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The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2â¢- and â¢OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.
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DNA , Água do Mar , Raios Ultravioleta , Urânio , Água do Mar/análise , Água do Mar/química , DNA/análise , China , Urânio/análise , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Limite de Detecção , Processos Fotoquímicos , Diaminas , Benzotiazóis/química , Compostos Orgânicos/análise , Compostos Orgânicos/química , QuinolinasRESUMO
Alfalfa (Medicago sativa) is one of the most widely cultivated forage crops in the world. However, alfalfa yield and quality are adversely affected by salinity stress. Nodulin 26-like intrinsic proteins (NIPs) play essential roles in water and small molecules transport and response to salt stress. Here, we isolated a salt stress responsive MsNIP2 gene and demonstrated its functions by overexpression in alfalfa. The open reading frame of MsNIP2 is 816 bp in length, and it encodes 272 amino acids. It has six transmembrane domains and two NPA motifs. MsNIP2 showed high identity to other known NIP proteins, and its tertiary model was similar to the crystal structure of OsNIP2-1 (7cjs) tetramer. Subcellular localization analysis showed that MsNIP2 protein fused with green fluorescent protein (GFP) was localized to the plasma membrane. Transgenic alfalfa lines overexpressing MsNIP2 showed significantly higher height and branch number compared with the non-transgenic control. The POD and CAT activity of the transgenic alfalfa lines was significantly increased and their MDA content was notably reduced compared with the control group under the treatment of NaCl. The transgenic lines showed higher capability in scavenging oxygen radicals with lighter NBT staining than the control under salt stress. The transgenic lines showed relative lower water loss rate and electrolyte leakage, but relatively higher Na+ content than the control line under salt stress. The relative expression levels of abiotic-stress-related genes (MsHSP23, MsCOR47, MsATPase, and MsRD2) in three transgenic lines were compared with the control, among them, only the expression of MsCOR47 was up-regulated. Consequently, this study offers a novel perspective for exploring the function of MsNIP2 in improving salt tolerance of alfalfa.
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Medicago sativa , Tolerância ao Sal , Tolerância ao Sal/genética , Medicago sativa/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Água/metabolismo , Regulação da Expressão Gênica de Plantas , SalinidadeRESUMO
BACKGROUND: The three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients. METHODS: Forty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients. RESULTS: For the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736-0.910, 0.895-0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05). CONCLUSIONS: The pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.
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Neoplasias Nasofaríngeas , Prótons , Humanos , Estudos de Viabilidade , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética , Quimiorradioterapia , Amidas , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/terapiaRESUMO
Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.
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Hematoporfirinas , Pectinas , Hematoporfirinas/química , Pectinas/farmacologia , Pectinas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologiaRESUMO
BACKGROUND: High expression of inhibitor of DNA binding 1 (ID1) correlates with poor prognosis in colorectal cancer (CRC). Aberrant enhancer activation in regulating ID1 transcription is limited. METHODS: Immunohistochemistry (IHC), quantitative RT-PCR (RT-qPCR) and Western blotting (WB) were used to determine the expression of ID1. CRISPR-Cas9 was used to generate ID1 or enhancer E1 knockout cell lines. Dual-luciferase reporter assay, chromosome conformation capture assay and ChIP-qPCR were used to determine the active enhancers of ID1. Cell Counting Kit 8, colony-forming, transwell assays and tumorigenicity in nude mice were used to investigate the biological functions of ID1 and enhancer E1. RESULTS: Human CRC tissues and cell lines expressed a higher level of ID1 than normal controls. ID1 promoted CRC cell proliferation and colony formation. Enhancer E1 actively regulated ID1 promoter activity. Signal transducer and activator of transcription 3 (STAT3) bound to ID1 promoter and enhancer E1 to regulate their activity. The inhibitor of STAT3 Stattic attenuated ID1 promoter and enhancer E1 activity and the expression of ID1. Enhancer E1 knockout down-regulated ID1 expression level and cell proliferation in vitro and in vivo. CONCLUSIONS: Enhancer E1 is positively regulated by STAT3 and contributes to the regulation of ID1 to promote CRC cell progression and might be a potential target for anti-CRC drug studies.
