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Find video protocols related to scientific articles indexed in Pubmed.
Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 08-12-2014
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We have demonstrated that GLP-1 improved myocardial functional recovery in acute myocardial ischemic injury. However, whether stimulation of the GLP-1 receptor (GLP-1R) with exendin-4, a selective GLP-1R agonist, could initiate a protective effect in the heart remains to be determined. Mouse myocardial infarction (MI) was created by ligation of the left descending artery. After 48 h of MI, animals were divided into the following groups (n = 5-7/group): 1) sham (animals that underwent thoracotomy without ligation), 2) MI [animals that underwent MI and received a daily dose of intraperitoneal injection (ip) of saline]; and 3) MI + exendin-4 [infarcted mice that received injections of exendin-4 (0.1 mg/kg ip)]. Two weeks later, cardiac function was assessed by echocardiography and an isovolumetrically perfused heart. Compared with control MI hearts, stimulation of GLP-1R improved cardiac function, which was associated with attenuation of myocardial hypertrophy, the mitigation of interstitial fibrosis, and an increase in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were preconditioned with exendin-4 at a dose of 100 nmol/l and then subjected to hydrogen peroxide exposure at concentrations of 50 and 100 ?mol/l. The exendin-4 treatment decreased lactate dehydrogenase leakage and increased cell survival. Notably, this event was also associated with the reduction of cleaved caspase-3 and caspase-9 and attenuation of reactive oxygen species production. Exendin-4 treatments improved mitochondrial respiration and suppressed the opening of mitochondrial permeability transition pore and protected mitochondria function. Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection and mitigating oxidative stress-induced injury.
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Aggregation and morphology control enables multiple cases of high-efficiency polymer solar cells.
Nat Commun
PUBLISHED: 07-24-2014
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Although the field of polymer solar cell has seen much progress in device performance in the past few years, several limitations are holding back its further development. For instance, current high-efficiency (>9.0%) cells are restricted to material combinations that are based on limited donor polymers and only one specific fullerene acceptor. Here we report the achievement of high-performance (efficiencies up to 10.8%, fill factors up to 77%) thick-film polymer solar cells for multiple polymer:fullerene combinations via the formation of a near-ideal polymer:fullerene morphology that contains highly crystalline yet reasonably small polymer domains. This morphology is controlled by the temperature-dependent aggregation behaviour of the donor polymers and is insensitive to the choice of fullerenes. The uncovered aggregation and design rules yield three high-efficiency (>10%) donor polymers and will allow further synthetic advances and matching of both the polymer and fullerene materials, potentially leading to significantly improved performance and increased design flexibility.
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Dinitrosopiperazine-mediated phosphorylated-proteins are involved in nasopharyngeal carcinoma metastasis.
Int J Mol Sci
PUBLISHED: 07-22-2014
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N,N'-dinitrosopiperazine (DNP) with organ specificity for nasopharyngeal epithelium, is involved in nasopharyngeal carcinoma (NPC) metastasis, though its mechanism is unclear. To reveal the pathogenesis of DNP-induced metastasis, immunoprecipitation was used to identify DNP-mediated phosphoproteins. DNP-mediated NPC cell line (6-10B) motility and invasion was confirmed. Twenty-six phosphoproteins were increased at least 1.5-fold following DNP exposure. Changes in the expression levels of selected phosphoproteins were verified by Western-blotting analysis. DNP treatment altered the phosphorylation of ezrin (threonine 567), vimentin (serine 55), stathmin (serine 25) and STAT3 (serine 727). Furthermore, it was shown that DNP-dependent metastasis is mediated in part through ezrin at threonine 567, as DNP-mediated metastasis was decreased when threonine 567 of ezrin was mutated. Strikingly, NPC metastatic tumors exhibited a higher expression of phosphorylated-ezrin at threonine 567 than the primary tumors. These findings provide novel insight into DNP-induced NPC metastasis and may contribute to a better understanding of the metastatic mechanisms of NPC tumors.
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Highly efficient inverted polymer solar cells based on a cross-linkable water-/alcohol-soluble conjugated polymer interlayer.
ACS Appl Mater Interfaces
PUBLISHED: 06-24-2014
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A cross-linkable water/alcohol soluble conjugated polymer (WSCP) material poly[9,9-bis(6'-(N,N-diethylamino)propyl)-fluorene-alt-9,9-bis(3-ethyl(oxetane-3-ethyloxy)-hexyl) fluorene] (PFN-OX) was designed. The cross-linkable nature of PFN-OX is good for fabricating inverted polymer solar cells (PSCs) with well-defined interface and investigating the detailed working mechanism of high-efficiency inverted PSCs based on poly[4,8-bis(2-ethylhexyloxyl)benzo[1,2-b:4,5-b']dithio-phene-2,6-diyl-alt-ethylhexyl-3-fluorothithieno[3,4-b]thiophene-2-carboxylate-4,6-diyl] (PTB7) and (6,6)-phenyl-C71-butyric acid methyl ester (PC71BM) blend active layer. The detailed working mechanism of WSCP materials in high-efficiency PSCs were studied and can be summarized into the following three effects: a) PFN-OX tunes cathode work function to enhance open-circuit voltage (Voc); b) PFN-OX dopes PC71BM at interface to facilitate electron extraction; and c) PFN-OX extracts electrons and blocks holes to enhance fill factor (FF). On the basis of this understanding, the hole-blocking function of the PFN-OX interlayer was further improved with addition of a ZnO layer between ITO and PFN-OX, which led to inverted PSCs with a power conversion efficiency of 9.28% and fill factor high up to 74.4%.
