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Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), has been implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are largely unknown. Our multistage hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 was the most profoundly dysregulated gene among RNA-editing enzyme family members in liver cancer. Targeted inactivation of ADAR1 inhibited the in vitro tumorigenesis of liver cancer cells. An integrative computational analyses of RNA-edited hotspots and the known editing frequency of miRNAs suggested that the miRNA miR-3144-3p was edited by ADAR1 during liver cancer progression. Specifically, ADAR1 promoted A-to-I editing of canonical miR-3144-3p to replace the adenosine at Position 3 in the seed region with a guanine (ED_miR-3144-3p(3_A Musashi RNA-binding protein 2 (MSI2) was a specific target of miR-3144-3p and that MSI2 overexpression was due to excessive ADAR1-dependent over-editing of canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as a specific gene target of ED_miR-3144-3p(3_A

PDF file - 1223K, S1 Aberrant regulation of HDAC2 in human gastric cancer S2 Effect of HDAC2 knockdown on cell cycle distribution in MKN-1 cells S3 Western blot analysis of cell cycle regulatory proteins in MKN-1. S4 HDAC2 knockdown induces apoptosis and autophagic cell death in human gastric cancer cell line

Aberrant regulation of histone deacetylase 2 (HDAC2) was reported for gastric cancers. However, responsive cancer genes in disease onset and progression are less understood. HDAC2 expression was studied by quantitative RT-PCR and Western blotting. The functional consequences of HDAC2 knockdown on cell-cycle regulation, programmed cell death, and gene target identification was investigated by flow cytometry, Western blotting, electron microscopy, anchorage-independent colony formation, and cell migration assay and by whole-genome microarray. Therapeutic efficacy of HDAC2 knockdown was determined in nude mice with small hairpin expressing human gastric cancer cells. Epigenetic regulation of p16INK4a was studied by methylation-specific PCR and chromatin-IP to evidence HDAC2 or acetylated-histone-H4 binding at gene specific promoter sequences. HDAC2 gene and protein expression was significantly upregulated in different histopathologic grades of human gastric cancers and cancer cell lines. HDAC2 inactivation significantly reduced cell motility, cell invasion, clonal expansion, and tumor growth. HDAC2 knockdown-induced G1–S cell cycle arrest and restored activity of p16INK4a and the proapoptotic factors. This treatment caused PARP cleavage and hypophosphorylation of the Rb-protein, repressed cyclinD1, CDK4, and Bcl-2 expression and induced autophagic phenotype, that is, LC3B-II conversion. Some gastric tumors and cancer cells displayed p16INK4a promoter hypermethylation but treatment with 5-aza-deoxycitidine restored activity. With others the methylation status was unchanged. Here, chromatin-IP evidenced HDAC2 binding. Nonetheless, expression of p16INK4a was restored by HDAC2 knockdown with notable histone-H4-acetylation, as determined by chromatin-IP. Thus, p16INK4a is regulated by HDAC2. HDAC2 is a bona fide target for novel molecular therapies in gastric cancers. Mol Cancer Res; 11(1); 62–73. ©2012 AACR.

Supplementary Figure S7 - PDF file 37K, Effects of miR-185 on GKN1 induced inhibited cell growth

Supplementary Figures and Tables

Supplementary Document - PDF file 159K, Supplemental document including Supplemental Table, Figure legends, material & methods and refference

