Immune-Related Genes can Serve as Potential Biomarkers for Predicting Severe Acute Pancreatitis.

We aimed to investigate immune-related candidate genes for predicting the severity of acute pancreatitis (AP). RNA sequencing profile GSE194331 was downloaded, and differentially expressed genes (DEGs) were investigated. Meanwhile, the infiltration of immune cells in AP were assessed using CIBERSORT. Genes related with the infiltration of immune cells were investigated using weighted gene co-expression network analysis (WGCNA). Furthermore, immune subtypes, micro-environment, and DEGs between immune subtypes were explored. Immune-related genes, protein-protein interaction (PPI) network, and functional enrichment analysis were further performed. Overall, 2533 DEGs between AP and healthy controls were obtained. After trend cluster analysis, 411 upregulated and 604 downregulated genes were identified. Genes involved in two modules were significantly positively related to neutrophils and negatively associated with T cells CD4 memory resting, with correlation coefficient more than 0.7. Then, 39 common immune-related genes were obtained, and 56 GO BP were enriched these genes, including inflammatory response, immune response, and innate immune response; 10 KEGG pathways were enriched, including cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, and IL-17 signaling pathway. Genes, including S100A12, MMP9, IL18, S100A8, HCK, S100A9, RETN, OSM, FGR, CAMP, were selected as genes with top 10 degree in PPI, and the expression levels of these genes increased gradually in subjects of healthy, mild, moderately severe, and severe AP. Our findings indicate a central role of immune-related genes in predicting the severity of AP, and the hub genes involved in PPI represent logical candidates for further study.

Study of a position-sensitive scintillator neutron detector prototype based on 6LiF/ZnS scintillator and silicon photomultiplier arrays readout.

Due to the shortage of the 3He gas and its rapidly increasing price, scintillator detectors, the advantages of which are high spatial resolution and capability of detection in real time, become widely used in many neutron instruments. In this work, a position-sensitive neutron detector consisting of a 6LiF/ZnS scintillation screen and a silicon photomultiplier array linked to a capacitive network to detect the positions of incident neutrons, is constructed and tested. To evaluate the detector performance, a series of neutron beam experiments with the detector prototype were performed in the BL20 at the China Spallation Neutron Source. The spatial resolution was measured, and the energy-selective neutron imaging and Bragg edge measurements of a 316L stainless steel sample were performed. A sub-millimeter spatial resolution could be obtained for the detector prototype under study. The detector with such a high spatial resolution is promising for applications in neutron scattering experimental installations, especially for neutron single-crystal diffractometers.

The Expression of IGFBP6 after Spinal Cord Injury: Implications for Neuronal Apoptosis.

IGFBP6, a member of the insulin-like growth factor-binding proteins family that contains six high affinity IGFBPs, modulates insulin-like growth factor (IGF) activity and also showed an independent effect of IGF, such as growth inhibition and apoptosis. However, the role of IGFBP6 in spinal cord injury (SCI) remains largely elusive. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IGFBP6 expression in the spinal cord. Our results showed that IGFBP6 was upregulated significantly after SCI, which was paralleled with the levels of apoptotic proteins p53 and active caspase-3. Immunofluorescent labeling showed that IGFBP6 was co-localizated with active caspase-3 and p53 in neurons. To further investigate the function of IGFBP6, an apoptosis model was established in primary neuronal cells. When IGFBP6 was knocked down by specific short interfering RNA (siRNA), the protein levels of active caspase-3 and Bax as well as the number of apoptotic primary neurons were significantly decreased in our study. Taken together, our findings suggest that the change of IGFBP6 protein expression plays a key role in neuronal apoptosis after SCI.

PKC iota promotes cellular proliferation by accelerated G1/S transition via interaction with CDK7 in esophageal squamous cell carcinoma.

Protein kinase C iota (PKCι) has been shown to play an important role in tumorigenesis of many cancers. It was reported that frequent amplification and overexpression of PKCi were correlated with resistance to anoikis in primary esophageal squamous cell carcinomas (ESCC). In this study, we clarified a novel role of PKCι on the cell cycle progression and proliferation in ESCC. Western blot and immunohistochemistry (IHC) analysis showed that the expression of PKCι was higher in ESCC tumor tissues and cell lines. Meanwhile, IHC stain revealed that PKCι was positively correlated with clinical pathologic variables such as tumor size, tumor grade, and tumor invasion, as well as ki67. Immunoprecipitation and immunofluorescence assay revealed that PKCι/CDK7 has the physical interaction and were co-located in the cell nucleus. And this direct interaction could increase the phosphorylation level of CDK7. In vitro studies such as starvation and refeeding assay along with PKCι-shRNA transfection assay demonstrated that PKCι expression promoted proliferation of ESCC cells. And knocking PKCi down by silencing RNA (siRNA) significantly caused cell cycle arrest at G0/G1 phase, decreased rate of colony formation, and alleviated cellular apoptosis. This research provide new insights into PKCi signaling to more deeply understand its cancer-promoting function in ESCC.

Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-κB activation in ulcerative colitis.

