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Mineral accumulation in membrane vesicles is widely suggested, but does not correlate with a definitive stage of mineralization. Conversely mineral deposition at non-physiologic sites where calcium and phosphate are adequate has been shown to be regulated in large part by pyrophosphate. All of these elements are present in vertebrate bone metabolism. A key biological element of bone formation is an epithelial-like cellular organization which allows control of phosphate, calcium and pH during mineralization.Patients with poorly controlled type 2 diabetes mellitus (T2DM) often experience delayed tooth extraction socket (TES) healing. Delayed healing is often associated with an aberrant inflammatory response orchestrated by either M1 pro-inflammatory or M2 anti-inflammatory macrophages. However, the precise mechanism for the attenuated TES healing remains unclear. Here we used diet-induced T2DM mice as a model to study TES. Compared with the control group, the T2DM group showed delayed TES healing and diminished expression of osteogenic and angiogenic genetic profiles. Meanwhile, we detected a more inflammatory profile, with more M1 macrophages and TNF-α expression and less M2 macrophages and PPARγ expression, in TES in the T2DM group when compared to control mice. In vitro co-culture models showed that M1 macrophages inhibited the osteogenic capacity of bone marrow stromal cells and the angiogenic capacity of endothelial cells while M2 macrophages showed an opposite effect. In addition, we constructed a gelatin/β-TCP scaffold with IL-4 to induce macrophage transformation towards M2 polarization. In vitro analyses of the hybrid scaffold revealed sustained release of IL-4 and a phenotype switch to M2 macrophages. Finally, we demonstrated that sustained IL-4 release significantly increased expression of osteogenic and angiogenic genetic profiles and improved TES healing in T2DM mice. Together, we report that increased M1 and decreased M2 macrophage polarization may be responsible for delayed TES healing in T2DM patients through abnormal expression of TNF-α and PPARγ. This imbalance negatively influences osteogenesis and angiogenesis, two of the most important biological factors in bone wound healing. Enhancing M2 macrophage polarization with IL-4 delivery system may represent a potential strategy for promoting the healing of TES in T2DM patients.Bone nonunion caused by bacterial infection accounts for bone fractures, bone trauma and bone transplantation surgeries. Severe consequences include delayed unions and amputation and result in functional limitations, work disability, and poor quality of life. However, the mechanism of bone nonunion remains unknown. In this study, we aimed to screen the miRNA biomarkers of bacterial bone infection and investigated whether miRNAs regulate the osteoblasts and thus contribute to bone nonunion. We established a miRNA-mRNA network based on high-throughput RNA sequencing to compare the model rabbits infected with Staphylococcus aureus with the control rabbits. After validation experiments, miRNA-331-3p and fibroblast growth factor 23 (FGF23) were found to be inversely correlated with the pathways of osteoblast mineralization and pathology of infected bone nonunion. In in vitro experiments, miRNA-331-3p was downregulated and FGF23 was upregulated in lipopolysaccharide (LPS)-induced mouse calvarial osteoblasts. Further studies of the mechanism showed that mutated of putative miRNA-331-3p can bind to FGF23 3′-untranslated region sites. click here MiRNA-331-3p acted as an osteoblast mineralization promoter by directly targeting FGF23. Downregulation of miRNA-331-3p led to inhibition of osteoblast mineralization by regulating the DKK1/β-catenin mediated signaling. Thus, we established an improved animal model and identified new bone-related biomarkers in the infected bone nonunion. The miRNA-331-3p biomarker was demonstrated to regulate osteoblast mineralization by targeting FGF23. The novel mechanism can be used as potential diagnostic biomarkers and therapeutic targets in the infected bone nonunion and other inflammatory bone disorders.To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.BACs-on-Beads (BoBs) assay and copy number variation sequencing (CNV-seq) are two frequently used methods in today’s prenatal diagnosis. Several studies were conducted to investigate the performance of each approach, but they were never compared side by side. In this article, a comprehensive comparison of BoBs and CNV-seq was conducted using 1876 amniotic fluid and umbilical cord blood samples collected from Fujian Provincial Maternity and Children’s Hospital between 2015 and 2019. Karyotyping was used as the gold standard for chromosome structure variation, and chromosomal microarray analysis was performed to validate inconsistent results. Overall, 174 cases of confirmed chromosome anomalies were detected, including 73 chromosomal aneuploidies, 10 mosaics, 30 pathogenic CNVs, and 61 other structural anomalies. BoBs and CNV-seq achieved a 100% concordance in all 55 pathogenic euchromosome aneuploidies, but CNV-seq had a higher detection rate in sex chromosome aneuploidy and mosaic identification. For CNV detection, all of the 20 pathogenic CNVs discovered by the BoBs assay also were identified by CNV-seq and 10 additional pathogenic CNVs were observed by CNV-seq. The results of this study showed that CNV-seq was a reliable and more favorable method in terms of detection rate, costs, and disease range. In combination with karyotyping, CNV-seq could improve the efficiency and accuracy of a prenatal diagnosis to alleviate maternal emotional anxiety and deduce birth defects.