Highlights • There is a vasogenic brain edema after SAH as shown by MRI. • Apoptosis/inflammation in endothelium induced enhanced vascular permeability. • Thrombomodulin preserved vascular integrity ...via activated protein C/PAR-1 through blocking p38MAPK-p53/NF-κB pathway.
Background
Dopamine (DA) is a negative modulator of gut motility. Monoamine oxidase‐B (MAO‐B) is an important metabolic enzyme degrading DA. Rasagiline, an irreversible MAO‐B inhibitor, is used to ...treat Parkinson’s disease because of its neuroprotective effect and increasing central DA. However, it is unclear whether MAO‐B exists in the colon and rasagiline increases colonic DA, thereby affecting colonic motility.
Methods
Immunohistochemistry, western blotting, enzyme activity assay, colonic motility recording, gut transit test, and high‐performance liquid chromatography‐electrochemical detection were employed in this study.
Key Results
Monoamine oxidase‐B was distributed in the colonic muscular layers including neurons and glias of rat and human. When oral treatment of rats with rasagiline for 4 weeks, in vitro colonic motility was significantly reduced, but it was greatly reversed by SCH‐23390, an antagonist of DA D1 receptor. The rasagiline‐treated rats also manifested decreased MAO‐B activity and increased DA content in the colonic muscular layer, but no alterations were detected in the protein expressions of D1 and D2 receptors, and MAO‐A and MAO‐B, as well as in the content of 5‐hydroxytryptamine and noradrenaline. Moreover, acute administration of rasagiline did not affect the colonic motility in vitro and the colonic DA level in rats, although MAO‐B activity was significantly inhibited.
Conclusions & Inferences
Monoamine oxidase‐B is abundant in the colonic muscular layer including myenteric plexus of rat and human. Long‐term administration of rasagiline can increase colonic DA thereby inhibiting colonic motility, suggesting that colonic MAO‐B could be a potential drug target for colonic dysmotility.
Monoamine oxidase‐B was distributed in the colonic muscular layers including neurons and glias of rat and human. Long‐term treatment of rasagiline significantly inhibited colonic monoamine oxidase‐B activity and increased the dopamine content, which may contribute to colonic hypomotility.
Alteration of human leukocyte antigen (HLA) expression, such as decreased HLA I (HLA‐A, ‐B and ‐C) antigens and elevated nonclassical HLA I antigens (HLA‐E, ‐F and ‐G), was reported to have an ...unfavorable prognosis in various cancers. In our study, HLA‐F expression in 105 primary esophageal squamous cell carcinoma (ESCC) lesions and 62 case‐matched adjacent normal tissues, and HLA I antigens among 68 cases were analyzed by immunohistochemistry. Data revealed that HLA‐F expression was observed in 58.1% (61/105) of the ESCC lesions and in 54.8% (34/62) of the normal esophageal tissues. Among the 62 case‐matched samples, HLA‐F expression (lesion vs. normal tissue) was upregulated, unchanged and downregulated in 13 (21.0%), 6 (9.6%) and 43 (69.4%) cases, respectively. Patients with HLA‐F positive had a worse survival than those with HLA‐F negative (p = 0.040). Patients with upregulated HLA‐F expression (lesion vs. normal tissue) had significantly worse survival than those with HLA‐F unchanged and downregulated (p = 0.010). Furthermore, decreased HLA I expression was observed in 41.2% (28/68) patients and was with worse prognosis in comparison to those with preserved HLA I expression (p = 0.001). Multivariate analysis using Cox's proportional hazards model revealed that upregulated HLA‐F expression (p = 0.026) and downregulated HLA I expression (p = 0.013) could be an independent unfavorable prognostic factor. In conclusion, our study provided the evidence that alteration of HLA I and HLA‐F antigen expression was associated with survival in patients with ESCC.
Microorganisms colonizing the plant rhizosphere provide a number of beneficial functions for their host. Although an increasing number of investigations clarified the great functional capabilities of ...rhizosphere microbial communities, the understanding of the precise mechanisms underlying the impact of rhizosphere microbiome assemblies is still limited. Also, not much is known about the various beneficial functions of the rhizosphere microbiome. In this review, we summarize the current knowledge of biotic and abiotic factors that shape the rhizosphere microbiome as well as the rhizosphere microbiome traits that are beneficial to plants growth and disease-resistance. We give particular emphasis on the impact of plant root metabolites on rhizosphere microbiome assemblies and on how the microbiome contributes to plant growth, yield, and disease-resistance. Finally, we introduce a new perspective and a novel method showing how a synthetic microbial community construction provides an effective approach to unravel the plant–microbes and microbes–microbes interplays.
In this paper, the remnant lamellae of Ti-45Al and Ti-48Al alloys were studied firstly. And then the dynamic softening mechanisms of α and γ phases during compression deformation were systematically ...investigated to understand the remnant lamellae formation. The results exhibit that the remnant lamellae in the deformed microstructure of TiAl alloy are related to content of α and γ phases. The main deformation softening mechanism of α phase is dynamic recovery (DRV) and continuous dynamic recrystallization (CDRX), which reveals that a larger strain is needed for DRX of α phase. And the main deformation softening mechanism of γ phase is the discontinuous dynamic recrystallization (DDRX), illustrating that it is easier for γ phase to be fine grains. Comparing with α phase, the degree of DRX in γ phase is higher under the same compression conditions, and the average grain size of dynamic recrystallized γ grain is smaller than the dynamic recrystallized α grain. So, the remnant lamellae in the deformed microstructure of Ti-45Al alloy with high content of α phase are more than those of Ti-48Al alloy. Ultimately, the effect of the dynamic softening mechanism of α and γ phases on the formation of remnant lamellae during hot deformation is determined.
