[Analysis of the Design and Renovation of Mid-sized Hospital's Local Area Network]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Nov, 2011  |  Pubmed ID: 22379781

To address several hospital network issues, this paper discusses the overall plan, design and renovation of hospital's Local Area Network, making full use of existing network facilities. The techniques, such as Physical Separation of Internal and External Network, HSRP, OSPF, All-Routers Networking Model, etc., create features of extensibility, manageability, high safety, stability and so on to the overall network, and provide a reliable network platform to the function of the information systems.

[Effect of YXXM Motif on Viral Replication of Subgroup J Avian Leukosis Virus]

Wei Sheng Wu Xue Bao = Acta Microbiologica Sinica. Dec, 2011  |  Pubmed ID: 22379808

It was reported that subgroup J avian leukosis virus strain NX0101 activates PI3K/Akt pathway during early infection in DF-1 cells. Whether there is YXXM motif in the amino acid sequence of NX0101 and the function of YXXM motif were studied.

[Compliance of Film-coated Praziquantel Tablets in Schistosomiasis Transmission-controlled Areas]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379821

To observe the compliance of film-coated praziquantel tablets in the schistosomiasis transmission controlled areas, so as to provide the evidence for the establishment of chemotherapy intervention measures in these areas.

[Quantitative Detection and Species Identificaton of Human Plasmodium Spp. by Using SYBR Green I Based Real-time PCR]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379826

To develop a real-time PCR method for human Plasmodium spp. qantitative detection and species identificaton.

[Cloning, Expression and Evaluation on Effect in Serological Diagnosis of Cysteine Protease of Clonorchis Sinensis]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379827

To clone and express the cysteine protease of Clonorchis sinensis and evaluate its effect on immunodiagnosis of human clonorchiasis.

[Surveillance and Forecast of Schistosomiasis Transmission in Chaohu Lake Area in Anhui Province, 2008-2010]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379830

To understand the dynamic changes of the potential prevalent factors of schistosomiasis in Chaohu Lake area so as to provide forecast information on the outbreak of schistosomiasis in the area.

[Health Education Needs for Malaria Control in Rural Residents in Hai'an County]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379834

To understand the status of knowledge, attitudes and practices (KAP) and health education needs for malaria prevention and treatment of rural residents in Hai'an County.

[Analysis of Imported Falciparum Malaria Cases of Nantong City from 2001 to 2010]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379835

OBJECTIVE: To analyze the characteristics of imported falciparum malaria cases of Nantong City in the recent ten years so as to provide the evidence for improving prevention and control of malaria in the future. METHODS: The data about imported falciparum malaria cases of Nantong City from 2001 to 2010 were collected and analyzed for the characteristics and distribution of the patients by the retrospective method. RESULTS; There were 79 imported falciparum malaria cases in the last 10 years. Totally 96.2% of patients were infected in Africa. Most of them were young people and worked for the construction services. Seasonal distribution difference was not obvious. CONCLUSIONS; The imported falciparum malaria epidemic is rising in Nantong City. Therefore, we should strengthen the anti-malaria health education to increase the self-protection of labors, and strengthen the training of medical stuff and also strengthen the monitoring of malaria epidemic.

[Effect of Enhanced UV-B Radiation on Metabolism and Berberine Content of Coptis Chinensis]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Nov, 2011  |  Pubmed ID: 22375379

To reveal the response of content berberine in root of Coptis chinensis to different intensity of UV-B radiation, and provide the theory basis for promoting the content of berberine.

[Analysis of Chemical Composition of Sini San by Ultra Performance Liquid Chromatography-electrospray Ionization-mass Spectrometry]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Nov, 2011  |  Pubmed ID: 22375389

To analyze and identify the chemical ingredients in Sini San by LC-MS.

[The Pharmacological Mechanism of Gastrodin on Calcitonin Gene-related Peptide of Cultured Rat Trigeminal Ganglion]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Dec, 2011  |  Pubmed ID: 22375417

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.

[Optimization of a Floating Osmotic Pump System of Ambroxol Hydrochloride Using Central Composite Design-response Surface Methodology and Its Pharmacokinetics in Beagle Dogs]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Dec, 2011  |  Pubmed ID: 22375427

This paper reported that a new type of floating osmotic pump of ambroxol hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.

[Distribution and Composition of Organochlorine Pesticides in Farmland Top Soils of Anhui Province]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Dec, 2011  |  Pubmed ID: 22384599

By using ultrasonic method and GC/ECD, this paper analyzed the distribution and composition of 8 kinds of organochlorine pesticides (alpha-HCH, beta-HCH, gamma-HCH, delta-HCH, op'-DDE, pp'-DDD, alpha-endosulfan, and chlorothalonil) in farmland top soils (0-20 cm) in 19 districts of Anhui Province, East China. The total concentration of the pesticides in the top soils ranged from 0 to 23.75 microg x kg(-1), among which, pp'-DDD and gamma-HCH were the major pollutants, with the mean concentration being 13.83 and 13.49 microg x kg(-1), respectively. As compared with the analyses in 1990, the present mean concentration of HCH had an obvious decreasing trend, but was still higher than that in the top soils in other regions of China and in other countries. The mean concentrations of OCPs, HCHs and pp'-DDD in the test top soils were 48.58, 28.64 and 13.83 microg x kg(-1), respectively, not surpassed the first grade level (< 50 microg x kg(-1)) of the China National Soil Environmental Quality Standards (GB 15618-1995), suggesting that the farmland top soils in these districts of Anhui Province were less polluted.

[Study on Influence of Thermoplastic Mask on Radiation Dermatitis for Patients with Laryngeal Cancer]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Dec, 2011  |  Pubmed ID: 22390033

To observe the protective effect of thermoplastic mask on radiation dermatitis for patients with laryngeal cancer.

[Effects of Different Cropping System and Fertilization on Functional Diversity in Soil Microbial Community of Chrysanthemum Morifolium]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Dec, 2011  |  Pubmed ID: 22393726

To study the effects of Chrysanthemum morifolium based on functional diversity in soil microbial community with different cropping system and fertilization and offer scientific basis for the establishment of the reasonable planting patterns.

[Effect of Habitat Processing Method on Phillyrin and Forsythiaside A of Forsythiae Fructus]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Dec, 2011  |  Pubmed ID: 22393731

To investigate the habitat processing method of Forsythiae Fructus based on the different indexes, and to choose the best habitat producing process.

Synthesis of Biomimetic Poly[2-(methacryloyloxy)ethyl Phosphorycholine]-coated Magnetite Nanoparticles Via Surface-initiated Atom Transfer Radical Polymerization

Journal of Nanoscience and Nanotechnology. Oct, 2011  |  Pubmed ID: 22400210

Modification of magnetite nanoparticles with biomimetic poly[2-(methacryloyloxy)ethyl phosphorycholine] (poly(MPC)) via surface-initiated atom transfer radical polymerization (ATRP) was carried out. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analyses (TGA) and zeta potential studies indicated that well defined poly (MPC) was successfully grafted on the surface of magnetite nanoparticles. X-ray diffraction results showed the structure of magnetite nanoparticles after surface modification was not changed. The poly (MPC)-coated magnetite nanoparticles had a mean transmission electron microscopy (TEM) diameter of 11 +/- 1.5 nm. The resulting nanomaterials were superparamagnetic at room temperature, exhibited good colloidal stability in aqueous media and good responsibility to magnetic field. Such magnetite nanoparticles with biomimetic surface have potential application in prolonging circulation time in vivo.

Morphology Modification of Silver Microstructures Fabricated by Multiphoton Photoreduction

Journal of Nanoscience and Nanotechnology. Oct, 2011  |  Pubmed ID: 22400224

We have investigated the morphology modification of silver microstructures fabricated by the multiphoton photoreduction process. The microstructures have been fabricated by a femtosecond laser under different irradiation time and repeated scanning numbers. Trans-4-[4-(dimethylamino)-N-methylstilbazolium] p-tosylate (DAST) was used as photosensitizer and effectively reduced the laser power to 0.66 mW. The increase of the irradiation time and repeated scanning induced more reduction in the multiphoton photoreduction microfabrication process, resulting in the optimization of the linewidth. The fusion of silver nanoparticles was confirmed, which led to the morphology change of silver microstructures for achieving the compact metallic microstructures. The result would provide an important protocol to fabricate the metallic microstructures for the electronic and photonic applications.

4-(Dimethylamino)butyric Acid@PtNPs As Enhancer for Solid-state Electrochemiluminescence Aptasensor Based on Target-induced Strand Displacement

Biosensors & Bioelectronics. Dec, 2011  |  Pubmed ID: 22387036

A solid-state electrochemiluminescence (ECL) aptasensor based on target-induced aptamer displacement for highly sensitive detection of thrombin was developed successfully using 4-(dimethylamino)butyric acid (DMBA)@PtNPs labeling as enhancer. Such a special aptasensor included three main parts: ECL substrate, ECL intensity amplification and target-induced aptamer displacement. The ECL substrate was made by modifying the complex of Pt nanoparticles (PtNPs) and tris(2,2-bipyridyl) ruthenium (II) (Ru(bpy)(3)(2+)) (Ru-PtNPs) onto nafion@multi-walled carbon nanotubes (nafion@MWCNTs) modified electrode surface. A complementary thrombin aptamer labeled by DMBA@PtNPs (Aptamer II) acted as the ECL intensity amplification. The thrombin aptamer (TBA) was applied to hybridize with the labeled complementary thrombin aptamer, yielding a duplex complex of TBA-Aptamer II on the electrode surface. The introduction of thrombin triggered the displacement of Aptamer II from the self-assembled duplex into the solution and the association of inert protein thrombin on the electrode surface, decreasing the amount of DMBA@PtNPs and increasing the electron transfer resistance of the aptasensor and thus resulting large decrease in ECL signal. With the synergistic amplification of DMBA and PtNPs to Ru(bpy)(3)(2+) ECL, the aptasensor showed an enlarged ECL intensity change before and after the detection of thrombin. As a result, the change of ECL intensity has a direct relationship with the logarithm of thrombin concentration in the range of 0.001-30nM. The detection limit of the proposed aptasensor is 0.4pM. Thus, the approach is expected to open new opportunities for protein diagnostics in clinical as well as bioanalysis in general.

[Detection of Core Antigen of Hepatitis Virus C in Patients Infected with Hepatitis Virus C and B]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Oct, 2011  |  Pubmed ID: 22409841

To observe the effect of hepatitis virus B on the detection rate of core antigen of hepatitis virus C in sera of chronic hepatitis C patients.

CaMoO4:x%Yb3+: a Novel Near-infrared Quantum-cutting Phosphors Via Cooperative Energy Transfer

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413244

An efficient near-infrared (NIR) dowmconversion (DC) has been demonstrated in the CaMoO4:Yb3+ phosphors. Very strong NIR emission around 998 nm from the 2F(7/2) --> 2F(5/2) transition of the Yb3+ has been observed under ultraviolet excitation. A similar broad excitation band due to the absorption of the host CaMoO4 has been recorded when the NIR emission of Yb3+ and the visible molybdate (MoO4(-2)) emission are monitored, which suggests an efficient energy transfer (ET) from the host to the Yb3+. The Yb3+ concentration-dependent luminescence properties and lifetimes of both the visible and NIR emissions have also been studied. The lifetime of the molybdate emission decreases rapidly with the increasing Yb3+ concentration, further verifying the efficient ET from the host to the Yb3+. Moreover, the low temperature measurements have also been carried out to investigate the ET mechanism in the phosphors. A cooperative energy transfer (CET) mechanism has been proposed to rationalize the DC effect. The newly studied CaMoO4:Yb3+ DC phosphors, which can convert the broadband emission of the MoO4(2-) into NIR emission of Yb3+ with a twofold increase in the photon number will have potential application in greatly enhancing the response of silicon-based solar cells with a relatively higher Yb3+ quenching concentration.

Bioactivity Study of the Titanium Plates Treated with Microarc Oxidation and Alkali

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413264

Microarc oxidation (MAO) and alkali treatment was used to modify the surface of titanium, which prepared different microstructure and nanostructure TiO2-based coating on titanium. The samples were analyzed by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and contact angle measuring instrument. The sample's surface treated by MAO process was microporous structure and looks like a crate. In vitro bioactivity experiment indicated that the hydroxyapatite precipitates was as squama and grew perpendicularly on the sample's surface. In vitro cell culture and MTT assay the MAO-NaOH samples showed distinct proliferation levels compared to the MAO samples. It has no toxicity to the growth of MSC cell and had better biocompatibility. According to the calculation of surface energy, that better hydrophilicity of materials will induce the more growth of hydroxyapatite.

Up-conversion Emissions Characteristics of Non-aqueous Sol-gel Derived RE3Al5O12 Nanocrystals

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413274

The RE3Al5O12 (REAG:Er3Al5O12, Er:Y3Al5O12 and Er:Yb3Al5O12) up-conversion (UC) nanocrystals have been prepared by the non-aqueous sol-gel method. The green and red UC emissions are attributed to the 2H(11/2), 4S(3/2) --> 4I(15/2) and 4F(9/2) --> 4I(15/2) transitions of Er3+, respectively, were obtained for all samples with a 975 nm semiconductor LD excitation. For Er3Al5O12 nanocrystals, the green and red UC emissions have similar intensities. Y and Yb ions have no evident effect on the peak positions, but strongly affected the intensities of the green and red UC emissions of the Er. A much higher intensity of the green relative to red UC emission was observed for Er:Y3Al5O12 nanocrystals, however, the red UC emission became predominant for Er:Yb3Al5O12 nanocrystals. It was suggested that the two-photon process was responsible for the green and red UC emissions mechanism for all the samples.

Up-conversion Fluorescence of Tm3+ and Gd3+ in Yb3+/Tm3+ Co-doped Gd2O3 Nanocrystals

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413275

Through a co-precipitation method Gd(OH)3:20%Yb3+, 1%Tm3+ nanorods were synthesized. After sintered at 900 degrees C for 1 h in air, the as-prepared Gd(OH)3:20%Yb3+, 1%Tm3+ nanorods were converted into Gd2O3:20%Yb3+, 1% Tm3+ nanocrystals. Crystalline phases, sizes, and morphologies of the two samples were characterized by X-ray diffraction and field emission scanning electron microscope. The up-conversion (UC) fluorescence spectra of the Gd2O3:20%Yb3+, 1%Tm3+ nanocrystals were recorded by using a fluorescence spectrophotometer with a 980 nm continuous wave laser diode as excitation source. The nanocrystals not only present characteristic blue and ultraviolet (UV) UC emissions of activated Tm3+, but also show UV UC emissions of host Gd3+. The experimental study suggests that the excitation power has great effects on UC fluorescence properties and the energy transfer from Tm3+ to Gd3+ is very efficient.

The Fabrication and Property of Hydrophilic and Hydrophobic Double Functional Bionic Chitosan Film

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413283

A new kind of hydrophobic bionic chitosan film was fabricated by simulating the surface structure of lotus leaf. The titanium oxide nanotube array was used as templates. Scanning electron microscopy (SEM) images show that one side of this films have nano-scale rough surface with spherical protrusions alike the surface of lotus leaf. The diameter of the protrusions is about 100 nm, which is equal to diameter of the titanium oxide nanotube. The water contact angle of chitosan films is up to 120 degrees and it is hydrophobic. The other side of the film is flat and the contact angle is 70 degrees. That indicated that the hydrophilism of natural materials is connected with the surface structures. The double functional chitosan films, one side is hydrophilic, the other is hydrophobic, can be made by an easy method. This method is non-toxic and clean. The double functional chitosan film will improve the application of chitosan films in medicine.

Optical High Temperature Sensor Based on Enhanced Green Upconversion Emissions in Er3+-Yb3+-Li+ Codoped TiO2 Powders

Journal of Nanoscience and Nanotechnology. Nov, 2011  |  Pubmed ID: 22413317

The Er3+-Yb3+-Li+ codoped TiO2 powders have been prepared by sol-gel method. The strong enhancement of green and red upconversion emissions were obtained for Er3+-Yb3+ codoped TiO2 by additional Li+ codoping and investigated using 976 nm semiconductor laser diode excitation. The enhanced upconversion emissions by the addition of Li+ resulted from the formation of Li compound with lower crystal field symmetry. The fluorescence intensity ratio (FIR) of green upconversion emissions from the transitions of 2H(11/2) --> 4I(15/2) and 4S(3/2) --> 4I(15/2) of Er3+ in the Er3+-Yb3+-Li+ codoped TiO2 has been studied as a function of temperature in the range of 300-925 K, and the maximum sensitivity was determined to be 0.0025 K(-1). Er3+-Yb3+-Li+ codoped TiO2 material with the highest operating temperature up to 925 K, has higher temperature sensitivity and fluorescence efficiency being a promising candidate for applications in optical high temperature sensor.

Nonvolatile Taste Compounds in Cooked Chinese Nanjing Duck Meat Following Postproduction Heat Treatment

Journal of Food Science. Jun, 2011  |  Pubmed ID: 22417411

  Taste-active compounds, including free amino acids, succinic acid and 5'-nucleotides, and chemical components including moisture, pH, protein, crude fat, and sodium chloride were evaluated in cooked and packaged Chinese Nanjing ducks following heat treatments including control, 99 °C for 40 min, 108 °C for 20 min, 92 °C microwave followed by water heating, 95 °C for 30 min, 121 °C for 25 min. Heat treatment decreased (P < 0.05) the content of Alamine and moisture and reduced the pH value in muscle, but increased (P < 0.05) the protein and 5'-nucleotides content. The 99 °C group had a significantly lower crude fat content compared with other groups (P < 0.05). The succinic acid content in the control group was significantly higher than in the 121 °C group (P < 0.05). Groups treated at higher temperatures (108 °C, 121 °C, and microwave) had similar equivalent umami concentrations and 5'-nucleotides, free amino acids content, as well as the derived bitter and sweet taste components compared with the groups treated at lower temperatures. It can be speculated that these differences account for the enhanced flavor of the meat in the 99 °C, 108 °C, 121 °C, and microwave groups compared with the untreated control. Therefore, heat treatment at lower temperature after packaging may prolong product shelf life without any detrimental effects on taste. The results of this study indicate that it is important to use lower temperatures in this type of food processing. However, it may be possible to modify the primary processing steps to improve the content of umami-like taste compounds such as 5'-nucleotides. Practical Application:  Heat treatment of packaged products is an effective method for eradication of microbes, therefore increasing the shelf-life. However, such treatment can result in major changes in the sensory perception of meat products, particularly the formation of off-flavors. This study investigated changes in taste-active compounds in duck meat following a number of types of heat treatment.

Optimization of Ultrasonic-assisted Enzymatic Hydrolysis for the Extraction of Luteolin and Apigenin from Celery

Journal of Food Science. Jun, 2011  |  Pubmed ID: 22417412

The extraction of flavonoids is of increasing interest because of their various pharmacological effects. This study is the first attempt for the ultrasonic-assisted enzymatic hydrolysis (USAEH) applied in the extraction of 2 bioactive flavonoid compounds in celery-luteolin and apigenin. The quantitative yields of luteolin and apigenin were determined by high-performance liquid chromatography (HPLC). To achieve high yields of extracted compounds, the procedure was optimized with regard to the relative parameters involved. The optimal conditions for enzymatic hydrolysis using pectinase treatment were a reaction time of 30 min and a concentration of 0.4 mg/mL at pH 3 for luteolin and pH 5.5 for apigenin. The optimal ultrasonic parameters were an exposure period of 30 min at a temperature of 25 °C using a power source of 80 W. Under these optimal conditions, the yields of luteolin and apigenin were increased to 42.5 and 25.3 mg/g, respectively, which represented a 26.1-fold and a 32.2-fold increase in the yields of these 2 compounds, respectively, compared with the control model of aqueous extraction without enzyme or ultrasonic treatment.

Fine Particulate Matter Constituents and Cardiopulmonary Mortality in a Heavily Polluted Chinese City

Environmental Health Perspectives. Mar, 2011  |  Pubmed ID: 22389181

Background: Although ambient fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) has been linked to adverse human health effects, the chemical constituents that cause harm are unknown. To our knowledge, the health effects of PM2.5 constituents have not been reported for a developing country.Objectives: We examined the short-term association between PM2.5 constituents and daily mortality in Xi'an, a heavily polluted Chinese city.Methods: We obtained daily mortality data and daily concentrations of PM2.5, organic carbon (OC), elemental carbon (EC), and 10 water-soluble ions for 1 January 2004 through 31 December 2008. We also measured concentrations of fifteen elements 1 January 2006 through 31 December 2008. We analyzed the data using overdispersed generalized linear Poisson models.Results: During the study period, the mean daily average concentration of PM2.5 in Xi'an was 182.2 µg/m3. Major contributors to PM2.5 mass included OC, EC, sulfate, nitrate, and ammonium. After adjustment for PM2.5 mass, we found significant positive associations of total, cardiovascular, or respiratory mortality with OC, EC, ammonium, nitrate, chlorine ion, chlorine, and nickel for at least one lag period. Nitrate demonstrated stronger associations with total and cardiovascular mortality than PM2.5 mass. For a 1-day lag, interquartile range increases in PM2.5 mass and nitrate (114.9 and 15.4 µg/m3, respectively) were associated with 1.8% [95% confidence interval (CI): 0.8%, 2.8%] and 3.8% (95% CI: 1.7%, 5.9%) increases in total mortality.Conclusions: Our findings suggest that PM2.5 constituents from the combustion of fossil fuel may have an appreciable influence on the health effects attributable to PM2.5 in Xi'an.

Local Synchronization of One-to-one Coupled Neural Networks with Discontinuous Activations

Cognitive Neurodynamics. Mar, 2011  |  Pubmed ID: 22379492

In this paper, local synchronization is considered for coupled delayed neural networks with discontinuous activation functions. Under the framework of Filippov solution and in the sense of generalized derivative, a novel sufficient condition is obtained to ensure the synchronization based on the Lyapunov exponent and the detailed analysis in Danca (Int J Bifurcat Chaos 12(8):1813-1826, 2002; Chaos Solitons Fractals 22:605-612, 2004). Simulation results are given to illustrate the theoretical results.

