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  • 1
    Publication Date: 2018-02-16
    Description: Purpose: The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer. Experimental Design: FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro cellular assays and in vivo mouse models. In addition, the N-glycosylation–defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression. Results: We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities in vitro . FAM198B also attenuated tumor growth and metastasis in vivo . We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability. Conclusions: Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma. Clin Cancer Res; 24(4); 916–26. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Publication Date: 2018-12-18
    Description: Strain-tunable magnetism at oxide domain walls Strain-tunable magnetism at oxide domain walls, Published online: 17 December 2018; doi:10.1038/s41567-018-0363-x Ferromagnetism is observed at ferroelastic domain walls in strontium titanate and its heterostructures with other oxides. Applying strain can reverse the magnetism. This suggests the possibility of device engineering using domain walls.
    Print ISSN: 1745-2473
    Electronic ISSN: 1745-2481
    Topics: Physics
    Published by Springer Nature
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  • 3
    Publication Date: 2018-03-30
    Description: Background/Aim: The aim of the present study was to investigate the efficacy of an ethanolic extract of gamboge (EEG), a traditional Chinese medicine (TCM), both in vitro on colon cancer cells and in vivo in an orthotopic mouse model of human colon cancer. Materials and Methods: The in vitro cytotoxicity of EEG on colon cancer cells was determined with the CCK8 proliferation assay and the Annexin V-PE/7-AAD apoptosis assay. Efficacy of EEG in vivo was evaluated in an orthotopic mouse model of human colon cancer implated with the green fluorescent protein-expressing human colon cancer cell line SW480-GFP. The tumor-bearing mice were treated with vehicle (0.2 ml/dose normal saline, po, daily), irinotecan (50 mg/kg/dose, ip, twice a week), 5-FU (15 mg/kg/dose, ip, every other day) as positive controls or EEG at doses of 12.5, 25 and 50 mg/kg/dose, po, daily. Real-time fluorescence imaging was performed to determine tumor inhibition in each treated group compared to the untreated controls. The protein expression of β-catenin, MMP-7, cyclin D1 and E-cadherin in the tumors was analyzed by immunohistochemistry. Results: EEG significantly induced proliferation inhibition and apoptosis of SW480 colon cancer cells in vitro in a dose-dependent manner. Tumor growth in the colon-cancer orthotopic model was significantly inhibited by irinotecan, 5-FU and all three doses of EEG. The efficacy of EEG was comparable to irinotecan and 5-FU. Irinotecan, 5-FU and 50 mg/kg EEG significantly decreased the protein expression of β-catenin and MMP-7. Cyclin D1 expression was decreased and E-cadherin expression was increased by irinotecan, 5-FU and all three doses of EEG. Conclusion: The present study demonstrates anti-tumor efficacy of EEG on colon cancer both in vitro and in vivo through inducing proliferation inhibition and apoptosis of SW480 colon cancer cells and inhibiting tumor growth, respectively. EEG exerts anti-tumor activity at least partly via down-regulation of the Wnt/β-catenin signaling pathway.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 4
    Keywords: DISEASE ; DISEASES ; GENE ; GENES ; PROTEIN ; PROTEINS ; RNA ; DNA ; recombination ; tumour ; BIOLOGY ; SEQUENCE ; chromosome ; NUMBER ; MUTATION ; inactivation ; REGION ; MUTATIONS ; EVOLUTION ; DEGRADATION ; CHROMOSOMES ; GENE FAMILY ; AID ; HUMAN GENOME SEQUENCE ; INACTIVATION CENTER ; LINKED MENTAL-RETARDATION ; MAMMALIAN Y-CHROMOSOME ; REPEAT HYPOTHESIS
    Abstract: The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence
    Type of Publication: Journal article published
    PubMed ID: 15772651
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  • 5
    Publication Date: 2018-01-04
    Description: Differential scanning calorimeter was used to extensively investigate the non-isothermal crystallization of polypropylene (PP)/layered double hydroxides (LDHs) nanocomposites prepared through wet solid-state shear milling. The corresponding crystallization kinetics was further investigated by using Ozawa, modified Avrami and combined Avrami–Ozawa method, respectively. The results showed that the Ozawa method could not well describe the crystallization kinetics of pure PP and its nanocomposites. Comparatively, the modified Avrami method as well as the combined Avrami–Ozawa method gives the satisfactory results. Under the effect of pan-milling, the produced LDH nano intercalated/exfoliated particles exhibit the inhibitive effect on the PP nucleation but more remarkable promotion effect on the spherulite growth, leading to enhancement in the overall crystallization rate. This is reflected in increase of the calculated fold surface free energy e and also the supercooling degree T required for crystallization nucleation. In addition, the polarized optical microscopy observation also verifies the higher spherulite growth rate of PP/LDHs nanocomposites than that of pure PP.
