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Mass spectrometry (MS)-based bottom-up proteomics and quantitative proteomic labeling strategies have led to unprecedented insights into systems biology and provided invaluable resources as a multifaceted analytical tool. We have utilized such techniques to analyze small GTPases of the Ras superfamily, which represent a class of crucial signaling molecules in cells, and the aberrant regulation of their expressions is implicated with various types of human diseases. In this dissertation, I report the development and applications of novel targeted quantitative proteomic methods for high-throughput and reproducible profiling of small GTPases in cultured human cells and patient-derived brain tissues that carry disease-related changes.In Chapter 2, I describe the development of a novel scheduled multiple-reaction monitoring (MRM)-based targeted quantitative proteomic method, in conjunction with stable isotope labeling by amino acids in cell culture (SILAC) for the quantification of more than 90 small GTPases in the paired primary/metastatic melanoma cell lines. The data reveal previously unrecognized roles of RAB38 in promoting melanoma metastasis in vitro.In Chapter 3, the established scheduled MRM-based method was further applied to assess the differential expression of small GTPases in wild-type MCF-7 and the paired tamoxifen-resistant breast cancer cells. The method facilitated robust quantification of 96 small GTPases, among which down-regulation of RAB31 was analyzed further and demonstrated to play a role in the development of acquired tamoxifen resistance.In Chapter 4, we extended the use of the scheduled MRM method to comprehensively investigate the differential expression of small GTPases in paired primary/metastatic colorectal cancer cell (CRC) lines SW480 and SW620. With this approach, 83 small GTPases were robustly quantified, leading to the identification of SAR1B as a potential suppressor for CRC metastasis. We also showed that diminished SAR1B expression could stimulate epithelial–mesenchymal transition (EMT), thereby promoting motility and in vitro metastasis of SW480 cells.In Chapter 5, I describe the development of a novel targeted quantitative proteomic assay based on MRM and the use of crude synthetic stable isotope-labeled (SIL) peptides as internal standards (IS) and surrogate standards (SS). By using this approach, we quantified ~80 small GTPases from lysates of frontal cortex from post-mortem Alzheimer’s disease (AD) patient brain tissue samples. The method displayed excellent throughput, sensitivity and reproducibility. Furthermore, we observed that the protein expression levels of Rab3A/C, Rab4A/B and Rab27B proteins, which are involved with synaptic and secretory vesicles, increased with degree of disease severity. The MRM quantification results were further verified by Western blotting.

Trimethyltin chloride (TMT) is a by-product in the synthesis of organotin, a plastic stabilizer. With the rapid development of industry, the occupational hazards caused by TMT cannot be ignored. TMT is a typical neurotoxicant, which mainly damages the limbic system and brainstem of the nervous system. Previous studies have demonstrated that the neurotoxicity induced by TMT is linked to the inhibition of energy metabolism, but the underlying mechanism remains elusive. In order to investigate the mechanism of TMT-induced inhibition of energy metabolism, C57BL/6 male mice were administered by IP injection in different TMT doses (0 mg/kg, 1.00 mg/kg, 2.15 mg/kg and 4.64 mg/kg) and times (1d, 3d and 6d), and then the changes of superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Na+-K+-ATPase activity in cerebral cortex, cerebellum, hippocampus, pons, medulla oblongata of mice, the expressions of Na+-K+-ATPase protein, AMP-activated protein kinase (AMPK), phosphorylated AMP-activated protein kinase(p-AMPK)and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) in hippocampus and medulla oblongata were measured; the effects of TMT on the viability, the activity of SOD, glutathione (GSH) and Na+-K+-ATPase, MDA level, and the expression of PGC-1α and Na+-K+-ATPase protein in N2a cells were measured by different TMT doses and times, in order to verify the experiments in vivo. Our results found that most of the mice showed depression, tremor, epilepsy, spasm and other symptoms after TMT exposure. Moreover, with the increase of TMT dose, the activity of Na+-K+-ATPase and the expressions of AMPK protein in the hippocampus and medulla oblongata of mice decreased, and the expressions of p-AMPK protein increased. Peroxidative damage was evident in hippocampus, medulla oblongata of mice and N2a cells, and the expression of PGC-1α and Na+-K+-ATPase protein was significantly down-regulated. Therefore, it is reasonable to believe that TMT-induced neurotoxic symptoms and inhibition of energy metabolism may be related to p-AMPK and down-regulation of PGC-1α in the hippocampus and medulla oblongata.

Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1β and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. However, the effects of mimecan in adrenal tissue on the hypothalamic-pituitary-adrenal (HPA) axis functions remain unknown. We demonstrated that the expression of mimecan in adrenal tissues is significantly downregulated by hypoglycemia and scalded stress. It was down-regulated by ACTH, but upregulated by glucocorticoids through in vivo and in vitro studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells in vivo and in vitro. Interestingly, compared to litter-mate mice, the diurnal rhythm of corticosterone secretion was disrupted under basal conditions, and the response to restraint stress was stronger in mimecan knockout mice. These findings suggest that mimecan stimulates corticosterone secretion in the adrenal tissues under basal conditions; however, the down-regulated expression of mimecan by increased ACTH secretion after stress in adrenal tissues might play a role in maintaining the homeostasis of an organism's responses to stress.

Background: A functional hypothalamic-pituitary-adrenal (HPA) axis is critical for host defenses to outside stimuli. The adrenal cortex is seemingly endowed with distinct functional units that are regulated by adrenocorticotropic hormone (ACTH). We have found that mimecan, a small leucine-rich proteoglycan expressed in the adrenal gland, has yet to be characterized in functional terms.Results: Herein, we have demonstrated the following properties: 1) adrenal mimecan expression in mouse models is significantly downregulated under hypoglycemia and scalded stress; 2) expression of mimecan in adrenal cells may be downregulated through ACTH or upregulated by glucocorticoid via related receptors (GRs); and 3) mimecan stimulates corticosterone secretion in adrenal tissues. The latter was proven using in vivo and in vitro studies to confirm the ACTH-independent activity of mimecan-maltose-binding protein (-MBP). Relative to litter-mate mice, the basal-state diurnal rhythm of corticosterone secretion is disrupted in mimecan knockout mice, and corticosterone secretion is increased under restraint stress conditions. Conclusions: These findings offer the first evidence that mimecan is key in regulating the HPA axis, assuming a critical role in adrenal responses to stress.

In the well environment of supercritical CO2 separate injection, the ordinary HNBR rubber is not only easy to be corroded, but also easy to be damaged during CO2 gas intrusion and rapid decompression. Therefore, a new modified HNBR was tested for corrosion resistance and heat resistance, and its molecular structure was characterized to verify its corrosion resistance and high temperature resistance. The Cortest high temperature and high pressure autoclave was used to simulate the conditions of high temperature, high pressure and high CO2 in the well. The test device was used to carry out the experiment about CO2 gas intrusion and rapid depressurization of the modified HNBR rubber. The experimental results show that the modified HNBR rubber not only has good corrosion and high temperature resistance, but also has good CO2 gas intrusion and rapid decompression resistance. It is recommended to be used under the downhole conditions of supercritical CO2 separate injection. The conclusions can provide a theoretical basis for the selection of rubber materials in supercritical CO2 separate injection wells.

In this work, combined approach of torrefaction deoxygenation pretreatment (TDP) and shape selective catalytic fast pyrolysis (SS-CFP) using bifunctional catalyst (metal modified HZSM-5) were employed to improve the yield of bio-BTX derived from the renewable starting material of lignin. Results showed that after TDP, the oxygen element could be removed effectively. The oxygen removal efficiency reached its maximum value of 22.27% at 300 °C, resulting in markedly decrease of unnecessary oxygenates in bio-oil. Compared to parent HZSM-5, all metal modified HZSM-5 (Ga/HZSM-5, Zn/HZSM-5, and Ga-Zn/HZSM-5) promoted the formation of bio-BTX. Zn/HZSM-5 showed the highest selective yield of bio-BTX because of the enhancement deoxygenation reaction of oxygenates and the aromatization reaction of olefins. The combined approach of TDP and SS-CFP remarkably improved the selective yield of bio-BTX, reaching the maximum value of 65.19%, which was much higher than that from single approach of TDP (33.84%) and SS-CFP (47.36%).

