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The computation of electromagnetic wave scatterings of a layered sphere is a canonical problem. Lorentz-Mie theory is suitable for plane wave incidence whereas spherically layered media theory can deal with arbitrary incident waves. Both theories suffer from the notorious numerical instabilities due to the involved Bessel functions with large order, small argument or high loss. Logarithmic derivative method has been proposed to solve the numerical issues with these theories. In this paper, by employing the equivalence between the asymptotic formulas of Bessel functions for small argument and for large order, the numerical issues with the spherically layered theory under both large order case and small argument case can be solved in a unified manner by canceling out the diverging terms in the asymptotic formulas. The derived stable formulas are simpler and faster than those based on logarithmic derivative method. It is shown that the derived formulas are good approximations to the canonical ones but are more numerically stable. The large lossy issue can be solved similarly.
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AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.
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Encéfalo , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Masculino , Femenino , Adulto , Imagen por Resonancia Magnética/métodos , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Adulto Joven , Mapeo Encefálico/métodos , Miopía Degenerativa/fisiopatología , Descanso/fisiologíaRESUMEN
We have successfully isolated and characterized the zinc carbamate complex (phen)Zn(OAc)(OC(=O)NHPh) (1; phen=1,10-phenanthroline), formed as an intermediate during the Zn(OAc)2 /phen-catalyzed synthesis of organic carbamates from CO2 , amines, and the reusable reactant Si(OMe)4 . Density functional theory calculations revealed that the direct reaction of 1 with Si(OMe)4 proceeds via a five-coordinate silicon intermediate, forming organic carbamates. Based on these results, the catalytic system was improved by using Si(OMe)4 as the reaction solvent and additives like KOMe and KF, which promote the formation of the five-coordinated silicon species. This sustainable and effective method can be used to synthesize various N-aryl and N-alkyl carbamates, including industrially important polyurethane raw materials, starting from CO2 under atmospheric pressure.
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BACKGROUND: Ezetimibe is a potent inhibitor of Niemann-Pick type C1-Like 1 and has been approved for the treatment of hypercholesterolemia. Our preliminary study showed that ezetimibe promotes cholesterol efï¬ux from vascular smooth muscle cells (VSMCs). Our aim was to investigate the cellular mechanisms underlying the ezetimibe actions. METHODS AND RESULTS: Rat VSMCs were converted to foam cells by incubation with cholesterol:methyl-ß-cyclodextrin. The intracellular free cholesterol, total cholesterol, and the ratio of cholesteryl ester to total cholesterol were decreased after the incubation of VSMCs with different concentrations of ezetimibe (3, 10, 30, and 30 µmol/l) or treated with 30 µmol/l of ezetimibe for different time periods (6, 12, 24, and 48 h). Our results also showed that the expression of caveolin-1, liver X receptor α, and ATP-binding cassette transporter ABCA1 was enhanced, but the expression of nSREBP-1c was decreased in a concentration- and time-dependent manner. RNA interference was used to determine the roles of caveolin-1 and SREBP-1 in the lipid-lowering effect of ezetimibe. The results showed that caveolin-1 was involved in the regulation of intracellular cholesterol content, and the expression of caveolin-1 was repressed by SREBP-1. CONCLUSION: The present study indicates that ezetimibe protects VSMCs from cholesterol accumulation by regulating the expression of lipid metabolism-related genes.
