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This work demonstrates a luminescent chemosensor based on silica cross-linked micellar nanoparticles (SCMNPs) designed by encapsulating a phenothiazine-derived Schiff base, (4E)-4-((10-dodecyl-10H-phenothiazin-7-yl)methyleneamino)-1,2-dihydro-1,5-dimethyl-2-phenylpyrazol-3-one (EDDP), for the selective detection of Fe3+. The encapsulation of EDDP inside SCMNPs (EDDP–SCMNPs) can avoid the metal (Fe3+/Fe2+)-promoted hydrolysis of EDDP and, thus, exhibit highly selective determination of Fe3+. The electron transfer (ET) from EDDP in the core to Fe3+ adsorbed on the shell of EDDP–SCMNPs was verified using UV-vis absorption, fluorescent emission and 3D fluorescence spectra. Moreover, EDDP–SCMNPs showed no sensing ability of Fe2+ due to the weak electron-accepting ability of Fe2+. Significantly, because of their ultrasmall size, nontoxicity, good water solubility and biocompatibility, EDDP-SCMNPs have potential applications in biological systems.

MiR-122, a pivotal liver specific miRNA, has been implicated in several liver diseases including hepatocellular carcinoma (HCC) and hepatitis C and B viral infection. This study aimed to explore epigenetic regulation of miR-122 in human hepatocellular carcinoma (HCC) cells and to examine the effect of hepatitis C virus (HCV) and hepatitis B virus (HBV). We performed microRNA microarray analysis and identified miR-122 as the most up-regulated miRNA (6-fold) in human hepatocellular cancer cells treated with 5′aza-2′deoxycytidine (5-Aza-CdR, DNA methylation inhibitor) and 4-phenylbutyric acid (PBA, histone deacetylation inhibitor). Real-time PCR analysis verified significant upregulation of miR-122 by 5′aza and PBA in HCC cells, and to a lesser extent in primary hepatocytes. Peroxisome proliferator activated receptor-gamma (PPARγ) and retinoid X receptor alpha (RXRα) complex was found to be associated with the DR1 and DR2 consensus site in the miR-122 gene promoter which enhanced miR-122 gene transcription. 5-Aza-CdR and PBA treatment increased the association of PPARγ/RXRα, but decreased the association of its co-repressors (N-CoR and SMRT), with the miR-122 DR1 and DR2 motifs. The aforementioned DNA-protein complex also contains SUV39H1, a H3K9 histone methyl transferase, which downregulates miR-122 expression. Our findings establish a novel role of the PPARγ binding complex for epigenetic regulation of miR-122 in human HCC cells. Moreover, we show that hepatitis B virus X protein (HBX) binds PPARγ and inhibits the transcription of miR-122, whereas hepatitis C viral particles exhibited no significant effect; these findings provide mechanistic insight into reduction of miR-122 in patients with HBV but not with HCV infection.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme in prostaglandin (PG) metabolism. This study provides important evidence for inhibition of hepatocellular carcinoma (HCC) growth by 15-PGDH through the 15-keto-prostaglandin E2 (15-keto-PGE2)/peroxisome proliferator-activated receptor-γ (PPARγ)/p21(WAF1/Cip1) signaling pathway. Forced overexpression of 15-PGDH inhibited HCC cell growth in vitro, whereas knockdown of 15-PGDH enhanced tumor growth parameters. In a tumor xenograft model in severe combined immunodeficiency mice, inoculation of human HCC cells (Huh7) with overexpression of 15-PGDH led to significant inhibition of tumor growth, whereas knockdown of 15-PGDH enhanced tumor growth. In a separate tumor xenograft model in which mouse HCC cells (Hepa1-6) were inoculated into syngeneic C57BL/6 mice, intratumoral injection of adenovirus vector expressing 15-PGDH (pAd-15-PGDH) significantly inhibited xenograft tumor growth. The antitumor effect of 15-PGDH is mediated through its enzymatic product, 15-keto-PGE2, which serves as an endogenous PPARγ ligand. Activation of PPARγ by 15-PGDH-derived 15-keto-PGE2 enhanced the association of PPARγ with the p21(WAF1/Cip1) promoter and increased p21 expression and association with cyclin-dependent kinase 2 (CDK2), CDK4 and proliferating cell nuclear antigen. Depletion of p21 by short hairpin RNA reversed 15-PGDH-induced inhibition of HCC cell growth; overexpression of p21 prevented 15-PGDH knockdown-induced tumor cell growth. These results show a key 15-PGDH/15-keto-PGE2-mediated activation of PPARγ and p21(WAF1/Cip1) signaling cascade that regulates hepatocarcinogenesis and tumor progression.

