Stereoselective Regulations of P-Glycoprotein by Ginsenoside Rh2 Epimers and the Potential Mechanisms From the View of Pharmacokinetics

Chirality is an interesting topic and it is meaningful to explore the interactions between chiral small molecules and stereoselective biomacromolecules, with pre-clinical and clinical significances. We have previously demonstrated that 20(S)-ginsenoside Rh2 is an effective P-glycoprotein (P-gp) inhibitor in vitro and in vivo. Considering the stereochemistry of ginsenoside Rh2, in our present study, the regulatory effects of 20(R)-Rh2 on P-gp were assayed in vivo, and the differential regulations of P-gp by ginsenoside Rh2 epimers in vivo were compared and studied. Results showed that 20(S)-Rh2 enhanced the oral absorption of digoxin in rats in a dose-dependent manner; 20(R)-Rh2 at low dosage increased the oral absorption of digoxin, but this effect diminished with elevated dosage of 20(R)-Rh2. Further studies indicated stereoselective pharmacokinetic profiles and intestinal biotransformations of Rh2 epimers. In vitro studies showed that Rh2 epimers and their corresponding deglycosylation metabolites protopanaxadiol (Ppd) epimers all exhibited stereoselective regulations of P-gp. In conclusion, in view of the in vitro and in vivo dispositions of Rh2 and the regulations of P-gp by Rh2 and Ppd, it is suggested that the P-gp regulatory effect of Rh2 in vivo actually is a double actions of both Rh2 and Ppd, and the net effect is determined by the relative balance between Rh2 and Ppd with the same configuration. Our study provides new evidence of the chiral characteristics of P-gp, and is helpful to elucidate the stereoselective P-gp regulation mechanisms of ginsenoside Rh2 epimers in vivo from a pharmacokinetic view

AngiotensinII Preconditioning Promotes Angiogenesis In Vitro via ERKs Phosphorylation

AngiotensinII (AngII) is involved in not only the formation of cardiac hypertrophy but also the development of cardiac remodeling both of which are associated with myocardial angiogenesis. This study was therefore performed to clarify the effects of AngII on the formation of vasculatures by cultured cardiac microvascular endothelial cells (CMVECs) after a long-period stimulation with or without the AngII preconditioning. Incubation with AngII for 18 hrs significantly impaired the formation of capillary-like tubes comparing to that without AngII. CMVECs with AngII pretreatment for 5 and 10 min formed more capillary-like tubes than those without AngII pretreatment, suggesting that preconditioning with AngII at a lower dose for a short period could prevent the further damage of CMVECs by a higher concentration of AngII. Moreover, AngII (10−7 M) stimulation for 5 and 10 min significantly induced the increase in extracellular signal-regulated protein kinases (ERKs) phosphorylation, and an ERKs inhibitor, PD98059, abrogated the increase in the formation of capillary-like tubes induced by the AngII-pretreatment. In conclusion, preconditioning with a lower concentration of AngII for a short period prevents the subsequent impairment of CMVECs by a higher dose of AngII, at least in part, through the increase in ERKs phosphorylation

A Fast Infrared Radiative Transfer Model for Overlapping Clouds

A fast infrared radiative transfer model (FIRTM2) appropriate for application to both single-layered and overlapping cloud situations is developed for simulating the outgoing infrared spectral radiance at the top of the atmosphere (TOA). In FIRTM2 a pre-computed library of cloud reflectance and transmittance values is employed to account for one or two cloud layers, whereas the background atmospheric optical thickness due to gaseous absorption can be computed from a clear-sky radiative transfer model. FIRTM2 is applicable to three atmospheric conditions: 1) clear-sky, 2) single-layered ice or water cloud, and 3) two simultaneous cloud layers in a column (e.g., ice cloud overlying water cloud). Moreover, FIRTM2 outputs the derivatives (i.e., Jacobians) of the TOA brightness temperature with respect to cloud optical thickness and effective particle size. Sensitivity analyses have been carried out to assess the performance of FIRTM2 for two spectral regions, namely the longwave (LW) band (587.3 - 1179.5/cm) and the short-to-medium wave (SMW) band (1180.1 - 2228.9/cm). The assessment is carried out in terms of brightness temperature differences (BTD) between FIRTM2 and the well-known discrete ordinates radiative transfer model (DISORT), henceforth referred to as BTD (F-D). The BTD (F-D) values for single-layered clouds are generally less than 0.8 K. For the case of two cloud layers (specifically ice cloud over water cloud), the BTD(F-D) values are also generally less than 0.8 K except for the SMW band for the case of a very high altitude (>15 km) cloud comprised of small ice particles. Note that for clear-sky atmospheres, FIRTM2 reduces to the clear-sky radiative transfer model that is incorporated into FIRTM2, and the errors in this case are essentially those of the clear-sky radiative transfer model

Integrated bioinformatics analysis of As, Au, Cd, Pb and Cu heavy metal responsive marker genes through Arabidopsis thaliana GEO datasets