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Anticolesterolemiantes/farmacología , Azetidinas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Transportador 1 de Casete de Unión a ATP/genética , Animales , Caveolina 1/genética , Colesterol/farmacología , Ezetimiba , Metabolismo de los Lípidos/genética , Receptores X del Hígado , Masculino , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/metabolismo , Receptores Nucleares Huérfanos/genética , ARN Interferente Pequeño/genética , Ratas Sprague-Dawley , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , beta-Ciclodextrinas/farmacologíaRESUMEN
OBJECTIVE: Drug use evaluation (DUE) criteria were established to assess the rational use of antibiotic prophylaxis (RUAP) in Type I incision operations (TOIO) during peri-operation period and to enhance pharmacists' responsibilities for antibiotic stewardship. METHODS: The criteria were set with a threshold based on a literature review and discussions with multidisciplinary experts. Patients who received TOIO from July 2008 to June 2012 were enrolled in the study. The percentage of prescriptions adhering to all items of criteria was 10% at baseline. RESULTS: According to DUEs and interviews by pharmacists, the percentages of prescriptions adhering to all items of criteria of DUE-1, DUE-3, DUE-5, and DUE-8 were 13.3, 20.0, 50.0 and 66.7%, respectively. The study showed that the most common inappropriate therapies were no indications for prophylaxis antibiotic use and inappropriate choices of antibiotics. Pharmacists finally disseminated DUE criteria and reports to prescribe and improve RUAP in TOIO at the hospital through the Drug and Therapeutics Committee (DTC). CONCLUSION: The study demonstrated that application of pharmacist- directed DUE is a useful strategy to detect, supervise and help correct challenges encountered during antibiotic prophylaxis in TOIO.
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Profilaxis Antibiótica , Revisión de la Utilización de Medicamentos , Farmacéuticos , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Prescripción Inadecuada , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Background: Sphingosine kinase 1 (SPHK1) is a key enzyme that catalyzes the phosphorylation of sphingosine. Recent studies reported SPHK1 to be associated with renal cell carcinoma (RCC) progression by inducing targeted therapy resistance. However, the expression and the clinical significance of SPHK1 on RCC in those having received targeted therapy have not been elucidated. The present study explored the expression of SPHK1 in RCC tissues from targeted therapy recipients, the correlation of SPHK1 with clinicopathological parameters, and the effect of SPHK1 on RCC patient prognosis. Methods: Differential gene expression analysis of RCC treated with and without targeted therapy was performed. The correlations of SPHK1 expression with clinical parameters of RCC were examined. Gene set enrichment analysis (GSEA) was performed to clarify the potential role of SPHK1 associated with targeted therapy resistance. The value of SPHK1 as a diagnostic marker for RCC was also evaluated. The Kaplan-Meier method was applied to analyze the correlation between SPHK1 expression and patient survival rate by using the clinical data from patients with RCC. Results: Significant overexpression of SPHK1 was detected in RCC treated with targeted therapy. SPHK1 expression was closely correlated with RCC progression-related clinicopathological parameters. Therefore, elevated SPHK1 could effectively diagnose RCC and distinguish RCC with an advanced clinical stage and a high pathological grade. SPHK1 was associated with the stemness of RCC cells via the activation of the Wnt, Hedgehog, or Notch signaling pathways in targeted drug-treated or untreated RCC. Survival analysis of a large cohort of RCC samples indicated overexpression of SPHK1 to be inversely correlated with the overall and disease-free survival of patients with RCC. Conclusions: Our study indicated that SPHK1 associated with targeted therapy resistance could serve as a potential prognostic marker and a valuable biomarker of response to angiogenic agents in RCC.
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OBJECTIVE: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. METHODS: Rat-derived VSMC cell line A10 treated with 50mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. RESULTS: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. CONCLUSION: Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1.
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Caveolina 1/metabolismo , Colesterol/metabolismo , Músculo Liso Vascular/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo , Lipoproteínas LDL/farmacología , Músculo Liso Vascular/efectos de los fármacos , Presión , Ratas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidoresRESUMEN
AIM: To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. METHODS: Morphological changes of atherosclerotic lesions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin- eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. RESULTS: The administration of 20 mg. kg(-1 ). d(-1 )curcumin to apoE-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg/L ox-lipid density lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 micromol/L) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free cholesterol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl- Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear translocation of SREBP-1, reduced caveolin-1 expression level, and upregulated cellular lipid levels. CONCLUSION: Curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.
