Thiolactomide: A New Homocysteine Thiolactone Derivative from Streptomyces sp. with Neuroprotective Activity.

A new homocysteine thiolactone derivative, thiolactomide (1), was isolated along with a known compound, N-acetyl homocysteine thiolactone (2), from a culture extract of soil-derived Streptomyces sp. RK88-1441. The structures of these compounds were elucidated by detailed NMR and MS spectroscopic analyses with literature study. In addition, biological evaluation studies revealed that compounds 1 and 2 both exert neuroprotective activity against 6-hydroxydopamine (6-OHDA)-mediated neurotoxicity by blocking the generation of hydrogen peroxide in neuroblastoma SH-SY5Y cells.

Comparing Metabolites and Functional Properties of Various Tomatoes Using Mass Spectrometry-Based Metabolomics Approach.

Tomato is one of the world's most consumed vegetables, and thus, various cultivars have been developed. Therefore, metabolic differences and nutrient contents of various tomatoes need to be discovered. To do so, we performed metabolite profiling along with evaluation of morphological and physicochemical properties of five representative tomato types. Common tomato cultivars, bigger and heavier than other tomatoes, contained higher levels of amino acids, organic acids, and lipids. On the contrary, cherry tomato cultivars contained a higher proportion of phenylpropanoids, lycopene, ß-carotene, and α-carotene than the other tomatoes. Also, the highest antioxidant activity and total phenolic and flavonoid contents were observed in cherry tomato cultivars. Furthermore, to understand metabolic distributions in various tomato cultivars, we constructed a metabolic pathway map. The higher metabolic flux distribution of most primary metabolite synthetic pathways was observed in common tomatoes, while cherry tomato cultivars showed a significantly elevated flux in secondary metabolite synthetic pathways. Accordingly, these results provide valuable information of different characteristics in various tomatoes, which can be considered while purchasing and improving tomato cultivars.

Effects of Nutrient and Water Supply During Fruit Development on Metabolite Composition in Tomato Fruits (Solanum lycopersicum L.) Grown in Magnesium Excess Soils.

Tomato cultivation in the greenhouse or field may experience high surplus salts, including magnesium (Mg2+), which may result in differences in the growth and metabolite composition of fruits. This study hypothesized that decreasing the supply of nutrients and/or water would enhance tomato fruit quality in soils with excess Mg2+ that are frequently encountered in the field and aimed to find better supply conditions. For tomato plants cultivated in plastic pots using a plastic film house soil, the fertilizer supply varied in either the nitrogen (N) or potassium (K) concentration, which were either 0.1 (lowest) or 0.75 times (lower) than the standard fertilizer concentrations. Water was supplied either at 30 (sufficient) or 80 kPa (limited) of the soil water potential. Lycopene content on a dry-weight basis (mg/kg) was enhanced by the combination of lowest N supply and sufficient water supply. However, this enhancement was not occurred by the combination of the lowest N supply and limited water supply. Sugars and organic acids were decreased by limiting the water supply. Therefore, we carefully suggest that an adjustment of nitrogen with sufficient watering could be one of strategies to enhance fruit quality in excess Mg2+ soils.

Comparative Metabolomics Unravel the Effect of Magnesium Oversupply on Tomato Fruit Quality and Associated Plant Metabolism.

In general, greenhouse cultivation involves the rampant application of chemical fertilizers, with the aim of achieving high yields. Oversaturation with mineral nutrients that aid plant growth, development, and yield may lead to abiotic stress conditions. We explore the effects of excess magnesium on tomato plant metabolism, as well as tomato fruit quality using non-targeted mass spectrometry (MS)-based metabolomic approaches. Tomato plants were subjected to three different experiments, including high magnesium stress (MgH), extremely high magnesium stress (MgEH), and a control with optimal nutrient levels. Leaves, roots, and fruits were harvested at 16 weeks following the treatment. A metabolic pathway analysis showed that the metabolism induced by Mg oversupply was remarkably different between the leaf and root. Tomato plants allocated more resources to roots by upregulating carbohydrate and polyamine metabolism, while these pathways were downregulated in leaves. Mg oversupply affects the fruit metabolome in plants. In particular, the relative abundance of threonic acid, xylose, fucose, glucose, fumaric acid, malic acid, citric acid, oxoglutaric acid, threonine, glutamic acid, phenylalanine, and asparagine responsible for the flavor of tomato fruits was significantly decreased in the presence of Mg oversupply. Altogether, we concluded that Mg oversupply leads to drastically higher metabolite transport from sources (fully expanded leaves) to sinks (young leaves and roots), and thus, produces unfavorable outcomes in fruit quality and development.

Physiological and Metabolomic Responses of Kale to Combined Chilling and UV-A Treatment.

Short-term abiotic stress treatment before harvest can enhance the quality of horticultural crops cultivated in controlled environments. Here, we investigated the effects of combined chilling and UV-A treatment on the accumulation of phenolic compounds in kale (Brassica oleracea var. acephala). Five-week-old plants were subjected to combined treatments (10 °C plus UV-A LED radiation at 30.3 W/m2) for 3-days, as well as single treatments (4 °C, 10 °C, or UV-A LED radiation). The growth parameters and photosynthetic rates of plants under the combined treatment were similar to those of the control, whereas UV-A treatment alone significantly increased these parameters. Maximum quantum yield (Fv/Fm) decreased and H2O2 increased in response to UV-A and combined treatments, implying that these treatments induced stress in kale. The total phenolic contents after 2- and 3-days of combined treatment and 1-day of recovery were 40%, 60%, and 50% higher than those of the control, respectively, and the phenylalanine ammonia-lyase activity also increased. Principal component analysis suggested that stress type and period determine the changes in secondary metabolites. Three days of combined stress treatment followed by 2-days of recovery increased the contents of quercetin derivatives. Therefore, combined chilling and UV-A treatment could improve the phenolic contents of leafy vegetables such as kale, without growth inhibition.

