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Background Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release. Methods We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes. Results After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated. Conclusion Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation.

Background. Although the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR- TKI) therapy has been proven in non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs presents a serious clinical problem. Hence, the identification of new therapeutic strategy is needed to treat EGFR-TKI-resistant NSCLC. Methods. Acquired EGFR-TKI-resistant lung cancer cell lines (HCC827, H1993, and H292 cells with acquired resistance to gefitinib or erlotinib) were used for cell-based studies. IncuCyte live cell analysis system and XFp analyzer were used for the determination of cell proliferation and energy metabolism, respectively. In vivo anticancer effect of phenformin was assessed in xenografts implanting HCC827 and gefitinib-resistant HCC827 (HCC827 GR) cells. Results. HCC827 GR and erlotinib-resistant H1993 (H1993 ER) cells exhibited different metabolic properties compared with their respective parental cells, HCC827, and H1993. In EGFR-TKI-resistant NSCLC cells, glycolysis markers including the glucose consumption rate, intracellular lactate level, and extracellular acidification rate were decreased; however, mitochondrial oxidative phosphorylation (OXPHOS) markers including mitochondria-driven ATP production, mitochondrial membrane potential, and maximal OXPHOS capacity were increased. Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells. Inhibition of OXPHOS resulted in a reduced NAD+/NADH ratio and intracellular aspartate levels. Recovery of glycolysis by hexokinase 2 overexpression in erlotinib-resistant H292 (H292 ER) cells significantly reduced the anticancer effects of phenformin. Conclusion. Long-term treatment with EGFR-TKIs causes reactivation of mitochondrial metabolism, resulting in vulnerability to OXPHOS inhibitor such as phenformin. We propose a new therapeutic option for NSCLC with acquired EGFR-TKI resistance that focuses on cancer metabolism.

Nano-polystyrene has gained considerable attention because of its growing accumulation in the environment. Although several studies have attempted to elucidate its action on physiological functions, studies investigating human metabolic disturbance were scarce. This study developed two investigative designs using exposure to human epithelial colorectal cells (Caco-2); the first exposed cells to a high concentration of 50 nm nano-polystyrene for 24 h (acute), whilst the second exposed cells to a relatively lower concentration for over 1.5 months (chronic). Exposure concentrations were determined based on bioassays: 10 and 80 μg mL−1 for the acute model and 0.1 μg mL−1 for the chronic exposure model. Following acute exposure, untargeted metabolic profiling revealed the alteration in lipid metabolic pathways, including steroid and arachidonic acid metabolism. On the other hand, chronic exposure induced relatively minor disturbances. However, there was still a potential effect on fatty acid biosynthesis, indicating that acute and chronic exposure to nano-polystyrene may disturb lipid homeostasis. We also confirmed changes in the expression levels of lipid transcriptional regulatory factor coding genes, namely sterol regulatory element-binding transcription factors 1 and 2. The total fatty acid composition was further investigated to verify metabolic disturbance by chronic exposure. Our findings indicated that both exposure conditions of high concentration with a short period and low concentration with an extended period to nano-polystyrene were associated with the cellular disturbance of the lipid metabolism.

Mitochondrial metabolism plays an essential role in various biological processes of cancer cells. Herein, we established an experimental procedure for the metabolic assessment of mitochondria in cancer cells. We examined procedures for mitochondrial isolation coupled with various mitochondrial extraction buffers in three major cancer cell lines (PANC1, A549, and MDA-MB-231) and identified a potentially optimal and generalized approach. The purity of the mitochondrial fraction isolated by the selected protocol was verified using specific protein markers of cellular components, and the ultrastructure of the isolated mitochondria was also analyzed by transmission electron microscopy. The isolation procedure, involving a bead beater for cell lysis, a modified sucrose buffer, and differential centrifugation, appeared to be a suitable method for the extraction of mitochondria from cancer cells. Electron micrographs indicated an intact two-layer membrane and inner structures of mitochondria isolated by this procedure. Metabolomic and lipidomic analyses were conducted to examine the metabolic phenotypes of the mitochondria-enriched fractions and associated bulk cancer cells. A total of 44 metabolites, including malate and succinate, occurred at significantly higher levels in the mitochondrial fractions, whereas 51 metabolites, including citrate, oxaloacetate, and fumarate of the Krebs cycle and the oncometabolites glutamine and glutamate, were reduced in mitochondria compared to that in the corresponding bulk cells of PANC1. Similar patterns were observed in mitochondria and bulk cells of MDA-MB-231 and A549 cell lines. A clear difference between the lipid profiles of bulk PANC1, MDA-MB-231, and A549 and corresponding mitochondrial fractions of these cell lines was detected by principal component analysis. In conclusion, we developed an experimental procedure for a large-scale metabolic assessment for suborganelle metabolic profiling and multiple omics data integration in cancer cells with broad applications.

