Enhancers are distal genomic elements critical for gene regulation and cell identify control during development and diseases. Many human cancers were found to associate with enhancer malfunction, due ...to genetic and epigenetic alterations, which in some cases directly drive tumour growth. Conventionally, enhancers are known to provide DNA binding motifs to recruit transcription factors (TFs) and to control target genes. However, recent progress found that most, if not all, active enhancers pervasively transcribe noncoding RNAs that are referred to as enhancer RNAs (eRNAs). Increasing evidence points to functional roles of at least a subset of eRNAs in gene regulation in both normal and cancer cells, adding new insights into the action mechanisms of enhancers. eRNA expression was observed to be widespread but also specific to tumour types and individual patients, serving as opportunities to exploit them as potential diagnosis markers or therapeutic targets. In this review, we discuss the brief history of eRNA research, their functional mechanisms and importance in cancer gene regulation, as well as their therapeutic and diagnostic values in cancer. We propose that further studies of eRNAs in cancer will offer a promising 'eRNA targeted therapy' for human cancer intervention.
A new direction for developing electrocatalysts for hydrogen fuel cell systems has emerged, based on the fabrication of 3D architectures. These new architectures include extended Pt surface building ...blocks, the strategic use of void spaces, and deliberate network connectivity along with tortuosity, as design components. Various strategies for synthesis now enable the functional and structural engineering of these electrocatalysts with appropriate electronic, ionic, and electrochemical features. The new architectures provide efficient mass transport and large electrochemically active areas. To date, although there are few examples of fully functioning hydrogen fuel cell devices, these 3D electrocatalysts have the potential to achieve optimal cell performance and durability, exceeding conventional Pt powder (i.e., Pt/C) electrocatalysts. This progress report highlights the various 3D architectures proposed for Pt electrocatalysts, advances made in the fabrication of these structures, and the remaining technical challenges. Attempts to develop design rules for 3D architectures and modeling, provide insights into their achievable and potential performance. Perspectives on future developments of new multiscale designs are also discussed along with future study directions.
3D Pt architectures have received tremendous attention owing to their superior structure and intrinsic properties, and are suited to fuel cell electrocatalyst applications. The fabrication methods and the effect of geometry on electrochemical processes for high‐performance 3D Pt electrocatalysts are reviewed. New design guidelines for the development of such electrocatalysts are proposed, considering future research directions.
Nickel-rich layered lithium transition-metal oxides, LiNi(1-x)M(x)O(2) (M = transition metal), have been under intense investigation as high-energy cathode materials for rechargeable lithium ...batteries because of their high specific capacity and relatively low cost. However, the commercial deployment of nickel-rich oxides has been severely hindered by their intrinsic poor thermal stability at the fully charged state and insufficient cycle life, especially at elevated temperatures. Here, we report a nickel-rich lithium transition-metal oxide with a very high capacity (215 mA h g(-1)), where the nickel concentration decreases linearly whereas the manganese concentration increases linearly from the centre to the outer layer of each particle. Using this nano-functional full-gradient approach, we are able to harness the high energy density of the nickel-rich core and the high thermal stability and long life of the manganese-rich outer layers. Moreover, the micrometre-size secondary particles of this cathode material are composed of aligned needle-like nanosize primary particles, resulting in a high rate capability. The experimental results suggest that this nano-functional full-gradient cathode material is promising for applications that require high energy, long calendar life and excellent abuse tolerance such as electric vehicles.
Enhancer RNA (eRNA) is a type of noncoding RNA transcribed from the enhancer. Although critical roles of eRNA in gene transcription control have been increasingly realized, the systemic landscape and ...potential function of eRNAs in cancer remains largely unexplored. Here, we report the integration of multi-omics and pharmacogenomics data across large-scale patient samples and cancer cell lines. We observe a cancer-/lineage-specificity of eRNAs, which may be largely driven by tissue-specific TFs. eRNAs are involved in multiple cancer signaling pathways through putatively regulating their target genes, including clinically actionable genes and immune checkpoints. They may also affect drug response by within-pathway or cross-pathway means. We characterize the oncogenic potential and therapeutic liability of one eRNA, NET1e, supporting the clinical feasibility of eRNA-targeted therapy. We identify a panel of clinically relevant eRNAs and developed a user-friendly data portal. Our study reveals the transcriptional landscape and clinical utility of eRNAs in cancer.