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Matrilin-3 chondrodysplasia mutations cause attenuated chondrogenesis, premature hypertrophy and aberrant response to TGF-? in chondroprogenitor cells.
Int J Mol Sci
PUBLISHED: 06-18-2014
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Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-? treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-?. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-? treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.
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Coronary heart disease: incidence, risk factors and interventions in Jiaozhou of Shandong province.
Chin. Med. J.
PUBLISHED: 06-17-2014
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Coronary heart disease (CHD) is the most common type of heart disease and cause of heart attacks. This study investigated the epidemiological characteristics of CHD and its risk factors in Jiaozhou, Shandong province, to ultimately find a way of reducing the prevalence of cardiovascular disease, and to provide a theoretical basis for establishing a cardiovascular disease management path under the regional medical collaborative mechanism.
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Enzymatic browning and antioxidant activities in harvested litchi fruit as influenced by apple polyphenols.
Food Chem
PUBLISHED: 04-18-2014
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'Guiwei' litchi fruit were treated with 5ga.i.L(-1) apple polyphenols (APP) and then stored at 25°C to investigate the effects on pericarp browning. APP treatment effectively reduced pericarp browning and retarded the loss of red colour. APP-treated fruit exhibited higher levels of anthocyanins and cyanidin-3-rutinoside, which correlated with suppressed anthocyanase activity. APP treatment also maintained membrane integrity and reduced oxidative damage, as indicated by a lower relative leakage rate, malondialdehyde content, and reactive oxygen species (ROS) generation. The data suggest that decompartmentalisation of peroxidase and polyphenoloxidase and respective browning substrates was reduced. In addition, APP treatment enhanced the activities of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase), as well as non-enzymatic antioxidant capacity (DPPH radical-scavenging activity and reducing power), which might be beneficial in scavenging ROS. We propose that APP treatment is a promising safe strategy for controlling postharvest browning of litchi fruit.
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Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5.
Molecules
PUBLISHED: 04-08-2014
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Matrilin-2 is a widely distributed, oligomeric extracellular matrix protein that forms a filamentous network by binding to a variety of different extracellular matrix proteins. We found matrilin-2 proteolytic products in transfected cell lines in vitro and in mouse tissues in vivo. Two putative cleavage sites were identified in the unique domain of matrilin-2; the first site was located between D851 and L852 in the middle of the domain and the second, at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminated the proteolysis of matrilin-2. While the first cleavage site was present in all matrilin-2 oligomers, the second cleavage site became apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3. Analysis using a variety of extracellular protease inhibitors suggested that this proteolytic activity was derived from a member or several members  of the ADAMTS family. Recombinant human ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2), but not ADAMTS-1, cleaved recombinant matrilin-2, thereby yielding matrilin-2 proteolytic peptides at the predicted sizes. These results suggest that ADAMTS-4 and ADAMTS-5 may destabilize the filamentous network in the extracellular matrix by cleaving matrilin-2 in both homo-oligomers and hetero-oligomers.
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Identification of novel signaling components in N,N'-dinitrosopiperazine-mediated metastasis of nasopharyngeal carcinoma by quantitative phosphoproteomics.
BMC Cancer
PUBLISHED: 03-25-2014
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Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer. N,N'-dinitrosopiperazine (DNP), a carcinogen with specificity for nasopharyngeal epithelium, facilitates NPC metastasis. However, the underlying mechanism is not known.
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HDAC4: mechanism of regulation and biological functions.
Epigenomics
PUBLISHED: 03-04-2014
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The acetylation and deacetylation of histones plays an important role in the regulation of gene transcriptions. Histone acetylation is mediated by histone acetyltransferase; the resulting modification in the structure of chromatin leads to nucleosomal relaxation and altered transcriptional activation. The reverse reaction is mediated by histone deacetylase (HDAC), which induces deacetylation, chromatin condensation and transcriptional repression. HDACs are divided into three distinct classes: I, II, and III, on the basis of size and sequence homology, as well as formation of distinct complexes. Among class II HDACs, HDAC4 is implicated in controlling gene expression important for diverse cellular functions. Basic and clinical experimental evidence has established that HDAC4 performs a wide variety of functions. Understanding the biological significance of HDAC4 will not only provide new insight into the mechanisms of HDAC4 involved in mediating biological response, but also form a platform to develop a therapeutic strategy to achieve clinical implications.
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Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model.
J. Allergy Clin. Immunol.
PUBLISHED: 02-09-2014
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The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet.
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A perceptual learning deficit in Chinese developmental dyslexia as revealed by visual texture discrimination training.
Dyslexia
PUBLISHED: 02-03-2014
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Learning to read involves discriminating between different written forms and establishing connections with phonology and semantics. This process may be partially built upon visual perceptual learning, during which the ability to process the attributes of visual stimuli progressively improves with practice. The present study investigated to what extent Chinese children with developmental dyslexia have deficits in perceptual learning by using a texture discrimination task, in which participants were asked to discriminate the orientation of target bars. Experiment l demonstrated that, when all of the participants started with the same initial stimulus-to-mask onset asynchrony (SOA) at 300?ms, the threshold SOA, adjusted according to response accuracy for reaching 80% accuracy, did not show a decrement over 5?days of training for children with dyslexia, whereas this threshold SOA steadily decreased over the training for the control group. Experiment 2 used an adaptive procedure to determine the threshold SOA for each participant during training. Results showed that both the group of dyslexia and the control group attained perceptual learning over the sessions in 5?days, although the threshold SOAs were significantly higher for the group of dyslexia than for the control group; moreover, over individual participants, the threshold SOA negatively correlated with their performance in Chinese character recognition. These findings suggest that deficits in visual perceptual processing and learning might, in part, underpin difficulty in reading Chinese.