Purpose: Gastrokine 1 (GKN1) functions to protect the gastric antral mucosa and promotes healing by facilitating restoration and proliferation after injury. GKN1 is downregulated in Helicobacter pylori–infected gastric epithelial cells and loss of GKN1 expression is closely associated with gastric carcinogenesis, but underlying mechanisms of the tumor-suppressing effects of GKN1 remain largely unknown.Experimental Design: AGS, MKN1, MKN28 gastric cancer cells and HFE-145 immortalized non-neoplastic gastric mucosal cells were transfected with GKN1 or shGKN1. We conducted molecular and functional studies of GKN1 and miR-185 and investigated the mechanisms of alteration. We also analyzed epigenetic alterations in 80 gastric cancer tissues.Results: Restoration of GKN1 protein suppressed gastric cancer cell growth by inducing endogenous miR-185 that directly targets epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. In addition, ectopic expression of GKN1 upregulated Tip60 and downregulated HDAC1 in an miR-185–independent manner, thereby inducing cell-cycle arrest by regulating cell-cycle proteins in gastric cancer cells. Notably, GKN1 expression was inversely correlated with DNMT1 and EZH2 expression in a subset of 80 gastric cancer tissues and various gastric cancer cell lines. Interestingly, it was found that GKN1 exerted a synergistic anti-cancerous effect with 5-fluorouracil on tumor cell growth, which suggests a possible therapeutic intervention method for gastric cancer.Conclusion: Our results show that GKN1 has an miR-185–dependent and -independent mechanism for chromatic and DNA epigenetic modification, thereby regulating the cell cycle. Thus, the loss of GKN1 function contributes to malignant transformation and proliferation of gastric epithelial cells in gastric carcinogenesis. Clin Cancer Res; 19(17); 4599–610. ©2013 AACR.

The roles of chromatin remodelers and their underlying mechanisms of action in cancer remain unclear. In this study, SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. SMARCB1 was highly upregulated in patients with liver cancer and was associated with poor prognosis. Loss- and gain-of-function studies in liver cells revealed that SMARCB1 loss led to reduced cell proliferation, wound healing capacity, and tumor growth in vivo. Although upregulated SMARCB1 appeared to contribute to switch/sucrose nonfermentable (SWI/SNF) complex stability and integrity, it did not act using its known pathways antagonism with EZH2 or association between TP53 or AMPK. SMARCB1 knockdown induced a mild reduction in global H3K27 acetylation, and chromatin immunoprecipitation sequencing of SMARCB1 and acetylated histone H3K27 antibodies before and after SMARCB1 loss identified Nucleoporin210 (NUP210) as a critical target of SMARCB1, which bound its enhancer and changed H3K27Ac enrichment and downstream gene expression, particularly cholesterol homeostasis and xenobiotic metabolism. Notably, NUP210 was not only a putative tumor supporter involved in liver cancer but also acted as a key scaffold for SMARCB1 and P300 to chromatin. Furthermore, SMARCB1 deficiency conferred sensitivity to doxorubicin and P300 inhibitor in liver cancer cells. These findings provide insights into mechanisms underlying dysregulation of chromatin remodelers and show novel associations between nucleoporins and chromatin remodelers in cancer.Significance:This study reveals a novel protumorigenic role for SMARCB1 and describes valuable links between nucleoporins and chromatin remodelers in cancer by identifying NUP210 as a critical coregulator of SMARCB1 chromatin remodeling activity.

Aberrant regulation of histone deacetylase 2 (HDAC2) contributes to malignant progression in various cancers, but the underlying mechanism leading to the activation of oncogenic HDAC2 remains unknown. In this study, we show that HDAC2 expression is upregulated in a large cohort of patients with human hepatocellular carcinoma, and that high expression of HDAC2 was significantly associated with poor prognosis of patients with hepatocellular carcinoma. We found that mTORC1/NF-κBp50 signaling is necessary for the growth factor–induced HDAC2 and is sustained in hepatocellular carcinoma, but not in normal hepatic cells. Growth factor–induced mTORC1 activates the nuclear translocation of NF-κBp50, where it binds to the intragenic sequences of the HDAC2 gene and promotes its transcription. Hepatocellular carcinoma tissues derived from chemical-induced mouse and rat liver cancer models validated that mTORC1 activation and NF-κBp50 nuclear translocation are essential for the transcriptional activation of oncogenic HDAC2 in hepatocellular carcinoma. In addition, we demonstrate that HDAC2 is required to maintain mTORC1 activity by stabilizing the mTOR/RAPTOR complex. Elevated expression of HDAC2 triggers a positive feedback loop that activates AKT phosphorylation via the transcriptional modulation of phosphoinositide signaling molecules. Bioinformatics analysis of HDAC2 signature and immunoblot analysis of mesenchymal genes also evidenced that HDAC2 plays a role in the malignant behavior of tumor cells by Snail induction and simultaneously E-cadherin suppression in hepatocellular carcinoma cells. These findings establish a molecular mechanism responsible for the activation of oncogenic HDAC2, which explains how growth factor–induced HDAC2 maintains mitogenic signaling and function during hepatocellular malignant progression and provide a novel strategy for therapeutic intervention in liver cancer. Cancer Res; 74(6); 1728–38. ©2014 AACR.

