Tangeretin Ameliorates Glucose-Induced Podocyte Injury through Blocking Epithelial to Mesenchymal Transition Caused by Oxidative Stress and Hypoxia

Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy (DN). The underlying mechanisms of podocyte injury facilitate finding of new therapeutic targets for DN treatment and prevention. Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties. This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia. Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1–20 μM tangeretin for up to 6 days. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks. Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes. However, the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes. Further, tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation. The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in diabetic mouse glomeruli. However, oral administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenes junction proteins. Glucose enhanced ROS production and HIF-1α induction in podocytes, leading to induction of oxidative stress and hypoxia. Similarly, in diabetic glomeruli reactive oxygen species (ROS) production and HIF-1α induction were observed. Furthermore, hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition (EMT) process and loss of slit diaphragm proteins and junction proteins in podocytes, which was inhibited by treating submicromolar tangeretin. Collectively, these results demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia.     

Distributed learning consensus control based on neural networks for heterogeneous nonlinear multiagent systems

This paper considers a novel distributed iterative learning consensus control algorithm based on neural networks for the control of heterogeneous nonlinear multiagent systems. The system's unknown nonlinear function is approximated by suitable neural networks; the approximation error is countered by a robust term in the control. Two types of control algorithms, both of which utilize distributed learning laws, are provided to achieve consensus. In the provided control algorithms, the desired reference is considered to be an unknown factor and then estimated using the associated learning laws. The consensus convergence is proven by the composite energy function method. A numerical simulation is ultimately presented to demonstrate the efficacy of the proposed control schemes.     

The Emi2 Protein of Saccharomyces cerevisiae is a Hexokinase Expressed under Glucose Limitation

Hexokinases catalyze glucose phosphorylation at the first step in glycolysis in eukaryotes. In the budding yeast Saccharomyces cerevisiae , three enzymes for glucose phosphorylation have long been known: Hxk1, Hxk2, and Glk1. In this study, we focus on Emi2, a previously uncharacterized hexokinase-like protein of S. cerevisiae . Our data show that the recombinant Emi2 protein (rEmi2), expressed in Escherichia coli , possesses glucose-phosphorylating activity in the presence of ATP and Mg ²⁺ . It was also found that rEmi2 phosphorylates not only glucose but also fructose, mannose and glucosamine in vitro . In addition, we examined changes in the level of endogenous Emi2 protein in S. cerevisiae in the presence or absence of glucose and a non-fermentable carbon source. We found that the expression of Emi2 protein is tightly suppressed during proliferation in high glucose, while it is strongly upregulated in response to glucose limitation and the presence of a non-fermentable carbon source. Our data suggest that the expression of the endogenous Emi2 protein in S. cerevisiae is regulated under the control of Hxk2 in response to glucose availability in the environment.     

Design and Fabrication of Concentration‐Gradient Generators with Two and Three Inlets in Microfluidic Chips

A simple and low‐cost method for designing and fabricating concentration‐gradient generators with two and three inlets is proposed which can generate different concentration gradients at varying flow velocities. The microchannel structure was designed in S‐shape and left‐right symmetry. The concentration‐gradient generator was simulated based on the finite element method. The microchannels were processed on a computer numerical control (CNC) engraving and milling machine on poly(methylmethacrylate) substrate, and then two concentration‐gradient generators were fabricated by hot bonding technology. The results of experiment and simulation were compared to prove the feasibility of the method. Flow velocity was an important factor for generating different concentration gradients. The concentration‐gradient profiles of the generators with two and three inlets present approximately linear and quadratic curves.     

Al2O3/Yttria‐Stabilized Zirconia Hollow‐Fiber Membrane Incorporated with Iron Oxide for Pb(II) Removal

Removal by absorptive ceramic membranes can simultaneously absorb and separate metal ions from water. Alumina/yttria‐stabilized zirconia (Al₂O₃/YSZ) hollow‐fiber membranes, fabricated using phase inversion and sintering process, were deposited with iron oxide by an in‐situ hydrothermal process. The results showed that α‐Fe₂O₃ was produced and incorporated across the membranes. A reduction in flux was recorded with the deposition of α‐Fe₂O_3. However, it improved the adsorption capacity for heavy metal adsorption. The adsorption‐separation test demonstrated that the optimized membrane is able to completely remove Pb(II) ions after two hours.     

Systematic convergence of nonlinear stochastic estimators on the Special Orthogonal Group SO(3)

This paper introduces two novel nonlinear stochastic attitude estimators developed on the Special Orthogonal Group with the tracking error of the normalized Euclidean distance meeting predefined transient and steady‐state characteristics. The tracking error is confined to initially start within a predetermined large set such that the transient performance is guaranteed to obey dynamically reducing boundaries and decrease smoothly and asymptotically to the origin in probability from almost any initial condition. The proposed estimators produce accurate attitude estimates with remarkable convergence properties using measurements obtained from low‐cost inertial measurement units. The estimators proposed in continuous form are complemented by their discrete versions for the implementation purposes. The simulation results illustrate the effectiveness and robustness of the proposed estimators against uncertain measurements and large initialization error, whether in continuous or discrete form.