Novel c-Myc-Targeting Compound N, N-Bis (5-Ethyl-2-Hydroxybenzyl) Methylamine for Mediated c-Myc Ubiquitin-Proteasomal Degradation in Lung Cancer Cells.

Aberrant cellular Myc (c-Myc) is a common feature in the majority of human cancers and has been linked to oncogenic malignancies. Here, we developed a novel c-Myc-targeting compound, N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD), and present evidence demonstrating its effectiveness in targeting c-Myc for degradation in human lung carcinoma. EMD exhibited strong cytotoxicity toward various human lung cancer cell lines, as well as chemotherapeutic-resistant patient-derived lung cancer cells, through apoptosis induction in comparison with chemotherapeutic drugs. The IC50 of EMD against lung cancer cells was approximately 60 µM. Mechanistically, EMD eliminated c-Myc in the cells and initiated caspase-dependent apoptosis cascade. Cycloheximide chase assay revealed that EMD tended to shorten the half-life of c-Myc by approximately half. The cotreatment of EMD with the proteasome inhibitor MG132 reversed its c-Myc-targeting effect, suggesting the involvement of ubiquitin-mediated proteasomal degradation in the process. We further verified that EMD strongly induced the ubiquitination of c-Myc and promoted protein degradation. c-Myc inhibition and apoptosis induction were additionally shown in hematologic malignant K562 cells, indicating the generality of the observed EMD effects. Altogether, we identified EMD as a novel potent compound targeting oncogenic c-Myc that may offer new opportunities for lung cancer treatment. SIGNIFICANCE STATEMENT: The deregulation of c-Myc is frequently associated with cancer progression. This study examined the effect of a new compound, N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD), in targeting c-Myc in several lung cancer cell lines and drug-resistant primary lung cancer cells. EMD induced dramatic c-Myc degradation through a ubiquitin-proteasomal mechanism. The promising anticancer and c-Myc-targeted activities of EMD support its use in potential new approaches to treat c-Myc-driven cancer.

Ni-Fe Cocatalysts on Magnesium Silicate Supports for the Depolymerization of Kraft Lignin.

This research aimed to synthesize magnesium silicate (MgSiO3) used as a support for Ni-Fe cocatalysts in the depolymerization of kraft lignin. Magnesium silicate was prepared by a hydrothermal method, followed by metal solution impregnation to obtain lignin depolymerization catalysts. The catalytic efficiency of kraft lignin depolymerization to valued phenolic compounds was studied by varying the ratios of Ni and Fe on the MgSiO3 support. Moreover, other factors such as temperature, reaction time, and catalyst recycling affected both the quality and quantity of the products studied. The results illustrated that the catalyst 10Ni10Fe/MS produced all lignin depolymerization products with the highest yield (14.29 wt %) using reaction conditions of 300 °C and 1 h. In addition, the main products were found to be catechol (11.38 wt %), guaiacol (1.51 wt %), and phenol (0.79 wt %). More importantly, the 10Ni10Fe/MS catalyst showed good reusability even after two recycling processes, and the obtained phenol and guaiacol were found to be 0.63 and 1.01 wt %, respectively.

The effect of alkali and Ce(III) ions on the response properties of benzoxazine supramolecules prepared via molecular assembly.

A series of benzoxazine monomer supramolecules with different substituted groups on their benzene ring was prepared with a Mannich reaction and characterized by FTIR, 1H-NMR and MS. The obtained products were 3,4-dihydro-3-(2'-hydroxyethylene)-6-methyl-2H-benzoxazine (BM1), 3,4-dihydro-3-(2'-hydroxyethylene)-6-ethyl-2H-benz-oxazine (BM2), and 3,4-dihydro-3-(2'-hydroxyethylene)-6-methoxy-2H-benzoxazine (BM3). The efficiency of alkali metal ion extraction from the products was determined with Pedersen's technique, while the complexation of the Ce(III) ion was confirmed by the Job's and the mole ratio methods. The evidence of complex formation between benzoxazine monomers and Ce(III) ions was obtained with FTIR and a computational simulation. Single phase ceria (CeO2) as observed with XRD was successfully prepared by calcinating the Ce(III)-benzoxazine monomer complexes at 600 °C for 2 h. In addition, the geometry of the ceria nanoparticles confirmed by TEM is spherical, with an average diameter of 10-20 nm.

4,4'-Diethyl-2,2'-[(N-cyclo-hexyl-imino)-bis-(methyl-ene)]diphenol.

The title compound, C(24)H(33)NO(2), exhibits an intra-molecular hydrogen bond between a phenol -OH group and the N atom. In the crystal, mol-ecules are connected by pairs of O-H⋯O hydrogen bonds.

4,4'-Dimeth-oxy-2,2'-[methyl-aza-ne-diyl-bis(methyl-ene)]diphenol.

The title compound, C(17)H(21)NO(4), shows an intra-molecular hydrogen bond between a phenol OH group and the N atom. In the crystal, mol-ecules are connected by pairs of O-H⋯O hydrogen bonds into inversion dimers.

