Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Severe Pulmonary Adverse Effects in Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) Regimen Plus Rituximab

BACKGROUND/AIMS: The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma. METHODS: A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients. RESULTS: The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002). CONCLUSIONS: Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.ope

Edge-carboxylated graphene nanoplatelets as oxygen-rich metal-free cathodes for organic dye-sensitized solar cells

Edge-carboxylated graphene nanoplatelets (ECGnPs) were synthesized by the simple, efficient and eco-friendly ball-milling of graphite in the presence of dry ice and used as oxygen-rich metal-free counter electrodes (CEs) in organic dye-sensitized solar cells (DSSCs), for the first time. The resultant ECGnPs are soluble in many polar solvents including 2-propanol due to the polar nature of numerous carboxylic acids at edges, allowing an electrostatic spray (e-spray) to be deposited on fluorine-doped SnO2 (FTO)/glass substrates. The ECGnP-CE exhibited profound improvements in the electrochemical stability for the Co(bpy)3 2+/3+ redox couple compared to the platinum (Pt)-CE. The charge transfer resistance (RCT), related to the interface between an electrolyte and a CE, was significantly reduced to 0.87 ?? cm2, much lower than those of (Pt)-CE (2.19 ?? cm 2), PEDOT:PSS-CE (2.63 ?? cm2) and reduced graphene oxide (rGO)-CE (1.21 ?? cm2). The DSSC based on the JK-303-sensitizer and ECGnP-CE displayed a higher photovoltaic performance (FF, Jsc, and ??, 74.4%, 14.07 mA cm-2 and 9.31%) than those with the Pt-CE (71.6%, 13.69 mA cm-2 and 8.67%), PEDOT:PSS (68.7%, 13.68 mA cm-2 and 8.25%) and rGO-CE (72.9%, 13.88 mA cm-2 and 8.94%).close3

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

An experimental investigation of performance of the integrated thermal management system in an induction coolant heater

Efforts to increase the distance travelled by electrically-driven vehicles include weight reduction of the vehicle, increase of battery efficiency, improvement of efficiency of the driving part etc. When the heating system is operated, reduced mileage of the electrically driven vehicle is about 30 ~ 50 %. In order to improve the efficiency of the battery, thermal management of the battery is important. Existing electrically-driven vehicles have two separate heaters, one for battery warm-up and the other for indoor heating, which increases the weight of vehicle. In this paper, an induction coolant heater has been investigated to enable not only fast warm-up of the battery but also indoor heating at the same time. The experiment was performed by changing the flow rate of cooling water flowing into the battery and the indoor heater at a ratio of 8:2, 5:5 and 2:8. The experimental results show that the warm-up time of the battery decreases with increasing flow rate to the battery, however, it is not linearly proportional to the flow rate

Effect of Resistance Exercise on the Lipolysis Pathway in Obese Pre- and Postmenopausal Women

Physical exercise may stimulate lipolytic activity within adipose tissue. Furthermore, resistance exercise may contribute to the more efficient reduction in adipose tissue mass and prevent the accumulation thereof in obese women. The purpose of this study was to examine the effects of regular resistance exercise for 12 weeks on the lipolysis pathway in women with obesity. Twenty-three pre- and postmenopausal women with body fat percentages of 30% or more were divided into the premenopausal group (n = 9) and the postmenopausal group (n = 14). All subjects participated in resistance exercise training for 12 weeks. Anthropometric and physical fitness tests were performed on all participants. Protein analyses were performed on extracted subcutaneous fatty tissue, and changes in the relevant protein levels in the samples were analyzed by Western blotting. All serum samples were submitted for enzyme-linked immunosorbent assay measurements of adipocyte factors. After 12 weeks, the adipose triglyceride lipase, monoacylglycerol lipase, and perilipin1 protein levels were significantly lower in the postmenopausal group than in the premenopausal group. The hormone-sensitive lipase protein levels were significantly higher in the postmenopausal group than in the premenopausal group. In addition, leptin concentrations were significantly decreased after resistance exercise in the postmenopausal group. Adiponectin concentrations were significantly increased after resistance exercise in both groups. These findings indicate that regular resistance exercise is effective in reducing the weight and body fat of obese premenopausal women, and in the secretion of adiponectin. On the other hand, postmenopausal women were found to have redeced weight and body fat, and were found to be positive for the secretion of adipokine factors. In addition, positive changes in lipolysis pathway factors in adipose tissue promote lipid degradation and reduce fat mass. Thus, regular resistance exercise shows positive changes in the lipolysis pathway more effectively in weight and body fat reduction in postmenopausal women than in premenopausal women

