The Al-water reaction has attracted considerable attention in the past few years, because it is an economically viable way to supply hydrogen for portable and kW-grade fuel cells. The water type is ...found to have a significant impact on Al-water reaction. In this work, the effect of trace species in water on Al-water reaction is investigated systematically. It is found that the trace organic acids originated from the decay of botanies and animals in nature and trace F super(-) ions, rather than other cations and anions, play a key role in the reaction dynamics of Al with water. The mechanism analyses reveal that the organic acids and F super(-) ions form complexes with aluminol groups on Al particle surfaces to impede the hydration process of Al surface oxide film and retard the reaction of Al with water. The present results imply that a suitable water should be chosen for the Al-water reaction to generate hydrogen. At the same time, the organic acids and trace F super(-) ions could be used as the agents to prevent undesirable Al-water reaction.
Previous works indicated that Al particle surfaces could be modified by fine γ‐Al2O3 grains, which can be used as a hydrogen‐generation material, where the fine γ‐Al2O3 grains were produced by the ...decomposition of the Al(OH)3 phase in the mixture. In this work, commercially available γ‐Al2O3 powder was directly used as the modification agent and mixed with Al powder and heat treated at an elevated temperature. It was found that the modified Al powder produced by directly using γ‐Al2O3 has an obvious shorter time for complete hydrogen generation than that using Al(OH)3‐produced γ‐Al2O3. Microstructure analyses revealed that directly using γ‐Al2O3 powder has a better coverage of fine γ‐Al2O3 grains on Al particle surfaces than the Al(OH)3‐produced γ‐Al2O3. This implies that a uniform distribution of modification agents on Al particle surfaces is an important factor for the Al–water reaction dynamics.
Abstract A multifunctional micellar drug carrier formed by the thermosensitive and biotinylated double-hydrophilic block copolymer (DHBC), biotin-poly(ethylene glycol)- block -poly( N ...-isopropylacrylamide- co - N -hydroxymethylacrylamide) (biotin-PEG- b -P(NIPAAm- co -HMAAm)), was designed and prepared. The P(NIPAAm- co -HMAAm) block with an molar feed ratio of NIPAAm and HMAAm (10:1) was identified to exhibit the reversible phase transition at the lower critical solution temperature (LCST) of 36.7 °C. Cytotoxicity study indicated that the biotin-PEG- b -P(NIPAAm- co -HMAAm) copolymer did not exhibit obvious cytotoxicity. The block copolymer was capable of self-assembling into micelle in water. Transmission electron microscopy showed that the self-assembled micelles were regularly spherical in shape. The anticancer drug methotrexate (MTX) was loaded in the micelles and the in vitro release behaviors of MTX at different temperatures were investigated. The association of biotin molecule with the copolymer was confirmed by a unique capillary electrophoresis immunoassay (CEIA) method based on enhanced chemiluminescence (CL) detection. The fluorescence spectroscopy analysis as well as confocal microscopy studies confirmed the DHBC drug carriers could specifically and efficiently bind to cancer cells with pretreatment of biotin-transferrin, suggesting that the multifunctionalized DHBC micelle may be a useful drug carrier for tumor targeting.
To investigate how microRNA-190 (miR-190) regulates FOXP2 genes in gastric cancer (GC) cell line SGC7901.
We identified that miR-190 could target FOXP2 genes by using dual luciferase enzyme assay. ...Precursor fragment transfection of miR-190 was performed with GC cell line SGC7901 and human gastric mucosal cell line GES-1. miR-190 expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and FOXP2 protein expression was measured by Western blotting.
