177 research outputs found
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Study on the Effect of Cuisine Tourism Resource on Touristsâ Willingness to Visit
This article aims at examining if touristsâ evaluation of cuisine tourism resource has a positive effect on their willingness to visit (WTV) the destination (H1). In Study 1, the content analysis of travelogues of 60 Chinese major tourist cities shows that the scenic spots have a significant effect on WTV, while the effect of cuisine tourism resource on WTV is not supported. Moreover, the tourist city Chengdu with both abundant scenic spots and cuisine resources is chosen for further research of how cuisine resources influence touristâ decisions. In term of 276 questionnaires (Study 2) and 30 interviewee (Study 3), the results show that the impact of the cuisine resource on WTV is moderated by the touristsâ evaluation on the scenic spots. Only when tourists have a high evaluation on scenic spots, the cuisine resource plays a positive impact on WTV, showing the auxiliary attraction of cuisine resource to tourists
Bioactive organic/inorganic hybrids with improved mechanical performance
New sol-gel functionalized poly-ethylene glycol (PEGM)/SiO2-CaO hybrids were prepared with interpenetrating networks of silica and PEGM through the formation of Si-O-Si bonds. Bioactive and mechanical properties were investigated for a series of hybrids containing varying organic/inorganic ratios and PEG molecular weights. In contrast to the unmodified PEG/SiO2-CaO hybrids, which rapidly dissolved and crumbled, the epoxy modified hybrids exhibited good mechanical properties and bioactivity. The compressive strength and Young's modulus were greater for higher molecular weight PEGM hybrids (PEGM600 compared to PEGM300). Compressive strengths of 138 MPa and 81 MPa were found for the 50: 50 and 60: 40 organic/inorganic hybrid samples respectively, which are comparable with cortical bone. Young's modulus values of âŒ800 MPa were obtained for the 50 : 50 and 60 : 40 organic/inorganic hybrids. Bioactivity tests were conducted by immersing the hybrids into simulated body fluid and observing the formation of apatite. Apatite formation was observed within 24 hours of immersion. PEGM600 hybrids showed enhanced apatite formation compared to PEGM300 hybrids. Increased apatite formation was observed with increasing organic/inorganic ratio. 70 : 30 and 60 : 40 hybrids exhibited the greatest apatite formation. All PEGM hybrids samples had good cell viability and proliferation. The 60 : 40 PEGM600 hybrids displayed the optimal combination of bioactivity and mechanical strength. The bioactivity of these hybrids, combined with the enhanced mechanical properties, demonstrate that these materials have significant potential for bone regeneration applications
Simultaneous determination of prodrug of Ginkgolide B and Ginkgolide B in rat plasma by LC-MS/MS
A simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established and validated for the determination of prodrug of ginkgolide B (PGB) and its metabolite, ginkgolide B (GB) in rat plasma. The separation was achieved on a Waters Symmetry Shield RP18 column (150 mm Ă 3.9 mm i.d., 5 ÎŒm particle size), using a mobile phase composed of methanol/water with 10 mM ammonium acetate (85:15, v/v) at a flow rate of 800 ÎŒL/min in 2 min. An API 3200 triple quadrupole mass spectrometer equipped with electrospray ionization source was operated in negative ionization mode. Multiple reaction monitoring (MRM) was performed to quantify PGB, GB and the internal standard (IS) at m/z transitions of 528.1 â 122.0, 423.4 â 367.3, 407.5 â 351.2, respectively. A good linearity was found. Intra- and inter-day precision, accuracy, extraction recovery, matrix effect and stability were validated to be within an acceptable range. The developed method was successfully applied to a pharmacokinetic study after intravenous administration of a 10 mg/kg dose of PGB to rats.Colegio de FarmacĂ©uticos de la Provincia de Buenos Aire
Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors
Objective Generalized DNA hypomethylation contributes to altered T cell function and gene expression in systemic lupus erythematosus (SLE). Some of the overexpressed genes participate in the disease process, but the full repertoire of genes affected is unknown. Methylation-sensitive T cell genes were identified by treating T cells with the DNA methyltransferase inhibitor 5-azacytidine and comparing gene expression with oligonucleotide arrays. CD70, a costimulatory ligand for B cell CD27, was one gene that reproducibly increased. We then determined whether CD70 is overexpressed on T cells treated with other DNA methylation inhibitors and on SLE T cells, and determined its functional significance. Methods Oligonucleotide arrays, real-time reverse transcriptionâpolymerase chain reaction, and flow cytometry were used to compare CD70 expression in T cells treated with 2 DNA methyltransferase inhibitors (5-azacytidine and procainamide) and 3 ERK pathway inhibitors known to decrease DNA methyltransferase expression (U0126, PD98059, and hydralazine). The consequences of CD70 overexpression were tested by coculture of autologous T and B cells with and without anti-CD70 and measuring IgG production by enzyme-linked immunosorbent assay. The results were compared with those of T cells from lupus patients. Results SLE T cells and T cells treated with DNA methylation inhibitors overexpressed CD70 and overstimulated B cell IgG production. The increase in IgG synthesis was abrogated by anti-CD70. Conclusion SLE T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. This increased B cell costimulation and subsequent immunoglobulin overproduction may contribute to drug-induced and idiopathic lupus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34311/1/20255_ftp.pd
