Notes

Cross-Domain Graph and or chart Anomaly Discovery.
Regucalcin (RGN) is a calcium (Ca(2+))-binding protein that displays a characteristic downregulated expression with aging in several tissues. Besides its role in regulating intracellular Ca(2+) homeostasis, RGN has been associated with the control of oxidative stress, cell proliferation, and apoptosis. Thus, the diminished expression of RGN with aging may contribute to the age-associated deterioration of cell function. In the present study, we hypothesized that the maintenance of high expression levels of RGN may prevent age-related alterations in the processes mentioned previously. First, we confirmed that RGN expression is significantly diminished in the prostate of 8-, 9-, 12-, and 24-months wild-type rats. Then, the effect of aging on lipid peroxidation, antioxidant defenses, cell proliferation, and apoptosis in the prostate of wild-type controls and transgenic rats overexpressing RGN (Tg-RGN) was investigated. The activity of glutathione and the antioxidant capacity were increased in Tg-RGN rats in response to the age-associated increase in thiobarbituric acid reactive substances levels, an effect not seen in wild type. Overexpression of RGN also counteracted the effect of aging increasing prostate cell proliferation. In contrast to wild-type animals, the prostate weight of Tg-RGN did not change with aging and was underpinned by the diminished expression of stem cell factor and c-kit, and increased expression of p53. In addition, aged Tg-RGN animals displayed increased expression (activity) of apoptosis regulators, therefore not showing the age-induced resistance to apoptosis observed in wild type. Altogether, these findings indicate the protective role of RGN against the development of age-related pathologies, such as, for example, prostate cancer.In this study a novel cyctochrome c modified nanocomposite electrochemical biosensor was developed for the electrochemical determination of rebaudioside A in different food samples. The electrode surface was fabricated with graphene oxide assimilated with gold nanoparticles decorated on multiwalled carbon nanotubes/cytochrome c. The developed biosensor exhibited a 10-fold enhancement in the differential pulse voltammetry signal carried out at pH 11.0 in a 0.1M borate buffer. Under the optimized conditions, Ip (µA) was proportional to the rebaudioside A concentration in the range of 0.001-0.05 mM (R(2)=0.8308) and 0.075-1.25 mM (R(2)=0.9920) with a detection limit (S/N=3) of 0.264 µM. Results of this study revealed that cyctochrome c was adsorbed tightly onto the surface of the modified electrode and showed an enzymatic catalytic activity towards the quasi-reversible reduction of rebaudioside A at -0.1 V (vs Ag/AgCl). The direct electron transfer by cytochrome c was further supported by HOMO-LUMO calculations performed at the density functional theory level. Additionally, the molecular docking simulations predicted a stronger binding affinity of rebaudioside A towards cytochrome c, thus supporting their host-guest relationship. The use of novel electrode materials in this study demonstrates the application of the electrochemical biosensor in the food industry.A novel, label-free, gold nanoparticles (AuNPs)-based chemiluminescence assay has been developed for the detection of fibrillar fibrin. The method relied on the interaction of fibrinogen (Fib) with AuNPs and the aggregated AuNPs induce a strong luminol-H2O2 chemiluminesecence (CL) signal. We prepared the 12-nm-diameter AuNPs which well dispersed in the solution. Fib was absorbed on the surface of AuNPs against the aggregation of AuNPs in 1.0M NaCl. Otherwise, Fib was catalyzed to form fibrillar fibrin in the presence of thrombin. The fibrin induced AuNPs aggregated in the presence of NaCl solution. The catalytic activity of aggregated AuNPs on the luminol-H2O2 CL reaction is greatly enhanced. This allows us to utilize the luminol-H2O2 CL system for quantitative analysis of thrombin, which was used to denote fibrosis degree of Fib. The assay showed a linear toward fibrillar fibrin concentration in the range of 2.7 × 10(-15)-2.7 × 10(-13)M with a correlation of 0.9920. The limit of detection for fibrin was experimentally determined to be 1 fM, based on a signal-to-noise ratio (S/N) of 3. SHP099 order Relative to conventional methods, this method offers the advantages of higher sensitivity and selectivity and lower cost, showing great potential for medical diagnosis.In this work, we report the application of streptavidin-coated quantum dot (strAV-QD) in molecular beacon (MB) microarray assays by using the strAV-QD to label the immobilized MB, avoiding target labeling and meanwhile obviating the use of amplification. The MBs are stem-loop structured oligodeoxynucleotides, modified with a thiol and a biotin at two terminals of the stem. With the strAV-QD labeling an "opened" MB rather than a "closed" MB via streptavidin-biotin reaction, a sensitive and specific detection of label-free target DNA sequence is demonstrated by the MB microarray, with a signal-to-background ratio of 8. The immobilized MBs can be perfectly regenerated, allowing the reuse of the microarray. The MB microarray also is able to detect single nucleotide polymorphisms, exhibiting genotype-dependent fluorescence signals. It is demonstrated that the MB microarray can perform as a 4-to-2 encoder, compressing the genotype information into two outputs.Circulating miRNAs are emerging as novel reliable biomarkers for early detection of cancer diseases. Through combining the advantages of electrochemical methods and nanomaterials with the selectivity of the oligo-hybridization-based biosensors, a novel electrochemical nanobiosensor for plasma miR-155 detection have demonstrated here, based on thiolated probe-functionalized gold nanorods (GNRs) decorated on the graphene oxide (GO) sheet on the surface of the glassy carbon electrode (GCE). The reduction signals of a novel intercalating label Oracet Blue (OB), were measured by differential pulse voltammetry (DPV) method. The transmission electron microscope (TEM) imaging, UV-vis spectrophotometry, cyclic