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Because of their combined effects of outstanding mechanical stability, high electrical conductivity, and high theoretical capacity, silicon (Si) nanoparticles embedded in carbon are a promising candidate as electrode material for practical utilization in Li-ion batteries (LIBs) to replace the conventional graphite. However, because of the poor ionic diffusion of electrode materials, the low-grade ultrafast cycling performance at high current densities remains a considerable challenge. In the present study, seeking to improve the ionic diffusion, we propose a novel design of mesoporous carbon skin on the Si nanoparticles embedded in carbon by hydrothermal reaction, poly(methyl methacrylate) coating process, and carbonization. The resultant electrode offers a high specific discharge capacity with excellent cycling stability (1140 mA h g–1 at 100 mA g–1 after 100 cycles), superb high-rate performance (969 mA h g–1 at 2000 mA g–1), and outstanding ultrafast cycling stability (532 mA h g–1 at 2000 mA g–1 after...

Pure BiVO4, B-doped BiVO4, Mg-doped BiVO4, and B–Mg co-doped BiVO4 were prepared using a mixed aqueous solution of bismuth nitrate (Bi(NO3)3) and ammonium vanadate (NH4VO3) using a hydrothermal method. The crystal structure and thermochromic behaviors of BiVO4 samples were investigated using X-ray diffraction, UV-Vis spectrophotometry, and in situ X-ray diffraction to compare the effects of the doping elements on the thermochromic behaviors of BiVO4. The results showed that B and Mg ions co-doped into the lattice of BiVO4 led to lattice deformation, higher impurity levels, more new band gap states, a narrower band gap, and an improvement in thermochromic behaviors than either ion alone. The thermochromic behavior of B4%–Mg4% co-doped BiVO4 was remarkably improved in comparison with the others owing to the synergistic effects of the co-doped ions.

OBJECTIVEThere has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created.METHODSThe model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done.RESULTSBy 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals.CONCLUSIONSA novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research tool to elucidate the pathogenesis of this type of syringomyelia, as well as the CSF hydrodynamics of the lumbar spinal cord.

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.

Phosphate overload contributes to mineral bone disorders associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and negligible in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+and phosphate absorption and homeostasis are unknown. Here we show that excessive intake of phytate with a low-Ca2+diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+diet and a risk factor for phosphate overloading and developing crystal nephropathies and bone disease.

Plant viruses have been engineered to express heterologous proteins and RNAs in plants for several decades. This viral system can now be applied to editing plant genomes. Virus vectors can deliver Cas proteins and guide RNAs, two key components of the CRISPR gene-editing system, into a plant cell without a complicated experimental procedure. In some cases, plant viruses move to meristematic cells and express gene-editing components in the cell, which results in the production of mutant seeds. Here, we focus on three main issues of the virus-induced genome editing (VIGE) technology in plants: (1) how to express the relatively large size of Cas proteins, (2) how to express guide RNA, and (3) how to increase the efficiency with which viruses are delivered into meristematic cells. We highlight recent advances in how plant virus vectors can be used efficiently in plant-genome editing.

This study aimed to investigate distinct neurometabolites in the anterior cingulate cortex (ACC), right and left thalamus, and insula of patients with fibromyalgia (FM) compared with healthy controls using proton magnetic resonance spectroscopy (MRS). Levels of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), total NAA (tNAA = NAA + NAAG), myo-inositol (ml), glutamine (Gln), glutamate (Glu), Glx (Glu + Gln), glycerophosphocholine (GPC), total choline (tCho = GPC + phosphocholine) and glutathione (GSH) levels relative to total creatine (tCr) levels including creatine (Cr) and phosphocreatine (PCr) and relative to Cr levels were determined in the ACC, right and left thalamus, and insula in 12 patients with FM and 13 healthy controls using MRS. In the ACC, NAA/tCr (P = 0.028) and tCho/tCr (P = 0.047) were higher in patients with FM. In the right and left insula, tNAA/tCr (P = 0.019, P = 0.007, respectively) was lower in patients with FM. Patients with FM showed lower levels of ml/Cr (P = 0.037) in the right insula than healthy controls. These findings are paramount to understand decisive pathophysiological mechanisms related to abnormal features in the brain and parasympathetic nervous systems in FM. We suggest that the results presented herein may be essential to understand hidden pathological mechanisms and also life system potential as protective and recovering metabolic strategies in patients with FM.

