Notes

Productive ligation associated with posterior tibial vein aneurysm done as outlined by intraoperative venography final results.
Neratinib inhibited FGF2 expression in activated HSCs and serum FGF2 level in the model, suggesting that neratinib possessed therapeutic potency against liver fibrosis and the potential for application against other fibrotic diseases.Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.In Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. #link# Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.Structural disorder is widespread in eukaryotic proteins and is vital for their function in diverse biological processes. It is therefore highly desirable to be able to predict the degree of order and disorder from amino acid sequence. link2 It is, however, notoriously difficult to predict the degree of local flexibility within structured domains and the presence and nuances of localized rigidity within intrinsically disordered regions. To identify such instances, we used the CheZOD database, which encompasses accurate, balanced, and continuous-valued quantification of protein (dis)order at amino acid resolution based on NMR chemical shifts. To computationally forecast the spectrum of protein disorder in the most comprehensive manner possible, we constructed the sequence-based protein order/disorder predictor ODiNPred, trained on an expanded version of CheZOD. ODiNPred applies a deep neural network comprising 157 unique sequence features to 1325 protein sequences together with the experimental NMR chemical shift data. Cross-validation for 117 protein sequences shows that ODiNPred better predicts the continuous variation in order along the protein sequence, suggesting that contemporary predictors are limited by the quality of training data. The inclusion of evolutionary features reduces the performance gap between ODiNPred and its peers, but analysis shows that it retains greater accuracy for the more challenging prediction of intermediate disorder.The emissions of [Formula see text] into the environment from the nuclear accidents in Chernobyl in 1986 and Fukushima in 2011 led to the need to decontaminate large areas to avert radiation doses to the population in the affected areas. To be able to perform cost-effective and sustainable remediation, knowledge is needed about how radiation doses can be minimized through optimized interventions such that the greatest possible reduction in radiation dose is obtained with the smallest possible negative impact on the area. Theoretical calculations have been performed to determine how radiation doses in single family houses in a typical Swedish residential suburb arise from a hypothetical [Formula see text] deposition on the ground. The intention was to highlight how remediation of different parts of the surroundings affects the radiation dose to the residents in a particular property. A Monte Carlo model of the houses and the environment in a suburban area was set up to allow calculations of the dose contributialso of relevance.Micro-concentrator solar cells enable higher power conversion efficiencies and material savings when compared to large-area non-concentrated solar cells. In this study, we use materials-efficient area-selective electrodeposition of the metallic elements, coupled with selenium reactive annealing, to form Cu(In,Ga)Se2 semiconductor absorber layers in patterned microelectrode arrays. This process achieves significant material savings of the low-abundance elements. The resulting copper-poor micro-absorber layers' composition and homogeneity depend on the deposition charge, where higher charge leads to greater inhomogeneity in the Cu/In ratio and to a patchy presence of a CuIn5Se8 OVC phase. Photovoltaic devices show open-circuit voltages of up to 525 mV under a concentration factor of 18 ×, which is larger than other reported Cu(In,Ga)Se2 micro-solar cells fabricated by materials-efficient methods. Furthermore, a single micro-solar cell device, measured under light concentration, displayed a power conversion efficiency of 5% under a concentration factor of 33 ×. These results show the potential of the presented method to assemble micro-concentrator photovoltaic devices, which operate at higher efficiencies while using light concentration.We sought to determine a mechanism by which L-arginine increases glucose-stimulated insulin secretion (GSIS) in β-cells by finding a protein with affinity to L-arginine using arginine-immobilized magnetic nanobeads technology. Glucokinase (GCK), the key regulator of GSIS and a disease-causing gene of maturity-onset diabetes of the young type 2 (MODY2), was found to bind L-arginine. L-Arginine stimulated production of glucose-6-phosphate (G6P) and induced insulin secretion. We analyzed glucokinase mutants and identified three glutamate residues that mediate binding to L-arginine. One MODY2 patient with GCKE442* demonstrated lower C-peptide-to-glucose ratio after arginine administration. In β-cell line, GCKE442* reduced L-arginine-induced insulin secretion compared with GCKWT. In addition, we elucidated that the binding of arginine protects glucokinase from degradation by E3 ubiquitin ligase cereblon mediated ubiquitination. We conclude that L-arginine induces insulin secretion by increasing G6P production by glucokinase through direct stimulation and by prevention of degradation.Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used 68Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by 68Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89Zr and 68Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of 68Ga-labeled CAR T cells is only one twenty-fourth of 89Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68Ga instead of 89Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.Cyanthillium cinereum (L.) H.Rob. is one of the most popular herbal smoking cessation aids currently used in Thailand, and its adulteration with Emilia sonchifolia (L.) DC. is often found in the herbal market. Therefore, the quality of the raw material must be considered. This work aimed to integrate macro- and microscopic, chemical and genetic authentication strategies to differentiate C. cinereum raw material from its adulterant. Different morphological features between C. cinereum and E. sonchifolia were simply recognized at the leaf base. For microscopic characteristics, trichome and pappus features were different between the two plants. HPTLC profiles showed a distinct band that could be used to unambiguously differentiate C. cinereum from E. sonchifolia. link3 Four triterpenoid compounds, β-amyrin, taraxasterol, lupeol, and betulin, were identified from the distinct HPTLC band of C. cinereum. The use of core DNA barcode regions; rbcL, matK, ITS and psbA-trnH provided species-level resolution to differentiate the two plants. Taken together, the integration of macroscopic and microscopic characterization, phytochemical analysis by HPTLC and DNA barcoding distinguished C. cinereum from E. sonchifolia. read more of C. cinereum obtained here can help manufacturers to increase the quality control of C. cinereum raw material in commercialized smoking cessation products.Research has shown that warming and drought change plant phenolics. However, much of this work has centered on the effects of individual abiotic stressors on single plant species rather than the concurrent effects of multiple stressors at the plant community level. To address this gap, we manipulated rainfall and air temperature to test for their individual and interactive effects on the expression of leaf phenolics at the community level for annual plant species occurring in two habitat types (under oak tree canopies or in open grasslands) in a Mediterranean savanna. We found that augmented temperature had a significant positive effect on the community-weighted mean of total phenolics whereas reduced rainfall had no effect. In addition, we found no evidence of interactive effects between climatic stressors and these patterns remained consistent across habitat types. Overall, this study points at increasing efforts to investigate the linkages between climate change and community-level shifts in plant secondary chemistry.
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