct electric field control of ferromagnetism and resistance behavior are highly desirable in the development of multifunctional data storage devices. In this paper, HfO2 nanoporous films have been fabricated on porous anodic alumina (PAA) substrates by DC-reactive magnetron sputtering. Electrically induced resistive switching (RS) and modulated room temperature ferromagnetism are simultaneously found in a Ag/HfO2/PAA/Al (Ag/HP/Al) heterostructure. The switching mechanism between low resistance state and high resistance state is generally attributed to the formation/rupture of conductive filaments which may consist of oxygen vacancies. The combination of the electric field control of magnetization change and RS makes HP films possible for the multifunctional data storage media materials.
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The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum capitatum in vivo and to conduct pharmacokinetic studies on the herb, a well-known Miao medicinal plant in China. Gallic acid, quercitrin, and quercetin were analysed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Protein precipitation in plasma samples was performed using methanol. For the determination of total forms of analytes, an additional process of hydrolysis was conducted using ß-glucuronidase and sulphatase. The analytes were separated on a BEH C18 column (50 mm × 2.1 mm; i.d., 1.7 µm) and quantified by multiple reaction monitoring (MRM) mode. The linear regression showed high linearity over a 729-fold dynamic range for the three analytes. The relative standard deviations of intra- and inter-day measurements were less than 9.5%, and the method was accurate to within -11.1% to 12.5%. The extraction recoveries for gallic acid, quercitrin, and quercetin were 94.3%-98.8%, 88.9%-98.8%, and 95.7%-98.5%, respectively. All samples were stable under short- and long-term storage conditions. The validated method was successfully applied to a comparative pharmacokinetic study of gallic acid, quercitrin, and quercetin in their free and total forms in rat plasma. The study revealed significantly higher exposure of the constituents in total forms for gallic acid and quercetin, while quercitrin was detected mainly in its corresponding free form in vivo. The established method was rapid and sensitive for the simultaneous quantification of free and total forms of multiple constituents of Polygonum capitatum extract in plasma.
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Ácido Gálico/sangre , Polygonum/química , Quercetina/análogos & derivados , Quercetina/sangre , Animales , Cromatografía Líquida de Alta Presión , Ácido Gálico/química , Ácido Gálico/farmacocinética , Masculino , Extractos Vegetales/química , Plantas Medicinales/química , Plasma/química , Quercetina/química , Quercetina/farmacocinética , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
To investigate the metabolism of quercitrin in rat intestinal flora and possible biological pathways, laying the foundation for the metabolic mechanism of traditional Chinese medicine glycosides ingredients. UPLC-Q-TOF-MS/MS method was established to detect the quercitrin and its metabolites with 0.1% formic acid solution(A)-0.1% formic acid acetonitrile(B) as the mobile phase for gradient elution at a flow rate of 0.3 mLâ¢min⻹. Electrospray negative ion mode was applied to analyze the metabolites of quercitrin in rat intestinal flora. Metabolite ToolsTM, mass defect filter(MDF) and other technologies were used to screen, analyze the metabolites and infer the chemical formula of the metabolites. The results showed that quercitrin would have degalactoside, deoxygenation and acetylation reactions, and the aglycone quercetin resulted from degalactoside would have further reactions such as hydroxylation, deoxygenation, reduction, and ring opening to achieve deoxygenation metabolite kaempferol, C2-C3 double bonds hydrogenation and reduction product taxifolin, and degalactoside product quercetin. The research results showed that quercitrin can be metabolized by rat intestinal flora, which could increase their hydrophobicity and chemical diversity.
