Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aß Aggregation Activity through Molecular Docking-Based Virtual Screening.

Discovery of novel multifunctional inhibitors targeting acetylcholinesterase (AChE) has becoming a hot spot in anti-Alzheimer's disease (AD) drug development. In the present study, four potent small molecule inhibitors (A01, A02, A03 and A04) of AChE with new chemical scaffold were identified. Inhibitor A03 displayed the most potent inhibition activity on AChE at enzymatic level with IC50 value of 180 nM, and high selectivity towards AChE over butyrylcholinesterase (BChE) by more than 100-fold. The binding modes of compounds A01-A04 were carefully analyzed by molecular docking and molecular dynamics (MD) simulation to provide informative clues for further structure modification. Finally, the anti-amyloid beta (Aß) aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment.

Syndioselective Polymerization of Vinylnaphthalene.

Coordination polymerizations of 1-vinylnaphthalene (1VN), 2-vinylnaphthalene (2VN) and 6-methoxy-2-vinylnaphthalene (MVN) are carried out at room temperature by using the half-sandwich scandium precursor FluSiMe3 Sc(CH2 SiMe3 )2 (THF) (1) and the constrained geometry configuration rare-earth metal precursors FluCH2 PyLn(CH2 SiMe3 )2 (THF)n [Flu = C13 H8 , Py = C5 H4 N; Ln = Sc (2a), n = 0; Ln = Lu (2b), Y(2c), n = 1]. Atactic poly(1VN) and perfect syndiotactic poly(2VN) and poly(MVN) are produced by precursors 2a-2c in a controlled way. Treatment of poly(MVN) with boron tribromide at -20 °C provides a syndiotactic poly(6-hydroxy-2-vinylnaphthalene).

Flame-Retardant and Transparent Unsaturated Polyester Based on P/N Liquid Flame Retardants and Modified Halloysite Nanotubes.

Unsaturated polyester resin (UPR) with excellent flame retardant is mainly obtained by adding large amounts of flame retardants, usually at the expense of mechanical properties. In this work, a reactive flame retardant containing phosphorus and nitrogen (DOPO-N) was successfully synthesized and incorporated in UPR as a crosslinker. The mechanical and flame-retardant properties of UPR composites were enhanced. UPR/30DOPO-N passed a UL-94 V-1 rating with a limiting oxygen index (LOI) of 30.8%. The tensile strength of UPR/30DOPO-N increased by 24.4%. On this basis, a small amount of modified HNTs (VHNTs) was added to further improve the flame-retardant properties of the composite. With the introduction of 3 wt% VHNTs, the composite passed the UL-94 V-0 rating. The peak of heat release rate (PHRR) and total heat release (THR) of it decreased by 60.7% and 48.3%, respectively. Moreover, the detailed flame-retarding mechanism of DOPO-N and VHNTs was investigated by thermogravimetric infrared spectroscopy (TG-IR), Raman spectra, and X-ray photoelectron spectroscopy (XPS). It was found that DOPO-N played a role in quenching the flame in the gas phase and cooperated with VHNTs to enhance the barrier effect in the condensed phase.

A New Phosphorous/Nitrogen-Containing Flame-Retardant Film with High Adhesion for Jute Fiber Composites.

In this work, a novel P/N flame-retardant monomer (PDHAA) was synthesized through reacting phenyl dichlorophosphate (PDCP) with N-hydroxyethyl acrylamide (HEAA). The structure of PDHAA was confirmed using Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (NMR) spectroscopy. PDHAA monomer and 2-hydroxyethyl methacrylate phosphate (PM-2) monomer were mixed at different mass ratios, to prepare UV-curable coatings, and then applied to the surface of fiber needled felts (FNFs), to improve their flame retardancy. PM-2 was introduced to reduce the curing time of the flame-retardant coatings and improve the adhesion between the coating and the fiber needled felts (FNFs). The research results indicated that the surface flame-retardant FNFs had a high limiting oxygen index (LOI) and rapidly self-extinguished in a horizontal combustion test and passed a UL-94 V-0 test. At the same time, the CO and CO2 emissions were greatly reduced, and the carbon residue rate was increased. In addition, the introduction of the coating improved the mechanical properties of the FNFs. Therefore, this simple and efficient UV-curable surface flame-retardant strategy has broad application prospects in the field of fire protection.

