From Stem Cells to Bone-Forming Cells

Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. In this review, we briefly define the cellular identity and function of osteoblasts and discuss the main populations of osteoprogenitor cells identified to date. We also provide examples of long-known and recently recognized regulatory pathways and mechanisms involved in the specification of the osteogenic lineage, as assessed by studies on mice models and human genetic skeletal diseases.     

The use of recycled low-density polyethylene films from protective prepreg for the development of nanocomposites with bentonite clay

Prepreg is a pre-impregnated composite fiber where a thermoset polymer matrix material is present. Before being used, these materials are kept at low temperatures and have a low-density polyethylene (LDPE) film for your protection. The increase in the use of structural composites based on prepregs causes an increase in the amount of protective LDPE film. This material is usually discarded or incinerated and can cause great damage to the environment. Thus, the present work aimed to study the feasibility of recycling up to 100% of protective LDPE (rLDPE) to develop blends-based nanocomposites with rLDPE/virgin LDPE (60/40, 70/30, 80/20, 90/10 and 100/0) with the addition of 5 wt% of compatibilizer agent (maleic anhydride grafted LDPE, LDPE-g-MA), and 1 wt% of bentonite (BNT) using a co-rotational twin-screw extruder, followed by hot pressing in a hydropneumatic press and die-cutting. Water absorption test, thermal aging resistance, morphological characterization by scanning electron microscopy, mechanical properties by Izod impact strength and tensile tests, and differential scanning calorimetry were performed. By the results, it was possible to verify the viability of 100% of the recycling of rLDPE. The results showed a good distribution of 1 wt% of BNT in the matrix, better mechanical properties when compared with virgin LDPE. Furthermore, the thermal properties, water absorption test, and thermal aging resistance showed no statistical differences between the samples. These results confirm the effectiveness and the environmental gain in the use of the recycled material.     

甲烷市场化合作计划——煤矿煤层气项目开发的机遇

煤矿煤层气的排放是全球甲烷排放的一个重要来源，“甲烷市场化合作计划”的发起是为了识别并开发相关的工程项目，减少煤矿、垃圾填埋场和石油天然气系统等各领域中的甲烷排放。煤矿煤层气项目是“甲烷市场化合作计划”的三个核心领域之一，对推动煤炭行业的甲烷减排发挥重要作用。     

Vitamin E acetate addition to poly(d,l)lactic acid modifies its mechanical behavior without affecting biocompatibility

Mechanical properties of poly(d,l )lactic acid films enriched with Vitamin E and Vitamin E Acetate (5–40% w/w) were investigated. The addition of both formulations resulted in increased polymer Young's modulus and tensile strength. Human foreskin fibroblasts and murine pre‐osteoblasts were used to assess the biocompatibility of polymers. Pre‐osteoblasts adhesion and proliferation were strongly decreased by Vitamin E, whereas Vitamin E Acetate did not alter cell proliferation. Collagen deposition was lower onto Vitamin E blended polymers than onto native and Vitamin E Acetate blended ones. Fibroblasts adhesion and proliferation were increased by both Vitamin E and Vitamin E Acetate addition. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39970.     

Discovery of 5′′‐Chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064): A Selective Orexin 2 Receptor Antagonist (2‐SORA) for the Treatment of Insomnia

The field of small‐molecule orexin antagonist research has evolved rapidly in the last 15 years from the discovery of the orexin peptides to clinical proof‐of‐concept for the treatment of insomnia. Clinical programs have focused on the development of antagonists that reversibly block the action of endogenous peptides at both the orexin 1 and orexin 2 receptors (OX₁R and OX₂R), termed dual orexin receptor antagonists (DORAs), affording late‐stage development candidates including Merck’s suvorexant (new drug application filed 2012). Full characterization of the pharmacology associated with antagonism of either OX₁R or OX₂R alone has been hampered by the dearth of suitable subtype‐selective, orally bioavailable ligands. Herein, we report the development of a selective orexin 2 antagonist (2‐SORA) series to afford a potent, orally bioavailable 2‐SORA ligand. Several challenging medicinal chemistry issues were identified and overcome during the development of these 2,5‐disubstituted nicotinamides, including reversible CYP inhibition, physiochemical properties, P‐glycoprotein efflux and bioactivation. This article highlights structural modifications the team utilized to drive compound design, as well as in vivo characterization of our 2‐SORA clinical candidate, 5′′‐chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064), in mouse, rat, dog, and rhesus sleep models.     

Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous T_helper peptide, and a TLR2 (Pam₃CysSK₄) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam₃CysSK₄‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam₃CysSK₄, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 .     

Morphological segmenting and neighborhood pixel-based locality preserving projection on brain fMRI dataset for semantic feature extraction: an affective computing study

Two specific chemical receptive fields of brain, namely the amygdala and the orbital-frontal cortex, are related to valence and arousal in medical experiments. Functional magnetic resonance imaging (fMRI), which is a noninvasive, repeatable, and atomical tool for medical imaging in clinic system, was widely used in affective computing; however, it faces its dataset processing difficulty for dimensional reduction as well as for decreasing the computational complexity. In addition, features extraction from those de-dimensionality datasets is a challenging issue. The current work solved the de-dimensionality issue by using some preprocessing algorithms including clustering, morphological segmenting, and locality preserving projection. In order to keep useful information in fMRI dataset for reduction process, improved neighborhood pixel-based locality preserving projection (NP-LPP) algorithm was addressed and continuously for feature extraction operating using Otsu weighted sum of histogram. Furthermore, a modified covariance power spectral density (MC-PSD) separately in an fMRI Valence–Arousal experiments was measured. The results were analyzed and compared with affective norms English words system. The experiments established that the proposed methods of NP-LPP effectively simplified high complexity of fMRI, and Otsu weighted sum of histogram exhibited superior performance for features extraction compared to the MC-PSD through the calculation root mean standard error. The current proposed method provided a potential application and promising research direction on human semantic retrieval through medical imaging dataset.