Peroxisome proliferator-activated receptor delta +294T > C polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

<p>Abstract</p> <p>Background</p> <p>The association of peroxisome proliferator-activated receptor delta (PPARD) +294T > C polymorphism and serum lipid levels is inconsistent in several previous studies. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The present study was undertaken to detect the association of PPARD +294T > C (rs2016520) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.</p> <p>Methods</p> <p>A total of 609 subjects of Bai Ku Yao and 573 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the PPARD +294T > C polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.</p> <p>Results</p> <p>The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (<it>P </it>< 0.001 for all). The frequency of T and C alleles was 77.50% and 22.50% in Bai Ku Yao, and 72.43% and 27.57% in Han (<it>P </it>< 0.01); respectively. The frequency of TT, TC and CC genotypes was 60.59%, 33.83% and 5.53% in Bai Ku Yao, and 52.18%, 40.50% and 7.32% in Han (<it>P </it>< 0.05); respectively. The subjects with CC genotype in Bai Ku Yao had higher serum LDL-C and ApoB levels and lower the ratio of ApoAI to ApoB than the subjects with TT and TC genotypes in females but not in males. The C allele carriers in Han had higher serum TC levels in males (<it>P </it>< 0.01) and ApoB levels in females (<it>P </it>< 0.05) than the C allele noncarriers. Serum TC and ApoB levels were correlated with genotypes in Han (<it>P </it>< 0.05 for each) but not in Bai Ku Yao. Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, cigarette smoking, and blood pressure in both ethnic groups.</p> <p>Conclusions</p> <p>These results suggest that the association of PPARD +294T > C polymorphism and serum lipid levels is different between the Bai Ku Yao and Han populations. The discrepancy between the two ethnic groups might partly result from different PPARD +294T > C polymorphism or PPARD gene-enviromental interactions.</p

Magnetic interactions in iron superconductors: A review

High temperature superconductivity in iron pnictides and chalcogenides emerges when a magnetic phase is suppressed. The multi-orbital character and the strength of correlations underlie this complex phenomenology, involving magnetic softness and anisotropies, with Hund's coupling playing an important role. We review here the different theoretical approaches used to describe the magnetic interactions in these systems. We show that taking into account the orbital degree of freedom allows us to unify in a single phase diagram the main mechanisms proposed to explain the (\pi,0) order in iron pnictides: the nesting-driven, the exchange between localized spins, and the Hund induced magnetic state with orbital differentiation. Comparison of theoretical estimates and experimental results helps locate the Fe superconductors in the phase diagram. In addition, orbital physics is crucial to address the magnetic softness, the doping dependent properties, and the anisotropies.Comment: Invited review article for a focus issue of Comptes Rendus Physique: 26 pages, 10 figures. Revised version, as accepted. Small changes throughout the text plus new subsection (Sec. IIIE

Docetaxel-Loaded Pluronic P123 Polymeric Micelles: in Vitro and in Vivo Evaluation

In this work, novel docetaxel (DTX) -loaded Tween 80-free Pluronic P123 (P123) micelles with improved therapeutic effect were developed. The freeze-dried DTX-loaded P123 micelles (DTX-micelles) were analyzed by HPLC, TEM and DLS to determine the DTX loading, micelle morphology, size, respectively. The in vitro cytotoxic activity of DTX-micelles in HepG2, A549 and malignant melanoma B16 cells were evaluated by MTT assay. The corresponding in vivo antitumor efficacy was assessed in Kunming mice bearing B16 tumor after intravenous administration. The DTX-loading and efficiency into the micelles were 2.12 ± 0.09% and 86.34 ± 3.32%, respectively. The DTX-micelles were spherical with a mean particle size of 50.7 nm and size distribution from 22 to 84 nm, which suggested that they should be able to selectively accumulate in solid tumors by means of EPR effect, with a zeta potential of −12.45 ± 3.24 mV. The in vitro release behavior of DTX from DTX-micelles followed the Weibull equation. Compared with Duopafei®, DTX-micelles showed higher cytotoxicity against HepG2 (P < 0.01), A549 (P < 0.05) and B16 (P < 0.01) cells. In addition, DTX-micelles exhibited remarkable antitumor activity and reduced toxicity on B16 tumor in vivo. The tumor inhibition rates (TIR) of DTX-micelles was 91.6% versus 76.3% of Duopafei® (P < 0.01). These results suggested that P123 micelles might be considered as an effective DTX delivery system

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice

Spectroscopic scanning tunneling microscopy insights into Fe-based superconductors