BCAT1 (branched-chain amino acid trasaminase1) expression is necessary for the progression of IDH1 wild-type (WT) glioblastoma multiforme (GBM), which is known to be associated with aggressive tumors. The purpose of our study is to investigate the bevacizumab resistance increased by the expression of BCAT1 in IDH1 WT GBM in a rat model, which was evaluated using DSC perfusion MRI. BCAT1 sh#1 inhibits cell proliferation and limits cell migration potential in vitro. In vivo MRI showed that the increase in both tumor volume and nCBV after bevacizumab treatment in IDH1 WT tumors was significantly higher compared with BCAT1 sh#1tumors. In a histological analysis, more micro-vessel reformation by bevacizumab resistance was observed in IDH1 WT tumors than BCAT1 sh#1 tumors. These findings indicate that BCAT1 expression in IDH1 WT GBM increases resistance to bevacizumab treatment, which could be assessed by DSC perfusion MRI, and that nCBV can be a surrogate imaging biomarker for the prediction of antiangiogenic treatment in GBM.

Purpose To investigate the effect of fat suppression on T2 mapping of the articular cartilage in the porcine knee joint using magnetic resonance imaging (MRI). Materials and Methods Eleven porcine knee joints were harvested en bloc with intact capsules. We performed T2 mapping of the articular cartilage in the medial femoral condyle at 3T either with (fat-suppressed T2 mapping) or without (conventional T2 mapping) fat suppression in the sagittal plane under two frequency-encoding directions: from superior to inferior (SI) and inferior to superior (IS). Two observers measured the T2 values of the medial femoral condyle cartilage in four regions: in the anterior oblique, central horizontal, posterior oblique, and posterior vertical portions. We evaluated reproducibility of the fat-suppressed and conventional T2 mapping by changing the frequency-encoding direction. Results The mean T2 values of fat-suppressed T2 mapping were significantly lower than those of conventional T2 mapping for five of eight comparisons (P < 0.017). The mean T2 values between fat-suppressed T2-SI and fat-suppressed T2-IS did not differ significantly in any region (P = 0.077–0.873). However, the mean T2 values of conventional T2-SI were significantly lower compared with conventional T2-IS in three of the regions (P < 0.05). The intraclass correlation coefficient (ICC) between the two fat-suppressed T2 maps was higher than the ICC between the two conventional T2 maps (0.276–0.800 vs. –0.032–0.455) for three regions. Conclusion Compared with conventional T2 mapping, fat-suppressed T2 mapping provides lower T2 values of the articular cartilage and more reproducible results for the porcine knee joint. J. Magn. Reson. Imaging 2016.

Purpose To compare the inner ear enhancement after intratympanic injection of two widely used gadolinium (Gd) agents by 9.4 T micro-magnetic resonance imaging (MRI) and to investigate the effects of Gd on the inner ear. Methods Twelve ears of six rats received intratympanic administration of 1/5 diluted Gd agents: gadoterate meglumine (Gd-DTPA) for the left ear and gadodiamide (Gd-DTPA-BMA) for the right ear. MRI was performed every 30 min from 1 to 4 h after administration. The normalized signal intensity was evaluated by quantitative analysis at each cochlear fluid compartment. Eight, six, and seven ears treated with Gd-DTPA, Gd-DPTA-BMA, and nothing as controls, respectively, were processed for histological evaluation after MRI. After hematoxylin & eosin staining, adverse inflammatory reactions were evaluated for turbid aggregation and lymphocytes. Results The perilymphatic enhancement of Gd-DTPA was superior to that of Gd-DTPA-BMA regardless of cochlear turn, compartment, and time point. Inflammatory reactions were found in 4/8 (50.0%) and 4/6 (66.6%) ears administered Gd-DTPA and Gd-DTPA-BMA, respectively. Regardless of the contrast agent used, inflammatory reactions were most definite in the scala tympani of the basal turn, i.e., near the round window. Slightly greater inflammatory reactions were observed in ears injected with Gd-DTPA-BMA compared to Gd-DTPA although the difference was not statistically significant. No inflammatory reaction was observed in any of the seven controls. The auditory brainstem response threshold was 11.8 ± 2.5 dB SPL before IT Gd injection and it did not change for up to 5 days (15.4 ± 6.6 dB SPL) post-injection. Conclusions Gd-DTPA was superior to Gd-DTPA-BMA for visualization of the inner ear. Administration of diluted Gd agents intratympanically may induce considerable inflammatory reactions in the inner ear.

