Education in inpatient children and young people’s mental health services

<p>As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA.</p

Nanochannel-Based Heterometallic {Co^IITb^III}‑Organic Framework for Fluorescence Recognition of Tryptophan and Catalytic Cycloaddition of Epoxides with CO₂

To pave the way for the salient application of metal–organic frameworks (MOFs) as realistic sensors, it is critical to screen or design the customized functional structure with specified prominent synergistic effects provided by its constituents, voids, specific surfaces, functional sites, etc. This prompts us to study the sensing performance of a honeycomb nanochannel of heterometallic MOFs previously invented. This structure has excellent physical and chemical properties of high specific surface area, good chemical stability, and highly open coexistence of Lewis acid–base sites. In this work, the highly robust sky-blue [CoTb(CO2)6(OH2)]-based heterometallic framework of {[(CH3)2NH2][CoTb(TDP)(H2O)]·3H2O·4DMF}n (NUC-31; H6TDP = 2,4,6-tri(2′,4′-dicarboxyphenyl)pyridine) was synthesized. The results of the fluorescence recognition experiment show that, compared with other amino acids, NUC-31 has an ultrastrong fluorescence quenching for tryptophan with a detection limit as low as 0.11 mM, which means that NUC-31 can be used as a potential fluorescence probe for the targeted detection of tryptophan of ecosystems. In addition, the catalytic experiment results indicated that NUC-31 has high activity for catalyzing the cycloaddition reaction of epoxides with CO2 under 75 °C and 1 atm. It is precisely due to NUC-31 having extremely unsaturated tetracoordinated Co(II) and hepta-coordinated Tb(III) metal ions as well as a high pore volume (65.1%), which makes the catalytic reaction conditions relatively mild. Therefore, this work certificated that nanoporous MOFs assembled from a multifunctional ligand with the highly open coexistent Lewis acid–base sites had a potential application not only in monitoring tryptophan in clinical scenarios but also as an effective heterogeneous catalyst

Nanochannel-Based Heterometallic {Co^IITb^III}‑Organic Framework for Fluorescence Recognition of Tryptophan and Catalytic Cycloaddition of Epoxides with CO₂

To pave the way for the salient application of metal–organic frameworks (MOFs) as realistic sensors, it is critical to screen or design the customized functional structure with specified prominent synergistic effects provided by its constituents, voids, specific surfaces, functional sites, etc. This prompts us to study the sensing performance of a honeycomb nanochannel of heterometallic MOFs previously invented. This structure has excellent physical and chemical properties of high specific surface area, good chemical stability, and highly open coexistence of Lewis acid–base sites. In this work, the highly robust sky-blue [CoTb(CO2)6(OH2)]-based heterometallic framework of {[(CH3)2NH2][CoTb(TDP)(H2O)]·3H2O·4DMF}n (NUC-31; H6TDP = 2,4,6-tri(2′,4′-dicarboxyphenyl)pyridine) was synthesized. The results of the fluorescence recognition experiment show that, compared with other amino acids, NUC-31 has an ultrastrong fluorescence quenching for tryptophan with a detection limit as low as 0.11 mM, which means that NUC-31 can be used as a potential fluorescence probe for the targeted detection of tryptophan of ecosystems. In addition, the catalytic experiment results indicated that NUC-31 has high activity for catalyzing the cycloaddition reaction of epoxides with CO2 under 75 °C and 1 atm. It is precisely due to NUC-31 having extremely unsaturated tetracoordinated Co(II) and hepta-coordinated Tb(III) metal ions as well as a high pore volume (65.1%), which makes the catalytic reaction conditions relatively mild. Therefore, this work certificated that nanoporous MOFs assembled from a multifunctional ligand with the highly open coexistent Lewis acid–base sites had a potential application not only in monitoring tryptophan in clinical scenarios but also as an effective heterogeneous catalyst

Top Ranked ExpMods and JAK2 ExpMod.

