HC 067047

HC-067047 is a potent and selective TRPV4 antagonist with IC50 values of 48 ± 6 nM, 133 ± 25 nM, and 17 ± 3 nM, respectively in human, rat, and mouse. Also inhibits the endogenous TRPV4-mediated response to 4α-PDH (IC50 = 22 nM). target: TRPV4 IC 50: 48 ± 6 nM (human), 133 ± 25 nM (rat) , and 17 ± 3 nM (mouse) 1) The reference for administration of HC-067047 is 10 mg/kg (i.P) 2) HC-067047 caused a significant reduction of the maximal micturition pressure in rats, which might be caused by an effect on TRPV4 in smooth muscle. 3) HC-067047 Reduces Pollakisuria and Increases Functional Bladder Capacity 4) HC-067047 exhibits high selectivity toward TRPV4: IC50 values were at least 100-fold higher for the closely related channels TRPV1, TRPV2, and TRPV3, and 10-fold higher for TRPM8 and hERG.

References:
[1]. Everaerts W et al. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19084-9.

Carrier Decay Properties of Mixed Cation Formamidinium-Methylammonium Lead Iodide Perovskite [HC(NH2)2]1-x[CH3NH3]xPbI3 Nanorods.[Pubmed:27973912]

J Phys Chem Lett. 2016 Dec 15;7(24):5036-5043.

Organic-inorganic lead iodide perovskites are efficient materials for photovoltaics and light-emitting diodes. We report carrier decay dynamics of nanorods of mixed cation formamidinium and methylammonium lead iodide perovskites [HC(NH2)2]1-x[CH3NH3]xPbI3 (FA1-xMAxPbI3) synthesized through a simple solution method. The structure and FA/MA composition ratio of the single-crystal FA1-xMAxPbI3 nanorods are fully characterized, which shows that the mixed cation FA1-xMAxPbI3 nanorods are stabilized in the perovskite structure. The photoluminescence (PL) emission from FA1-xMAxPbI3 nanorods continuously shifts from 821 to 782 nm as the MA ratio (x) increases from 0 to 1 and is shown to be inhomogeneously broadened. Time-resolved PL from individual FA1-xMAxPbI3 nanorods demonstrates that lifetimes of mixed cation FA1-xMAxPbI3 nanorods are longer than those of the pure FAPbI3 or MAPbI3 nanorods, and the FA0.4MA0.6PbI3 displays the longest average PL lifetime of about 2 mus. These results suggest that mixed cation FA1-xMAxPbI3 perovskites are promising for high-efficiency photovoltaics and other optoelectronic applications.

Quantitative EEG (QEEG) Measures Differentiate Parkinson's Disease (PD) Patients from Healthy Controls (HC).[Pubmed:28167911]

Front Aging Neurosci. 2017 Jan 23;9:3.

Objectives: To find out which Quantitative EEG (QEEG) parameters could best distinguish patients with Parkinson's disease (PD) with and without Mild Cognitive Impairment from healthy individuals and to find an optimal method for feature selection. Background: Certain QEEG parameters have been seen to be associated with dementia in Parkinson's and Alzheimer's disease. Studies have also shown some parameters to be dependent on the stage of the disease. We wanted to investigate the differences in high-resolution QEEG measures between groups of PD patients and healthy individuals, and come up with a small subset of features that could accurately distinguish between the two groups. Methods: High-resolution 256-channel EEG were recorded in 50 PD patients (age 68.8 +/- 7.0 year; female/male 17/33) and 41 healthy controls (age 71.1 +/- 7.7 year; female/male 20/22). Data was processed to calculate the relative power in alpha, theta, delta, beta frequency bands across the different regions of the brain. Median, peak frequencies were also obtained and alpha1/theta ratios were calculated. Machine learning methods were applied to the data and compared. Additionally, penalized Logistic regression using LASSO was applied to the data in R and a subset of best-performing features was obtained. Results: Random Forest and LASSO were found to be optimal methods for feature selection. A group of six measures selected by LASSO was seen to have the most effect in differentiating healthy individuals from PD patients. The most important variables were the theta power in temporal left region and the alpha1/theta ratio in the central left region. Conclusion: The penalized regression method applied was helpful in selecting a small group of features from a dataset that had high multicollinearity.