FOXP2-3'-untranslated region (UTR) in miR-190 transfection group was significantly decreased as compared with other groups. There were no significant differences in fluorescence signals of FOXP2mut-3'-UTR in each group. Therefore, it was assumed that miR-190 can target FOXP2 genes. Through RT-PCR verification, it was observed that the expression level of miR-190 was significantly higher in GC cell line SGC7901 than in human gastric mucosa cell line GES-1 after transfection with miR-190 mimics. The expression level of miR-190 was significantly higher in GES-1 cells than in SGC7901 cells after transfection with miR-190 inhibitors. Western blotting results showed the expression level of FOXP2 was significantly lower in GC cell line SGC7901 than in GES-1 cells. Compared with blank, mimics control, and inhibitors control groups, the miR-190 mimics group showed significantly enhanced proliferation, migration, and invasion abilities, while miR-190 inhibitors group showed decreased abilities toward proliferation, migration, and invasion (P<0.05). The transcription level of miR-190 and the expression level of FOXP2 in tumor tissues and adjacent normal tissues in GC patients were verified to be consistent with those of cell line experiments.
Upregulation of miR-190 can lead to downregulation of FOXP2 protein expression. miR-190 may serve as a potential target for GC diagnosis.
The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine-rich RING motif, a zinc-binding domain found in a variety of regulatory proteins. Here we ...describe a novel protein that interacts in vivo with the N-terminal region of BRCA1. This BRCA1-associated RING domain (BARD1) protein contains an N-terminal RING motif, three tandem ankyrin repeats, and a C-terminal sequence with significant homology to the phylogenetically conserved BRCT domains that lie near the C terminus of BRCA1. The BARD1/BRCA1 interaction is disrupted by BRCA1 missense mutations that segregate with breast cancer susceptibility, indicating that BARD1 may be involved in mediating tumour suppression by BRCA1.
We recently reported that proteinase-activated receptors type I (PAR-1) are coupled to both negative and positive invasion pathways in colonic and kidney cancer cells cultured on collagen type I ...gels. Here, we found that treatments with the cell-permeant analog 8-Br-cGMP and the soluble guanylate cyclase activator BAY41-2272, and Rho kinase (ROK) inhibition by Y27632 or a dominant negative form of ROK lead to PAR-1-mediated invasion through differential Rac1 and Cdc42 signaling. Hypoxia or the counteradhesive matricellular protein SPARC/BM-40 (SPARC: secreted protein acidic rich in cysteine) overexpressed during cancer progression also commutated PAR-1 to cellular invasion through the cGMP/protein kinase G (PKG) cascade, RhoA inactivation, and Rac1-dependent or -independent signaling. Cultured primary cancer cells isolated from peritoneal and pleural effusions from patients with colon cancer or other malignant tumors harbored PAR-1, as shown by RT-PCR and FACS analyses. These malignant effusions also contained high levels of activated thrombin and fibrin, and induced a proinvasive response in HCT8/S11 human colorectal cancer cells. Our data underline the essential role of the tumor microenvironment and of several commutators targeting cGMP/PKG signaling and the RhoA-ROK axis in the control of PAR-1 proinvasive activity and metastatic potential of cancer cells in distant organs and peritoneal or pleural cavities. We also add new insights into the mechanisms linking the coagulation mediators thrombin and PAR-1 in the context of blood coagulation disorders and venous thrombosis often observed in cancer patients, as described in 1865 by Armand Trousseau.
