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To investigate the impact of Sitagliptin against obesity and the underlying mechanism. Obese immature mice were treated with 10, 30, and 90 mg/kg Sitagliptin, respectively. The body weights were recorded and the level of serum biochemical indexes were detected. The visceral fat ratio of each mouse was determined. The pathological change in adipose tissues was determined by HE staining, while F4/80 and CD206 levels in adipose tissues were determined by the immunohistochemical analysis. Lipid formation was evaluated by Oil red O staining assay. RAW264.7 cells were stimulated using oxLDL, followed by being incubated with different concentrations of Sitagliptin. The release of ADPN, IL-6, IL-1ß, TNF-α, and the activity of SOD, was measured by ELISA assay. Western blotting was applied to determine adipsin, Nrf2, Keap1, and HO-1 protein levels. ROS level was checked using the DCFH-DA assay. RT-PCR assay was utilized to detect the mRNA levels of IL-6, IL-1ß, TNF-α, Nrf2, Keap1, and HO-1. The body weight gain, infiltration of multinucleated cells, enlarged size of adipocytes, increased lipid accumulation, elevated visceral fat ratio, declined ADPN level, upregulated adipsin, and disordered serum biochemical indexes in obese immature mice were statistically significantly reversed by Sitagliptin. Excessive release of inflammatory factors and upregulated F4/80 and CD206 were observed in obese immature mice, which were statistically significantly repressed by Sitagliptin. Furthermore, the elevated MDA level, increased SOD activity, and inhibited Nrf2 pathway in obese immature mice were significantly reversed by Sitagliptin. In oxLDL stimulated RAW264.7 cells, increased release of inflammatory factors, ROS, and MDA, elevated SOD activity, and inactivated Nrf2 pathway were observed, which were statistically significantly abolished by the treatment of Sitagliptin. Sitagliptin alleviated obesity in immature mice by inhibiting inflammation and oxidative stress.
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The frost damage behavior of recycled aggregates concrete (RAC) in a cold region is inherently more complex due to the incorporation of recycled coarse aggregate (RCA). In real-world service environments, the combined effects of mechanical loading and environmental conditions further make RAC's damage mechanism more intricate. This study explores the impact of uniaxial compressive loading (at 0.1fc, 0.3fc, and 0.5fc, respectively), freeze-thaw cycles, and chloride penetration on the relative dynamic elastic modulus (RDEM), mass transport properties, and microstructure of RAC with varying RCA replacement ratios. The results indicate that specimens loaded at 0.3fc exhibit enhanced frost resistance, with reduced water absorption and chloride ion content. Additionally, a damage model is developed to quantify the effects of mechanical loading, freeze-thaw cycles, and chloride penetration on RDEM degradation. The investigation using X-ray computed tomography (X-CT), mercury intrusion porosimetry (MIP), and scanning electron microscopy (SEM) techniques reveals that as compressive stress levels increase, the microstructural density and porosity of RAC initially decrease before increasing. Moreover, the RDEM of RAC decreases with decreasing pore sphericity. Compared to the R100-S55 samples, the pore sphericity of R100-S55-0.5fc samples increased by 60.4 % in the range of 0.4-0.5, resulting in a decrease of approximately 17.72 % in the RDEM. Furthermore, the initial sorptivity of frost-damaged RAC exhibits a significant linear relationship with porosity. Overall, this study elucidates the evolving trends of mass transport properties and microstructure in RAC under loading and freeze-thaw conditions, laying a theoretical groundwork for the widespread application of RCA.
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Metallic nanomaterials (MNMs) possess unique properties that have led to their widespread application in fields such as electronics and medicine. However, concerns about their interactions with environmental factors and potential toxicity to aquatic life have emerged. There is growing evidence suggesting MNMs can have detrimental effects on aquatic ecosystems, and are potential for bioaccumulation and biomagnification in the food chain, posing risks to higher trophic levels and potentially humans. While many studies have focused on the general ecotoxicity of MNMs, fewer have delved into their trophic transfer within aquatic food chains. This review highlights the ecotoxicological effects of MNMs on aquatic systems via waterborne exposure or dietary exposure, emphasizing their accumulation and transformation across the food web. Biomagnification factor (BMF), the ratio of the contaminant concentration in predator to that in prey, was used to evaluate the biomagnification due to the complex nature of aquatic food chains. However, most current studies have BMF values of less than 1 indicating no biomagnification. Factors influencing MNM toxicity in aquatic environments include nanomaterial properties, ion variations, light, dissolved oxygen, and pH. The multifaceted interactions of these variables with MNM toxicity remain to be fully elucidated. We conclude with recommendations for future research directions to mitigate the adverse effects of MNMs in aquatic ecosystems and advocate for a cautious approach to the production and application of MNMs.