First and Second Law Thermodynamic Analyses of Hybrid Nanofluid with Different Particle Shapes in a Microplate Heat Exchanger

The improvement in the quantitative and qualitative heat transfer performances of working fluids is trending research in the present time for heat transfer applications. In the present work, the first and second law analyses of a microplate heat exchanger with single-particle and hybrid nanofluids are conducted. The microplate heat exchanger with single-particle and hybrid nanofluids is analyzed using the computational fluid dynamics approach with symmetrical heat transfer and fluid flow analyses. The single-particle Al2O3 nanofluid and the hybrid Al2O3/Cu nanofluid are investigated for different nanoparticles shapes of sphere (Sp), oblate spheroid (OS), prolate spheroid (PS), blade (BL), platelet (PL), cylinder (CY) and brick (BR). The first law characteristics of NTU, effectiveness and performance index and the second characteristics of thermal, friction and total entropy generation rates and Bejan number are compared for Al2O3 and Al2O3/Cu nanofluids with considered different-shaped nanoparticles. The OS- and PL-shaped nanoparticles show superior and worse first and second law characteristics, respectively, for Al2O3 and Al2O3/Cu nanofluids. The hybrid nanofluid presents better first and second law characteristics compared to single-particle nanofluid for all nanoparticle shapes. The Al2O3/Cu nanofluid with OS-shaped nanoparticles depicts maximum values of performance index and Bejan number as 4.07 and 0.913, respectively. The first and second law characteristics of the best combination of the Al2O3/Cu nanofluid with OS-shaped nanoparticles are investigated for various volume fractions, different temperature and mass flow rate conditions of hot and cold fluids. The first and second law characteristics are optimum at higher hot fluid temperature, lower cold fluid temperature, lower hot and cold fluid mass flow rates. In addition, the first and second law characteristics have improved with increase in volume fraction

Experimental Study on Heating Performances of Integrated Battery and HVAC System with Serial and Parallel Circuits for Electric Vehicle

The objective of the present study is to conduct experiments for investigating heating performances of integrated system with serial and parallel circuits for battery and heating ventilation and air conditioning system (HVAC) of electric vehicles under various operating conditions. In addition, the artificial neural network (ANN) model is proposed to accurately predict the heating performances of integrated system with serial and parallel circuits for battery and HVAC. A test bench of integrated system with serial and parallel circuits has been developed for establishing the trade-off between battery heating and HVAC heating. The heating performances namely, battery out temperature, battery temperature rise rate, battery heating capacity, HVAC heating capacity and total heating capacity are evaluated experimentally for the integrated system with serial and parallel circuits. The behavior of various heating performances is evaluated under influence of flow rate and heater power. Battery out temperature reaches 40 °C within 10 min with rise rate of 2.17 °C/min for the integrated system with serial circuit and that within 20 min with rise rate of 1.22 °C/min for the integrated system with parallel circuit. Integrated system with serial circuit shows higher HVAC heating capacity than integrated system with parallel circuit which are 5726.33 W and 3869.15 W, respectively. ANN model with back-propagation algorithm, Levenberg-Marquardt training variant, Tan-sigmoidal transfer function and 20 hidden neurons presents the accurate prediction of heating performances of the integrated system with serial and parallel circuits for battery and HVAC