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1.
Macromol Rapid Commun ; : e2100116, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938056

RESUMO

Polymer-based film capacitors with high breakdown strength and excellent flexibility are crucial in the field of advanced electronic devices and electric power systems. Although massive works are carried to enhance the energy storage performances, it is still a great challenge to improve the energy density of polymer composites under the premise of large-scale industrial production. Herein, a general strategy is proposed to improve the intrinsic breakdown strength and energy storage performances by blending core-shell structured methyl methacrylate-butadiene-styrene (MBS) rubber particles into a polymer matrix. Good compatibility and uniform dispersion state of MBS particles are observed in the matrix. Polarizing microscopy images show that blended films exhibit clear reduction of crystalline grains with the addition of MBS particles. Accordingly, an increased breakdown strength of 515 MV m-1 and discharged energy density of 12.33 J cm-3 are observed in poly(vinylidene fluoride-co-hexafluoropropylene)-based composite films. Through comprehensive characterizations, it is believed that the superior energy storage performance of composite films is attributed to decreased crystalline grains, improved mechanical properties, and restriction on carrier motion. These results provide a novel design of dielectric polymers for high breakdown strength and discharged energy density applications.

2.
J Hazard Mater ; 412: 125298, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33951874

RESUMO

In this study, magnetic zeolitic imidazolate frameworks (ZIF-8) was prepared by a one-step method, where its evolution involved the coprecipitation reactions concomitant with the self-assembly reactions. Structural characterizations indicated that magnetic ZIF-8 showed irregular polyhedral morphology with a large specific surface area (696.5 m2/g) and saturation magnetization (4.31 emu/g). The as-prepared magnetic ZIF-8 enhanced the adsorption performance of As(III) and As(V), compared with bare Fe3O4. The pseudo second-order kinetic model (R2 = 0.9627 and 0.9893 for As(III) and As(V), respectively) and the Langmuir model (R2 = 0.9441 for As(III) and 0.9851 for As(V)) can fit the adsorption process well, confirming the nature of single-layer homogeneous chemisorption. The adsorption capacity was 30.87 and 17.51 mg/g, and their corresponding values of PC were 2.664 and 1.286 L/g, for As(III) and As(V), respectively. Solution pH showed an adverse effect on As(V) adsorption whereas no obvious effect on As(III). The ionic strength and coexisting ions had not obvious influence on adsorption of As(III) and As(V). The adsorption mechanism was explored and discussed based on the detailed spectroscopy analysis. This adsorbent can be recovered magnetically after use, which is promising for the practical application.

3.
J Immunol Res ; 2021: 6638119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954205

RESUMO

Background: Maternal supplementation with 1α,25-dihydroxyvitamin D3 (VD3) has immunologic effects on the developing fetus through multiple pathways. This study was aimed at investigating the effects of VD3 supplementation on immune dysregulation in the offspring during allergic rhinitis. Methods: Different doses of VD3 as well as control were given to pregnant female mice. Ovalbumin (OVA) challenge and aluminum hydroxide gel in sterile saline were used to induce allergic rhinitis in offspring mice. Nasal lavage fluids (NLF) were collected, and eosinophils were counted in NLF 24 hours after the OVA challenge. Th1, Th2, Th17, and Treg subtype-relevant cytokines, including IFN-γ, IL-4, IL-10, IL-17, TGF-ß, and OVA-IgE levels from the blood and NLF of offspring mice, were detected by the enzyme-linked immunosorbent assay (ELISA) method. The Treg subtype was analyzed by flow cytometry. Treg cells were purified from offspring and were adoptively transferred to OVA-sensitized allogenic offspring mice. The outcomes were assessed in allogenic offspring. Results: Our data showed that VD3 supplementation significantly decreased the number of eosinophils, basophils, and lymphocytes in the peripheral blood and NLF. The proportion of CD4+CD25+FoxP3+Tregs had a positive correlation with VD3 in a dose-dependent manner. The levels of serum IgE, IL-4, and IL-17 were decreased while the expressions of IFN-γ, IL-10, and TGF-ß were significantly enhanced in VD3 supplementation groups. Adoptive transfer CD4+CD25+FoxP3+Tregs of VD3 supplementation groups promoted Th1 and suppressed Th2 responses in the offspring during allergic rhinitis. Conclusion: Our findings indicated that low dose VD3 supply in pregnant mice's diet suppressed Th2 and Th17 responses in allergic rhinitis by elevating the Th1 subtype and the proportion of CD4+CD25+FoxP3+Tregs in offspring. It suggested that low dose VD3 supply may have the potential to act as a new therapeutic strategy for allergic rhinitis.