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Caveolina 1/metabolismo , Colesterol/metabolismo , Curcumina/farmacología , Músculo Liso Vascular/metabolismo , Transducción de Señal , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Técnica del Anticuerpo Fluorescente Indirecta , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Distribución Aleatoria , Ratas , Factores de TiempoRESUMEN
Several zinc salts were employed as catalysts for the synthesis of carbamates directly from aromatic amines, CO2 , and silicate esters. Zn(OAc)2 offered the best performance among the salts tested. The addition of an N-donor ligand such as 1,10-phenanthroline increased the yield. The best catalytic performance of Zn(OAc)2 can be explained by carboxylate-assisted proton activation. The interaction between the substrate and the catalyst can be observed by chemical shifts in 1 H and 15 Nâ NMR spectra. Isocyanate was a key intermediate, which was generated from amine and CO2 . Silicate ester was finally converted to siloxane, which was determined by 29 Siâ NMR. The commercially available catalyst system could be reused. The yield of isolated carbamate could reach up to 96 % with various substrates, and the catalytic reaction was amine-selective in the presence of other functional groups.
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Carbamatos/síntesis química , Dióxido de Carbono/química , Zinc/química , Aminas/química , Carbamatos/química , Ácidos Carboxílicos/química , Catálisis , Técnicas de Química Sintética , Silicatos/químicaRESUMEN
A direct synthesis of carbamates from amines and carbon dioxide in the presence of Ti(OR)4 (R=nBu (1), Me (2), Et (3), nPr (4)) was investigated. Aniline was reacted with titanium n-butoxide (1) in the presence of carbon dioxide (5â MPa) to give the corresponding n-butyl N-phenylcarbamate (BPC) in nearly quantitative yield (99 %) within 20â min. Furthermore, 1 could be regenerated upon reaction with n-butanol during water removal. The recovered 1 could then be reused in a subsequent reaction.
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AIM: To investigate whether cytosolic heat shock protein 90 (HSP90) acts as a molecular chaperone on the activated extracellular signal-regulated kinase 1/2 (ERK1/2) and cell proliferation stimulated by reactive oxygen species (ROS) in rat vascular smooth muscle cells (VSMC). METHODS: VSMC were exposed to 1 micromol/L LY83583 (6-anilinoquinoline-5,8-quinolinedione, producer of ROS) for 120 min in the presence or absence of 5 micromol/L geldanamycin, a specific inhibitor of HSP90. Then the total, soluble, and insoluble proteins of the cells were collected. HSP90, ERK1/2, and phosphor-ERK1/2 in the cell lysate were measured by Western blotting. The interaction of HSP90 and phosphor-ERK1/2 was analyzed by immunoprecipitation assay, and the nuclear phosphor-ERK1/2 was measured by Western blotting and immunofluorescence. Cell proliferation was tested by cell counting and 3-(4,5-dimethylthiazol-2-y1)-3,5-di-phenyltetrazolium bromide (MTT). RESULTS: The cytosolic HSP90 of VSMC was upregulated by LY83583 in a time-dependent manner with the peak at 120 min, which is consistent with the late peak of phosphor-ERK1/2. Immunoprecipitation and Western blotting analyses showed that LY83583 increased the interaction of HSP90 with phosphor-ERK1/2, the phosphor-ERK1/2 level, and the soluble phosphor-ERK1/2 level by 1.8-, 2.5-, and 2.9-fold, respectively. In contrast, the insoluble phosphor-ERK1/2 of VSMC was decreased. Interestingly, LY83583 treatment promoted the nuclear phosphor-ERK1/2 by 7.6-fold as confirmed by Western blotting and immunofluorescence assays. Furthermore, cell counting and the MTT assay showed that LY83583 stimulated VSMC proliferation with the increased expression of HSP90 and levels of soluble and nuclear phosphor-ERK1/2. Pretreatment of geldanamycin antagonized the effect of LY83583. CONCLUSION: HSP90 could mediate the oxidative stress-stimulated, late-phase activation of ERK1/2 and VSMC proliferation by promoting the ERK1/2 phosphorylation, the association of itself with phosphor-ERK1/2, and the solubility and nuclear translocation of phosphor-ERK1/2.