Mitochondrial glutamate transporter SLC25A22 uni-directionally export glutamate for metabolic rewiring in radioresistant glioblastoma.

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Radiotherapy, one of the standard treatments for GBM patients, could induce GBM radioresistance via rewiring cellular metabolism. However, the precise mechanism attributing to GBM radioresistance or targeting strategies to overcome GBM radioresistance are lacking. Here, we demonstrate that SLC25A22, a mitochondrial bi-directional glutamate transporter, is upregulated and showed uni-directionality from mitochondria to cytosol in radioresistant GBM cells, resulting in accumulating cytosolic glutamate. However, mitochondrial glutaminolysis-mediated TCA cycle metabolites and OCR are maintained constantly. The accumulated cytosolic glutamate enhances the glutathione (GSH) production and proline synthesis in radioresistant GBM cells. Increased GSH protects cells against ionizing radiation (IR)-induced reactive oxygen species (ROS) whereas increased proline, a rate-limiting substrate for collagen biosynthesis, induces extracellular matrix (ECM) remodeling, leading to GBM invasive phenotypes. Finally, we discover that genetic inhibition of SLC25A22 using miR-184 mimic decreases GBM radioresistance and aggressiveness both in vitro and in vivo. Collectively, our study suggests that SLC25A22 upregulation confers GBM radioresistance by rewiring glutamate metabolism, and SLC25A22 could be a significant therapeutic target to overcome GBM radioresistance.

Electrocatalytic Oxygen Reduction Reaction of Graphene Oxide and Metal-Free Graphene in an Alkaline Medium.

Graphene is a well-known two-dimensional material with a large surface area and is used for numerous applications in a variety of fields. Metal-free carbon materials such as graphene-based materials are widely used as an electrocatalyst for oxygen reduction reactions (ORRs). Recently, more attention has been paid to developing metal-free graphenes doped with heteroatoms such as N, S, and P as efficient electrocatalysts for ORR. In contrast, we found our prepared graphene from graphene oxide (GO) by the pyrolysis method under a nitrogen atmosphere at 900 °C has shown better ORR activity in aqueous 0.1 M potassium hydroxide solution electrolyte as compared with the electrocatalytic activity of pristine GO. At first, we prepared various graphene by pyrolysis of 50 mg and 100 mg of GO in one to three alumina boats and pyrolyzed the samples under a N2 atmosphere at 900 °C. The prepared samples are named G50-1B to 3B and G100-1B and G100-2B. The prepared GO and graphenes were also analyzed under various characterization techniques to confirm their morphology and structural integrity. The obtained results suggest that the ORR electrocatalytic activity of graphene may differ based on the pyrolysis conditions. We found that G100-1B (Eonset, E1/2, JL, and n values of 0.843, 0.774, 4.558, and 3.76) and G100-2B (Eonset, E1/2, and JL values of 0.837, 0.737, 4.544, and 3.41) displayed better electrocatalytic ORR activity, as did Pt/C electrode (Eonset, E1/2, and JL values of 0.965, 0.864, 5.222, and 3.71, respectively). These results display the wide use of the prepared graphene for ORR and also can be used for fuel cell and metal-air battery applications.

Evaluation of PVC-Type Insulation Foam Material for Cryogenic Applications.

