Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach

Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies < -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI

Identification and characterization of circular RNAs in mammary gland tissue from sheep at peak lactation and during the nonlactating period

Circular RNAs are a class of noncoding RNA with a widespread occurrence in eukaryote tissues, and with some having been demonstrated to have clear biological function. In sheep, little is known about the role of circular RNAs in mammary gland tissue, and therefore an RNA sequencing approach was used to compare mammary gland tissue expression of circular RNAs in 9 Small Tail Han sheep at peak lactation, and subsequently when they were not lactating. These 9 sheep had their RNA pooled for analysis into 3 libraries from peak lactation and 3 from the nonlactating period. A total of 3,278 and 1,756 circular RNAs were identified in the peak lactation and nonlactating mammary gland tissues, respectively, and the expression and identity of 9 of them was confirmed using reverse transcriptase-polymerase chain reaction analysis and DNA sequencing. The type, chromosomal location and length of the circular RNAs identified were ascertained. Forty upregulated and one downregulated circular RNAs were characterized in the mammary gland tissue at peak lactation compared with the nonlactating mammary gland tissue. Gene ontology enrichment analysis revealed that the parental genes of these differentially expressed circular RNAs were related to molecular function, binding, protein binding, ATP binding, and ion binding. Five differentially expression circular RNAs were selected for further analysis to predict their target microRNAs, and some microRNAs reportedly associated with the development of the mammary gland were found in the constructed circular RNA–microRNA network. This study reveals the expression profiles and characterization of circular RNAs at 2 key stages of mammary gland activity, thereby providing an improved understanding of the roles of circular RNAs in the mammary gland of sheep

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Spatial Distribution and Risk Factors of Highly Pathogenic Avian Influenza (HPAI) H5N1 in China

Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004–2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance positives in 2007–2009 appeared to have had lower antibody response to vaccination. The distribution of HPAI H5N1 risk in China appears more limited geographically than previously assessed, offering prospects for better targeted surveillance and control interventions

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups

Single-marker and haplotype analyses for detecting parent-of-origin effects using family and pedigree data

published_or_final_versionStatistics and Actuarial ScienceDoctoralDoctor of Philosoph

Surface Subsidence Analysis by Multi-Temporal InSAR and GRACE: A Case Study in Beijing

The aim of this study was to investigate the relationship between surface subsidence and groundwater changes. To investigate this relationship, we first analyzed surface subsidence. This paper presents the results of a case study of surface subsidence in Beijing from 1 August 2007 to 29 September 2010. The Multi-temporal Interferometric Synthetic Aperture Radar (multi-temporal InSAR) technique, which can simultaneously detect point-like stable reflectors (PSs) and distributed scatterers (DSs), was used to retrieve the subsidence magnitude and distribution in Beijing using 18 ENVISAT ASAR images. The multi-temporal InSAR-derived subsidence was verified by leveling at an accuracy better than 5 mm/year. Based on the verified multi-temporal InSAR results, a prominent uneven subsidence was identified in Beijing. Specifically, most of the subsidence velocities in the downtown area were within 10 mm/year, and the largest subsidence was detected in Tongzhou, with velocities exceeding 140 mm/year. Furthermore, Gravity Recovery and Climate Experiment (GRACE) data were used to derive the groundwater change series and trend. By comparison with the multi-temporal InSAR-derived subsidence results, the long-term decreasing trend between groundwater changes and surface subsidence showed a relatively high consistency, and a significant impact of groundwater changes on the surface subsidence was identified. Additionally, the spatial distribution of the subsidence funnel was partially consistent with that of groundwater depression, i.e., the former possessed a wider range than the latter. Finally, the relationship between surface subsidence and groundwater changes was determined