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Fibrotic scarring and impaired myocardial calcium homeostasis serve as the two main factors in the pathology of heart failure following myocardial infarction (MI), leading to poor prognosis and death in patients. Serca2a is a target of interest in gene therapy for MI-induced heart failure via the regulation of intracellular calcium homeostasis and, subsequently, enhancing myocardial contractility. A recent study also reported that Serca2a ameliorates pulmonary fibrosis by blocking nuclear factor kB (NF-kB)/interleukin-6 (IL-6)-induced (SMAD)/TGF-ß signaling activation, while the effect in MI-induced myocardial fibrosis remains to be addressed. Here, we loaded Serca2a plasmids into type 1 collagen-targeting nanoparticles to synthesize the GKWHCTTKFPHHYCLY-Serca2a-Liposome (GSL-NPs) for targeted treatment of myocardial infarction. We showed that GSL-NPs were effectively targeted in the scar area in MI-induced mice within tail-vein delivery for 48 h. Treatment with GSL-NPs improved cardiac functions and shrank fibrotic scars after MI in mice by up-regulating Serca2a. In cardiac fibroblasts, GSL-NPs alleviated hypoxia-induced fibrotic progression partly by inhibiting NF-kB activation. Furthermore, treatment with GSL-NPs protected cardiomyocyte calcium homeostasis and enhanced myocardial contractility during hypoxia. Together, we demonstrate that type I collagen-targeted liposome delivery of Serca2a may benefit patients with myocardial infarction by inhibiting fibrotic scarring as well as modulation of calcium homeostasis.
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Human blood group antigen has important biological functions, and transfusion of incompatible blood can cause alloimmunization and may lead to serious hemolytic reactions. Currently, serological methods are most commonly used in blood group typing. However, this technique has certain limitations and cannot fully meet the increasing demand for the identification of blood group antigens. This study describes a next-generation sequencing (NGS) technology platform based on exon and flanking region capture probes to detect full coding exon and flanking intron regions of the 36 blood group systems, providing a new high-throughput method for the identification of blood group antigens. The 871 capture probes were designed for the exon and flanking intron sequences of 36 blood group system genes, and synchronization analysis for 36 blood groups was developed. The library for NGS was tested using the MiSeq Sequencing Reagent Kit (v2, 300 cycles) by Illumina NovaSeq, and the data were analyzed by the CLC Genomics Workbench 21.0 software. A total of 199 blood specimens have been sequenced for the 41 genes from 36 blood groups. Among them, heterozygote genotypes were found in the ABO, Rh, MNS, Lewis, Duffy, Kidd, Diego, Gerbich, Dombrock, Globoside, JR, LAN, and Landsteiner-Wiene blood group systems. Only the homozygous genotype was found in the remaining 22 blood group systems. The obtained data in the NGS method shows a good correlation (99.98 %) with those of the polymerase chain reaction-sequence-based typing. An NGS technology platform for 36 blood group systems genotyping was successfully established, which has the characteristics of high accuracy, high throughput, and wide coverage.
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The international engineering education community has reached a consensus regarding the need to enhance engineering students' awareness of and capability to provide sustainable services in their future careers. Based on a modified college impact model, this study analyzed the impacts of curricular emphasis, curricular instruction, and sustainability-related career self-efficacy on the sustainability-related career expectations of engineering students and investigated the moderating effects of gender on the relationships among the research variables. The results show that both curricular emphasis and curricular instruction have direct positive effects on the sustainability-related career expectations of engineering students; sustainability-related career self-efficacy plays a partial mediating role in this process; and gender significantly moderates the influence of curricular emphasis and curricular instruction on sustainability-related career expectations. The findings of this study provide empirical evidence that can be used by higher education institutions and engineering educators to enhance the belief of engineering students in their ability to solve sustainability-related issues in their future careers and promote the diversification of engineering education.
