Search

[Display omitted] • Two polysaccharides were obtained from unprocessed and Lactobacillus fermented litchi pulp (named LP and LPF, respectively). • LPF was more readily utilized by bacteria than LP. • LPF enhanced the levels of short-chain fatty acids than LP. • LPF increased the growth of Bifidobacterium , Prevotella , and Bacteroides than LP. • Structure-prebiotic activity relationship of litchi polysaccharides was elaborated. In this study, litchi polysaccharides were obtained from unfermented or fermented pulp by Lactobacillus fermentum (denoted as LP and LPF, respectively). The differences between LP and LPF in the colonic fermentation characteristics and modulatory of gut microbiota growth and metabolism were investigated with an in vitro fecal fermentation model. Results revealed that the strategies of gut bacteria metabolizing LP and LPF were different and LPF with lower molecular weight (Mw) was readily utilized by bacteria. The monosaccharide utilization sequence of each polysaccharide was Ara > Gla > GalA > GlcA ≈ Glu ≈ Man. Moreover, LPF promoted stronger proliferation of Bifidobacterium , Megamonas , Prevotella , and Bacteroides and higher SCFAs production (especially acetic and butyric acids) than LP. Correlation analysis further revealed that Mw could represent an essential structural feature of polysaccharides associated with its microbiota-regulating effect. Overall, Lactobacillus fermentation pre-treatment of litchi pulp promoted the fermentation characteristics and prebiotic activities of its polysaccharide. [ABSTRACT FROM AUTHOR]

Aims The present study aims to investigate the role of Akt in the regulation of urinary bladder organ hypertrophy caused by partial bladder outlet obstruction (pBOO). Main methods Male rats were surgically induced for pBOO. Real-time PCR and western blot were used to examine the levels of mRNA and protein. A phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the activity of endogenous Akt. Key findings The urinary bladder developed hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I collagen and α-smooth muscle actin (αSMA) were increased in pBOO bladder when compared to sham control. The phosphorylation (activation) levels of Akt1 (p-Ser 473 ), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1 were also increased in pBOO bladder. LY294002 treatment reduced the phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I collagen and αSMA in pBOO bladder. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002 treatment partially reduced the bladder weight caused by pBOO. Significance pBOO-induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated protein synthesis in pBOO bladder contributes to type I collagen and αSMA but not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in treatment of urinary bladder hypertrophy following pBOO. [ABSTRACT FROM AUTHOR]

In the device-to-device (D2D) underlaying LTE-Advanced (LTE-A) systems, unlike the existing works which formulate the resources sharing problem as a disjoint coalition formation game, in this letter we propose a novel overlapping coalition formation game (OCFG) based scheme to coordinate the interference between these two subsystems. By sharing uplink spectrums, in this game each D2D pair is allowed to join multiple coalitions simultaneously to improve the spectral efficiency and maximize the system utility. The merge-and-split rule is designed to adapt to the dynamic environment and a discrete-time Markov chain based analysis is utilized to present the stability. Compared with traditional methods, simulations demonstrate the significant performance enhancement of the proposed algorithm in terms of the complexity and D2D system sum throughput. [ABSTRACT FROM AUTHOR]

Based on the previous work in our group and the principle of computer-aided drug design, a series of novel β-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo . Compound 8l had moderate DPP4 inhibitory activity (IC 50 = 0.05 μM) and good oral bioavailability ( F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC 50 = 0.01 μM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles ( F = 22.8%, t 1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9. [ABSTRACT FROM AUTHOR]