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Microbioma Gastrointestinal , Quercetina/análogos & derivados , Animales , Cromatografía Líquida de Alta Presión , Quercetina/metabolismo , Ratas , Espectrometría de Masas en TándemRESUMEN
A series of ultrathin TiO2/Ti films with iridescent structural colors were fabricated on high-purity titanium sheets via a one-step anodization procedure. Tunable color in the films can be obtained by adjusting the anodization time and can be adjusted across the entire visible range. It was found that all the films displayed highly saturated colors. Trichromatic coordinates of color x, y were delineated, and the color was identified by positioning the x and y values in the Commission International de I'Eclairage chromaticity diagram. Theoretical and experimental results of the changes in the structural color according to the principle of complementary colors are consistent with the experimental results. The TiO2/Ti films may have potential in color displays, decoration, and anticounterfeiting technology.
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Docetaxel (DTX) resistance poses a significant challenge in the treatment of prostate cancer (PCa), often leading to chemotherapy failure. This study investigates the ability of piperine, a compound derived from black pepper, to enhance the sensitivity of PCa cells to DTX and elucidates its underlying mechanism. We established a DTX-resistant PCa cell line, DU145/DTX, to conduct our experiments. Through a series of assays, including MTT for cell viability, flow cytometry for apoptosis, Transwell for cell migration and invasion, and western blot for protein expression analysis, we assessed the effects of piperine on these cellular functions and on the Notch signaling pathway components. Our results demonstrated that we successfully established the DTX-resistant PCa cell line DU145/DTX. Piperine effectively decreased the viability of both DU145 and its DTX-resistant counterpart, DU145/DTX, in a concentration and time-dependent manner when used alone and in combination with DTX. Notably, piperine also induced apoptosis and reduced the migration and invasion capabilities of these cells. At the molecular level, piperine down-regulated the Notch pathway by inhibiting Notch1 and Jagged1 signaling, as well as reducing the expression of downstream effectors Hey1 and hes family bHLH transcription factor 1. The study concludes that piperine's ability to modulate the Notch signaling pathway and induce apoptosis highlights its potential as a complementary treatment for DTX-resistant PCa, paving the way for the use of traditional Chinese medicinal compounds in modern oncology treatment strategies.
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Alcaloides , Apoptosis , Benzodioxoles , Movimiento Celular , Docetaxel , Resistencia a Antineoplásicos , Piperidinas , Alcamidas Poliinsaturadas , Neoplasias de la Próstata , Transducción de Señal , Alcamidas Poliinsaturadas/farmacología , Alcamidas Poliinsaturadas/química , Humanos , Benzodioxoles/farmacología , Benzodioxoles/química , Alcaloides/farmacología , Alcaloides/química , Piperidinas/farmacología , Piperidinas/química , Docetaxel/farmacología , Masculino , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Receptores Notch/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Receptor Notch1/metabolismoRESUMEN
The simple and sensitive detection of miRNA-122 in blood is crucially important for early hepatocellular carcinoma (HCC) diagnosis. In this work, a platinum microelectrode (PtµE) was prepared and electrodeposited with molybdenum disulfide (MoS2) and gold nanoparticles (AuNP), respectively, and denoted as PtµE/MoS2/Au. The prepared PtµE/MoS2/Au was used as the microsensor for the detection of miRNA-122 combined with the probe DNA as a biorecognition element which is the complementary strand of miRNA-122. The PtµE/MoS2/Au conjugated with the probe DNA modified with sulfydryl units was used as the micro-biosensor for the detection of miRNA-122. The square wave voltammetry was performed for the quantitative detection of miRNA-122 using [Fe(CN)6]4-/3- as a mediator. Under the optimized conditions, the PtµE/MoS2/Au micro-biosensor shows a linear detection toward miRNA-122 ranging from 10-11 to 10-8 M (S = 6.9 nA dec-1, R2 = 0.9997), and the detection limit is 1.6 × 10-12 M (3σ/b). The PtµE/MoS2/Au micro-biosensor demonstrates good selectivity against other types of proteins and small molecules, and has good reproducibility. Moreover, the PtµE/MoS2/Au micro-biosensor was successfully applied for the measurement of miRNA-122 in real blood samples. Herein, the proposed detection assay could be a potential tool in HCC clinical diagnostics with high sensitivity.
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Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.