Preparation of carbon black/silicone rubber composites with large-area-homogeneous-low electrical-resistance used as electroplating matrix.

Conductive carbon black (CCB) is an important filler in stretchable conductive silicone rubber (CSR) composites. However, due to the active oxygen-containing groups on CCB, introducing it into silicone rubber (SR) may cause SR to not completely cure. Surface modification of CCB may ease the problem but at the cost of reducing the electrical conductivity of pristine CCB. In this work, the curing and crosslinking performance of CCB/SR is detected in detail, the hydroxyl groups (-OH) carried by CCB can react with the silicon-hydrogen group (Si-H) with the existence of Pt catalyst, causing insufficiency of the hydrosilylation reaction thus hindering the solidifying process of silicon rubber. To take advantage of this reaction, more hydrogen silicone oil (PHMS) possessing silicon-hydrogen bonds is introduced into the system to improve the curing degree as well as fix the CCB in the crosslinked network. Due to the lock-in effect of CCB, the resistance of CSR samples is stable after several hundred bending cycles, and the composite's tensile strength is three times that of the pure SR samples. Besides, the size of the composites can expand to dozens of centimeters or even a few meters with uniform electric conductivity. This composite has resistance as low as 10.20 Ω and is suitable to make electroplating mold, and a rapid plating rate of 2.4 mm/24 h can be achieved. Meanwhile, the overall properties make this CSR composite have potential applications in mold manufacture, flexible electronics, and other related fields.

A Highly Effective, UV-Curable, Intumescent, Flame-Retardant Coating Containing Phosphorus, Nitrogen, and Sulfur, Based on Thiol-Ene Click Reaction.

In this paper, a flame-retardant, UV-cured coating was prepared on the fiber composites' (FC) surface via a thiol-ene click reaction using pentaerythritol tetra(3-mercaptopropionate) (PETMP), triallyl cyanurate (TAC), and 2-hydroxyethyl methacrylate phosphate (PM-2). The synergistic effectiveness of phosphorus (P), nitrogen (N), and sulfur (S) was studied in detail by changing the proportion of these reactants. Sample S4(N3P2)6, with a molar ratio of N and P elements of 3:2, and the thiol and vinyl groups of 4:6 had the highest LOI value (28.6%) and was self-extinguishing in the horizontal combustion test. It had the lowest peak heat release rate (PHRR) value (279.25 kW/m2) and total smoke production (2.18 m2). Moreover, the thermogravimetric analysis (TG) showed that the decomposition process of the coated composites was delayed. The conversion rate of the double bond and the thiol of S4(N3P2)6 was 100% and 92.0%, respectively, which showed that the cross-linked network structure was successfully formed. The tensile strength and the flexural strength of coated composites improved, and the transparency of the coating can reach 90%. These characteristics showed that the UV-cured coatings could be used in industrial production to effectively prevent fires.

Synthesis of a grape-like conductive carbon black/Ag hybrid as the conductive filler for soft silicone rubber.

Conductive silicone rubber (CSR) is an outstanding stretchable conductive composite due to its excellent mechanical properties and stable conductivity. In this paper, silver nanoparticles were deposited on carbon black (CB) through a reduction reaction. The uniform dispersion of silver particles on the surface of CB as well as the grape-like branch structure of hybrid particles was formed by the condensation reaction of the hydroxyl groups of CB with (3-mercaptopropyl) trimethoxysilane (KH-590), along with the interattraction between sulfhydryl groups of KH-590 and silver ions. This sulfhydryl modified conductive carbon black/Ag hybrid filler (SMCB@Ag) avoided the high processing viscosity of CSR caused by the hydroxyl groups of CB. The percolation threshold of CSR made from SMCB@Ag was 5.5 wt% according to the percolation equation. With the addition amount of SMCB@Ag increasing to 10 wt%, the conductivity of CSR increased from 10-5 to about 101. Moreover, the conductivity of this CSR showed excellent stability with extension of storage time and increase of stretching-recovery cycles.

