Constructing Nitrogen-Doped Carbon Hierarchy Structure Derived from Metal-Organic Framework as High-Performance ORR Cathode Material for Zn-Air Battery.

The development of efficient and low-cost catalysts for cathodic oxygen reduction reaction (ORR) in Zn-air battery (ZAB) is a key factor in reducing costs and achieving industrialization. Here, a novel segregated CoNiPt alloy embedded in N-doped porous carbon with a nanoflowers (NFs)-like hierarchy structure is synthesized through pyrolyzing Hofmann-type metal-organic frameworks (MOFs). The unique hierarchical NFs structure exposes more active sites and facilitates the transportation of reaction intermediates, thus accelerating the reaction kinetics. Impressively, the resulting 15% CoNiPt@C NFs catalyst exhibits outstanding alkaline ORR activity with a half-wave potential of 0.93 V, and its mass activity is 7.5 times higher than that of commercial Pt/C catalyst, surpassing state-of-the-art noble metal-based catalysts. Furthermore, the assembled CoNiPt@C+RuO2 ZAB demonstrates a maximum power density of 172 mW cm-2 , which is superior to that of commercial Pt/C+RuO2 ZAB. Experimental results reveal that the intrinsic ORR mass activity is attributed to the synergistic interaction between oxygen defects and pyrrolic/graphitic N species, which optimizes the adsorption energy of the intermediate species in the ORR process and greatly enhances catalytic activity. This work provides a practical and feasible strategy for synthesizing cost-effective alkaline ORR catalysts by optimizing the electronic structure of MOF-derived catalysts.

Ring finger protein 12 activates AKT signalling to promote the progression of liver cancer by interacting with EGFR.

Liver cancer is one of the most common solid tumours, and ranks as the third leading cause of cancer-associated mortality around the world. This study has linked RNF12 to the pathogenesis of liver cancer. Based on the analysis of patient samples and database data, high RNF12 expression was found in liver cancer, in correlation with worse clinicopathological features and a poor prognosis. Meantime, RNF12 could promote the progression of liver cancer in vitro and in vivo. Mechanistically, RNF12 could interact with EGFR and decrease the internalization of EGFR to activate EGF/EGFR signalling. In addition, PI3K-AKT signalling takes part in the regulation of liver cancer cell proliferation and migration of RNF12. And AKT inhibitor MK2206 could reverse RNF12-mediated cellular proliferation and migration in liver cancer. The possibility of the physical interaction between RNF12 and EGFR might lay a foundation to develop intervention strategies for liver cancer prevention and therapy.

Long noncoding RNA MAPKAPK5-AS1 promotes metastasis through regulation miR-376b-5p/ECT2 axis in hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the most common diseases threatening human health worldwide. However, the molecular mechanisms of HCC are still unclear. Here, we identified a differentially expressed lncRNA called MAPKAPK5-AS1(abbreviation: MK5-AS1) and elucidated its role and molecular mechanism in the development of HCC. METHODS: Real-time PCR (RT-PCR) was used to verify the expression of MK5-AS1 in hepatocarcinoma cell lines and tumor tissues of HCC patients. The biological functions of MK5-AS1 in HCC cells was assessed both in vitro and in vivo assays. The Lncbase, miRDB and TargetScan databases were used to predict the lncRNA-miRNA-mRNA interactions. RNA immunoprecipitation (RIP) and double luciferase reporter gene assays further verified the interactions. RESULTS: MK5-AS1 expression was significantly upregulated in HCC tissues and cell lines. Furthermore, high MK5-AS1 expression was positively associated with tumor progression and poor prognosis. In vitro and in vivo experiments confirmed that overexpressed MK5-AS1 promoted migration and invasion of HCC cells. Bioinformatics analysis based on Lncbase, miRDB and TargetScan databases showed MK5-AS1 competitively bound to miR-376b-5p that prevented epithelial cell transforming sequence 2 (ECT2) from miRNA-mediated degradation, thus facilitated HCC metastasis. CONCLUSION: Our results established a tumor promotive role of MK5-AS1 in HCC pathogenesis.

LINC01980 induced by TGF-beta promotes hepatocellular carcinoma metastasis via miR-376b-5p/E2F5 axis.

Hepatocellular carcinoma (HCC) is one of the most aggressive human malignancies worldwide. However, the molecular mechanism of HCC metastasis is largely unknown. Long non-coding RNA (lncRNA) plays a key role in gene regulation, and dysregulation of lncRNA is critical to cancer metastasis. LINC01980 has been reported in ESCC recently, but the mechanism underlying its function in HCC is still unknown. In this study, we found that LINC01980 was upregulated and associated with notably poor overall survival in HCC patients. Functionally, LINC01980 played a carcinogenic role and promoted HCC metastasis. Mechanically, LINC01980 enhanced the E2F5 expression via competitively binding miR-376b-5p, thereby inducing epithelial-mesenchymal transition and promoting HCC cells migration and invasion. In addition, LINC01980-mediated HCC cells metastasis was dependent on E2F5. What's more, TGF-ß activated LINC01980 transcription through the canonical TGF-ß/SMAD signaling pathway in HCC. In conclusion, LINC01980, activated by the canonical TGF-ß/SMAD pathway, promoted HCC metastasis via miR-376b-5p/E2F5 axis. Therefore, LINC01980 might be a potential prognostic biomarker and therapeutic target of HCC.