Construction of Rice Site-specific Chloroplast Transformation Vector and Transient Expression of EGFP Gene in Dunaliella Salina

Journal of Biomedical Nanotechnology. Dec, 2011  |  Pubmed ID: 22416579

Chloroplast is a new hotspot in the field of plant transformation system of plant genetic engineering. Plastid transformation has several advantages: high expression, multiple expressed genes in a single transformation event, absence of gene silencing, et al. A series of elements for construction of dicistronic site-specific integration expression vector of rice chloroplast have been cloned, including trnl-trnA (rice chloroplast homologous recombination fragments), Prrn (16S rRNA operon promotor), PpsbA (the 3' untranslated region of the chloroplastpsbA gene), hptll gene (encoding hygromycin phosphotransferase) and EGFP (encoding enhanced green fluorescence protein). All the elements were constructed into a rice chloroplast dicistronic expression vector pCTE04 (-trnl-Prrn-RBS-hptlI-RBS-EGFP-PpsbA- trnA-). Then pCTE04 was introduced into chloroplasts of Dunaliella salina through particle bombardment. Strong green fluorescence was observed in chloroplasts of some bombarded Dunaliella salina cells under a stereo fluorescence microscope, indicating that pCTE04 could be expressed in Dunaliella salina chloroplasts transiently. It provides a solid foundation for further genetic engineering in rice chloroplast transformation.

EBV-encoded LMP1 Triggers Regulation of the ERK-mediated Op18/stathmin Signaling Pathway in Association with Cell Cycle

Cancer Science. Mar, 2012  |  Pubmed ID: 22417000

The mitogen-activated protein kinases (MAPKs) are activated by a variety of cellular stimuli to participate in a series of signaling cascades and mediate diverse intracellular responses. One potential target of the MAPKs is Op18/stathmin, a molecule that acts as an integrator of diverse cell signaling pathways and regulates the dynamics of microtubules, which are involved in modulating a variety of cellular processes, including cell cycle progression and cell growth. Our study focused on the regulation of the MAPK-mediated Op18/stathmin signaling pathway, which is triggered by the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene in nasopharyngeal carcinoma cells. The results showed that the activity of MAPK, which was induced by LMP1, varied with cell cycle progression; LMP1 upregulated the phosphorylation of ERK during the G1/S phase but negatively regulated the phosphorylation of ERK during the G2/M phase. We found that the regulation of Op18/stathmin signaling by LMP1 was mainly mediated through ERK. The inhibition of LMP1 expression attenuated the interaction of ERK with Op18/stathmin and promoted microtubule depolymerization. These findings indicate the existence of a new cell cycle-associated signaling pathway in which LMP1 regulates ERK-mediated Op18/stathmin signaling. © 2012 Japanese Cancer Association.

Direct Arylation of Imidazo[1,2-a]pyridine at C-3 with Aryl Iodides, Bromides, and Triflates Via Copper(I)-Catalyzed C-H Bond Functionalization

Organic Letters. Mar, 2012  |  Pubmed ID: 22417233

A convenient method for the copper(I)-catalyzed arylation of substituted imidazo[1,2-a]pyridine has been developed. This method is applicable to a variety of aryl electrophiles, including bromides, iodides, and triflates. It represents the first general process for C-3 arylation of substituted imidazo[1,2-a]pyridine by Cu(I) catalysis to construct various functionalized imidazo[1,2-a]pyridine core π-systems.

Brightly Photoluminescent Phosphor Materials Based on Silicon Quantum Dots with Oxide Shell Passivation

Optics Express. Jan, 2012  |  Pubmed ID: 22379666

We demonstrate silicon-based phosphor materials which exhibit bright photoluminescence from near-infra-red to green. The colloidal composites which are composed of silicon quantum dots (SiQDs) attached on micro-size silicon particles are synthesized by electrochemical etching of silicon wafers and then dispersed in ethanol. Subsequently, isotropic etching by HF/HNO3 mixture controls the size so as the emission wavelength of SiQDs, and forms an oxide passivating shell. The phosphors can further react with alkoxysilanes to form a stable suspension in non-polar solvents for solution-processing. The resulting red-light-emitting SiQD-based phosphors in chloroform exhibit photoluminescence external quantum efficiency of 15.9%. Their thin films can be efficiently excited by InGaN light-emitting diodes and are stable in room condition.

Gq Modulates the Termination of Phototransduction and Prevents Retinal Degeneration

The Journal of Biological Chemistry. Mar, 2012  |  Pubmed ID: 22389492

Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2+-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel Gαq mutant allele, which has defects in both activation and deactivation. We revealed that Gq modulates the termination of the light response and that metarhodopsin/Gq interaction affects subsequent Arr2/Rh1 binding, which mediates the deactivation of metarhodopsin. We further showed that the Gαq mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Rh1/Arr2 complexes. Our study revealed the roles of Gq in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.

From Retinal Waves to Activity-dependent Retinogeniculate Map Development

PloS One. 2012  |  Pubmed ID: 22389669

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

An Updated Review of the Efficacy of Cupping Therapy

PloS One. 2012  |  Pubmed ID: 22389674

Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy.

Adaptive Response in Mice Exposed to 900 MHz Radiofrequency Fields: Primary DNA Damage

PloS One. 2012  |  Pubmed ID: 22389679

The phenomenon of adaptive response (AR) in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm(2) power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR.

Prolonged Exposure to Insulin Induces Mitochondrion-Derived Oxidative Stress Through Increasing Mitochondrial Cholesterol Content in Hepatocytes

Endocrinology. Feb, 2012  |  Pubmed ID: 22374974

We addressed the link between excessive exposure to insulin and mitochondrion-derived oxidative stress in this study and found that prolonged exposure to insulin increased mitochondrial cholesterol in cultured hepatocytes and in mice and stimulated production of reactive oxygen species (ROS) and decreased the reduced glutathione to glutathione disulfide ratio in cultured hepatocytes. Exposure of isolated hepatic mitochondria to cholesterol alone promoted ROS emission. The oxidative stress induced by the prolonged exposure to insulin was prevented by inhibition of cholesterol synthesis with simvastatin. We further found that prolonged exposure to insulin decreased mitochondrial membrane potential and the increased ROS production came from mitochondrial respiration complex I. Finally, we observed that prolonged exposure to insulin decreased mitochondrial membrane fluidity in a cholesterol synthesis-dependent manner. Together our results demonstrate that excess exposure to insulin causes mitochondrion-derived oxidative stress through cholesterol synthesis in hepatocytes.

The Intranuclear Release of a Potential Anticancer Drug from Small Nanoparticles That Are Derived from Intracellular Dissociation of Large Nanoparticles

Biomaterials. Mar, 2012  |  Pubmed ID: 22417622

Transporting drug-containing nanoparticles into the nucleus of cancer cells through nucleopores and then releasing the drug intranuclearly provide an efficient strategy to overcome the drug resistance mechanisms evolved by cancer cells. However, limited by the diameter of nucleopores, nanoparticles capable of going through nucleopores should be small enough, whereas the nanoparticles with the small size may have short circulation time in blood and low accumulation in solid tumors. We solved this dilemma successfully by preparing kinetically frozen large compound nanoparticles (sized 128 nm) of complex of oligolysine/iridium(III) compound (a potential anticancer drug) that can dissociate into small ones in lysosome environment. The small nanoparticles retain their small size in cytosol after escaping from the lysosomes, so that they can enter the nucleus actively through nucleaopores, with the help of oligolysine segments on the surfaces of nanoparticles acting as the nuclear targeting moieties. It is significant that the nanoparticles can release the contained Ir compound within the nucleus. Further study reveals that the release is triggered by DNA interaction with the nanoparticles, which is responsible for the observation that the release occurs only in the nucleus. We believe that the present study, representing the first example of DNA triggered intranuclear release from nanoparticles, will provide a promising pathway for chemotherapy.

Randomized Phase II Study of Concurrent Cisplatin/etoposide or Paclitaxel/carboplatin and Thoracic Radiotherapy in Patients with Stage III Non-small Cell Lung Cancer

Lung Cancer (Amsterdam, Netherlands). Mar, 2012  |  Pubmed ID: 22418243

OBJECTIVE: To evaluate the activity and safety of concurrent thoracic radiotherapy (TRT) plus weekly paclitaxel/carboplatin (PC) regimen compared with widely used cisplatin/etoposide (PE) regimen in patients with unresectable stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned to receive the following treatments: PE arm, cisplatin (50mg/m(2)) on days 1, 8, 29, and 36 and etoposide (50mg/m(2)) on days 1-5 and 29-33 plus 60Gy of TRT; PC arm, weekly concurrent carboplatin (AUC=2) and paclitaxel (45mg/m(2)) plus 60Gy of TRT. RESULTS: A total of 65 patients were randomized (PE arm, n=33; PC arm, n=32). The 3-year overall survival (OS) was significantly better in the PE arm than in the PC arm (33.1% vs. 13%, P=.04). The incidence of Grade 3/4 neutropenia was 78.1% in the PE arm and 51.5% in the PC arm (P=.05). The rate of Grade 2 or greater radiation pneumonitis was 25% in the PE arm and 48.5% in the PC arm (P=.09). CONCLUSIONS: Compared to PE regimen, weekly PC regimen cannot be recommended since it failed to achieve an improvement in either OS or PFS.

Conformal Phosphor Coating Using Capillary Microchannel for Controlling Color Deviation of Phosphor-converted White Light-emitting Diodes

Optics Express. Feb, 2012  |  Pubmed ID: 22418314

We demonstrated a conformal phosphor coating method for phosphor-converted white light-emitting diodes (LEDs) using capillary microchannel formed by a fixture. The mixture of the phosphor particles and the silicone spontaneously flows in capillary microchannel and was pinned at the edge of the fixture due to the surface tension effect. The present coating method was applied to different packaging types with both the conventional chip and the vertical injection chip. Experimental results show this method can efficiently improve the angular color uniformity (ACU). Compared with those samples packaged by conventional dispensing coating, angular color correlated temperature (CCT) deviation of the test samples by the present method can reduce from 1500K to 200K for the average CCT 5200K from -90°to +90 view angles, and reduce from 5000K to 1000K for the average CCT 9150K. Additionally, this method can prevent the packaging non-consistency that the average CCT varies from package to package due to the deviation of phosphor-silicone mixture volume. In the experiments, even when the phosphor-silicone mixture volume varies from 0.3µl to 0.5µl, the deviation of the average CCT is less than 80K.

A Domain-based Model for Predicting Large and Complex Pseudoknotted Structures

RNA Biology. Feb, 2012  |  Pubmed ID: 22418848

Pseudoknotted structures play important structural and functional roles in RNA cellular functions at the level of transcription, splicing and translation. However, the problem of computational prediction for large pseudoknotted folds remains. Here we develop a domain-based method for predicting complex and large pseudoknotted structures from RNA sequences. The model is based on the observation that large RNAs can be separated into different structural domains. The basic idea is to first identify the domains and then predict the structures for each domain. Assembly of the domain structures gives the full structure. The use of the domain-based approach leads to a reduction of computational time by a factor of about ~N ( 2) for an N-nt sequence. As applications of the model, we predict structures for a variety of RNA systems, such as regions in human telomerase RNA (hTR), internal ribosome entry site (IRES) and HIV genome. The lengths of these sequences range from 200-nt to 400-nt. The results show good agreements with the experiments.

Isoprenoids and Related Pharmacological Interventions: Potential Application in Alzheimer's Disease

Molecular Neurobiology. Mar, 2012  |  Pubmed ID: 22418893

Two major isoprenoids, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, serve as lipid donors for the posttranslational modification (known as prenylation) of proteins that possess a characteristic C-terminal motif. The prenylation reaction is catalyzed by prenyltransferases. The lipid prenyl group facilitates to anchor the proteins in cell membranes and mediates protein-protein interactions. A variety of important intracellular proteins undergo prenylation, including almost all members of small GTPase superfamilies as well as heterotrimeric G protein subunits and nuclear lamins. These prenylated proteins are involved in regulating a wide range of cellular processes and functions, such as cell growth, differentiation, cytoskeletal organization, and vesicle trafficking. Prenylated proteins are also implicated in the pathogenesis of different types of diseases. Consequently, isoprenoids and/or prenyltransferases have emerged as attractive therapeutic targets for combating various disorders. This review attempts to summarize the pharmacological agents currently available or under development that control isoprenoid availability and/or the process of prenylation, mainly focusing on statins, bisphosphonates, and prenyltransferase inhibitors. Whereas statins and bisphosphonates deplete the production of isoprenoids by inhibiting the activity of upstream enzymes, prenyltransferase inhibitors directly block the prenylation of proteins. As the importance of isoprenoids and prenylated proteins in health and disease continues to emerge, the therapeutic potential of these pharmacological agents has expanded across multiple disciplines. This review mainly discusses their potential application in Alzheimer's disease.

Phytoecdysteroids from the Roots of Achyranthes Bidentata Blume

Molecules (Basel, Switzerland). 2012  |  Pubmed ID: 22418932

Two new phytoecdysteroids, (25S)-20,22-O-(R-ethylidene)inokosterone (1) and 20,22-O-(R-3-methoxycarbonyl)propylidene-20-hydroxyecdysone (2), together with six known phytoecdysteroids 3-8 were isolated from the roots of Achyranthes bidentata Blume. The new structures were established on the basis of spectroscopic studies and chemical evidences. The absolute configuration at C-25 in the structure of known compound 3 was determined by chemical and spectroscopic means.

Highly Enantioselective [4 + 2] Cycloadditions of Allenoates and Dual Activated Olefins Catalyzed by N-acyl Aminophosphines

Organic & Biomolecular Chemistry. Mar, 2012  |  Pubmed ID: 22419060

An asymmetric organocatalytic [4 + 2] cycloaddition between α-substituted allenoates and dual activated olefins using bifunctional N-acyl aminophosphine catalysts is described. The use of 2-cyano acrylate derived olefins led to the first successful incorporation of an electrophile derived from an aliphatic aldehyde into this reaction.

Catalytically Active Single-Atom Sites Fabricated from Silver Particles

Angewandte Chemie (International Ed. in English). Mar, 2012  |  Pubmed ID: 22419271

Silver chains fabricated from supported silver particles were embedded in Hollandite-type manganese oxide, thereby exposing single silver atoms as catalytically active sites. Excellent oxygen activation and high catalytic activity in the oxidation of formaldehyde was observed.

Comprehension of the Unique Characteristics of Traditional Chinese Medicine

The American Journal of Chinese Medicine. 2012  |  Pubmed ID: 22419419

Traditional Chinese Medicine (TCM) has made great contributions to human history, especially in China, as has been recorded for thousands of years. The characteristics of TCM in both theory and practice make it different from Conventional Western Medicine (CWM). The characteristics of TCM include phenomenological, philosophical, and methodological aspects. This paper briefly discusses some historical turning points and innovations in TCM development in China, explores human body enigmas such as the heart, compares different aspects of TCM and CWM, and identifies the unique characteristics of TCM treatment, as compared to other medical systems.

[Double Balloon Endoscopy in Diagnosis of Patients with Obscure Gastrointestinal Bleeding]

Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences. Jan, 2012  |  Pubmed ID: 22419472

Objective: To assess the diagnostic value of double balloon endoscopy (DBE) for obscure gastrointestinal bleeding (OGIB) Methods: The data of 103 OGIB patients who underwent DBE from January 2007 to September 2010 in the First Affiliated Hospital, Zhejiang University School of Medicine were retrospectively analyzed. Results: DBE was successfully performed in all 103 patients without complications. Of 103 patients, 66(64.1 %) had positive DBE findings and 28 had surgery procedures(27.2 %). Ninety-four patients finally acquired positive diagnosis, including small intestine tumor(31.1 %), angiodysplasia(22.3 %), exulceratio simplex(9.7 %), Crohn's disease(6.8 %), diverticulum(4.9 %), abdominal purpure(4.9 %), etc. Lesions occurred more frequently in proximal small intestine than in distal small intestine (56.3 % Compared with 30.1 %, P<0.001). Conclusion: DBE is a safe, effective and reliable procedure for the diagnosis of OGIB.

Band-Edge Electronic Structure of β-In(2) S(3) : The Role of S or P Orbitals of Atoms at Different Lattice Positions

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Mar, 2012  |  Pubmed ID: 22419557

As a promising solar-energy material, the electronic structure and optical properties of Beta phase indium sulfide (β-In(2) S(3) ) are still not thoroughly understood. This paper devotes to solve these issues using density functional theory calculations. β-In(2) S(3) is found to be an indirect band gap semiconductor. The roles of its atoms at different lattice positions are not exactly identical because of the unique crystal structure. Additonally, a significant phenomenon of optical anisotropy was observed near the absorption edge. Owing to the low coordination numbers of the In3 and S2 atoms, the corresponding In3-5s states and S2-3p states are crucial for the composition of the band-edge electronic structure, leading to special optical properties and excellent optoelectronic performances.

Distinct Roles of Dopamine D3 Receptors in Modulating Methamphetamine-induced Behavioral Sensitization and Ultrastructural Plasticity in the Shell of the Nucleus Accumbens

Journal of Neuroscience Research. Apr, 2012  |  Pubmed ID: 22420045

Persistent changes in behavior and psychological function that occur as a consequence of exposure to drugs of abuse are thought to be mediated by the structural plasticity of specific neural circuits such as the brain's dopamine (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc) accompany drug-induced enduring behavioral and molecular changes, yet ultrastructural changes in synapses following repeated exposure to drugs have not been well studied. The current study examines the role of DA D3 receptors in modulating locomotor activity induced by both acute and repeated methamphetamine (METH) administration and accompanying ultrastructural plasticity in the shell of NAc in mice. We found that D3 receptor mutant (D3−/−) mice exhibited attenuated acute locomotor responses as well as the development of behavioral sensitization to METH compared with wild-type mice. In the absence of obvious neurotoxic effects, METH induced similar increases in synaptic density in the shell of NAc in both wild-type and D3−/− mice. These results suggest that D3 receptors modulate locomotor responses to both acute and repeated METH treatment. In contrast, the D3 receptor is not obviously involved in modulating baseline or METH-induced ultrastructural changes in the NAc shell.

Induction of Immune Tolerance in Mice with a Novel Mucosal Nanoemulsion Adjuvant and Self-antigen

Nanomedicine (London, England). Mar, 2012  |  Pubmed ID: 22420425

Aim: The aim of this study was to investigate the impact of a novel nanoemulsion (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in mice as a study model. Materials & methods: Mice received NE or NE + mTg by nasal delivery. At 1 week after the second nasal delivery of NE with or without mTg, all mice were immunized with mTg and lipopolysaccharides to induce experimental autoimmune thyroiditis. Results: Compared with controls, mTg-NE-treated mice had much more antigens accumulated in the nasal passage and thymus and developed a milder form of thyroiditis. This was accompanied by an increase in IL-10, IL-17 and reduced IFN-γ. The production of anti-mTg antibodies was significantly decreased in mTg-NE-treated mice. The percentage of Tregs in cervical lymph nodes was higher in mTg-NE-treated mice than NE-treated mice. Furthermore, Foxp3 and TGF-β levels were prominently enhanced in mTg-NE-treated mice. Conclusion: This study indicates that a low dose of mTg in NE can significantly enhance antigen uptake and Tregs, resulting in inhibition of experimental autoimmune thyroiditis development. Original submitted: 17 September 2011; Revised submitted: 5 December 2011.

Highly Efficient Synthesis of N-Substituted Isoindolinones and Phthalazinones Using Pt Nanowires As Catalysts

Organic Letters. Mar, 2012  |  Pubmed ID: 22420427

A series of N-substituted isoindolinones have been successfully synthesized through the reductive C-N coupling and intramolecular amidation of 2-carboxybenzaldehyde and amines. This one-pot synthesis gives excellent yields using ultrathin Pt nanowires as catalysts under 1 bar of hydrogen. These unsupported catalysts can also be used for the synthesis of phthalazinones in high yield when hydrazine or phenyl hydrazine is used instead of amines.

Multifunctional Mercapto-tacrine Derivatives for Treatment of Age-related Neurodegenerative Diseases

Journal of Medicinal Chemistry. Mar, 2012  |  Pubmed ID: 22420827

Cooperating mercapto group with tacrine in a single molecular, novel multifunctional compounds have been designed and synthesized. These mercapto-tacrine derivatives displayed a synergistic pharmacological profile of long-term potentiation enhancement, cholinesterase inhibition, neuroprotection and less hepatotoxicity, emerging as promising molecules for the therapy of age-related neurodegenerative diseases.

Oncogene-induced Senescence Results in Marked Metabolic and Bioenergetic Alterations

Cell Cycle (Georgetown, Tex.). Apr, 2012  |  Pubmed ID: 22421146

Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is viewed as an important barrier to tumorgenesis. Surprisingly, relatively little is known about the metabolic changes that accompany and therefore may contribute to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras-induced senescence. Profiling approximately 300 different intracellular metabolites reveals that cells that have undergone OIS develop a unique metabolic signature that differs markedly from cells undergoing replicative senescence. A number of lipid metabolites appear uniquely increased in OIS cells, including a marked increase in the level of certain intracellular long chain fatty acids. Functional studies reveal that this alteration in the metabolome reflects substantial changes in overall lipid metabolism. In particular, Ras-induced senescent cells manifest a decline in lipid synthesis and a significant increase in fatty acid oxidation. Increased fatty acid oxidation results in an unexpectedly high rate of basal oxygen consumption in cells that have undergone OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1, the rate-limiting step in mitochondrial fatty acid oxidation, restores a pre-senescent metabolic rate and, surprisingly, selectively inhibits the secretory, pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells demonstrate profound alterations in their metabolic and bioenergetic profiles, particularly with regards to the levels, synthesis and oxidation of free fatty acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be related to these underlying changes in cellular metabolism.

The Glucagon Receptor is Involved in Mediating the Body Weight Lowering Effects of Oxyntomodulin

Obesity (Silver Spring, Md.). Mar, 2012  |  Pubmed ID: 22421924

Oxyntomodulin (OXM) is a peptide secreted postprandially from the L-cells of the gut that has a weak affinity for both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR). Peripheral administration of OXM in humans and rodents causes weight loss reducing food intake and increasing energy expenditure. It has been suggested that OXM modulates energy intake solely through GLP1R agonism. Because glucagon decreases food intake in rodents and humans, we examined whether activation of the GCGR is involved in the body weight lowering effects of OXM. We identified an equipotent GLP1R-selective peptide agonist that differs from OXM by only one residue (Q3→E, OXMQ3E), but has no significant GCGR agonist activity in vitro and ∼100-fold reduced ability to stimulate liver glycogenolysis. Chronic treatment of obese mice with OXM and OXMQ3E demonstrated that OXM exhibits superior weight loss and lipid lowering efficacy, and antihyperglycemic activity that is comparable to the corresponding GLP1R-selective agonist. Studies in Glp1r(-/-) mice and co-administration of OXM and a glucagon receptor antagonist revealed that the anti-obesity effect of OXM requires activation of both GLP1R and GCGR. Our data provide new insight into the mechanism of action of OXM and suggest that activation of GCGR is involved in the body weight-lowering action of OXM.

