Mangiferin Ameliorates Obesity-Associated Inflammation and Autophagy in High-Fat-Diet-Fed Mice: In Silico and In Vivo Approaches.

Obesity-induced insulin resistance is the fundamental cause of metabolic syndrome. Accordingly, we evaluated the effect of mangiferin (MGF) on obesity and glucose metabolism focusing on inflammatory response and autophagy. First, an in silico study was conducted to analyze the mechanism of MGF in insulin resistance. Second, an in vivo experiment was conducted by administering MGF to C57BL/6 mice with high-fat-diet (HFD)-induced metabolic disorders. The in silico analysis revealed that MGF showed a high binding affinity with macrophage-related inflammatory cytokines and autophagy proteins. In the in vivo study, mice were divided into three groups: normal chow, HFD, and HFD + MGF 150 mg/kg. MGF administration to obese mice significantly improved the body weight, insulin-sensitive organs weights, glucose and lipid metabolism, fat accumulation in the liver, and adipocyte size compared to HFD alone. MGF significantly reduced the macrophages in adipose tissue and Kupffer cells, inhibited the gene expression ratio of tumor necrosis factor-α and F4/80 in adipose tissue, reduced the necrosis factor kappa B gene, and elevated autophagy-related gene 7 and fibroblast growth factor 21 gene expressions in the liver. Thus, MGF exerted a therapeutic effect on metabolic diseases by improving glucose and lipid metabolism through inhibition of the macrophage-mediated inflammatory responses and activation of autophagy.

Estimation of stature from femur length measured using computed tomography after the analysis of three-dimensional characteristics of femur bone in Korean cadavers.

Estimation of stature is a basic and important forensic procedure in identifying decomposed or skeletonized bodies. Due to advances in radiologic equipment, forensic science frequently uses computed tomography (CT) and software to apply these findings to investigations. Technical developments have increased the accuracy of the measurement of various bones. However, there are still some inaccuracies, such as defining correct landmarks in three-dimensional (3D) images. Femur length is frequently used for calculation of stature, but because it is a 3D structure, the digital image may not always correlate with the femur length measured with an osteometric board. However, more studies are now showing that the maximum femur length calculated in 3D imagery is comparable to the maximum femur length calculated using an osteometric board. This study used digitalized data of the femur obtained from the CT image through the specialized software. The digitalized femur images were put on the virtual osteometric board, which helped us to understand the anatomic characteristics of the femur and to confirm that the maximum femur lengths calculated in 3D images are similar to the results obtained using an osteometric board. These data were used to obtain a stature estimation formula for the Korean population.

Sudden infant death syndrome in Korea: a retrospective analysis of autopsy-diagnosed cases.

This study aimed to elucidate the demographic and sleeping environmental factors associated with sudden infant death syndrome (SIDS) in Korea. The autopsy reports of all SIDS cases reported to the National Forensic Service and Seoul National University College of Medicine between 1996 and 2008 were reviewed for data collection and analysis to identify the risk factors for SIDS. Analysis of the 355 SIDS cases reported within the study period revealed that of the 168 (47.3%) cases for which sleeping position before death had been reported, 75 (44.7%) cases had occurred after placement in prone or side position. Of the 204 (57.5%) cases for which bed-sharing situation had been reported, 121 (59.3%) deaths had occurred during bed-sharing, of which 54 (44.6%) infants were under 3 months of age, a significantly younger age than that of the non-bed-sharing cases (P = 0.0279). Analysis of the results indicated no tendency toward an increase or decrease in the use of a prone or side position. Rather, there was a statistically significant increasing trend for bed-sharing over the study period (OR, 1.087; 95% CI, 1.004-1.177; P = 0.04). These findings indicate the need for nationwide educational programs promoting a safe sleeping environment to enhance SIDS prevention.

Successfully Managing Severe Anemia in a Trauma Patient Who Refused Blood Transfusion: A Case Report.

BACKGROUND Surgical management in patients who undergo traumatic blood loss but who refuse blood transfusion can be challenging, but physicians and surgeons must comply with the wishes and beliefs of their patients. This report describes the management of severe anemia, with hemoglobin level of 2.5 g/dL, in a 71-year-old male Korean trauma patient who declined blood transfusion. CASE REPORT A 71-year-old man was admitted to hospital with severe blood loss following trauma. He declined blood transfusion due to his religious belief as a Jehovah's Witness. On day 4, the patient's hemoglobin level dropped from 7.7 to 3.9 g/dL. Despite the need for blood transfusion, the patient refused. Hence, therapeutic strategies, including crystalloid fluid resuscitation, bleeding control, vasopressor support, erythropoietin administration, supplementation with iron, folic acid, and vitamin B12, coagulopathy correction, oxygen consumption reduction, and mechanical ventilation were implemented. Following 16 days of supportive management, the hemoglobin reached 7.4 g/dL. However, it suddenly decreased on day 41 (2.5 g/dL) due to episodes of melena secondary to an actively bleeding gastric ulcer, which was successfully managed with endoscopic hemostasis. Despite increased vasopressor dosage and addition of vasopressin and hydrocortisone, the patient became unresponsive with persistent hypotension. Methylene blue was used as the final therapeutic agent. The patient responded well and subsequently recovered without blood transfusion. CONCLUSIONS This report has presented the clinical challenges of managing the case of a patient who requires but declines blood transfusion and has highlighted the approach to clinical care while respecting the wishes of the patient.

