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991.
    
Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.  相似文献   
992.
Simple SummaryTuberculosis is the leading cause of mortality from a single infectious agent and is among the top 10 causes of death worldwide. Despite that, few studies focus on regulatory elements such as small non-coding RNAs in tuberculosis. This pilot work applied Next Generation Sequencing techniques to evaluate the global miRNA expression profile of patients with active tuberculosis; their respective healthy physicians, who are at constant risk of infection; and a second group of healthy controls. In addition, we observed miRNA–gene interactions affected by exposure to the bacteria. Our findings indicate a list of miRNAs that could be used as potential biomarkers to improve treatment strategies at early stages. We also observed modified pathways related to the immune response due to differential miRNA expression profiles. Finally, we alert and encourage the development of new strategies to avoid long-term exposure of healthy physicians, considering how closely related their miRNA profile was to tuberculosis patients using current safety protocols.AbstractThe role of regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humans and it is still a challenge to prevent and treat. Control of the infection, as well as its diagnosis, are still complex and current treatments used are linked to several side effects. This study aimed to identify possible biomarkers for tuberculosis by applying NGS techniques to obtain global miRNA expression profiles from 22 blood samples of infected patients with tuberculosis (n = 9), their respective healthy physicians (n = 6) and external healthy individuals as controls (n = 7). Samples were run through a pipeline consisting of differential expression, target genes, gene set enrichment and miRNA–gene network analyses. We observed 153 altered miRNAs, among which only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results indicate that miRNAs may be involved in immune modulation by regulating gene expression in cells of the immune system. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.  相似文献   
993.
    
The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.  相似文献   
994.
995.
    
Different types of scaffolds are used to reconstruct muscle volume loss injuries. In this experimental study, we correlated ultrasound observations with histological findings in a muscle volume loss injury reconstructed with autologous adipose tissue. The outcome is compared with decellularized and porous matrix implants. Autologous adipose tissue, decellularized matrix, and a porous collagen matrix were implanted in volumetric muscle loss (VML) injuries generated on the anterior tibial muscles of Wistar rats. Sixty days after implantation, ultrasound findings were compared with histological and histomorphometric analysis. The muscles with an autologous adipose tissue implant exhibited an ultrasound pattern that was quite similar to that of the regenerative control muscles. From a histological point of view, the defects had been occupied by newly formed muscle tissue with certain structural abnormalities that would explain the differences between the ultrasound patterns of the normal control muscles and the regenerated ones. While the decellularized muscle matrix implant resulted in fibrosis and an inflammatory response, the porous collagen matrix implant was replaced by regenerative muscle fibers with neurogenic atrophy and fibrosis. In both cases, the ultrasound images reflected echogenic, echotextural, and vascular changes compatible with the histological findings of failed muscle regeneration. The ultrasound analysis confirmed the histological findings observed in the VML injuries reconstructed by autologous adipose tissue implantation. Ultrasound can be a useful tool for evaluating the structure of muscles reconstructed through tissue engineering.  相似文献   
996.
    
The in situ formation of mullite (Al6Si4O13) is a complex process based on solid-state reactions strongly affected by the characteristics of Al2O3 and SiO2 sources. This study investigated the combined effects of variable SiO2/Al2O3 ratios and the presence of low-melting-point impurities on the physical properties and microstructure of in situ alumina-mullite ceramics. Two grades of synthetic amorphous silica, known as microsilica, of similar physical properties and significant differences in the content of alkali-based impurities (0.8 and 3.6 wt%), were combined with thin calcined alumina particles in different proportions (from silica-free up to stoichiometric mullite), pressed and sintered. The samples were tested for total porosity, flexural strength, and pore size distribution, and their crystalline phases and microstructures formed were investigated. Small amounts of both microsilica grades (up to 8.9 wt%) hindered the densification of the alumina-mullite matrix and favored grain growth events, increasing porosity and reducing strength. For samples containing higher microsilica loads (16.4–28.2 wt%), the impurities content significantly affected the amount of liquid phases formed. Such impurities altered the ratio and shape of the pores and the total amount of mullite after sintering. Therefore, different microstructures and levels of flexural strength and total porosity were observed.  相似文献   
997.
    