Abstract: The goal of this study was to investigate the effects of antioxidant supplementation on the quality of flow cytometrically-sorted boar spermatozoa. The effects of ascorbic acid-2-glucoside (AA-2G) on the sex-sorting process were evaluated using a variety of concentrations. The effects of different antioxidants (AA-2G, l-glutathione, and vitamin E) on the viability and lifespan of boar spermatozoa were also compared during sorting. Furthermore, the effect of AA-2G on acrosome intactness, the capacitation ability of sorted boar spermatozoa and pregnancy efficiency after artificial insemination (AI) at different sorting-to-insemination intervals were examined. Greater (P <0.05) percentages of motile spermatozoa and acrosome intactness and longer storage time periods were observed in the AA-2G-supplemented group when compared with the other antioxidant-supplemented or control groups. At an AA-2G concentration of 0.068mg/mL, the motility characteristics (i.e., straightness (STR), velocity according to the average path (VAP), and amplitude of the sperm head lateral displacement (ALH)) of the sex-sorted boar spermatozoa were greater (P <0.05) than in those treated with other AA-2G concentrations. The capacitation rate of boar spermatozoa in the AA-2G-supplemented group was less (P <0.05) than that in the control group. After sorting-to-insemination interval of 10h, the pregnancy rates after AI with boar spermatozoa for the AA-2G-supplemented group were 59.25%, while the control group remains no sufficient quality semen. This study demonstrates that AA-2G supplementation can improve the quality of flow cytometrically sorted boar spermatozoa and that the optimal concentration of AA-2G for sorting is 0.068mg/mL. [Copyright &y& Elsevier]

Abstract: The combustion assisted thermal spray systems are being used to apply coatings to prevent surface degradation. They offer a highly attractive way to modify the surface properties of the substrate to extend the product life. In addition to the materials being sprayed, the quality of combustion assisted thermal spray coating depends greatly on the flow behavior of reacting gases and particle dynamics. The present study investigates the effect of gas phase and its interaction with particles through the nozzle of a thermal spray gun by developing a comprehensive mathematical model. The objective is to develop a predictive understanding of various design parameters of combustion assisted thermal spray systems. The model was developed by considering the conservation of mass, momentum and energy of reacting gases. The particle dynamics was decoupled from the gas phase dynamics since the particle loading in the spray process is very low. The developed model was employed to investigate the influence of various design parameters on the coating quality of thermal spray process. [Copyright &y& Elsevier]

In this work, aiming at finding a novel, potent, and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor with good pharmacokinetic profiles for the treatment of diabetes, we focus on modifying the sugar moiety of SGLT2 inhibitors, which dominates the binding with glucose binding site of hSGLT, via removing the C-6 hydroxy group to adjust the physicochemical properties and target-recognition manners of SGLT2 inhibitors. In addition, tofogliflozin containing a special O -spiroketal C -arylglucoside scaffold, displayed good efficacy and bioavailability both in animals and in humans. Therefore, a series of 6-deoxy O -spiroketal C -arylglucosides as novel SGLT2 inhibitors were designed, synthesized, and evaluated in this work. The structure-activity relationship (SAR) research on this novel series and a comprehensive in vitro and in vivo biological evaluation afforded compound 39 with high in vitro hSGLT2 inhibitory activity (IC 50 = 4.5 nM), good pharmacokinetic profiles, and more remarkable efficacy in C57BL/6J mice and Sprague-Dawley rats than marketed drug tofogliflozin. Image 1 • Novel 6-deoxy O -spiroketal C -arylglucosides as SGLT2 inhibitors were designed, synthesized, and evaluated. • The structure-activity relationship (SAR) of this novel series of 31 compounds was demonstrated. • Compound 39 demonstrated higher potency of inhibiting hSGLT2 than dapagliflozin (IC 50 = 4.5 nM vs 8.3 nM). • Compound 39 displayed greater efficacy than tofogliflozin on urinary glucose excretion and oral glucose tolerance in mice. • The half-life of compound 39 in mice was longer than tofogliflozin after oral administration (5.95 h vs 2.57 h). [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone modulates airway vagal preganglionic neurons. Airway vagal preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent dye and identified in medullary slices, and their responses to corticotropin-releasing hormone (200 nmol L −1 ) were examined using whole-cell patch clamp. The results show that under current clamp, corticotropin-releasing hormone (200 nmol L −1 ) depolarized airway vagal preganglionic neurons and significantly increased the rate of their spontaneous firing. Under voltage clamp, corticotropin-releasing hormone caused a tonic inward current and significantly facilitated the spontaneous glutamatergic and GABAergic inputs of these neurons. Corticotropin-releasing hormone had no impact on the spontaneous glycinergic inputs of these neurons. In the preexistence of tetrodotoxin (1 μmol L −1 ), corticotropin-releasing hormone had no impact on the miniature excitatory or inhibitory postsynaptic currents, but still induced a tonic inward current and significantly increased the input resistance. The responses induced by corticotropin-releasing hormone were prevented by Antalarmin hydrochloride (50 μmol L −1 ), an antagonist of type 1 corticotropin-releasing hormone receptors, but insensitive to Astressin 2B (200 nmol L −1 ), an antagonist of type 2 corticotropin-releasing hormone receptors. These results suggest that corticotropin-releasing hormone excites airway vagal preganglionic neurons via activation of its type 1 receptors at multiple sites, which includes a direct postsynaptic excitatory action and presynaptic facilitation of both glutamatergic and GABAergic inputs. In stress, corticotropin-releasing hormone might be able to activate the airway vagal nerves and, consequently, participate in induction or exacerbation of airway disorders. [ABSTRACT FROM AUTHOR]

