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Abstract Background In common wheat (Triticum aestivum L.), allelic variations in the high-molecular-weight glutenin subunits Glu-B1 locus have important effects on grain end-use quality. The Glu-B1 locus consists of two tightly linked genes encoding x- and y-type subunits that exhibit highly variable frequencies. However, studies on the discriminating markers of the alleles that have been reported are limited. Here, we developed 11 agarose gel-based PCR markers for detecting Glu-1Bx and Glu-1By alleles. Results By integrating the newly developed markers with previously published PCR markers, nine Glu-1Bx locus alleles (Glu-1Bx6, Glu-1Bx7, Glu-1Bx7*, Glu-1Bx7 OE, Glu-1Bx13, Glu-1Bx14 (−) , Glu-1Bx14 (+)/Bx20, and Glu-1Bx17) and seven Glu-1By locus alleles (Glu-1By8, Glu-1By8*, Glu-1By9, Glu-1By15/By20, Glu-1By16, and Glu-1By18) were distinguished in 25 wheat cultivars. Glu-1Bx6, Glu-1Bx13, Glu-1Bx14 (+)/Bx20, Glu-1By16, and Glu-1By18 were distinguished using the newly developed PCR markers. Additionally, the Glu-1Bx13 and Glu-1Bx14 (+)/Bx20 were distinguished by insertions and deletions in their promoter regions. The Glu-1Bx6, Glu-1Bx7, Glu-1By9, Glu-1Bx14 (−), and Glu-1By15/By20 alleles were distinguished by using insertions and deletions in the gene-coding region. Glu-1By13, Glu-1By16, and Glu-1By18 were dominantly identified in the gene-coding region. We also developed a marker to distinguish between the two Glu-1Bx14 alleles. However, the Glu-1Bx14 (+) + Glu-1By15 and Glu-1Bx20 + Glu-1By20 allele combinations could not be distinguished using PCR markers. The high-molecular-weight glutenin subunits of wheat varieties were analyzed by ultra-performance liquid chromatography and sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and the findings were compared with the results of PCR analysis. Conclusions Seven Glu-1Bx and four Glu-1By allele detection markers were developed to detect nine Glu-1Bx and seven Glu-1By locus alleles, respectively. Integrating previously reported markers and 11 newly developed PCR markers improves allelic identification of the Glu-B1 locus and facilitates more effective analysis of Glu-B1 alleles molecular variations, which may improve the end-use quality of wheat.

This study characterized the diversity of 367 barley collections from 27 different countries, including 5 control cultivars, using several phenotypic traits. Morphological traits, including spike type, grain morphology, cold damage, and lodging rate, exhibited wide variations. Eighteen accessions matured early, while four accessions had longer culm and spike lengths than the controls. The ranges of total phenolic content (TPC), β-glucan content, ABTS•+ scavenging activity, DPPH• scavenging activity, and reducing power (RP) were 1.79–6.79 mg GAE/g, 0.14–8.41 g/100 g, 3.07–13.54 mg AAE/100 g, 1.56–6.24 mg AAE/g, and 1.31–7.86 mg AAE/g, respectively. Betaone, one of the controls, had the highest β-glucan content. Two accessions had β-glucan levels close to Betaone. Furthermore, 20 accessions exhibited increased TPC compared to the controls, while 5 accessions displayed elevated ABTS•+ scavenging activity. Among these, one accession also exhibited higher DPPH• scavenging activity and RP simultaneously. Based on the statistical analysis of variance, all the quantitative traits were significantly affected by the difference in origin (p < 0.05). On the other hand, grain morphology significantly affected biochemical traits. Multivariate analysis classified barley accessions into eight groups, demonstrating variations in quantitative traits. There were noteworthy correlations between biochemical and agronomical traits. Overall, this study characterized several barley varieties of different origins, anticipating future genomic research. The barley accessions with superior performances could be valuable alternatives in breeding.

Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is unclear. This study aims to investigate the effect of policosanol on osteogenic differentiation in MC3T3-E1 cells and zebrafish models. Administration of policosanol into MC3T3-E1 induced the expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). Alkaline phosphatase activity and extracellular mineralization also increased. Policosanol promoted activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-induced genes (INSIGs) expression and regulation of INSIGs modulated osteoblast differentiation. AMPK activation through transfection of the constitutively active form of AMPK (CA-AMPK) increased INSIGs expression, whereas policosanol-induced INSIGs expression was suppressed by inhibitor of AMPK (Com. C). Furthermore, the osteogenic effects of policosanol were verified in zebrafish. Amputated caudal fin rays were regenerated by policosanol treatment. Taken together, these results show that policosanol increases osteogenic differentiation and contributes to fin regeneration in zebrafish via AMPK-mediated INSIGs expression, suggesting that policosanol has potential as an osteogenic agent.

