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Curcumin restrains hepatocellular carcinoma further advancement depending on the regulating your circ_0078710/miR-378b/PRIM2 axis.
Together, our findings reveal a novel function of TREM2 in mediating TMEM59 protein degradation and demonstrate the importance of TMEM59 homeostasis in maintaining TREM2-mediated microglial activities.While restoration of coronary blood flow to the ischemic heart is the most effective strategy for reducing infarct size, reperfusion injury represents a significant limiting factor on clinical outcomes in myocardial infarction patients. Ischemic preconditioning (IPC) has been shown to inhibit reperfusion injury and represents an attractive model for studying cardioprotective signal transduction pathways. Long non-coding RNAs (lncRNAs) are a structurally and functionally heterogenous class of RNA transcripts with unknown roles in IPC-induced cardioprotection. Through microarray-based expression profiling of 31,423 lncRNAs in cardiac tissue from IPC mice, we identified the nuclear transcript Neat1 to be rapidly and robustly decreased in response to IPC. siRNA-mediated knock down of Neat1 reduced apoptosis and necrosis in murine cardiomyocytes (CM) and human iPS-derived CMs in response to prolonged hypoxia and hypoxia-reoxygenation, assessed with Annexin V/propidium iodide-staining, a Caspase 3/7 activity assay, LDH release, and western blot for cleaved Caspase 3. Mechanistically, Neat1 was shown to regulate processing of pro-apoptotic microRNA-22 (miR-22) in murine and human CM nuclei using a luciferase reporter assay. Hypoxia-induced downregulation of Neat1 was shown to result in accumulation of unprocessed pri-miRNA and decreased availability of biologically active miRNA, including miR-22. Addition of exogenous synthetic miR-22 reversed the protective effect of Neat1 knock down in human iPS-CM. this website In conclusion, we have identified the nuclear lncRNA Neat1 as part of a conserved oxygen-sensitive feedback mechanism by regulation of miRNA processing and a potential target in cardioprotection.Living in a group allows individuals to decrease their defenses, enabling other beneficial behaviors such as foraging. The detection of a threat through social cues is widely reported, however, the safety cues that guide animals to break away from a defensive behavior and resume alternate activities remain elusive. Here we show that fruit flies display a graded decrease in freezing behavior, triggered by an inescapable threat, with increasing group sizes. Furthermore, flies use the cessation of movement of other flies as a cue of threat and its resumption as a cue of safety. Finally, we find that lobula columnar neurons, LC11, mediate the propensity for freezing flies to resume moving in response to the movement of others. By identifying visual motion cues, and the neurons involved in their processing, as the basis of a social safety cue this study brings new insights into the neuronal basis of safety in numbers.Altering electrochemical interfaces by using electrolyte effects or so-called "electrolyte engineering" provides a versatile means to modulate the electrochemical response. However, the long-standing challenge is going "beyond cyclic voltammetry" where electrolyte effects are interrogated from the standpoint of the interfacial properties of the electrode/electrolyte interface. Here, we employ ferrocene-terminated self-assembled monolayers as a molecular probe and investigate how the anion-dictated electrochemical responses are translated in terms of the electronic and structural properties of the electrode/monolayer/electrolyte interface. We utilise a photoelectron-based spectroelectrochemical approach that is capable of capturing "snapshots" into (1) anion dependencies of the ferrocene/ferrocenium (Fc/Fc+) redox process including ion-pairing with counter anions (Fc+-anion) caused by differences in Fc+-anion interactions and steric constraints, and (2) interfacial energetics concerning the electrostatic potential across the electrode/monolayer/electrolyte interface. Our work can be extended to provide electrolyte-related structure-property relationships in redox-active polymers and functionalised electrodes for pseudocapacitive energy storage.Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (TAILS) we had characterized proteolytic signatures in a porcine wound healing model and identified two neo-N termini derived from proteolytic cleavage of the focal adhesion protein and mechanotransducer zyxin. Here, we assign these proteolytic events to the activity of either caspase-1 or serine protease HtrA1 and analyze the biological relevance of the resultant zyxin truncations. By cellular expression of full-length and truncated zyxin proteins, we demonstrate nuclear translocation of a C-terminal zyxin fragment that could also be generated in vitro by HtrA1 cleavage and provide evidence for its anti-apoptotic activities, potentially by regulating the expression of modulators of cell proliferation, protein synthesis and genome stability. Targeted degradomics correlated endogenous generation of the same zyxin fragment with increased cell density in human primary dermal fibroblasts. Hence, this newly identified HtrA1-zyxin protease signaling axis might present a novel mechanism to transiently enhance cell survival in environments of increased cell density like in wound granulation tissue.Geometric-phase metasurfaces, recently utilized for controlling wavefronts of circular polarized (CP) electromagnetic waves, are drastically limited to the cross-polarization modality. Combining geometric with propagation phase allows to further control the co-polarized output channel, nevertheless addressing only similar functionality on both co-polarized outputs for the two different CP incident beams. Here we introduce the concept of chirality-assisted phase as a degree of freedom, which could decouple the two co-polarized outputs, and thus be an alternative solution for designing arbitrary modulated-phase metasurfaces with distinct wavefront manipulation in all four CP output channels. Two metasurfaces are demonstrated with four arbitrary refraction wavefronts, and orbital angular momentum modes with four independent topological charge, showcasing complete and independent manipulation of all possible CP channels in transmission. This additional phase addressing mechanism will lead to new components, ranging from broadband achromatic devices to the multiplexing of wavefronts for application in reconfigurable-beam antenna and wireless communication systems.
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