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Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Camundongos , Animais , Isoniazida/efeitos adversos , Rifampina/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptor 4 Toll-Like/metabolismo , Fígado , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
A chiral bispyrene macrocycle designed for exclusive intermolecular excimer fluorescence upon aggregation was synthesized by a double hydrothiolation of a bis-enol ether macrocycle followed by intramolecular oxidation of free thiols. Unusually high stereoselectivity was achieved for the thiol-ene additions under templated conditions and Et3 B/O2 radical initiation. After enantiomer separation (chiral stationary phase HPLC), aqueous conditions provoked aggregation. Detailed structural evolution was afforded by ECD/CPL monitoring. Three regimes can be observed and characterized by strong modifications in chiroptical patterns under, at, or above a 70 % H2 O : THF threshold. In luminescence, high glum dissymmetry factors values were obtained, up to 0.022, as well as a double sign inversion of CPL signals during the aggregation, a behavior rationalized by time-dependent density functional theory (TDDFT) calculations. Langmuir layers of enantiopure disulfide macrocycles were formed at the air-water interface and transferred onto solid substrates to afford Langmuir-Blodgett films, which were then studied by AFM and UV/ECD/fluorescence/CPL.
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Pereskia aculeata Miller, a member of the Cactaceae family, is a plant with pharmacological potential due to its containing compounds with various biological activities, which include anti-inflammatory, anti-cancer and analgesic activities. In this study, we evaluated the anti-inflammatory effects of an ethanolic extract of P. aculeata Miller (EEPA) and the signalling pathways by which it exerts these effects. In vitro, EEPA inhibited the secretion of inflammatory factors NO, IL-6 and PGE2 in ipopolysaccharide-stimulated RAW264.7 macrophages (P<0.05). Treatment of RAW264.7 cells with EEPA also significantly decreased the levels of P-P38 and P-MK2, while upregulating the expression of TTP (P<0.05). In vivo anti-inflammatory activity assays revealed that EEPA reduced the degree of foot and joint swelling, the splenic index and the serum concentrations of TNF-α and IL-6 in in adjuvant-induced arthritis rats (P<0.05). Similarly, EEPA treatment of mice inhibited the acetic acid-induced exudation of Evans blue dye from peritoneal capillaries and significantly prolonged heat-stimulated pain response time (P<0.05). Taken together, these results suggest that EEPA exerts anti-inflammatory effects in vitro and in vivo. Thus, this study provides experimental and technical support for the development of a novel anti-inflammatory treatment based on P. aculeata Miller.
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Cactaceae , Interleucina-6 , Ratos , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Etanol , Transdução de SinaisRESUMO
BACKGROUND: The metabolic profile of human aortic tissues is of great importance. Among the analytical platforms utilized in metabolomics, LC-MS provides broad metabolome coverage. The non-targeted metabolomics can comprehensively detect the entire metabolome of an organism and find the metabolic characteristics that have significant changes in the experimental group and the control group and elucidate the metabolic pathway concerning the recognized metabolites. Employing non-targeted metabolomics is helpful to develop biomarkers for disease diagnosis and disease pathology research; for instance, Aortic aneurysm (AA) and Aortic dissection (AD). AIM: This study sought to describe the non-targeted analysis of 18 aortic tissue samples, comparing between AA and AD. MATERIAL & METHODS: Our experimental flow included dividing the samples into (AA, nine samples) and (AD, nine samples), SCIEX quadrupole timeofflight tandem mass spectrometer (TripleTOF) 6600+ mass spectrometer data refinement, MetDNA database analysis, and pathway analysis. We performed an initial validation by setting quality control parameters to evaluate the stability of the analysis system during the computer operation. We then used the repeatability of the control samples to examine the stability of the instrument during the entire analysis process to ensure the reliability of the results. RESULTS: Our study found 138 novel metabolites involved in galactose metabolism. DISCUSSION: 138 novel metabolites found in this study will be further studied in the future. CONCLUSION: Our study found 138 novel metabolites between AA and AD, which will provide viable clinical data for future studies aimed to implement galactose markers in aortic tissue analysis.