The interest in bioconversion through fermentation of sprouts produced in smart farms is increasing due to their potential health benefits. Codonopsis lanceolata (CL) is reported to alleviate inflammatory conditions, but much research is still needed to determine which types and parts of CL are most effective. This study investigated the anti-inflammatory effects of a fermented extract of CL sprouts’ aerial part (F-CSA) against LPS-stimulated RAW 264.7 macrophages and mice. In the screening test, F-CSA showed the most substantial anti-inflammatory effect among several samples, containing the highest total flavonoids, tannins, and polyphenols. UPLC-ESI-Q/TOF-MS and HPLC analysis revealed that F-CSA had the highest amount of luteolin among all the CL samples analyzed. F-CSA reduced the release of inflammatory cytokines and mediators such as NO and PGE2 by inhibiting the expression levels of iNOS and COX-2 in LPS-stimulated macrophages. Further, we found that the anti-inflammatory effects of F-CSA were mediated by inhibiting the JNK/NF-κB signaling pathway. Moreover, F-CSA improved survival rates and reduced plasma levels of NO and IL-6 in CD1 mice stimulated with LPS. These findings suggest that F-CSA, which contains luteolin, can alleviate inflammation in LPS-induced RAW 264.7 cells and a CD1 mouse model by inhibiting the JNK/NF-κB signaling pathways.

Overexpression of Glu-1Bx7 via allele 1Bx7OE significantly contributes to high dough strength in some wheat varieties and is useful for improving wheat quality. However, the proportion of wheat varieties containing Bx7OE is quite low. In this study, four cultivars containing 1Bx7OE were selected, and among the selected varieties, Chisholm (1Ax2*, 1Bx7OE + 1By8*, and 1Dx5 + 1Dx10) was crossed with Keumkang, a wheat variety that contains 1Bx7 (1Ax2*, 1Bx7 + 1By8, and 1Dx5 + 1Dx10). SDS-PAGE and UPLC analyses showed that the expression of the high-molecular-weight glutenin subunit (HMW-GS) 1Bx7 was significantly higher in NILs (1Ax2*, 1Bx7OE + 1By8*, and 1Dx5 + 1Dx10) compared with that in Keumkang. Wheat quality was analyzed with near infrared reflectance spectroscopy by measuring the protein content and SDS-sedimentation of NILs. The protein content of NILs (12.94%) was 21.65% higher than that of Chisholm (10.63%) and 4.54% higher than that of Keumkang (12.37%). In addition, the SDS-sedimentation value of NILs (44.29 mL) was 14.97% and 16.44% higher than that of Keumkang (38.52 mL) and Chisholm (38.03 mL), respectively. This study predicts that the quality of domestic wheat can be improved by crossbreeding with 1Bx7OE-containing cultivars.

The selection of wheat varieties with high arabinoxylan (AX) levels could effectively improve the daily consumption of dietary fiber. However, studies on the selection of markers for AX levels are scarce. This study analyzed AX levels in 562 wheat genotypes collected from 46 countries using a GWAS with the BLINK model in the GAPIT3. Wheat genotypes were classified into eight subpopulations that exhibited high genetic differentiation based on 31,926 SNP loci. Eight candidate genes were identified, among which those encoding F-box domain-containing proteins, disease resistance protein RPM1, and bZIP transcription factor 29 highly correlated with AX levels. The AX level was higher in the adenine allele than in the guanine alleles of these genes in the wheat collection. In addition, the AX level was approximately 10% higher in 3 adenine combinations than 2 guanine, 1 adenine, and 3 guanine combinations in genotypes of three genes (F-box domain-containing proteins, RPM1, and bZIP transcription factor 29). The adenine allele, present in 97.46% of AX-95086356 SNP, exhibited a high correlation with AX levels following classification by country. Notably, the East Asian wheat genotypes contain high adenine alleles in three genes. These results highlight the potential of these three SNPs to serve as selectable markers for high AX content.

