Search

Graphene is a very promising optoelectronic material and has gained more and more attention. Due to the significance of computer-aided design of graphene, several simulation modeling methods have been developed. In this paper, a brief review of some widely used computational electromagnetic algorithms and corresponding software packages for graphene modeling is provided. The advantages and drawbacks of each method are discussed and numerical examples of these methods are given to illustrate their performance and application.

Methyl-CpG-binding protein 2 (MeCP2) plays a key role in liver fibrosis. However, the potential mechanism of MeCP2 in liver fibrosis remains unclear. Early reports suggest that LncRNA H19 is important epigenetic regulator with critical roles in cell proliferation, but its role in hepatic fibrosis remains elusive. Sprague-Dawley rats liver fibrosis was generated by 12-weeks treatment with CCl4 intraperitoneal injection. HSC-T6 cells were used in vitro study. The expression levels of MeCP2, H19, IGF1R, α-SMA, and Col1A1 were estimated by Western blotting, qRT-PCR and Immunohistochemistry. HSC-T6 cells were transfected with MeCP2-siRNA, pEGF-C1-MeCP2, pEX-3-H19, and H19-siRNA. Finally, cell proliferation ability was assessed by the MTT assay. Here, we found that H19 was significantly down-regulated in HSCs and fibrosis tissues, and an opposite pattern is observed for MeCP2 and IGF1R. Silencing of MeCP2 blocked HSCs proliferation. Knockdown of MeCP2 elevated H19 expression in activated HSCs, and over-expression of MeCP2 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on IGF1R expression. Overexpression of H19 in HSCs repressed the expression of IGF1R, and an opposite pattern is observed for H19 silenced. In addition, we reported that overexpression of H19 inhibited the TGF-β1-induced proliferation of HSCs. Furthermore, MeCP2 negative regulation of H19 by targeting the protein IGF1R. Taken together, these results demonstrated that MeCP2 silencing of H19 can alter the IGF1R overexpression, thus contributing to HSCs proliferation. These data could suggest the development of combination therapies that target the MeCP2.

This study aims to investigate the preclinical performance and mechanism of a novel strategy of aFGF-loaded heparin-modified microbubbles (aFGF-HMB) combined with ultrasound-targeted microbubble destruction (UTMD) technique for diabetic cardiomyopathy (DCM) prevention. Type 1 diabetic rats were induced by streptozotocin. Twelve weeks after intervention, indexes from transthoracic echocardiography and cardiac catheterization showed that the left ventricular function in the aFGF-HMB/UTMD group was significantly improved compared with diabetes control (DM). From Picrosirius Red staining and TUNEL staining, the aFGF-HMB/UTMD group showed significant difference from the other groups. The cardiac collagen volume fraction (CVF) and myocardial cell apoptosis index (AI) in aFGF-HMB/UTMD group decreased to 7.2 % and 7.11 % respectively, compared with the DM group (CVF = 24.5 % and AI =20.3 % respectively). The results of myocardial microvascular density (MCD) also proved the strongest inhibition of aFGF-HMB/UTMD group on DCM progress. CD31 staining of aFGF-HMB/UTMD group reached 22 n/hrp, much higher than that of DM group (9 n/hrp). These results confirmed that the abnormalities including left ventricular dysfunction, myocardial fibrosis, cardiomyocytes apoptosis and microvascular rarefaction could be suppressed by twice weekly aFGF treatments for 12 consecutive weeks (free aFGF or aFGF-HMB+/-UTMD), with the strongest improvements observed in the aFGF-HMB/UTMD group (P

Ocotillol-type saponins have a wide spectrum of biological activities. Previous studies indicated that the configuration at the C24 position may be responsible for their stereoselectivity in pharmacological action and pharmacokinetics. Natural ocotillol-type saponins share a 20(S)-form but it has been found that the 20(R)-stereoisomers have different pharmacological effects. The semisynthesis of 20(R)-ocotillol-type saponins has not been reported and it is therefore worthwhile clarifying their crystal structures. Two C24 epimeric 20(R)-ocotillol-type saponins, namely (20R,24S)-20,24-epoxydammarane-3β,12β,25-triol, C30H52O4, (III), and (20R,24R)-20,24-epoxydammarane-3β,12β,25-triol monohydrate, C30H52O4·H2O, (IV), were synthesized, and their structures were elucidated by spectral studies and finally confirmed by single-crystal X-ray diffraction. The (Me)C—O—C—C(OH) torsion angle of (III) is 146.41 (14)°, whereas the corresponding torsion angle of (IV) is −146.4 (7)°, indicating a different conformation at the C24 position. The crystal stacking in (III) generates anR44(8) motif, through which the molecules are linked into a one-dimensional double chain. The chains are linkedvianonclassical C—H...O hydrogen bonds into a two-dimensional network, and further stacked into a three-dimensional structure. In contrast to (III), epimer (IV) crystallizes as a hydrate, in which the water molecules act as hydrogen-bond donors linking one-dimensional chains into a two-dimensional network through intermolecular O—H...O hydrogen bonds. The hydrogen-bonded chains extend helically along the crystallographicaaxis and generate aC44(8) motif.

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.

