Anthracycline chemicals with anthracyclinone structure exert antitumor effects by inhibiting angiogenesis and lymphangiogenesis in a xenografted gastric tumor model.

BACKGROUND: It is vital to screen or develop alternative therapeutic drugs with higher curative characteristics and fewer side effects for the clinical treatment of gastric cancer. METHODS: Gastric cancer cells were exposed to different auramycin G doses while determining the impact on cell viability, migration, and invasion. Then the antitumor effects of auramycin G, 5-fluorouracil (5-Fu) and their combination were evaluated. Furthermore, the molecular mechanisms of angiogenesis and lymphangiogenesis regulated by auramycin G and its analogs were investigated. RESULTS: Auramycin G inhibited cell viability in a dose-dependent manner, with a 50% inhibitory concentration of 23.72 ± 6.36 mg/L and 32.54 ± 5.91 mg/L for AGS and MGC803 cells, respectively. The migration and invasion of gastric cancer cells were significantly inhibited by 10 mg/L auramycin G, which was consistent with the down-regulation of the VEGFR2-VEGFA-pPI3K-pAkt-pErk1 and VEGFR3-VEGFC-pPI3K-pAkt-pmTOR proteins. Notably, the average tumor weights were significantly reduced in both the auramycin G (2.21 ± 0.45 g) of 50 mg/kg body weight and auramycin G + 5-fluorouracil (5-Fu) groups (1.33 ± 0.28 g), compared with the control (3.73 ± 0.56 g). Considering that auramycin G decreased the growth of blood and lymphatic vessels while reducing the degree of tumor malignancy, it effectively suppressed tumors by regulating the angiogenic and lymphangiogenic pathways. CONCLUSION: The present study confirmed that auramycin G displayed a prominent antitumor activity in gastric tumor models, both in vitro and in vivo. Moreover, it was confirmed that auramycin G played a specific role in certain gastric cancer cell types, while the mechanism was validated to be associated with angiogenesis- and lymphangiogenesis-related pathway suppression.

Bone marrow mesenchymal stem cells inhibit cardiac hypertrophy by enhancing FoxO1 transcription.

Bone marrow-derived mesenchymal stem cells (BMSCs) have therapeutic potential for certain heart diseases. Previous studies have shown that stem cells inhibit cardiac hypertrophy; however, it is necessary to explore the mechanisms underlying this effect. This study aimed to investigate the possible mechanism underlying the inhibitory effect of BMSCs on cardiomyocyte hypertrophy. We induced cardiomyocyte hypertrophy in cultured rat cells through isoproterenol (ISO) treatment with or without BMSC coculture. A microarray was performed to analyze messenger RNA expression in response to ISO treatment and BMSC coculture. Pathway enrichment analysis showed that the expression of differential genes was closely related to the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and that the expression of forkhead box O 1 (FoxO1) was significantly increased in the presence of BMSCs. Furthermore, we determined the expression levels of p-AMPK/AMPK and p-FoxO1/FoxO1 by western blot analysis. The expression of p-AMPK/AMPK was upregulated, whereas that of p-FoxO1/FoxO1 was downregulated upon coculturing with BMSCs. The AMPK-specific antagonist Compound C inhibited the downregulation of p-FoxO1/FoxO1 induced by the BMSC coculture. Furthermore, treatment with the specific FoxO1 antagonist AS1842856 reduced the inhibitory effects of BMSCs on cardiomyocyte hypertrophy in vivo and in vitro. Our present study demonstrates the inhibition of cardiomyocyte hypertrophy by BMSCs, which occurs partly through the AMPK-FoxO1 signaling pathway.

CREB/Wnt10b mediates the effect of COX-2 on promoting BMP9-induced osteogenic differentiation via reducing adipogenic differentiation in mesenchymal stem cells.

Bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic factors, which may be a potential candidate for bone tissue engineering. However, the osteogenic capacity of BMP9 still need to be further enhanced. In this study, we determined the effect of Wnt10b on BMP9-induced osteogenic differentiation in mesenchymal stem cell (MSCs) and the possible mechanism underlying this process. We introduced the polymerase chain reaction (PCR), Western blot analysis, histochemical stain, ectopic bone formation, and microcomputed tomography analysis to evaluate the effect of Wnt10b on BMP9-induced osteogenic differentiation. Meanwhile, PCR, Western blot analysis, chromatin immunoprecipitation, and immunoprecipitation were used to analyze the possible relationship between BMP9 and Wnt10b. We found that BMP9 upregulates Wnt10b in C3H10T1/2 cells. Wnt10b increases the osteogenic markers and bone formation induced by BMP9 in C3H10T1/2 cells, and silencing Wnt10b decreases these effects of BMP9. Meanwhile, Wnt10b enhances the level of phosphorylated Smad1/5/8 (p-Smad1/5/8) induced by BMP9, which can be reduced by silencing Wnt10b. On the contrary, Wnt10b inhibits adipogenic markers induced by BMP9, which can be decreased by silencing Wnt10b. Further analysis indicated that BMP9 upregulates cyclooxygenase-2 (COX-2) and phosphorylation of cAMP-responsive element binding (p-CREB) simultaneously. COX-2 potentiates the effect of BMP9 on increasing p-CREB and Wnt10b, while silencing COX-2 decreases these effects. p-CREB interacts with p-Smad1/5/8 to bind the promoter of Wnt10b in C3H10T1/2 cells. Our findings suggested that Wnt10b can promote BMP9-induced osteogenic differentiation in MSCs, which may be mediated through enhancing BMP/Smad signal and reducing adipogenic differentiation; BMP9 may upregulate Wnt10b via the COX-2/p-CREB-dependent manner.

Stimulated emission in GaN-based laser diodes far below the threshold region.

We identify that the stimulated emission of GaN laser diodes (LDs) emerges far below the traditionally recognized threshold from both optical and electrical experiments. Below the threshold, the linear-polarized stimulated emission has been the dominating part of overall emission and closely related to resonant cavity. Its intensity increases super linearly with current while that of spontaneous emission increases almost linearly. Moreover, the separation of quasi-Fermi levels of electrons and holes across the active region has already exceeded the photon emission energy, namely, realized the population-inversion.

Ferric phosphate hydroxide microcrystals for highly efficient visible-light-driven photocatalysts.

Fe4(OH)3(PO4)3 microcrystals are successfully synthesized by a simple hydrothermal method. Due to a possible self-etching mechanism, different morphologies of Fe4(OH)3(PO4)3 microcrystals are obtained. Several reactions with different temperatures and times are performed to confirm the supposed self-etching mechanism. Moreover, as a result of their different micro/nanostructures, these microcrystals present different photocatalytic activities for visible-light-driven photodegragadation of methylene blue.

Rational design of hierarchically nanostructured NiTe@CoxSy composites for hybrid supercapacitors with impressive rate capability and robust cycling durableness.

The hierarchically nanostructured NiTe@CoxSy composites are constructed on a foamed nickel substrate by a two-step electrode preparation process. Structural characterization shows the dense growing of CoxSy nanosheets around NiTe nanorods forms a hierarchical nanostructure which possesses synergetic effects from both compositional and structural complementarity, more pathways for ion/electrolyte transport, richer redox active sites, and better conductivity. Thanks to the rational design of this hierarchical structure, NiTe@CoxSy delivers a high areal capacitance of 7.7F cm-2 at 3 mA cm-2 and achieves the improved capacitance retention of 97.9% after 10,000 cycles. Of particular importance is the successful fabrication of NiTe@CoxSy//activated carbon hybrid supercapacitors. This hybrid device has a wide operating voltage window, high areal energy density of 0.48 mWh cm-2 at 2.55 mW cm-2, impressive rate capability of 62.3% even after a 20-fold increase of the current density, and a 115.1% of initial capacitance retention after 15,000 cycles. Meanwhile, two tandem such hybrid devices can easily drive a pair of mini fans or light up a heart-like pattern assembled by 10 red LEDs. These experimental results not only demonstrate that the hierarchically nanostructured NiTe@CoxSy composites can serve as a prospective candidate electrode; but also develop a novel strategy about how to achieve high-performance stockpile equipment by rationale designing a desirable nanostructures.