Enhanced Fluorescent Chemosensor for Ag(+) in Absolute Aqueous Solution and Living Cells: An Experimental and Theoretical Study

The Analyst. Mar, 2012  |  Pubmed ID: 22421929

Rosamine derivative , bearing macrocyclic ligand [15]aneNO(2)S(2) as receptor, was synthesized as an enhanced fluorescent chemosensor for Ag(+) in absolute aqueous solution. The fluorescence images in living cells show the potential application of . The difference of fluorescence enhancement process after binding with Ag(+)/Hg(2+) in acetonitrile/water solution was first proved by theoretical calculations.

Mesenchymal Stem Cells: a Double-edged Sword in Regulating Immune Responses

Cell Death and Differentiation. Mar, 2012  |  Pubmed ID: 22421969

Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS(-/-) MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5(-/-)CXCR3(-/-) mice, the immune-promoting effect of iNOS(-/-) MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs.Cell Death and Differentiation advance online publication, 16 March 2012; doi:10.1038/cdd.2012.26.

Temperature Sensing and In Vivo Imaging by Molybdenum Sensitized Visible Upconversion Luminescence of Rare-Earth Oxides

Advanced Materials (Deerfield Beach, Fla.). Mar, 2012  |  Pubmed ID: 22422477

A novel high excited state energy transfer pathway to overcome the phonon quenching effect in rare-earth (RE) oxide upconversion (UC) materials is reported. In Er(Tm)-Yb oxide systems, an extraordinary enhancement of UC luminescence efficiency with four orders of magnitude is realized by Mo co-doping. The RE oxides with significant UC efficiency are successfully utilized for temperature sensing and in vivo imaging.

Immediate Intraportal Transplantation of Human Bone Marrow Mesenchymal Stem Cells Prevents Death from Fulminant Hepatic Failure in Pigs

Hepatology (Baltimore, Md.). Mar, 2012  |  Pubmed ID: 22422600

The effectiveness of human bone marrow mesenchymal stem cell (hBMSC) transplantation to treat acute and chronic liver injury has been demonstrated in animal models and in a few nonrandomized clinical trials. However, no studies have investigated hBMSC transplantation in the treatment of fulminant hepatic failure (FHF), especially in large animal (pig) models. The aim of this study is to demonstrate the safety, effectiveness and underlying mechanism of hBMSC transplantation for treating FHF in pigs through the intraportal route. Human BMSCs (3×10(7) ) were transplanted into FHF pigs via the intraportal route or peripheral vein immediately after D-galactosamine injection, and a sham group underwent intraportal transplantation without cells (IPT, PVT and CTL groups, respectively, n = 15/group). All of the animals in the PVT and CTL groups died of FHF within 96 hours. In contrast, 13 of 15 animals in the IPT group achieved long-term survival (>6 months). Immunohistochemistry demonstrated that the transplanted hBMSC-derived hepatocytes in surviving animals were widely distributed in the hepatic lobules and the liver parenchyma from weeks 2 to 10. Thirty percent of the hepatocytes were hBMSC-derived. However, the number of transplanted cells was significantly decreased at week 15. Only a few single cells were scattered in the regenerated liver lobules at week 20, and the liver tissues exhibited a nearly normal structure. Conclusion: Immediate IPT of hBMSCs is a safe and effective treatment for FHF. The transplanted hBMSCs may quickly participate in liver regeneration via proliferation and transdifferentiation into hepatocytes during the initial stage of FHF. This method can possibly be used in future clinical therapy. (HEPATOLOGY 2012.).

Angiofibroma in the Right Atrium and Inferior Vena Cava

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Apr, 2012  |  Pubmed ID: 22423070

Spline Confidence Bands for Functional Derivatives

Journal of Statistical Planning and Inference. Jun, 2012  |  Pubmed ID: 22423174

We develop in this paper a new procedure to construct simultaneous confidence bands for derivatives of mean curves in functional data analysis. The technique involves polynomial splines that provide an approximation to the derivatives of the mean functions, the covariance functions and the associated eigenfunctions. We show that the proposed procedure has desirable statistical properties. In particular, we first show that the proposed estimators of derivatives of the mean curves are semiparametrically efficient. Second, we establish consistency results for derivatives of covariance functions and their eigenfunctions. Most importantly, we show that the proposed spline confidence bands are asymptotically efficient as if all random trajectories were observed with no error. Finally, the confidence band procedure is illustrated through numerical simulation studies and a real life example.

Cellular Translocation of a γ-AApeptide Mimetic of Tat Peptide

Molecular Pharmaceutics. Mar, 2012  |  Pubmed ID: 22413929

Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a γ-AApeptide mimetic of Tat (48-57) can cross the cell membranes and enter the cytoplasm and nucleus of cells, with efficiency comparable or better than Tat peptide (48-57). Deletion of the four side chains of the γ-AApeptide attenuates translocation capability. We also establish that the γ-AApeptide is even less toxic than the Tat peptide against mammalian cells. In addition to their low toxicity, γ-AApeptides are resistant to protease degradation, which may prove to be advantageous over α-peptides for further development of molecular transporters for intracellular delivery.

Novel Patented Src Kinase Inhibitor

Current Medicinal Chemistry. Mar, 2012  |  Pubmed ID: 22414081

Src family of protein tyrosine kinases (SFKs) plays key roles in the regulation of signal transductions in cellular processes. However, hyper-activated SFKs lead to uncontrolled cell proliferation and cancers. Src-targeted compounds were developed to block the cell proliferation signal transductions for cancer therapy. Src kinase domain inhibitors were designed, synthesized and evaluated as anticancer agents, while the patents applied at the same time. Great progress has been made in the Src kinase inhibitor area. Herein, some predominant patents about Src kinase inhibitors of the recent years are reviewed.

Distribution Trends of Gastric Polyps: An Endoscopy Database Analysis of 24 121 Northern Chinese Patients

Journal of Gastroenterology and Hepatology. Mar, 2012  |  Pubmed ID: 22414211

Background and Aim:  Traditionally the most common gastric polyps are hyperplastic polyps (HPs). However, in the last two decades, fundic gland polyps (FGPs) have greatly increased in western countries. We aimed to re-evaluate and compare the distribution of gastric polyps in a northern Chinese population in 2000 and 2010. Methods:  Consecutive patients with gastric polyps detected in 2000 and 2010 were analyzed and biopsies were re-evaluated. Data including patients' age, sex, symptoms and the number, size, location, Helicobacter pylori (H. pylori) infection of polyps were recorded. Results:  A total of 6,784 and 17,337 patients underwent esophagogastroduodenoscopy in 2000 and 2010, 68 and 183 patients were diagnosed with gastric polyps, respectively. H. pylori infection decreased from 54.4% to 37.7% (p= 0.017). Overall, spectrum of gastric polyps changed (P < 0.001). HPs accounted for 28.3% and decreased from 48.5% to 20.8%, adenoma/carcinoma and inflammatory polyps also decreased. FGPs were present in 50.6% and increased from 8.8% to 66.1%. The location of polyps was also changed with an increase of polyps in gastric corpus. There was a high proportion of FGPs in females, while adenomas/adenocarcinomas were more common in males. The distribution pattern was similar in young and elderly patients. Conclusions:  Spectrum change of gastric polyps was observed over the past 10 years in the northern Chinese population most likely due to the higher proportion of FGPs. Further studies are required to investigate the reasons and confirm whether it will lead to a different management strategy in China. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Measurement of Hemoglobin in Whole Blood Using a Partial Least Squares Regression Model with Selected Second Derivative Near Infrared Transmission Spectral Signals

Biochemical and Biophysical Research Communications. Mar, 2012  |  Pubmed ID: 22414693

In this work, we propose a signal selection procedure for determination of hemoglobin (Hb) concentration in whole blood using near infrared (NIR) transmission spectral signals. A dataset of 190 whole blood NIR transmission spectra with reference Hb concentrations was used to evaluate the method. Spectral signals were selected based on the squared correlation coefficient (R(2)) between the signal and the Hb concentration. An improved uninformative variable elimination (UVE) procedure was performed to remove redundant signals from the primary selected signal set. A partial least squares (PLS) regression model was built with the final selected signals and the corresponding Hb concentrations. The results indicate that the proposed method is effective at increasing the predictive power of the NIR-PLS spectral model for determining Hb concentration in whole blood samples.

Evaluation of Antibacterial Effects by Atmospheric Pressure Nonequilibrium Plasmas Against Enterococcus Faecalis Biofilms In Vitro

Journal of Endodontics. Apr, 2012  |  Pubmed ID: 22414847

The aim of this study was to evaluate the in vitro antibacterial activity by atmospheric pressure nonequilibrium plasmas (APNPs) as an effective approach against bacterial biofilms in root canal systems during endodontic therapy.

Preventing the Wound-induced Deterioration of Yali Pears by Chitosan Coating Treatments

Food Science and Technology International = Ciencia Y Tecnologia De Los Alimentos Internacional. Mar, 2012  |  Pubmed ID: 22414935

Yali pears (Pyrus bretschneideri Rehd.) are susceptible to mechanical damage. In this study, the protective effects of chitosan treatments on the quality of bruised pears were evaluated. The fruit were treated with 1.5% chitosan before or after bruise damage, respectively. Then, the fruit were stored at 16 °C and 85-90% relative humidity. Postharvest quality parameters were analyzed during the storage. Bruise damage accelerated the decrease of firmness and the ratio of sugar to acid, while a delay of firmness and sugar-to-acid ratio in those pears treated with chitosan before or after was found. Meanwhile, chitosan treatments both before and after damage delayed the color changes caused by damage, inhibited disease incidence increase, and enhanced the bruise recovery during the storage. Our results suggested that chitosan treatment could be used to control the physiological responses induced by bruise damage.

Synthesis and Characterization of Novel Chiral NHC-palladium Complexes and Their Application in Copper-free Sonogashira Reactions

Dalton Transactions (Cambridge, England : 2003). Mar, 2012  |  Pubmed ID: 22415100

A new series of chiral N-heterocyclic carbene (NHC) palladium complexes were synthesized from a relatively inexpensive amino acid, l-phenylalanine. All these compounds were fully characterized by (1)H-NMR, (13)C-NMR and elemental analysis. The X-ray molecular structures of two of the complexes were reported. The catalytic activity of the four palladium complexes was successfully tested in the Sonogashira reaction under copper free conditions in air. The palladium complex provided good activity in the Sonogashira coupling reaction.

A Genetically Encoded Copper(i) Sensor Based on Engineered Structural Distortion of EGFP

Chemical Communications (Cambridge, England). Mar, 2012  |  Pubmed ID: 22415114

We report a genetically encoded fluorescent sensor for in vivo copper(i) imaging based on engineered intramolecular mechanical strain and structural distortion of EGFP.

Role of Dutasteride in Pre-clinical ETS Fusion-positive Prostate Cancer Models

The Prostate. Mar, 2012  |  Pubmed ID: 22415461

BACKGROUND: Androgens play a crucial role in prostate cancer, hence the androgenic pathway has become an important target of therapeutic intervention. Previously we discovered that gene fusions between the 5'-untranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases. The resulting aberrant overexpression of ETS genes drives tumor progression. METHODS: Here, we evaluated the expression levels of 5α-reductase isoenzymes in prostate cancer cell lines and tissues. We tested the effect of dutasteride, a 5α-reductase inhibitor, in TMPRSS2-ERG fusion-positive VCaP cell proliferation and cell invasion. We also evaluated the effect of dutasteride on the TMPRSS2-ERG fusion gene expression. Finally, we tested dutasteride alone or in combination with an anti-androgen in VCaP cell xenografts tumor model. RESULTS: Our data showed that 5α-reductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the conversion of testosterone to DHT, are highly expressed in metastatic prostate cancer compared to benign and localized prostate cancer. Dutasteride treatment attenuated VCaP cell proliferation and invasion. VCaP cells pre-treated with dutasteride showed a reduction in ERG and PSA expression. In vivo studies demonstrated that dutasteride in combination with the anti-androgen bicalutamide significantly decreased tumor burden in VCaP cell xenograft model. CONCLUSIONS: Our findings suggest that dutasteride can inhibit ERG fusion-positive cell growth and in combination with anti-androgen, significantly reduce the tumor burden. Our study suggests that anti-androgens used in combination with dutasteride could synergistically augment the therapeutic efficacy in the treatment of ETS-positive prostate cancer. Prostate © 2012 Wiley Periodicals, Inc.

Highly Efficient Heterogeneous Gold-catalyzed Direct Synthesis of Tertiary and Secondary Amines from Alcohols and Urea

ChemSusChem. Mar, 2012  |  Pubmed ID: 22415929

Urea, the white gold: The efficient synthesis of tertiary and secondary amines is achieved by heterogeneous gold-catalyzed direct amination of stoichiometric alcohols with urea in good to excellent yields. Via a hydrogen autotransfer pathway, the reactions of primary alcohols with urea give tertiary amines exclusively, while secondary alcohols selectively afford secondary amines.

Intravenous Injection of Mesenchymal Stem Cells is Effective in Treating Liver Fibrosis

World Journal of Gastroenterology : WJG. Mar, 2012  |  Pubmed ID: 22416179

To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis.

Quantification of Choline Concentration Following Liver Cell Apoptosis Using H Magnetic Resonance Spectroscopy

World Journal of Gastroenterology : WJG. Mar, 2012  |  Pubmed ID: 22416190

To evaluate the feasibility of quantifying liver choline concentrations in both normal and apoptotic rabbit livers in vivo, using (1)H magnetic resonance spectroscopy ((1)H-MRS).

[Effect of BYDV-MP Nuclear Localization Signal on the Movement of PVX]

Bing Du Xue Bao = Chinese Journal of Virology / [bian Ji, Bing Du Xue Bao Bian Ji Wei Yuan Hui]. Jan, 2012  |  Pubmed ID: 22416348

Abstract:By using PVX derived vector pGR107, the effect of BYDV-MP nuclear localization signal on the movement of PVX was studied. BYDV-MP was cloned into pGR107 using GFP as an indicator. BYDV-MP was then shown to induce the systemic infection and exacerbate the symptom of PVX through infecting Nicotiana benthamiana. When the PVX gene encoding 25kD protein, which functioned as a systematic movemnet protein,was deleted and the above experiment was repeated, the result showed that BYDV-MP could compensate the systemic movement of PVX. A serial mutants with substitutions on the fifth, sixth and seventh amino acids of BYDV-MP nuclear localization signal was further constructed. It was found that the mutants at the fifth, sixth amino acids in BYDV-MP nuclear localization signal could only delay or weaken systemic movement of PVX whereas the mutant at seventh amino acid could entirely inhibit systemic movement of PVX.

Systematic Evaluation of Supported Liquid Extraction in Reducing Matrix Effect and Improving Extraction Efficiency in LC-MS/MS Based Bioanalysis for 10 Model Pharmaceutical Compounds

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Feb, 2012  |  Pubmed ID: 22410088

In past a few years, there has been a large increase in the application of supported liquid extraction (SLE) for LC-MS/MS based bioanalysis due to its distinct practical advantage in reduced time cost, ease of operation and the feasibility for automation. The main purpose of this study was to systematically evaluate supported liquid extraction in reducing matrix effect and improving extraction efficiency/recovery under various extraction conditions with 10 model pharmaceutical compounds in liquid chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS) analysis. Selected compounds have diverse physicochemical properties where logP ranges from 0.1 to 6.24 and pK(a) ranges from 4.0 to 11.1. The factors that may have the impact on the recovery of analytes and phospholipids (PL) were assessed. Over 75% recovery was achieved for every analyte under its respectively optimized extraction conditions where the selection of the polarity of extraction solvent and buffered pH can be critical for efficient recovery. Furthermore, the matrix effect was assessed by postextraction spike and postcolumn infusion method. The matrix effect was considerably reduced for all analytes under most extraction conditions evaluated for SLE, compared with protein precipitation (PPT) method. The correlation between matrix effect and residual phospholipids in sample extract was clearly shown. Although analyte-dependent matrix effect was observed prominently in sample extract prepared by PPT, it was minimized by SLE sample preparation process that effectively removes the majority of phospholipids. Sample extracted by ethyl acetate contained more phospholipids and demonstrated stronger matrix effect than by other organic solvents. Water-miscible organic content, such as methanol and acetonitrile in samples prior to loading has significant impact on PL recovery when eluting with methyl tert-butyl ether. However, isopropanol does not enhance the recovery of PL when adding to dichloromethane for elution. In addition, the compromise between improved extraction efficiency by SLE and reduced matrix effect is sometimes necessary to yield clean extract with acceptable recovery. The effective removal of phospholipids and reduction of matrix effect, while achieving good recovery for all pharmaceutical compounds with diverse physicochemical properties, demonstrated that SLE is a valuable alternative technique to liquid-liquid extraction (LLE) in high throughput LC-MS/MS based bioanalysis.

Bioactivity of Horseradish Peroxidase Entrapped in Silica Nanospheres

Biosensors & Bioelectronics. Feb, 2012  |  Pubmed ID: 22410482

Interest in the fabrication of micro/nanoreactors for evaluation of the function of biomolecules in biological processes, enzymatic reaction kinetics occurring inside the nanospace is rapidly increasing. With a simple reverse-micelle microemulsion method, horseradish peroxidase (HRP), a model biomolecule, was herein skillfully confined in silica nanoshells (HRP@SiO(2)) and its biocatalytical behaviors were investigated in detail. Spectroscopic measurements showed that the entrapped HRP molecules retained their native structure and had high enzymatic activity toward 3,3',5,5'-tetramethylbenzidine (TMB) with Michaelis constant (K(m)) of 3.02×10(-5)molL(-1). The entrapped HRP displayed a good direct electron transfer behavior and sensitive electrocatalytic response toward the reduction of H(2)O(2), which could be enhanced using thionine and o-phenylenediamine (o-PD) as electron mediators. When using thionine as mediator, the mass transport between the substrates in electrolyte and HRP confined in silica nanospheres through the mesoporous tunnels was slower than that of o-PD, which slowed down the electron transfer between heme in HRP in the confined nanospace and the electrode, and resulted in low sensitivity to H(2)O(2) with thionine as mediator when compared to o-PD.

Vacuolar Protein Sorting 35 Asp620Asn Mutation is Rare in the Ethnic Chinese Population with Parkinson's Disease

Parkinsonism & Related Disorders. Mar, 2012  |  Pubmed ID: 22410496

Vacuolar protein sorting 35 (VPS35) Asp620Asn mutation has been identified in late-onset familial Parkinson's disease (PD) patients of Swiss and Austrian descent as well as sporadic PD patients in the United States. In order to determine the contribution of VPS35 mutations in mainland Chinese PD patients and to better understand the association between VPS35 and PD, we sequenced all 17 exons of VPS35 in 32 probands of presumed autosomal-dominant, late-onset familial PD and 35 normal controls. Meanwhile, we analyzed VPS35 Asp620Asn mutation in 512 PD patients. A total of 371 subjects without neurological disorders from the same region in China were set as a control group. We did not find any VPS35 coding region mutation in 32 familial PD patients. VPS35 Asp620Asn mutation was either not found in 480 PD patients. Our results suggested that VPS35 Asp620Asn may be not associated with PD in Chinese population.

Curcumin Inhibits LPS-Induced CCL2 Expression Via JNK Pathway in C6 Rat Astrocytoma Cells

Cellular and Molecular Neurobiology. Mar, 2012  |  Pubmed ID: 22410671

The important role of neuroinflammation in many chronic and acute pathological conditions of the central nervous system is widely recognized. Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. This study investigated the inhibitory effect of curcumin on lipopolysacharide (LPS)-induced chemokine CCL2 (or monocyte chemoattractant protein-1, MCP-1) production and whether the effect is mediated by mitogen-activated protein kinases (MAPKs) in the rat astrocytoma cell C6. We observed that LPS (1 μg/ml) induced the upregulation of CCL2 mRNA and protein in C6. Treatment with curcumin (2.5, 10, and 25 μM) decreased the expression of CCL2 mRNA and protein in a dose-dependent manner under treatment with LPS. Additionally, the c-jun N-terminal kinase (JNK) inhibitor (SP600125) dose-dependently inhibited LPS-induced CCL2 upregulation, whereas the MAPK kinase (MEK) inhibitor (PD98059) only had a mild effect and the p38 MAPK inhibitor (SB203580) had no effect. Finally, western blot showed that LPS induced rapid JNK activation and curcumin reduced LPS-induced phosphoJNK (pJNK) expression at 30 min after LPS stimulation. These data suggest that the anti-neuroinflammatory effect of curcumin relates to the downregulation of CCL2 expression through the JNK pathway in astrocytoma cells, which indicates a possible benefit from the use of curcumin in the treatment of neuroinflammation-associated disorders.

Improved Algorithm for Phase-to-height Mapping in Phase Measuring Profilometry

Applied Optics. Mar, 2012  |  Pubmed ID: 22410995

An improved algorithm for phase-to-height mapping in phase-measuring profilometry (PMP) is proposed, in which the phase-to-height mapping relationship is no longer restricted to the condition that the optical axes of the imaging system must be orthogonal to the reference plane in the basic PMP. Only seven coefficients independent of the coordinate system need to be calibrated, and the system calibration can be accomplished using only two different gauge blocks, instead of more than three different standard planes. With the proposed algorithm, both the phase measurement and system calibration can be completed simultaneously, which makes the three-dimensional (3-D) measurement faster and more flexible. Experiments have verified its feasibility and validity.