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PDF file - 3559KB, Supplementary Figure S1. HDAC2 gene expression and GSEA results for genes up-regulated in the HDAC2-associated signature in HCC large cohort studies. Supplementary Figure S2. Representative immunohistochemical staining of phospho-mTOR, mTOR, and HDAC2 expression in non-cancerous hepatic cells and HCC cells. Supplementary Figure S3. The ectopic overexpression of HDAC2 induces AKT activation. Supplementary Figure S4. mRNA expression data of genes encoding kinase or phosphatase in the phosphoinositide signaling pathway. Supplementary Figure S5. A schematic illustration of the phosphoinositide signaling pathway regulated by HDAC2 in HCC cells. Supplementary Figure S6. HDAC2 induced the migration of liver cancer cells. Supplementary Figure S7. Synergistic anti-growth effect of Sorafenib and HDAC2 knock-down on HCC cells. Supplementary Figure S8. Growth factor-induced HDAC2 mediates a positive feedback loop to mTORC1 stabilization and AKT activation.

PDF file - 220KB, Supplementary Table S1. A List of 3,039 Genes Correlated with HDAC2 Gene Expression from a HCC Large Cohort Study. Supplementary Table S2. Overlap of the HDAC2-Correlated Gene Set with Other Existing Gene Sets. Supplementary Table S3. Molecular Concept Map Analysis of HDAC2-Specific Genes in Liver Cancer Cells.

A dynamic molecular interaction between cancer and the surrounding normal cells is mediated through exosomes. We investigated whether exosomes derived from gastric cancer cells affected the fate of the surrounding gastric epithelial cells.We analyzed the cell viability and immortalization of primary normal stomach epithelial cells (PNSECs) after treatment with exosomes derived from AGS gastric cancer cells and/or H. pylori CagA. Cell proliferation and apoptosis were analyzed by BrdU incorporation, flow-cytometry, and colony formation assays. We examined telomere length, expression and activity of telomerase, and expression of telomere-related genes in PNSECs treated with cancer exosomes, and in 60 gastric cancer and corresponding mucosal tissues. The differentially expressed genes and transcriptional regulation of telomere-related genes were verified using real-time qPCR and ChIP analyses, respectively.Gastric cancer exosomes increased cell viability and the population-doubling levels but inhibited the cellular senescence and apoptosis of PNSECs. The internalization of cancer exosomes in PNSECs dramatically increased the number of surviving colonies and induced a multilayer growth and invasion into the scaffold. Treatment of PNSECs with cancer exosomes markedly increased the expression and activity of telomerase and the T/S ratio and regulated the expression of the telomere-associated genes, heat-shock genes, and hedgehog genes. Compared to gastric mucosae, gastric cancer showed increased hTERT expression, which was positively correlated with telomere length. Interestingly, seven (46.7%) of 15 non-cancerous gastric mucosae demonstrated strong telomerase activity.These results suggest that gastric cancer exosomes induced the transformation and field cancerization of the surrounding non-cancerous gastric epithelial cells.

With growing interest in the bulk production of the alternative energy carrier hydrogen, dry-reforming of methane using carbon dioxide has attracted great interest as one of the possible carbon capture and utilization (CCU) technologies and hydrogen production methods. An integrated system combining the dry-reforming and water gas shift reactions is suggested to improve the productivity of hydrogen, and a system has also been developed for high-purity hydrogen production from a single system using the sorption-enhanced reaction concept. To realize the proposed system, we develop the Ru-doped Sr0.92Y0.08TiO3 perovskite catalysts and investigate their characteristics using various analyses. The prepared catalysts exhibit excellent CH4 conversion of 92.2% for the dry-reforming reactions at 800 °C without performance degradation by coke formation. Moreover, high-purity hydrogen (>99.5%) is directly produced by the proposed integrated system using anthropogenic greenhouse gases as reactants, and the efficiency is further enhanced by recycling the captured CO2 to the dry-reforming reactor.

Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), is implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are currently largely unknown. Our multi-step hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 is the most dysregulated gene among the RNA editing enzyme families in liver cancer. Targeted inactivation of ADAR1 inhibits in vitro tumorigenesis of liver cancer cells. Integrative computational analyses of RNA editing hotspots and the editing frequency of miRNAs suggested miR-3144-3p a potential mRNA edited by ADAR1 in liver cancer progression. ADAR1 promoted A-to-I editing of the canonical miR-3144-3p to change position 3 adenosine in the seed region to guanine (ED_miR-3144-3p(3_A Musashi RNA-binding protein 2 (MSI2) is a specific target of miR-3144-3p, and that MSI2 overexpression is due to ADAR1-dependent over-editing of the canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as specific target gene for ED_miR-3144-3p(3_A

Background: Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), is implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are currently largely unknown.Method: Our multi-step hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 is the most dysregulated gene among the RNA editing enzyme families in hepatocellular carcinoma (HCC). Targeted inactivation of ADAR1 inhibits in vitro tumorigenesis of HCC cells. Integrative computational analyses of RNA editing hotspots and the editing frequency of miRNAs suggested miR-3144-3p a potential mRNA edited by ADAR1 in hepatocellular carcinogenesis.Result: Through direct sequencing of ADAR1-knocked-down or -overexpressing cells, we demonstrated that ADAR1 promoted A-to-I editing of the canonical miR-3144-3p to change position 3 adenosine in the seed region to guanine (ED_miR-3144-3p(3_AMusashi RNA-binding protein 2 (MSI2) is a specific target of miR-3144-3p, and that MSI2 overexpression is due to ADAR1-dependent over-editing of the canonical miR-3144-3p in HCC cells. Notably miR-3144-3p treatments showed similar to in vitro anti-tumor activities of ADAR1-specifc siRNA in HCC. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as specific target gene for ED_miR-3144-3p(3_AConclusions: Our findings suggest that aberrant regulation of ADAR1 augments oncogenic MSI2 via overediting the canonical miR-3144-3p, and the resultant ED_miR-3144-3p(3_A

A compact ethanol fuel processor with an all-in-one design of the auto-thermal reforming (ATR) and water-gas-shift (WGS) reactors was developed. The fuel processor has unique features, such as the ...

Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early‐stage HCC (single tumor 0.8. In our validation study, serum exo‐miR‐4661‐5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo‐miRs and serum AFP. The panel composed of exo‐miR‐4661‐5p and exo‐miR‐4746‐5p was identified as the most accurate biomarker for early‐stage HCC (AUROC = 0.947, 95% confidence interval = 0.889‐0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo‐miR‐4661‐5p–based serum panel is a promising diagnostic marker for early‐stage HCC., The present study derived potential serum exosomal microRNA panels for hepatocellular carcinoma (HCC) using a systematic, genome‐wide biomarker discovery approach. Serum exosomal microRNA‐4661‐5p–based panel is a potent diagnostic biomarker for early stage HCC and could also be used as a prognostic indicator in patients with HCC.

Micron-sized Ni–Al alloy powders (Ni–x wt.%Al, x = 40, 50, 60) were synthesized using the low-temperature chemical alloying (LTCA) at 500 °C. The three different as-prepared Ni–Al alloy powders were composed of Ni2Al3 and/or NiAl3 phases while achieving thermodynamic equilibrium compositions (Ni–40 wt%Al, Ni2Al3; Ni–50 wt%Al, the coexistence of Ni2Al3 and NiAl3; Ni–60 wt%Al, NiAl3). The LTCA method demonstrates that it is capable of producing Al-rich Ni–Al alloy powders while maintaining a particle size similar to that of the starting Ni particles. The three Ni–Al alloy powders were used as precursor materials to fabricate porous nickel catalysts through a selective aluminum leaching process, followed by the enlargement of the surface area. Alteration of the material characteristics with respect to the leaching time was investigated using XRD, FESEM-EDS, TEM, XPS, TPR, BET, and particle size analysis. The nickel skeletal catalysts with the increased BET-surface areas (50–111 m2/g) displayed high reactivity toward ammonia decomposition.

Formate received a significant attention as storing H2 in chemical bonds to the concept of H2 carriers. In this report, hydrogen generation from formate was optimized systematically by varying reac...

