Experimental study of an organic Rankine cycle system with radial inflow turbine and R123

A new micro radial inflow turbine is developed fora mini organic Rankine cycle (ORC) system in this study. With R123 as the working fluid, the turbine operational characteristics and performance are investigated by experiments. Based on the experimental data, the maximum rotational speed of the radial inflow turbine reaches53564r/min, and the maximum output power of the turbine is3.386kW and the maximum electric power reaches1.884kW. When the turbine rotational speed is34586r/min, the system isentropic and electromechanical efficiencies achieve the maximum values of 83.6% and65.3% respectively. Both the turbine isentropic and thermal efficiencies increase with the heat source temperature

Role of the hepatocyte nuclear factor-1beta (HNF-1beta) C-terminal domain in Pkhd1 (ARPKD) gene transcription and renal cystogenesis.

Hepatocyte nuclear factor-1beta (HNF-1beta) is a homeodomain-containing transcription factor that regulates tissue-specific gene expression in the kidney and other epithelial organs. Mutations of HNF-1beta produce congenital cystic abnormalities of the kidney, and previous studies showed that HNF-1beta regulates the expression of the autosomal recessive polycystic kidney disease (ARPKD) gene, Pkhd1. Here we show that the C-terminal region of HNF-1beta contains an activation domain that is functional when fused to a heterologous DNA-binding domain. An HNF-1beta deletion mutant lacking the C-terminal domain interacts with wild-type HNF-1beta, binds DNA, and functions as a dominant-negative inhibitor of a chromosomally integrated Pkhd1 promoter. The activation of the Pkhd1 promoter by wild-type HNF-1beta is stimulated by sodium butyrate or coactivators CREB (cAMP-response element)-binding protein (CBP) and P/CAF. The interaction with CBP and P/CAF requires the C-terminal domain. Expression of an HNF-1beta C-terminal deletion mutant in transgenic mice produces renal cysts, increased cell proliferation, and dilatation of the ureter similar to mice with kidney-specific inactivation of HNF-1beta. Pkhd1 expression is inhibited in cystic collecting ducts but not in non-cystic proximal tubules, despite transgene expression in this nephron segment. We conclude that the C-terminal domain of HNF-1beta is required for the activation of the Pkhd1 promoter. Deletion mutants lacking the C-terminal domain function as dominant-negative mutants, possibly by preventing the recruitment of histone acetylases to the promoter. Cyst formation correlates with inhibition of Pkhd1 expression, which argues that mutations of HNF-1beta produce kidney cysts by down-regulating the ARPKD gene, Pkhd1. Expression of HNF-1alpha in proximal tubules may protect against cystogenesis

Hexarelin protects rodent pancreatic B-cells function from cytotoxic effects of streptozotocin involving mitochondrial signalling pathways in vivo and in vitro

Mitochondrial functions are crucial for pancreatic β-cell survival and glucose-induced insulin secretion. Hexarelin (Hex) is a synthetic small peptide ghrelin analogue, which has been shown to protect cardiomyocytes from the ischemia-reperfusion process. In this study, we used in vitro and in vivo models of streptozotocin (STZ)-induced β-cell damage to study the protective effect of Hex and the associated mechanisms. We found that STZ produced a cytotoxic effect in a dose- and time-dependent manner in MIN6 cells (a mouse β-cell line). Hex (1.0 μM) decreased the STZ-induced damage in β-cells. Rhodamine 123 assay and superoxide DHE production assay revealed that Hex ameliorated STZ-induced mitochondrial damage and excessive superoxide activity in β-cells. In addition, Hex significantly reduced STZ-induced expression of cleaved Caspases-3, Caspases-9 and the ratio of proapoptotic protein Bax to anti-apoptotic protein Bcl-2 in MIN6 cells. We further examined the in vivo effect of Hex in a rat model of type 1 diabetes induced by STZ injection. Hex ameliorated STZ-induced decrease in plasma insulin and protected the structure of islets from STZ-induced disruption. Hex also ameliorated STZ-induced expression of cleaved Caspase- 9 and the Bax in β-cells. In conclusion, our data indicate that Hex is able to protects β- cell mass from STZ-caused cytotoxic effects involving mitochondrial pathways in vitro and in vivo. Hex may serve as a potential protective agent for the management of diabetes