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Constructing platinum-like materials with excellent catalytic activity and low cost has great significance for hydrogen evolution reaction (HER) during electrolysis of water. Herein, palladium nanoparticles (NPs) deposition on the surface of Co NPs using nitrogen-doped carbon (NC) as substrate, denoted as N-ZIFC/CoPd-30, are manufactured and served as HER electrocatalysts. Characterization results and density functional theory calculations validate that Pd-Co heterojunctions with NC acting as "electron donators" promote the Pd species transiting to the electron-rich state based on an efficient electron transfer mechanism, namely the N-C polar bonds induced strong metal-support interaction effect. The electron-rich Pd sites are beneficial to HER. Satisfactorily, N-ZIFC/CoPd-30 have only low overpotentials of 16, 162, and 13 mV@-10 mA cm-2 with the small Tafel slopes of 98 mV/decade, 126 mV/decade, and 72 mV/decade in pH of 13, 7, and 0, respectively. The success in fabricating N-ZIFC/CoPd opens a promising path to constructing other platinum-like electrocatalysts with high HER activity.
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Building narrow band gap semiconductors and fast separation of photogenerated electron-hole (e--h+) structures are of great significance for photocatalytic process. In this contribution, the CeO2-x/C3-yN4/Ce(CO3)(OH) double S-scheme heterojunctions with atomic vacancies tunable band gap (2.54 eV) have been designed and fabricated as a boost photocatalyst for enrofloxacin (ENR) photodegradation. Compared with the control samples, the experimental results indicate that the typical sample (CeO2-x/C3-yN4/Ce(CO3)(OH)-2) achieves the highest ENR photodegradation efficiency (93.6 %) in 240 min under a pH of 6, and the possible photodegradation pathways are also proposed. The superior performance is ascribed to the CeO2-x/C3-yN4/Ce(CO3)(OH) double S-scheme heterojunctions for selective recombination of photogenerated electrons with weak-reduction ability in conduction band (CB) of CeO2-x, C3-yN4 and the photogenerated holes with weak-oxidation nature in valance band (VB) of C3-yN4, Ce(CO3)(OH), which increase the retention rate of photogenerated electrons in CB of Ce(CO3)(OH) and photogenerated holes in VB of CeO2-x to degrade ENR. This is the first systematic study of CeO2-x/C3-yN4/Ce(CO3)(OH) double S-scheme heterojunctions for ENR photodegradation.
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Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Among the 317 patients, 40.1%, 25.2%, 24.6% and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five-year survival rates were 75.5%, 67.3%, 74.1% and 51.1% in DCM, HCM, LVNC and RCM, respectively. The ten-year survival rates were 60.1%, 56.1%, 57.2% and 41.3% in DCM, HCM, LVNC and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations. CONCLUSIONS: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause. TRIAL REGISTRATION: MR-50-23-011798. WHAT IS KNOWN: ⢠Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases and one of the leading causes of heart failure in children due to the lack of effective treatments. ⢠There remains scarce data on Asian pediatric populations though emerging studies have assessed the clinical characteristics and outcomes of CM. WHAT IS NEW: ⢠A retrospective study was conducted and the follow-up records were established to investigate the clinical characteristics, the profile of gene mutations and prognostic outcomes of children with CM in Western China. ⢠CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.
