Effects of gypenoside L-containing Gynostemma pentaphyllum extract on fatigue and physical performance: A double-blind, placebo-controlled, randomized trial.

This study was conducted to investigate the effect of Gynostemma pentaphyllum extract containing gypenoside L (GPE) on improving the cognitive aspects of fatigue and performance of the motor system. One hundred healthy Korean adults aged 19-60 years were randomized to the treatment (GPE for 12 weeks) and control groups, and efficacy and safety-related parameters were compared between the two groups. Maximal oxygen consumption (VO2 max) and O2 pulse were significantly higher in the treatment group than in the control group (p = 0.007 and p = 0.047, respectively). After 12 weeks, the treatment group showed significant changes such as decreases in the levels of free fatty acids (p = 0.042). In addition, there were significant differences in the rating of perceived exertion (RPE) (p < 0.05) and value of temporal fatigue between the treatment and control groups on the multidimensional fatigue scale (p < 0.05). Moreover, the level of endothelial nitric oxide synthase (eNOS) in the blood was significantly higher in the treatment group than in the control group (p = 0.047). In summary, oral administration of GPE has a positive effect on resistance to exercise-induced physical and mental fatigue.

Comparative study of estrogenic activities of phytoestrogens using OECD in vitro and in vivo testing methods.

With growing scientific interest in phytoestrogens, a number of studies have investigated the estrogenic potential of phytoestrogens in a wide variety of assay systems. However, evaluations of individual phytoestrogens with different assay systems make it difficult for predicting their relative estrogenic potency. The objective of this study was to compare estrogenic properties of fifteen known phytoestrogens using an estrogen receptor-α (ER-α) dimerization assay and Organization for Economic Cooperation and Development (OECD) standardized methods including in vitro estrogen receptor (ER) transactivation assay using VM7Luc4E2 cells and in vivo uterotrophic assay using an immature rat model. Human ER-α dimerization assay showed positive responses of eight test compounds and negative responses of seven compounds. These results were consistently found in luciferase reporter assay results for evaluating ER transactivation ability. Seven test compounds exhibiting relatively higher in vitro estrogenic activities were subjected to uterotrophic bioassays. Significant increases in uterine weights were only found after treatments with biochanin A, 8-prenylnaringenin, and coumestrol. Importantly, their uterotrophic effects were lost when animals were co-treated with antagonist of ER, indicating their ER-dependent effects in the uterus. In addition, analysis of estrogen responsive genes revealed that these phytoestrogens regulated uterine gene expressions differently compared to estrogens. Test methods used in this study provided a high consistency between in vitro and in vivo results. Thus, they could be used as effective screening tools for phytoestrogens, particularly focusing on their interactions with ER-α.

Development and characterization of a human cell line-based transactivation assay to assess thyroid EDCs.

Thyroid hormones (THs) are one of the most important hormones, playing key roles in the regulation of various physiological functions. Although THs have important function in human, in vitro test methods based on human cells are currently insufficient to effectively screen and test TH-related endocrine disrupting chemicals (EDCs). We established a TH agonist TA assay using the adenocarcinomic human alveolar basal epithelial cell line A549 to test and screen potential TH agonists. To establish the TH agonist TA assay, a TRE-secNluc-IRES-EGFP reporter cassette was constructed and transfected into the A549 cell line using a retrovirus. We evaluated the TH agonistic properties of several chemicals which were tested by existing thyroid agonists testing method (OECD GD 207). Comparing the results of the TH agonist TA assay with the OECD GD 207, T3, T4, tiratricol, and tetrac (natural TH and 3,3',5,5'-tetraiodothyroacetic acid derivatives), which are TH agonists according to the OECD GD 207, also tested positive in the TH agonist TA assay using the A549 cell line. These results suggested that the TH agonist TA assay developed in this study using a human cell line can provide the information, such as accuracy and specificity to TH agonistic properties of chemicals.

Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line.