In this study, the weldability of as-cast CM247LC superalloy was metallurgically evaluated for turbine blade applications in terms of its hot cracking behavior and susceptibility. For this purpose, a real blade was manufactured using a directional solidification casting process, and gas tungsten arc welding was performed at the tip and cavity of the upper blade. Hot cracking was confirmed in the heat-affected zone of the gas tungsten arc welds, and the cracks were characterized as liquation cracks. Metallurgical solutions to suppress the liquation cracking susceptibility were derived via visualization-based spot-Varestraint test. The alloy subjected to aging treatment exhibited the lowest liquation cracking susceptibility (liquation cracking temperature range: 66 K), while the as-cast alloy specimen exhibited the highest (liquation cracking temperature range: 620 K). The metallurgical mechanisms of the liquation cracking susceptibility of as-cast CM247LC welds were elucidated via microstructural analyses and thermodynamic calculations. The suppressed liquation cracking susceptibility of the aged CM247LC could be explained as follows: (i) reduced MC-type carbide, which lowered the local solidus temperature compared with the equilibrium solidus temperature of CM247LC and (ii) increased solidus temperature owing to γ’ precipitation γ’ within the γ matrix. To validate the suppressed liquation cracking susceptibility of the aged CM247LC specimen in real welding, it was subjected to gas tungsten arc welding. The results indicated considerable suppression of liquation cracking compared with as-cast welds; in particular, the reduced liquation cracking temperature range was well-reflected in the welding.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of Moringa concanensis leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that M. concanensis treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, M. concanensis inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of M. concanensis ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, M. concanensis could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that M. concanensis exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β.

Wheat is highly susceptible to heat stress, which significantly reduces grain yield. In this study, we used RNA-seq technology to analyze the transcript expression at three different time-points after heat treatment in three cultivars differing in their susceptibility to heat stress: Jopum, Keumkang, and Olgeuru. A total of 11,751, 8850, and 14,711; 10,959, 7946, and 14,205; and 22,895, 13,060, and 19,408 differentially-expressed genes (log2 fold-change > 1 and FDR (padj) < 0.05) were identified in Jopum, Keumkang, and Olgeuru in the control vs. 6-h, in the control vs. 12-h, and in the 6-h vs. 12-h heat treatment, respectively. Functional enrichment analysis showed that the biological processes for DEGs, such as the cellular response to heat and oxidative stress—and including the removal of superoxide radicals and the positive regulation of superoxide dismutase activity—were significantly enriched among the three comparisons in all three cultivars. Furthermore, we investigated the differential expression patterns of reactive oxygen species (ROS)-scavenging enzymes, heat shock proteins, and heat-stress transcription factors using qRT-PCR to confirm the differences in gene expression among the three varieties under heat stress. This study contributes to a better understanding of the wheat heat-stress response at the early growth stage and the varietal differences in heat tolerance.

Bone health: Enzyme protects against damage during stress An antioxidant enzyme actively works to reduce bone synthesis under oxidative stress conditions in order to protect bone cells from damage and cell death. Bone is generated by cells called osteoblasts, which differentiate from stem cells. In osteoporosis and diabetes, excessive reactive oxygen species (ROS) within cells can disrupt osteoblast differentiation. South Korean researchers led by Eun-jung Kim at Kyungpook National University, Daegu, and Won-Gu Jang at Daegu University, Gyeongbuk, have shown that an antioxidant enzyme, peroxiredoxin II (PrxII), helps regulate bone formation under oxidative stress. The team generated PrxII-deficient mice and compared them with healthy normal mice. Under oxidative stress conditions, the mice had higher bone mass and higher expression of genes related to bone formation than the normal mice. PrxII limits osteoblast differentiation during elevated ROS by influencing associated protein activity and signalling pathways.

Sprouting is associated with nutritional value, as microgreens stimulate the accumulation of health-promoting phytochemicals. The purpose of this study was to examine the growth rates and cell protection activity against oxidative stress in sprouts of seven wheat varieties, and to investigate the influence of low temperatures on their phytochemical characteristics. Among the seven wheat varieties (five Korean varieties, Australian standard white, and Chinese wild-type wheat germplasm), purple wheat (Ariheuk) had the fastest growth pattern for 8 days and provided the most protection to skin cells and hepatocytes against oxidative stress. Following low-temperature treatment (

Since the onset of the COVID-19 pandemic, there has been a growing demand for effective and safe disinfectants. A novel use of chlorine dioxide (ClO2) gas, which can satisfy such demand, has been reported. However, its efficacy and safety remain unclear. For the safe use of this gas, the stable release of specific concentrations is a must. A new type of ClO2 generator called Dr.CLOTM has recently been introduced. This study aimed to investigate: (1) the effects of Dr.CLOTM on inhibiting adenoviral amplification on human bronchial epithelial (HBE) cells; and (2) the acute inhalation safety of using Dr.CLOTM in animal models. After infecting HBE cells with a recombinant adenovirus, the inhibitory power of Dr.CLOTM on the virus was expressed as IFU/mL in comparison with the control group. The safety of ClO2 gas was indirectly predicted using mice by measuring single-dose inhalation toxicity in specially designed chambers. Dr.CLOTM was found to evaporate in a very constant concentration range at 0–0.011 ppm/m3 for 42 days. In addition, 36–100% of adenoviral amplification was suppressed by Dr.CLOTM, depending on the conditions. The LC50 of ClO2 gas to mice was approximately 68 ppm for males and 141 ppm for females. Histopathological evaluation showed that the lungs of female mice were more resistant to the toxicity from higher ClO2 gas concentrations than those of male mice. Taken together, these results indicate that Dr.CLOTM can be used to provide a safe indoor environment due to its technology that maintains the stable concentration and release of ClO2 gas, which could suppress viral amplification and may prevent viral infections.