With the International Maritime Organization (IMO) reinforcing environmental regulations on the shipbuilding industry, the demand for fuels, such as liquefied natural gas (LNG) and liquefied petroleum gas (LPG), has soared. Therefore, the demand for a Liquefied Gas Carrier for such LNG and LPG also increases. Recently, CCS carrier volume has been increasing, and damage to the lower CCS panel has occurred. To withstand liquefied gas loads, the CCSs should be fabricated using a material with improved mechanical strength and thermal performance compared with the conventional material. This study proposes a polyvinyl chloride (PVC)-type foam as an alternative to commercial polyurethane foam (PUF). The former material functions as both insulation and a support structure primarily for the LNG-carrier CCS. To investigate the effectiveness of the PVC-type foam for a low-temperature liquefied gas storage system, various cryogenic tests, namely tensile, compressive, impact, and thermal conductivity, are conducted. The results illustrate that the PVC-type foam proves stronger than PUF in mechanical performance (compressive, impact) across all temperatures. In the tensile test, there are reductions in strength with PVC-type foam but it meets CCS requirements. Therefore, it can serve as insulation and improve the overall CCS mechanical strength against increased loads under cryogenic temperatures. Additionally, PVC-type foam can serve as an alternative to other materials in various cryogenic applications.

DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma.

Glioblastoma (GBM) currently has a dismal prognosis. GBM cells that survive radiotherapy contribute to tumor progression and recurrence with metabolic advantages. Here, we show that diacylglycerol kinase B (DGKB), a regulator of the intracellular concentration of diacylglycerol (DAG), is significantly downregulated in radioresistant GBM cells. The downregulation of DGKB increases DAG accumulation and decreases fatty acid oxidation, contributing to radioresistance by reducing mitochondrial lipotoxicity. Diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the formation of triglycerides from DAG, is increased after ionizing radiation. Genetic inhibition of DGAT1 using short hairpin RNA (shRNA) or microRNA-3918 (miR-3918) mimic suppresses radioresistance. We discover that cladribine, a clinical drug, activates DGKB, inhibits DGAT1, and sensitizes GBM cells to radiotherapy in vitro and in vivo. Together, our study demonstrates that DGKB downregulation and DGAT1 upregulation confer radioresistance by reducing mitochondrial lipotoxicity and suggests DGKB and DGAT1 as therapeutic targets to overcome GBM radioresistance.

Stereotactic body radiotherapy using helical tomotherapy for hepatocellular carcinoma: clinical outcome and dosimetric comparison of Hi-ART vs. Radixact.

Background: Helical tomotherapy (HT), a unique rotational dose delivery machine, has been updated from Hi-ART to Radixact. We retrospectively evaluated the treatment outcomes of stereotactic body radiotherapy (SBRT) using HT for hepatocellular carcinoma (HCC) and compared the dosimetric details of Hi-ART and Radixact. Methods: Between April 2014 and November 2020, 28 patients with HCC were treated with SBRT using HT for a cure at Soonchunhyang University College of Medicine, Bucheon. According to the Barcelona Clinic Liver Cancer classification, 9 patients had stage 0 disease, 12 had stage A, 4 had stage B, and 3 had stage C. The tumor size ranged from 1 cm to 8 cm (median, 2 cm). The SBRT dose ranged from 40 to 60 Gy (median, 48 Gy) with 4 fractions. Twenty-three patients were treated with Hi-ART and 5 patients were treated with Radixact. To compare the dosimetric parameters between Hi-ART and Radixact, we created treatment plans with the same constraints, pitch, modulation factor, and field width for the same patient in pairs. Results: The median follow-up time from the date of SBRT administration was 24 months (range, 3-67 months). The local failure-free survival and intrahepatic failure-free survival rates were 96% and 58% at 1 year, 84% and 36% at 2 years, and 76% and 18% at 3 years, respectively. The overall survival rate was 93% at 1 year, 93% at 2 years, and 53% at 3 years, respectively. When the paired treatment plans were reviewed, the beam-on time and intermediate dose-spillage were found to be significantly reduced in Radixact than Hi-ART (P<0.001). With regard to normal organ sparing, the irradiated dose to the total liver, normal liver, heart, and kidney was significantly lower with Radixact (P<0.001). Conclusions: SBRT using HT for HCC showed favorable treatment outcomes. Radixact, the latest version, physically improved treatment efficiency by reducing treatment time and provided better organ sparing than Hi-ART.

Cryogenic Reliability Evaluation of Glass Fabric-Reinforced Composites Using Novel Slip-Prevention Method.