Smartwatch User Interface Implementation Using CNN-Based Gesture Pattern Recognition.

In recent years, with an increase in the use of smartwatches among wearable devices, various applications for the device have been developed. However, the realization of a user interface is limited by the size and volume of the smartwatch. This study aims to propose a method to classify the user's gestures without the need of an additional input device to improve the user interface. The smartwatch is equipped with an accelerometer, which collects the data and learns and classifies the gesture pattern using a machine learning algorithm. By incorporating the convolution neural network (CNN) model, the proposed pattern recognition system has become more accurate than the existing model. The performance analysis results show that the proposed pattern recognition system can classify 10 gesture patterns at an accuracy rate of 97.3%.

Pentaminomycins A and B, Hydroxyarginine-Containing Cyclic Pentapeptides from Streptomyces sp. RK88-1441.

Two new cyclic peptides, pentaminomycins A (1) and B (2), were isolated from cultures of Streptomyces sp. RK88-1441. Based on the interpretation of the NMR, UV, IR, and MS data, the planar structures of 1 and 2 were elucidated as cyclic pentapeptides with a modified amino acid residue, N5-hydroxyarginine (N5-OH-Arg). The absolute configurations of the constituent amino acid residues were determined by the advanced Marfey's method. Localization of l- and d-amino acids in the sequence was ascertained by chiral analysis of the fragment peptide obtained from a partial hydrolysate; amino acids were identified by LC-MS. Pentaminomycin A (1) reduced α-MSH-stimulated melanin synthesis by suppressing the expression of melanogenic enzymes including tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2).

The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells.

Glioblastoma (GBM) is the most aggressive and malignant form of primary brain cancer. Despite recent advances in cancer treatment, it remains a substantially incurable disease. Accordingly, more effective GBM therapeutic options are urgently required. In the present study, we investigated the anticancer effect of a ginsenoside metabolite, compound K (CK), against GBM cells. CK significantly inhibited not only growth, but also metastatic ability of U87MG and U373MG cells. CK arrested cell cycle progression at the G0/G1 phase with a decrease in the expression levels of cyclin D1 and cyclin D3 in both cell types. CK also induced apoptosis in GBM cells through nuclear condensation, an increase in ROS generation, mitochondrial membrane potential depolarization, and activation of caspase-3, caspase-9 and poly(ADP-ribose) polymerase (PARP). Furthermore, CK inhibited phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, contributing to the antiproliferative and apoptotic effects. Moreover, CK suppressed the self-renewal capacity as well as the invasiveness of U87MG and U373MG GBM stem-like cells (GSCs) by inducing a reduction in the expression of GSC markers, such as CD133, Nanog, Oct4 and Sox2. Taken together, our findings suggest that CK may potentially be useful for GBM treatment.

Polyketides and Anthranilic Acid Possessing 6-Deoxy-α-l-talopyranose from a Streptomyces Species.

A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose. The absolute configuration of a polyketide extender unit of 3 was determined by applying the J-based configuration analysis and modified Mosher's method. Ulleungoside (1) and naphthomycin A (7) showed in vitro inhibitory effects against indoleamine 2,3-dioxygenase activity. Further bioevaluation revealed that compounds 1 and 7 had moderate antiproliferative activities against several cancer cell lines, and compounds 5 and 6, which are members of the piericidin family, induced autophagosome accumulation.

Structures and biological activities of azaphilones produced by Penicillium sp. KCB11A109 from a ginseng field.

Twelve metabolites, including five highly oxygenated azaphilones, geumsanols A-E, along with seven known analogues were isolated from Penicillium sp. KCB11A109, a fungus derived from a ginseng field. Their structures were assigned by spectroscopic means (NMR and MS), and stereochemistries were determined by extensive spectroscopic analyses ((1)H-(1)H coupling constants, NOESY, and HETLOC) and chemical derivatizations (modified Mosher's method and acetonide formation). The isolates were evaluated for their anticancer, antimicrobial, antimalarial activities, and phenotypic effects in zebrafish development. Of these compounds possessing no pyranoquinone core, only geumsanol E exhibited cytotoxic activities and toxic effects on zebrafish embryos, suggesting that a double bond at C-11 and C-12 is important for biological activity.

Etoposide Induces Necrosis Through p53-Mediated Antiapoptosis in Human Kidney Proximal Tubule Cells.

The p53 protein is an important transcription factor that modulates signaling pathways for both cell death and survival. Its antiapoptotic mechanisms that correlate with necrotic and apoptotic cell death are not well understood. Here, we report that etoposide promotes progression of the DNA damage response as well as necrotic morphological changes including plasma membrane rupture using carbon nanotube-tipped/atomic force microscopy (CNT/AFM) probes in human kidney proximal tubule (HK-2) cells. Inhibition of p53 abrogated cell cycle arrest and led to a decrease in the expression levels of repair proteins that were induced by DNA damage. Mitochondrial biogenesis and cytosolic production of reactive oxygen species were also reduced after p53 inhibition; the latter change induced mitochondrial superoxide accumulation and mitochondrial damage, which triggered the activation of caspase 3. Inhibition of p53 also led to a loss of cell adhesion and converted necrotic cell death to apoptotic cell death, with appreciable cell shrinkage and appearance of apoptotic bodies that were observed using CNT/AFM probes. Thus, our study demonstrated that p53 protects against apoptosis, and leads to etoposide-induced necrosis. These results are expected to aid in the understanding of mechanism of antiapoptosis and its relationship to cell death.