Prognosis and clinical features analysis of EMT-related signature and tumor Immune microenvironment in glioma.

Background: As the most common primary malignant intracranial tumor, glioblastoma has a poor prognosis with limited treatment options. It has a high propensity for recurrence, invasion, and poor immune prognosis due to the complex tumor microenvironment. Methods: Six groups of samples from four datasets were included in this study. We used consensus ClusterPlus to establish two subgroups by the EMT-related gene. The difference in clinicopathological features, genomic characteristics, immune infiltration, treatment response and prognoses were evaluated by multiple algorithms. By using LASSO regression, multi-factor Cox analysis, stepAIC method, a prognostic risk model was constructed based on the final screened genes. Results: The consensusClusterPlus analyses revealed two subtypes of glioblastoma (C1 and C2), which were characterized by different EMT-related gene expression patterns. C2 subtype with the worse prognosis had the more malignant clinical and pathology manifestations, higher Immune infiltration and tumor-associated molecular pathways scores, and poorer response to treatment. Additionally, our EMT-related genes risk prediction model can provide valuable support for clinical evaluations of glioma. Conclusions: The assessment system and prediction model displayed good performance in independent prognostic risk assessment and individual patient treatment response prediction. This can help with clinical treatment decisions and the development of effective treatments.

Laser Shock Peening of SiCp/2009Al Composites: Microstructural Evolution, Residual Stress and Fatigue Behavior.

SiC particle reinforced aluminum alloy has a wide application in the aerospace industries. In this study, laser shock peening (LSP), an advanced surface modification technique, was employed for SiCp/2009Al composite to reveal its microstructure, microhardness and residual stress evolution. After peening, high densities of dislocations were induced in the aluminum substrate, and stacking faults were introduced into the SiC particle. The microhardness was increased from 155-170 HV to 170-185 HV, with an affected depth of more than 1.5 mm. Compressive residual stresses of more than 200 MPa were introduced. The three-point bending fatigue of the base material, laser peened and milled after laser peened specimens with artificial crack notch fabricated by a femtosecond laser was investigated. The average fatigue lives of laser peened and milled after laser peened specimens were increased by up to 10.60 and 2.66 times, compared with the base material. This combined fundamental and application-based research seeks to comprehensively explore the applicability of LSP on metal matrix composite.

Neural model of disinhibitory interactions in the modified Poggendorff illusion.

Visual illusions can be strengthened or weakened with the addition of extra visual elements. For example, in the Poggendorff illusion, with an additional bar added, the illusory skew in the perceived angle can be enlarged or reduced. In this paper, we show that a nontrivial interaction between lateral inhibitory processes in the early visual system (i.e., disinhibition) can explain such an enhancement or degradation of the illusory effect. The computational model we derived successfully predicted the perceived angle in the Poggendorff illusion task that was modified to include an extra thick bar. The concept of disinhibition employed in the model is general enough that we expect it can be further extended to account for other classes of geometric illusions.

Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil.

The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion-solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100-600 microm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200-500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.

A neural model of the scintillating grid illusion: disinhibition and self-inhibition in early vision.

A stationary display of white discs positioned on intersecting gray bars on a dark background gives rise to a striking scintillating effect--the scintillating grid illusion. The spatial and temporal properties of the illusion are well known, but a neuronal-level explanation of the mechanism has not been fully investigated. Motivated by the neurophysiology of the Limulus retina, we propose disinhibition and self-inhibition as possible neural mechanisms that may give rise to the illusion. In this letter, a spatiotemporal model of the early visual pathway is derived that explicitly accounts for these two mechanisms. The model successfully predicted the change of strength in the illusion under various stimulus conditions, indicating that low-level mechanisms may well explain the scintillating effect in the illusion.

A HPLC method for the analysis of germacrone in rabbit plasma and its application to a pharmacokinetic study of germacrone after administration of zedoary turmeric oil.

A validated new, simple and highly sensitive reversed-phase HPLC method is developed for studying the pharmacokinetics of germacrone after intravenous administration of zedoary turmeric oil (ZTO) oil-in-water microemulsion. The method did not require a complex and expensive equipment. A high extraction recovery (>80%) of germacrone was obtained. Linear calibration curves obtained with the peak-area ratio (y) of germacrone to internal standard (tanshinoneIIA) versus drug concentration (x) were found to be linear between 8.08 and 808 ng/ml. The limit of quantitation was 8.08 ng/ml. The monitored compounds were completely separated from others in ZTO and from endogenous species in plasma by HPLC. Pharmacokinetic investigations were performed on 18 male rabbits after intravenous administration of ZTO microemulsion via the ear vein at germacrone doses of 3.2, 6.4 and 9.6 mg/kg. The plasma concentration-time data fit to a two-compartment intravenous model with a weight of 1/C(2) (C: germacrone concentration in plasma). Germacrone exhibited linear pharmacokinetics after intravenous administration of ZTO microemulsion to rabbits over the germacrone dose range 3.2-9.6 mg/ml.

A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.

To enhance in vivo absorption of zedoary turmeric oil (ZTO) and develop new formulations of a water-insoluble oily drug, novel ZTO microspheres with self-emulsifying ability, called self-emulsifying microspheres here, were prepared in a liquid system by the quasi-emulsion solvent diffusion method. The microspheres containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LG), Talc and Aerosil 200 formed the stable surfactant-free emulsion when exposed to the pH 6.8 phosphate buffer, and were significantly different from the conventional self-emulsifying systems (SES), defined as isotropic mixtures of oil, surfactant and drug. Micromeritic properties, the efficiency of emulsification and the drug-release rate of the resultant microspheres were investigated. The bioavailability of the microspheres to the conventional self-emulsifying formulation for oral administration was evaluated in 12 healthy rabbits. A HPLC method was employed to determine the plasma concentration of Germacrone, an indexical component found in ZTO. The release rates of ZTO and Germacrone from the microspheres were enhanced significantly with increasing amounts of dispersing agents, and the efficiency of self-emulsification greatly depended on the HPMCAS-LG/Aerosil 200 ratio. The emulsion droplets released from the microspheres were much smaller than that of the conventional SES. The microsphere bioavailability (F) to the conventional SES for oral administration was 157.7%. Our method greatly improved the bioavailability of the water-insoluble oily drug from the self-emulsifying microspheres over the conventional SES and it is useful for the oily drug to form solid preparations.

[Absorption of zedoary oil in rat intestine using in situ single pass perfusion model].

AIM: To study the absorption of zedoary oil in intestine of rat. METHODS: In situ single pass perfusion model was used and the concentrations of three components in perfusate were determined by HPLC in combination with diode array detection. RESULTS: The P(app) s of curcumol, curdione and germacrone were all low and had no significant difference (P > 0.05) at zedoary oil concentration of 0.4, 0.8 and 1.2 mg x mL(-1) in transmucosal fluid or in four different regions of intestine of rat [duodenum, jejunum, ileum, colon]. The absorption rates of germacrone and curdione were faster than curcumol's in this study. CONCLUSION: The zedoary oil concentration in transmucosal fluid had no significant effect on the P(app) s within the scope of 0.4-1.2 mg x mL(-1). The absorption of curcumol, curdione and germacrone showed the passive diffusion process, and didn't contain a special absorption window.