Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery

BackgroundThe incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood.ObjectivesIdentify the mechanisms by which the hydrophilic and lipophilic statins pravastatin and atorvastatin preserve endothelial function after irradiation.MethodsCultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice subjected to 12 Gy head-and-neck irradiation were pretreated with statins and tested for endothelial dysfunction, nitric oxide production, oxidative stress, and various mitochondrial phenotypes at 24 and 240 h after irradiation.ResultsBoth pravastatin (hydrophilic) and atorvastatin (lipophilic) were sufficient to prevent the loss of endothelium-dependent relaxation of arteries after head-and-neck irradiation, preserve the production of nitric oxide by endothelial cells, and suppress the cytosolic reactive oxidative stress associated with irradiation. However, only pravastatin inhibited irradiation-induced production of mitochondrial superoxide; damage to the mitochondrial DNA; loss of electron transport chain activity; and expression of inflammatory markers.ConclusionsOur findings reveal some mechanistic underpinnings of the vasoprotective effects of statins after irradiation. Whereas both pravastatin and atorvastatin can shield from endothelial dysfunction after irradiation, pravastatin additionally suppresses mitochondrial injury and inflammatory responses involving mitochondria. Clinical follow-up studies will be necessary to determine whether hydrophilic statins are more effective than their lipophilic counterparts in reducing the risk of cardiovascular disease in patients undergoing radiation therapy

CMRxRecon: An open cardiac MRI dataset for the competition of accelerated image reconstruction

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a limitation of CMR is its slow imaging speed, which causes patient discomfort and introduces artifacts in the images. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have not been publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. Manual segmentations of the myocardium and chambers of all the subjects are also provided within the dataset. Scripts of state-of-the-art reconstruction algorithms were also provided as a point of reference. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community. Researchers can access the dataset at https://www.synapse.org/#!Synapse:syn51471091/wiki/.Comment: 14 pages, 8 figure

Genomic mosaicism due to homoeologous exchange generates extensive phenotypic diversity in nascent allopolyploids

Allopolyploidy is an important process in plant speciation, yet newly formed allopolyploid species typically suffer from extreme genetic bottlenecks. One escape from this impasse might be homoeologous meiotic pairing, during which homoeologous exchanges (HEs) generate phenotypically variable progeny. However, the immediate genome-wide patterns and resulting phenotypic diversity generated by HEs remain largely unknown. Here, we analyzed the genome composition of 202 phenotyped euploid segmental allopolyploid individuals from the 4th selfed generation following chromosomal doubling of reciprocal F1 hybrids of crosses between rice subspecies, using whole genome sequencing. We describe rampant occurrence of HEs that, by overcoming incompatibility or conferring superiority of hetero-cytonuclear interactions, generate extensive and individualized genomic mosaicism across the analyzed tetraploids. We show that the resulting homoeolog copy number alteration in tetraploids affects known-function genes and their complex genetic interactions, in the process creating extraordinary phenotypic diversity at the population level following a single initial hybridization. Our results illuminate the immediate genomic landscapes possible in a tetraploid genomic environment, and underscore HE as an important mechanism that fuels rapid phenotypic diversification accompanying the initial stages of allopolyploid evolution

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Anomaly Detection Based on Mining Six Local Data Features and BP Neural Network

Key performance indicators (KPIs) are time series with the format of (timestamp, value). The accuracy of KPIs anomaly detection is far beyond our initial expectations sometimes. The reasons include the unbalanced distribution between the normal data and the anomalies as well as the existence of many different types of the KPIs data curves. In this paper, we propose a new anomaly detection model based on mining six local data features as the input of back-propagation (BP) neural network. By means of vectorization description on a normalized dataset innovatively, the local geometric characteristics of one time series curve could be well described in a precise mathematical way. Differing from some traditional statistics data characteristics describing the entire variation situation of one sequence, the six mined local data features give a subtle insight of local dynamics by describing the local monotonicity, the local convexity/concavity, the local inflection property and peaks distribution of one KPI time series. In order to demonstrate the validity of the proposed model, we applied our method on 14 classical KPIs time series datasets. Numerical results show that the new given scheme achieves an average F1-score over 90%. Comparison results show that the proposed model detects the anomaly more precisely

