Long noncoding RNA lnc_217 regulates hepatic lipid metabolism by modulating lipogenesis and fatty acid oxidation

Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, lnc_217, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of lnc_217 was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of lnc_217 not only decreased de novo lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid β- oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that lnc_217 may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.

Anionic structural effect in liquid–liquid separation of phenol from model oil by choline carboxylate ionic liquids

Phenolic compounds exist in crude oil as pollutants, and their removal is vital important for the refining and further application of oils. In traditional separation approaches, strong acid and strong base have to be used to remove these compounds, which may cause serious environmental problems. In this work, 19 kinds of cholinium ionic liquids have been developed to separate phenol from model oil by liquid–liquid extraction. Structural effect of anions of the ionic liquids in the separation is systematically investigated. It is found that depending on the chemical structure of ionic liquids, phenol can be removed from toluene with single-step removal efficiency from 86 to 99% under optimal conditions. The type of substituent groups and the-CH_2 number between two carboxylates have obvious effect on the removal efficiency, and more hydrophilic ionic liquids have a stronger extraction performance for phenol. Furthermore, thermodynamic,^(13) C NMR,~1 H NMR and density functional theory calculations have been performed to characterize the extraction process and to understand the extraction mechanism. It is shown that the extraction of phenol from oil to ionic liquid is a favorable process, and this process is mainly driven by enthalpy change. The formation of the hydrogen bond between anion of the ionic liquid and-OH of phenol is the main driving force for the extraction of phenol from oil to the ionic liquids.

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development.However,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of TFs.Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor complexes.In this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA cells.Importantly,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA.Furthermore,we identified KRAS signaling as a common pathway downstream of EHF and AJUBA.Applicably,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo.In conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway.Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

Smart ionic liquid/water mixture system with dual stimuli-response to temperature and CO_(2)

Stimuli-responsive materials have important applications in chemistry and chemical engineering.Here,we synthesized five different polyetheramine-fatty acids(PEFA)ionic liquids(ILs),possessing the dual stimuli-responsive ability to temperature and CO_(2).These PEFA ILs have reversible lower critical solution temperature(LCST)phase behavior over a wide temperature range of 37-91℃,and reversible heterogeneous-homogeneous phase transition towards the addition and removal of CO_(2).Furthermore,the droplet size of the IL-water mixture system increased from 6.5 to 21.0 nm as the temperature increased from 25 to 56℃,and then recovered to 6.5 nm when the temperature decreased to 25℃.The addition and removal of CO_(2)also reversibly modulated the droplet size of the system.Results from nuclear magnetic resonance(NMR)and Fourier transform infrared(FTIR)spectra further showed that the temperature-dependent conformation of polyether amine chain in the cation dominates the temperature response,while the reversible formation of bicarbonate and fatty acids(FA)from CO_(2)and anion controls the CO_(2)-based reversible phase transition.Molecular simulations revealed a microscopic response mechanism of the IL-water system to temperature and CO_(2),and a synergistic effect between the dual stimuli of temperature and CO_(2).These findings may provide a basis for the rational design and understanding of ILs-based stimuli-responsive materials and nanoreactors.

光响应离子液体的结构与性能调控

光响应离子液体是一类兼具光刺激响应和离子液体双重特性的功能材料。在紫外/可见光照下,这类“智能型”离子液体的结构会发生变化,从而引起物理化学性质和相关体系性能的显著变化,以满足某些特定过程的需要。光刺激具有信号稳定、刺激部位精准、可快速切换、刺激过程不引入其他物质等优点,在刺激响应离子液体的结构与性质调控中具有独特的优势。本文以光响应离子液体的结构-性质-性能关系为主线,对光响应离子液体的光致异构化、物理化学性质调制、簇集行为调控、光致相转移及离子液体参与构筑的光响应乳液相行为调控等方面的研究进展进行了评述,分析了该领域研究中存在的主要问题,并对其发展前景进行了展望。

Maturity Assessment of the Lower Cambrian and Sinian Shales Using Multiple Technical Approaches

The Lower Cambrian Niutitang and Sinian Doushantuo shales are the most important and widespread source rocks and target layers in South China. Reliable data of the thermal maturity of organic matter(OM) is widely used to assess hydrocarbon generation and is a key property used in determining the viability and hydrocarbon potential of these new shales. Nevertheless, traditional thermal maturity indicators are no longer suited to the vitrinite-lack marine shales. This study aims to combine high throughput Raman and infrared spectroscopy analysis to confirm and validate the thermal maturity in comparison with the bitumen reflectance(R_(b)). Raman parameters such as the differences between the positions of the two bands(V_(G)–V_(D)) are strong parameters for calculating the thermal maturity in a large vitrinite reflectance(R_(o)) ranging from 1.60% to 3.80%. The infrared spectroscopy analysis indicates that the aromatic C=C bands and CH_(2)/CH_(3) aliphatic groups both are closely correlated with thermal maturity. The calculated R_(o) results from Raman and infrared spectroscopy are in strong coincidence with the R_(b). The relationships between R_(b) and pore volumes/surface areas(calculated from N_(2) adsorption) indicate that the sample with R_(b) of 3.40% has the lowest pore volumes and surface areas. Focused ion beam scanning electron microscopy(FIB-SEM) observations of OM pores indicate that R_(o) of approximately 3.60% may be an upper limit for OM porosity development. Obviously, kerogen Raman and infrared spectroscopy can indicate methods for reducing the risk in assessing maturity with practical, low-cost accurate results. Exploration of shale gas in the high maturity(>3.40%–3.60%) region carries huge risks.