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SET domain containing lysine methyltransferase 7 (SETD7) belongs to the protein lysine methyltransferase family and can catalyze the monomethylation of histone H3K4, which plays a vital role in the regulation of cell cycle, cell differentiation, DNA damage response and chromatin remodeling through K/R-S/T-K (K is lysine residue) sites and the recognition of substrates mediated by SET, i-SET, and

Although emerging evidence suggests that developmental dyslexia shows deficits in visual-spatial attention, previous studies have also confirmed that visual-spatial attention may be particularly important for reading among Chinese children with dyslexia. However, the visual-spatial attention deficit of dyslexic Chinese children has not been fully investigated. Therefore, the present study employed the cue-target paradigm and examined whether the earlier processing of visual-spatial attention deficit would be found in Chinese children with dyslexia. More importantly, we combined read level match design to determine the process of visual-spatial attention in Chinese children with dyslexia related to developmental delay or cognitive deficits. Results showed that developmental dyslexia (DD) group exhibited no cueing effect in the cue-target tasks when the stimulus onset synchronies (SOAs) were set to 100 ms, as compared with the children’s chronological age (CA). With the cueing effect as the index, we also observed that the CA group had a robust facilitation effect in early processing of visual-spatial attention. Importantly, the DD group presented an impaired facilitation effect as the same reading level (RL) group controls when SOAs were 100 ms and 350 ms. These findings suggested that impaired facilitation effect in Chinese dyslexic children is due to a developmental delay.

A single-shot imaging system with multiple frames has been developed, which can record sequential multiple frames by delaying multiple optical images with fiber bundles and then capturing the images with a single intensified camera. The observed optical object is imaged through four lenses onto the end faces of four sets of fiber bundles. These fiber bundles with different lengths can provide different delays for delivering optical images, which determine the inter-frame separation times. The optical images exported from the fiber bundles are captured with a single intensified CMOS camera simultaneously. This imaging system has been applied for investigating the dynamic x-ray spot of the rod-pinch diode via a combination of scintillators, which are used to convert x-ray images to optical images. Four sequential x-ray images in a single shot have been obtained, which show the dynamic development of the rod-pinch x-ray spot. The results experimentally reveal the dynamics of the electrons flow bombarding the rod, which roughly agrees with the theoretical modeling of the rod-pinch diode.

The sesquiterpene lactone costunolide (CTL) has attracted much attention due to its antitumor effect on a variety of malignant tumors. However, the effect of CTL on hypopharyngeal squamous cell carcinoma (HSCC) remains unclear. This study aimed to examine the effects of this sesquiterpene lactone on HSCC FaDu cells.The FaDu cell line was treated with CTL and/or cisplatin. CCK-8 was used to examine cell viability. Annexin-FITC/PI and Hoechst 33258 staining were used to measure apoptosis. Reactive oxygen species (ROS) were analysed by MitoSOX Red staining. Protein expression was examined by Western blotting.CTL (0, 2, 4, 6, 8, 10, 20, 30, and 40 µM) dose-dependently induced cytotoxicity in FaDu cells. CTL increased ROS production and induced apoptosis in FaDu cells. Moreover, CTL synergized with cisplatin to induce apoptosis in FaDu cells. In addition, the caspase inhibitor Z-DEVD-FMK attenuated CTL-induced apoptosis. Western blot analysis showed that CTL increased the expression levels of cleaved caspase-3 and Bax and decreased the expression levels of Bcl-2, phospho-AKT and phospho-NF-κB.In conclusion, these data demonstrate that CTL induced apoptosis and enhanced cisplatin-induced cytotoxicity in HSCC FaDu cells.

The adrenergic system contributes to the stress‐induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE‐induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE‐induced phosphorylation of cAMP response element‐binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR‐373 and transcriptionally activated its expression. miR‐373 expression was shown to be necessary for NE‐induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR‐373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1–miR‐373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer., We propose a NE–CREB1–miR‐373 signaling axis in human colon cancer cells. NE promotes the progression of colon cancer via CREB1 activity‐dependent transcription, enhancing the expression of oncogenic miR‐373 and reducing the expression of the miR‐373 targets APC and TIMP2. This novel NE‐CREB1‐miR‐373 signaling axis may potentially serve as a new therapeutic target for colorectal cancer.

