Hsa_circ_0015278 Regulates FLT3-ITD AML Progression via Ferroptosis-Related Genes.

AML with the FLT3-ITD mutation seriously threatens human health. The mechanism by which circRNAs regulate the pathogenesis of FLT3-ITD mutant-type AML through ferroptosis-related genes (FerRGs) remains unclear. Differentially expressed circRNAs and mRNAs were identified from multiple integrated data sources. The target miRNAs and mRNAs of the circRNAs were predicted using various databases. The PPI network, ceRNA regulatory network, GO, and KEGG enrichment analyses were performed. The "survival" and the "pROC" R packages were used for K-M and ROC analysis, respectively. GSEA, immune infiltration analysis, and clinical subgroup analysis were performed. Finally, circRNAs were validated by Sanger sequencing and qRT-PCR. In our study, 77 DECircs-1 and 690 DECircs-2 were identified. Subsequently, 11 co-up-regulated DECircs were obtained by intersecting DECircs-1 and DECircs-2. The target miRNAs of the circRNAs were screened by CircInteractome, circbank, and circAtlas. Utilizing TargetScan, ENCORI, and miRWalk, the target mRNAs of the miRNAs were uncovered. Ultimately, 73 FerRGs were obtained, and the ceRNA regulatory network was constructed. Furthermore, MAPK3 and CD44 were significantly associated with prognosis. qRT-PCR results confirmed that has_circ_0015278 was significantly overexpressed in FLT3-ITD mutant-type AML. In summary, we constructed the hsa_circ_0015278/miRNAs/FerRGs signaling axis, which provides new insight into the pathogenesis and therapeutic targets of AML with FLT3-ITD mutation.

Chitosan-Gelatin Scaffolds Incorporating Decellularized Platelet-Rich Fibrin Promote Bone Regeneration.

Platelet-rich fibrin (PRF), which functions as a growth factor carrier, has been extensively used to promote soft and hard tissue repair. However, whether decellularized PRF (DPRF) maintains its bioactive effects is unknown. Chitosan/gelatin(C/G) base scaffolds display appropriate biocompatibility and mechanical properties, but they lack biological activity. Thus, the incorporation of DPRF into the C/G scaffold can theoretically improve both the bioactivity of the C/G scaffold and the strength of PRF. In this study, DPRF was prepared using a method combining repeated freeze-thawing and enzymatic digestion. Also, DPRF-loaded chitosan-gelatin scaffolds (C/G/DPRF) were fabricated, using C/G scaffolds as controls. The osteogenic potential of scaffolds was investigated in vitro and in vivo. Compared with the C/G scaffold, C/G/DPRF had a larger pore size (280.8 ± 11.7 µm vs 235.0 ± 11.6 µm; P < 0.05), increased water uptake ratio (13.90 ± 0.09 vs 11.05 ± 0.10; P < 0.05), and similar porosity (90.50 ± 0.87 vs 90.65 ± 0.67; P > 0.05) but reduced compressive modulus (0.81 ± 0.02 MPa vs 1.17 ± 0.05 MPa; P < 0.05). In vitro, C/G/DPRF scaffolds accelerated attachment, proliferation, and osteogenesis-related marker expression of bone marrow stem cells. In vivo, C/G/DPRF scaffolds led to enhanced bone healing and defect closure in a rat calvarial defect model. Thus, we concluded that DPRF remains bioactive and the prepared C/G/DPRF scaffold is a promising material for bone regeneration.

Identification of the Perturbed Metabolic Pathways Associating With Renal Fibrosis and Evaluating Metabolome Changes of Pretreatment With Astragalus polysaccharide Through Liquid Chromatography Quadrupole Time-Of-Flight Mass Spectrometry.

Renal fibrosis is glomerulosclerosis and renal tubulointerstitial fibrosis caused by the increase of interstitial cells and intercellular substances and the accumulation of extracellular matrix, and is a common pathological manifestation of renal disease progressing to end-stage renal failure. It has proved that Astragalus polysaccharide (AP) has curative effect on renal disease; however, its therapeutic mechanism on renal fibrosis is still unclear. Metabolomics approach provides an opportunity to identify novel molecular biomarkers. The purpose of this study is to study the changes of serum metabolic profile of rats with unilateral tubal ligation and replication of renal fibrosis model and the therapeutic effect of AP on it. The blood samples of rats in the control group, renal fibrosis model group, and AP treatment group collected on the 21st day were analyzed by metabolomics method based on UPLC-Q-TOF-MS. Principal component analysis (PCA) showed that clustering was obvious and significantly separated, and paired partial least squares discriminant analysis (OPLS-DA) was used for further analysis. Combined with the network databases such as HMDB and KEGG and a large number of literatures, 32 potential biomarkers related to renal fibrosis were preliminarily screened out and further verified by MS/MS secondary debris information. After pretreatment with AP, 20 biomarkers were significantly regulated, and correlated with phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, etc. It also revealed the metabolic changes of renal fibrosis and intervention effect of AP. These data uncover a link between metabolism and the molecular mechanism with potential implications in the understanding of the intervention effect of AP. Conclusively, UPLC-Q-TOF-MS-based metabolomics can be valuable and promising strategy to understand the disease mechanism and natural drug pretreatment.

Implementation Efficiency of Corporate Social Responsibility in the Construction Industry: A China Study.

Corporate social responsibility (CSR), as companies' commitment to the sustainable development of the whole society, is an important approach for construction companies to respond to the emerging social and environmental issues. As the improvement of CSR efficiency leads to the reduction of CSR cost, CSR efficiency is becoming increasingly prominent for construction companies. In this research, the three-stage data envelopment analysis (DEA) model is adopted to analyze the CSR efficiency of Chinese construction companies in the period of 2012⁻2016. The findings of this research are as follows: (1) the efficiency of the Chinese construction companies in fulfilling CSR has not yet reached an optimal level; (2) the effect of institutional factors on CSR efficiency is complex and non-linear; and (3) the improvement of the CSR efficiency in the Chinese construction industry relies on both optimizing the institutional environment and enhancing the management capacity of CSR efficiency. These findings can not only provide empirical evidence for the government to formulate targeted policy-making regarding marketization to promote construction companies' efficient commitment of CSR, but also provide construction company managers a valuable reference to benchmarking the CSR efficiency to help them find self-improvement ways to improve CSR efficiency performance.