Inflammatory cytokines and lncRNAs are closely associated with tumorigenesis. Herein, we reveal inflammatory cytokines IL6 cooperates with long noncoding RNA CUDR to trigger the malignant transformation of human embryonic stem cells-derived hepatocyte-like stem cells. Mechanistically, IL6 cooperates with CUDR to cause MELLT3 to interact with SUV39h1 mRNA3′UTR and promote SUV39h1 expression. Moreover, the excessive SUV39h1 also increases tri-methylation of histone H3 on nineth lysine (H3K9me3). Intriguingly, under inflammatory conditions, H3K9me3 promotes the excessive expression and phosphorylation of NF-κB, and in turn, phorsphorylated NF-κB promotes the expression and phosphorylation of Stat3. Furthermore, that the phosphorylated Stat3 loads onto the promoter region of miRs and lncRNAs. Ultimately, the abnormal expression of miRs and lncRNAs increased telomerase activity, telomere length and microsatellite instability (MSI), leading to malignant transformation of hepatocyte-like stem cells.

The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2. Strikingly, the excessive TRF2 interacts with HULC or MALAT1 to form the complex that loads on the telomeric region, replacing the CST/AAF and recruiting POT1, pPOT1, ExoI, SNM1B, HP1 α. Accordingly, the telomere is greatly protected and enlonged. Furthermore, the excessive HULC plus MALAT1 reduced the methylation of the TERC promoter dependent on TRF2, increasing the TERC expression that causes the increase of interplay between TRET and TERC. Ultimately, the interaction between RFC and PCNA or between CDK2 and CyclinE, the telomerase activity and the microsatellite instability (MSI) are significantly increased in the liver cancer stem cells. Our demonstrations suggest that haploinsufficiency of HULC/MALAT1 plays an important role in malignant growth of liver cancer stem cell.

A head-related transfer function (HRTF) measurement was conducted to explore the 3-D audio displays with 58 male pilot participants in free field of acoustics in hemi-anechoic room. 50 items of head-related anthropometric parameters were measure by 3D probe. 13 elevations (φ) from −40° to +80° and 723 azimuths (θ) were selected to position 3-D sound in test, and head-related impulse responses (HRIR) were collected by omnidirectional microphones inserted bi-ears of pilots. The first HRTF database of Chinese male pilots was built with more than 6.86 hundred millions digital data. It suggested that some asymmetries were found in HRIR and anthropometry of right–left ears by analysis.

This paper illustrates the visualization method of transient sound propagation in 3-dimensional semi-closed sound field in which a rectangular shape of room is modeled by applying the finite-difference time-domain (FDTD) method. As a direct time-domain simulation the technique of FDTD owns unique advantage in solving acoustic problems in closed and semi-closed rooms. To ensure the accuracy of the FDTD, some attention is paid in this paper on the key problems such as: numerical stability, numerical error, boundary condition, and the excitation signal. This paper uses slicing to visualize the 3-dimensional semi-closed sound field, and that validity is proved by the visualization of a 2-dimensional semi-closed sound field.

SummaryTumorigenesis is caused by an uncontrolled cell cycle and the altered expression of many genes. Here, we report a gene CREPT that is preferentially expressed in diverse human tumors. Overexpression of CREPT accelerates tumor growth, whereas depletion of CREPT demonstrates a reversed effect. CREPT regulates cyclin D1 expression by binding to its promoter, enhancing its transcription both in vivo and in vitro, and interacting with RNA polymerase II (RNAPII). Interestingly, CREPT promotes the formation of a chromatin loop and prevents RNAPII from reading through the 3′ end termination site of the gene. Our findings reveal a mechanism where CREPT increases cyclin D1 transcription during tumorigenesis, through enhancing the recruitment of RNAPII to the promoter region, possibly, as well as chromatin looping.

Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with cyclooxygenase-2 (COX-2) for the production of PGE(2). Although COX-2 is known to mediate the growth and progression of several human cancers including hepatocellular carcinoma (HCC), the role of mPGES-1 in hepatocarcinogenesis is not well established. This study provides novel evidence for a key role of mPGES-1 in HCC growth and progression. Forced overexpression of mPGES-1 in two HCC cell lines (Hep3B and Huh7) increased tumor cell growth, clonogenic formation, migration and invasion, whereas knockdown of mPGES-1 inhibited these parameters, in vitro. In a mouse tumor xenograft model, mPGES-1-overexpressed cells formed palpable tumors at earlier time points and developed larger tumors when compared with the control (P

Microsomal prostaglandin E synthase-1 (mPGES-1) is a rate-limiting enzyme that is coupled with cyclooxygenase (COX)-2 in the synthesis of prostaglandin E2. Although COX-2 is involved in the development and progression of various human cancers, the role of mPGES-1 in carcinogenesis has not been determined. We investigated the role of mPGES-1 in human cholangiocarcinoma growth.We used immunohistochemical analyses to examine the expression of mPGES-1 in formalin-fixed, paraffin-embedded human cholangiocarcinoma tissues. The effects of mPGES-1 on human cholangiocarcinoma cells were determined in vitro and in SCID mice. Immunoblotting and immunoprecipitation assays were performed to determine the levels of PTEN and related signaling molecules in human cholangiocarcinoma cells with overexpression or knockdown of mPGES-1.mPGES-1 is overexpressed in human cholangiocarcinoma tissues. Overexpression of mPGES-1 in human cholangiocarcinoma cells increased tumor cell proliferation, migration, invasion, and colony formation; in contrast, RNA interference knockdown of mPGES-1 inhibited tumor growth parameters. In SCID mice with tumor xenografts, mPGES-1 overexpression accelerated tumor formation and increased tumor weight (P.01), whereas mPGES-1 knockdown delayed tumor formation and reduced tumor weight (P.01). mPGES-1 inhibited the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), leading to activation of the epidermal growth factor/phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways in cholangiocarcinoma cells. mPGES-1-mediated inhibition of PTEN is regulated through blocking of early growth response-1 sumoylation and binding to the 5'-untranslated region of the PTEN gene.mPGES-1 promotes experimental cholangiocarcinogenesis and tumor progression by inhibiting PTEN.

Objectives Glucagon-like peptide 2 (GLP2) is involved in the regulation of energy absorption and metabolism. Despite the importance of the GLP2 signalling mechanisms on osteoclast, little has been studied on how GLP2 works during osteoclastogenesis. Materials and methods RAW264.7 cells were infected with rLV-Green-GLP2. The induction of osteoclasts was performed by RANKL. TRAP were detected by RT-PCR, Western blotting and staining. Total nitric oxide and total NOS activity were measured. Cells apoptosis was detected by Hoest33258 and Annix V staining. Animal test, chromatin immunoprecipitation (CHIP), co-immunoprecipitation(IP) and luciferase reporter assay were also performed. Results We indicate that GLP2 is associated with osteoporosis-related factors in aged rats, including BALP, TRAP, IL6, TNFα, Nitric Oxide (NO), iNOS, calcitonin and occludin. Moreover, GLP2 is demonstrated to result in negative action during proliferation of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Furthermore, GLP2 decreases osteoclasts induced from monocyte/macrophage cells RAW264.7 as well as the serum TRAP activity in aged rats. Mechanistic investigations reveal GLP2 enhances the expression of iNOS through stimulating the activity of TGFβ-Smad2/3 signalling in osteoclasts. In particular, inhibition of TGFβ fully abrogates this function of GLP2 in osteoclasts. Strikingly, overexpression of GLP2 significantly increases the product of nitric oxide via iNOS which promotes apoptosis of osteoclasts by decreasing bcl2 or increasing caspase3. Thereby, the ability of GLP2 to regulate apoptosis depends on TGFβ-Smad2/3-iNOS-NO signalling pathway since total NOS inhibitor L-NMMA specifically inhibits the actions by GLP2. Conclusions GLP2 induces apoptosis via TGFβ-Smad2/3 signalling, which contributes to the inhibition of the proliferation of osteoclasts and which may provide potential therapeutic targets for the treatment of osteoporosis.

Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. Herein, we demonstrate CUDR could enhance the human embryonic stem cells (ESC) differentiation into hepatocyte-like cells by reducing trimethylation on histone H3 twenty-seventh lysine (H3K27me3). On the other hand, excessive CUDR triggers hepatocyte-like cells malignant transformation. Mechanistically, we identify CUDR causes highly upregulated in liver cancer (HULC) and β-catenin abnormal expression by inhibiting HULC promoter methylation and promoting β-catenin promoter-enhancer chromatin looping formation mediated by CUDR-ccctc-binding factor (CTCF) complex, which recruits more RNA polII and P300. Strikingly, HULC and β-catenin activity are crucial for CUDR oncogenic function. These findings provide the first demonstration that CUDR plays a positive potential role in liver cancer stem cell through the cascade of CUDR-HULC/CUDR-β-catenin signaling, and offer insights into a novel link between long noncoding RNA (lncRNA) and the epigenetic modification in cancer stem cells.

Industrialization process of patent technology is one of the most important marks to evaluate patent technology innovation ability, which affects their own survival and development in the competition. But the ratio of industrialization is still very low, because there are some restricted risks through the industrialization process. So, if a reasonable risk assessment system for industrialization of patent technology could been put forward based on the analyst for the risks, and some suitable theory could been applied for the assessment, it would do great contribution, offer objective database and implementation guidance to the industrialization of patent technology .Aim at risk assessment for industrialization of patent technology, the paper puts forward the construction of the patent industrialization index system based on the analyst for the risks. And BPNN theory could be applied for the assessment. As a case study, A University has been chosen for an example to prove the correctness of the conclusion and effectiveness of the assessment.

miR-17-92 is an oncogenic miRNA cluster implicated in the development of several cancers; however, it remains unknown whether the miR-17-92 cluster is able to regulate cholangiocarcinogenesis. This study was designed to investigate the biological functions and molecular mechanisms of the miR-17-92 cluster in cholangiocarcinoma. In situ hybridization and quantitative RT-PCR analysis showed that the miR-17-92 cluster is highly expressed in human cholangiocarcinoma cells compared with the nonneoplastic biliary epithelial cells. Forced overexpression of the miR-17-92 cluster or its members, miR-92a and miR-19a, in cultured human cholangiocarcinoma cells enhanced tumor cell proliferation, colony formation, and invasiveness, in vitro. Overexpression of the miR-17-92 cluster or miR-92a also enhanced cholangiocarcinoma growth in vivo in hairless outbred mice with severe combined immunodeficiency (SHO-Prkdc(scid)Hr(hr)). The tumor-suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), was identified as a bona fide target of both miR-92a and miR-19a in cholangiocarcinoma cells via sequence prediction, 3' untranslated region luciferase activity assay, and Western blot analysis. Accordingly, overexpression of the PTEN open reading frame protein (devoid of 3' untranslated region) prevented miR-92a- or miR-19a-induced cholangiocarcinoma cell growth. Microarray analysis revealed additional targets of the miR-17-92 cluster in human cholangiocarcinoma cells, including APAF-1 and PRDM2. Moreover, we observed that the expression of the miR-17-92 cluster is regulated by IL-6/Stat3, a key oncogenic signaling pathway pivotal in cholangiocarcinogenesis. Taken together, our findings disclose a novel IL-6/Stat3-miR-17-92 cluster-PTEN signaling axis that is crucial for cholangiocarcinogenesis and tumor progression.