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Dissecção Aórtica , Galactose , Biomarcadores/metabolismo , Humanos , Metaboloma , Metabolômica/métodos , Reprodutibilidade dos TestesRESUMO
Marchantia polymorpha L. (MPL), a common type of liverwort, has been used as herbal medicine to improve liver function in China for many years. Although modern studies revealed that MPL contains various polyphenols, terpenoids, and bis[bibenzyls], its biological effects on liver function have never been systemically studied in any animal model. In this study, flavonoids were extracted from MPL and the components in the MPL flavonoids as well as the antioxidant capacity of MPL flavonoids were analysed. A rat model of liver injury was induced by intraperitoneal injection of 10% carbon tetrachloride (CCl4). MPL flavonoids were administered daily at a dose of 50, 100, and 200 mg/kg body weight to the rats for 2 weeks prior to injection of CC14. Treatment with MPL flavonoids, especially at a dose of 200 mg/kg, attenuated CCl4-induced increases in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, nitric oxide, malondialdehyde, tumour necrosis factor-α, interleukin-1ß, and interleukin-6, as well as reductions in superoxide dismutase and glutathione peroxidase. Microarray analyses showed that co-treatment with MPL flavonoids and CCl4 up-regulated many antioxidant and anti-apoptotic genes, but down-regulated several pro-inflammatory genes, compared to treatment with CCl4 alone. PCR and western blot assays further identified that MPL flavonoids increased GPX1, TMX1, TXN, and XIAP expression, but decreased IL-1 and IL1RAP expression and inhibited Jak/stat3 signalling. In conclusion, MPL flavonoids exerted hepatoprotective effects via antioxidant and gene regulatory mechanisms. (Altern Ther Health Med.
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Doença Hepática Induzida por Substâncias e Drogas , Marchantia , Animais , Antioxidantes/farmacologia , Tetracloreto de Carbono/metabolismo , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Flavonoides/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Fígado , Marchantia/metabolismo , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , RatosRESUMO
Since the needs and expectations of communities towards their urban environments often vary, landscape management strategies can often be prone to fail in the absence of social considerations. It is therefore incumbent on policy-makers to investigate and attempt to reconcile diverse community perceptions toward the natural and built environment for more equitable governance. This is of particular interest when planning and managing nature-based solutions (NBS) for river protection. We considered this challenge in understanding human values, perceptions and behaviour in a multilayered ecosystem that includes waterways, NBS, green open spaces, and a built environment. This paper analyses perceptions and behaviour around a public urban park next to the Georges River in Sydney Australia, utilizing a proxy-based approach and a mixed-method comprising community surveys and behavioural mapping. The results showed that while users perceive the significance of the urban river environment differently, naturalistic (ecological), humanistic (recreational) and utilitarian (well-being) values are dominant. Urban river catchments are highly valued for recreational purposes, with a strong perception of potential flooding hazards. Through exploring the literature, we recognized that the dominancy of leisure-related values around urban river catchments can be generalized to similar cases worldwide. While NBS, as an urban stormwater management solution, address some user values (e.g., naturalistic) around urban river catchments, they may lack further delivery of humanistic and utilitarian values due to the poor integration with recreational and cultural spaces. It was also the case around the Georges River, where low prominence of cultural features was observed. We concluded that NBS development around Georges River and other urban river catchments should incorporate socio-cultural considerations and community values, in particular the ones related to leisure. The gaps between users' beliefs and behaviour do not greatly challenge governance, provided that the decision-makers utilise these gaps for optimising management actions.
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Ecossistema , Rios , Austrália , Inundações , Humanos , ÁguaRESUMO
Sponge iron is a potential material for nitrogen removal, but lack of a study about nitrogen removal in a membrane bioreactor (MBR) coupled with sponge iron. The performances and mechanisms of nitrogen removal of SI-MBR were investigated and compared it with that in GAC-MBR. The results showed that the average rate of organic matter removal in the SI-MBR was 92.74%, which was higher than that in the GAC-MBR (87.48%). And the average effluent NO2--N and NO3--N concentration in the SI-MBR (0.02 mg/L and 3.73 mg/L) was lower than that in the GAC-MBR (0.05 mg/L and 7.51 mg/L). Meanwhile, the highest nitrification rate and denitrification rate was respectively 3.544 ± 0.25 mg/(g VSS·h) and 6.643 ± 0.2 mg/(g VSS·h) in the SI-MBR, which was higher than that (3.094 ± 0.25 mg/(g VSS·h) and (6.376 ± 0.2 mg/(g VSS·h)) in the GAC-MBR. Additionally, the bacterial activities (e.g., DHA activity and respiratory activity) were obviously enhanced through the iron ion from sponge iron. The bacterial community in the SI-MBR system was more richness and diverse than that in the GAC-MBR. Ultimately, the mechanisms of enhanced biological nitrogen removal with sponge iron in MBR were analyzed. On the surface of sponge iron, the DIRB and FOB could use the iron ion from sponge iron as the electron transfer to improve the nitrogen and organic removal. With sponge iron, there is not only the nitrification bacteria and heterotrophic denitrifying microorganism enriched, but also the autotrophic denitrifying bacteria abounded obviously. The autotrophic denitrifying bacteria could use Fe(II) as an electron donor to achieve denitrification and enhance the nitrogen removal.