We investigated a therapeutic strategy for recurrent malignant gliomas using mesenchymal stem cells (MSC), expressing cytosine deaminase (CD), and prodrug 5-Fluorocytosine (5-FC) as a more specific and less toxic option. MSCs are emerging as a novel cell therapeutic agent with a cancer-targeting property, and CD is considered a promising enzyme in cancer gene therapy which can convert non-toxic 5-FC to toxic 5-Fluorouracil (5-FU). Therefore, use of prodrug 5-FC can minimize normal cell toxicity. Analyses of microarrays revealed that targeting DNA damage and its repair is a selectable option for gliomas after the standard chemo/radio-therapy. 5-FU is the most frequently used anti-cancer drug, which induces DNA breaks. Because dihydropyrimidine dehydrogenase (DPD) was reported to be involved in 5-FU metabolism to block DNA damage, we compared the survival rate with 5-FU treatment and the level of DPD expression in 15 different glioma cell lines. DPD-deficient cells showed higher sensitivity to 5-FU, and the regulation of DPD level by either siRNA or overexpression was directly related to the 5-FU sensitivity. For MSC/CD with 5-FC therapy, DPD-deficient cells such as U87MG, GBM28, and GBM37 showed higher sensitivity compared to DPD-high U373 cells. Effective inhibition of tumor growth was also observed in an orthotopic mouse model using DPD- deficient U87MG, indicating that DPD gene expression is indeed closely related to the efficacy of MSC/CD-mediated 5-FC therapy. Our results suggested that DPD can be used as a biomarker for selecting glioma patients who may possibly benefit from this therapy.

β-tricalcium phosphate (β-TCP, Ca3(PO4)2) is biodegradable ceramics with chemical and mineral compositions similar to those of bone. It is a potential candidate for bone repair surgery, and substituting the Fe ions can improve its biological behavior. In this study, we investigated the effect of Fe ions on the structural deviation andin vitrobehavior ofβ-TCP. Fe-dopedβ-TCP were synthesized by the co-precipitation method, and the heat treatment temperature was set at 1100 °C. The chemical state of the Fe-dopedβ-TCP was analyzed by x-ray photoelectron spectroscopy, while structural analysis was carried out by Rietveld refinement using the x-ray diffraction results. Fe ions existed in both Fe2+and Fe3+states and occupied the Ca-(4) and Ca-(5) sites. Fe ions enhanced the degradation ofβ-TCP and resorption behavior onto the surface ofβ-TCP during the immersion test. As a result, Fe ion improves the initial cell adhesion and proliferation behavior ofβ-TCP.

Supercapacitor performance comparison depending on the various oxide film thickness of aluminum foil was studied. The study was focused on the anodic behavior of organic solvent based cylindrical supercapacitor. The study aimed to see correlation between the active material current collector interface changes and the performance of the supercapacitor such as capacitance, ESR or gas generation depending on varying Al current collector oxidation pre-treatment. The results of performance test showed that electrode degradation of the interface between active material coating layer and the Al current collector are influenced by the oxidation pre-treatment process. Furthermore, the supercapacitor performance test by using long time period stored Al foil as a current collector (which is naturally oxidized at room temperature) was conducted to see how long the Al foil for supercapacitor can be stored without notable performance degradation.

Ojjective The aim of this study was to find peripheral biomarkers and central metabolites affecting neuroinflammation in complex regional pain syndrome (CRPS) patients using [11C]-(R)-PK11195 positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Methods Using MRS and PET, we measured associations between neurometabolites and neuroinflammation in 12 CRPS patients and 11 healthy controls. Also, we investigated various peripheral parameters that may affect neuroinflammation in CRPS. Results We found positive correlations of Lipid (Lip)13a/total creatine (tCr) and Lip09/tCr with neuroinflammation, the distribution volume ratio (DVR) of [11C]-(R)-PK11195 in the right and left insula in CRPS patients. However, these correlations were not found in controls. High hemoglobin levels correlated with decreased neuroinflammation (the DVR of [11C]-(R)-PK11195) in the right thalamus and left insula in healthy controls. We found that high levels of glucose and pH correlated with increased neuroinflammation, but high levels of CO2, basophil, and creatinine were associated with decreased neuroinflammation in the left thalamus and the right and left insula in CRPS patients. Conclusions This is the first report indicating that elevated neuroinflammation levels are associated primarily with lipids in the brain and pH, glucose, CO2, basophil, and creatinine in the peripheral parameters in CRPS patients. Our results suggest that characterizing the peripheral biomarkers and central metabolites affecting neuroinflammation is essential to understanding the pathophysiology of CRPS.