Expanding undifferentiated induced pluripotent stem (iPS) cells in vitro is a basic requirement for application of iPS cells in both fundamental research and clinical regeneration. In this study, we intended to establish a simple, low cost and efficient method for the long-term self-renewal of mouse induced pluripotent stem (miPS) cells without using feeder-cells and adhesive proteins. Three scaffolds were selected for the long-term subculture of miPS cells over two months starting from passages 14 to 29: 1) a gelatin coated polystyrene (Gelatin-PS) that is a widely used scaffold for self-renewal of mouse embryonic stem (mES) cells; 2) a neutral hydrogel poly(N,N-dimethylacrylamide) (PDMAAm); and 3) a negatively charged hydrogel poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS). Each passaged miPS cells on these scaffolds were cryopreserved successfully and the revived cells showed high viability and proliferation. The passaged miPS cells maintained a high undifferentiated state on all three scaffolds and a high level of pluripotency by expressing differentiation markers in vitro and forming teratomas in SCID mice with derivatives of all three germ layers. Compared to Gelatin-PS, the two hydrogels exhibited much better self-renewal performance in terms of high proliferation rate and level of expression of undifferentiated gene markers as well as efficiency in pluripotent teratoma formation. Furthermore, the PNaAMPS hydrogel demonstrated a slightly higher efficiency and simpler operation of cell expansion than the PDMAAm hydrogel. To conclude, PNaAMPS hydrogel is an excellent feeder-free scaffold because of its simplicity, low cost and high efficiency in expanding a large number of miPS cells in vitro.

A novel CdII-coordination framework [Cd(C4O4)(btb)(H2O)2]n (1) constructed by squaric acid (H2C4O4) and secondary N-donor spacer 1,4-bis(1,2,4-triazol-4-yl)butane (btb) is presented, which displays 2D → 3D inclined polycatenate framework consisting of two of sets of equivalent 2D 44-sql layers and (4,6)-connected self-catenated H-bonding topology. In addition, the thermal stability and photo-luminescence property of 1 were also investigated.

The presence of congruent features may suggest to the brain that stimuli in different modalities are due to a common cause. Previous work has presented conflicting results regarding the impact of congruence on simultaneity judgments, widely thought to be related to judgments of common cause. Here, a novel experimental paradigm using a single changing multi-sensory object is described, with the goal of contrasting results obtained using a single multi-sensory target with those obtained from previous work using arrays of moving dots and staggered asynchronous pairs of targets. Some preliminary results from a pilot validating the experimental procedure are discussed.

Cardiac fibroblasts proliferation is the most important pathophysiological character of cardiac fibrosis while the underlying mechanisms are still incompletely known. MicroRNAs (miRNAs) regulate gene expression by binding to specific sites. Studies have been indicated that miRNA-29a play a key role in cardiac fibrosis. VEGF-A carries out its functions through MAPK signaling pathway in cardiac fibrosis. Existing proofs predict that the VEGF-A is one of the potential targets of miRNA-29a. We therefore probe the role of miRNA-29a and its latent target VEGF-A during cardiac fibrosis. In our study, miRNA-29a was down-regulated while VEGF-A was up-regulated in cardiac fibrosis tissues. The rat cardiac fibroblasts that were transfected with miRNA-29a inhibitor exhibited low-expression of miRNA-29a, enhanced VEGF-A protein and mRNA expression. Nevertheless, the cardiac fibroblasts transfected with miRNA-29a mimics obtained the opposite expression result. Furthermore, over-expression of miRNA-29a suppresses cardiac fibroblasts proliferation. In conclusion, these results suggested that miRNA-29a suppresses cardiac fibrosis and fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway implicating that miRNA-29a might play a role in the treatment of cardiac fibrosis.

Hepatic stellate cells (HSCs) activation is an essential event during liver fibrogenesis. A major pathway is the transition of HSCs into hepatic myofibroblasts. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. Overexpression of this protein results in an increase of global methylation levels. Treatment of HSCs with DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC) blocks the cell proliferation. 5-azadC also prevents loss of Ras GTPase activating-like protein 1 (RASAL1) expression that occurs during HSCs proliferation. To further explore the underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis was caused by DNA methylation. Results demonstrated that hypermethylation of RASAL1 is associated with the perpetuation of fibroblast activation and fibrogenesis in the liver. knockdown of MeCP2 using siRNA technique increased RASAL1 in both mRNA and protein level in myofibroblasts. These studies demonstrated that MeCP2 and DNA methylation may provide molecular mechanisms for perpetuated fibroblast activation and fibrogenesis in the liver.

Sensor utilizing metamaterials have opened up a new field of considerable interest. We extend here the works of our group about metamaterial sensor based on Whispering Gallery Mode (WGM), which is constructed with a microring resonator sensor coated with metamaterial layer. We demonstrate that our sensor possesses higher sensitivity than the traditional sensor since the amplification and penetration of evanescent wave by metamaterials.