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Neoplasias do Colo , Neoplasias Colorretais , Animais , Camundongos , Humanos , Fator de Transcrição STAT3/metabolismo , Camundongos Nus , Sequências Reguladoras de Ácido Nucleico , Proliferação de Células , Neoplasias do Colo/genética , DNA , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Movimento Celular , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismoRESUMO
It is still a challenge to accurately determine dissolved sulfide due to its susceptibility to contamination and loss during transportation, storage, and analysis in the laboratory, thus highlighting the necessity for its sensitive field analysis. Herein, a robust nozzle electrode point discharge (NEPD) enhanced oxidation coupling with chemical vapor generation (CVG) is described for the highly efficient and flameless conversion of sulfide (S2-) to SO2. Subsequently, a portable and low-power consumption gas phase molecular fluorescence spectrometry (GP-MFS) was constructed for the highly selective and sensitive determination of the generated SO2 via detecting its molecular fluorescence excited by a zinc hollow cathode lamp. Under optimal conditions, a limit of detection (LOD) of 0.1 µM was obtained for dissolved sulfide with a relative standard deviation (RSD, n = 11) of 2.6%. The accuracy and practicability of the proposed method were validated by the analyses of two certified reference materials (CRMs) and several river and lake water samples with satisfactory recoveries of 99%-107%. This work confirms that NEPD enhanced oxidation is a low energy consumption yet highly efficient method for the flameless oxidation of hydrogen sulfide and thus is suitable for the easy field detection of dissolved sulfide in environmental water by CVG-GP-MFS.
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PURPOSE: To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients diagnosed with N3 nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: A total of 787 patients with newly diagnosed N3 NPC treated with IC + CCRT or CCRT alone were included. Progression-free survival (PFS) was the primary endpoint. We balanced variables using propensity score matching (PSM). Kaplan-Meier curves with log-rank tests were applied to evaluate the survival condition of each group. Independent prognostic factors were identified using the Cox regression analysis. RESULTS: PSM assigned 228 patients to IC + CCRT and CCRT alone groups. Survival analysis for the matched data set showed that IC + CCRT achieved better survival outcomes compared with CCRT alone, and significant difference was observed in 5-year PFS [74.8% (95%CI 69.2 â¼ 80.9%) vs 65.4% (95%CI 59.4 â¼ 72.0%), P = 0.008], 5-year OS [(77.4%(95%CI 71.9 â¼ 83.3%) vs66.3%(95%CI 60.3 â¼ 72.9%), P = 0.005)] and 5-year distant metastasis-free survival (DMFS)[(81.8%(95%CI 76.7 â¼ 87.2%) vs72.4%(95%CI 66.7 â¼ 78.7%), P = 0.007)] between the two treatment groups. In multivariate analysis, IC + CCRT remained an independent protective factor for PFS (adjusted HR, 0.603; 95% CI, 0.433-0.841; P = 0.003), OS (adjusted HR, 0.568; 95% CI, 0.406-0.793; P < 0.001), and DMFS (adjusted HR, 0.541; 95% CI, 0.364-0.805; P = 0.002). CONCLUSION: More chemotherapy should be considered in patients with N3 NPC because of its ability to improve survival time. This could be from the use of IC or adjuvant metronomic chemotherapy.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Quimioterapia de Indução , Pontuação de Propensão , Quimiorradioterapia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
93Mo is an important radionuclide in view of radioactive waste repository because of its long half-life and high mobility in the environment. 93Mo decays by electron capture without any measurable gamma ray emission. The concentration of 93Mo in most of the radioactive waste is many orders of magnitude lower than the major activation product radionuclides, which makes the accurate determination of 93Mo a big challenge. A new analytical method for the determination of 93Mo in sulfuric acid media from nuclear power reactor was developed. 93Mo was separated from most of the radionuclides by cation exchange chromatography followed by the removal of sulfate by CaSO4 precipitation. A further purification of 93Mo, especially from anion species of 51Cr and 125Sb, was achieved by anion exchange chromatography and a short alumina column separation. The chemical yield of 93Mo in the entire separation procedure reached about 75%, and the decontamination factors for all potential interfering radionuclides were 1.5 × 106-1.6 × 108. The purified 93Mo was measured by liquid scintillation counting through counting its low-energy Auger electrons. A detection limit of 2 mBq/g for 93Mo in 50 g sample was achieved by this method, which enables the quantitative determination of 93Mo in most of the radioactive samples in the decommissioning waste and coolant water of nuclear power reactors. The developed method has been successfully applied to determine 93Mo in coolant water of nuclear power reactors, providing a robust analytical approach of 93Mo for the radiological characterization of radioactive wastes.
