The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, ...particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin
by simulating hypoxia with CoCl
in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl
hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-β/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-β/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-β/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-β/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-β/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.
Due to the complexity of the structure and surface property of metal oxide catalysts, hydrophobization of metal oxide catalysts is a great challenge. The hydrophobization strategy and effects of ...hydrophobization on the surface property and catalytic performance of metal oxide catalysts deserve rigorous investigations. Herein, we adopt stearic acid to functionalize the surface of a Cu/ZnO catalyst by bridging stearic acid molecules with the Cu/ZnO catalyst surface. After functionalization, the hydrophobicity of the Cu/ZnO catalyst is greatly reinforced, while its structure and catalytic performance remain nearly unchanged. The hydrophobic Cu/ZnO catalyst exhibits a very positive inhibitory effect on the unfavorable water–gas shift reaction (WGSR) in one-step synthesis of dimethyl ether (DME) from syngas (CO + H2), while the catalytic activity of the hydrophobic Cu/ZnO catalyst for methanol synthesis is not affected. Lower CO2 selectivity and higher DME selectivity over the hydrophobic Cu/ZnO-4 catalyst, better than those of untreated catalyst, are obtained facilely. The promoted catalytic performance of the hydrophobic Cu/ZnO catalyst demonstrates that the surface hydrophobicity of heterogeneous catalysts is worthy of more attention for enriching their catalytic roles.
The issue of employability has already become a well-delineated topic of study among interpreting educators. However, the current literature still lacks descriptive research on interpreting students' ...employability development and ignores the developmental effects of interpreter competences in this process. Moreover, the advantage of using career adaptability for measurement is also under-researched. This exploratory case study aims at taking an initial step forward, surveying interpreting students' career adaptability development and the developmental effects of different interpreter competences on major adaptability resources, and ultimately diagnosing curriculum problems and making modifications accordingly. Thirty grade 2019 interpreting students from three Chinese universities contributed to data collection, through six questionnaires in a two-wave survey. The results highlight that, throughout the Chinese MTI program, interpreting students could become more concerned and well prepared for their future (concern), more curious to explore themselves and their surroundings (curiosity), and more capable of solving problems (confidence). The results also indicate that students' knowledge and language competence serve as the major facilitators in this process, and that other interpreter competences, such as psychological competence, transfer competence, professionalism, and cross-cultural competence, are also instrumental. In order to further boost their adaptability constructs, the results suggest that students' language and knowledge competence, professionalism, and cross-cultural and mental agility still need to be improved. Five suggestions for curriculum revision have been raised accordingly. As an initial effort, the current study will hopefully inspire further studies on interpreting students' career adaptability and add more knowledge to the curriculum design from this viewpoint.
High-grade serous ovarian carcinoma (HGSOC) is a cancer with dismal prognosis due to the limited effectiveness of existing chemo- and immunotherapies. To elucidate mechanisms mediating sensitivity or ...resistance to these therapies, we developed a fast and flexible autochthonous mouse model based on somatic introduction of HGSOC-associated genetic alterations into the ovary of immunocompetent mice using tissue electroporation. Tumors arising in these mice recapitulate the metastatic patterns and histological, molecular, and treatment response features of the human disease. By leveraging these models, we show that the ability to undergo senescence underlies the clinically observed increase in sensitivity of homologous recombination (HR)-deficient HGSOC tumors to platinum-based chemotherapy. Further, cGas/STING-mediated activation of a restricted senescence-associated secretory phenotype (SASP) was sufficient to induce immune infiltration and sensitize HR-deficient tumors to immune checkpoint blockade. In sum, our study identifies senescence propensity as a predictor of therapy response and defines a limited SASP profile that appears sufficient to confer added vulnerability to concurrent immunotherapy and, more broadly, provides a blueprint for the implementation of electroporation-based mouse models to reveal mechanisms of oncogenesis and therapy response in HGSOC.
A kind of corrosion-resistant Ni-Mo-P composite coating was deposited on the surface of AZ91D magnesium alloy substrate by electroless plating method with different concentration of Ce(NO3)3 and ...Nd(NO3)3. The deposition mechanism of Ni-Mo-P composite coating was explored. Furthermore, the effects of Ce(NO3)3 and Nd(NO3)3 concentration on the microstructure and properties of Ni-Mo-P composite coatings were studied. Results indicated that the Ni-Mo-P composite coatings prepared by adding the optimal concentration of Ce(NO3)3 and Nd(NO3)3 had few defects. Meanwhile, the deposition rate of the composite coatings and the adhesion between the coating and the magnesium alloy substrate were improved. When the concentration of Ce(NO3)3 and Nd(NO3)3 were 0.10 and 1.00 g/L, the NiMo-P composite coatings had the minimum corrosion rate of 0.826 and 0.681 g/m2·h, respectively. Herein, compared with the addition of Ce(NO3)3 , the Nd(NO3)3 added Ni-Mo-P composite coating has the maximum arc radius of capacitive resistance and significant improvement corrosion resistance.