Pericardial effusion (PE) can develop in patients with virtually any condition that affects the pericardium, including acute pericarditis and a variety of systemic disorders. Thus, definite differentiation of malignant pericardial effusion and rapid diagnosis are known to have therapeutic and prognostic importance. The aim of this study was to identify novel molecular markers for the detection of cancer in patients with pericardial disorder. We performed one-way ANOVA analysis of whole transcriptome scans of 18 PEs from the patients with pericardial disorder including cancer. It resulted in 4385 outlier genes. Hierarchical clustering analysis showed two distinct clusters [cancer patient’s PEs (G1 + G2) vs. non-cancer PEs (G3)] within the dendrogram. To identify cancer-specific molecular signature, Welch’s t test of G1 and G3 was performed and 1639 gene elements were suggested as stringent classifiers between cancer PE and non-cancer PE. Gene set enrichment analysis of PE signature suggested that CD24, SDC1, and ST14 were strong molecular markers for identifying cancer patients among patients with pericardial disorder. Our results suggest that etiology-specific molecular signatures can discriminate cancer patients within pericardial disorder patients. CD24, SDC1, and ST14 are strong molecular markers for such discrimination.

The high morbidity rate of hepatocellular carcinoma (HCC) is mainly linked to late diagnosis. Early diagnosis of this leading cause of mortality is therefore extremely important. We designed a gene selection strategy to identify potential secretory proteins by predicting signal peptide cleavage sites in amino acid sequences derived from transcriptome data of human multistage HCC comprising chronic hepatitis, liver cirrhosis and early and overt HCCs. The gene selection process was validated by the detection of molecules in the serum of HCC patients. From the computational approaches, 10 gene elements were suggested as potent candidate secretory markers for detecting HCC patients. ELISA testing of serum showed that hyaluronan mediated motility receptor (HMMR), neurexophilin 4 (NXPH4), paired like homeodomain 1 (PITX1) and thrombospondin 4 (THBS4) are early-stage HCC diagnostic markers with superior predictive capability in a large cohort of HCC patients. In the assessment of differential diagnostic accuracy, receiver operating characteristic curve analyses showed that HMMR and THBS4 were superior to α-fetoprotein (AFP) in diagnosing HCC, as evidenced by the high area under the curve, sensitivity, specificity, accuracy and other values. In addition, comparative analysis of all four markers and AFP combinations demonstrated that HMMR-PITX1-AFP and HMMR-NXPH4-PITX1 trios were the optimal combinations for reaching 100% accuracy in HCC diagnosis. Serum proteins HMMR, NXPH4, PITX1 and THBS4 can complement measurement of AFP in diagnosing HCC and improve identification of patients with AFP-negative HCC as well as discriminate HCC from non-malignant chronic liver disease.

Previously, we demonstrated that recovery of Histone deacetylase 6 (HDAC6) elicited let-7i-5p suppression to de-repress the thrombospondin-1 (TSP1) expression, and thereby it occupied CD47 receptor to block CD47-SIRPα mediated anti-phagocytosis of macrophage in liver cancer. NRT-YHD_001 is a modified antisense miRNA of let-7i-5p for liver cancer treatment. NRT-YHD_001 was substituted with O-methoxyethyl and phosphothioate for stability, and N-acetylgalactosamine was attached for specific delivery to the liver. In in vitro phagocytosis assay, NRT-YHD_001 showed macrophage phagocytosis activity with similar or better results compared to non-modified antisense let-7i-5p (AS_let-7i-5p). In addition, it was confirmed that NRT-YHD_001 inhibited endogenous let-7i-5p of liver cancer cells and activated macrophage phagocytosis at 4°C or 25°C for up to 2 weeks. When NRT-YHD_001 activity was investigated in vivo after 1 week, 2 weeks, and 4 weeks after administration of single dose NRT-YHD_001 to the tail vein of a mouse, NRT-YHD_001 was not degraded, and let-7i-5p was inhibited while maintaining activity in liver tissue for 2 weeks after injection. To investigate the in vivo therapeutic effect, a mouse spontaneous (Ras-transgenic) liver cancer model was used and compared with the sorafenib-administered group. After administration of NRT-YHD_001 and sorafenib each week at the time when liver mass was detected, the tumor size and growth rate were compared. As a result, the NRT-YHD_001 administration group showed significant therapeutic effect compared to sorafenib. These results showed that NRT-YHD_001 had a strong anticancer effect by converting the macrophage of don't eat me into eat me signal in the tumor microenvironment of liver cancer, thereby removing or inhibiting liver cancer cells. Keywords: let-7i-5p, macrophage, phagocytosis, liver cancer, NRT-YHD_001 Citation Format: Suk Woo Nam, Sangyean Kim, Min Jeong Na, Eunbi Shin, Jin Woong Ha, Soyoung Jeon, Jeong Hwan Yoon. In vivo therapeutic validation of NRT-YHD_001, a novel macrophage checkpoint inhibitor, in liver cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5165.

