PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis

Dimethylation of histone H3 lysine 9 （H3K9me2） is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.

Computed tomography-based delta radiomics of tumor core_edge combination for systemic treatment response evaluation in pancreatic cancer

Background:As a systemic disease,pancreatic cancer(PC)can be treated systemically to raise the R0 resection rate and enhance patient prognosis.The best ways to assess the treatment response to systemic treatment of patients with PC are still lacking.Methods:A total of 122 PC patients were enrolled;25 of these patients were used as an independent testing set.According to the pathologic response,PC patients were classified into the responder and nonresponder groups.The whole tumor,core,edge,and peritumoral were segmented from the enhanced computed tomography(CT)images.Machine-learning models were created by extracting the variations in radionics features before and after therapy(delta radiomics features).Finally,we compared the performance of models based on radiomics features,changes in tumor markers,and radiologic evaluation.Results:The model based on the core(area under curve[AUC]=0.864)and edge features(AUC=0.853)showed better performance than that based on the whole tumor(AUC=0.847)or peritumoral area(AUC=0.846).Moreover,the tumor core_edge combination model(AUC=0.899)could better increase confidence in treatment response than using either of them alone.The accuracies of models based on changes in tumor markers and radiologic evaluation were relatively poorer than of the radiomics model.Moreover,Patients predicted to respond to therapy using the radiomics model showed a relatively longer overall survival(43 vs 27 months),although there were no significant differences(P=.063).Conclusions:The tumor core_edge combination delta radiomics model is an effective approach to evaluate pathologic response in PC patients with systemic treatment.

Model-based adaptive non-null interferometry for freeform surface metrology

A model-based adaptive non-null interferometry （MANI） is proposed for steep optical freeform surfaces in situ testing. The deformable mirror （DM） affording the flexible compensation is monitored with the beam in the interferometer by a wavefront sensor. The residual wavefront aberration in the non-null interferogram is eliminated by the multi-configuration ray tracing algorithm based on the system model, especially the DM surface model. The final figure error can be extracted together with the surface misalignment aberration correction. Experiments proving the feasibility of the MANI are shown.

Glucocorticoid receptor–IRS-1 axis controls EMT and the metastasis of breast cancers

Glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes that are important for various biological functions, including tumor growth and metastatic progression. However, the cellular and biological effects of GR remain poorly understood. Here, we investigated the role of GR and its underlying mechanism in mediating breast cancer cell survival and metastasis. We observed that the GR levels were increased in drug-resistant breast cancer cells and in metastatic breast cancer samples. GR promoted tumor cell invasion and lung metastasis in vivo. The GR expression levels were negatively correlated with the survival rates of breast cancer patients. Both ectopic expression and knockdown of GR revealed that GR is a strong inducer of epithelial-to-mesenchymal transition (EMT), which is consistent with its effects on cell survival and metastasis. GR suppressed the expression of insulin receptor substrate 1 (IRS-1) by acting as an IRS-1 transcriptional repressor. In addition, GR has an opposite effect on the expression levels of IRS-2, indicating that GR is able to differentially regulate the IRS-1 and IRS-2 expression. The cellular and biological effects elicited by GR were consistent with the reduced levels of IRS-1 observed in cancer cells, and GR-mediated IRS-1 suppression activated the ERK2 MAP kinase pathway, which is required for GR-mediated EMT. Taken together, our results indicate that GR–IRS-1 signaling axis plays an essential role in regulating the survival, invasion, and metastasis of breast cancer cells.

Calculation model for water influx and controlled reserves for CBM wells with high water yield

Compared with conventional gas reservoir,percolation mechanism of coalbed methane(CBM)is completely different,it is remarkably affected by adsorption/desorption performance,pressure variation and coalbed characteristics.Then it is difficult to calculate the controlled reserves of CBM wells.Moreover,the connection of edge-bottom water or interbedded water by fractures or faults may largely increase the water yield and drainage period,leading to obvious water invasion in some CBM wells.There are few literature about the predicted production for CBM wells with high water yield.Focusing on the unconventional CBM reservoir,methods of pseudo geological reserves and production index curves are adopted to establish the calculation model of water influx and controlled reserves.It further confirms that the calculation model is successfully applicated on the CBM wells at the middle part of Qinshui Basin in China.