BACKGROUND:Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE:To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS:Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION:Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.

OBJECTIVE To explore the ameliorative effect and mechanism of emodin on infectious preterm rats. METHODS The infectious preterm rat model was established and divided into model group， emodin group （60 mg/kg， i.g.）， IKK activation group （2 μg pcDNA3.1-IKK recombinant plasmid via tail vein）， emodin+IKK activation group （i.g. 60 mg/kg emodin+2 μg pcDNA3.1-IKK recombinant plasmid via tail vein）， with 14 rats in each group. Another 14 pregnant female rats were set up as control group. Each group received corresponding intervention for 7 days. The muscle tension of the uterine muscle strip， and the indicator levels of serum inflammation [interleukin 1β （IL-1β）， IL-6， tumor necrosis factor α（TNF-α）] and oxidative stress [superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）] were detected； the pathological morphological changes of uterine tissue in rats were observed； the protein expressions of NOD-like receptor protein 3 （NLRP3）， cleaved-caspase-1 and IKK/IκB/NF-κB signaling pathway were detected. RESULTS Compared with control group， a large number of inflammatory cells infiltrated into the smooth muscle layer of uterus in model group with irregular cell distribution； the uterine muscle strip muscle tone， serum levels of IL-1β， IL-6， TNF-α and MDA， protein expressions of NLRP3， cleaved-caspase-1， IKK， IκB and NF-κB p65 in uterine tissue were significantly increased in model group， and the serum levels of SOD and CAT were significantly decreased （P＜0.05）. Compared with the model group， the infiltration of inflammatory cells in the uterine smooth muscle layer was reduced in the emodin group， and all quantitative indexes were significantly improved （P＜0.05）； the infiltration of inflammatory cells in the uterine smooth muscle layer was increased in IKK activation group， and all quantitative indexes further deteriorated （P＜0.05）. Activation of IKK could significantly reduce the improvement effect of emodin on the above indexes in infectious preterm rats （P＜0.05）. CONCLUSIONS Emodin can relieve inflammation and oxidative stress in infectious preterm rats by inhibiting the IKK/IκB/NF-κB signaling pathway， thus improving uterine smooth muscle contraction.

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.