Super-enhancers (SEs) consist of a cluster of many enhancers bound to a great number of transcription factors. They are critical cis-regulatory elements that determine the identity of various human ...cell types. During tumorigenesis, DNA mutations and indels, chromosomal rearrangements, three-dimensional chromatin structural changes, and viral infections mediate oncogenic SE activation, and activated SEs have been found to regulate the expression of oncogenic genes. Inhibition specifically targeted to oncogenic SE assembly and activation provides a novel powerful therapeutic strategy for various cancers. In this paper, we first introduce the current understanding of oncogenic SE assembly and activation and then summarize the pathogenic factors and mechanism of oncogenic SE activation. Next, we elaborate on the oncogenic functions of SEs in cancers and the application of SEs as therapeutic targets. Finally, we turn our focus to the use of SEs in basic research and clinical trials.
Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, ...the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF‐AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells (P < .05). MiR‐212‐5p was identified as the most important miRNA linker between lncMIF‐AS1 and NDUFA4, which was negatively regulated by lncMIF‐AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF‐AS1/miR‐212‐5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.
Our findings showed that lncMIF‐AS1 is involved in gastric cancer tumorigenesis as a tumor activator gene. Through upregulation of NDUFA4, lncMIF‐AS1 promotes gastric cancer cell proliferation and repressed apoptosis. Moreover, we showed that lncMIF‐AS1 activates NDUFA4 expression by sponging to miR‐212‐5p in gastric cancer cells. And inhibition of lnvMIF‐AS1/miR‐212‐5p/NDUFA4 may provide an attractive therapeutic target for the treatment of gastric cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In China, alfalfa (
L.) often grows in marginal land with poor soil fertility and suboptimal climate conditions. Alfalfa production cannot meet demands both in yield and quality. It is necessary to ...apply fertilizers to achieve high yields and produce high-quality alfalfa in China. However, there is no understanding on the impact of fertilizer application on alfalfa production and the possible optimal application rates across China.
We conducted a meta-analysis to explore the contribution of fertilizer application to the yield and quality of alfalfa based on a dataset from 86 studies published between 2004 and 2022.
The results showed that fertilizer application not only increased alfalfa yield by 19.2% but also improved alfalfa quality by increasing crude protein (CP) by 7.7% and decreasing acid detergent fibre by 2.9% and neutral detergent fibre by 1.8% overall compared to the non-fertilizer control levels. The combined nitrogen (N), phosphorus (P) and potassium (K) and combined NP fertilizer applications achieved the greatest yield and CP concentration increases of 27.0% and 13.5%, respectively. Considering both yield and quality, the optimal rate of fertilizer application ranged from 30 to 60 kg ha
for N, 120 to 150 kg ha
for P and less than 120 kg ha
for K. Meta-analysis further showed that the effect of fertilizer application on yield was greater in low soil organic matter (SOM) soils than in high SOM soils. In conclusion, fertilizer application is an effective strategy to improve the yield and quality of alfalfa in China, especially that grown in low SOM soils. This study is helpful for optimizing fertilization schedules of alfalfa in China.
seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA ...recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, which regulates target genes transcription. In tumorigenesis, DNA insertion, deletion, translocation, focal amplification and carcinogen factor mediate oncogenic SE generation, meanwhile, oncogenic SE transcribes into tumor-related seRNA, termed as oncogenic seRNA. Oncogenic seRNA participates in tumorigenesis through activating various signal-pathways. The recent reports showed that oncogenic seRNA implicates in a widespread range of cytopathological processes in cancer progression including cell proliferation, apoptosis, autophagy, epithelial-mesenchymal transition, extracellular matrix stiffness and angiogenesis. In this article, we comprehensively summarized seRNA's characteristics and functions, and emphatically introduced inducible formation of oncogenic seRNA and its functional mechanisms. Lastly, some research strategies on oncogenic seRNA were introduced, and the perspectives on cancer therapy that targets oncogenic seRNA were also discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recently, super-enhancers (SEs) have been identified as a unique type of transcriptional regulation involved in cancer development. SEs exhibit a size, high transcription factor density, and strong ...binding to the transcriptional machinery compared with typical enhancers. SEs play an essential role in cell growth, differentiation, and disease initiation and progression including tumorigenesis. In particular, cancer-specific SEs have been proven to be key oncogenic drivers types of tumor cells. Furthermore, it has been confirmed that cancer-specific SEs can mediate the dysregulation of signaling pathways and promote cancer cell growth. Additionally, therapeutic strategies directly targeting SE components, for example, by disrupting SE structure or inhibiting SE cofactors, have shown a good curative effect on various cancers.