4.
Chem Commun (Camb) ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942828

RESUMO

New tunable catalytic [2+2] cycloaddition/silane-mediated conjugate transfer reductions of yne-allenones have been developed, by which substituent-diverse cyclobutarenes with generally good yields were selectively synthesized by adjusting Fe-H and Cu-H catalytic systems. Use of the Fe-H system triggers 1,6-conjugate reduction to dihydrocyclobuta[a]naphthalen-4-ols whereas the Cu-H complex enables 1,4-conjugate reduction to cyclobuta[a]naphthalen-4(2H)-ones.

5.
J Mol Histol ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33954843

RESUMO

Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. The relationship between PSMB4 and cardiomyocyte apoptosis during myocardial I/R is unknown. In this study, PSMB4 expression increased in rat myocardial I/R model, positively correlated with cleaved caspase-3 expression, negatively correlated with Bcl-2 expression. In vitro, neonatal ventricle cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed to mimic myocardial I/R. PSMB4 silence promoted cardiomyocyte apoptosis and IκBα expression, inhibited the activation of NF-κB. On the contrary, PSMB4 overexpession inhibited cardiomyocyte apoptosis and IκBα expression, promoted the activation of NF-κB. Additionally, PSMB4-IκBα interaction was identified, suggesting that PSMB4 might participate in the proteasome dependent degradation of IκBα. The data indicates that PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial I/R, which can supply novel molecular target for the treatment of ischemic heart disease.

6.
Org Lett ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955758

RESUMO

A new asymmetric catalytic conjugate reduction of yne-allenones to synthesize enantioenriched cyclobuta[a]naphthalen-4(2H)-ones has been established that uses copper-bisphosphine complexes as catalysts and gives excellent regio- and enantioselectivities (≥99% ee) in most cases. This protocol tolerates a broad scope of substrates, exhibits high compatibility with various substituents, and gives excellent stereoselectivity, providing a catalytic and efficient entry to fabrication of synthetically important chiral 6-6-4 tricarbocyclic scaffolds.

7.
PLoS Pathog ; 17(4): e1009530, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33909701

RESUMO

Multi-functional DEAD-box helicase 5 (DDX5), which is important in transcriptional regulation, is hijacked by diverse viruses to facilitate viral replication. However, its regulatory effect in antiviral innate immunity remains unclear. We found that DDX5 interacts with the N6-methyladenosine (m6A) writer METTL3 to regulate methylation of mRNA through affecting the m6A writer METTL3-METTL14 heterodimer complex. Meanwhile, DDX5 promoted the m6A modification and nuclear export of transcripts DHX58, p65, and IKKγ by binding conserved UGCUGCAG element in innate response after viral infection. Stable IKKγ and p65 transcripts underwent YTHDF2-dependent mRNA decay, whereas DHX58 translation was promoted, resulting in inhibited antiviral innate response by DDX5 via blocking the p65 pathway and activating the DHX58-TBK1 pathway after infection with RNA virus. Furthermore, we found that DDX5 suppresses antiviral innate immunity in vivo. Our findings reveal that DDX5 serves as a negative regulator of innate immunity by promoting RNA methylation of antiviral transcripts and consequently facilitating viral propagation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33798070

RESUMO

Graph representation and learning is a fundamental problem in machine learning area. Graph Convolutional Networks (GCNs) have been recently studied and demonstrated very powerful for graph representation and learning. Graph convolution (GC) operation in GCNs can be regarded as a composition of feature aggregation and nonlinear transformation step. Existing GCs generally conduct feature aggregation on a full neighborhood set in which each node computes its representation by aggregating the feature information of all its neighbors. However, this full aggregation strategy is not guaranteed to be optimal for GCN learning and also can be affected by some graph structure noises, such as incorrect or undesired edge connections. To address these issues, we propose to integrate elastic net based selection into graph convolution and propose a novel graph elastic convolution (GeC) operation. In GeC, each node can adaptively select the optimal neighbors in its feature aggregation. The key aspect of the proposed GeC operation is that it can be formulated by a regularization framework, based on which we can derive a simple update rule to implement GeC in a self-supervised manner. Using GeC, we then present a novel GeCN for graph learning. Experimental results demonstrate the effectiveness and robustness of GeCN.