Endocrine-disrupting chemicals (EDCs) interfere with the biological activity of hormones. Among EDC's, (anti-)androgenic compounds potentially cause several androgen-related diseases. To improve the accuracy of an in vitro transactivation assay (TA) for detection of (anti-)androgenic compounds, We established the glucocorticoid receptor (GR) knockout 22Rv1/MMTV cell line by using an RNA-guided engineered nuclease (RGEN)-derived CRISPR/Cas system. The 22Rv1/MMTV GRKO cell line was characterized and validated by androgen receptor (AR)-mediated TA assay compared with the AR-TA assay using 22Rv1/MMTV. In conclusion, the AR-TA assay with the 22Rv1/MMTV GRKO cell line was more accurate, excluding the misleading signals derived from glucocorticoids or equivalent chemicals, and might be an effective method for screening potential (anti-)androgenic compounds.

Identification of plant compounds that disrupt the insect juvenile hormone receptor complex.

Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile hormone antagonists (PJHANs). Using the yeast two-hybrid system transformed with the mosquito JH receptor as a reporter system, we demonstrate that PJHANs affect the JH receptor, methoprene-tolerant (Met), by disrupting its complex with CYCLE or FISC, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants: Lindera erythrocarpa and Solidago serotina. They are effective in causing mortality of mosquito larvae at relatively low LD50 values. Topical application of two diterpenes caused reduction in the expression of Met target genes and retardation of follicle development in mosquito ovaries. Hence, the newly discovered PJHANs may lead to development of a new class of safe and effective pesticides.

Plant-derived compounds regulate formation of the insect juvenile hormone receptor complex.

Insect growth regulators (IGRs) are attractive pest control agents due to their high target specificity and relative safety to the environment. Recently, plants have been shown to synthesize IGRs that affect the insect juvenile hormone (JH) as a part of their defense mechanisms. Using a yeast two-hybrid system transformed with the Aedes aegypti JH receptor as a reporter system, we identified several JH agonists (JHAs) and antagonists (JHANs) causing retardation in the ovarian development of female Asian tiger mosquito, Aedes albopictus, from plant essential oil compounds. While the JHAs increased the expression of a JH-induced gene, the JHANs caused a reduction in the expression of the same gene. The compounds identified in this study could provide insights into plant-insect interactions and may be useful for the development of novel IGR insecticides.

Coincidence of Persistent Müllerian duct syndrome and testicular tumors in dogs.

BACKGROUND: Persistent Müllerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism in dogs, is an abnormal sexual phenotype in males that is characterized by the existence of a hypoplastic oviduct, uterus, and cranial part of the vagina. Dogs suffering from PMDS are often accompanied by cryptorchidism. To date, it has been mainly found in the Miniature Schnauzer breed. CASE PRESENTATION: In this report, two cases of PMDS with a malignant testicular tumor originating from cryptorchidism in breeds other than the Miniature Schnauzer breed are described. The patients were a seven-year-old male Maltese dog and a 17-year-old male mixed-breed dog weighing 3.8 kg. They also exhibited an enlarged prostate with or without abscess and an elevated serum estradiol level and were surgically treated to remove the testicular tumor and Müllerian duct derivatives. CONCLUSIONS: It is recommended that PMDS should be differentially diagnosed by ultrasonography and that orchiectomy be performed at an early age in patients suspected to have cryptorchidism to prevent the ectopic testes from becoming tumorous.

High-angle tilt boundary graphene domain recrystallized from mobile hot-wire-assisted chemical vapor deposition system.

Crystallization of materials has attracted research interest for a long time, and its mechanisms in three-dimensional materials have been well studied. However, crystallization of two-dimensional (2D) materials is yet to be challenged. Clarifying the dynamics underlying growth of 2D materials will provide the insight for the potential route to synthesize large and highly crystallized 2D domains with low defects. Here, we present the growth dynamics and recrystallization of 2D material graphene under a mobile hot-wire assisted chemical vapor deposition (MHW-CVD) system. Under local but sequential heating by MHW-CVD system, the initial nucleation of nanocrystalline graphenes, which was not extended into the growth stage due to the insufficient thermal energy, took a recrystallization and converted into a grand single crystal domain. During this process, the stitching-like healing of graphene was also observed. The local but sequential endowing thermal energy to nanocrystalline graphenes enabled us to simultaneously reveal the recrystallization and healing dynamics in graphene growth, which suggests an alternative route to synthesize a highly crystalline and large domain size graphene. Also, this recrystallization and healing of 2D nanocrystalline graphenes offers an interesting insight on the growth mechanism of 2D materials.