CQMUH-011 Inhibits LPS-Induced Microglia Activation and Ameliorates Brain Ischemic Injury in Mice.

Excessive microglial activation-mediated neuroinflammation is closely involved in the pathogenesis of several neurological diseases. CQMUH-011, as a novel adamantane sulfonamide compound, has been shown anti-inflammatory properties in activated macrophages (RAW264.7). However, the role of CQMUH-011 in microglial activation-induced neuroinflammation and neuroprotective properties has yet to be elucidated. In the present study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-stimulated primary microglia in vitro and transient middle cerebral artery occlusion (t-MCAO)-induced acute cerebral ischemia/reperfusion (I/R) injury in vivo. The results demonstrated that CQMUH-011 significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß by LPS-stimulated primary microglia. In addition, CQMUH-011 inhibited the proliferation of activated microglia by arresting the cell cycle at the G1/S phase accompanied by downregulating the expression of cell cycle regulatory proteins such as proliferating cell nuclear antigen (PCNA) and cyclin D1. CQMUH-011 was seen to induce apoptosis in activated microglia by regulating the expression of Bax and Bcl-2. Furthermore, CQMUH-011 markedly attenuated the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) as well as the phosphorylation levels of nuclear factor-kappa (NF-κB) subunit p65, inhibitory kappa B-alpha (IκBα), and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK) and p38 kinases. In vivo, CQMUH-011 administration significantly improved neurological function and infarct volume, and ameliorated the inflammatory cytokines and microglia amount around the injury site of mice. In conclusion, these results suggested that CQMUH-011 has a notable anti-inflammatory effect and protects mice from I/R injure. Thus, CQMUH-011 may be a candidate drug for the treatment of cerebral ischemia patients.

[Study of rotator phase and phase transition of short-chain alkane by means of Raman spectroscopy].

Raman spectroscopy was used to investigate the phase transition of n-hexacosane for real-time cooling run. In the cooling process, the n-hexacosane experienced the melt phase --> rotator phase --> monoclinic crystal phase transition. The changes in band intensity and frequency in the CH2 bending, CH2 twisting, skeletal C-C stretching, and CH3 rocking regions were mainly analyzed in order to know the changing sequence and process of these vibrational modes, and to reflect the relationship between these vibrational modes and molecular structure. Besides, the changes in band intensity and frequency revealed both transitions, particularly when using band components related to gauche bonds. Our research shows that Raman spectroscopy is an effective tool to monitor the phase transition of n-alkanes or even long-chain polymers. In addition, by analyzing the Raman peaks in 800-1 500 cm(-1) in the cooling process of n-hexacosane, the temperature range of rotator phase was obtained, proving that Raman spectroscopy can be used to observe the rotator phase occurring during the phase transition of paraffin.

In Situ Preparation of Amphibious ZnO Quantum Dots with Blue Fluorescence Based on Hyperbranched Polymers and their Application in Bio-Imaging.

A new strategy for preparing amphibious ZnO quantum dots (QDs) with blue fluorescence within hyper-branched poly(ethylenimine)s (HPEI) was proposed in this paper. By changing [Zn2+]/[OH-] molar ratio and heating time, ZnO QDs with a quantum yields (QY) of 30% in ethanol were obtained. Benefiting from the amphibious property of HPEI, the ZnO/HPEI nanocomposites in ethanol could be dissolved in chloroform and water, acquiring a QY of 53%, chloroform and 11% in water. By this strategy, the ZnO/HPEI nano-composites could be applied in not only in optoelectronics, but also biomedical fields (such as bio-imaging and gene transfection). The bio-imaging application of water-soluble ZnO/HPEI nanocomposites was investigated and it was found that they could easily be endocytosed by the COS-7 cells, without transfection reagent, and they exhibited excellent biological imaging behavior.

[Study of reference and order parameter of Raman spectroscopy research on alkane phase transition].

Raman spectroscopy was used to investigate the order-disorder phase transition of n-eicosane for real-time cooling run. At the phase transition temperature, the integrated intensity of the 1 300 cm(-1) spectra range changes greatly, which requires further consideration of 1 300 cm(-1) as a reference in the research on polymer and biomembrane using Raman spectroscopy. The experiment support was provided for doubt about order parameter based on 1 130 cm(-1) that it did not refer to generally accepted interpretation of an order parameter and it proved that the order definition could just be used as a relative measure method for disorder.

[Low-temperature-dependent Raman study on A1 (LO) mode of 6H-SiC].

Variable temperature method was lent for low temperature Raman study on bulk monocrystal 6H-SiC in the temperature range from 80 to 320 K. Some Raman folding modes of 6H-SiC were assigned in the spectrum. The peak position and line width of optical phonon A1 (LO) versus temperature mainly below RT was focused on by 3-phonon and 4-phonon models. The result showed that as the temperature decreased the line width decreased, while the peak position shifted to high wave number. It was found that as the temperature varied below 160 K, the change in peak position and line width was little, different from it was at RT, revealing that the line type of A1 (LO) mode was mainly decided by the phonon characteristics and the effect of temperature could be ignored when it was below 160 K. It was showed that 4-phonon model was closer to the experiment data for fitting. Both the third and forth anharmonic vibration contributed to the spectrum, while the former was the main process. Moreover, the phonon lifetime became longer when the temperature fell because of the decrease in the atomic thermal motion.

[Research on AlInGaN quaternary alloys as MQW barriers in GaN-based laser diodes].

InGaN/GaN, InGaN/InGaN and InGaN/AlInGaN multi-quantum-well (MQW) laser diodes (LDs) were grown on (0001) sapphire substrate by metalorganic chemical vapor deposition (MOCVD). The GaN (0002) synchrotron X-ray diffraction (XRD), electroluminescence (EL) and optical power-current (L-I) measurement reveal that AlInGaN quaternary alloys as barriers in MQWs can improve the crystal quality, optical emission performance, threshold current and slope efficiency of the laser diode structure to a large extent compared with other barriers. The relevant mechanisms are that: 1. The Al component increases the barrier height of the MQWs so that more current carriers will be caught in. 2. The In component counteracts the strain in the MQWs that decreases the dislocations and defects, thereby the nonradiative recombination centers are decreased. 3. The In component decreases the piezoelectric electric field that makes the electrons and the holes recombine more easily.

Changes in the levels of 12/15-lipoxygenase, apoptosis-related proteins and inflammatory factors in the cortex of diabetic rats and the neuroprotection of baicalein.

This study was designed to investigate the neuroprotective effects of baicalein and the effect of the cortical 12/15-lipoxygenase (12/15-LOX) pathway on diabetic cognitive dysfunction. Our results showed that spatial learning and memory ability, as well as cortex neurons, were significantly impaired after the onset of diabetes. The fasting blood glucose and random blood glucose levels in the model group were significantly higher than those in the normal group. The levels of TG and TC in the plasma of the model group were significantly increased, but there was no significant difference in the LDL level. The insulin content in the plasma of diabetic rats was significantly lower than that of the normal group. The levels of inflammatory factors and 12(S)-HETE were significantly increased in diabetic rats, as were the protein expression levels of cPLA2, 12/15-LOX, p38MAPK, phospho-p38MAPK, caspase-3, caspase-9 and Aß1-42; by contrast, protein expression of Bcl-2 was significantly decreased. Administration of baicalein was shown to improve the spatial learning and memory ability and significantly decrease the levels of inflammatory cytokines. However, baicalein did not significantly influence the levels of blood glucose, lipids or insulin in rats. Baicalein treatment significantly protected diabetes rats from neuron death; significantly attenuated the overexpression of cPLA2, 12/15-LOX, p38MAPK, phospho-p38MAPK, caspase-3, caspase-9 and Aß1-42; and upregulated the expression of Bcl-2. These findings suggest that baicalein improves the cognitive function of diabetic rats by directly acting in the brain rather than by regulating the levels of blood glucose, lipids or insulin. In addition, baicalein can protect rat cortical neurons from damage caused by diabetes via inhibiting the 12/15-LOX pathway and relieving inflammation and apoptosis of the central nervous system.

Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat.

The present study was designed to observe the effect of COX2/PGD2-related autophagy on brain injury in type 2 diabetes rats. The histopathology was detected by haematoxylin-eosin staining. The learning and memory functions were evaluated by Morris water maze. The levels of insulin and PGD2 were measured by enzyme-linked immunosorbent assay. The expressions of COX2, p-AKT(S473), p-AMPK(T172), Aß, Beclin1, LC3BII, and p62 were measured by immunohistochemistry and Western blotting. In model rats, we found that the body weight was significantly decreased, the blood glucose levels were significantly increased, the plasma insulin content was significantly decreased, the learning and memory functions were impaired and the cortex and hippocampus neurons showed significant nuclear pyknosis. The levels of COX2, p-AKT(S473), PGD2, Aß, Beclin1 and p62 were significantly increased, whereas the expression of p-AMPK(T172) and LC3BII was significantly decreased in the cortex and hippocampus of model rats. In meloxicam-treated rats, the body weight, blood glucose and the content of plasma insulin did not significantly change, the learning and memory functions were improved and nuclear pyknosis was improved in the cortex and hippocampus neurons. The expression of p-AMPK(T172), Beclin1 and LC3BII was significantly increased, and the levels of COX2, p-AKT(S473), PGD2, Aß, and p62 were significantly decreased in the cortex and hippocampus of meloxicam-treated rats. Our results suggested that the inhibition of COX2/PGD2-related autophagy was involved in the mechanism of brain injury caused by type 2 diabetes in rats.

[A Raman study of ZnO powders with ZnO2 as precursor].

Raman spectra of ZnO powders prepared by firing ZnO2 precipitate were reported in detail for the first time. By comparing the spectra with that of the sample fabricated by another method and analyzing frequency difference between the focused-laser irradiated samples with different firing temperature in preparation, it was concluded that the -333 cm(-1) peak is ascribed to E2 (high)-E2 (low) and the -661 cm(-1) peak to its overtone. In addition, a new interpretation for the observed Raman peaks between 400 and 500 cm(-1) in ZnO2 powders was presented based on the IR data and ab initio calculation.

[Effect of the film of gold nanowire arrays on surface enhanced Raman scattering].

Metal nanowire arrays as surface-enhanced Raman scattering substrate, could bring high enhancement effect. According to the electromagnetic enhancement theory, the high enhancement factors come from the strong electromagnetic coupling between nanowires in the arrays. Gold nanowire arrays and gold nanobrushes were prepared by electro-deposition of gold into alumina template coated with gold film, then chemically etching alumina directly or rubbing gold film and chemically etching alumina. SEM showed the nanowires around 60 nm in diameter with length around 600 nm in the nanobrushes. In the gold nanobrushes, local nanowires collect in bundles after complete dissolution of alumina matrix due to the transverse tension during drying in the air. The two kinds of samples are different in structure. But optical transmission measurements of the two samples in the direction perpendicular to the substrate both showed plasma-enhanced absorption around 640-650 nm. The authors choose 4-mercaptopyridine (4-MP) as the probe molecules because 4-MP chemically adsorb on Au nanowires tightly by monolayer and align perpendicular to Au surface. SERS experiments were performend with a 632.8 nm laser. SERS signals come from the back scattering of the incident light propagating perpendicular to the Au substrates. And the Raman spectra were collected at morethan 10 different points on each sample. A strong, locally inhomogeneous surface-enhanced Raman spectrum of 4-MP adsorbed on Au nanobrushes with enhancement factor as high as 1 x 10(6) was observed. At the same time, SERS of 4-MP from the gold nanowire arrays under the same experiment conditions showed the enhancement factor around 10(2). Considering the optical transmission measurements of the two samples, the enhancement factors both come from resonance field enhancement. According to the difference of the two kinds of samples, the higher enhancement factors of gold nanobrushes are related with the gold film. According to the localization theory of electromagnetic field, the field around the upper part of the nanowires of the nanobrushes is far stronger than that of the bottom part and on the film. So the gold film introduced higher enhancement factors in SERS The spectrum of 4-MP also showed that the CT mechanism affects the enhancement factors.

