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Background Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs). Methods and results Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue. Conclusions Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.

Hydrocephalus is a severe complication that can result from intracerebral hemorrhage, especially if this hemorrhage extends into the ventricles. Our previous study indicated that the NLRP3 inflammasome mediates cerebrospinal fluid hypersecretion in the choroid plexus epithelium. However, the pathogenesis of posthemorrhagic hydrocephalus remains unclear, and therapeutic strategies for prevention and treatment are lacking. In this study, an Nlrp3−/− rat model of intracerebral hemorrhage with ventricular extension and primary choroid plexus epithelial cell culture were used to investigate the potential effects of NLRP3-dependent lipid droplet formation and its role in the pathogenesis of posthemorrhagic hydrocephalus. The data indicated that NLRP3-mediated dysfunction of the blood–cerebrospinal fluid barrier (B-CSFB) accelerated neurological deficits and hydrocephalus, at least in part, through the formation of lipid droplets in the choroid plexus; these lipid droplets interacted with mitochondria and increased the release of mitochondrial reactive oxygen species that destroyed tight junctions in the choroid plexus after intracerebral hemorrhage with ventricular extension. This study broadens the current understanding of the relationship among NLRP3, lipid droplets and the B-CSFB and provides a new therapeutic target for the treatment of posthemorrhagic hydrocephalus. Strategies to protect the B-CSFB may be effective therapeutic approaches for posthemorrhagic hydrocephalus.

Impact hydroforming (IHF), as a novel sheet metal forming technology with the advantages of high strain rate forming and flexible liquid loading, is highly suitable for efficiently manufacturing aluminum complex-shaped sheet parts. In this paper, deformation characteristics of complex sheet parts under IHF are systematically investigated. The mechanical properties of 2024 aluminum alloy under a wide range of strain rates (10−3 s−1–3.3×103 s−1) were studied. It indicated that the elongation of 2024 aluminum alloy was improved by 116.01% under strain rates of 3.306 × 103 s−1, referring to 10−3 s−1. Further, a complex-shaped part with symmetrical and asymmetrical structures was selected. The deformation characteristics of sheet and role of inertial effect under IHF were investigated with well-developed solid–liquid coupling finite element (SLC-FE) model with high accuracy. Differentiating deformation tendency is found for symmetrical structure with notably prior deformation at central zone, showing a “bulging” profile at initial forming stage. Whereas, synchronous deformation is presented for asymmetrical structure with a “flat” profile. Additionally, distinctive inertial effect was observed at different positions change for both symmetrical and asymmetrical structures, in which lower values were resulted at their central regions. Meanwhile, the inertial effect evolved with the impacting speed. Specially, larger difference of inertial effect was observed with increasing impacting speed.

Goldfish (Carassius auratus) have long fascinated evolutionary biologists and geneticists because of their diverse morphological and color variations. Recent genome-wide association studies have provided a clue to uncover genomic basis underlying these phenotypic variations, but the causality between phenotypic and genotypic variations have not yet been confirmed. Here, we edited proposed candidate genes to recreate phenotypic traits and developed a rapid biotechnology approach which combines gene editing with high-efficiency breeding, artificial gynogenesis, and temperature-induced sex reversal to establish homozygous mutants within two generations (approximately eight months). We first verified that low-density lipoprotein receptor-related protein 2B (lrp2aB) is the causal gene for the dragon-eye variation and recreated the dragon-eye phenotype in side-view Pleated-skirt Lion-head goldfish. Subsequently, we demonstrated that the albino phenotype was determined by both homeologs of oculocutaneous albinism type II (oca2), which has subfunctionalized to differentially govern melanogenesis in the goldfish body surface and pupils. Overall, we determined two causal genes for dragon-eye and albino phenotypes, and created four stable homozygous strains and more appealing goldfish with desirable traits. The developed biotechnology approach facilitates precise genetic breeding, which will accelerate re-domestication and recreation of phenotypically desirable goldfish.

Background Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. Methods Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. Results In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM. Conclusions Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.