This review recognizes a unique calcium phosphate (CaP) phase known as monetite or dicalcium phosphate anhydrous (DCPA, CaHPO4), and presents an overview of its properties, processing, and ...applications in orthopedics. The motivation for the present effort is to highlight the state-of-the-art research and development of monetite and propel the research community to explore more of its potentials in orthopedics. After a brief introduction of monetite, we provide a summary of its various synthesis routes like dehydration, solvent-based, energy-assisted processes and also discuss the formation of different crystal structures with respect to the synthesis conditions. Subsequently, we discuss the material's noteworthy physico-chemical properties including the crystal structure, vibrational spectra, solubility, thermal decomposition, and conversion to other phases. Of note, we focus on the biological (in vitro and in vivo) properties of monetite, given its ever-increasing popularity as a biomaterial for medical implants. Appropriately, we discuss various orthopedic applications of monetite as bone cement, implant coatings, granules for defect fillers, and scaffolds. Many in vitro and in vivo studies confirmed the favorable osteointegration and osteoconduction properties of monetite products, along with a better balance between implant resorption and new bone formation as compared to other CaP phases. The review ends with translational aspects of monetite and presents thoughts about its possible future research directions. Further research may explore but not limited to improvements in mechanical strength of monetite-based scaffolds, using monetite particles as a therapeutic agent delivery, and tissue engineering strategies where monetite serves as the biomaterial.
This is the first review that focusses on the favorable potential of monetite for hard tissue repair and regeneration. The article accurately covers the “Synthesis-Structure-Property-Applications” correlations elaborating on monetite's diverse material properties. Special focus is put on the in vitro and in vivo properties of the material highlighting monetite as an orthopedic material-of-choice. The synthesis techniques are discussed which provide important information about the different fabrication routes for monetite. Most importantly, the review provides comprehensive knowledge about the diverse biomedical applications of monetite as granules, defect--specific scaffolds, bone cements and implant coatings. This review will help to highlight monetite's potential as an effective regenerative medicine and catalyze the continuing translation of this bioceramic from the laboratory to clinics.
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The experimental stress–strain data from isothermal hot compression tests over a wide range of temperatures (1073–1473K), strains (0.1–0.5) and strain rates (0.001–1s−1) were employed to formulate a ...suitable constitutive model to predict the elevated-temperature deformation behaviour in a Ti-modified austenitic stainless steel (alloy D9). It was observed that the Johnson–Cook (JC) model in its original form is inadequate to provide good description of flow behaviour of alloy D9 in the above hot working domain. This has been attributed to the inadequacy of the JC model to incorporate the coupled effects of strain and temperature and of strain rate and temperature. A modified constitutive model based on the Zerilli–Armstrong model has been proposed for considering the effects of thermal softening, strain rate hardening and isotropic hardening as well as the coupled effects of temperature and strain and of strain rate and temperature on flow stress. The proposed modified constitutive model could predict the elevated-temperature flow behaviour of alloy D9 over the specified hot working domain of alloy D9 with good correlation and generalization.
As the carrier of genetic information, the DNA double helix interacts with many natural ligands during the cell cycle, and is amenable to such intervention in diseases such as cancer biogenesis. ...Proteins bind DNA in a site-specific manner, not only distinguishing between the geometry of the major and minor grooves, but also by making close contacts with individual bases within the local helix architecture. Over the last four decades, much research has been reported on the development of small non-natural ligands as therapeutics to either block, or in some cases, mimic a DNA-protein interaction of interest. This review presents the latest findings in the pursuit of novel synthetic DNA binders. This article provides recent coverage of major strategies (such as groove recognition, intercalation and cross-linking) adopted in the duplex DNA recognition by small molecules, with an emphasis on major works of the past few years.
