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Free radical mediated alkylation of alkenes is a challenging and largely unmet goal. Disclosed here is a conceptually novel "polarity umpolung" strategy for radical alkylation of alkenes using a portfolio of easily accessed, difunctional alkylating reagents. This strategy is achieved by substituting inherently nucleophilic alkyl radicals with electrophilic sulfone-bearing surrogates, thus inverting the usual mode of reactivity. Along with alkylation, either an heteroaryl or oximino group is concurrently incorporated into the alkenes by a consecutive docking and migration process, leading to valuable products. The reaction displays a broad functional-group tolerance under mild reaction conditions. The protocol opens new vistas for the late-stage modification of complex natural products and drug molecules containing alkene moieties. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.The toddler and preschool years are a time of significant development in both expressive and receptive communication abilities. However, little is known about the neurobiological underpinnings of language development during this period, likely due to difficulties acquiring functional neuroimaging data. Functional Near Infrared Spectroscopy (fNIRS) is a motion-tolerant neuroimaging technique that assesses cortical brain activity and can be used in very young children. Here, we use fNIRS during perception of communicative and non-communicative speech and gestures in typically developing 2- and 3-year-olds (Study 1, n=15, n=12 respectively) and in a sample of 2-year-olds with both fNIRS data collected at age 2 and language outcome data at age 3 (study 2, n=18). In Study 1, 2- and 3-year-olds differentiated between communicative and noncommunicative stimuli as well as between speech and gestures in the left lateral frontal region. However, 2-year-olds showed different patterns of activation from 3-year-olds in right medial frontal regions. In Study 2, which included two toddlers identified with early language delays along with 16 typically developing toddlers, neural differentiation of communicative stimuli in the right medial frontal region at age 2 predicted receptive language at age 3. Specifically, after accounting for variance related to verbal ability at age 2, increased neural activation for communicative gestures (versus both communicative speech and noncommunicative gestures) at age 2 predicted higher receptive language scores at age 3. These results are discussed in the context of the underlying mechanisms of toddler language development and use of fNIRS in prediction of language outcomes. This article is protected by copyright. All rights reserved.Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe the synthesis of iminopyrrolidine-2-carboxylic acid derivatives using chiral glutamine, oxo components, and isocyanide building blocks in an unprecedented Ugi-3-component reaction. We used I-DOT, a positive-pressure-based low-volume and non-contact dispensing technology to prepare more than 1000 different derivatives in a fully automated fashion. In general, the reaction is stereoselective, proceeds in good yields, and tolerates a wide variety of functional groups. GSK343 cost We exemplify a pipeline of fast and efficient nanomole-scale scouting to millimole-scale synthesis for the discovery of a useful novel reaction with great scope. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Dermatophytes are the aetiological factors of a majority of superficial fungal infections. What distinguishes them from other pathogenic filamentous fungi is their unique ability to degrade keratin. The remarkable ability of this group of fungi to survive in different ecosystems results from their morphological and ecological diversity as well as high adaptability to changing environmental conditions. Paradoxically, despite the progress in medicine, the prevalence of dermatophyte infections is increasing from year to year. At the beginning of the third millennium, practical diagnostic and therapeutic options are still very limited. This review focuses on understanding the major problems in this aspect of dermatophyte infections and indicates future strategies and perspectives for novel approaches to identification and drugs for elimination of dermatophytes. Particular importance is placed on development of a strategy for a diagnostic pathway and implementation of rapid and reliable diagnostics methods designed by international teams. Furthermore, among compounds that currently arouse great interest, representatives of terpenoids, alkaloids, saponins, flavonoids and essential oils deserve attention. Many of these compounds are undergoing clinical trials as potential antifungal agents, and future research should focus on attempts at determination of the applicability of tested substances. Finally, the advantages and disadvantages in implementation of new diagnostic paths and medicinal substances for routine use are indicated. © 2020 The Society for Applied Microbiology.Designing protected area configurations to maximise biodiversity is a critical conservation goal. The configuration of protected areas can significantly impact the richness and identity of the species found there; one large patch supports larger populations but can facilitate competitive exclusion. Conversely, many small habitats spreads risk but may exclude predators that typically require large home ranges. Identifying how best to design protected areas is further complicated by monitoring programs failing to detect species. Here we test the consequences of different protected area configurations using multi-trophic level experimental microcosms. We demonstrate that for a given total size, many small patches generate higher species richness, are more likely to contain predators, and have fewer extinctions compared to single large patches. However, the relationship between the size, number of patches, and species richness was greatly affected by insufficient