Design and simulation of locally enhanced microchannel heat sink for diode partially pumped slab laser

With the power level of diode-pumped solid-state laser (DPSSL) rising continuously, its thermal effect has become the main problem limiting the laser performance. In this paper, based on the heat distribution of diode partially end-pumped slab (Innoslab) laser, a shunt rectangular microchannel heat sink with locally enhanced heat dissipation is designed. Firstly, multi-stage parallel short channels are designed in the heat concentration area to enhance the solid-liquid heat exchange in this area, and the effects of structure and working conditions on its heat dissipation performance are investigated. Secondly, the copper layer is introduced into the end face of the low thermal conductivity crystal to form a high thermal conductivity path, which alleviates the heat accumulation inside the crystal. Under a certain condition, compared with the traditional liquid-cooled plate system, the maximum temperature of the laser crystal is reduced from 169.62 to 118.18 °C, the pressure drop is reduced by 66.75%, and the total mass of the system is reduced to 4.87% of the original system, which effectively improves the practical performance of the device

Experimental and Numerical Research on Open-Hole Strength and Damage Mechanism of Regularly Arrayed Short Fiber Reinforced Polymer Composite

Laminates with unidirectionally arrayed chopped strands (UACS) are one of the advanced short fiber reinforced polymer composites (SFRP) with significant application prospect, which greatly improves mechanical properties compared to the traditional SFRP, meanwhile ensuring excellent flowability. In practice, composite laminate with an open hole is one of the typical connective components, and it is necessary to clarify the allowable load and damage tolerance performance of notched structures. In the present study, UACS laminates were fabricated using the continuous carbon fiber reinforced polymer (CFRP) prepreg, on which regularly arrayed bi-angled slits were introduced by a commercial numerical control cutter. The tensile strength and strain distribution around the open hole of the notched UACS laminate were experimentally investigated, while the damage progression near the open hole of the notched UACS laminate was analyzed by the finite element method (FEM). The tensile strength of the notched UACS laminate was measured at 298 MPa, which is about 60% of the strength of the unnotched UACS laminate. The simulation results match well with the experimental results, although there is a little overestimate on strength, by about 5% and 7%, for unnotched and notched UACS laminates, respectively. The final critical failure mode for the notched UACS laminate is mainly dominated by the delamination instead of the fiber breakage in the unnotched UACS laminate

In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS

Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion

Highly thermally conductive flame-retardant epoxy nanocomposites with reduced ignitability and excellent electrical conductivities

A highly efficient phenylphosphonate-based flame-retardant epoxy resin (FREP) was firstly prepared from phenylphosphonic dichloride (PPDCl) and allylamine (AA). Functionalized graphite nanoplatelets (fGNPs) fillers were then performed to fabricate the fGNPs/FREP nanocomposites via mixing followed by casting method. The thermally conductive coefficient (λ), thermal diffusivity (α), flame retardancy, electrical conductivities and thermal stabilities of the fGNPs/FREP nanocomposites were all enhanced with the increasing addition of fGNPs fillers. The λ and α value of the fGNPs/FREP nanocomposite with 30 wt% fGNPs fillers was increased to 1.487 W/mK and 0.990 mm2/s, about 7 times and 6 times for that of pure FREP matrix (0.234 W/mK and 0.170 mm2/s), respectively. And the corresponding electrical conductivity was also increased to 5.0 × 10−4 S/cm, far better than that of pure FREP matrix (1.0 × 10−12 S/cm). In comparison with that of pure FREP, the THR and TSP value of the fGNPs/FREP nanocomposite with 15 wt% fGNPs fillers was decreased by 37% and 32%, respectively, char yield was increased by 13%, and LOI value was increased from 31% to 37%. However, the peak of heat release rate of the fGNPs/FREP nanocomposite became worse due to its high thermal conductivity. Nanoindentation revealed that there was negligible influence of fGNPs fillers on the hardness values and Young's modulus of the fGNPs/FREP nanocomposites