Glass fabric-reinforced composites are the main insulating material components of the secondary barrier of cargo containment systems (CCSs), because they prevent liquefied natural gas (LNG) leakage during transport. Nevertheless, it is difficult to evaluate the material performance of glass fabric-reinforced composites at cryogenic temperatures (-163 °C) because it takes approximately 7 days to prepare the test specimens and because the slip-based test frequently fails. Although glass fabric-reinforced composites for the secondary barrier of LNG CCSs show various structural vulnerabilities, enhancing their material performance is significantly limited owing to the reasons mentioned above. This study evaluated the structural vulnerabilities and failure characteristics of glass fabric-reinforced composites by using the slip-prevention test method to determine the level difference and adhesive vacancies. The failure surface and the thermal expansion of the composites were also observed, to analyze their mechanical characteristics. By adopting our proposed test procedure, the failure rate of the experiment decreased by approximately 80%, and the sample preparation time for manufacturing was significantly shortened, to 1 day.

Proposing a new solution for marine debris by utilizing on-board low-temperature eco-friendly pulverization system.

Developing an effective and efficient recycling process for marine debris (MD) is one of the most urgent issues to maintain environmental sustainability on Earth. However, restricted storage capacities and secondary pollution (e.g., microbial adhesion, putrefaction) limit the proper MD recycling. Here, we proposed a complete eco-friendly low-temperature MD pulverizing system that utilizes excessive liquefied natural gas (LNG) cold energy (LCE) in an LNG propulsion ship to improve the efficiency and effectiveness of MD recycling. The prototype design of the low-temperature pulverization (LTP) system showed that consumable refrigerant (liquid nitrogen) up to 2831 kg per hour could be substituted. Furthermore, with a 20% ship output, 1250 kg of MD could be treated with 363 kg of additional refrigerant. In addition, LTP systems utilizing LCE could increase the storage capacity by more than 10 times compared to bulk MD while minimizing the required energy consumption. To determine the feasibility of LTP for MD recycling, four types of plastics obtained from actual MD from a coastal area in Busan, Korea were classified and tested.

Influence of Silica-Aerogel on Mechanical Characteristics of Polyurethane-Based Composites: Thermal Conductivity and Strength.

Polyurethane foam (PUF) has generally been used in liquefied natural gas (LNG) carrier cargo containment systems (CCSs) owing to its excellent mechanical and thermal properties over a wide range of temperatures. An LNG CCS must be designed to withstand extreme environmental conditions. However, as the insulation material for LNGC CCSs, PUF has two major limitations: its strength and thermal conductivity. In the present study, PUFs were synthesized with various weight percentages of porous silica aerogel to reinforce the characteristics of PUF used in LNG carrier insulation systems. To evaluate the mechanical strength of the PUF-silica aerogel composites considering LNG loading/unloading environmental conditions, compressive tests were conducted at room temperature (20 °C) and a cryogenic temperature (-163 °C). In addition, the thermal insulation performance and cellular structure were identified to analyze the effects of silica aerogels on cell morphology. The cell morphology of PUF-silica aerogel composites was relatively homogeneous, and the cell shape remained closed at 1 wt.% in comparison to the other concentrations. As a result, the mechanical and thermal properties were significantly improved by the addition of 1 wt.% silica aerogel to the PUF. The mechanical properties were reduced by increasing the silica aerogel content to 3 wt.% and 5 wt.%, mainly because of the pores generated on the surface of the composites.

Synthesis and Investigation of Cryogenic Mechanical Properties of Chopped-Glass-Fiber-Reinforced Polyisocyanurate Foam.