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N,N'-dinitrosopiperazine-mediated AGR2 is involved in metastasis of nasopharyngeal carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Nasopharyngeal carcinoma (NPC) has a high metastatic character in the clinic, but its mechanism is not clear. As a carcinogen with organ specificity for the nasopharyngeal epithelium, N,N'-Dinitrosopiperazine (DNP) is involved in NPC metastasis. Herein, our data revealed that anterior gradient 2 (AGR2) was overexpressed in human NPC tissues, particularly in cervical lymph node metastatic NPC (LMNPC). High AGR2 expression was associated with NPC metastasis. Importantly, DNP induced AGR2 expression, and increased cell motility and invasion in the NPC cell line 6-10B. However, DNP-mediated cell motility and invasion was dramatically decreased when transfected with siRNA-AGR2. Further, AGR2 directly regulated cathepsin (CTS) B and D by binding them in vitro. These results indicate that DNP induces AGR2 expression, regulates CTSB and CTSD, increases cell motility and invasion, and promotes NPC tumor metastasis. Therefore, DNP-mediated AGR2 expression may be an important factor in prolific NPC metastasis.
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Preparation and characterization of bionic bone structure chitosan/hydroxyapatite scaffold for bone tissue engineering.
J Biomater Sci Polym Ed
PUBLISHED: 09-23-2013
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Three-dimensional oriented chitosan (CS)/hydroxyapatite (HA) scaffolds were prepared via in situ precipitation method in this research. Scanning electron microscopy (SEM) images indicated that the scaffolds with acicular nano-HA had the spoke-like, multilayer and porous structure. The SEM of osteoblasts which were polygonal or spindle-shaped on the composite scaffolds after seven-day cell culture showed that the cells grew, adhered, and spread well. The results of X-ray powder diffractometer and Fourier transform infrared spectrometer showed that the mineral particles deposited in the scaffold had phase structure similar to natural bone and confirmed that particles were exactly HA. In vitro biocompatibility evaluation indicated the composite scaffolds showed a higher degree of proliferation of MC3T3-E1 cell compared with the pure CS scaffolds and the CS/HA10 scaffold was the highest one. The CS/HA scaffold also had a higher ratio of adhesion and alkaline phosphate activity value of osteoblasts compared with the pure CS scaffold, and the ratio increased with the increase of HA content. The ALP activity value of composite scaffolds was at least six times of the pure CS scaffolds. The results suggested that the composite scaffolds possessed good biocompatibility. The compressive strength of CS/HA15 increased by 33.07% compared with the pure CS scaffold. This novel porous scaffold with three-dimensional oriented structure might have a potential application in bone tissue engineering.
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Long-Term Fluorescent Cellular Tracing by the Aggregates of AIE Bioconjugates.
J. Am. Chem. Soc.
PUBLISHED: 05-22-2013
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There is a great demand for long-term cellular tracers because of their great importance in monitoring biological processes, pathological pathways, therapeutic effects, etc. Herein we report a new type of fluorescence "turn-on" probe for tracing live cells over a long period of time. We synthesized the fluorogenic probe by attaching a large number of tetraphenylethene (TPE) labels to a chitosan (CS) chain. The resultant TPE-CS bioconjugate shows a unique aggregation-induced emission (AIE) behavior. It is nonfluorescent when dissolved but becomes highly emissive when its molecules are aggregated. The AIE aggregates can be readily internalized by HeLa cells. The cellular staining by the TPE-CS aggregates is so indelible that it enables cell tracing for as long as 15 passages. The internalized AIE aggregates are kept inside the cellular compartments and do not contaminate other cell lines in the coculture systems, permitting the differentiation of specific cancerous cells from normal healthy cells.
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Pd-catalyzed coupling reaction of fluorinated propargyl amidines with aryl iodides.
Org. Biomol. Chem.
PUBLISHED: 05-17-2013
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Catalyzed by ligand free Pd(OAc)(2), 2,5-disubstituted imidazole was prepared in good yield by the reaction of fluorinated propargyl amidines with iodoarene. Mechanistic studies indicated that this transformation occurs through a nitropalladation-reductive elimination pathway.
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Low-temperature conditioning induces chilling tolerance in Hayward kiwifruit by enhancing antioxidant enzyme activity and regulating en-dogenous hormones levels.
J. Sci. Food Agric.
PUBLISHED: 03-27-2013
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To understand the mechanisms leading to the enhanced chilling tolerance of kiwifruit by low-temperature conditioning (LTC, 12 °C for 3 days), this study investigated the effect of LTC on chilling tolerance and changes in antioxidant enzyme activities and endogenous hormones.
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Fabrication of chitosan nanoparticles with aggregation-induced emission characteristics and their applications in long-term live cell imaging.