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Cardiomiopatías , Cardiomiopatía Dilatada , Cardiomiopatía Hipertrófica , Cardiomiopatía Restrictiva , Niño , Humanos , Estudios Retrospectivos , Perfil Genético , Cardiomiopatías/genética , Cardiomiopatía Restrictiva/complicaciones , Cardiomiopatía Restrictiva/genética , Cardiomiopatía Dilatada/genéticaRESUMEN
OBJECTIVES: To evaluate the image quality and utility of virtual monoenergetic images (VMI) of dual-layer spectrum computed tomography (DLSCT) in assessing preoperative T-stage for early rectal adenocarcinoma (ERA). METHODS: This retrospective study included 67 ERA patients (mean age 62 ± 11.1 years) who underwent DLSCT and MR examination. VMI 40-200 keV and poly energetic image (PEI) were reconstructed. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and tumor contrast of different energy levels were calculated and compared, respectively. Two radiologists independently assess the image quality of the VMIs and PEI using 5-point scales. The diagnostic accuracies of DLSCT and HR-MRI for ERA T-staging were evaluated and compared. RESULTS: The maximum noise was observed at VMI 40 keV, and noise at VMI 40-200 keV in the arterial and venous phases showed no significant difference (all p > 0.05). The highest SNR and CNR were obtained at VMI 40 keV, significantly greater than other energy levels and PEI (all p < 0.05). Tumor contrast was more evident than PEI at 40-100 keV in the arterial phase and at 40 keV in the venous phase (all p < 0.05). When compared with PEI, VMI 40 keV yielded the highest scores for overall image quality, tumor visibility, and tumor margin delineation, especially in the venous phase (p < 0.05). The overall diagnostic accuracy of DLSCT and HR-MRI for T-stage was 65.67 and 71.64% and showed no significant difference (p > 0.05). CONCLUSIONS: VMI 40 keV improves image quality and accuracy in identifying lesions, providing better diagnostic information for ERA staging. CRITICAL RELEVANCE STATEMENT: Low-keV VMI from DLSCT can improve tumor staging accuracy for early rectal carcinoma, helping guide surgical intervention decisions, and has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC. KEYPOINTS: ⢠Compared with PEI, low-keV VIM derived from DLSCT, particularly at the 40 keV, significantly enhanced the objective and subjective image quality of ERA. ⢠Using VMI 40 keV helped increase lesion detectability, leading to improved diagnostic accuracy for ERA. ⢠Low-keV VMI from DLSCT has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC.
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OBJECTIVE: In the process of cochlear implantation surgery, it is crucial to develop a method to control the temperature during the drilling of the implant channel since high temperatures can result in damage to bone and nerve tissue. METHODS: This paper simplified the traditional point heat source temperature rise model and proposed a novel extreme peck drilling model to quantitatively calculate the maximum temperature rise value. It is also innovatively introduced a new method for calculating the best peck drilling duty cycle to strictly control the maximum temperature rise value. Besides, the neural network is trained with virtual data to identify two important thermal parameters in the temperature rise model. RESULTS: In the experiment of epoxy resin and temporal bone, the difference between predicted maximum temperature and actual maximum temperature was less than 1.5 °C, and the error rate was less than 10%. And the error source was analyzed by variational mode decomposition, along with discussion of potential solutions. In the temperature control experiment, the model successfully controlled the maximum temperature rise within 10 °C.For cochlear implantation surgery, we also divide the implantation channel into different stages based on the bone density in CT images to identify thermal parameters and calculate drilling strategies. CONCLUSION: This method provides a new strategy for accurate and effective control of borehole heat generation. SIGNIFICANCE: These achievements provide new ideas and directions for research in cochlear implantation surgery and related fields, and are expected to have extensive application in medical practice.
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Implantación Coclear , Temperatura , Implantación Coclear/métodos , Huesos , CalorRESUMEN
Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI.The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1α (HNF-1α) and pregnane X receptor (PXR).These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.
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Lesión Renal Aguda , Cisplatino , Ratas , Animales , Cisplatino/efectos adversos , Cisplatino/metabolismo , Transportadores de Anión Orgánico Sodio-Independiente/genética , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo , Proteína 1 de Transporte de Anión Orgánico/genética , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Indicán/toxicidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Riñón/metabolismoRESUMEN
Water is a precious resource of paramount importance on Earth, playing a critical role in the evolution of life [...].