Polyisocyanurate foam (PIF) has been adopted as a liquefied natural gas (LNG) insulating material owing to its various mechanical merits such as high structural stability and mechanical strength, and excellent insulating ability. In an attempt to increase the mechanical strength of PIF, chopped-glass-fiber-reinforced polyisocyanurate foam (CGR-PIF) was synthesized by adding chopped glass fibers to polyol and isocyanate, which are the raw materials used in the polymerization process for producing PIF. The main objective is to closely observe the compression material characteristics of PIF and CGR-PIF in terms of the cryogenic temperature. Therefore, compressive tests were conducted at cryogenic temperature including low temperatures, and microscopic images were obtained to analyze the cell size and distribution that affects the mechanical and thermal properties of the foam. Furthermore, recovery ratio and weight loss which are important factors of brittle fracture were evaluated, and the applicability of the foams to a cryogenic environment was evaluated. Finally, thermal conductivity, an important parameter of insulation, was evaluated. The obtained results confirm that the compressive strength of CGR-PIF significantly increases at cryogenic temperatures; moreover, a relatively higher thermal conductivity was observed in the case of CGR-PIF as compared to that of PIF owing to the chopped glass fibers.

Treatment outcomes of helical tomotherapy for hepatocellular carcinoma in terms of intermediate-dose spillage.

BACKGROUND: Although helical tomotherapy (HT) tends to increase intermediate-dose spillage by increasing of low-dose region, this has not been fully determined in the clinical setting. Therefore, we investigated treatment outcomes of HT for hepatocellular carcinoma (HCC) with respect to intermediate-dose spillage. METHODS: We retrospectively reviewed 20 HCC patients, who received high-dose radiotherapy (RT) using HT with radical intent between April 2014 and September 2017. In accordance with the Barcelona Clinic Liver Cancer (BCLC) classification, stage was 0 in 7 patients, A in 3 patients, B in 5 patients, and C in 5 patients. Baseline Child-Pugh class was A in 18 patients and B in 2 patients. The median tumor size was 2.5 cm (range, 1-11 cm). Helical intensity-modulated radiotherapy (IMRT) technique was applied in all patients: among these, 13 patients were treated with stereotactic body radiotherapy (SBRT). The median fraction size was 12 Gy (range, 2-15 Gy), and the median total dose was 50 Gy (range, 44-60 Gy). Intermediate-dose spillage was assessed by the Radiation Therapy Oncology Group recommendation from 22 HT planning data, as follows: R50% means the ratio of the 50% prescription isodose volume to the planning target volume (PTV). RESULTS: The median follow-up period after HT was 22 months. The local progression-free survival (LPFS) and progression-free survival (PFS) rates were 89% and 59% at 1 year, and 82% and 30% at 2 years, respectively. The overall survival rate was 100% at 1 year and 85% at 2 years, respectively. In terms of intermediate-dose spillage, minor or major deviations were noted in the R50% of 20 HT plans (91%). However, 1 patient (5%) experienced classic radiation-induced liver disease, and severe toxicity ≥ grade 3 was not reported. CONCLUSIONS: Although HT for HCC tends to increase intermediate-dose spillage, the treatment results were favorable with that reported in other published studies.

Ultrasensitive detection of hydrogen peroxide and dopamine using copolymer-grafted metal-organic framework based electrochemical sensor.

We reported the synthesis of a copolymer- and metal-organic framework-based electrochemical sensor, UiO-66-NH2@P(ANI-co-ANA) using the polymerization method for the highly sensitive and selective detection of hydrogen peroxide (H2O2) and dopamine (DA). The as-synthesized material was characterized via Fourier transform infrared spectroscopy, X-ray diffraction analysis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis. The electrochemical characteristics of the proposed sensor were evaluated via impedance spectroscopy and cyclic voltammetry (CV). The electrochemical oxidation of DA and the reduction of H2O2 were determined via CV, square-wave voltammetry, and chronoamperometric techniques. The fabricated sensor exhibited a wide linear range of 25-500 µM, with a sensitivity of 1396.1 µAµM-1cm-2 and a limit of detection of 0.6 µM, for the electrochemical reduction of H2O2. Additionally, it exhibited a wide linear range of 10-110 µM, with a sensitivity of 1110.2 µAµM-1cm-2 and a limit of detection of 0.3 µM, for the electrochemical detection of DA. The practical utility of the fabricated sensor was evaluated via the detection of H2O2 in milk samples and DA in human urine samples.