2-{[(2-Hy-droxy-3,5-dimethyl-benz-yl)(meth-yl)amino]-meth-yl}-4,6-dimethyl-phenol.

In the title compound, C(19)H(25)NO(2), the dihedral angle between the benzene rings is 53.15 (8)°. One of the -OH groups forms an intra-molecular O-H⋯N link, generating an S(6) ring. The other -OH group forms an inter-molecular O-H⋯N hydrogen bond in the crystal, generating centrosymmetric R(2) (2)(20) loops.

Hydroxyapatite coating on an aluminum/bioplastic scaffold for bone tissue engineering.

Three-dimensional printing can produce scaffolds with shapes and dimensions tailored for practical clinical applications. Enhanced osteoconductivity of such scaffolds is generally desired. Hydroxyapatite (HA) is an inorganic ceramic that can be used to coat such scaffolds and to accelerate healing during the bone restoration process. In this study, HA-coated aluminum/bioplastic scaffolds were fabricated, and their structural characteristics and osteoconductivity were evaluated. Aluminum/bioplastic scaffolds were fabricated by three-dimensional printing, and HA slurries with solids loadings of 10-20 vol% were used for coating. As solids loadings increased, the thickness of the coating layers slightly increased, whereas pore sizes decreased. The average compressive strength was comparable to that of cancellous bone. Potential osteoconductivity was tested by simulated body fluid immersion for 28 days, and the formation of the HA phase on the surface along with a weight increase indicates the potential bioactivity of the samples.

A Comprehensive Evaluation of Mechanical, Thermal, and Antibacterial Properties of PLA/ZnO Nanoflower Biocomposite Filaments for 3D Printing Application.

Functionalities of 3D printing filaments have gained much attention owing to their properties for various applications in the last few years. Innovative biocomposite 3D printing filaments based on polylactic acid (PLA) composited with ZnO nanoflowers at varying contents were successfully fabricated via a single-screw extrusion technique. The effects of the varying ZnO nanoflower contents on their chemical, thermal, mechanical, and antibacterial properties were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and tensile testing, as well as qualitative and quantitative antibacterial tests, respectively. It was found that the ZnO nanoflowers did not express any chemical reactions with the PLA chains. The degrees of the crystallinity of the PLA/ZnO biocomposite filaments increased when compared with those of the neat PLA, and their properties slightly decreased when increasing the ZnO nanoflower contents. Additionally, the tensile strength of the PLA/ZnO biocomposite filaments gradually decreased when increasing the ZnO nanoflower contents. The antibacterial activity especially increased when increasing the ZnO nanoflower contents. Additionally, these 3D printing filaments performed better against Gram-positive (S. aureus) than Gram-negative (E. coli). This is probably due to the difference in the cell walls of the bacterial strains. The results indicated that these 3D printing filaments could be utilized for 3D printing and applied to medical fields.

Novel recovery of nano-structured ceria (CeO(2)) from Ce(III)-benzoxazine dimer complexes via thermal decomposition.

N,N-bis(2-hydroxybenzyl)alkylamines, benzoxazine dimers, are the major product produced from benzoxazine monomers on mono-functional phenol by the one step ring opening reaction. Due to the metal responsive property of benzoxazine dimers, in this present work, N,N-bis(5-methyl-2-hydroxybenzyl)methylamine (MMD), N,N-bis (5-ethyl-2-hydroxybenzyl)methylamine (EMD), and N,N-bis(5-methoxy-2-hydroxybenzyl) methyl amine (MeMD), are considered as novel ligands for rare earth metal ion, such as cerium(III) ion. The complex formed when the clear and colorless solutions of cerium nitrate and benzoxazine dimers were mixed, results in a brown colored solution. The metal-ligand ratios determined by the molar ratio and the Job's methods were found to be in a ratio of 1:6. To clarify the evidence of the complex formation mechanism, the interactions among protons in benzoxazine dimers both prior to and after the formation of complexes were determined by means of (1)H-NMR, 2D-NMR and a computational simulation. The single phase ceria (CeO(2)) was successfully prepared by thermal decomposition of the Ce(III)-benzoxazine dimer complexes at 600 °C for 2 h, was then characterized using XRD. In addition, the ceria powder investigated by TEM is spherical with an average diameter of 20 nm.

Golden Glittering Biocomposite Fibers from Poly(lactic acid) and Nanosilver-Coated Titanium Dioxide with Unique Properties; Antimicrobial, Photocatalytic, and Ion-Sensing Properties.

