We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes ...to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.
Activation of Akt signaling pathway has been suggested involving in chemoresistance, metastasis and tumorigenesis of gastric cancer. However, the mechanism of Akt regulation in gastric cancer is not ...fully understood. RUNX3, which was first identified as a transcription factor, suppresses gastric tumorigenesis through regulating expression of target genes. Here, we found that restoration of RUNX3 significantly downregulates the protein and mRNA expression of Akt1 in gastric cancer cell lines, AGS and SNU-1. Knockdown of RUNX3 upregulates protein and mRNA expression of Akt1 in normal gastric epithelial cell line, GES-1. The negative correlation of RUNX3 and Akt expression and downstream β-catenin/cyclin D1 effectors was further confirmed in AGS and GES-1 cell lines, as well as clinical specimens of gastric cancer. We identified two RUNX3-binding sites in Akt1 promoter and the binding of RUNX3 on Akt1 promoter significantly inhibits Akt1 expression. The RUNX3-mediated inhibition of Akt1 caused β-catenin protein degradation and then cyclin D1 downregulation. Restoration of cyclin D1 reverses cell growth inhibition and G1 phase arrest induced by RUNX3 in gastric cancer cells. Our results show that loss of RUNX3 expression can enhance the Akt1-mediated signaling pathway and promote the tumorigenesis process in human gastric cancer.
A variety of carbon materials varying from 0D to 2D,
i.e.
0D nanoparticles, 1D carbon nanotubes (CNTs) and 2D reduced graphene oxide (rGO) are selected to
in situ
combine with Ni-Mn layered double ...hydroxide (LDH) to prepare electrode materials for supercapacitors. Through a simple solution method, hierarchical Ni-Mn LDH/carbon composites can be easily fabricated. A comparative study is carried out on the sandwich-like LDH/rGO, flower-like LDH/carbon black, turbostratic-structured LDH/CNTs and ternary LDH/CNTs/rGO for their structure, morphology, porous properties and electrochemical performances. The results show that the ternary Ni-Mn LDH/CNTs/rGO composite yields the highest specific capacitance of 1268 F g
−1
in 2 M KOH electrolyte and a long lifespan, exhibiting great potential for supercapacitor applications. Meanwhile, investigation on the influence of the cation species of MOH (M = Li
+
, Na
+
or K
+
) and the alkali concentration of the KOH electrolyte illustrates that increasing the concentration of the KOH electrolyte can benefit the capacitive performance of the electrode and that NaOH shows great advantages as an electrolyte for the Ni-Mn LDH/CNTs/rGO electrode due to its high capacitance and small resistance.
A variety of carbon materials varying from 0D to 2D,
i.e.
0D nanoparticles, 1D carbon nanotubes (CNTs) and 2D reduced graphene oxide (rGO) are selected to
in situ
combine with Ni-Mn layered double hydroxide (LDH) to prepare electrode materials for supercapacitors.
It is generally believed that the strength of the polymer–nanoparticle interaction controls the modification of near-interface segmental mobility in polymer nanocomposites (PNCs). However, little is ...known about the effect of covalent bonding on the segmental dynamics and glass transition of matrix-free polymer-grafted nanoparticles (PGNs), especially when compared to PNCs. In this article, we directly compare the static and dynamic properties of poly(2-vinylpyridine)/silica-based nanocomposites with polymer chains either physically adsorbed (PNCs) or covalently bonded (PGNs) to identical silica nanoparticles (R NP = 12.5 nm) for three different molecular weight (MW) systems. Interestingly, when the MW of the matrix is as low as 6 kg/mol (R NP/R g = 5.4) or as high as 140 kg/mol (R NP/R g= 1.13), both small-angle X-ray scattering and broadband dielectric spectroscopy show similar static and dynamic properties for PNCs and PGNs. However, for the intermediate MW of 18 kg/mol (R NP/R g = 3.16), the difference between physical adsorption and covalent bonding can be clearly identified in the static and dynamic properties of the interfacial layer. We ascribe the differences in the interfacial properties of PNCs and PGNs to changes in chain stretching, as quantified by self-consistent field theory calculations. These results demonstrate that the dynamic suppression at the interface is affected by the chain stretching; that is, it depends on the anisotropy of the segmental conformations, more so than the strength of the interaction, which suggests that the interfacial dynamics can be effectively tuned by the degree of stretchinga parameter accessible from the MW or grafting density.