The mechanism of atopic dermatitis (AD) is modulated by the release of cytokines and chemokines through the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Topical steroids are used to treat AD, but some people need safer anti-inflammatory drugs to avoid side effects. Mentha arvensis has been used as a herbal plant with medicinal properties, but its anti-inflammatory effects have not been elucidated in an AD model. In this study, we investigated the anti-inflammatory effects of M. arvensis essential oil (MAEO) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and HaCaT cells (human epidermal keratinocyte). Additionally, we examined the ameliorating effects of the MAEO in a dinitrochlorobenzene (DNCB)-induced murine model of AD. We found, in both RAW 264.7 cells and HaCaT cells, MAEO inhibited LPS-stimulated inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 and proinflammatory cytokines, including IL-1β and IL-6, due to the suppression of COX-2 and iNOS expression. In LPS-stimulated macrophages, we also observed that MAEO inhibited the phosphorylation of ERK and P65. Furthermore, MAEO treatment attenuated AD symptoms, including the dermatitis score, ear thickness, epidermal thickness and infiltration of mast cells, in a DNCB-induced animal model of AD. Overall, our findings suggest that MAEO exerts anti-inflammatory and anti-atopic dermatitis effects via inhibition of the ERK/NF-κB signaling pathway.

The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1β, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK/JNK/NF-κB signaling cascades and production of IL-6.

This study investigated the kind of seed dormancy and seed germination of Gentiana triflora var. japonica (Kusn.) H. Hara for developing a seed propagation method. The seeds were collected in October 2020 from plants at Mt. Sobaeksan, Korea. In a water imbibition experiment, seed weights increased by >101.9% of their initial masses over 12 h. Effects of incubation temperature (5, 15, 20, 25, 15/6, or 25/15 °C), cold stratification period (5 °C; 0, 4, 8, or 12 weeks), and gibberellic acid (GA3; 0, 10, 100, or 1000 mg∙L−1) and potassium nitrate treatment (KNO3; 0, 1000, 2000, or 4000 mg∙L−1) on seed germination were investigated to characterize seed dormancy. These seeds exhibited underdeveloped embryos during seed dispersal. The seeds failed to reach the final germination of 15.0% after treatment at 5, 15, 20, 25, 15/6, or 25/15 °C. After cold stratification for 8 weeks, the germination increased dramatically by >90.0% compared to that at 0 weeks. After the GA3 treatment, the germination reached >80.0% within 5 days. The final germination was 90.0% in the 100 mg∙L−1 GA3 treatment group. However, the KNO3 treatment had no effect on seed germination. Therefore, the G. triflora var. japonica seeds exhibited non-deep simple morphophysiological dormancy.

Selecting wheat with favorable spike characteristics has been a popular breeding strategy to improve sink capacity and yield potential. In the present study, quantitative trait loci (QTLs) for yield potential traits were identified using a recombinant inbred line (RIL) population derived from the cross between Taejoong and Keumkang, two Korean wheat cultivars. A linkage map encompassing a total genetic length of 6544.8 cM was constructed using 838 single nucleotide polymorphisms from the 35K Axiom Wheat Breeder’s Array. We detected eight QTLs for four yield potential traits that are consistently identified in at least two of the three environments, that is, one for days to heading date (QDHD-1 on chromosome 7B), three for spike length (QSL-1, QSL-2, and QSL-3 on chromosomes 1D, 5A, and 6A, respectively), one for tiller number (QTN-1 on chromosome 5B), and three for length of center rachis (QLCR-1, QLCR-2, and QLCR-3 on chromosomes 1B, 5B, and 6A, respectively). Notably, Taejoong contributed the alleles for long spike at all three spike length QTLs with the additive effects of 0.6 cm, 0.6 cm, and 0.9 cm at QSL-1, QSL-2, and QSL-3, respectively. No significant two-way or three-way interaction was observed among QSL-1, QSL-2, and QSL-3, indicating that pyramiding the Taejoong alleles at the three QTLs can increase spike length additively. While the Taejoong alleles at QSL-1, QSL-2, and QSL-3 were associated with increased days to heading date, more kernels per spike, and reduced tiller number per plant, the extent of the pleiotropic effects were different among the three QTLs. Due to the limited number of molecular markers and mapping resolution, further work is required to narrow down the identified QTLs and characterize their effects more precisely. Our results would provide useful information for modulating spike characteristics and improving yield potential in wheat breeding programs.