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(1) Background: The cabbage flea beetle (CFB; Phyllotreta striolata) seriously damages the production of Chinese flowering cabbage (CFC; Brassica campestris L. ssp. chinensis var. utilis), which is a key leafy vegetable in South China. A large number of chemical insecticides have been sprayed to control this pest; as a result, residues and resistances are becoming an issue. It is necessary to develop biocontrol technologies to address this issue. (2) Methods: Fungal strains were selected based on bioactivity against CFB, and CFC seed pelletization with fungal conidia was subject to evaluation of control efficacy against CFB. The effective mixture of fungus and chemical insecticide was determined based on safety and joint toxicology tests. (3) Results: The screening of 103 strains from 14 genera identified the Metarhizium anisopliae strain MaGX19S02 (Ma) as the one with the highest virulence. The LC50s of Ma to CFB adult and second instar larvae on day 9 post-treatment were 3.04 × 106 and 27.2 × 106 spores/mL, respectively. In the pot test, the pelletization of CFC seeds with Ma conidia (50/25/12.5 mg in 1 g seed with 4 g fillers) demonstrated significant CFB mortalities (45-82%) 20 days after the larvae were introduced. In the field test, the seed pelletization achieved 57-81% control efficacy 14 days after sowing. Furthermore, the combination of Ma with chlorfenapyr (Chl) demonstrated a synergistic effect against CFB; based on this result, we prepared the mixture formulation of 20% Ma-Chl wettable powder (WP). The assessment of the effects of 20% Ma-Chl WP (500× diluent) against CFB revealed 93.33% mortality in the pot test and 61.3% control efficacy in the field test on day 7 post-treatment. (4) Conclusions: The findings demonstrate the potential of Ma to control CFB in the field. Seed pelletization with Ma conidia effectively controlled CFB larvae and protected CFC seedlings, wherein a mixture formulation of 20% Ma-Chl WP had substantial efficacy in controlling CFB adults. Our research provides new methods for CFB biocontrol.
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The resistance of sperm to freezing varies widely among boars. The semen ejaculate of different boars can be grouped into poor freezability ejaculate (PFE) and good freezability ejaculate (GFE). In this study, five Yorkshire boars each of the GFE and PFE were selected by comparing the changes in sperm motility before and after cryopreservation. Firstly, we found that the sperm plasma membrane of the PFE group showed weak integrity after PI and 6-CFDA staining. Then the electron microscopy results verified that the plasma membrane condition of all segments of GFE was better than that of PFE segments. Furthermore, the lipid composition of sperm plasma membranes in GPE and PFE sperm was analyzed by using mass spectrometry, and 15 lipids showed differences between the two groups. Among those lipids, only phosphatidylcholine (PC) (14:0/20:4) and phosphatidylethanolamine (PE) (14:0/20:4) were higher in PFE. The remaining lipid contents, including those of dihydroceramide (18:0/18:0), four hexosylceramides (18:1/20:1, 18:0/22:1, 18:1/16:0, 18:1/18:0), lactosylceramide (18:1/16:0), two hemolyzed phosphatidylethanolamines (18:2, 20:2), five phosphatidylcholines (16:1/18:2, 18:2/16:1, 14:0/20:4, 16:0/18:3, 18:1/20:2), and two phosphatidylethanolamines (14:0/20:4, 18:1/18:3), were all positively correlated with resistance to cryopreservation (p < 0.05, r > 0.6). Moreover, we analyzed the metabolic profile of sperm using untarget metabolomic. KEGG annotation analysis revealed that the altered metabolites were mainly involved in fatty acid biosynthesis. Finally, we determined that the contents of oleic acid, oleamideetc, N8-acetylspermidine etc., were different between GFE and PFE sperm. In summary, the different lipid metabolism levels and long-chain polyunsaturated fatty acids (PUFAs) in plasma membrane may be key factors contributing to differences in sperm resistance to cryopreservation among boars.
