Cell Cycle Regulators and Lineage-Specific Therapeutic Targets for Cushing Disease

Cell cycle proteins are critical to pituitary development, but their contribution to lineage-specific tumorigenesis has not been well-elucidated. Emerging evidence from in vitro human tumor analysis and transgenic mouse models indicates that G1/S-related cell cycle proteins, particularly cyclin E, p27, Rb, and E2F1, drive molecular mechanisms that underlie corticotroph-specific differentiation and development of Cushing disease. The aim of this review is to summarize the literature and discuss the complex role of cell cycle regulation in Cushing disease, with a focus on identifying potential targets for therapeutic intervention in patients with these tumors

Morin Protects Channel Catfish From Aeromonas hydrophila Infection by Blocking Aerolysin Activity

Aeromonas hydrophila (A. hydrophila) is an opportunistic bacterial pathogen widely distributed in the environments, particular aquatic environment. The pathogen can cause a range of infections in both human and animals including fishes. However, the application of antibiotics in treatment of A. hydrophila infections leads to the emergence of resistant strains. Consequently, new approaches need to be developed in fighting this pathogen. Aerolysin, the chief virulence factor produced by pathogenic A. hydrophila strains has been employed as target identifying new drugs. In our present study, we found that morin, a flavonoid without anti-bacterial activity isolated from traditional Chinese medicine, could directly inhibit the hemolytic activity of aerolysin. To determine the binding sites and the action of mechanism of morin against AerA, several assays were performed. Ser36, Pro347, and Arg356 were identified as the main binding sites affecting the conformation of AerA and resulted in block of the heptameric formation. Moreover, morin could protect Vero cells from cell injury mediated by aerolysin. In vivo study showed that morin could provide a protection to channel catfish against A. hydrophila infection. These results demonstrated that morin could be developed as a promising candidate for the treatment of A. hydrophila infections by decreasing the pathogenesis of A. hydrophila

Soil Erosion Influencing Factors in the Semiarid Area of Northern Shaanxi Province, China

The semiarid loess area in north Shaanxi Province is one of the most serious areas of water erosion of China. Vegetation, rainfall, soil, and topography are the most dominant natural factors affecting soil erosion; and land disturbance/restoration is a significant factor influencing runoff and sediment yield in this area. According to the research, the results showed: (1) the relative impacts of the four factors on runoff were rainfall > soil > topography > vegetation, and the relative impacts of the factors on sediment yield were soil > runoff > rainfall > topography > vegetation; (2) during a period of the preliminary stage after land disturbance, topography was the most critical factor for the runoff, while sediment yield was soil. During a period of land restoration after land disturbance, runoff was primarily affected by vegetation, while sediment yield was rainfall; (3) this study showed Hippophae rhamnoides + Pinus tabulaeformis and Hippophae rhamnoides were the best vegetation type for reducing runoff and sediment yield, especially if the slope is less than 20°. Land disturbance is caused by human activities in semiarid regions, and in order to reduce the runoff and sediment yield quickly and effectively, artificial measures should be taken for rehabilitation of the disturbed lands

(7R,8S,9S,12S)-1-(4-Chloro­benz­yloxy)-13,14-didehydro-12-hy­droxy-2,13-dimeth­oxy-N-methyl­morphinane

The title compound, C26H30ClNO4, a sinomenine derivative, has five six-membered rings, two of which are aromatic, with a dihedral angle of 34.13 (20)° between these. The N-containing ring and the fourth ring exhibit chair conformations, while the fifth ring approximates an envelope conformation. A single inter­molecular O—H⋯N hydrogen-bonding inter­action gives a one-dimensional chain structure which extends along the a axis. The absolute configuration for the mol­ecule has been determined

DNA methylation repatterning accompanying hybridization, whole genome doubling and homoeolog exchange in nascent segmental rice allotetraploids