Abstract The present work introduced a framework to investigate the effectiveness of proton boron fusion therapy (PBFT) at the cellular level. The framework consisted of a cell array generator program coupled with PHITS Monte Carlo package with a dedicated terminal-based code editor that was developed in this work. The framework enabled users to model large cell arrays with normal, all boron, and random boron filled cytoplasm, to investigate the underlying mechanism of PBFT. It was found that alpha particles and neutrons could be produced in absence of boron mainly because of nuclear reaction induced by proton interaction with 16O, 12C and 14N nuclei. The effectiveness of PBFT is highly dependent on the incident proton energy, source size, cell array size, buffer medium thickness layer, concentration and distribution of boron in the cell array. To quantitatively assess the effectiveness of PBFT, of the total energy deposition by alpha particle for different cases were determined. The number of alpha particle hits in cell cytoplasm and nucleus for normal and 100 ppm boron were determined. The obtained results and the developed tools would be useful for future development of PBFT to objectively determine the effectiveness of this treatment modality.

Background: Oligomeric amyloid beta (oAβ) is a toxic factor that acts in the early stage of Alzheimer’s disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAβ has a crucial role in the early diagnosis, monitoring, and treatment of AD. Purpose: The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent. Methods: We developed an MRI contrast agent by conjugating Gd-DOTA-DNA aptamer called ob5 to evaluate its ability to detect oAβ deposits in the brain using MRI. A total of 10 control mice, 9 3xTg AD mice, and 11 APP/PS/Tau AD mice were included in this study, with the age of each model being 16 or 36 weeks. A T1- weighted image was acquired at the time points before (0 min) and after injection of the contrast agent at 5, 10, 15, 20, and 25 min. The analyses were performed to compare MRI signal differences among the three groups and the time-dependent signal differences in different mouse models. Results: Both 3xTg AD and APP/PS/Tau AD mouse models had higher signal enhancement than control mice at all scan-time points after injection of our contrast media, especially in bilateral hippocampal areas. In particular, all Tg AD mouse models aged 16 weeks showed a higher contrast enhancement than those aged 36 weeks. For 3xTg AD and APP/PS/Tau AD groups, the signal enhancement was significantly different among the five time points (0 min, 5 min, 10 min, 15 min, 20 min, and 25 min) in multiple ROI areas, typically in the bilateral hippocampus, left thalamus, and left amygdala. Conclusion: The findings of this study suggest that the expression of the contrast agent in different AD models demonstrates its translational flexibility across different species. The signal enhancement peaked around 15–20 min after injection of the contrast agent. Therefore, our novel contrast agent targeting oAβ has the potential ability to diagnose early AD and monitor the progression of AD. [ABSTRACT FROM AUTHOR]

Background. Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. Method. We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. Results. Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3β (GSK-3β) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. Conclusion. The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3β activity, highlighting Nrf2-HO-1 and GSK-3β as potential therapeutic targets in diabetic nephropathy.

INTRODUCTION:The purpose of this research is to evaluate the prospects for the use of 4-(trans-18F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide (18F-Mefway) in comparison to 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) for the quantification of 5-HT1A receptors in human subjects. METHOD:Five healthy male controls were included for two positron emission tomography (PET) studies: 18F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, 18F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio). RESULT:Although the pattern of regional uptakes in the 18F-Mefway PET was similar to that of the 18F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in 18F-Mefway PET was almost half of that in 18F-FCWAY PET. The skull uptake in 18F-Mefway PET was only 25% of that in 18F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for 18F-Mefway were 17-40% lower than those of 18F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in 18F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in 18F-Mefway PET. CONCLUSION:As 18F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, 18F-Mefway may appear less favorable than 18F-FCWAY. However, in contrast to 18F-FCWAY, the resistance to in vivo defluorination of 18F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, 18F-Mefway may be a good candidate PET radioligand for 5-HT1A receptor imaging in human.

