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.
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
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.
China has pledged to peak carbon emissions before 2030 and strive to achieve carbon neutrality before 2060. However, the significant variations of provincial carbon emissions make it unclear whether ...they can jointly fulfill the national carbon peak and neutrality goal. Thus, this study predicts the emission trajectories at provincial level in China by employing the extended STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) model to see the feasibility and time of reaching peak carbon emissions and carbon neutrality. We found that most provinces can achieve peak emission before 2030 but challenging to achieve carbon neutrality before 2060, even considering the ecological carbon sink. The provincial neutrality time is concentrated between 2058 and 2070; the sooner the carbon emission peaks, the earlier the carbon neutral will be realized. The aggregated carbon emissions at provincial level show that China can achieve its carbon emission peak of 9.64–10.71 Gt before 2030, but it is unlikely to achieve the carbon neutrality goal before 2060 without carbon capture, utilization, and storage (CCUS). With high CCUS development, China is expected to achieve carbon neutrality in 2054–2058, irrespective of the socio-economic scenarios. With low CCUS development, China's carbon neutrality target will be achieved only under the accelerated-improvement scenario, while it will postpone to 2061 and 2064 under the continued-improvement and the business-as-usual scenarios, respectively.
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.
Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism, is the third most common vascular disease in the world and seriously threatens the lives of patients. ...Currently, the effect of conventional treatments on DVT is limited. Endothelial progenitor cells (EPCs) play an important role in the resolution and recanalization of DVT, but an unfavorable microenvironment reduces EPC function. Non-coding RNAs, especially long non-coding RNAs and microRNAs, play a crucial role in improving the biological function of EPCs. Non-coding RNAs have become clinical biomarkers of diseases and are expected to serve as new targets for disease intervention. A theoretical and experimental basis for the development of new methods for preventing and treating DVT in the clinic will be provided by studies on the role and molecular mechanism of non-coding RNAs regulating EPC function in the occurrence and development of DVT. To summarize, the characteristics of venous thrombosis, the regulatory role of EPCs in venous thrombosis, and the effect of non-coding RNAs regulating EPCs on venous thrombosis are reviewed. This summary serves as a useful reference and theoretical basis for research into the diagnosis, prevention, treatment, and prognosis of venous thrombosis.
A Molecular “A‐Type” Tangled Metallocube Ma, Li‐Li; Li, Yang; Li, Xin ...
Angewandte Chemie International Edition,
August 26, 2022, Letnik:
61, Številka:
35
Journal Article
Recenzirano
Tangled cubes feature the topology of typical Platonic cubes, with their “faces” traversed by edges in different ways. This study generates an “A‐type” tangled metallocube from the reaction of ...binuclear gold‐NHC complex and H2S. The tangled cube topology was validated by multinuclear nuclear magnetic resonance (NMR) spectroscopy, high‐resolution electrospray‐ionization (HR‐ESI) mass spectrometry, and single‐crystal X‐ray diffraction analysis. This study offers a simple and effective approach to designing and fabricating new, topologically unique molecular structures.
A molecular “A‐type” tangled metallocube has been generated by the reaction of a binuclear gold‐N‐heterocyclic carbene (NHC) complex and H2S. The tangled cube topology with 8 (μ3‐S)Au3+ units and 12 bis‐NHC ligands was validated by NMR spectroscopy, mass spectrometry, and single‐crystal X‐ray diffraction analysis.
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.
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