Purpose: The purpose of our study was to investigate the effect of different slice thicknesses and/or interslice gaps on longitudinal and transverse relaxation times (T1 and T2) measured by a multi-dynamic, multi-echo (MDME) sequence. Materials and Methods: This retrospective study included nine healthy subjects who underwent MDME sequence (at 3T) with four different combinations of slice thicknesses and/or interslice gaps: slice thickness of 4 mm and interslice gap of 0 mm (TH4/G0), TH4/G1, TH5/G0, and TH5/G1. T1 and T2 were measured in various brain regions by a qualified neuroradiologist with 8 years of clinical experience: the frontal white matter (WM), occipital WM, genu, splenium, frontal cortex, thalamus, putamen, caudate head, and cerebrospinal fluid (CSF). The paired samples t-test was used to investigate the effect of different slice thicknesses and interslice gaps (TH4/G0 versus TH4/G1 and TH5/G0 versus TH5/G1). P < 0.013 was considered statistically significant. Results: T2 in all brain regions and T1 in the frontal WM, putamen, and CSF did not significantly change for different slice thicknesses and/or gaps (Ps > 0.013). In addition, T1 in all brain regions of interest did not significantly change between TH4/G0, TH4/G1, TH5/G0 and TH5/G1. However, T1 in some of the brain regions was higher with TH4/G0 than with TH5/G0 (occipital WM, frontal cortex, and caudate head) and with TH4/G1 than with TH5/G1 (occipital WM, genu, splenium and thalamus, all Ps < 0.013). Conclusion: T2 estimated using the MDME sequence was stable regardless of slice thickness or gap. Although the sequence seems to provide stable relaxation values, identical slice thicknesses need to be used for follow-up to prevent potential T1 changes.

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food matrices, interactions between NPs and food components occur, which can affect biological systems. In this study, interactions between ZnO NPs and saccharides were investigated by measuring changes in hydrodynamic radius, zeta potential and solubility and by quantifying amounts of adsorbed saccharides on NPs; acacia honey, sugar mixtures (containing equivalent amounts of fructose, glucose, sucrose and maltose) and monosaccharide solutions were used as model compounds. Biological responses of NPs dispersed in different saccharides were also evaluated in human intestinal cells and rats in terms of cytotoxicity, cellular uptake, intestinal transport and oral absorption. The results demonstrate that the hydrodynamic radii and zeta potentials of NPs were highly affected by saccharides. In addition, trace nutrients influenced NP/saccharide interactions and interactive effects between saccharides on the interactions were found. NPs in all saccharides increased inhibition of cell proliferation and enhanced cellular uptake. Oral absorption of NPs was highly enhanced by 5% glucose, which is in-line with intestinal transport result. These findings show that ZnO NPs interact with saccharides and these interactions affects biological responses.

In this paper, we propose a family of lightweight block ciphers CHAM that has remarkable efficiency on resource-constrained devices. The family consists of three ciphers, CHAM-64/128, CHAM-128/128, and CHAM-128/256 which are of the generalized 4-branch Feistel structure based on ARX (Addition, Rotation, XOR) operations.

// Ja Eun Kim 1,* , Hye Rim Cho 2,* , Wen Jun Xu 3,* , Ji Young Kim 1 , Sung Kwon Kim 4 , Seung-Ki Kim 1,5 , Sung-Hye Park 6 , Hyeonjin Kim 2 , Se-Hoon Lee 7 , Seung Hong Choi 2 , Sunghyouk Park 3 and Chul-Kee Park 1 1 Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea 2 Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea 3 College of Pharmacy, Natural Product Research Institute, Seoul National University, Sillim-dong, Gwanak-gu, Seoul, Korea 4 Department of Neurosurgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea 5 Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Jongno-gu, Seoul, Korea 6 Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea 7 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Chul-Kee Park, email: // Sunghyouk Park, email: // Seung Hong Choi, email: // Keywords : brain tumors, oncology, 5-ALA, fluorescence, IDH1, glioma, NADPH Received : March 01, 2015 Accepted : April 22, 2015 Published : May 10, 2015 Abstract Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has become the main treatment modality in malignant gliomas. However unlike glioblastomas, there are inconsistent result about fluorescence status in WHO grade III gliomas. Here, we show that mutational status of IDH1 is linked to 5-ALA fluorescence. Using genetically engineered malignant glioma cells harboring wild type (U87MG-IDH1 WT ) or mutant (U87MG-IDH1 R132H ) IDH1 , we demonstrated a lag in 5-ALA metabolism and accumulation of protoporphyrin IX (PpIX) in U87MG-IDH1 R132H cells. Next, we used liquid chromatography–mass spectrometry (LC-MS) to screen for tricarboxylic acid (TCA) cycle-related metabolite changes caused by 5-ALA exposure. We observed low baseline levels of NADPH, an essential cofactor for the rate-limiting step of heme degradation, in U87MG-IDH1 R132H cells. High levels of NADPH are required to metabolize excessive 5-ALA, giving a plausible reason for the temporarily enhanced 5-ALA fluorescence in mutant IDH1 cells. This hypothesis was supported by the results of metabolic screening in human malignant glioma samples. In conclusion, we have discovered a relationship between enhanced 5-ALA fluorescence and IDH1 mutations in WHO grade III gliomas. Low levels of NADPH in tumors with mutated IDH1 is responsible for the enhanced fluorescence.