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Desnitrificação , Nitrogênio , Bactérias , Reatores Biológicos/microbiologia , Ferro , NitrificaçãoRESUMO
The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate-activated protein kinase/ nuclear factor erythroid 2-related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll-like receptor 4 (TLR-4)/ nuclear factor kappa-B (NF-κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR-4 knockout (-/- ) mice. For this, we evaluated the expression levels of SREBP-1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR-4/ NF-κB inflammatory pathway, DCP inhibits TLR-4, up-regulates the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduces the expression of phospho(p)-NF-κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up-regulates the expression of p-AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.
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Proteínas Quinases Ativadas por AMP/metabolismo , Acanthaceae/química , Fígado/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Animais , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-ß, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.
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The effects of hepatocyte nuclear factors (HNFs) have been established in various tumors; however, the roles of HNF-1ß in colorectal cancer progression are never been found. In the present study, HNF-1ß expression was initially detected in clinical tissue samples and online datasets and HNF-1ß was found to be highly expressed in colorectal cancer tissues. In addition, a positive correlation existed between HNF-1ß expression and the overall survival of patients with colorectal cancer. In vitro and in vivo experiments revealed that HNF-1ß suppressed the stemness and migration of colorectal cancer cells. Combined with microRNAs (miRNAs) based on transcriptome-sequencing analysis, mechanistic studies showed that HNF-1ß directly bound to miR-200b promoter and thus promoted miR-200b expression, this HNF-1ß/miR-200b resulted in the downregulation of the expression of miR-200b downstream effectors. Furthermore, HNF-1ß inhibits the stemness and migration of colorectal cancer cells through miR-200b. This study reveals a novel HNF-1ß/miR-200b axis responsible for the stemness of colorectal cancer cells.
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Biomarcadores Tumorais/metabolismo , Movimento Celular , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Fator 1-beta Nuclear de Hepatócito/metabolismo , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Transcriptoma , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Double hydrothiolation of bis enol ether macrocycles was achieved under photo-mediated conditions. The thiol-ene reactions afford a fully regioselective anti-Markovnikov post-functionalization. Thanks to the use of ethanedithiol as reagent, moderate to excellent diastereoselectivity was accomplished leading to macrocycles containing four defined stereocenters in only three steps from 1,4-dioxane, tetrahydrofuran (THF) or tetrahydropyran (THP).
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Medial degeneration of aorta wall is the principal feature of aortic dissection (AD). Sirtuin 1 (SIRT1) plays essential protective effect on many aortic-associated disease. However, it is still unclear whether SIRT1participates in the process of medial degeneration-mediated AD. The purpose of this study is to explore the association between SIRT1 and AD process. qRT-PCR was used to evaluate the transcriptional level of genes involved in study. Protein levels and acetylation detection were measured by Western blotting. The regulatory relations between AP-1 and decorin was assessed by luciferase reporter gene assay. Acute aortic dissection (AAD) mice model was constructed by feeding with ß-aminopropionitrile monofumarate (BAPN). Haematoxylin and eosin (HE) and Mallory staining were performed for pathological analysis. In clinical aorta tissue of thoracic aortic dissection (TAD), the expression of SIRT1, activator protein 1 (AP-1) and decorin were in accordant trend. AP-1 expression which acts on Decorin promoter region is possibly regulated in a SIRT1-mediated deacetylation dependent manner. Resveratrol or SRT1720-initiated SIRT1 activation ameliorated BAPN-induced AAD symptoms accompanied by the activation of AP-1/decorin signaling and decorin-mediated programmed cell death 4 (PDCD4) expression by inhibiting miR-21 and miR-181b. These data suggest that SIRT1/AP-1/decorin signal cascades possibly play a part role in the process of AD. Our research demonstrate that activation of SIRT1 protects against AAD symptoms by enhancing AP-1-mediated decorin expression and downstream PDCD4 signaling pathway. Possibly, SIRT1 is served as a protective factor of AD and targeting SIRT1 therapy might be an attractive therapeutic approaches for AD treatment.