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Resíduos Radioativos , Ânions/análise , Resíduos Radioativos/análise , Radioisótopos , Ácidos Sulfúricos , Água/análiseRESUMO
Onobrychis viciifolia (sainfoin) is one of the most high-quality legume forages, which is rich in proanthocyanidins that is beneficial for the health and production of animals. In this study, proanthocyanidins and total flavonoids in leaves of 46 different sainfoin germplasm resources were evaluated, and it showed that soluble proanthocyanidin contents varied greatly in these sainfoin germplasm resources, but total flavonoids did not show significant difference. Transcriptome sequencing with high and low proanthocyanidins sainfoin resulted in the identification of totally 52,926 unigenes in sainfoin, and they were classed into different GOC categories. Among them, 1,608 unigenes were differentially expressed in high and low proanthocyanidins sainfoin samples, including 1,160 genes that were upregulated and 448 genes that were downregulated. Analysis on gene enrichment via KEGG annotation revealed that the differentially expressed genes were mainly enriched in the phenylpropanoid biosynthetic pathway and the secondary metabolism pathway. We also analyzed the expression levels of structural genes of the proanthocyanidin/flavonoid pathway in roots, stems, and leaves in the high proanthocyanidin sainfoin via RT-qPCR and found that these genes were differentially expressed in these tissues. Among them, the expression levels of F3'5'H and ANR were higher in leaves than in roots or stems, which is consistent with proanthocyanidins content in these tissues. Among MYB genes that were differentially expressed, the expression of OvMYBPA2 was relatively high in high proanthocyanidin sainfoin. Over-expression level of OvMYBPA2 in alfalfa hairy roots resulted in decreased anthocyanin content but increased proanthocyanidin content. Our study provided transcriptome information for further functional characterization of proanthocyanidin biosynthesis-related genes in sainfoin and candidate key MYB genes for bioengineering of proanthocyanidins in plants.
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Aquaporins (AQP) are distributed ubiquitously in plants, and they play important roles in multiple aspects of plant growth and development, as well as in plant resistance to various environmental stresses. In this study, 43 MsAQP genes were identified in the forage crop Medicago sativa. All the MsAQP proteins were clustered into four subfamilies based on sequence similarity and phylogenetic relationship, including 17 TIPs, 14 NIPs, 9 PIPs and 3 SIPs. Analyses of gene structure and conserved domains indicated that the majority of the deduced MsAQP proteins contained the signature transmembrane domains and the NPA motifs. Analyses on cis-acting elements in the promoter region of MsAQP genes revealed the presence of multiple and diverse stress-responsive and hormone-responsive cis-acting elements. In addition, by analyzing the available and comprehensive gene expression data of M. truncatula, we screened ten representative MtAQP genes that were responsive to NaCl or drought stress. By analyzing the sequence similarity and phylogenetic relationship, we finally identified the corresponding ten salt- or drought-responsive AQP genes in M. sativa, including three MsTIPs, three MsPIPs and four MsNIPs. The qPCRs showed that the relative expression levels of these ten selected MsAQP genes responded differently to NaCl or drought treatment in M. sativa. Gene expression patterns showed that most MsAQP genes were preferentially expressed in roots or in leaves, which may reflect their tissue-specific functions associated with development. Our results lay an important foundation for the future characterization of the functions of MsAQP genes, and provide candidate genes for stress resistance improvement through genetic breeding in M. sativa.
