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uscle atrophy is associated with better physical QOL outcomes; and (3) more severe myelopathy with gait impairment is associated with poorer mental QOL outcomes.Radiation therapy is the mainstay in the treatment of lung cancer, and lung fibrosis is a radiotherapy-related major side effect that can seriously reduce patient's quality of life. Nevertheless, effective strategies for protecting against radiation therapy-induced fibrosis have not been developed. Hence, we investigated the radioprotective effects and the underlying mechanism of the standardized herbal extract PM014 on radiation-induced lung fibrosis. Ablative radiation dose of 75 Gy was focally delivered to the left lung of mice. We evaluated the effects of PM014 on radiation-induced lung fibrosis in vivo and in an in vitro model. Lung volume and functional changes were evaluated using the micro-CT and flexiVent system. Fibrosis-related molecules were evaluated by immunohistochemistry, western blot, and real-time PCR. A orthotopic lung tumour mouse model was established using LLC1 cells. Irradiated mice treated with PM014 showed a significant improvement in collagen deposition, normal lung volume, and functional lung parameters, and these therapeutic effects were better than those of amifostine. PM104 attenuated radiation-induced increases in NF-κB activity and inhibited radiation-induced p65 translocation, ROS production, DNA damage, and epithelial-mesenchymal transition. PM104 effectively alleviated fibrosis in an irradiated orthotopic mouse lung tumour model while not attenuating the efficacy of the radiation therapy by reduction of the tumour. Standardized herbal extract PM014 may be a potential therapeutic agent that is able to increase the efficacy of radiotherapy by alleviating radiation-induced lung fibrosis.Genome editing has become one of the key technologies for plant breeding. However, in polyploid species such as chrysanthemum, knockout of all loci of multiple genes is needed to eliminate functional redundancies. We identified six cDNAs for the CmDMC1 genes involved in meiotic homologous recombination in chrysanthemum. Since all six cDNAs harbored a homologous core region, simultaneous knockout via TALEN-mediated genome editing should be possible. We isolated the CmDMC1 loci corresponding to the six cDNAs and constructed a TALEN-expression vector bearing a CmDMC1 target site containing the homologous core region. After transforming two chrysanthemum cultivars with the TALEN-expression vector, seven lines exhibited disruption of all six CmDMC1 loci at the target site as well as stable male and female sterility at 10-30 °C. This strategy to produce completely sterile plants could be widely applicable to prevent the risk of transgene flow from transgenic plants to their wild relatives.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The interaction (oblique collision) of two ion acoustic solitons (IASs) in a magnetized relativistic degenerate plasma with relativistic degenerate electrons and non-degenerate cold ions is studied. The extended Poincaré-Lighthill-Kuo (PLK) method is used to obtain two Korteweg deVries (KdV) wave equations that describe the interacting IASs, then the phase shifts due to interaction are calculated. We studied influence of the fluid number density on the interaction process, interacting solitons phase shifts and also phase velocities. The introduced model is valid for astrophysical objects with high density matter such as white dwarfs, neutron stars, degenerate electrons gas in metals and laboratory degenerate plasma. An inverse proportionality between the phase shifts, phase velocity and the equilibrium electron fluid number density [Formula see text] was established in the range [Formula see text]. We found that the soliton waves get sharper (narrower) and higher with increasing the electrons fluid number density [Formula see text], and hence less spacial occupying. The phase shifts and the phase velocity remain approximately unchanged in the range of [Formula see text]. The impact of the obliqueness angle [Formula see text] on the soliton interaction process is also studied.The radiological incidents and terrorism have demanded the need for the development of rapid, precise, and non-invasive technique for detection and quantification of exposed dose of radiation. Though radiation induced metabolic markers have been thoroughly investigated, but reproducibility still needs to be elucidated. The present study aims at assessing the reliability and reproducibility of markers using nuclear magnetic resonance (NMR) spectroscopy and further deriving a logistic regression model based on these markers. C57BL/6 male mice (8-10 weeks) whole body γ-irradiated and sham irradiated controls were used. Urine samples collected at 24 h post dose were investigated using high resolution NMR spectroscopy and the datasets were analyzed using multivariate analysis. Fifteen distinguishable metabolites and 3 metabolic pathways (TCA cycle, taurine and hypotaurine metabolism, primary bile acid biosynthesis) were found to be amended. ROC curve and logistic regression was used to establish a diagnostic model as Logit (p) = log (p/1 - p) = -0.498 + 13.771 (tau) - 3.412 (citrate) - 34.461 (α-KG) + 515.183 (fumarate) with a sensitivity and specificity of 1.00 and 0.964 respectively. The findings demonstrate the proof of concept and the potential of NMR based metabolomics to establish a prediction model that can be implemented as a promising mass screening tool during triage.The CRISPR-Cas12a RNA-guided complexes have tremendous potential for nucleic acid detection but are limited to the picomolar detection limit without an amplification step. Here, we develop a platform with engineered crRNAs and optimized conditions that enabled us to detect various clinically relevant nucleic acid targets with higher sensitivity, achieving a limit of detection in the femtomolar range without any target pre-amplification step. https://www.selleckchem.com/products/tenapanor.html By extending the 3'- or 5'-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discover a self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA and with significant improvement in specificity for target recognition. Particularly, the 7-mer DNA extension to crRNA is determined to be universal and spacer-independent for enhancing the sensitivity and specificity of LbCas12a-mediated nucleic acid detection. We perform a detailed characterization of our engineered ENHANCE system with various crRNA modifications, target types, reporters, and divalent cations.
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