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Dissecção Aórtica/genética , Dissecção Aórtica/metabolismo , Proteínas Reguladoras de Apoptose/genética , Decorina/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator de Transcrição AP-1/metabolismo , Acetilação , Dissecção Aórtica/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Decorina/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , Camundongos , Regiões Promotoras Genéticas , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição AP-1/genéticaRESUMO
Lack of microbial contamination is crucial for drinking water quality and safety. Chlorine-resistant bacteria in drinking water distribution systems pose a threat to drinking water quality. A bacterium was isolated from an urban water supply network in northern China and identified as Pseudomonas peli by 16S rDNA gene analysis. This P. peli strain had high chlorine tolerance. The CT value (the product of disinfectant concentration and contact time) to achieve 3 lg unit (i.e. 99.9%)-inactivation of this P. peli isolate was 51.26-90.36 mg min/L, inversely proportional to the free chlorine concentration. Chlorine dioxide could inactivate the bacterium faster and more efficiently than free chlorine, as shown by flow cytometry. Thiazole orange plus propidium iodide staining indicated that free chlorine and chlorine dioxide inactivated P. peli primarily by disrupting the integrity and permeability of the cell membrane. The P. peli was also sensitive to ultraviolet (UV) radiation; a UV dose of 40 mJ/cm2 achieved 4 lg unit (99.99%)-inactivation. The Hom model was more suitable for analyzing the disinfection kinetics of P. peli than the Chick and Chick-Watson models.
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Desinfetantes , Purificação da Água , Bactérias , China , Cloro , Desinfecção , Pseudomonas , Raios Ultravioleta , Abastecimento de ÁguaRESUMO
Anaerobic digestion, the principal method of stabilizing biosolids in wastewater treatment plants (WWTPs), can efficiently and largely attenuate the antibiotic resistances in biosludge. This study aims to investigate the effect of oxidative pretreatment with ultrasound irradiation combined with ozone (US/O3) on the mesophilic and thermophilic anaerobic digestion (MAD and TAD) for the biosludge bearing trace fluoroquinolones contaminants-levofloxacin (LEVO) which was widely used in recent years. During the oxidation, the trace-level LEVO was almost completely degraded. The methanogenic activity in US/O3 pretreated TAD dosed 0.1 mg/L LEVO was much higher than those in single MAD and TAD, therefore leading to a remarkable increase in biogas production. The identification of levofloxacin intermediates during chemical degradation was analyzed using LCMS technique and the reaction pathway based on them was proposed. Hydroxyl radicals provided by US/O3 contributed to oxidative ring opening of LEVO as well as degradation of other biomacromolecules in the biosludge. Besides, the quinoline resistance genes-qnrA and qnrS declined significantly by 1-2 orders of magnitude in US/O3-pretreated TAD, indicating that the active radicals produced by US/O3 oxidized and degraded LEVO and therefore inactivated the antibiotic resistant bacteria or genes in the biosolids. Meanwhile, the composition and structure of the microbial community altered and the diversity and richness of total bacterial and potential human pathogens decreased, the pattern of which was correlated with LEVO-resistant genes. Among the well-known AD-related phylum including Bacteroidetes, Firmicutes, Methanobacteria as well as Thermotogae which has been previously detected in TAD and performed organic hydrolysis and degradation, the potential LEVO-resistant bacteria were probably affiliated to Actinobacteria, Bacteroidetes, Proteobacteria, Thermotogae. This study revealed the contribution of US/O3 pretreatment to the anaerobic digestion in terms of ARGs reduction for trace-LEVO- exposed biosludge and could provide useful guidance for controlling the dissemination of ARB and ARGs in sewage sludge.