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Aquaporinas , Secas , Aquaporinas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloreto de Sódio/metabolismo , Estresse Fisiológico/genéticaRESUMO
Thoracic radiotherapy increases the risk of radiationinduced heart damage (RIHD); however, the molecular mechanisms underlying these changes are not fully understood. The aim of the present study was to investigate the effects of radiation on the mouse heart using highthroughput proteomics. Male C57BL/6J mice were used to establish a model of RIHD by exposing the entire heart to 16 Gy highenergy Xrays, and cardiac injuries were verified using a cardiac echocardiogram, as well as by measuring serum brain natriuretic peptide levels and conducting H&E and Masson staining 5 months after irradiation. Proteomics experiments were performed using the heart apex of 5month irradiated mice and control mice that underwent shamirradiation. The most significantly differentially expressed proteins were enriched in 'cardiac fibrosis' and 'energy metabolism'. Next, the cardiac fibrosis and changes to energy metabolism were confirmed using immunohistochemistry staining and western blotting. Extracellular matrix proteins, such as collagen type 1 α 1 chain, collagen type III α 1 chain, vimentin and CCCTCbinding factor, along with metabolismrelated proteins, such as fatty acid synthase and solute carrier family 25 member 1, exhibited upregulated expression following exposure to ionizing radiation. Additionally, the myocardial mitochondria inner membranes were injured, along with a decrease in ATP levels and the accumulation of lactic acid in the irradiated heart tissues. These results suggest that the high doses of ionizing radiation used lead to structural remodeling, functional injury and fibrotic alterations in the mouse heart. Radiationinduced mitochondrial damage and metabolic alterations of the cardiac tissue may thus be a pathogenic mechanism of RIHD.
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Metabolismo Energético/efeitos da radiação , Fibrose/metabolismo , Coração/efeitos da radiação , Animais , Colágeno Tipo III/metabolismo , Fibrose/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Miocárdio/patologia , Proteômica , Raios X/efeitos adversosRESUMO
Agropyron pectinatum is a perennial forage widely cultivated in China, and it belongs to the Gramineous family. In this study, we assembled the complete chloroplast genome of A. pectinatum. The whole chloroplast genome of A. pectinatum is 135,041 bp in length, comprising a pair of inverted repeat (IR) regions (20,821 bp) that are separated by a large single copy (LSC) region (80,632 bp) and a small single copy (SSC) region (12,767 bp). The chloroplast genome of A. pectinatum contains 133 genes, and 87 of them are protein-coding genes, 38 are tRNA, and eight are rRNA genes. The chloroplast genome of A. pectinatum could provide valuable information for varieties identification and evolution of the Agropyron Gaertn.
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A pilot-scale airlift bioreactor (ALBR) system was built and operated continuously for refinery excess sludge (RES) reduction. Combined ALBR and function-enhanced microbes (composed of photosynthetic bacteria and yeast) were integrated into the system. The pilot-scale ALBR was operated for 62 days, and the start-up time was 7 d. Continuous operation showed that the sludge reduction efficiency was more than 56.22%, and the water quality of the effluent was satisfactory. This study focused on investigating the effects of hydraulic retention time (HRT) on the stability of the system and the effect of sludge reduction. Under different HRT conditions of 40, 26.7, 20, and 16 h, the sludge reduction rates reached 56.22%, 73.24%, 74.09%, and 69.64%, respectively. The removal rates of chemical oxygen demand (COD) and total nitrogen (TN) decreased with decreasing HRT, whereas the removal rate of NH4+-N increased. The removal rate of total phosphorus (TP) was approximately 30%. Results indicate that the ALBR and function-enhanced microbe system can reduce sludge and treat sewage simultaneously, and the effluent is up to the national emission standard. Addition of function-enhanced microbes can promote the degradation of petroleum hydrocarbon substances in the sludge, especially alkanes with low carbon numbers. This study suggests that the optimal HRT for the system is 16 h. The total operation cost of the ALBR combined with the function-enhanced microbe system can be reduced by 50% compared with the cost of direct treatment of the RES system.