Lipidomics is a subfield of metabolic phenotyping that focuses on high-throughput profiling and quantification of lipids. Essential roles of lipidomics in translational and clinical research have emerged, especially over the past decade. Most lipidomic pipelines have been developed using mass spectrometry (MS)-based methods. Because of the complexity of the data, generally, computational demands are much higher in untargeted lipidomic studies. In the current paper, we primarily discussed the recent advances in untargeted liquid chromatography–mass spectrometry-based lipidomics, covering various facets from analytical strategies to functional interpretations. The current practice of tandem MS-based lipid annotation in untargeted lipidomics studies was demonstrated. Notably, we highlighted the essential characteristics of machine learning models, together with a data partitioning strategy, to facilitate appropriate modeling and validation in metabolic phenotyping studies. Critical aspects of data sharing were briefly mentioned. Finally, certain recommendations were suggested toward more standardized and sustainable lipidomics analysis strategies as independent platforms, and as members of the omics family.

Background Although the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR- TKI) therapy has been proven in non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs presents a serious clinical problem. Hence, the identification of new therapeutic strategy is needed to treat EGFR-TKI-resistant NSCLC. MethodsAcquired EGFR-TKI resistant lung cancer cell lines (HCC827, H1993 and H292 cells with acquired resistance to gefitinib or erlotinib) were used for cell-based studies. IncuCyte live cell analysis system and XFp analyzer were used for the determination of cell proliferation and energy metabolism, respectively. In vivo anti-cancer effect of phenformin was assessed in xenografts implanting HCC827 and gefitinib-resistant HCC827 (HCC827 GR) cells. ResultsHCC827 GR and erlotinib-resistant H1993 (H1993 ER) cells exhibited different metabolic properties compared with their respective parental cells, HCC827 and H1993. In EGFR-TKI-resistant NSCLC cells, glycolysis markers including the glucose consumption rate, intracellular lactate level, and extracellular acidification rate were decreased; however, mitochondrial oxidative phosphorylation (OXPHOS) markers including mitochondria-driven ATP production, mitochondrial membrane potential, and maximal OXPHOS capacity were increased. Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells. Inhibition of OXPHOS resulted in a reduced NAD+/NADH ratio and intracellular aspartate levels. Recovery of glycolysis by hexokinase 2 overexpression in erlotinib-resistant H292 (H292 ER) cells significantly reduced the anti-cancer effects of phenformin.Conclusion Long-term treatment with EGFR-TKIs causes reactivation of mitochondrial metabolism, resulting in vulnerability to OXPHOS inhibitor such as phenformin. We propose a new therapeutic option for NSCLC with acquired EGFR-TKI resistance that focuses on cancer metabolism.

Many studies have analyzed the effects of β-cryptoxanthin (BCX) on osteoporosis and bone health. This systematic review and meta-analysis aimed at providing quantitative evidence for the effects of BCX on osteoporosis. Publications were selected and retrieved from three databases and carefully screened to evaluate their eligibility. Data from the final 15 eligible studies were extracted and uniformly summarized. Among the 15 studies, seven including 100,496 individuals provided information for the meta-analysis. A random effects model was applied to integrate the odds ratio (OR) to compare the risk of osteoporosis and osteoporosis-related complications between the groups with high and low intake of BCX. A high intake of BCX was significantly correlated with a reduced risk of osteoporosis (OR = 0.79, 95% confidence interval (CI) 0.70–0.90, p = 0.0002). The results remained significant when patients were stratified into male and female subgroups as well as Western and Asian cohorts. A high intake of BCX was also negatively associated with the incidence of hip fracture (OR = 0.71, 95% CI 0.54–0.94, p = 0.02). The results indicate that BCX intake potentially reduces the risk of osteoporosis and hip fracture. Further longitudinal studies are needed to validate the causality of current findings.