•The remnant lamellae in deformed microstructure of TiAl alloy are related to the phase fraction (α and γ phases).•The deformation softening mechanism of α phase is mainly dynamic recovery and continuous dynamic recrystallization.•The deformation softening mechanism of γ phase is mainly discontinuous dynamic recrystallization.•The formation process of remnant lamellae during hot deformation is determined.
The limitation of 16S rRNA gene sequencing (DNA-based) for microbial community analyses in water is the inability to differentiate live (dormant cells as well as growing or non-growing metabolically ...active cells) and dead cells, which can lead to false positive results in the absence of live microbes. Propidium-monoazide (PMA) has been used to selectively remove DNA from dead cells during downstream sequencing process. In comparison, 16S rRNA sequencing (RNA-based) can target live microbial cells in water as both dormant and metabolically active cells produce rRNA. The objective of this study was to compare the efficiency and sensitivity of DNA-based, PMA-based and RNA-based 16S rRNA Illumina sequencing methodologies for live bacteria detection in water samples experimentally spiked with different combination of bacteria (2 gram-negative and 2 gram-positive/acid fast species either all live, all dead, or combinations of live and dead species) or obtained from different sources (First Nation community drinking water; city of Winnipeg tap water; water from Red River, Manitoba, Canada). The RNA-based method, while was superior for detection of live bacterial cells still identified a number of 16S rRNA targets in samples spiked with dead cells. In environmental water samples, the DNA- and PMA-based approaches perhaps overestimated the richness of microbial community compared to RNA-based method. Our results suggest that the RNA-based sequencing was superior to DNA- and PMA-based methods in detecting live bacterial cells in water.
With the rapid increases in processing speed and memory of low-cost computers, it is not surprising that various advanced computational learning tools such as neural networks have been increasingly ...used for analyzing or modeling highly nonlinear multivariate engineering problems. These algorithms are useful for analyzing many geotechnical problems, particularly those that lack a precise analytical theory or understanding of the phenomena involved. In situations where measured or numerical data are available, neural networks have been shown to offer great promise for mapping the nonlinear interactions (dependency) between the system’s inputs and outputs. Unlike most computational tools, in neural networks no predefined mathematical relationship between the dependent and independent variables is required. However, neural networks have been criticized for its long training process since the optimal configuration is not known a priori. This paper explores the use of a fairly simple nonparametric regression algorithm known as multivariate adaptive regression splines (MARS) which has the ability to approximate the relationship between the inputs and outputs, and express the relationship mathematically. The main advantages of MARS are its capacity to produce simple, easy-to-interpret models, its ability to estimate the contributions of the input variables, and its computational efficiency. First the MARS algorithm is described. A number of examples are then presented that explore the generalization capabilities and accuracy of this approach in comparison to the back-propagation neural network algorithm.
Abstract
Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. ...The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion.
MGMT
promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries
MGMT
genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these
MGMT
rearrangements in glioma cells and demonstrated that the
MGMT
genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.
Grazing can directly or indirectly influence carbon (C) inputs, turnover, and retention in grassland soil. However, relative to the plant response to grazing, belowground biota and process responses ...are more complex and often do not correlate with the aboveground responses. Ungulate grazing involves three mechanisms; defoliation (removal of plant shoot tissue), dung and urine return, and trampling. An evaluation of the relative roles of these mechanisms and their combinations in grazing can explain the causes of changes in grasslands, thereby explaining soil C sequestration in a steppe ecosystem. In this study, we examined changes in plant attributes, soil abiotic characteristics, and the soil microbial community in response to mowing (M), dung and urine addition (DU), simulated trampling (T), and their combinations by conducting a 3-yr experiment in a steppe ecosystem in Inner Mongolia, China. Most of the variation in the grazing effects on grasslands was explained by defoliation through decreased plant production and soil respiration and altered vegetation composition. Dung and urine return was second to defoliation in explaining grazing effects on grassland, and led to increasing plant C inputs to the soil, while simultaneously, potential loss of soil C due to the increase of the abundance of bacteria and soil respiration eventually accelerated soil C cycling. An interaction between defoliation and trampling on microbial growth was observed in our study: trampling increased the abundance of total bacteria, fungi, and arbuscular mycorrhizal fungi (AMF) only in the no-mowing plots. Trampling led to plant allocation to belowground tissues and increased the abundance of fungi and AMF, which are critical for soil C sequestration, and trampling with defoliation further decreased the abundance of soil microbes, which may decelerate soil C cycling and increase its retention time. These results indicate that defoliation and dung and urine return play major roles in explaining grazing effects on grassland systems, including plant, soil, and microbial parameters, but the trampling effects and the interaction between defoliation and trampling are two key factors that contribute to explaining the overall effects of grazing on soil C sequestration in a typical steppe ecosystem in Inner Mongolia.
Zirconium diboride (ZrB2) was densified (>98% relative density) at temperatures as low as 1850°C by pressureless sintering. Sintering was activated by removing oxide impurities (B2O3 and ZrO2) from ...particle surfaces. Boron oxide had a high vapor pressure and was removed during heating under a mild vacuum (∼150 mTorr). Zirconia was more persistent and had to be removed by chemical reaction. Both WC and B4C were evaluated as additives to facilitate the removal of ZrO2. Reactions were proposed based on thermodynamic analysis and then confirmed by X‐ray diffraction analysis of reacted powder mixtures. After the preliminary powder studies, densification was studied using either as‐received ZrB2 (surface area ∼1 m2/g) or attrition‐milled ZrB2 (surface area ∼7.5 m2/g) with WC and/or B4C as a sintering aid. ZrB2 containing only WC could be sintered to ∼95% relative density in 4 h at 2050°C under vacuum. In contrast, the addition of B4C allowed for sintering to >98% relative density in 1 h at 1850°C under vacuum.
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