9.
Chemosphere ; 278: 130492, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33838415

RESUMO

In this study, a new adsorbent, polyvinyl alcohol (PVA) and graphene oxide (GO), was prepared, characterized and used for the removal of Sr2+ from aqueous solution. In PVA/GO composite, the inter-lamellar spacing of adjacent GO layers was dramatically enlarged due to the intercalation of PVA molecules, such a unique architecture significantly mitigated the aggregation of GO layers, which facilitated the accessible exposure of active sites and the mass transfer of strontium ions (Sr2+), thus enhancing the adsorption capacity toward Sr2+. The adsorption of Sr2+ by PVA/GO composite conformed to the pseudo second-order kinetic model (R2 = 0.9994), the Langmuir model (R2 = 0.9042), and the Freundlich model (R2 = 0.9598). The complexation interaction between Sr2+ and oxygen atoms/π-electron domain of PVA/GO composite was primarily responsible for the adsorption mechanism, based on the characterization results of X-ray photoelectron spectroscopy (XPS), scanning electron microscope equipped with energy dispersion spectroscopy (SEM-EDS) and powder X-ray diffraction (PXRD).

10.
Biotechnol Bioeng ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829485

RESUMO

Bacillus coagulans, a thermophilic facultative anaerobe, is a favorable chassis strain for the biosynthesis of desired products. In this study, B. coagulans was converted into an efficient malic acid producer by metabolic engineering and promoter engineering. Promoter mapping revealed that the endogenous promoter Pldh was a tandem promoter. Accordingly, a promoter library was developed, covering a wide range of relative transcription efficiencies with small increments. A reductive tricarboxylic acid pathway was established in B. coagulans by introducing the genes encoding pyruvate carboxylase (pyc), malate dehydrogenase (mdh), and phosphoenolpyruvate carboxykinase (pckA). Five promoters of various strengths within the library were screened to fine-tune the expression of pyc to improve the biosynthesis of malic acid. In addition, genes involved in the competitive metabolic pathways were deleted to focus the substrate and energy flux toward malic acid. Dual-phase fed-batch fermentation was performed to increase the biomass of the strain, further improving the titer of malic acid to 25.5 g/L, with a conversion rate of 0.3 g/g glucose. Our study is a pioneer research using promoter engineering and genetically modified B. coagulans for the biosynthesis of malic acid, providing an effective approach for the industrialized production of desired products using B. coagulans.

11.
Biomed Chromatogr ; : e5150, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33894005

RESUMO

A simple, sensitive and fully automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of cilostazol (CIL) and its active metabolite, 3,4-dehydro cilostazol (CIL-M) in human plasma. Plasma samples were processed by protein precipitation in 2 mL 96-deep-well plates and all liquid transfer steps were realized through robotic liquid handing workstation, enabled the whole procedure very fast, compared to the reported methods. Analytes separation was successfully achieved on UPLC BEH C18 column (2.1*100 mm,1.7 µm) with mobile phase A (5 mM ammonium formate containing 0.1% formic acid) and mobile phase B (methanol) at a flow rate of 0.30 mL/min. The total run time was 3.5 min per sample. Mass spectrometric detection was conducted by ESI in positive ion multiple reaction monitoring mode. Calibration curves were linear over the concentration range of 1.0-800 ng/mL for CIL and 0.05-400 ng/mL for CIL-M. The coefficient of variation for the assay's precision was 12.3%, and the accuracy was 88.8-99.8%. It was fully validated and successfully applied to assess the influence of CYP genotypes on the pharmacokinetics of CIL after oral administration of 50 mg tablet formulations of CIL to healthy Chinese volunteers. The results suggest that, in Chinese population, the genotype of CYP3A5 affect the plasma exposure of cilostazol.