Protective effect of polysaccharide from Sophora japonica L. flower buds against UVB radiation in a human keratinocyte cell line (HaCaT cells).

Natured botanical extract has attracted considerable attention recently in the field of skin anti-ultraviolet (UV) radiation. As a medicinal herb, Sophora japonica flower buds contained several components such as flavonoids, isoflavonoids, triterpenes, alkaloids and polysaccharides, which have multiple pharmacological properties except hemostatic agents which have been used in China and Korea for centuries. The purpose of our study was to investigate whether polysaccharide extracted from Sophora japonica L. flower buds (PS) was able to attenuate UVB-induced damage using a human keratinocyte cell line (HaCaT cells). HaCaT cells were pretreated with PS in a serum-free medium for 2 h and then irradiated with different doses of UVB rays. The results showed that the PS attenuated UVB-induced cytotoxicity which was verified by MTT method and morphology feature assay. UVB exposure (30-120 mJ/cm2) reduced HaCaT cells viability significantly following with the increased irradiation dose 24 h later, while pretreatment with PS (0.25-2.0 mg/mL) attenuated UVB-induced cytotoxicity significantly and increased cell viability in a dose-dependent manner except 30 mJ/cm2 group. The PS reduced the ROS generation, down-regulated the expression of phosphor-JNK and phosphor-p38 MAPK proteins significantly through MAPK pathway in UVB-irradiated HaCaT cells. It also decreased the apoptosis rate at low dose of UVB ray and protected the cells from apoptosis which had been identified by the down-regulated level of active-caspase3 in UVB-irradiated HaCaT cells. In conclusion, PS pretreatment protected HaCaT keratinocytes from UVB irradiation-induced skin injuries effectively, and the underlying mechanism may involve MAPK signaling pathway which contribute to apoptotic cell death. However, further studies especially whose using human systems are needed to determine efficacy of PS in vivo.

Hydrothermal Synthesis of Cellulose-Derived Carbon Nanospheres from Corn Straw as Anode Materials for Lithium ion Batteries.

As a most attractive renewable resource, biomass has the advantages of low pollution, wide distribution and abundant resources, promoting its applications in lithium ion batteries (LIBs). Herein, cellulose-derived carbon nanospheres (CCS) were successfully synthesized by hydrothermal carbonization (HTC) from corn straw for use as an anode in LIBs. The uniform distribution and cross-linked structure of carbon nanospheres were obtained by carefully controlling reaction time, which could not only decrease the transport pathway of lithium ions, but also reduce the structural damage caused by the intercalation of lithium ions. Especially, obtained after hydrothermal carbonization for 36 h, those typical characteristics make it deliver excellent cycling stability as well as the notable specific capacity of 577 mA h g-1 after 100 cycles at 0.2C. Hence, this efficient and environment-friendly method for the fabrication of CCS from corn straw could realize the secondary utilization of biomass waste, as well as serve as a new choice for LIBs anode materials.

Biomimetic Growth of Hydroxyapatite on Electrospun CA/PVP Core⁻Shell Nanofiber Membranes.

