Characterization of a new selective glucocorticoid receptor modulator with anorexigenic activity.

Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss in both high fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Taken together, Zj7, as a selective GR modulator, showed beneficial metabolic activities, in part by suppressing GR activity in non-classical GREs in orexigenic genes. This study demonstrates that a potential anorexigenic molecule may allow GRE-specific inhibition of GR transcriptional activity, which is a promising approach for the treatment of metabolic disorders.

Aeroallergen Sensitization Status in South Korea From 2018 to 2021.

OBJECTIVES: Studies on the aeroallergen sensitization status of South Koreans based on large-scale data are lacking. METHODS: We analyzed data from 368,156 multiple allergosorbent tests collected by a domestic medical diagnosis company from 3,735 hospitals nationwide from 2018 to 2021. We additionally collected sex, age, and regional data. If the level of an aeroallergen was 0.35 IU/mL or more, the test result for that aeroallergen was defined as positive, and positive cases were defined as those where one aeroallergen was positive. The positive ratio (PR) for aeroallergens was calculated using positive cases. RESULTS: In total, 347,996 cases were analyzed, excluding cases with missing data. The percentage of positive cases was 56.7%, which was highest in adolescents (74.1%) and lowest in the elderly (47.0%). All four types of mites had high PRs (0.382-0.655), and mold had low PRs (0.023-0.058). Among pollens, the PRs of grasses were generally high (more than 0.14), followed by weeds (approximately 0.10), and the PRs of woods was less than 0.1. For animals, cats and dogs had the highest PRs, at 0.231 and 0.183, respectively. The value for cockroaches was also high, at 0.211. The PRs of indoor aeroallergens, such as mites, molds, and animals, were high in adolescents, and those of pollen and cockroaches were high in the elderly. In Jeju, the PR of Japanese cedars was extremely high (0.222). CONCLUSION: Koreans were found to be sensitized to a wide variety of aeroallergens. There were significant differences in sensitization patterns according to age and region.

Residual Compressive Strength of Short Tubular Steel Columns with Artificially Fabricated Local Corrosion Damage.

Corrosion is considered as one of the main factors in the structural performance deterioration of steel members. In this study, experimental and numerical methods were used to assess the reduction in compressive strength of short tubular steel columns with artificially fabricated local corrosion damage. The corrosion damage was varied with different depths, heights, circumferences, and locations along the column. A parametric numerical study was performed to establish a correlation between the residual compressive strength and the severity of corrosion damage. The results showed that as the corrosion depth, height and circumference increased, the compressive strength decreased linearly. As for the corrosion height, the residual compressive strength became constant after decreasing linearly when the corrosion height was greater than the half-wavelength of buckling of the short columns. An equation is presented to evaluate the residual compressive strength of short columns with local corrosion wherein the volume of the corrosion damage was used as a reduction factor in calculating the compressive strength. The percentage error using the presented equation was found to be within 11.4%.

Anthropogenic gadolinium in lakes and rivers near metrocities in Korea.

We measured dissolved rare earth elements (REEs) in the water samples from Shihwa Lake (SL), which was assumed to be highly polluted, and in the downstream portion of the Han River (HR), which runs through Seoul, Korea. Among the investigated REEs, only gadolinium (Gd) was found to be significantly enhanced after REE concentrations were shale-normalized (SN). The calculated Gd anomaly (Gd/Gd* = 3 × GdSN/(SmSN + 2 × TbSN)) was about 1.5 ± 0.1 (n = 16) in SL and 1.6 ± 0.3 in the HR (n = 26) water relative to other types of natural water such as groundwater, seawater, and river water in uncontaminated areas (Gd/Gd* ∼ 1.2, n > 400). These significant Gd anomalies seem to be due to the inputs of anthropogenic Gd (Gdanth), especially from the use of Gd-based contrast agents for magnetic resonance imaging (MRI) tests from a number of hospitals and medical institutes surrounding our study areas. The amount of Gdanth was estimated to be 190 ± 80 g and 680 ± 360 kg Gd in SL and the HR (watersheds in our study area), respectively. The Gdanth flux to the Yellow Sea from the HR is estimated to be 530 ± 330 g Gd d-1. These results suggest that quantitative evaluation of anthropogenic REEs in natural waters near big cities is needed, because considerable amounts of REEs are now used by modern high-tech industries.

Unexpectedly high dimethyl sulfide concentration in high-latitude Arctic sea ice melt ponds.