Early Lung Cancer Detection Using the Self-Evaluation Scoring Questionnaire and Chest Digital Radiography: A 3-Year Follow-up Study in China

Journal of Digital Imaging : the Official Journal of the Society for Computer Applications in Radiology. Mar, 2012  |  Pubmed ID: 22411060

The standard definition of high-risk individuals for lung cancer was not uniform and the value of chest digital radiography (DR) in lung cancer screening was still unproven. The aim of this study was to assess whether the original questionnaire named as "Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer" combined with DR examinations could detect early stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer had been designed in previous studies. Subjects with scores over 116 points were regarded as high-risk individuals and underwent the current DR scans at least once a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of the scoring questionnaire combined with DR scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were diagnosed with lung cancer in the first, second, and third year, respectively, indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31) of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the 31 cases, 28 were defined as detected cancers, while the other three were interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with DR scans is a cost-effective and safe approach to detect early stage of lung cancer.

Three-dimensional Domain Swapping in the Protein Structure Space

Proteins. Feb, 2012  |  Pubmed ID: 22411444

Since the proposal of three-dimensional (3D) domain swapping, many 3D domain-swapped structures have been reported. However, when compared with the vast protein structure space, it is still unclear whether 3D domain swapping is a general mechanism for protein assembly. Here, we investigated this possibility by constructing a dataset consisting of more than 500 domain-swapped structures. The domain-swapped structures were mapped into the protein structure space. We found that about 10% of protein folds and 5% of protein families contain domain-swapped structures. When comparing the domain-swapped structures in a family/superfamily, we found that proteins within a family/superfamily can swap in different ways. Interface analysis revealed that the hinge loops contributed more than half of the open interface in 70% of bona fide domain-swapped dimers, indicating that the hinge loops play an important role in stabilizing the domain-swapped conformations. Our study supports the suggestion that domain swapping is a general property of all proteins and will facilitate further understanding the mechanism of 3D domain swapping. Proteins 2012. © 2012 Wiley Periodicals, Inc.

Cobalt-Doping-Induced Synthesis of Ceria Nanodisks and Their Significantly Enhanced Catalytic Activity

Small (Weinheim an Der Bergstrasse, Germany). Mar, 2012  |  Pubmed ID: 22411586

High-quality cobalt-doped ceria nanostructures with triangular column, triangular slab, and disklike shapes are synthesized by tuning the doping amount of cobalt nitrate in a facile hydrothermal reaction. The cobalt-doped ceria nanodisks display significantly enhanced catalytic activity in CO oxidation due to exposed highly active crystal planes and the presence of numerous surface defects.

The Effects of Nanofiber Topography on Astrocyte Behavior and Gene Silencing Efficiency

Macromolecular Bioscience. Mar, 2012  |  Pubmed ID: 22411782

Astrocyte-nanofiber interactions are studied by culturing primary rat cortical astrocytes on poly[caprolactone-co-(ethyl ethylene phosphate)] electrospun nanofibers and solvent-cast films (two-dimensional control). The results indicate that nanofiber topography significantly suppresses astrocyte proliferation and enhances apoptosis, without altering cellular activation as compared to films. Moreover, nanofiber topography enhances gene-silencing efficiency in astrocytes. The results suggest that nanofibers may serve as potential substrates for nerve regeneration by suppressing astrocyte growth and may further facilitate the use of gene-silencing to enhance CNS regeneration.

Selective Disruption of High Sensitivity Heat Activation but Not Capsaicin Activation of TRPV1 Channels by Pore Turret Mutations

The Journal of General Physiology. Mar, 2012  |  Pubmed ID: 22412190

The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.

Poly[[tetra-aqua-di-μ(4)-oxalato-μ(2)-oxalato-dineo-dymium(III)] Dihydrate]

Acta Crystallographica. Section E, Structure Reports Online. Mar, 2012  |  Pubmed ID: 22412435

The title compound, {[Nd(2)(C(2)O(4))(3)(H(2)O)(4)]·2H(2)O}(n), was synthesized hydro-thermally in the presence of bis-(carb-oxy-ethyl-germanium) sesquioxide. It is isostructural with the corresponding Pr compound [Yang et al. (2009). Acta Cryst. E65, m1152-m1153]. The Nd(3+) cation is nine-coordinated and its coordination polyhedron can be described as a distorted tricapped trigonal prism. Two Nd(3+) ions are connected by two O atoms from two oxalate ions to give a dinuclear Nd(2) unit. The unit is further linked to four others via four oxalate ions yielding a layerparallel to (0-11). The linkages between the layers by neighbouring oxalate anions lead to a three-dimensional framework with channels along the c axis. The coordinating and free water mol-ecules are located in the channels and make contact with each other and the host framework by weak O-H⋯O hydrogen bonds.

2,2'-{[4,6-Bis(octyl-amino)-1,3,5-triazin-2-yl]aza-nedi-yl}diethanol

Acta Crystallographica. Section E, Structure Reports Online. Mar, 2012  |  Pubmed ID: 22412528

In the title compound, C(23)H(46)N(6)O(2), the two hy-droxy groups are located on opposite sides of the triazine ring. One of the hy-droxy groups links with the triazine N atom via an intra-molecular O-H⋯N hydrogen bond. Inter-molecular O-H⋯N and N-H⋯O hydrogen bonding is observed in the crystal structure. π-π stacking is also observed between parallel triazine rings of adjacent mol-ecules, the centroid-centroid distance being 3.5944 (14) Å.

5-Methyl-3,3-bis-(morpholin-4-yl)-1-[2-(morpholin-4-yl)eth-yl]-2,3-dihydro-1H-indol-2-one

Acta Crystallographica. Section E, Structure Reports Online. Mar, 2012  |  Pubmed ID: 22412685

In the title compound, C(23)H(34)N(4)O(4), the morpholine rings adopt chair conformations. The N atom of the indol-2-one group is linked to the N atom of one morpholine ring through a flexible ethyl group with an almost cif conformation. In the crystal, molecules are linked by C-H⋯O interactions into infinite chains along the c direction. The almost parallel infinite chains are further inter-connected via other sets of C-H⋯O inter-actions, forming a three-dimensional framework.

Cigarette Smoke Upregulates Rat Coronary Artery Endothelin Receptors in Vivo

PloS One. 2012  |  Pubmed ID: 22412974

Cigarette smoking is a strong cardiovascular risk factor and endothelin (ET) receptors are related to coronary artery diseases. The present study established an in vivo secondhand smoke (SHS) exposure model and investigated the hypothesis that cigarette smoke induces ET receptor upregulation in rat coronary arteries and its possible underlying mechanisms.

Cribriform-morular Variant of Papillary Thyroid Carcinoma: Characteristic Histologic Feature of Adenomatous Polyposis. A Case Report

Annales D'endocrinologie. Mar, 2012  |  Pubmed ID: 22387099

We report the case of a 24-year-old woman with familial adenomatous polyposis and diagnosed with cribriform-morular variant of papillary thyroid carcinoma. Neck ultrasound and computed tomography identified multiple nodules in the thyroid gland and neck lymph nodes. The cytological analysis was compatible with the diagnosis of papillary cancer of the thyroid. Total thyroidectomy with lymph node dissection was performed. The histological analysis established the diagnosis of cribriform-morular variant of papillary thyroid carcinoma. Despite preoperative findings suggesting an aggressive form of thyroid cancer with lymph node involvement, the final diagnosis was a variant of papillary thyroid carcinoma often associated with familial adenomatous polyposis and known to have a good prognosis.

P28GANK Prevents Degradation of Oct4 and Promotes Expansion of Tumor-Initiating Cells in Hepatocarcinogenesis

Gastroenterology. Feb, 2012  |  Pubmed ID: 22387393

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), although little is known about their stem cell-like properties. METHODS: We quantified levels of p28 (GANK) (Gankyrin), OV6, and Oct4 in 130 human HCC samples using immunohistochemistry. Magnetic-activated cell sorting was used to isolate OV6(+) HCC cells. T-IC properties were evaluated by quantitative reverse transcription PCR, flow cytometry, and spheroid formation. We used a co-immunoprecipitation assay to study interactions among p28 (GANK), Oct4, and WWP2. Tumorigenicity and pulmonary metastasis were examined in nonobese-diabetic and severe combined immunodeficient mice. RESULTS: In HCC samples, high levels of p28 (GANK) correlated with expansion of OV6(+) tumor cells; the combination of high levels of p28 (GANK) and OV6 was associated with progression of HCC. p28 (GANK) was predominantly expressed in liver T-ICs, isolated by magnetic sorting, and undifferentiated primary HCC spheroids. Increased levels of p28 (GANK) in T-ICs increased their percentages in HCC samples, expression of stem cell genes, self-renewal potential, chemoresistance in vitro, and tumorigenicity and ability to develop into pulmonary metastases in mice. Conversely, knockdown of p28 (GANK) reduced their T-IC properties. p28 (GANK) likely activates liver T-ICs by impeding ubiquitination and degradation of the transcription factor Oct4 by WWP2. In support of this concept, levels of p28 (GANK) correlated with those of Oct4 in HCC samples. CONCLUSIONS: p28(GANK) activates and maintains liver T-ICs in HCCs by preventing degradation of Oct4. Inhibitors of p28 (GANK) might therefore be developed to inactivate T-ICs and slow tumor progression.

C-terminal Region of 48-kDa Rhoptry Protein for Serological Detection of Babesia Caballi Antibodies in Horses

Parasitology International. Feb, 2012  |  Pubmed ID: 22387861

A recombinant C-terminal antigen derived from Babesia caballi 48-kDa rhoptry protein (rBc48/CT) was made for the development of a serologically diagnostic test. Antiserum raised against the rBc48/CT reacted specifically with the corresponding native protein by Western blotting and the indirect fluorescent antibody test (IFAT). Next, an indirect enzyme-linked immunosorbent assay (Bc48/CT-ELISA) and an immunochromatographic test based on the Bc48/CT (Bc48/CT-ICT) were constructed and employed for the detection of an antibody to B. caballi in a variety of equine sera. The results of Bc48/CT-ELISA and Bc48/CT-ICT were highly concordant with those of IFAT and ELISA, with full-length protein of Bc48 used as the reference tests. Our results demonstrate the success of Bc48/CT as antigen for the serological diagnosis of B. caballi infection in horses.

Downregulation of MiR-210 Expression Inhibits Proliferation, Induces Apoptosis and Enhances Radiosensitivity in Hypoxic Human Hepatoma Cells in Vitro

Experimental Cell Research. Feb, 2012  |  Pubmed ID: 22387901

Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1α (HIF-1α) and miR-210 expression and cell arrest in the G(0)/G(1) phase in all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the G(0)/G(1) phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells.

Imatinib Induces H2AX Phosphorylation and Apoptosis in Chronic Myelogenous Leukemia Cells in Vitro Via Caspase-3/Mst1 Pathway

Acta Pharmacologica Sinica. Mar, 2012  |  Pubmed ID: 22388075

Aim:Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142) is required for tumor cell apoptosis. The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.Methods:BCR-ABL-positive K562 cells were used. Microscopy, Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms.Results:Treatment of K562 cells with imatinib (1-8 μmol/L) induced phosphorylation of H2AX at Ser139 and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX maintained a higher level in the cells. Meanwhile, imatinib (1-8 μmol/L) activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1), and induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD (40 μmol/L) reduced imatinib-induced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells. Imatinib (4 μmol/L) induced expression of Williams-Beuren syndrome transcription factor (WSTF), but not wild-type p53-induced phosphatase 1 (Wip1) in K562 cells.Conclusion:The caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.

Probing the Arabidopsis Flagellin Receptor: FLS2-FLS2 Association and the Contributions of Specific Domains to Signaling Function

The Plant Cell. Mar, 2012  |  Pubmed ID: 22388452

FLAGELLIN SENSING2 (FLS2) is a transmembrane receptor kinase that activates antimicrobial defense responses upon binding of bacterial flagellin or the flagellin-derived peptide flg22. We find that some Arabidopsis thaliana FLS2 is present in FLS2-FLS2 complexes before and after plant exposure to flg22. flg22 binding capability is not required for FLS2-FLS2 association. Cys pairs flank the extracellular leucine rich repeat (LRR) domain in FLS2 and many other LRR receptors, and we find that the Cys pair N-terminal to the FLS2 LRR is required for normal processing, stability, and function, possibly due to undescribed endoplasmic reticulum quality control mechanisms. By contrast, disruption of the membrane-proximal Cys pair does not block FLS2 function, instead increasing responsiveness to flg22, as indicated by a stronger oxidative burst. There was no evidence for intermolecular FLS2-FLS2 disulfide bridges. Truncated FLS2 containing only the intracellular domain associates with full-length FLS2 and exerts a dominant-negative effect on wild-type FLS2 function that is dependent on expression level but independent of the protein kinase capacity of the truncated protein. FLS2 is insensitive to disruption of multiple N-glycosylation sites, in contrast with the related receptor EF-Tu RECEPTOR that can be rendered nonfunctional by disruption of single glycosylation sites. These and additional findings more precisely define the molecular mechanisms of FLS2 receptor function.

Antitumor Potential of SLPI Promoter Controlled Recombinant Caspase-3 Expression in Laryngeal Carcinoma

Cancer Gene Therapy. Mar, 2012  |  Pubmed ID: 22388454

The purpose of this study is to develop a specific and efficient targeted gene therapy candidate approach for laryngeal carcinomas. Several promoters of human squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest efficiency and specificity, and was used to control the expression of a recombinant active caspases-3 (revCasp3), which could trigger apoptosis without activation of its upstream cascade elements once expressed in a cell, in an adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase-3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth without obvious loss of body weight and obvious hepatic toxicity. In summary, our study showed the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene therapy for laryngeal squamous cell carcinoma, which needs further systematic investigation.Cancer Gene Therapy advance online publication, 2 March 2012; doi:10.1038/cgt.2012.5.

Licochalcone A Inhibits Lipopolysaccharide-induced Inflammatory Response in Vitro and in Vivo

Journal of Agricultural and Food Chemistry. Mar, 2012  |  Pubmed ID: 22400806

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its anti-microbial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we found that Lico A exerted potent anti-inflammatory effects in vitro and in vivo models induced by LPS. The concentrations of TNF-α，Interleukin (IL)-6 and Interleukin (IL)-1β in the culture supernatants of RAW 264.7 cells determined at different time points following LPS administration. LPS (10μg) was instilled intranasally (i.n.) in 50 μl PBS to induce acute lung injury, twenty-four hours after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) p65 protein were analyzed by western blotting. Our results showed that Lico A significant reduce the amount of inflammatory cells, W/D ratio, protein leakage, MPO activity and enhances SOD activity in mice with LPS-induced ALI. ELISA results indicated that Lico A can significantly down-regulate TNF-α, Interleukin (IL)-6 and Interleukin (IL)-1β levels in vitro and in vivo. And we further demonstrated that Lico A exert anti-inflammation effect in vivo models of acute lung injury through suppresses NF-κB activation and p38/ERK MAPK signaling in a dose dependent manner.

Entropy Generation Across Earth's Collisionless Bow Shock

Physical Review Letters. Feb, 2012  |  Pubmed ID: 22401049

Earth's bow shock is a collisionless shock wave but entropy has never been directly measured across it. The plasma experiments on Cluster and Double Star measure 3D plasma distributions upstream and downstream of the bow shock allowing calculation of Boltzmann's entropy function H and his famous H theorem, dH/dt≤0. The collisionless Boltzmann (Vlasov) equation predicts that the total entropy does not change if the distribution function across the shock becomes nonthermal, but it allows changes in the entropy density. Here, we present the first direct measurements of entropy density changes across Earth's bow shock and show that the results generally support the model of the Vlasov analysis. These observations are a starting point for a more sophisticated analysis that includes 3D computer modeling of collisionless shocks with input from observed particles, waves, and turbulences.

[Bundle Therapy for Septic Shock in Children]

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue = Chinese Critical Care Medicine = Zhongguo Weizhongbing Jijiuyixue. Mar, 2012  |  Pubmed ID: 22401164

Top Quark Production Asymmetries A_{FB}^{t} and A_{FB}^{ℓ}

Physical Review Letters. Feb, 2012  |  Pubmed ID: 22401195

A large forward-backward asymmetry is seen in both the top quark rapidity distribution A_{FB}^{t} and in the rapidity distribution of charged leptons A_{FB}^{ℓ} from top quarks produced at the Tevatron. We study the kinematic and dynamic aspects of the relationship of the two observables arising from the spin correlation between the charged lepton and the top quark with different polarization states. We emphasize the value of both measurements, and we conclude that a new physics model which produces more right-handed than left-handed top quarks is favored by the present data.

Discovery of Oxazole-based PDE4 Inhibitors with Picomolar Potency

Bioorganic & Medicinal Chemistry Letters. Feb, 2012  |  Pubmed ID: 22401864

Optimization of oxazole-based PDE4 inhibitors has led to the discovery of a series of quinolyl oxazoles, with 4-benzylcarboxamide and 5-α-aminoethyl groups which exhibit picomolar potency against PDE4. Selectivity profiles and in vivo biological activity are also reported.

Estrogen-independent Effects of ER-α36 in ER-negative Breast Cancer

Steroids. Feb, 2012  |  Pubmed ID: 22402113

Estrogen receptor-alpha 36 (ER-α36) is a variant of ER-α that has been found to be expressed in conventional ER (ER-α66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study, ER-α36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-α36-specific microRNA hairpin vector and established stable ER-α36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-α36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-α36 may be a strategy for treating ER-negative breast cancers.

A Line-profile Based Double Partial Fusion Method for Acquiring Planning CT of Oversized Patients in Radiation Treatment

Journal of Applied Clinical Medical Physics / American College of Medical Physics. 2012  |  Pubmed ID: 22402380

True 3D CT dataset for treatment planning of an oversized patient is difficult to acquire due to the bore size and field of view (FOV) reconstruction. This project aims to provide a simple approach to reconstruct true CT data for oversize patients using CT scanner with limited FOV by acquiring double partial CT (left and right side) images. An efficient line profile-based method has been developed to minimize the difference of the CT numbers in the overlapping region between the right and left images and to generate a complete true 3D CT dataset in the natural state. New image processing modules have been developed and integrated to the Insight Segmentation & Registration Toolkit (ITK 3.6) package. For example, different modules for image cropping, line profile generation, line profile matching, and optimized partial image fusion have been developed. The algorithm has been implemented for images containing the bony structure of the spine and tested on 3D CT planning datasets from both phantom and real patients with satisfactory results in both cases. The proposed optimized line profile-based partial registration method provides a simple and accurate method for acquiring a complete true 3D CT dataset for an oversized patient using CT scanning with small bore size, that can be used for accurate treatment planning.

Borondipyrromethene-derived Cu(2+) Sensing Chemodosimeter for Fast and Selective Detection

Organic & Biomolecular Chemistry. Mar, 2012  |  Pubmed ID: 22402504

Here, we report a new Cu(2+)-selective fluorescent turn-on probe BODIPY-EP, in which the 2-pyridinecarboxylic acid is connected to a 6-hydroxyindole-based BODIPY platform through an ester linkage. The ester bond of BODIPY-EP is selectively hydrolyzed by the reaction with Cu(2+) under mild and neutral conditions to generate BODIPY-OH, showing strong characteristic fluorescence of BODIPY-OH. The favorable features of BODIPY-EP towards Cu(2+) include fast response, large fluorescence enhancement and high selectivity. We further demonstrated that the membrane-permeable probe reacts with intracellular Cu(2+) and exhibits bright fluorescence in living cells.

SKLB1028, a Novel Oral Multikinase Inhibitor of EGFR, FLT3 and Abl, Displays Exceptional Activity in Models of FLT3-driven AML and Considerable Potency in Models of CML Harboring Abl Mutants

Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. Mar, 2012  |  Pubmed ID: 22402607

Asian Medicine: Exploitation of Plants

Science (New York, N.Y.). Mar, 2012  |  Pubmed ID: 22403370

A Mitochondria-Dependent Pathway Mediates the Apoptosis of GSE-Induced Yeast

PloS One. 2012  |  Pubmed ID: 22403727

Grapefruit seed extract (GSE), which has powerful anti-fungal activity, can induce apoptosis in S. cerevisiae. The yeast cells underwent apoptosis as determined by testing for apoptotic markers of DNA cleavage and typical chromatin condensation by Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and 4,6'-diaminidino-2-phenylindole (DAPI) staining and electron microscopy. The changes of ΔΨmt (mitochondrial transmembrane potential) and ROS (reactive oxygen species) indicated that the mitochondria took part in the apoptotic process. Changes in this process detected by metabonomics and proteomics revealed that the yeast cells tenaciously resisted adversity. Proteins related to redox, cellular structure, membrane, energy and DNA repair were significantly increased. In this study, the relative changes in the levels of proteins and metabolites showed the tenacious resistance of yeast cells. However, GSE induced apoptosis in the yeast cells by destruction of the mitochondrial 60 S ribosomal protein, L14-A, and prevented the conversion of pantothenic acid to coenzyme A (CoA). The relationship between the proteins and metabolites was analyzed by orthogonal projections to latent structures (OPLS). We found that the changes of the metabolites and the protein changes had relevant consistency.

[Numerical Analysis on Hemodynamics of Cerebral Aneurysm Clip]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Feb, 2012  |  Pubmed ID: 22404017

Computational fluid dynamics (CFD) was used to numerically investigate the blood flow in 3-D models of human preoperative and posteroperative of cerebral aneurysm clip, and the feasibility of surgical operation was evaluated by the calculated hemodynamics parameters. Mimics software was used to reconstruct the models from CT angiograms, and numerical simulation of blood flow at different time in a cardiac circle was performed. Comparison analysis of blood flow in three models of human preoperative and posteroperative of cerebral aneurysm clip was conducted in terms of blood velocity distribution, wall shear stress (WSS) distribution and pressure distribution. The results demonstrated that blood velocity and WSS were significantly increased, and pressure was obviously decreased.