Emerging roles and potential clinical applications of long non-coding RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most common highly malignant tumors in humans, as well as the leading cause of cancer-related death worldwide. Growing evidence has indicated that lncRNAs are implicated in different molecular mechanisms, including interactions with DNA, RNA, or protein, so that to regulate the gene expression at epigenetic, transcriptional, or posttranscriptional level. Moreover, the mechanism of action of lncRNA is closely related to its subcellular localization. An increasing number of studies have certified that lncRNA plays a significant biological function in the occurrence and development of hepatocellular carcinoma, such as involving in cell proliferation, metastasis, apoptosis, ferroptosis, autophagy, and reprogramming of energy metabolism. As a result, lncRNA has great potential as a novel biomarker for diagnosis or therapeutics of hepatocellular carcinoma. In this review, we highlight the correlation between subcellular localization of lncRNA and its mechanism of action, discuss the biological roles of lncRNA and the latest research advances in hepatocellular carcinoma, and emphasize the potential of lncRNA as a therapeutic target for advanced patients of hepatocellular carcinoma.

Pan-cancer analysis combined with experimental validation revealed IL4I1 as an immunological and prognostic biomarker.

Interleukin-4-induced gene 1 (IL4I1) is a secreted l-phenylalanine oxidase that deaminates phenylalanine to phenylpyruvate, releasing H2O2 and NH3 in the process. IL4I1 is mainly secreted by inflammatory antigen presenting cells and is involved in the regulation of adaptive immune responses. Furthermore, it has been reported that IL4I1 is overexpressed in a variety of tumor tissues and affects tumor development. We explored the expression patterns, correlation with clinical traits and prognostic value of IL4I1 using public databases and microarray data from sample banks. Subsequently, we used the downloaded data to score tumor stromal cells and immune cell infiltration and analyzed the correlation between IL4I1 and immune cells or immune-related molecules in combination with TIMER2.0 and GEPIA databases. The analysis showed that IL4I1 was associated with the infiltration status of various immune cells. Finally, stable IL4I1-overexpressing hepatocellular carcinoma (HCC) cell lines were established to investigate the effect of IL4I1 on cell proliferation and motor capacity. All of these results suggest that IL4I1 is a potential biomarker and therapeutic target.

LncRNA influence sequential steps of hepatocellular carcinoma metastasis.

As a class of new and crucial molecules involved in the regulation of biological function, long noncoding RNA (lncRNA) have obtained widespread attention in recent days. While it was thought that lncRNA would be redundant in the past, it is proved that lncRNA identify a class of molecular that regulate the homeostasis including hepatocellular carcinoma in the present. All kinds of lncRNA have been implicated in a various of diseases, particularly in tumorigenesis and metastasis. But the mechanisms how they act is still not entirely clear. Metastasis is a major factor affecting long-term survival in hepatocellular carcinoma (HCC) patients. Recently, growing numbers of experiments demonstrate that there is close connection between lncRNA and HCC metastasis. Here, we will briefly introduce a series of steps (primary tumor growth, angiogenesis, epithelial-to-mesenchymal transition, invasion, intravasation, survival in circulatory system, extravasation, dormancy and subsequent secondary tumor growth) of tumor metastasis, its classical but promising theories, the role of lncRNA in metastasis and the possible mechanisms involved. LncRNA, as potentially new and important tumor diagnostic and therapeutic molecules, has attracted much attention in recent years.

The Emerging Roles of circFOXO3 in Cancer.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs which are mainly formed by reverse splicing of precursor mRNAs. They are relatively stable and resistant to RNase R because of their covalently closed structure without 5' caps or 3' poly-adenylated tails. CircRNAs are widely expressed in eukaryotic cells and show tissue, timing, and disease specificity. Recent studies have found that circRNAs play an important role in many diseases. In particular, they affect the proliferation, invasion and prognosis of cancer by regulating gene expression. CircRNA Forkhead box O3 (circFOXO3) is a circRNA confirmed to be abnormally expressed in a variety of cancers, including prostate cancer, hepatocellular carcinoma, glioblastoma, bladder cancer, and breast cancer, etc. At present, the feature of circFOXO3 as a molecular sponge is widely studied to promote or inhibit the development of cancers. However, the diverse functions of circFOXO3 have not been fully understood. Hence, it is important to review the roles of circFOXO3 in cancers. This review has summarized and discussed the roles and molecular mechanism of circFOXO3 and its target genes in these cancers, which can help to enrich our understanding to the functions of circRNAs and carry out subsequent researches on circFOXO3.