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DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Metilación de ADN , Pronóstico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Inmunomodulación , Microambiente Tumoral/genéticaRESUMEN
Electron microscopy, an important technique that allows for the precise determination of structural information with high spatiotemporal resolution, has become indispensable in unravelling the complex relationships between material structure and properties ranging from mesoscale morphology to atomic arrangement. However, beam-sensitive materials, particularly those comprising organic components such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), would suffer catastrophic damage from the high energy electrons, hindering the determination of atomic structures. A low-dose approach has arisen as a possible solution to this problem based on the integration of advancements in several aspects: electron optical system, detector, image processing, and specimen preservation. This article summarizes the transmission electron microscopy characterization of MOFs and COFs, including local structures, host-guest interactions, and interfaces at the atomic level. Revolutions in advanced direct electron detectors, algorithms in image acquisition and processing, and emerging methodology for high quality low-dose imaging are also reviewed. Finally, perspectives on the future development of electron microscopy methodology with the support of computer science are presented.
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Intragrain impurities can impart detrimental effects on the efficiency and stability of perovskite solar cells, but they are indiscernible to conventional characterizations and thus remain unexplored. Using in situ scanning transmission electron microscopy, we reveal that intragrain impurity nano-clusters inherited from either the solution synthesis or post-synthesis storage can revert to perovskites upon irradiation stimuli, leading to the counterintuitive amendment of crystalline grains. In conjunction with computational modelling, we atomically resolve crystallographic transformation modes for the annihilation of intragrain impurity nano-clusters and probe their impacts on optoelectronic properties. Such critical fundamental findings are translated for the device advancement. Adopting a scanning laser stimulus proven to heal intragrain impurity nano-clusters, we simultaneously boost the efficiency and stability of formamidinium-cesium perovskite solar cells, by virtual of improved optoelectronic properties and relaxed intra-crystal strain, respectively. This device engineering, inspired and guided by atomic-scale in situ microscopic imaging, presents a new prototype for solar cell advancement.
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The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites. Compared to planar Fe-Cu dual-atomic sites, vertically stacked Fe-Cu geometry in FePc@2D-Cu-N-C possesses highly optimized scaffolds, favorable substrate affinity, and fast electron transfer. These characteristics of FePc@2D-Cu-N-C SAzyme induces biomimetic O2 activation through homogenous enzymatic pathway, resembling functional and mechanistic similarity to natural cytochrome c oxidase. Furthermore, it presents an appealing alternative of cytochrome P450 3A4 for drug metabolism and drug-drug interaction. These findings are expected to deepen the fundamental understanding of atomic-level design in next-generation bio-inspired nanozymes.
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Biomimética , Complejo IV de Transporte de Electrones , Biocatálisis , Transporte de Electrón , Ingeniería , CatálisisRESUMEN
Engineering piezo/ferroelectricity in two-dimensional materials holds significant implications for advancing the manufacture of state-of-the-art multifunctional materials. The inborn nonstoichiometric propensity of two-dimensional transition metal dichalcogenides provides a spiffy ready-available solution for breaking inversion centrosymmetry, thereby conducing to circumvent size effect challenges in conventional perovskite oxide ferroelectrics. Here, we show the extendable and ubiquitous piezo/ferroelectricity within nonstoichiometric two-dimensional transition metal dichalcogenides that are predominantly centrosymmetric during standard stoichiometric cases. The emerged piezo/ferroelectric traits are aroused from the sliding of van der Waals layers and displacement of interlayer metal atoms triggered by the Frankel defects of heterogeneous interlayer native metal atom intercalation. We demonstrate two-dimensional chromium selenides nanogenerator and iron tellurides ferroelectric multilevel memristors as two representative applications. This innovative approach to engineering piezo/ferroelectricity in ultrathin transition metal dichalcogenides may provide a potential avenue to consolidate piezo/ferroelectricity with featured two-dimensional materials to fabricate multifunctional materials and distinguished multiferroic.