Change in Portal Pressure and Clinical Outcome in Cirrhotic Patients with Gastric Varices after Plug-Assisted Retrograde Transvenous Obliteration.

Background/Aims: Plug-assisted retrograde transvenous obliteration (PARTO) is widely used to manage gastric varices with a portosystemic shunt. It is not clear whether portal pressure and the incidence of complications increase after PARTO. The aim of this study was to determine the changes in portal pressure and the associated changes in liver function, ascites, hepatic encephalopathy, and especially esophageal varix (EV) after PARTO. Methods: From March 2012 to February 2018, 54 patients who underwent PARTO were analyzed retrospectively. The parameters collected included liver function and episodes of cirrhotic complications before and at 1 and 6 months after PARTO. Results: The analysis of 54 patients showed improvement in liver function during the 6-month follow-up period (Model for End-Stage Liver Disease score: change from 11.46±4.35 to 10.33±2.96, p=0.021). Among these 54 patients, 25 patients were evaluated for their hepatic venous pressure gradient (HVPG) before and after PARTO (change from 12.52±3.83 to 14.68±5.03 mm Hg; p<0.001). Twenty-five patients with portal pressure measured before and after PARTO were evaluated for risk factors affecting liver function improvement and EV deterioration. No factor associated with portal pressure was affected by liver function improvement. Post-PARTO portal pressure was a risk factor affecting EV deterioration (HVPG-post: odds ratio, 1.341; 95% confidence interval, 1.017 to 1.767; p=0.037). Conclusions: The artificial blockade of the portosystemic shunt evidently leads to an increase in HVPG. Liver function was improved over the 6-month follow-up period. Portal pressure after PARTO was a significant risk factor for EV deterioration. Portal pressure measurement is helpful for predicting the patient's clinical outcome.

Variation of Mechanical Characteristics of Polyurethane Foam: Effect of Test Method.

Polyurethane foam (PUF), a representative insulation material, not only prevents heat conduction but can also support a load. Particular interest in rigid PUF proliferated over the past several years in fields where extreme environments are applied. A closed-cell structure which forms the interior of rigid PUF serves to maximize the utilization of these polymeric foams. Rigid PUF is more sensitive to external conditions such as temperature or restraint than other structural materials such as steel. Depending on the market trends in which utilization of a cryogenic environment is expanding, the tendency of material behavior resulting from the binding effect also needs to be investigated. However, most conventional compression test method standards applicable to rigid PUF do not adequately reflect the restraints. Therefore, this study proposes a method for evaluating the mechanical performance of materials in a more reliable manner than that of conventional tests. Experimental observation and analysis validated this compression evaluation method in which constraints are considered. Consequently, the compressive strength of rigid PUF compared to the results of the conventional test showed a difference of up to 0.47 MPa (approximately 23%) at cryogenic temperatures. This result suggests that there are important factors to consider when assessing performance from a material perspective in an environment where rigid PUF insulation is utilized. It is believed that the test methods newly proposed in this study will provide an experimental framework that can be applied to the evaluation criteria of material properties and reflected in structural design.

Refractive corneal inlay for presbyopia in emmetropic patients in Asia: 6-month clinical outcomes.