Metamaterials are artificial media structured on a size scale smaller than the wavelength of external stimuli, and may provide novel tools to significantly enhance the sensitivity and resolution of the sensors. In this paper, we derive the dispersion relation of cylindrical dielectric waveguide loaded on double negative metamaterial (DNM) layer, and compute the resonant frequencies and electric field distribution of the corresponding Whispering-Gallery-Modes (WGM). Theoretical results of resonant frequency and electric field distribution are in good agreement with the simulation results. We show that the DNM sensor based on microring resonator possesses higher sensitivity than the traditional microring sensor since the amplification of evanescent wave, and with the increase of metamaterial layer thickness, the sensitivity will be increased greatly. It might open an avenue for designing perfect sensors.

Differentiation of embryoid bodies (EBs) into particular cell lineages has been extensively studied. There is an increasing interest in the effect of soft hydrogel scaffolds on the behavior of EBs, such as the initial adhesion, dynamic morphology change, and differentiation. In this study, without adding any other bioactive factors in the serum-containing medium, dynamic behaviors of mouse EBs loaded on the surface of hydrogels with different surface charge and chemical structures are investigated. EBs adhered quickly to negatively charged poly(sodium p-styrene sulfonate) (PNaSS) hydrogels, which facilitates EBs spreading, migration, and differentiation into three germ layers with high efficiency of cardiomyocytes differentiation, similar to that on gelatin coated polystyrene (PS) culture plate. While on neutral poly(acrylamide) (PAAm) hydrogels, EBs maintained the initial spherical morphology with high expression of pluripotency-related markers in the short culture periods, and then showed the significantly greater levels of selected endoderm markers after long-time culture. EBs cultured on negatively charged poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS) gels demonstrated the analogous behaviors with that of neutral PAAm gels at early differentiation phase (day 4+1). Then, their adhesion, spreading and differentiation were quite similar to that on negatively charged PNaSS gels. The correlation between surface properties of hydrogels and EBs differentiation was discussed.

Microgrid is a distributed power generation system, and is also an effective solution for the connection of grids with high level of distributed energy resources. This paper reviews the microgrid test beds and demonstrated projections in many countries, with emphasis on the communication and control techniques. We arrive at the conclusion that new strategies for communication and control are urgently needed in future power grid.

The first invisibility cloak was proposed by Pendry et al. [Science 312, 1780 (2006)]. But the object enclosed in this original cloak is “blind", that is, it cannot see the outside world, since no electromagnetic waves can reach within the cloaked space. Based on the concept of complementary media, we propose a reciprocal invisibility cloak, in which the hidden object can see the outside world, but its presence cannot be detected by electromagnetic wave. The performance of the cloak has been verified by full-wave simulations.

Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells (ECs) proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young’s modulus (E) and zeta potential (ζ) of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly(2-acrylamido-2-methylpropanesulfonic sodium) (PNaAMPS) and poly(sodium p-styrene sulphonate) (PNaSS), can directly promote cell proliferation, with no need of surface modification by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young’s modulus (E) and zeta potential (ζ) of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide (DMAAm). It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζ critical = −20.83 mV and ζ critical = −14.0 mV for poly(NaAMPS-co-DMAAm) and poly(NaSS-co-DMAAm), respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young’s modulus (E) of the hydrogels, especially when E > 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relationship between physic-chemical properties of synthetic hydrogels and cell responses is essential to design optimal soft and wet scaffolds for tissue engineering.

We measured the gene expression, glycocalyx content, and surface properties of human coronary artery endothelial cells (HCAECs) cultured on poly(sodium p-styrene sulfonate) (PNaSS) hydrogels with various levels of elasticity ranged in 3-300 kPa. We found that all HCAECs reached confluence on these hydrogels while retaining the similar expression of EC-specific markers to that on polystyrene (PS), a widely used scaffold in cell culture in vitro. Real-time polymerase chain reaction (PCR) and glycosaminoglycan (GAG) assay showed that the amount of EC-specific glycocalyx secreted by HCAECs cultured on PNaSS gels was higher than that cultured on PS, and it increased with an increase of gel elasticity. Furthermore, the HCAECs cultured on PNaSS gels showed excellent property against platelet adhesion and lower surface friction than that on PS. The platelet adhesion and surface friction of HCAECs cultured on PNaSS gels also depend on the elasticity of gels. The largest amount of EC-specific glycocalyx, excellent blood compatibility, and the lowest friction were observed when the elastic modulus of the gel was larger than 60 kPa. Overall, HCAECs cultured on these hydrogels have better properties than those cultured on PS scaffold, demonstrating the PNaSS gels can be used as potential tissue engineering material for blood vessels.

The adding of ZnMgO asymmetric double barriers (ADB) in p-ZnO: (Li, N)/n-ZnO homojunction affects the p–n junction device performance prominently. Two different homojunctions are fabricated on Si (100) substrates by pulsed laser deposition; one is the traditional p-ZnO: (Li, N)/n-ZnO homojunction with different thicknesses named as S1 (250 nm) and S2 (500 nm), the other is the one with ADB embedded in the n-layer named as Q (265 nm). From the photoluminescence spectra, defect luminescence present in the S-series devices is effectively limited in the Q device. The current–voltage curve of the Q device shows Zener-diode rectification property because the two-dimensional electron gas tunnels through the narrow ZnMgO barrier under a reverse bias, thus decreasing the working p–n homojunction thickness from 500 nm to 265 nm. The ADB-modified homojunction shows higher carrier mobility in the Q device. The electroluminescence of the ZnO homojunction is improved in Q compared to S2, because the holes in p-type ZnO (Li, N) can cross the wide ZnMgO barrier under a forward bias voltage into the ZnO quantum well. Therefore, electron–hole recombination occurs in the narrow bandgap of n-type ZnO, creating an ultraviolet light-emitting diode using the ZnO homojunction.

