Highlights • Two regimens as the first line treatment in adult LCH were compared. • Two regimens for the treatment of adult SS-m or MS LCH showed similar efficacy. • Treatment with two regimens was ...associated with a high recurrence rate.
Aims The aims of the present study are to determine the miRNA expression signature in rat hearts after ischaemic preconditioning (IP) and to identify an IP-regulated miRNA, miR-21, in IP-mediated ...cardiac protection, and the potential cellular and molecular mechanisms involved. Methods and results The miRNA expression signature was investigated in rat hearts. Among the 341 arrayed miRNAs, 40 miRNAs were differentially expressed (21 up and 19 down) in rat hearts with IP, compared with their controls. Some of these differentially expressed miRNAs were further verified by quantitative reverse transcriptase–polymerase chain reaction. Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo. Conclusion The results suggest that miRNAs are involved in IP-mediated cardiac protection. Identifying the roles of IP-regulated miRNAs in cardiac protection may provide novel therapeutic and preventive targets for ischaemic heart disease.
•PEO coatings were formed in K2ZrF6-containing electrolyte.•K2ZrF6 is capable to optimize the microstructure of PEO coating.•Corrosion resistance of PEO coatings is effected by K2ZrF6 concentration ...in the electrolyte.•Potentiodynamic polarization results are well matched with the EIS test results.•Long time immersion test confirmed the electrochemical results.
ZrO2-containing ceramic coatings formed on the AZ31 Mg alloy were fabricated in an alkaline electrolyte containing sodium phosphate and potassium fluorozirconate (K2ZrF6) by plasma electrolytic oxidation (PEO). X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) techniques were used to study the phase structure and composition of the coatings. It is indicated that the coatings formed in the K2ZrF6-containing electrolyte were composed of MgO, MgF2 and t-ZrO2. Morphological investigation carried out by scanning electron microscopy (SEM) and stereoscopic microscopy, revealed that the uniformity of coatings increased and roughness of coatings decreased after the addition of K2ZrF6. Electrochemical investigation was achieved by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) test. The results showed that the PEO coating formed in K2ZrF6-containing electrolyte exhibited an improved corrosion resistance than that of the coating formed in K2ZrF6-free electrolyte. In addition, the polarization and EIS tests results both showed that the suitable concentration (2.5g/l) of K2ZrF6 is of significant ability to improve the corrosion resistance of coatings. However, 5g/l and 10g/l K2ZrF6 has a negative effect on improving the corrosion resistance of PEO coatings compared with the coating formed in 2.5g/l K2ZrF6-containing electrolyte.
Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and ...metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.
Uniform magnetite, hematite, and goethite nanocrystals were prepared through an attractive method based on an oleic acid/alcohol/water system. By adjusting the synthetic parameters (base ...concentration, alcohol content, categories of alcohols, etc.), the controlled synthesis of uniform magnetite, hematite, and goethite nanocrystals can be easily achieved. Detailed investigations on the effect of the experimental parameters on the morphology of the final products and the phase transitions among the magnetite, hematite, and goethite phases were carried out. Finally, a method of doping other metal ions into magnetite was developed and the magnetic properties of magnetite doped with different metal elements were studied.
Uniform magnetite, hematite, and goethite nanocrystals are obtained through an attractive method based on an oleic acid/alcohol/water system. All the products can be well dispersed in a cyclohexane solvent to form transparent colloids with vivid colors (see figure). The influence of the preparation conditions as well as the magnetic properties of doped magnetite particles are revealed.
