LncRNA018392 promotes the proliferation of Liaoning cashmere goat skin fibroblasts by upregulating CSF1R through binding to SPI1.

BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.

Effect of neurogenic bowel dysfunction symptoms on quality of life after a spinal cord injury.

BACKGROUND: Neurogenic bowel dysfunction (NBD) is a common problem among people with spinal injury; management of bowel dysfunction and related problems are considered significant factors in daily life after injury. But despite the critical relevance of bowel dysfunction in the daily life of SCI survivors, there have been few published studies on the management of NBD. So, this study aimed to describe the bowel programmers utilized by people with SCI in China and the impact of bowel dysfunction on the quality of life (QoL). DESIGN: A cross-sectional online survey. SETTING: Rehabilitation Medicine Department of Wuhan's Tongji Hospital. PARTICIPANTS: SCI patients who had been diagnosed with neurogenic bowel dysfunction and who were receiving regular medical monitoring at the rehabilitation medicine department were invited to participate in our study. OUTCOME MEASURES: A neurogenic bowel dysfunction (NBD) score is a questionnaire developed to evaluate the severity of neurogenic bowel dysfunction. A Short Form-12 (SF-12) was designed to measure the quality of life in people with SCI. Demographic and medical status information was extracted from their medical records. RESULTS: The two questionnaires were sent to 413 SCI patients. Two hundred ninety-four subjects (43.1 ± 14.5 years of age; men, 71.8%) responded. Most of the respondents performed their bowel movement daily 153 (52.0%), a defecation time was 31-60 min among 70 (23.8%) of them, 149 (50.7%) used medication (drops or liquid) to treat constipation, and 169 (57.5%) used digital stimulation more than once per week to boost the bowel evacuation. This study found a significant association between the QoL score and the time used for each defecation, autonomic dysreflexia (AD) symptoms, taking medication to treat fecal incontinence, using digital stimulation, having uncontrollable flatus and perianal skin problems. CONCLUSION: Management of bowel dysfunction is complex and associated with QoL in people with SCI. Items of the NBD questionnaire that greatly deteriorated the QoL were time in one defecation > 60 min, symptoms of AD during or before defecation, taking medication (drops or liquid), and using digital stimulation. Dealing with those problems can improve the life quality of spinal cord injury survivors.

Jiedu Quyu Decoction mitigates monocrotaline-induced right-sided heart failure associated with pulmonary artery hypertension by inhibiting NLRP3 inflammasome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Right-side heart failure could accelerate mortality in patients of pulmonary hypertension, Jiedu Quyu Decoction (JDQYF) was used to manage pulmonary hypertension, but its right-sided heart protective effect associated with pulmonary artery hypertension is still unclear. AIM OF THE STUDY: Here, we evaluated the therapeutic effect of JDQYF on monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension in Sprague-Dawley (SD) rats and investigated the potential mechanism of action. MATERIALS AND METHODS: The main chemical components of JDQYF were detected and analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. The effects of JDQYF were investigated using a rat model of monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension. We assessed the morphology of cardiac tissue using histopathology and the structure and function of the right heart using echocardiography. The biomarkers of heart failure, atrial natriuretic peptide and B-type natriuretic peptide, as well as serum pro-inflammatory markers, interleukin (IL)-1ß, and IL-18, were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the mRNA and protein expression levels of NLRP3 (NOD-, LRR-, and pyrin domain-containing 3), capase-1, IL-1ß, and IL-18 in the right heart tissue were examined by real-time quantitative reverse transcription PCR and western blotting. RESULTS: JDQYF improved ventricular function, alleviated pathological lesions in the right cardiac tissue, reduced the expression levels of biomarkers of heart failure and serum pro-inflammatory factors (IL-1ß and IL-18), and downregulated the mRNA and protein expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 in the right cardiac tissue. CONCLUSIONS: JDQYF possesses cardioprotective effect against right heart failure induced by pulmonary arterial hypertension, possibly owing to reduction of cardiac inflammation through the inhibition of NLRP3 inflammasome activation.

NHC-Activations on α-, ß-, γ-, and Beyond.

Over the recent decades, due to the special electronic characteristics and diverse reactivities, N-heterocyclic carbene (NHC) has received significant interest in organocatalyzed reactions. The formation of Breslow intermediates by NHC can convert into acyl anion equivalent, enolates, homoenolate, acyl azolium, and vinyl enolate etc., and the cycloaddition reactions of these species has attracted lots of attention. In this review, we focus on the summry of the development of NHC-activation of carbonyl carbon (or imine carbon) in situ, α-, ß-, γ-, and beyond, and the cycloaddition reaction of these species.