Herein, a theranostic liposome (QSC-Lip) integrated with superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into one platform is constructed to target glioma under magnetic targeting (MT) for guiding surgical resection of glioma. Transmission electron microscopy and X-ray photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs in liposome. Besides, CGT is also effectively encapsulated into the liposome with an encapsulation efficiency of ∼88.9%. QSC-Lip exhibits a diameter of 100 ± 1.24 nm, zeta potential of -17.10 ± 0.11 mV, and good stability in several mediums. Moreover, each cargo shows a biphasic release pattern from QSC-Lip, a rapid initial release within initial 10 h followed by a sustained release. Cellular uptake of QSC-Lip is significantly enhanced by C6 cells under MT. In vivo dual-imaging studies show that QSC-Lip not only produces an obvious negative-contrast enhancement effect on glioma by magnetic resonance imaging but also makes tumor emitting fluorescence under MT. The dual-imaging of QSC-Lip guides the accurate resection of glioma by surgery. Besides, CGT is also specifically distributed to glioma after administration of QSC-Lip under MT, resulting in an effective inhibition of tumors. The integrated liposome may be a potential carrier for theranostics of tumor.

Using Vary-temperature Scanning Tunnelling Microscopy (VT-STM), the geometric and electronic structures of technological important Sr/Si(100)-2×3 surface were investigated. Two important findings explained in this research. First, a phenomenon similar to quantum corral observed in the empty state STM image that near the bottom of the conduction band. This is aroused from the surface vacancies and phase boundary in the Sr/Si(100)-2×3 surface. And a new Sr/Si(100)-2×6 reconstructed structure coexist with Sr/Si(100)-2×3 surface has been prepared by accurately controlling the annealing temperature, both surface’s geometric structures can be described by dimer vacancy model. Second, tip-induced band bending phenomenon was observed in the Sr/Si(100)-2×3 surface at substrate temperature range from 76K to 300K. Experimental LDOS results from n and p-type silicon substrate confirms 0.3eV up the motion of the valence band minimum compare with bare Si(100)-2×1 surface. Buckled and unbuckled silicon dimer coexisting in the Sr/Si(100)-2×3 reconstructed surface contribute to the tip-induced band bending and energy band gap widen phenomenon. Which confirms that Sr atoms transfer electrons to the nearby silicon dimers, make the first layer silicon dimers kept at unbuckled state. Published version

As soft and wet scaffolds, hydrogels are attractive materials for tissue engineering due to their similarity in structure and properties to living tissue. For designing hydrogels as potential artificial tissues, some basic requirements, such as a high level of cellular viability, suitable viscoelasticity, and high mechanical strength are required. However, it is difficult to develop a hydrogel that satisfies even two of these requirements at the same time. In this review, our recent advances in developing synthetic hydrogels as cell culture scaffold are summarized. We found that endothelial cells (ECs) can proliferate directly on some synthetic hydrogels with negative charge, so long as the hydrogels have a Zeta potential lower than c.a. -20mV, and the cell behavior can be controlled by adjusting the hydrogel's charge density. Furthermore, confluent EC monolayers cultured on the hydrogels show excellent platelet compatibility, compared to EC monolayer cultured on a polystyrene plate. On the basis of the above study, we have further developed micro-patterned hydrogels for selective cell spreading, proliferation, and orientation. We have also developed tough hydrogels on which cells show viability. These results will promote the potential applications of synthetic hydrogels in tissue engineering.

Five new chemiluminescent aryl acridiniumcarboxylate esters 6–10, with a linker group in an ortho- or meta-position of the phenoxy ring, have been synthesized. The ortho- derivatives 6, 7 and 9 show significant improvement in the quantum yield of chemiluminescence and slower chemiluminescence kinetics compared to the unsubstituted para- derivative, 1, while the ortho- derivative 8 shows quicker chemiluminescence kinetics and a lower quantum yield of chemiluminescence. The meta- derivative 10 shows similar chemiluminescent properties to that of its para-substituted analogue.

The effects of NO3- stress on the growth and the magnesium absorption of cucumber seedlings were investigated after 1 and 14 d of suboptimal temperature [18 °C/12 °C (day/night)] treatment. The results indicated that the growth, net photosynthetic rate, transpiration rate, Fv/Fm and ΦPSII of cucumber seedlings were significantly inhibited by NO3- stress under suboptimal temperature. The magnesium content of cucumber seedlings was also significantly decreased compared with control treatment, especially in the IV treatment (suboptimal temperature +140 mmol · L(-1) NO3- + 1 mmol · L(-1) Mg2+), and the antagonistic impact of magnesium ion absorption on the absorption of potassium and calcium ion was observed. The magnesium deficiency symptom of cucumber seedlings could be partly alleviated by increasing the concentration of magnesium ion in the nutrient solution.

