When face-centered cubic (FCC) metals and alloys with low stacking fault energy (SFE) are irradiated by high-energy particles or deformed at high speed, stacking fault tetrahedra (SFTs), which are a ...type of vacancy cluster defect, are often formed. Therefore, SFTs were expected to form in the CoCrFeMnNi equiatomic high-entropy alloy (HEA). However, no SFT was observed in the CoCrFeMnNi HEA with high-speed plastic deformation even after annealing at 873 K. To elucidate this mechanism, the binding energy of vacancy clusters in the CoCrFeMnNi HEA was calculated based on first principles. The binding energy of the di-vacancy cluster was positive (average of 0.25 eV), while that of the tri-vacancy cluster was negative (average of - 0.44 eV), suggesting that the possibility of formation of a tri-vacancy cluster was low. The inability to form a cluster containing three vacancies is attributed to the excellent irradiation resistance of the CoCrFeMnNi HEA. However, if an extra vacancy is added to a tri-vacancy cluster (with negative binding energy), the binding energy of the subsequent tetra-vacancy cluster may become positive. This suggests that it is possible to form vacancy clusters in the CoCrFeMnNi HEA when high-energy ion or neutron irradiation causes cascade damage.
Nonmonotonic variation with collision energy (sqrts_{NN}) of the moments of the net-baryon number distribution in heavy-ion collisions, related to the correlation length and the susceptibilities of ...the system, is suggested as a signature for the quantum chromodynamics critical point. We report the first evidence of a nonmonotonic variation in the kurtosis times variance of the net-proton number (proxy for net-baryon number) distribution as a function of sqrts_{NN} with 3.1 σ significance for head-on (central) gold-on-gold (Au+Au) collisions measured solenoidal tracker at Relativistic Heavy Ion Collider. Data in noncentral Au+Au collisions and models of heavy-ion collisions without a critical point show a monotonic variation as a function of sqrts_{NN}.
Semiconductor compounds are widely used for photocatalytic hydrogen production applications, where photogenerated electron-hole pairs are exploited to induce catalysis. Recently, powders of a ...metallic oxide (Sr
NbO
, 0.03<x<0.20) were reported to show competitive photocatalytic efficiencies under visible light, which was attributed to interband absorption. This discovery expanded the range of materials available for optimized performance as photocatalysts. Here we study epitaxial thin films of SrNbO
and find that their bandgaps are ∼4.1 eV. Surprisingly, the carrier density of the conducting phase exceeds 10
cm
and the carrier mobility is only 2.47 cm
V
s
. Contrary to earlier reports, the visible light absorption at 1.8 eV (∼688 nm) is due to the plasmon resonance, arising from the large carrier density. We propose that the hot electron and hole carriers excited via Landau damping (during the plasmon decay) are responsible for the photocatalytic property of this material under visible light irradiation.
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor ...prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity. Inhibition of glycolysis preferentially causes severe ATP depletion and massive cell death in FLT3/ITD leukemia cells. Glycolytic inhibitors significantly enhances the cytotoxicity induced by FLT3 tyrosine kinase inhibitor sorafenib. Importantly, such combination provides substantial therapeutic benefit in a murine model bearing FLT3/ITD leukemia. Our study suggests that FLT3/ITD mutation promotes Warburg effect, and such metabolic alteration can be exploited to develop effective therapeutic strategy for treatment of AML with FLT3/ITD mutation via metabolic intervention.
Summary
What is known and objectives
Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study ...was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling.
Methods
A total of 47 sets of rich‐time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients. The pathophysiological data of these patients were recorded. CYP3A5*3 and ABCB1 genotypes were determined for each patient. The PPK model for TAC was established by nonlinear mixed‐effects modelling (nonmem). The impact of pathophysiology and genotype on PPK parameters was evaluated. Bayesian estimators for the area under concentration‐time curve (AUC) of TAC were validated.
Results
A two‐compartment model with lag time was found to be the most suitable model for the pooled full PK and TDM data for Chinese liver transplant patients. The CL/F, V2/F, Q/F, V3/F, Ka and lag time were 17.4±0.81 L/h, 165±44.1 L, 54.9±25.8L/h, 594±87.5 L, 0.51±0.095 L/h and 1.57±0.34 h. Post‐operative day (POD), creatinine clearance (CLcr) and ABCB1 C3435T genotypes were found to have significant influences on CL/F (P<.01). ABCB1 C3435T genotypes showed a significant correlation with V2/F (P<.01). C0–C2 and C0–C2–C4 were shown to be suitable for the estimation of AUC in Chinese liver transplant patients.
What is new and conclusion
A PPK model for TAC was established successfully in Chinese liver transplant patients. POD, CLcr and ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The AUC of TAC in Chinese liver transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.
Visual predictive check based on the final model in patients with ABCB1 CC (A), CT (B) and TT (C) genotypes. A population pharmacokinetic (PPK) model for tacrolimus (TAC) was established successfully based on 47 sets of rich time PK and 1234 conventional therapeutic drug monitoring (TDM) data Chinese liver transplant patients. ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The area under concentration‐time curve (AUC) of TAC in Chinese liver‐transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from ...oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC via ROS-mediated damage in vitro. In vivo experiments further shows that silencing G6PD with lentivirus or non-viral gene delivery vector enhances oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus, this study indicates that G6PD is a potential prognostic biomarker and a promising target for CRC therapy.
The controlled growth of high-quality graphene on a large scale is of central importance for applications in electronics and optoelectronics. To minimize the adverse impacts of grain boundaries in ...large-area polycrystalline graphene, the synthesis of large single crystals of monolayer graphene is one of the key challenges for graphene production. Here, we develop a facile surface-engineering method to grow large single-crystalline monolayer graphene by the passivation of the active sites and the control of graphene nucleation on copper surface using the melamine pretreatment. Centimeter-sized hexagonal single-crystal graphene domains were successfully grown, which exhibit ultrahigh carrier mobilities exceeding 25 000 cm2 V–1 s–1 and quantum Hall effects on SiO2 substrates. The underlying mechanism of melamine pretreatments were systematically investigated through elemental analyses of copper surface in the growth process of large single-crystals. This present work provides a surface design of a catalytic substrate for the controlled growth of large-area graphene single crystals.
Towards super-clean graphene Lin, Li; Zhang, Jincan; Su, Haisheng ...
Nature communications,
04/2019, Volume:
10, Issue:
1
Journal Article
Peer reviewed
Open access
Impurities produced during the synthesis process of a material pose detrimental impacts upon the intrinsic properties and device performances of the as-obtained product. This effect is especially ...pronounced in graphene, where surface contamination has long been a critical, unresolved issue, given graphene's two-dimensionality. Here we report the origins of surface contamination of graphene, which is primarily rooted in chemical vapour deposition production at elevated temperatures, rather than during transfer and storage. In turn, we demonstrate a design of Cu substrate architecture towards the scalable production of super-clean graphene (>99% clean regions). The readily available, super-clean graphene sheets contribute to an enhancement in the optical transparency and thermal conductivity, an exceptionally lower-level of electrical contact resistance and intrinsically hydrophilic nature. This work not only opens up frontiers for graphene growth but also provides exciting opportunities for the utilization of as-obtained super-clean graphene films for advanced applications.
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