Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters–ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.     

Mass spectrometry and the cellular surfaceome

The collection of exposed plasma membrane proteins, collectively termed the surfaceome, is involved in multiple vital cellular processes, such as the communication of cells with their surroundings and the regulation of transport across the lipid bilayer. The surfaceome also plays key roles in the immune system by recognizing and presenting antigens, with its possible malfunctioning linked to disease. Surface proteins have long been explored as potential cell markers, disease biomarkers, and therapeutic drug targets. Despite its importance, a detailed study of the surfaceome continues to pose major challenges for mass spectrometry-driven proteomics due to the inherent biophysical characteristics of surface proteins. Their inefficient extraction from hydrophobic membranes to an aqueous medium and their lower abundance compared to intracellular proteins hamper the analysis of surface proteins, which are therefore usually underrepresented in proteomic datasets. To tackle such problems, several innovative analytical methodologies have been developed. This review aims at providing an extensive overview of the different methods for surfaceome analysis, with respective considerations for downstream mass spectrometry-based proteomics.     

Iterative inflow-implicit outflow-explicit finite volume scheme for level-set equations on polyhedron meshes

In this paper, we propose a cell-centered finite volume method for advective and normal flows on polyhedron meshes which is second-order accurate in space and time for smooth solutions. In order to overcome a time restriction caused by CFL condition, an implicit time discretization of inflow fluxes and an explicit time discretization of outflow fluxes are used in an iterative procedure. For an efficient computation, an 1-ring face neighborhood structure is introduced. Since it is limited to access unknown variables in an 1-ring face neighborhood structure, an iterative procedure is proposed to resolve the limitation of assembled linear system. Two types of gradient approximations, an inflow-based gradient and an average-based gradient, are studied and compared from the point of numerical accuracy. Numerical schemes are tested for an advective and a normal flow of level-set functions illustrating a behavior of the proposed method for an implicit tracking of a smooth and a piecewise smooth interface.     

Limit load and failure mechanisms of soda lime glass foam

Foamed glass is widely used in the industry as an insulating material. However, its mechanical properties are not well-investigated yet. Foamed glass is produced from glass waste that causes discrepancy in mechanical properties of the final product. This paper shows a way to increase the limit of the load capacity of foamed glass, which is very fragile and sensitive to mechanical and thermal loading conditions. In this paper, three different methods of load application on cellular glass structure (rough contact, resin and flour interfaces) and their influence on failure mechanisms were investigated in detail. The results of numerical analyses, based on finite elements method and compression strength tests using the digital image correlation method, indicate that the overall strength of the material is limited by boundary effects. A careful adjustment of the interface property is the main factor to draw useful conclusions and to extend load limits of cellular glass in engineering applications.     

The Role of the Mizar Mathematical Library for Interactive Proof Development in Mizar

The Mizar system is one of the pioneering systems aimed at supporting mathematical proof development on a computer that have laid the groundwork for and eventually have evolved into modern interactive proof assistants. We claim that an important milestone in the development of these systems was the creation of organized libraries accumulating all previously available formalized knowledge in such a way that new works could effectively re-use all previously collected notions. In the case of Mizar, the turning point of its development was the decision to start building the Mizar Mathematical Library as a centrally-managed knowledge base maintained together with the formalization language and the verification system. In this paper we show the process of forming this library, the evolution of its design principles, and also present some data showing its current use with the modern version of the Mizar proof checker, but also as a rich corpus of semantically linked mathematical data in various areas including web-based and natural language proof presentation, maths education, and machine learning based automated theorem proving.     

Crystallization of 2D Hybrid Organic–Inorganic Perovskites Templated by Conductive Substrates

2D hybrid organic–inorganic perovskites are valued in optoelectronic applications for their tunable bandgap and excellent moisture and irradiation stability. These properties stem from both the chemical composition and crystallinity of the layer formed. Defects in the lattice, impurities, and crystal grain boundaries generally introduce trap states and surface energy pinning, limiting the ultimate performance of the perovskite; hence, an in-depth understanding of the crystallization process is indispensable. Here, a kinetic and thermodynamic study of 2D perovskite layer crystallization on transparent conductive substrates are provided—fluorine-doped tin oxide and graphene. Due to markedly different surface structure and chemistry, the two substrates interact differently with the perovskite layer. A time-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) is used to monitor the crystallization on the two substrates. Molecular dynamics simulations are employed to explain the experimental data and to rationalize the perovskite layer formation. The findings assist substrate selection based on the required film morphology, revealing the structural dynamics during the crystallization process, thus helping to tackle the technological challenges of structure formation of 2D perovskites for optoelectronic devices.