Background microRNAs (miRs) have been reported to regulate cell biological functions. To explore the underlying mechanism of miR-21 involvement in patients with atrial fibrosis and atrial fibrillation (AF). Methods In total, 49 patients (24 AF, sinus rhythm 25) aged 33–68 years old, including heart valve replacement surgery and cardiac catheterisation. The pathological changes and collagen depositions was analysed by Masson’s Trichrome Staining. miR-21, TGF-β1, Smad2, p-Smad2, WWP-1, collagen I and collagen III expression were analysed by Western blotting, qRT-PCR, miR one step qRT-PCR, respectively. Treatment human cardiac fibroblasts with TGF-β1, qRT-PCR and Western blotting to find changes in miR-21, Smad2 and WWP-1 levels. Transfected human cardiac fibroblasts with miR-21 mimic and miR-21 inhibitor. Finally, cell proliferation ability was assessed by the MTT assay and flow cytometry. Results Compared to sinus rhythm (SR) group, the collagen volume fraction was significantly increased in AF patients. The levels of the TGF-β1, collagen I and collagen III were significantly elevated in AF group. In AF patients, the expression of miR-21 was increased, while the expression of WWP-1 was decreased. Transfected cardiac fibroblasts with miR-21 mimic increased miR-21 expression and decreased WWP-1 expression, whereas miR-21 inhibitor causes the opposite effects. Additionally, we demonstrated that knockdown miR-21 targeted up-regulation of WWP-1 may suppress cardiac fibroblasts proliferation. Conclusion These indicated that miR-21 inhibits cardiac fibroblasts proliferation by inactivating the TGF-β1/Smad2 signaling pathway via up-regulation of WWP-1.

Atrial fibrillation (AF) is the most common sustained arrhythmia. AF is a complex disease that results from genetic and environmental factors and their interactions. In recent years, numerous studies have shown that epigenetic mechanisms significantly participate in AF pathogenesis. Even though a poor understanding of the molecular and electrophysiologic mechanisms of AF, accumulated evidence has suggested that the relevance of epigenetic changes in the development of AF. The aim of this review is to describe the present knowledge about the epigenetic regulatory features significantly participates in AF, and look ahead on new perspectives of epigenetic mechanisms research. Epigenetic regulatory features such as DNA methylation, histone modification, and microRNA influence gene expression by epigenetic mechanisms and by directly binding to various factor response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of factors-induced epigenetic alterations as informative factors in the risk assessment process. In this review, new insight into the epigenetic mechanisms in AF pathogenesis is discussed, with special emphasis on DNA methylation, histone modification, and microRNA. Further studies are needed to reveal the potential targets of epigenetic mechanisms, and it can be developed as a therapeutic target for AF.

Malignant gliomas especially glioblastoma (GBM) are poorly responsive to the current treatments. Cilengitide (CGT) is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins avβ3 and avβ5 over-expressed on GBM cells. However, clinical translation of this therapy has been limited by issues including fast blood clearance, high kidney and liver uptake, poor blood-brain barrier (BBB) penetration, low tumor specificity and rapid washout from tumors. In this study, these issues were tackled in an integrated manner using a multi-stage strategy combining ultrasound-targeted microbubble destruction (UTMD) with CGT nanotherapy. CGT nanoparticles (CGT-NP) prepared using gelatin and Poloxamer 188-grafted heparin copolymer demonstrated significant apoptotic and cytotoxic effects in C6 GBM cells. Biodistribution study in a rat GBM model demonstrated buildup of high CGT level in tumors subjected to CGT-NP+UTMD combined therapy. The tumor CGT level in these animals was increased over 3-fold, tumor retention of CGT prolonged and renal clearance significantly reduced when compared with free CGT with or without UTMD. CGT-NP+UTMD treatment was further shown to extend the median survival period from less than 20days in the control and about 30days in free CGT group to about 80days. This was achieved with low CGT dosing level (2mg/kg twice weekly). In situ monitoring of GFAP, Ki67, caspase-3, Beclin-1, and LC-3 in the tumor samples together with TUNEL assay, transmission electron microscope imaging and Western blot assay all demonstrated high apoptotic and autophagy activities induced by the combined therapy. In conclusion, this study has provided extensive preclinical data supporting the use of this combined therapy to overcome the limitations of standard CGT treatment of gliomas.

Cardiac fibrosis is an important pathological feature of cardiac remodeling in heart diseases. The molecular mechanisms of cardiac fibrosis are unknown. Genomic analyses estimated that many noncoding DNA regions generate noncoding RNAs (ncRNAs). ncRNAs have emerged as key molecular players in the regulation of gene expression in different biological processes. Recent studies have started to reveal the importance of ncRNAs in heart development and suggest also an involvement in cardiac fibrosis. These molecules are emerging as important regulators of cellular process. Here, we review particularly focuses on the involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long noncoding RNAs (LncRNAs) in the regulation of cardiac fibrosis. Furthermore, we review the functions and role of ncRNAs in cardiac biology and discuss these reports and the therapeutic potential of ncRNAs for cardiac fibrosis associated with fibroblast activation and proliferation.

