Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not ...been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus‐mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR‐3120‐5P, and MMP‐1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP‐1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR‐3120‐5P binding site. Suppression of WTAPP1 by miR‐3120‐5P decreased the level of MMP‐1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR‐3120‐5p, regulates MMP‐1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863–12
The long noncoding RNA Wilms tumor 1 associated protein pseudogene 1, a molecular decoy for miR‐3120‐5p, regulates MMP‐1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in endothelial progenitor cells.
MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an ...irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.
MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non‐coding RNAs that affect post‐transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, ...migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual‐luciferase reporter assay, qRT‐PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK‐8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR‐205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR‐205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F‐actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down‐regulation of miR‐205 played the opposite role in EPCs. Importantly, this study demonstrated that miR‐205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro‐angiogenesis effects of miR‐205 in EPCs and established it as a potential target for DVT treatment.
This paper presents an open-circuit (OC) fault diagnostic method of inverters in closed-loop controlled permanent magnet synchronous motor drive systems based on current residual vector (CRV). This ...method can get rid of effects of the load and the main controller to obtain reliable detection. The motor drive system is a hybrid system composed of discrete switching signal events and continuous current state variables, which evolves in certain law driven by discrete events. At the base of analyzing operation modes of the system, a mixed logical dynamic (MLD) model of the motor drive system is built to estimate motor currents. Consequently, the proposed fault diagnostic scheme is constructed by the healthy current estimator based on the MLD model in parallel with the plant. When an OC fault occurs, the CRV between the estimator and the plant will show featured amplitude and phase, and hence the fault can be detected. The method utilizes variables already used by the main controller, avoiding the use of extra sensors. During the implementation, amplitude threshold and phase sector are used in order to avoid effects of measurement errors, model parameter errors and noises, which improves the reliability and robustness. Simulation and experimental results validate the proposed diagnostic method, and the diagnostic duration can be reduced within a quarter of fundamental wave period.
Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase ...separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, N
exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.
Three distinct cell types are present within the 64-cell stage mouse blastocyst. We have investigated cellular development up to this stage using single-cell expression analysis of more than 500 ...cells. The 48 genes analyzed were selected in part based on a whole-embryo analysis of more than 800 transcription factors. We show that in the morula, blastomeres coexpress transcription factors specific to different lineages, but by the 64-cell stage three cell types can be clearly distinguished according to their quantitative expression profiles. We identify
Id2 and
Sox2 as the earliest markers of outer and inner cells, respectively. This is followed by an inverse correlation in expression for the receptor-ligand pair
Fgfr2/
Fgf4 in the early inner cell mass. Position and signaling events appear to precede the maturation of the transcriptional program. These results illustrate the power of single-cell expression analysis to provide insight into developmental mechanisms. The technique should be widely applicable to other biological systems.
► Robust methodology for single cell gene expression analysis in early embryos ► Zygotic activation of
Sox2 occurs in inner cells of the morula ►
Fgf4/
Fgfr2 inverse correlation evident within the early inner cell mass ► Fgf signaling precedes the primitive endoderm transcriptional program
A new class of supramolecular metallacycles capable of undergoing photochemical reactions and in situ release of cyclobutanes in solution is described. The molecular metallacycles were generated ...through coordination‐driven self‐assembly of dinuclear metal‐carbene complexes as organometallic clips with olefin‐functionalized bridging ligands. Photolysis of these molecular metallacycles in situ led to structural interconversion and release of the formed cyclobutane products with quantitative conversion. Further modifications of the obtained cyclobutanes provided a series of new species containing the cyclobutane skeleton.
Catch and release: Photolysis of the pictured molecular metallacycles in situ leads to quantitative cycloaddition and release of the stereoselectively formed cyclobutane products. The pendant groups on the products include pyridyl, imidazole, benzimidazoles, and carboxylic derivatives.
Cyclic GMP‐AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase‐activating protein‐(SH3 ...domain)–binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid‐phase condensation state. Using high‐resolution microscopy, we show that in resting cells, cGAS exhibits particle‐like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre‐condensed cGAS undergoes liquid–liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA‐induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA – but not RNA – treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
Synopsis
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
G3BP1 primes cGAS for its prompt activation.
G3BP1 engages cGAS in a primary condensation state.
DNA‐ but not RNA‐interaction leads to the dissociation of G3BP1 from cGAS.
Green tea compound epigallocatechin gallate (EGCG) inhibits G3BP1‐promoted cGAS phase condensation and activation.
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function ...as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer.
Since the industrial revolution, modern society has experienced rapid technological development, which has greatly increased the demand for energy, and cheap energy for production will be more and ...more difficult to obtain. In the past decades, energy depletion and environmental pollution have attracted people's attention, and prompted people to explore advanced and green energy storage and conversion technologies. Supercapacitors have attracted extensive attention due to their great potential to meet the requirements of high energy density and high power density, but their excellent performance largely depends on the development of advanced electrode materials. Carbon materials are widely used in supercapacitors, but the preparation of high-performance carbon materials still needs harsh conditions. Therefore, there is an urgent need to develop effective methods to produce high-performance carbon materials with limited environmental impact by using renewable resources. Biomass is an important precursor of carbon materials due to its unique structure, abundant resources, biodegradability and low cost. Porous carbons transformed from biomass as a new type of high-performance sustainable material have attracted extensive attention due to the advantages, such as good porosity, large specific surface area, good graphitization degree,
etc
. Although there have been many studies and summaries on porous carbon materials transformed from biomass, improvements and additions are still needed. This paper further summarizes the latest progress of biomass-derived porous carbon materials in the field of supercapacitors, and the preparation methods of biomass-based porous carbon materials are newly classified from the perspective of the preparation process. Secondly, the design methods and strategies of high-performance biomass-based porous carbon materials are analyzed in detail. The application of biomass-based porous carbon materials in advanced supercapacitors is reviewed. Finally, the challenges and prospects for the future development of biomass-based carbon materials are discussed. This review shows the great potential of high-performance biomass-based porous carbon materials, provides good design ideas for their application in the field of high-performance supercapacitors, and is expected to stimulate new discoveries and promote the practical application of biomass-based porous carbon materials in the field of more energy storage and conversion.
This paper shows a new classification of preparing biomass-based porous carbon materials. The design of high-performance biomass-based porous carbon materials and their recent progress in the field of supercapacitors are reviewed.
PDF