Efficient high-power frequency doubling of distributed Bragg reflector tapered laser radiation in a periodically poled MgO-doped lithium niobate planar waveguide.

We report on efficient single-pass, high-power second-harmonic generation in a periodically poled MgO-doped LiNbO3 planar waveguide using a distributed Bragg reflector tapered diode laser as a pump source. A coupling efficiency into the planar waveguide of 73% was realized, and 1.07 W of visible laser light at 532 nm was generated. Corresponding optical and electro-optical conversion efficiencies of 26% and 8.4%, respectively, were achieved. Good agreement between the experimental data and the theoretical predictions was observed.

Risk Factors of Unfavorable Outcomes, Major Bleeding, and All-Cause Mortality in Patients with Venous Thromboembolism.

PURPOSE: This study aimed to analyze the clinical outcomes of venous thromboembolism (VTE) patients and identify the risk factors for VTE-related unfavorable outcomes, major bleeding, and 30-day all-cause mortality. MATERIALS AND METHODS: From January 2016 to December 2020, 198 patients with confirmed VTE were enrolled. Potential risk factors for unfavorable outcomes, major bleeding, and all-cause mortality were analyzed. RESULTS: VTE-related unfavorable outcomes developed in 13.1%, while 30-day all-cause mortality was 8.6%. In the multivariate analysis, a pulse ≥110/min and respiratory rate ≥30/min were statistically significant predictors for VTE-related unfavorable outcomes. Diabetes was a significant risk factor for major bleeding. In addition, a history of malignancy, no anticoagulation treatment, and need for mechanical ventilation were significant predictors of all-cause mortality. CONCLUSION: VTE-related mortality and morbidity rates remained high. In cases of tachycardia and tachypnea, early aggressive treatment is needed to prevent unfavorable outcomes. Patients with risk factors should be closely monitored.

Reduced dose-limiting toxicity of intraperitoneal mitoxantrone chemotherapy using cardiolipin-based anionic liposomes.

Intraperitoneal chemotherapy confers limited clinical benefit as a result of the dose-limiting toxicity of anticancer drugs. We aimed to develop optimized liposomes for mitoxantrone (MTO) administration that provide high encapsulation efficiency and increase the therapeutic index. Cationic MTO was loaded onto anionic liposomes by electrostatic surface complexation. The anticancer activity was evaluated in a peritoneal carcinomatosis model. The retention of MTO at the tumor site was monitored by molecular imaging. MTO loading efficiencies by electrostatic complexation were >95% for all anionic liposomes but <5% for neutral liposomes. Among anionic liposomes, cardiolipin liposomes (CLs) exhibited the strongest binding affinity for MTO, the highest anticancer activity, and the lowest toxicity. MTO delivered by CLs showed prolonged retention at tumor sites. Unlike free MTO showing significant cardiotoxicity, MTO administered in CLs provided negligible cardiotoxicity. CL-mediated delivery may increase the therapeutic index of MTO chemotherapy by prolonged retention and reduced cardiotoxicity.

Integrated optical modulator for signal up-conversion over radio-on-fiber link.

An integrated optical modulator, which consists of a dual-sideband suppressed carrier (DSB-SC) modulator cascaded with a single-sideband (SSB) modulator, is proposed for signal up-conversion over Radio-on-Fiber. Utilizing a single-drive domain inverted structure in both modulators, balanced modulations were obtained without complicated radio frequency (RF) driving circuits and delicate RF phase adjustments. Intermediate frequency (IF) band signal was up-conversed to 60GHz band by using the fabricated device and was transmitted over optical fiber. Experiment results show that the proposed device enables millimeter wave generation and signal transmission without any power penalty caused by chromatic dispersion.

Effects of Electric Cortical Stimulation (ECS) and Transcranial Direct Current Stimulation (tDCS) on Rats With a Traumatic Brain Injury.