High capacity electrodes based on a Si composite anode and a layered composite oxide cathode, Ni‐rich LiNi0.75Co0.1Mn0.15O2, are evaluated and combined to fabricate a high energy lithium ion battery. ...The Si composite anode, Si/C‐IWGS (internally wired with graphene sheets), is prepared by a scalable sol–gel process. The Si/C‐IWGS anode delivers a high capacity of >800 mAh g−1 with an excellent cycling stability of up to 200 cycles, mainly due to the small amount of graphene (∼6 wt%). The cathode (LiNi0.75Co0.1Mn0.15O2) is structurally optimized (Ni‐rich core and a Ni‐depleted shell with a continuous concentration gradient between the core and shell, i.e., a full concentration gradient, FCG, cathode) so as to deliver a high capacity (>200 mAh g−1) with excellent stability at high voltage (∼4.3 V). A novel lithium ion battery system based on the Si/C‐IWGS anode and FCG cathode successfully demonstrates a high energy density (240 Wh kg−1 at least) as well as an unprecedented excellent cycling stability of up to 750 cycles between 2.7 and 4.2 V at 1C. As a result, the novel battery system is an attractive candidate for energy storage applications demanding a high energy density and long cycle life.
A novel lithium‐ion battery system based on a Si/C composite anode internally wired with a small amount of graphene sheet (∼6 wt%) and a nano‐structured layered‐composite cathode successfully demonstrates a high energy density (240 Wh kg−1 at least) as well as an unprecedented excellent cycling stability of up to 750 cycles between 2.7 and 4.2 V at 1C.
The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we ...characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.
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•MINT-seq is of high sensitivity to characterize m6A methylome on nascent RNAs•There is a pervasive but also selective m6A deposition to long and stable eRNAs•m6A-eRNAs recruit YTHDC1 to enhancers to stimulate enhancer and gene activation•m6A-eRNA/YTHDC1 phase separate to facilitate transcriptional condensate formation
Lee, Wang, Xiong, et al. characterized nascent RNA m6A methylome in human cells, finding a pervasive existence of m6A-marked eRNAs. These m6A-modified eRNAs recruit the nuclear m6A reader YTHDC1 to partition into liquid-like condensates, which facilitate formation of transcriptional activator condensates and therefore gene activation.
Nanostructural design renders several breakthroughs for the construction of high-performance materials and devices including energy-storage systems. Although attempts made toward electrode ...engineering have improved the existing drawbacks, nanoengineering is still hindered by some issues. To achieve practical applications of lithium–sulfur (Li–S) batteries, it is difficult to attain a high areal capacity with stable cycling. Physical encapsulation via nanostructural design not only can resolve the issue of lithium polysulfide dissolution during the electrochemical cycling, but also can offer significant contact resistance, which in turn can decrease the kinetics, particularly at a high sulfur loading. Thus, we demonstrate an electrospun carbon nanofiber (CNF) matrix for a sulfur cathode. This simple design enables a high mass loading of 10.5 mg cm–2 with a high specific capacity and stable cycling. The CNF–sulfur complex can deliver a high areal capacity of greater than 7 mAh cm–2, which is related to the excellent electrical conductivity of one-dimensional species. Moreover, we have observed that the reacted sulfur species have adhered well to the junction of the CNF network with specific wetting angles, which are induced by the cohesive force between the narrow gaps in the matrix that trapped the viscous polysulfides during cycling. The results of this study open new avenues for the design of high-areal-capacity Li–S batteries.
