On the dynamics of a class of nonclassical parabolic equations

AbstractWe consider the first initial and boundary value problem of nonclassical parabolic equations ut−μΔut−Δu+g(u)=f(x) on a bounded domain Ω, where μ∈[0,1]. First, we establish some uniform decay estimates for the solutions of the problem which are independent of the parameter μ. Then we prove the continuity of solutions as μ→0. Finally we show that the problem has a unique global attractor Aμ in V2=H2(Ω)∩H01(Ω) in the topology of H2(Ω); moreover, Aμ→A0 in the sense of Hausdorff semidistance in H01(Ω) as μ goes to 0

Copy number variants in locally raised Chinese chicken genomes determined using array comparative genomic hybridization

BACKGROUND: Copy number variants contribute to genetic variation in birds. Analyses of copy number variants in chicken breeds had focused primarily on those from commercial varieties with nothing known about the occurrence and diversity of copy number variants in locally raised Chinese chicken breeds. To address this deficiency, we characterized copy number variants in 11 chicken breeds and compared the variation among these breeds. RESULTS: We presented a detailed analysis of the copy number variants in locally raised Chinese chicken breeds identified using a customized comparative genomic hybridization array. We identified 833 copy number variants contained within 308 copy number variant regions. The median and mean sizes of the copy number variant regions were 14.6 kb and 35.1 kb, respectively. Of the copy number variant regions, 138 (45%) involved gain of DNA, 159 (52%) involved loss of DNA, and 11 (3%) involved both gain and loss of DNA. Principal component analysis and agglomerative hierarchical clustering revealed the close relatedness of the four locally raised chicken breeds, Shek-Ki, Langshan, Qingyuan partridge, and Wenchang. Biological process enrichment analysis of the copy number variant regions confirmed the greater variation among the four aforementioned varieties than among the seven other breeds studied. CONCLUSION: Our description of the distribution of the copy number variants and comparison of the differences among the copy number variant regions of the 11 chicken breeds supplemented the information available concerning the copy number variants of other Chinese chicken breeds. In addition to its relevance for functional analysis, our results provided the first insight into how chicken breeds can be clustered on the basis of their genomic copy number variation

Effect of sequential treatment with syndrome differentiation on acute exacerbation of chronic obstructive pulmonary disease and "AECOPD Risk-Window": study protocol for a randomized placebo-controlled trial

BACKGROUND: Frequent chronic obstructive pulmonary disease (COPD) exacerbation is a major cause of hospital admission and mortality. It has been reported that Traditional Chinese Medicine (TCM) may relieve COPD symptoms and reduce the incidence of COPD exacerbations, thus improving life quality of COPD patients. The acute exacerbation of COPD risk-window (AECOPD-RW) is the period after an exacerbation and before the patient returns to baseline. In the AECOPD-RW, patients are usually at increased risk of a second exacerbation, which may lead to hospital admission and high mortality. It may be beneficial for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients to receive interventions during AECOPD-RW. During exacerbations the treatment principle is to eliminate exogenous pathogens, whereas the AECOPD-RW treatment principle focuses on enhancing body resistance. METHODS/DESIGN: A prospective, multi-center, single-blinded, double-dummy and randomized controlled clinical trial is being conducted to test the therapeutic effects of a sequential two stage treatment, which includes eliminating pathogen and strengthening vital qi with syndrome differentiation. A total of 364 patients will be enrolled in this study with 182 in each treatment group (TCM and control). Patients received medication (or control) according to their assigned group. TCM for AECOPD were administered twice daily to patients with AECOPD over 7 to 21 days, followed by TCM for AECOPD-RW over 28 days. All patients were followed for six months. The clinical symptoms, the modified medical research council dyspnea (MMRC) scale and exacerbations were used as the primary outcome measures. Pulmonary function, quality of life and mortality rate were used as secondary outcome measures. DISCUSSION: It is hypothesized that sequentially eliminating pathogens and strengthening vital qi treatments with syndrome differentiation will have beneficial effects on reducing the frequency and duration of acute exacerbation, relieving symptoms and improving quality of life for COPD patients. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, ChiCTR-TRC-11001460

Identification of Metabolites and Metabolic Pathways Related to Treatment with Bufei Yishen Formula in a Rat COPD Model Using HPLC Q-TOF/MS

As a traditional Chinese medicine, Bufei Yishen Formula (BYF) is widely used in China as an effective treatment for chronic obstructive pulmonary disease (COPD). Because of the component complexity and multiple activities of Chinese herbs, the mechanism whereby BYF affects COPD is not yet fully understood. Herein, pulmonary function experiments and histomorphological assessments were used to evaluate the curative effect of BYF, which showed that BYF had an effect on COPD. Additionally, a high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC QTOF/MS) metabonomics method was used to analyze the mechanism of the actions of BYF on rats with COPD induced by a combination of bacteria and smoking. Partial least squares discriminate analysis (PLS-DA) was used to screen biomarkers related to BYF treatment. Candidate biomarkers were selected and pathways analysis of these metabolites showed that three types of metabolic pathways (unsaturated fatty acid metabolism-related pathways, phenylalanine metabolism-related pathways, and phospholipid metabolism-related pathways) were associated with BYF treatment. Importantly, arachidonic acid and related metabolic pathways might be useful targets for novel COPD therapies