Objective This study investigated peripheral and central metabolites affecting depression, anxiety, suicidal ideation, and anger in complex regional pain syndrome (CRPS) patients. Methods Metabolite levels were determined in the right and left thalamus and insula, in 12 CRPS patients using magnetic resonance spectroscopy (MRS). Results There were positive correlations between valine (Val)/tNAA (N-acetylaspartate+N-acetylaspartylglutamate) and the anxiety, and a negative correlation between glutamine (Gln)/NAA and the depression. There were positive correlations between alanine (Ala)/Gln and the depression and suicidal ideation, between glutamate (Glu)/Gln and the depression and suicidal ideation, between N-acetylaspartylglutamate (NAAG)/Gln and the depression. There was a positive correlation between Ala/NAAG and the trait anger and a negative correlation between creatine (Cr)/N-acetylaspartate (NAA) and the trait anger. There was a negative correlation between Cr/Glx (Glu+Gln) and the trait anger. High hemoglobin and alkaline phosphatase were associated with low pain levels, but CO2 and chloride showed positive correlations with pain levels in CRPS patients. Peripheral glucose, CO2 and chloride were associated with depression, anxiety, anger and suicidal ideation. Conclusion The specific central and peripheral metabolites were associated with psychological disorders including depression, anxiety, suicidal ideation and anger in CRPS patients, showing pathological interactions between a painful body and mind.

Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is now a widely-used modality for glioblastoma (GBM) treatment. However, intratumoral heterogeneity of fluorescence intensity may reflect different onco-metabolic programs. Here, we investigated the metabolic mechanism underlying the heterogeneity of 5-ALA fluorescence in GBM. Using an in-house developed fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on the basis of their fluorescence intensity, which was characterized as strong, weak, and none. Expression profiling by RNA-sequencing revealed 77 genes with a proportional relationship and 509 genes with an inverse relationship between gene expression and fluorescence intensity. Functional analysis and in vitro experiments confirmed glutaminase 2 (GLS2) as a key gene associated with the fluorescence heterogeneity. Subsequent metabolite profiling discovered that insufficient NADPH due to GLS2 underexpression was responsible for the delayed metabolism of 5-ALA and accumulation of protoporphyrin IX (PpIX) in the high fluorescence area. The expression level of GLS2 and related NADPH production capacity is associated with the regional heterogeneity of 5-ALA fluorescence in GBM.

Nanoparticles (NPs) have been widely utilized in the food industry as additives with their beneficial characteristics, such as improving sensory property and processing suitability, enhancing functional and nutritional values, and extending shelf-life of foods. Silica is used as an anti-caking agent to improve flow property of powered ingredients and as a carrier for flavors or active compounds in food. Along with the rapid development of nanotechnology, the sizes of silica fall into nanoscale, thereby raising concerns about the potential toxicity of nano-sized silica materials. There have been a number of studies carried out to investigate possible adverse effects of NPs on the gastrointestinal tract. The interactions between NPs and surrounding food matrices should be also taken into account since the interactions can affect their bioavailability, efficacy, and toxicity. In the present study, we investigated the interactions between food additive silica NPs and food matrices, such as saccharides, proteins, lipids, and minerals. Quantitative analysis was performed to determine food component-NP corona using HPLC, fluorescence quenching, GC-MS, and ICP-AES. The results demonstrate that zeta potential and hydrodynamic radius of silica NPs changed in the presence of all food matrices, but their solubility was not affected. However, quantitative analysis on the interactions revealed that a small portion of food matrices interacted with silica NPs and the interactions were highly dependent on the type of food component. Moreover, minor nutrients could also affect the interactions, as evidenced by higher NP interaction with honey rather than with a simple sugar mixture containing an equivalent amount of fructose, glucose, sucrose, and maltose. These findings provide fundamental information to extend our understanding about the interactions between silica NPs and food components and to predict the interaction effect on the safety aspects of food-grade NPs.