<p>Derivation of the JAK2 hotspot associated with aortic dissection: (A) The spin-glass module detection algorithm is applied to an integrated mRNA expression interactome to identify differential expression hotspots. The edges in the network are weighted according to the average of the absolute regularized t-statistics of the genes making up the edge (Methods). The edge weights are colour coded as indicated. (B) Detection of 8 non-redundant highly exclusive differential expression hotspots/modules (ExpMods) associated with aortic dissection, ranked according to their modularity values and all passing an adjusted <i>P</i>-value threshold of 0.05. The gene symbols of the seeds are shown. (C) Zoomed-in version of the JAK2 ExpMod. Both edge color and width encode the edge weights, as indicated. The Limma t-statistics of each gene (node) are shown as indicated. Observe how JAK2 defines the hub of this module, and forms dense subnetworks with other genes that are strongly differentially expressed e.g. IL-6/IL-6R, CCL2, KITLG and EPOR.</p

The top 25 most significant genes from Limma analysis.

a<p>AvExp: average expression.</p>b<p>logFC: log2-fold-change (i.e a logFC>1 means fold-change larger than 2).</p>c<p>t: regularized Limma t-statistic.</p

Table1_Up-Regulation of p53/miR-628-3p Pathway, a Novel Mechanism of Shikonin on Inhibiting Proliferation and Inducing Apoptosis of A549 and PC-9 Non–Small Cell Lung Cancer Cell Lines.DOCX

Shikonin (SHK) is a pleiotropic agent with remarkable cell growth inhibition activity against various cancer types, especially non–small cell lung cancer (NSCLC), but its molecular mechanism is still unclear. Our previous study found that miR-628-3p could inhibit the growth of A549 cells and induce its apoptosis. Bioinformatics analysis predicted that miR-628-3p promoter sequence contained p53 binding sites. Considering the regulatory effect of SHK on p53, we speculate that SHK may inhibit the growth and induce apoptosis of NSCLC cells by up-regulating miR-628-3p. CCK-8 and EdU assay confirmed the inhibitory effect of SHK on A549 and PC-9 cells. Meanwhile, quantitative reverse transcription–polymerase chain reaction and Western blot showed that SHK could promote the expression of p53 and miR-628-3p in a dose-dependent manner. Overexpression of p53 or miR-628-3p can inhibit the growth and promote apoptosis of A549 and PC-9 cells, while silencing p53 or miR-628-3p has the opposite effect. Dual luciferase reporting assay and ChIP (chromatin immunoprecipitation) assay further verified the direct interaction between p53 and the promoter of miR-628-3p. Gene knockdown for p53 or miR-628-3p confirmed that SHK inhibits the growth and induces apoptosis of A549 and PC-9 cells at least partly by up-regulating p53/miR-628-3p signaling pathway. Therefore, these novel findings provide an alternative approach to target p53/miR-628-3p axis and could be used for the development of new treatment strategies for NSCLC.</p

JAK2 protein-protein interaction network by STRING analysis.

<p>The network nodes are proteins. Seven differently colored lines represent 7 types of evidence used in predicting the associations. A red line indicates the presence of fusion evidence; a green line - neighborhood evidence; a blue line - coocurrence evidence; a purple line - experimental evidence; a yellow line - textmining evidence; a light blue line - database evidence; a black line - coexpression evidence.</p

Experimental design.

<p>The flowchart schematizes the experimental steps of the statistical analysis of microarray data.</p

table3~5.csv

Supplementary materials for the Table 3-5 of Improving Generalization of Glaucoma Detection on Fundus Images via Feature Alignment between Augmented View

Validation of gene expression by real-time PCR.

<p>The expression of JAK2, IL-6, KITLG and CCL2 in the dissected aorta was validated by real-time PCR analyses. Expression levels in control aortas were set to 1. Data represent the mean ± SEM.</p