Waterways to Greenways: A Case Study in Shangjie, Zhengzhou, Henan, China

This case study introduces how we used a water sensitive approach to plan a storm water and sponge city project, which expanded into a holistic green infrastructure project. The project is in the Shangjie district in city of Zhengzhou, Henan China. The whole site is 61.16 km² including several waterways. The city is expanding into areas that were previously agricultural. Developers and city both desire to improve the ecological value of the city to boost the economic growth of the Shangjie district. The main goal for the client is to transform the existing industrial city into a more resilient and livable ecological region. Our approach is to holistically solve the region\u27s increasing demand for flood control and storm water management, and to improve ecological and recreational values along these riparian corridors. We propose additional waterways and water bodies to act as green infrastructure, then link the greenways to existing or proposed parks to form a comprehensive greenway network. Our multidisciplinary team conducted detailed investigations and collaborated extensively. The team consists of hydraulic engineers, civil engineers, environmental planners, landscape planners, urban planners, economic planners, and others. We used a variety of technologies, including GIS, Infoworks, remote sensing technology, MIKE model, and lab tests

FoxM1B regulates NEDD4-1 expression, leading to cellular transformation and full malignant phenotype in immortalized human astrocytes.

Our recent studies have shown that the FoxM1B transcription factor is overexpressed in human glioma tissues and that the level of its expression correlates directly with glioma grade. However, whether FoxM1B plays a role in the early development of glioma (i.e., in transformation) is unknown. In this study, we found that the FoxM1B molecule causes cellular transformation and tumor formation in normal human astrocytes (NHA) immortalized by p53 and pRB inhibition. Moreover, brain tumors that arose from intracranial injection of FoxM1B-expressing immortalized NHAs displayed glioblastoma multiforme (GBM) phenotypes, suggesting that FoxM1B overexpression in immortalized NHAs not only transforms the cells but also leads to GBM formation. Mechanistically, our results showed that overexpression of FoxM1B upregulated NEDD4-1, an E3 ligase that mediates the degradation and downregulation of phosphatase and tensin homologue (PTEN) in multiple cell lines. Decreased PTEN in turn resulted in the hyperactivation of Akt, which led to phosphorylation and cytoplasmic retention of FoxO3a. Blocking Akt activation with phosphoinositide 3-kinase/Akt inhibitors inhibited the FoxM1B-induced transformation of immortalized NHAs. Furthermore, overexpression of FoxM1B in immortalized NHAs increased the expression of survivin, cyclin D1, and cyclin E, which are important molecules for tumor growth. Collectively, these results indicate that overexpression of FoxM1B, in cooperation with p53 and pRB inhibition in NHA cells, promotes astrocyte transformation and GBM formation through multiple mechanisms

FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients

Bufei Yishen Granules Combined with Acupoint Sticking Therapy Suppress Inflammation in Chronic Obstructive Pulmonary Disease Rats: Via JNK/p38 Signaling Pathway

The present study was initiated to explore the mechanism of the effects of Bufei Yishen granules combined with acupoint sticking therapy (Shu-Fei Tie) on inflammation regulated by c-Jun N-terminal kinase (JNK) and p38 MAPK signaling in COPD rats. Seventy-two rats were divided into healthy control (Control), Model, Bufei Yishen (BY), acupoint sticking (AS), Bufei Yishen + acupoint sticking (BY + AS), and aminophylline (APL) groups (n=12 each). COPD rats were exposed to cigarette smoke and bacteria and were given the various treatments from weeks 9 through 20; all animals were sacrificed at the end of week 20. MCP-1, IL-2, IL-6, and IL-10 concentrations in BALF and lung tissue as well as JNK and p38 mRNA and protein levels in lung were measured. The results showed that all the four treatment protocols (BY, AS, BY + AS, and APL) markedly reduced the concentrations of IL-2, IL-6, and MCP-1 and levels of JNK and p38 MAPK mRNA, and the effects of Bufei Yishen granules combined with acupoint sticking therapy were better than acupoint sticking therapy only and aminophylline. In conclusion, the favorable effect of Bufei Yishen granules combined with Shu-Fei Tie may be due to decreased inflammation through regulation of the JNK/p38 signaling pathways

Compound Heterozygous CHAT Gene Mutations of a Large Deletion and a Missense Variant in a Chinese Patient With Severe Congenital Myasthenic Syndrome With Episodic Apnea

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders caused by genetic defects in neuromuscular junctions. Mutations in CHAT, encoding choline acetyltransferase, cause congenital myasthenic syndrome with episodic apnea (CMS-EA), a rare autosomal recessive disease characterized by respiratory insufficiency with cyanosis and apnea after infections, fever, vomiting, or excitement. To date, no studies have reported deletions comprised of multiple exons. Here, using next generation sequencing, we identified compound heterozygous mutations, namely a large maternally inherited deletion, including exons 4, 5, and 6, and a paternally inherited missense variant (c.914T>C [p.Ile305Thr]) in CHAT in a Chinese patient with a severe phenotype of CMS-EA. Furthermore, the large deletion was also validated by real-time fluorescence quantitative polymerase chain reaction. The patient was a 10-month-old boy, who presented with a weak cry and feeding difficulties soon after birth, ptosis at 4 months old, episodic apnea after fever at 9 months old, and respiratory insufficiency with cyanosis and apnea that required intubation after a respiratory tract infection at 10 months old. Unfortunately, he died in the Pediatric Intensive Care Unit soon after hospitalization. The patient’s elder sister had similar clinical manifestations, and she died prior to the age of 2 months old without a diagnosis. Genotype-phenotype correlation analysis revealed that loss-of-function mutations in exons 4–6 of CHAT might cause more severe CMS-EA. To our knowledge, this is the first study to show compound heterozygous CHAT mutations consisting of a large deletion and missense mutation in a patient with CMS-EA