Molybdenum (Mo), tungsten (W), and stainless steel (SS) are widely used as important structure materials and first wall materials in fusion devices, while liquid lithium (Li) limiter/divertor can provide an attractive option for withstanding high heat load and solving life-time problem of first wall. Studying the compatibility of these materials exposed to liquid Li is significant for the application in Mo, W, and SS in fusion reactors. The corrosion behaviors of Mo, W, and 304SS exposed to static liquid Li at 600 K up to 1320 h under high vacuum with pressure 10−4 Pa were investigated. After exposure to liquid Li, it was found that the weight loss of Mo, W, and 304SS increases with corrosion time, but the total amount is moderate. 304SS specimens produce a non-uniform corrosion behavior because of Cr, Ni, and carbon (C) elements selectivity depletion and formation of carbides compound near surface. Mo and W surface microstructures are unchanged. 304SS surface hardness increases with corrosion products because these particles include C element, which increases by 49 HV after exposed to liquid Li for 1320 h, while Mo and W surface hardness are unchanged by the reason of their excellent corrosion resistance.

2,4,6-Triamino-1,3,5-trinitrobenzene is the attractive insensitive high energetic material used extensively in the military and civil fields. Combined with the double-films theory, the global gas-liquid chemical reaction kinetics of 2,4,6-triamino-1,3,5-trinitrobenzene was developed by means of the infinitesimal material balance calculation. The raw material concentration and reactive temperature effects on the crystallization of 2,4,6-triamino-1,3,5-trinitrobenzene were investigated by the batch experiments. The reactive crystallization kinetics associated ammonia feeding rate of 2,4,6-triamino-1,3,5-trinitrobenzene, including nucleation as well as crystal growth, was systematically investigated in the heterogonous semi-batch procedure. The nucleation and crystal growth kinetic exponents were estimated by the linear least-squares method. The crystallization kinetic results indicated that nucleation rate strongly increased but liner growth rate decreased with the increasing of ammonia feeding rate. In terms of manufacturing coarse 2,4,6-triamino-1,3,5-trinitrobenzene, it was found that a slow ammonia feeding rate and a low raw material concentration were feasible under the present experimental conditions.

Reduction of hydrogen content in deuterium-fueled fusion plasmas is important not only to avoid diluting reacting core deuterons but also so as to allow the optimization of hydrogen-minority-heating efficiency in those fusion devices which employ ion-cyclotron-radio-frequency heating systems. In EAST, the amount of hydrogen released from plasma-facing components has been shown to depend strongly on both their composition and their temperature. As measured by thermal desorption spectroscopy, the hydrogen inventory in graphite – used in EAST as lower divertor material – has been determined to be >25 times larger than that of tungsten which comprises the upper divertor. This difference in hydrogen inventory is attributed mostly to the intrinsically porous nature of bulk graphite. Thus the main source of hydrogen release into EAST discharges was identified as the graphite tiles used in the lower divertor. The hydrogen content in EAST plasmas were clearly reduced by first employing a high-temperature vacuum baking of all graphite tiles and then renewing a 100–200 μm thick SiC coating before an EAST experimental run campaign. Subsequent active surface conditioning of all wall components with elemental silicon and then with elemental lithium were seem to again reduce the plasma hydrogen content significantly – with lithium proving to be more effective than silicon. Combining these several techniques, H/(H + D) levels as low as ∼3% have been achieved in EAST discharges. Additionally, the effects of lithium thickness on H surface implantation and retention has been re-examined semi-quantitatively using data from a previous run campaign. These data suggest that relatively thick Li films coated on the first wall can effectively isolate the rich source of hydrogen stored in the porous bulk of the underlying graphite from the deuterium-fueled plasma so as to minimize hydrogen release. Finally an operational maneuver whereby a diverted plasma is repetitively switched from an upper single null configuration to a lower single null configuration is presented. This switching maneuver has been shown to suppress hydrogen influx into a 35s-long EAST discharge by alternately mitigating the rise in divertor temperature.