Quantification of the Spatial Distribution of Rectally Applied Surrogates for Microbicide and Semen in Colon with SPECT and Magnetic Resonance Imaging

British Journal of Clinical Pharmacology. Mar, 2012  |  Pubmed ID: 22404308

Aims: We sought to quantitatively describe the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to rationally develop rectal microbicides to target and prevent HIV infection. Methods: Eight subjects were dosed rectally with radiolabeled and gadolinium-labeled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance (MR) imaging, and direct assessment via sigmoidoscopic brushes. Concentration-distance curves were generated using an algorithm for fitting SPECT data in 3-dimensions. Three novel concentration-distance parameters were defined to quantitatively describe the distribution of radiolabels: maximal distance (D(max) ), distance at maximal concentration (D(Cmax) ), mean residence distance (D(ave) ). Results: The SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1 hour and 24 hours post-dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (D(max) ), 10 cm (8.6-12) to 18 cm (13-26); distance at maximal concentration (D(Cmax) ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3); mean residence distance (D(ave) ), 4.3 cm (3.5-5.1) to7.6 cm (5.3-11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT. Conclusions: Rectal microbicide surrogates migrated retrograde during the 24 hours following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

P27(kip1) Upregulated by HnRNPC1/2 Antagonizes CagA (a Virulence Factor of Helicobacter Pylori)-Mediated Pathogenesis

Helicobacter. Apr, 2012  |  Pubmed ID: 22404445

Background and Aims:  Infection by Helicobacter pylori is one of the major contributing factors of chronic active gastritis and peptic ulcer and is closely associated with the occurrence and progression of gastric cancer. CagA protein is a major virulence factor of H. pylori that interacts with SHP-2, a true oncogene, to interfere with cellular signaling pathways; CagA also plays a crucial role in promoting the carcinogenesis of gastric epithelial cells. However, currently, the molecular mechanisms of gastric epithelial cells that antagonize CagA pathogenesis remain inconclusive. Methods:  We showed that AGS gastric cancer cells transfected with CagA exhibited the inhibition of proliferation and increased activity of caspase 3/7 using two-dimensional gel electrophoresis and secondary mass spectrometry (MS/MS). Results:  It was found that the AGS gastric cancer cells stably expressing CagA displayed significantly increased the expression of 16 proteins, including hnRNPC1/2. Further analysis revealed that hnRNPC1/2 significantly boosted the expression of the p27(kip1) protein. Conclusion: Our data suggested that hnRNPC1/2 upregulates p27(kip1) expression and the subsequent suppression of cell proliferation and induction of apoptosis, thereby providing an important mechanism whereby gastric epithelial cells antagonize CagA-mediated pathogenesis.

Exome Sequencing Reveals Mutations in TRPV3 As a Cause of Olmsted Syndrome

American Journal of Human Genetics. Mar, 2012  |  Pubmed ID: 22405088

Olmsted syndrome (OS) is a rare congenital disorder characterized by palmoplantar and periorificial keratoderma, alopecia in most cases, and severe itching. The genetic basis for OS remained unidentified. Using whole-exome sequencing of case-parents trios, we have identified a de novo missense mutation in TRPV3 that produces p.Gly573Ser in an individual with OS. Nucleotide sequencing of five additional affected individuals also revealed missense mutations in TRPV3 (which produced p.Gly573Ser in three cases and p.Gly573Cys and p.Trp692Gly in one case each). Encoding a transient receptor potential vanilloid-3 cation channel, TRPV3 is primarily expressed in the skin, hair follicles, brain, and spinal cord. In transfected HEK293 cells expressing TRPV3 mutants, much larger inward currents were recorded, probably because of the constitutive opening of the mutants. These gain-of-function mutations might lead to elevated apoptosis of keratinocytes and consequent skin hyperkeratosis in the affected individuals. Our findings suggest that TRPV3 plays essential roles in skin keratinization, hair growth, and possibly itching sensation in humans and selectively targeting TRPV3 could provide therapeutic potential for keratinization or itching-related skin disorders.

Individual- and Area-level Unemployment Influence Smoking Cessation Among African Americans Participating in a Randomized Clinical Trial

Social Science & Medicine (1982). Feb, 2012  |  Pubmed ID: 22405506

African Americans suffer disproportionately from the adverse health consequences of smoking, and also report substantially lower socioeconomic status than Whites and other racial/ethnic groups in the U.S. Although socioeconomic disadvantage is known to have a negative influence on smoking cessation rates and overall health, little is known about the influence of socioeconomic status on smoking cessation specifically among African Americans. Thus, the purpose of the current study was to characterize the impact of several individual- and area-level indicators of socioeconomic status on smoking cessation among African Americans. Data were collected as part of a smoking cessation intervention study for African American smokers (N = 379) recruited from the Houston, Texas, metropolitan area, who participated in the study between 2005 and 2007. The separate and combined influences of individual-level (insurance status, unemployment, education, and income) and area-level (neighborhood unemployment, education, income, and poverty) indicators of socioeconomic status on continuous smoking abstinence were examined across time intervals using continuation ratio logit modeling. Individual-level analyses indicated that unemployment was significantly associated with reduced odds of smoking abstinence, while higher income was associated with greater odds of abstinence. However, only unemployment remained a significant predictor of abstinence when unemployment and income were included in the model together. Area-level analyses indicated that greater neighborhood unemployment and poverty were associated with reduced odds of smoking abstinence, while greater neighborhood education was associated with higher odds of abstinence. However, only neighborhood unemployment remained significantly associated with abstinence status when individual-level income and unemployment were included in the model. Overall, findings suggest that individual- and area-level unemployment have a negative impact on smoking cessation among African Americans. Addressing unemployment through public policy and within smoking cessation interventions, and providing smoking cessation treatment for the unemployed may have a beneficial impact on tobacco-related health disparities.

Drug-eluting Stents Versus Coronary Artery Bypass Graft Surgery in Left Main Coronary Artery Disease: A Meta-analysis of Early Outcomes from Randomized and Nonrandomized Studies

The Journal of Thoracic and Cardiovascular Surgery. Mar, 2012  |  Pubmed ID: 22405674

OBJECTIVE: The present meta-analysis aimed to compare the short-term safety and efficacy of drug-eluting stents and coronary artery bypass graft surgery for patients with left main coronary artery disease. METHODS: Fourteen relevant studies were identified from 5 electronic databases. End points included mortality, stroke, myocardial infarction, repeat revascularization, and major adverse cardiac and cerebrovascular events. RESULTS: Results indicate that all-cause mortality was similar between drug-eluting stents and coronary artery bypass grafting at 30 days and at follow-up beyond 1 year. Likewise, the incidence of myocardial infarction was similar between drug-eluting stents and coronary artery bypass grafting at 12 months and at follow-up beyond 1 year. However, drug-eluting stents were associated with a lower incidence of all-cause mortality at 12 months and a higher incidence of myocardial infarction at 30 days compared with coronary artery bypass grafting. Drug-eluting stents were consistently associated with a higher incidence of repeat revascularization, whereas coronary artery bypass grafting had a higher incidence of stroke. The incidence of major adverse cardiac and cerebrovascular events was similar between the 2 groups at 30 days but higher for drug-eluting stents at 12 months and beyond. CONCLUSIONS: Patients treated by drug-eluting stents in randomized controlled trials and observational studies in the current literature are often a preselected subgroup with less complex lesions compared with the overall target population. Results drawn from these studies should be viewed with caution. Coronary artery bypass grafting is associated with a lower incidence of major adverse cardiac and cerebrovascular events at 1 year and beyond, and thus should be regarded as the standard of treatment. However, drug-eluting stents may have a role for selected patients with percutaneously amenable left main disease who are poor surgical candidates.

The Effects of Starvation on Digestive Tract Function and Structure in Juvenile Southern Catfish (Silurus Meridionalis Chen)

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. Mar, 2012  |  Pubmed ID: 22405802

The size and functional capacity of the gastrointestinal (GI) tract and associated organs vary in response to environmental cues. The GI tract and associated organs are also very metabolically active in animals. Hence, animals may reduce the size and function of their GI tract to conserve energy when deprived of food. The main aims of this study were to investigate how Silurus meridionalis regulates the function and structure of its GI tract and associated organs during starvation. Starvation induced a decrease in both maintenance metabolism (MO(2rest), decreased by approximately 50%) and respiratory frequency (indicated by double side gill activity and notated as f(R), decreased by 29%). Lipase, trypsin and aminopeptidase-A showed a similar reduction in mass-specific activities during starvation, but pepsin and α-amylase did not. The starvation of experimental fish resulted in a significant reduction in body weight, the wet mass of the liver and the digestive-somatic system, the hepato-somatic index and the condition factor whereas the wet masses of the GI tract, pancreas, gall bladder and the relative intestinal length did not vary significantly during starvation. The reduction in liver wet mass was the main reason for the decrease in the wet mass of digestive-somatic system in this species. Only the mucosal area of the PI was affected significantly by starvation, decreasing by 34% at the end of the experiment. S. meridionalis displayed a decreasing intestinal mucosal area towards the distal intestine, and this gradient was not affected by starvation. The morphology and structure of both the GI tract and the liver were greatly down-regulated, as indicated by decreases in liver cell size, the mucosal thickness of the stomach and intestine, the density of goblet cells and microvilli surface area (MVSA), implying that food deprivation greatly impaired the digestive and absorptive functions of the GI tract in S. meridionalis. When deprived of food, S. meridionalis can endure harsh periods of starvation and adaptively down-regulate the function and structure of the digestive tract with physiological and biochemical strategies.

Interaction Energy Evaluation of Soluble Microbial Products (SMP) on Different Membrane Surfaces: Role of the Reconstructed Membrane Topology

Water Research. Feb, 2012  |  Pubmed ID: 22406287

Soluble microbial products (SMP), a majority of organic matter in effluents, play a key role in membrane fouling. A series of filtration experiments were conducted, and demonstrated that the flux decrement rate was in order of cellulose acetate membrane (CA, 65.4%), polyvinylidene fluoride (PVDF, 47.9%) and polyether sulfones (PES, 29.2%). Results showed that the fouling behavior of membrane should be predicted from the combined knowledge of solution chemistry, surface chemical properties and surface morphology. To better understand the interactions between the SMP and different membranes, a technique for reconstructing the membrane surface topology was developed on the basis of statistical parameters obtained from atomic force microscopy. The interaction energy, represented by extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) potential, was calculated by surface element integration, allowing exploring the interaction energy profiles for different surfaces and providing considerable insights into the role of such interactions on the macroscopic fouling behavior. The resulting interaction energy differed considerably from the corresponding interaction between perfectly smooth surfaces. The great influence of protrusion on the membrane surface was to reduce the primary energy barrier height, thus rendering rough surface more favorable for deposition. An attractive energy region was immediately surrounded by each positive asperity as demonstrated in the roughness-engendered interaction energy maps. As the SMP approached closer to the membrane, they had a high probability of getting trapped in the attractive energy region, leading to a more rapid loss of flux than smooth membrane.

Ca-Mg-Zn Bulk Metallic Glasses As Bioresorbable Metals

Acta Biomaterialia. Mar, 2012  |  Pubmed ID: 22406910

A series of six unique Ca-based bulk metallic glasseswere synthesised and characterised. The glasses were designed to be comprised solely of the biocompatible elements Ca, Mg and Zn,with the view of their potential use as bioresorbable metals for orthopaedic applications. The alloys had a critical casting thickness of up to 4.5mm.Mechanical and thermophysical testing revealed a Young's modulus (stiffness) of ∼40GPa.Glass transition temperatures ranged from 119to 129°C, above which the alloyscan be formed like a thermoplastic polymer. In vitrobiocorrosion testing using a combination of polarisation and mass loss techniques revealed that the corrosion rate of these alloys is relatively rapidalthough, in some cases, may be tailored through alloy composition.

N-3 Polyunsaturated Fatty Acids Inhibit Lipopolysaccharide-induced Microglial Activation and Dopaminergic Injury in Rats

Neurotoxicology. Mar, 2012  |  Pubmed ID: 22406923

Increasing evidence indicates that neuroinflammation plays an important role in neurotoxins-induced neurodegenerations. Microglia are a type of glial cells in the brain and play as the first and main form of active immune defense in the central nervous system. Accumulated data suggest that the activation of microglia plays a critical role in neurotoxicities induced by environmental toxicants. So the inhibition of microglia has been proven to be an effective strategy against neurotoxic effects. In the present study, we found that n-3 polyunsaturated fatty acids can inhibit both microglial activation and dopaminergic injury in the substantia nigra of Sprague-Dawley rats induced by lipopolysaccharide, one of the major constituents of the outer membrane of Gram-negative bacteria. Moreover, n-3 polyunsaturated fatty acids inhibited lipopolysaccharide-induced activation of nuclear factor-κB, an important transcription factor involved in microglial activation. Taken together, our results provided the first in vivo evidence that n-3 polyunsaturated fatty acids can inhibit the damage of dopaminergic neurons induced by lipopolysaccharide through their inhibitory effects on nuclear factor-κB-dependent microglial activation.

Resveratrol Sensitized Leukemia Stem Cell-like KG-1a Cells to Cytokine-induced Killer Cells-mediated Cytolysis Through NKG2D Ligands and TRAIL Receptors

Cancer Biology & Therapy. May, 2012  |  Pubmed ID: 22406996

Human promyeloblastic leukemia KG-1a cells exhibit many characteristics similar to leukemia stem cells, which are resistant to chemotherapeutic drugs and hyposensitive to cytotoxic cells. Resveratrol (RES), as a member of plant polyphenols, has gained considerable attention due to its ability to prevent cancer from progressing. In this study, the potential of RES to sensitize KG-1a cells to cytolysis of cytokine-induced killer cells (CIKs) through NKG2D ligands and TNF-related apoptosis-inducing ligand (TRAIL) receptors were investigated. Twenty-five micromolars RES was found to inhibit approximately 50% of KG-1a cell growth and had the least growth-inhibition effect on peripheral blood mononuclear cells (PBMCs) after 24 h. Utilizing cytokines including interleukin-2 (IL-2) and interleukin-15 (IL-15) to activate PBMCs, we obtained substantial CD3 (+) CD56 (+) natural killer cell-like T lymphocytes that secreted cytokine interferon-γ (IFN-γ) and expressed NKG2D and TRAIL on their surfaces (i.e., cytokine-induced killer cells, CIKs). RES was shown to render KG-1a cells susceptible to CIK-mediated cytolysis estimated by LDH-release assay. This heightened sensitivity correlated with an increase in cell-surface expression of NKG2D ligands and death receptor 4 (DR4), coupled with a downregulation of cell-surface expression of decoy receptor 1 (DcR1) in KG-1a cells. Blocking NKG2D ligands or TRAIL with monoclonal antibodies could abrogate CIKs-mediated cytolysis. These results demonstrated that increased sensitivity of KG-1a cells, modulated by RES to alloreactive CIKs-mediated cytolysis is a phenomenon attributable to induced expression of NKG2D ligands and activation of TRAIL pathway. Thus, resveratrol combined with alloreactive CIKs merits clinical evaluation as a novel and effective immunotherapy strategy to eliminate residual leukemia stem cells.

Immunohistochemical Evidence of the Prognostic Value of Hedgehog Pathway Components in Primary Gallbladder Carcinoma

Surgery Today. Mar, 2012  |  Pubmed ID: 22407314

PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.

Real-time Bioluminescence and Tomographic Imaging of Gastric Cancer in a Novel Orthotopic Mouse Model

Oncology Reports. Mar, 2012  |  Pubmed ID: 22407359

Gastric cancer is the second leading cause of cancer mortality worldwide. Understanding the multistep process of carcinogenesis of gastric cancer is pivotal to develop novel therapeutic strategies. Molecular imaging in preclinical cancer models bridges the gap of laboratory-based experiment and clinical translation. To this end, the human gastric cancer cell line SGC-7901 was established to stably express luciferase and GFP by lentiviral transduction (SGC7901-Luc-GFP). Preclinical models were developed by orthotopic transplantation of SGC-7901-Luc-GFP into the sub-serosal layer of the stomach of immunocompromised mice. Tumor progression and therapeutic responses were dynamically tracked by bioluminescence imaging (BLI). Bioluminescence tomography (BLT) was used to monitor stereoscopic morphological and signal changes during tumor progression. Good correlation between cell number and bio-luminescence/fluorescence intensity was observed (R2=0.9983/r2=0.9974) in vitro. Tumor progression and therapeutic response could be successfully followed directly by BLI. Importantly, BLT provided a more accurate spatial location and tomographic quantification of the internal lesion. In conclusion, our novel bioluminescence-based preclinical gastric cancer models enable superior, noninvasive monitoring gastric cancer progression and their drug responses. The BLT technique in particular, may have great potential for future oncological studies.

Secreted Luciferase for In Vivo Evaluation of Systemic Protein Delivery in Mice

Molecular Biotechnology. Mar, 2012  |  Pubmed ID: 22407720

A naturally secreted Gaussia luciferase (Gluc) has been utilized as a reporter for bioluminescence imaging (BLI) evaluation. However, the potential application of Gluc for in vivo monitoring of systemic protein delivery, as well as its natural biodistribution, has not been studied. To examine Gluc secretion and uptake profile, we injected Gluc-encoding plasmids into mice by hydrodynamic tail-vein injection. Whole-body BLI showed that imaging quantification obtained at pawpad was directly correlated to blood Gluc activities. When gene expression was restricted to the liver by the use of a hepatic promoter, in vivo Gluc biodistribution analysis revealed the kidney/bladder, stomach/intestine, and lung as the major uptake organs. Three-dimensional BLI identified liver/stomach and lung as the main internal luminescent sources, demonstrating the feasibility of detecting major uptake organs in live animals by 3D BLI with high-background signals in circulation. Notably, Gluc levels in capillary-depleted brain samples from Gluc-injected mice were comparable to controls, suggesting that Gluc may not cross the blood-brain barrier. Gluc uptake kinetics and intracellular half-life were assessed in various types of cell lines, implicating the involvement of non-specific pinocytosis. These results suggest that Gluc-based system may provide a useful tool for in vivo evaluation of protein/agent biodistribution following systemic delivery.

Copper-Catalyzed Di- and Trifluoromethylation of α,β-Unsaturated Carboxylic Acids: A Protocol for Vinylic Fluoroalkylations

Angewandte Chemie (International Ed. in English). Mar, 2012  |  Pubmed ID: 22407851

Dual action: The Lewis acid CuF(2) ⋅2 H(2) O efficiently catalyzes the reaction between electrophilic fluoroalkylating agents and α,β-unsaturated carboxylic acids by dually activating both reactants, thus affording di- and trifluoromethyl alkenes in high yields with excellent E/Z selectivity.

Quantification of PML/RARa Transcript After Induction Predicts Outcome in Children with Acute Promyelocytic Leukemia

International Journal of Hematology. Mar, 2012  |  Pubmed ID: 22407853

Reports on the use of the real-time quantitative polymerase chain reaction (RQ-PCR) for childhood acute promyelocytic leukemia (APL) therapy are scarce. This study describes the prognostic significance of quantification of the PML-RARa transcript in children with APL. Since January 2004, we have analyzed 40 children treated with all-trans-retinoic acid ± arsenic trioxide in induction. Thirty-nine patients (97.5%) entered complete remission. The 5-year rates of disease-free survival (DFS) and overall survival in these patients were 73.1 and 91.4%, respectively. By employing a standardized RQ-PCR protocol for minimal residual disease (MRD) monitoring, we determined that less than 1 normalized copy number (NCN) after induction indicates higher probability of a more favorable treatment outcome. After induction therapy, thirteen out of 38 (34.2%) patients in hematologic remission showed a negative RQ-PCR result (less than 1 NCN), which was correlated with the lower probability of relapse (100 and 55.2% DFS at 5 years in the negative and positive RQ-PCR groups, respectively; P = 0.018). PML/RARa-based MRD monitoring by RQ-PCR may allow us to identify subgroups of patients at low risk of relapse after induction.

The Effect of C-Terminal Helix on the Stability of FF Domain Studied by Molecular Dynamics Simulation

International Journal of Molecular Sciences. 2012  |  Pubmed ID: 22408419

To investigate the effect of C-terminal helix on the stability of the FF domain, we studied the native domain FF3-71 from human HYPA/FBP11 and the truncated version FF3-60 with C-terminal helix being deleted by molecular dynamics simulations with GROMACS package and GROMOS 43A1 force field. The results indicated that the structures of truncated version FF3-60 were evident different from those of native partner FF3-71. Compared with FF3-71, the FF3-60 lost some native contacts and exhibited some similar structural characters to those of intermediate state. The C-terminal helix played a major role in stabilizing the FF3-71 domain. To a certain degree, the FF domain had a tendency to form an intermediate state without the C-terminal helix. In our knowledge, this was the first study to examine the role of C-terminal helix of FF domain in detail by molecular dynamics simulations, which was useful to understand the three-state folding mechanism of the small FF domain.

A Novel LMP1 Antibody Synergizes with Mitomycin C to Inhibit Nasopharyngeal Carcinoma Growth in Vivo Through Inducing Apoptosis and Downregulating Vascular Endothelial Growth Factor

International Journal of Molecular Sciences. 2012  |  Pubmed ID: 22408448

Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC.

Surface Modification of PBT Nonwoven Fabrics Used for Blood Filtration and Their Blood Compatibility Study

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. Mar, 2012  |  Pubmed ID: 22409280

It is necessary to remove residual leukocytes to prevent the blood transfusion-related adverse reactions. This paper describes a facile approach for the surface modification of commercial PBT nonwoven fabrics (PBTNF), used for blood filtration, followed by immobilizing polyvinylpyrrolidone (PVP). The whole blood filtration results revealed that the five types of PBTNF-PVPs' leucocytes retention rates and erythrocyte recovery rates increased to 96% and 92% compared with the untreated PBTNF. The blood compatibilities results indicated that PVP modified PBTNFs have good blood compatibility, suggesting that PVP-modified PBTNF is a very promising blood filter for selective removal of leukocytes.