Several pieces of evidence indicate that the microglial P2X 7 receptor (P2X 7 R) regulate cardiovascular activities. We explored the possible roles of microglial P2X 7 R in the PVN mediated sympathoexcitatory responses in acute myocardial infarction (AMI) rat. Sprague–Dawley rats underwent coronary artery ligation to induce AMI. The rats received intraperitoneal administration of the P2X 7 R antagonist Brilliant Blue-G (BBG, 25 or 50 mg kg −1 , once a day for 5 days) prior to myocardial ischemia. Other rats received bilateral microinjection of P2X 7 R-siRNA (0.015 or 0.03 nmol 0.1 μl per side, once a day for 2 days) targeting P2X 7 R mRNA into the PVN prior to myocardial ischemia. First, we examined the ATP levels and protein expression P2X 7 R in the PVN in different ischemia time groups, and we found that the change of P2X 7 R was positive correlated with the ATP levels in a time-dependent manner. The double-immunofluorescence evidence showed that P2X 7 R was mainly co-localizated with the microglial marker Iba-1 in the PVN. Second, gene knockdown of P2X 7 R with P2X 7 -siRNA or inhibition of P2X 7 R with BBG reduce the mRNA and protein expression of IL-1β and TNF-α in the PVN of AMI rat. Third, microinjected P2X 7 -siRNA also suppressed the up-regulation of P2X 7 R, oxytocin and vasopressin in the PVN of AMI rats. Fourth, P2X 7 -siRNA and BBG also attenuated the renal sympathetic nerve activity (RSNA) in the AMI rats. Our results indicate that microglial P2X 7 R activation in PVN mediating the production of proinflammatory cytokines that activate oxytocinergic and vasopressinergic neuron, which augmented the RSNA in the AMI rat. [ABSTRACT FROM AUTHOR]