In China, alfalfa (
L.) is often grown on marginal land with poor soil fertility and suboptimal climate conditions. Soil salt stress is one of the most limiting factors for alfalfa yield and quality, ...through its inhibition of nitrogen (N) uptake and N fixation.
To understand if N supply could improve alfalfa yield and quality through increasing N uptake in salt-affected soils, a hydroponic experiment and a soil experiment were conducted. Alfalfa growth and N fixation were evaluated in response to different salt levels and N supply levels.
The results showed that salt stress not only significantly decreased alfalfa biomass, by 43%-86%, and N content, by 58%-91%, but also reduced N fixation ability and N derived from the atmosphere (%Ndfa) through the inhibition of nodule formation and N fixation efficiency when the salt level was above 100 mmol Na
SO
L
. Salt stress also decreased alfalfa crude protein by 31%-37%. However, N supply significantly improved shoot dry weight by 40%-45%, root dry weight by 23%-29%, and shoot N content by 10%-28% for alfalfa grown in salt-affected soil. The N supply was also beneficial for the %Ndfa and N fixation for alfalfa with salt stress, and the increase reached 47% and 60%, respectively. Nitrogen supply offset the negative effects on alfalfa growth and N fixation caused by salt stress, in part through improving plant N nutrition status. Our results suggest that optimal N fertilizer application is essential to alleviate the loss of growth and N fixation in alfalfa in salt-affected soils.
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•Many Rh catalysts were tested for N2O decomposition under diesel conditions.•Rh/CeO2 is the only catalyst with good activity in a wet feed after aging.•Aging does not deactivate ...Rh/CeO2 but significantly increases its activity.•Removal O2 from the catalyst has been demonstrated to be the rate limiting step.
Numerous Rh catalysts were evaluated for N2O decomposition for automotive applications. Some Rh-containing spinel materials exhibit excellent fresh activities in the absence of H2O but become inactive after hydrothermal aging or when tested in a wet feed. Rh catalysts supported on zeolites can be very active in a dry feed even after aging but are extremely sensitive to H2O. Rh/CeO2 is an exceptional catalyst for this reaction in the presence of both H2O and O2. Hydrothermal aging (750 °C/20 h) significantly increases its activity. A similar activity enhancement was found by calcining the support before Rh impregnation. XPS results show a surface enrichment of Rh species on the aged Rh/CeO2 catalyst relative to the fresh catalyst. Aberration corrected STEM images reveal that Rh is buried in the bulk on the fresh catalyst and pulled out onto the surface of the support after thermal treatments. All catalysts are inhibited by H2O with the zeolite-based Rh catalysts being the worst. The aged Rh/CeO2 catalyst is less sensitive to H2O relative to others. DRIFTS data show that H2O sensitivity is related to catalyst hydrophilicity; a high coverage of OH groups on a catalyst reduces its N2O decomposition activity. H2-TPR results show that a Rh/CeO2 catalyst can be readily reduced at < 100 °C. On a reduced Rh/CeO2 catalyst, near complete N2O conversion can be obtained with a lean feed at 250 °C for a duration equivalent to its oxygen storage capacity. The N2O-DRIFTS experiments over a pre-reduced Rh/CeO2 catalyst show that Ce3+ sites are quickly oxidized to Ce4+ upon contacting N2O at room temperature, resulting N2 and adsorbed O, with the latter being an efficient oxidizer. Based on these results, a N2O decomposition mechanism is proposed for the Rh/CeO2 catalyst.