Anticonvulsant activities of α-asaronol ((E)-3'-hydroxyasarone), an active constituent derived from α-asarone.

BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice. RESULTS: In our results, α-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its metabolic parent compound (α-asarone). Additionally, α-asaronol displayed a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240 mg/kg and 115 mg/kg in the relevant test, respectively. CONCLUSION: The results of the present study revealed α-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that α-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's syndrome

Estimating Artificial Impervious Surface Percentage in Asia by Fusing Multi-Temporal MODIS and VIIRS Nighttime Light Data

Impervious surfaces have important effects on the natural environment, including promoting hydrological run-off and impeding evapotranspiration, as well as increasing the urban heat island effect. Obtaining accurate and timely information on the spatial distribution and dynamics of urban surfaces is, thus, of paramount importance for socio-economic analysis, urban planning, and environmental modeling and management. Previous studies have indicated that the fusion of multi-source remotely sensed imagery can increase the accuracy of prediction for impervious surface information across large areas. However, the majority of them are limited to the use of specific data sources to construct a few features with which it can be challenging to characterize adequately the variation in impervious surfaces over large areas. Thus, impervious surface maps are often presented with high uncertainty. In response to this problem, we proposed the use of multi-temporal MODIS and Visible Infrared Imaging Radiometer Suite (VIIRS) nighttime light data to construct a more general and robust feature set for large-area artificial impervious surface percentage (AISP) prediction. Three fusion methods were proposed for application to multi-temporal MODIS surface reflectance product (MOD09A1) and Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) Day/Night Band (DNB) data to construct three different types of features: spectral features, index features (band calculations), and fusion features. These features were then used as variables in a random-forest-based AISP prediction model. The model was fitted to China and then applied to predict AISP across Asia. Fifteen typical cities from different regions of Asia were selected to assess the accuracy of the prediction model. The use of multi-temporal MODIS and VIIRS DNB data was found to significantly increase the accuracy of prediction for large-area AISP. The feature set constructed in this research was demonstrated to be suitable for large-area AISP prediction, and the random forest model based on optimization of the selected features achieved the highest accuracy, amongst benchmarks, with testing R2 of 0.690, and testing RMSE of 0.044 in 2018, respectively. In addition, to further test the performance of the proposed method, three existing impervious products (GAIA, HBASE, and NUACI) were used to compare quantitatively. The results showed that the predicted AISP achieved superior performance in comparison with others in some areas (e.g., arid areas and cloudy areas)

Quantifying the effects of external factors on the behavior of vertical wicking in a warp stretch woven fabric

Wicking ability of textiles is a key indicator in determining the physiological comfort provided by a fabric. The property is shaped by various factors internal and external to the fabric. Herein, the effects of some external factors such as the degree of (fabric) extension, the wetting liquid’s temperature and relative humidity on the vertical wicking behavior of a previously prepared warp stretch woven fabric were investigated. The fabric, which could be reversibly extended up to 60%, was prepared using a nylon/spandex air-covered yarn in the warp and cotton yarn in the weft. The results indicated that these external factors had a great influence on the vertical wicking equilibrium height with the degree of fabric extension having a more pronounced effect compared with the other two factors. Furthermore, extension and relative humidity were negatively related to the height of the vertical wicking, whilst an increase in liquid temperature resulted in an increase in vertical wicking height. The underlying mechanisms associated with these effects were examined using a specially constructed test chamber and tensioning device. The experimental data were also verified using the classical Laughlin-Davies model, and the results demonstrated the proposed wicking model could be used to predict the changes in fabric wicking height. These findings provide a more in-depth understanding of the wicking behavior of stretchable textiles in a comprehensive and objective manner

www.mdpi.com/journal/ijms Detection of Promyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARα) Fusion Gene with Functionalized Graphene Oxide

Abstract: An attempt was made to use functionalized graphene oxide (GO) to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene), a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by a polyethylene glycol grafting. It is found that the functionalized GO can selectively adsorb the fluorescein isothiocyanate (FITC)-labeled single-stranded DNA probe and quench its fluorescence. The probe can be displaced by the PML/RARα fusion gene to restore the fluorescence, which can be detected by laser confocal microscopy and flow cytometry. These can be used to detect the presence of the PML/RARα fusion gene. This detection method is verified to be fast, simple and reliable

MDM4 overexpressed in acute myeloid leukemia patients with complex karyotype and wild-type TP53.

Acute myeloid leukemia patients with complex karyotype (CK-AML) account for approximately 10-15% of adult AML cases, and are often associated with a poor prognosis. Except for about 70% of CK-AML patients with biallelic inactivation of TP53, the leukemogenic mechanism in the nearly 30% of CK-AML patients with wild-type TP53 has remained elusive. In this study, 15 cases with complex karyotype and wild-type TP53 were screened out of 140 de novo AML patients and the expression levels of MDM4, a main negative regulator of p53-signaling pathway, were detected. We ruled out mutations in genes associated with a poor prognosis of CK-AML, including RUNX1 or FLT3-ITD. The mRNA expression levels of the full-length of MDM4 (MDM4FL) and short isoform MDM4 (MDM4S) were elevated in CK-AML relative to normal karyotype AML (NK-AML) patients. We also explored the impact of MDM4 overexpression on the cell cycle, cell proliferation and the spindle checkpoint of HepG2 cells, which is a human cancer cell line with normal MDM4 and TP53 expression. The mitotic index and the expression of p21, BubR1 and Securin were all reduced following Nocodazole treatment. Moreover, karyotype analysis showed that MDM4 overexpression might lead to aneuploidy or polyploidy. These results suggest that MDM4 overexpression is related to CK-AML with wild-type TP53 and might play a pathogenic role by inhibiting p53-signal pathway

Impact behavior of nylon kernmantle ropes for high-altitude fall protection

Aiming at the problem that the existing rope falling device can only detect the impact force and cannot synchronously detect the impact displacement, this paper introduces a large-range high-precision displacement sensor and constructs a rope impact force-displacement detection device. Taking the nylon kernmantle rope for high-altitude fall protection commonly used in aerial work and rock climbing as the research object, the impact response behavior of the rope when drop mass is dropped once and repeatedly is systematically studied, and the impact force and impact displacement are discussed. Further, the evolution of the elastic modulus of the rope is discussed and this could provide theoretical support for the design of the impact-resistant rope structure and the rope impact protection

Prometaphase and mitotic of MDM4FL and MDM4S-expressing cells.

<p>A: Chromosome spread of a prometaphase vector control cell. B: Premature sister chromatid separation in an MDM4S prometaphase cell (indicated by arrows). C: Polyploidy in a MDM4S cell. D: Endoreduplication of a MDM4FL cell.</p

The relative expression levels of <i>MDM4FL</i> and <i>MDM4S</i> mRNA.

<p>The relative expression levels of <i>MDM4FL</i> and <i>MDM4S</i> mRNA.</p