General Drag Correlations for Particle-Fluid System

Particle-fluid flows are commonly encountered in industrial applications. It is of great importance to understand the fundamentals governing the behavior of such a flow system for better process design, control, and optimization. Generally, the particle-fluid flow behavior is strongly influenced by the interaction forces between fluid and particles. Among the various kinds of particle-fluid interaction forces, the drag force is the most essential. This chapter reviews the modeling of drag force for particle-fluid systems: from single particle to multiple particles, monosize to multisize, spherical to nonspherical, and Newtonian fluid to non-Newtonian fluid. Typical drag correlations in the literature are compared and assessed in terms of physical meaning, consistency, and generality

Expression of the NRF2

Reduced nuclear factor erythroid 2-related factor 2 (NRF2) pathway activity was reported in models of chronic kidney disease (CKD). Pharmacological activation of NRF2 is supposed to improve renal function, but data concerning the NRF2 activity in human CKD are lacking. We investigated the NRF2 target NAD(P)H:quinone oxidoreductase 1 (NQO1) as a readout parameter for NRF2 activity in monocytes of CKD patients (n=63) compared to those of healthy controls (n=16). The NQO1 gene expression was quantified using real-time PCR and the protein content by in-cell Western assays. We found a 3-4-fold increase in NQO1 gene expression in CKD 1–5 (n=29; 3.5 for NQO1/ribosomal protein L41; p<0.001). This was accompanied by a 1.1-fold increase in NQO1 protein (p=0.06). Cardiovascular disease prevalence was higher in CKD 1–5 patients with higher compared to those with lower NQO1 gene expression (p=0.02). In advanced uremia, in dialysis patients (n=34), NQO1 gene expression was less robustly upregulated than that in CKD 1–5, while NQO1 protein was not upregulated. We conclude that in mononuclear cells of CKD patients, the NRF2 pathway is activated by coexisting pathogenic mechanisms, but in advanced uremia, the effectiveness of this upregulation is reduced. Both processes could interfere with pharmacological NRF2 activation

Orexin Receptor-1 in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Electroacupuncture

Electroacupuncture (EA) has been used to treat numerous diseases, including hypertension. This study aimed to investigate the long-term effect and underlying mechanisms of EA stimulation at the LI11 point on the hypertension and sympathetic nerve activity in two-kidney, one-clip (2K1C) hypertensive rats. EA (0.1–0.4 mA, 2 and 15 Hz) was applied to the acupoints LI11 overlying the deep radial nerve once a day for 6 weeks. The mean arterial pressure (MAP) and heart rate (HR) were determined by radiotelemetry, and the sympathetic nerve activity was evaluated by telemetric analyses of the low-frequency component of blood pressure (BP) and by plasma epinephrine and norepinephrine levels. The results showed 6 weeks of EA significantly lowered the increased BP effectively, inhibited the enhanced sympathetic nerve activities and attenuated cardiac hypertrophy in 2K1C hypertensive rats. The level of orexin receptor-1 (OX1R) in the rostral ventrolateral medulla (RVLM) after EA treatment was markedly reduced in 2K1C rats, while there was no difference in the RVLM expression of orexin receptor-2 (OX2R) in 2K1C and 2K1C+EA rats. Moreover, the increased pressor and depressor responses to microinjection of orexin A or OX1R antagonist SB408124 into the RVLM of 2K1C rats were significantly blunted by the EA treatment. These findings suggest that BP-lowering effect of EA on renovascular hypertension may be through inhibition of central sympathetic activities and modulation of functional orexin receptors in the RVLM

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C)) to the pathogenic one (PrP(Sc)). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants within the transmembrane region undergo an ER-stress mediated cell apoptosis

Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion

Intra-endolysosomal Ca(2+) release is required for endolysosomal membrane fusion with intracellular organelles. However, the molecular mechanisms for intra-endolysosomal Ca(2+) release and the downstream Ca(2+) targets involved in the fusion remain elusive. Previously, we demonstrated that endolysosomal P2X4 forms channels activated by luminal adenosine triphosphate in a pH-dependent manner. In this paper, we show that overexpression of P2X4, as well as increasing endolysosomal P2X4 activity by alkalinization of endolysosome lumen, promoted vacuole enlargement in cells and endolysosome fusion in a cell-free assay. These effects were prevented by inhibiting P2X4, expressing a dominant-negative P2X4 mutant, and disrupting the P2X4 gene. We further show that P2X4 and calmodulin (CaM) form a complex at endolysosomal membrane where P2X4 activation recruits CaM to promote fusion and vacuolation in a Ca(2+)-dependent fashion. Moreover, P2X4 activation-triggered fusion and vacuolation were suppressed by inhibiting CaM. Our data thus suggest a new molecular mechanism for endolysosomal membrane fusion involving P2X4-mediated endolysosomal Ca(2+) release and subsequent CaM activation

Advances in bioorganic molecules inspired degradation and surface modifications on Mg and its alloys

Mg alloys possess biodegradability, suitable mechanical properties, and biocompatibility, which make them possible to be used as biodegradable implants. However, the uncontrollable degradation of Mg alloys limits their general applications. In addition to the factors from the metallic materials themselves, like alloy compositions, heat treatment process and microstructure, some external factors, relating to the test/service environment, also affect the degradation rate of Mg alloys, such as inorganic salts, bioorganic small molecules, bioorganic macromolecules. The influence of bioorganic molecules on Mg corrosion and its protection has attracted more and more attentions. In this work, the cutting-edge advances in the influence of bioorganic molecules (i.e., protein, glucose, amino acids, vitamins and polypeptide) and their coupling effect on Mg degradation and the formation of protection coatings were reviewed. The research orientations of biomedical Mg alloys in exploring degradation mechanisms in vitro were proposed, and the impact of bioorganic molecules on the protective approaches were also explored