Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of ...cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.
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•67 Brazilian coffees were analyzed for their δ13C, δ18O, δ2H and δ15N signatures.•Organic coffee presented higher δ15N values.•k-Nearest neighbors was not efficient in classifying ...coffees from different sites.•Support vector machines correctly classified coffees from São Paulo.•Linear discriminant analysis correctly classified conventional coffees.
Authentication of ground coffee has become an important issue because of fraudulent activities in the sector. In the current work, sixty-seven Brazilian coffees produced in different geographical origins using organic (ORG, n = 25) and conventional (CONV, n = 42) systems were analyzed for their stable isotope ratios (δ13C, δ18O, δ2H, and δ15N). Data were analyzed by inferential analysis to compare the factors whereas linear discriminant analysis (LDA), k-nearest neighbors (k-NN), and support vector machines (SVM) were used to classify the coffees based on their origin. ORG and CONV cultivated coffees could not be differentiated according to C stable isotope ratio (δ13C; p = 0.204), but ORG coffees presented higher values of the N stable isotope ratio (δ15N; p = 0.0006). k-NN presented the best classification results for both ORG and CONV coffees (87% and 67%, respectively). SVM correctly classified coffees produced in São Paulo (75% accuracy), while LDA correctly classified 71% of coffees produced in Minas Gerais.
•Developed a new colorimetric method for ascorbic acid detection.•The colorimetric detection of ascorbic acid is rapid, sensitive and selective.•Photo-synthesized silver NCs are powerful for growth ...of silver nanoparticles.
In this work, we report a colorimetric method for detection of ascorbic acid based on growth of silver nanoparticles by a simple and green photo-catalytic route. This route contains two steps, photo-synthesis of silver nanoclusters (NCs) with papain under UV irradiation, and catalytic growth of silver nanoparticles (NPs) in the presence of ascorbic acid. The produced silver NCs at the first step is excellent catalyzer that could quickly catalyze the growth of silver NPs by Ag+ and ascorbic acid in 1min at room temperature. And thus, in the second step, the color of the mixture changed from colorless to yellow and a strong absorption band near 420nm could be found in their absorption spectra owing to localized surface plasmon resonance (LSPR) of produced silver NPs. We found that the absorbance changes at 420nm have a good relationship with ascorbic acid concentration, and established a spectrophotometric method for the sensing of ascorbic acid in the range from 0.25 to 50.0μM, with a limit of detection (LOD) as low as 79.2nM. We also established a colorimetric assay of ascorbic acid by analyzing the yellow value (Y%) of the silver NPs photographs using cyan, magenta and yellow (CMY) color mode. The lowest detection concentration of ascorbic acid for colorimetric assay by the photographs could be estimated to ∼1μM. Moreover, the method for ascorbic acid detection also has high selectivity. Potential interferes, such as glucose, dopamine, uric acid and cysteine will not affect the detection of ascorbic acid.
Objective The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic ...lymphohistiocytosis (HLH) in febrile children. Study design In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. Results Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. Conclusions The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.
In this study, an integrated collaborative learning and knowledge map approach was developed for online teacher professional development. An online teacher education environment based on that ...approach was constructed. To investigate the interaction between the knowledge map and collaborative learning strategies on teachers' learning performance and self-efficacy of group learning, a 2 × 2 experiment was acted out. The study subjects were 179 in-service teachers from primary schools in China. The participants were divided into four groups to learn theories and cases of educational research methods using different online learning strategies (individual learning or collaborative learning) and knowledge map strategies (using a knowledge map or not). The results revealed two notable findings. First, both the knowledge map and collaborative learning strategies were significantly conducive to enhance the teachers' learning performance. Second, the interaction between the two kinds of strategies showed that the knowledge map strategy was potential to promote the self-efficacy of group learning among teachers who used the collaborative learning strategy. Thus, we conclude that the collaborative construction of group knowledge map could be an effective approach to promote teachers' knowledge construction and provide visual interaction support for teachers' online professional development.
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with ...schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
Glial glutamate transporter 1 (GLT‐1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further ...explained. The aim of this study was to investigate whether peroxisome proliferator‐activated receptor gamma (PPARγ) participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT‐1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up‐regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT‐1 was studied in rat cortical astrocyte‐neuron cocultures. We found that IPC 45 min of oxygen glucose deprivation (OGD) protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up‐regulation of GLT‐1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT‐1 up‐regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT‐1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose‐dependently attenuated the up‐regulation of GLT‐1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT‐1 during the acquisition of BIT induced by IPC.
