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A single nucleotide variant present between two otherwise identical nucleic acids will have unexpected functional consequences frequently. Here, a neoteric single nucleotide variation (SNV) detection assay that integrates two complementary nanotechnology systems, nanoassembly technology and an ingenious nanopore biosensing platform, has been applied to this research. Specifically, we set up a detection system to reflect the binding efficiency of the polymerase and nanoprobe through the difference of nanopore signals and then explore the effect of base mutation at the binding site. In addition, machine learning based on support vector machines is used to automatically classify characteristic events mapped by nanopore signals. Our system reliably discriminates single nucleotide variants at binding sites, even possessing the recognition among transitions, transversions, and hypoxanthine (base I). Our results demonstrate the potential of solid-state nanopore detection for SNV and provide some ideas for expanding solid-state nanopore detection platforms.

ABSTRACTThermal ablation is widely used in the treatment of lung cancer and is beneficial for the overall survival of patients in clinic. However, there is barely a priority in which ablation system should be chosen under different periods of tumor progression in lung cancer. The present study investigated different modes of thermal ablation systems in mice with transplanted Lewis lung carcinoma tumors and their various biological effects in local regions using untargeted metabolomics. The results showed that thermal ablation could significantly suppress tumor growth and the differentially expressed metabolites of tumors after ablation relative to untreated tumors concentrated on organic compounds, organic acids and derivatives, nucleosides, nucleotides, and lipids. The upregulated metabolites indicated an inflammatory reaction in the ablation groups at an early stage after ablation. Steroid hormone and tryptophan metabolism, which are associated with immune responses, were modulated after both cryoablation and hyperthermal ablation. Characteristically, the results also indicated that cryoablation suppressed glucose oxidation and carbohydrate metabolism of tumor, while hyperthermal ablation suppressed lipid metabolism of tumor. In conclusion, thermal ablation could inhibit tumor growth under either freezing or heating modes with characteristic different biological effects on tumors.

ABSTRACTMonolithic self-glazed zirconia is a new type of biomimetic zirconia that has been successfully used as crown and bridge restorations in the anterior and posterior regions. It exhibits excellent biomechanics and aesthetic properties through completely digital processing technology. This case presents a young patient’s aesthetic rehabilitation with self-glazed ultra-thin zirconia veneers by closing the scattered diastema in the aesthetic zone of the anterior teeth with a fully digital workflow. The restorations exhibited excellent aesthetic outcomes with a minimally invasive concept and superior mechanical properties over glass-based ceramic veneers. The application of full-contour monolithic ultra-thin self-glazed zirconia restorations in the anterior aesthetic zone constitutes a reliable, fully digital clinical workflow.

ABSTRACTWith the recent interest in more efficient, comfortable, precise and minimally invasive surgical procedures and postoperative repairs, such as crown lengthening, there has been increasing research on the application of full digital technology in clinical scenarios. This clinical case describes an approach to crown lengthening and aesthetic restoration in a digital workflow using net-shaped self-glazed zirconia crowns. The findings of the study demonstrated the high compatibility of self-glazed zirconia with the full digital process. The presented approach ensured a higher degree of precision in crown lengthening prostheses, improved patient comfort and shortened clinical chairside time while achieving both aesthetic and functional requirements of anterior teeth in a timely and efficient manner.

Monolithic self-glazed zirconia is a new type of biomimetic zirconia that has been successfully used as crown and bridge restorations in the anterior and posterior regions. It exhibits excellent biomechanics and aesthetic properties through completely digital processing technology. This case presents a young patient's aesthetic rehabilitation with self-glazed ultra-thin zirconia veneers by closing the scattered diastema in the aesthetic zone of the anterior teeth with a fully digital workflow. The restorations exhibited excellent aesthetic outcomes with a minimally invasive concept and superior mechanical properties over glass-based ceramic veneers. The application of full-contour monolithic ultra-thin self-glazed zirconia restorations in the anterior aesthetic zone constitutes a reliable, fully digital clinical workflow.

With the recent interest in more efficient, comfortable, precise and minimally invasive surgical procedures and postoperative repairs, such as crown lengthening, there has been increasing research on the application of full digital technology in clinical scenarios. This clinical case describes an approach to crown lengthening and aesthetic restoration in a digital work?ow using net-shaped self-glazed zirconia crowns. The findings of the study demonstrated the high compatibility of self-glazed zirconia with the full digital process. The presented approach ensured a higher degree of precision in crown lengthening prostheses, improved patient comfort and shortened clinical chairside time while achieving both aesthetic and functional requirements of anterior teeth in a timely and efficient manner.

