Tissue regeneration requires coordination between resident stem cells and local niche cells1,2. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity3 was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol. We identified and isolated different senescent cell types from damaged muscles of young and old mice. Deeper transcriptome, chromatin and pathway analyses revealed conservation of cell identity traits as well as two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and ageing. Senescent cells create an aged-like inflamed niche that mirrors inflammation associated with ageing (inflammageing4) and arrests stem cell proliferation and regeneration. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. By contrast, transplantation of senescent cells delays regeneration. Our results provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle, and uncover unproductive functional interactions between senescent cells and stem cells in regenerative niches that can be overcome. As senescent cells also accumulate in human muscles, our findings open potential paths for improving muscle repair throughout life.
In this work, we doped sulfur into the oxygen layers of a lithium-rich layered metal oxide (LNMO) cathode material for lithium-ion batteries to improve the structural stability and cycling performance.
The efficiency of dolomite to remove phosphate from aqueous solutions was investigated. The experimental results showed that the removal of phosphate by dolomite was rapid (the removal rate over 95% in 60 min) when the initial phosphate concentration is at the range of 10-50 mg/L. Several kinetic models including intraparticle diffusion model, pseudo-first-order model, Elovich model, and pseudo-second-order model were employed to evaluate the kinetics data of phosphate adsorption onto dolomite and pseudosecond-order model was recommended to describe the adsorption kinetics characteristics. Further analysis of the adsorption kinetics indicated that the phosphate removal process was mainly controlled by chemical bonding or chemisorption. Moreover, both Freundlich and Langmuir adsorption isotherms were used to evaluate the experimental data. The results indicated that Langmuir isotherm was more suitable to describe the adsorption characteristics of dolomite. Maximum adsorption capacity of phosphate by dolomite was found to be 4.76 mg phosphorous/g dolomite. Thermodynamic studies showed that phosphate adsorption was exothermic. The study implies that dolomite is an excellent low cost material for phosphate removal in wastewater treatment process.
Copy number variation (CNV) and abnormal expression of microRNAs (miRNAs) always lead to deregulation of genes in cancer, including gastric cancer (GC). However, little is known about how CNVs affect the expression of miRNAs. By integrating CNV and miRNA profiles in the same samples, we identified eight miRNAs (miR-1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2) that were located in the amplified regions and were upregulated in GC. In particular, amplification of miR-23a-27a-24-2 cluster and miR-181c-181d cluster frequently occurred at 19p13.13 and were confirmed by genomic real-time PCR in another 25 paired GC samples. Moreover, in situ hybridization (ISH) experiments represented that mature miR-23a was increased in GCs (75.5%, 40/53) compared with matched normal tissues (28.6%, 14/49, P = 0.001). Knocking down of miR-23a expression inhibited BGC823 cell growth in vitro and in vivo. In addition, the potential target genes of miR-23a were investigated by integration of mRNA profile and miRNA TargetScan predictions, we found that upregulation of miR-23a and downregulation of metallothionein 2A (MT2A) were detected simultaneously in 70% (7/10) of the miRNA and mRNA profiles. Furthermore, an inverse correlation between miR-23a and MT2A expression was detected in GCs and normal tissues. Through combining luciferase assay, we confirmed that MT2A is a potential target of miR-23a. In conclusion, these results suggest that integration of CNV-miRNA-mRNA profiling is a powerful tool for identifying molecular signatures, and that miR-23a might play a role in regulating MT2A expression in GC.
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