Entropic Dynamic Time Warping Kernels for Co-Evolving Financial Time Series Analysis.

Network representations are powerful tools to modeling the dynamic time-varying financial complex systems consisting of multiple co-evolving financial time series, e.g., stock prices. In this work, we develop a novel framework to compute the kernel-based similarity measure between dynamic time-varying financial networks. Specifically, we explore whether the proposed kernel can be employed to understand the structural evolution of the financial networks with time associated with standard kernel machines. For a set of time-varying financial networks with each vertex representing the individual time series of a different stock and each edge between a pair of time series representing the absolute value of their Pearson correlation, our start point is to compute the commute time (CT) matrix associated with the weighted adjacency matrix of the network structures, where each element of the matrix can be seen as the enhanced correlation value between pairwise stocks. For each network, we show how the CT matrix allows us to identify a reliable set of dominant correlated time series as well as an associated dominant probability distribution of the stock belonging to this set. Furthermore, we represent each original network as a discrete dominant Shannon entropy time series computed from the dominant probability distribution. With the dominant entropy time series for each pair of financial networks to hand, we develop an entropic dynamic time warping kernels through the classical dynamic time warping framework, for analyzing the financial time-varying networks. We show that the proposed kernel bridges the gap between graph kernels and the classical dynamic time warping framework for multiple financial time series analysis. Experiments on time-varying networks extracted through New York Stock Exchange (NYSE) database demonstrate that the effectiveness of the proposed method.

Learning Backtrackless Aligned-Spatial Graph Convolutional Networks for Graph Classification.

In this paper, we develop a novel backtrackless aligned-spatial graph convolutional network (BASGCN) model to learn effective features for graph classification. Our idea is to transform arbitrary-sized graphs into fixed-sized backtrackless aligned grid structures and define a new spatial graph convolution operation associated with the grid structures. We show that the proposed BASGCN model not only reduces the problems of information loss and imprecise information representation arising in existing spatially-based graph convolutional network (GCN) models, but also bridges the theoretical gap between traditional convolutional neural network (CNN) models and spatially-based GCN models. Furthermore, the proposed BASGCN model can both adaptively discriminate the importance between specified vertices during the convolution process and reduce the notorious tottering problem of existing spatially-based GCNs related to the Weisfeiler-Lehman algorithm, explaining the effectiveness of the proposed model. Experiments on standard graph datasets demonstrate the effectiveness of the proposed model.

Learning Aligned Vertex Convolutional Networks for Graph Classification.

Graph convolutional networks (GCNs) are powerful tools for graph structure data analysis. One main drawback arising in most existing GCN models is that of the oversmoothing problem, i.e., the vertex features abstracted from the existing graph convolution operation have previously tended to be indistinguishable if the GCN model has many convolutional layers (e.g., more than two layers). To address this problem, in this article, we propose a family of aligned vertex convolutional network (AVCN) models that focus on learning multiscale features from local-level vertices for graph classification. This is done by adopting a transitive vertex alignment algorithm to transform arbitrary-sized graphs into fixed-size grid structures. Furthermore, we define a new aligned vertex convolution operation that can effectively learn multiscale vertex characteristics by gradually aggregating local-level neighboring aligned vertices residing on the original grid structures into a new packed aligned vertex. With the new vertex convolution operation to hand, we propose two architectures for the AVCN models to extract different hierarchical multiscale vertex feature representations for graph classification. We show that the proposed models can avoid iteratively propagating redundant information between specific neighboring vertices, restricting the notorious oversmoothing problem arising in most spatial-based GCN models. Experimental evaluations on benchmark datasets demonstrate the effectiveness.

Knockdown of ASH1L methyltransferase induced apoptosis inhibiting proliferation and H3K36 methylation in bovine cumulus cells.

This study aims to investigate the expression and function of absent, small, or homeotic 1-like (ASH1L) methyltransferase in bovine cumulus cells in order to reveal by which mechanisms ASH1L regulates epigenetic modification and apoptosis in cumulus cells. The location of ASH1L and the methylation pattern of H3K36 were detected using immunofluorescence staining in cumulus cells. Quantitative PCR (qPCR) and western blotting were used to screen for effective siRNA targeting the ASH1L gene. Also, the mRNA expression levels of apoptosis-related genes and polycomb inhibitory complex genes were estimated by qPCR after knocking down the ASH1L gene in bovine cumulus cells. Cell proliferation and apoptosis were measured with the CCK-8 method and Annexin V-FITC by flow cytometry, respectively. The results of immunofluorescence analysis showed that ASH1L is located in the nucleus of bovine cumulus cells and is distributed in a dotted pattern. ASH1L knockdown in cumulus cells induced a decrease in the levels of H3K36me1/2/3 methylation (P < 0.05). Additionally, ASH1L knockdown inhibited cell proliferation, increased the apoptosis rate, and upregulated the expression of apoptosis genes CASPASE-3, BAX and BAX/BCL-2 ratio (P < 0.05). Meanwhile, the mRNA expression levels of EZH2 and SUZ12, two subunits of PRC2 protein, were increased in cells with ASH1L knockdown (P < 0.05). Therefore, the expression of ASH1L methyltransferase and its function in on the apoptosis of bovine cumulus cells were first studied. The mechanism by which ASH1L regulates the histone methylation and apoptosis in cumulus cells was also revealed.