Prostaglandin E2 (PGE2) is a potent lipid mediator that plays a key role in inflammation and carcinogenesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE2, which leads to PGE2 biotransformation. In this study, we showed that the 15-PGDH-derived 15-keto-PGE2 is an endogenous peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand that causes PPAR-γ dissociation from Smad2/3, allowing Smad2/3 association with the TGF-β receptor I and Smad anchor for receptor activation and subsequent Smad2/3 phosphorylation and transcription activation in human cholangiocarcinoma cells. The 15-PGDH/15-keto-PGE2-induced Smad2/3 phosphorylation resulted in the formation of the pSmad2/3-TAP63-p53 ternary complex and their binding to the TAP63 promoter, inducing TAP63 autotranscription. The role of TAP63 in 15-PGDH/15-keto-PGE2-induced inhibition of tumor growth was further supported by the observation that knockdown of TAP63 prevented 15-PGDH-induced inhibition of tumor cell proliferation, colony formation, and migration. These findings disclose a novel 15-PGDH-mediated 15-keto-PGE2 signaling cascade that interacts with PPAR-γ, Smad2/3, and TAP63. Background: 15-PGDH catalyzes PGE2 oxidation to form 15-keto-PGE2. Results: 15-PGDH-derived 15-keto-PGE2 is a PPAR-γ ligand that causes Smad2/3 association with TGFBRI/SARA and induces formation of pSmad2/3-TAP63-p53 ternary complex. Conclusion: 15-PGDH-mediated 15-keto-PGE2 signaling cascade interacts with PPAR-γ, Smad2/3, and TAP63. Significance: Induction of 15-PGDH expression or administration of 15-keto-PGE2 may represent a promising anti-cancer therapeutic strategy.

Texture compression is an important technique widely adopted in graphics processing units (GPUs) nowadays to reduce memory bandwidth consumption. However, modern texture compression schemes cannot generate satisfactory visual qualities for both alpha channel and color channel of texture images. In this paper we present a novel texture compression scheme, called CATC (Complexity-Aware Texture Compression), based on the insight into the essential differences between transparency and color. CATC defines new texture compression data formats and compresses the alpha channel and color channel of texture image flexibly. CATC employs clustering algorithm combined with the linear interpolation method to compress the alpha channel of texture images. If the alpha values are of low complexity, CATC takes advantage of the free bits in compressed block of alpha channel to compress color channel of texture image. While keeping the same compression ratio as the de facto standard texture compression scheme, CATC improves both the two channels' compression quality. The average PSNR score of alpha channel is improved by about 0.2 dB, and the average PSNR score of color channel can be increased by up to 7.17 dB over a set of test images, which makes CATC a better substitute for the standard texture compression scheme.

miR-24-2 has been shown as one of the most important down-regulated miRNAs in human cancers. However, its potential implication in hepatoma has not been investigated. In this study, we showed that ...

NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is responsible for the catabolism of prostaglandins in a variety of cell types such as inflammation an dtumorigenesis. In this study we showed that forced overexpression of 15-PGDH in human cholangiocarcinoma cells (CCLP1) suppressed tumor cell growth, invasion and clonogenic formation capacity. In contrast, 15-PGDH knockdown in CCLP1 cells enhanced tumor cell growth, invasion and clonogenic formation. Flow cytometry analysis revealed that 15-PGDH overexpression induced cell cycle arrest at G1/S checkpoint. When implanted into SCID mice, 15-PGDH overexpressed CCLP1 cells formed smaller xenograft tumors, whereas 15-PGDH-depleted cells formed larger xenograft tumors when compared with each of the corresponding controls (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1179. doi:1538-7445.AM2012-1179

Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with cyclooxygenase-2 (COX-2) for the production of PGE2. Although COX-2-derived PGE2 is known to participate in the development and progression of several human cancers including hepatocellular carcinoma (HCC), the role of mPGES-1 in carcinogenesis remains poorly understood. This study provides novel evidence for an important role of mPGES-1 in human HCC. Forced overexpression of mPGES-1 in two HCC cell lines (Hep3B and Huh7) promoted tumor cell growth and increased clonogenic formation capacity, in vitro. Conversely, mPGES-1 knockdown inhibited tumor cell growth and prevented clonogenic formation. Overexpression of mPGES-1 in Hep3B and Huh7 cells also increased cell invasion and migration/repair capacity, whereas knockdown of mPGES-1 reduced these parameters. Flowcytometric analysis revealed that mPGES-1 knockdown caused cell cycle arrest at G1/S checkpoint. In SCID mouse tumor xenograft model, mPGES-1 overexpressed cells formed palpable tumors at earlier time points and developed larger tumor nodules when compared to the control cells (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 247. doi:10.1158/1538-7445.AM2011-247