Ginseng, officially known asWe compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes.After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated.Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of

Since the introduction of the first monoclonal antibody, biopharmaceuticals and biotherapeutic products manufactured in cellular factories are on the rise in modern medicine and therapeutics. Dynamic and real-time innovation strategies for operational implementation of biotherapeutic production are rapidly emerging. The advances in related fields such as genome editing technology, systems biology, and machine learning/artificial intelligence are expected to introduce innovative solutions in every aspect of the mammalian cell culture-based biotherapeutic production. This conceptual review offers a synthesis of the prospects and challenges of integration of multiomics technologies, and an integrative biology vision to cellular factories and biotherapeutic innovation.

Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention. This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline, randomized controlled trials on the effects of ginger were investigated. Accordingly, 109 eligible papers were fully extracted in terms of study design, population characteristics, evaluation systems, adverse effects, and main outcomes. The reporting quality of the included studies was assessed based on the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials and integrated together with studies that investigated the same subjects. The included studies that examined the improvement of nausea and vomiting in pregnancy, inflammation, metabolic syndromes, digestive function, and colorectal cancer’s markers were consistently supported, whereas other expected functions were relatively controversial. Nevertheless, only 43 clinical trials (39.4%) met the criterion of having a ‘high quality of evidence.’ In addition to the quality assessment result, small populations and unstandardized evaluation systems were the observed shortcomings in ginger clinical trials. Further studies with adequate designs are warranted to validate the reported clinical functions of ginger.

Perfluorinated compounds (PFCs) are widely used in consumer products because of their remarkable endurance. However, their distinct stability prolongs degradation, resulting in bioaccumulation in the environment which is a severe environmental issue. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are principal constituents in the PFCs. In this study, the potential toxic effects of PFOS and PFOA were evaluated by adopting an in vivo animal model, Caenorhabditis elegans (C. elegans). The uptake of PFCs was confirmed by the quantification of internal concentration in C. elegans. Metabolomics and lipidomics were applied along with reproduction assay and reactive oxygen species (ROS) assay. In the C. elegans exposed to PFOS and PFOA, amino acids including phenylalanine, tyrosine, and tryptophan, were significantly affected. Also, various species that belong to glycerophospholipids and triacylglycerol were perturbed in the exposed groups. The alteration patterns of the lipidome in PFOS and PFOA treated C. elegans were significantly different. Additionally, dichlorodihydrofluorescein diacetate (H2DCFDA)-based ROS assay revealed increased internal ROS in PFOS (1.5 fold, p-value = 0.0067) and PFOA (1.46 fold, p-value = 0.0253) groups. Decrease in reproduction was confirmed in PFOS (0.53 fold, p-value

Steroidomics, an analytical technique for steroid biomarker mining, has received much attention in recent years. This systematic review and functional analysis, following the PRISMA statement, aims to provide a comprehensive review and an appraisal of the developments and fundamental issues in steroid high-throughput analysis, with a focus on cancer research. We also discuss potential pitfalls and proposed recommendations for steroidomics-based clinical research. Forty-five studies met our inclusion criteria, with a focus on 12 types of cancer. Most studies focused on cancer risk prediction, followed by diagnosis, prognosis, and therapy monitoring. Prostate cancer was the most frequently studied cancer. Estradiol, dehydroepiandrosterone, and cortisol were mostly reported and altered in at least four types of cancer. Estrogen and estrogen metabolites were highly reported to associate with women-related cancers. Pathway enrichment analysis revealed that steroidogenesis; androgen and estrogen metabolism; and androstenedione metabolism were significantly altered in cancers. Our findings indicated that estradiol, dehydroepiandrosterone, cortisol, and estrogen metabolites, among others, could be considered oncosteroids. Despite noble achievements, significant shortcomings among the investigated studies were small sample sizes, cross-sectional designs, potential confounding factors, and problematic statistical approaches. More efforts are required to establish standardized procedures regarding study design, analytical procedures, and statistical inference.

