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A new glycoside (1) along with six known analogues (1-7) were isolated from Codonopsis pilosula collected at Shanxi in China. The structure of 1 was established based on comprehensive spectroscopic data and literature comparison. The anti-inflammatory effects of isolated compounds were further investigated in LPS-induced RAW264.7 macrophage.
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Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Herpesvirus Humano 4 , Quimiorradioterapia/efeitos adversosRESUMO
A simple but efficient strategy to improve the ability of adsorptive denitrogenation (ADN) of MIL-101(M101) was studied by the in situ encapsulation of phosphomolybdic acid (PMA) and the subsequent purification of the as-synthesized product by the NH4F solution. After the NH4F treatment, the vast majority of PMA was removed, loss of organic ligand (BDC) was observed, and the fluorination of the hydroxyl group in the M101 structure occurred. The ADN activities of the Cr-MOF matrix composites before and after fluorination were studied in detail. The rest of PMA interacts strongly with M101 and assists the ADN activity. Coordination unsaturated metal sites (CUS) in M101 are formed after fluorination and also contribute to ADN activity. Further, fluoride anions replace most of the hydroxide groups in M101, which can promote the ADN of quinoline (QUI) and indole (IND) through an acid-base interaction and N-atom coordination with the CUS in M101. P-M101-F 5% exhibits the highest adsorptive capacity and excellent regeneration ability. Special emphasis in this work is placed on structure modulation (including PMA doping, CUS creation, and fluorination) of M101 for enhancing ADN activity, which provides a useful scaffold for future research in the rational design of MOF-based ADN catalysts.
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Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.
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It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Relevância Clínica , Linfócitos T CD8-Positivos/patologia , Metástase Linfática/patologia , Carcinoma/genética , Carcinoma/patologia , Linfonodos/patologiaRESUMO
BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Masculino , Humanos , Feminino , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Recidiva Local de Neoplasia/radioterapia , Neoplasias Nasofaríngeas/radioterapia , HemorragiaRESUMO
Amino acid permeases (AAPs) play important roles in plant amino acid transport and nitrogen metabolism. In this study, we carried a comprehensive analysis for apple genes encoding AAPs using bioinformatics and molecular biology. Eleven MdAAPs were identified by a genome-wide search and comparative genomic analysis revealed relatively conserved gene composition, transmembrane characteristics, and protein structures. Phylogenetic tree construction and analysis of the conserved motifs of MdAAPs and AtAAPs showed that AAPs can be classified into three groups (I, II, and III). We compared the promoters of the identified genes and did gene functional annotation and qRT-PCR and found a relationship between apple AAPs and nitrogen deficiency. The expression profile data implied that MdAAPs exhibit diversified distributions and functions in different tissues.
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Malus , Sistemas de Transporte de Aminoácidos/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Malus/genética , Malus/metabolismo , Nitrogênio/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BEL1-like homeodomain (BLH) family genes as homeodomain transcription factors are found ubiquitously in plants to play important regulatory roles in reproductive development, morphological development, and stress response. Although BLH proteins have been reported in some species, there is little information about BLH genes in peach. In this study, we identified 11 peach PpBLH genes based on the conserved domain. Phylogenetic analysis suggested that the PpBLH proteins could be divided into five groups, which might be involved in different aspects of morphogenesis. Genomics structure analysis revealed that there were four exons in the PpBLH gene, and the length of the third exon was 61 bp. Chromosomal location analysis showed that the PpBLH genes were not distributed uniformly on six chromosomes. Promoter analysis showed that the promoter sequences of six PpBLH genes contained multiple cis-acting elements for hormones and stress. Six PpBLH genes were cloned by RT-PCR, and PpBLH1, PpBLH4, and PpBLH7 showed different expression patterns in the tested fruits under common temperature and high temperature. Y2H results indicated that PpBLH7 andPpBLH10 interacted with the PpOFP6 protein, and PpBLH1 interacted with the PpOFP1, PpOFP2, PpOFP4, and PpOFP13 proteins. These results provide new insight for further study of PpBLH genes, and construction of regulatory networks of PpBLH proteins in the growth, development, and stress response of peach.