The study of the corrosion behaviors of structural materials exposed to liquid lithium (Li) is very important for the application of liquid Li as a potential plasma-facing or blanket material in future fusion device. It was demonstrated that the temperature plays an important role in the corrosion process. The corrosion behaviors of 304 stainless steel (304SS) in static liquid Li at 600 K and 640 K for 1320 h under high vacuum have been compared in the present work. The results show that the weight loss and corrosion depth of the 304SS specimens in static liquid Li at 640 K are about 3 times more than those at 600 K. After exposure to liquid Li, all the surfaces produce non-uniform damage which includes pitting and grain boundary corrosion. The surface damage of 304SS specimens at 640 K is more serious than that at 600 K. The corrosion mechanisms include physical dissolution and chemical corrosion; the effect of the latter on the corrosion behavior at 640 K is much more than that at 600 K.

Sandwich-like MgO@Carbon (MgO@C) nanocomposoites were fabricated using a one-pot hydrothermal route for the removal of organic dyes. The effects of contact time, pH value, carbon thickness, inorganic ions, and temperature on the sorption capacity of MgO@C were investigated. Compared with pure MgO nanoparticles and carbon bulks, the as-obtained sandwich-like MgO@C exhibited much higher sorption capacity for methyl orange due to the enhanced electrostatic interaction between anionic dye molecules and positively charged MgO@C nanocomposite. The sorption capacity of MgO@C increased with the increase of specific surface and pore volume, and the MgO@C-3 with a carbon thickness of around 5 nm exhibited the highest adsorption efficiency. The adsorption isotherm and kinetics of dye over MgO@C were well fitted by the Langmuir isotherm model and pseudo-second-order adsorption model, respectively. Further investigation indicated that the sorption process of methyl orange over sandwich-like MgO@C was controlled by the external mass transfer and intraparticle diffusion, and was a spontaneous and exothermic adsorption process.

As the most abundant aromatic bio-polymer in nature, lignin can be converted into bio-BTX via the shape selective catalytic fast pyrolysis process (SS-CFP). In this work, three types of MWL were isolated from softwood (Chinese fir), hardwood (poplar), and herbaceous biomass (corn stover), namely CF-MML, P-MWL, and CS-MWL. The chemical structural of lignin was analyzed by gel permeation chromatography (GPC), 2D-HSQC-NMR, and 31P NMR. Five types of the parent zeolites (HZSM-5 (25), HZSM-5 (85), Al-MCM-41, HY, and USY) and the Zn modified HZSM-5 (25) with different loading amounts (1% to 4%) were screened. Results showed that CF-MWL had the highest carbon content (59.90%). P-MWL had highest content of β-O-4 linkage (53.90%) and Mw (2778 g/mol). Among the five parent zeolites, HZSM-5 (25) was the most effective catalyst to produce bio-BTX with the highest selective yield of 56.56% at the optimal operation parameters. As a bi-functional catalyst, the incorporation of Zn on zeolite promoted the formation of BTX, where metal promoted the reaction rates of de‑oxygenation reaction and aromatization reaction, while the HZSM-5 remains the ability of shape selectivity. The maximum selective yields of BTX were 65.02% (CF-MWL) > 63.77% (CS-MWL) > 63.41% (P-MWL) when the Zn loading amount was 2%.

We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between October 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m2 of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m2 of irinotecan. For all patients, the irinotecan dose was increased by 30 mg/m2 every two cycles until grade ≥3 adverse events or severe adverse events developed, following which the dose was reverted to and maintained at the previously tolerated level. The oral regorafenib dose was adjusted to 120 mg/day daily. The median follow-up period was 10.0 months (1.0-21.0 months). The disease control rate was 69.2%, whereas the median progression-free survival and overall survival were 9.5 and 13.0 months, respectively. Our findings indicate that regorafenib plus FOLFIRI with irinotecan dose escalation based on UGT1A1 genotyping in previously treated patients with mCRC and with UGT1A1*1/*1 and UGT1A1*1/*28 genotypes is clinically effective and yields improved oncological outcomes.