Conventional treatment of obesity reduces fat in mature adipocytes but leaves them with lipogenic enzymes capable of rapid resynthesis of fat, a likely factor in treatment failure. Adenovirus-induced ...hyperleptinemia in normal rats results in rapid nonketotic fat loss that persists after hyperleptinemia disappears, whereas pair-fed controls regain their weight in 2 weeks. We report here that the hyperleptinemia depletes adipocyte fat while profoundly down-regulating lipogenic enzymes and their transcription factor, peroxisome proliferator-activated receptor (PPAR) gamma in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPAR alpha, normally low in adipocytes, are up-regulated, as are uncoupling proteins 1 and 2. This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor alpha, and leptin, and by the appearance of the preadipocyte marker Pref-1. These findings suggest a strategy for the treatment of obesity by alteration of the adipocyte phenotype
ABSTRACT
Leptin resistance has been implicated in the pathogenesis of obesity‐related complications involving abnormalities of lipid metabolism that resemble those of old age. To determine whether ...development of leptin resistance in advancing age might account for such abnormalities, we compared the effects of hyperleptinemia (>40 ng/ml) induced in 2–month‐old and 18–month‐old lean wild‐type (+/+) Zucker diabetic fatty rats by adenovirus gene transfer. The decline in food intake, body weight, and body fat in old rats was only 25%, 50%, and 16%, respectively, of the young rats. Whereas in young rats plasma free fatty acids fell 44% and triacylglycerol (TG) 94%, neither changed in the rats. In hyperleptinemic young rats, adipocyte expression of preadipocyte factor 1 increased dramatically and leptin mRNA virtually disappeared;there was increased expression of acyl CoA oxidase, carnitine palmitoyl transferase 1, and their transcription factor peroxisome proliferator‐activated receptor α, accounting for the reduction in body fat. These hyperleptinemia‐induced changes were profoundly reduced in the old rats. On a high‐fat diet, old rats consumed 28% more calories than the young and gained 1.5 × as much fat, despite greater endogenous hyperleptinemia. Expression of a candidate leptin resistance factor, suppressor of cytokine signaling 3 (SOCS‐3), was compared in the hypothalamus and white adipocytes of young and old rats before and after induction of hyperleptinemia;hypothalamic SOCS‐3 mRNA was ~3× higher in old rats before, whereas it was 3× higher in WAT after, hyperleptinemia. We conclude that the anorexic and antilipopenic actions of leptin decline with age, possibly through increased SOCS‐3 expression, and that this could account for the associated abnormalities in lipid metabolism of the elderly.—Wang, Z.‐W., Pan, W.‐T., Lee, Y., Kakuma, T., Zhou, Y.‐T., Unger, R. H. The role of leptin resistance in the lipid abnormalities of aging. FASEB J. 15, 108–114 (2001)
To test the hypothesis that the physiologic liporegulatory role of hyperleptinemia is to prevent steatosis during caloric excess, we induced obesity by feeding normal Harlan Sprague-Dawley rats a 60% ...fat diet. Hyperleptinemia began within 24 h and increased progressively to 26 ng/ml after 10 weeks, correlating with an approximately 150-fold increase in body fat (r = 0.91, p < 0.0001). During this time, the triacylglycerol (TG) content of nonadipose tissues rose only 1-2.7-fold implying antisteatotic activity. In rodents without leptin action (fa/fa rats and ob/ob and db/db mice) receiving a 6% fat diet, nonadipose tissue TG was 4-100 times normal. In normal rats on a 60% fat diet, peroxisome proliferator-activated receptor alpha protein and liver-carnitine palmitoyltransferase-1 (l-CPT-1) mRNA increased in liver. In their pancreatic islets, fatty-acid oxidation increased 30% without detectable increase in the expression of peroxisome proliferator-activated receptor-alpha or oxidative enzymes, whereas lipogenesis from 14Cglucose was slightly below that of the 4% fat-fed rats (p < 0.05). Tissue-specific overexpression of wild-type leptin receptors in the livers of fa/fa rats, in which marked steatosis is uniformly present, reduced TG accumulation in liver but nowhere else. We conclude that a physiologic role of the hyperleptinemia of caloric excess is to protect nonadipocytes from steatosis and lipotoxicity by preventing the up-regulation of lipogenesis and increasing fatty-acid oxidation.
The kinetics of the Al–water reaction promoted by an ultrasonically prepared Al(OH)
3
suspension is investigated. It is found that the induction time for the beginning of the Al–water reaction ...decreases and the reaction rate increases with increasing suspension concentration, volume, and temperature, because the Al–water reaction is exothermic. When the weight ratio of Al to water increases to 1 : 15, there is almost no induction time, and more than 80% of Al in the Al(OH)
3
suspension is consumed within 40 min, which is comparable to the behavior of Al in NaOH solution. A collision model based on Brownian motion is proposed to analyze the reaction process, which shows that the contact between Al and Al(OH)
3
particles and the reaction heat are two key factors that control the reaction progress.