A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and ...tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A topological meron features a non-coplanar structure, whose order parameters in the core region are perpendicular to those near the perimeter. A meron is half of a skyrmion, and both have potential ...applications for information carrying and storage. Although merons and skyrmions in ferromagnetic materials can be readily obtained via inter-spin interactions, their behaviour and even existence in ferroelectric materials are still elusive. Here we observe using electron microscopy not only the atomic morphology of merons with a topological charge of 1/2, but also a periodic meron lattice in ultrathin PbTiO
films under tensile epitaxial strain on a SmScO
substrate. Phase-field simulations rationalize the formation of merons for which an epitaxial strain, as a single alterable parameter, plays a critical role in the coupling of lattice and charge. This study suggests that by engineering strain at the nanoscale it should be possible to fabricate topological polar textures, which in turn could facilitate the development of nanoscale ferroelectric devices.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
H5N1 avian influenza virus (AIV) has emerged as a pathogenic entity for a variety of species, including humans, in recent years. Here we report an outbreak among migratory birds on Lake Qinghaihu, ...China, in May and June 2005, in which more than a thousand birds were affected. Pancreatic necrosis and abnormal neurological symptoms were the major clinical features. Sequencing of the complete genomes of four H5N1 AIV strains revealed them to be reassortants related to a peregrine falcon isolate from Hong Kong and to have known highly pathogenic characteristics. Experimental animal infections reproduced typical highly pathogenic AIV infection symptoms and pathology.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
► A novel single-ion conducting polymer electrolyte, lithium polyvinyl alcohol oxalate borate (LiPVAOB), was prepared. ► It is from the reaction of poly(vinyl alcohol) with boric acid, lithium ...hydroxide and oxalic acid. ► The prepared materials act as single-ion polymer electrolytes. ► Their electrochemical window can be stable up to 7V (vs. Li+/Li). ► They are of great attraction for high voltage lithium ion batteries with high energy density.
In this study, a novel single-ion conducting polymer electrolyte, lithium polyvinyl alcohol oxalate borate (LiPVAOB), from the reaction of poly(vinyl alcohol) (PVA) with different molar ratio of boric acid, oxalic acid and lithium carbonate was prepared. The prepared materials were characterized by Fourier transformation infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetry (TG), differential thermal analysis (DTA), electrochemical impedance spectroscopy (EIS) and linear sweep voltammetry. Ionic conductivity of these polymer electrolytes from adding an assistant (about 20wt.% propylene carbonate) is dependent on molar ratio of the reactants and can up to 6.11×10−6Scm−1 at ambient temperature. Their electrochemical window can be stable up to 7V (vs. Li+/Li), which is of great attraction for high voltage lithium ion batteries with high energy density.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
▶ The effect of Ag content on the mechanical properties of Sn–Ag–Cu lead-free solders was studied systematically and the Ag content and strain rate-dependent material constitutive models have been ...developed for the first time. The effect of Ag content on the microstructures of Sn–Ag–Cu solder was also studied. The effect of Ni doping on the mechanical properties of Sn–1.0Ag–0.5Cu solder was also investigated and the temperature and strain rate-dependent material constitutive model has been developed for Sn–1.0Ag–0.5Cu–0.02Ni solder, which is essential for finite element simulation for assessment of reliability of electronic assembly with such solder.
In this paper, the tensile tests were conducted at 25
°C to investigate the effect of Ag content and Ni doping on the microstructures and mechanical properties of Sn–3.0Ag–0.5Cu, Sn–2.0Ag–0.5Cu, Sn–1.0Ag–0.5Cu, Sn–1.0Ag–0.5Cu–0.05Ni and Sn–1.0Ag–0.5Cu–0.02Ni solders. The effect of strain rate on mechanical properties was investigated for each solder using stain rates of 10
−5
s
−1, 10
−4
s
−1, 10
−3
s
−1, 10
−2
s
−1 and 10
−1
s
−1. In addition, the effect of temperature on mechanical properties was investigated for Sn–1.0Ag–0.5Cu–0.02Ni solder by conducting tests at −35
°C, 25
°C, 75
°C and 125
°C. Test results show that the elastic modulus, yield stress and ultimate tensile strength increase with increasing strain rate and Ag content, but they decrease with increasing temperature. The elastic modulus, yield stress and ultimate tensile strength are lower and the elongation is larger for Sn–1.0Ag–0.5Cu–0.05Ni solder compared with Sn–1.0Ag–0.5Cu–0.02Ni solder. The strain rate and Ag content dependent mechanical property models have been developed for Sn–Ag–Cu solders for the first time. In addition, the temperature and rate-dependent mechanical property models have also been developed for Sn–1.0Ag–0.5Cu–0.02Ni solder. The microstructures of solders were also analyzed. The Ag content affects Ag
3Sn intermetallic compound dispersion and Sn dendrite size. The microstructures of solder have fine Sn dendrites and more dispersed IMC particles for the high Ag content solder, which makes the solder exhibit high strength and yield stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Though widely used in modelling nano- and micro- structures, Eringen’s differential model shows some inconsistencies and recent study has demonstrated its differences between the integral model, ...which then implies the necessity of using the latter model. In this paper, an analytical study is taken to analyze static bending of nonlocal Euler-Bernoulli beams using Eringen’s two-phase local/nonlocal model. Firstly, a reduction method is proved rigorously, with which the integral equation in consideration can be reduced to a differential equation with mixed boundary value conditions. Then, the static bending problem is formulated and four types of boundary conditions with various loadings are considered. By solving the corresponding differential equations, exact solutions are obtained explicitly in all of the cases, especially for the paradoxical cantilever beam problem. Finally, asymptotic analysis of the exact solutions reveals clearly that, unlike the differential model, the integral model adopted herein has a consistent softening effect. Comparisons are also made with existing analytical and numerical results, which further shows the advantages of the analytical results obtained. Additionally, it seems that the once controversial nonlocal bar problem in the literature is well resolved by the reduction method.