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Microbiota , Ozônio , Anaerobiose , Humanos , Levofloxacino , EsgotosRESUMO
Purpose: As a neurodegenerative disease, spinal cord injury can lead to the loss of autonomic function, muscle function, or sensation. This study is designed to identify the key genes implicated in the excitability of motor neurons following spinal cord injury. Materials and methods: The GSE19701 dataset was obtained from Gene Expression Omnibus. It includes a total of 31 motor neurons after spinal cord injury (samples at day 0, 2, 7, 21 and 60 following injury). After the data were preprocessed by the Robust Multi-array Average method, soft clustering analysis was conducted by the Fuzzy C-Means method in the Mfuzz package to identify the differentially expressed genes. Afterward, the differentially expressed genes were analyzed with enrichment analysis using the DAVID online tool. Based on Cytoscape software, a protein-protein interaction network was constructed and then module analysis was carried out. Furthermore, miRNA-differentially expressed gene pairs were downloaded from the miRWalk2.0 database and the miRNA regulatory network was visualized by Cytoscape software. Results: We found 218 upregulated genes and 526 downregulated genes. In the protein-protein interaction network, Uba3, Sumo1, and Pik3ca had higher scores, and Uba3 interacted with Sumo1. Among the eight modules identified from the protein-protein interaction network, module 1 and 8 were significantly enriched in pathways related to degenerative diseases of the nervous system. Additionally, Pdcd4 was targeted by miR-21 in the miRNA regulatory network. Conclusion: Uba3, Sumo1, Pik3ca and miR-21 targeting Pdcd4 might be responsible for the excitability of motor neurons after spinal cord injury.
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Bases de Dados Genéticas , Redes Reguladoras de Genes/genética , Neurônios Motores/fisiologia , Traumatismos da Medula Espinal/genética , Animais , Análise por Conglomerados , Vértebras Lombares , Masculino , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Pollution build-up and wash-off processes are often included in urban stormwater quality models. However, these models are often unreliable and have poor performance at large scales and in complicated catchments. This study tried to improve stormwater quality models by adopting the genetic programming (GP) approach to generate new build-up algorithms for three different pollutants (total suspend solids - TSS, total phosphorus - TP and total nitrogen - TN). This was followed by testing of the new models (also traditional build-up and wash-off models as benchmark) using data collected from different catchments in Australia and the USA. The GP approach informed new sets of build-up algorithms with the inclusion of not just the typical antecedent dry weather period (ADWP), but also other less 'traditional' variables - previous rainfall depth for TSS and maximum air temperatures for TP and TN simulation. The traditional models had relatively poor performance (Nash-Sutcliffe coefficient, Eâ¯<â¯0.0), except for TP at Gilby Road (GR) (Eâ¯=â¯0.21 in calibration and 0.43 in validation). Improved performance was observed using the models with new build-up algorithms informed by GP. Taking TP at GR for example, the best performing model had E of 0.46 in calibration and 0.54 in validation. The best performing models for TSS, TP, and TN are often different, suggesting that specific models shall be used for different pollutants. Insights into further improvements possible for stormwater quality models were given. It is recommended that in addition to the typical build-up and wash-off process, new generations of stormwater quality models should be able to account for the non-conventional pollutant sources (e.g. cross-connections, septic tank leakage, illegal discharges) through stochastic approaches. Emission inventories with information like intensity-frequency-duration (IFD) of pollutant loads from each type of non-conventional source are suggested to be built for stochastic modelling.
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Chuva , Poluentes Químicos da Água , Algoritmos , Austrália , Monitoramento Ambiental , Movimentos da ÁguaRESUMO
To support sustainable urban planning and the design of water pollution mitigation strategies, the spatial and temporal trends of water quality in urban streams needs to be further understood. This study analyses over ten years of surface water quality data from 53 upstream catchments (20 of them predominated by a single type of land use) and two lowland sites across Greater Melbourne, Australia. We evaluated the impact of various catchment characteristics, especially urban land uses, on spatial and temporal urban water quality trends. Here, we focused on common urban pollutants: total suspended solids (TSS), total phosphorous (TP), total nitrogen (TN), zinc (Zn), copper (Cu) and nickel (Ni). Site median nutrient and heavy metal concentrations were negatively correlated with the catchment's elevation and its average annual rainfall. Further analysis shows that such trends were driven by the geographical pattern of Melbourne - i.e. low-laying sites tend to have less rainfall and be more urbanised. Only median concentrations of heavy metals (Zn and Cu) were correlated to catchment imperviousness. Further characterising of the urban environment was done into specific land uses (residential, industrial and commercial), yet median concentrations of all pollutants were not significantly correlated with land uses. This is because simple metrics, such as land use proportions, do not adequately reflect the significant variability in pollution sources that can exist even within the same land use type. Indeed, our temporal analysis found that the water quality difference between catchments with similar land uses is likely caused by their site-specific pollutant sources (construction and illegal discharge) and environmental management actions (wastewater management actions) regardless of similarities in land use. A 3-stage urbanisation cycle (development, operation and renewal) is suggested to further explain the urban water quality variance, but more data from small areas of an urban catchment is required to directly understand the unique impact of each urbanisation stage on water quality.