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Esgotos , Eliminação de Resíduos Líquidos , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Nitrogênio , FósforoRESUMO
Despite the increased interest and great progress obtained on arsenic test, it is still a challenge to accomplish the on-site determination of arsenic in rice due to the expensive instrumentation and harsh digestion process. In this work, MnFe2O4 micromotors were found to retain high catalytic activity to simultaneously produce large amounts of hydroxyl radicals and O2 bubbles in the presence of H2O2. Interestingly, the generated bubbles autonomously propel the micromotors and prevent them from depositing, thus keeping their high catalytic activity. As a result, a MnFe2O4 micromotors enhanced digestion method was developed for the field digestion of rice samples within 100 min only using H2O2, which was further utilized to realize the on-site detection of arsenic in rice by coupling with the Gutzeit method followed headspace solid phase extraction. A quantification limit of 40 µg kg-1 was obtained for the determination of arsenic in rice. Owing to their capabilities of the efficient and rapid adsorption of arsenic and continuous movement, a MnFe2O4 micromotors enhanced solid phase extraction was also established for the sensitive determination of arsenic in water with a 1 µg L-1 of quantification limit. The accuracy of the developed method was validated via analysis of a Certified Reference Material of rice (GBW10043) and a series of rice and water samples with satisfactory results, showing promising potential in the sensitive on-site detection of arsenic in rice and water samples.
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Arsênio , Oryza , Digestão , Peróxido de Hidrogênio , Extração em Fase Sólida , ÁguaRESUMO
The objective of this study was to investigate the influence of inulin (IL) and maltodextrin (MD) as matrix formers on the physical properties of drug nanocrystal-embedded microparticles (NEM) during spray-drying and storage. The redispersibility, aerodynamic performance and phase behaviour of NEM/MD and NEM/IL stored at different water activity (aw) values were evaluated. NEM with 2â¯g/g (relative to the weight of drug) of IL and MD exhibited the excellent performance after spray-drying. The water activity significantly influenced the redispersibility and aerodynamic performance of NEM/MD and NEM/IL. The NEM/MD presented a higher Tg at all aw values than did NEM/IL. The moisture-induced collapse of the amorphous glassy matrix of IL and MD could be responsible for the poor redispersibility and aerodynamic performance of NEM/IL and NEM/MD, respectively. The NEM/MD exhibited better aerodynamic performance at high aw (0.528) than did NEM/IL. Therefore, MD could be an excellent matrix former for inhalable NEM.
