A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

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.     

Effects of Cooling Rate and Component on the Microstructure and Mechanical Properties of Mg–Zn–Y Alloys

The microstructure and mechanical properties of Mg–6Zn–1Y and Mg–6Zn–3Y(wt%) alloys under different cooling rates were investigated. The results show that the second dendrite arm spacing(SDAS) of Mg–6Zn–1Y and Mg–6Zn–3Y is reduced by 32 and 30% with increasing cooling rates(Rc) from 10.2 to 23 K/s, which can be predicted using a empirical model of SDAS=68 R 0:45:45cand SDAS=73 R 0c, respectively. The compressive strength of both alloys increases with increasing the cooling rate, which is attributed to the increase of volume fraction(Vf) of secondary phases under high cooling rate. The interaction of the cooling rate and component with SDAS has been theoretically analyzed using interdependence theory.     

Single-Crystalline TiO2(B) Nanobelts with Unusual Large Exposed {100} Facets and Enhanced Li-Storage Capacity

The {100} facet of single-crystalline TiO₂(B) is an ideal platform for inserting Li ions, but it is hard to be obtained due to its high surface energy. Here, the single-crystalline TiO₂(B) nanobelts from H₂Ti₃O₇ with nearly 70% {100} facets exposed are synthesized, which significantly enhances Li-storage capacity. The first-principle calculations demonstrate an ab in-plane 2D diffusion through the exposed {100} facets. As a consequence, the nanobelts can significantly accommodate Li ions in LiTiO₂ formula with specific capacity up to 335 mAh g⁻¹, which is in good agreement with the electrochemical characterizations. Coating with conductive and protective poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), the cut-off discharge voltage is as low as 0.5 V, leading to a capacity of 160.7 mAh g⁻¹ after 1500 cycles with a retention rate of 66% at 1C. This work provides a practical strategy to increase the Li-ion capacity and cycle stability by tailoring the crystal orientation and nanostructures.     

Improving weld formability by a novel dual-rotation bobbin tool friction stir welding

A novel dual-rotation bobbin tool friction stir welding (DBT-FSW) was developed, in which the upper shoulder (US) and lower shoulder (LS) have different rotational speeds. This process was tried to weld 3.2 mm thick aluminum-lithium alloy sheets. The metallographic analysis and torque measurement were carried out to characterize the weld formability. Experimental results show that compared to conventional bobbin tool friction stir welding, the DBT-FSW has an excellent process stability, and can produce the defect-free joints in a wider range of welding parameters. These can be attributed to the significant improvement of material flow caused by the formation of a staggered layer structure and the unbalanced force between the US and LS during the DBT-FSW process.     

Unsteady free convection of second‐grade nanofluid with a new time‐space fractional heat conduction

The Caputo and Caputo–Fabrizio derivative are applied to study a second‐grade nanofluid over a vertical plate. A comparative analysis is presented to study the unsteady free convection of a second‐grade nanofluid with a new time–space fractional heat conduction. The governing equations with mixed time–space fractional derivatives are non‐dimensionalized and solved numerically, and a comparison between the Caputo and the Caputo–Fabrizio models is made. It is found that the temperature is higher for the Caputo–Fabrizio fractional model than the Caputo model, but the higher velocity only exists near the vertical plate for the Caputo–Fabrizio model than the Caputo model. Moreover, the velocity for the Caputo model will exceed the Caputo–Fabrizio model as y evolves.     

Synthesis of amino-cosubstituted polyorganophosphazenes and fabrication of their nanoparticles for anticancer drug delivery

The development of safe drug carriers is cardinal in cancer therapy, which can target the cancer cells and release the loaded drug on-demand without damaging the healthy cells of the body. In our work, we synthesized three different biodegradable polymers, poly[(ethyl aminobezoate) (ethyl glycinato) phosphazenes] (PABGPs), in different mole ratio of side groups. The successful synthesis of these PABGPs was confirmed by ¹H NMR, ³¹P NMR, FT-IR, and gel permeation chromatography. These PABGPs were fabricated into drug (camptothecin, CPT, a hydrophobic anticancer drug) loaded nanoparticles. These drug-loaded nanoparticles showed good drug release behaviors under normal physiological conditions (pH 7.4 and temperature 37°C). These PABGPs-based nanoparticles may find their application as effective drug carriers for cancer therapy.