Sleep deprivation (SD) is known to be associated with metabolic disorders and chronic diseases. Complex metabolic alterations induced by SD at omics scale and the associated biomarker candidates have been proposed. However, in vivo systemic and local metabolic shift patterns of the metabolome and lipidome in acute and chronic partial SD models remain to be elucidated. In the present study, the serum, hypothalamus, and hippocampus CA1 of sleep-deprived rats (SD rats) from acute and chronic sleep restriction models were analyzed using three different omics platforms for the discovery and mechanistic assessment of systemic and local SD-induced dysregulated metabolites. We found a similar pattern of systemic metabolome alterations between two models, for which the area under the curve (AUC) of receiver operating characteristic curves was AUC = 0.847 and 0.930 with the pseudotargeted and untargeted metabolomics approach, respectively. However, SD-induced systemic lipidome alterations were significantly different and appeared to be model-dependent (AUC = 0.374). Comprehensive pathway analysis of the altered lipidome and metabolome in the hypothalamus indicated the abnormal behavior of eight metabolic and lipid metabolic pathways. The metabolic alterations of the hippocampus CA1 was subtle in two SD models. Collectively, these results extend our understanding of the quality of sleep and suggest metabolic targets in developing diagnostic biomarkers for better SD control.

There is a growing concern regarding the toxic effects of terrestrial nanoplastic contaminants. However, an all-encompassing phenotyping- and omics-based strategy for the toxicity assessment of nanoplastics with different surface properties on soil living organisms remains to be established. Herein, we devised a comprehensive phenotyping and multi-omic profiling method to examine the molecular disturbance of nanopolystyrene (PS)-exposed Caenorhabditis elegans. The exposure time was 24 h with either 1 μg/mL or 10 μg/mL of PS. We found that PS considerably affected the reproduction and locomotion, as well as increased the oxidative stress of worms regardless of their surface properties. Nevertheless, each type of PS affected the metabolome and lipidome of the nematodes differently. Uncharged PS (PS-N) triggered significant metabolic disturbances, whereas the metabolic influences from PS-NH2 and PS-COOH were subtle. The dysregulated transcriptome profiles of PS-N were strongly associated with the metabolic pathways. Besides, the altered expression of several genes associated with autophagy and longevity was observed. Collectively, we demonstrated that comprehensive phenotyping and omics-based profiling establish a practical framework that allows us to gain deeper insights into the maladaptive consequences of PS in nematodes. It can be utilized for the evaluation of other environmental contaminants in the terrestrial ecosystem.

Samsung Display LCD RD Revised May 3, 2012; Accepted May 10, 2012) Abstract: For the application of photo-detector as active layer, we have studied how to deposit SiGe thin film using an independent Si target and Ge target, respectively. Both targets were synthesized by purity of 99.999%. Plasma generators were generated by radio frequency (rf, 13.56 MHz) and direct current (dc) power. When Ge and Si targets were sputtered by dc and rf power, respectively, we could observe the growth of highly crystalline Ge thin film at the temperature of 400℃ from the result of raman spectroscopy and X-ray diffraction method. However, SiGe thin film did not deposit above method. Inversely, we changed target position like that Ge and Si targets were sputtered by rf and dc power, respectively. Although Ge crystalline growth without Si target sputtering deteriorated considerably, the growth of SiGe thin film was observed with increase of Si dc power. SiGe thin film was evaluated as microcrystalline phase which included (111) and (220) plane by X-ray diffraction method.Keywords: Microcrystalline SiGe, Sputtering, Raman spectroscopy, IR detector, Touch screen

This study was conducted to identify main carotenoids in red pepper and to investigate pigment stability during drying and storage. The main pigments in saponified extracts were capsanthin, zeaxanthin, β-cryptoxanthin, β-carotene, and an unknown peak, which was considered to be capsorubin by spectrophotometry and liquid chromatography/mass spectrometry (LC/MS). Myristoylcapsanthin, lauroylmyristoylcapsanthin, and myristoylpalmitoylcapsanthin were identified from unsaponified extracts analyzing fragment ions by LC/MS. In capsanthin stability, the difference in drying method had the most influence until 2-mo storage, whereas after 2-mo storage, temperature became the major factor. Myristoylpalmitoylcapsanthin was more stable than myristoylcapsanthin during storage.

