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.
A facile, scalable route to new nanocomposites that are based on carbon nanotubes/heteroatom‐doped carbon (CNT/HDC) core–sheath nanostructures is reported. These nanostructures were prepared by the ...adsorption of heteroatom‐containing ionic liquids on the walls of CNTs, followed by carbonization. The design of the CNT/HDC composite allows for combining the electrical conductivity of the CNTs with the catalytic activity of the heteroatom‐containing HDC sheath layers. The CNT/HDC nanostructures are highly active electrocatalysts for the oxygen reduction reaction and displayed one of the best performances among heteroatom‐doped nanocarbon catalysts in terms of half‐wave potential and kinetic current density. The four‐electron selectivity and the exchange current density of the CNT/HDC nanostructures are comparable with those of a Pt/C catalyst, and the CNT/HDC composites were superior to Pt/C in terms of long‐term durability and poison tolerance. Furthermore, an alkaline fuel cell that employs a CNT/HDC nanostructure as the cathode catalyst shows very high current and power densities, which sheds light on the practical applicability of these new nanocomposites.
A facile, scalable route for the synthesis of new nanocomposites that are based on carbon nanotubes/heteroatom‐doped carbon (CNT/HDC) core–sheath nanostructures has been developed. The CNT/HDC nanostructures exhibit excellent electrocatalytic activity, kinetics, and durability for the oxygen reduction reaction, and they also performed well as the cathode catalysts in alkaline fuel cells.
To develop a novel cell-based assay to evaluate the androgenic endocrine-disrupting properties of chemical substances, we established a method to detect ligand-mediated androgen receptor (AR) ...dimerization in stably transfected human cell lines using a bioluminescence resonance energy transfer (BRET) system. Using stably transfected human embryonic kidney (HEK-293) cells, the BRET-based AR dimerization assay was optimized as a novel test method and was validated using test chemicals recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The BRET-based AR dimerization assay showed high accuracy, sensitivity, and specificity for the detection of androgenic endocrine-disrupting chemicals (EDCs), and the assay protocol is adequate for practical use. This dimerization assay is based on ligand-mediated hormone receptor dimerization and can provide accurate information about androgenic endocrine-disrupting properties at the cellular level, complementing conventional binding and transactivation assays.
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•The androgen receptor (AR) binding assay using the bioluminescence resonance energy transfer (BRET).•The human cell based in vitro binding assay to detect androgenic endocrine disrupting chemicals.•Establishment of stably transfected HEK 293 cell line for BRET-based AR binding assay.•The novel binding assay that can complement or replace conventional binding assays.
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.
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•The AOP approach for risk assessment of chemicals with (anti-)estrogenicity.•Development of human cell-based ERα dimerization assay using BRET technique.•An in vitro assay method to measure chemical-mediated ERα dimerization.•Validation of the dimerization assay by 72 chemicals recommended by ICCVAM report.•Link the dimerization assay to pre-existing assays for the AOP framework.
Endocrine-disrupting chemicals (EDCs) are found in food and various other substances, including pesticides and plastics. EDCs are easily absorbed into the body and have the ability to mimic or block ...hormone function. The radioligand binding assay based on the estrogen receptors binding affinity is widely used to detect estrogenic EDCs but is limited to radioactive substances and requires specific conditions. As an alternative, we developed a human cell-based dimerization assay for detecting EDC-mediated ER-alpha (ERα) dimerization using bioluminescence resonance energy transfer (BRET). The resultant novel BRET-based on the ERα dimerization assay was used to identify the binding affinity of 17β-estradiol (E2), 17α-estradiol, corticosterone, diethylhexyl phthalate, bisphenol A, and 4-nonylphenol with ERα by measuring the corresponding BRET signals. Consequently, the BRET signals from five chemicals except corticosterone showed a dose-dependent sigmoidal curve for ERα, and these chemicals were suggested as positive chemicals for ERα. In contrast, corticosterone, which induced a BRET signal comparable to that of the vehicle control, was suggested as a negative chemical for ERα. Therefore, these results were consistent with the results of the existing binding assay for ERα and suggested that a novel BRET system can provide information about EDCs-mediated dimerization to ERα.
Lifting scheme for streamflow data in river networks Park, Seoncheol; Oh, Hee‐Seok
Applied statistics/Journal of the Royal Statistical Society. Series C, Applied statistics,
March 2022, 2022-03-01, 20220301, Letnik:
71, Številka:
2
Journal Article
Recenzirano
Odprti dostop
This paper presents a new multiscale method for analysing water pollutant data located in river networks. The main idea of the proposed method is to adapt the conventional lifting scheme, reflecting ...the characteristics of streamflow data in the river network domain. Due to the complexity of the data domain structure, it is difficult to apply the lifting scheme to the streamflow data directly. To solve this problem, we propose a new lifting scheme algorithm for streamflow data that incorporates flow‐adaptive neighbourhood selection, flow proportional weight generation and flow‐length adaptive removal point selection. A nondecimated version of the proposed lifting scheme is also provided. The simulation study demonstrates that the proposed method successfully performs a multiscale analysis of streamflow data. Furthermore, we provide a real data analysis of water pollutant data observed on the Geum‐River basin compared to the existing smoothing method.
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.
•The thyroid hormone agonist transactivation assay with the human cell line.•Establishment of a stably transfected A549 cell with a thyroid hormone-responsive reporter system.•The advanced assay showed high accuracy and specificity for screening of thyroid hormone agonists.
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.
•The androgen transactivation assay with the 22Rv1/MMTV GRKO cell line.•NR3C1 gene knockout in 22Rv1/MMTV cells by using CRISPR/Cas9 genome editing.•The assay method with no cross-talk between receptors of androgen and glucocorticoid.•The advanced assay showed high accuracy for screening of (anti-)androgenic compounds.
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.
•Comparative estrogenicity of fifteen phytoestrogens was evaluated using ER-α dimerization assay and OECD test methods.•Test methods used in this study provided a high consistency between in vitro and in vivo results.•Phytoestrogens regulated uterine gene expressions differently compared to estrogens.•Coumestrol and 8-prenylnaringenin showed the most potent estrogenic effects with ER-α-mediated actions.
Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, ...multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin‐methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1‐ and 1.4‐fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro‐conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.
Electrically conductive hydrogel‐based nerve guidance conduits are fabricated by polymerization of a graphene oxide (GO)‐incorporated gelatin‐methacrylate (GelMA) hydrogel, and subsequently chemically reduced. GelMA and reduced GO (rGO) show good tissue compatibility and can promote nerve regeneration. The r(GO/GelMA) conduit has the requirements of an ideal nerve guidance conduit with appropriate mechanical and electrical properties.
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