Versatile high-power pulsed electron-beam accelerators that meet the requirements of pulsed high-power specifications are needed for appropriate applications in medical industry, defense, and other industries. The pulsed electron beam accelerator comprising a Marx generator and Blumlein pulse forming line (PFL) is designed to accelerate the electron beams at the level of 1 MeV when electrostatically discharging. The performance specifications of Marx generators consisting of a 100 kV DC power supply, R-L-C circuit, and high voltage switch are at a maximum 800 kV. At this time, by using the capacitance mismatching principle between the Marx generator and the Blumlein PFL under the law of preserving the amount of charge, it is possible to generate a high voltage in the form of a square pulse up to about 1.1 MV, as much as 1.37 times the charged voltage of the Marx generator. As a result, energy transmission from the Marx generator with a high efficiency of about 85% to the Blumlein PFL is possible. The aim of this study is that the pulsed high-power electron-beam accelerator can be used to change the diode impedance, and the energy of the accelerated electron beam reaches a level of 1 MeV with the square pulse width of about 100 ns at the flat-top in the range of relativistic electron beam generation. Performance tests were securely carried out by installing a dummy load based on CuSO4 solution varying the diode impedance to deter damage to the circuit by preventing reflected waves from being generated in the load. [ABSTRACT FROM AUTHOR]

Background: Mortality is higher in patients with chronic kidney disease (CKD) than in the general population, but little information is available on CKD-related mortality that is representative of the Korean population. Our objective was to investigate mortality risk in Korean patients with CKD. Methods: We identified patients with incident CKD who had not undergone dialysis or kidney transplantation between January 1, 2003 and December 31, 2007 in Korea using the database of the Korean National Health Insurance Service-National Sample Cohort, and stratified the population into the following three groups: group 1 (n = 1,473), controls; group 2 (n = 2,212), patients with diabetes or hypertension, but without CKD; and group 3 (n = 2,212), patients with CKD. We then monitored them for all-cause mortality until December 2013. Results: A total of 1,473 patients were included in this analysis. During the follow-up period, 941 patients in group 3 died (134 deaths/1,000 person-years) compared with 550 deaths in the group 2 (34 deaths/1,000 person-years) and 459 deaths in group 1 (30 deaths/1,000 person-years). The rate ratio for mortality rate was 4.5, and the hazard ratio for mortality was 4.88 (95% confidence interval [CI], 4.36-5.47, P < 0.001) in patients in group 3 compared with age- and sex-matched controls (group 1). The rate ratio for mortality rate was 4.0, and the hazard ratio for mortality was 4.36 (95% CI, 3.92-4.85, P < 0.001) in patients in group 3 compared with patients in group 2. Conclusion: In this nationally representative sample cohort, excess mortality was observed in Korean patients with incident CKD. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. Conclusion: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

Among the metal–oxide nanoparticles, pure and doped zinc oxide (ZnO) has been widely studied due to their potential applications, such as electrical, thermal and optical materials. In this context, samples of undoped ZnO and Cr-doped ZnO powders were prepared using a solution-combustion route. The formation of the combustion products was confirmed by X-ray diffraction analysis. The samples were well characterized using the Fourier transform infrared spectroscopy and scanning electron microscopy techniques. In the sample, photoluminescence studies showed that ZnO could be excited at 267 nm, while an ultraviolet emission centred at ~383 nm was exhibited. Antibacterial-activity testing was carried out using the disc-diffusion method. [ABSTRACT FROM AUTHOR]

Purpose We investigated the effects of hypothyroidism on serotonin 1A receptors in the rat brain in vivo. Methods Five surgically thyroidectomized male Sprague–Dawley (SD) rats and five hypophysectomized SD rats were used as animal models of hypothyroidism; the same number of sham-operated SD rats served as age-matched controls. After hypothyroidism was confirmed by thyroid function tests, serotonin positron emission tomography (PET) was performed for 120 min. All PET data were spatially normalized to T2-weighted magnetic resonance imaging templates; then, time-activity curves of the hippocampus, septum, and cerebellum were extracted using predefined volume-of-interest templates. Non-displaceable binding values in the hippocampus and septum were calculated using a multilinear reference tissue model and parametric maps were constructed. Both volume-of-interest and voxel-based analyses showed higher brain uptake in the thyroidectomized and hypophysectomized rats compared to the respective sham-operated rats. Results Time-activity curves showed that the brain uptake values for the thyroidectomized and hypophysectomized groups were 21–52% higher than were those in the respective control groups. In the thyroidectomized group, the binding potential values for the hippocampus and septum were 20–26% higher than were those in the sham-thyroidectomized group. In the hypophysectomized group, the binding value for the hippocampus was 23% higher than was that in the sham-hypophysectomized group, whereas the septal binding was not significantly different from that in the sham-hypophysectomized group. Parametric maps for the hypothyroidism also showed significantly higher binding values than did those for the controls. Conclusion Our results demonstrate that hypothyroidism elevates serotonin 1A receptor binding in the limbic system. [ABSTRACT FROM AUTHOR]

