Borupmitchell3509

fe will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs.Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia. Here, twenty-three biguanide derivatives were designed and synthesized based on the principles of bioisosteres. These derivatives were evaluated for the activity of antiplatelet thrombosis in vivo. We found that N-trifluoromethanesulfonyl biguanide derivative, compound b10, uniquely prevented cerebral infarction as well as neuronal function injury, and significantly decrease the mortality rate of ischemic stroke in the middle cerebral artery occlusion mice without significant side effects. We verified that b10 directly inhibited platelets thrombus formation and decreased the compactness of stroke thrombi. Particularly, b10 exhibited good potency to inhibit human platelet activation including platelet aggregation, adhesion, pseudopodia formation, integrin GPIIb/IIIa activation, CD62P expression and clot retraction. Meanwhile, the pharmacokinetics assessment showed that b10 had satisfying pharmacological characteristics including a longer duration and a higher oral absorption ratio than its parent compound. In addition, b10 remarkably ameliorated not only stroke related to platelet thrombosis but also carotid artery thrombus formation. It is concluded that the novel potent antiplatelet thrombotic agent derived from biguanide is a promising candidate for stroke treatment.Two series of novel 1, 2, 4-triazole benzoyl arylamine derivatives were prepared and screened for their activities against three pathogens of Gaeumannomyces graminis var.tritici, Sclerotinia sclerotiorum and Fusarium graminearum using the mycelium growth inhibition method in vitro. The results indicated that most of the synthesized derivatives displayed antifungal activities. Compounds 6c-d and 6f-g exhibited lower EC50s against all the three pathogens. Among of them, the compound 6g displayed the most potent antifungal activities with EC50 values of 0.01, 0.19 and 0.12 μg mL-1 respectively. The structure and activity relationship showed that election-withdrawing group at pata-position of aniline was favorable for high activities, and the preferred groups were alkoxy carbonyls. These results proposed that the compound 6g can be a lead compound for development of novel fungicide.Purpose To perform a detailed evaluation of dose calculation accuracy and clinical feasibility of Mobius3D. Of particular importance, multileaf collimator (MLC) modeling accuracy in the Mobius3D dose calculation algorithm was investigated. Methods Mobius3D was fully commissioned by following the vendor-suggested procedures, including dosimetric leaf gap (DLG) optimization. The DLG optimization determined an optimal DLG correction factor which minimized the average difference between calculated and measured doses for 13 patient volumetric-modulated arc therapy (VMAT) plans. Two sets of step-and-shoot plans were created to examine MLC and off-axis open fields modeling accuracy of the Mobius3D dose calculation algorithm MLC test set and off-axis open field test set. The test plans were delivered to MapCHECK for the MLC tests and an ionization chamber for the off-axis open field test, and these measured doses were compared to Mobius3D-calculated doses. Results The mean difference between the calculated and measured doses across the 13 VMAT plans was 0.6% with an optimal DLG correction factor of 1.0. The mean percentage of pixels passing gamma from a 3%/1 mm gamma analysis for the MLC test set was 43.5% across the MLC tests. For the off-axis open field tests, the Mobius3D-calculated dose for 1.5 cm square field was -4.6% lower than the chamber-measured dose. selleck kinase inhibitor Conclusions It was demonstrated that Mobius3D has dose calculation uncertainties for small fields and MLC tongue-and-groove design is not adequately taken into consideration in Mobius3D. Careful consideration of DLG correction factor, which affects the resulting dose distributions, is required when commissioning Mobius3D for patient-specific QA.Purpose The luminescence images of water during the irradiation of carbon-ions provide useful information such as the ranges and the widths of carbon-ion beams. However, measured luminescence images show higher intensities in shallow depths and wider lateral profiles than those of the dose distributions. These differences prevent the luminescence imaging of water from being applied to a quality assurance for carbon-ion therapy. We assumed that the differences were due to the contaminations of Cerenkov-light from the secondary electrons of carbon-ions as well as the prompt gamma photons in the measured image. In this study, we applied a correction method to a luminescence image of water during the irradiation of carbon-ion beams. Methods We estimated the distribution of the Cerenkov-light in water during the irradiation of carbon-ions by Monte Carlo simulation and subtracted the simulated Cerenkov-light from the depth and lateral profiles of the measured luminescence image for 241.5 MeV/u-carbon-ions. Results With these corrections, we successfully obtained depth and lateral profiles whose distributions are almost identical to the dose distributions of carbon-ions. The high intensities in the shallow depth areas decreased and the Bragg peak intensity increased. The beam widths of the measured images approached those of the ionization chamber. Conclusions These results indicate that the luminescence imaging of water with our proposed correction has potential to be used for dose distribution measurements for carbon-ion therapy dosimetry.