12.
Radiother Oncol ; 160: 32-39, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839202

RESUMO

BACKGROUND AND PURPOSE: To determine rates of xerostomia after intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) for oropharyngeal cancer (OPC) and identify dosimetric factors associated with xerostomia risk. MATERIALS AND METHODS: Patients with OPC who received IMRT (n = 429) or IMPT (n = 103) from January 2011 through June 2015 at a single institution were studied retrospectively. Every 3 months after treatment, each patient completed an eight-item self-reported xerostomia-specific questionnaire (XQ; summary XQ score, 0-100). An XQ score of 50 was selected as the demarcation value for moderate-severe (XQs ≥ 50) and no-mild (XQs < 50) xerostomia. The mean doses and percent volumes of organs at risk receiving various doses (V5-V70) were extracted from the initial treatment plans. The dosimetric variables and xerostomia risk were compared using an independent-sample t-test or chi-square test. RESULTS: The median follow-up time was 36.2 months. The proportions of patients with moderate-severe xerostomia were similar in the two treatment groups up to 18 months after treatment. However, moderate-severe xerostomia was less common in the IMPT group than in the IMRT group at 18-24 months (6% vs. 20%; p = 0.025) and 24-36 months (6% vs. 20%; p = 0.01). During the late xerostomia period (24-36 months), high dose/volume exposures (V25-V70) in the oral cavity were associated with high proportions of patients with moderate-severe xerostomia (all p < 0.05), but dosimetric variables regarding the salivary glands were not associated with late xerostomia. CONCLUSION: IMPT was associated with less late xerostomia than was IMRT in OPC patients. Oral cavity dosimetric variables were related to the occurrence of late xerostomia.

13.
Chemistry ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818851

RESUMO

Surface adsorbates and surrounding matrix species have been demonstrated to affect the properties of nanoscale ferroelectrics and nanoscale ferroelectric composites; potentially counteracting performance losses that can occur in small particle sizes. In this work, the effects of nonpolar oleic acid (OA) and polar tetrafluoroborate (BF4 - ) ligand capping on the surface of various sizes of BaTiO3 nanocubes have been investigated with combined neutron diffraction and neutron pair distribution function (PDF), density functional theory (DFT), and ab initio molecular dynamics (AIMD) methods. The low real space PDF region provides an unobstructed view of rhombohedral (split short and long) Ti-O distances in BaTiO3 nanocubes, mimicking the well-established order-disorder local structure found in bulk BaTiO3 . Interestingly, the intermediate-range order in nanocubes is found to be orthorhombic, rather than tetragonal. It is concluded that polar ligands adsorbed at BaTiO3 surfaces stabilize the correlation length scale of local rhombohedral distortions in ferroelectric nanoparticles relative to nonpolar ligands.

14.
Plants (Basel) ; 10(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808465

RESUMO

Agrobacterium-mediated transformation of epicotyl segment has been used in Citrus transgenic studies. The approach suffers, however, from limitations such as occasionally seed unavailability, the low transformation efficiency of juvenile tissues and the high frequency of chimeric plants. Therefore, a suspension cell culture system was established and used to generate transgenic plants in this study to overcome the shortcomings. The embryonic calli were successfully developed from undeveloped ovules of the three cultivars used in this study, "Sweet orange"-Egyptian cultivar (Citrus sinensis), "Shatangju" (Citrus reticulata) and "W. Murcott" (Citrus reticulata), on three different solid media. Effects of media, genotypes and ages of ovules on the induction of embryonic calli were also investigated. The result showed that the ovules' age interferes with the callus production more significantly than media and genotypes. The 8 to 10 week-old ovules were found to be the best materials. A cell suspension culture system was established in an H+H liquid medium. Transgenic plants were obtained from Agrobacterium-mediated transformation of cell suspension as long as eight weeks subculture intervals. A high transformation rate (~35%) was achieved by using our systems, confirming BASTA selection and later on by PCR confirmation. The results demonstrated that transformation of cell suspension should be more useful for the generation of non-chimeric transgenic Citrus plants. It was also shown that our cell suspension culture procedure was efficient in maintaining the vigor and regeneration potential of the cells.