BACKGROUND: To evaluate the 6-month clinical outcomes of Flexivue Microlens refractive corneal inlay in emmetropic patients in Asia for the surgical compensation of presbyopia. METHODS: In this retrospective study, corneal inlay implantation was done using a femtosecond laser. The follow-up period was 6 months. Near/intermediate/distant visual acuities, refraction, keratometry, defocus curve, wavefront aberrations, contrast sensitivity, Scheimpflug corneal scanning, endothelial cell density, dry eye test, confocal microscopy scanning, and patient questionnaires were evaluated. RESULTS: The inlay implantation was performed in 21 eyes from June 2015 to April 2017. 6 months after surgery, the uncorrected near visual acuity of the operated eyes increased significantly from 0.55 ± 0.22 logMAR preoperatively to 0.25 ± 0.15 logMAR (p < 0.05) but mean bilateral uncorrected distant visual acuity did not change significantly (p = 0.90). Total higher-order aberration and spherical aberration increased, and the contrast sensitivity of the operated eyes decreased. Endothelial cell density and central corneal thickness did not change from preoperative values. Patient satisfaction for near vision was increased 6 months after implantation, and 50.0% of patients were independent of near spectacles. Explantation was done in 2 cases. CONCLUSION: The Flexivue Microlens refractive corneal inlay was effective for improving near visual acuity at 6 months follow-up But proportion of spectacle independency and patient satisfaction were lower in this Korean population than in previous reports. Further study with a longer follow-up period is needed.

Biocidal effect of thymol and carvacrol on aquatic organisms: Possible application in ballast water management systems.

Ballast water is essential for maintaining the balance and integrity of a ship. However, exchanging ballast water resulted in discharging water of different origins in vessel recipient ports, and this may have caused ecosystem disturbance or aquatic pollution. The ballast water management (BWM) system is essential for the purification and disinfection of the ballast water that is taken up. Because current BWM systems widely use biocides for the treatment of aquatic organisms, the biocides may result in unintended toxicity of the discharged ballast water. In this study, we suggested thymol and carvacrol as chemical biocides for BWM systems and investigated their effectiveness using Artemia salina and Escherichia coli. Thymol and carvacrol showed biocidal effects in our study. A combination of these substances showed a synergistic increase in the biocidal effects. Moreover, carvacrol naturally degrades after disinfection, which indicates that natural substances may be promising candidates to increase the efficacy and reduce unwanted side effects of the BWM system.

RNF138-mediated ubiquitination of rpS3 is required for resistance of glioblastoma cells to radiation-induced apoptosis.

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.

A new constitutive model for simulation of softening, plateau, and densification phenomena for trabecular bone under compression.

A new type of constitutive model and its computational implementation procedure for the simulation of a trabecular bone are proposed in the present study. A yield surface-independent Frank-Brockman elasto-viscoplastic model is introduced to express the nonlinear material behavior such as softening beyond yield point, plateau, and densification under compressive loads. In particular, the hardening- and softening-dominant material functions are introduced and adopted in the plastic multiplier to describe each nonlinear material behavior separately. In addition, the elasto-viscoplastic model is transformed into an implicit type discrete model, and is programmed as a user-defined material subroutine in commercial finite element analysis code. In particular, the consistent tangent modulus method is proposed to improve the computational convergence and to save computational time during finite element analysis. Through the developed material library, the nonlinear stress-strain relationship is analyzed qualitatively and quantitatively, and the simulation results are compared with the results of compression test on the trabecular bone to validate the proposed constitutive model, computational method, and material library.

Preparation of Cu@Cu2O Nanocatalysts by Reduction of HKUST-1 for Oxidation Reaction of Catechol.

HKUST-1, a copper-based metal organic framework (MOF), has been investigated as a catalyst in various reactions. However, the HKUST-1 shows low catalytic activity in the oxidation of catechol. Therefore, we synthesized Fe3O4@HKUST-1 by layer-by layer assembly strategy and Cu@Cu2O by reduction of HKUST-1 for enhancement of catalytic activity. Cu@Cu2O nanoparticles exhibited highly effective catalytic activity in oxidation of 3,5-di-tert-butylcatechol. Through this method, MOF can maintain the original core-shell structure and be used in various other reactions with enhanced catalytic activity.