Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice

Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27−/− mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27−/− mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27−/− mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27−/− and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27−/− mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1α were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27−/− mice. Remarkably, Fsp27−/− MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity

Numerical Studies of Propeller Exciting Bearing Forces under Nonuniform Ship’s Nominal Wake and the Influence of Cross Flows

Propeller exciting forces are the main causes of stern vibrations. In this paper, three-dimension exciting bearing forces of one blade and the whole propeller under nonuniform ship’s wake were predicted, and the influence of cross flows on these exciting forces was studied. All simulations were carried out using a commercial solver, STAR-CCM+. To obtain the nominal wake for studying propeller exciting forces, flow field around a bare hull was simulated. Numerical results were widely validated by measured data, especially the velocity field at the propeller plane. Harmonic characteristics of the nonuniform ship’s wake were studied. Then, a propeller under uniform inflow and nonuniform ship’s wake with/without cross flows was simulated. Free-water surface and hull boundary were considered using a specially designed dummy stern. Results show that the influence of cross flows on propeller exciting forces is obvious. As for the exciting forces of one blade, the cross flows have greater influence on the axial force. As for the exciting forces of the whole propeller, the cross flows have greater influence on the transverse and vertical forces, and if the cross flows in ship’s wake are not considered, the amplitudes of the main harmonics of transverse and vertical forces increase obviously

Free and Bound Phenolics of Buckwheat Varieties: HPLC Characterization, Antioxidant Activity, and Inhibitory Potency towards α-Glucosidase with Molecular Docking Analysis

Free and bound phenolic fractions from six buckwheat varieties were investigated for their compositions, antioxidant activities, and inhibitory effects on α-glucosidase. The results showed that different buckwheat varieties have significant differences in phenolic/flavonoid contents, and these contents were found in higher quantities in free form than in bound form. HPLC results revealed that rutin, quercetin, and kaempferol-3-O-rutinoside were the most abundant components in free and bound forms, whereas dihydromyricetin was found only in the bound form. Free phenolics showed higher antioxidant activities of DPPH, ABTS+, OH•, and FRAP than those of bound phenolics. Strong inhibitory effects against α-glucosidase by the free/bound phenolic fractions were found in all buckwheat varieties, and free phenolics showed stronger α-glucosidase inhibition than that of the corresponding bound phenolics. More importantly, the main phenolic compounds observed in the buckwheat varieties were subjected to molecular docking analysis to provide insight into their interactions with α-glucosidase. The contributions by individual phenolics to the observed variation was analysed by Pearson correlation coefficient analysis and principal component analysis. The present study provides a comprehensive comparison for the phenolic fractions of buckwheat varieties and identify the main contributors to antioxidant and α-glucosidase inhibitory activity

Use of the PiCCO system in critically ill patients with septic shock and acute respiratory distress syndrome: a study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hemodynamic monitoring is very important in critically ill patients with shock or acute respiratory distress syndrome(ARDS). The PiCCO (Pulse index Contour Continuous Cardiac Output, Pulsion Medical Systems, Germany) system has been developed and used in critical care settings for several years. However, its impact on clinical outcomes remains unknown.</p> <p>Methods/design</p> <p>The study is a randomized controlled multi-center trial. A total of 708 patients with ARDS, septic shock or both will be included from January 2012 to January 2014. Subjects will be randomized to receive PiCCO monitoring or not. Our primary end point is 30-day mortality, and secondary outcome measures include ICU length of stay, days on mechanical ventilation, days of vasoactive agent support, ICU-free survival days during a 30-day period, mechanical-ventilation-free survival days during a 30-day period, and maximum SOFA score during the first 7 days.</p> <p>Discussion</p> <p>We investigate whether the use of PiCCO monitoring will improve patient outcomes in critically ill patients with ARDS or septic shock. This will provide additional data on hemodynamic monitoring and help clinicians to make decisions on the use of PiCCO.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT01526382</p

Prognostic value of neutrophil count to albumin ratio in patients with decompensated cirrhosis