Macromol Rapid Commun
PUBLISHED: 01-16-2013
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Chitosan with tetraphenylethene pendants (TPE-CS) are synthesized by reaction between amine and isothiocyanate groups of chitosan and tetraphenylethene (TPE), respectively. Nanoparticles of TPE-CS (TPE-CS NPs) are fabricated by ionic gelation method. The NPs are uniform in size, spherical in shape, monodispersed, and positive in surface charge. The suspension of TPE-CS NPs emits strong blue fluorescence under photoexcitation due to the aggregation-induced emission characteristics of the TPE moieties. The NPs can be internalized into cytoplasm through endocytosis pathway and retain inside the live cells to image the cells. Cytotoxicity assay reveals that TPE-CS NPs are cytocompatible and thus can be used for long-term live cell imaging.
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UV-induced nuclear import of XPA is mediated by importin-?4 in an ATR-dependent manner.
PLoS ONE
PUBLISHED: 01-01-2013
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Xeroderma pigmentosum Group A (XPA) is a crucial factor in mammalian nucleotide excision repair (NER) and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that are responsible for the UV (ultraviolet)-induced nuclear import of XPA. We found that, in addition to the nuclear localization signal (NLS) of XPA, importin-?4 or/and importin-?7 are required for the XPA nuclear import. Further investigation indicated that, importin-?4 and importin-?7 directly interacted with XPA in cells. Interestingly, the binding of importin-?4 to XPA was dependent on UV-irradiation, while the binding of importin-?7 was not, suggesting a role for importin-?7 in nuclear translocation of XPA in the absence of DNA damage, perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent with the previous report of a dependence of UV-induced XPA nuclear import on ataxia telangiectasia and Rad3-related protein (ATR) in S-phase, knockdown of ATR reduced the amount of XPA interacting with importin-?4. In contrast, the GTPase XPA binding protein 1 (XAB1), previously proposed to be required for XPA nuclear import, showed no effect on the nuclear import of XPA in our siRNA knockdown analysis. In conclusion, our results suggest that upon DNA damage transport adaptor importin-?4 imports XPA into the nucleus in an ATR-dependent manner, while XAB1 has no role in this process. In addition, these findings reveal a potential new therapeutic target for the sensitization of cancer cells to chemotherapy.
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N,N-dinitrosopiperazine--mediated heat-shock protein 70-2 expression is involved in metastasis of nasopharyngeal carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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N,N-Dinitrosopiperazine (DNP) is invovled in nasopharyngeal carcinoma (NPC) development and metastasis, and it shows organ specificity to the nasopharyngeal epithelium. Herein, we demonstrate that DNP induces heat-shock protein (HSP) 70-2 expression in NPC cells (6-10B) at a non-cytotoxic concentration. DNP induced HSP70-2 expression in a dose- and time- dependent manner, but showed no effect on other HSP70 family members. Furthermore, DNP also increased HSP70-2 RNA transcription through directly binding to the hypoxia-responsive elements (HRE) and heat shock elements (HSE) located in the HSP70-2 promoter. DNP-mediated HSP70-2 expression might act through enhancing the transcription of HSP70-2 RNA. Importantly, DNP induced motility and invasion of 6-10B cells dose- and time-dependently, and DNP-mediated NPC metastasis was confirmed in nude mice, which showed high HSP70-2 expression in the metastatic tumor tissue. However, the motility and invasion of NPC cells that were stably transfected using short interfering RNA against HSP70-2 could not effectively induce DNP. These results indicate that DNP induces HSP70-2 expression through increasing HSP70-2 transcription, increases the motility and invasion of cells, and promotes NPC tumor metastasis. Therefore, DNP mediated HSP70-2 expression may be an important factor of NPC-high metastasis.
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Reduction of latent infection and enhancement of disease resistance in muskmelon by preharvest application of harpin.
J. Agric. Food Chem.
PUBLISHED: 11-16-2011
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Latent infection was analyzed when harpin at 50 mg/L was sprayed on muskmelon 4 times at four different stages: florescence, young fruit, fruit enlarging, and netting periods. Results showed that the latent infection was significantly lower in sprayed muskmelons than in the control fruit. Meanwhile, the activities of peroxidase, phenylalanine ammonia-lyase, ?-1,3-glucanase, and chitinase increased significantly in the fruit treated with harpin. It also resulted in an increase of contents of total phenolic compounds, flavanoids, and lignin. In addition, the treatment of harpin increased the activity of superoxide dismutase, enhanced the content of hydrogen peroxide, and reduced catalase activity. Furthermore, harpin treatments contributed to the reinforcement of cell walls of pericarp in fruit, the reduction of postharvest decay, and the improvement of postharvest qualities. These results suggested that harpin effectively participated in inducing resistance and could be a new strategy for preventing latent infection in muskmelon.
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GATA-2 mediated regulation of normal hematopoietic stem/progenitor cell function, myelodysplasia and myeloid leukemia.
Int. J. Biochem. Cell Biol.
PUBLISHED: 10-23-2011
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Unremitting blood cell production throughout the lifetime of an organism is reliant on hematopoietic stem cells (HSCs). A rare and relatively quiescent cell type, HSCs are, on entry into cell cycle fated to self-renew, undergo apoptosis or differentiate to progenitors (HPCs) that eventually yield specific classes of blood cells. Disruption of these HSC fate decisions is considered to be fundamental to the development of leukemia. Much effort has therefore been placed on understanding the molecular pathways that regulate HSC fate decisions and how these processes are undermined in leukemia. Transcription factors have emerged as critical regulators in this respect. Here we review the participation of zinc finger transcription factor GATA-2 in regulating normal hematopoietic stem and progenitor cell functionality, myelodysplasia and myeloid leukemia.
