MiR-122-5p attenuates endothelial-to-mesenchymal transition induced by oxygen and glucose deprivation/reperfusion

Endothelial-to-mesenchymal transition (EndoMT) is a common phenomenon in vascular diseases, while the role of endothelial dysfunction in central vascular disease remains to be further investigated. MiR-122 is an inflammation-associated non-coding RNA that participates in multiple human disease, but whether miR-122 plays as a critical role in EndoMT induced by ischaemic stroke is unknown. Although BAI2 is known as a brain-specific inhibitor protein of angiogenesis, few studies of BAI2 examined EndoMT. This study investigated the mechanism of EndoMT and the miR-122/BAI2 axis in oxygen-glucose deprivation/reperfusion (OGD/R)-mediated EndoMT. A transient middle cerebral artery occlusion (tMCAO) model and OGD/R treatment were used to mimic the ischaemia-reperfusion injury. The colocalization of CD31 and α-SMA was elevated in the peri-infarct area of tMCAO mice. The expression of miR-122 was decreased in the peri-infarct area of tMCAO mice. Downregulation of miR-122, Occludin, and ZO-1 was observed in human brain microvascular endothelial cells (HBMECs) after OGD/R treatment, while α-SMA expression was increased in HBMECs after OGD/R treatment. MiR-122 overexpression reduced the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. MiR-122 negatively regulated BAI2 expression, and OGD/R treatment enhanced BAI2 expression. Knockdown the expression of BAI2 suppressed the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. In conclusion, miR-122 overexpression attenuates OGD/R-mediated EndoMT by targeting BAI2

Comparison of the Electrochemical Performance and Thermal Stability for Three Kinds of Charged Cathodes

The electrochemical performance and thermal stability of Li(Ni0.5Co0.2Mn0.3)O2, LiMn2O4, and LiFePO4 are investigated by the multi-channel battery cycler, electrochemical workstation, thermogravimetric analysis (TGA) and C80 instrument in this work. For electrochemical performance, Li(Ni0.5Co0.2Mn0.3)O2 shows the highest specific capacity but the worst cycle stability. For the thermal stability, the experimental results of thermogravimetry and C80 indicate that the charged Li(Ni0.5Co0.2Mn0.3)O2 has the worst thermal stability compared with charged LiFePO4 and LiMn2O4. It is also testified by calculating the chemical kinetic parameters of cathode materials based on the Arrhenius law. The pure Li(Ni0.5Co0.2Mn0.3)O2 starts to self-decompose at around 250°C with total heat generation of −88 J/g. As for a full battery, the total heat generation is −810 J/g with exothermic peak temperature of 242°C. The present results show that thermal runaway is more likely to occur for Li(Ni0.5Co0.2Mn0.3)O2 with the full battery

Iterative phase contrast CT reconstruction with novel tomographic operator and data-driven prior

Breast cancer remains the most prevalent malignancy in women in many countries around the world, thus calling for better imaging technologies to improve screening and diagnosis. Grating interferometry (GI)-based phase contrast X-ray CT is a promising technique which could make the transition to clinical practice and improve breast cancer diagnosis by combining the high three-dimensional resolution of conventional CT with higher soft-tissue contrast. Unfortunately though, obtaining high-quality images is challenging. Grating fabrication defects and photon starvation lead to high noise amplitudes in the measured data. Moreover, the highly ill-conditioned differential nature of the GI-CT forward operator renders the inversion from corrupted data even more cumbersome. In this paper, we propose a novel regularized iterative reconstruction algorithm with an improved tomographic operator and a powerful data-driven regularizer to tackle this challenging inverse problem. Our algorithm combines the L-BFGS optimization scheme with a data-driven prior parameterized by a deep neural network. Importantly, we propose a novel regularization strategy to ensure that the trained network is non-expansive, which is critical for the convergence and stability analysis we provide. We empirically show that the proposed method achieves high quality images, both on simulated data as well as on real measurements

PND-Net: Physics based Non-local Dual-domain Network for Metal Artifact Reduction

Metal artifacts caused by the presence of metallic implants tremendously degrade the reconstructed computed tomography (CT) image quality, affecting clinical diagnosis or reducing the accuracy of organ delineation and dose calculation in radiotherapy. Recently, deep learning methods in sinogram and image domains have been rapidly applied on metal artifact reduction (MAR) task. The supervised dual-domain methods perform well on synthesized data, while unsupervised methods with unpaired data are more generalized on clinical data. However, most existing methods intend to restore the corrupted sinogram within metal trace, which essentially remove beam hardening artifacts but ignore other components of metal artifacts, such as scatter, non-linear partial volume effect and noise. In this paper, we mathematically derive a physical property of metal artifacts which is verified via Monte Carlo (MC) simulation and propose a novel physics based non-local dual-domain network (PND-Net) for MAR in CT imaging. Specifically, we design a novel non-local sinogram decomposition network (NSD-Net) to acquire the weighted artifact component, and an image restoration network (IR-Net) is proposed to reduce the residual and secondary artifacts in the image domain. To facilitate the generalization and robustness of our method on clinical CT images, we employ a trainable fusion network (F-Net) in the artifact synthesis path to achieve unpaired learning. Furthermore, we design an internal consistency loss to ensure the integrity of anatomical structures in the image domain, and introduce the linear interpolation sinogram as prior knowledge to guide sinogram decomposition. Extensive experiments on simulation and clinical data demonstrate that our method outperforms the state-of-the-art MAR methods.Comment: 19 pages, 8 figure

Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study

BACKGROUND: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). METHODS: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. FINDINGS: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46-0.84), lower levels of body mass index (BMI) (β = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (β = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (β = -0.29, 95% CI = -0.39 to -0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. INTERPRETATION: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. FUNDING: Funding information is provided in the Acknowledgements

Achieving 19% efficiency in non-fused ring electron acceptor solar cells via solubility control of donor and acceptor crystallization

Non-fused ring electron acceptors (NFREAs) potentially have lower synthetic costs than their fused counterparts. However, the low backbone planarity and the presence of bulky substituents adversely affect the crystallinity of NFREAs, impeding charge transport and the formation of bicontinuous morphology in organic solar cells. Here we show that a binary solvent system can individually control the crystallization and phase separation of the donor polymer (for example, D18) and the NFREA (for example, 2BTh-2F-C2). We select solvents such as chloroform and o-xylene that evaporate at different temperatures and rates and have different solubility for D18. Upon evaporation of chloroform, D18 starts to assemble into fibrils. Then, the evaporation of o-xylene induces the rapid formation of a fibril network that phase segregates 2BTh-2F-C2 into pure domains and leads to a bicontinuous morphology. The well-defined interpenetrating network morphology affords an efficiency of 19.02% on small-area cells and 17.28% on 1 cm2 devices

Increased dose efficiency of breast CT with grating interferometry

Refraction-based x-ray imaging can overcome the fundamental contrast limit of computed tomography (CT), particularly in soft tissue, but so far has been constrained to high-dose ex vivo applications or required highly coherent x-ray sources, such as synchrotrons. Here we demonstrate that grating interferometry (GI) is more dose efficient than conventional CT in imaging of human breast under close-to-clinical conditions. Our system, based on a conventional source and commercial gratings, outperformed conventional CT for spatial resolutions better than 263 µm and absorbed dose of 16 mGy. The sensitivity of GI is constrained by grating fabrication, and further progress will lead to significant improvements of clinical CT

Aflatoxin B1 Degradation and Detoxification by Escherichia coli CG1061 Isolated From Chicken Cecum

Aflatoxin B1 (AFB1) is one of the most hazardous mycotoxins contamination in food and feed products, which leads to hepatocellular carcinoma in humans and animals. In the present study, we isolated and characterized an AFB1 degrading bacteria CG1061 from chicken cecum, exhibited an 93.7% AFB1 degradation rate by HPLC. 16S rRNA gene sequence analysis and a multiplex PCR experiment demonstrated that CG1061 was a non-pathogenic Escherichia coli. The culture supernatant of E. coli CG1061 showed an 61.8% degradation rate, whereas the degradation rates produced by the intracellular extracts was only 17.6%, indicating that the active component was constitutively secreted into the extracellular space. The degradation rate decreased from 61.8 to 37.5% when the culture supernatant was treated with 1 mg/mL proteinase K, and remained 51.3% when that treated with 100°C for 20 min. We postulated that AFB1 degradation was mediated by heat-resistant proteins. The content of AFB1 decreased rapidly when it was incubated with the culture supernatant during the first 24 h. The optimal incubation pH and temperature were pH 8.5 and 55°C respectively. According to the UPLC Q-TOF MS analysis, AFB1 was bio-transformed to the product C16H14O5 and other metabolites. Based on the results of in vitro experiments on chicken hepatocellular carcinoma (LMH) cells and in vivo experiments on mice, we confirmed that CG1061-degraded AFB1 are less toxic than the standard AFB1. E. coli CG1061 isolated from healthy chicken cerum is more likely to colonize the animal gut, which might be an excellent candidate for the detoxification of AFB1 in food and feed industry

Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3

Human MRG15 is a transcription factor that plays a vital role in embryonic development, cell proliferation and cellular senescence. It comprises a putative chromo domain in the N-terminal part that has been shown to participate in chromatin remodeling and transcription regulation. We report here the crystal structure of human MRG15 chromo domain at 2.2 Å resolution. The MRG15 chromo domain consists of a β-barrel and a long α-helix and assumes a structure more similar to the Drosophila MOF chromo barrel domain than the typical HP1/Pc chromo domains. The β-barrel core contains a hydrophobic pocket formed by three conserved aromatic residues Tyr26, Tyr46 and Trp49 as a potential binding site for a modified residue of histone tail. However, the binding groove for the histone tail seen in the HP1/Pc chromo domains is pre-occupied by an extra β-strand. In vitro binding assay results indicate that the MRG15 chromo domain can bind to methylated Lys36, but not methylated Lys4, Lys9 and Lys27 of histone H3. These data together suggest that the MRG15 chromo domain may function as an adaptor module which can bind to a modified histone H3 in a mode different from that of the HP1/Pc chromo domains