Background Current environmental pollution factors, particularly the distribution and diffusion of heavy metals in soil and water, are a high risk to local environments and humans. Despite striking advances in methods to detect contaminants by a variety of chemical and physical solutions, these methods have inherent limitations such as small dimensions and very low coverage. Therefore, identifying novel contaminant biomarkers are urgently needed. Methods To better track heavy metal contaminations in soil and water, integrated bioinformatics analysis to identify biomarkers of relevant heavy metal, such as As, Cd, Pb and Cu, is a suitable method for long-term and large-scale surveys of such heavy metal pollutants. Subsequently, the accuracy and stability of the results screened were experimentally validated by quantitative PCR experiment. Results We obtained 168 differentially expressed genes (DEGs) which contained 59 up-regulated genes and 109 down-regulated genes through comparative bioinformatics analyses. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of these DEGs were performed, respectively. GO analyses found that these DEGs were mainly related to responses to chemicals, responses to stimulus, responses to stress, responses to abiotic stimulus, and so on. KEGG pathway analyses of DEGs were mainly involved in the protein degradation process and other biologic process, such as the phenylpropanoid biosynthesis pathways and nitrogen metabolism. Moreover, we also speculated that nine candidate core biomarker genes (namely, NILR1, PGPS1, WRKY33, BCS1, AR781, CYP81D8, NR1, EAP1 and MYB15) might be tightly correlated with the response or transport of heavy metals. Finally, experimental results displayed that these genes had the same expression trend response to different stresses as mentioned above (Cd, Pb and Cu) and no mentioned above (Zn and Cr). Conclusion In general, the identified biomarker genes could help us understand the potential molecular mechanisms or signaling pathways responsive to heavy metal stress in plants, and could be applied as marker genes to track heavy metal pollution in soil and water through detecting their expression in plants growing in those environments

Specific two-photon imaging of live cellular and deep-tissue lipid droplets by lipophilic AIEgens at ultra-low concentration

Lipid droplets are highly associated with obesity, diabetes, inflammatory disorders and cancer. A reliable two-photon dye for specific lipid droplets imaging in live cells and live tissues at ultra-low concentration has rarely been reported. In this work, four new aggregation-induced emission luminogens (AIEgens) based on the naphthalene core were designed and synthesized for specific two-photon lipid droplets staining. The new molecules, namely NAP AIEgens, exhibit large Stokes shift (>110 nm), high solid-state fluorescence quantum yield (up to 30%), good two-photon absorption cross section (45–100 GM at 860 nm), high biocompatibility and good photostability. They could specifically stain lipid droplets at ultra-low concentration (50 nM) in a short time of 15 min. Such ultra-low concentration is the lowest value for lipid droplets staining in live cells reported so far. In vitro and ex vivo two-photon imaging of lipid droplets in live cells and live mice liver tissues were successfully demonstrated. In addition, selective visualization of lipid droplets in live mice liver tissues could be achieved at a depth of about 70 μm. These excellent properties render them as promising candidates for investigating lipid droplets-associated physiological and pathological processes in live biological samples

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health

Spanning capacity analysis of self-anchored suspension bridges based on the stability and compression strength of stiffening girder

Considerable axial compression stress exists in the stiffening girder of self-anchored suspension bridges. Therefore, failures of self-anchored suspension bridges will be either due to material failure or instability of the stiffening girder, which will be the major concerns. In this study, the spanning capacity of self-anchored suspension bridges is studied based both on the stability and compression strength of the stiffening girder. Theoretical analysis reveals that, due to the elastic supports provided by the main cables and suspenders, in-plane elastic buckling of the stiffening girder is prevented. However, the stiffening girder may still buckle in the transverse direction. The extreme span length of self-anchored suspension bridges increases as the rise-to-span ratio increases. For general bridge designs, when the rise-to-span ratio is smaller than that of a bridge-specific turn point value, the spanning capacity of self-anchored suspension bridges is directly proportional to the rise-to-span ratio; however, when the rise-to-span ratio is larger than that of the turn point value, the spanning capacity of self-anchored suspension bridges is proportional to the 1/3rd power of the rise-to-span ratio. Besides, the spanning capacity of self-anchored suspension bridges will increase as the width or yielding strength of the stiffening girder increases

The influence of chess training on pupils’ self-efficacy， self-esteem and social anxiety

Background With the 2001 announcement about three chess games in school, go, Chinese chess and chess, the three upsurge of popularity is set off in the country. Chess started late in China and was originally considered as an intellectual sport related to intelligence. Its role in psychological characteristics has not received enough attention from people. Objective In order to study the influence of chess training on pupils' self-efficacy, self-esteem and social anxiety. Methods 121 pupils from Jinding No.1 primary school are selected as study subjects and divided into experimental group and control group. The experiment group is the community group of 31 pupils, and the control group is the non-community group of 90 pupils. Using General Self-Efficacy Scale, Self-Esteem Scale, and Social Anxiety Scale for Children, the scales are used to test, and the pupils are observed and the teachers and parents are interviewed. Results There are significant differences in self-efficacy, self-esteem and social anxiety between the community and the non-community pupils. Conclusion It shows that a certain intensity of chess training has a greater impact on pupils' self-efficacy, self-esteem and social anxiety

The influence of chess training on pupils’ self-efficacy， self-esteem and social anxiety

Background With the 2001 announcement about three chess games in school, go, Chinese chess and chess, the three upsurge of popularity is set off in the country. Chess started late in China and was originally considered as an intellectual sport related to intelligence. Its role in psychological characteristics has not received enough attention from people. Objective In order to study the influence of chess training on pupils' self-efficacy, self-esteem and social anxiety. Methods 121 pupils from Jinding No.1 primary school are selected as study subjects and divided into experimental group and control group. The experiment group is the community group of 31 pupils, and the control group is the non-community group of 90 pupils. Using General Self-Efficacy Scale, Self-Esteem Scale, and Social Anxiety Scale for Children, the scales are used to test, and the pupils are observed and the teachers and parents are interviewed. Results There are significant differences in self-efficacy, self-esteem and social anxiety between the community and the non-community pupils. Conclusion It shows that a certain intensity of chess training has a greater impact on pupils' self-efficacy, self-esteem and social anxiety