ABSTRACT
Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a sex-stratified study design. We compared transcriptomics data of postmortem brain samples from patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) with transcriptomics data of postmortem control brains from individuals without a known history of psychiatric disease. We found that brain samples from females with SCZ, BD, and ASD showed a higher burden of transcriptomic dysfunction than did brain samples from males with these disorders. This observation was supported by the larger number of differentially expressed genes (DEGs) and a greater magnitude of gene expression changes observed in female versus male brain specimens. In addition, female patient brain samples showed greater overall connectivity dysfunction, defined by a higher proportion of gene coexpression modules with connectivity changes and higher connectivity burden, indicating a greater degree of gene coexpression variability. We identified several gene coexpression modules enriched in sex-biased DEGs and identified genes from a genome-wide association study that were involved in immune and synaptic functions across different brain cell types. We found a number of genes as hubs within these modules, including those encoding SCN2A, FGF14, and C3. Our results suggest that in the context of psychiatric diseases, males and females exhibit different degrees of transcriptomic dysfunction and implicate immune and synaptic-related pathways in these sex differences.
Subject(s)
Autopsy , Brain , Mental Disorders , Sex Characteristics , Transcriptome , Humans , Female , Male , Transcriptome/genetics , Brain/metabolism , Brain/pathology , Mental Disorders/genetics , Mental Disorders/pathology , Bipolar Disorder/genetics , Bipolar Disorder/metabolism , Bipolar Disorder/pathology , Schizophrenia/genetics , Schizophrenia/metabolism , Schizophrenia/pathology , Gene Expression Profiling , Genome-Wide Association Study , Adult , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/metabolism , Autism Spectrum Disorder/pathology , Gene Regulatory Networks , Middle AgedABSTRACT
Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration.
Subject(s)
Biocompatible Materials/chemistry , Bone Regeneration/physiology , Bone and Bones/physiology , Ceramics/chemistry , Tissue Scaffolds/chemistry , Biocompatible Materials/pharmacology , Bone Regeneration/drug effects , Bone and Bones/cytology , Bone and Bones/drug effects , Cell Differentiation/drug effects , Ceramics/pharmacology , Humans , Nanostructures/chemistry , Porosity , Tissue Engineering/methods , Tissue Engineering/trendsABSTRACT
A tetragonal polyvinyl alcohol (PVA) scaffold with 3D orthogonal periodic porous architecture was fabricated via selective laser sintering (SLS) technology. The scaffold was fabricated under the laser power of 8 W, scan speed of 600 mm min(-1), laser spot diameter of 0.8 mm and layer thickness of 0.15 mm. The microstructure analysis showed that the degree of crystallization decreased while the PVA powder melts gradually and fuses together completely with laser power increasing. Thermal decomposition would occur if the laser power was further higher (16 W or higher in the case). The porous architecture was controllable and totally interconnected. The porosity of the fabricated scaffolds was measured to be 67.9 ± 2.7% which satisfies the requirement of micro-pores of the bone scaffolds. Its bioactivity and biocompatibility were also evaluated in vitro as tissue engineering (TE) scaffolds. In vitro adhesion assay showed that the amount of pores increased while the scaffold remains stable and intact after immersion in simulated body fluid for seven days. Moreover, the number of MG-63 cells and the bridge between cells increased with increasing time in cell culture. The present work demonstrates that PVA scaffolds with well-defined porous architectures via SLS technology were designed and fabricated for bone TE.