Neural probes are made on silicon substrate using a micromachining process with low temperature steps only. A deep silicon etch ("Bosch") process was used for the probe shaping. CMOS compatibility of the process was checked and reported in this paper. Test transistor patterns generated using standard CMOS fabrication line were exposed to a post-CMOS probe making process including dielectric deposition, gold metalization and the dry etching step, while changes of test transistor characteristics were monitored. Threshold voltage was found virtually unchanged for both nand p-type MOS transistors. When excess plasma exposure was done, however, non-trivial shift in p-MOS threshold was observed.

Accurate measurement of blood flow is usually very difficult and invasive to make in spite of its important roles in clinical diagnosis. Therefore, an alternative method capable of determining the cardiac output non-invasively will be of good use. Furthermore, measurement of blood velocity with high resolution either in the heart or in any part of circulatory system without any cardiac catheterization would play an important role in the evaluation of patients with circulatory disorders. The MRI phase contrast technique (PC-MRI) can be used for this purpose. It can provide flow velocity information in addition to anatomic imaging by applying bipolar gradient in the velocity encoding direction. We can obtain velocity encoded MR images computed by the phase difference between two images acquired with different gradient first moments but identical zeroth moments. We combined phase contrast sequence and cine method to acquire the velocity map across the entire cardiac cycle. ECG gating was used for triggering. We calculated volume flow by pixel unit velocity analysis in the region of interest. Also by visualizing the velocity profile dynamically with 3D representation, we could assess more easily how the appearances of blood flow patterns are. The proposed method was tested both with a phantom where a pulsatile waveform was generated by ventricular assistance device and in vivo at the heart of normal volunteer on a GE 1.5 T scanner. As a conclusion, the dynamically represented 3D images obtained by the cine PC method could be confirmed as a good method for assessment of cardiac function.

Monitoring over a 12 month period in the Sanae creek flow in acid mine drainage, Donghae coal mine area, demonstrates that the concentrations of dissolved metals and sulphate are highest during autumn when water flow in the creek is at its lowest. The highest pH values of the stream were measured in April and May, whereas the lowest pH was recorded in October. The Fe concentration of stream water rapidly decreased downstream due to the precipitation of Fe oxyhydroxide and/or oxyhydroxysulfate phases in the stream. Mineral precipitates in the creek in the Donghae mine area show various colours such as brownish yellow (Munsell colour 9.5 YR hues), reddish brown (Munsell colour 3.5 YR hues) and white depending on seasons and distance from the pollution source in the creek. Such phenomena are attributed to the variation in pH and chemical composition of stream water caused by seasonal factors. The measured pH ranges in stream water of the brownish yellow, white and reddish brown precipitates are pH 3.2-4.5, 4.5-6.0 and 5.3-6.9, respectively.

The study attempts to characterize the acoustic emission from a moving actuator type, totally implantable, electromechanical, artificial heart. In vitro measurements were made on the acoustic emission from the artificial heart using a highly sensitive measuring microphone, under various operating conditions. Time-frequency spectral analysis, based on the reduced interference distribution kernel, was employed to identify the effects of control parameters of the artificial heart on the acoustic emission. The control parameters considered in this study were the electric current supplied to the d.c. motor of the artificial heart, stroke angle, and the initial interventricular space pressure. The measured acoustic signals were seen to be nonstationary even if a beat cycle yields the periodical repetition by the heart rate. It was shown that the primary spectral peak occurred at 370 Hz under normal operating conditions: stroke angle 140°, initial interventricular space pressure 0 mmHg, and current level 15. The current level used here has no unit and is not directly related to the actual current but controls the motor speed. The primary peak frequency linearly increased with the current level, but was insensitive to the initial interventricular space pressure. When the current level was high, several secondary peaks appeared above 1100 Hz which did not exist at low current levels. The time-frequency energy distribution revealed that the primary frequency, representing the rotational velocity of the motor, was apparent around the middle of both systolic and diastolic periods, and reached its maximum. In contrast, the secondary high-pitched sounds appeared as the cycle approached the end of the systolic period of the left ventricle. It seems that these high-frequency spectral peaks resulted from sac folding and gear sliding. The influence of the motor current on acoustic spectra becomes more significant if the stroke angle of the actuator is increased.