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Prunus persica , Prunus persica/genética , Prunus persica/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Família Multigênica , Genoma de Planta , Estresse FisiológicoRESUMO
We examined nitrogen use efficiency of 15N-urea of 15-year-old 'Gala' apple trees by broadcast fertilization (T1), nitrogen fertilization with drip irrigation (T2) and nitrogen fertilization with subsurface irrigation (T3), to further improve the water and fertilizer integration technology for apple orchard and to improve nitrogen utilization efficiency. The results showed that leaf area, chlorophyll, and leaf nitrogen content of leaves were significantly higher in T3 treatment than those in T1 and T2 treatments. Soil mineral nitrogen content (20-40 cm) in each period followed the order of T3>T2>T1, while that in 0-20 cm followed an order of T2>T3>T1. The Ndff value at organ level (the contribution rate of the 15N amount absorbed by various organs of the tree to the total nitrogen content of the organ) was the highest in T3 treatment in each period, followed by T2 and T1 treatments. The utilization rate of 15N in the fruit ripening period followed an order of T3>T2>T1. The 15N utilization rate of T3 reached 24.2%, being 1.19 and 1.65 times of T2 and T1, respectively. The 15N distribution rate in the fruits during the fruit maturity stage was the highest in T1 treatment, while that in the storage organs was the highest in T2 treatment and that in the reproduction organs was the highest in T3 treatment. The single fruit weight, yield, soluble solids, hardness, soluble sugar and sugar-acid ratio were the highest in T3 treatment, followed by T2 and T1 treatments. In summary, nitrogen application by percolation irrigation (subsurface application) significantly promoted leaf growth and nitrogen utilization of apple tree, and improved fruit yield and quality.
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Malus , Fertilizantes , Frutas , Nitrogênio , Solo , ÁguaRESUMO
INTRODUCTION: The fascin-1 protein is a cytoskeleton-like protein, which can prompt structural changes in cell membranes and affect the integrity of intercellular relations to promote invasion and metastasis of tumor cells. In this study, we researched the expression of fascin-1 in glioma. MATERIAL AND METHODS: The fascin-1 protein and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Then, we analyzed the relationship between the expression of fascin-1 protein and the clinical pathological characteristics of patients with glioma. Finally, the fascin-1 protein expression status and prognosis of glioma patients were investigated. RESULTS: The fascin-1 protein was mainly located in the cytoplasm of cells from glioma. The high expression rate of fascin-1 protein in glioma tissue was higher than that of normal brain tissue. At same time, we found that high fascin-1 protein expression was significantly correlated with World Health Organization (WHO) grading of glioma patients. The results survival analysis suggested high expression of fascin-1 protein in glioma patients with a shorter survival time. Multivariate analysis showed that high expression of fascin-1 protein was an independent predictor of the prognosis of patients with glioma. CONCLUSIONS: High expression of the fascin-1 protein indicates poor prognosis for glioma patients.
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Sheep is an important livestock in the world providing meat, milk and wool for human beings. With increasing human population, the worldwide needs of production of sheep have elevated. To meet the needs, the assistant reproductive technology including ovine in vitro embryo production (ovine IVP) is urgently required to enhance the effective production of sheep in the world. To learn the status of ovine IVP, we collected some publications related to ovine IVP through PubMed and analyzed the progress in ovine IVP made in the last five years (2012-2017). We made comparisons of these data and found that the recent advances in ovine IVP has been made slowly comparable to that of ovine IVP two decades ago. Therefore, we suggested two strategies or approaches to tackle the main problems in ovine IVP and expect that the efficiency of ovine IVP could be improved significantly when the approaches would be implemented.
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Due to the implementation of more stringent specifications in sulfur content for gasoline , a deep understanding of the active phase of Co-Mo/Al2O3 catalysts is necessary to the development of hydrodesulphurization (HDS) catalysts. A series of Co-Mo/Al2O3 HDS catalysts with different metal loading were studied by laser Raman spectra. The existence form and the content of the active component of the catalyst were obtained by Raman spectra. The result shows that the percentage of characteristic Raman bands 940 cm(-1) correlates linearly with the HDS selectivity, which can be used as an experimental evidence for developing industrial selective HDS catalysts. Raman spectra of sulfided catalysts show that the bands of oxidic catalysts at 839 and 940 cm(-1) disappeared, and simultaneously, the bands of Mo-S at 372 and 408 cm(-1) emerged, which indicate that the oxidic sample is sulfided completely.