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Inulina/química , Nanopartículas/química , Polissacarídeos/química , Administração por Inalação , Inulina/administração & dosagem , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polissacarídeos/administração & dosagem , Propriedades de SuperfícieRESUMO
The objective of this study was to understand the influence of the water adsorption and glass transition of matrix formers on redispersibility in water of drug nanocrystals-aggregated particles(NAP) during storage, and the critical storage strategy for NAP powders were determined based on the Guggenheim-Anderson-de Boer (GAB) and the Gordon-Taylor models. Apigenin was used as model drug. Six kinds of matrix formers sucrose(SU), lactose(LA), trehalose(TR), inulin(IN), maltodextrin(MA) and PVPK30(PV) were used to prepare apigenin nanocrystals-aggregated particles (AN-NAPs). The results demonstrated that the adsorption isotherms curves of six kinds of matrix formers based AN-NAPs all showed typical II (S) type adsorption. The water activity significantly influenced the redispersibility of AN-NAP, which could be attributed to the microstructure collapse of amorphous matrix induced by moisture adsorption at high water activity or high moisture. MD based AN-NAP(AN-NAP/MD) exhibited much better redispersibility at high water activity(0.689) compared with the other amorphous matrix formers. MD was able to significantly enlarge the Tg of AN-NAP system and prevent from aggregation of AN-NAP compared to other matrix formers. And the critical water activity and moisture content of AN-NAPs were in the ranges of 0.015-0.545 and 0.0412-0.1508 g water/g dry matter, respectively. Of all amorphous matrix based NAPs, the critical water activity of AN-NAP/MD was the highest (0.545), and the critical moisture content was 0.1003 g water/g dry matter, and followed by TR based on AN-NAP. MD could be used as an excellent matrix former for nanocrystals-aggregated particles during storage. Therefore, the roles of water adsorption and glass transition of matrix formers on redispersibility of drug nanocrystals-aggregated particles during storage was successful elucidated, and the critical storage strategy was proposed based on the GAB model and the Gordon-Taylor model.
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Apigenina/administração & dosagem , Excipientes/química , Nanopartículas/química , Tecnologia Farmacêutica/métodos , Água/química , Adsorção , Portadores de Fármacos/química , Estabilidade de Medicamentos , Pós/química , Temperatura , VitrificaçãoRESUMO
The objective of this study is to use cellulose nanocrystals (CNC) combining with carboxymethyl cellulose sodium (CMC-Na) and hydroxypropyl methylcellulose (HPMC) as stabilizer to prepare novel redispersible camellia oil Pickering emulsions powder (CO-PEP). Cellulose nanocrystals modified with carboxymethyl cellulose sodium (CNCC) was prepared by homogenization technology. CNCC seemed to be rod-like particles with mean particle size of 124.2 ± 2.5 nm. And the cellulose structure, crystal state and thermal property of CNCC remained unchanged during the homogenization. The combination of CNC and CMC-Na in CNCC might be dependent of physical interaction. The mean particle size of optimum CO-PE/0.25%CNCC was 0.569 ± 0.023 µm. The CNCC based particle stabilizer might form the distinctive barrier layer around oil droplet. The redispersibility results demonstrated that 50% HPMC based CO-PEP formed large composite particle with high drug loading ability and exhibited superior redispersibility. Novel redispersible powdered Pickering emulsions could be prepared by cellulose nanocrystals combining with water-soluble cellulosic derivatives.
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Celulose/química , Nanopartículas/química , Pós , Celulose/análogos & derivados , Emulsões/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
BACKGROUND: To improve the dissolution and bioavailability of poorly soluble drugs, novel nanosuspensions using co-processed nanocrystalline cellulose-sodium carboxymethyl starch (NCCS) as a synergetic stabilizer were first designed. METHODS: Co-processed NCCS was prepared by means of homogenization. Poorly soluble baicalin (BCA) was used as a model drug. BCA nanosuspension (BCA-NS/NCCS) using co-processed NCCS as a dispersant was prepared via homogenization and further converted into the dried BCA nanosuspension particle (BCA-NP/NCCS) via spray drying. The influence of NCCS on the dispersion efficiency of BCA-NS/NCCS was investigated. Morphology and crystal characteristic of NCCS and BCA-NP were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of NCCS as a stabilizer for BCA-NS/NCCS and BCA-NP. RESULTS: The optimum 50% concentration of NCCS (nanocrystalline cellulose [NCC]:sodium carboxymethyl starch [SCS]=60:40) could be mostly beneficial for formation and stability of BCA-NS/NCCS. NCCS could completely prevent aggregation of BCA-NP during spray drying and enhance the redispersibility as well as dissolution of spray-dried BCA-NP, which might be attributed to "brick-concrete"-based barrier effect of NCCS and the swelling capacity of superdisintegrant SCS. The crystal state of NCC and BCA presented in BCA-NP/NCCS remained unchanged during the homogenization. The BCA-NP/NCCS exhibited a fast dissolution rate and significantly enhanced bioavailability of BCA. The AUC(0-∞) of the BCA-NP/NCCS (8,773.38±718.18 µg/L·h) was 2.01 times (P<0.05) as high as that of the crude BCA (4,354.61±451.28 µg/L·h). CONCLUSION: This study demonstrated that novel surfactant-free nanosuspensions could be prepared using co-processed NCCS as a synergetic stabilizer and also provided a feasible strategy to improve the dissolution and oral bioavailability of poorly soluble drug.