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N,N-dinitrosopiperazine-mediated ezrin protein phosphorylation via activation of Rho kinase and protein kinase C is involved in metastasis of nasopharyngeal carcinoma 6-10B cells.
J. Biol. Chem.
PUBLISHED: 08-30-2011
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N,N-Dinitrosopiperazine (DNP) is a carcinogen for nasopharyngeal carcinoma (NPC), which shows organ specificity to nasopharyngeal epithelium. Herein, we demonstrate that DNP induces fiber formation of NPC cells (6-10B) and also increases invasion and motility of 6-10B cells. DNP-mediated NPC metastasis also was confirmed in nude mice. Importantly, DNP induced the expression of phosphorylated ezrin (phos-ezrin) at threonine 567 (Thr-567) dose- and time-dependently but had no effect on the total ezrin expression at these concentrations. Furthermore, DNP-induced phos-ezrin expression was dependent on increased Rho kinase and protein kinase C (PKC) activity. DNP may activate Rho kinase through binding to its pleckstrin homology and may activate PKC through promoting its translocation to the plasma membrane in vivo. DNP-induced phos-ezrin was associated with induction of fiber growth in 6-10B cells. However, DNP could not induce motility and invasion of NPC cells containing ezrin mutated at Thr-567. Similarly, DNP could not induce motility and invasion of the cells containing siRNAs against Rho or PKC. These results indicate that DNP induces ezrin phosphorylation at Thr-567, increases motility and invasion of cells, and promotes tumor metastasis. DNP may be involved in NPC metastasis through regulation of ezrin phosphorylation at Thr-567.
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Fluorogenic Zn(II) and chromogenic Fe(II) sensors based on terpyridine-substituted tetraphenylethenes with aggregation-induced emission characteristics.
ACS Appl Mater Interfaces
PUBLISHED: 08-23-2011
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Terpyridine-containing tetraphenylethenes (TPEs) are synthesized and their optical and metal sensing properties are investigated. They are practically nonluminescent in the solution state but become highly emissive as nanoparticle suspensions in poor solvents or thin films in the solid state, demonstrating a novel phenomenon of aggregation-induced emission (AIE). The emission of the nanoaggregates of TPEs is pH-sensitive: it is decreased and eventually quenched upon protonation of their terpyridine units because of their AIE nature. The TPEs can work as "turn-off" fluorescent chemosensors for metal ions and display different fluorescence responses to various metal ions. A characteristic red shift in the emission spectra is observed in the presence of Zn(2+), which facilitates the discrimination of Zn(2+) from other metal ions. Because of the metal-to-ligand-charge-transfer process, terpyridine-substituted TPEs display an obvious magenta color upon selectively binding with Fe(2+), allowing a rapid identification of Fe(2+) in the aqueous media by naked eyes.
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XPA-mediated regulation of global nucleotide excision repair by ATR Is p53-dependent and occurs primarily in S-phase.
PLoS ONE
PUBLISHED: 06-22-2011
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Cell cycle checkpoints play an important role in regulation of DNA repair pathways. However, how the regulation occurs throughout the cell cycle remains largely unknown. Here we demonstrate that nucleotide excision repair (NER) is regulated by the ATR/p53 checkpoint via modulation of XPA nuclear import and that this regulation occurs in a cell cycle-dependent manner. We show that depletion of p53 abrogated the UV-induced nuclear translocation of XPA, while silencing of Chk1 or MAPKAP Kinase-2 (MK2) had no effect. Inhibition of p53 transcriptional activities and silencing of p53-Ser15 phosphorylation also reduced the damage-induced XPA nuclear import. Furthermore, in G1-phase cells the majority of XPA remained in the cytoplasm even after UV treatment. By contrast, while most of the XPA in S-phase cells was initially located in the cytoplasm before DNA damage, UV irradiation stimulated bulk import of XPA into the nucleus. Interestingly, the majority of XPA molecules always were located in the nucleus in G2-phase cells no matter whether the DNA was damaged or not. Consistently, the UV-induced Ser15 phosphorylation of p53 occurred mainly in S-phase cells, and removal of cyclobutane pyrimidine dimers (CPDs) was much more efficient in S-phase cells than in G1-phase cells. Our results suggest that upon DNA damage in S phase, NER could be regulated by the ATR/p53-dependent checkpoint via modulation of the XPA nuclear import process. In contrast, the nuclear import of XPA in G(1) or G(2) phase appears to be largely independent of DNA damage and p53.
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Differential DNA damage responses in p53 proficient and deficient cells: cisplatin-induced nuclear import of XPA is independent of ATR checkpoint in p53-deficient lung cancer cells.