Abstract: Several pieces of evidence indicate that the rostral ventrolateral medulla (RVLM) is probably one of the key neural structures mediating the pressor effects of orexins in the brain. Nitric oxide synthase/nitric oxide (NOS/NO) system in the RVLM modulates cardiovascular activities. Our experiments were designed to test the hypothesis that orexin-A (OXA) is involved in the mechanism of stress-induced hypertension (SIH) by adjusting NOS/NO system in the RVLM. The stress-induced hypertensive rats (SIHR) model was established by electric foot-shocks and noises. Here we examined the expression of OXA immunoreactive (OXA-IR) cells in the lateral hypothalamus (LH) and the protein level of orexin 1 receptor (OX1R) in the RVLM of SIHR, and we found that the expressions of OXA-IR and OX1R were higher than those of the control group. The double-staining immunohistochemical evidence showed that OX1R immunoreactive (OX1R-IR) cells and neuronal nitric oxide synthase (nNOS) or inducible nitric oxide synthase (iNOS) immunoreactive (IR) cells were co-localizated in the RVLM. Microinjection of OXA (10, 50, 100 pmol/100 nl) into the unilateral (right) RVLM of control rats or SIHR produced pressor and tachycardiac effects in a dose-dependent manner. SB-408124 (100 pmol/100 nl, an antagonist of OX1R) or TCS OX2 29 (100 pmol/100 nl, an antagonist of OX2R) partly abolished the cardiovascular effects of exogenously-administrated OXA into the RVLM of control rats and SIHR, and lowered the increased systolic blood pressure (SBP) and heart rate (HR) of SIHR, with no difference in statistical significance between the two antagonists'' effects. Microinjection into the RVLM of both control and SIHR groups of 7-Ni (0.05 pmol/100 nl, nNOS inhibitor) or Methylene Blue [100 pmol/100 nl, an inhibitor of soluble guanylate cyclase (sGC)] suppressed the OXA-induced increase of SBP and HR, whereas microinjection of AG (1, 10, 100 pmol/100 nl) had no obvious effects on the OXA-induced increase of SBP and HR. Our results indicate that OXA in the RVLM may participate in the central regulation of cardiovascular activities in SIHR, and OX1R and OX2R both have important roles in it. The cardiovascular effects of OXA in the RVLM may be induced by nNOS-derived NO, which activated sGC-associated signaling pathway. [Copyright &y& Elsevier]

Abstract: Aims: To investigate the cardiovascular regulatory mechanism of adenosine A2A receptor (A2AR) in the rostral ventrolateral medulla (RVLM) in acute myocardial ischemic (AMI) rats. Main methods: The animal model of AMI was established by ligating the left anterior descending coronary artery (LAD). The A2AR expression was examined by immunohistochemistry, western blot and real-time PCR. CGS21680 and SCH58261 (an agonist and antagonist of A2AR) were respectively microinjected into the RVLM. In a subgroup of rats, PD98059 (an antagonist of extracellular signal-regulated kinase (ERK1/2)) was microinjected prior to CGS21680 administration. Phosphorylation of ERK1/2 was examined by western blot. Key findings: Our results demonstrated that A2AR immunoreactive positive neurons, the expressions of protein and mRNA of A2AR in the RVLM of AMI group were increased compared with the sham group. Microinjection CGS21680 into the RVLM inhibited mean arterial pressure (MAP) and heart rate (HR) in both AMI and sham groups. The inhibition was significantly greater in AMI group than in sham group. The cardiovascular effects of CGS21680 mentioned above were almost abolished by prior administration of PD98059. The increase of ERK1/2 in the RVLM with the cardiovascular responses was induced by CGS21680 in AMI rats; this effect was also blocked by SCH58261. Significance: This study reveals that the activated A2AR in the RVLM underlies the depressor and bradycardiac responses in AMI rats via phosphorylation of ERK1/2 increasing. [Copyright &y& Elsevier]

Abstract: The functional polymer containing carbazole unit, [(poly(9-(4-vinylbenzyl)-9H-carbazole) (PVBK)], was successfully prepared via nitroxide-mediated living free-radical polymerization of 9-(4-vinylbenzyl)-9H-carbazole (VBK). The controlled features of the polymerization were confirmed by the linear increase in the molecular weight with the monomer conversion while keeping the relative narrow molecular weight distribution (M w/M n ⩽1.51), and successful chain extension with styrene. The resulting polymer absorbed light in the 305–355nm range and exhibited fluorescent emission at 350nm. The fluorescent intensity of the polymer was lower than that of monomer and was affected by the properties of the different solvents, which decreased in the following order: DMF>THF>CHCl3 at the same concentration of carbazole units. The fluorescence intensity of the polymer was apparently influenced by chromophore concentration, and the maximum value was obtained when the carbazole unit concentration was around 8×10−5 mol/L. Moreover, it was shown that the strong fluorescence of PVBK can be quenched by methyl acrylate (MA). [Copyright &y& Elsevier]