Amidoselenation and Amidotelluration of Alkenes using Oxygen as Terminal Oxidant.

A protocol has been established for oxygen-mediated amidoselenation and amidotelluration of alkenes under mild conditions. This method provides a simple route to a series of structurally diverse ß-amido selenides and ß-amido tellurides in moderate to high yields. The wide substrate scope, good functional group tolerance, ease of large-scale preparation and potential for product derivatization make this reaction attractive for the synthesis of nitrogen-, selenium- and tellurium-containing molecules.

Self-template synthesis of hollow ellipsoid Ni-Mn sulfides for supercapacitors, electrocatalytic oxidation of glucose and water treatment.

In this work, we have successfully developed a simple self-template route for preparation of hollow ellipsoid Ni-Mn sulfides. This route involves the synthesis of solid Ni-Mn ellipsoids via a chemical precipitation method. Then, using thioacetamide (TAA) as the sulfur source, the solid Ni-Mn ellipsoids can be easily converted to hollow ellipsoid Ni-Mn sulfides in ethanol via sulfidation reaction. The as-synthesized hollow ellipsoid Ni-Mn sulfides possess large specific surface areas and porous structures. Benefiting from these structural and compositional advantages, the electrochemical performance of the hollow ellipsoid Ni-Mn sulfides is studied. As expected, the hollow ellipsoid Ni-Mn sulfides show a high specific capacitance of 1636.8 F g-1 at 2.0 A g-1 and good cycling stability (only 4.9% loss after 4000 cycles) as electrode materials for supercapacitors. Furthermore, electrocatalytic oxidation of glucose based on the synthesized hollow ellipsoid Ni-Mn sulfides is also performed. The hollow ellipsoid Ni-Mn sulfides present high sensitivity and selectivity, good stability and a low detection limit (0.02 µM). In addition, the as-synthesized hollow ellipsoid Ni-Mn sulfides exhibit good ability to remove the Congo red dyes from water, which gives them potential application in water treatment. The current work makes a major contribution to the design and preparation of hollow metal sulfide structures, as well as their potential applications in supercapacitors, electrocatalytic oxidation of glucose and water treatment.

Novel shape evolution of BaMoO4 microcrystals.

Dendritic BaMoO(4) microcrystals with lengths of about 5-15 microm were synthesized simply under ambient conditions by a microemulsion-mediated method within an ultrashort time. The products were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and field-emission scanning electron microscopy (FESEM), which showed that the products were in pure tetragonal BaMoO(4) structure and that an individual dendrite had a long central stem with four array shrunken branches. Detailed studies revealed that the formation of these 3-D structures was strongly dependent on the composition of the microemulsion. At prolonged aging time, the dendrites evolved into rods and further into particles, driven by the lattice distortion energy required to evolve the crystal from a metastable to a stable state. This novel crystal shape evolution provides insight into crystallization behavior given that the growth history and shape evolution process have traditionally been poorly understood.

Synthesis of single crystal CdMoO4 octahedral microparticles via microemulsion-mediated route.

The single crystal octahedra of tetragonal CdMoO4 were synthesized on large scale via a microemulsion-mediated hydrothermal route at 120 degrees C for 10 h. The structures, compositions and morphologies of the as-prepared products were characterized by X-ray power diffraction pattern, field emission scanning electronic microscopy, transmission electron microscopy. Further studies reveal that the octahedral CdMoO4 crystal has eight equivalent exposed crystal faces {101}. The possible growth mechanism of the CdMoO4 octahedral is based on the anisotropic growth habit of CdMoO4 crystals and the selective absorption of surfactant molecules CTAB on the faces of the prime crystals, and the reaction time, composition of the microemulsions and temperature have considerable effects on the final morphology of CdMoO4.