Int J Biochem Mol Biol
PUBLISHED: 06-07-2011
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Nucleotide excision repair (NER) and ataxia telangiectasia mutated (ATM)/ATR (ATM- and RAD3-related) DNA damage checkpoints are among the major pathways that affect the chemotherapeutic efficiency of the anticancer drug cisplatin. Xeroderma pigmentosum group A (XPA) protein plays a crucial role in NER including both global genome repair (GG-NER) and transcription-coupled repair (TC-NER) subpathways, and has been a potential target for improving cisplatin therapeutic effects. We report here that XPA translocates from the cytosol into the nucleus after DNA damage induced by UV irradiation and cisplatin, a mimetic of UV damage, in human cells with or without p53 deficiency. However, the damage-induced response of XPA nuclear import was significantly slower in p53-deficient cells than in p53-proficient cells. We also found that while XPA is imported into the nucleus upon cisplatin or UV damage in an ATR-dependent manner in p53-proficient A549 lung cancer cells, the ATR checkpoint pathway has no effect on the XPA nuclear import in p53-deficient H1299 lung cancer cells. Similarly, the XPA nuclear translocation is not regulated by ATM checkpoint or by p38MAPK/MK2 either. Our findings suggest that NER is independent on the major DNA damage checkpoint pathways in H1299 (p53(-/-)) cells and that DNA damage responses are mechanistically different between p53-proficient and p53-deficient cells. Our results also highlight the possibility of selectively targeting XPA nuclear import as a way to sensitize cisplatin anticancer activity, but targeting ATR/ATM-dependent checkpoints may not be helpful in killing p53-deficient cancer cells.
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Preparation and properties of three-dimensional hydroxyapatite/chitosan nanocomposite rods.
Biomed Mater
PUBLISHED: 07-06-2010
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To meet the demand for the bone fracture internal fixation, hydroxyapatite/chitosan (HA/CS) nanocomposite rods were reinforced via a covalently crosslinking method. The bending strength and bending modulus of the crosslinked HA/CS (5/100, wt/wt) rods could arrive at 178 MPa and 5.2 GPa, respectively, increased by 107% and 52.9% compared with uncrosslinked HA/CS (5/100, wt/wt) rods. XRD analysis indicated that the crystallinity of CS decreased after the network structure formed. CS crystal plane space (d) became smaller after crosslinking, but HA nanoparticles could prevent the decrease of d. HA nanoparticles (100 nm in length, 20-30 nm in width) were uniformly dispersed in a CS matrix. Increasing the content of HA, the acicular morphology of HA particles became vague, but crosslinking could make the acicular morphology clear over again, because the size of HA nanoparticles became smaller after crosslinking. A microstructure was observed by SEM, indicating that a layer-by-layer structure of the composite rods became much tighter through crosslinking, and the cracks turned around when they reached another layer to absorb energy. Consequently, HA/CS nanocomposite rods with high mechanical performance should be one novel device used for internal fixation of bone fracture.
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Neural deficits in second language reading: fMRI evidence from Chinese children with English reading impairment.
Neuroimage
PUBLISHED: 06-01-2010
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In alphabetic language systems, converging evidence indicates that developmental dyslexia represents a disorder of phonological processing both behaviorally and neurobiologically. However, it is still unknown whether, impaired phonological processing remains the core deficit of impaired English reading in individuals with English as their second language and how it is represented in the neural cortex. Using functional magnetic resonance imaging, the present study investigated the neural responses to letter rhyming judgment (phonological task) and letter same/different judgment (orthographic task) in Chinese school children with English and Chinese reading impairment compared to typically developing children. Whole brain analyses with multiple comparison correction revealed reduced activation within the left lingual/calcarine gyrus during orthographic processing in children with reading impairment compared to typical readers. An independent region of interest analysis showed reduced activation in occipitotemporal regions during orthographic processing, and reduced activation in parietotemporal regions during phonological processing, consistent with previous studies in English native speakers. These results suggest that similar neural deficits are involved for impaired phonological processing in English as both the first and the second language acquired. These findings pose implications for reading remediation, educational curriculum design, and educational policy for second language learners.
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Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA damage via physical interaction with xeroderma pigmentosum group A.
J. Biol. Chem.
PUBLISHED: 07-08-2009
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In response to DNA damage, eukaryotic cells activate a series of DNA damage-dependent pathways that serve to arrest cell cycle progression and remove DNA damage. Coordination of cell cycle arrest and damage repair is critical for maintenance of genomic stability. However, this process is still poorly understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint are the major pathways responsible for repair of UV-induced DNA damage. Here we show that ATR physically interacts with the NER factor Xeroderma pigmentosum group A (XPA). Using a mass spectrometry-based protein footprinting method, we found that ATR interacts with a helix-turn-helix motif in the minimal DNA-binding domain of XPA where an ATR phosphorylation site (serine 196) is located. XPA-deficient cells complemented with XPA containing a point mutation of S196A displayed a reduced repair efficiency of cyclobutane pyrimidine dimers as compared with cells complemented with wild-type XPA, although no effect was observed for repair of (6-4) photoproducts. This suggests that the ATR-dependent phosphorylation of XPA may promote NER repair of persistent DNA damage. In addition, a K188A point mutation of XPA that disrupts the ATR-XPA interaction inhibits the nuclear import of XPA after UV irradiation and, thus, significantly reduced DNA repair efficiency. By contrast, the S196A mutation has no effect on XPA nuclear translocation. Taken together, our results suggest that the ATR-XPA interaction mediated by the helix-turn-helix motif of XPA plays an important role in DNA-damage responses to promote cell survival and genomic stability after UV irradiation.
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Comments on serious anaphylaxis caused by nine Chinese herbal injections used to treat common colds and upper respiratory tract infections.
Regul. Toxicol. Pharmacol.