Over the past few years, investigators in Brazil have been uncovering numerous corruption and money laundering schemes at all levels of government and in the country's largest corporations. It is estimated that between 2% and 5% of the global GDP is lost annually because of such practices, not only directly impacting public services and private sector development but also strengthening organized crime. However, most law enforcement agencies do not have the capability to carry out systematic corruption risk assessment leveraging on the availability of data related to public procurement. The currently prevailing approach employed by Brazilian law enforcement agencies to detect companies involved in potential cases of fraud consists in receiving circumstantial evidence or complaints from whistleblowers. As a result, a large number of companies involved in fraud remain undetected and unprosecuted. The decision support system (DSS) described in this work addresses these existing limitations by providing a tool for systematic analysis of public procurement. It allows the law enforcement agencies to establish priorities concerning the companies to be investigated. This DSS incorporates data mining algorithms for quantifying dozens of corruption risk patterns for all public contractors inside a specific jurisdiction, leading to improvements in the quality of public spending and to the identification of more cases of fraud. These algorithms combine operations research tools such as graph theory, clusterization, and regression analysis with advanced data science methods to allow the identification of the main risk patterns, such as collusion between bidders, conflicts of interest (e.g., a politician who owns a company contracted by the same government body where he or she was elected), and companies owned by a potentially straw person used for disguising its real owner (e.g., beneficiaries of cash conditional transfer programs). The DSS has already led to a detailed analysis of large public procurement datasets, which add up to more than 50 billion dollars. Moreover, the DSS provided strategic inputs to investigations conducted by federal and state agencies.  相似文献   
998.
A review of the N2O-N emission from crop residues was conducted based on new data published during the last decade. The result indicated that factors as type of crop, biochemical quality of residues, agricultural management, climate and season of the year, soil properties and soil moisture play a significant role in the rate of N2O-N emissions. An emission factor (EF) equal to 1.055% of N applied in plant residues – derived from a simple linear regression of emitted N2O-N (kg ha?1) on N applied in crop residues (kg ha?1) – represent an estimate that explains about 60% of emission variations. However, the EF of N applied in plant residues is not a constant but a variable coefficient that depends on environmental and management variables. The following two linear models – that estimate emitted N2O-N (kg ha?1) as a function of the variables N (kg ha?1) applied in plant residues (NPR), rain (mm), temperature (°C) and temperature2(°C2) – were fitted to the dataset with 45 observations obtained from the reviewed literature. $$\hskip1.5pc\hbox{N}_{2}\hbox{O}\hbox{-}\hbox{N}=-4.154+0.00955\hbox{ NPR}+1.7278\hbox{ ApM}+0.003996\hbox{ Rain }+0.6242\hbox{ Tem }-0.0230\hbox{ Tem}^{2}$$ and $$\hbox{N}_{2}\hbox{O}\hbox{-}\hbox{N}= 0.6535 + [-0.0404 + 0.0078\hbox{ ApM }+ 0.000044\hbox{ Rain }+ 0.00567\hbox{ Tem }-0.0001975\hbox{ Tem}^{2}]\hbox{ NPR }$$ Both models provided almost equally good statistical fit to the data, with R 2=0.832 and R 2=0.829, respectively, and most regression coefficients being significant at $P < 0.01$ . Because of its internal structure, the second model is more appealing as it represents N2O-N emission as a transformation that is affected by management and environmental variables. The following expression – that correspond to the quantities in the square bracket at the right hand side of the second model – is the coefficient for the variable N applied in crop residues, and represent the emission factor as a function of application method of plant residues, rain, temperature and temperature2. $$\hskip3.5pc\hbox{EF }=-0.0404+0.0078\hbox{ ApM }+0.000044\hbox{Rain }+0.00567\hbox{ Tem }- 0.0001975\hbox{ Tem}^{2}$$ Standardization of research methodologies and data gathering and reporting, including kind of crop, N content of applied residues, agricultural management, length of the measuring period, climate, soils properties, soil temperature and water content, would facilitate further advances in studies oriented to increase the precision of N2O-N emission estimates.  相似文献   
999.
The synthesis and chemical characterization of two new trans platinum complexes, trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] (1) and trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] (2) are described. Their ability to interact with 5'-GMP by themselves and in the presence of reducing agents in the case of trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)] were tested. Circular dichroism, electrophoretic mobility in agarose gel, and atomic force microscopy studies showed that the interaction of complex 1 with DNA is stronger than that of complex 2. Cytotoxicity tests against HL-60 tumor cells also showed higher activity for trans-[PtCl(2)NH(3)(4-hydroxymethylpyridine)] than for trans-[PtCl(4)NH(3)(4-hydroxymethylpyridine)]. Complex 1 presents similar behavior to cisplatin, but with a lower IC(50) at 24 h. Complex 1 also showed high apoptosis induction.  相似文献   
1000.
Ozonation reactions are very important in vegetable oil chemistry since their ozonation products are involved in antimicrobial effect in therapeutical uses for several microbiological etiology diseases. Information on the spectroscopic characterization of the products generated by ozonolysis of sunflower oil is limited. In the present study ozonized sunflower oil with 650 mmol-equiv/kg of peroxide index is chemically characterized. Ozonation of sunflower oil produced ozonides, aldehydes and hydroperoxides which were identified by 1H, 13C and two-dimensional 1H Nuclear Magnetic Resonance (NMR). The virgin sunflower oil and ozonized sunflower oil show very similar 1H NMR spectra except for the resonances at δ = 9.74 and δ = 9.63 ppm that correspond to both triplet from aldehydic protons, δ = 5.6 ppm (olefinic signal from hydroperoxides), and δ = 5.15 ppm (multiplet from ozonides methylic protons). Other resonance assignments are based on the connectivities provided by the proton scalar coupling constants. These are the following: δ = 3.15 ppm (doublet from methylenic group in α position respect to olefinic proton), δ = 2.45 ppm (multiplet from methylenic group allylic to ozonides methynic protons) and δ = 1.62 ppm (multiplet methylenic protons in β position respect to ozonides methynic protons). From the 13C NMR and 1H-13C two- dimensional spectrum of the ozonized sunflower oil, the presence of ozonides was confirmed by the signals δ = 103.43 and δ = 103.49 ppm, respectively. The others new signals found in δ = 42.5 and δ = 42.76 ppm confirm the presence of methylenic carbons from hydroperoxides and ozonides. These results indicate that NMR Spectroscopy can provide valuable information about the amount of reaction compounds of ozonized vegetable oil. From the chemical structural elucidation of ozonated sunflower oils, relevant biochemical and chemical information can be achieved.  相似文献   
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