Apoptosis and MicroRNA Aberrations in Cancer

Clinical and Experimental Pharmacology & Physiology. Mar, 2012  |  Pubmed ID: 22409455

1. Carcinogenesis rises from the malfunction of genes that control cell growth and division. Therefore, the most effective method of hindering tumourigenesis is to induce the death of immortalised cancer cells. 2. Apoptosis or programmed cell death has shown the most promises in impairing cancer growth. A variety of proteins are involved in regulation of apoptosis and malfunction of any regulators may cause cell proliferation. 3. MicroRNAs have been shown to play a central role in the regulation of cell cycle, including apoptosis. MicroRNAs are involved in post-transcriptional gene suppression and have been implicated in the regulation of cell differentiation and development. 4. MicroRNA aberrations in the regulation of apoptosis leads to tumourigenesis. 5. This review assesses the current knowledge of apoptotic regulations in cancer and the influence of microRNA aberrations in tumourigenesis. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

Analysis of the Inhibition and Remodeling of Islet Amyloid Polypeptide Amyloid Fibers by Flavanols

Biochemistry. Mar, 2012  |  Pubmed ID: 22409724

Islet amyloid polypeptide (IAPP, amylin) is responsible for amyloid formation in type 2 diabetes and in transplanted islets. The flavanol, (-)-Epigallocatechin-3-gallate [EGCG; (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl3,4,5-trihydroxybenzoate] is an effective inhibitor of amyloid formation by IAPP, however, the interactions required for the inhibition of IAPP amyloid formation and for the remodeling of amyloid fibers are not known. A range of features have been proposed to be critical for EGCG protein interactions, including interactions with aromatic residues, interactions with amino groups, or sulfhydryls. Using a set of IAPP analogs we show that none of these are required. Studies in which EGCG is added to the lag phase of amyloid formation suggest that it interacts with intermediates as well as with monomers and amyloid. The features of EGCG required for effective inhibition were examined. The stereoisomer of EGCG, (-)-Gallocatechin gallate (GCG), is an effective inhibitor, although less so than EGCG. Removing the gallate ester moiety leads to EGC which is a less effective inhibitor. Removing only the 3-hydroxyl group of the tri-hydroxyphenyl ring leads to a compound which has more pronounced effects on the lag phase than EGC, but is less effective at reducing the amount of amyloid. Elimination of both the 3-hydroxy group and the gallate ester results in loss of activity. EGCG remodels IAPP amyloid fibers, but does not fully resolubilize them to unstructured monomers and the remodeling is not the reverse of amyloid assembly. The ability of the compounds to remodel IAPP amyloid closely follows their relative ability to inhibit amyloid formation.

Polyphosphate Kinase 1 is Required for the Pathogenesis Process of Meningitic Escherichia Coli K1 (RS218)

Future Microbiology. Mar, 2012  |  Pubmed ID: 22393893

Aim: Polyphosphate kinase 1 (PPK1), encoded by the ppk1 gene, is one of the major enzymes to reversibly catalyze the synthesis of polyphosphate (poly P) from the terminal phosphate of ATP. Poly P confers resistance to stress in a number of bacterial species but its role in the virulence of meningitic bacterial pathogens is unknown. The aim of this study was to determine the role of PPK1 in the pathogenesis of Escherichia coli meningitis. Materials & methods: An isogenic in-frame ppk1 deletion mutant (PD44) of E. coli K1 strain E44 was constructed and characterized. Human brain microvascular endothelial cells and neonatal rats were used as the in vitro and in vivo models, respectively, to evaluate bacterial adhesion/invasion and the abilities of bacteria crossing the blood-brain barrier (BBB) to cause meningitis. The survival of PD44 and E44 under osmotic and acid stress conditions were also examined. Results: Poly P levels in E44 were clearly higher than those in PD44, especially at the stationary phase (SP). The ppk1 deletion mutant PD44 also showed poor survival rates during osmotic shock and acidic challenge, which the bacteria would face during pathogenesis. In vitro and in vivo assays revealed that PD44 was defective in bacterial adhesion and translocation across the BBB. By using the Evans blue method, we found that E44-induced permeability of the BBB in neonatal rats was significantly higher than that of the animals infected with PD44. Cytokine ELISA results showed that the TNF-α and IL-1β levels in the serum and brain tissues of the neonatal rats infected with PD44 were lower than that of the E44 group. A more obvious meningeal inflammation could be observed in the brain tissues of the rats infected with E44 when compared with that of the PD44 group by histopathological examination. Furthermore, the mRNA expression of IbeR, which is an RpoS-like regulator contributing to the SP regulation in E44, was found to be decreased in PD44 when compared with the parent strain. PD44 was also deficient in mRNA expression of the invasin IbeA, the adhesin FimH and the outer member protein A, which contributes to E44 penetration across BBB and resistance to the stimulations of low pH and high osmolarity. Conclusion: These results indicate that ppk1 plays an important role in stress adaption and virulence in meningitic E. coli K1 strain E44, and controls the relevant phenotypes by modulating the expression of the SP regulatory gene ibeR and the virulence genes ibeA, fimH and ompA.

Pv12, a 6-Cys Antigen of Plasmodium Vivax, is Localized to the Merozoite Rhoptry

Parasitology International. Feb, 2012  |  Pubmed ID: 22394409

Pf12 in Plasmodium falciparum has been characterized as a merozoite surface protein and the Pf12 gene is actively transcribed during schizont stage. An orthologous gene, Pv12, has been identified in genome of P. vivax, but the protein product has not been characterized. The Pv12 is a 362 amino acid long polypeptide encoded by a single exon gene PVX_113775, for which orthologous genes have been identified in other Plasmodium species by bioinformatic approaches. Pv12 contains two predicted six-cysteine (6-Cys) domains, which may be constrained by predicted disulfide bonds, and a transmembrane domain and a predicted GPI anchor attachment site in C-terminal region. The recombinant Pv12 protein is recognized by serum antibodies of patients naturally exposed to P. vivax and the native Pv12 protein from parasite extract is also recognized by immune mouse serum. The Pv12 is localized in rhoptry; an apical organelle of the merozoite, and the localization pattern of Pv12 is distinct from that of Pf12 in P. falciparum. The present study suggests that Pv12 is immunogenic in humans during parasite infection and it could play an important role in erythrocyte invasion.

Development and Validation of a HPLC Method for the Determination of Diacetyl in Beer Using 4-nitro-o-phenylenediamine As the Derivatization Reagent

Journal of Agricultural and Food Chemistry. Mar, 2012  |  Pubmed ID: 22394515

Diacetyl is a natural byproduct of fermentation and known to be an important flavor compound in many food products. Due to the potential undesirable effects of diacetyl on health safety and beer flavor, determination of its concentration in beer samples is essential and its analytical methods have attracted close attention recently. The aim of the present work is to develop and validate a novel HPLC method for the quantification of diacetyl in beer based on the derivatization reaction of diacetyl with 4-nitro-o-phenylenediamine (NPDA). After the derivatization with NPDA in pH 3.0 at 45 °C for 20 min, the diacetyl was separated on a kromasil C18 column at room temperature in the form of the resulting 6-nitro-2,3-dimethylquinoxaline and detected by the UV detector at 257 nm. The results showed the correlation coefficient for the method was 0.9992 in the range of 0.0050-10.0 mg L-1 and the limit of detection was 0.0008 mg L-1 at a signal-to-noise ratio of 3. The applicability of the proposed method was evaluated in the analysis of beer samples with the recoveries range of 94.0% to 99.0 % and RSDs range of 1.20% to 3.10%. The concentration levels of diacetyl detected in beer samples from 12 brands ranged from 0.034 to 0.110 mg L-1. The proposed method showed efficient chromatographic separation, excellent linearity, and good repeatability that can be applied to quantification of diacetyl in beer samples.

[Prokaryotic Expression and Purification of Human GST-Cdc25C Fusion Protein and Preliminary Detection of Its Function]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Mar, 2012  |  Pubmed ID: 22394631

To clone prokaryotic expression vector of Cdc25C, purify the fusion protein of GST-Cdc25C, and identify its function preliminarily.

Relaxation of the Rigid Backbone of an Oligoamide-foldamer-based α-helix Mimetic: Identification of Potent Bcl-x(L) Inhibitors

Organic & Biomolecular Chemistry. Mar, 2012  |  Pubmed ID: 22395339

By conducting a structure-activity relationship study of the backbone of a series of oligoamide-foldamer-based α-helix mimetics of the Bak BH3 helix, we have identified especially potent inhibitors of Bcl-x(L). The most potent compound has a K(i) value of 94 nM in vitro, and single-digit micromolar IC(50) values against the proliferation of several Bcl-x(L)-overexpressing cancer cell lines.

Targeting MicroRNA-30a-mediated Autophagy Enhances Imatinib Activity Against Human Chronic Myeloid Leukemia Cells

Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. Mar, 2012  |  Pubmed ID: 22395361

A major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib and other BCR-ABL tyrosine kinase inhibitors. MicroRNAs (miRNAs) are small RNA molecules that influence gene expression by post-transcriptional regulation of messenger RNA. It is not yet clear how miRNAs are able to regulate the effectiveness of imatinib in CML. Here, we show that imatinib markedly inhibits expression of miR-30a in human chronic myeloid leukemia cells. miR-30a is a potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. miR-30a mimic or knockdown of autophagy genes (ATGs) such as Beclin 1 and ATG5 by shRNA enhances imatinib-induced cytotoxicity and promotes mitochondria-dependent intrinsic apoptosis. In contrast, knockdown of miR-30a by antagomir-30a increases the expression of Beclin 1 and ATG5, and inhibits imatinib-induced cytotoxicity. These findings indicate that dysregulation of miR-30a may interfere with the effectiveness of imatinib-mediated apoptosis by an autophagy-dependent pathway, thus representing a novel potential therapeutic target in CML.Leukemia accepted article preview online, 7 March 2012; doi:10.1038/leu.2012.65.

Study on the Enantioselectivity Inhibition Mechanism of Acetyl-coenzyme A Carboxylase Toward Haloxyfop by Homology Modeling and MM-PBSA Analysis

Journal of Molecular Modeling. Mar, 2012  |  Pubmed ID: 22395649

Acetyl-coenzyme A carboxylase (ACCase) has been identified as one of the most important targets of herbicide Aryloxyphenoxypropionates (APPs). ACCase shows different enantioselectivity toward APPs, and only (R)-enantiomers of APPs have the herbicidal activity. In order to deeply understand the enantioselective recognition mechanism of ACCase, (R)-haloxyfop, which is a typical commercial herbicide from APPs, is selected and the relative binding free energy between ACCase and (R)-haloxyfop is investigated and compared with that between ACCase and (S)-haloxyfop by homology modeling and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method. Further free energy analysis reveals that the preference of ACCase toward (R)-haloxyfop is mainly driven by Van der Waals interaction. The analysis of the interaction between the active site residues of ACCase CT domain and (R)-haloxyfop shows the van der Waals interactions have a close relationship with the addition effect of each residue. An understanding of the enantioselective recognition mechanism between ACCase and haloxyfop is desirable to discover novel chiral herbicides.

Intensification of β-poly(L: -malic Acid) Production by Aureobasidium Pullulans Ipe-1 in the Late Exponential Growth Phase

Journal of Industrial Microbiology & Biotechnology. Mar, 2012  |  Pubmed ID: 22395899

β-Poly(malic acid) (PMLA) has attracted industrial interest because this polyester can be used as a prodrug or for drug delivery systems. In PMLA production by Aureobasidium pullulans ipe-1, it was found that PLMA production was associated with cell growth in the early exponential growth phase and dissociated from cell growth in the late exponential growth phase. To enhance PMLA production in the late phase, different fermentation modes and strategies for controlling culture redox potential (CRP) were studied. The results showed that high concentrations of produced PMLA (above 40 g/l) not only inhibited PMLA production, but also was detrimental to cell growth. Moreover, when CRP increased from 57 to 100 mV in the late exponential growth phase, the lack of reducing power in the broth also decreased PMLA productivity. PMLA productivity could be enhanced by repeated-batch culture to maintain cell growth in the exponential growth phase, or by cell-recycle culture with membrane to remove the produced PMLA, or by maintaining CRP below 70 mV no matter which kind of fermentation mode was adopted. Repeated-batch culture afforded a high PMLA concentration (up to 63.2 g/l) with a productivity of 1.15 g l(-1) h(-1). Cell-recycle culture also confirmed that PMLA production by the strain ipe-1 was associated with cell growth.

EBV-Encoded LMP1 Upregulates Igκ 3'Enhancer Activity and Igκ Expression in Nasopharyngeal Cancer Cells by Activating the Ets-1 Through ERKs Signaling

PloS One. 2012  |  Pubmed ID: 22396784

Accumulating evidence indicates that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We previously found that the expression of the kappa light chain protein in NPC cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In the present study, we used NPC cell lines as models and found that LMP1-augmented kappa production corresponds with elevations in ERKs phosphorylation. PD98059 attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced kappa light chain gene expression. Luciferase reporter assays demonstrate that immunoglobulin κ 3' enhancer (3'E(κ)) is active in Igκ-expressing NPC cells and LMP1 upregulates the activity of 3'E(κ) in NPC cells. Moreover, mutation analysis of the PU binding site in 3'E(κ) and inhibition of the MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1-enhanced 3'E(κ) activity is partly regulated by this site. PD98059 treatment also leads to a concentration-dependent inhibition of LMP1-induced Ets-1 expression and phosphorylation, which corresponds with a dose-dependent attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression. Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a decrease of Ig kappa light chain expression. Gel shift assays using nuclear extracts of NPC cells indicate that the transcription factor Ets-1 is recruited by LMP1 to the PU motif within 3'E(κ)in vitro. ChIP assays further demonstrate Ets-1 binding to the PU motif of 3'E(κ) in cells. These results suggest that LMP1 upregulates 3'E(κ) activity and kappa gene expression by activating the Ets-1 transcription factor through the ERKs signaling pathway. Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3' enhancer through activating transcription factors in non-B epithelial cancer cells.

Immunomodulation for Gastrointestinal Infections

Expert Review of Anti-infective Therapy. Mar, 2012  |  Pubmed ID: 22397571

The intestinal epithelium provides a barrier between a variety of luminal antigens and provides the components of intestinal innate and adaptive immunity. It is crucial that at this interface, the epithelial cell layer and the components of the intestinal immunity interact with dietary and bacterial antigens in a regulated way to maintain homeostasis. Failure to tightly control immune reactions can be detrimental and result in inflammation. In the current review, we described the regulatory mechanisms controlling host-immune homeostasis and the role of regulatory CD4(+) T cells, with a special emphasis in the regulatory T-cell subsets (Tregs). Furthermore, the participation of innate cell cross-talk in the polarization of intestinal immune responses is also evaluated. Finally, the recent characterization of host responses to normal commensal flora, the role of bacteria and bacterial factors in the maintenance of immunomodulation, and the disruption of this balance by bacterial enteric pathogens is also summarized.

Measurements of Secondary Organic Aerosol Formed from OH-initiated Photo-oxidation of Isoprene Using On-line Photoionization Aerosol Mass Spectrometry

Environmental Science & Technology. Mar, 2012  |  Pubmed ID: 22397593

Isoprene is a significant source of atmospheric organic aerosol; however, the secondary organic aerosol (SOA) formation and involved chemical reaction pathways have remained to be elucidated. Recent works have shown that the photo-oxidation of isoprene leads to form SOA. In this study, the chemical composition of SOA from the OH-initiated photo-oxidation of isoprene, in the absence of seed aerosols, was investigated through the controlled laboratory chamber experiments. Thermal desorption/tunable vacuum-ultraviolet photoionization time-of-flight aerosol mass spectrometry (TD-VUV-TOF-PIAMS) was used in conjunction with the environmental chamber to study SOA formation. The mass spectra obtained at different photon energies and the photoionization efficiency (PIE) spectra of the SOA products can be obtained in real time. Aided by the ionization energies (IE) either from the ab initio calculations or the literatures, a number of SOA products were proposed. In addition to methacrolein, methyl vinyl ketone, and 3-methyl-furan, carbonyls, hydroxycarbonyls, nitrates, hydroxynitrates, and other oxygenated compounds in SOA formed in laboratory photo-oxiadation experiments were identified, some of them were investigated for the first time. Detailed chemical identification of SOA is crucial for understanding the photo-oxidation mechanisms of VOCs and the eventual formation of SOA. Possible reaction mechanisms will be discussed.

Photocatalytic and Photoelectric Properties of Cubic Ag(3)PO(4) Sub-microcrystals with Sharp Corners and Edges

Chemical Communications (Cambridge, England). Mar, 2012  |  Pubmed ID: 22398441

Herein, we demonstrate a complex-precipitation strategy for high-yield fabrication of single-crystalline Ag(3)PO(4) sub-microcubes with sharp corners, edges, and smooth surfaces, which exhibit much higher photocatalytic activities and photoelectric conversion properties than spherical Ag(3)PO(4) particles and commercial N-doped TiO(2) under visible light irradiation.

New Legislation in China Balancing the Rights of Both Doctors and Patients

Medicine, Science, and the Law. Jan, 2012  |  Pubmed ID: 22399037

Evaluating the Nucleus Effect on the Dynamic Indentation Behavior of Cells

Biomechanics and Modeling in Mechanobiology. Mar, 2012  |  Pubmed ID: 22399164

The effect of the nucleus on the cell mechanical behavior was investigated based on the dynamic indentation response of cells under a spherical tip. A "two-component" cell model (including cytoplasm and nucleus) is used, and the dynamic indentation behavior is studied by a semiempirical method, which is established based on fitting the numerical simulation results of the quasi-static indentation response of cells. We found that the "routine analysis" (based on the Hertz's contact solution of homogeneous model) significantly overestimated the nucleus effect on the overall cell indentation response due to the effects of the Hertz contact radius and the substrate stiffening. These effects are significantly stronger in the "two-component" cell model than in the homogeneous model. The inaccuracy created by the "routine analysis" slightly increases with the modulus ratio of nucleus to cytoplasm and the volume fraction of nucleus. Finally, the error sensitivity to the geometrical parameters used in the model is discussed, which shows the indentation analysis is not very sensitive to these parameters, and the reasonable assumptions for these parameters are effective. This systematic analysis can provide a useful guideline to understanding the mechanical behavior of cells and nuclei.

Adenovirus-Mediated Dual Gene Expression of Human Interleukin-10 and Hepatic Growth Factor Exerts Protective Effect Against CCl(4)-Induced Hepatocyte Injury in Rats

Digestive Diseases and Sciences. Mar, 2012  |  Pubmed ID: 22399249

BACKGROUND: Hepatocyte injury is a common pathological cause of various liver diseases. Due to a lack of an effective preventive treatment, gene therapy has become an interesting approach to prevent and alleviate liver injury. AIMS: A protective effect of adenovirus-mediated dual gene expression of human interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in rats. METHODS: An adenoviral vector carrying the hIL-10 and hHGF genes was constructed, and its protective effect against rat hepatocyte injury was investigated both in vivo and in vitro. RESULTS: In the in vitro CCl(4)-induced cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an adenoviral vector resulted in production of anti-hepatocyte biological factors by an autocrine mechanism, then significantly improved hepatocyte viability. In the in vivo rat model, synergistic effects of these two gene products protected hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration, hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby preserving liver function. CONCLUSION: Adenovirus-mediated dual gene expression of hIL-10 and hHGF effectively protected against liver damage by likely regulating immune responses to reduce hepatocyte injury and by promoting hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has significant potential in the field of liver disease therapeutics and constitutes one of the most promising current strategies for gene therapy.

Phase II Study of Panobinostat and Bortezomib in Patients with Pancreatic Cancer Progressing on Gemcitabine-based Therapy

Anticancer Research. Mar, 2012  |  Pubmed ID: 22399627

This single-arm, phase II study was designed to determine the efficacy and safety of panobinostat and bortezomib in patients with advanced pancreatic cancer.

Healthcare Utilization Among Patients with Depression Before and After Initiating Duloxetine in the United Kingdom

Journal of Medical Economics. Mar, 2012  |  Pubmed ID: 22390770

Abstract Objective Duloxetine is indicated for treatment of major depressive disorders in the United Kingdom. While clinical trials have documented its clinical effectiveness, little is known regarding the relationship between duloxetine use and healthcare utilization in community practice. This study quantifies the impact of treatment with duloxetine on healthcare utilization among patients with depression and those with depression and co-existing pain. Methods Depressed adults initiating duloxetine during 1/1/2006 - 9/30/2007 were identified from the General Practice Research Database (GPRD). All-cause hospitalization, accident/emergency visits, specialist referrals, and analgesic use in the 12 months before (pre-period) and after (post-period) duloxetine initiation were compared. Generalized Estimating Equation models evaluated the pre-post change in the odds of hospitalization. Results 909 patients were identified, 413 had pre-period unexplained pain (UPain). Rates of hospitalization declined from the pre- to the post-period. Fewer UPain patients received analgesics post-duloxetine initiation. Multivariate analyses confirmed that the odds of hospitalization were lower after duloxetine initiation. UPain patients with pre-period anticonvulsant use had lower odds of hospitalization in the post-period and the reduction in odds was significantly larger than that of patients without pre-period anticonvulsants. While patients with pre-period anxiolytic use, alcohol/drug dependence, or sleep disorders did not show statistically significant pre-post change in the odds of hospitalization, these changes were significantly different from patients without these conditions. Limitations The study did not include a comparison group of patients who were non-users of duloxetine. Prevalence of chronic conditions might be underestimated due to coding in the GPRD. Medications were assumed to be taken as prescribed. Study results are not generalizable beyond the population covered by UK's primary care system. Conclusions All-cause hospitalization rates lowered among depressed patients and fewer UPain patients received analgesics post-duloxetine initiation. The reduction in the odds of hospitalization was most pronounced among UPain patients receiving pre-period anticonvulsants.

Klebsiella Pneumoniae Resistant to Third-generation Cephalosporins in Five African and Two Vietnamese Major Towns: Multiclonal Population Structure with Two Major International Clonal Groups, CG15 and CG258

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. Feb, 2012  |  Pubmed ID: 22390772

Clin Microbiol Infect ABSTRACT: The molecular epidemiology of third-generation cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in developing countries is poorly documented. From February 2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven major towns in Maghreb (Morocco), West Africa (Senegal, Côte d'Ivoire), Central Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their genetic diversity, assessed by multilocus sequence typing, was high (60 sequence types), reflecting multiclonality. However, two major clonal groups, CG15 (n = 23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all participating centres. The two major clonal groups have previously been described in other parts of the world, indicating their global spread. The high diversity of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns at the local level indicates that most isolates were epidemiologically unrelated. The isolates were characterized by the presence of multiple resistance determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and bla(CTX-M-15) genes in 61 isolates (45%) belonging to 31 sequence types. These isolates were detected across a large geographical area including Cameroon (n = 1), Vietnam (n = 4), Madagascar (n = 10), Côte d'Ivoire (n = 12), Morocco (n = 13) and Senegal (n = 21). These results have major implications for patient management and highlight a potential reservoir for resistance determinants.