PUBLISHED: 01-23-2009
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Reports describing severe allergic shock and fatality following treatment of a common cold or upper respiratory tract infection (URTI) with a Chinese herbal injection were collected. Our analysis of the risks associated with this treatment suggested that the potential risk of serious, or even lethal, anaphylaxis should preclude its use in treating common colds and URTIs. In light of our findings herein, we propose the following five suggestions for improving the clinical safety of delivering Chinese herbal injections as medical treatments. First, Chinese herbal injections should not be delivered in the clinic to treat patients in accordance with Bian zheng lun zhi (broad-spectrum application based on holistic Traditional Chinese Medicine (TCM) theory and methodology), but rather they should be administered to target specific indicated disease processes. Second, Chinese herbal injection indications should be based on the results of double-blind randomized controlled clinical trials. Third, Chinese herbal injections should be used only in cases involving severe disease or to rescue patients in critical condition; they should not be used to treat mild, relatively innocuous diseases, such as common colds and upper respiratory tract infections, given the risk of doing harm. Fourth, Chinese herbal injection formulas should include materials from only a single or a small number of plant sources in known quantities. Fifth, more studies examining the toxicology and allergenic potential of Chinese herbal injections are needed.
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A high-carbohydrate diet effects on the A allele of hepatic lipase polymorphism on the apoB100/apoAI ratio in young Chinese males.
Adv Clin Exp Med
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Diet induces changes in plasma lipid profiles, and the plasma lipid profiles vary among different genetic backgrounds.
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Identification of xyloglucan endotransglucosylase/hydrolase genes (XTHs) and their expression in persimmon fruit as influenced by 1-methylcyclopropene and gibberellic acid during storage at ambient temperature.
Food Chem
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Xyloglucan endotransglucosylase/hydrolase (XTH) is thought to contribute to fruit softening by degrading xyloglucan that is a predominant hemicellulose in the cell wall. In this study, two full-length XTH genes (DKXTH1 and DKXTH2) were identified from Fupingjianshi persimmon fruit, and the expression level of both XTH genes was investigated during softening for 18-24 d using RT-qPCR. Sequence analysis showed that DKXTH1 and DKXTH2 contained a putative open reading frame of 861 and 876 bp encoding polypeptides of 287 and 292 amino acid residues, respectively, which contained the conserved DEIDFEFLG motif of XTH, a potential N-linked glycosylation signal site. RT-qPCR analysis showed that DKXTH1 and DKXTH2 in untreated fruit had different expression patterns during fruit softening, in which maximum expression occurred on days 3 and 12 of ripening, respectively. 1-Methylcyclopropene (1-MCP) and gibberellic acid (GA(3)) treatments delayed the softening and ethylene peak of persimmon fruit, as well as suppressed the expression of both XTH genes, especially DKXTH1. These results indicated that the expression of both XTH genes might be ethylene dependent action, and closely related to softening of persimmon in the early (DKXTH1) and later (DKXTH2) ripening stages.
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Gold(I)-catalyzed aminohalogenation of fluorinated N-aryl-N-propargyl amidines for the synthesis of imidazole derivatives under mild conditions.
Chemistry
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A procedure for the synthesis of fluorinated imidazole derivatives from propargyl amidines has been developed. Under gold(I) catalysis, propargyl amidines were converted into 5-fluoromethyl imidazoles in the presence of Selectfluor through a cascade cyclization/fluorination process. In contrast, imidazole-5-carbaldehydes were obtained in high yields when N-iodosuccinimide (NIS) was used as the halogenating reagent. The polarity of the solvent and light had significant impact on the formation of the carbaldehydes. These transformations showed excellent functional-group tolerance. An unfluorinated substrate with an electron-withdrawing group also underwent aminohalogenation to give the corresponding product in good yield. Mechanistic investigation revealed the general pathways of these transformations.
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Dual stimuli-responsive N-phthaloylchitosan-graft-(poly(N-isopropylacrylamide)-block-poly(acrylic acid)) copolymer prepared via RAFT polymerization.
Carbohydr Polym
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In order to develop stimuli-responsive hydrogel, chitosan graft copolymer with chitosan back-bone and poly(N-isopropylacrylamide)-block-poly(acrylic acid) (PNIPAAm-b-PAA) branch chains was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization in DMF. The chain transfer agent was obtained by modification of chitosan with 3-benzylsulfanyl thiocarbonylsulfanyl propionic acid (BPATT) with 68% the degree of substitute. The graft polymerizations possessed controlled/living characteristics. The behavior of the graft copolymer in aqueous solution was investigated by dynamic light scattering, transmission electron microscopy, and UV-visible spectrophotometer. N-Phthaloylchitosan-graft-(poly(N-isopropylacrylamide)-block-poly(acrylic acid)) copolymer (N-phthaloylchitosan-g-(PNIPAAm-b-PAA)) could assemble to micelles in aqueous solution in range of 200-300 nm with narrow size distribution, and the hydrodynamic diameter could be controlled dependent on length of branch chains and temperature. The LCST values of micelle could be modulated from 34 to 40 °C by controlling the constitution of branch chains, pH, and concentration.
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Proteomic analysis on N, N-dinitrosopiperazine-mediated metastasis of nasopharyngeal carcinoma 6-10B cells.
BMC Biochem.
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Nasopharyngeal carcinoma (NPC) has a high metastatic feature. N,N-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its mechanism is not clear. The aim of this study is to reveal the pathogenesis of DNP-involved metastasis. 6-10B cells with low metastasis are from NPC cell line SUNE-1, were used to investigate the mechanism of DNP-mediated NPC metastasis.
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One-pot synthesis of chitosan-g-(PEO-PLLA-PEO) via "click" chemistry and "SET-NRC" reaction.
Carbohydr Polym
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For the development of biocompatible and degradable biomaterials, a kind of well-defined graft copolymer consisting of chitosan back-bone and amphiphilic PEO-PLLA-PEO branch chains was synthesized by Cu(0) catalyzed one-pot strategy combining "click" chemistry and single electron transfer-nitroxide radical coupling (SET-NRC) reaction. First, the precursors of 6-azide-N-phthaloyl-chitosan, TEMPO-PEO-alkyne and mPEO-PLLA-Br were designed and produced. Then, the one-pot coupling reactions between these precursors were performed in the presence of nanosized Cu and PMDETA. The efficiencies of the coupling reactions were greater than 90% determined by the FTIR and ESR spectra. The structure of graft copolymer with 43% of the grafting ratio was confirmed by the spectral analysis. This work provided a route to prepare chitosan graft copolymer.
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Distinct roles of two alternative splice variants of matrilin-2 in protein oligomerization and proteolysis.
Mol Med Rep
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Matrilin-2 (matn2) contains a unique domain, between the second von Willebrand factor A (vWFA) domain and the C-terminal coiled-coil domain, with no sequence homology with other family members. Complementary DNA (cDNA) sequence analysis of matn2 expression in both mice and humans revealed an alternative splice site in the region of the unique domain, which forms a short and a long splicing variant (containing an additional 19 amino acids). However, the expression heterogeneity of the alternative spliced variants, and the roles of the unique domain in oligomerization and proteolysis of matn2 are unknown. In this study, we examined the expression of the two alternative splice variants of matn2 in several skeletal and non-skeletal tissues by reverse transcription-polymerase chain reaction. Both splice variants of matn2 were detected at the mRNA level in all tissues studied. To explore the biochemical significance, several minigene constructs containing the second vWFA domain, the unique domain (with either a long or short form) and the coiled-coil domain of mouse mini matn2 were generated. Ectopic expression of these constructs demonstrated that the long form of matn2 is capable of self-assembling into several oligomeric forms, including a tetramer, trimer, pentamer or multimer; but the short form is only capable of forming a tetramer, trimer or dimer. Moreover, we observed that the splice variants of matn2 are important in modulating matn2 cleavage when co-expressed with matrilin-1 or matrilin-3. These results indicate that the two alternative splice variants have distinct roles in the processes of post-translational modification of matn2, which may have an impact on the homeostasis of the matrilin filamentous network of the extracellular matrix.
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A high carbohydrate diet induces the beneficial effect of the CC genotype of hepatic lipase C-514T polymorphism on the apoB100/apoAI ratio only in young Chinese males.
Scand. J. Clin. Lab. Invest.
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Both diet and genetic background have profound effects on plasma lipid profiles. It was hypothesized that a high carbohydrate (high-CHO) diet could affect the ratios of serum lipids and apolipoproteins (apo) differently in subjects with different genotypes of the C-514T hepatic lipase rs1800588 polymorphism. Fifty-six healthy university students were given a stabilization diet of 54.1% carbohydrate for 7 days, followed with a high-CHO diet of 70.1% carbohydrate for 6 days. Body composition, serum lipids, apolipoproteins and the hepatic lipase C-514T rs1800588 polymorphism were analyzed. The ratios of serum lipids and apolipoproteins were calculated afterwards. At baseline, females have significantly lower waist circumference (WC) (CC genotype: p?=?0.049; T carriers: p?=?0.015) and waist-to-hip ratio (WHR) (CC genotype: p?=?0.019; T carriers: p?=?0.000) than males. When compared with those before the high-CHO diet, the body mass index (BMI) (p?=?0.043) and WC (p?=?0.048) were significantly decreased in the male T carriers, the TG/HDL-C ratios were significantly increased in females (CC genotype: p?=?0.047; T carriers: p?=?0.003). The TC/HDL-C ratios were significantly decreased in males (CC genotype: p?=?0.000; T carriers: p?=?0.003). And the LDL-C/HDL-C ratios were significantly decreased in all subjects (males with the CC genotype: p?=?0.001; male T carriers: p?=?0.000; females with the CC genotype: p?=?0.018; female T carriers: p?=?0.006). However, the apoB100/apoAI ratio was only significantly decreased in male CC genotype after the high-CHO diet (p?=?0.005).
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Rh-catalyzed intramolecular sp2 C-H bond difluoromethylenation.
Chem. Commun. (Camb.)
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A new Rh-catalyzed intramolecular coupling reaction of a CF(2)Br group with a 2-aryl of indole or pyrrole via C-H bond activation is presented. This reaction represents a new way of incorporating difluoromethylene groups into organic compounds. Preliminary mechanistic studies suggest that this reaction might not occur via a conventional free radical pathway.
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Au(I)-catalyzed intramolecular hydroamination of the fluorinated N-aryl-N-propargyl amidines: mild conditions for the synthesis of 2-fluoroalkyl imidazole derivatives.
Org. Lett.
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The gold(I)-catalyzed synthesis of 2-fluoroalkyl imidazole derivatives was developed. Catalyzed by gold(I), propargyl amidines underwent a 5-exo-dig cyclization to afford 2-fluoroalkyl-5-methyl imidazoles. Also, 2-fluoroalkyl imidazole-5-carbaldehydes were obtained in the presence of NIS. A mechanism investigation manifested the probable process and the carbonyl oxygen derived from O(2).
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