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Introduction: Acute kidney injury (AKI) is a prevalent complication of coronavirus disease 2019 (COVID-19) and is closely linked with a poorer prognosis. The aim of this study was to develop and validate an easy-to-use and accurate early prediction model for AKI in hospitalized COVID-19 patients. Methods: Data from 480 COVID-19-positive patients (336 in the training set and 144 in the validation set) were obtained from the public database of the Cancer Imaging Archive (TCIA). The least absolute shrinkage and selection operator (LASSO) regression method and multivariate logistic regression were used to screen potential predictive factors to construct the prediction nomogram. Receiver operating curves (ROC), calibration curves, as well as decision curve analysis (DCA) were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. Results: A predictive nomogram for AKI was developed based on arterial oxygen saturation, procalcitonin, C-reactive protein, glomerular filtration rate, and the history of coronary artery disease. In the training set, the nomogram produced an AUC of 0.831 (95% confidence interval [CI]: 0.774-0.889) with a sensitivity of 85.2% and a specificity of 69.9%. In the validation set, the nomogram produced an AUC of 0.810 (95% CI: 0.737-0.871) with a sensitivity of 77.4% and a specificity of 78.8%. The calibration curve shows that the nomogram exhibited excellent calibration and fit in both the training and validation sets. DCA suggested that the nomogram has promising clinical effectiveness. In addition, the median length of stay (m-LS) for patients in the high-risk group for AKI (risk score ≥ 0.122) was 14.0 days (95% CI: 11.3-16.7 days), which was significantly longer than 8.0 days (95% CI: 7.1-8.9 days) for patients in the low-risk group (risk score <0.122) (hazard ratio (HR): 1.98, 95% CI: 1.55-2.53, p < 0.001). Moreover, the mortality rate was also significantly higher in the high-risk group than that in the low-risk group (20.6 vs. 2.9%, odd ratio (OR):8.61, 95%CI: 3.45-21.52). Conclusions: The newly constructed nomogram model could accurately identify potential COVID-19 patients who may experience AKI during hospitalization at the very beginning of their admission and may be useful for informing clinical prognosis.
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Lesión Renal Aguda , COVID-19 , Humanos , COVID-19/diagnóstico , Lesión Renal Aguda/diagnóstico , Nomogramas , Pacientes , Polipéptido alfa Relacionado con CalcitoninaRESUMEN
Background: The mental health of medical students is an issue worthy of attention, especially during COVID-19. Many studies have shown that depression and anxiety are the main problems faced by medical students. To assess the pooled prevalence of depression and anxiety among medical students worldwide, we conducted this meta-analysis. Methods: According to PRISMA, we used a computerized strategy to search studies in EMBASE, PubMed, PsycArticles, Web of Science, and China Biology Medicine disc. The pooled prevalence of depression and anxiety was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis. Sensitivity analysis and publication bias were also carried out in this meta-analysis. Results: Of 1316 studies, 41 studies were selected based on 36608 medical students. The pooled depression prevalence was 37.9% (95% CI: 30.7-45.4%), and pooled anxiety prevalence was 33.7% (95% CI: 26.8-41.1%). The prevalence of depression and anxiety among medical students varied by gender, country, and continent. Conclusion: The data reported that the prevalence of depression and anxiety among medical students during COVID-19 was relatively higher than those of the general population and the healthcare workers. The impact of COVID-19 on medical students and how to protect the mental health of medical students are needed to determine through further research. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021274015], identifier [CRD42021274015].