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Nanoestructuras , Contaminantes Químicos del Agua , Humanos , Ecosistema , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Cadena Alimentaria , Nanoestructuras/toxicidad , Estado NutricionalRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung condition that occurs in premature infants who undergo prolonged mechanical ventilation and oxygen therapy. Existing treatment methods have shown limited efficacy, highlighting the urgent need for new therapeutic strategies. Artesunate (AS) is a compound known for its potential anti-inflammatory properties, and studies have shown its protective effects against acute lung injury. However, its impact on BPD and the underlying mechanisms remain unclear. OBJECTIVE: To investigate the effect and underlying mechanism of AS on chronic hyperoxiainduced BPD in neonatal mice. METHOD: Full-term C57BL/6J mice were randomly assigned to the Air+lactate Ringer's solution (L/R) group, O2 + L/R group, and O2 + AS group. Analysis was performed using assay methods such as ELISA, RT-qPCR, hematoxylin-eosin staining, and Western blotting. RESULTS: Compared with the O2+L/R group, the expression of inflammatory factors in the serum, tissue, and BALF of the O2+AS group was significantly reduced, the lung function of the mice was improved, and the inflammatory infiltrates were significantly alleviated. AS inhibited the mRNA expression of inflammatory factors in mice. We found that the expression of nuclear p65 and cytoplasmic p-IκBα in the NF-κB pathway was inhibited after adding AS. CONCLUSION: AS ameliorated chronic hyperoxia-induced BPD in neonatal mice probably by inhibiting the expression of NF-κB pathway and inflammatory factors.
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Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased ß-catenin expression and inhibited the activation of Wnt/ß-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of ß-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.
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MicroARNs , Neoplasias Ováricas , Femenino , Humanos , Apoptosis , Astrocitos/patología , beta Catenina/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Hipoxia , MicroARNs/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Microambiente TumoralRESUMEN
With the rapid development of human lunar exploration projects, the lunar base establishment and resource utilization are on the way, and hence it is urgent and significant to reasonably predict engineering properties of the lunar regolith, which remains to be unclear due to limited lunar samples currently accessible for geotechnical tests. In this contribution, we aim to address this outstanding challenge from the perspective of granular material mechanics. To this end, the 3D multi-aspect geometrical characteristics and mechanical properties of Chang'e-5 lunar samples are for the first time evaluated with a series of non-destructive microscopic tests. Based on the measured particle surface roughness and Young's modulus, the interparticle friction coefficients of lunar regolith particles are well predicted through an experimental fitting approach using previously published data on terrestrial geomaterials or engineering materials. Then the residual friction angle of the lunar regolith under low confining pressure is predicted as 53° to 56° according to the particle overall regularity and interparticle friction coefficients of Chang'e-5 lunar samples. The presented results provide a novel cross-scale method to predict engineering properties of the lunar regolith from particle scale information to serve for the future lunar surface engineering construction.
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Alkali-activated slag concrete (ASC) is regarded as one of the most promising sustainable construction materials for replacing ordinary Portland cement concrete (OPC) due to its comparable strength and outstanding durability in challenging environments. In this study, the corrosion of steel bars embedded in ASC and OPC was studied by means of an electrically accelerated corrosion test of steel bars in concrete. Meanwhile, the bond performance of the corroded steel bars embedded in ASC was tested and compared with corresponding OPC groups. The results showed that ASC and OPC behaved differently in terms of bond deterioration. The high chemical resistance of ASC decreased the corrosion of steel bars and, thus, increased the residue bond strength and the bond stiffness.
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The precipitation of calcium carbonate (CaCO3) is a key mechanism in carbon capture applications relying on mineralization. In that regard, Ca-rich cementitious binders offer a unique opportunity to act as a large-scale carbon sink by immobilizing CO2 as calcium carbonate by mineralization. However, the atomistic mechanism of calcium carbonate formation is still not fully understood. Here, we study the atomic scale nucleation mechanism of an early stage amorphous CaCO3 gel based on reactive molecular dynamics (MD) simulations. We observe that reactive MD offers a notably improved description of this reaction as compared to classical MD, which allows us to reveal new insights into the structure of amorphous calcium carbonate gels and formation kinetics thereof.
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Carbonato de Calcio , Simulación de Dinámica Molecular , Carbonato de Calcio/químicaRESUMEN
Background: Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods: The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot. Results: AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1ß, IL-18, IL-6, IL-8, MCP-1, and TNF-α in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice. Conclusion: AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.
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This paper presents a comprehensive investigation of the bond characteristics of steel bar reinforced geopolymer concrete (GPC). The ASTM A944 beam end tests were conducted on GPC beams reinforced with plain or ribbed bars. The bond-slip curves and the bond strength of GPC beams were obtained. The relationship between the bond stress and relative slip in plain and ribbed bar reinforced GPC has been represented by empirical formulae. The bond testing results were compared with those of corresponding ordinary Portland cement concrete (OPC) using statistical hypothesis tests. The results of hypothesis testing showed that GPC was significantly superior to OPC in terms of bond capability with plain bars and bond stiffness with ribbed bars. The statistical analysis indicated that the bond-slip relations derived for OPC are inapplicable to GPC; thus, new bond-slip relations are suggested to estimate the development of bond stress and relative slip between GPC and steel bars.