Influence of plasma conditions on the intensity ratio calibration curve during laser induced breakdown spectroscopy analysis.

Quantitative prediction of elemental concentration or concentration ratio of solid samples can be achieved by laser induced breakdown spectroscopy if a calibration curve that is little influenced by plasma conditions could be obtained. This work demonstrates that such a calibration curve is available for copper indium gallium diselenide (CuIn(1-x)Ga(x)Se2) thin film solar cells for properly selected spectral lines. The possible changes of calibration curves based on the selected spectral lines are discussed in consideration of self-absorption in optically thick plasma and the dependency of spectral line properties on plasma temperature.

Receptor mediated biological activities of phytoestrogens.

Phytoestrogens are plant-derived compounds that have chemical structures and functions similar to estrogen. Phytoestrogens act as ligand-inducible transcription factors involved in cellular growth by binding to estrogen receptors (ERs), specifically ER alpha (ERα) and beta (ERß). Through this mechanism, phytoestrogens have a physiological function similar to that of the female hormone 17ß-estradiol (E2), which can be useful in treating osteoporosis, cardiovascular disease, and cancer. Furthermore, phytoestrogens have been found to elicit various cellular responses depending on their affinity for ERs; in particular, they show a greater affinity with for ERß. This study aimed to comprehensively analyze the mode of action of eight phytoestrogens, namely kaempferol, coumestrol, glycitein, apigenin, daidzein, genistein, equol, and resveratrol, by evaluating their estrogenic activity as ER ligands. Based on the bioluminescence resonance energy transfer (BRET)-based ER dimerization and transactivation assay results, all the phytoestrogens tested were identified as estrogen agonists by mediating ERα and ERß dimerization. The specific binding and functions of ERα and ERß were distinguished by differentiating between their dimerization activity. In addition, this study contributes to advancing our understanding of the overall mechanism of action involving both ERs.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Independence of elemental intensity ratio on plasma property during laser-induced breakdown spectroscopy.

The authors report that the elemental composition ratio of Ga to In in a CuIn(1-x)Ga(x)Se(2) compound semiconductor, a thin-film solar cell material, can be measured with little influence of plasma property changes by laser-induced breakdown spectroscopy (λ = 1064 nm, τ = 5 ns). It is shown that the similarity in excitation energy levels of the selected Ga and In emission lines and the fact that these elements belong to the same group of the periodic table are the critical factors ensuring the independence of intensity ratio on plasma conditions.

Comprehensive analysis of cellular estrogen signaling in representative estrogen receptor ligands.

The estrogen receptor (ER)-mediated signaling pathway in physiological and biochemical aspects is very important in the environment, including food. The physiological action of estrogen is mediated by ER alpha (ERα) and beta (ERß), whose physiological action on estrogenic substances is complex because of the relatively low ligand-binding domain (LBD) similarity of the two ERs. In this study, the comprehensive activity of representative ER ligands was evaluated by using BRET-based ERα and ERß dimerization and ER transactivation assays to differentiate the specific binding and function of ERα and ERß from 12 representative natural and synthetic estrogenic substances. Results revealed that 11 chemicals mediated receptor ERα and ERß dimerization, 7 out of 12 chemicals were confirmed to be estrogen agonists, and 5 chemicals were antagonistic. Overall, this study demonstrated consistency between BRET dimerization and transactivation responses, supporting potential supplementary application of mechanism-based BRET assays as high-throughput screening methods for evaluation of potential endocrine-disrupting activity of environmental agents. This study also provided information about receptor specificity of ligand-mediated estrogenic activity via dimerization assays and elucidated cellular estrogen signaling pathways.