Allopolyploidization, which entails interspecific hybridization and whole genome duplication (WGD), is associated with emergent genetic and epigenetic instabilities that are thought to contribute to adaptation and evolution. One frequent genomic consequence of nascent allopolyploidization is homoeologous exchange (HE), which arises from compromised meiotic fidelity and generates genetically and phenotypically variable progenies. Here, we used a genetically tractable synthetic rice segmental allotetraploid system to interrogate genome‐wide DNA methylation and gene expression responses and outcomes to the separate and combined effects of hybridization, WGD and HEs. Progenies of the tetraploid rice were genomically diverse due to genome‐wide HEs that affected all chromosomes, yet they exhibited overall methylome stability. Nonetheless, regional variation of cytosine methylation states was widespread in the tetraploids. Transcriptome profiling revealed genome‐wide alteration of gene expression, which at least in part associates with changes in DNA methylation. Intriguingly, changes of DNA methylation and gene expression could be decoupled from hybridity and sustained and amplified by HEs. Our results suggest that HEs, a prominent genetic consequence of nascent allopolyploidy, can exacerbate, diversify and perpetuate the effects of allopolyploidization on epigenetic and gene expression variation, and hence may contribute to allopolyploid evolution

Computational and experimental studies on the CO2 adsorption of layered double hydroxide intercalated by anionic surfactant

The Mg[sbnd]Al, Ca[sbnd]Al, Zn[sbnd]Al and Mg[sbnd]Fe layered double hydroxides intercalated by sodium dodecyl sulfate was prepared by a co-precipitation method. These materials were characterized by elemental analysis, Powder X-ray diffraction (XRD) and N2 physical adsorption and desorption. Adsorption of CO2 on the samples was investigated by thermogravimetric analysis at 30 °C under 1 bar. The samples had a CO2 adsorption capacity in the range of 0.35–0.58 mmol/g. Ca[sbnd]Al layered double hydroxide intercalated by sodium dodecyl sulfate (SDS) had the highest CO2 adsorption capacity. The layered structures were analyzed by using quantum chemical calculation methods. The simulation results showed that CO2 adsorption capacity was correlated to the ELUMO and the density of Lowest Unoccupied Molecular Orbital (LUMO). The higher ELUMO and density of LUMO orbitals promoted the formation of O-H…O hydrogen bonds, which leaded to the higher CO2 adsorption capacity

(7R,8S,9S,12S)-1-Benz­yloxy-13,14-didehydro-12-hy­droxy-2,13-dimeth­oxy-N-methyl­morphinane

In the title compound, C26H31NO4, a sinomenine derivative, the angle between the two aromatic rings is 53.34 (4)°. The N-containing ring is in a chair conformation, while the other two non-planar rings are in a half-boat conformation. In the crystal, mol­ecules are linked by O—H⋯N inter­actions into a C(8) chain along [100]

Association Analysis of MET

To investigate the association of MET SNPs with gender disparity in thyroid tumors, as well as the metastasis and prognosis of patients, 858 patients with papillary thyroid carcinoma (PTC), 556 patients with nodular goiter, and 896 population-based normal controls were recruited. The genotyping of MET SNPs was carried out using the Sequenom MassARRAY system. The distribution of MET SNPs (rs1621 and rs6566) was different among groups. Gender stratification analysis revealed a significant association between the rs1621 genotype and PTC in female patients (P=0.037), but not in male patients (P>0.05). For female patients, the rs1621 AG genotype was significantly higher in patients with PTC than in normal controls (P=0.01) and revealed an increasing risk of PTC (OR: 1.465, 95% CI: 1.118–1.92). However, association analysis of the rs1621 genotype with metastasis and prognosis revealed no significant correlation in both male and female patients. The findings of our study showed that polymorphism of SNP locus rs1621 in MET gene may be associated with gender disparity in PTC. Higher AG genotypes in rs1621 were correlated with PTC in female patients, but not in male patients

System Pharmacology-Based Strategy to Decode the Synergistic Mechanism of Zhi-zhu Wan for Functional Dyspepsia

Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term “stuffiness and fullness,” FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the “multi-component” and “multi-target” feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte