Biphasic Effect of Curcumin on Morphine Tolerance: A Preliminary Evidence from Cytokine/Chemokine Protein Array Analysis

The aim of this study was to evaluate the effect of curcumin on morphine tolerance and the corresponding cytokine/chemokine changes. Male ICR mice were made tolerant to morphine by daily subcutaneous injection for 7 days. Intraperitoneal injections of vehicle, low-dose or high-dose curcumin were administered 15 min after morphine injection, either acutely or chronically for 7 days to test the effect of curcumin on morphine-induced antinociception and development of morphine tolerance. On day 8, cumulative dose-response curves were generated and the 50% of maximal analgesic dose values were calculated and compared among groups. Corresponding set of mice were used for analyzing the cytokine responses by antibody-based cytokine protein array. Acute, high-dose curcumin enhanced morphine-induced antinociception. While morphine tolerance was attenuated by administration of low-dose curcumin following morphine injections for 7 days, it was aggravated by chronic high-dose curcumin following morphine injection, suggesting a biphasic effect of curcumin on morphine-induced tolerance. Of the 96 cytokine/chemokines analyzed by mouse cytokine protein array, 14 cytokines exhibited significant changes after the different 7-day treatments. Mechanisms for the modulatory effects of low-dose and high-dose curcumin on morphine tolerance were discussed. Even though curcumin itself is a neuroprotectant and low doses of the compound serve to attenuate morphine tolerance, high-doses of curcumin might cause neurotoxicity and aggravate morphine tolerance by inhibiting the expression of antiapoptotic cytokines and neuroprotective factors. Our results indicate that the effect of curcumin on morphine tolerance may be biphasic, and therefore curcumin should be used cautiously

Benthic Fluxes of Dissolved Organic Carbon from Gas Hydrate Sediments in the Northern South China Sea

Hydrocarbon vents have recently been reported to contribute considerable amounts of dissolved organic carbon (DOC) to the oceans. Many such hydrocarbon vents widely exist in the northern South China Sea (NSCS). To investigate if these hydrocarbon vent sites release DOC, we used a real-time video multiple-corer to collect bottom seawater and surface sediments at vent sites. We analyzed concentrations of DOC in these samples and estimated DOC fluxes. Elevated DOC concentrations in the porewaters were found at some sites suggesting that DOC may come from these hydrocarbon vents. Benthic fluxes of DOC from these sediments were 28 to 1264 µmol m−2 d−1 (on average ~321 µmol m−2 d−1 which are several times higher than most DOC fluxes in coastal and continental margin sediments. The results demonstrate that the real-time video multiple-corer can precisely collect samples at vent sites. The estimated benthic DOC flux from the methane venting sites (8.6 x 106 mol y-1, is 24% of the DOC discharge from the Pearl River to the South China Sea, indicating that these sediments make an important contribution to the DOC in deep waters

Mutation and Lineage Analysis of DNMT3A in BCR-ABL1-negative Chronic Myeloproliferative Neoplasms

SummaryIn addition to the JAK2 V617F mutation, somatic mutation in DNMT3A has been described in BCL-ABL1-negative myeloproliferative neoplasms (MPNs). We have screened for DNMT3A exon 23 mutations in 130 adult Taiwanese patients with chronic phase myeloproliferative neoplasms. Only one somatic DNMT3A R882H mutation was identified in one JAK2 V617F mutation-positive essential thrombocythemia patient (1/91, 1%). Both mutations were detected in the CD34+-, CD19+-, peripheral blood mononuclear cell- and granulocyte-enriched fractions, but were not detected in the CD3+-enriched fraction by lineage analysis. Our findings suggest that DNMT3A mutation is not prevalent in MPNs, and further study is needed to clarify its role in the molecular pathogenesis of myeloproliferative neoplasms

Efficient Phase Unwrapping Architecture for Digital Holographic Microscopy

This paper presents a novel phase unwrapping architecture for accelerating the computational speed of digital holographic microscopy (DHM). A fast Fourier transform (FFT) based phase unwrapping algorithm providing a minimum squared error solution is adopted for hardware implementation because of its simplicity and robustness to noise. The proposed architecture is realized in a pipeline fashion to maximize throughput of the computation. Moreover, the number of hardware multipliers and dividers are minimized to reduce the hardware costs. The proposed architecture is used as a custom user logic in a system on programmable chip (SOPC) for physical performance measurement. Experimental results reveal that the proposed architecture is effective for expediting the computational speed while consuming low hardware resources for designing an embedded DHM system

Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options

Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p

Bis-Tridentate Iridium(III) Phosphors Bearing Functional 2-Phenyl-6-(imidazol-2-ylidene)pyridine and 2-(Pyrazol-3-yl)-6-phenylpyridine Chelates for Efficient OLEDs

Proligands to the monoanionic tridentate chelate 4-(tert-butyl)-2-(2,4-difluorophenyl)-6-(3-isopropyl-imidazol-2-ylidene)pyridine ((phpyim-H2)PF6) and dianionic tridentate chelates derived from functional 2-pyrazol-3-yl-6-phenylpyridine chelates, i.e. L1-H2–L5-H2, have been synthesized and characterized. Treatment of (phpyim-H2)PF6 with [Ir(COD)(μ-Cl)]2 in the presence of sodium acetate, followed by heating at 200 °C with 1 equiv of the dianionic chelate, afforded the respective charge-neutral, bis-tridentate Ir(III) complexes [Ir(phpyim)(Ln)] (1–5; n = 1–5). The hydride complex [Ir(phpyim)(L5-H)(H)] (6) was made when the “one-pot” reaction of (phpyim-H2)PF6, [Ir(COD)(μ-Cl)]2, and L5-H2 was carried out at 140 °C. Complex 6 is likely an intermediate in the formation of 5, as it is converted to 5 on heating to 200 °C. Compounds 1–6 have been characterized by NMR spectroscopy and, in the cases of 1, 5, and 6, by X-ray structural analysis. TD-DFT computations confirmed that the emission bands are derived from 3MLCT transitions involving the chelates L1–L5, resulting in a wide range of emission wavelengths from 473 (cyan) to 608 nm (orange-red) observed for 1 – 5. A series of green- and red-emitting organic light-emitting diodes (OLEDs) with a simplified trilayer architecture were fabricated using the as-prepared Ir(III) complexes 2 and 5, respectively. A maximum external quantum efficiency of 18.8%, a luminance efficiency of 58.5 cd/A, and a power efficiency of 57.4 lm/W were obtained for the green-emitting OLEDs (2), which compares with 15.4%, 10.4 cd/A, and 9.0 lm/W obtained for the red-emitting OLEDs (5). The high efficiencies of these OLED devices suggest great potential for these bis-tridentate Ir(III) metal phosphors in the fabrication of multicolored OLED devices