voltammetry (CV), field emission scanning electron microscope (FE-SEM) imaging and energy dispersive spectroscopy (EDS) were proved the right synthesis of the GNRs and correct assembly of the modified electrode. The electrochemical signal had a linear relationship with the concentration of the target miRNA ranging from 2.0 fM to 8.0 pM, and the detection limit was 0.6 fM. Furthermore, the nanobiosensor showed high Specificity, and was able to discriminate sharply between complementary target miRNA, single-, three-base mismatch, and non-complementary miRNA. Alongside the outstanding sensitivity and selectivity, this nanobiosensor had great storage ability, reproducibility, and showed a decent response in the real sample analysis with plasma. In conclusion, the proposed electrochemical nanobiosensor could clinically be used in the early detection of the breast cancer, by direct detection of the plasma miR-155 in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.A sensing platform, combined amino acid labeling kit and a double-generation gold nanoparticle (DG-AuNP) chip, was designed to prove the existence of weak but crucial binding between the DV (dengue virus) and its CLEC5A receptor. At first, we have designed a kit combining the novel fluorescence turn-on sensors for lysine, arginine and cysteine amino acids. Advantages of this kit are that emission on-off switching can increase the signal-to-noise ratio and the virus must be fluorescently labelled with sufficient numbers of fluorophores because the lysine, arginine and cysteine residues of viral proteins are labelled simultaneously. Consequently, this kit can be used to light-on single DV spot both in solution and in cell under fluorescence microscopy. Second, the labeling kit was used to examine the DV binding to the CLEC5A-coated DG-AuNP chip. Based on our study, the double-generation gold nanoparticle construction of chip can support more coating areas for receptor CLEC5A and then, support more binding opportunities for DV. Meanwhile, the grooves between nanohemispheres will provide the extra driving force for DV stacking. We try to give a proof that this sensing platform is very useful for detection of weak binding mechanism.Thrombin plays a key role in thrombosis and hemostasis. The abnormal level of thrombin in body fluids may lead to different diseases, such as rheumatoid arthritis, glomerulonephritis, etc. Detection of thrombin level in blood and/or urine is one of important methods for medical diagnosis. Here, a bioluminescent sensor is developed for non-invasively and rapidly detecting thrombin in urine. The sensor is assembled through conjugating gold nanoparticles (Au NPs) and a recombinant protein containing Renilla luciferase (pRluc) by a peptide, which is thrombin specific substrate. The luciferase-catalyzed bioluminescence can be quenched by peptide-conjugating Au NPs. In the presence of thrombin, the short peptide conjugating luciferase and Au NPs is digested and cut off, which results in the recovery of bioluminescence due to the release of luciferase from Au NPs. The bioluminescence intensity at 470 nm is observed, and increases with increasing concentration of thrombin. The bioluminescence intensity of this designed sensor is significantly recovered when the thrombin digestion time lasts for 10 min. In addition, a similar linear relationship between luminescence intensity and the concentration of thrombin is found in the range of 8 nM to 8 μM in both buffer and human urine spiked samples. The limit of detection is as low as 80 pM. It is anticipated that our nanosensor could be a promising tool for clinical diagnosis of thrombin in human urine.In this work, a dual-signaling electrochemiluminescence (ECL) ratiometric sensing approach for the detection of HL-60 cancer cells was reported for the first time. G-C3N4 nanosheets and Ag-PAMAM-luminol nanocomposits (Ag-PAMAM-luminol NCs) were prepared and served as reductive-oxidative and oxidative-reductive ECL emitters respectively. DNA probe functionalized Ag-PAMAM-luminol NCs would hybridize with aptamers modified onto magnetic beads. In the presence of HL-60 cells, the aptamer would conjugate with the target cell and release Ag-PAMAM-luminol NCs. After magnetic separation, released Ag-PAMAM-luminol NCs would hybridize with capture DNA on g-C3N4 nanosheets. ECL from g-C3N4 nanosheets coated on ITO electrode at -1.25 V (vs SCE) could be quenched by Ag-PAMAM-luminol NCs due to the resonance energy transfer (RET) from g-C3N4 nanosheets to Ag NPs. Meanwhile, Ag-PAMAM-luminol brought the ECL signal of luminol at +0.45 V (vs SCE). Thus, the concentration of HL-60 cancer cells could be quantified by both the quenching of ECL from g-C3N4 nanosheets and the enhancement of ECL from luminol. link2 By measuring the ratio of ECL intensities at two excitation potentials, this approach could achieve sensitive and reliable detection for cancer cells in a wide range from 200 cells/mL to 9000 cells/mL with the detection limit of 150 cells (S/N=3).
Pulmonary hypertension (PH) is often found in cystic fibrosis (CF) patients affected by end-stage lung disease but its impact on outcome remains unclear. link3 Pulmonary arterial compliance (PAC) is an important determinant of right ventricle (RV) workload and it is a strong predictor of survival in other forms of PH. The aim of this study is to investigate whether PAC is a predictor of long-term prognosis in a population of CF patients affected by advanced lung disease.

Between 2000 and 2014, 178 patients with CF have been evaluated for lung transplantation in our CF Center. Right heart catheterization (RHC) and follow up data were retrievable and analyzed in 141 of them. PAC was defined as the ratio between stroke volume (SV) and pulse pressure (PP) at heart catheterization. The association of PAC with survival was tested at 4 years and compared to other hemodynamic parameters.

PH prevalence was 56.4%. Most patients had mild elevation of pulmonary artery pressure (PAP). No difference in mortality was observed in patients with PH compared to patients with normal PAP (HR 0.
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