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Introduction: Cholic acid (CA) is a natural steroid useful in treating chronic bronchitis and cholecystitis. On the other hand, its potential impact on osteoarthritis (OA) is unknown. Objective: Using an in vitro and in vivo osteoarthritis model, we sought to assess the chondroprotective properties of CA. Methods: We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells. Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection. Furthermore, how CA affects the OA model in SpragueDawley (SD) rats was evaluated. Results: CA significantly suppressed the up-regulation of the interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP-13) and the downregulation of aggrecan and type II collagen A1 (COL2A) in chondrocytes treated tumor necrosis factor-alpha (TNF-α). Differentially expressed genes (DEG) enrichment revealed IL-17, TNF, chemokine, cytokine-cytokine receptor, toll-like receptor, and nucleotide oligomerization domain-like receptor were the primary signaling pathways. The enriched DEGs included CXCL6, CCL20, MMP3, CXCL3, CXCL11, CCL5, CXCL10, MMP9, MMP13, and CXCL2; these DEGs are involved in inflammatory responses and their expression induced by TNF-α was reversed by CA treatment. CA inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha (IκBα) phosphorylation induced by TNF-α. Furthermore, CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α), glucose regulatory protein 78 (GRP78), and sirtuin 1 (SIRT1), and down-regulation of phosphorylation of AMP-activated protein kinase-α (p-AMPKα) in TNF-α-treated chondrocytes. Conclusions: CA significantly ameliorated cartilage degradation in the OA rat model. CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5FU) and its derivatives have been widely used for cancer treatment; however they fail to achieve selective chemotherapy. Herein, this work highlights a successful development of a pH-sensitive aliphatic 5-fluorouracil (5FU) derivative prodrug, which is synthesized via chemically linking 5FU and stearyl alcohol (SA) using ortho ester linkage. It can further self-assemble into a synergistic small molecule nanodrug through a noncovalent interaction with doxorubicin (DOX). The nanodrug displays precise structure and high drug loading (more than 15% of drug loading content (DLC) and 87% of drug loading efficiency (DLE)). SA and ortho ester linkages endow the nanodrug with high lipophilicity on tumor cell membrane and tumoral intracellular pH response, respectively. The nanodrug also exhibits a slightly negatively charged surface (−0.513 mV) at physiological pH (7.4) and a large-to-small size change from 176.2 to 128.9 nm at tumoral intracellular pH (5.0). These superior characteristics endow the nanodrugs with blood circulation stability, selective tumor accumulation, improved cellular uptake, efficient drug release, as well as synergistic effect on tumor cells, thereby significantly inhibiting tumor growth (smaller than initial tumor size), reducing side effects, and prolonging survival time. Thus, such a pH-sensitive small molecule nanodrug self-assembled from the aliphatic 5FU derivative and DOX has a great potential for selective synergistic cancer therapy, greatly advancing their clinical use. [ABSTRACT FROM AUTHOR]

Using ternary molten salt with a molar ratio of NaCl:KCl:CsCl = 30:24.5:45.5 and ZrCl4 as raw materials to prepare a NaCl-KCl-CsCl-Cs2ZrCl6 composite electrolyte. Characterizing by XRD, ICP-AES, optical microscopy and SEM-EDS, the results showed that when the molar ratio of CsCl:ZrCl4 ≥ 2:1, Cs2ZrCl6 was generated according to the stoichiometric reaction; when the molar ratio of CsCl:ZrCl4 < 2:1, CsCl in molten salt was almost completely converted to Cs2ZrCl6, and there was a ZrCl4 phase. When the molar ratio of CsCl:ZrCl4 = 2:1, with the increase of the reaction temperature and reaction time, the concentration of zirconium ions first increased and then decreased. The optimized preparation process conditions are: the 2:1 molar ratio of CsCl to ZrCl4 in NaCl-KCl-CsCl, 500 °C of reaction temperature of and 3 h of reaction time. Under this condition, 99.68% conversion rate from ZrCl4 to Cs2ZrCl6 was obtained. Taking the prepared NaCl-KCl-CsCl-Cs2ZrCl6 composite electrolyte as a raw material, a preliminary study of molten salt electrolytic refining zirconium was carried out, and a refined zirconium product with a dendrite of 10.61 mm was obtained under the conditions of a zirconium ions concentration of 5%, an electrolysis temperature of 750 °C, a current density of 0.1 A/cm2, and an electrolysis time of 9 h, indicating that the composite electrolyte can be used for the electrolytic refining of zirconium. [ABSTRACT FROM AUTHOR]

Ni-20Cr-Eu2O3 composites were designed as new control rod materials and were synthesized from Ni, Cr, and Eu2O3 mixture powders via ball milling and vacuum hot pressing. During ball milling, Eu2O3 was fined, nano-crystallized, amorphized, and then dissolved into matrix. The effect of Eu2O3 content on the microstructure and mechanics was researched, and the corresponding mechanism was discussed. The relative densities, grain sizes, and microhardness increased when Eu2O3 content increased. According to the TEM observations, Eu2O3 particles showed a semi-coherent relationship with the matrix. The results of mechanical property testing showed that the ultimate tensile strength, yield strength, and elongation decreased with the Eu2O3 content increased. The maximum ultimate tensile strength, yield strength, and elongation were 741 MPa, 662 MPa, and 4%, respectively, with a 5 wt.% Eu2O3 addition. The experimental strengths were well matched with the theoretical values calculated by the strengthening mechanisms indicating that this method was highly effective for predicting the mechanical properties of Ni-20Cr-Eu2O3 composites. [ABSTRACT FROM AUTHOR]

Nitride film as a hydrogen permeation barrier on zirconium hydride has seldom been studied. In this work, the zirconium nitride films were prepared on zirconium hydride in an atmosphere of N2 and N2 + H2 at 500~800 °C, with a holding time of 5 h and 20 h, and the mechanisms of film growth and hydrogen permeation were analyzed. The results showed that the film growth was mostly influenced by the temperature, followed by the reaction atmosphere and the holding time. The hydrogen could increase the nitrogen diffusivity during the formation of zirconium nitride films. The in situ nitriding conditions were optimized as 800 °C, N2 + H2 atmosphere, and 5~20 h. The chemical composition of ZrN-based films was mainly comprised of Zr and N, with a minor content of O. In addition, the film exhibited a major phase of ZrN, accompanied by the coexistence of ZrO2, ZrO, ZrN(NH2), and ZrN0.36H0.8, as well as O-H and N-H bonds based on the XPS analysis. The as-prepared ZrN base films in the present study exhibited superior hydrogen permeation resistance to other ZrO2 films previously reported. The hydrogen permeation resistance of the films could be attributed to the following mechanisms, including the chemical capture of hydrogen by the above-mentioned compounds and bonds; the physical barrier of continuous and dense film incurred from the volume effect of different compounds based on Pilling–Bedworth model and the different nitrogen diffusion coefficients at different temperatures. [ABSTRACT FROM AUTHOR]