Neutron and x-ray imaging are essential ways to diagnose a pulsed radiation source. The three-dimensional (3D) intensity distribution reconstructed from two-dimensional (2D) radiation images can significantly promote research regarding the generation and variation mechanisms of pulsed radiation sources. Only a few ([Formula: see text]) projected images at one moment are available due to the difficulty in building imaging systems for high-radiation-intensity and short-pulsed sources. The reconstruction of a 3D source with a minimal number of 2D images is an ill-posed problem that leads to severe structural distortions and artifacts of the image reconstructed by conventional algorithms. In this paper, we present an iterative method to reconstruct a 3D source using spherical harmonic decomposition. Our algorithm improves the representation ability of spherical harmonic decomposition for 3D sources by enlarging the order of the expansion, which is limited in current analytical reconstruction algorithms. Prior knowledge of the source can be included to obtain a reasonable solution. Numerical simulations demonstrate that the reconstructed image quality of the iterative algorithm is better than that of the analytical algorithm. The iterative method can suppress the effect of noise in the integral projection image and has better robustness and adaptability than the analytical method.

Background Colorectal cancer (CRC) is one of the most common malignant tumors with high recurrence and mortality. Thymine DNA glycosylase (TDG) is one of the key molecules involved in base excision repair pathway. Recently, more and more attentions have been paid to the role of TDG on tumor development. However, the specific functions of TDG in CRC remain unclear. Methods The biological functions of TDG and DNA methyltransferase 3 alpha (DNMT3A) in CRC were evaluated using migration and invasion assay. Tumor metastasis assay was performed in nude mice to detect the role of TDG in vivo. The interaction of TDG with DNMT3A was determined by co-immunoprecipitation (Co-IP). Chromatin immunoprecipitation analysis (CHIP) was applied to predict the DNA binding site of DNMT3A. We also performed methylation-specific PCR (MSP) to detect the changes in TIMP2 methylation levels. Results We found that TDG could inhibit the migration and invasion of human colon cancer cells in vitro and in vivo. TDG promoted the ubiquitination and degradation of DNMT3A by binding with it. Interference with siDNMT3A also inhibited the migration and invasion of human colon cancer cells. Further ChIP, MSP, and rescue experiments data confirmed that TDG accelerated the degradation of DNMT3A, and then significantly regulated the transcription and expression of TIMP2, thereby affecting the migration and invasion of human colon cancer cells. Conclusion Our findings reveal that TDG inhibit the migration and invasion of human colon cancer cells through DNMT3A-TIMP2 axis which may be potential therapeutic strategies in the development and treatment of CRC.

Little is known about the role of the spleen in mediating systemic inflammatory responses in severe acute pancreatitis (SAP). We investigated the role played by the spleen in rats after SAP induction. Splenectomy was performed at designated time points after SAP induction. Pancreatic tissue and serum samples were collected and subjected to histologic, immunohistochemical, and immunologic analyses. After SAP induction, the splenic immune response was enhanced during SAP progression, as shown by the increased diameter of the splenic periarterial lymphatic sheath and the thickness of the splenic marginal zone. Rats with splenectomy developed acute pancreatitis more slowly than rats without splenectomy. In addition, pancreatic tissues of rats with splenectomy contained lower levels of serum amylase, tumor necrosis factor-α, and IL-6 and exhibited less acinar cell death, leukocyte infiltration, and interstitial edema than those of rats without splenectomy. Compared with splenectomy alone, cotreatment with splenectomy and the administration of splenic cells originating from a rat with SAP 12 hours after induction increased systemic inflammation in SAP rats. Splenic factors exacerbated SAP-associated liver and lung injury and accentuated intestinal mucosal barrier dysfunction. Splenectomy altered the serum cytokine profile in rats with SAP. In a rat model of SAP, the spleen exacerbated the systematic inflammatory responses and injury to multiple organs, indicating a new role for the spleen in SAP.