Optical imaging techniques are widely used for in vivo preclinical studies, and it is well known that the Geant4 Application for Emission Tomography (GATE) can be employed for the Monte Carlo (MC) modeling of light transport inside heterogeneous tissues. However, the GATE MC toolkit is limited in that it does not yet include optical lens implementation, even though this is required for a more realistic optical imaging simulation. We describe our implementation of a biconvex lens into the GATE MC toolkit to improve both the sensitivity and spatial resolution for optical imaging simulation. The lens implemented into the GATE was validated against the ZEMAX optical simulation using an US air force 1951 resolution target. The ray diagrams and the chargecoupled device images of the GATE optical simulation agreed with the ZEMAX optical simulation results. In conclusion, the use of a lens on the GATE optical simulation could improve the image quality of bioluminescence and fluorescence significantly as compared with pinhole optics. [ABSTRACT FROM AUTHOR]

The thymidine analogue 3'-deoxy-3'-[18F]fluorothymidine, or [18F]fluorothymidine ([18F]FLT), is used to measure tumor cell proliferation with positron emission tomography (PET) imaging technology in nuclear medicine. FLT is phosphorylated by thymidine kinase 1 (TK1) and then trapped inside cells; it is not incorporated into DNA. Imaging with 18F-radiolabeled FLT is a noninvasive technique to visualize cellular proliferation in tumors. However, it is difficult to distinguish between [18F]FLT and its metabolites by PET imaging, and quantification has not been attempted using current imaging methods. In this study, we successfully acquired in vivo 19F spectra of natural or nonradioactive 3'-deoxy-3'-fluorothymidine ([19F]FLT) and its monophosphate metabolite (FLT-MP) in a tumor xenograft mouse model using 9.4T magnetic resonance imaging (MRI). This preliminary result demonstrates that 19F magnetic resonance spectroscopy (MRS) with FLT is suitable for the in vivo assessment of tumor aggressiveness and for early prediction of treatment response. [ABSTRACT FROM AUTHOR]

While early studies on the Korean long distance anaphor caki describe it to be subject-oriented in that it can only take subject antecedents, similarly to long distance anaphors in many other languages, more recent studies observe that it can take non-subject antecedents as well, especially in the context of certain verbs. This paper presents a visual-world eye-tracking study that tested whether the antecedent potential of caki in an embedded subject position is a function of the matrix subject, the matrix verb, or both, and whether the subject and the verb effects constrain the interpretation of caki in the same way as null pronouns, a commonly used pronominal form in Korean. These questions were addressed through an investigation of how the subject effect and the verb effect were manifested in processing these pronouns. We found that when caki, but not null pronouns, was first processed, there were more fixations to the images representing the matrix subject than the images representing the matrix object regardless of the matrix verb. We further found that the proportions of fixations to the images in both caki and null trials changed after the processing of some sentential verbs. These findings demonstrate that while null pronoun interpretation is a function of the verb effect only, caki-interpretation is a function of both the subject and the verb effect, supporting a multiple-constraints approach to anaphor resolution. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains. [ABSTRACT FROM AUTHOR]

Purpose: Attenuation correction (AC) is important in quantitative positron emission tomography (PET) imaging of medium-sized animals such as the cat. However, additional time for transmission (TX) scanning and tracer uptake is required in PET studies with animal-dedicated PET scanners because post-injection TX scanning is not available in these systems. The aim of this study was to validate a template-guided AC (TGAC) method that does not require TX PET data for AC in cat 2-deoxy-2-[F-(18)fluoro-D-glucose (FDG) brain PET imaging.Methods: PET scans were acquired using a microPET Focus 120 scanner. TX data were obtained using a (68)Ge point source before the injection of FDG. To generate the attention map (mu-map) template for the TGAC, a target image of emission (EM) PET was selected, and spatial normalization parameters of individual EM data onto the target were reapplied to the corresponding mu-maps. The inverse transformations of the mu-map template into the individual spaces were performed, and the transformed template was forward projected to generate the AC factor. The TGAC method was compared with measured AC (MAC) and calculated AC (CAC) methods using region of interest (ROI) and SPM analyses.Results: The ROI analysis showed that the activity of the TGAC EM PET images strongly correlated with those of the MAC data (y = 0.98x + 0.01, R(2) = 0.96). In addition, no significant difference was observed in the SPM analysis. By contrast, the CAC showed a significantly higher uptake in the deep gray regions compared to the MAC (corrected P < 0.05). The ROI correlation with MAC was worse than with the TGAC (R(2) = 0.84). In SPM analysis for the voxel-wise group comparisons between before and after the induction of deafness, only the TGAC showed equivalent results with the MAC.Conclusions: The TGAC was reliable in cat FDG brain PET studies in terms of compatibility with the MAC method. The TGAC might be a useful option for increasing study throughput and decreasing the probability of subject movement. In addition, it might reduce the possible biological effects of long-term anesthesia on the cat brain in investigations using animal-dedicated PET scanners. [ABSTRACT FROM AUTHOR]

