Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

Effect of microwave heating time on the gel properties of chicken myofibrillar proteins and their formation mechanism

The present work was conducted to illustrate the mechanism of gel formation of myofibrillar proteins (MPs) under different microwave heating times. The results showed that the denaturation enthalpy (ΔH) of the MPs significantly decreased when the heating time increased from 3 to 9 s and then completely disappeared as the heating time progressed, indicating that the MPs gradually denatured and subsequently aggregated with increasing heating time, which was further verified by the changes in the secondary structure, electrophoretic bands, and gel properties (e.g., water holding capacity and textural profiles) of the MPs. Microstructural images indicated that the MP gel formed under 12 s had the most compact network, indicating that extended microwave heating time could induce quality deterioration of MP gels. Moreover, the hydrophobic forces, electrostatic forces, and disulphide bonds of the MPs gradually intensified with increasing microwave heating time, suggesting that both non-covalent and covalent bonds could promote molecular denaturation and subsequent aggregation of MPs. In addition, correlation analysis revealed that the changes in the molecular conformation of MPs induced by different microwave heating times could effectively regulate the formation of MP gels and their related properties.     

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.     

Structural silicone sealants after exposure to laboratory test for durability assessment

During the service life of structural sealant glazing (SSG) facades, the load-bearing capacity of the silicone bonds needs to be guaranteed. Laboratory tests can assess the durability of SSG-systems based on mechanical characteristics of the bond after simultaneous exposure to both climatic and mechanical loads. This article studies how the material characteristics of two common structural sealants are affected by laboratory and field exposure. Dynamic mechanical analysis (DMA) confirms a reduction in the dynamic modulus of exposed silicone samples. Results from thermogravimetric analysis, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and small-angle X-ray scattering/wide-angle X-ray scattering show differences between the two sealants and indicate no/minor changes in the composition and morphology of the laboratory and field exposed sealants. Mechanical characterization methods, such as DMA, and tensile and shear testing of the structural bond, are shown to be sensitive toward the combined climatic and mechanical loadings, and are hence suitable for studying degradation mechanisms of structural sealants.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Influence of temperature on acoustic emission source location accuracy in underground structure

An acoustic emission (AE) experiment was carried out to explore the AE location accuracy influenced by temperature. A hollow hemispherical specimen was used to simulate common underground structures. In the process of heating with the flame, the pulse signal of constant frequency was stimulated as an AE source. Then AE signals received by each sensor were collected and used for comparing localization accuracy at different temperatures. Results show that location errors of AE keep the same phenomenon in the early and middle heating stages. In the later stage of heating, location errors of AE increase sharply due to the appearance of cracks. This provides some beneficial suggestions on decreasing location errors of structural cracks caused by temperature and improves the ability of underground structure disaster prevention and control.     

Theoretical estimation of dielectric loss of oxide glasses using nonequilibrium molecular dynamics simulations

To theoretically explore amorphous materials with a sufficiently low dielectric loss, which are essential for next-generation communication devices, the applicability of a nonequilibrium molecular dynamics simulation employing an external alternating electric field was examined using alkaline silicate glass models. In this method, the dielectric loss is directly evaluated as the phase shift of the dipole moment from the applied electric field. This method enabled us to evaluate the dielectric loss in a wide frequency range from 1 GHz to 10 THz. It was observed that the dielectric loss reaches its maximum at a few THz. The simulation method was found to qualitatively reproduce the effects of alkaline content and alkaline type on the dielectric loss. Furthermore, it reasonably reproduced the effect of mixed alkalines on the dielectric loss, which was observed in our experiments on sodium and/or potassium silicate glasses. Alkaline mixing was thus found to reduce the dielectric loss.     

Xanthohumol for Human Malignancies: Chemistry,Pharmacokinetics and Molecular Targets

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure–activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.