DNA-binding protein A (dbpA) is reported to be upregulated in many cancers and associated with tumor progress. The present study aimed to investigate the role of dbpA in 5-Fluorouracil (5-FU)-resistant and Oxaliplatin (L-OHP)-resistant colorectal cancer (CRC) cells. We found that 5-FU and L-OPH treatment promoted the expression of dbpA. Enhanced dbpA promoted the drug resistance of SW620 cells to 5-FU and L-OHP. DbpA knockdown inhibited cell proliferation, induced cell apoptosis and cell cycle arrested in SW620/5-FU and SW620/L-OHP cells. Besides, dbpA shRNA enhanced the cytotoxicity of 5-FU and L-OHP to SW620/5-FU and SW620/L-OHP cells. Meanwhile, dbpA shRNA inhibited the activation of the Wnt/β-catenin pathway that induced by 5-FU stimulation in SW620/5-FU cells. Activation of the Wnt/β-catenin pathway or overexpression of Chk1 abrogated the promoting effect of dbpA downregulation on 5-FU sensitivity of CRC cells. Importantly, downregulation of dbpA suppressed tumor growth and promoted CRC cells sensitivity to 5-FU in vivo. Our study indicated that knockdown of dbpA enhanced the sensitivity of colorectal cancer cells to 5-FU via Wnt/β-catenin/Chk1 pathway, and DbpA may be a potential therapeutic target to sensitize drug resistance colorectal cancer to 5-FU and L-OHP. This article is protected by copyright. All rights reserved.

Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract with a high degree of malignancy and poor clinical prognosis. There is considerable evidence that long non-coding RNA (lncRNA) is associated with the progression of GC. However, as a lncRNA, the relationship between LINC01224 and GC remains unclear. Methods: The expression and correlation of LINC01224, miR-193a-5p and YES1 in GC were analyzed by using the database information of TCGA and GTEx. We collected tumor tissues and paired paracancerous tissue specimens from 76 GC patients to detect the expression levels of LINC01224, miR-193a-5p and YES1, and further analyzed the correlation between LINC01224 and clinicopathological features. The effect of LINC01224 on GC cell phenotype was detected by CCK-8, EdU, flow cytometry and clone formation. A subcutaneous tumor model was established to analyze the growth of GC cells after LINC01224 gene knockout. The interaction among LINC01224, miR-193a-5p and YES1 were determined by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay. Results: We found that a novel oncogene LINC01224 was highly expressed in GC, which was positively correlated with TNM staging and shortened overall survival time. LINC01224 gene knockdown inhibits GC cell proliferation, induces apoptosis and G1 phase arrest. Mechanistically, LINC01224 promotes the expression of YES1 in GC cells by competitively binding to miR-193a-5p. Interestingly, miR-193a-5p inhibitors and up-regulation of YES1 reversed the effects of knock-down LINC01224 on the proliferation, apoptosis and cell cycle of GC cells, whereas transfected mutant LINC01224 plasmids did not. Conclusion: Our findings confirm that LINC01224 is a potential prognostic marker of GC. LINC01224/miR-193a-5p/YES1 axis plays a vital role in the proliferation, cell cycle and apoptosis of GC cells, which provides a potentially important diagnostic and therapeutic target for GC. Funding Statement: This study was supported by scientific and technological project of Xi'an[2017113SF/YX007(11)], Shaanxi Provincal project of scientific and technological innovation team (2017KCT-28) and Shaanxi Natural Science Foundation (2020JQ-947), NSFC (8142012), Shaanxi Natural Science Foundation (2015JQ8321), Shaanxi Natural Science Foundation (2019JM-547), Operating Expenses of Basic Scientific Research Project of Xi'an Jiaotong University (xzy012019112), scientific and technological project of Xi'an (2019114613YX001SF03). Declaration of Interests: The authors declare that they have no conflicts of interests. Ethics Approval Statement: The study was conducted with the approval of the ethics committee of Shaanxi provincial people's hospital. All patients in the study signed written informed consent before enrollment. All animal experiments were conducted under the international commission's guidelines for the care and use of laboratory animals with a protocol approved by the Ethics Committee of Shaanxi Provincial People's Hospital.

Background: There is an urgent need for the identification of new, clinically useful biomarkers of CRC to enhance diagnostic and prognostic capabilities. Methods: We performed proteomic profiling on serum samples from paired pre- and post-operative CRC patients, colorectal polyps patients and healthy controls using an approach combining magnetic bead-based weak cation exchange and matrix-assisted laser desorption ionization-time of flight mass spectrometry. We next performed liquid chromatography-electrospray ionization-tandem mass spectrometry to identify the proteins and selected potential biomarker based on bioinformatics analysis of the TCGA and GEO dataset. We examined SETD7 expression in serum and tissue samples by ELISA and immunohistochemistry respectively and explored the biological function of SETD7 in vitro. Findings: 85 differentially expressed peptides were identified. Five peptides showing the most significant changes in abundance across paired pre- and post-operation CRC patients, colorectal polyps patients and healthy controls were identified as peptide regions of FGA, MUC5AC and SETD7. Bioinformatics analysis suggested that the up-regulation of SETD7 in CRC is relatively specific. Validation studies showed that SETD7 expression increased from healthy controls to those with colorectal polyps and finally CRC patients, and decreased after surgery. The sensitivity and specificity of SETD7 were 92.17% and 81.08%, with a high diagnostic value (AUC = 0.9477). In addition, SETD7 expression was significantly correlated with tumor stage and microsatellite instability. Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest and increased apoptosis. Interpretation: Our data indicate that SETD7 could serve as a potential diagnostic and prognostic biomarker for CRC. Keywords: Colorectal cancer, Proteomics, Serum biomarker, SETD7