Dimethyl sulfide (DMS) production in the northern Arctic Ocean has been considered to be minimal because of high sea ice concentration and extremely low productivity. However, we found DMS concentration (1-33 nM) in melt ponds on sea ice at a very high latitude (78°N) in the central Arctic Ocean to be up to ten times that in the adjacent open ocean (<3 nM). We divided melt ponds into three categories: freshwater melt ponds, brackish melt ponds, and open saline melt ponds. Melt ponds from each category had different formation mechanisms and associated DMS contents. Closed brackish ponds (salinity of >20) had particularly high DMS concentration. Water in brackish ponds was mixed with open ocean water in the past via a hole at the bottom of the floe that kept the pond open to the ocean; therefore, unlike freshwater melt ponds, brackish ponds became sites of DMS accumulation. Our results suggest that continuous increase in melt pond coverage on Arctic sea ice could considerably impact future Arctic climate as well as enhancing DMS concentration in the Arctic atmosphere.

Distribution and accumulation of artificial radionuclides in marine products around Korean Peninsula.

We investigated the distributions of the artificial radionuclides 137Cs, 239+240Pu, and 90Sr in the various marine products around Korean Peninsula collected in 2015-2017. The activities of 137Cs, 239+240Pu, and 90Sr were in the ranges of 12.2-258.4 mBq kg-1, 0.014-1.879 mBq kg-1, and 11.3-18.3 mBq kg-1, respectively. The higher 239+240Pu (a factor of 10-50) relative to fishes were observed in mollusks. 137Cs in fishes were significantly enriched with growths. The calculated concentration factors (CFs) of 137Cs, 239+240Pu, and 90Sr in marine products were 7-143, 3-407, and 15-25, respectively. Overall, no noticeable artificial radioactivity was detected in marine organisms when comparing these results with previous data reported before the Fukushima nuclear accident and recommended CF values. The annual effective doses of 137Cs, 239+240Pu, and 90Sr by seafood consumption in South Korea were estimated to be 1.1 × 10-4, 1.6 × 10-5 and, 2.9 × 10-5 mSv yr-1, respectively, which is insignificant relative to that of natural radionuclides.

A Method for Estimating Time-Dependent Corrosion Depth of Carbon and Weathering Steel Using an Atmospheric Corrosion Monitor Sensor.

In this study, a time-dependent corrosion depth estimation method using atmospheric corrosion monitor (ACM) sensor data to evaluate time-dependent corrosion behaviors is proposed. For the time-dependent corrosion depth estimation of uncoated carbon steel and weathering steel, acceleration corrosion tests were conducted in salt-spray corrosion environments and evaluated with a corrosion damage estimation method using ACM sensing data and corrosion loss data of the tested steel specimens. To estimate the time-dependent corrosion depth using corrosion current by an ACM sensor, the relationship between the mean corrosion depth calculated from the weight loss method and the corrosion current was evaluated. The mean corrosion depth was estimated by calculating the corrosion current and evaluating the relationship between the mean corrosion depth and corrosion current during the expected period. From the test and estimation results, the corrosion current demonstrated a good linear correlation with the mean corrosion depth of carbon steel and weathering. The calculated mean corrosion depth is nearly the same as that of the tested specimen, which can be well used to estimate corrosion rate for the uncoated carbon steel and weathering steel.

Synthesis and Irreversible Thermochromic Sensor Applications of Manganese Violet.

An irreversible thermochromic material based on manganese violet (MnNH4P2O7) is synthesized. The crystal phase, chemical composition, and morphology of the synthesized material are analyzed using X-ray diffraction, scanning electron microscopy coupled with energy-dispersive X-ray spectrometry, and Fourier-transform infrared spectroscopy. The absorption spectra of the synthesized material are obtained using a UV-Vis spectrometer, and the thermochromism exhibited by the powdered samples at high temperatures is also investigated. The as-synthesized manganese violet pigment consists of pure α-MnNH4P2O7 phase. In addition, the synthesized pigment largely consists of hexagonal crystals with a diameter of hundreds of nanometers. On heating, the pigment simultaneously loses H2O and NH3 in two successive steps at approximately 330⁻434.4 °C and 434.4⁻527 °C, which correspond to the formation of an intermediate phase and of Mn2P4O12, respectively. An overall mass loss of 14.22% is observed, which is consistent with the expected 13.79%. An irreversible color change from violet to white is observed after exposure of the synthesized manganese violet pigment at 400 °C for 30 min. This is attributed to the oxidation of ammonia to hydroxylamine, which then decomposes to nitrogen and water, or alternatively to the direct oxidation of ammonia to nitrogen. Furthermore, we demonstrate the potential application of synthesized manganese violet in the production of irreversible thermochromic paint by mixing with potassium silicate solution as a binder and deionized water as a solvent at a specific ratio. The thermochromic paint is then applied in fabrication of irreversible thermochromic sensors by coating it onto a steel plate surface. Finally, we show that manganese violet-based irreversible thermochromic sensors are able to detect temperatures around 400 °C by changing color from violet to white/milky.