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Fosfatidiletanolaminas , Preservación de Semen , Porcinos , Masculino , Animales , Fosfatidiletanolaminas/metabolismo , Semen , Motilidad Espermática , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides/metabolismo , Criopreservación/veterinaria , Criopreservación/métodos , Membrana CelularRESUMEN
In this study, the hydrochloric acid from rare earth oxalic acid precipitation mother liquor was separated by electrodialysis (ED) with different anion exchange membranes, including selective anion exchange membrane (SAEM), polymer alloy anion exchange membrane (PAAEM), and homogenous anion exchange membrane (HAEM). In addition to actual wastewater, nine types of simulated solutions with different concentrations of hydrochloric acid and oxalic acid were used in the experiments. The results indicated that the hydrochloric acid could be separated effectively by electrodialysis with SAEM from simulated and real rare earth oxalic acid precipitation mother liquor under the operating voltage 15 V and ampere 2.2 A, in which the hydrochloric acid obtained in the concentrate chamber of ED is of higher purity (>91.5%) generally. It was found that the separation effect of the two acids was related to the concentrations and molar ratios of hydrochloric acid and oxalic acid contained in their mixtures. The SEM images and ESD-mapping analyses indicated that membrane fouling appeared on the surface of ACS and CSE at the diluted side of the ED membrane stack when electrodialysis was used to treat the real rare earth oxalic acid precipitation mother liquor. Fe, Yb, Al, and Dy were found in the CSE membrane section, and organic compounds containing carbon and sulfur were attached to the surface of the ACS. The results also indicated that the real rare earth precipitation mother liquor needed to be pretreated before the separation of hydrochloric acid and oxalic acid by electrodialysis.
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OBJECTIVES: Lymph node (LN) metastasis is an important prognostic factor in rectal cancer (RC). However, accurate identification of LN metastasis can be challenged for radiologists. The aim of our study was to assess the utility of MRI radiomics based on T2-weighted images (T2WI) and amide proton transfer-weighted (APTw) images for predicting LN metastasis in RC preoperatively. METHODS: A total of 125 patients with pathologically confirmed rectal adenocarcinoma (RA) from January 2019 to June 2021 who underwent preoperative MR were enrolled in this retrospective study. Radiomics features were extracted from high-resolution T2WI and APTw images of primary tumor. The most relevant radiomics and clinical features were selected using correlation and multivariate logistic analysis. Radiomics models were built using five machine learning algorithms including support vector machine (SVM), logical regression (LR), k- nearest neighbor (KNN), naive bayes (NB), and random forest (RF). The best algorithm was selected for further establish the clinical- radiomics model. The receiver operating characteristic curve (ROC) analysis was used to assess the performance of radiomics and clinical-radiomics model for predicting LN metastasis. RESULTS: The LR classifier had the best prediction performance, with AUCs of 0.983 (95% CI 0.957-1.000), 0.864 (95% CI 0.729-0.972), 0.851 (95% CI 0.713-0.940) on the training set, validation, and test sets, respectively. In terms of prediction, the clinical-radiomics combined model outperformed the radiomics model. The AUCs of the clinical-radiomics combined model in the validation and test sets were 0.900 (95% CI 0.785-0.986), and 0.929 (95% CI 0.721-0.943), respectively. CONCLUSION: The radiomics model based on high-resolution T2WI and APTw images can predict LN metastasis accurately in patients with RA.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Metástasis Linfática/diagnóstico por imagen , Protones , Estudios Retrospectivos , Teorema de Bayes , Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/patología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/secundarioRESUMEN
OBJECTIVE: To identify and analysis three ABO variant Bw subtypes. METHODS: Serological assays were carried out to identify the ABO blood group of the proband. ABO gene was identified by Sanger sequencing. RESULTS: The genotype of three individuals are ABO*Bw.11/0.01.02, ABO*Bw.12/0.01.01, ABO*Bw.34/A1.02, receptively. Sequencing results showed that there were c.695T>C, c.278C>T, c.889G>A, resulting in variants in Leu232Pro, Pro93Leu and Glu297Lys, receptively. CONCLUSION: Bw11, Bw12 and Bw34 subgroups were identified, and gene testing can be used as a supplement to determine the ABO blood group subtypes.