MicroRNA (miRNA) processing is a critical step in mature miRNA production. Its dysregulation leads to an increase in miRNA isoforms with heterogenous 5′-ends (isomiRs), which can recognize distinct target sites because of their shifted seed sequence. Although some miRNA genes display productive expression of their 5′-isomiRs in cancers, how their production is controlled and how 5′-isomiRs affect tumor progression have yet to be explored. In this study, based on integrative analyses of high-throughput sequencing data produced by our group and publicly available data, we demonstrate that primary miR-21 (pri-miR-21) is processed into the cancer-specific isomiR isomiR-21-5p | ±1, which suppresses growth hormone receptor (GHR) in liver cancer. Treatment with antagomirs against isomiR-21-5p | ±1 inhibited the in vitro tumorigenesis of liver cancer cells and allowed the recovery of GHR, whereas the introduction of isomiR-21-5p | ±1 mimics attenuated these effects. These effects were validated in a mouse model of spontaneous liver cancer. Heterogeneous nuclear ribonucleoprotein C and U2 small nuclear RNA auxiliary factor 2 were predicted to bind upstream of pre-miR-21 via a poly-(U) motif and influence Drosha processing to induce the production of isomiR-21-5p | ±1. Our findings suggest an oncogenic function for the non-canonical isomiR-21-5p | ±1 in liver cancer, and its production was shown to be regulated by hnRNPC.

Modern H2-based energy storage and conversion devices require a polymer electrolyte membrane (PEM) fuel cell–based integrated power system with synergistic heat integration. The key issue in integrated power systems is developing a PEM that can operate at 200–300 °C. However, currently used phosphoric-acid-based high-temperature PEM fuel cells limited stability at higher operating temperatures. Herein, we introduce a cerium hydrogen phosphate (CeHP) PEM that conducts protons above 200 °C through a self-assembled network (SAN). The SAN-CeHP-PBI reached maximum power densities of 2.4 W cm-2 and operate stably for over 7000 minute without any voltage decay at 250 ℃ under H2/O2 and anhydrous conditions. The developed fuel cell can be combined with an external hydrogen generator that uses a liquid hydrogen carrier such as N-ethylcarbazole and methanol as fuel, thus achieving a high energy efficiency. The thermal stability and fuel flexibility of these SAN-CeHP-PBI demonstrate potential for commercial applications.

Early detection of cancer provides effective treatment and saves lives. The objective of this study was to determine whether serum gastrokine 1 (GKN1) protein is a gastric cancer‐specific diagnostic biomarker. The serum concentration of GKN1 in healthy individuals (median: 6.34 ng/μL, interquartile range (IQR): 5.66‐7.54 ng/μL) was significantly higher compared with the levels in gastric cancer patients (median: 3.48 ng/μL, IQR: 2.90‐4.11 ng/μL; P, The serum GKN1 protein levels were lower in the gastric cancer patients compared to healthy individuals. The serum levels of GKN1 protein have clearly distinguished the gastric cancer patients from healthy individuals. The serum GKN1 protein could serve as an excellent diagnostic biomarker for early detection of gastric cancer.

