Influence of Structure Parameters of Flux Diverters on Performance of Superconducting Energy Storage Coil

This article studies the influence of flux diverters (FDs) on energy storage magnets using high-temperature superconducting (HTS) coils. Based on the simulation calculation of the H equation finite-element model, FDs are placed at both ends of HTS coils, and the position and structure are optimized. The impact of the diverter structural parameters on the energy storage of the HTS energy storage magnet is explored, and an optimized diverter structure is designed. The rectangle is the most basic structure of FDs, so this article first optimizes the structure of the rectangular FDs and then performs various slotting treatments on the optimized FDs. By comparison, it is concluded that the concave FDs have the best energy storage effect. Then, based on the optimization of the concave FDs, a Γ-shaped structure is obtained, further improving the magnet's energy storage effect. The conclusion of the influence factors can be applied to the optimization design of diverter structures and provide a new perspective for improving energy storage.</p

A novel risk stratification model for STEMI after primary PCI: global longitudinal strain and deep neural network assisted myocardial contrast echocardiography quantitative analysis

BackgroundIn ST-segment elevation myocardial infarction (STEMI) with the restoration of TIMI 3 flow by percutaneous coronary intervention (PCI), visually defined microvascular obstruction (MVO) was shown to be the predictor of poor prognosis, but not an ideal risk stratification method. We intend to introduce deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis and propose a better risk stratification model.Methods194 STEMI patients with successful primary PCI with at least 6 months follow-up were included. MCE was performed within 48 h after PCI. The major adverse cardiovascular events (MACE) were defined as cardiac death, congestive heart failure, reinfarction, stroke, and recurrent angina. The perfusion parameters were derived from a DNN-based myocardial segmentation framework. Three patterns of visual microvascular perfusion (MVP) qualitative analysis: normal, delay, and MVO. Clinical markers and imaging features, including global longitudinal strain (GLS) were analyzed. A calculator for risk was constructed and validated with bootstrap resampling.ResultsThe time-cost for processing 7,403 MCE frames is 773 s. The correlation coefficients of microvascular blood flow (MBF) were 0.99 to 0.97 for intra-observer and inter-observer variability. 38 patients met MACE in 6-month follow-up. We proposed A risk prediction model based on MBF [HR: 0.93 (0.91–0.95)] in culprit lesion areas and GLS [HR: 0.80 (0.73–0.88)]. At the best risk threshold of 40%, the AUC was 0.95 (sensitivity: 0.84, specificity: 0.94), better than visual MVP method (AUC: 0.70, Sensitivity: 0.89, Specificity: 0.40, IDI: −0.49). The Kaplan-Meier curves showed that the proposed risk prediction model allowed for better risk stratification.ConclusionThe MBF + GLS model allowed more accurate risk stratification of STEMI after PCI than visual qualitative analysis. The DNN-assisted MCE quantitative analysis is an objective, efficient and reproducible method to evaluate microvascular perfusion

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS

ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association

Abstract The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development. However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear. Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo. In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway. Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC

Formation of monometallic Au and Pd and bimetallic Au–Pd nanoparticles confined in mesopores via Ar glow-discharge plasma reduction and their catalytic applications in aerobic oxidation of benzyl alcohol

Successfully prepared via Ar glow-discharge plasma reduction, Au–Pd bimetallic nanoparticles were highly active in the selective oxidation of benzyl alcohol, showing a rate constant of 0.50 h−1, which was 12.5 and 2× that of Au and Pd monometallic catalysts, respectively. Characterization analyses attributed the enhancement in both activity and selectivity to a Pd-rich shell/Au-rich core structure with abundant surface-coordination-unsaturated Pd atoms of those effectively confined and well-dispersed Au–Pd nanoparticles. As a green, efficient, and safe protocol, plasma reduction outperformed conventional H2 thermal reduction due to the different particle nucleation and growth mechanism, which afforded modified morphology and surface chemistry of metal nanoparticles. Further oxidation and re-reduction of plasma-reduced Au–Pd catalyst resulted in the atomic rearrangement of nanoparticles, leading to inferior catalytic performance

Induction of multiple subroutines of regulated necrosis in murine macrophages by natural BH3-mimetic gossypol

Macrophages are critical sentinel cells armed with multiple regulated necrosis pathways, including pyroptosis, apoptosis followed by secondary necrosis, and necroptosis, and are poised to undergo distinct form(s) of necrosis for tackling dangers of pathogenic infection or toxic exposure. The natural BH3-mimetic gossypol is a toxic phytochemical that can induce apoptosis and/or pyroptotic-like cell death, but what exact forms of regulated necrosis are induced remains largely unknown. Here we demonstrated that gossypol induces pyroptotic-like cell death in both unprimed and lipopolysaccharide-primed mouse bone marrow-derived macrophages (BMDMs), as evidenced by membrane swelling and ballooning accompanied by propidium iodide incorporation and lactic acid dehydrogenase release. Notably, gossypol simultaneously induces the activation of both pyroptotic and apoptotic (followed by secondary necrosis) pathways but only weakly activates the necroptosis pathway. Unexpectedly, gossypol-induced necrosis is independent of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, as neither inhibitor for the NLRP3 pathway nor NLRP3 deficiency protects the macrophages from the necrosis. Furthermore, necrotic inhibitors or even pan-caspase inhibitor alone does not or only partly inhibit such necrosis. Instead, a combination of inhibitors composed of pan-caspase inhibitor IDN-6556, RIPK3 inhibitor GSK′872 and NADPH oxidase inhibitor GKT137831 not only markedly inhibits the necrosis, with all apoptotic and pyroptotic pathways being blocked, but also attenuates gossypol-induced peritonitis in mice. Lastly, the activation of the NLRP3 pathway and apoptotic caspase-3 appears to be independent of each other. Collectively, gossypol simultaneously induces the activation of multiple subroutines of regulated necrosis in macrophages depending on both apoptotic and inflammatory caspases

Gracilaria lemaneiformis Polysaccharide as Integrin-Targeting Surface Decorator of Selenium Nanoparticles to Achieve Enhanced Anticancer Efficacy

The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to α_vβ₃ integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP–SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP–SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP–SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP–SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via α_vβ₃ integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP–SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs

Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients.

A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin-angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO2/FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections