To gain insight into factors that lead to dissociation of Bax from a complex with Hsp70 during apoptosis, we recently constructed a fluorescence resonance energy transfer (FRET) system composed of ...the Hsp70‐YFP (YFP=yellow fluorescent protein) fusion protein and fluorescent amino acid (ANAP=6‐acetyl(naphthalen‐2‐ylamino)‐2‐aminopropanoic acid)‐containing Bax (Bax‐ANAP), which was produced by using the genetic code expansion technique. In the current study, the FRET system was employed to elucidate how brefeldin A (an endoplasmic reticulum stress inducer), chlorpromazine and apoptozole (lysosomal membrane destabilizers), bafilomycin A1 (an inhibitor of lysosomal acidification) as well as raptinal and Az‐TPP‐O3 (mitochondria‐targeted apoptosis inducers) affect the interaction between Bax and Hsp70. Analyses of single live cell images together with results of co‐immunoprecipitation assays reveal that brefeldin A, chlorpromazine, and apoptozole promote dissociation of the Bax/Hsp70 complex through activation of the activator BH3‐only protein. However, the results show that bafilomycin A1, raptinal, and Az‐TPP‐O3 have no influence on the interaction of Bax with Hsp70. The combined observations made in the current and previous studies demonstrate that the FRET system consisting of Bax‐ANAP and Hsp70‐YFP is highly useful to understand apoptotic processes associated with the Bax–Hsp70 interaction.
Understanding interactions: To elucidate how organelle‐targeting substances affect the Bax–Hsp70 interaction, a FRET system of Hsp70‐YFP and ANAP‐Bax was employed. Our results reveal that brefeldin A, chlorpromazine and apoptozole promote dissociation of the Bax/Hsp70 complex but bafilomycin A1, raptinal and Az‐TPP‐O3 have no influence on the interaction of Bax with Hsp70.
Tumor necrosis factor receptor-associated factor (TRAF) proteins are key signaling molecules that function in various cellular signaling events including immune response, cell death and survival, ...development, and thrombosis. Their roles in cellular signaling are mediated mostly by direct interactions with various receptors via the TRAF domain. To determine how specific TRAF domains can interact with various receptors with a limited binding interface and how similar binding interfaces of TRAF family members can recognize their specific binding partners, extensive structural studies on TRAF family proteins have been conducted for several decades. In this review, we discuss the current understanding of the structural and molecular diversity of the TRAF domain and TRAF-binding motifs in many receptors according to available structural information.
The Fourth Industrial Revolution is coming, and it is changing almost all aspects of human life, including the culture of quality and quality management (QM) in industry. This paper first examines ...the essence of the Fourth Industrial Revolution and its impact on our lives. Next, new concepts of quality as well as QM are discussed as follows. First, we analyse the multiway flow of QM in the stages of plan - design - production - marketing - sales, and data-oriented multiway interactions for creating new value and quality are discussed. Second, four distinctive approaches are introduced for implementing the multiway flow in real-world applications. The four approaches, which utilise Big Data, Artificial Intelligence (AI), Internet of Things (IoT), and more, are composite dimension, team creativity, total inspection, and new valuation. Finally, we argue for the necessity of combining quality experts with data scientists to prepare well for the coming Fourth Industrial Revolution.
Herein we report the first small molecule that disrupts the survivin-Smac interaction taking place in mitochondria. The inhibitor, PZ-6-QN, was identified by initially screening a phenothiazine ...library using a fluorescence anisotropy assay and then conducting a structure-activity relationship study. Mutagenesis and molecular docking studies suggest that PZ-6-QN binds to survivin similarly to the known Smac peptide, AVPI. The results of the effort also show that PZ-6-QN exhibits good anticancer activity against various cancer cells. Moreover, cell-based mechanistic studies provide evidence for the proposal that PZ-6-QN enters mitochondria to inhibit the survivin-Smac interaction and promotes release of Smac and cytochrome c from mitochondria into the cytosol, a process that induces apoptosis in cancer cells. Overall, the present study suggests that PZ-6-QN can serve as a novel chemical probe for study of processes associated with the mitochondrial survivin-Smac interaction and it will aid the discovery of novel anticancer agents.
Metal cations and anions are essential for versatile physiological processes. Dysregulation of specific ion levels in living organisms is known to have an adverse effect on normal biological events. ...Owing to the pathophysiological significance of ions, sensitive and selective methods to detect these species in biological systems are in high demand. Because they can be used in methods for precise and quantitative analysis of ions, organic dye-based ratiometric fluorescent probes have been extensively explored in recent years. In this review, recent advances (2015-2019) made in the development and biological applications of synthetic ratiometric fluorescent probes are described. Particular emphasis is given to organic dye-based ratiometric fluorescent probes that are designed to detect biologically important and relevant ions in cells and living organisms. Also, the fundamental principles associated with the design of ratiometric fluorescent probes and perspectives about how to expand their biological applications are discussed.
Synthetic ratiometric fluorescent probes are useful to detect metal cations and anions.
