The purpose of this study was to investigate the biological effect of miR‐16 on myocarditis and the underlying molecular mechanism. H9c2 cells were treated with 10 µg/mL lipopolysaccharide (LPS) for ...12 hours to form a myocarditis injury model. We observed that LPS treatment distinctly decreased the level of miR‐16 in H9c2 cells. Upregulation of miR‐16 increased cell proliferation and reduced cell apoptosis. Then, CD40 was predicted and verified as a target gene of miR‐16 by TargetScan and luciferase reporter assay, respectively. Furthermore, the messenger RNA and protein expression of CD40 are negatively regulated by miR‐16. The relative expression of inflammatory factors was dramatically decreased by the miR‐16 mimic. Cells cotransfected with miR‐16 mimic and si‐CD40 could significantly abolish the injury of cardiomyocytes caused by myocarditis. Our study illustrated that the upregulation of miR‐16 has a protective effect on LPS‐damaged H9c2 cells, which may be achieved by regulating CD40 and the nuclear factor kappa B pathway.
Polycyclic aromatic molecules are promising functional materials for a wide range of applications, especially in organic electronics. However, their largely hydrophobic nature has impeded further ...applications. As such, imparting high solubility/hydrophilicity to polycyclic aromatic molecules leads to a breakthrough in this research field. Herein, we report the synthesis of diazapentabenzocorannulenium, a cationic nitrogen‐embedded buckybowl bearing a central imidazolium core, by a bottom‐up strategy from polycyclic aromatic azomethine ylide. X‐ray crystallography analyses have revealed a bowl‐shaped molecular structure that is capable of forming charge‐segregated one‐dimensional columns by bowl‐in‐bowl packing. In addition to its fluorescence capabilities and high dispersibility in water, the molecule was found to selectively localize in the mitochondria of various tumor cells, showing potential as viable mitochondria‐selective fluorescent probes.
Two exceeds one: Diazapentabenzocorannulenium, a cationic corannulene derivative bearing an internal imidazolium core, was prepared by a bottom‐up synthetic strategy. The introduction of positive charge and two nitrogen atoms into corannulene resulted in remarkable molecular properties, such as the formation of charge‐segregated one‐dimensional columns, high dispersibility in water, and selective introduction into the mitochondria of tumor cells.
Heterogeneous noble‐metal‐based catalysis plays an essential role in the production of fine chemicals. Rh‐based catalysts are one of the most active candidates for indole synthesis. However, it is ...still highly desired to develop heterogeneous Rh‐based catalysts with high activity and selectivity. In this work, a general, facile wet‐chemical method is reported to synthesize ultrathin amorphous/crystalline heterophase Rh and Rh‐based bimetallic alloy nanosheets (NSs), including RhCu, RhZn, and RhRu. Impressively, the amorphous/crystalline heterophase Rh NSs exhibit enhanced catalytic activity toward the direct synthesis of indole compared to the crystalline counterpart. Importantly, the obtained amorphous/crystalline heterophase RhCu alloy NSs can further enhance the selectivity to indole of >99.9% and the conversion is 100%. This work demonstrates the importance of phase engineering and metal alloying in the rational design and synthesis of tandem heterogeneous catalysts toward fine chemical synthesis.
Ultrathin Rh and RhM (M = Cu, Zn, Ru) alloy nanosheets with amorphous/crystalline heterophases are successfully synthesized. In tandem catalysis to directly synthesize indole, the amorphous/crystalline heterophase Rh nanosheets (NSs) outperform their crystalline counterpart, demonstrating much higher catalytic activity. Impressively, the amorphous/crystalline heterophase RhCu NSs show dramatically enhanced indole selectivity of over 99.9% and excellent activity.
Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrP
) that are able to template the conversion of the native form of the ...protein (PrP
), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrP
(residues 23-231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170-229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrP
, we propose that two α-helices in the C-terminal domain of PrP
are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.
Reduced-reference image quality assessment (RRIQA) methods estimate image quality degradations with partial information about the ldquoperfect-qualityrdquo reference image. In this paper, we propose ...an RRIQA algorithm based on a divisive normalization image representation. Divisive normalization has been recognized as a successful approach to model the perceptual sensitivity of biological vision. It also provides a useful image representation that significantly improves statistical independence for natural images. By using a Gaussian scale mixture statistical model of image wavelet coefficients, we compute a divisive normalization transformation (DNT) for images and evaluate the quality of a distorted image by comparing a set of reduced-reference statistical features extracted from DNT-domain representations of the reference and distorted images, respectively. This leads to a generic or general-purpose RRIQA method, in which no assumption is made about the types of distortions occurring in the image being evaluated. The proposed algorithm is cross-validated using two publicly-accessible subject-rated image databases (the UT-Austin LIVE database and the Cornell-VCL A57 database) and demonstrates good performance across a wide range of image distortions.
Many state-of-the-art perceptual image quality assessment (IQA) algorithms share a common two-stage structure: local quality/distortion measurement followed by pooling. While significant progress has ...been made in measuring local image quality/distortion, the pooling stage is often done in ad-hoc ways, lacking theoretical principles and reliable computational models. This paper aims to test the hypothesis that when viewing natural images, the optimal perceptual weights for pooling should be proportional to local information content, which can be estimated in units of bit using advanced statistical models of natural images. Our extensive studies based upon six publicly-available subject-rated image databases concluded with three useful findings. First, information content weighting leads to consistent improvement in the performance of IQA algorithms. Second, surprisingly, with information content weighting, even the widely criticized peak signal-to-noise-ratio can be converted to a competitive perceptual quality measure when compared with state-of-the-art algorithms. Third, the best overall performance is achieved by combining information content weighting with multiscale structural similarity measures.
•The construction progress of HL-2M as the modification of HL-2A tokamak is introduced.•HL-2M project scope and design schemes show that it is actually a new tokamak.•The main features, design and ...fabrication of tokamak components are stated.•The construction of tokamak auxiliary systems involved in the project is briefly introduced.
HL-2M is a medium-sized copper-conductor tokamak under construction at the Southwestern Institute of Physics (SWIP). HL-2M project will construct a totally new tokamak machine, with other system upgrades from present existing tokamak at SWIP. The project is progressing. The machine components, coils, vacuum vessel, support, etc. are in the stage of fabrication in factories and to be delivered sequentially in next year for tokamak assembly. The scheme of machine assembly has been made. Other components or systems involved go forward into different construction stages. The progress of the component developments is mainly presented.
Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar ...metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.
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.
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