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In Alzheimer's disease (AD), several studies have reported blood-brain barrier (BBB) breakdown with compromised function. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are transport proteins localized at the BBB luminal membrane and play an important role in the clearance of amyloid-β (Aβ). The purpose of this study was to investigate the effect of pharmacological inhibition of Aβ efflux transporters on BBB function and Aβ accumulation and related pathology. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that modulate the integrity of a cell-based BBB model, which identified elacridar as a disruptor of the monolayer integrity. Elacridar, an investigational compound known for its P-gp and BCRP inhibitory effect and widely used in cancer research. Therefore, it was used as a model compound for further evaluation in a mouse model of AD, namely TgSwDI. TgSwDI mouse is also used as a model for cerebral amyloid angiopathy (CAA). Results showed that P-gp and BCRP inhibition by elacridar disrupted the BBB integrity as measured by increased IgG extravasation and reduced expression of tight junction proteins, increased amyloid deposition due to P-gp, and BCRP downregulation and receptor for advanced glycation end products (RAGE) upregulation, increased CAA and astrogliosis. Further studies revealed the effect was mediated by activation of NF-κB pathway. In conclusion, results suggest that BBB disruption by inhibiting P-gp and BCRP exacerbates AD pathology in a mouse model of AD, and indicate that therapeutic drugs that inhibit P-gp and BCRP could increase the risk for AD.The Nash equilibrium plays a crucial role in game theory. Most of results are based on classical resources. Our goal in this paper is to explore multipartite zero-sum game with quantum settings. We find that in two different settings there is no strategy for a tripartite classical game being fair. Interestingly, this is resolved by providing dynamic zero-sum quantum games using single quantum state. https://www.selleckchem.com/products/nx-1607.html Moreover, the gains of some players may be changed dynamically in terms of the committed state. Both quantum games are robust against the preparation noise and measurement errors.Mitochondrial homeostasis refers to the balance of mitochondrial number and quality in a cell. It is maintained by mitochondrial biogenesis, mitochondrial fusion/fission, and the clearance of unwanted/damaged mitochondria. Mitophagy represents a selective form of autophagy by sequestration of the potentially harmful mitochondrial materials into a double-membrane autophagosome, thus preventing the release of death inducers, which can trigger programmed cell death (PCD). Recent advances have also unveiled a close interconnection between mitophagy and mitochondrial dynamics, as well as PCD in both mammalian and plant cells. In this review, we will summarize and discuss recent findings on the interplay between mitophagy and mitochondrial dynamics, with a focus on the molecular evidence for mitophagy crosstalk with mitochondrial dynamics and PCD.The main objective of the present study was to evaluate the antioxidant capacity of hydroxytyrosol derived from synthetic (HTs) and organic (HTo) sources, and citrus (C) extract, by incorporating them in a dry-cured meat product fuet. Firstly, antioxidant extracts were tested in an oxidized pork meat model system, avoiding by 100% the protein oxidation against AAPH and AMVN. After that, four batches of fuet were made, namely Control, HTs, HTo, and C, which incorporated antioxidant extracts as substitutes of synthetic additives. A hundred-day shelf-life study was carried out. The incorporation of phenolic extracts neither affected proximal composition, nor ripening process (airing losses, aw, and pH), nor color development. However, the incorporation of HT increased Fe, Mn, and Si mineral content. At the same time, HT extracts inhibited lipid and protein oxidation and microbiological growth by 50%. Regarding sensory analysis, HTo was the most unpalatable (extract flavor apparition), while HTs and C samples were equally accepted as the Control sample. In addition, HT fuet samples showed two-fold higher antioxidant activity and total phenolic content than the Control sample. In conclusion, the use of HTs in dry-cured sausages was demonstrated to be the best option to the development of clean label meat products, with promising antioxidant properties and the best standards of quality and acceptability.The modern food system is seeing a change in consumption patterns provoked by several drivers-including ethical, health, and environmental concerns-that are increasing the sales of meat analog foods. This change is accompanied by increased research and development activities in the area of plant-based meats. The aim of the present review is to describe methods that are being employed by scientists to analyze and characterize the properties of meat alternatives and to propose standardized methods that could be utilized in the future. In particular, methods to determine the proximate composition, microstructure, appearance, textural properties, water-holding properties, cooking resilience, and sensory attributes, of plant-based meat are given. The principles behind these methods are presented, their utility is critically assessed, and practical examples will be discussed. This article will help to guide further studies and to choose appropriate methods to assess raw materials, processes, products, and consumption behavior of meat analogs.The selective paste intrusion (SPI) describes a selective binding, additive manufacturing method. SPI bonds thin layers of aggregate by cement paste locally. Currently, SPI can achieve higher compressive strength, durability, and easier unpacking behavior compared to other selective binding methods suitable for the production of concrete structures. Particle-bed based methods not only achieve much higher surface resolutions than depositing (extrusion)-based additive manufacturing methods but also have no restrictions in freedom of form. However, the mechanical performance of SPI components strongly depends on the void content between the individual layers and thus the penetration behavior of the cement paste. This paper presents direction-dependent measurements of the strength and durability of SPI-printed components compared to casted specimens with the same mixing composition. The results show compressive strength values between 70 and 78 MPa after 7 d, flexural strength of 1/10 without reinforcement, a high freeze-thaw resistance, no detectable carbonation after 182 days of exposure under ambient CO2-conditions, and after 28 days under increased CO2 content of 2 vol % as well as low chloride penetration resistances.
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