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991.
Ahmed Bari Daniel Grenier Jabrane Azelmat Saeed Ali Syed Abdulrahman M. Al‐Obaid Eric C. Hosten 《Chemical biology & drug design》2019,94(4):1750-1759
In continuation with our research program on the development of novel bioactive molecules, we report herein the design and synthesis of a series of diversified heterocycles ( 4 – 22 ). The synthesized compounds were evaluated for their anti‐inflammatory activity. The chemical structures of the newly synthesized compounds have been confirmed by NMR, FTIR, and microanalysis. 相似文献
992.
Elmeri M. Jokinen Pekka A. Postila Mira Ahinko Sanna Niinivehmas Olli T. Pentikinen 《Chemical biology & drug design》2019,94(4):1799-1812
A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific small‐molecule inhibitors are actively sought after for their antipsychotic and neuroprotective effects. The F‐NiB combines features from both fragment‐based drug discovery and negative image‐based (NIB) screening methodologies to facilitate rational drug discovery. The selected structural parts of protein‐bound ligand(s) are seamlessly combined with the negative image of the target's ligand‐binding cavity. This cavity‐ and fragment‐based hybrid model, namely its shape and electrostatics, is used directly in the rigid docking of ab initio generated ligand 3D conformers. In total, 14 compounds were acquired using the F‐NiB methodology, 3D quantitative structure–activity relationship modeling, and pharmacophore modeling. Three of the small molecules inhibited PDE10A at ~27 to ~67 μM range in a radiometric assay. In a larger context, the study shows that the F‐NiB provides a flexible way to incorporate small‐molecule fragments into the drug discovery. 相似文献
993.
Feng Dong 《Nanotoxicology》2019,13(3):339-353
Silver nanoparticles (AgNP) undergo various transformations into different Ag species in the environment, which determines their toxicity in microorganisms. In aerobic condition, AgNPs release Ag+ that causes cell inactivation. Limited information is known about the AgNP-cell interaction in oxygen-free environment. Here we compared the transformation and antibacterial effects of AgNPs in aerobic and anaerobic environment. The bacterium Pseudomonas aeruginosa was relatively not susceptible to Ag+ or AgNP in anaerobic environment, indicated by near two orders of magnitude greater of anaerobic minimum inhibitory concentration (MIC) than the aerobic counterpart. In anaerobic environment, the dissolved Ag concentration decreased due to the reduction of Ag+. Electron microscopy images showed the formation of new AgNPs and aggregates, preferably on cell surface or associated with extracellular polymer substances (EPS) matrix. Accumulating AgNPs onto the cells could cause membrane damage, cytoplasm release or bacterial death. Meanwhile, EPS and cell lysate were very likely to bind AgNPs, facilitating the extensively assembling of AgNPs into large aggregates. This reduced the effective Ag exposure to cells and might contribute to the detoxification in anaerobic environment. Further, flow cytometry analysis quantified that bacterial membrane was largely intact under the treatment of AgNPs in anaerobic condition compared to the dose–response manner in aerobic condition. 相似文献
994.
Helena Codina-Martínez Benjamín Fernández-García Carlos Díez-Planelles Álvaro F. Fernández Sara G. Higarza Manuel Fernández-Sanjurjo Sergio Díez-Robles Eduardo Iglesias-Gutiérrez Cristina Tomás-Zapico 《Scandinavian journal of medicine & science in sports》2020,30(2):238-253
Endurance training promotes exercise-induced adaptations in brain, like hippocampal adult neurogenesis and autophagy induction. However, resistance training effect on the autophagy response in the brain has not been much explored. Questions such as whether partial systemic autophagy or the length of training intervention affect this response deserve further attention. Therefore, 8-week-old male wild-type (Wt; n = 36) and systemic autophagy-deficient (atg4b−/−, KO; n = 36) mice were randomly distributed in three training groups, resistance (R), endurance (E), and control (non-trained), and in two training periods, 2 or 14 weeks. R and E maximal tests were evaluated before and after the training period. Forty-eight hours after the end of training program, cerebral cortex, striatum, hippocampus, and cerebellum were extracted for the analysis of autophagy proteins (LC3B-I, LC3B-II, and p62). Additionally, hippocampal adult neurogenesis was determined by doublecortin-positive cells count (DCX+) in brain sections. Our results show that, in contrast to Wt, KO were unable to improve R after both trainings. Autophagy levels in brain areas may be modified by E training only in cerebral cortex of Wt trained for 14 weeks, and in KO trained for 2 weeks. DCX + in Wt increased in R and E after both periods of training, with R for 14 weeks more effective than E. Interestingly, no changes in DCX + were observed in KO after 2 weeks, being even undetectable after 14 weeks of intervention. Thus, autophagy is crucial for R performance and for exercise-induced adult neurogenesis. 相似文献
995.