Human cell-based estrogen receptor beta dimerization assay.

Estrogen is not only responsible for important functions in the human body, such as cell growth, reproduction, differentiation, and development, but it is also deeply related to pathological processes, such as cancer, metabolic and cardiovascular diseases, and neurodegeneration. Estrogens and other estrogenic compounds have transcriptional activities through binding with the estrogen receptor (ER) to induce ER dimerization. The two estrogen receptor subtypes, estrogen receptor alpha (ERα) and estrogen receptor beta (ERß), show structural differences and have different expression ratios in specific cells and tissues. Currently, the methods for confirming the estrogenic properties of compounds are the binding (Test guideline no. 493) and transactivation (Test guideline no. 455) assays provided by the Organization for Economic Co-operation and Development (OECD). In a previous study, we developed an ERα dimerization assay based on the bioluminescence resonance energy transfer (BRET) system, but there are currently no available tests that can confirm the effect of estrogenic compounds on ERß. Therefore, in this study, we developed a BRET-based ERß dimerization assay to confirm the estrogenic prosperities of compounds. The BRET-based ERß dimerization assay was verified using nine representative ER ligands and the results were compared with the dimerization activity of ERα. In conclusion, our BRET-based ERß dimerization assay can provide information on the ERß dimerization potential of estrogenic compounds.

Effect of Annealing Temperature on the Structural and Electrochemical Properties of Hydrothermally Synthesized NiCo2O4 Electrodes.

In this study, a porous Ni-foam support was employed to enhance the capacitance of nickel cobaltite (NiCo2O4) electrodes designed for supercapacitors. The hydrothermal synthesis method was employed to grow NiCo2O4 as an active material on Ni-foam. The NiCo2O4 sample derived from hydrothermal synthesis underwent subsequent post-heat treatment at temperatures of 250 °C, 300 °C, and 350 °C. Thermogravimetric analysis of the NiCo2O4 showed that weight loss due to water evaporation occurs after 100 °C and enters the stabilization phase at temperatures above 400 °C. The XRD pattern indicated that NiCo2O4 grew into a spinel structure, and the TEM results demonstrated that the diffraction spots (DSs) on the (111) plane of the sample annealed at 350 °C were more pronounced than those of other samples. The specific capacitance of the NiCo2O4 electrodes exhibited a decrease with increasing current density across all samples, irrespective of the annealing temperature. The electrode annealed at 350 °C recorded the highest specific capacitance value. However, the capacity retention rate of the NiCo2O4 electrode revealed a deteriorating trend, declining to 88% at 250 °C, 75% at 300 °C, and 63% at 350 °C, as the annealing temperature increased.

Comprehensive assessment of the estrogenic activity of resin composites.

Resin-based dental composites have been developed to restore decayed teeth or modify tooth color due to their excellent physical and chemical properties. Such composites may have intrinsic toxicity due to components released into the mouth during the early stage of polymerization, and afterward as a result of erosion or material decomposition. In addition, resin-based dental composites have potential environmental pollutant by elution of monomers and degradation. Since certain monomers of resin matrices are synthesized from bisphenol A (BPA), which acts as an estrogenic endocrine disruptor, these resin matrices may have estrogenic activity. Therefore, the estrogenic endocrine-disrupting activity of various dental composites should be evaluated. In this study, we evaluated the estrogenic endocrine-disrupting activity of 10 resin composites by using a BRET-based estrogen receptor (ER)α and ERß dimerization assays and ER transactivation assay. BPA, BisDMA, BisGMA, BisEMA, TEGDMA, HMBP, and DMPA mediated ERα dimerization, and BPA, BisDMA, and DMPA also mediated ERß dimerization. Except for UDMA and CQ, all the compounds were identified as estrogen agonists or antagonists. In-depth information for the safe use of dental composites was acquired, and it was confirmed how the component of dental composites acts in the ER signaling pathway. Further studies on the low-dose and long-term release of these compounds are needed to ensure the safe use of these resin-based dental composites.