The Encyclopedia of DNA Elements (ENCODE) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin ...states and DNA methylation patterns. The ENCODE project generates data utilizing a variety of techniques that can enrich for regulatory regions, such as chromatin immunoprecipitation (ChIP), micrococcal nuclease (MNase) digestion and DNase I digestion, followed by deeply sequencing the resulting DNA. As part of the ENCODE project, we have developed a Web-accessible repository accessible at http://factorbook.org. In Wiki format, factorbook is a transcription factor (TF)-centric repository of all ENCODE ChIP-seq datasets on TF-binding regions, as well as the rich analysis results of these data. In the first release, factorbook contains 457 ChIP-seq datasets on 119 TFs in a number of human cell lines, the average profiles of histone modifications and nucleosome positioning around the TF-binding regions, sequence motifs enriched in the regions and the distance and orientation preferences between motif sites.
Wide-field calcium imaging is often used to measure brain dynamics in behaving mice. With a large field of view and a high sampling rate, wide-field imaging can monitor activity from several distant ...cortical areas simultaneously, revealing cortical interactions. Interpretation of wide-field images is complicated, however, by the absorption of light by hemoglobin, which can substantially affect the measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multiwavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, we develop a spatially detailed regression-based method to estimate hemodynamics. This Spatial Model is based on a linear form of the Beer-Lambert relationship but is fit at every pixel in the image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence. The improvement is pronounced near blood vessels and, in contrast with the Beer-Lambert equations, can remove vascular artifacts along the sagittal midline and in general permits more accurate fluorescence-based determination of neuronal activity across the cortex.
This paper addresses a well-known and strong source of contamination in wide-field calcium-imaging data: hemodynamics. To guide researchers toward the best method to separate calcium signals from hemodynamics, we compare the performance of several methods in three commonly used mouse lines and present a novel regression model that outperforms the other techniques we consider.
Background
Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens.
Objective
To ...gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients.
Methods
We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls.
Results
A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares‐discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t‐test, including trimethylamine N‐oxide, l‐arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N‐oxide was 3.922 times in patients with syphilis than healthy controls.
Conclusion
Trimethylamine N‐oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum.
Aims
To evaluate the antibacterial efficacy of novel antimicrobial peptides (AMPs) against multidrug‐resistant (MDR) Salmonella enterica serovar Choleraesuis (Salm. Choleraesuis) and to delineate the ...AMP‐responsive mechanisms of wild‐type (WT) and MDR strains.
Methods and Results
Proteomic approaches were performed based on two‐dimensional gel electrophoresis and liquid chromatography‐electrospray ionization‐quadrupole‐ time‐of‐flight tandem mass spectrometry to analyse the protein profiles of these two strains upon exposure to AMP GW‐Q6. Quantitative real‐time PCR was conducted to determine the mRNA expression level of the target genes. Furthermore, lipopolysaccharide (LPS) competition analysis was used to verify whether LPS may serve as the potential binding target when AMP approach and adhere to the bacterial surface.
Conclusions
The minimal inhibitory concentration assay revealed that our AMPs were even more effective against the MDR strains (4–32 μg ml−1), compared with those for the WT (8–64 μg ml−1). LPS dose‐dependently suppressed the GW‐Q6 antimicrobial activity. Clusters of orthologous groups analysis showed that the majority of the AMP‐responsive proteins were involved in cell envelope biogenesis and outer membrane, translation and chaperones.
Significance and Impact of the Study
These results indicated that the novel AMP GW‐Q6 serves as a potential candidate for antimicrobial drug development against MDR strains. These findings will also be helpful for expanding our knowledge on the molecular mechanisms of AMP–microbe interaction and the pathogenicity of salmonellosis caused by MDR strains of Salm. Choleraesuis.
In this paper, we develop a model for the timing and deterrence of terrorist attacks due to exogenous dynamics. The defender moves first and the attacker second in a two-stage game which is repeated ...over T periods. We study the effects of dynamics of several critical components of counter-terrorism games, including the unit defence costs (eg, immediately after an attack, the defender would easily acquire defensive funding), unit attack costs (eg, the attacker may accumulate resources as time goes), and the asset valuation (eg, the asset valuation may change over time). We study deterministic dynamics and conduct simulations using random dynamics. We determine the timing of terrorist attacks and how these can be deterred.
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