Hepatocellular carcinoma (HCC) has a dismal prognosis in part because of multi-drug resistance (MDR). Baicalein is a flavonoid extracted from Radix Scutellariae with anti-HCC activity. We tested the effects of Baicalein on multi-drug resistant HCC cells (Bel7402/5-FU) known to be resistant to the anticancer drugs 5-FU and Epirubicin. Flow cytometry analysis showed that treatment with 5??g/ml and 10??g/ml Baicalein resulted in increases in the intra-cellular concentrations of Rho123 and Epirubicin in the corresponding group of cells compared to untreated cells, illustrating that Baicalein reverses MDR in Bel7402/5-FU cells. Bel7402/5-FU cells displayed increased P-glycoprotein (P-gp)-mediated drug efflux. However, this efflux was inhibited in cells pre-incubated in Baicalein for 48?h. Moreover, Baicalein induced apoptosis and autophagy and decreased P-gp and Bcl-xl expression levels. All of these results indicate that Baicalein can reverse P-gp-mediated MDR in HCC and may thus be useful for the treatment of drug-resistant HCC.

Accumulating studies confirmed that luteolin, a common dietary flavonoid which is widely distributed in plants and has diverse beneficial biological function, including anti-oxidant, anti-inflammation and anticancer properties. However, the detail mechanisms of luteolin on GC are poorly understood. Here, we investigated the anticancer effect of luteolin in GC cells in vitro and in vivo. Luteolin reduced the cell viability in a time and dose-dependent manner. Luteolin significantly inhibited cell cycle progress, colony formation, proliferation, migration, invasion and promoted apoptosis in vitro and in vivo. Luteolin also regulated these biological effects associated regulators. Mechanically, luteolin treatment regulated Notch1, PI3K, AKT, mTOR, ERK, STAT3 and P38 signaling pathways and modulated a series of miRNAs expression. These findings provide novel insight into the molecular function of luteolin which suggest its potential as a therapeutic agent for human GC.

Although there has been tremendous progress in the treatment of hepatocellular carcinoma over the past decades, multidrug resistance to chemotherapy and targeted therapy remains a major hindrance in its successful management. Multidrug resistance, whether intrinsic or extrinsic, is a multifactorial process that includes enhanced drug efflux, decreased drug uptake, intracellular sequestration, metabolic alterations, aberrant apoptotic and autophagic signaling, changes in tumor microenvironment, and acquisition of stem cell-like properties by the cancer cells. Although many experimental strategies have been developed to overcome drug resistance, translation of the knowledge to the clinic has not been crowned with success. This chapter provides an overview of the role of multidrug resistance in hepatocellular carcinoma and the potential approaches to overcome this obstacle.

Little is known about the role of the spleen in mediating systemic inflammatory responses in severe acute pancreatitis (SAP). We investigated the role played by the spleen in rats after SAP induction. Splenectomy was performed at designated time points after SAP induction. Pancreatic tissue and serum samples were collected and subjected to histologic, immunohistochemical, and immunologic analyses. After SAP induction, the splenic immune response was enhanced during SAP progression, as shown by the increased diameter of the splenic periarterial lymphatic sheath and the thickness of the splenic marginal zone. Rats with splenectomy developed acute pancreatitis more slowly than rats without splenectomy. In addition, pancreatic tissues of rats with splenectomy contained lower levels of serum amylase, tumor necrosis factor-α, and IL-6 and exhibited less acinar cell death, leukocyte infiltration, and interstitial edema than those of rats without splenectomy. Compared with splenectomy alone, cotreatment with splenectomy and the administration of splenic cells originating from a rat with SAP 12 hours after induction increased systemic inflammation in SAP rats. Splenic factors exacerbated SAP-associated liver and lung injury and accentuated intestinal mucosal barrier dysfunction. Splenectomy altered the serum cytokine profile in rats with SAP. In a rat model of SAP, the spleen exacerbated the systematic inflammatory responses and injury to multiple organs, indicating a new role for the spleen in SAP.