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Sistema del Grupo Sanguíneo ABO , Tipificación y Pruebas Cruzadas Sanguíneas , Sistema del Grupo Sanguíneo ABO/genética , Alelos , Exones , Genotipo , Humanos , Fenotipo , Análisis de SecuenciaRESUMEN
Glioblastoma (GBM) is the most malignant tumor in human brain. High invasiveness of this tumor is the main reason causing treatment failure and recurrence. Previous study has found that LACTB is a novel tumor suppressor in breast cancer. Moreover, the function of LACTB in other tumors and mechanisms involving LACTB were also reported. However, the role and relevant mechanisms of LACTB in GBM invasion remains to be revealed. Our aim is to investigate the role LACTB in GBM migration and invasion. We found that LACTB was downregulated in gliomas compared to normal brain tissues. Overexpression of LACTB suppressed migration and invasion of LN229 and U87 cell lines. Mechanistically, LACTB overexpression downregulated the mesenchymal markers. Moreover, LACTB overexpression downregulated the expression of RHOC and inhibited RHOC/Cofilin signaling pathway. The study suggests that LACTB suppresses migration and invasion of GBM cell lines via downregulating RHOC/Cofilin signaling pathway. These findings suggest that LACTB may be a potential treatment target of GBM.
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Neoplasias Encefálicas , Glioblastoma , Factores Despolimerizantes de la Actina/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Humanos , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Invasividad Neoplásica , Transducción de Señal/fisiología , beta-Lactamasas/genética , Proteína rhoC de Unión a GTP/genética , Proteína rhoC de Unión a GTP/metabolismoRESUMEN
Identification of adsorption centers with atomic levels of adsorbents is crucial to study the adsorption of formaldehyde (HCHO), especially for an in-depth understanding of the mechanism of HCHO capture. Herein, we investigate the HCHO adsorption performance of one-dimensional (1D) nanoporous boron nitride (BN) fiber, and explore the adsorption mechanism by density functional theory (DFT) calculations, including adsorption energy change and Bader charge change, and experimental study as well. Research shows that the 1D nanoporous BN fiber possesses a high concentration of Lewis pairs, which act as Lewis acid and Lewis base sites associated with the fiber's electron-deficient and electron-rich features. It is worth noting that the HCHO removal efficiency of a typical sample is as high as 91%. This work may open the door to the field of adsorption of other pollutants by constructing Lewis pairs in the future.
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A rapid and sensitive UHPLC-MS/MS method was developed and fully validated for the quantification of verinurad in rat plasma. Lesinurad was used as an internal standard (IS), and simple protein precipitation was utilized to prepare the analytes from the matrix. Chromatographic separation was carried out on a Zorbax SB C18 column. The mobile phase consisted of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B) at a flow rate of 0.3 mL/min. The short run time of 4 min made it possible to analyze more than 300 samples per day. The ion transitions were quantified in negative mode with multiple reaction monitoring (MRM) transitions of 347.1 â 261.1 for verinurad and 404.2 â 178.9 for the IS. The validated linear ranges of verinurad were 10-5000 ng/mL in rat plasma. The validated UHPLC-MS/MS method was further applied to the pharmacokinetic study of verinurad in rat plasma after intragastric (2 mg/kg) and intravenous (1 mg/kg) administrations. The pharmacokinetic study revealed that verinurad showed high clearance and high bioavailability (78.1%). To the best of our knowledge, this is the first report of the bioavailability study of verinurad.
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Espectrometría de Masas en Tándem , Agua , Acetonitrilos , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión/métodos , Formiatos , Naftalenos , Propionatos , Piridinas , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: To explore the molecular basis for an individual with a rare variant of Bw37 phenotype. METHODS: Tube agglutination testing was used to determine the ABO blood groups. Genotyping were carried out using polymerase chain reaction-sequence specific primer (PCR-SSP) and direct sequencing for exons 6 and 7 of the ABO locus. RESULTS: Serologic testing of the proband showed that he was weak B for the positive ABO blood typing and B for the negative blood typing. The genotype of him was determined as B/B by PCR-SSP. DNA sequencing showed that he has harbored c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A variants, which have resulted in p.R176G, p.G235S and p.G268A substitutions. The genotypes of the proband and his mother were identified as ABO*Bw37/B101 and ABO*O.01.02/ABO*O.01.01, respectively. CONCLUSION: Serological identification combined with genotyping should be considered for the verification of ABO subtypes.