Although ground measurements have contributed to revealing the association between ambient air pollution and health effects in epidemiological studies, exposure measurement errors are likely to be ...caused because of the sparse spatial distribution of ground monitors. In this study, we estimate daily ground NO2 concentrations in the New England region, U.S., for the period 2005–2010 using satellite remote sensing data in combination with land use regression. To estimate ground-level NO2 concentrations, we constructed a mixed effects model by taking advantage of spatial and temporal variability in satellite Ozone Monitoring Instrument (OMI) tropospheric column NO2 densities. Using fine-scale land use parameters, we derived NO2 concentrations at point locations, which can be further used for subject-specific exposure estimates in epidemiological studies. A mixed effects model showed a reasonably high predictive power for daily NO2 concentrations (cross-validation R 2 = 0.79). We observed that the model performed similarly in each season, year, and state. The spatial patterns of model estimates reflected emission source areas (such as high populated/traffic areas) in the study region and revealed the seasonal characteristics of NO2. This study suggests that a combination of satellite remote sensing and land use regression can be useful for both spatially and temporally resolved exposure assessments of NO2.
•CNCs have features that promote hydration of un-hydrated areas in cement.•Hydration products increased up to 18% compared to plain specimen without CNCs.•The results of the durability evaluation of ...the fiber-reinforced specimens to improve the CNC mixing ratio and ductility behavior showed significant strength improvement at the mixing ratio of 0.8 (vol%).•Excellent results even in long-term durability through the effect of reducing voids in cement due to increased hydration products.
As part of the study for the development of sustainable construction new materials for fiber reinforced high-toughness cement composite (ECC) using wood-based cellulose nanocrystals (hereinafter referred to as CNCs), this study assessed the applicability of CNCs through epidemiological performance assessment and long-term durability assessment. CNCs were prepared in the form of suspensions after dispersion and replaced with mixing water. The mixing rate of CNCs was 0.4, 0.8, 1.2 vol% Compared to cement, and the fiber types were Flax and Steel fiber. First, the amount of hydration products produced by the addition of CNCs was up to about 7% higher than that of plain specimen, and the value of strength was up to 20% at 0.8 vol%. Of steel fiber reinforced. Therefore, to evaluate the long-term durability according to the optimum mixing ratio of CNCs 0.8 vol%, compressive strength after freezing and thawing, acceleration carbonation, and chloride ion penetration resistance test were conducted. In the case of freezing-thawing, the strength ratio was lower than that of plain specimen, but the strength value itself increased by about 20% after freezing thawing. In the carbonation promotion test, the carbonation depth was reduced by about 60% compared to plain specimen. In the case of chlorine ion penetration resistance, the fiber-reinforced test specimens showed high value due to voids in the adhesion surface with cement due to the use of chlorine ions, but the C08 test specimen showed a resistance value of 5% lower than plain specimen confirming the validity of CNCs.
Summary
Co3O4/RuO2@nitrogen‐doped graphene oxide (NGO) composite materials were synthesized through a sonication‐assisted thermal reduction method in the presence of cobalt and ruthenium starting ...reagents for supercapacitor and gas sensor applications. The composite materials were characterized using various analytical tools to confirm the structural and morphological properties. The synthesized Co3O4/RuO2@NGO composites showed the nanostructured grains anchored on the NGO surface. The electrochemical storage performance was studied by using cyclic voltammetry, galvanostatic charge discharge, and electrochemical impedance spectroscopy using a two‐electrode asymmetric configuration. The prepared Co3O4/RuO2@NGO electrode exhibited a maximum capacitance of ~149 F/g at an applied current of ~0.5 A/g, an energy density of 20.69 Wh kg−1, and at a power density of 250 W kg−1. The cycling behavior of the fabricated asymmetric capacitor revealed a 90% capacitance retention after 5000 cycles. Moreover, the prepared composite material was used successfully for dimethyl methylophosphonate (DMMP) vapor detection, showing excellent sensitivity, selectivity, and stability. Therefore, the constructed Co3O4/RuO2@NGO composite is a suitable material for supercapacitors and DMMP gas‐detection applications.
Co3O4/RuO2@nitrogen doped graphene oxide (NGO) composite materials were synthesized through a sonication assisted thermal reduction method. From the supercapacitive and gas sensing performance tests, the novel composite shows the feasibility for supercapacitors and DMMP gas detection applications.
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