Assuntos
Celulose/química , Flavonoides/farmacologia , Nanopartículas/química , Amido/análogos & derivados , Suspensões/química , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Elasticidade , Flavonoides/farmacocinética , Masculino , Tamanho da Partícula , Ratos Wistar , Reologia , Solubilidade , Amido/química , Eletricidade Estática , ViscosidadeRESUMO
Breviscapine (BVP) is a flavonoid compound with strong neuroprotective and anti-platelet aggregation effect. The objective of this study is to design novel BVP nanocrystals modified by natural panax notoginseng saponins (PNS) for enhancing dissolution and anti-platelet aggregation effect of BVP. BVP nanocrystals modified by PNS (BVP-NC/PNS) were firstly prepared by coupling homogenization technology and freeze-drying technology, and BVP nanocrystals modified by RH40 (BVP-NC/RH40) as reference for comparison. The morphology, crystals characterization, dissolution behavior and anti-platelet aggregation effect of BVP-NC/PNS was systemically evaluated. The results demonstrated that the PNS could effectively maintain stability of BVP-NC at suspensions state dependent of its surface activity and the electrostatic repulsion effect. Combination of PNS and trehalose could prevent the aggregation of BVP-NC/PNS during freeze-drying. The PXRD and DSC results demonstrated that the BVP crystal state in BVP-NC/PNS was not changed owing to PNS modification and homogenization treatment. And the freeze-dried BVP-NC could easily recover back to BVP-NS and significantly improve the dissolution of BVP. The AUC(0-∞) of the BVP-NC/PNS was 4.54 times as high as that of the coarse BVP, but not significantly different compared to that of BVP-NC/RH40 (p < 0.05). The anti-platelet aggregation results demonstrated that, BVP-NC/PNS group showed more effective inhibition on PAF-induced platelet aggregation compared with corresponding control groups, which might attribute to the enhanced bioavailability of BVP and synergistic effect of PNS with BVP. In conclusion, PNS could be used as an alternative stabilizer for preparation of BVP-NC, and BVP-NC modified by PNS is a promising formulation strategy for enhancing oral bioavailability and anti-platelet aggregation of BVP.
Assuntos
Flavonoides/farmacocinética , Nanopartículas/química , Panax notoginseng/química , Inibidores da Agregação Plaquetária/farmacocinética , Saponinas/química , Administração Oral , Animais , Disponibilidade Biológica , Flavonoides/química , Flavonoides/farmacologia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Difração de Raios XRESUMO
Phenylenevinylene terpyridine (mepvpt) shows chelation enhanced fluorescence (CHEF) with Cd(II) and chelation quenched fluorescence (CHQF) with Zn(II), respectively. To understand the behaviors, we studied their intrinsic optical properties using DFT/TDDFT methods. The results show that fluorescence quantum yields (FQY) of mepvpt, mepvpt-Cd and mepvpt-Zn are low due to high ISC rates from higher excited states rather than the S1 excited state. When mepvpt chelates Cd(II), the molecular structure becomes more planar and S3,4â¯ââ¯S0 radiation rates become higher than that of mepvpt, which results in CHEF. When mepvpt chelates Zn(II), a new S4â¯ââ¯S0 emission with low oscillator strength occurs and high S4â¯ââ¯Tn ISC rates appear, which leads to CHQF. This proposed mechanism of metal fluorescence enhancing/quenching suggests a design strategy for single-molecular multi-analyte sensors.