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to ...investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae. A series of in vitro and in vivo assays were performed to elucidate the function of FERMT1 in CC metastasis and underlying mechanisms. The upregulated expression of FERMT1 in CC tissues correlated positively with that of Slug, N-cadherin and β-catenin, but correlated inversely with E-cadherin expression. Altered FERMT1 expression led to marked changes in the proliferation, migration, invasion and EMT markers of CC cells both in vitro and in vivo. Investigations of underlying mechanisms found that FERMT1 interacted directly with β-catenin and activated the Wnt/β-catenin signaling pathway by decreasing the phosphorylation level of β-catenin, enhancing β-catenin nuclear translocation and increasing the transcriptional activity of β-catenin/TCF/LEF. Activation of the Wnt/β-catenin pathway by CHIR99021 reversed the effect of FERMT1 knockdown, whereas inhibition of the Wnt/β-catenin pathway by XAV939 impaired the effect of FERMT1 overexpression on EMT and cell motility. In conclusion, findings of this study suggest that FERMT1 activates the β-catenin transcriptional activity to promote EMT in CC metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sanguinarine (SAG) is an alkaloid derived from the root of Sanguinaria canadensis with demonstrated anti-inflammatory, antioxidant, and antimicrobial properties. SAG is routinely used in animal feed ...as an alternative to antibiotics. However, its effect on intestinal microbiota in fish has not been clarified. Herein, we evaluated the effect of SAG on immune response, digestive enzyme activity, intestinal histology, and microbiota in Koi carp to gain a better understanding of the intestinal microbes. Three hundred fish were randomly assigned to four treatment groups consisting of basal diet alone or basal diet supplemented with three doses of SAG (50, 150, or 450 mg/kg). Blood was collected at the end of the feeding periods from 36 fish (n = 9 per treatment) and analyzed for serum parameters. Intestinal samples were collected to evaluate digestive enzyme activity, intestinal histology, mRNA expression of cytokines and bacterial community. Then remaining fish (n = 66 per treatment) were then challenged with exposure to Aeromonas hydrophila (A. hydrophila) to assess cumulative survival. The results indicated that dietary SAG decreased serum interleukin (IL)-1β in SAG-50 mg/kg (P = .0045), and IL-6 in SAG-50 mg/kg and SAG-150 mg/kg (P = .0021). The level of lysozyme (P < .0001), complement C3 (P = .0013) and glutathione peroxidase (GPx) (P < .0001) increased in all SAG-treated groups. The level of superoxide dismutase activity (SOD) increased in SAG-50 mg/kg (P < .0001), but malondialdehyde (MDA) decreased in SAG-50 mg/kg and SAG-150 mg/kg (P < .0001). Lipase activity was significantly decreased in SAG-50 mg/kg (P < .0001). No difference was observed in intestinal villus height, crypt depth, muscle thickness, and ratio of villus height to crypt depth (V/C ratio) in any group. Furthermore, SAG decreased the expression of TNF-α (P < .0001) and IL-1β (P < .0001) in the intestine. The 7-day cumulative survival increased in all SAG-treated groups (P = .0029). Moreover, low dose SAG induced changes in the β-diversity of bacterial community structure (P = .050). In conclusion, dietary SAG showed anti-inflammatory and anti-oxidative effects in koi carp. SAG enhanced non-specific immunity and survival in response to A. hydrophila infection. These SAG-mediated benefits may be associated with the structure of intestinal bacterial community.
•Dietary sanguinarine showed anti-inflammation and anti-oxidant effects in koi carp.•Sanguinarine enhanced innate immune response, and elevated the resistance against A. hydrophila infection.•Low dosage of sanguinarine induced changes in Beta-diversity of bacterial community structure (P = .050).•Sanguinarine-mediated benefits may be associated with the structure of intestinal bacterial community.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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