We report the fabrication and catalytic performance evaluation of highly active and stable nickel (Ni)-based structured catalysts for ammonia dehydrogenation with nearly complete conversion using nonprecious metal catalysts. Low-temperature chemical alloying (LTCA) followed by selective aluminum (Al) dealloying was utilized to synthesize foam-type structured catalysts ready for implementation in commercial-scale catalytic reactors. The crystalline phases of Ni-Al alloy (NiAl

SWItch/Sucrose Non-Fermentable (SWI/SNF) is a multiprotein complex essential for the regulation of eukaryotic gene expression. SWI/SNF complex genes are genetically altered in over 20% of human malignancies, but the aberrant regulation of the SWI/SNF subunit genes and subsequent dysfunction caused by abnormal expression of subunit gene in cancer, remain poorly understood. Among the SWI/SNF subunit genes, SMARCA4, SMARCC1, and SMARCA2 were identified to be overexpressed in human hepatocellular carcinoma (HCC). Modulation of SMARCA4, SMARCC1, and SMARCA2 inhibited in vitro tumorigenesis of HCC cells. However, SMARCA4-targeting elicited remarkable inhibition in an in vivo Ras-transgenic mouse HCC model (Ras-Tg), and high expression levels of SMARCA4 significantly associated with poor prognosis in HCC patients. Furthermore, most HCC patients (72-86%) showed SMARCA4 overexpression compared to healthy controls. To identify SMARCA4-specific active enhancers, mapping, and analysis of chromatin state in liver cancer cells were performed. Integrative analysis of SMARCA4-regulated genes and active chromatin enhancers suggested 37 genes that are strongly activated by SMARCA4 in HCC. Through chromatin immunoprecipitation-qPCR and luciferase assays, we demonstrated that SMARCA4 activates Interleukin-1 receptor-associated kinase 1 (IRAK1) expression through IRAK1 active enhancer in HCC. We then showed that transcriptional activation of IRAK1 induces oncoprotein Gankyrin and aldo-keto reductase family 1 member B10 (AKR1B10) in HCC. The regulatory mechanism of the SMARCA4-IRAK1-Gankyrin, AKR1B10 axis was further demonstrated in HCC cells and in vivo Ras-Tg mice. Our results suggest that aberrant overexpression of SMARCA4 causes SWI/SNF to promote IRAK1 enhancer to activate oncoprotein Gankyrin and AKR1B10, thereby contributing to hepatocarcinogenesis.

BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis. Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β (Aβ) production. AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production. METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzyme-linked immunosorbent assay, Western blot, immunoprecipitation, real-time quantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E (ApoE), and β-secretase 1 (Bace1) in 55 gastric mucosae. RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3, -9, and poly ADP ribose polymerase were elevated in floating HFE-145shNKX6.3 cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145shNKX6.3 cells. In gastric mucosae with atrophy, expression of Aβ peptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβ oligomeric forms and decreased cell viability in HFE-145shNKX6.3 cells. Additionally, NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2. CONCLUSION NKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells.

Biofuels such as sewage gas and landfill gas, which can be used as fuels in solid oxide fuel cells, have suitable composition of CH4 and CO2 for dry reforming. We developed an Sr0.92Y0.08Ti1−xRuxO3−d material as an anode for solid oxide fuel cells that use biofuels as a direct fuel and show an excellent performance in dry reforming. The Pechini method was used to synthesize the material using ruthenium substitution in the titanium site of an Sr0.92Y0.08TiO3−d (SYT) material. X-ray diffraction analysis confirmed that the perovskite phase of the synthesized catalyst was maintained. Ruthenium-loaded catalysts were prepared by coprecipitating ruthenium onto SYT to compare with the Sr0.92Y0.08Ti1−xRuxO3−d. The differences between Sr0.92Y0.08Ti1−xRuxO3−d and ruthenium-loaded SYT materials during methane dry reforming and the thermal stability during long-term operation were evaluated. In particular, SYTRu10 exhibited higher methane conversion and carbon dioxide conversion than Ru10-loaded SYT at the temperature range of 600–900 °C and stable performance even in long-term operation. X-ray fluorescence and Brunauer–Emmett–Teller measurements were performed to measure the composition of the catalysts and the specific surface area, pore size, and pore volume of the catalysts. X-ray photoelectron spectroscopy and temperature-programmed reduction were used to investigate the state and behavior of ruthenium. Furthermore, transmission electron microscopy was performed to analyze the shape of the catalyst before and after the reaction.