To date, a large number of long non-coding RNAs (lncRNAs) have been recently discovered through functional genomics studies. Importantly, lncRNAs have been shown, in many cases, to function as master ...regulators for gene expression and thus, they can play a critical role in various biological functions and disease processes including cancer. Although the lncRNA-mediated gene expression involves various mechanisms, such as regulation of transcription, translation, protein modification, and the formation of RNA-protein or protein-protein complexes, in this review, we discuss the latest developments primarily in important cell signaling pathways regulated by lncRNAs in cancer.
Archean cratons have map patterns and rock associations that are diagnostic of the Wilson Cycle. The North China Craton (NCC) consists of several distinctly different tectonic units, but the ...delineation and understanding of the significance of individual sutures and the rocks between them has been controversial. We present an actualistic tectonic division and evolution of the North China Craton based on Wilson Cycle and comparative tectonic analysis that uses a multi-disciplinary approach in order to define sutures, their ages, and the nature of the rocks between them, to determine their mode of formation and means of accretion or exhumation, and propose appropriate modern analogues. The eastern unit of the craton consists of several different small blocks assembled between 2.6 and 2.7Ga ago, that resemble fragments of accreted arcs from an assembled archipelago similar to those in the extant SW Pacific. A thick Atlantic-type passive margin developed on the western side of the newly assembled Eastern Block by 2.6–2.5Ga. A >1300km-long arc and accretionary prism collided with the margin of the Eastern Block at 2.5Ga, obducting ophiolites and ophiolitic mélanges onto the block, and depositing a thick clastic wedge in a foreland basin farther into the Eastern Block. This was followed by an arc-polarity reversal, which led to a short-lived injection of mantle wedge-derived melts to the base of the crust that led to the intrusion of mafic dikes and arc-type granitoid (TTG) plutons with associated metamorphism. By 2.43Ga, the remaining open ocean west of the accreted arc closed with the collision of an oceanic plateau now preserved as the Western Block with the collision-modified margin of the Eastern Block, causing further deformation in the Central Orogenic Belt. 2.4–2.35Ga rifting of the newly amalgamated continental block formed a rift along its center, and new oceans within the other two rift arms, which removed a still-unknown continental fragment from its northern margin. By 2.3Ga an arc collided with a new Atlantic-type margin developed over the rift sequence along the northern margin of the craton, and thus was converted to an Andean margin through arc-polarity reversal.
Andean margin tectonics affected much of the continental block from 2.3 to 1.9Ga, giving rise to a broad E-W swath of continental margin magmas, and retro-arc sedimentary basins including a foreland basin superimposed on the passive northern margin. The horizontal extent of these tectonic components is similar to that across the present-day Andes in South America. From 1.88 to 1.79Ga a granulite facies metamorphic event was superimposed across the entire continental block with high-pressure granulites and eclogites in the north, and medium-pressure granulites across the whole craton to the south. The scale and duration of this post-collisional event is similar to that in Central Asia that resulted from the Cenozoic India-Asia collision. The deep crustal granulites and volcanic rocks on the surface today, interpreted to be anatectic melts from deep crustal granulites, are similar to high-grade metamorphic rocks and partial melts presently forming at mid-crustal levels beneath Tibet. Structural fabrics in lower-crustal migmatites related to this event reveal that they flowed laterally parallel to the collision boundary, in a way comparable to what is speculated to be happening in the deep crust of the Himalayan/Tibetan foreland. We relate this continent-continent collision to the collision of the North China Craton with the postulated Columbia (Nuna) Continent. The NCC broke out of the Columbia Continent between 1753–1673Ma, as shown by the formation of a suite of anorthosite, mangerite, charnockite, and alkali-feldspar granites in an ENE-striking belt along the northern margin of the craton, whose intrusion was followed by the development of rifts and graben, mafic dike swarms, and eventually an Atlantic-type passive margin that signaled the beginning of a long period of tectonic quiescence and carbonate deposition for the NCC during Sinian times, which persisted into the Paleozoic. The style of tectonic accretion in the NCC changed at circa 2.5Ga, from an earlier phase of accretion of arcs that are presently preserved in horizontal lengths of several hundred kilometers, to the accretion and preservation of linear arcs several thousand kilometers long with associated oceanic plateaus, microcontinents, and accretionary prisms. The style of progressively younger and westward outward accretion of different tectonic components is reminiscent of the style of accretion in the Superior Craton, and may signal the formation of progressively larger landmasses at the end of the Archean (perhaps like the Kenorland Continent), then into the Paleoproterozoic, culminating in the assembly of the Columbia (Nuna) Continent at 1.9–1.8Ga.
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in ...breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH
subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.
