The pattern of plasma BCAA concentration and liver Bckdha gene expression in GK rats during T2D progression

Background: This study was conducted to measure the concentration of branched chain amino acid(BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki(GK) rats during type 2 diabetes(T2D)progression.Methods: We measured the concentration of BCAA in GK rats, induced T2D cynomolgus monkeys and T2D humans by liquid chromatography tandem mass spectrometry, and used real-time quantitative PCR to analyze the gene expression of Bckdha and Bckdk, which encode the rate-limiting enzymes in catabolism of,respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase.Results: In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks(P < 0.05 and P < 0.01, respectively), while the expression of Bckdha in GK rat liver was increased at 4 and 8 weeks(1.62-fold and1.93-fold, respectively). The BCAA concentrations were significantly reduced in diet-induced T2D cynomolgus monkeys(P < 0.01), but significantly increased in T2D humans(P < 0.001).Conclusions: Our results showed that BCAA concentrations changed at different times and by different amounts in different species and during different periods of T2D progress, and the significant changes of BCAA concentration in the three species indicated that BCAA might participate in the progress of T2D. The results suggested that the increased expression of Bckdha in GK rat liver might partially explain the reduced plasma BCAA concentration at 4 and 8 weeks. Further studies are required to investigate the exact mechanism of BCAA changes in non-obese T2D.

Linear gyrokinetic simulations of reversed shear Alfvén eigenmodes and ion temperature gradient modes in DIII-D tokamak

Global linear gyrokinetic simulations using realistic DIII-D tokamak geometry and plasma profiles find co-existence of unstable reversed shear Alfvén eigenmodes(RSAE)with low toroidal mode number n and electromagnetic ion temperature gradient(ITG)instabilities with higher toroidal mode number n.For intermediate n?=?[10,12],RSAE and ITG co-exist and overlap weakly in the radial domain with similar growth rates but different real frequencies.Both RSAE and ITG growth rates decrease less than 5%when compressible magnetic perturbations are neglected in the simulations.The ITG growth rates increase less than 7%when fast ions are not included in the simulations.Finally,the effects of trapped electrons on the RSAE are negligible.

Verification of Energetic-Particle-Induced Geodesic Acoustic Mode in Gyrokinetic Particle Simulations

The energetic-particle-induced geodesic acoustic mode(EGAM)is studied using gyrokinetic particle simulations in tokamak plasmas.In our simulations,exponentially growing EGAMs are excited by energetic particles with a slowing-down distribution.The frequencies of EGAMs are always below the frequencies of GAMs,which is due to the non-perturbative contribution of energetic particles(EPs).The mode structures of EGAMs are similar to the corresponding mode structures of GAMs.Our gyrokinetic simulations show that a high EP density can enhance the EGAM growth rate,due to high EP free energy,and that EPs’temperature and the pitch angle of the distribution modify the EGAM frequency/growth rate by means of the resonance condition.Kinetic effects of the thermal electrons barely change the EGAM frequency,and have a weak damping effect on the EGAM.Benchmarks between the gyrokinetic particle simulations and a local EGAM dispersion relation exhibit good agreement in terms of EGAM frequency and growth rate.

Temperature Gradient, Toroidal and Ion FLR Effects on Drift-Tearing Modes

The influences of the temperature gradient and toroidal effects on drift-tearing modes have been studied using the Gyrokinetic Toroidal code.After the thermal force term is introduced into the parallel electron force balance equation,the equilibrium temperature gradient can cause a significant increase in the growth rate of the drift-tearing mode and a broadening of the mode structure.The simulation results show that the toroidal effects increase the growth rate of the drift-tearing mode,and the contours of the perturbation field“squeeze”toward the stronger field side in the poloidal section.Finally,the hybrid model for fluid electrons and kinetic ions has been studied briefly,and the dispersion relation of the drift-tearing mode under the influence of ion finite Larmor radius effects is obtained.Compared with the dispersion relation under the fluid model,a stabilizing effect of the ion finite Larmor radius is observed.

PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program.Phosphoenolpyruvate carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis.The onco-genesis and progression of tumors are closely related to cancer stem cells.It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma.Herein,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited tumorigenesis.Moreover,PCK1 increased the sensitivity of hepatocellular carci-noma cells to sorafenib.Furthermore,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation.Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib.Thus,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

Impact of hospital size on healthcare information system effectiveness: evidence from healthcare data analytics

With the rapid development of information technology, the increasing use ofmobile digital devices and efforts from the whole society, the healthcareinformation systems (HISs) are moving towards a new era. However, there isstill a lack of clear understanding of the benefits of HIS at the hospital leveland the influential factors for HIS effectiveness. In this study, we propose aresearch framework to explain how HIS implementation improves hospitalperformance. Our results reinforce the positive effect of HIS on hospitalperformance. In particular, we found that HIS implementation increases boththe cost and revenue of the hospitals, but the increasing effect in revenue ismuch bigger than the increasing effect in cost. We also found that althoughboth small and big hospitals benefit from the implementation of HIS, the effectof size is different. Size has a positive effect on hospital performance for smallhospitals but has a negative effect on big hospitals. This indicates that thecompetitive advantage of economies of scale disappears for big hospitalsbecause the level of information transparency becomes lower and transactioncosts become higher as size increases.

Analysis of the different locomotive wireless multi-traction synchronous control systems for heavy-haul combined trains and their performance

This paper looks at the heavy-haul combined train composed of different types of locomotives and its distributed power control system with a combination of 800 MHz and TD-LTE wireless communication.It analyses some key characteristic parameters that affect the synchronism and communication of the differential wireless multi-traction synchronous control systems for heavy-haul combined trains.At the same time,in order to reduce the latency of instruction and information transfer between different types of locomotives,improve the time-limit certainty of wireless transmission and optimize the control quality of multi-traction control systems for heavy-haul combined trains,a synchronism optimization strategy based on the Markov decision process on the basis of Petri networkconstruction is proposed.Relevant experiments and tests are carried out to verify the effectiveness of the synchronism optimization of the control system,which provides a guarantee for improving the differential wireless multi-traction synchronous control system for combined trains and optimizing train control.