Technical Efficiency of Regional Public Hospitals in China Based on the Three-Stage DEA.

Many countries are facing the increasing cost of healthcare services and the low efficiency of public hospitals. These issues are also evident in China. This paper offers a comprehensive assessment of the efficiency of public hospitals operating in China's 31 regions. The impact of the third round of reform of the health system in 2009 is assessed based on the three-stage data envelopment analysis procedure. The time period from 2011 to 2018 is covered in this study. Due to different functions performed by the public hospitals and other ones, the number of patients with infectious diseases is incorporated as an output variable reflecting the social function. The outpatient visits and inpatient visits are considered to reflect the outputs related to the private functions. The results imply an increase in the mean efficiency of public hospitals from 0.927 to 0.981 after taking the impact of environmental variables and statistic noise into account. These results indicate that the efficiency of public hospitals is dependent in the operational environment. There are 11 regions whose hospitals operate on the efficiency frontier during the whole period covered. Therefore, the Chinese government should reasonably design and apply the regulatory tools to improve the efficiency of public hospitals.

Long Non-Coding RNA and mRNA Profiling in Early-Stage Bovine Embryos Treated with Glutathione.

We measured differential expression profiles of genes and long non-coding RNA (lncRNA) using RNA sequencing in bovine embryos with or without glutathione (GSH) treatment. Bovine embryos fertilized in vitro were treated with GSH to blastocyst. Embryos at the 8-16-cell and morula stages were collected, with embryos without GSH treatment as the control. RNA was isolated, amplified, and sequenced. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) were identified and bioinformatic analyses carried out. Transcript levels were confirmed using quantitative RT-PCR. A total of 4100 DEGs were identified, of which 3952 were in GSH-treated morulae and 884 in untreated morulae. More gene ontology (GO) terms were associated with GSH treatment than with control conditions. KEGG analysis showed that glutathione metabolism, citrate cycle, and metabolic pathways involving glycine, serine, and threonine were observed only in GSH-treated embryos. Among 4273 DElncRNAs identified, 59 were potentially important in GSH-treated embryo development, including 14 involved in glutathione metabolism. The 59 DElncRNAs co-expressed with protein-coding mRNAs involved similar GO terms and pathways as the DEGs. This appears to be the first comprehensive profiling of DEGs and DElncRNAs in bovine embryos fertilized in vitro with or without GSH, and the first systematic screen of potential lncRNAs in bovine embryos.

A Quantum-Inspired Similarity Measure for the Analysis of Complete Weighted Graphs.

We develop a novel method for measuring the similarity between complete weighted graphs, which are probed by means of the discrete-time quantum walks. Directly probing complete graphs using discrete-time quantum walks is intractable due to the cost of simulating the quantum walk. We overcome this problem by extracting a commute time minimum spanning tree from the complete weighted graph. The spanning tree is probed by a discrete-time quantum walk which is initialized using a weighted version of the Perron-Frobenius operator. This naturally encapsulates the edge weight information for the spanning tree extracted from the original graph. For each pair of complete weighted graphs to be compared, we simulate a discrete-time quantum walk on each of the corresponding commute time minimum spanning trees and, then, compute the associated density matrices for the quantum walks. The probability of the walk visiting each edge of the spanning tree is given by the diagonal elements of the density matrices. The similarity between each pair of graphs is then computed using either: 1) the inner product or 2) the negative exponential of the Jensen-Shannon divergence between the probability distributions. We show that in both cases the resulting similarity measure is positive definite and, therefore, corresponds to a kernel on the graphs. We perform a series of experiments on publicly available graph datasets from a variety of different domains, together with time-varying financial networks extracted from data for the New York Stock Exchange. Our experiments demonstrate the effectiveness of the proposed similarity measures.

Exogenous glutathione improves intracellular glutathione synthesis via the γ-glutamyl cycle in bovine zygotes and cleavage embryos.