15.
Food Chem ; 356: 129728, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33836362

RESUMO

Alginate is a low-cost polysaccharide found abundantly in seaweeds which consists of mannuronate and guluronate, and it is considered a sustainable gum source for dietary fiber. To solve the high viscosity-related problems while retaining its physiological properties, four partially degraded alginate products (PDA1-4) with molecular weight of 1.05-0.40 × 105 g mol-1 and intrinsic viscosity of 170.9-38.9 mL g-1 were enzymatically prepared and characterized. 1H Nuclear magnetic resonance analysis showed the used alginate lyase had a preference to degrade guluronate-blocks. PDA1 and PDA2 presented random coil conformation, whereas PDA3 and PDA4 displayed compact spherical-coil conformation over random coil conformation in solution. In vitro assays suggested a glucose-adsorption capacity order of PDA1 < PDA2 < alginate < PDA3 < PDA4 and a glucose-diffusion retardation capacity order of PDA3 < PDA1 ≤ alginate < PDA2 < PDA4, indicating that partially degraded alginate reinforced the hypoglycemic effect, especially mannuronate-rich PDA4. Overall, the study may have important implications for development of PDA as dietary fiber with potential hypoglycemic activity.

16.
Cell Cycle ; 20(5-6): 591-602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651657

RESUMO

Cholangiocarcinoma (CCA) is a variety of biliary epithelial tumors involving intrahepatic, perihilar and distal bile duct. It is the most common malignant bile duct tumor in the liver and the second most common primary liver cancer, whose molecular mechanism not fully understood. Specifically, the relationship between CCA and chondroitin polymerizing factor (CHPF) is still not clear. In this study, detection of clinical specimens was performed to preliminarily study the role of CHPF in CCA. CCA cells with CHPF knockdown were constructed for in vitro study, which was also used in the construction of mice xenograft model for investigating the role of CHPF in the development of CCA. The results demonstrated that CHPF was significantly upregulated in CCA tissues compared with normal tissues. High expression of CHPF was correlated with more advanced tumor grade. Moreover, knockdown of CHPF significantly inhibited cell proliferation, cell migration, promoted cell apoptosis and arrest cell cycle in G2 phase in vitro, as well as suppressed tumor growth in vivo. In conclusion, CHPF was identified as a tumor promotor in the development and metastasis of CCA, which may provide a novel therapeutic target for the targeted therapy against CCA.

17.
J Am Chem Soc ; 143(12): 4809-4816, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33730847

RESUMO

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating the electrons from the d-orbitals to the empty antibonding molecular orbitals of double bonds (π*) via back-bonding. Thus, the uncoordinated double bond, as a more reactive partner on the basis of the principle of vinylogy, can directly attack imines, furnishing a formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between 1,3-dienes and imines with a nucleophilic group is also compatible, by trapping in situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, vinylogous activation, and compatibility with both conjugated neutral polyenes and electron-deficient polyenes, is elucidated by control experiments and density functional theory (DFT) calculations.

18.
Zhongguo Gu Shang ; 34(3): 269-74, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787174

RESUMO

OBJECTIVE: To compare the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) with a tibialis anterior allograft (TAA)versus hamstring tendon autograft (HTA) after 10 years follow-up. METHODS: A clinical data of 107 patients who underwent arthroscopic ACLR with a single bundle tendon between March 2007 and March 2010 was retrospectively analyzed. Among the patients, 48 patients were reconstructed with a tibialis anterior allograft (TAA group), including 26 males and 22 females, ranging in age from 16 to 38 years, with a mean of 27.2±6.2 years;59 patients were reconstructed with a hamstring tendon autograft (HTA group), including 31 males and 28 females, ranging in age from 16 to 40 years, with a mean of 28.0±7.6 years. The preoperative tibial anterior displacement and knee joint function, as well as knee joint stability, tibial anterior displacement and knee joint function at 10 years after operation were observed. Lachman test was used to evaluate the forward joint stability and pivot shift test to evaluate the rotational stability of the knee;KT-2000 side-to-side difference (SSD) was used to measure tibial anterior displacement;International Knee Documentation Committee(IKDC) score and Lysholm score were used to evaluate knee function. RESULTS: The incisions of both groups were healed by first intention, and no early complications occurred after operation. All patients were followed-up 10 to 13 years, the mean time was 11.7 years. There was no graft failure were found during the follow up period. The KT-2000 SSD of the TAA group and the HTA group at ten years after operation were 1.9±0.7 and 1.8±0.6 respectively, which were significantly improved than 8.8±0.9 and 8.6±1.0 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). The total Lysholm score of the TAA group and the HTA group at ten years after operation were 90.4±4.4 and 90.7±3.4 respectively, which were significantly improved than 51.4±13.3 and 51.2±14.6 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). The total IKDC score of the TAA group and the HTA group at ten years after operation were 91.5±4.1 and 90.9±3.2 respectively, which were significantly improved than 45.8±12.2 and 47.0±14.5 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). No significant difference were found between the two groups in Lachman test and pivot shift test at 10 years after operation (P>0.05). CONCLUSION: The TAA and HTA have equal long term effect in ACL reconstruction, doctors and patients can choose the graft according to the actual situation.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Adolescente , Adulto , Aloenxertos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia , Autoenxertos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Eur J Drug Metab Pharmacokinet ; 46(3): 427-436, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33779967