International audience; BACKGROUND:The widespread use of praziquantel for the treatment of schistosomiasis has led to concerns over the potential development of drug resistance. Therefore, the discovery of novel antischistosomal agents is imperative. In this study, a series of praziquantel and endoperoxide conjugates were synthesized and evaluated as potential antischistosomal agents.RESULTS:Some compounds exhibited high efficacy against both adult and juvenile Schistosoma, in in vitro studies. Structure-activity relationship (SAR) analysis revealed that compounds with amide bond linker and cyclopentyl adjacent to the 1,2,4,5-tetraxane pharmacophore displayed the highest efficacy. Overall, compounds showed consistent activity against Schistosoma japonicum and Schistosoma mansoni. In vivo study resulted in moderate but statistically significant activity.CONCLUSION:Important preliminary results were obtained from thorough activity evaluation of praziquantel-endoperoxide conjugates. Further pharmacokinetic property investigation is necessary to improve in vivo efficacy.

An efficient method for the synthesis of new benzimidazoline derivatives (IV) (18 examples) via a one-pot three-component reaction of phenylenediamines with aromatic aldehydes and Ar2O is given.

Objectives: Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. HDAC6 is a transcriptional regulator of the histone deacetylase family, subfamily 2. Previous studies have shown that HDAC6 plays critical roles in transcription regulation and proliferation events. However, the precise mechanisms of how HDAC is associated with cardiac fibrosis progression have not yet been elucidated. Methods: Fifty adult male Sprague-Dawley (SD) rats were randomly divided into two groups. Cardiac fibrosis was produced by common isoprenaline and cardiac fibroblasts were harvested from SD neonate rats and cultured. The expression of HDAC6, RASSF1A, α-SMA and collagen I were measured by Western blotting and qRT-PCR. Small interfering (si)RNA of HDAC6 affects the proliferation of cardiac fibroblasts and the regulation of RASSF1A/ERK1/2 signaling pathways. Results: In this study, we found that mRNA and protein levels of HDAC6 were upregulated in cardiac fibrosis tissues and activated cardiac fibroblast cells. Inhibition of HDAC6 by siRNA or the inhibitor tubacin attenuated the TGF-β1-induced myofibroblast markers. In contrast, HDAC6 knockdown using siRNA inhibited cardiac fibroblast cell proliferation. Furthermore, we demonstrated that knockdown of HDAC6 elevated RASSF1A expression in activated cardiac fibroblasts, and treatment of cardiac fibroblasts with the HDAC6 inhibitor tubacin also elevated RASSF1A expression. Conclusions: The results of this study suggest that a previously unknown mechanism of HDAC6 inactivation of RASSF1A controls cardiac fibroblast proliferation and fibrosis.

Cardiac fibroblast activation is a pivotal cellular event in cardiac fibrosis. Numerous studies have indicated that epigenetic modifications control cardiac fibroblast activation. Greater knowledge of the role of epigenetic modifications could improve understanding of the cardiac fibrosis pathogenesis.The aim of this review is to describe the present knowledge about the important role of non-coding RNA (ncRNA) transcripts in epigenetic gene regulation in cardiac fibrosis and looks ahead on new perspectives of epigenetic modification research. Furthermore, we will discuss examples of ncRNAs that interact with histone modification or DNA methylation to regulate gene expression.MicroRNAs (miRNAs) and long ncRNAs (lncRNAs) modulate several important aspects of function. Recently, some studies continue to find novel pathways, including the important role of ncRNA transcripts in epigenetic gene regulation. Targeting the miRNAs and lncRNAs can be a promising direction in cardiac fibrosis treatment. We discuss new perspectives of ncRNAs that interact with histone modification or DNA methylation to regulate gene expression, others that are targets of these epigenetic mechanisms. The emerging recognition of the diverse functions of ncRNAs in regulating gene expression by epigenetic mechanisms suggests that they may represent new targets for therapeutic intervention.

Ethnopharmacological relevance In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo. Materials and methods Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α were examined, respectively. Results HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2′-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-β1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions. Conclusion We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-β1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients.

The present study is the first investigation of the chemical composition, antioxidant, antimicrobial and anti-inflammatory activities of the stem and leaf essential oils from Piper flaviflorum C.DC (SEOP and LEOP), a plant that has been consumed as a wild vegetable, and used as medicine, and spice by the ethnic groups in Xishuangbanna, SW China. Analyzed by GC-MS, 42 and 30 components were identified representing 90.1% and 95.3% of the SEOP and LEOP, with (E)-nerolidol (16.7% and 40.5%), beta-caryophyllene (26.6% and 14.6%) and elixene (5.3% and 12.3%) as their main constituents, respectively. Our results indicate that SEOP and LEOP have good anti-inflammatory activity by significantly inhibiting NO production induced by LPS in RAW 264.7 cells at 0.04 per thousand without effect on cell viability, and negligible antioxidant activity in both ABTS and FRAP assays. Moreover, the LEOP showed comparable activity with the positive control (tigecycline) against Aspergillus fumigatus, with MIC and MBC values ranging from 256 to 1024 microg/mL. The anti-inflammatory activity in LPS-induced RAW 264.7 cells is worthy of further investigation to discover the possible mechanisms of the NO production inhibition effect of these essential oils.

The content of gamma-aminobutyric acid in the aerial part of Panax notoginseng in different productive area was determined by using high performance liquid chromatography. HPLC analysis was made on a C18 (4.6 mm x 250 mm,5 microm) with acetonitrile and water containing 4.1 g x L(-1) sodium acetate as mobile phase. The detection wavelength was 254 nm. The HPLC method showed good linearity within the range of 0.01 - 1.03 g x L(-1). The average recovery of GABA in the stems and leaves of P. notoginseng and the flowers of P. notoginseng was 101.7% (RSD 1.1%, n = 3) and 97.3% (RSD 0.38%, n = 3), respectively. The contents of GABA in the samples of different productive areas were not significant different, and the average contents of GABA in the stems and leaves of P. notoginseng and the flowers of P. notoginseng were 0.49% and 0.53%. This method was simple and reliable, and it was suitable for the determination of gamma-aminobutyric acid in the aerial part of P. notoginseng.

Colorectal cancer is a major health problem worldwide. The aim of this study was to determine a role of microRNA-21 (miRNA-21) in colorectal cancer (CRC) and to elucidate miRNA-21 regulation of hTERT by phosphatase and tensin homologue (PTEN). Protein and mRNA samples were extracted with 30 CRC samples and one CRC cell lines. The expression of miRNA-21, hTERT, PTEN in CRC tissues and CRC cell lines was measured by real-time fluorescent quantitative PCR, Western blotting. Cell viability was detected by MTT and cell cycle assay. In this study, we show that the expression of miRNA-21 was overexpressed in CRC tissue and CRC cell lines compared with the control group. The effects of miRNA-21 were then assessed in MTT assays through in vitro transfection with a miRNA-21 mimic or inhibitor. PTEN has been identified as a target gene of miRNA-21 in CRC cell lines. Moreover, Western blot and qRT-PCR analyses revealed that miRNA-21 increased the expression of human telomerase reverse transcriptase (hTERT) via the PTEN/ERK1/2. In addition, Western blot analyses confirmed that an inverse correlation between PTEN and hTERT levels of high miRNA-21 RNA-expressing CRC tissues and cell lines. Finally, these data indicate that miRNA-21 regulates hTERT expression via the PTEN/ERK1/2 signaling pathway, therefore controlling CRC cell line growth. MiRNA-21 may serve as a novel therapeutic target in CRC.

We have previously reported that enhanced excitability of dorsal root ganglia (DRG) neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R) sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

Detection and direction finding of illegal emission source is the core issue of radio monitoring network. However, the performances of traditional fixed stations and mobile stations which are based on energy detection and work individually are often compromised with multipath fading and shadowing in urban environment. To mitigate the impact of these issues, a cooperative compressed spectrum sensing model which consists of several sensing nodes and a fusion node is proposed in this paper. The maximum-minimum eigenvalue based detection method is applied to the sensing model. Simulation results show that cooperative compressed sensing provides an efficient way to sense radio signal which is sparse at frequency domain.

Protein phosphatase 2A (PP2A) negatively regulates tumorigenic signaling pathways, in part, by supporting the function of tumor suppressors like p53. The PP2A methylesterase PME-1 limits the activity of PP2A by demethylating its catalytic subunit. Here, we report the finding that PME-1 overexpression correlates with increased cell proliferation and invasive phenotypes in endometrial adenocarcinoma cells, where it helps maintain activated ERK and Akt by inhibiting PP2A. We obtained evidence that PME-1 could bind and regulate protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related protein phosphatase 6 (PP6). When the PP2A, PP4, or PP6 catalytic subunits were overexpressed, inhibiting PME-1 was sufficient to limit cell proliferation. In clinical specimens of endometrial adenocarcinoma, PME-1 levels were increased and we found that PME-1 overexpression was sufficient to drive tumor growth in a xenograft model of the disease. Our findings identify PME-1 as a modifier of malignant development and suggest its candidacy as a diagnostic marker and as a therapeutic target in endometrial cancer. Cancer Res; 74(16); 4295–305. ©2014 AACR.

Cardiac fibrosis is characterized by net accumulation of extracellular matrix (ECM) proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. More specifically, cardiac fibroblasts are activated by a variety of pathological stimuli, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of cardiac fibrosis. DNA methylation is an important epigenetic mechanism, which often occurs in response to environmental stimuli and is crucial in regulating gene expression. The aberrant methylation of CpG island promoters of selected genes is the prominent epigenetic mechanism by which gene transcription can be effectively silenced. Aberrant hypermethylation of a few selected genes such as RASSF1A plays an important role in facilitating fibrotic fibroblast activation and in driving fibrosis. In this review we will discuss the mechanisms of DNA methylation and their implications for cardiac fibroblasts activation and fibrosis. Control of DNA methylation may serve as a new strategy for anti-fibrotic therapy.