Cover Image for this issue: doi: 10.1111/jnc.14532.
Open Science: This manuscript was awarded with the Open Materials Badge
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Ischemic preconditioning (IPC) could induce neuron ischemic tolerance. During this process, IPC activated PPARγ in astrocytes, then the activation of PPARγ triggered the up‐regulation of GLT‐1 and contributed to the induction of neuroprotection by IPC in vivo and in vitro. It could be concluded that astrocytic PPARγ participates in the induction of neuron ischemic tolerance by IPC via regulating GLT‐1.
Cover Image for this issue: doi: 10.1111/jnc.14532.
Selective histone deacetylase (HDAC) inhibitors have emerged as a potential anti-latency therapy for persistent human immunodeficiency virus type 1 (HIV-1) infection. We utilized a combination of ...small molecule inhibitors and short hairpin (sh)RNA-mediated gene knockdown strategies to delineate the key HDAC(s) to be targeted for selective induction of latent HIV-1 expression. Individual depletion of HDAC3 significantly induced expression from the HIV-1 promoter in the 2D10 latency cell line model. However, depletion of HDAC1 or -2 alone or in combination did not significantly induce HIV-1 expression. Co-depletion of HDAC2 and -3 resulted in a significant increase in expression from the HIV-1 promoter. Furthermore, concurrent knockdown of HDAC1, -2, and -3 resulted in a significant increase in expression from the HIV-1 promoter. Using small molecule HDAC inhibitors of differing selectivity to ablate the residual HDAC activity that remained after (sh)RNA depletion, the effect of depletion of HDAC3 was further enhanced. Enzymatic inhibition of HDAC3 with the selective small-molecule inhibitor BRD3308 activated HIV-1 transcription in the 2D10 cell line. Furthermore, ex vivo exposure to BRD3308 induced outgrowth of HIV-1 from resting CD4+ T cells isolated from antiretroviral-treated, aviremic HIV+ patients. Taken together these findings suggest that HDAC3 is an essential target to disrupt HIV-1 latency, and inhibition of HDAC2 may also contribute to the effort to purge and eradicate latent HIV-1 infection.
Background
A recent consensus statement in Europe has suggested that the fasting time for clear liquid in children can be shortened to 1 hour before a surgery. However, the study to show that 1‐hour ...fasting time for clear fluids is safe in young children is still lacking. This study aimed to investigate the gastric emptying time for carbohydrate‐rich drink and regular 5% glucose solution in children aged 3‐7 years.
Methods
After overnight fasting, individuals were randomly assigned to ingest 5 mL kg−1 of either carbohydrate‐rich drink or 5% glucose solution. One week later, the same subjects were asked to ingest the other one. Ultrasonography was performed to examine the gastric contents. Gastric antral cross‐sectional area was measured, and the gastric fluid volume was calculated before and after fluid ingestion within 120 minutes. The primary outcome was the gastric emptying time for both the clear fluids calculated using the antral cross‐sectional area and logarithms of gastric fluid volume. The degrees of thirst and hunger of two drinks were evaluated using a visual analogue scale as the secondary outcomes.
Results
Data from 16 individuals were analyzed. In the glucose solution group, the antral cross‐sectional area and logarithms of gastric fluid volume returned to baseline at 30 minutes after ingestion. However, in the carbohydrate‐rich drink group, the median interquartile range; range antral cross‐sectional area (3.69 2.64‐5.15; 1.83‐8.93 cm2 vs 2.41 2.10‐2.96; 1.81‐4.37 cm2, P < .001) and mean (95% confidence interval) logarithms of gastric fluid volume (2.54 2.30‐2.79 mL vs 2.12 1.94‐2.30 mL, P = .048) were still higher than at 60 minutes and returned to the baseline values at 90 minutes after ingestion, respectively. The degree of thirst was lower in the glucose solution group than that in the carbohydrate‐rich drink group.
Conclusions
Gastric emptying of carbohydrate‐rich drink is slower than that of 5% glucose solution but the residual gastric fluid volume is low one hour after ingestion of 5 mL kg−1 of either fluid.
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