Excitotoxicity of TNF alpha derived from KA activated microglia on hippocampal neurons in vitro and in vivo

National Key Natural Science Foundation of China [30230140]P>Highly activated microglia and followed excessive expression of inflammatory cytokines are associated with neuroexcitotoxic injuries. We use electrophysiological techniques, ELISA, western-blot, RT-PCR assay and TUNEL method to explore whether over-produced tumor necrosis factor alpha (TNF alpha) released from activated microglia results in neuronal injuries, and further causes apoptosis through increasing excitotoxicity of hippocampal neurons. Our data showed that kainic acid (KA) activated microglia highly expressed TNF alpha, mRNA and protein. KA activated microglia conditioned media ((KA-MCM) significantly enhanced the amplitude of the population spike at rat's hippocampal CA3 region. It also increased the Ca2+ current amplitude and density in cultured hippocampal neurons, as well as the high expression of NMDAR1, iNOS, and caspase 3 mRNA and protein at both hippocampal neurons and tissues. KA-MCM also increased TUNEL-positive cells in hippocampal neurons, whereas addition of anti-TNF alpha to the KA-MCM before its application significantly reduced those effects. These studies suggest that TNF alpha derived from KA activated microglia increases excitotoxicity of hippocampal neurons, and might induce neuronal apoptosis in vitro and in vivo

A transcriptional network in polycystic kidney disease

Mutations in cystic kidney disease genes represent a major genetic cause of end-stage renal disease. However, the molecular cascades controlling the expression of these genes are still poorly understood. Hepatocyte Nuclear Factor 1β (HNF1β) is a homeoprotein predominantly expressed in renal, pancreatic and hepatic epithelia. We report here that mice with renal-specific inactivation of HNF1β develop polycystic kidney disease. We show that renal cyst formation is accompanied by a drastic defect in the transcriptional activation of Umod, Pkhd1 and Pkd2 genes, whose mutations are responsible for distinct cystic kidney syndromes. In vivo chromatin immunoprecipitation experiments demonstrated that HNF1β binds to several DNA elements in murine Umod, Pkhd1, Pkd2 and Tg737/Polaris genomic sequences. Our results uncover a direct transcriptional hierarchy between HNF1β and cystic disease genes. Interestingly, most of the identified HNF1β target gene products colocalize to the primary cilium, a crucial organelle that plays an important role in controlling the proliferation of tubular cells. This may explain the increased proliferation of cystic cells in MODY5 patients carrying autosomal dominant mutations in HNF1β

Expression of Bax/Bcl-2 and activated Caspase 3 and 9 caused by STZ and Hex.

<p>The MIN6 cells were treated with 1.0 mM STZ and/or 1.0 μM Hex, the alterations of Bax/Bcl-2, cleaved Caspase-3 and cleaved Caspase-9 were detected by Western blot. The upper panels show the representative immunoblots for each protein. (A) Hex significantly decreased the ratio of Bax to Bcl-2 increased by STZ treatment. (B and C) Hex significantly decreased the STZ-induced expression of cleaved Caspase-3 and cleaved Caspase-9. The data are presented as the mean ± SEM (n = 4). *p < 0.05, **p < 0.01, ***p < 0.001, compared with the control group; ##p < 0.01, ###p < 0.001, compared with the STZ group.</p

Hex reduced STZ-induced mitochondrial damage and in pancreatic cells.

<p>The MIN6 and α-TC6 cells were treated with 1.0 mM STZ and 1.0 μM Hex alone or in combination. Cell viability of (A) the MIN6 and (B) α-TC6 cells was measured by MTS assay (n = 6). The MIN6 cells were then treated with 1.0 mM STZ and 1.0 μM Hex alone or in combination. (C) The changes in the mitochondrial potential of the MIN6 were determined by Rhodamine 123 assay. (D) Cell superoxide activity of the MIN6 was detected by superoxide DHE production. The data are presented as the mean ± SEM (n = 8). *p < 0.05, compared with the control group; #p < 0.05, ##p < 0.01, compared with the STZ group.</p