Synthesis and Thermochromic Properties of Cr-Doped Al2O3 for a Reversible Thermochromic Sensor.

An inorganic thermochromic material based on Cr-doped Al2O3 is synthesized using a solid-state method. The crystal structure, chemical composition, and morphology of the synthesized material are analyzed using X-ray diffraction, scanning electron microscopy coupled with an energy-dispersive X-ray spectrometer, and Fourier transform infrared (FT-IR) spectroscopy. The color performances of the synthesized material are analyzed using a UV-VIS spectrometer. Finally, the thermochromism exhibited by the powdered samples at high temperatures is investigated. The material exhibits exceptional thermochromic property, transitioning from pink to gray or green in a temperature range of 25-600 °C. The change in color is reversible and is dependent on the surrounding temperature and chromium concentration; however, it is independent of the exposure time. This novel property of Cr-doped Al2O3 can be potentially employed in reversible thermochromic sensors that could be used not only for warning users of damage due to overheating when the environmental temperature exceeds certain limits, but also for detecting and monitoring the temperature of various devices, such as aeronautical engine components, hotplates, and furnaces.

Characteristics of the horizontal and vertical distributions of dimethyl sulfide throughout the Amundsen Sea Polynya.

We investigated horizontal and vertical distributions of DMS in the upper water column of the Amundsen Sea Polynya and Pine Island Polynya during the austral summer (January-February) of 2016 using a membrane inlet mass spectrometer (MIMS) onboard the Korean icebreaker R/V Araon. The surface water concentrations of DMS varied from <1 to 400nM. The highest DMS (up to 300nM) were observed in sea ice-polynya transition zones and near the Getz ice shelf, where both the first local ice melting and high plankton productivity were observed. In other regions, high DMS concentration was generally accompanied by higher chlorophyll and ΔO2/Ar. The large spatial variability of DMS and primary productivity in the surface water of the Amundsen Sea seems to be attributed to melting conditions of sea ice, relative dominance of Phaeocystis Antarctica as a DMS producer, and timing differences between bloom and subsequent DMS productions. The depth profiles of DMS and ΔO2/Ar were consistent with the horizontal surface data, showing noticeable spatial variability. However, despite the large spatial variability, in contrast to the previous results from 2009, DMS concentrations and ΔO2/Ar in the surface water were indistinct between the two major domains: the sea ice zone and polynya region. The discrepancy may be associated with inter-annual variations of phytoplankton assemblages superimposed on differences in sea-ice conditions, blooming period, and spatial coverage along the vast surface area of the Amundsen Sea.

Decreased Serum Epinephrine in Children With Positive Skin Prick Test.

OBJECTIVES: To evaluate the association between catecholamine levels and skin prick test results among children. METHODS: Two hundred eight first grade children from one elementary school were invited to participate in this study. Skin prick test (SPT) for six allergens (2 house dust mites, cat, dog, mugwort, and pollen mixture) was performed, and patient demographic information was recorded. The parents were surveyed using questionnaires about rhinitis-related symptoms. Finally, venous blood sampling was done to measure catecholamine levels (epinephrine, norepinephrine, and dopamine) by high-performance liquid chromatography. RESULTS: Out of 208 children, 174 (106 boys and 68 girls) enrolled in this study. Ninety-six of the children (55%) had negative SPT (nonsensitization group), while 78 (45%) had a positive SPT to at least one of six allergens (sensitization group). The diagnosis of chronic rhinitis was more prevalent in the sensitization group (35.9%) than nonsensitization group (26.0%), however the finding was not significant (P=0.186). Epinephrine levels were decreased between the sensitization group compared to the nonsensitization group (P=0.004). There was no difference in norepinephrine and dopamine levels (P>0.05). CONCLUSION: Epinephrine levels are lower in children with positive SPT compared to controls, however, the level of the catecholamine was not associated with the presence or absence of rhinitis symptoms.

Reduction in oxidative stress biomarkers after adenotonsillectomy.

OBJECTIVES: A number of otolaryngic conditions such as chronic tonsillitis, adenoid hypertrophy, and obstructive sleep apnea are associated with oxidative stress and elevated levels of serum oxidants. The objective of this study is to measure changes in urine biomarkers of oxidative stress in children after adenotonsillectomy. METHODS: Twenty-two children with sleep disordered breathing (SDB) with tonsil and adenoid hypertrophy were enrolled prior to adenotonsillectomy. Controls consisted of 20 healthy children. Urine samples were collected from all patients. Levels of three urinary biomarkers for oxidative status, 8-hydroxy-2-deoxyguanosine (8-OxodG), F(2)-isoprostane, and malondialdehyde (MDA) were measured using high performance liquid chromatography. For the study group, urine samples were repeated 3 weeks after surgery. RESULTS: In the study group, preoperative urinary levels of 8-OxodG were higher than in controls (p=0.015). Levels decreased after surgery compared to preoperative levels (p=0.002), and reached control levels (p=0.167) at 3 weeks. Levels of urinary F(2)-isoprostane were similar in both groups (p=0.252), but decreased significantly after surgery (p=0.020). CONCLUSIONS: Children with SDB have elevated levels of urinary 8-OxodG, a marker of oxidative stress. Adenotonsillectomy results in decreased 8-OxodG and F(2)-isoprostane. These findings suggest that urine analysis may represent a valuable tool for the measurement of oxidative stress.

Ionic liquid flow along the carbon nanotube with DC electric field.

Liquid pumping can occur along the outer surface of an electrode under a DC electric field. For biological applications, a better understanding of the ionic solution pumping mechanism is required. Here, we fabricated CNT wire electrodes (CWEs) and tungsten wire electrodes (TWEs) of various diameters to assess an ionic solution pumping. A DC electric field created by a bias of several volts pumped the ionic solution in the direction of the negatively biased electrode. The resulting electro-osmotic flow was attributed to the movement of an electric double layer near the electrode, and the flow rates along the CWEs were on the order of picoliters per minute. According to electric field analysis, the z-directional electric field around the meniscus of the small electrode was more concentrated than that of the larger electrode. Thus, the pumping effect increased as the electrode diameter decreased. Interestingly in CWEs, the initiating voltage for liquid pumping did not change with increasing diameter, up to 20 µm. We classified into three pumping zones, according to the initiating voltage and faradaic reaction. Liquid pumping using the CWEs could provide a new method for biological studies with adoptable flow rates and a larger 'Recommended pumping zone'.

Optical detection of paraoxon using single-walled carbon nanotube films with attached organophosphorus hydrolase-expressed Escherichia coli.

In whole-cell based biosensors, spectrophotometry is one of the most commonly used methods for detecting organophosphates due to its simplicity and reliability. The sensor performance is directly affected by the cell immobilization method because it determines the amount of cells, the mass transfer rate, and the stability. In this study, we demonstrated that our previously-reported microbe immobilization method, a microbe-attached single-walled carbon nanotube film, can be applied to whole-cell-based organophosphate sensors. This method has many advantages over other whole-cell organophosphate sensors, including high specific activity, quick cell immobilization, and excellent stability. A device with circular electrodes was fabricated for an enlarged cell-immobilization area. Escherichia coli expressing organophosphorus hydrolase in the periplasmic space and single-walled carbon nanotubes were attached to the device by our method. Paraoxon was hydrolyzed using this device, and detected by measuring the concentration of the enzymatic reaction product, p-nitrophenol. The specific activity of our device was calculated, and was shown to be over 2.5 times that reported previously for other whole-cell organophosphate sensors. Thus, this method for generation of whole-cell-based OP biosensors might be optimal, as it overcomes many of the caveats that prevent the widespread use of other such devices.

Rare earth element distributions and fractionation in plankton from the northwestern Mediterranean Sea.