Golden glittering biocomposite fibers from poly(lactic acid) (PLA) and nanosilver-coated titanium dioxide (Ag/TiO2) were successfully prepared via a melt spinning process. Various contents of 10% Ag/TiO2/PLA masterbatch were diluted with PLA in concentrations of 5, 10, 15, 20, 25, and 30 phr, respectively. The physical, mechanical, thermal, and antibacterial properties of the obtained fibers were investigated. The results indicated that the glittering biocomposite fiber had a light, yellow-gold color and a slightly rough surface. Tenacity and elongation at break of the glittering biocomposite fibers were lower than those of the pristine PLA fiber. The thermal properties of the glittering composite fibers also decreased with increasing masterbatch content. The PLA/PEG-10 biocomposite fiber with good spinnability and mechanical properties was suitably used for preparing the golden glittering composite fabric by the knitting process. Moreover, the golden glittering biocomposite fabrics exhibited antibacterial activity against certain microbes, for example, Staphylococcus aureus, Bacillus subtilis, and Candida albicans. The prepared fabric has significant potential for use in eco-friendly textile products and antibacterial fabrics. Besides, our novel textiles showed not only the photocatalytic property needed to degrade organic dyes such as methylene blue in water but also the ion-sensing property for mercury(II) ions by changing the textile color from yellow to colorless.

Structure and properties of in situ reactive blend of polylactide and thermoplastic starch.

In this study, in situ reactive extrusion of polylactide and thermoplastic starch modified with chloropropyl trimethoxysilane coupling agent (PLA/mTPS) is proposed. The success of covalent bond formation between PLA matrix and mTPS phase is clarified by two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy with 1H1H TOCSY mode. This chemically bound PLA with starch gives the remarkable compatibility in the PLA/mTPS film, with not only a decreased glass transition temperature (47 °C) but also an increased crystallinity of PLA (Χc of 50%). It consequently increases oxygen barrier significantly and also enhances the film flexibility as observed from the drastic increase of elongation at break (from 3% to 50%). Moreover, the PLA/mTPS 60/40 (w/w) film exhibits the accelerated degradation as compared with pure PLA film.

Titanium dioxide and fluoropolymer-based coating for smart fabrics with antimicrobial and water-repellent properties.

In the coronavirus disease 2019 pandemic, protective clothing is required for medical staff at risk of infection. This study proposes functional smart fabrics with antimicrobial and water-repellent properties, using titanium dioxide (TiO2) and fluoropolymer-based precursors as coating materials. Experimental results indicated a uniform distribution of TiO2 particles with an average size below 200 nm throughout the fabric. A zone of inhibition test revealed that the fabric inhibited bacterial growth, specifically of Staphylococcus aureus and Klebsiella pneumoniae, before and after 10 wash cycles of the fabric. In wetting angle measurements, the contact angles of water droplets on the fabric ranged from 120° to 139°. A water repellency test confirmed that the coated fabrics retained their water-repellent property after 10 wash cycles.

Crystal structure and Hirshfeld surface analysis of the product of the ring-opening reaction of a di-hydro-benzoxazine: 6,6'-[(cyclo-hexyl-aza-nedi-yl)bis-(methyl-ene)]bis-(2,4-di-methyl-phenol).

In the title unsymmetrical tertiary amine, C24H33NO2, which arose from the ring-opening reaction of a di-hydro-benzoxazine, two 2,4-di-methyl-phenol moieties are linked by a 6,6'-(cyclo-hexyl-aza-nedi-yl)-bis-(methyl-ene) bridge: the dihedral angle between the dimethyl-phenol rings is 72.45 (7)°. The cyclo-hexyl ring adopts a chair conformation with the exocyclic C-N bond in an equatorial orientation. One of the phenol OH groups forms an intra-molecular O-H⋯N hydrogen bond, generating an S(6) ring, and a short intra-molecular C-H⋯O contact is also present. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into C(10) chains propagating along the [100] direction. The Hirshfeld surface analysis of the title compound confirms the presence of these intra- and inter-molecular inter-actions. The corresponding fingerprint plots indicate that the most significant contacts in the crystal packing are H⋯H (76.4%), H⋯C/C⋯H (16.3%), and H⋯O/O⋯H (7.2%).

Synthesis and characterization of Ogataea thermomethanolica alcohol oxidase immobilized on barium ferrite magnetic microparticles.

Alcohol oxidase catalyzes the oxidation of primary alcohols into the corresponding aldehydes, making it a potential biocatalyst in the chemical industry. However, the high production cost and poor operational stability of this enzyme are limitations for industrial application. Immobilization of enzyme onto solid supports is a useful strategy for improving enzyme stability. In this work, alcohol oxidase from the thermotolerant methylotrophic yeast Ogataea thermomethanolica (OthAOX) was covalently immobilized onto barium ferrite (BaFe12O19) magnetic microparticles. Among different conditions tested, the highest immobilization efficiency of 71.0 % and catalytic activity of 34.6 U/g was obtained. Immobilization of OthAOX onto magnetic support was shown by Fourier-Transformed infrared microscopy, scanning electron microscopy and X-ray diffraction. The immobilized OthAOX worked optimally at 55 °C and pH 8.0. Immobilization also improved thermostability, in which >65% of the initial immobilized enzyme activity was retained after 24 h pre-incubation at 45 °C. The immobilized enzyme showed a greater catalytic efficiency for oxidation of methanol and ethanol than free enzyme. The immobilized enzyme could be recovered by magnetization and recycled for at least three consecutive batches, after which 70% activity remained. The properties of the immobilized enzyme suggest its potential industrial application for synthesis of aldehyde.