Di (2-ethylhexyl) phthalate Disorders Lipid Metabolism via TYK2/STAT1 and Autophagy in Rats.

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.

Easy Applied Gelatin-Based Hydrogel System for Long-Term Functional Cardiomyocyte Culture and Myocardium Formation.

Harnessing biomaterials for in vitro tissue construction has long been a research focus because of its powerful potentials in tissue engineering and pharmaceutical industry. Myocardium is a critical cardiac tissue with complex multiple muscular layers. Considering the specific characters of native cardiac tissues, it is necessary to design a biocompatible and biomimetic platform for cardiomyocyte culture and myocardium formation with sustained physiological function. In this study, we developed gelatin-based hydrogels chemically cross-linked by genipin, a biocompatible cross-linker, as cell culture scaffolds. Moreover, to achieve and maintain the functionality of myocardium, for instance, well-organized cardiomyocytes and synchronized contractile behavior, we fabricated gelatin-based hydrogels with patterned microstructure using a microcontact printing technique. Furthermore, graphene oxide (GO), with unprecedented physical and chemical properties, has also been incorporated into gelatin for culturing cardiomyocytes. Our results show that micropatterned genipin-cross-linked gelatin hydrogels are very helpful to promote alignment and maturation of neonatal rat ventricular cardiomyocytes. More interestingly, the presence of GO significantly enhances the functional performance of cardiomyocytes, including an increase in contraction amplitude and cardiac gene expression. The cultured cardiomyocytes reach a well-synchronized contraction within 48 h of cell seeding and keep beating for up to 3 months. Our study provides a new and easy-to-use gelatin-based scaffold for improving physiological function of engineered cardiac tissues, exhibiting promising applications in cardiac tissue engineering and drug screening.

Multifunctional 3D electrode platform for real-time in situ monitoring and stimulation of cardiac tissues.

Cardiovascular diseases are a major cause of death around the world underlining the importance of efficient treatments including novel medication. In vitro models of cardiac tissues are highly desired for monitoring electrophysiological response to screen pharmaceutical compounds at an early stage. Here, we report a platinum based 3D pillar electrode platform with cell growth guiding channel, which allows integrated, continuous electrical stimulation and recording of the cardiac tissues. This platform was successfully used to culture beating cardiomyocytes over weeks. The Pt-PDMS pillar electrode showed an impedance of 2.5 ±â€¯0.3 kΩ at 10 Hz that is stable for using in cell cultures at 37 °C. Electrically pacing the cells improved maturation of the cardiac tissues. Contraction activities of 3D cardiac tissues were monitored in real-time through the pillar electrodes to evaluate physiological parameters. Adding 100 nM Isoproterenol clearly increased the spontaneous beating rate and decreased the extracellular field potential duration of the microtissues observed with electrical recording through the pillar electrodes. Overall, this platform has a potential to be applied in drug screening for in situ monitoring the biophysical parameters of the heart tissue in real-time.

MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart disease and its role in heart development.

The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups. The expressions of miR-34a, NOTCH-1, Jagged1, Hes1, Hey2 and Csx in cardiac tissues and ECCs were determined by both RT-qPCR and western blotting methods. MTT assay and flow cytometry were conducted for cell proliferation and apoptosis measurement. A dual luciferase reporter assay was applied to demonstrate that NOTCH-1 was the target gene of miR-34a. In comparison to the normal group, the expressions of miR-34a, Jagged1, Hes1 and Hey2 displayed up-regulated levels, while the expressions of NOTCH-1 and Csx were down-regulated in the CHD group. Compared with the blank and NC groups, the miR-34a mimics and siRNA-NOTCH-1 groups displayed reduced expressions of NOTCH-1 and Csx as well as a decreased proliferation rate, higher miR-34a, Jagged1, Hes1 and Hey2 expressions and an increased rate of apoptosis; while an reverse trend was observed in the miR-34a inhibitors group. The expressions of MiR-34a recorded increased levels in the miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups, however no changes in the expressions of NOTCH-1, Jagged1, Hes1, Hey2, Csx, as well as cell proliferation and apoptosis were observed when compared to the blank and NC groups. The results of our study demonstrated that miR-34a increases the risk of CHD through its downregulation of NOTCH-1 by modulating the Notch signaling pathway.

A series of 4,5,9,10-tetrahydropyrene-based tetraarylethenes: synthesis, structures and solid-state emission behavior.

By controlling the number of 4,5,9,10-tetrahydropyrene segments around the tetraarylethene core, a series of 4,5,9,10-tetrahydropyrene-based tetraarylethenes were synthesized and structurally characterized. An aggregation-induced emission (AIE) study indicated that all the compounds are AIE active: they are weak emitters in good solvents but highly emissive in the condensed phase, and hence are potential solid-state emitters. Their optical properties, electrochemical properties and theoretical calculations were investigated, and the results prove that the π-conjugation degree of these compounds increases with the increasing number of 4,5,9,10-tetrahydropyrene units. However, the fluorescence quantum yield in the solid state doesn't increase with increasing π-conjugation. We studied the reason for this by analyzing the crystal structures of some compounds, and proposed that the close degree of molecular packing in the solid state may be responsible for it. Loose packing of tetraarylethenes in the solid state can restrict the rotation of the aromatic rings but cannot constrain other non-radiative pathways efficiently, such as vibration, which leads to the unpredictable emission of the compounds.

[An improved physical model to correct topographic effects in remotely sensed imagery].

Topographic correction for remotely sensed imagery is an important preprocessing step in order to improve the retrieval accuracy of land surface spectral reflectance in mountainous area. Various kinds of topographic correction models have been proposed in the literature. Each model has its advantages and limitations. In consideration of the limitations of the topographic correction models in the literature, an improved Shepherd topographic correction model is proposed in this paper. Diffuse irradiance is an essential factor in the physically based topographic correction model. While in the Shepherd model (originally proposed by Shepherd et al. in 2003), accuracy of the method to compute the diffuse irradiance is relatively low; therefore, the accuracy of the land surface spectral reflectance retrieved with the Shepherd model is impacted. In order to improve the accuracy of diffuse irradiance, hence the accuracy of land surface spectral reflectance, a different method (named the Perez model), is used to obtain the diffuse irradiance with higher accuracy in the improved Shepherd model. Landsat 5 Thematic Mapper (TM) imagery acquired on July 12th 2006, over the mountainous areas in the north of Beijing city, was employed to retrieve land surface spectral reflectance with the improved Shepherd topographic correction model and 6S (Second Simulation of the Satellite Signal in the Solar Spectrum) atmospheric radiative transfer model. Correction results were tested with three different methods. Testing result shows that the improved Shepherd topographic correction model can achieve a good correction result and is better than Shepherd and C topographic correction model. What is more, this improved model is physically based and can be applied to all kinds of optical satellite imagery.

Bioremediation of cadmium by growing Rhodobacter sphaeroides: kinetic characteristic and mechanism studies.

The removal kinetic characteristic and mechanism of cadmium by growing Rhodobacter sphaeroides were investigated. The removal data were fitted to the second-order equation, with a correlation coefficient, R2=0.9790-0.9916. Furthermore, it was found that the removal mechanism of cadmium was predominantly governed by bioprecipitation as cadmium sulfide with biosorption contributing to a minor extent. Also, the results revealed that the activities of cysteine desulfhydrase in strains grown in the presence of 10 and 20 mg/l of cadmium were higher than in the control, while the activities in the presence of 30 and 40 mg/l of cadmium were lower than in the control. Content analysis of subcellular fractionation showed that cadmium was mostly removed and transformed by precipitation on the cell wall.

Biological synthesis of semiconductor zinc sulfide nanoparticles by immobilized Rhodobacter sphaeroides.

A novel, clean biological transformation reaction by immobilized Rhodobacter sphaeroides has been developed for the synthesis of zinc sulfide (ZnS) nanoparticles with an average diameter of 8 nm. The nanoparticles were examined by X-ray diffraction, transmission electron microscopy, energy dispersive analyses of X-rays, UV-vis optical absorption and photoluminescence spectra. The average diameter of ZnS nanoparticles varied according to the culture time.