The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy ...and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.
Cancer cell molecular mimicry of stem cells (SC) imbues neoplastic cells with enhanced proliferative and renewal capacities. In support, numerous mediators of SC self-renewal have been evinced to ...show oncogenic potential. We have recently reported that short-hairpin RNA-mediated knockdown of the embryonic stem cell (ESC) self-renewal gene NANOG significantly reduced the clonogenic and tumorigenic capabilities of various cancer cells. In this study, we sought to test the potential pro-tumorigenic functions of NANOG, particularly, in prostate cancer (PCa). Using qRT-PCR, we first confirmed that PCa cells expressed NANOG mRNA primarily from the NANOGP8 locus on chromosome 15q14. We then constructed a lentiviral promoter reporter in which the -3.8-kb NANOGP8 genomic fragment was used to drive the expression of green fluorescence protein (GFP). We observed that NANOGP8-GFP(+) PCa cells showed cancer stem cell (CSC) characteristics such as enhanced clonal growth and tumor regenerative capacity. To further investigate the functions and mechanisms of NANOG in tumorigenesis, we established tetracycline-inducible NANOG-overexpressing cancer cell lines, including both PCa (Du145 and LNCaP) and breast (MCF-7) cancer cells. NANOG induction promoted drug resistance in MCF-7 cells, tumor regeneration in Du145 cells and, most importantly, castration-resistant tumor development in LNCaP cells. These pro-tumorigenic effects of NANOG were associated with key molecular changes, including an upregulation of molecules such as CXCR4, IGFBP5, CD133 and ALDH1. The present gain-of-function studies, coupled with our recent loss-of-function work, establish the integral role for NANOG in neoplastic processes and shed light on its mechanisms of action.
The detonation of a sub-Chandrasekhar-mass white dwarf (WD) has emerged as one of the most promising Type Ia supernova (SN Ia) progenitor scenarios. Recent studies have suggested that the rapid ...transfer of a very small amount of helium from one WD to another is sufficient to ignite a helium shell detonation that subsequently triggers a carbon core detonation, yielding a "dynamically driven double-degenerate double-detonation" SN Ia. Because the helium shell that surrounds the core explosion is so minimal, this scenario approaches the limiting case of a bare C/O WD detonation. Motivated by discrepancies in previous literature and by a recent need for detailed nucleosynthetic data, we revisit simulations of naked C/O WD detonations in this paper. We disagree to some extent with the nucleosynthetic results of previous work on sub-Chandrasekhar-mass bare C/O WD detonations; for example, we find that a median-brightness SN Ia is produced by the detonation of a 1.0 WD instead of a more massive and rarer 1.1 WD. The neutron-rich nucleosynthesis in our simulations agrees broadly with some observational constraints, although tensions remain with others. There are also discrepancies related to the velocities of the outer ejecta and light curve shapes, but overall our synthetic light curves and spectra are roughly consistent with observations. We are hopeful that future multidimensional simulations will resolve these issues and further bolster the dynamically driven double-degenerate double-detonation scenario's potential to explain most SNe Ia.
Soil acidification is a major problem in soils of intensive Chinese agricultural systems. We used two nationwide surveys, paired comparisons in numerous individual sites, and several long-term ...monitoring-field data sets to evaluate changes in soil acidity. Soil pH declined significantly (P < 0.001) from the 1980s to the 2000s in the major Chinese crop-production areas. Processes related to nitrogen cycling released 20 to 221 kilomoles of hydrogen ion (H⁺) per hectare per year, and base cations uptake contributed a further 15 to 20 kilomoles of H⁺ per hectare per year to soil acidification in four widespread cropping systems. In comparison, acid deposition (0.4 to 2.0 kilomoles of H⁺ per hectare per year) made a small contribution to the acidification of agricultural soils across China.
We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and ...metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P=0.0001) and lymph node metastasis of NSCLC (P=0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3'-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P=0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.
Carbon nanotubes (CNTs)/aluminum (Al) composites with various interfacial reaction degrees were fabricated by powder metallurgy at sintering temperature range of 700–900 K (75–96% melting point of ...Al). Interfacial reaction product, aluminum carbide (Al4C3), was formed in Al matrix composites (AMCs) reinforced by homogeneously-dispersed CNTs. Microscopy observations revealed three types of temperature-dependent interfaces, i) clean CNT-Al interfaces without interfacial carbide, ii) CNT-Al4C3-Al interfaces for partially reacted CNTs with Al4C3 nanoparticles, and iii) Al4C3-Al interface for in-situ Al4C3 nanorods evolved from completely reacted CNTs. Interfacial Al4C3 on partially reacted CNTs led to significant improvement of interfacial strength and consequent enhancement of load transfer efficiency in AMCs, compared to those composites without carbide. The load transfer mechanism of CNTs in composites was confirmed by the pull-out phenomena during in-situ tensile tests. The role of interfacial carbide played in determining the load transfer efficiency of CNTs was discussed. This study may provide new insights into the interfacial phenomena and load transfer mechanism in CNT-reinforced metal matrix composites.
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Slowing down the shuttle: C@S nanocomposites (see TEM images) based on mesoporous, hollow carbon capsules were generated by a template‐based approach. As the cathode material in a Li–S secondary ...battery, they display outstanding electrochemical features attributed to sequestration of elemental sulfur in the carbon capsules and to its favorable effect in limiting polysulfide shuttling as well as to enhanced electron transport from the sulfur.
Abstract
Background
Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, ...Hubei.
Aim
This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China.
Design
This study was a retrospective case series.
Methods
Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020.
Results and discussion
Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5–57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3–8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1–2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia.
Conclusions
Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.
We present an efficient time-stepping scheme for simulations of the coupled Navier–Stokes Cahn–Hilliard equations for the phase field approach. The scheme has several attractive characteristics: (i) ...it is suitable for large density ratios, and numerical experiments with density ratios up to 1000 have been presented; (ii) it involves only constant (time-independent) coefficient matrices for all flow variables, which can be pre-computed during pre-processing, so it effectively overcomes the performance bottleneck induced by variable coefficient matrices associated with the variable density and variable viscosity; (iii) it completely de-couples the computations of the velocity, pressure, and the phase field function. Strategy for spectral-element type spatial discretizations to overcome the difficulty associated with the large spatial order of the Cahn–Hilliard equation is also discussed. Ample numerical simulations demonstrate that the current algorithm, together with the Navier–Stokes Cahn–Hilliard phase field approach, is an efficient and effective method for studying two-phase flows involving large density ratios, moving contact lines, and interfacial topology changes.
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