Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Re-evaluation of Radiation-Energy Transfer to an Extraction Solvent in a Minor-Actinide-Separation Process Based on Consideration of Radiation Permeability

ABSTRACT

Absorbed-dose estimation is essential for evaluation of the radiation tolerance of minor-actinide-separation processes. We propose a dose-evaluation method based on radiation permeability, with comparisons of heterogeneous structures seen in the solvent-extraction process, such as emulsions forming in the mixture of the organic and aqueous phases. A demonstration of radiation-energy-transfer simulation is performed with a focus on the minor-actinide-recovery process from high-level liquid waste with the aid of the Monte Carlo radiation-transport code PHITS. The simulation results indicate that the dose absorbed by the extraction solvent from alpha radiation depends upon the emulsion structure, and that from beta and gamma radiation depends upon the mixer-settler-apparatus size. Non-negligible contributions of well-permeable gamma rays were indicated in terms of the plant operation of the minor-actinide-separation process.     

Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors

C34, a 34-mer fragment peptide, is contained in the HIV-1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti-HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six-helix bundle formation by these C34 dimeric derivatives. Addition of a Gly-Cys(CH₂CONH₂)-Gly-Gly motif at the N-terminal position of a C34 monomeric derivative significantly increased the anti-HIV-1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV-1 fusion inhibitors.     

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree

Objectives: The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes.

Methods: First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10?kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation.

Results: Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors.

Conclusions: This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.     

Solvent free mechanochemical synthesis of MnO2 for the efficient degradation of Rhodamine-B

MnO₂ nanorods were synthesized by mechanochemical processing with subsequent heat treatment and their photocatalytic activity was studied on the decolourization of aqueous solution of Rhodamine B at different pH levels. A solid state redox reaction 2KMnO₄ + MnCl₂ → 3MnO₂ + 2KCl + O₂ was activated during mechanical milling. Excess KCl salt was added in the starting powder mixture to prevent agglomeration of MnO₂ nanoparticles. The milling resulted in the production of amorphous MnO₂ nanoparticles with a high surface area of 204 m² g^?1. Crystalline MnO₂ nanorods of diameters about 15–20 nm were produced by heating the as-milled powder at 350 °C for 1 h in air. Amorphous MnO₂ nanoparticles showed higher degradation rate of Rhodamine B than crystalline MnO₂ nanorods under simulated sunlight. The degradation rate was higher under acidic conditions. This work demonstrates the potential for cost effective, green and scalable synthesis of MnO₂ nano-catalysts for environmental applications.     

Mechanisms of orientational and photoelastic birefringence generation of methacrylates for the design of zero–zero‐birefringence polymers

The intrinsic birefringence Δn⁰ and photoelastic coefficient C of poly(methyl methacrylate), poly(2,2,2‐trifluroethyl methacrylate), poly(phenyl methacrylate), and poly(2,2,3,3,3‐pentafluorophenyl methacrylate) were determined. We categorized these methacrylate polymers into four birefringence‐types, even though their molecular structures differed only by the substituents on the side chains. Based on the results of Δn⁰ and C, novel polymers that exhibit neither orientational nor photoelastic birefringence, i.e., zero–zero‐birefringence polymers, were designed and synthesized by quaternary copolymerization system. Furthermore, we confirmed that the mechanisms of orientational birefringence and photoelastic birefringence generation were different in these methacrylate polymers. The conformation of the repeat unit of the polymers was nearly constant during the generation of orientational birefringence. In contrast, the conformation of the repeat unit of the polymers changed during the generation of photoelastic birefringence in the glassy state. These findings demonstrated the reasonability of evaluating orientational and photoelastic birefringence separately, as well as the adequacy of the classification of polymers into four birefringence‐types. Given these results and the fact that zero–zero‐birefringence polymers could be prepared successfully by four‐birefringence type monomers, we demonstrated the reasonability of the method for designing the zero–zero‐birefringence polymers. POLYM. ENG. SCI., 55:1330–1338, 2015. © 2015 Society of Plastics Engineers     

An efficient manufacturing method for I-shaped cross-sectional CFRP beam with arbitrary arrangement of carbon fiber using electro-activated resin molding

Abstract

The I-shaped cross-sectional beam of CFRP (CFRP I-beam) is usually manufactured by the continuous protrusion method. Carbon fibers can only be arranged in the longitudinal direction. The CFRP I-beam with arbitrary arrangement of carbon fiber was manufactured with applying the electro-activated deposition molding method. The carbon fiber fabric was immersed in the deposition solution and energized, epoxy resin precipitated around carbon fiber and impregnated. The resin-impregnated fabric was installed to the mold, and the CFRP I-beam was fabricated. The CFRP I-beam was subjected to three-point bending tests, and the relationship between load-deflection was simulated by finite-element analysis.     

Direct Growth of Germanene at Interfaces between Van der Waals Materials and Ag(111)

Germanene, a 2D honeycomb germanium crystal, is grown at graphene/Ag(111) and hexagonal boron nitride (h-BN)/Ag(111) interfaces by segregating germanium atoms. A simple annealing process in N₂ or H₂/Ar at ambient pressure leads to the formation of germanene, indicating that an ultrahigh-vacuum condition is not necessary. The grown germanene is stable in air and uniform over the entire area covered with a van der Waals (vdW) material. As an important finding, it is necessary to use a vdW material as a cap layer for the present germanene growth method since the use of an Al₂O₃ cap layer results in no germanene formation. The present study also proves that Raman spectroscopy in air is a powerful tool for characterizing germanene at the interfaces, which is concluded by multiple analyses including first-principles density functional theory calculations. The direct growth of h-BN-capped germanene on Ag(111), which is demonstrated in the present study, is considered to be a promising technique for the fabrication of future germanene-based electronic devices.     

Interface control for resolved CFD-DEM with capillary interactions

In this work, a resolved CFD–DEM coupling model for the simulation of gas-liquid-solid flows is developed: the interface capturing method based on the colour function is employed for fluids (i.e. a gas and liquid) whilst Discrete Element Method (DEM) is used for particles. The Volume Penalisation (VP) method is adopted to consider the hydrodynamic interactions between fluids and particles along with the Immersed Free Surface (IFS) method, which artificially extends the gas-liquid interface into the interior of the particle to account for the wettability. The unique point of the proposed model is that the thickness of the gas-liquid interface can be controlled by using both interface compression and diffuse interface techniques simultaneously. From the simulation results, it is presented that the accurate evaluation of the surface tension force as well as the capillary force can be achieved by appropriately controlling the interface thickness. Moreover, the major two methods in the literature to calculate the capillary force are compared in this work. The validity of the proposed model is presented for both static and dynamic cases. The behaviour of two colliding particles with a dynamic liquid bridge is then simulated to demonstrate the applicability of the proposed model to a complex three-phase system.