Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers

Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (¹⁵QKLVFF²⁰, ¹⁶KLVFF²⁰, ¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and ¹⁵QKLV¹⁸), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides ¹⁷LVFF²⁰, NA-¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and NA-¹⁶KLVF¹⁹ (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-¹⁶KLVF¹⁹ possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of ¹⁶KLVF¹⁹. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-¹⁶KLVF¹⁹ may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective.     

Increase of regression speed of combustion through oxidizer doping

This paper presents an innovative method to increase the regression speed of a solid fuel grain by using oxidizer doping. The results obtained on a propulsion application showing the performance parameters as an output of a numerical model are provided. Two models are given that predict the regression speed increase for embedding wires and for oxidizer doping with a factor of ～2 to 3. Also, it is shown that this increase of the regression speed by using a low oxidizer doping percentage, which is based on the assumption that at a higher doping rate the combustion instabilities, can lead to detonations. Next, a thermochemical model for the combustion within the oxidizer doping model is afforded. For this model, the burn is assumed to take place around the surface of each of the oxidizer particles, being composed of two different burning processes: one is the burning on the surface of the solid fuel grain and the other is the burning between the solid fuel and the solid oxidizer. For a non-doped fuel grain, the burning takes place only on the surface of the fuel grain. Finally, a potential application of such propulsion units to small satellite launchers is presented, and a case study of such a vehicle intended to place a 50 kg payload on a low earth orbit (300 to 500 km altitude) is described. The modelling proposed is based on the assumption that the use of solid methane makes this launcher environmentally friendly.     

Functional cyclodextrins. 1. Chloroacetylated cyclodextrins

The paper discusses the synthesis of the chloroacetylated derivatives of α-, β- and γ-cyclodextrins. These novel functionalized products can be used both in the synthesis of some conjugates with bioactive substances by covalent bonding and/or for inclusion of hydrophobic compounds.     

Scattering in a Spin-Charge Separated Non-Fermi Liquid

The electron self-energy due to the scattering on nonmagnetic impurities in a spin-charge separated non-Fermi liquid is calculated. The frequency dependence of the inverse scattering time is proportional to , for the case when the anomalous parameter = 0, and to ¹⁺ for 0. The scattering time is cutoff dependent when the anomalous parameter is nonzero.     

Effect of aqueous comonomer solubility on the surfactant-free emulsion copolymerization of methyl methacrylate

Surfactant-free emulsion copolymerization was used to prepare methyl methacrylate-hydroxyethyl methacrylate (MMA-HEA) and methyl methacrylate-hydroxypropyl methacrylate (MMA-HPMA) latex particles. Also, glycidyl methacrylate (GMA) was grafted onto the surface of the preformed MMA-HPMA latex particles by seeded surfactant-free emulsion copolymerization. The copolymerization reactions were conducted at 75 °C using a water-soluble initiator, potassium persulfate (KPS). The morphologies of copolymer latex particles were observed using Scanning electron microscopy (SEM). The influence of different reactions parameters (the MMA saturation concentration (Sr), the KPS concentration and the aqueous solubility of the comonomers (HEA or HPMA)) on the particles average diameter and particles size dispersity was investigated. The experimental results showed that the increase of initiator concentration induces in all investigated cases the increase of particles average diameter, while the presence of HEA or HPMA as comonomers in the copolymerization reaction of MMA (1,000% Sr) lead to a decrease of particles average diameter. At small KPS concentration the latex is monodisperse, the increase of the initiator concentration leading to the formation of polydisperse latex. In the case of grafting reaction of GMA onto the monodisperse preformed MMA-HEA latex particles, although the average diameter of the final particles doubles the latex remains quasi-monodisperse.     

New multifunctional textile biomaterials for the treatment of leg venous insufficiency

Acryloyl monomers have been synthesized by reaction of β-cyclodextrin and troxerutin with acryloyl chloride and grafted on a knitted material obtained from polyamide 6.6 and polyurethane fibers. Polyamide grafted with β-cyclodextrin derivative binds troxerutin as a physical complex. The obtained biomaterials have been tested in vivo on rats for their ability to deliver troxerutin (a flebotonic drug) to different skin areas (epidermis, dermis and vascular wall). The results showed that the new synthesized materials can act as multifunctional bioactive textiles that can display both compression (given by the textile material) and sustained venotonic and haemostatic properties (given by the troxerutin delivered from biomaterial to the skin).     

Bacterial Cellulose Hybrid Composites with Calcium Phosphate for Bone Tissue Regeneration

Bacterial cellulose (BC) is a unique microbial biopolymer with a huge number of significant applications in the biomedical field, including bone tissue engineering. The present study proposes to obtain and characterize BC hybrid composites with calcium phosphate as biocompatible and bioactive membranes for bone tissue engineering. BC precursor membranes were obtained in static culture fermentation, and after purification, were oxidized to obtain 2,3-dialdehyde bacterial cellulose (DABC). Calcium phosphate-BC oxidized membranes were produced by successive immersion in precursor solutions under ultrasonic irradiation. The samples were characterized for their physicochemical properties using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy grazing incidence X-ray diffraction (GI-XRD), solid-state ¹³C nuclear magnetic resonance (CP/MAS ¹³C NMR), and complex thermal analysis. In vitro cell studies were also performed to evaluate the influence of modified morphological characteristics on cell adhesion and proliferation. The results showed an increase in porosity and biodegradability for DABC hybrid composites compared with BC. In vitro cell studies have revealed that both hybrid composites favor cell adhesion to the surface. The new BC and DABC hybrid composites with calcium phosphate could be considered promising materials for bone tissue regeneration.     

Bacterial cellulose–assisted synthesis of glass-ceramic scaffolds with TiO2 crystalline domains

Glass-ceramic 3D porous structures were obtained by from a polymeric template, which was successively loaded with calcium phosphates, by chemical reaction and a dried gel based on barium and titanium by physical attachment. The resulting composite was subjected to a freeze-drying procedure in order to maintain the spongy morphology. Under the effect of the subsequent thermal treatment at temperatures above 1000°C, the biocellulose membrane was completely removed, the mineral phases combined with each other through intense diffusion processes, and the mineral scaffolds acquired enough mechanical strength to become self-sustained. The as-prepared and thermally treated samples were characterized from physicochemical and biological point of view. The only crystalline phase emerged in the final masses was TiO₂, while the microstructure was individualized as peculiar 3D architectures with porous and branched appearance. All prepared materials were proven to be biocompatible with the mesenchymal stem cells, showing no cytotoxic effect and suitability for the field of tissue engineering.