RESUMO

BACKGROUND AND OBJECTIVE: Eltrombopag is the first oral, small-molecule, non-peptide thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. This study investigated the pharmacokinetics of eltrombopag in healthy Chinese subjects and evaluated the effect of sex and genetic polymorphisms on its variability. METHODS: Forty-eight healthy subjects were administered a single dose of eltrombopag (25 mg). Plasma concentrations of eltrombopag were determined using a validated liquid chromatography-tandem mass spectrometry method, and platelet counts were determined by blood tests. CYP1A2 rs762551, CYP2C8*3 rs10509681, CYP2C8*3 rs11572080, UGT1A1 rs887829, UGT1A3 rs3806596, and BCRP rs2231142 polymorphisms were genotyped by Sanger sequencing. A back-propagation artificial neural network (BP-ANN) model was constructed to predict pharmacokinetics based on physiological factors and genetic polymorphism data. RESULTS: Compared with male subjects, female subjects who received a single 25-mg dose of eltrombopag exhibited a significantly increased mean maximum plasma concentration (Cmax) and significantly decreased apparent clearance. Additionally, CYP1A2 rs762551 C>A single nucleotide polymorphism influenced distribution and elimination. C-allele carriers exhibited 30% higher systemic exposure and 20% lower apparent clearance compared with homozygous A-allele carriers. Mean percentage increases in platelet counts from baseline to Day 5 were 9.38% and 17.06% in male and female subjects, respectively. The BP-ANN model had a high goodness-of-fit index and good coherence between predicted and measured concentrations (R = 0.98979). CONCLUSION: Sex and CYP1A2 rs762551 C>A were associated with the pharmacokinetic variability of eltrombopag in healthy Chinese subjects. Females exhibited a better platelet-elevating effect compared with males administered the same dosage. The developed BP-ANN model based on physiological factors and genetic polymorphism data could be promising for applications in pharmacokinetic studies. TRIAL REGISTRATIONS: https://www.Chinadrugtrials.org.cn CTR20190898.

20.
Clin Imaging ; 78: 8-13, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706069

RESUMO

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) in distinguishing adenomatous gallbladder polyps from cholesterol gallbladder polyps. METHODS: A total of 164 patients with gallbladder polyps were retrospectively analyzed. All patients underwent B-mode ultrasound (US) and CEUS before cholecystectomy. Gallbladder polyps were divided into cholesterol polyp group and adenomatous polyp group according to pathology. Differences in patient's age, gender, maximum polyp size, number, presence of gallstones, vascularity and stalk width measured by US and vascular stalk width measured by CEUS were tested between the two groups. The diagnostic performance of specific US features was evaluated. The independent factors related with adenomatous polyps were analyzed by multiple logistic regression analyses. RESULTS: There were 114 cholesterol polyps and 50 adenomatous polyps in 164 patients analyzed in the study. Differences in maximum size, vascularity, and stalk width of the gallbladder polyp were significant between the two groups (p < 0.05), whereas differences in patient's age, gender, number of gallbladder polyp, and presence of gallstones between the two groups were not (p > 0.05). Stalk width was wider than vascular stalk width between the two groups (p < 0.05). Vascular stalk width was also statistically different between the two groups (p < 0.05). The diagnostic performance of vascular stalk width was more significant than stalk width. Only vascular stalk width and vascularity were independent factors related with adenomatous polyps. CONCLUSION: Vascular stalk width measured by CEUS is more accurate than stalk width measured by grayscale US in distinguishing adenomatous polyps from cholesterol polyps.

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