Sam68 (Src-associated substrate during mitosis of 68 KDa), also known as KHDRBS1 (KH domain containing, RNA binding, signal transduction associated 1), belongs to the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Sam68 is implicated in various cellular processes including RNA metabolism, apoptosis, signal transduction. Previous researches demonstrated that Sam68 regulated nuclear transcription factor kappa B (NF-κB) to induce inflammation. However, the expression and biological functions of Sam68 in ulcerative colitis (UC) are not clear. In this study, we reported for the first time that Sam68 was up-regulated in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced mouse colitis model, we observed the overexpression of Sam68 accompanied with increased levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators (p-p65 and p-IκB) in colitis IECs. Co-localization of Sam68 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of NF-κB-mediated IEC apoptosis. Applying TNF-α-treated HT-29 cells as an in vitro IEC inflammation model, we confirmed the positive correlation amomg Sam68, NF-κB activation and caspase-dependent apoptosis. Immunofluorescence and immunoprecipitation assay identified nuclear translocation and physical interaction of Sam68 and NF-κB subunits in TNF-α-treated HT-29 cells. Besides, depletion of Sam68 by RNA interference greatly alleviated NF-κB activation and apoptosis in TNF-α-treated HT-29 cells. Taken together, our results indicated that Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-κB activation in UC.

ErbB3 binding protein 1 (EBP1) participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.

ErbB3 binding protein-1 (EBP1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, differentiation and apoptosis. Previous data demonstrated that EBP1 regulates phosphorylation of Akt to drive tumor progress. However, the expression and biological functions of EBP1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that EBP1 was down-regulated in intestinal epithelial cell (IECs) of patients with UC. In DSS-induced colitis, we observed the down-regulation of EBP1 accompanied with the elevated levels of proinflammatory cytokines (IL-1ß, IL-6 and IL-8) and Akt activation indicators (phosphorylated Akt) in colitis IECs, indicating the possible involvement of EBP1 in regulation of intestinal inflammation via mediating Akt in UC. Employing the TNF-α-treated HT-29 cells as an IEC inflammatory model, we confirmed the negative correlation of EBP1 with Akt activation and Akt-dependent inflammation progress in vitro. EBP1 knocking down and over-expression significantly regulated TNF-α-induced Akt activation and proinflammatory cytokines expression in HT-29 cells. Taken together, our data suggested that EBP1 participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.

[Studies on corrosion property of the anodic coating on the Mg alloy by micro-FTIR mapping].

Micro-FTIR mapping technology was used to monitor the amount and distribution of Mg(OH)2 on the anodic coating of magnesium alloy which was immersed in the 7.3 Wt% Na2SO4 solution for different time. In the solution, part of the MgO on the surface of the Mg alloy could gradually transform into Mg(OH)2 which could be detached from the Mg alloy surface and dis- solved into the solution. With immersion time of 2 h in 7.3 Wt% Na2SO4 solution 2h, FTIR mapping results showed that FTIR absorption signal of Mg(OH)2 was strongest and Mg(OH)2 was most on the surface of the anodic coating. After 4 hours, the content of Mg(OH)2 began to decrease, and the Mg alloy was etched gradually. The FTIR mapping results of another component Al2O3 with immersion time were almost similar to those of Mg(OH)2. The impedance of the oxide film was also analyzed using electrochemical impedance spectroscopy. It showed that the impedance changed with the immersion time and conformed to the corrosion law of the oxide coating. This research has a good guidance and application value for characterization of the anodic coating on magnesium alloy.

Involvement of guanylate cyclase and K+ channels in relaxation evoked by ferulate nitrate in rat aorta artery.

Vasorelaxant properties of N-2-(ferulamidoethyl)-nitrate (ferulate nitrate, FLNT), a newly synthesized nitrate, were compared with those of isosorbide dinitrate, nicorandil, nitroglycerin, and 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) in rat aorta pre-contracted by phenylephrine. FLNT produced vasorelaxation in a concentration-dependent manner (0.1 - 100 µM). The degree of relaxation induced by FLNT was similar to that induced by isosorbide dinitrate. In addition, removal of endothelium did not affect the relaxant effect of FLNT. FLNT caused a rightward shift of the cumulative concentration-response curves of phenylephrine and reduced the maximal efficacy of contraction. 1H-[1,2,4]Oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM) and K(+)-channel blockers charybdotoxin (CHT, 0.1 µM) and BaCl(2) (1 µM) reduced the relaxant effect of FLNT in the endothelium-denuded arteries, whereas glibenclamide (1 µM) and 4-aminopyridine (1 mM) failed to influence FLNT-induced vasorelaxation. Furthermore, in the presence of ODQ, both CHT (0.1 µM) and BaCl(2) (1 µM) still significantly reduced the relaxation evoked by FLNT. Pretreatment of vessels with hydroxocobalamin, a nitric oxide scavenger, abolished the FLNT effect. These findings demonstrate that FLNT induces relaxation of the rat aorta rings endothelium-independently. Furthermore, we demonstrated that FLNT-induced vasorelaxation is related to its stimulation of soluble guanylate cyclase and activation of K(+) channels.