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Investigation of corrosion behavior of stainless steel served as one kind of structure materials exposed to liquid lithium (Li) is one of the keys to apply liquid Li as potential plasma facing materials (PFM) or blanket coolant in the fusion device. Corrosion experiments of 304 austenite stainless steel (304 SS) were carried out in static liquid Li at 600 K and up to1584 h at high vacuum with pressure less than 4 × 10−4 Pa. After exposure to liquid Li, it was found that the weight of 304 SS slightly decreased with weight loss rate of 5.7 × 10−4 g/m2/h and surface hardness increased by about 50 HV. Lots of spinel-like grains and holes were observed on the surface of specimens measured by SEM. By further EDS, XRD and metallographic analyzing, it was confirmed that the main compositions of spinel-like grains were M23C6 carbides, and 304 SS produced a non-uniform corrosion behavior by preferential grain boundary attack, possibly due to the easy formation of M23C6 carbides and/or formation of Li compound at grain boundaries.

The energetic material 3-(4-aminofurazan-3-yl)-4-(4-nitrofurazan-3-yl)furazan (ANTF) with low melting-point was synthesized by means of an improved oxidation reaction from 3,4-bis(4′-aminofurazano-3′-yl)furazan. The structure of ANTF was confirmed by 13C NMR spectroscopy, mass spectrometry, and the crystal structure was determined by X-ray diffraction. ANTF crystallized in monoclinic system P21/c, with a crystal density of 1.785 g cm−3 and crystal parameters a=6.6226(9) A, b=26.294(2) A, c=6.5394(8) A, β=119.545(17)°, V=0.9907(2) nm3, Z=4, μ=0.157 mm−1, F(000)=536. The thermal stability and non-isothermal kinetics of ANTF were studied by differential scanning calorimetry (DSC) with heating rates of 2.5, 5, 10, and 20 K min−1. The apparent activation energy (Ea) of ANTF calculated by Kissinger’s equation and Ozawa’s equation were 115.9 kJ mol−1 and 112.6 kJ mol−1, respectively, with the pre-exponential factor lnA=21.7 s−1. ANTF is a potential candidate for the melt-cast explosive with good thermal stability and detonation performance.

In the present work, a new strategy is used to economically synthesize an oligomeric ionic liquid from conventional phenolic epoxy resin. This oligomeric ionic liquid is further blended with PVdF-co-HFP and organic liquid electrolyte to prepare a high performance, nonflammable gel polymer membrane. Although the liquid electrolyte uptake is low ( −1 at 30 °C and 6.6 mS cm −1 at 80 °C, respectively. The AC impedance results show that the interfacial compatibility between this gel polymer electrolyte and the electrodes is good. These two factors result in high cell capacity under different charge/discharge rates. Further, excellent cell-cycle stability after being charged and discharged 100 cycles is also demonstrated with the columbic efficiency to be up to 99. Due to the existence of the oligomeric ionic liquid, this novel gel polymer electrolyte exhibits superior dimensional stability; that is, at high temperature (150 °C) the dimensional change is less than 1%. Notably, the electrolyte’s limiting oxygen index can be as high as 29, meaning that it achieves the flame-retardant requirement under a normal atmosphere, which is essential to the safety of lithium ion batteries. These features allow this novel gel polymer electrolyte to function as a high performance and high safety lithium ionic conductor as well as a separator for lithium-ion batteries.

This study employs the polyfluorene composite (called Green B) with several colors of quantum dots to generate the high-color-rendering index (CRI) white LEDs. The Green B polymer is a good candidate to manufacture the hybrid w-LED because of its good quantum efficacy. The hybrid w-LEDs are fabricated by the mixing of Green B with yellow quantum dots and red quantum dots or orange quantum dots to obtain the correlated color temperatures of 3500 and 5500 K. The use of the hybrid polymer/QDs w-LEDs is proved to be beneficial as QD w-LEDs can improve the CRI up to 90 in 3500 K. The luminous efficiency of such devices can be as high as 17.2l m/W.