The prediction of long non-coding RNA (lncRNA) subcellular localization is essential to the understanding of its function and involvement in cellular regulation. Traditional biological experimental ...methods are costly and time-consuming, making computational methods the preferred approach for predicting lncRNA subcellular localization (LSL). However, existing computational methods have limitations due to the structural characteristics of lncRNAs and the uneven distribution of data across subcellular compartments. We propose a discrete wavelet transform (DWT)-based model for predicting LSL, called DlncRNALoc. We construct a physicochemical property matrix of a 2-tuple bases based on lncRNA sequences, and we introduce a DWT lncRNA feature extraction method. We use the Synthetic Minority Over-sampling Technique (SMOTE) for oversampling and the local fisher discriminant analysis (LFDA) algorithm to optimize feature information. The optimized feature vectors are fed into support vector machine (SVM) to construct a predictive model. DlncRNALoc has been applied for a five-fold cross-validation on the three sets of benchmark datasets. Extensive experiments have demonstrated the superiority and effectiveness of the DlncRNALoc model in predicting LSL.
Cardamonin has promising potential in cancer prevention and therapy by interacting with proteins and modifying the expressions and activities, including factors of cell survival, proliferation, and ...angiogenesis. In our precious study, we have demonstrated that cardamonin suppressed vascular endothelial growth factor- (VEGF-) induced angiogenesis as evaluated in the mouse aortic ring assay. It is also known that microRNAs (miRNAs) play important roles in angiogenesis. Herein, we hypothesized whether antiangiogenesis effect of cardamonin in human umbilical vein endothelial cells (HUVECs) triggered by VEGF was associated with miRNAs. We found that cardamonin reduced the miR-21 expression induced by VEGF in HUVECs. Treatment with miR-21 mimics abolished the effects of cardamonin on VEGF-induced cell proliferation, migration, and angiogenesis in HUVECs. However, treatment with miR-21 inhibitors presented the opposite effects, indicating the vital role of miR-21 in this process. Our study provides a new insight of the preliminary mechanism of anti-VEGF-induced angiogenesis by cardamonin in HUVECs.
In order to minimize the thermal elongation of high-speed spindle of gear form grinding machine, an optimization method for thermal behavior is proposed in this paper. The influence of constrained ...modes of bearings on the positional accuracy of the spindle is discussed, and the optimum constrained mode is obtained. An objective function of thermal contact resistance is established according to the semi-empirical formula to optimize the routes of heat transfer in the spindle assemblies through the constrained optimization method. The simulation and experimental results show that the temperature rise of the grinding wheel shaft and its associated components are all very small, and the thermal elongation of the grinding wheel shaft is about zero.
The electroless Ni–Mo–P/CNTs composite coatings were applied on AZ91D magnesium alloys, and the effects of CNTs concentration on the microstructure, micro-indentation hardness, wear and corrosion ...behaviors of the composite coatings were studied. Meanwhile, the mechanism of wear and corrosion resistance for coatings was investigated. The results suggested that the surface morphology of the composite coating fabricated at 0.4 g/L CNTs concentration was smooth and compact, and the maximum micro-indentation hardness and minimum friction coefficient were achieved as 1263.54 HV and 0.201, respectively. The worn surface morphologies showed that the carbon film formed by the optimal concentration of CNTs was covered on the coating surface, which acted as solid lubricant to enhance the abrasion resistance of the composite coating. Furthermore, the coating deposited with 0.4 g/L CNTs concentration had excellent corrosion resistance, which could be attributed to the fine and dense structure which prevented the intrusion of corrosive liquid.
WC-12%Co-6%Cr coatings were deposited by high-velocity oxygen-fuel spraying technology (HVOF) on 42CrMo steel, and then, the sealing treatment was carried out by sol–gel aluminum phosphate inorganic ...sealing agent. The phases and porosity of the coatings before and after sealing were characterized by XRD and metallographic grayscale method, and high-temperature sliding wear tests were carried out at five different temperatures. The results showed that the coating/substrate bonding was mainly mechanical bonding with metallurgical bonding, and the high-temperature friction and wear mechanism of the coating was mainly contact fatigue and oxidation wear. The porosity of the coating was significantly reduced by aluminum phosphate sealing treatment, which was less than 2%, and the density was significantly improved. With the increase in wear temperature, the wear rate of the coatings increased, and the effect of phosphate sealing on reducing the wear loss was gradually weakened, and the highest service temperature was found near 450 °C.
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