Recombinant Zebrafish ␥-Glutamyl Hydrolase Exhibits Properties and Catalytic Activities Comparable with Those of Mammalian Enzyme

ABSTRACT: A cDNA encoding for zebrafish ␥-glutamyl hydrolase (␥GH) was cloned and inserted into a pET43.1a vector via SmaI and EcoRI sites and expressed in Rosetta (DE3) cells as a Nus-His-tag fusion enzyme (NH-z␥GH). After induction with isopropyl thiogalactoside, the enzyme was purified with a Ni-Sepharose column, and approximately 8 mg of pure enzyme was obtained per liter of culture. The primary sequence of the recombinant z␥GH was similar to mammalian ␥GH. Folate is an essential B vitamin and participates in the biosynthesis and metabolism of nucleic acids, proteins, several amino acids, methyl groups, many neurotransmitters, and some vitamins. Mammalian cells are unable to synthesize folates de novo and therefore depend on their food for the supply of folates. Naturally occurring folates are synthesized as poly-␥-glutamate forms (folylpolyglutamate) but are absorbed and transported most efficiently as folylmonoglutamates. The conversion of folylpolyglutamates in dietary food to folylmonoglutamates is catalyzed by carboxypeptidase II (EC 3.4.22.12) in mammals. In a recent study, ␥-glutamyl hydrolase (␥GH, EC 3.4.19.9), a lysosomal cysteine peptidase, was reported to be the enzyme responsible for hydrolyzing dietary folate in rat small intestine Consistent with this notion, the activity of ␥GH to hydrolyze the ␥-glutamyl peptide bonds of folylpolyglutamates has rendered this enzyme a potential target of antifolate chemotherapy and, at the same time, a primary component in regulating the intracellular levels of some antifolate drugs. Antifolate drugs, such as methotrexate, owe much of their effectiveness to being substrates for both folylpoly-␥-glutamate synthetase and ␥GH. Removal of ␥-linked glutamate residues decreases the retention and activity of these drugs. A polymorphism resulting in reduced catalytic activity of ␥GH was observed to be associated with greater accumulation of long-chain methotrexate polyglutamate forms The determination of individual folate derivatives in serum of patients receiving antifolate chemotherapy and in foods is an important current protocol. The first step in these determinations is converting folylpolyglutamates to folylmonoglutamates by ␥GH. Cur- The amino acid numbering used for z␥GH in this study is numbered starting from the first methionine in the full-length peptide with the signal peptide. Article, publication date, and citation information can be found a

Deploying Image Deblurring across Mobile Devices: A Perspective of Quality and Latency

Recently, image enhancement and restoration have become important applications on mobile devices, such as super-resolution and image deblurring. However, most state-of-the-art networks present extremely high computational complexity. This makes them difficult to be deployed on mobile devices with acceptable latency. Moreover, when deploying to different mobile devices, there is a large latency variation due to the difference and limitation of deep learning accelerators on mobile devices. In this paper, we conduct a search of portable network architectures for better quality-latency trade-off across mobile devices. We further present the effectiveness of widely used network optimizations for image deblurring task. This paper provides comprehensive experiments and comparisons to uncover the in-depth analysis for both latency and image quality. Through all the above works, we demonstrate the successful deployment of image deblurring application on mobile devices with the acceleration of deep learning accelerators. To the best of our knowledge, this is the first paper that addresses all the deployment issues of image deblurring task across mobile devices. This paper provides practical deployment-guidelines, and is adopted by the championship-winning team in NTIRE 2020 Image Deblurring Challenge on Smartphone Track.Comment: CVPR 2020 Workshop on New Trends in Image Restoration and Enhancement (NTIRE

Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online)

BACKGROUND: The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. RESULTS: Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO , to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. CONCLUSION: This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment

Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level

<p>Abstract</p> <p>Background</p> <p>Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats.</p> <p>Methods</p> <p>One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured.</p> <p>Results</p> <p>Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea.</p> <p>Conclusion</p> <p>These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.</p

Low-molecular-weight fucoidan ameliorates calcium-deficient-diet–induced bone loss and osteoarthritis via CaSR level regulation

Fucoidans—sulfated and fucosylated polysaccharides extracted from brown seaweed—reportedly accelerate bone growth and prevent osteoarthritis (OA) progression. In this study, we examined the effects of low-molecular-weight fucoidan (LMF) on the molecular mechanism of extracellular calcium concentration in vitro and in vivo. In MG63 cells, LMF significantly increased the activity of alkaline phosphatase (ALP) and expression of calcium-sensing receptor (CaSR), runt-related transcription factor 2 (Runx2), and osteoprotegerin (OPG) under low- and normal-[Ca+2]0 conditions, but only decreased the expression of receptor activator of the nuclear factor κB ligand (RANKL) under normal-[Ca+2]0 conditions. In the calcium-deficient diet model, LMF significantly increased body length, growth rate, bone-specific ALP secretion, trabecular number, and CaSR protein expression, without body weight changes. In the OA model, LMF significantly increased bone volume and CaSR protein expression and reduced joint inflammation. Overall, our results indicate that LMF reduced calcium-deficient-diet–induced bone loss and OA via CaSR level regulation

Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression

Propylene Glycol Improves Stability of the Anti-Inflammatory Compounds in Scutellaria baicalensis Extract

Scutellaria baicalensis root extracts have been useful for external skin care and have been commercialized for years. Here, a comprehensive study was conducted to investigate the difference between 20% propylene glycol (PG) and water used as the storage solvent for a time course analysis of their remaining biological activities and ingredient compositions versus their freshly prepared conditions. Of the four major components in the 20% PG solvent, more than 80% of the components were retained after storage for two months, but in water only baicalin and wogonin were retained. The relative antibacterial activities, antioxidant properties and anti-inflammatory activities of the 20% PG solvent group were better than those of the water solvent group. Taken together, we demonstrated that these activities improved when PG, a common solvent used in many product formulas, was used as the storage solvent for the S. baicalensis extract

A facile approach from waste to resource: Reclaimed rubber-derived membrane for dye removal

The polymer precursor plays a vital role in the membrane structure, as well as its permeance and rejection capability. In general, the polymer utilized in research is purified many times to obtain a higher purity, thus resulting in expensive and energy-consuming raw materials for membranes. Herein, we propose a facile method to prepare a nanofiltration hollow fiber membrane via reclaimed rubber recovered from waste tires as a precursor. The permeation tests reveal that the rubber-derived membrane with 12 wt% precursor concentration and three internal coating times exhibited the best performance for dye removal, with a methyl blue rejection rate of up to 93.1%. After three further filtration cycles, the permeate permeance obtained from the R1-12-L3 membrane could be maintained at 8.3 LMH/bar with a methyl blue rejection rate of 98.1%. These experimental results indicate that the rubber-derived hollow fiber membrane could be a feasible alternative for wastewater purification due to its low-cost, high-performing, and self-cleaning properties