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Understanding the impacts of human trampling on ecological environment is necessary for the utilization and management of recreational areas. Qilian Mountain National Park is one of the first pilot ...areas of the national park system in China, which is also the most popular tourist destinations suitable for hiking and camping. However, there have been very few studies on human trampling in the Qilian Mountains region. We conducted a controlled trampling experiment to explore the short-term impacts of different trampling intensities (0, 50, 200, 500, and 1000 passes) on soil and vegetation in a grassland in the park. At 0–5, 5–10 and 10–20 cm soil depth, some selected soil properties were measured. Human trampling had negative impacts on surface soil properties, aboveground plant cover and height in the study area. At 0–5 cm soil depth, compared to the control site, bulk density, soil organic matter and soil penetration resistance respectively increased from 0.66 to 0.79 g/cm3, 5.5–6.5% and 9.64–13.7 kg/cm2 after 1000 passes. Soil saturated hydraulic conductivity, water holding capacity and total porosity decreased from 0.29 to 0.23 mm/min, 31.62–24.07% and 46.22–34.67%, respectively. Soil properties were degraded both on the topsoil(0–5 cm) and midsoil(5–10 cm), with the greatest degradation occurring at 1000 passes, followed by 500 passes. The total vegetation cover and mean vegetation height decreased significantly with increasing trampling intensities. After different passes, the relative vegetation cover and height showed a curvilinear decrease. A reasonable threshold of visitors should be controlled between 500 and 1000 passes to ensure the quality of the landscape. Our findings suggest that human trampling of highly sensitive and fragile alpine grasslands has a significant impact and may further impede their function. Therefore, it is urgent to protect the ecological environment of alpine grasslands.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article proposes a new satellite-based framework for global-scale remote sensing that is integrated with on-orbit cloud computing and artificial intelligence (AI) services. These spaced-based ...services cover the entire earth surfaces using massive low earth orbit (LEO) satellite constellation. Global-scale sensing of earth resources must be supported by massive number of LEO satellites equipped with cloud/AI computing services in real time. New satellite computer architectural features are presented along with some satellite constellation deployment topologies. We design satellite-based computers to support on-orbit remote sensing and AI scene analysis. This demands real-time performance without transmitting the sensed data back to earth for delayed processing. Notable space data services include on-orbit data sensing of large areas, machine learning from earth resources data, earth scene/event analysis, geomorphology observation, smart city management, disaster relief, global healthcare Internet of Things, environmental ecology protection, etc. We attempt to achieve high-efficiency earth resources utilization along with green energy, low cost, and robustness in real-life services.
Oncogenic super-enhancers (SEs) generate noncoding enhancer/SE RNAs (eRNAs/seRNAs) that exert a critical function in malignancy through powerful regulation of target gene expression. Herein, we show ...that a JUN-mediated seRNA can form R-loop to regulate target genes to promote metastasis of nasopharyngeal carcinoma (NPC). A combination of global run-on sequencing, chromatin-immunoprecipitation sequencing, and RNA sequencing was used to screen seRNAs. A specific seRNA associated with NPC metastasis (seRNA-NPCM) was identified as a transcriptional regulator for N-myc downstream-regulated gene 1 (NDRG1). JUN was found to regulate seRNA-NPCM through motif binding. seRNA-NPCM was elevated in NPC cancer tissues and highly metastatic cell lines, and promoted the metastasis of NPC cells in vitro and in vivo. Mechanistically, the 3' end of seRNA-NPCM hybridizes with the SE region to form an R-loop, and the middle segment of seRNA-NPCM binds to heterogeneous nuclear ribonucleoprotein R (hnRNPR) at the promoter of distal gene NDRG1 and neighboring gene tribbles pseudokinase 1 (TRIB1). These structures promote chromatin looping and long-distance chromatin interactions between SEs and promoters, thus facilitating NDRG1 and TRIB1 transcription. Furthermore, the clinical analyses showed that seRNA-NPCM and NDRG1 were independent prognostic factors for NPC patients. seRNA-NPCM plays a critical role in orchestrating target gene transcription to promote NPC metastasis.
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