Lundekragelund3566

gage with learning content needs exploration.Cellular senescence is characterized by an irreversible cell cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP), which is a major contributor to aging and age-related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases. However, it is still unknown whether senescent cell clearance alleviates cognitive dysfunction during the aging process. To investigate this, we first conducted single-nuclei and single-cell RNA-seq in the hippocampus from young and aged mice. We observed an age-dependent increase in p16Ink4a senescent cells, which was more pronounced in microglia and oligodendrocyte progenitor cells and characterized by a SASP. We then aged INK-ATTAC mice, in which p16Ink4a -positive senescent cells can be genetically eliminated upon treatment with the drug AP20187 and treated them either with AP20187 or with the senolytic cocktail Dasatinib and Quercetin. We observed that both strategies resulted in a decrease in p16Ink4a exclusively in the microglial population, resulting in reduced microglial activation and reduced expression of SASP factors. Importantly, both approaches significantly improved cognitive function in aged mice. Our data provide proof-of-concept for senolytic interventions' being a potential therapeutic avenue for alleviating age-associated cognitive impairment.The bacterium strain Ideonella sakaiensis 201-F6 is able to hydrolyze low-crystallinity PET films at 30 °C due to two enzymes named PETase and MHETase. Since its discovery, many efforts have been dedicated to elucidating the structure and features of those two enzymes, and various authors have highlighted the necessity to optimize both the substrate binding site and the global structure in order to enhance the stability and catalytic activity of these PET biocatalysts so as to make them more suitable for industrial applications. In this review, the strategies adopted by different research groups to investigate the structure and functionality of both PETase and MHETase in depth are described, emphasizing the advantages provided by the use of computational methods to complement and drive experiments. Subsequently, the modifications implemented with protein engineering are discussed. The versatility of the enzymes secreted by I. sakaiensis enables the prediction that they will find several applications in the disposal of PET debris, encouraging a prioritization of efforts in this prolific research field.As a new member of 2D materials, 2D tellurium (Te) has recently attracted much attention due to its intriguing properties. Through hydrothermal processing, 2D Te with tunable thickness and size has been realized, and its growth mechanism has also been studied. However, the tailored growth of 2D Te nanoflakes with symmetrical morphologies and interfacial moiré fringes has never been reported. Here, 2D Te nanoflakes have been prepared using the hydrothermal method, and mirror-symmetrical shapes (including "V-shape," "heart-shape," and "paper airplane-shape") with obvious moiré fringes in the middle of the nanoflakes are observed. Comprehensive transmission electron microscopy (TEM) techniques are utilized for structural characterization of these nanoflakes, especially the moiré fringes in the symmetry axis region of the nanoflakes. The systematic analyses of the moiré fringes and the observation of obvious overlapping edges of the composing nanoflakes from the cross-sectional samples reveal the possible mechanism of morphological evolution for these symmetrical nanoflakes. These details may fill the research gap in the controllable growth of 2D Te nanomaterials, pave the way for the fabrication of 2D Te moiré superlattices and in-plane homojunctions, and promote their future versatile applications.Glioblastoma (GBM) is the most common and deadliest tumor of the central nervous system. GBM has poor prognosis and glioma stem cells (GSCs) are implicated in tumor initiation and therapy resistance. Estrogen receptor β (ERβ) is expressed in GBM and exhibit tumor suppressive function. However, the role of ERβ in GSCs and the therapeutic potential of ERβ agonists on GSCs remain largely unknown. Here, we examined whether ERβ modulates GSCs stemness and tested the utility of two ERβ selective agonists (LY500307 and Liquiritigenin) to reduce the stemness of GSCs. The efficacy of ERβ agonists was examined on GSCs isolated from established and patient derived GBMs. Our results suggested that knockout of ERβ increased the proportion of CD133+ and SSEA+ positive GSCs and overexpression of ERβ reduced the proportion of GSCs in GBM cells. Overexpression of ERβ or treatment with ERβ agonists significantly inhibited the GSCs cell viability, neurosphere formation, self-renewal ability, induced the apoptosis and reduced expression of stemness markers in GSCs. RNA sequencing analysis revealed that ERβ agonist modulate pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that ERβ overexpression or agonist treatment reduced glutamate receptor signaling pathway and induced apoptotic pathways. In orthotopic models, ERβ overexpression or ERβ agonists treatment significantly reduced the GSCs mediated tumor growth and improved the mice overall survival. Immunohistochemical studies demonstrated that ERβ overexpression decreased SOX2 and GRM3 expression and increased expression of GFAP in tumors. These results suggest that ERβ activation could be a promising therapeutic strategy to eradicate GSCs.

Emergence profile design is important for stable peri-implant tissues and esthetically pleasing results with dental implant restorations, influenced by factors, such as, implant position and surrounding soft tissues. Different aspects of the emergence profile have been described, but detailed explanations of the different zones and corresponding designs are missing. This article describes the esthetic biological contour concept (EBC), differentiating important areas of the emergence profile and recommending particular designs for those zones.