OBJECTIVE: To evaluate the effects of electric cortical stimulation (ECS) and transcranial direct current stimulation (tDCS) on motor and cognitive function recovery and brain plasticity in focal traumatic brain injury (TBI) of rats model. METHODS: Forty rats were pre-trained to perform a single pellet reaching task (SPRT), rotarod test (RRT), and Y-maze test for 14 days, then a focal TBI was induced by a weight drop model on the motor cortex. All rats were randomly assigned to one of the three groups: anodal ECS (50 Hz and 194 µs) (ECS group), tDCS (0.1 mA, 50 Hz and 200 µs) (tDCS group), and no stimulation as a control group. Four-week stimulation, including rehabilitation, was started 3 days after the operation. SPRT, RRT, and Y-maze were measured from day 1 to day 28 after the TBI was induced. Histopathological and immunohistochemistry staining evaluations were performed at 4 weeks. RESULTS: SPRT was improved from day 7 to day 26 in ECS, and from day 8 to day 26 in tDCS compared to the control group (p<0.05). SPRT of ECS group was significantly improved on days 3, 8, 9, and 17 compared to the tDCS group. Y-maze was improved from day 8 to day 16 in ECS, and on days 6, 12, and 16 in the tDCS group compared to the control group (p<0.05). Y-maze of the ECS group was significantly improved on day 9 to day 15 compared to the tDCS group. The c-Fos protein expression was better in the ECS group and the tDCS group compared to the control group. CONCLUSION: Electric stimulation in rats modified with a focal TBI is effective for motor recovery and brain plasticity. ECS induced faster behavioral and cognitive improvements compared to tDCS during the recovery period of rats with a focal TBI.

Production of recombinant polyhedra containing Cry1Ac fusion protein in insect cell lines.

Insect cell lines and the control of infection for obtaining the maximum amount of polyhedrin-CrylAc-polyhedrin fusion protein from Bactrus in monolayer and suspension culture systems were tested. Growth rates of the Trichoplusia ni (High-Five) cell line in both culture systems were better than the other insect cell lines, Spodoptera fiugiferda (Sf-9, Sf-21), Trichoplusia ni (Tn5), and Spodoptera exigua (Se301). The expression of the fusion protein in a monolayer culture showed that Se301 cells were 2.3-4.8 times more productive on a per cell basis than the other cell lines. However, in suspension culture, only High-Five cells were productive. High-Five cells infected with Bactrus at a multiplicity of infection (MOI) of 5 and a cell density of 3.0 x 10(5) cells per ml were more productive than the other infection condition in a suspension culture suitable for a large-scale production of baculovirus. In conclusion, for the large-scale production of Bactrus in vitro, High-Five cells showing good growth and high productivity are suitable.

Leaky modes of curved long-range surface plasmon-polariton waveguide.

A three-dimensional method for obtaining the bending losses and field distributions of bent surface plamon-polariton waveguides is presented. The method is based on a so called 'method of line', which discretises potential in the direction of the metal-widths, and leads to Airy-equations in the radial direction. From the results obtained. It is confirmed that thiner metal waveguide enable longer-ranging propagation of surface plasmon-polariton mode, but the weakened confinement requires larger bending radii on order to keep radiation loss.

Differential regulation of the histone chaperone HIRA during muscle cell differentiation by a phosphorylation switch.

Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.

Foliar spray of validamycin a or validoxylamine a controls tomato fusarium wilt.

ABSTRACT Tomato wilt, caused by the soilborne fungus Fusarium oxysporum f. sp. lycopersici, is effectively controlled by a foliar spray of validamycin A (VMA) or validoxylamine A (VAA) (>/=10 mug/ml); however, neither VMA nor VAA is antifungal in vitro. In pot tests, the effect of a foliar application of VMA or VAA at 100 mug/ml lasted for 64 days. Plants sprayed with VMA or VAA accumulated salicylic acid and had elevated expression of the systemic acquired resistance (SAR) marker genes P4 (PR-1), Tag (PR-2), and NP24 (PR-5). Foliar spray of VMA also controlled late blight and powdery mildew of tomato. The disease control by VMA and VAA lasted up to 64 days after treatment, was broad spectrum, and induced the expression of PR genes, all essential indicators of SAR, suggesting that VMA and VAA are plant activators. The foliar application of plant activators is a novel control method for soilborne diseases and may provide an economically feasible alternative to soil fumigants such as methyl bromide.

Effects of parasitic modes in high-speed LiNbO(3) optical modulators.

The characteristics of RF parasitic modes and the methods to suppress leakage phenomena in LiNbO(3) optical modulators were studied. The high frequency RF power transmission characteristics were simulated and experimented in the respects of LiNbO(3) wafer thickness, the kind of material contacting the back surface of the modulator chip, the gap and width of the CPW (co-planar waveguide) electrodes. An appropriate RF electrode geometry, to minimize coupling efficiency between co-planar waveguide and substrate mode, is proposed. Experimental results prove that the approaches made in this work are effective for broadening of modulation bandwidth.