The motivation for this work was to investigate the relationship between the fractal characteristics of the acoustic emission (AE) correlation and the mechanical damage of different ratios of tantalum–niobium tailings CPB materials. The AE parameters of the tailings CPB materials under uniaxial compression were obtained by an AE test. On this basis, the fractal dimensions of the AE parameters were derived, and the change rule of the fractal parameters during the entire specimen damage was obtained by analysis. The results showed that the minimum value of the fractal dimension was generally within a stress-level range of 70% to 90%. While approaching the peak value of the stress, the amplitude fractal dimension displayed an increasing trend. The AE amplitude, event rate, energy rate, and spatial distribution exhibited fractal characteristics. In the investigation of the AE fractal, the fractal dimension of the amplitude was more concentrated, which exhibited that it was more accurate to determine the failure of a cemented paste backfill (CPB). Therefore, the study focused on using the amplitude fractal dimension value to monitor the failure of the CPB. This feature provides a reference for the control of the stability of the surrounding rock by backfilling the goaf with CPB.

Context The aberrant expression or alternation of miRNA in the pathogenesis of aldosterone-producing adenomas (APAs) is still largely unknown. Objective We investigated the role of miRNA-203 (screened from miRNA microarrays) and elucidated its effects on the Wnt/β-catenin pathway regarding aldosterone production and cell proliferation in APAs. Methods miR-203 expression was upregulated or downregulated by transfecting miR-203 mimics or inhibitors into primary APA cells, the human adrenocortical cell line HAC15, and C57BL/6 mice. In vitro and biochemical data were correlated with the respective clinical parameters of APAs to evaluate their clinical importance. Results The expression of miR-203 in human APA samples was significantly lower than that of peritumor adrenal samples. Tumoral miR-203 abundance correlated negatively with both plasma aldosterone level and tumor size in patients with APAs. miR-203 inhibitors increased aldosterone production and cell proliferation in HAC15 cells, and restoration of expression via miR-203 mimics showed decreased cell proliferation and aldosterone hypersecretion in APA cell cultures. In vivo selective inhibition of miR-203 via intra-adrenal injection of miR-203 inhibitors in mice led to a substantial increase in systolic blood pressure and plasma aldosterone levels. Additionally, the dual-luciferase reporter assay demonstrated that WNT5A is a direct target of miR-203. Furthermore, plasma Wnt5a levels in adrenal vein sampling were helpful in differentiating tumor localization, and preoperative plasma Wnt5a levels predicted the cure of hypertension after adrenalectomy. Conclusion We have demonstrated that attenuated miR-203 expression in APAs increases aldosterone production and the tumorigenesis of adrenal cells by activating the Wnt5a/β-catenin pathway.

Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristic curves (AUC) and a multivariate generalized additive model (GAM) were applied to predict these outcomes of interest. Urinary HJV differentiated patients with/without AKI, advanced AKI or composite outcome after surgery (p p p ponding AUC values of 0.768 and 0.828, respectively. The performance of creatinine-adjusted HJV was also superior to NGAL in predicting advanced AKI (AUC = 0.784 and 0.694; p = 0.037) and composite outcome (AUC = 0.842 and 0.676; p = 0.002). The integration of HJV into the Cleveland Clinic score for advanced AKI led to a significant increase in risk stratification (net reclassification improvement [NRI] = 0.598; p

Background and Purpose Cannabinoid (CB) ligands have been demonstrated to have utility as novel therapeutic agents for the treatment of pain, metabolic conditions and gastrointestinal (GI) disorders. However, many of these ligands are centrally active, which limits their usefulness. Here, we examine a unique novel covalent CB receptor ligand, AM841, to assess its potential for use in physiological and pathophysiological in vivo studies.

Partial replacement of fluoroacrylates in the monomer composition is able to reduce the free energy of polymer-stabilised blue phase liquid crystal (PSBPLC) due to their low surface tension. The ease of blue phase platelet texture formation is observed under fast cooling and short annealing time before ultraviolet irradiation. The peak driving voltages are dramatically decreased from 9% to 16% in the resulting PSBPLCs. In addition, the hysteresis is completely suppressed in the PSBPLC containing 3FM-M1. The other PSBPLC containing fluoroacrylates retain very small hysteresis (△V

