9-n-Butyl-9,9′-bi[9H-fluorene]

In the title compound, C30H26, the dihedral angle between the two fluorene ring systems is 61.75 (4)°

9-Chloro­methyl-9-[(9H-fluoren-9-yl)meth­yl]-9H-fluorene

In the title compound, C28H21Cl, the dihedral angle between the two fluorene ring systems is 71.97 (4)°. There is an intra­molecular C—H⋯Cl hydrogen bond. In the crystal structure, the centroid-to-centroid distance between stacked fluorene ring systems is ca 4.22 Å, which indicates that there are no π–π stacking inter­actions between them

Deep Reinforcement Learning for Image-to-Image Translation

Most existing Image-to-Image Translation (I2IT) methods generate images in a single run of a deep learning (DL) model. However, designing such a single-step model is always challenging, requiring a huge number of parameters and easily falling into bad global minimums and overfitting. In this work, we reformulate I2IT as a step-wise decision-making problem via deep reinforcement learning (DRL) and propose a novel framework that performs RL-based I2IT (RL-I2IT). The key feature in the RL-I2IT framework is to decompose a monolithic learning process into small steps with a lightweight model to progressively transform a source image successively to a target image. Considering that it is challenging to handle high dimensional continuous state and action spaces in the conventional RL framework, we introduce meta policy with a new concept Plan to the standard Actor-Critic model, which is of a lower dimension than the original image and can facilitate the actor to generate a tractable high dimensional action. In the RL-I2IT framework, we also employ a task-specific auxiliary learning strategy to stabilize the training process and improve the performance of the corresponding task. Experiments on several I2IT tasks demonstrate the effectiveness and robustness of the proposed method when facing high-dimensional continuous action space problems

Inhibition of cyclin-dependent kinase 7 down-regulates yes-associated protein expression in mesothelioma cells.

Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM

MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans

Background: MicroRNAs (miRNAs) are recognized as one of the most important families of noncoding RNAs that serve as important sequence-specific post-transcriptional regulators of gene expression. Identification of miRNAs is an important requirement for understanding the mechanisms of post-transcriptional regulation. Hundreds of miRNAs have been identified by direct cloning and computational approaches in several species. However, there are still many miRNAs that remain to be identified due to lack of either sequence features or robust algorithms to efficiently identify them. Results: We have evaluated features valuable for pre-miRNA prediction, such as the local secondary structure differences of the stem region of miRNA and non-miRNA hairpins. We have also established correlations between different types of mutations and the secondary structures of pre-miRNAs. Utilizing these features and combining some improvements of the current premiRNA prediction methods, we implemented a computational learning method SVM (support vector machine) to build a high throughput and good performance computational pre-miRNA prediction tool called MiRFinder. The tool was designed for genome-wise, pair-wise sequences from two related species. The method built into the tool consisted of two major steps: 1) genome wide search for hairpin candidates and 2) exclusion of the non-robust structures based on analysis of 18 parameters by the SVM method. Results from applying the tool for chicken/human and D. melanogaster/D. pseudoobscura pair-wise genome alignments showed that the tool can be used for genome wide pre-miRNA predictions. Conclusion: The MiRFinder can be a good alternative to current miRNA discovery software. This tool is available at http://www.bioinformatics.org/mirfinder/

Dihydromyricetin attenuates depressive-like behaviors in mice by inhibiting the AGE-RAGE signaling pathway

Depression is a complex mental disorder, affecting approximately 280 million individuals globally. The pathobiology of depression is not fully understood, and the development of new treatments is urgently needed. Dihydromyricetin (DHM) is a natural flavanone, mainly distributed in Ampelopsis grossedentata. DHM has demonstrated a protective role against cardiovascular disease, diabetes, liver disease, cancer, kidney injury and neurodegenerative disorders. In the present study, we examined the protective effect of DHM against depression in a chronic depression mouse model induced by corticosterone (CORT). Animals exposed to CORT displayed depressive-like behaviors; DHM treatment reversed these behaviors. Network pharmacology analyses showed that DHM’s function against depression involved a wide range of targets and signaling pathways, among which the inflammation-linked targets and signaling pathways were critical. Western blotting showed that CORT-treated animals had significantly increased levels of the advanced glycation end product (AGE) and receptor of AGE (RAGE) in the hippocampus, implicating activation of the AGE-RAGE signaling pathway. Furthermore, enzyme-linked immunosorbent assay (ELISA) detected a marked increase in the production of proinflammatory cytokines, interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNFα) in the hippocampus of CORT-treated mice. DHM administration significantly counteracted these CORT-induced changes. These findings suggest that protection against depression by DHM is mediated by suppression of neuroinflammation, predominantly via the AGE-RAGE signaling pathway

Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

Recent reports show that ER stress plays an important role in diabetic retinopathy (DR), but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ). The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP), and synoviolin(HRD1) were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month

Serum cytokine profiling analysis for zheng differentiation in chronic hepatitis B

Approval document of the research protocol by the Medical Ethics Committee of Shuguang Hospital

Survival after alcohol septal ablation versus conservative therapy in obstructive hypertrophic cardiomyopathy

Background: The impact of alcohol septal ablation (ASA) on the survival of patients with drug-refractory obstructive hypertrophic cardiomyopathy (HCM) remains unresolved. The aim of this study was to compare survival after ASA vs. conservative therapy. Methods: We studied a consecutive cohort of 274 patients with severe drug-refractory obstructive HCM, 229 in ASA group and 45 in conservative group. The primary endpoint was a composite of all-cause mortality and aborted cardiac arrest. Results: With a median follow-up of 4.3 years, primary endpoint occurred in 13 (5.7%) patients in the ASA group, and 8 (17.8%) patients in the conservative group. The 5- and 10-year survival free from primary endpoint of the ASA group (94.5% and 93.0%, respectively) was significantly better than that of the conservative group (78.3% and 72.2%, respectively, log-rank p = 0.009). Independent determinants of primary endpoint were ASA therapy (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.08–0.60; p = 0.003) and maximal septal thickness (HR 1.14; 95% CI 1.03–1.27; p = 0.011). Conclusions: In patients with severe drug-refractory obstructive HCM, survival after ASA is favorable and better than that of conservative therapy. ASA seems to improve survival