An Involvement of SR-B1 Mediated PI3K-Akt-eNOS Signaling in HDL-induced Cyclooxygenase 2 Expression and Prostacyclin Production in Endothelial Cells

Biochemical and Biophysical Research Communications. Feb, 2012  |  Pubmed ID: 22390933

It is well-known that sphingosine-1-phosphate (S1P), the phospholipid content of HDL, binding to S1P receptors can raise COX-2 expression and PGI(2) release through p38MAPK/CREB pathway. In the present study we assess the action of SR-B1 initiated PI3K-Akt-eNOS signaling in the regulation of COX-2 expression and PGI(2) production in response to HDL. We found that apoA1 could increase PGI(2) release and COX-2 expression in ECV 304 endothelial cells. Furthermore, SR-B1 was found to be involved in HDL induced up-regulation of COX-2 and PGI(2). Over-expressed SR-B1 did not significantly increase the expression of COX-2 and the PGI(2) levels, but knock-down of SR-B1 by siRNA could significantly attenuate COX-2 expression and PGI(2) release together with p38MAPK and CREB phosphorylation. Consistently, the declines of p-p38MAPK, p-CREB, COX-2 and PGI(2) were also observed after incubation with LY294002 (25μmol/L; PI3K special inhibitor) or l-NAME (50μmol/L; eNOS special inhibitor). In addition, we demonstrated the increases of PGI(2) release, COX-2 expression and p38MAPK phosphorylation, when nitric oxide level was raised through the incubation of l-arginine (10 or 20nmol/L) in endothelial cells. Taking together, our data support that SR-B1 mediated PI3K-Akt-eNOS signaling was involved in HDL-induced COX-2 expression and PGI(2) release in endothelial cells.

Macrophage Immunomodulatory Activity of Extracellular Polysaccharide (PEP) of Antarctic Bacterium Pseudoaltermonas Sp.S-5

International Immunopharmacology. Mar, 2012  |  Pubmed ID: 22391090

Antarctic bacteria are a novel source of polysaccharides which might have potential applications as biological response modifiers (BRM). A heteropolysaccharide (PEP) was isolated from the liquid culture broth of the Antarctic bacterium Pseudoaltermonas sp.S-5. PEP contained Mannose, Glucose, and Galactose in a ratio of 4.8:50.9:44.3. High performance gel permeation chromatography of this polysaccharide showed a unimodal profile, and the molecular weight was 397kDa. PEP was studied for its immunological effects on peritoneal macrophage cells. Morphological alterations were observed in macrophages treated with PEP. In vitro exposure to PEP increased the occurrence of activated macrophages and endocytic index in a dose-dependent pattern (2.5-50μg/ml) after 24h of incubation, since increase of 136% and 133% was detected in the activated macrophage percentage and endocytic index respectively compared to untreated cells. At 200μg/ml PEP caused a greatest increase (44.5%) in NO production when compared to the control group; however, this polysaccharide did not affect respiratory burst in the absence of PMA. Furthermore, it was demonstrated that PEP induces macrophages to secrete tumor necrosis factor (TNF)-α and interleukin (IL)-1β. These results suggested that PEP from Pseudoaltermonas sp.S-5 can be classified as a BRM.

[Effects of Interferon-α Combined with Homoharringtonine on K562 Cell Proliferation and β-Catenin Expression]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jan, 2012  |  Pubmed ID: 22391162

The study was aimed to investigate the synergistical effect of interferon-α (IFN-α) and homoharringtonine (HHT) on the proliferation, apoptosis, cell cycle of K562 cells and the expression of β-catenin. The proliferation, apoptosis, cell cycle and β-catenin mRNA expression of K562 cells treated with IFN-α and/or HHT were assayed with MTT, flow cytometry or RT-PCR respectively. The results showed that HHT alone, but not IFN-α alone, displayed a proliferation inhibition, apoptosis induction, G(0)/G(1) phase block and down-regulation of β-catenin expression in K562 cells with concentration- and time-dependent manners. The expression level of β-catenin mRNA after being treated with HHT was 0.5576 ± 0.0373, which were lower than that in control group (0.9369 ± 0.0142). The down-regulation of β-catenin expression in group of IFN-α combined with HHT was higher significantly than that in HHT group (0.3737 ± 0.0529 vs 0.5576 ± 0.0373, P < 0.05). Otherwise, HHT combined with IFN-α did not demonstrate obvious toxicologic effect on bone marrow mononuclear cells. It is concluded that IFN-α combined with HHT can enhance the cytotoxic effect of HHT on K562 cells, which may be associated with down-regulation of β-catenin expression.

[Predicating the Sensibility of Patients with Multiple Myeloma to Glucocorticoid by Cochaperone P23]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Jan, 2012  |  Pubmed ID: 22391176

This study was aimed to investigate the sensitive index for predicting the sensitivity of patients with multiple myeloma (MM) to glucocorticoid (GC). MM1.S, MM1.R cell lines and 10 MM patients sensitive or non-sensitive to GC were enrolled in this study. The expression of heat shock protein 90 (HSP90) and P23 in peripheral blood mononuclear cells (PBMNC) of MM patients was detected by Western blot, and its relation with GC resistence was explored. The results showed that there were no differences in HSP90, GR and IκB-α expressions among MM1.S, MM1.R, PBMNC of normal persons and MM patients, while there was apparent difference in P23; along with increasing of dexamethasone dose, the survival rate of MM1.S decreased, but that of MM1.R did not change so obviously. Among 7 cases with P23 low expression, combination treatment scheme with GC was effective in 6 cases (86%), uneffective in 1 cases (14%); while among 3 cases with P23 high expression, 1 cases (33%) showed effective to combination treatment with GC, 2 cases (67%) showed uneffective (P < 0.05). It is concluded that the P23 expression may predict the sensitivity of MM patients to GC and may be used as index for guiding clinical treatment.

L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

Antimicrobial Agents and Chemotherapy. Mar, 2012  |  Pubmed ID: 22391529

A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by Nonoxynol-9 (N9), the clinical trial-failed anti-HIV-1 microbicide candidate, in a refined murine model of agent-induced cervicovaginal inflammation. We found that L-selectin and P-selectin had obviously different patterns of detection than the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukine 6 (IL-6). These two soluble selectins correlated better than MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds: benzalkonium chloride (BZK), sodium dodecyl sulfate (SDS), but not by two non-proinflammatory compounds: carboxymethylcelluose (CMC, microbicide excipients) and tenofivor (TFV, microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of HIV and other sexually transmitted pathogens.

Evaluation of the Prognostic Value of TGF-β Superfamily Type I Receptor and TGF-β Type II Receptor Expression in Nasopharyngeal Carcinoma Using High-throughput Tissue Microarrays

Journal of Molecular Histology. Mar, 2012  |  Pubmed ID: 22391627

Gene expression profiling had revealed that TGF-β superfamily type I receptor (also known as activin receptor-like kinase-1, ALK1) and TGFβR2 (TGF-β type II receptor) were down-regulated in nasopharyngeal carcinoma (NPC) (P < 0.05, respectively). However, no study with significantly large clinical samples to address the relevance of ALK1 and TGFβR2 in NPC progression or in patient outcomes has been reported. This study aims to assess the possible correlations of ALK1 and TGFβR2 expression with NPC progression and their potential prognostic predictive ability in NPC outcomes. ALK1 and TGFβR2 mRNA and protein levels were detected by qRT-PCR and NPC tissue microarray (TMA), which included 742 tissue cores. Both mRNA and protein levels of ALK1 and TGFβR2 were significantly lower in the cancer tissues compared with the non-cancerous tissues (P < 0.05). Epstein-Barr virus small RNA (EBER-1) hybridization signals in NPC showed significant associations with ALK1 and TGFβR2 proteins (P = 0.000 and 0.003, respectively). In the final logistic regression analysis model, the abnormal expression of ALK1 and TGFβR2 were found to be independent contributors to nasopharyngeal carcinogenesis (P = 0.000 and 0.000, respectively). A survival analysis revealed that ALK1 (Disease Free Survival (DFS): P = 0.002, Overall Survival (OS): P = 0.007) and TGFβR2 (DFS: P = 0.072, OS: P = 0.045) could predict the prognosis of NPC patients. The positive expression of ALK1 and TGFβR2 were independent risk factors for DFS and OS in multivariate analyses (DFS: P = 0.001 and 0.420, respectively; OS: P = 0.018 and 0.047, respectively). These results suggest that ALK1 and TGFβR2 may be useful prognostic biomarkers in NPC.

Androgen Receptor is Overexpressed in Boys with Severe Hypospadias, and ZEB1 Regulates Androgen Receptor Expression in Human Foreskin Cells

Pediatric Research. Apr, 2012  |  Pubmed ID: 22391641

Introduction:ZEB1 is overexpressed in patients with severe hypospadias. We examined the interaction between ZEB1 and the androgen receptor (AR) in vitro and the expression of AR in boys with hypospadias.Results:ZEB1 and AR colocalize to the nucleus. Estrogen upregulated ZEB1 and AR expression. Chromatin immunoprecipitation (ChIP) demonstrated that ZEB1 binds to an E-box sequence in the AR gene promoter. AR expression is higher in subjects with severe hypospadias than those with mild hypospadias and control subjects (P < 0.05). ZEB1 physically interacts with AR in human foreskin cells.Discussion:AR is overexpressed in patients with severe hypospadias. Environmental estrogenic compounds may increase the risk of hypospadias by facilitating the interaction between ZEB1 and AR.Methods:Hs68 cells, a fibroblast cell line derived from neonatal human foreskin, were exposed to 0, 10, and 100 nmol/l of estrogen, after which the cellular localization of ZEB1 and AR was assessed using immunocytochemistry. To determine if ZEB1 interacted with the AR gene, ChIP was performed using ZEB1 antibody and polymerase chain reaction (PCR) for AR. Second, AR expression was quantified using real-time PCR and western blot in normal subjects (n = 32), and subjects with mild (n = 16) and severe hypospadia (n = 16).

Automatic Measurement of Renal Volume in Children Using 99mTc Dimercaptosuccinic Acid SPECT: Normal Ranges With Body Weight

Clinical Nuclear Medicine. Apr, 2012  |  Pubmed ID: 22391704

: The purpose of this study was to automate volume measurement of pediatric kidneys using Technetium-99m-dimercaptosuccinic acid (Tc DMSA) SPECT. Assessment of renal size is essential in making an accurate clinical diagnosis and in evaluating normal and abnormal renal growth. Existing techniques for measuring renal length and volume are often observer-dependent and are limited by interobserver variability.

Isolation and Functional Characterization of a Transcription Factor VpNAC1 from Chinese Wild Vitis Pseudoreticulata

Biotechnology Letters. Mar, 2012  |  Pubmed ID: 22391737

NAC (for NAM, ATAF1, 2, and CUC2) family genes encode plant-specific transcription factors that play important roles in plant development regulation and in abiotic and biotic stresses. However, the function of NAC genes in grapevines is not clear. A novel NAC transcription factor, designated as VpNAC1, was isolated from Chinese wild Vitis pseudoreticulata. It belongs to the TERN subgroup and is a nuclear-targeting protein and functions as a transcriptional activator. Moreover, VpNAC1 was induced by the fungus Erysiphe necator and the exogenous hormones, particularly salicylic acid, methyl jasmonate and ethylene. Over-expression of VpNAC1 in tobacco plants enhanced their resistance to Erysiphe cichoracearum and Phytophthora parasitica var. nicotianae Tucker. These results suggest that VpNAC1 acts as a positive regulator in biotic stresses.

Correction of Arterial Input Function in Dynamic Contrast-enhanced MRI of the Liver

Journal of Magnetic Resonance Imaging : JMRI. Mar, 2012  |  Pubmed ID: 22392876

PURPOSE: To develop a postprocessing method to correct saturation of arterial input function (AIF) in T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for quantification of hepatic perfusion. MATERIALS AND METHODS: The saturated AIF is corrected by parameterizing the first pass of the AIF as a smooth function with a single peak and minimizing a least-squares error in fitting the liver DCE-MRI data to a dual-input single-compartment model. Sensitivities of the method to the degree of saturation in the AIF first-pass peak and the image contrast-to-noise ratio were assessed. The method was also evaluated by correlating portal venous perfusion with an independent overall liver function measurement. RESULTS: The proposed method corrects the distorted AIF with a saturation ratio up to 0.45. The corrected AIF improved hepatic arterial perfusion by -23.4% and portal venous perfusion by 26.9% in a study of 12 patients with liver cancers. The correlation between the mean voxelwise portal venous perfusion and overall liver function measurement was improved by using the corrected AIFs (R(2) = 0.67) compared with the saturated AIFs (R(2) = 0.39). CONCLUSION: The method is robust for correcting AIF distortion and has the potential to improve quantification of hepatic perfusion for assessment of liver tissue response to treatment in patients with hepatic cancers. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.

Transferred Melanoma-specific CD8+ T Cells Persist, Mediate Tumor Regression, and Acquire Central Memory Phenotype

Proceedings of the National Academy of Sciences of the United States of America. Mar, 2012  |  Pubmed ID: 22393002

Adoptively transferred tumor-specific T cells offer the potential for non-cross-resistant therapy and long-term immunoprotection. Strategies to enhance in vivo persistence of transferred T cells can lead to improved antitumor efficacy. However, the extrinsic (patient conditioning) and intrinsic (effector cell) factors contributing to long-term in vivo persistence are not well-defined. As a means to enhance persistence of infused T cells in vivo and limit toxicity, 11 patients with refractory, progressive metastatic melanoma received cyclophosphamide alone as conditioning before the infusion of peripheral blood mononuclear cell-derived, antigen-specific, CD8(+) cytotoxic T-lymphocyte (CTL) clones followed by low-dose or high-dose IL-2. No life-threatening toxicities occurred with low-dose IL-2. Five of 10 evaluable patients had stable disease at 8 wk, and 1 of 11 had a complete remission that continued for longer than 3 y. On-target autoimmune events with the early appearance of skin rashes were observed in patients with stable disease or complete remission at 4 wk or longer. In vivo tracking revealed that the conditioning regimen provided a favorable milieu that enabled CTL proliferation early after transfer and localization to nonvascular compartments, such as skin and lymph nodes. CTL clones, on infusion, were characterized by an effector memory phenotype, and CTL that persisted long term acquired phenotypic and/or functional qualities of central memory type CTLs in vivo. The use of a T-cell product composed of a clonal population of antigen-specific CTLs afforded the opportunity to demonstrate phenotypic and/or functional conversion to a central memory type with the potential for sustained clinical benefit.

In Vitro Release and in Vitro-in Vivo Correlation for Silybin Meglumine Incorporated into Hollow-type Mesoporous Silica Nanoparticles

International Journal of Nanomedicine. 2012  |  Pubmed ID: 22393284

The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles.

Enhancing the Specificity and Efficiency of Polymerase Chain Reaction Using Polyethyleneimine-based Derivatives and Hybrid Nanocomposites

International Journal of Nanomedicine. 2012  |  Pubmed ID: 22393296

There is a general necessity to improve the specificity and efficiency of the polymerase chain reaction (PCR), and exploring the PCR-enhancing mechanism still remains a great challenge. In this paper we report the use of branched polyethyleneimine (PEI)-based derivatives and hybrid nanocomposites as a novel class of enhancers to improve the specificity and efficiency of a nonspecific PCR system. We show that the surface-charge polarity of PEI and PEI derivatives plays a major role in their effectiveness to enhance the PCR. Positively charged amine-terminated pristine PEI, partially (50%) acetylated PEI (PEI-Ac(50)), and completely acetylated PEI (PEI-Ac) are able to improve PCR efficiency and specificity with an optimum concentration order of PEI < PEI-Ac(50) < PEI-Ac, whereas negatively charged carboxyl-terminated PEI (PEI-SAH; SAH denotes succinamic acid groups) and neutralized PEI modified with both polyethylene glycol (PEG) and acetyl (Ac) groups (PEI-PEG-Ac) are unable to improve PCR specificity and efficiency even at concentrations three orders of magnitude higher than that of PEI. Our data clearly suggests that the PCR-enhancing effect is primarily based on the interaction between the PCR components and the PEI derivatives, where electrostatic interaction plays a major role in concentrating the PCR components locally on the backbones of the branched PEI. In addition, multiwalled carbon nanotubes modified with PEI and PEI-stabilized gold nanoparticles are also able to improve the PCR specificity and efficiency with an optimum PEI concentration less than that of the PEI alone, indicating that the inorganic component of the nanocomposites may help improve the interaction between PEI and the PCR components. The developed PEI-based derivatives or nanocomposites may be used as efficient additives to enhance other PCR systems for different biomedical applications.

Reelin Is Involved in Transforming Growth Factor-β1-Induced Cell Migration in Esophageal Carcinoma Cells

PloS One. 2012  |  Pubmed ID: 22393371

Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the developing cerebral cortex, plays an important role in neuronal migration, but its role in cell migration and cancer metastasis is largely unclear. Here, we showed that cell motility was significantly increased in KYSE-510 cells by TGF-β1 treatment. Moreover, TGF-β1 decreased RELN mRNA expression and overexpression of Reelin at least partly reversed TGF-β1-induced cell migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin expression by TGF-β1 was through Snail, one transcription factor which was induced by TGF-β1 in KYSE-510 cells. RELN promoter activity was reduced in parallel with the induction of Snail after TGF-β1 treatment and Snail suppressed both RELN promoter activity and expression through binding to E-box sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced cell migration in KYSE-510 cells, together with the increase of mesenchymal markers expression. Taken together, Reelin is an essential negative regulator in the TGF-β1-induced cell migration process, and is suppressed by TGF-β pathway at the transcriptional level through Snail regulation. Therefore, the correlation of Reelin and TGF-β pathway was critical in cancer metastasis, and Reelin could be one potential anti-metastasis target in future clinical practice.

Glycerolipid Acyltransferases in Triglyceride Metabolism and Energy Homeostasis-potential As Drug Targets

Endocrine, Metabolic & Immune Disorders Drug Targets. Mar, 2012  |  Pubmed ID: 22385114

Glycerolipid acyltransfereases play important roles in physiological and pathophysiological processes of triglyceride (TAG) metabolism and energy balance. Glycerol-3-phosphate acyltransferases (GPATs) are key enzymes in the triglyceride biosynthetic pathway. In addition to the mitochondrial GPAT1 that was first cloned and studied, novel microsomal enzyme isoforms have been discovered in recent years. The potential function of one of the GPATs, GPAT4, was studied in GPAT4 deficient mice that suggested its role in TAG synthesis in multiple tissues. Monoacylglycerol and diacylglycerol acyltransferases (MGAT2 and DGAT1) are important enzymes involved in intestinal triglyceride absorption, and studies in recent years from knockout mice have revealed their important role in whole body energy metabolism through changes in intestinal TAG absorption kinetics. Both MGAT2 and DGAT1 mice are resistant to diet-induced obesity and have improved insulin sensitivity and hepatic TAG accumulation. These data suggest that these enzymes are intimately involved in TAG metabolism and whole body energy homeostasis and that inhibition of these enzymes may provide therapeutic benefits for metabolic disorders such as obesity, metabolic syndrome, and type 2 diabetes.

Synthesis and Cytotoxic Evaluation of Quinazolin-4(3H)-one Derivatives Bearing Thiocarbamate, Thiourea or N-Methyldithiocarbamate Side Chains

Medicinal Chemistry (Shariqah (United Arab Emirates)). Feb, 2012  |  Pubmed ID: 22385175

We have previously found that the dithiocarbamate derivatives of quinazolin-4(3H)-one could act as cytotoxic agents against a panel of human tumor cell lines. To investigate the contribution of dithiocarbamate moiety to the cytotoxic activity, three series of novel quinazolin-4(3H)-one derivatives bearing thiocarbamate, thiourea or Nmethyldithiocarbamate side chains were synthesized and tested for their cytotoxic activity against human cancer cell lines A549, MCF-7, HeLa, HT29 and HCT-116 by MTT assay. The results showed that transformation of the dithiocarbamate moiety in lead compound I to thiocarbamate or thiourea led to a decrease or loss of cytotoxic activity. Some N-alkylated analogs of lead compound II preferentially inhibited the proliferation of A549 cells, although their potencies were not improved in comparison with the unalkylated counterparts. The structure-activity relationship obtained in this research will be beneficial for further synthesis and discovery of effective cytotoxic agents.

Separation of Soybean Isoflavone Aglycone Homologues by Ionic Liquid-Based Extraction

Journal of Agricultural and Food Chemistry. Mar, 2012  |  Pubmed ID: 22385305

The separation of compound of interest from its structural similar homologues is an important and challenging problem in producing high-purity natural products, such as the separation of genistein from other soybean isoflavone aglycone (SIA) homologues. The present work provided a novel method for separating genistein from its structural similar homologues by ionic liquid (IL)-based liquid-liquid extraction using hydrophobic IL-water or hydrophilic IL/water-ethyl acetate biphasic systems. Factors that influence the distribution equilibrium of SIAs, including the structure and concentration of IL, pH values of the aqueous phase and temperature, were investigated. Adequate distribution coefficients and selectivities over 7.0 were achieved with hydrophilic IL/water-ethyl acetate biphasic system. Through a laboratory scale simulation of fractional extraction process containing 4 extraction stages and 4 scrubbing stages, genistein was separated from the SIA homologues with a purity of 95.3% and a recovery higher than 90%.

Single-cell Exome Sequencing Reveals Single-nucleotide Mutation Characteristics of a Kidney Tumor

Cell. Mar, 2012  |  Pubmed ID: 22385958

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

Identification of a Novel PRRT2 Mutation in Patients with Paroxysmal Kinesigenic Dyskinesias and C.649dupC As a Mutation Hot-spot

Parkinsonism & Related Disorders. Mar, 2012  |  Pubmed ID: 22386217

Generation and Characterization of HD(5) and C-terminal Mutant HD(5m) Transgenic Rats

Brain Research. Feb, 2012  |  Pubmed ID: 22386496

Dopamine D(1)-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD(5) and mutant human hD(5) (hD(5m)) transgenic rats. The C-terminal juxtamembrane domain of mutant hD(5) was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD(5) and hD(5m) receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D(5) receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD(5) and hD(5m) receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D(1)-like receptor agonist, SKF83959, could induce anxiety in hD(5m) receptor transgenic rats but had no effect on the anxiety-like behavior in D(5) receptor transgenic and wild-type rats.