An In vitro dimerization assay for the adverse outcome pathway approach in risk assessment of human estrogen receptor α-mediated endocrine-disrupting chemicals.

The adverse outcome pathway (AOP) has been recently proposed as an effective framework for chemical risk assessment. The AOP framework offers the advantage of effectively integrating individual in vitro studies and in silico prediction models. Thus, the development of an effective testing method to measure key events caused by chemicals is essential for chemical risk assessment through a fully developed AOP framework. We developed a human cell-based estrogen receptor α (ERα) dimerization assay using the bioluminescence resonance energy transfer (BRET) technique and evaluated the ERα dimerization activities of 72 chemicals. Fifty-one chemicals were identified to mediate dimerization of ERα, and the BRET-based ERα dimerization assay could effectively measure the events that mediated dimerization of ERα by the estrogenic chemicals. These results were compared with the results of pre-existing assay to determine whether the BRET-based ERα dimerization assay could be employed as an in vitro test method to provide scientific information for explaining key events as a part of the AOP framework. Consequently, we propose that the BRET-based ERα dimerization assay is suitable for measuring the chemical-mediated dimerization of ERα, a key event in the AOP framework for cellular-level risk assessment of estrogenic chemicals.

Variations in the Physical Properties of RF-Sputtered CdS Thin Films Observed at Substrate Temperatures Ranging from 25 °C to 500 °C.

CdS films with a wide range of substrate temperatures as deposition parameters were fabricated on Corning Eagle 2000 glass substrates using RF magnetron sputtering. The crystallographic structure, microscopic surface texture, and stoichiometric and optical properties of each CdS film deposited at various substrate temperatures were observed to be highly temperature-dependent. The grown CdS thin films revealed a polycrystalline structure in which a cubic phase was mixed based on a hexagonal wurtzite phase. The relative intensity of the H(002)/C(111) peak, which represents the direction of the preferential growth plane, enhanced as the temperatures climbed from 25 °C to 350 °C. On the contrary, the intensity of the main growth peak at the higher temperatures of 450 °C and 500 °C was significantly reduced and exhibited amorphous-like behavior. The sharp absorption edge revealed in the transmission spectrum shifted from the long wavelength to the short wavelength region with the rise in the substrate temperature. The bandgap showed a tendency to widen from 2.38 eV to 2.97 eV when the temperatures increased from 25 °C to 350 °C. The CdS films grown at the temperatures of 450 °C and 500 °C exhibited glass-like transmittance with almost no interference fringes of light, which resulted in wide bandgap values of 3.09 eV and 4.19 eV, respectively.

Skyline query processing in sensor network based on data centric storage.

Data centric storages for sensor networks have been proposed to efficiently process multi-dimensional range queries as well as exact matches. Usually, a sensor network does not process only one type of the query, but processes various types of queries such as range queries, exact matches and skyline queries. Therefore, a sensor network based on a data centric storage for range queries and exact matches should process skyline queries efficiently. However, existing algorithms for skyline queries have not considered the features of data centric storages. Some of the data centric storages store similar data in sensor nodes that are placed on geographically similar locations. Consequently, all data are ordered in a sensor network. In this paper, we propose a new skyline query processing algorithm that exploits the above features of data centric storages.

Shape- and Size-Controlled Palladium Nanocrystals and Their Electrocatalytic Properties in the Oxidation of Ethanol.

Pd nanoparticles (PdNPs) were synthesized in an aqueous environment via the reduction of K2PdCl4 by a surfactant under a high temperature. Highly monodisperse spherical PdNPs and multi-pod PdNPs with a controlled size ranging from 18 to 50 nm were prepared in high yields by varying the concentration of cetyltrimethylammonium chloride. The structural and optical properties of the synthesized Pd NPs were characterized by transmission electron microscopy, X-ray diffraction and UV-vis spectroscopy. The spherical and multi-pod PdNPs exhibited catalytic properties that were unique to their size and shape and presented efficient electrocatalytic activities toward the ethanol oxidation reaction.