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关键词： triazolo[1,5-a]pyrimidine   iodine   triphenylphosphine   C-O activation   amination   ball milling   mechanochemistry  

摘要： A novel, solvent-free method for the direct amination of [1,2,4]triazolo[1,5-a]pyrimidin-7-ones has been developed via mechanochemical ball milling. Utilizing a Ph3P-I2 system as a C-O bond activator, this one-pot protocol efficiently overcomes the poor solubility of these substrates in conventional solvents. Optimization revealed that chloro(trimethyl)silane (TMSCl) is essential for achieving high yields by sequestering trace water. The reaction scope is broad, providing access to 32 derivatives in 54-87% yield from both aromatic and aliphatic amines, with good tolerance for functional groups such as CF3, Br, Cl, and F.

关键词： type 1 diabetes   postprandial glycemia   resistant starch   retrogradation   continuous glucose monitoring  

摘要： Background: Carbohydrate quality and culinary processing can meaningfully alter postprandial glycemia in people with type 1 diabetes (T1D). Cooling gelatinized starch promotes retrogradation and increases resistant starch (RS), potentially attenuating postprandial glucose excursions. Objectives: We investigated whether pasta cooled after cooking (24 h at 4 degrees C) and reheated before consumption improves postprandial glycemia in adults with T1D without increasing hypoglycemia risk under routine insulin pump bolus-calculator dosing. Methods: In this randomized, single-blind, crossover study, 32 adults with T1D treated with continuous subcutaneous insulin infusion (CSII) consumed two standardized pasta-based meals (50 g of available carbohydrate): freshly cooked pasta and cooled/reheated pasta. Participants administered rapid-acting insulin boluses calculated by their pump bolus calculator 10 min before the meal. Interstitial glucose was recorded for 180 min using flash glucose monitoring. Results: Compared with freshly cooked pasta, cooled/reheated pasta produced lower maximum glycemia (10.7 vs. 12.6 mmol/L, p = 0.0001), lower maximum glycemic rise (2.8 vs. 4.7 mmol/L, p < 0.0001), lower incremental area under the curve (iAUC;211.9 vs. 524.8 mmol/L & times;180 min, p < 0.0001), and a shorter time-to-peak (65 vs. 125 min, p = 0.014). Resistant starch content increased after cooling (12.88 +/- 0.06 vs. 8.03 +/- 0.08 g/100 g). The number of hypoglycemic episodes did not differ between conditions. Conclusions: Cooling and reheating pasta therefore increased RS and attenuated postprandial glycemia in adults with T1D without increasing early postprandial hypoglycemia in the studied setting.

关键词： Traumatic brain injury   Biomarkers   Cytokines   Enzyme-linked immunoassays   Brain damage   Cerebrospinal fluid   Interleukins   Socioeconomic aspects of health  

摘要： Background Traumatic brain injury (TBI) is diagnosed using radiological imaging and biomarker analysis, each with certain limitations. Accurate and accessible detection of TBI is essential for its treatment. Since interleukin (IL)-1 beta and IL-18 are key neuroinflammatory cytokines, we aim to investigate the regulation of IL-1 beta and IL-18 in TBI patients and assess their potential as biomarkers of TBI. Methods Forty TBI and 40 healthy subjects were recruited for this study. The Glasgow coma scale (GCS) was used to assess the clinical severity of TBI. Spearman's rank-order correlation was employed to find the association between GCS scores and IL levels of TBI patients. An enzyme-linked immunosorbent assay (ELISA) with human IL-1 beta and IL-18 ELISA kits was conducted to measure the serum IL-1 beta and IL-18 levels. The area under the curve (AUC), sensitivity, and specificity were measured to assess the potential of IL-1 beta and IL-18 as biomarkers. Results The patients had mild-to-moderate TBI (mTBI) with a mean GCS score of 11.05 +/- 1.67. A negative correlation was found between GCS scores and IL levels, while IL-1 beta and IL-18 were positively correlated with each other. IL-1 beta levels in the TBI and healthy subjects were 1882.19 +/- 796.72 pg/mL and 1473.50 +/- 333.045 pg/mL, respectively, with a significant difference (p = 0.001). Moreover, the IL-18 levels in TBI subjects (25.92 +/- 14.81 ng/L) were also significantly higher (p < 0.001) compared to those of the control group subjects (19.14 +/- 2.99 ng/L). The IL-1 beta exhibited an AUC of 0.72 with 72.5% sensitivity and 70% specificity, at a cut-off point of 1527.25 (pg/mL), while IL-18 had an AUC of 0.78 with 77.5% sensitivity and 72.7% specificity, at a cut-off point of 19.645 (ng/L). Conclusions IL-1 beta and IL-18 levels were increased remarkably in mTBI patients and exhibited fair potential as biomarkers for the diagnosis and prognosis of TBI.

关键词： Lower paleolithic   MIS 11   Medzhybizh   core-and-flake industry   Oldowan   technological trajectory  

摘要： This study investigates the technological trajectory and reduction strategies of the lithic assemblage from layer III of Medzhybizh 1 (MIS 11). Low raw material utilization, opportunistic methods, and short operational sequences characterize the industry. Rather than being exclusively focused on flake production, the technological trajectory appears aimed at obtaining sharp-edged pieces from a variety of blank types. Detached flakes and pebble fragments were seldom subjected to further modification. The analysis of assemblage structure, toolkit composition, and cha & icirc;ne op & eacute;ratoire indicates that layer III of Medzhybizh 1 represents an atypical example within the context of MIS 11, highlighting the variability of core-and-flake industries in the European Lower Paleolithic.