The EBC concept considers specific parameters for proper design of the emergence profile of implant-supported restorations. Understanding the different zones of the emergence profile and their relation to factors like implant position, implant design, and soft tissue thickness is key. The suggested guidelines are geared toward providing more stable and esthetic results when restoring dental implants in the esthetic zone.

Each of the zones described in the EBC concept have a specific function in the design of the emergence profile. Understanding the importance and specific design features of the EBC zones facilitates esthetic and biologically sound treatment outcomes with interim and definitive implant restorations.

Proper emergence profile design supports esthetic outcomes and provides favorable biological response to implant-supported restorations.

Proper emergence profile design supports esthetic outcomes and provides favorable biological response to implant-supported restorations.Protocols for specifying human primordial germ cell-like cells (hPGCLCs) from human embryonic stem cells (hESCs) remain hindered by differences between hESC lines, their derivation methods, and maintenance culture conditions. This poses significant challenges for establishing reproducible in vitro models of human gametogenesis. Here, we investigated the influence of activin A (ActA) during derivation and maintenance on the propensity of hESCs to differentiate into PGCLCs. We show that continuous ActA supplementation during hESC derivation (from blastocyst until the formation of the post-inner cell mass intermediate [PICMI]) and supplementation (from the first passage of the PICMI onwards) is beneficial to differentiate hESCs to PGCLCs subsequently. Moreover, comparing isogenic primed and naïve states prior to differentiation, we showed that conversion of hESCs to the 4i-state improves differentiation to (TNAP [tissue nonspecific alkaline phosphatase]+/PDPN [podoplanin]+) PGCLCs. Those PGCLCs expressed several germ cell markers, including TFAP2C (transcription factor AP-2 gamma), SOX17 (SRY-box transcription factor 17), and NANOS3 (nanos C2HC-type zinc finger 3), and markers associated with germ cell migration, CXCR4 (C-X-C motif chemokine receptor 4), LAMA4 (laminin subunit alpha 4), ITGA6 (integrin subunit alpha 6), and CDH4 (cadherin 4), suggesting that the large numbers of PGCLCs obtained may be suitable to differentiate further into more mature germ cells. Finally, hESCs derived in the presence of ActA showed higher competence to differentiate to hPGCLC, in particular if transiently converted to the 4i-state. Our work provides insights into the differences in differentiation propensity of hESCs and delivers an optimized protocol to support efficient human germ cell derivation.

Despite all advantages provided by the digital workflow, its application in clinical practice is still more focused on device manufacturing and clinical execution than on treatment planning and communication. The most challenging phases of treatment, comprehensive planning, diagnosis, risk assessment, and decision-making, are still performed without significant assistance from digital technologies. This article proposes a new dental software classification based on the digital workflow timeline, considering the moment of patient's case acceptance as key in this classification, and presents the ideal software tools for each phase.

The proposed classification will help clinicians and dental laboratories to choose the most appropriate software during the treatment planning phase and integrate virtual plans with other software platforms for digitally guided execution. A dento-facial interdisciplinary planning platform virtually simulates interdisciplinary clinical procedures and assists in the decision-making process.

The suggested classification assists professionals in different phases of the digital workflow and provides guidelines for improvement and development of digital technologies before treatment plan acceptance by the patient.

Three-dimensional interdisciplinary simulations allow clinicians to visualize how each dental procedure influences further treatments. With this treatment planning approach, predictability of different procedures in restorative dentistry, orthodontics, implant dentistry, periodontal, and oral maxillofacial surgery is improved.

Three-dimensional interdisciplinary simulations allow clinicians to visualize how each dental procedure influences further treatments. With this treatment planning approach, predictability of different procedures in restorative dentistry, orthodontics, implant dentistry, periodontal, and oral maxillofacial surgery is improved.The olfactory epithelium (OE) possesses unique lifelong neuroregenerative capacities and undergoes constitutive neurogenesis throughout mammalian lifespan. Two populations of stem cells, frequently dividing globose basal cells (GBCs) and quiescent horizontal basal cells (HBCs), readily replace olfactory neurons throughout lifetime. Although lineage commitment and neuronal differentiation of stem cells has already been described in terms of transcription factor expression, little is known about external factors balancing between differentiation and self-renewal. We show here that expression of the CXC-motif chemokine receptor 4 (CXCR4) distinguishes both types of stem cells. Extensive colocalization analysis revealed exclusive expression of CXCR4 in proliferating GBCs and their neuronal progenies. learn more Moreover, only neuronal lineage cells were derived from CXCR4-CreER-tdTomato reporter mice in the OE. Furthermore, Cre-tdTomato mice specific for HBCs (Nestin+ and Cytokeratin14+) did not reduce CXCR4 expression when bred to mice bearing floxed CXCR4 alleles, and did not show labeling of the neuronal cells.