As pyrenesulfonic acid (PSA) is added to sulfonated poly(styrene-b-isoprene-b-styrene) (s-SIS), a novel effect on the conductivity of polyelectrolytes results. In this study, s-SIS was sulfonated to two different degrees to obtain s-SISL (ion-exchange capacity (IEC): 0.92) and s-SISH (IEC: 1.20). After PSA was added to the s-SISL, the proton conductivity increased significantly and reached an optimum at a PSA addition of 4% (s-SISL4.0), where the conductivity (0.6 × 10−2 S cm−1) was 6.0 times higher than s-SISL without PSA (0.1 × 10−2 S cm−1). Similarly, when PSA was added to s-SISH (IEC: 1.20), the proton conductivity achieved an optimum at a PSA addition of 2% (s-SISH2.0), at which point the proton conductivity (5.3 × 10−2 S cm−1) was 26 times that of s-SISH without PSA (0.2 × 10−2 S cm−1). From the TEM analyses of the s-SISH membrane in the presence of different PSA concentrations, this doping PSA effect can be interpreted by means of the interaction between the aromatic ring on the PSA and the aromatic ring on the hydrophobic polystyrene segments of the s-SIS block copolymer. This effect of doping an amphiphilic compound to polyelectrolytes to intensify the conductivity can be widely applied to numerous kinds of polyelectrolytes.

Genetic diversity of 299 inbred indica rice varieties, including 33 introduced varieties, applied in Guangdong Province of China were assessed using 20 ILP (intron length polymorphism) and 34 SSR (simple sequence repeat) markers. Totally, 154 loci were screened for the 299 varieties, with the average number of alleles (Na), rare alleles (Nr), and polymorphism information content (PIC) scored at 3.4, 0.7 and 0.32, respectively. The Nei's genetic distance (GD) was estimated ranging from 0 to 0.7529 with an average of 0.4797. There was no significant difference of Na, Nr, PIC or GDs between the introduced and local varieties. Neighbor-joining (NJ) analysis showed that the 299 varieties failed into three main distinct groups, and the 33 introduced varieties were distributed over all the groups or subgroups. Model-based cluster analysis demonstrated that only 73 (24.4%) of the 299 varieties and 7 (21.2%) of the 33 introduced varieties could be distinctly classified into the three groups. Analysis of molecular variance showed that within the groups divided by NJ analysis, the genetic variations revealed by ILP, SSR and these two combined were 7.7%, 5.6% and 6.6%, and within the groups divided by region (Guangdong local and the introduced varieties), the genetic variables were 2.1%, 4.6%, 5.4%, respectively. These results suggested that the genetic diversity of the 299 inbred rice varieties in Guangdong Province was low, simultaneously relationship among varieties was poor and close in all kind of groups. Hence, it is very necessary to extend the genetic diversity during the breeding and selection practical procedure.

In this paper, we introduce a new two-sided resonator based on the split-ring resonators to the permittivity measurement at microwave frequencies. The samples with specified thickness are placed on a well designed sensor, so that relatively large frequency offsets due to the samples can be detected to retrieve the permittivity. Analysis and simulations validate that by applying this method, permittivity can be linearly retrieved from the measured frequency offsets. The measurement setup can be conveniently calibrated with a given sample with known permittivity.

This study developed flexible light-emitting diodes (LEDs) with warm white and neutral white light. A simple ultraviolet flip-chip sticking process was adopted for the pumping source and combined with polymer and quantum dot (QD) films technology to yield white light. The polymer-blended flexible LEDs exhibited higher luminous efficiency than the QD-blended flexible LEDs. Moreover, the polymer-blended LEDs achieved excellent color-rendering index (CRI) values (Ra = 96 and R9 = 96), with high reliability, demonstrating high suitability for special applications like accent, down, or retrofit lights in the future. In places such as a museum, kitchen, or surgery room, its high R9 and high CRI characteristics can provide high-quality services.

High-performance polymer solar cells are conventionally fabricated on the rigid and costly indium-tin-oxide (ITO) glass substrates, which are incompatible with the roll-to-roll process with low cost. This study shows that polymer solar cells can be made on ITO-free flexible stainless steel with only a moderate compromise in power conversion efficiency. A blend of poly (3-hexylthiophene) (P3HT) and (6,6)-phenyl-C61-butyric acid methyl ester (PCBM) was used as the active material for the inverted structure. The bottom electrode was an alloy of Al and Au spontaneously formed from a bi-layer during thermal annealing of the active layer. This alloy had a low work function of 3.9 eV, and a high resistance to oxide formation throughout the entire process. Semi-transparent Ag was used as the top electrode. These solar cells on stainless steel had an efficiency of 2.6%. The majority of the loss came from the top electrode transmission at approximately 60%. This all-metal approach makes roll-to-roll polymer cell fabrication possible.

