Z -number is the general representation of real-life information with reliability, and it has adequate description power from the point of view of human perception. This study develops an innovative ...method for addressing multicriteria group decision-making (MCGDM) problems with Z -numbers under the condition that the weight information is completely unknown. Processing Z -numbers requires effective support of reliable tools. Then, the normal cloud model can be employed to analyze the Z -number construct. First, the potential information involved in Z -numbers is invoked, and a novel concept of normal Z + -value is proposed with the aid of the normal cloud model. The operations, distance measurement, and power aggregation operators of normal Z + -values are defined. Moreover, an MCGDM method is developed by incorporating the defined distance measurement and power aggregation operators into the MultiObjective Optimization by Ratio Analysis plus the Full Multiplicative Form. Finally, an illustrative example concerning air pollution potential evaluation is provided to demonstrate the proposed method. Its feasibility and validity are further verified by a sensitivity analysis and comparison with other existing methods.
Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a ...key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex.
Abstract
Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved ...cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.
The mechanism of phagophore closure remains unclear due to technical limitations in distinguishing unclosed and closed autophagosomal membranes. Here, we report the HaloTag-LC3 autophagosome ...completion assay that specifically detects phagophores, nascent autophagosomes, and mature autophagic structures. Using this assay, we identify the endosomal sorting complexes required for transport (ESCRT)-III component CHMP2A as a critical regulator of phagophore closure. During autophagy, CHMP2A translocates to the phagophore and regulates the separation of the inner and outer autophagosomal membranes to form double-membrane autophagosomes. Consistently, inhibition of the AAA-ATPase VPS4 activity impairs autophagosome completion. The ESCRT-mediated membrane abscission appears to be a critical step in forming functional autolysosomes by preventing mislocalization of lysosome-associated membrane glycoprotein 1 to the inner autophagosomal membrane. Collectively, our work reveals a function for the ESCRT machinery in the final step of autophagosome formation and provides a useful tool for quantitative analysis of autophagosome biogenesis and maturation.
Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg
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Facet development during platinum nanocube growth Liao, Hong-Gang; Zherebetskyy, Danylo; Xin, Huolin ...
Science (American Association for the Advancement of Science),
08/2014, Letnik:
345, Številka:
6199
Journal Article
Recenzirano
An understanding of how facets of a nanocrystal develop is critical for controlling nanocrystal shape and designing novel functional materials. However, the atomic pathways of nanocrystal facet ...development are mostly unknown because of the lack of direct observation. We report the imaging of platinum nanocube growth in a liquid cell using transmission electron microscopy with high spatial and temporal resolution. The growth rates of all low index facets are similar until the {100} facets stop growth. The continuous growth of the rest facets leads to a nanocube. Our calculation shows that the much lower ligand mobility on the {100} facets is responsible for the arresting of {100} growing facets. These findings shed light on nanocrystal shape-control mechanisms and future design of nanomaterials.
Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy ...are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to “switch” autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to address how sphingolipids mediate the “switch” between the cell survival and cell death. As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid-modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk between apoptosis and autophagy may be critical for enhancing the chemotherapeutic efficacy of these agents.
The high‐voltage induced undesirable surface passivation bilayer (cathode/electrolyte interface and cation‐densified surface phase) of LiCoO2 inevitably leads to battery degradation. Herein, a ...continual/uniform enamel‐like olivine layer on LiCoO2 surface is fabricated by employing a high‐speed mechanical fusion method . The enamel‐like layer suppresses interfacial side reactions by tuning EC dehydrogenation, contributing to an ultrathin and stable cathode/electrolyte interface. The strong bonding affinity between LiCoO2 and enamel‐like layer restrains both lattice oxygen loss and associated layered‐to‐spinel structural distortion. Moreover, the thermal stability of highly delithiated LiCoO2 is improved, as both the onset temperatures of layered‐to‐spinel transition and O2 evolution are simultaneously postponed. Stable operation of LiCoO2 at 4.6 V high‐voltage and 55 °C elevated temperature (both >85% capacity retention after 200 cycles) is achieved. This facile and scalable high‐speed solid‐phase coating strategy establishes a technical paradigm to enhance surface/interface stability of high‐energy‐density cathode candidates by constructing an ideal enamel‐like surface layer.
A high‐speed solid‐state coating method using mechanical fusion to fabricate an LiFe0.4Mn0.6PO4 olivine enamel‐like layer on lithium cobalt oxide is proposed. The coating contributes to fabricating thin/stable cathode–electrolyte interphase from outside‐in and restraining surface Co3O4 formation from inside‐out, preventing block of Li+ diffusion and over‐consumption of active Li. It is believed that this facile/scalable method can establish a technical criterion for multifarious surface‐modified electrode candidates.
•This study introduces PLTSs to summarize numerous online review information in a statistical manner.•A cloud model is employed to deal with probabilistic linguistic information.•PLTSs are converted ...and a novel concept of probability linguistic integrated cloud is proposed.•Two information fusion tools are presented to fuse substantial information.•An applicable hotel decision support model is developed for tourists.
Hotel selection on tourism websites has been a prevailing trend in traveling in recent years, and selecting a suitable hotel is a high-risk decision for millions of tourists because of the intrinsic imperceptibility of the provided products. Decision support models for hotel selection have drawn the interest of numerous scholars. The problem is that some existing models cannot address substantial amounts of online information, and they neglect the influence of interrelationships among different criteria on tourists’ decisions. To cover these defects, an applicable hotel decision support model is developed for tourists utilizing online reviews on TripAdvisor.com. Considering a great deal of review information associated with hotels posted by numerous tourists on TripAdvisor.com, probabilistic linguistic term sets (PLTSs) are introduced to summarize this information statistically. Processing qualitative concepts requires effective support of reliable tools; then, a cloud model can be employed to deal with probabilistic linguistic information. First, PLTSs are converted, and a novel concept of probabilistic linguistic integrated cloud (PLIC) is proposed. Moreover, the essential algorithms and distance measure of PLICs are defined. Two information fusion tools are subsequently presented based on Heronian mean operator. Then, the hotel decision support model is established. Finally, a hotel selection problem on TripAdvisor.com is provided to demonstrate the model. Its stability and validity are further verified by a sensitivity analysis and comparison with other extant methods.
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