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Rios , Poluentes Químicos da Água , Austrália , Monitoramento Ambiental , Qualidade da ÁguaRESUMO
Software-defined radio (SDR) is a good solution for complying with the existing and incoming protocols for emerging wireless sensor networks (WSN) and internet of things (IoT) applications. The frequency synthesizer in a SDR tranceiver usually consists of a phase locked loop (PLL) and a post synthesizer. The PLL is the narrow band signal source and the post synthesizer generates wideband outputs by mixing and dividing. Compared with a frequency synthesizer utilizing the wideband PLL, this synthesizer features relatively constant loop parameters and mitigates the requirement for the oscillator. In this paper, a quadrature single side-band (QSSB) mixer with the proposed passive negative resistance (PNR) for frequency mixing in a post synthesizer is presented. The PNR is achieved by biasing the Metal-Oxide-Semiconductor Field-Effect Transistors (MOSFET) of the cross-coupled pair at the deep-triode region periodically and incorporates an inductor and a cap-array as the mixer load. Compared with the traditional single side-band mixers utilizing Inductor-Capacitor (LC) resonant loads or quality factor enhanced (Q-enhanced) LC resonant loads, which suffer from a selectivity versus working range trade-off, the mixer employing the proposed loading structure provides not only a wide operating range, but also a superior image side-band rejection ratio (ISRR). Moreover, the oscillating risk in conventional mixers adopting Q-enhanced LC resonant loads is eliminated. A wideband frequency synthesizer employing the proposed mixer was implemented in a TSMC 0.18 µm CMOS process and the mixer performed ISRR of 40â»57 dB and 30â»57 dB across 2.5â»3 GHz and 2.3â»3.2 GHz, respectively. The power consumption of the QSSB mixer, including buffer, is 18 mA from a 1.8 V supply and the active area is 0.445 mm². The measurement results provide validation that the proposed QSSB mixer is suitable for wideband software-defined frequency synthesizers and other frequency generating systems.
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Naringin (NA) is one of typical flavanone glycosides widely distributed in nature and possesses several biological activities including antioxidant, anti-inflammatory, and antiapoptotic. The aim of this study was to develop solid dispersion (SD) and to improve the dissolution rate and oral bioavailability of NA. NA-SD was prepared by the traditional preparation methods using PEG6000, F68, or PVP K30 as carrier at different drug to carrier ratios. According to the results of solubility and in vitro dissolution test, the NA-PEG6000 (1:3) SD was considered as an optimal formulation to characterize by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and powder X-ray diffraction. Furthermore, oral bioavailabilities of NA-PEG6000 (1:3) SD and NA-suspension with the same dosage were investigated in SD rats. The results confirmed the formation of SD and the pharmacokinetic parameters of NA-PEG6000 (1:3) SD (Cmax = 0.645 ± 0.262 µg/ml, AUC0-t = 0.471 ± 0.084 µg/ml h) were higher than that of NA-suspension (Cmax = 0.328 ± 0.183 µg/ml, AUC0-t = 0.361 ± 0.093 µg/ml h). Based on the results, the SD is considered as a promising approach to enhance the dissolution rate and oral bioavailability of NA.
Assuntos
Flavanonas/química , Animais , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Masculino , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, shows higher metastases and relapse rates than other subtypes. The metastasis of TNBC is the main reason for the death of TNBC patients. Increasing evidence has shown that inhibiting the metastasis of TNBC is a good method for TNBC treatment. Here, VSP-17 was designed and synthesized as an agonist of PPARγ, evidenced by upregulating the expression of CD36 and increasing the activity of PPARγ reporter gene. VSP-17 obviously inhibited the migration and invasion process of MDA-MB-231 cells but showed little effect on the viability of MDA-MB-231 cells. Notably, VSP-17 could selectively promote the expression of E-cadherin without affecting the expression of BRMS1, CXCL12, MMP9, Orai1, Stim1, TGF-ß, and VEGF. In addition, VSP-17 significantly suppressed the metastasis of liver and promoted the expression of E-cadherin in MDA-MB-231 xenograft model. In conclusion, VSP-17 inhibited the metastasis process of TNBC via upregulating the expression of E-cadherin.