Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

M2M energy saving strategy in 5G millimeter wave system

Telecommunication Systems - Machine to Machine technology has a broad application prospect in the 5G network, but there is a bottleneck in the energy consumption of intelligent devices powered by...     

Highly oriented α-Al2O3 transparent ceramics shaped by shear force

Alumina platelets were arranged horizontally in submicron alumina particles by shear force in the flow of slurries during casting. The obtained alumina green bodies with platelets were pressureless-sintered in vacuum, producing ceramics with thoroughly oriented grains and high transmittance. The effects of sintering parameters on the densification, microstructure evolution, and orientation degree of alumina ceramics were investigated and discussed. The results showed that the densification, grain size, orientation degree, and in-line transmittance were increased with increasing sintering temperature. The enhancement of orientation degree was mainly coherent with grain growth. The grain-oriented samples exhibited a much higher in-line transmittance (at 600 nm) of 61 % than that of the grain random sample (29 %). Moreover, the transmission remained a high level in the ultraviolet range (<300 nm).     

Effect of nitriding atmosphere on the morphology of AlN nanofibers from solution blow spinning

High purity AlN fiber is a promising thermal conductive material. In this work, AlN fibers were prepared using solution blow spinning followed by nitridation under N₂ or NH₃ atmosphere. Soluble polymer, such as polyaluminoxane, and allyl-functional novolac resin were adopted as raw materials to form homogeneous distribution of Al₂O₃ and C nanoparticles within the fibers, which could inhibit the growth of alumina crystal and promote their nitridation process. The effect of nitriding atmosphere on the fiber morphology was investigated. XRD results showed that complete nitridation was achieved at 1300 °C in the NH₃ or at 1500 °C in the N₂ atmosphere. Hollowed fiber structure was observed when fiber was nitrided in N₂ at high temperature, which was caused by gaseous Al gas diffusion, and this phenomenon was eliminated in NH₃ atmosphere. The nitridation mechanisms in different atmosphere were analyzed in detail. It was demonstrated that the nitridation of Al₂O₃ fibers in the NH₃ atmosphere offered the favored AlN morphology and chemical quality. Flexible AlN fiber with O content of 0.7 wt% was achieved after nitriding in NH₃ at 1400 °C. The high quality AlN can be used in thermal conductive composite materials.     

Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory,Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair

Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials.     

Influence of CO2 inleakage on the slight-alkalization of generator internal cooling water

The slight-alkalization of generator internal cooling water (GICW) is widely used to inhibit the corrosion of hollow copper conductor and thereby ensure the safe operation of the generator. CO₂ inleakage is increasingly identified as a potential security risk for GICW system. In this paper, the influence of CO₂ inleakage on the slight-alkalization of GICW was theoretically discussed. Based on the equilibriums of the CO₂-NaOH-H₂O system, CO₂ inleakage saturation was derived to quantify the amount of the dissolved CO₂ in GICW. This parameter can be directly calculated with the measured conductivity and the [Na⁺] of GICW. The influence of CO₂ inleakage on the slight-alkalization conditioning of GICW and the measurement of its water quality parameters were then analyzed. The more severe the inleakage, the narrower the water quality operation ranges of GICW, resulting in the more difficult the slight-alkalization conditioning of GICW. The temperature calibrations of the conductivity and the pH value of GICW show non-linear correlations with the amount of CO₂ inleakage and the NaOH dosage. This study provides insights into the influence of CO₂ inleakage on the slight-alkalization of GICW, which can serve as the theoretical basis for the actual slight-alkalization when CO₂ inleakage occurs.