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging ...from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
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•Profiling of 10 human skin SCCs and matched normals via scRNA-seq, ST, and MIBI•Tumor-specific keratinocytes (TSKs) reside within a fibrovascular niche at leading edges•Distinct ligand-receptor and spatial niche associations for tumor and stromal cells.•Subpopulation essential tumorigenic gene networks defined by in vivo CRISPR screening
Integration of high-dimensional multi-omics approaches to characterize human cutaneous squamous cell carcinoma identifies a tumor-specific keratinocyte population as well as the immune infiltrates and heterogeneity at tumor leading edges.
Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and ...neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.
•Assessment of cellular response on 3-D printed macroporous PEEK scaffolds.•Macropores with uniform sizes and reproducibility were successfully fabricated.•Effects of the scaffolds’ macropores on ...osteoblast cellular functions were analyzed.•800 µm pore sizes provided greater surface area and enhanced cell-cell connection.•Highlights importance of additive manufacturing in fabricating bio-scaffolds.
This article reports on the fabrication and evaluation of 3-D printed polyetheretherketone (PEEK) scaffolds with controlled macroporosity. Specifically, uniform macropore sizes ranging from 800 to 1800 µm by design were generated by varying processing parameters. It is expected that the 3-D printing ability to obtain customized macropores can help arriving at the optimum pore size in scaffolds to encourage bone regeneration. This study conclusively showed optimal cell adhesion and proliferation in scaffolds containing uniform pores of an average size of 800 μm. A construct containing a wide distribution of pores cannot come to this conclusion. In this context, the precision and reproducibility of additive manufacturing in scaffold fabrication play an important role.
▶ Constitutive analysis of various austenitic stainless steels was performed. ▶ The materials show strain hardening, strain rate hardening and thermal softening. ▶ They show coupled effect of ...temperature and strain, and temperature and strain rate. ▶ The modified Zerilli-Armstrong (MZA) model has been applied to predict flow stress. ▶ MZA model could predict the elevated temperature flow behaviour of the materials.
High temperature flow behaviour of various grades of austenitic stainless steels viz. 304L, 304, 304 (as-cast), 316L and 15Cr–15Ni–Ti modified austenitic stainless steels (alloy D9) were analyzed by performing isothermal hot compression tests in a wide range of temperatures (1073
K to 1473
K for 304L, 304, 304 (as-cast), 316L and 1123
K to 1523
K for alloy D9) and strain rates (0.001–1
s
−1). It has been observed that all these materials show strain hardening, strain rate hardening, thermal softening, coupled effect of temperature and strain, and temperature and strain rate on flow stress in the hot working domain. The modified Zerilli–Armstrong (MZA) model which considers the above significant effects on flow stress has been applied to predict the flow behaviour of these materials. The material constants of the MZA model for each material have been evaluated and subsequently applied to predict the flow stress. It has been demonstrated that the MZA model could adequately represent the elevated temperature flow behaviour of these materials over the entire ranges of strain, strain rate and temperature.
We present the first global inventory of the spatial distribution and density ofconstructed impervious surface area (ISA). Examples of ISA include roads, parking lots,buildings, driveways, sidewalks ...and other manmade surfaces. While high spatialresolution is required to observe these features, the new product reports the estimateddensity of ISA on a one-km² grid based on two coarse resolution indicators of ISA - thebrightness of satellite observed nighttime lights and population count. The model wascalibrated using 30-meter resolution ISA of the USA from the U.S. Geological Survey.Nominally the product is for the years 2000-01 since both the nighttime lights andreference data are from those two years. We found that 1.05% of the United States landarea is impervious surface (83,337 km²) and 0.43 % of the world's land surface (579,703km²) is constructed impervious surface. China has more ISA than any other country(87,182 km²), but has only 67 m² of ISA per person, compared to 297 m² per person in theUSA. The distribution of ISA in the world's primary drainage basins indicates that watersheds damaged by ISA are primarily concentrated in the USA, Europe, Japan, China and India. The authors believe the next step for improving the product is to include reference ISA data from many more areas around the world.
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