A p-type ZnO thin film was prepared using arsenic diffusion via the ampoule-tube method. This was followed by fabrication of a ZnO p–n homojunction using n-type ZnO and characterization of the device properties. The ZnO thin film exhibited p-type characteristics, with a resistivity of 2.19×10−3 Ω cm, a carrier concentration of 1.73×1020/cm3, and a mobility of 26.7 cm2/V s. Secondary ion mass spectrometer analysis confirmed that in- and out-diffusion occurred simultaneously from the external As source and the GaAs substrate. The device exhibited the rectification characteristics of a typical p–n junction; the forward voltage at 20 mA was approximately 5.5 V. The reverse-bias leakage current was very low—0.1 mA for −10 V; the breakdown voltage was −11 V. The ampoule-tube method for fabricating p-type ZnO thin films may be useful in producing ultraviolet ZnO LEDs and other ZnO-based devices. [ABSTRACT FROM AUTHOR]

Small animal PET scanning with 18F-FDG has been increasingly used in the studies using murine tumor models. The aim of this study was to obtain multimodal tumor images with the use of small animal PET and clinical CT by using hardware guidance and a registration method. PET imaging studies were performed with a dedicated small animal PET scanner. Static PET images of mice with liver and lung tumors were scanned for 20 minute by the use of hardware guidance with 1% activity of the injected dose. The CT images obtained with the use of a clinical CT scanner can be used to improve the anatomical localization of uptake in PET images. 124I-FIAU-PET was obtained from mice containing an orthotopic hepatocellular carcinoma (HCC). Contrast enhanced CT images were obtained at three hours after injection of contrast agent. The PET and CT images were fused using hardware fiducial markers that were manually identified in both data sets. The PET and CT images were precisely registered by the use of a small animal contour point in both data sets to perform a point-based rigid registration. The registered images in the HCC model and a lung metastatic tumor model showed good agreement of tumor region on the both PET and CT images. The use of PET and contrast enhanced CT allowed a precise and improved detection of tumors in liver and lung models. Multimodal imaging with small animal PET and clinical CT images was useful in the detection of metastatic tumors and this multimodal imaging registration method can improve the quantitative accuracy and interpretation of tracer. [ABSTRACT FROM AUTHOR]

201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time–activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant ( K 1) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time–activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBFSPECT) correlated well with the MBF values obtained by the radio-labelled microspheres (MBFMS) (MBFSPECT = −0.067 + 1.042 × MBFMS, p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO2) may be quantified using positron emission tomography (PET) with 15O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of 15O2, H215O, and C15O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO2 from a single PET acquisition with a sequential administration of 15O2 and H215O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO2 obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEFA−V) for a physiologically wide range when changing the arterial PaCO2 (gOEF=1.03gOEFA−V +0.01, P<0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO2. In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO2. These results show that this fast technique has an ability for accurate assessment of CBF/CMRO2 and also allows multiple assessment at different physiologic conditions.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1209–1224. doi:10.1038/sj.jcbfm.9600118; published online 4 May 2005 [ABSTRACT FROM AUTHOR]

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with non-uniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90° and 45° relative to the object’s axis. This system satisfies Tuy’s condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with 99mTc solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using 99mTc-hydroxymethylene diphosphonate. Feldkamp’s filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of bio-physiological functions in small animals. [ABSTRACT FROM AUTHOR]

The values of cerebral blood flow (CBF) and vascular volume (V0) can be estimated using H215O dynamic PET and the two-compartment model. In this study, we present a method that can generate parametric images of both CBF and V0, with improvement of image quality, by a single computational procedure. This method is based on the two-compartment model, and employs linear least square algorithm and cluster analysis for parameter estimation and suppressing noise on image data, respectively. The results in computer simulation showed that this method could provide the reduction of error in parameter estimation, as well as noise on parametric images of both CBF and V0, and the smaller effect of changes of CBF and V0 on the estimation of both parameters. In the PET study, this method could provide the images of CBF and V0 with improvement in quality, compared with those without clustering by showing the clear location of arterial vascular components on the V0 image. In the simulation, the error in parameter estimation was sufficiently small for K1, but not for V0. These results reveal that the presented method has the potential to make a contribution to the improved diagnosis of cerebral vascular disease and activation. [Copyright &y& Elsevier]

Presents a study that developed and evaluated an input function detector system that can be applied to both positron emission tomography (PET) and single photon emission computed tomography (SPECT). Physiological functions that can be assessed quantitatively using PET and SPECT devices; Factors that were taken into account to develop a continuous monitoring system of input function; Electronic circuit diagram for PET studies.