Peroxo Species Formed in the Bulk of Silicate Cathodes
Oxygen redox in Liârich oxides may boost the energy density of lithiumâion batteries by incorporating oxygen chemistry in solid cathodes. However, oxygen redox in the bulk usually entangles with voltage hysteresis and oxygen release, resulting in a prolonged controversy in literature on oxygen transformation. Here, we report spectroscopic evidence of peroxo species formed and confined in silicate cathodes amid oxygen redox at high voltage, accompanied by Co/Co redox dominant at low voltage. Firstâprinciples calculations reveal that localized electrons on dangling oxygen drive the OâO dimerization. The covalence between the binding cation and the OâO dimer determines the degree of electron transfer in oxygen transformation. Dimerization induces irreversible structural distortion and slow kinetics. But peroxo formation can minimize the voltage drop and volume expansion in cumulative cationic and anionic redox. These findings offer insights into oxygen redox in the bulk for the rational design of highâenergyâdensity cathodes
Population pharmacokinetics of FCN-159, a MEK1/2 inhibitor, in adult patients with advanced melanoma and neurofibromatosis type 1 (NF1) and model informed dosing recommendations for NF1 pediatrics
Objective: FCN-159 is a highly active mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor in patients with advanced melanoma and neurofibromatosis type 1 (NF1). We report a population pharmacokinetic (PopPK) model-based analysis of FCN-159 and its application to inform dose selection for NF1 pediatric trials.Methods: PK data collected from patients with advanced melanoma and NF1 in two clinical studies (NCT03932253 and NCT04954001) were analyzed using a non-linear mixed effects model. The adult model was adapted by incorporating allometric scaling for PK projection in 2â17Â years old children. Pediatric exposure in different body surface area (BSA) bins was simulated to identify nominal doses (i.e., dose amounts given as integers) and BSA bin cutoffs to achieve exposure comparable to adultsâ optimal exposure across the entire pediatric BSA range.Results: The final dataset consisted of 45 subjects with a total of 1030Â PK samples. The PK of FCN-159 was well-described by a 2-compartment model with first-order linear elimination and delayed first-order absorption. Covariates, including BSA, age, sex, albumin, total protein, and cancer type, were identified as statistically significant predictors of FCN-159 disposition. Simulations based on the final model projected daily doses of 4Â mg/m2 QD with optimized BSA bin cutoffs would allow fixed nominal doses within each bin and result in steady state exposure approximating the adult exposure observed at the recommended phase 2 dose (RP2D) in NF1, which is 8Â mg QD.Conclusion: The developed population PK model adequately described the PK profile of FCN-159, which was adapted using allometric scaling to inform dose selection for NF1 pediatric trials
Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice
Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Massonâs trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury
Galectin-3 synergizes with CD47 to Suppress Phagocytosis and T cell immunity in Peritoneal Metastases of Gastric Adenocarcinoma
View full abstracthttps://openworks.mdanderson.org/leading-edge/1061/thumbnail.jp
Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases
UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a don\u27t eat me signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal3) expression correlated with CD47 expression, and coexpression of Gal3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal3-deficient tumor cells into either wild-type and Lgals3-/- mice led to a reduction in M2 macrophages and increased T-cell responses compared with Gal3 wild-type tumor cells, indicating that tumor cell-derived Gal3 plays a more important role in GAC progression and phagocytosis than host-derived Gal3. Dual blockade of Gal3 and CD47 collaboratively suppressed tumor growth, increased phagocytosis, repolarized macrophages, and boosted T-cell immune responses. These data uncovered that Gal3 functions together with CD47 to suppress phagocytosis and orchestrate immunosuppression in GAC with PC, which supports exploring a novel combination therapy targeting Gal3 and CD47.
SIGNIFICANCE: Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma
Corrigendum: The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis
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