Iron or zinc deficiency is one of the most important nutritional disorders which causes health problem. However, food fortification with minerals often induces unacceptable organoleptic changes during preparation process and storage, has low bioavailability and solubility, and is expensive. Nanotechnology surface modification to obtain novel characteristics can be a useful tool to overcome these problems. In this study, the efficacy and potential toxicity of dispersible Fe or Zn supplement coated in dextrin and glycerides (SunActive FeTM and SunActive ZnTM) were evaluated in terms of cytotoxicity, intestinal transport, and bioavailability, as compared with each counterpart without coating, ferric pyrophosphate (FePP) and zinc oxide (ZnO) nanoparticles (NPs), respectively. The results demonstrate that the cytotoxicity of FePP was not significantly affected by surface modification (SunActive FeTM), while SunActive ZnTM was more cytotoxic than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive FeTM were significantly higher than those of its counterpart material, which was in good agreement with enhanced oral absorption efficacy after a single-dose oral administration to rats. These results seem to be related to dissolution, particle dispersibility, and coating stability of materials depending on suspending media. Both SunActiveTM products and their counterpart materials were determined to be primarily transported by microfold (M) cells through the intestinal epithelium. It was, therefore, concluded that surface modification of food fortification will be a useful strategy to enhance oral absorption efficiency at safe levels.

The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in the oncogenesis. Although similarities in structure and enzyme activity for the two isotypic mutations have been suggested, the difference in their cellular localization and biochemical properties suggests differential effects on the metabolic oncogenesis. Using U87 cells transfected with either wild-type (WT) and mutant (MT) IDH genes, the MT-IDH1 and MT-IDH2 cells were compared with NMR-based metabolomics. When normalized with the respective WT-IDH cells, the general metabolic shifts of MT-IDH1 and IDH2 were almost opposite. Subsequent analysis with LC-MS and metabolic pathway mapping showed that key metabolites in pentose phosphate pathway and tricarboxylic acid cycle are disproportionately altered in the two mutants, suggesting different activities in the key metabolic pathways. Notably, lactate level was lower in MT-IDH2 cells which produced more 2-HG than MT-IDH1 cells, indicating that the Warburg effects can be overridden by the production of 2-HG. We also found that the effect of a mutant enzyme inhibitor is mainly reduction of the 2-HG level rather than general metabolic normalization. Overall, the metabolic alterations in the MT-IDH1 and 2 can be different and seem to be commensurate with the degree of 2-HG production. The R132H and R172K mutations of isocitrate dehydrogenase 1 and 2, respectively, (IDH1 and IDH2) have neomorphic activity of generating 2-hydroxyglutarate (2-HG) which has been implicated in oncogenesis. The mutant cell's metabolic shifts from the respective wild type cells were almost opposite, with lactate level being lower in the IDH2 mutant only, implicating an overridden Warburg effect. The metabolic effect of an IDH1 mutant inhibitor was limited to 2-HG lowering.

Background/Aims: Bleeding is one of the major complications of a colorectal polypectomy. The aim of this study was to identify the risk of delayed bleeding, particularly after a colorectal endoscopic mucosal resection (EMR) without prophylactic clipping. Methods: Between April 2014 and August 2014, patients who underwent colorectal EMR (≥6 mm and

With recent rapid advancement of visualization technologies, recognized research work for improving construction safety management practices has been conducted for identifying safety risks as well as worker onsite training. However, most of the previous studies were limited to reflect the site safety management process, which normally consists of planning–education–inspection phases. This study proposes a framework for a novel safety management and visualization system (SMVS) that integrates building information modeling (BIM), location tracking, augmented reality (AR), and game technologies. A prototype system has been developed and tested based on an illustrative accident scenario. The potentials and technical limitations of the prototype SMVS have been evaluated by site safety experts. A case study was also implemented, whose results show that the SMVS has a great potential to improve the identification of field safety risks, increase the risk recognition capacity of workers, and enhance the real-time communication between construction manager and workers.

To investigate the effect of fat suppression on TEleven porcine knee joints were harvested en bloc with intact capsules. We performed TThe mean TCompared with conventional T2 J. Magn. Reson. Imaging 2017;45:1076-1081.