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Plant roots generally enhance soil strength and stabilize slopes through hydro-mechanical effects, especially in forested areas prone to shallow slope failure. Forest fires can severely weaken the hydro-mechanical contribution of roots to slopes, however, the hydro-mechanical characteristics of soil-root systems (SRS) affected by wildfire remain poorly understood. To obtain insight into the post-fire hydro-mechanical characteristics of SRS, a subalpine conifer forested area in Sichuan Province, China that suffered a wildfire on March 30, 2019 was continuously monitored over two consecutive years. Samples from zones with different degrees of burn severity were collected and tests both for roots and SRS were performed. The results revealed a substantial decline in root number, which decreased by 46%-58% two years after the wildfire in the medium- and high-severity areas. The tensile strength tests indicated a reduction of root tensile strength by 36%-47% for roots with diameters less than 2 mm. The shear strength of the SRS determined from saturated direct shear tests strongly and had degraded by 55%-82% two years after the wildfire because of root death and reduced root reinforcement. The results of hydraulic conductivity tests over the same time period indicated an abrupt reduction of SRS hydraulic conductivity within several months after the fire owing to ash clogging and the formation of a hydrophobic layer. After more time had elapsed, however, hydraulic conductivity had increased unexpectedly by a factor of 2.2-3.2 greater than that of unburned soil. We attribute this observation to the formation of macropore flow pathways from decayed roots, which was observed by scanning electron microscopy. The findings presented here provide important insight into the temporal changes of the hydro-mechanical characteristics of SRS in burned areas and their associated mechanisms and could be a useful reference to better evaluate post-wildfire stability of subalpine conifer forest in similar environmental conditions.
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Incendios , Incendios Forestales , China , Bosques , SueloRESUMEN
Long non-coding RNAs (lncRNAs) have been proposed as potential targets in OSCC gene therapy. Thus, the study aims to analyze how they exert functions in OSCC. LINC00958, AIM2, Gasdermin D (GSDMD) and tumor protein p53 (TP53) expression levels are analyzed by Quantitative Real-time PCR (qPCR) or Western blotting (WB) in OSCC cells lines. The roles of LINC00958 in cell proliferation, cell death, and GSDMD expression respectively were analyzed by Cell Counting Kit-8 (CCK8) assay, flow cytometry and Immunofluorescence (IF) assay. In addition, expressions of pyroptosis- and autophagy-related proteins are evaluated by WB detection. The targeted binding of LINC00958 and miR-4306 or AIM2 mRNA is predicted by bioinformatics analysis and detected by biodual luciferase system. RIP and qPCR assays analyze whether LINC00958 interacts with SIRT1. We found that LINC00958 showed upregulation in OSCC cells compared to normal oral epithelial cells. LINC00958 silencing significantly suppressed OSCC cell proliferation, induced cell death and reduced autophagy. LINC00958 regulated the levels of miR-4306 which binds to the 3'UTR of AIM2, and interacts with and modulates SIRT1 protein expression. LINC00958 regulated GSDMD and AIM2 levels, as well as p53 and SIRT1 levels. SIRT1 overexpression markedly reversed aforementioned effects of LINC00958. LINC00958 not only downregulated miR-4306 levels to activate the pyroptosis pathway mediated by AIM2 and promoted cancer cell survival but also induced a decrease in SIRT protein expression to further reduce p53 levels.
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Proteínas de Unión al ADN/genética , MicroARNs/genética , Neoplasias de la Boca/genética , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Muerte Celular/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/metabolismo , Neoplasias de la Boca/metabolismo , ARN Largo no Codificante/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
This paper studies the statistical correlation in mechanical characteristics of class F fly ash based geopolymer concrete (CFGPC). Experimentally measured values of the compressive strength, elastic modulus and indirect tensile strength of CFGPC specimens made from class F fly ash (CFA) were presented and analyzed. The results were compared with those of corresponding ordinary Portland cement concrete (OPCC) using statistical hypothesis tests. Results illustrated that when possessing similar compressive and tensile strength, the elastic modulus for CFGPC is significantly lower than that of OPCC. The corresponding expressions recommended by standards for the case of OPCC is proved to be inaccurate when applied in the case of CFGPC. Statistical regression was used to identify tendencies and correlations within the mechanical characteristics of CFGPC, as well as the empirical equations for predicting tensile strength and elastic modulus of CFGPC from its compressive strength values. In conclusion, CFGPC and OPCC has significant differences in terms of the correlations between mechanical properties. The empirical equations obtained in this study could provide relatively accurate predictions on the mechanical behavior of CFGPC.