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The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.  相似文献   
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Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.  相似文献   
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Physically based simulation of human hair is a well studied and well known problem. But the “pure” physically based representation of hair (and other animation elements) is not the only concern of the animators, who want to “control” the creation and animation phases of the content. This paper describes a sketch-based tool, with which a user can both create hair models with different styling parameters and produce animations of these created hair models using physically and key frame-based techniques. The model creation and animation production tasks are all performed with direct manipulation techniques in real-time.  相似文献   
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The GC/MS and NMR analysis of the reaction products of naphthalene with 1-bromohexane were reported. The products obtained were suggested to have six isomers of linear hexylnaphthalene and the structure of each isomer was determined by GC/MS and NMR spectra. For the first time, the unique chemical shift data were obtained. The content of each isomer calculated by 1H NMR and 13C NMR spectra was consistent with that by GC/MS spectra, which confirmed the accuracy of NMR data.  相似文献   
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The study of the micromammalian parasite complexes in the Belorussian part of the evacuation zone of the Chernobyl nuclear station revealed 13 species of Coccidia and 30 species of ectoparasitic Arthropoda. Total increase of abundance and biodiversity of both parasites and their hosts was observed. The part of ectoparasites being epidemically hazardous was significantly increased. An analysis of a long-term dynamics of parasite abundance reveals their adaptation to new conditions in the Belorussia.  相似文献   
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Unlike the glanders agent, the superficial structures of the melioidosis agent were demonstrated to be responsible for marked was immunosuppressive activity. Some antigenic fractions suppressing the blast transformation of lymphocytes, reducing the count of T helpers and profoundly potentiating the infection in vivo were isolated from P. pseudomallei cells. The immunogenic and immunosuppressive activities of both agents' superficial structures were studied by high performance chromatography. Antigenic complexes that were able to protect immunized laboratory animals against fatal infections and to prevent bacterial carriage due to the activation of T cells and to the bacterial activity of macrophages were identified. A composition comprising several immunogens was found to provide an additive protective action against both causative agents. Therefore, the composition may be considered to be a prototype of a molecular antipseudomonadic vaccine.  相似文献   
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Polyarteritis nodosa is a rare disorder and a form of systemic vasculitis. A 48 year-old female was admitted to the hospital because menorrhagia and pelvic pain in February 1993. The patient underwent exploratory laparotomy resulting in a total hysterectomy and bilateral salpingo-oophorectomy for myoma of uterus and a right adnexal cystic mass. Histopathologic examination revealed left ovarian periarteritis nodosa. Further investigation and 9 months follow-up failed to show any systemic involvement. To our knowledge the isolated ovarian polyarteritis nodosa is the first case in the literature.  相似文献   
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