Excess reactive oxygen species (ROS) generated in embryos during in vitro culture damage cellular macromolecules and embryo development. Glutathione (GSH) scavenges ROS and optimizes the culture system. However, how exogenous GSH influences intracellular GSH and improves the embryo developmental rate is poorly understood. In this study, GSH or GSX (a stable GSH isotope) was added to the culture media of bovine in vitro fertilization embryos for 7 days. The cleavage rate, blastocyst rate, and total cell number of blastocysts were calculated. Similarly to GSH, GSX increased the in vitro development rate and embryo quality. We measured intracellular ROS, GSX, and GSH for 0-32-hr postinsemination (hpi) in embryos (including zygotes at G1, S, and G2 phases and cleaved embryos) cultured in medium containing GSX. Intracellular ROS significantly decreased with increasing intracellular GSH in S-stage zygotes (18 hpi) and cleaved embryos (32 hpi). γ-Glutamyltranspeptidase ( GGT) and glutathione synthetase ( GSS) messenger RNA expression increased in zygotes (18 hpi) and cleaved embryos treated with GSH, consistent with the tendency of overall GSH content. GGT activity increased significantly in 18 hpi zygotes. GGT and GCL enzyme inhibition with acivicin and buthionine sulfoximine, respectively, decreased cleavage rate, blastocyst rate, total cell number, and GSH and GSX content. All results indicated that exogenous GSH affects intracellular GSH levels through the γ-glutamyl cycle and improves early embryo development, enhancing our understanding of the redox regulation effects and transport of GSH during embryo culture in vitro.

Phytochrome B Negatively Affects Cold Tolerance by Regulating OsDREB1 Gene Expression through Phytochrome Interacting Factor-Like Protein OsPIL16 in Rice.

Cross talk between light signaling and cold signaling has been elucidated in the model plant Arabidopsis and tomato, but little is known about their relationship in rice. Here, we report that phytochrome B (phyB) mutants exhibit improved cold tolerance compared with wild type (WT) rice (Oryza sativa L. cv. Nipponbare). The phyB mutants had a lower electrolyte leakage index and malondialdehyde concentration than the WT, suggesting that they had greater cell membrane integrity and less lipid peroxidation. Real-time PCR analysis revealed that the expression levels of dehydration-responsive element binding protein 1 (OsDREB1) family genes, which functions in the cold stress response in rice, were increased in the phyB mutant under normal and cold stress conditions. PIFs are central players in phytochrome-mediated light signaling networks. To explore the relationship between rice PIFs and OsDREB1 gene expression, we produced overexpression lines of rice PIF genes. OsDREB1 family genes were up-regulated in OsPIL16-overexpression lines, which had improved cold tolerance relative to the WT. Chromatin immunoprecipitation (ChIP)-qPCR assay revealed that OsPIL16 can bind to the N-box region of OsDREB1B promoter. Expression pattern analyses revealed that OsPIL16 transcripts were induced by cold stress and was significantly higher in the phyB mutant than in the WT. Moreover, yeast two-hybrid assay showed that OsPIL16 can bind to rice PHYB. Based on these results, we propose that phyB deficiency positively regulates OsDREB1 expression through OsPIL16 to enhance cell membrane integrity and to reduce the malondialdehyde concentration, resulting in the improved cold tolerance of the phyB mutants.

Rediocide A, an Insecticide, induces G-protein-coupled receptor desensitization via activation of conventional protein kinase C.

In order to identify small-molecule antagonists of Methuselah (Mth), a Drosophila G-protein-coupled receptor (GPCR) involved in life-span control, a library of natural compounds was screened, and it was found that rediocide A (1), a daphnane ester from the roots of Trigonostemon reidioides and used currently for flea control, potently inhibited calcium mobilization mediated by this receptor. Compound 1 inhibited calcium mobilization in GPCRs other than Mth, indicating that the inhibitory effect was not due to receptor antagonism but rather to a more general mechanism. It was found that 1 can induce GPCR desensitization and internalization, and such effects were mediated by the activation of conventional protein kinase C.

[Expression and function analysis of chemokine receptor CCR6 in HEK293 cells].

AIM: To construct a cell line which stably expresses human chemokine receptor 6 (CCR6). METHODS: The human CCR6 cDNA and plasmid G were co-transfected into HEK 293 cells and the clones stably expressing CCR6 were picked out. The expression of CCR6 in HEK293 cells was detected by RT-PCR, Western blotting, immunofluorescence test, calcium mobilization and in vitro chemotaxis assay. RESULTS: The transfected HEK293 cells could stably express functional human CCR6. CONCLUSION: Successfully establish a cell line which stably express human CCR6 and lays the foundation for its biological function's study and specific antagonist screening.