Characterization and function analysis of a novel gene, Hc-maoc-1, in the parasitic nematode Haemonochus contortus.[Pubmed:28166831]

Parasit Vectors. 2017 Feb 6;10(1):67.

BACKGROUND: Enoyl-CoA hydratase (MAOC) is required for the biosynthesis of the fatty acid-derive side chains of the ascaroside via peroxisome beta-oxidation in the free-living nematode Caenorhabditis elegans. The derivative of dideoxy-sugar, ascarylose is used as dauer pheromones or daumones to induce development of the stress-resistant dauer larvae stage. METHODS: Hc-maoc-1 gene was obtained by searching the Wellcome Trusts Sanger Institute's H. contortus genomic database. qRT-PCR was performed to analyse the transcriptional levels of Hc-maoc-1 with different developmental stages as templates. IFA was carried out to determine the expression pattern in L3 larvae and micro-injection was used to verify the promoter activity of 5'-flanking region of Hc-maoc-1. Overexpression and RNAi experiments were applied in N2 strain to ascertain the gene function of Hc-maoc-1. RESULTS: The full-length cDNA of Hc-maoc-1 was 900 bp in length, which contained eight exons separated by seven introns and possessed the Hotdog domain and the MaoC-like domain, together with several other residues and a hydratase 2 motif. It was transcribed throughout the lifecycle and peaked in the fourth-stage larvae (L4) of H. contortus; however, its transcription level decreased in diapausing L4. The protein expression and location of Hc-MAOC-1 were mainly in the intestine of L3 larvae. Overexpression of Ce-maoc-1 and Hc-maoc-1 in C. elegans showed extended lifespan and increased body size. The protein Ce-MAOC-1 and Hc-MAOC-1 were localized in the intestine with a punctate pattern. In C. elegans, knockdown of Ce-maoc-1 conferred shortened lifespan and body lengths, decreased brood size and increased lipid storage. CONCLUSION: Caenorhabditis elegans was used as a model organism to ascertain the function of Hc-maoc-1 in H. contortus. Our results showed the similar characteristics and functions with Ce-maoc-1 and provided evidences of the potential functions of Hc-maoc-1 in biosynthesis of daumones in H. contortus.

Investigation on the structure-activity relationship of BaO promoting Pd/CeO2-ZrO2 catalysts for CO, HC and NOx conversions.[Pubmed:28262870]

Phys Chem Chem Phys. 2017 Mar 15;19(11):7844-7852.

Four different synthetic routes (co-precipitation, oxidation-precipitation, citric acid sol-gel and reversed microemulsion) are adopted to prepare barium modified Pd/CeO2-ZrO2 catalysts and their catalytic activity towards CO, HC and NOx conversions is studied. The surface and bulk properties of these catalysts are characterized via XRD, N2 adsorption, XPS, UV-Raman, H2-TPR, and in situ DRIFTS. The catalyst prepared via the co-precipitation method exhibits the optimum three-way catalytic behavior, which is mainly due to its superior redox ability, whereas the oxidation-precipitation synthesis renders the catalyst with the best homogeneity and thermal resistance. However, for the catalyst prepared via the sol-gel route, its worst NOx reduction capacity is verified by the scarce appearance of negatively charged Pd(0)-N[double bond, length as m-dash]O(delta-) species, which is related to the faster dissociation of NO based on in situ DRIFTS, and the abundance of surface CO-Pd(+) species reveals its unsatisfactory deep oxidizability of the HC reactant.

HC-067047 is a potent and selective TRPV4 antagonist and reversibly inhibits currents through the human, rat, and mouse TRPV4 orthologs with IC50 values of 48 nM, 133 nM, and 17 nM, respectively.

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