Rare earth element (REE) concentrations were measured for the first time in plankton from the northwestern Mediterranean Sea. The REE concentrations in phytoplankton (60-200 µm) were 5-15 times higher than those in four size fractions of zooplankton: 200-500 µm, 500-1000 µm, 1000-2000 µm and >2000 µm. The concentrations within these zooplankton fractions exhibited the same ranges with some variation attributed to differences in zooplankton taxonomy. The REE concentrations in plankton were poorly related to the reported REE concentrations of seawater, but they correlated well with the calculated REE(3+), concentrations especially with regard to middle REE (MREEs) and heavy REEs (HREEs). Plankton and seawater revealed different PAAS-normalised REE distributions, with the greatest differences observed in the light REEs. Interestingly, a comparison of PAAS-normalized sediment particles from the study of Fowler et al. (1992) showed concentrations of the same order of magnitude and a similar REE distribution without MREE enrichment. Based on this comparison, we propose a conceptual model that emphasizes the importance of biological scavenging of REEs (especially LREEs) in surface waters.

Electrochemical oxidation of hydrolyzed poly oxymethylene-dimethyl ether by PtRu catalysts on Nb-doped SnO(2-δ) supports for direct oxidation fuel cells.

We synthesized Pt and PtRu catalysts supported on Nb-doped SnO(2-δ) (Pt/Sn0.99Nb0.01O(2-δ), PtRu/Sn0.99Nb0.01O(2-δ)) for direct oxidation fuel cells (DOFCs) using poly oxymethylene-dimethyl ether (POMMn, n = 2, 3) as a fuel. The onset potential for the oxidation of simulated fuels of POMMn (methanol-formaldehyde mixtures; n = 2, 3) for Pt/Sn0.99Nb0.01O(2-δ) and PtRu/Sn0.99Nb0.01O(2-δ) was less than 0.3 V vs RHE, which was much lower than those of two commercial catalysts (PtRu black and Pt2Ru3/carbon black). In particular, the onset potential of the oxidation reaction of simulated fuels of POMMn (n = 2, 3) for PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C in nitrogen atmosphere was less than 0.1 V vs RHE and is thus considered to be a promising anode catalyst for DOFCs. The mass activity (MA) of PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C was more than five times larger than those of the commercial catalysts in the measurement temperature range from 25 to 80 °C. Even though the MA for the methanol oxidation reaction was of the same order as those of the commercial catalysts, the MA for the formaldehyde oxidation reaction was more than five times larger than those of the commercial catalysts. Sn from the Sn0.99Nb0.01O(2-δ) support was found to have diffused into the Pt catalyst during the sintering process. The Sn on the top surface of the Pt catalyst accelerated the oxidation of carbon monoxide by a bifunctional mechanism, similar to that for Pt-Ru catalysts.

Anti-angiogenic effect of KR-31831 on corneal and choroidal neovascularization in rat models.

PURPOSE: We attempt to determine the effect and mechanism of KR-31831 in rat models of corneal neovascularization and choroidal neovascularization (CNV). METHODS: Corneal neovascularization was induced by silver nitrate cauterization. Balanced salt solution (for control), KR-31831 (0.1 mg/mL), and bevacizumab (10 mg/mL) were applied topically with or without subsequent subconjunctival injection (10 µL). The degree of corneal neovascularization was compared among treatments. The effects of intravitreal (0.1 and 0.3 mg/mL) and intraperitoneal (25 mg/kg) of KR-31831, and intravitreal injection of bevacizumab (2.5 mg/mL) were compared in a laser-induced CNV model. FITC-dextran was used to observe the choroid vessels and to evaluate vessel leakage by fluorescence intensity. RESULTS: In the silver nitrate cauterized rat, topical KR-31831 (P = 0.008) or bevacizumab (P = 0.008) reduced effectively the area of corneal neovascularization compared to control on day 14. This was reduced further by additional subconjunctival injection of KR-31831 (P = 0.024) and bevacizumab (P = 0.016). After KR-31831 application, vascular endothelial growth factor (VEGF) receptor 2 and matrix metalloproteinase (MMP)-2 expression was decreased in the cornea. In the CNV model, intravitreal (0.3 mg/mL) and intraperitoneal KR-31831 inhibited significantly the CNV area (P = 0.008 and P = 0.008, respectively) and fluorescence leakage (P = 0.008 and P = 0.032, respectively). This effect was more significant compared to intravitreal bevacizumab in terms of the CNV area (P = 0.032 and P = 0.008, respectively) and fluorescence leakage (P = 0.016 and P = 0.008, respectively). CONCLUSIONS: The anti-angiogenic effect of KR-31831 was comparable in the cornea and more effective in the choroid compared to that of bevacizumab, and it may exert its effect by VEGF signaling and MMP-2.

Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-κB inactivation in RAW 264.7 macrophages.

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-α, and IL-1ß mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IκB kinase ß (IKKß), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-ß-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-κB activations.