The printability of materials used in extrusion based 3D printing is one of the most important properties especially when fabricating objects with architectural complexities. However, this parameter ...is influenced by several factors (temperature, components, and additives) which makes thorough evaluation and classification challenging. In this study, the printability of food-ink for 3D food printing applications was evaluated by systematically adapting evaluation techniques such as dimensional stability test, handling properties assessment, and shear rheology test using edible hydrocolloid as reference materials. Methylcellulose (MC) was selected as a suitable reference material for its capability to simulate the printability of various types of food applications. In dimensional stability test, the concentrations of reference hydrocolloid mixture that could fabricate structures with height of 20, 40, and 80 mm without significant collapse were 9%, 11%, and 13%, respectively. The deformation behavior and handling properties of printed foods were classified based on the reference material produced at various concentrations (5%–20%). Shear modulus of all samples were in complete agreement with simulation results based on the dimensional stability test indicating that the printability of foods can be predicted and classified by comparing its properties to reference material. The newly established classification system of printability was categorized into grades A, B, C, and D according to the dimensional stability and degree of handling. The validity of this classification system was verified by 3D-printing tests.
•Hydrocolloids was used as a reference material to simulate the printability of various types of food applications.•The deformation behavior and handling properties of selected food were classified based on the reference material.•A printability classification system was established based on the capability in dimensional stability and degree of handling.
Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In ...addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue‐adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA‐catechol (HA‐CA) hydrogel via oxidative crosslinking. HA‐CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose‐derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA‐CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA‐CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA‐CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue‐adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.
Bioinspired, catechol‐modified hyaluronic acid (HA) hydrogel is highly biocompatible and exhibits improved tissue adhesiveness in comparison to HA hydrogel crosslinked via photopolymerization. Tissue adhesive catechol‐modified HA hydrogel can mediate highly effective, minimally invasive cell therapy in defected models such as liver resection and myocardial infarction.
We aim to examine the effects of a newly developed peptide derived from CPNE7 (Cpne7-DP) in tertiary dentin formation and peritubular space occlusion, and comprehensively evaluate its potential as a ...bioactive therapeutic agent. Human dental pulp cells (HDPCs) and a mouse pre-odontoblast cell line, MDPC-23, were chosen for in vitro studies to characterize lineage-specific cell responses after Cpne7-DP treatment. Whether Cpne7-DP reproduces the dentin regenerative potential of CPNE7 was tested using a beagle dog model by generating dentinal defects of various degrees in vivo. Peritubular space occlusion was further examined by scanning electron microscopy and microleakage test, while overall mineralization capacity of Cpne7-DP was tested ex vivo. CPNE7 promotes tubular dentin formation under both shallow and deep dentinal defects, and the functional peptide Cpne7-DP induces odontoblast-like differentiation in vitro, mineralization ex vivo, and tubular dentin formation in in vivo beagle dog dentin exposure and pulp exposure models. Moreover, Cpne7-DP leads to peritubular space occlusion and maintains stability under different conditions. We show that CPNE7 and its derivative functional peptide Cpne7-DP promotes dentin regeneration in dentinal defects of various degrees and that the regenerated hard tissue demonstrates the characteristics of true dentin. Limitations of the current dental materials including post-operative hypersensitivity make biological repair of dentin a field of growing interest. Here, we suggest that the dual functions of Cpne7-DP in tubular dentin formation and peritubular space occlusion are promising for the treatment of dentinal loss and sensitivity.
Streaming media platform opens new ways for celebrity endorsement. Based on the researches related to celebrity endorsement and match-up hypothesis, this study explores the influences of various ...matches on the consumer attitudes within the context of live streaming shopping with internet celebrities in China. Results suggest that product-source fit affects the perceived source attractiveness and trustworthiness, while product-content fit affects utilitarian and hedonic attitude toward the content. Source trustworthiness, hedonic attitude and self-product fit increased the intention to buy. This study develops and tests an integrative model of internet celebrity endorsement by investigating congruence effects on live streaming viewers.
Summary
This report presents the synthesis of MnO2/Co3O4 with N and S co‐doped graphene oxide (GO) hybrid composite by hydrothermal route for supercapacitor and photosensor applications. MnO2/Co3O4 ...nanoflakes and nanoparticles were directly grown on dual N and S doped GO sheets, where doping was achieved using a single reagent thiourea in one‐pot synthesis. Individual Co3O4 and MnO2 electrodes have poor reversibility and cycling properties due to electrolytic instability and low electrical conductivities. However, the hybrid provides good catalytic properties, and combined with highly conducting two‐dimensional GO it can reduce mismatching properties due to high conductivity and layered structure. The incorporated composite sheet‐like structure provides good mechanical strength with high conductivity, permitting easy ion penetration into the electrode, and providing considerably more active surfaces. Thus, the proposed hybrid material delivers significantly improved performance for supercapacitor and/or photosensor applications, achieving 614 F.g−1 specific capacitance at 1 Ag−1, and exceeding 95% retention up to 10 000 cycles. This composite material also shows good photosensing with 1 order of increased current under visible light.
Hydrothermally synthesized MnO2/Co3O4@N, S co‐doped GO hybrid composite is studied for energy storage and photosensing applications. Dual N and S doping has been achieved using single reagent thiourea. This synthesized composite showed 614 F.g−1 specific capacitance at 1 A.g−1 with above 95% retention up to 10000 cycles. Good photosensing with one order of current increase under visible light has been obtained.
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