In the first three years since the discovery of Fe-based high Tc superconductors, scanning tunneling microscopy (STM) and spectroscopy have shed light on three important questions. First, STM has demonstrated the complexity of the pairing symmetry in Fe-based materials. Phase-sensitive quasiparticle interference (QPI) imaging and low temperature spectroscopy have shown that the pairing order parameter varies from nodal to nodeless s\pm within a single family, FeTe1-xSex. Second, STM has imaged C4 -> C2 symmetry breaking in the electronic states of both parent and superconducting materials. As a local probe, STM is in a strong position to understand the interactions between these broken symmetry states and superconductivity. Finally, STM has been used to image the vortex state, giving insights into the technical problem of vortex pinning, and the fundamental problem of the competing states introduced when superconductivity is locally quenched by a magnetic field. Here we give a pedagogical introduction to STM and QPI imaging, discuss the specific challenges associated with extracting bulk properties from the study of surfaces, and report on progress made in understanding Fe-based superconductors using STM techniques.Comment: 36 pages, 23 figures, 229 reference

A new integrated and homogenized global monthly land surface air temperature dataset for the period since 1900

A new dataset of integrated and homogenized monthly surface air temperature over global land for the period since 1900 [China Meteorological Administration global Land Surface Air Temperature (CMA-LSAT)] is developed. In total, 14 sources have been collected and integrated into the newly developed dataset, including three global (CRUTEM4, GHCN, and BEST), three regional and eight national sources. Duplicate stations are identified, and those with the higher priority are chosen or spliced. Then, a consistency test and a climate outlier test are conducted to ensure that each station series is quality controlled. Next, two steps are adopted to assure the homogeneity of the station series: (1) homogenized station series in existing national datasets (by National Meteorological Services) are directly integrated into the dataset without any changes (50% of all stations), and (2) the inhomogeneities are detected and adjusted for in the remaining data series using a penalized maximal t test (50% of all stations). Based on the dataset, we re-assess the temperature changes in global and regional areas compared with GHCN-V3 and CRUTEM4, as well as the temperature changes during the three periods of 1900–2014, 1979–2014 and 1998–2014. The best estimates of warming trends and there 95% confidence ranges for 1900–2014 are approximately 0.102 ± 0.006 °C/decade for the whole year, and 0.104 ± 0.009, 0.112 ± 0.007, 0.090 ± 0.006, and 0.092 ± 0.007 °C/decade for the DJF (December, January, February), MAM, JJA, and SON seasons, respectively. MAM saw the most significant warming trend in both 1900–2014 and 1979–2014. For an even shorter and more recent period (1998–2014), MAM, JJA and SON show similar warming trends, while DJF shows opposite trends. The results show that the ability of CMA-LAST for describing the global temperature changes is similar with other existing products, while there are some differences when describing regional temperature changes

Two-photon dual imaging platform for in vivo monitoring cellular oxidative stress in liver injury

Oxidative stress reflects an imbalance between reactive oxygen species (ROS) and antioxidants, which has been reported as an early unifying event in the development and progression of various diseases and as a direct and mechanistic indicator of treatment response. However, highly reactive and short-lived nature of ROS and antioxidant limited conventional detection agents, which are influenced by many interfering factors. Here, we present a two-photon sensing platform for in vivo dual imaging of oxidative stress at the single cell-level resolution. This sensing platform consists of three probes, which combine the turn-on fluorescent transition-metal complex with different specific responsive groups for glutathione (GSH), hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). By combining fluorescence intensity imaging and fluorescence lifetime imaging, these probes totally remove any possibility of crosstalk from in vivo environmental or instrumental factors, and enable accurate localization and measurement of the changes in ROS and GSH within the liver. This precedes changes in conventional biochemical and histological assessments in two distinct experimental murine models of liver injury. The ability to monitor real-time cellular oxidative stress with dual-modality imaging has significant implications for high-accurate, spatially configured and quantitative assessment of metabolic status and drug response

Electronic beam shifts in monolayer graphene superlattice

Electronic analogue of generalized Goos-H\"{a}nchen shifts is investigated in the monolayer graphene superlattice with one-dimensional periodic potentials of square barriers. It is found that the lateral shifts for the electron beam transmitted through the monolayer graphene superlattice can be negative as well as positive near the band edges of zero-$\bar{k}$ gap, which are different from those near the band edges of Bragg gap. These negative and positive beam shifts have close relation to the Dirac point. When the condition $q_A d_A= -q_B d_B= m \pi$ ($m=1,2,3...$) is satisfied, the beam shifts can be controlled from negative to positive when the incident energy is above the Dirac point, and vice versa. In addition, the beam shifts can be greatly enhanced by the defect mode inside the zero-$\bar{k}$ gap. These intriguing phenomena can be verified in a relatively simple optical setup, and have potential applications in the graphene-based electron wave devices.Comment: 5 pages, 4 figures, submitted on Oct. 15, 201