To investigate the feasibility of parameterizing macromolecule (MM) resonances directly from short echo time (TE) spectra rather than pre-acquired, TInitial line parameters for metabolites and MMs were set for rat brain spectra acquired at 9.4 Tesla upon a priori knowledge. Then, MM line parameters were optimized over several steps with fixed metabolite line parameters. The proposed method was tested by estimating metabolite TThe metabolite TThe MM parameterization directly from short-TE spectra is feasible. Further development of the method may allow for better representation of spectral baseline with negligible T

This study aims to produce the transgenic mice (TG) engineered for magnetic resonance imaging (MRI) studies based on the ubiquitous expression of ferritin MRI reporter gene in diverse tissues.Transgenic mice (TG) expressing myc-tagged human heavy chain ferritin (myc-hFTH) under the control of a ubiquitous CAG promoter were produced. The expression of myc-hFTH in diverse tissues of the myc-hFTH TG was assessed by RT-PCR, Western blotting, and immunohistochemistry. The iron accumulation and the deposition of ferritin aggregates in tissues of myc-hFTH TG and WT were analyzed by Prussian blue staining and transmission electron microscopy. The myc-hFTH TG (n = 9) and wild-type mice (WT) (n = 4) were subjected to MRI on 9.4 T MR scanner. An eight-point T(2)* mapping was performed using a multiple gradient echo sequence, and T(2)* value was estimated pixel by pixel by using a routine least-squares fitting algorithm.We generated the myc-hFTH TG expressing myc-hFTH in brain, heart, liver, lung, spleen, pancreas, kidney, and intestine. The myc-hFTH TG showed no apparent pathological symptoms and no histological changes compared to WT. The expression of myc-hFTH in the brain and liver tissues of myc-hFTH TG led to a significant decrease in T(2)* values, as shown by noninvasive MRI, compared to WT (P 0.05, TG vs. WT).This study demonstrates that the novel myc-hFTH TG, which expresses an MRI reporter in many tissues, would be a valuable animal model of FTH-based molecular imaging in which to study potential therapies for cell and tissue grafting using an MRI technique. These mice could also serve to study disease related with iron metabolism.

Purpose: To investigate whether a correlation exists between perfusion parameters obtained from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and prognostic factors or immunohistochemical subtypes of breast cancers. Materials and Methods: Quantitative parameters (Ktrans, kep, and ve) of 70 invasive ductal carcinomas were obtained using DCE-MRI as a postprocessing procedure. Correlations between parameters and prognostic factors, including tumor size, axillary nodal status, histologic grade, nuclear grade, expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, bcl-2, and human epidermal growth factor receptor 2 (HER2) and subtypes categorized as luminal (ER or PR-positive), triple negative (ER or PR-negative, HER2-negative), and HER2 (ER and PR-negative, HER2 overexpression) were analyzed. Results: Mean Ktrans was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.007), with a high nuclear grade than with a low nuclear grade (P = 0.002), and with ER negativity than ER positivity (P = 0.056). Mean kep was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.005), with a high nuclear grade than with a low nuclear grade (P = 0.001), and with ER negativity than with ER positivity (P = 0.043). Mean ve was lower in tumors with a high histologic grade than with a low histologic grade (P = 0.038) and with ER negativity than with ER positivity (P = 0.015). Triple-negative cancers showed a higher mean kep than the luminal type (P = 0.015). Conclusion: Breast cancers with higher Ktrans and kep, or lower ve, had poor prognostic factors and were often of the triple-negative subtype. J. Magn. Reson. Imaging 2012;36:145–151. © 2012 Wiley Periodicals, Inc.

Cellular MRI with a reporter gene offers the opportunity to track small numbers of tumor cells and to study metastatic processes in their earliest developmental stages in the target organs of interest. This study demonstrates the feasibility of using the MR reporter ferritin for the noninvasive imaging and quantification of metastatic melanoma cells in the lymph nodes (LNs) of living mice. A B16F10 murine melanoma cell line expressing human ferritin heavy chain (hFTH) and green fluorescent protein (GFP) was constructed to allow the detection of cells by MRI and fluorescence imaging. Stable overexpression of hFTH and GFP in B16F10 murine melanoma cells was feasible and showed no cellular toxicity. In addition, hFTH cells were detectable by 9.4-T MRI in vitro and in vivo, yielding significant changes in T2* relative to control cells. In BALB/c nude mice, the presence of hFTH- and GFP-expressing metastatic melanoma cells in deep-seated axillary LNs was demonstrated as areas of low T2* on MRI, but the same LNs were not visible by fluorescence imaging because the light was unable to penetrate the tissue. Furthermore, the metastatic volume of each LN, which was assessed by cumulative histogram analysis of the T2* MRI data, correlated well with tumor burden, which was determined by histology (r = −0.8773, p = 0.0001). This study is the first to use MRI and an MR reporter gene for both the visualization and quantification of metastatic cancer cells in LNs. Copyright © 2011 John Wiley & Sons, Ltd.