996.
Mark A. Tully Ilona McMullan Nicole E. Blackburn Jason J. Wilson Brendan Bunting Lee Smith Frank Kee Manuela Deidda Maria Giné-Garriga Laura Coll-Planas Dhayana Dallmeier Michael Denkinger Dietrich Rothenbacher Paolo Caserotti 《Scandinavian journal of medicine & science in sports》2020,30(10):1957-1965
997.
Kirkke Reisberg Eva-Maria Riso Jaak Jürimäe 《Scandinavian journal of medicine & science in sports》2020,30(11):2251-2263
The purpose of the study was to assess the longitudinal associations of physical activity (PA) with body composition and physical fitness (PF) at the 12-month follow-up during the transition from kindergarten to school in Estonian children aged 6 to 8 years (n = 147). PA and sedentary behavior (SB) were assessed using the accelerometer. Body composition was measured from triceps and subscapular skinfold thicknesses and PF using PREFIT test battery. SB at the mean age of 6.6 year had negative relation with upper and lower body strength and motor fitness at the mean age of 7.6 year in adjusted models. Light PA (LPA) and moderate PA(MPA) at 6.6 year were positively and SB was negatively associated with fat-free mass index (FFMI) at 7.6 year after adjustments for confounders [vigorous PA (VPA), total awake wear time, child's sex, age at measurement]. Substituting 5 min/d of SB at 6.6 year with 5 min of VPA was related to higher FFMI at 7.6 year. In adjusted models, VPA at 6.6 year was positively associated with cardiorespiratory fitness at 7.6 year, greater baseline VPA or moderate-to-vigorous PA (MVPA) predicted greater upper body strength a year later and LPA, MPA, VPA, MVPA at 6.6 year were positively related to lower body strength at follow-up. In adjusted analysis greater VPA at 6.6 year was related to better motor fitness at follow-up. Promoting higher-intensity PA and reducing SB at preschool may have long-term effects on body composition and PF in children at the first grade. 相似文献
998.
999.
1000.
《Gait & posture》2020
BackgroundAge-related cognitive decline may be delayed with appropriate interventions if those at high risk can be identified prior to clinical symptoms arising. Gait variability assessment has emerged as a promising candidate prognostic indicator, however, it remains unclear how sensitive gait variability is to early changes in cognitive abilities.Research questionDo community-dwelling adults over 65 years of age with subjective memory complaints differ from those with no subjective memory concerns in terms of laboratory-measured or free-living gait variability?MethodsThis cross-sectional study recruited 24 (age = 73.5(SD 6.4) years) community-dwelling people with subjective memory complaints and twenty seven (age = 70.9(4.3) years) individuals with no subjective memory concerns. A sample of 9 individuals with diagnosed mild dementia were also assessed (age = 86.5(7.0) years). Gait variability was assessed in a laboratory during walking at preferred pace (single-task) and while counting backward by seven (dual-task). Sixteen passes over a 4.88 m walkway in each condition were recorded and step length and duration variability was analysed. Free-living gait was assessed with a waist-worn accelerometer by identifying gait bouts of at least one min duration, and the mean multiscale sample entropy in one mins non-overlapping epochs is reported. Statistical inferences were based on analysis of variance using sex and group as the factors.ResultsNo difference between those with subjective memory complaints and those without were observed in either laboratory- or free-living gait variability estimates. Both laboratory- and free-living gait variability were higher in those with mild dementia compared to the other groups.SignificanceAssuming that subjective memory complaints are on the pathway from cognitively intact to cognitively frail, the findings raise the hypothesis that subjective memory complaints occur earlier in the pathophysiology than measurable changes in laboratory or free living gait. Alternatively the gait variability assessments utilised may have been too insensitive. 相似文献