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BACKGROUND: Oct4 is a major transcription factor related to stem cell self-renewal and differentiation. To fulfill its functions, it must be able to enter the nucleus and remain there to affect transcription. KPNA2, a member of the karyopherin family, plays a central role in nucleocytoplasmic transport. The objective of the current study was to examine the association between Oct4 and KPNA2 expression levels with regard to both the clinicopathological characteristics and prognoses of patients with non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemistry was used to detect the expression profile of Oct4 and KPNA2 in NSCLC tissues and adjacent noncancerous lung tissues. Real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression profiles of Oct4 and KPNA2 in lung cancer cell lines. Small interfering RNAs were used to deplete Oct4 and KPNA2 expressions. Double immunofluorescence was used to detect Oct4 expression in KPNA2 knockdown cells. Co-immunoprecipitation was used to detect the interaction of Oct4 and KPNA2. RESULTS: Oct4 was overexpressed in 29 of 102 (28.4%) human lung cancer samples and correlated with differentiation (P = 0.002) and TNM stage (P = 0.003). KPNA2 was overexpressed in 56 of 102 (54.9%) human lung cancer samples and correlated with histology (P = 0.001) and differentiation (P = 0.045). Importantly, Oct4 and KPNA2 expression levels correlated significantly (P < 0.01). Expression of Oct4 and KPNA2 was associated with short overall survival. In addition, depleting Oct4 and KPNA2 expression using small interfering RNAs inhibited proliferation in lung cancer cell lines. Real-time polymerase chain reaction and western blotting analysis indicated that reduction of KPNA2 expression significantly reduced mRNA and nucleoprotein levels of Oct4. Double immunofluorescence analysis revealed that nuclear Oct4 signals were reduced significantly in KPNA2 knockdown cells. Co-immunoprecipitation experiments revealed that KPNA2 interacts with Oct4 in lung cancer cell lines. CONCLUSION: Oct4 and KPNA2 play an important role in NSCLC progression. Oct4 nuclear localization may be mediated by its interaction with KPNA2.
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Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Fator 3 de Transcrição de Octâmero/genética , alfa Carioferinas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/metabolismo , Ligação Proteica , alfa Carioferinas/metabolismoRESUMO
The mechanism of horizontal subsurface-flow constructed wetland (HSSF CW) and its design guidelines were introduced for the design of a constructed wetland. A numerical model Subwet was proposed to aid the design of constructed wetland. The design of a horizontal subsurface-flow wetland was simulated by utilizing Subwet model. The treatment efficiency for a year round operation was obtained from the modelling. The factors which have effects on treatment efficiencies were analyzed and investigated in this study. The recommendations on optimizing and improving the HSSF CW design were provided. This case study of Subwet model demonstrated the applicability of this model in the design of constructed wetland. It can provide theoretical basis for the design of constructed wetland.
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Modelos Teóricos , Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Biodegradação Ambiental , China , Planejamento AmbientalRESUMO
BACKGROUND: Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple. RESULTS: Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation. CONCLUSIONS: Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Temperatura Baixa , Malus/genética , Proteínas de Plantas/metabolismo , Aclimatação , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Malus/metabolismo , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteólise , Análise de Sequência de DNA , Estresse Fisiológico , Especificidade por Substrato , Sumoilação , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , UbiquitinaçãoRESUMO
Improvement of the selectivity of hydrodesulfurization (HDS) for hydrogenation (HYD) of olefins is crucial to produce sulfur-free (S < 0.001%) gasoline from fluid catalytic-cracked (FCC) gasoline. A series of sulfided CoMo/Al2O3 catalysts with different metal loading were prepared by pore-filling impregnation. MoS2 and COMoS active phases on the surface of sulfided COMo/Al2O3 catalyst were identified and analyzed quantitatively by XPS and in-situ FTIR of adsorbed CO. The results reveal that the increase in COMoS phase on the catalyst surface improves the HDS activity and selectivity. And the HDS selectivity correlates linearly with the ratio of active site number of CoMoS and MoS2, the higher the ratio of active site number of CoMoS and MoS2, the better the HDS selectivity. In situ variable temperature FTIR analysis shows that CoMoS phase has stronger electron accepting ability than MoS2. The strong electron deficient property of CoMoS active sites is the main reason for its excellent HDS activity and selectivity.