    Keywords: materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 6
    Publication Date: 2018-08-02
    Description: Difunctionalization of alkenes is a valuable and versatile chemical transformation that could quickly build complex molecules. Extensive efforts have been made, and great achievement, such as Sharpless aminohydroxylation and dihydroxylation, has been reached. However, in marked contrast to the extensive research of aminohydroxylation and dihydroxylation, directly using thiophenols/thiols and O/N-nucleophiles to perform the difunctionalization of alkenes that form the C–S and C–O/N bonds together is still underexplored. The main issue is that thiophenols/thiols are often easily overoxidized to sulfoxides or sulphones under such essential oxidation conditions. We demonstrate an electrochemical oxidative oxysulfenylation and aminosulfenylation of alkenes. A critical feature of this transformation is that neither external chemical oxidants nor metal catalysts are required. This electrochemical oxidative synthetic strategy could also be applied for the hydroxysulfenylation and acyloxysulfenylation of alkenes.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 7
    Publication Date: 2018-08-08
    Description: B lymphocytes use B cell receptors (BCRs) to recognize membrane-bound antigens to further initiate cell spreading and contraction responses during B cell activation. We combined traction force microscopy and live-cell imaging to profile the origin, dynamics, and function of traction force generation in these responses. We showed that B cell activation required the generation of 10 to 20 nN of traction force when encountering antigens presented by substrates with stiffness values from 0.5 to 1 kPa, which mimic the rigidity of antigen-presenting cells in vivo. Perturbation experiments revealed that F-actin remodeling and myosin- and dynein-mediated contractility contributed to traction force generation and B cell activation. Moreover, membrane-proximal BCR signaling molecules (including Lyn, Syk, Btk, PLC-2, BLNK, and Vav3) and adaptor molecules (Grb2, Cbl, and Dok-3) linking BCR microclusters and motor proteins were also required for the sustained generation of these traction forces. We found a positive correlation between the strength of the traction force and the mean fluorescence intensity of the BCR microclusters. Furthermore, we demonstrated that isotype-switched memory B cells expressing immunoglobulin G (IgG)–BCRs generated greater traction forces than did mature naïve B cells expressing IgM-BCRs during B cell activation. Last, we observed that primary B cells from patients with rheumatoid arthritis generated greater traction forces than did B cells from healthy donors in response to antigen stimulation. Together, these data delineate the origin, dynamics, and function of traction force during B cell activation.
    Print ISSN: 1945-0877
    Topics: Medicine
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  • 8
    Publication Date: 2018-09-14
    Description: Although organic photovoltaic (OPV) cells have many advantages, their performance still lags far behind that of other photovoltaic platforms. A fundamental reason for their low performance is the low charge mobility of organic materials, leading to a limit on the active-layer thickness and efficient light absorption. In this work, guided by a semi-empirical model analysis and using the tandem cell strategy to overcome such issues, and taking advantage of the high diversity and easily tunable band structure of organic materials, a record and certified 17.29% power conversion efficiency for a two-terminal monolithic solution-processed tandem OPV is achieved.
    Keywords: Chemistry, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-06-05
    Description: Systemic lupus erythematosus (SLE) is an autoimmune disease posing threats to multiple organs in the human body. As a typical manifestation of SLE, lupus nephritis is characterized by a series of pathological changes in glomerulus as well as accumulation of pathogenic autoreactive IgG with complement in the kidney that dramatically disrupts renal functions. Activation-induced deaminase (AID), which governs both somatic hypermutation (SHM) and class-switch recombination (CSR), has been shown to be essential for the regulation of SLE. However, the relative contributions of SHM and CSR to SLE pathology have not been determined. Based on the available AID G23S mice, we successfully established an AID G23S MRL/lpr mouse model, in which SHM is specifically abolished, although CSR is largely unaffected. We found that the abrogation of SHM effectively alleviated SLE-associated histopathological alterations, such as expansion of the mesangial matrix and thickening of the basement membrane of Bowman’s capsule as well as infiltration of inflammatory cells. Compared with SLE mice, AID G23S MRL/lpr mice exhibited decreased proteinuria, blood urea nitrogen, and creatinine, indicating that the loss of SHM contributed to the recovery of renal functions. As a consequence, the life span of those SHM-deficient MRL/lpr mice was extended. Together, we provide direct evidence pinpointing a vital role of SHM in the control of SLE development.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 10
    Publication Date: 2018-07-05
    Description: Micro-arc oxidation (MAO) is a plasma-assisted electrochemistry method to prepare protective ceramic coatings on aluminium alloys. Alloy elements of the Al-alloy substrate, such as Si, Cu, Mg and Li, have effects on the microstructure and composition of the MAO coatings. Usually, silicon distributes in the cast Al–Si alloy substrate as small laths and they cover approximately 10% of the substrate surface. Therefore, their effects on the growth process and microstructure of the MAO coatings are worthy of notice. In the present study, oxide coatings with a thickness of 15–18 µm were prepared on the ZL109 Al–Si alloy by MAO. The phase content, surface morphology and element distribution of the coatings were investigated by X-ray diffraction, grazing incidence X-ray diffraction, scanning electron microscope, and electron probe micro-analysis respectively. The average hardness of the coatings was 622.3 ± 10.2 HV 0.05 . The adhesive strength of the coatings is 40.55 ± 2.55 N, and the adhesion of the coatings could be rated as 5B by tape test according to ASTM D3359-17 standard test methods, which indicated a high adhesive strength between the MAO coating and substrate. The effects of silicon laths on surface morphology and composition of the coatings were discussed, and a model was put forward to describe the growth process of the MAO coatings on cast Al–Si alloys. The authors believe that the high silicon content of the substrate has no adverse influence on the structure and properties of the MAO coating on the ZL109 alloy.
    Keywords: materials science, structural engineering
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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