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BACKGROUND: The combination of shear wave elastography (SWE) and gray-scale ultrasound is widely used in the measurement of female pelvic floor muscle. However, the value of gray-scale ultrasound combined with SWE in the evaluation of primipara pregnancy and delivery is still controversial. METHODS: Using the PubMed, Web of Science, Spring and Science Direct databases, clinical studies on gray-scale ultrasound combined with SWE on the diagnosis of primiparous pregnancy and childbirth published from January 2010 to December 2020 were searched. The RevMan5.3 software was used to conduct a meta-analysis of the indicators of gray-scale ultrasound combined with SWE for primiparas and non-primiparas, including: age, body mass index (BMI), gestational age at examination, gestational age at delivery, fetal weight, cervical length, shear wave velocity (SWV), front lip SWV, back lip SWV, Young's modulus and SWE index. Heterogeneity of the assessment results was tested using Cochran's chi-square. RESULTS: A total of 13 articles were included. Age, BMI before delivery, gestational age (when gray-scale ultrasound was combined with SWE examination), gestational age at delivery, neonatal weight, cervical depth, SWV of placental margin, SWV of anterior lip, SWV of posterior lip and Young's modulus of the study group were significantly different from those of the control group. The elastic modulus of the perineal body and the SWE of the anterior lip of the study group were significantly higher than those of the control group [mean difference (MD) =8.11, 4.39, 95% confidence interval (CI): 3.90-12.31, 0.94-7.83; Z=3.78, 2.49, P=0.0002, 0.01]. The SWE of the posterior lip in the study group was significantly lower than that in the control group (MD =-4.34, 95% CI: -7.23 to 1.44; Z=2.93, P=0.003). DISCUSSION: The number of cases in the control group in the included articles was significantly more than that in the observation group, and there were fewer descriptions of gray-scale ultrasound combined with SWE indicators in the included articles. There may be a certain degree of bias for indicators without obvious heterogeneity, and further analysis was required through a large number of clinical verifications. However, this study can provide certain reference values for the diagnosis of primipara pregnancy.
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Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Recién Nacido , Placenta , Embarazo , UltrasonografíaRESUMEN
Unloading-induced bone loss is a critical complication characterized by the imbalance of bone formation and resorption induced by long-term confinement in bed or spaceflight. CD31hiEmcnhi (type H) vessel is a specific subtype of capillary, which was coupled with osteogenesis. However, the change of type H vessel and its contributions to the unloading-induced bone loss remains undisclosed. Herein, we found that bone formation and the number of type H vessels were synchronously reduced in the hindlimb-unloading (HU) mice. Panax quinquefolium saponin (PQS) could increase bone mass, osteoblast function and the number of type H vessels in the HU mice. In vitro, PQS treatment accelerated HMECs migration, augmented the total tube loops and increased the secretion of VEGF and Noggin. Primary osteoblasts function was obviously increased when treated with supernatant from PQS-treated HMECs. These effects of PQS were substantially counteracted when VEGF and Noggin in HMECs were knocked down by siRNA. These results demonstrated that unloading-induced bone loss is coupled with reduction of type H vessels and PQS performs preventive function via promoting type H vessel angiogenesis, which is closely associated with endothelial cell-derived VEGF and Noggin.
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Enfermedades Óseas Metabólicas , Saponinas , Animales , Masculino , Ratones , Osteoblastos , Osteogénesis , Saponinas/farmacologíaRESUMEN
Short-chain fatty acids (SCFAs) are mainly produced by microbiota through the fermentation of carbohydrates in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and have been shown to be important in the maintenance of host health. In this study, head kidney macrophages (HKMs) were isolated and cultured from turbots. We found that the antibacterial activity of HKMs was increased after these cells were incubated with sodium butyrate, sodium propionate or sodium acetate. Interestingly, our results showed that all three SCFAs enhanced the expression of hypoxia inducible factor-1 α (HIF-1α) in HKMs, and further study confirmed that butyrate augmented the oxygen consumption of these cells. Moreover, HIF-1α inhibition diminished the butyrate-promoted intracellular bacterial killing activity of macrophages, and SCFAs also raised the gene expression and activity of lysozymes in HKMs via HIF-1α signaling. In addition, our results suggested that butyrate induced HIF-1α expression and the bactericidal activity of HKMs through histone deacetylase inhibition, while G protein-coupled receptors did not contribute to this effect. Finally, we demonstrated that butyrate induced a similar response in the murine macrophage cell line RAW264.7. In conclusion, our results demonstrated that SCFAs promoted HIF-1α expression via histone deacetylase inhibition, leading to the enhanced production of antibacterial effectors and increased bacterial killing of macrophages.