monitoring, and could lead to incorrect conservation decisions, especially for higher trophic levels. © 2020 John Wiley & Sons Ltd/CNRS.AIMS This study aims to explore nurses' demographic data, assertiveness, psychosocial work condition, and workplace bullying, and find the predictors of workplace bullying. METHODS This study adopted a cross-sectional design. A stratified sample comprising 241 nurses from a regi onal teaching hospitals in Taiwan was selected from the 10th to the 23rd September, 2018. Data were analysed by using the SPSS Statistics 17.0. Descriptive statistics (frequency, percentage, mean, and standard deviation), one-way Anova, t test, Pearson's correlation, and multiple linear regressions were used. RESULTS The results showed that the participants with "past bullying experience," "lower self-assertiveness," "higher work psychological demands," "lower workplace justice," "lower labour participation," and "lower overall social support" are more likely to experience workplace bullying. CONCLUSIONS Hospital managers should pay attention to the problem of nursing workplace bullying. First of all, hospital managers should encourage curriculum on nursing workplace bullying and incorporate nursing workplace bullying prevention training courses in curriculum planning. © 2020 John Wiley & Sons Australia, Ltd.PURPOSE Published epidemiological studies on the association between finasteride use and the risk of male breast cancer have been inconclusive due to methodological limitations including a few male breast cancer cases included. Determinants of male breast cancer have been studied, but it remains unexplored whether these are also related to finasteride use and thereby constitute potential confounders. This study aimed to assess whether there are differences between finasteride users and nonusers with regard to numerous potential confounders. METHODS In total, 246 508 finasteride users (≥35 years) were identified in the prescription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). An equal number of nonusers were sampled. The directed acyclic graph (DAG) methodology was used to identify potential confounders for the association between finasteride and male breast cancer. A logistic regression model compared finasteride users and nonusers with regard to potential confounders that were measurable in registries and population surveys. RESULTS Finasteride users had higher odds of testicular abnormalities (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exogenous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabetes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry or in high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), living in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70; 0.50-0.99) compared to nonusers. CONCLUSIONS Systematic differences between finasteride users and nonusers were found emphasizing the importance of confounder adjustment of associations between finasteride and male breast cancer. © 2020 John Wiley & Sons Ltd.Treatment with Lipitor is associated with several adverse impacts. Here we investigated the effects of low Lipitor nanoparticles (atorvastatin calcium nanopartilcle [AC-NP]), with size less than 100 , on enzymes of lipid metabolism and inflammation in cardiac, hepatic, and brain tissues of hypercholestremic adult male rats. Adult male rats were divided into five experimental groups. In group 1, the intact control (normal pellet diet), animals were fed a normal control diet; the other four groups were fed a high-fat diet (HFD) for 6 weeks. After 6 weeks, groups from 2 to 5 were assigned as a positive control (HFD), HFD + Lipitor, HFD + AC-NP-R1, or HFD + AC-NP-R2. Different treatments were administrated orally for two regimen periods (R1 daily and R2 once every 3 days). The treatment was conducted for two consecutive weeks. The HFD group faced a significant elevation in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), associated with a significant reduction in low-density lipoprotein receptor (LDL-R) along with cholesterol 7 α-hydroxylase enzyme in hepatic tissues, compared with the control group. Also, the HFD group induced hepatic, cardiac, and brain inflammation, evidenced by increased hepatic oxidative stress markers and cardiac homocysteine, together with elevated proinflammatory cytokines interleukin-1β (IL-1β) and IL-6 levels in brain tissue, compared with the control group. Different AC-NP treatments significantly augmented both mRNA LDL-R and mRNA 7α-hydroxylase expression in hepatic tissues, associated with significant depletion in mRNA HMG-CoA expression, compared with HFD + Lipitor. The inflammation symptoms were ameliorated by the AC-NP treatments, compared to HFD + Lipitor. Lipitor encapsulation in NP formulation results in increased efficiency and reduced dose-related adverse effects known to be associated with the Lipitor chronic administration. © 2020 Wiley Periodicals, Inc.Liver cancer is a malignant tumor that occurs in the liver and has a high mortality rate. We strived to detect the role and mechanism of circRNA-0072309 in liver cancer. Hep3B cell line was transfected with pc-circ and si-circ for viability, colony formation, apoptosis, migration, and invasion tests, which were individually performed by CCK-8, colony formation detection, flow cytometry assay, migration and invasion assays. What is more, the luciferase reporter assay was conducted to determine the target relationship between the circRNA-0072309 and microRNA (miR)-665. The expression of circRNA-0072309 was examined by qRT-PCR. The expression of proteins was examined via western blot. CircRNA-0072309 was lowly expressed in liver cancer tissues and positively associated with 5-year survival rate. The viability, colony formation, invasive and migratory ability were inhibited by abundant circRNA-0072309, which promoted cell apoptosis on the contrary. CircRNA-0072309 knockdown induced opposite effects, but could not affect apoptosis.
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