ABSTRACTIn the clinical application of traditional porcelain-fused-to-metal crowns and bridges, porcelain chipping has appeared as the major problems encountered by dentists. Once fracture occurs, neither aesthetics nor chewing efficiency remains. It is difficult to meet clinical needs with current repairing options. Self-glazed zirconia has been developed recently and is widely used in crowns, bridges, and veneering owing to its high strength, low wear on opposite teeth, and aesthetic appeal. In this study, we explore the application prospect of the chipped porcelain-fused-to-metal restoration repaired by the novel self-glazed zirconia veneering with a digital workflow. The results demonstrated that self-glazed zirconia can meet both the aesthetical and functional requirements of anterior and molar teeth in a timely and efficient manner.

ABSTRACTThis clinical case report describes the fabrication of monolithic self-glazed zirconia prostheses via a digital workflow, for full-arch rehabilitation in a patient with a severely worn dentition. Prostheses composed of self-glazed zirconia are less prone to chipping, and have a lower risk of progressive wear of the opposing natural teeth. The use of a digital workflow not only ensures a higher degree of precision in the fabrication of self-glazed zirconia prostheses, but it also greatly improves patient comfort, and reduces the clinical chairside time required for adjustments.

ABSTRACTSelf-glazed zirconia has been recently developed and widely used in crowns owing to its high strength, low wear on opposite teeth, and aesthetic appearance. This clinical study was to explore the application prospect of the bridge restoration made by self-glazed zirconia with a digital process. The results demonstrated that self-glazed zirconia could meet both the aesthetics and functional requirements of anterior and molar teeth in a time-saving and efficient manner.

Self-glazed zirconia has been recently developed and widely used in crowns owing to its high strength, low wear on opposite teeth, and aesthetic appearance. This clinical study was to explore the application prospect of the bridge restoration made by self-glazed zirconia with a digital process. The results demonstrated that self-glazed zirconia could meet both the aesthetics and functional requirements of anterior and molar teeth in a time-saving and efficient manner.

In the clinical application of traditional porcelain-fused-to-metal crowns and bridges, porcelain chipping has appeared as the major problems encountered by dentists. Once fracture occurs, neither aesthetics nor chewing efficiency remains. It is difficult to meet clinical needs with current repairing options. Self-glazed zirconia has been developed recently and is widely used in crowns, bridges, and veneering owing to its high strength, low wear on opposite teeth, and aesthetic appeal. In this study, we explore the application prospect of the chipped porcelain-fused-to-metal restoration repaired by the novel self-glazed zirconia veneering with a digital workflow. The results demonstrated that self-glazed zirconia can meet both the aesthetical and functional requirements of anterior and molar teeth in a timely and efficient manner.

This clinical case report describes the fabrication of monolithic self-glazed zirconia prostheses via a digital workflow, for full-arch rehabilitation in a patient with a severely worn dentition. Prostheses composed of self-glazed zirconia are less prone to chipping, and have a lower risk of progressive wear of the opposing natural teeth. The use of a digital workflow not only ensures a higher degree of precision in the fabrication of self-glazed zirconia prostheses, but it also greatly improves patient comfort, and reduces the clinical chairside time required for adjustments.

TREM2 is exclusively expressed by microglia in the brain and is strongly linked to the risk for Alzheimer’s disease (AD). As microglial responses modulated by TREM2 are central to AD pathogenesis, enhancing TREM2 signaling has been explored as an AD therapeutic strategy. However, the effective therapeutic window targeting TREM2 is unclear. Here, by using microglia-specific inducible mouse models overexpressing human wild-type TREM2 (TREM2-WT) or R47H risk variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition and neuritic dystrophy only during the early amyloid seeding stage, whereas TREM2-R47H exacerbates amyloid burden during the middle amyloid rapid growth stage. Single-cell RNA sequencing reveals suppressed disease-associated microglia (DAM) signature and reduced DAM population upon TREM2-WT expression in the early stage, whereas upregulated antigen presentation pathway is detected with TREM2-R47H expression in the middle stage. Together, our findings highlight the dynamic effects of TREM2 in modulating AD pathogenesis and emphasize the beneficial effect of enhancing TREM2 function in the early stage of AD development.

Nanopore has been studied for a lot of applications in DNA sequencing, multifarious single-molecule detection, detection of molecular conformational change, and biomolecular interaction. There are many categories of nanopores, such as biological nanopores, solid-state nanopores and newly developed hybrid nanopores. All of them play an important role in the detection of DNA structures because of their unique properties, such as the nano-scale pore size, dynamic detection in solution, and low sample loading. This review elaborates on the detection of several DNA structures by nanopore, including the dynamic analysis of conformational changes, and the factors that promote conformational changes. In addition, the detection of DNA origami, a type of artificial structured DNA, is also discussed. In these tests, current signals were produced by the interaction of analyte and nanopore. The signals were often studied by the statistical features of the currents’ amplitude, duration time, or both of them. Finally, taking advantage of the nanopore's ability to detect the conformational changes of these folds, the application of DNA structures detection in nanopore is introduced.

APOE4 exacerbates α-synuclein pathology in a synucleinopathy mouse model, and APOE4genotype associates with increased α-synuclein pathology in humans.