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Ácidos Grasos Volátiles/farmacología , Peces Planos/inmunología , Riñón Cefálico/citología , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Macrófagos/efectos de los fármacos , Animales , Ácido Butírico/farmacología , Células Cultivadas , Edwardsiella tarda , Regulación de la Expresión Génica , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Activación de Macrófagos , Macrófagos/fisiología , Ratones , Muramidasa/metabolismo , Óxido Nítrico/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Propionatos/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Acetato de Sodio/farmacologíaRESUMEN
Previous studies have shown an attenuating effect of ginsenoside Re on myocardial injury induced by hypoxia/reoxygenation (H/R). However, the underlying mechanism remains unclear. This study was designed to determine the underlying mechanism by which ginsenoside Re protects from myocardial injury induced by H/R. HL-1 cells derived from AT-1 mouse atrial cardiomyocyte tumor line were divided into control, H/R, and H/R + ginsenoside Re groups. Cell viability was measured by CCK-8 assay. ATP levels were quantified by enzymatic assays. Signaling pathway was predicted by network pharmacology analyses and verified by luciferase assay and gene-silencing experiment. The relationship between ginsenoside Re and its target genes and proteins was analyzed by docking experiments, allosteric site analysis, real-time PCR, and ubiquitination and immunoprecipitation assays. Our results showed that ginsenoside Re treatment consistently increased HL-1 cell viability and significantly up-regulated ATP levels after H/R-induced injury. Network pharmacology analysis suggested that the effect of ginsenoside Re was associated with the regulation of the Hypoxia-inducing factor 1 (HIF-1) signaling pathway. Silencing of HIF-1α abrogated the effect of ginsenoside Re on HL-1 cell viability, which was restored by transfection with an HIF-1α-expressing plasmid. Results of the bioinformatics analysis suggested that ginsenoside Re docked at the binding interface between HIF-1α and the von Hippel-Lindau (VHL) E3 ubiquitin ligase, preventing VHL from binding HIF-1α, thereby inhibiting the ubiquitination of HIF-1α. To validate the results of the bioinformatics analysis, real-time PCR, ubiquitination and immunoprecipitation assays were performed. Compared with the mRNA expression levels of the H/R group, ginsenoside Re did not change expression of HIF-1α mRNA, while protein level of HIF-1α increased and that of HIF-1α[Ub]n decreased following ginsenoside Re treatment. Immunoprecipitation results showed that the amount of HIF-1α bound to VHL substantially decreased following ginsenoside Re treatment. In addition, ginsenoside Re treatment increased the expression of GLUT1 (glucose transporter 1) and REDD1 (regulated in development and DNA damage response 1), which are targets of HIF-1α and are critical for cell metabolism and viability. These results suggested that Ginsenoside Re treatment attenuated the myocardial injury induced by H/R, and the possible mechanism was associated with the inhibition of HIF-1α ubiquitination.
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Voltage control of room-temperature ferromagnetism has remained a big challenge which will greatly influence the multifunctional memory devices. In this paper, porous TiO2 thin films were deposited by dc-reactive magnetron sputtering onto ordered porous anodic alumina (PAA) substrates. Voltage-driving room-temperature resistance and magnetization switching without external magnetic field are simultaneously found in an Ag/TiO2/PAA/Al (Ag/TP/Al) device. Further analysis indicates that the formation/rupture of oxygen vacancy defect-based conductive filaments would be responsible for the changes of resistivity and magnetization. Our present results suggest that the TP nanoporous composite film material may therefore be used to achieve voltage control of magnetism and resistance switching in the future multifunctional memory devices. The Ag/TP/Al devices can also be used for new spintronic devices, neuromorphic operations, and alternative logic circuits and computing.