Bacillus subtilis XF-1 has been used as a biocontrol agent of clubroot disease of crucifers infected by Plasmodiophora brassicae, an obligate pathogen. In order to maximize the growth inhibition of the pathogen, random mutagenesis using N-methyl-N′-nitro-N-nitrosoguanidine was applied to strain XF-1. The efficacy of 226 selected mutants was assessed against the growth of an indicator fungal pathogen: Fusarium solani using agar plate assay and the disruptive effects on the resting spores of P. brassicae. Four mutants exhibited inhibition activity significantly higher than the wild type. The cell extracts of these mutants and the XF-1 were subjected to matrix-assisted laser desorption ionization-time of flight mass spectra analysis, and three families of cyclic lipopeptides (CLPs) fengycin, surfactin and iturin were identified from the parental strain and the screened mutants. However, the relative contents and compound diversity changed after mutagenesis, and there was slight variation in the surfactin and fengycin. Notably, only 5 iturin components were discovered from the wild strain XF-1, but 13 were obtained from the mutant strains, and the relative CLPs contents of all mutant strains increased substantially. The results suggested that CLPs might be one of main biocontrol mechanisms of the clubroot disease by XF-1. The 4 mutants are far more effective than the parental strain, and they would be promising biocontrol candidates not only against P. brassicae but probably other plant diseases caused by fungi. Electronic supplementary material The online version of this article (doi:10.1007/s12088-014-0471-y) contains supplementary material, which is available to authorized users.

MicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of cardiac hypertrophy [(1)][1]. However, the precise mechanisms of miRNA-29a in cardiac hypertrophy are still unclear. A recent report in the Journal by Roncarati et al. [(2)][2] indicated that correlation

Cardiac fibrosis contributes to the pathogenesis of atrial fibrillation (AF). The molecular mechanisms underlying the cardiac fibrosis remain unclear. However, Ras association domain family 1 isoform A (RASSF1A) is a regulatory tumor suppressor, which is important for pathogenesis of cardiac fibrosis and fibroblasts activation. Moreover, DNA methylation plays a central role in the maintenance of cardiac fibrosis. DNA methyltransferases 3A (DNMT3A) is a critical participant in the epigenetic silencing of regulatory genes. Here, we report that the downregulation of RASSF1A in cardiac fibrosis is associated with DNMT3A. Treatment of cardiac fibroblasts with DNMT3A inhibitor 5-AzadC blocked proliferation. 5-AzadC also prevented the loss of RASSF1A expression that occurs during activated cardiac fibroblasts. To determine the underlying molecular mechanisms, we hypothesized that cardiac fibrosis is controlled by DNMT3A. We demonstrated that downregulation of RASSF1A is associated with cardiac fibrosis and fibroblasts activation. Knockdown of DNMT3A elevated RASSF1A expression in activated cardiac fibroblasts. Moreover, we investigated the effect of RASSF1A on the Ras/ERK pathway. Upregulation of p-ERK1/2 was detected in activated cardiac fibroblasts with decreased RASSF1A expression. Our results have shown that DNMT3A likely plays an essential role in RASSF1A mediated upregulation of ERK1/2 in rat cardiac fibrosis. DNMT3A and RASSF1A may serve as a new mechanism for cardiac fibrosis.

Substituted aryl acridinium esters, 2,6-dimethyl-4-(2-succinimidyloxycarbonylethyl)phenyl 10-methylacridinium-9-carboxylate trifluoromethanesulphonate (3), 2,6-dimethoxy-4-(2-succinimidyloxycarbonylethyl)phenyl 10-methylacridinium-9-carboxylate trifluoromethanesulphonate (4), 2-methoxy-4-(2-succinimidyloxycarbonylethyl)phenyl 10-methylacridinium-9-carboxylate trifluoromethanesulphonate (5) and 2,6-dibromo-4-(2-succinimidyloxycarbonylethyl)phenyl 10-methylacridinium-9-carboxylate trifluoromethanesulphonate (6), have been synthesised and coupled to immunoglobulinG(IgG). The chemiluminescent properties and hydrolytic stabilities of the conjugates have also been examined. The different substituents on the phenoxy ring affected the chemiluminescent efficiency and kinetics. All the human IgG conjugates of these substituted acridinium esters demonstrated much higher stability than the conjugate of the corresponding unsubstituted acridinium ester

Synthetic routes to S-(trifluoromethyl)phenyl-4-fluorophenylsulfonium triflate (8), S-(trifluoromethyl)phenyl-2,4-difluorophenylsulfonium triflate (9), S-(trifluoromethyl)phenyl-3-nitrophenylsulfonium triflate (10), and S-(trifluoromethyl)-4-fluorophenyl-3-nitrophenylsulfonium triflate (11) are described. They are stable molecules and conveniently prepared by treating phenyl trifluoromethyl sulfoxide with benzene and its derivatives. These novel electrophilic trifluoromethylating agents react under mild conditions with a variety of aromatic rings (p-hydroquinone, pyrrole, and aniline) to give trifluoromethylated compounds (2-trifluoromethyl-p-hydroquinone, 2-trifluoromethylpyrrole, 2-trifluoromethylaniline, and 4-trifluoromethylaniline) in moderate to high yields. The electrophilic trifluoromethylating potential can be altered by placing electron-withdrawing substituents on the benzene rings.