The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update

Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-apoptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and lncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.published_or_final_versio

KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations

Outsourcing CO2 within China

Recent studies have shown that the high standard of living enjoyed by people in the richest countries often comes at the expense of CO2 emissions produced with technologies of low efficiency in less affluent, developing countries. Less apparent is that this relationship between developed and developing can exist within a single country’s borders, with rich regions consuming and exporting high-value goods and services that depend upon production of low-cost and emission-intensive goods and services from poorer regions in the same country. As the world’s largest emitter of CO2, China is a prominent and important example, struggling to balance rapid economic growth and environmental sustainability across provinces that are in very different stages of development. In this study, we track CO2 emissions embodied in products traded among Chinese provinces and internationally. We find that 57% of China’s emissions are related to goods that are consumed outside of the province where they are produced. For instance, up to 80% of the emissions related to goods consumed in the highly developed coastal provinces are imported from less developed provinces in central and western China where many low–value-added but high–carbon-intensive goods are produced. Without policy attention to this sort of interprovincial carbon leakage, the less developed provinces will struggle to meet their emissions intensity targets, whereas the more developed provinces might achieve their own targets by further outsourcing. Consumption-based accounting of emissions can thus inform effective and equitable climate policy within China

Thermal-magnetic noise measurement of spin-torque effects on ferromagnetic resonance in MgO-based magnetic tunnel junctions

Thermal-magnetic noise at ferromagnetic resonance (T-FMR) can be used to measure magnetic perpendicular anisotropy of nanoscale magnetic tunnel junctions (MTJs). For this purpose, T-FMR measurements were conducted with an external magnetic field up to 14 kOe applied perpendicular to the film surface of MgO-based MTJs under a dc bias. The observed frequency-field relationship suggests that a 20 A CoFeB free layer has an effective demagnetization field much smaller than the intrinsic bulk value of CoFeB, with 4PiMeff = (6.1 +/- 0.3) kOe. This value is consistent with the saturation field obtained from magnetometry measurements on extended films of the same CoFeB thickness. In-plane T-FMR on the other hand shows less consistent results for the effective demagnetization field, presumably due to excitations of more complex modes. These experiments suggest that the perpendicular T-FMR is preferred for quantitative magnetic characterization of nanoscale MTJs.Comment: 10 pages, 3 figures, accepted by AP

Simulation of an Extreme Precipitation Event Using Ensemble-Based WRF Model in the Southeastern Coastal Region of China

Extreme weather events have increased significantly in the past decades due to global warming. As a robust forecast and monitoring tool of extreme weather events, regional climate models have been widely applied on local scales. This study presented a simulation of an extreme precipitation event in the Southeastern Coastal Region of China (SEC), where floods, typhoons, and mountain torrents occur frequently using the Weather Research and Forecast model (WRF) driven by GEFS (The Global Ensemble Forecast System) ensemble members (one control run and 20 ensemble members) from 01 UTC 14 June to 18 UTC 16 June 2010. The observations of hourly precipitation records from 68 meteorological stations in the SEC were applied to validate the WRF ensemble simulations with respect to 3-hourly cumulative precipitation (3hP), 6-hourly cumulative precipitation (6hP) and total cumulative precipitation (TCP). The results showed that all WRF 20 ensemble outputs could capture the extreme precipitation events fairly well with the Pearson correlation coefficient ranging from 0.01 to 0.82 and 0.16 to 0.89 for 3 and 6hP, respectively. The normalized root mean square error was comparable between the control run and 20 ensembles for 3hP (0.67 vs. 0.63) and 6hP (0.51 vs. 0.53). In general, WRF underestimated the observations for TCP. The control run (En00) modeled 28.1% less precipitation, while the 20 ensembles modeled 3.9% to 55.5% less precipitation than observations. The ensemble member 12 (En12) showed the best TCP simulation with the smallest bias. The average of 20 ensembles simulated 31.7% less precipitation than observations. The total precipitation was not captured by WRF with a significant bias that ranged from −203.1 to 112.3 mm. The storm centers were generally not captured by WRF in this case study. WRF ensembles underestimated the observation in the central Fujian Province while overestimated in the northern and southern Fujian Province. Although the average of ensembles can reduce the uncertainty to a certain extent, the individual ensemble (e.g., En12) may be more reliable on local scales

When energy trading meets blockchain in electrical power system: The state of the art

With the rapid growth of renewable energy resources, energy trading has been shifting from the centralized manner to distributed manner. Blockchain, as a distributed public ledger technology, has been widely adopted in the design of new energy trading schemes. However, there are many challenging issues in blockchain-based energy trading, e.g., low efficiency, high transaction cost, and security and privacy issues. To tackle these challenges, many solutions have been proposed. In this survey, the blockchain-based energy trading in the electrical power system is thoroughly investigated. Firstly, the challenges in blockchain-based energy trading are identified and summarized. Then, the existing energy trading schemes are studied and classified into three categories based on their main focuses: energy transaction, consensus mechanism, and system optimization. Blockchain-based energy trading has been a popular research topic, new blockchain architectures, models and products are continually emerging to overcome the limitations of existing solutions, forming a virtuous circle. The internal combination of different blockchain types and the combination of blockchain with other technologies improve the blockchain-based energy trading system to better satisfy the practical requirements of modern power systems. However, there are still some problems to be solved, for example, the lack of regulatory system, environmental challenges and so on. In the future, we will strive for a better optimized structure and establish a comprehensive security assessment model for blockchain-based energy trading system.This research was funded by Beijing Natural Science Foundation (grant number 4182060).Scopu

Universal behavior of giant electroresistance in epitaxial La0.67Ca0.33MnO3 thin films

We report a giant resistance drop induced by dc electrical currents in La0.67Ca0.33MnO3 epitaxial thin films. Resistance of the patterned thin films decreases exponentially with increasing current and a maximum drop shows at the temperature of resistance peak Tp. Variation of resistance with current densities can be scaled below and above Tp, respectively. This work can be useful for the future applications of electroresistance.Comment: 13 pages, 4 figure

Polyphenylene as an Active Support for Ru-Catalyzed Hydrogenolysis of 5-Hydroxymethylfurfural

Selective transformation of biomass feedstocks to platform molecules is a key pursuit for sustainable chemical production. Compared to petrochemical processes, biomass transformation requires the defunctionalization of highly polar molecules at relatively low temperatures. As a result, catalysts based on functional organic polymers may play a prominent role. Targeting the hydrogenolysis of the platform chemical 5-hydroxymethylfurfural (5-HMF), here, we design a polyphenylene (PPhen) framework with purely sp2-hybridized carbons that can isolate 5-HMF via π–π stacking, preventing hemiacetal and humin formation. With good swellability, the PPhen framework here has successfully supported and dispersed seven types of metal particles via a newly developed swelling-impregnation method, including Ru, Pt, Au, Fe, Co, Ni, and Cu. Ru/PPhen is studied for 5-HMF hydrogenolysis, achieving a 92% yield of 2,5-dimethylfuran (DMF) under mild conditions, outperforming the state-of-the-art catalysts reported in the literature. In addition, PPhen helps perform a solventless reaction, achieving direct 5-HMF to DMF conversion in the absence of any liquid solvent or reagent. This approach in designing support–reactant/solvent/metal interactions will play an important role in surface catalysis