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INTRODUCTION: Following our recent finding that Ucp2 knockout promotes ferroptosis, we aimed to examine whether UCP2 alleviates myocardial ischemia/reperfusion injury (MI/RI) by inhibiting ferroptosis. METHODS: The left anterior descending coronary arteries of wild-type and Ucp2-/- C57BL/6 mice were ligated for 30 min and reperfused for 2 h to establish an MI/RI model. The effects of UCP2 on ferroptosis and MI/RI were determined by echocardiography, 2,3,5-triphenylttrazolium chloride staining, hematoxylin-eosin staining, Masson's trichrome staining, Sirius red staining, and analysis of myocardial injury markers and ferroptosis indicators. Ferrostatin-1 (Fer-1) and erastin (Era) were used to investigate whether UCP2 alleviated MI/RI by inhibiting ferroptosis and the molecular mechanism. RESULTS: UCP2 was upregulated in the MI/RI model in WT mice. Deletion of Ucp2 exacerbated ferroptosis, altered the expression levels of multiple ferroptosis-related genes, and significantly exacerbated MI/RI. Knockout of Ucp2 promoted ferroptosis induced by Era and inhibited the antiferroptotic effects of Fer-1. Knockout of Ucp2 activated the p53/TfR1 pathway to exacerbate ferroptosis. CONCLUSION: Our results showed that UCP2 inhibited ferroptosis in MI/RI, which might be related to regulation of the p53/TfR1 pathway.
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Modelos Animais de Doenças , Ferroptose , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Proteína Desacopladora 2 , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/genética , Proteína Desacopladora 2/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/deficiência , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Masculino , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , CamundongosRESUMO
Dental mesenchymal stem cells (DMSCs) are crucial in tooth development and periodontal health, and their multipotential differentiation and self-renewal ability play a critical role in tissue engineering and regenerative medicine. Methylation modifications could promote the appropriate biological behavior by postsynthetic modification of DNA or protein and make the organism adapt to developmental and environmental prompts by regulating gene expression without changing the DNA sequence. Methylation modifications involved in DMSC fate include DNA methylation, RNA methylation, and histone modifications, which have been proven to exert a significant effect on the regulation of the fate of DMSCs, such as proliferation, self-renewal, and differentiation potential. Understanding the regulation of methylation modifications on the behavior and the immunoinflammatory responses involved in DMSCs contributes to further study of the mechanism of methylation on tissue regeneration and inflammation. In this review, we briefly summarize the key functions of histone methylation, RNA methylation, and DNA methylation in the differentiation potential and self-renewal of DMSCs as well as the opportunities and challenges for their application in tissue regeneration and disease therapy.
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Using atomic force microscopy, we have shown that friction on graphene/h-BN superlattice structures may exhibit unusual moiré-scale stick slip in addition to the regular ones observed at the atomic scale. Such dual-scale slip instability will lead to unique length-scale dependent energy dissipation when the different slip mechanisms are sequentially activated. Assisted by an improved theoretical model and comparative experiments, we find that accumulation and unstable release of the in-plane strain of the graphene layer is the key mechanism underlying the moiré-scale behavior. This work highlights the distinct role of the internal state of the van der Waals interfaces in determining the rich dynamics and energy dissipation of layer-structured materials.
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The Raman peak position shift rate per strain (RSS) coefficient of graphene is crucial for quantitative strain measurement by Raman spectroscopy. Despite its essential role, the experimentally measured RSS values are found to be highly scattered and many times significantly lower than the theoretical prediction. Here, using in situ Raman spectroscopy with a tensile test system, we resolve this controversy by examining the Raman characteristics of graphene derived from chemical vapor deposition (CVD) transferred on polymer substrates. Our experiments show that the Raman 2D-peak position of CVD graphene can shift nonlinearly with applied strain, in contrast to its intrinsically linear trait. More importantly, the resultant RSS coefficient at the steady state is much lower than the theoretical prediction. By analyzing atomic force microscopy (AFM) phase images and full width at half-maximum (FWHM) of Raman spectra, we attribute the abnormal behavior to nanometer-scale inhomogeneity of the graphene/substrate contact interface. Assisted by a simplified discrete interface slip model, we correlate the evolution of nanometer-scale inhomogeneity with that of the apparent Raman response. The theoretical model provides a useful tool for understanding and optimizing the contact interface behavior of various two-dimensional materials on substrates; the revealed mechanism is critical for correct interpretation of data obtained by Raman or any other spectroscopies based on homogenized laser signals.
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Two-dimensional (2D) materials have seen a broad range of applications in electronic and optoelectronic applications; however, full realization of this potential hitherto largely hinges on the quality and performance of the electrical contacts formed between 2D materials and their surrounding metals/semiconductors. Despite the progress in revealing the charge injecting mechanisms and enhancing electrical conductance using various interfacial treatments, how the microstructure of contact interfaces affects local electrical conductivity is still very limited. Here, using conductive atomic force microscopy (c-AFM), for the first time, we directly confirm the conjecture that the electrical conductivity of physisorbed 2D material-metal/semiconductor interfaces is determined by the local electronic charge transfer. Using lattice-resolved conductivity mapping and first-principles calculations, we demonstrate that the electronic charge transfer, thereby electrical conductivity, can be fine-tuned by the topological defects of 2D materials and the atomic stacking with respect to the substrate. Our finding provides a novel route to engineer the electrical contact properties by exploiting fine atomic interactions; in the meantime, it also suggests a convenient and nondestructive means of probing subtle interactions along 2D heterogeneous interfaces.
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Two-dimensional (2D) materials possess outstanding lubrication property with their thicknesses down to a few atomic layers, but they are easily susceptible to sliding induced degradation or ubiquitous chemical modification. Maintaining the superior lubricating performance of 2D materials in a harsh working environment is highly desirable yet grandly challenging. Here we show that by proper alignment of graphene on a Ge(111) substrate, friction of graphene could be well preserved at an ultra-low level even after fluorination or oxidation. This behaviour is experimentally found to be closely related to the suppression of molecular-level deformation of graphene within the moiré superlattice structure. Atomistic simulations reveal that the formation of an interconnected meshwork with enhanced interfacial charge density imposes a strong anchoring effect on graphene even under chemical modification. Modulating molecular-level deformation by interfacial confinements may offer a unique strategy for tuning the mechanical or even chemical properties of 2D materials.