Hepatocellular carcinoma (HCC) is one of the most fatal cancers with common features of invasion and metastasis. Recent evidence indicate that the long noncoding RNA NORAD is a potential oncogene and ...is significantly upregulated in several cancers. However, the general biological role and clinical value of NORAD in HCC remains unknown. Here, NORAD expression was measured in 29 paired tumor and paratumor tissues via quantitative real‐time polymerase chain reaction (qPCR). The effects of NORAD on HCC cell malignant potential were investigated via NORAD overexpression and knockdown both in vitro and in vivo. The mechanism of competitive endogenous RNAs (ceRNAs) was acquired and identified by bioinformatics analyses and luciferase assays. Moreover, the impact of NORAD level on the transforming growth factor β (TGF‐β) pathway was further determined by qPCR. We found that HCC tissues had a high level of NORAD compared with the paratumor tissues, and NORAD upregulation was associated with the shorter overall survival of patients with HCC. Furthermore, NORAD overexpression was demonstrated to promote HCC cell migration and invasion. Mechanically, NORAD might function as a ceRNA to regulate miR‐202‐5p, which served as a tumor‐suppressing microRNA via the TGF‐β pathway. We address that NORAD has a tumor‐promoting effect in HCC and describes a novel mechanism whereby NORAD regulates the TGF‐β pathway as a ceRNA of Homo sapiens (hsa)‐miR‐202‐5p.
Here, we reported a novel axis that NORAD could act as a competitive endogenous RNA to modulate miR‐202‐5p expression, which targets the 3′‐untranslated regions of transforming growth factor β receptors to regulate the transforming growth factor β pathway. It indicated an oncogenic role of NORAD in hepatocellular carcinoma (HCC) and may contribute to HCC research and treatment.
With this expected future advance of HVDC, the use of gas insulated transmission lines (GIL) for dc application are getting increasingly interesting. For now, the problem of surface charge ...accumulation on gas-insulator interface is one of the critical factors for the development of DC-GIL. In many previous works, the model of surface charge accumulation on insulator was investigated. However, the quantitative relationship between temperature and surface charge accumulation on insulator was not exactly obtained since the lack of complicated heat transfer progress in the model. In this paper, the heat transfer surface charge accumulation model of operating DC-GIL was developed, including the nonlinear relationship between volume current in gas and electric field. Moreover, the space charge was also considered in the model. Based on the developed model, temperature distributions in DC-GIL insulator under different current are obtained. Afterwards, the temperature impact on space charge density in the insulator, the saturation time of surface charge accumulation, the surface charge on the insulator surface, and the electric field distribution on the insulator were investigated. It was proven that the tangential component of the electric field reaches to 5.3 kV/mm on lower interface and 5.0 kV/mm on upper interface for Ti=378 K. This value increase 17.8% on lower interface and 17.6% on upper interface along with the conductor temperature from 298 K to 378 K. The data can be referred in the insulation design of DC-GIL.
In recent years, sustainable management of construction waste has garnered increasing attention. However, most previous studies mainly focused on turning construction wastes into recycled aggregates, ...whereas, recycling of those construction wastes below 5 mm has often been challenged or ignored. This study attempted to effectively deal with such recycled fine powders by employment of granulation technology to produce artificial aggregates with a diameter of 5–20 mm. The optimal granulation parameters were identified through a systematic experimental test. Moreover, the effect of water and cement content, as well as curing regimes, on the properties (such as shape and strength) of the prepared artificial aggregates was also investigated. More importantly, influence of normal curing and CO2 curing on the strength development of artificial aggregates was examined and compared. In doing so, the scheme of preparation of artificial aggregates with optimal strength was developed. Findings from this study provide an alternative and viable solution to effectively dealing with construction wastes in an environmentally-friendly way and serve as a reference for follow-up studies in the future. Meanwhile, the carbonated artificial aggregate can be potentially used to replace natural aggregates in the preparation of low-strength concrete and blocks.
Hepatocellular carcinoma (HCC) has a complex and changeable tumor microenvironment. Despite emerging evidence focusing on autophagy process within immune cells, the function and regulatory mechanism ...of macrophage autophagy in tumor progression remains unclear. Our results of multiplex-immunohistochemistry and RNA-sequencing identified the reduced levels of autophagy in tumor macrophages in the HCC microenvironment, associated with a poor prognosis and increased microvascular metastasis in HCC patients. Specifically, HCC suppressed the macrophage autophagy initiation through the up-regulation of mTOR and ULK1 phosphorylation at Ser757. Knockdown of autophagy-related proteins to further inhibit autophagy significantly boosted the metastatic potential of HCC. Mechanistically, the accumulation of NLRP3 inflammasome mediated by autophagy inhibition promoted the cleavage, maturation, and release of IL-1β, which facilitated the HCC progression, eventually accelerating HCC metastasis via the epithelial-mesenchymal transition. Autophagy inhibition provoked macrophage self-recruitment through the CCL20-CCR6 signaling was also a crucial account of HCC progression. Recruited macrophages mediated the cascade amplification of IL-1β and CCL20 to form a novel pro-metastatic positive feedback loop through promoting HCC metastasis and increased macrophage recruitment, respectively. Notably, targeting IL-1β/IL-1 receptor signaling impaired lung metastasis induced by macrophage autophagy inhibition in a mice HCC lung metastasis model. In summary, this study highlighted that inhibition of tumor macrophage autophagy facilitated HCC progression by increasing IL-1β secretion via NLRP3 inflammasome accumulation and by macrophage self-recruitment through the CCL20 signaling pathway. Interruption of this metastasis-promoting loop by IL-1β blockade may provide a promising therapeutic strategy for HCC patients.
Background & Aims The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched ...for mutations in human ICC tumor samples and investigated how they affect ICC cell function. Methods We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). Results Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3 . Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3 L232R and PTPN3 L384H , which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. Conclusions Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3 . Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence.
Galloping of overhead transmission lines (OHTLs) may induce conductor breakage and tower collapse, and there is no effective method for long distance distribution on-line galloping monitoring. To ...overcome the drawbacks of the conventional galloping monitoring systems, such as sensitivity to electromagnetic interference, the need for onsite power, and short lifetimes, a novel optical remote passive measuring system is proposed in the paper. Firstly, to solve the hysteresis and eccentric load problem in tension sensing, and to extent the dynamic response range, an 'S' type elastic element structure with flanges was proposed. Then, a tension experiment was carried out to demonstrate the dynamic response characteristics. Moreover, the designed tension sensor was stretched continuously for 30 min to observe its long time stability. Last but not the least, the sensor was mounted on a 70 m conductor model, and the conductor was oscillated at different frequencies to investigate the dynamic performance of the sensor. The experimental results demonstrate the sensor is suitable for the OHTL galloping detection. Compared with the conventional sensors for OHTL monitoring, the system has many advantages, such as easy installation, no flashover risk, distribution monitoring, better bandwidth, improved accuracy and higher reliability.
Getting distilled water through solar energy is a green and sustainable way to purify water. The reduction of the evaporation enthalpy by hydrogels greatly improves the efficiency of water ...purification. However, the lack of heat localization functionality leads to low energy utilization efficiency, which seriously affects the performance of hydrogel-based evaporators. Herein, inspired by the hierarchical porous channel and thin structure of cormorant wings, a hydrogel thin film with interconnected micrometer macro-pores channels is proposed for simultaneous sufficient heat localization at the evaporation interface and adequate water supply. Benefiting from the macro-porous thin film structure, a device prepared from the hydrogel film can reduce the heat loss by 88% by reducing the heat transfer cross-sectional area and achieve a sustained water evaporation rate of 4.14 kg m
−2
h
−1
with 98% energy efficiency under 1 sun after shape optimization. Remarkably, the low raw material usage of thin film makes the cost as low as $0.87 m
−2
. Furthermore, the synthesis method of this macro-porous thin film structure can be generalized to a range of hydrogels, thus serving as a universal technology for improving heat localization. This work demonstrates the application of macro-porous hydrogel thin film evaporators in green and sustainable water purification.
We develop a macro-porous hydrogel film strategy for solar water purification inspired by the structure of cormorant wings. The evaporation rate can reach 4.14 kg m
−2
h
−1
and the energy efficiency can reach 98% under one sun.
Separating the impact of climate change and human activities on runoff is an important topic in hydrology, and a large number of methods and theories have been widely used. In this paper, we review ...the current papers on separating the impacts of climate and human activities on runoff, summarize the progress of relevant research methods and applications in recent years, and discuss future research needs and directions.
Advanced detection of RNA modifications, especially N6-methyladenosine, paves the way for transcriptome-wide, single-cell, and stoichiometric modification profiling at single-nucleotide ...resolution.RNA modification databases, tumor atlases, drug-like compound libraries, and machine learning have accelerated therapeutic development focused on epitranscriptomics.Novel RNA modification engineering tools based on the CRISPR/Cas technology or endogenous RNA modification machinery can be applied to uncover causal relationships between individual modification sites and phenotypic outcomes.
The epitranscriptomics field has undergone tremendous growth since the discovery that the RNA N6-methyladenosine (m6A) modification is reversible and is distributed throughout the transcriptome. Efforts to map RNA modifications transcriptome-wide and reshape the epitranscriptome in disease settings have facilitated mechanistic understanding and drug discovery in the field. In this review we discuss recent advancements in RNA modification detection methods and consider how these developments can be applied to gain novel insights into the epitranscriptome. We also highlight drug discovery efforts aimed at developing epitranscriptomic therapeutics for cancer and other diseases. Finally, we consider engineering of the epitranscriptome as an emerging direction to investigate RNA modifications and their causal effects on RNA processing at high specificity.
The epitranscriptomics field has undergone tremendous growth since the discovery that the RNA N6-methyladenosine (m6A) modification is reversible and is distributed throughout the transcriptome. Efforts to map RNA modifications transcriptome-wide and reshape the epitranscriptome in disease settings have facilitated mechanistic understanding and drug discovery in the field. In this review we discuss recent advancements in RNA modification detection methods and consider how these developments can be applied to gain novel insights into the epitranscriptome. We also highlight drug discovery efforts aimed at developing epitranscriptomic therapeutics for cancer and other diseases. Finally, we consider engineering of the epitranscriptome as an emerging direction to investigate RNA modifications and their causal effects on RNA processing at high specificity.
The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of ...αB‐Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB‐Crystallin expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB‐Crystallin promotes HCC progression in vivo and in vitro. We demonstrate that αB‐Crystallin overexpression fosters HCC progression by inducing epithelial‐mesenchymal transition (EMT) in HCC cells through activation of the extracellular‐regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB‐Crystallin complexes with and elevates 14‐3‐3ζ protein, leading to up‐regulation of ERK1/2 activity. Moreover, overexpression of αB‐Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra‐1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB‐Crystallin and 14‐3‐3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB‐Crystallin overexpression. Conclusion: These data suggest that the αB‐Crystallin‐14‐3‐3ζ complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals αB‐Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. (HEPATOLOGY 2013)
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