Abstract Our study aimed to investigate the prognostic value of neutrophil count to albumin ratio (NAR) in predicting short-term mortality of patients with decompensated cirrhosis (DC). A total of 623 DC patients were recruited from a retrospective observational cohort study. They were admitted to our hospital from January 2014 to December 2015. NAR of each patient was calculated and analyzed for the association with 90-day liver transplantation-free (LT-free) outcome. The performance of NAR and the integrated model were tested by a receiver-operator curve (ROC) and C-index. The 90-day LT-free mortality of patients with DC was 10.6%. NAR was significantly higher in 90-day non-survivors than in survivors (The median: 1.73 vs 0.76, P < 0.001). A threshold of 1.40 of NAR differentiated patients with a high risk of death (27.45%) from those with a low risk (5.11%). By multivariate analysis, high NAR was independently associated with poor short-term prognosis (high group: 5.07 (2.78, 9.22)). NAR alone had an area under the ROC curve of 0.794 and C-index of 0.7789 (0.7287, 0.8291) in predicting 90-day mortality. The integrated MELD–NAR (iMELD) model had a higher area under the ROC (0.872) and C-index (0.8558 (0.8122, 0.8994)) than the original MELD in predicting 90-day mortality. NAR can be used as an independent predictor of poor outcomes for patients with DC during short-term follow-up

The Effect of Prophylactic Lamivudine plus Adefovir Therapy Compared with Lamivudine Alone in Preventing Hepatitis B Reactivation in Lymphoma Patients with High Baseline HBV DNA during Chemotherapy.

Prophylactic antiviral therapy is essential for lymphoma patients with high baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited data on the optimal options. The present study was designed to compare the efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with, pre-chemotherapy HBV DNA load ≥2000 IU/ml. We retrospectively analyzed the medical records of 86 lymphoma patients with baseline HBV DNA load ≥2000 IU/ml during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1, 2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty-five patients received LAM and 21 received LAM+ADV. The rate was significantly lower in the LAM+ADV group compared with the LAM group for HBV reactivation (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p   =  0.349), and chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis of factors associated with HBV reactivation in these patients, LAM+ADV treatment and HBeAg negative were the independent protective factors. Therefore, LAM+ADV should be considered for antiviral prophylaxis in lymphoma patients with pre-chemotherapy HBV DNA load ≥2000 IU/ml. Further study is warranted to confirm these findings

Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A.

Reactivation of fetal hemoglobin (HbF) in adults ameliorates the severity of the common β-globin disorders. The transcription factor BCL11A is a critical modulator of hemoglobin switching and HbF silencing, yet the molecular mechanism through which BCL11A coordinates the developmental switch is incompletely understood. Particularly, the identities of BCL11A cooperating protein complexes and their roles in HbF expression and erythroid development remain largely unknown. Here we determine the interacting partner proteins of BCL11A in erythroid cells by a proteomic screen. BCL11A is found within multiprotein complexes consisting of erythroid transcription factors, transcriptional corepressors, and chromatin-modifying enzymes. We show that the lysine-specific demethylase 1 and repressor element-1 silencing transcription factor corepressor 1 (LSD1/CoREST) histone demethylase complex interacts with BCL11A and is required for full developmental silencing of mouse embryonic β-like globin genes and human γ-globin genes in adult erythroid cells in vivo. In addition, LSD1 is essential for normal erythroid development. Furthermore, the DNA methyltransferase 1 (DNMT1) is identified as a BCL11A-associated protein in the proteomic screen. DNMT1 is required to maintain HbF silencing in primary human adult erythroid cells. DNMT1 haploinsufficiency combined with BCL11A deficiency further enhances γ-globin expression in adult animals. Our findings provide important insights into the mechanistic roles of BCL11A in HbF silencing and clues for therapeutic targeting of BCL11A in β-hemoglobinopathies. Proc Natl Acad Sci U S A 2013 Apr 16; 110(16):6518-23

The incidence, risk factors and outcomes of early bloodstream infection in patients with malignant hematologic disease after unrelated cord blood transplantation: a retrospective study

Abstract Background Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. Methods There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. Results Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). Conclusions Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival