•An Euler-Euler large eddy simulation (EELES) approach is developed.•First to study scale-adaptive of EELES model for predicting dispersed bubbly flow.•−25/3 law of power spectrum densities is first ...found in high frequency region.•A grid comparable to bubble size can be effective for EELES.
Euler-Euler large eddy simulation (EELES) of transient dispersed turbulent bubbly flows in a laboratory scale square cross-sectioned bubble column has been presented. The main objective is to investigate the scale-adaptive of EELES model for predicting the dispersed bubbly flows. The sub-grid modeling is based on the Smagorinsky kernel with dynamic CS constant. The bubble induced turbulence and various interfacial forces including drag, lift, and virtual mass forces are incorporated in the model. Good quantitative agreement with previous experimental measurements by a two-camera particle image velocimetry (PIV) is obtained both for the fluctuating velocities and the mean velocities. More instantaneous details of two-phase flow characteristic in the bubble column have been captured by LES, including the multi-scale vortex structures, fluctuation characteristics of liquid motion and rotating buoyancy motion of bubbles. Predicted turbulence effective viscosity by unsteady Reynolds-Averaged Navier–Stokes (RANS) approach is nearly thirty times larger than LES, the turbulent dissipation is so strong that it cannot be used to predict the multi-scale fluctuation characteristics inside the bubble column. The classical −5/3 law of power spectrum densities (PSD) of liquid vertical velocity is hold properly in the low frequency region. For high frequency region, the classical −5/3 law does not hold properly, the decay is too fast, where the slope is around −25/3. The current EELES can be effectively used for studying the transient two-phase flow when a grid comparable to the bubble diameter is used, not just for the condition that the grid size is larger than the bubble diameter.
radix (AR) is one of the most widely used traditional Chinese herbal medicines. Modern pharmacological studies and clinical practices indicate that AR possesses various biological functions, ...including potent immunomodulation, antioxidant, anti-inflammation and antitumor activities. To date, more than 200 chemical constituents have been isolated and identified from AR. Among them, isoflavonoids, saponins and polysaccharides are the three main types of beneficial compounds responsible for its pharmacological activities and therapeutic efficacy. After ingestion of AR, the metabolism and biotransformation of the bioactive compounds were extensive in vivo. The isoflavonoids and saponins and their metabolites are the major type of constituents absorbed in plasma. The bioavailability barrier (BB), which is mainly composed of efflux transporters and conjugating enzymes, is expected to have a significant impact on the bioavailability of AR. This review summarizes studies on the phytochemistry, pharmacology and pharmacokinetics on AR. Additionally, the use of AR as a personalized medicine based on the BB is also discussed, which may provide beneficial information to achieve a better and more accurate therapeutic response of AR in clinical practice.
A coupled three-dimensional finite-volume computational model has been developed to simulate the transient fluid flow, heat transfer and solidification processes in a vertical-bending continuous ...casting caster. The turbulence of molten steel inside the liquid pool is calculated using the large eddy simulation (LES). The enthalpy–porosity approach is used to simulate the heat transfer and solidification of steel in the caster. Based on the fractal theory and the conservation of mass, a kind of inclusion cluster model was developed. A new criterion was developed using the user-defined functions to model the motion and entrapment of inclusion cluster in the caster based on the Lagrangian approach. Firstly, the predicted growth of solidified shell was compared with the plant measurements, and the asymmetrical flow pattern was compared with the dye-injection observations of water model experiments. Secondly, the validated model was used to predict the instantaneous motion and entrapment distribution, statistical data, escape and entrapment positions of different inclusion clusters in the caster. Many known phenomena and other new predictions were reproduced in this part, and the center inclusion band defects in the steel plates found by the UT method can be interpreted using the current model. Finally, two methods were proposed to optimize the inclusion cluster motion and entrapment in the caster.
Display omitted
•Transient flow, solidification and particle transport were studied using LES.•An inclusion cluster model was developed using fractal theory and mass conservation.•A criterion was developed to model the motion and entrapment of inclusion cluster.•Predicted center inclusion band agrees well with plant ultrasonic flaw detection maps.
KRAS (kirsten rat sarcoma viral oncogene) is a member of the RAS family. KRAS mutations are one of most dominant mutations in colorectal cancer (CRC). The impact of KRAS mutations on the prognosis ...and survival of CRC patients drives many research studies to explore potential therapeutics or target therapy for the KRAS mutant CRC. This review summarizes the current understanding of the pathological consequences of the KRAS mutations in the development of CRC; and the impact of the mutations on the response and the sensitivity to the current front-line chemotherapy. The current therapeutic strategies for treating KRAS mutant CRC, the difficulties and challenges will also be discussed.
An Euler-Euler large eddy simulation (LES) of transient gas-liquid turbulence flow in a bubble column was conducted to investigate the adaptiveness of various sub-grid scale (SGS) models. The ...performance of three SGS models, respectively the standard Smagorinsky model, the wall-adapting local eddy (WALE) model and the Dynamic model, on the predictions of bubbly flow was studied. Comparison between SGS models for time-averaged and transient velocities, gas void fraction, power spectrum density (PSD), SGS turbulent dissipation, SGS turbulent kinetic energy, and Reynolds stress is conducted. The transient multi-scale irregular vortex structures, fluctuation characteristics of liquid motion and spiral floating motion of bubbles can be well captured by LES. The Dynamic model and WALE model with CW = 0.325 give reasonably better agreement with the time-averaged experimental data. The transient fluctuation behavior of gas-liquid turbulent flow can be correctly captured by the current Euler-Euler LES model, whatever the SGS model. The classical −5/3 law of PSD of vertical liquid velocity is hold properly in the low frequency region. The slope of PSD is around −25/3 at the high frequency region. The Smagorinsky model and WALE model are sensitive to the model constant, at least for the energy transfer of high frequency. The molecular dissipation is negligible compared to the SGS turbulent dissipation. The Dynamic model gives higher predictions for fluctuation amplitude and time-averaged values of both SGS turbulent dissipation rate profile and SGS turbulent kinetic energy profile than other SGS models. A certain calculation time is needed to reach the dynamic stable state in LES, and the specific time is related to the scale of the calculation model.
Display omitted
•Adaptiveness of various SGS models in LES for two-phase turbulent flow is studied.•First to study SGS turbulent dissipation, SGS turbulent kinetic energy, and Reynolds stress tensor for bubbly flow.•A certain calculation time is needed to reach dynamic stability process in LES.
•Phenol:dichloromethane (2:1, v:v) surpassed other conventional extraction methods.•Ethanol precipitation (−80 °C, 5 min) was the optimal drying conditions.•The developed workflow provided a ...quantitative range of 0.25–1000 nM.•MS parameters were optimized through the central composite design.
Liquid chromatography tandem mass spectrometry has been a widely used technique for quantifying oligonucleotides in biological samples. However, lack of simple and efficient sample cleanup approach remains a challenge. Our study aimed to evaluate the major factors during the sample pretreatment process for developing optimal sample preparation workflow for oligonucleotides. In this study, we have employed a model formed with rat plasma containing a 16 mer oligonucleotide standard in order to comprehensively optimize the sample preparation procedures. These included liquid-liquid extraction (LLE), solid-phase extraction (SPE), protein precipitation (PPT) and LLE combined with SPE. LLE with phenol: dichloromethane (2:1, v:v) was found to be the most efficient sample cleanup procedure with low cost and less toxicity. Followed by the extraction, ethanol precipitation (-80 °C, 5 min) was determined to be the optimal drying conditions. Also, mass spectrometric parameters were tuned to optimal conditions. It was found that the central composite design suite was proved to be highly practical for optimizing MS parameters. Finally, the thoroughly optimized sample preparation workflow was fully validated. The developed assay provided a quantitative range of 0.25–1000 nM, with accuracy and precision were < 7.45% and < 12.20%, respectively. Matrix effect and carryover were also evaluated and no significant effect was observed.
Although silybin serves as a well-known hepatoprotective agent with prominent anti-inflammatory, anti-oxidant and anti-fibrotic activities, its low bioavailability limits its application in the ...treatment of chronic liver diseases. However, novel formulation products with increased solubility were not sufficient to achieve pharmacologically meaningful concentrations of silybin in the clinical studies even used at high dosage.
We hypothesized that inhibiting efflux transporter(s) and/or glucuronidation by piperine might enhance the bioavailability and efficacy of silybin.
Pharmacokinetics of silybin given alone or in-combination with piperine was determined by a validated LC-MS method. A CCl4 induced rat model of liver injury was prepared and verified for comparing the effects of silybin and combination treatment. To investigate the underlying mechanism, the inhibition effects of piperine on transportation of silybin were performed in Caco-2 and transfected MDCKII cell lines as well as sandwich–cultured rat hepatocytes (SCH). Human liver microsomes incubation was used for exploring the modulation effects of piperine on the phase-2 metabolism of silybin.
In the present study, we demonstrated for the first time that piperine as a bioenhancer increased the bioavailability of silybin (146%– 181%), contributing to a boosted therapeutic effect in CCl4-induced acute liver-injury rat model. The underlying mechanisms involved that piperine enhanced the absorption of silybin by inhibiting the efflux transporters including MRP2 and BCRP but not MDR1 in Caco-2 and transfected MDCKII cell lines. Moreover, piperine could inhibit the biliary excretion of silybin and conjugated metabolites in sandwich–cultured rat hepatocytes. Notably, we found that piperine did not affect the phase-2 metabolism of silybin.
Efflux transporters play an important role in the pharmacokinetic behavior of flavolignans, and modulating these transporters by bioenhancer such as piperine could enhance the in vivo absorption of silybin, leading to more effective treatments.
Display omitted
Microsized carbon spheres with the refined interior structure are highly desired, while it is challenging to achieve controllability limited to synthetic strategy. Herein, a novel architectural ...approach is proposed for developing interior multi-chamber carbon microspheres (MCMs) with the help of a liquid template. We focus on building “rooms” in fruit wine yeast and yielding “fungi house,” which apply to other kinds of yeast. The size and number of the “room” can be controlled. To the best of our knowledge, such biomass-derived carbon spheres with defined interior structures have never been reported yet. When used as electrodes for supercapacitors and capacitive deionization, the exemplified MCM exhibits specific capacitance 339.31 F g
−1
at 0.5 A g
−1
and a salt adsorption capacity of 21.61 mg g
−1
at 1.2 V, as well as excellent rate performance and cycle stability. Given the structure-dependent property, the architectural approach broadens the avenue to develop advanced materials.
Graphical abstract
PDF