Ceruloplasmin is an iron‐export ferroxidase that is abundant in plasma and also expressed in glia. We found a ∼80% loss of ceruloplasmin ferroxidase activity in the substantia nigra of idiopathic ...Parkinson disease (PD) cases, which could contribute to the pro‐oxidant iron accumulation that characterizes the pathology. Consistent with a role for ceruloplasmin in PD etiopathogenesis, ceruloplasmin knockout mice developed parkinsonism that was rescued by iron chelation. Additionally, peripheral infusion of ceruloplasmin attenuated neurodegeneration and nigral iron elevation in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model for PD. These findings show, in principle, that intravenous ceruloplasmin may have therapeutic potential in PD. Ann Neurol 2013;73:554–559
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to ...investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae. A series of in vitro and in vivo assays were performed to elucidate the function of FERMT1 in CC metastasis and underlying mechanisms. The upregulated expression of FERMT1 in CC tissues correlated positively with that of Slug, N-cadherin and β-catenin, but correlated inversely with E-cadherin expression. Altered FERMT1 expression led to marked changes in the proliferation, migration, invasion and EMT markers of CC cells both in vitro and in vivo. Investigations of underlying mechanisms found that FERMT1 interacted directly with β-catenin and activated the Wnt/β-catenin signaling pathway by decreasing the phosphorylation level of β-catenin, enhancing β-catenin nuclear translocation and increasing the transcriptional activity of β-catenin/TCF/LEF. Activation of the Wnt/β-catenin pathway by CHIR99021 reversed the effect of FERMT1 knockdown, whereas inhibition of the Wnt/β-catenin pathway by XAV939 impaired the effect of FERMT1 overexpression on EMT and cell motility. In conclusion, findings of this study suggest that FERMT1 activates the β-catenin transcriptional activity to promote EMT in CC metastasis.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
Compared to non-cavitating flow, cavitating flow is much complex owing to the numerical difficulties caused by cavity generation and collapse. In this paper, the cavitating flow around a NACA66 ...hydrofoil is studied numerically with particular emphasis on understanding the cavitation structures and the shedding dynamics. Large Eddy Simulation (LES) was coupled with a homogeneous cavitation model to calculate the pressure, velocity, vapor volume fraction and vorticity around the hydrofoil. The predicted cavitation shedding dynamics behavior, including the cavity growth, break-off and collapse downstream, agrees fairly well with experiment. Some fundamental issues such as the transition of a cavitating flow structure from 2D to 3D associated with cavitation-vortex interaction are discussed using the vorticity transport equation for variable density flow. A simplified one-dimensional model for the present configuration is adopted and calibrated against the LES results to better clarify the physical mechanism for the cavitation induced pressure fluctuations. The results verify the relationship between pressure fluctuations and the cavity shedding process (e.g. the variations of the flow rate and cavity volume) and demonstrate that the cavity volume acceleration is the main source of the pressure fluctuations around the cavitating hydrofoil. This research provides a better understanding of the mechanism driving the cavitation excited pressure pulsations, which will facilitate development of engineering designs to control these vibrations.
•H2 was produced by catalytic gasification of biomass in presence of Ni/CeO2/Al2O3 catalysts.•Ni/Al2O3 catalyst is more effective for enhancing the H2 yield and tar cracking.•Higher temperatures were ...significantly resulted in tar cracking and hydrogen production.•An increase in residence time was caused a considerable decrease in the tar yield.
Air-steam gasification of wood residue was explored in a research scale fluidized bed. Catalytic activity of two different kinds of metal catalysts (Ni/CeO2/Al2O3) with various catalyst loadings (20, 30, and 40%) was also investigated at various residence time (20, 40, and 60min) and gasification temperature (750, 825, and 900°C). Non-catalytic experiments were also carried out to determine the optimum conditions for tar cracking and hydrogen/syngas production. Results were revealed that the high temperature (∼900°C) and high catalyst loading (∼40%) are favorable for tar cracking and high-purity hydrogen production. It was also found that for a residence time of 60min, the tar cracking at the presence of Ni/CeO2/Al2O3 is 196% more than that of the case without any catalyst, while at the presence of Ni/Al2O3 it drops to 162%. Finally, the experiments were showed that Ni/CeO2/Al2O3 is more suitable for biomass conversion and hydrogen production than Ni/Al2O3.
Pecan (Carya illinoinensis) is sensitive to Zn, which is involved in basic physiological and biochemical processes.
To explore the growth and physiology of pecan in response to Zn application, we ...used 1‐year‐old annual grafted seedlings (Pawnee) and applied four concentrations of Zn fertilizer (0.05, 0.10, 0.20 and 0.40 g·plant−1); a control (CK; no Zn fertilization) was also included. The growth characteristics, anatomical structure of the leaves and photosynthesis were assessed.
Compared with the CK, photosynthesis and chlorophyll (Chl) fluorescence parameters, leaf area and leaf structure significantly increased at Zn concentrations of 0.05 and 0.10 g·plant−1. In addition, growth of pecan at the seedling stage increased in response to moderate Zn application. In contrast, treatment with 0.20 and 0.40 g·Zn·plant−1 dramatically decreased these physiological indices and inhibited pecan growth.
The results show that moderate soil Zn application promotes pecan growth and development by increasing photosynthesis. However excess Zn concentrations were not conducive to seedling growth. The concentration of 0.1 g·Zn·plant−1 was best when considering long‐term soil Zn applications, providing a theoretical foundation for microelement management of pecan.
Moderate Zn application promoted the growth and development of pecan by improving photosynthesis‐related physiological mechanisms.