In this study, cellulose acetate (CA)/polyvinylpyrrolidone (PVP) core⁻shell nanofibers were successfully fabricated by electrospinning their homogeneous blending solution. Uniform and cylindrical nanofibers were obtained when the PVP content increased from 0 to 2 wt %. Because of the concentration gradient associated with the solvent volatilization, the composite fibers flattened when the PVP increased to 5 wt %. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) results confirmed the existence of a hydrogen bond between the CA and PVP molecules, which enhanced the thermodynamic properties of the CA/PVP nanofibers, as shown by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) results. To analyze the interior structure of the CA/PVP fibers, the water-soluble PVP was selectively removed by immersing the fiber membranes in deionized water. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that the PVP component, which has a low surface tension, was driven to the exterior of the fiber to form a discontinuous phase, whereas the high-content CA component inclined to form the internal continuous phase, thereby generating a core⁻shell structure. After the water-treatment, the CA/PVP composite fibers provided more favorable conditions for mineral crystal deposition and growth. Energy-dispersive spectroscopy (EDS) and FTIR proved that the crystal was hydroxyapatite (HAP) and that the calcium to phosphorus ratio was 1.47, which was close to the theoretical value of 1.67 in HAP. Such nanofiber membranes could be potentially applicable in bone tissue engineering.

Improved thermal properties of epoxy resin modified with polymethyl methacrylate-microencapsulated phosphorus-nitrogen-containing flame retardant.

Epoxy resin (EP) composites with improved thermal resistance were fabricated. To solve the problem of low thermal resistance derived from phosphazene flame-retardant additives, we designed a system based on flame-retardant microcapsules P(H), with hexaphenoxycyclotriphosphazene as the core and polymethyl methacrylate as the shell. The core-shell structure was characterized and confirmed. The thermal resistance of the cured EP composites containing 1 wt% P(H) microcapsules was improved because of the increased glass transition temperatures. The P(2.75H)/EP composites can reach a limited oxygen index of 30.5% and V-1 rating in UL-94 tests. Heat and gas release rates were reduced during combustion tests. Residual images implied that the P(H) microcapsules may promote the formation of a flame-retardant char layer. Pyrolysis analysis demonstrated that the P(H) microcapsules can decompose in two procedures to produce flame-retardant gas components. Therefore, the flame-retardant mechanism involved the flame inhibition effect in the gas phase, and the charring effect in the condensed phase.

Metabolizable lanthanum-coordination nanoparticles as efficient radiosensitizers for solid tumor therapy.

The clinical potential of radiotherapy cannot be realised as expected due to the inherent radioresistance of tumors. To overcome these problems, radiosensitizers containing heavy metal elements have been used in radiotherapy as efficient radiation dose enhancers. In the present study, we report the design and preparation of novel lanthanum-coordination nanoparticles, and their application as nano-sized radiosensitizers in radiotherapy against solid tumors. Via a simple one-pot hydrothermal route, these nanoparticles were fabricated without any expensive chemical reagents. The polyvinylpyrrolidone molecules used in a typical synthesis could highly enhance the dispersity and bio-compatibility of these nanoparticles. In vitro toxicity studies demonstrated that these nanoparticles had low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. Upon exposure to high energy X-ray radiation, these nanoparticles possessed excellent radiosensitization effects and induced serious cellular death both in vitro and in vivo. In addition, time-dependent bio-distribution and long-term toxicity results for these nanoparticles after intravenous administration indicated their high bio-compatibility. More importantly, these metabolizable nanoparticles could be cleared up after intravenous administration along with time passing. These significant findings promise the prospective use of these nanoparticles as vigorous X-ray radiation-mediated therapeutic agents in coming cancer treatments.

Metabolites from Aspergillus versicolor, an endolichenic fungus from the lichen Lobaria retigera.

Three new anthraquinone derivatives (1-3) and one new artifact (4) were isolated, along with six known anthraquinone derivatives (5-10) and three xanthones (11-13), from a culture of an endolichenic fungus, Aspergillus versicolor, that was isolated from the lichen Lobaria retigera. The structures of these substances were determined on the basis of 1D and 2D (COSY, HMQC, and HMBC) NMR and MS analyses. The substances 1-4 were also tested for their cytotoxic activity.