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A real time investigation of chemical reaction process of quercetin with various concentrations of sodium hydroxide was performed by using an intensified spectroscopic detector ICCD. The time resolved UV-Vis absorption spectra of 5 x 10(-5) mol x L(-1) quercetin respectively reacting with sodium hydroxide at concentrations of 2, 0.2, 0.1, 0.04 and 0.02 mol x L(-1) were acquired. A total of 200 spectra with the same exposure time of 0.1 ms for each spectrum but different time interval between two consecutive spectra were recorded for each reaction. The first 50 spectra have the time interval of 20 ms, the next 50 have 1 s, and the last 100 have 2 s. Results indicate that quercetin reacted with sodium hydroxide easily and there was an intermediate product formed during the reaction, with different concentrations of reactants, the changes of absorption bands were the same, but the moments at which the changes happened were different and the total reaction time was various from 1 s to 100 s. Spectra recorded showed the disappearing process of the typical bands centered at 254 and 374 nm of pure quercetin, the growing and disappearing processes of a new band centered at 427 nm of the intermediate product, and the growing process of the new band centered at 314 nm of the final product obviously. No other transient spectroscopic data are currently available on the reaction of quercrtin with sodium hydroxide, the results obtained in the present work provide useful experimental data for the study of the microscopic process of the reaction.
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OBJECTIVE: To investigate the ultrasonographic indexes in the evaluation of complete penile erection after oral administration of sildenafil citrate in men with normal erectile function. METHODS: The subjects lay supine, with the penis raised upwards, its back clinging to the abdomen. The probe was placed at the base of the ventral side of the penis for longitudinal and transverse section scanning. Observations were made on the corpus cavernosum, deep artery and deep dorsal vein of the penis at the time of flaccidity and complete erection after oral administration of sildenafil citrate, respectively. RESULTS: The examinations were acceptable to all the subjects both physically and psychologically, and all were completed successfully with no complications. Compared with the flaccid state of the penis, obvious changes were observed in the state of complete erection, including marked increases in the diameter of the corpus cavernosum ([18.57 +/- 2.50] mm, increased by [106.8 +/- 62.1]%), the inside diameter of the deep artery ([1.18 +/- 0.26] mm, increased by [54.9 +/- 29.0]%), the peak systolic velocity ([32.5 +/- 10.7] cm/s, increased by [209.3 +/- 112.9]%), and the systolic acceleration ([5.71 +/- 2.71] cm/s2, increased by [179.3 +/- 138.2]%). CONCLUSION: Oral administration of sildenafil citrate followed by ultrasonography is a new approach to the objective evaluation of penile erection, characterized by convenience, safety, non-invasiveness, non-complication, easy acceptability and easy clinical application.
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Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/diagnóstico por imagem , Piperazinas/farmacologia , Sulfonas/farmacologia , Adulto , Humanos , Masculino , Purinas/farmacologia , Citrato de Sildenafila , UltrassonografiaRESUMO
OBJECTIVE: To investigate the state of oxidative stress in the subjects with different levels of serum uric acid and to explore the cause of endothelial dysfunction induced by hyperuricemia. METHODS: Male subjects with normal serum uric acid or hyperuricemia were enrolled in this study. According to the levels of serum uric acid, all the participants were divided into five groups. Every group consisted of about fifty subjects. Plasma malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. In the mean time plasma nitric oxide (NO), plasminogen activator inhibitor-1 (PAI-1), endothelin-1 (ET-1) and other biochemical variables were also determined. RESULTS: When the serum uric acid level was more than 380 micromol/L, the levels of plasma MDA, SOD, GSH-Px, PAI-1 and ET-1 became higher, while the level NO became lower (P < 0.05). However SOD and GSH-Px became much lower when the serum uric acid level was more than 420 micromol/L. Multivariate stepwise regressive analysis showed that PAI-1 was positively related to MDA, UA, HOMA-IR and TG, but negatively related to SOD and NO (t = -3.64 - 6.08, P < 0.05). ET-1 was positively related to MDA, UA, HOMA-IR and negatively related to NO, GSH-Px and SOD (t = -4.75 - 6.35, P < 0.05). CONCLUSIONS: It is indicated that oxidative stress became much obvious when the serum uric acid level was more than 380 micromol/L. Oxidative stress, high serum uric acid level and insulin resistance may result in endothelial dysfunction.
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Endotélio Vascular/metabolismo , Hiperuricemia/metabolismo , Estresse Oxidativo , Ácido Úrico/sangue , Estudos de Casos e Controles , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Guan Xin II decoction (GX II) is a widely used traditional Chinese medicine (TCM) formula for the treatment of coronary heart diseases. However, the comprehensive chemical analysis of the formulated GX II is not clarified yet. An HPLC-DAD-ESI-MSn method was established to analyze GX II and its five component herbs, respectively. A total of 57 compounds, including phenolic acids, glycosides, flavonoids, and alkaloids were identified or tentatively characterized on the basis of their mass spectra or by comparison with reference standards. This is the first time that the chemical composition of GX II was elucidated by LC/MS. The established method will be used for quality control and pharmacokinetic studies of GX II.