Wavelength selective single and dual-channel dropping in a periodically poled Ti:LiNbO(3) waveguide.

All-optical wavelength selective single and dual channel dropping by sum frequency generation has been demonstrated in a periodically poled Ti:LiNbO(3) waveguide, which has two second harmonic phase-matching peaks. Less than -17 dB of channel dropping extinction ratio was observed with coupled pump power of 325 mW.

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug.

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug.

Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA.

For delivery of siRNA, chitosan (CS) was derivatized with poly-l-arginine (PLR) and polyethylene glycol (PEG). The formation of polyplexes with siRNA was confirmed by gel retardation. The PLR-grafted CS formed nanosized particles with siRNA. PLR-grafted CS showed higher cellular delivery efficiency of siRNA than did CS, pegylated CS, PLR, or pegylated PLR. The extent of reduction in the expression of fluorescent proteins was highest following treatment of the cells using PLR derivatives of CS in complexes with specific siRNAs. Cell viability was greater in populations treated with pegylated CS-PLR than in those treated with PLR. Hemolysis of erythrocytes was reduced upon conjugation of PLR with CS. The delivery of siRNAs via pegylated CS-PLR revealed little dependence on serum. Molecular imaging techniques revealed that the intratumoral administration of red fluorescent protein-specific siRNA in complexes with pegylated CS-PLR significantly silenced the expression of red fluorescent proteins in tumor tissues in vivo. These results indicate that pegylated CS-PLR might be useful for in vivo delivery of therapeutic siRNAs.

Birefringent waveguide sensor using a polarizer rotating technique.

A birefringence measurement system is introduced to get high phase resolution for detection of low contents of biochemicals. By using a fixed quarter-wave plate and a rotating polarizer, the phase difference between two orthogonal polarizations is transformed into phase delay of output sinusoidal signal. Analyzing the output phase, birefringence change could be detected with a phase noise of 0.14 degrees. As well as the birefringence measurement system, an optical evanescent waveguide sensor was developed. A rib-type silica waveguide overlaid with TiO2 film was fabricated, and a developed birefringence measurement technique was employed in evaluating a refractive index change on waveguide surface. For the fabricated waveguide with a 40-nm-thick TiO2 film, experiment results showed that the minimum detectable index change was 5.9x10(-7).

Anionic amino acid-derived cationic lipid for siRNA delivery.

Viable siRNA therapeutic strategies require the concurrent development of effective and safe delivery systems. Here, we described the synthesis of a new cationic lipid, N,N''-dioleylglutamide (DG), and evaluated DG-based liposomes as an siRNA delivery system. DG, an amino acid derivative, was synthesized by peptide bond linkage of oleylamine to each carboxylic acid group of glutamic acid. Gel retardation assays showed that DG-based cationic liposomes and siRNA began to form complexes from the N/P ratio of 1.8. The viability of A549, HeLa and WM266.4 cells was significantly higher after treatment with DG-based liposomes than with Lipofectamine 2000 and cationic 3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol)-based liposomes. The DG-based cationic liposomes could effectively deliver a fluorescent model siRNA into A549, HeLa, and WM266.4 human cancer cell lines, showing at least 2-fold higher fluorescence mean intensity values than did Lipofectamine 2000. When survivin-specific siRNA was delivered to cells in lipoplexes, survivin mRNA levels were reduced by DG-based liposomes to the higher extent than Lipofectamine 2000 and DC-Chol-based liposomes. When red fluorescent protein (RFP)-expressing cells were treated with RFP-specific siRNA (siRFP), RFP expression significantly decreased in cells treated with DG-based liposomes. Molecular imaging revealed that intratumoral injection of siRFP and DG-based liposome complexes significantly reduced fluorescence in RFP-expressing tumor tissues in mice. These results suggest that DG-based cationic liposomes would be of value for cellular delivery and in vivo local delivery of siRNA.

Clinico-pathological characteristics of congenital pulmonary lymphangiectasis: report of two cases.

Congenital pulmonary lymphangiectasis (CPL) is a rare, poorly documented disease, characterized by abnormal dilatation of pulmonary lymphatics without lymphatic proliferation. This disease is seen almost exclusively in infancy and early childhood. It can usually be divided into primary (congenital) and secondary forms. The primary form presents in neonates, and the patients mostly die due to the respiratory distress, shortly after birth. The authors experienced two cases of primary CPL in a 13-day-old male neonate and a one-day-old male neonate, showing prominent lymphatic dilatation in the septal, subpleural, and peri-bronchial tissue throughout both lungs. The latter case was associated with congenital cardiac anomaly including single ventricle. These are unique cases of CPL in Korea of which the diagnosis was established through post-mortem examination. Therefore, the authors report these two cases with primary CPL with a review of the literature.