A series of supported silver salts of heteropolyacid AgxH3-xPW/SiO2 (x=0.5, 1.0, 1.5, 2.0, 2.5, 3.0) were synthesized and showed high reactivity and stability in tetrahydrofuran polymerization, which were due to the saltsʹ insolubility in polar solvent. The amount of Ag ion replaced in the salt and the amount of the salt loaded on the silica significantly influenced the catalytic performance. Change in the Ag content of the supported silver salt altered the crystal phase composition of the silver tungstophoric acid and catalystʹs acid strength. The AgxH3-xPW/SiO2 catalyst had the highest acid strength and the highest polymerization activity when x=2.0. When the Ag2HPW loading was 30% (mass fraction), the catalyst exhibited the best dispersion and highest activity for the polymerization of tetrahydrofuran. Compared with the conventional silica supported heteropolyacid (HPW/SiO2) catalyst, the present 30%Ag2HPW/SiO2 displayed excellent reusability, with its reactivity only slightly declining after 4 reuses. Through the introduction of the Ag ion, the stability of the novel supported 30%Ag2HPW/SiO2 was significantly improved and the obtained polymer product, polytetrahydrofuran, had a stable average molecular weight.

Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP) is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route ofH. pyloriparallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP andH. pyloriexposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma). The viability of the AGS cell line was significantly lower in 80 μM-DEHP andH. pylori(MOI = 100 : 1) coexposure than DEHP orH. pylorialone. DEHP andH. pyloricoexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhanceH. pyloricytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP andH. pyloricoexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis.

National Key Basic Research Program of China (973) [2010CB732303]; National Natural Science Foundation of China [21033006, 21373169]; Program for Changjiang Scholars and Innovative Research Team in Universities, China [IRT1036]

A series of lateral junctions consisting of NiFe/Al2O3/p-Si/Al2O3/NiFe have been investigated for the understanding of manipulating the electronic spin in semiconducting channel. Devices with various conducting channel lengths between two electrodes were fabricated using a top-down technique. An ion beam sputtering was used for the required film stack and an electron beam lithography in combination with ion beam etching technique were adopted for patterning. The current-voltage measurements reveal a remarkable phenomenon of current enhancement, indicating a formation of the interface state in such devices. This transport behavior associated with trapping assistance has also been demonstrated with a fitting based on Poole-Frenkel effect. The results also show that a transition from trapping assisted process to direct tunneling process occurs when the semiconducting channel length is below 1 μm. In addition, the current enhancement may be suppressed with increasing the thickness of the oxide layer.

We numerically calculate the spectral reflectivity of the silicon nitride (Si 3 N 4 ) sub-wavelength structure (SWS) using a two-dimensional finite element simulation. The geometry-dependent effective reflectance of the Si 3 N 4 SWS over the wavelength ranging from 400 nm to 1000 nm is examined and the structure of Si 3 N 4 SWS is further optimized for the lowest effective reflectance. A p–n junction solar cell efficiency based on the optimized Si 3 N 4 SWS is also calculated, resulting in an improvement of 0.98% in efficiency than that of single layer antireflection coatings.

Three Devonian reefs (bioherms) from Yunnan and Guangxi, southern China, are studied in detail. Six microfacies types are differentiated. Colonial rugose corals (Columnaria, Disphyllum and Hexagonaria) at Qujing, tabulate corals (Alveolites) with massive stromatoporoids (Actinostroma and Stromatoporella) and sponges at Panxi, and massive stromatoporoids (Actinostroma, Trupetostroma and Stromatoporella) at Yangshuo belong to the most important reef builders. All the three reefs studied clearly reveal a successive evolution history. They developed on the carbonate banks, shallow carbonate platforms and platform margins in the Late Givetian and terminated in the Frasnian due to sea-level falls related to local uplifts of platforms. This coincides with a eustatic fall of relative sea level at the Frasnian/Famennian transition.