The control of dendritic cell (DC) migration into lymph nodes (LNs) is important for the development of more effective DC-based immunotherapies. This study was undertaken to evaluate, dynamically and noninvasively, prostaglandin E2 (PGE2)-enhanced migration of DCs using a 1.5 T clinical MR scanner. DC2.4 cells were labeled with superparamagnetic iron oxide (SPIO), a clinically approved MRI contrast agent. DCs were stimulated with tumor necrosis factor-α and interferon-γ in the presence or absence of PGE2. Before and after subcutaneous injection of labeled DCs into the hind leg footpads of mice, MRI detailing the extent of DC migration into popliteal LNs was performed using a 1.5 T clinical MR scanner. SPIO labeling did not influence the viability, endocytic activity, migratory ability and/or co-stimulatory molecule expression of DCs. PGE2 enhanced significantly chemokine receptor-7 expression and the migration of DCs (p < 0.05). After subcutaneous injection of DCs, there were decreases in MR signal intensity in popliteal LNs at 24 h post-injection; in PGE2-treated cells, the MR signal intensity was significantly lower (decrease of 86.6 ± 2.5%) than in PGE2-untreated cells (decrease of 70.0 ± 4.2%) (p < 0.05). Histological analyses with the conventionally used Prussian blue stain demonstrated that the PGE2-treated DCs migrated more deeply into the center of LNs. PGE2-enhanced migration of SPIO-labeled DCs into LNs can be detected using a 1.5 T clinical MR scanner. Our results suggest that in vivo MRI of DC migration is a useful imaging method to predict DC therapy with a high rate of efficacy and to improve DC-based immunotherapy, thereby reducing costs compared with current treatments in clinical trials.

The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ( 1 H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE = 5000/20/2.2 ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7 μl) and hippocampus (6 μl) of C57BL/6 mice at 9.4 T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine + phosphocreatine (Cr + PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development.

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per-voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 +/- 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 +/- 30 to 1220 +/- 30 ms for the first slice, with an increase of 610 +/- 20 ms over a four-slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per-slice ATTs were employed in ASL cerebral blood flow quantification and the in-slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (approximately 80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL-based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters.

Background The aim of this study was to assess peripheral measures and central metabolites associated with lipids using magnetic resonance spectroscopy. Results Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy controls participated. Using magnetic resonance spectroscopy, we measured the levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine (tCr) levels in the right and left thalamus. We found negative correlations of Lip13a/tCr in the right thalamus with red blood cells or neutrophils, but a positive correlation between Lip13a/tCr and lymphocytes in the controls. We found negative correlations between Lip09/tCr and peripheral pH or platelets in the controls. There were positive correlations between Lip09a/tCr and myo-inositol/tCr, between Lip13a/tCr and N-acetylaspartate (NAA)/tCr, and between Lip09/tCr and NAA/tCr in healthy controls. On the other hand, there were positive correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients. There were significant correlations between Lip13a/tCr or Lip09/tCr and different peripheral measures depending on the side of the thalamus (right or left) in CRPS patients. Conclusion This is the first report indicating that abnormal interactions of Lip13a and Lip09 in the thalamus with peripheral measures and central metabolites may mediate the complex pathophysiological mechanisms underlying CRPS.

Three new sesterterpenoids, phorbaketals A (1), B (2), and C (3) which have a spiroketal of the hydrobenzopyran moiety, were isolated from the Korean marine sponge Phorbas sp. Their complete structures were elucidated by spectral and chemical methods. They exhibited moderate cytotoxicity against human colorectal, hepatoma, and lung cancer cell lines. Furthermore, the cultivation of the bacterial fraction from the sponge afforded compound 1.

While the use of situated cognition theory in teacher education programmes has the potential to teach prospective teachers, research on teacher knowledge and learning from a situated perspective has been slow to emerge in reference to prospective teacher education. In this paper, we present a situated case-based knowledge framework to explain the development of prospective teachers’ knowledge and beliefs. The framework includes conceptual case knowledge, strategic case knowledge, and the shared identities and beliefs of practicing teachers. In addition, we summarize findings from a study wherein the situated case-based knowledge framework was applied to support prospective teachers’ learning, as well as discuss implications for research and practice.

Recent work in case-based reasoning (CBR) reinforces the importance of situated learning, expert cases, and authentic tasks and activities for novice learners. As novices engage CBR environments, they apprentice in the experts’ practices while developing the understanding, knowledge and skill of a given community. This study examined how prospective teachers, as novices in a semester-long course, engaged and developed expert-like practices using the case knowledge of experienced teachers who teach with technology. By engaging experienced teachers’ knowledge and skill via Web-enhanced cases, prospective teachers refined their understanding of teaching culture and teaching with technology as they transitioned to the teaching community.