The CDEX-1 experiment conducted a search of low-mass (< 10GeV/c super(2)) weakly interacting massive particles dark matter at the China Jinping Underground Laboratory using a p-type point-contact ...germanium detector with a fiducial mass of 915 g at a physics analysis threshold of 475 eVee. We report the hardware setup, detector characterization, data acquisition, and analysis procedures of this experiment. No excess of unidentified events is observed after the subtraction of the known background. Using 335.6 kg-days of data, exclusion constraints on the weakly interacting massive particle-nucleon spin-independent and spin-dependent couplings are derived.
•NiAl-LDH nanosheets are in situ grown on carbon nanotubes pre-coated by Al2O3.•NiAl-LDH/CNTs exhibits a specific capacitance of 1500Fg−1 at 1Ag−1 with a good cycling stability.•The ...NiAl-LDHs/CNTs//AC asymmetric supercapacitor shows a high electrochemical performance.
Binary composite consisting of nickel aluminum-layered double hydroxides (LDHs) nanosheets and carbon nanotubes (CNTs) is fabricated by a solution method. The CNTs are pre-coated by γ-Al2O3. The structural characterization and morphological observation demonstrate that Ni–Al hydroxide crystals with hydrotalcite structure are in situ deposited on the surface of CNTs. The as-prepared binary composite combines the pseudo-capacitive of Ni–Al LDHs with double-layer capacitive of carbon nanotubes. CNTs can improve the electrical conductivity and decrease the electrochemical polarization of the composite. Electrochemical measurements of the Ni–Al LDHs/CNTs material show a much better electrochemical performance than pure Ni–Al LDHs. It can yield a high specific capacitance of 1500Fg−1 at 1Ag−1, with 70.3% retention at 10Ag−1 in 2M KOH and a good cycling stability. An asymmetric capacitor is assembled with Ni–Al LDHs/CNTs as a positive electrode and activated carbon as the negative electrode. It can cycle reversibly in a potential window of 1.8V, and exhibits a high specific capacitance of 115Fg−1 and a high energy density of 52Whkg−1 at 1Ag−1 as well as an excellent cycling stability.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung ...cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.
Abstract
Context
Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma ...levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin.
Objective
The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action.
Methods
Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults.
Results
Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues.
Conclusions
Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway.
Circulating FGF21 levels respond acutely to insulin but not glucose. A high-fat diet impairs this response. The postprandial rise in the ratio of bioactive to total FGF21 is attenuated in T2D.
Although nitrous oxide (N2O) emissions from composting contribute to the accelerated greenhouse effect, it is difficult to implement practical methods to mitigate these emissions. In this study, the ...effects of biochar amendment during pig manure composting were investigated to evaluate the inter-relationships between N2O emission and the abundance of denitrifying bacteria. Analytical results from two pilot composting treatments with (PWSB, pig manure + wood chips + sawdust + biochar) or without (PWS, pig manure + wood chips + sawdust) biochar (3% w/w) demonstrated that biochar amendment not only lowered NO2 –-N concentrations but also lowered the total N2O emissions from pig manure composting, especially during the later stages. Quantification of functional genes involved in denitrification and Spearman rank correlations matrix revealed that the N2O emission rates correlated with the abundance of nosZ, nirK, and nirS genes. Biochar-amended pig manure had a higher pH and a lower moisture content. Biochar amendment altered the abundance of denitrifying bacteria significantly; less N2O-producing and more N2O-consuming bacteria were present in the PWSB, and this significantly lowered N2O emissions in the maturation phase. Together, the results demonstrate that biochar amendment could be a novel greenhouse gas mitigation strategy during pig manure composting.
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