PURPOSE Early diagnosis is crucial to improve outcomes for pancreatic cancer patients (PC). The present study is designed to identify differently expressed peptides involved in PC as potential biomarkers. EXPERIMENTAL DESIGN The serum proteome of 22 PC patients, 12 pancreatitis patients (PP), and 45 healthy controls (HC) are analyzed using magnetic bead-based weak cation exchange (MB-WCX) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Next, a supervised neural network (SNN) algorithm model is established by ClinProTools and the candidate biomarker identified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Finally, the candidate biomarker is validated in tissue samples. RESULTS The SNN algorithm model discriminates PC from HC with 92.97% sensitivity and 94.55% specificity. Seventy-six differentially expressed peptides are identified, seven of which are significantly different among PC, PP, and HC (p < 0.05). Only one peak (m/z: 1466.99) tends to be upregulated in samples from HC, PP, and PC, which is identified as region of RNA-binding motif protein 6 (RBM6). In subsequent tissue analysis, it is verified that RBM6 expression is significantly higher in PC tissues than paracancerous tissue. CONCLUSIONS AND CLINICAL RELEVANCE The results indicate that RBM6 might serve as a candidate diagnostic biomarker for PC. CLINICAL RELEVANCE Methods used in this study could generate serum peptidome profiles of PC, PP, and HC, and present an approach to identify potential biomarkers for diagnosis of this malignancy.

Large thick aperture imaging method is proposed to measure the radiation intensity distribution of radiation source whose size is several centimetres. The new method contains two steps which are coded imaging and image reconstruction. Geant4 is used to simulate the coded imaging process. Wiener filter, Lucy-Richardson, Regularized filter, blind deconvolution and CT reconstruction method are realized using Matlab software. Wiener filter and Regularized filter produce artifacts. CT reconstruction method can’t reveal the right size of60Co-γ source because of the overlapping of knife edge images. Both L-R and blind deconvolution are effective. If the aperture is moved 0 mm, 2 mm, 4 mm, 6 mm along x-axis, the reconstruction result using L-R method has a larger correlation coefficient with source image. However, L-R method gets bad result if the aperture rotates more than 1.4°. Under this condition, blind deconvolution is the better choice.

When used in digital radiography, ICCD camera will be inevitably irradiated by x-ray and the output image will degrade. In this research, we separated ICCD camera into two optical-electric parts, CCD camera and MCP image intensifier, and irradiated them respectively on Co-60 gamma ray source and pulsed x-ray source. By changing time association between radiation and the shutter of CCD camera, the state of power supply of MCP image intensifier, significant differences have been observed in output images. A further analysis has revealed the influence of the CCD chip, readout circuit in CCD camera, and the photocathode, microchannel plate and fluorescent screen in MCP image intensifier on image quality of an irradiated ICCD camera. The study demonstrated that compared with other parts, irradiation response of readout circuit is very slight and in most cases negligible. The interaction of x-ray with CCD chip usually behaves as bright spots or rough background in output images, which depends on x-ray doses. As to the MCP image intensifier, photocathode and microchannel plate are the two main steps that degrade output images. When being irradiated by x-ray, microchannel plate in MCP image intensifier tends to contribute a bright background in output images. Background caused by the photocathode looks more bright and fluctuant. Image responses of fluorescent screen in MCP image intensifier in ICCD camera and that of a coupling fiber bundle are also evaluated in this presentation.

In this paper, based on the mechanism of CCD camera, an event-based simulation method of γ-ray-induced transient noise was developed, which applying MCNP5 Code based on Monte Carlo methods. On the mono-energy γ-ray sources, the transient noises of two different CCD cameras have been measured at different doses (from 0.001mR to 1mR) and different incidence angles. The 60 Co and 137 Cs were used as the mono-energy γ-ray sources, and the Compton Scattering technique were adopted to get lower energy γ-ray sources. In order to get the pure transient noise induced by γ-ray, a method was advanced for extracting the transient noise from the image mixed the background noise. And the transient noise was characterized, including the number of noise clusters, the noise intensity spectrum and the size spectrum of noise clusters. The variation characteristics of noise have been draw from the simulation and experiment, which induced by γ-rays of different dose, or different energy or different incidence angle.