Comparison of the Effects of Five Pretreatment Methods on Enhancing the Enzymatic Digestibility and Ethanol Production from Sweet Sorghum Bagasse

Bioresource Technology. Feb, 2012  |  Pubmed ID: 22386628

To improve the enzymatic digestibility of sweet sorghum bagasse and bioethanol production, five pretreatment methods have been investigated and compared, including (1) dilute NaOH solution autoclaving pretreatment, (2) high concentration NaOH solution immersing pretreatment, (3) dilute NaOH solution autoclaving and H(2)O(2) immersing pretreatment, (4) alkaline peroxide pretreatment and (5) autoclaving pretreatment. Among them, the best result was obtained when sweet sorghum bagasse was dilute NaOH solution autoclaving and H(2)O(2) immersing pretreatment. The highest cellulose hydrolysis yield, total sugar yield and ethanol concentration were 74.29%, 90.94g sugar/100g dry matter and 6.12g/L, respectively, which were 5.88, 9.54 and 19.13 times higher than the control. Moreover, the FTIR and SEM analysis illustrated significant molecule and surface structure changes of the sweet sorghum bagasse after pretreatments.

Involvement of Calcitonin Gene-related Peptide and CCL2 Production in CD40-mediated Behavioral Hypersensitivity in a Model of Neuropathic Pain

Neuron Glia Biology. Mar, 2012  |  Pubmed ID: 22377050

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro-nociceptive role after peripheral nerve injury upon its release from primary afferent neurons in preclinical models of neuropathic pain. We previously demonstrated a critical role for spinal cord microglial CD40 in the development of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity. Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral hypersensitivity. First, L5Tx was found to significantly induce CGRP expression in wild-type (WT) mice up to 14 days post-L5Tx. This increase in CGRP expression was reduced in CD40 knockout (KO) mice at day 14 post-L5Tx. Intrathecal injection of the CGRP antagonist CGRP8-37 significantly blocked L5Tx-induced mechanical hypersensitivity. In vitro, CGRP induced glial IL-6 and CCL2 production, and CD40 stimulation added to the effects of CGRP in neonatal glia. Further, there was decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx. However, CGRP8-37 did not significantly affect spinal cord CCL2 production following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes to the maintenance of behavioral hypersensitivity following peripheral nerve injury in part through two distinct pathways, the enhancement of CGRP expression and spinal cord CCL2 production.

Wls-mediated Wnts Differentially Regulate Distal Limb Patterning and Tissue Morphogenesis

Developmental Biology. Feb, 2012  |  Pubmed ID: 22377357

Wnt proteins are diffusible morphogens that play multiple roles during vertebrate limb development. However, the complexity of Wnt signaling cascades and their overlapping expression prevent us from dissecting their function in limb patterning and tissue morphogenesis. Depletion of the Wntless (Wls) gene, which is required for the secretion of various Wnts, makes it possible to genetically dissect the overall effect of Wnts in limb development. In this study, the Wls gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of mesenchymal Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion of ectodermal Wls resulted in agenesis of distal limb tissue and premature regression of the distal mesenchyme. These observations suggested that Wnts from the two germ layers differentially regulate the pool of undifferentiated distal limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts sustain mesenchymal cell proliferation and survival in a manner distinct from Fgf. Ectodermal Wnts were also shown for the first time to be essential for distal tendon/ligament induction, myoblast migration and dermis formation in the limb. These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis.

Luteolin Downregulates TLR4, TLR5, NF-κB and P-p38MAPK Expression, Upregulates the P-ERK Expression, and Protects Rat Brains Against Focal Ischemia

Brain Research. Feb, 2012  |  Pubmed ID: 22377454

BACKGROUND: Inflammatory damage is known to be involved in ischemic stroke. Luteolin has been proved to elicit a series of biologic effects through its anti-inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigate the potential neuroprotective role of luteolin in ischemic stroke and the underlying mechanisms. METHODS: Male Sprague-Dawley rats were subjected to pMCAO and luteolin was administered intraperitoneally immediately after surgery, then once daily thereafter. Neurological deficit, infarct volume, and brain water content were measured at 24h and 72h after stroke. The expression of TLR4, TLR5, and NF-κB were measured by real-time PCR, immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular signal-regulated kinase (ERK) were detected by IHC, and Western blot. RESULTS: Compared with pMCAO group, luteolin significantly alleviated neurological deficit, decreased infarct volume and suppressed edema after ischemic stroke, which were accompanied with decreased expression of TLR4, TLR5, NF-κB and p-p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05). CONCLUSIONS: Luteolin protected the brain from the damage caused by pMCAO, and this effect may be through downregulation of TLR4, TLR5, NF-κB, p38MAPK and upregulation of ERK expression.

Analysis of the Status of Subject Recruitment in Clinical Trials in Shandong, China

Journal of Empirical Research on Human Research Ethics : JERHRE. Feb, 2012  |  Pubmed ID: 22378130

although subject recruitment for clinical trials in Shandong has been carried out with an awareness of international regulatory and ethical frameworks, there have been some defects in the recruitment process. The objective of this study is to analyze the current status of subject recruitment in Shandong. We conducted a survey among 198 principal investigators (PIs) and 543 subjects. The results were summarized and calculated as a percentage according to the responses to each question by PIs and subjects. This survey indicated that the ethics committee should strengthen the review of subject recruitment and enhance ethics training among board members. PIs should seek to improve the recruitment process.

In Vivo and in Situ Imaging of Head and Neck Squamous Cell Carcinoma Using Near-infrared Fluorescent Quantum Dot Probes Conjugated with Epidermal Growth Factor Receptor Monoclonal Antibodies in Mice

Oncology Reports. Feb, 2012  |  Pubmed ID: 22378320

In this study, we applied near-infrared fluorescent quantum dots (NIRF-QDs) for non-invasive in vivo and in situ imaging of head and neck squamous cell carcinoma (HNSCC). The U14 squamous cancer cell line with high expression of epidermal growth factor receptor (EGFR) was implanted subcutaneously into the head and neck regions of nude mice to establish HNSCC models. NIRF-QDs with an emission wavelength of 800 nm (NIRF-QD800) were conjugated with EGFR monoclonal antibodies to develop the QD800-EGFR Ab probe. In vivo and in vitro studies demonstrated that the QD800-EGFR Ab probe can specifically bind EGFR expressed on U14 cells. U14 squamous cell carcinoma in the head and neck can be clearly visualized by in vivo imaging after intravenous injection of QD800-EGFR Ab probes. The results suggested that in situ imaging using NIRF-QD-EGFR Ab probes has unique advantages and prospects for the investigation of tumor development, early diagnosis and personalized therapy of HNSCC.

Bilayer-fish-scale Ultrabroad Terahertz Bandpass Filter

Optics Letters. Mar, 2012  |  Pubmed ID: 22378434

A bilayer fish-scale metamaterial is experimentally demonstrated to function as a broad bandpass filter in the terahertz regime. The measured 3 dB-bandwidth for normal incidence is 1.13 THz with a high transmittance. The measured transmission spectrum is described well by a model based on an RLC circuit and multiple reflections. The filter is relatively insensitive to incidence angles up to 45°.

Orthogonal-reference-pattern-modulated Shift Multiplexing for Collinear Holographic Data Storage

Optics Letters. Mar, 2012  |  Pubmed ID: 22378444

A novel hybrid shift multiplexing method for collinear holographic data storage (CHDS) by using orthogonal reference patterns (RPs) is proposed, analyzed, and demonstrated. For this method, holograms are multiplexed by not only shifting the media but also using different RPs. Compared with the traditional method, the shift pitch for the hybrid method is substantially reduced because of the selectivity introduced by different RPs. The interpage cross talk due to Bragg mismatch and degeneracy for multiplexing holograms in the same volume by using orthogonal RPs is also attenuated by utilizing the shift selectivity of the hologram. A 1.5 μm shift pitch is experimentally achieved by using three amplitude RPs in a system that would be 4.5 μm with only one RP. This new method offers an alternative to significantly increase the data density and transfer rate of the CHDS system given that the media has ideal properties.

Spin Polarization Separation of Light Reflected at Brewster Angle

Optics Letters. Mar, 2012  |  Pubmed ID: 22378460

A spin polarization separation of reflected light is observed, when a linearly polarized Gaussian beam impinges on an air-glass interface at Brewster angle. In the far-field zone, spins of photons are oppositely polarized in two regions along the direction perpendicular to incident plane. Spatial scale of this polarization is related to optical properties of dielectric and can be controlled by experimental configuration. We believe that this study benefits the manipulation of spins of photons and the development of methods for investigating optical properties of materials.

Writing Affects the Brain Network of Reading in Chinese: A Functional Magnetic Resonance Imaging Study

Human Brain Mapping. Feb, 2012  |  Pubmed ID: 22378588

We examined the hypothesis that learning to write Chinese characters influences the brain's reading network for characters. Students from a college Chinese class learned 30 characters in a character-writing condition and 30 characters in a pinyin-writing condition. After learning, functional magnetic resonance imaging collected during passive viewing showed different networks for reading Chinese characters and English words, suggesting accommodation to the demands of the new writing system through short-term learning. Beyond these expected differences, we found specific effects of character writing in greater activation (relative to pinyin writing) in bilateral superior parietal lobules and bilateral lingual gyri in both a lexical decision and an implicit writing task. These findings suggest that character writing establishes a higher quality representation of the visual-spatial structure of the character and its orthography. We found a greater involvement of bilateral sensori-motor cortex (SMC) for character-writing trained characters than pinyin-writing trained characters in the lexical decision task, suggesting that learning by doing invokes greater interaction with sensori-motor information during character recognition. Furthermore, we found a correlation of recognition accuracy with activation in right superior parietal lobule, right lingual gyrus, and left SMC, suggesting that these areas support the facilitative effect character writing has on reading. Finally, consistent with previous behavioral studies, we found character-writing training facilitates connections with semantics by producing greater activation in bilateral middle temporal gyri, whereas pinyin-writing training facilitates connections with phonology by producing greater activation in right inferior frontal gyrus. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

ROS-Inducible DNA Cross-Linking Agent As a New Anticancer Prodrug Building Block

Chemistry (Weinheim an Der Bergstrasse, Germany). Feb, 2012  |  Pubmed ID: 22378607

Down at the crossed code: Novel arylboronic ester and biarylboronic ester derivatives were synthesized. Compound 1 can be activated by hydrogen peroxide to release 2,5-bis(trimethylammonium)-benzyl-1,4-diol (2), which leads to interstrand cross-link formation and DNA alkylation. Compound 1 provides a novel building block for the development of H(2) O(2) -targeting anticancer prodrugs.

The Dependence of Extracted Current on Discharge Gas Pressure in Neutral Beam Ion Sources on HL-2A Tokamak

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380084

The discharge gas pressure is a key factor to influence the extracted current of ion source. In this paper, the dependence of extracted current on discharge gas pressure was investigated in detail at different arc discharge currents. The discharge gas pressure with a very broad range (0.1 Pa-2.7 Pa) was scanned for the first time. It is turned out that, with the increasing of discharge gas pressure, the extracted current increases and the arc voltage decreases at different arc currents; however, when the discharge gas pressure exceeds a certain value, the extracted current decreases. For the same discharge gas pressure, the higher the arc current, the higher the arc voltage and the extracted current are. The arc efficiency was also calculated, and its dependence on gas pressure was almost the same with the dependence of extracted current on gas pressure, but at the same discharge gas pressure, the lower the arc current, the higher the arc efficiency is and the lower the extracted current is.

Performance and Operation of Advanced Superconducting Electron Cyclotron Resonance Ion Source SECRAL at 24 GHz

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380167

SECRAL (superconducting ECR ion source with advanced design in Lanzhou) ion source has been in routine operation for Heavy Ion Research Facility in Lanzhou (HIRFL) accelerator complex since May 2007. To further enhance the SECRAL performance in order to satisfy the increasing demand for intensive highly charged ion beams, 3-5 kW high power 24 GHz single frequency and 24 GHz +18 GHz double frequency with an aluminum plasma chamber were tested, and some exciting results were produced with quite a few new record highly charged ion beam intensities, such as (129)Xe(35+) of 64 eμA, (129)Xe(42+) of 3 eμA, (209)Bi(41+) of 50 eμA, (209)Bi(50+) of 4.3 eμA and (209)Bi(54+) of 0.2 eμA. In most cases SECRAL is operated at 18 GHz to deliver highly charged heavy ion beams for the HIRFL accelerator, only for those very high charge states and very heavy ion beams such as (209)Bi(36+) and (209)Bi(41+), SECRAL has been operated at 24 GHz. The total operation beam time provided by SECRAL up to July 2011 has exceeded 7720 hours. In this paper, the latest performance, development, and operation status of SECRAL ion source are presented. The latest results and reliable long-term operation for the HIRFL accelerator have demonstrated that SECRAL performance for production of highly charged heavy ion beams remains improving at higher RF power with optimized tuning.

Development of DRAGON Electron Cyclotron Resonance Ion Source at Institute of Modern Physics

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380175

A new room temperature electron cyclotron resonance (ECR) ion source, DRAGON, is under construction at IMP. DRAGON is designed to operate at microwaves of frequencies of 14.5-18 GHz. Its axial solenoid coils are cooled with evaporative medium to provide an axial magnetic mirror field of 2.5 T at the injection and 1.4 T at the extraction, respectively. In comparison to other conventional room temperature ECR ion sources, DRAGON has so far the largest bore plasma chamber of inner diameter of 126 mm with maximum radial fields of 1.4-1.5 T produced by a non-Halbach permanent sextupole magnet.

A 2.45 GHz Electron Cyclotron Resonance Proton Ion Source and a Dual-lens Low Energy Beam Transport

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380176

The structure and preliminary commissioning results of a new 2.45 GHz ECR proton ion source and a dual-lens low energy beam transport (LEBT) system are presented in this paper. The main magnetic field of the ion source is provided by a set of permanent magnets with two small electro-solenoid magnets at the injection and the extraction to fine tune the magnetic field for better microwave coupling. A 50 keV pulsed proton beam extracted by a three-electrode mechanism passes through the LEBT system of length of 1183 mm. This LEBT consists of a diagnosis chamber, two Glaser lenses, two steering magnets, and a final beam defining cone. A set of inner permanent magnetic rings is embedded in each of the two Glaser lenses to produce a flatter axial-field to reduce the lens aberrations.

Status of the Laser Ion Source at IMP

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380282

A laser (Nd:YAG laser, 3 J, 1064 nm, 8-10 ns) ion source has been built and under development at IMP to provide pulsed high-charge-state heavy ion beams to a radio frequency quadrupole (RFQ) for upgrading the IMP accelerators with a new low-energy beam injector. The laser ion source currently operates in a direct plasma injection scheme to inject the high charge state ions produced from a solid target into the RFQ. The maximum power density on the target was about 8.4 × 10(12) W∕cm(2). The preliminary experimental results will be presented and discussed in this paper.

Study of Ion Beam Transport from the SECRAL Electron Cyclotron Resonance Ion Source at the Institute of Modern Physics

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380331

Ion beam transport from the Superconducting Electron Cyclotron Resonance ion source with Advanced design in Lanzhou (SECRAL) electron cyclotron resonance ion source was studied at the Institute of Modern Physics during 2010. Particle-in-cell simulations and experimental results have shown that both space charge and magnetic aberrations lead to a larger beam envelope and emittance growth. In the existing SECRAL extraction beam line, it has been shown that raising the solenoid lens magnetic field reduces aberrations in the subsequent dipole and results in lower emittance. Detailed beam emittance measurements are presented in this paper.

Reproducibility of Registration-based Measures of Lung Tissue Expansion

Medical Physics. Mar, 2012  |  Pubmed ID: 22380392

Purpose: Lung function depends on lung expansion and contraction during the respiratory cycle. Respiratory-gated CT imaging and 3D image registration can be used to locally estimate lung tissue expansion and contraction (regional lung volume change) by computing the determinant of the Jacobian matrix of the image registration deformation field. In this study, the authors examine the reproducibility of Jacobian-based measures of lung tissue expansion in two repeat 4DCT acquisitions of mechanically ventilated sheep and free-breathing humans.Methods: 4DCT image data from three white sheep and nine human subjects were used for this analysis. In each case, two 4DCT studies were acquired for each subject within a short time interval. The animal subjects were anesthetized and mechanically ventilated, while the humans were awake and spontaneously breathing based on respiratory pacing audio cues. From each 4DCT data set, an image pair consisting of a volume reconstructed near end inspiration and a volume reconstructed near end exhalation was selected. The end inspiration and end exhalation images were registered using a tissue volume preserving deformable registration algorithm and the Jacobian of the registration deformation field was used to measure regional lung expansion. The Jacobian map from the baseline data set was compared to the Jacobian map from the followup data by measuring the voxel-by-voxel Jacobian ratio.Results: In the animal subjects, the mean Jacobian ratio (baseline scan Jacobian divided by followup scan Jacobian, voxel-by-voxel) was 0.9984±0.021 (mean ± standard deviation, averaged over the entire lung region). The mean Jacobian ratio was 1.0224±0.058 in the human subjects. The reproducibility of the Jacobian values was found to be strongly dependent on the reproducibility of the subject's respiratory effort and breathing pattern.Conclusions: Lung expansion, a surrogate for lung function, can be assessed using two or more respiratory-gated CT image acquisitions. The results show that good reproducibility can be obtained in anesthetized, mechanically ventilated animals, but variations in respiratory effort and breathing patterns reduce reproducibility in spontaneously-breathing humans. The global linear normalization can globally compensate for breathing effort differences, but a homogeneous scaling does not account for differences in regional lung expansion rates. Additional work is needed to develop compensation procedures or normalization schemes that can account for local variations in lung expansion during respiration.

Phosphorylated CaMKII Postsynaptic Binding to NR2B Subunits in the Anterior Cingulate Cortex Mediates Visceral Pain in Visceral Hypersensitive Rats

Journal of Neurochemistry. Mar, 2012  |  Pubmed ID: 22380661

The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is upregulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of CaMKII in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension (CRD) induced visceromotor response (VMR) in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr(286) protein levels were increased in 180%, 220% and 304% fold in the postsynaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr(286) bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed VMR in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B- P-CaMKII-Thr(286) protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at postsynaptic site, modulates visceral pain in viscerally hypersensitive state. © 2012 The Authors Journal of Neurochemistry© 2012 International Society for Neurochemistry.

Enhanced Proliferation and Functions of in Vitro Expanded Human Hair Follicle Outer Root Sheath Cells by Low Oxygen Tension Culture

Tissue Engineering. Part C, Methods. Mar, 2012  |  Pubmed ID: 22380865

Introduction: Human hair follicle outer root sheath (hORS) cells are known to contain hair follicle stem cells and play an important role in healing large size wounds, and thus can serve as the cell source for skin engineering. This study investigated the effect of low oxygen tension culture on hORS cell proliferation potential and functional maintenance during in vitro expansion. Materials and methods: Spared post-surgery scalp tissues were donated by 15 patients aged from 20-45 (13 males and 2 female) and were randomly divided into three groups and isolated hORS cells were combined into three pooled cell samples. They were cultured either in 4% O2 or 21% O2 and were analyzed for cell proliferation, colony forming efficiency (CFE) and their ability in forming engineered skin in vitro. Results: The results showed that freshly isolated hORS cells expressed CD200 (22.88±8.76), CK15 (62.57±4.72), CD29 (22.53±2.49/strong and 29.80±4.09/dim) and CD49f (28.07±15.76/strong and 49.73±5.65/dim). When exposed in 4%O2, hORS cells proliferated significantly faster than the cells in 21%O2 for the first three passages (p<0.05), could better maintain cobblestone morphology, respectively generate 3.63 folds more and 23.26 folds more cell yields after 1 and 3 passages. Additionally, enhanced colony forming efficiency with significantly higher total and holoclone colony numbers were found in 4%O2 group than in 21%O2 group (p<0.05) for the first three passages along with better maintained CK 15 expression. Furthermore, hORS cells expanded in 4%O2 could form better epidermal structure of in vitro engineered skin comparing to the skin engineered by the control cells. Conclusion: The low oxygen culture method of hORS cells is simple, low cost, less labor intensive and less biosafety concern, which may potentially be applied in skin engineering and clinical application.

[Fungal Infection Induced by Cryptococcus Neoformans Aerosol Inhalation in Immunosuppressed Balb/c Mice]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Feb, 2012  |  Pubmed ID: 22381750

To explore the feasibility of inducing fungal infection by Cryptococcus neoformans aerosol inhalation in immunosuppressed Balb/c mice.

Identification of Three H1N1 Influenza Virus Groups with Natural Recombinant Genes Circulating from 1918 to 2009

Virology. May, 2012  |  Pubmed ID: 22381928

In this study, we identify a recombinant pb1 gene, a recombinant MP segment and a recombinant PA segment. The pb1 gene is recombined from two Eurasia swine H1N1 influenza virus lineages. It belongs to a H1N1 swine clade circulating in Europe and Asia from 1999 to 2009. The mosaic MP segment descends from H7 avian and H1N1 human virus lineages and pertains to a large human H1N1 virus family circulating in Asia, Europe and America from 1918 to 2007. The recombinant PA segment originated from two swine H1N1 lineages is found in a swine H1N1 group prevailing in Asia and Europe from 1999 to 2003. These results collectively falsify the hypothesis that influenza virus do not evolve by homologous recombination. Since recombination not only leads to virus genome diversity but also can alter its host adaptation and pathogenecity; the genetic mechanism should not be neglected in influenza virus surveillance.

A Hierarchical Architecture S/MWCNT Nanomicrosphere with Large Pores for Lithium Sulfur Batteries

Physical Chemistry Chemical Physics : PCCP. Mar, 2012  |  Pubmed ID: 22382743

A hierarchical S/MWCNT nanomicrosphere for lithium/sulfur batteries with a high power and energy density as well as an excellent cycle life is introduced. Sulfur was uniformly coated on the surface of functional MWCNTs, which serves as a carbon matrix, to form a typical nanoscale core-shell structure with a sulfur layer of thickness 10-20 nm. Then the nanoscale sulfur intermediate composite was ball-milled to form interwoven and porous sphere architecture with large pores (around 1 μm to 5 μm). Different from most sulfur/carbon materials with micropore and mesopore structure, the micrometre scale S/MWCNT nanomicrosphere with a large pore structure could also exhibit high sulfur utilization and cycle retention. It could maintain a reversible capacity of 1000 mA h g(-1) after 100 cycles at 0.3 A g(-1) current density. And it even remained 780 mA h g(-1) after 200 cycles at 0.5 A g(-1) and 650 mA h g(-1) after 200 cycles at 1 A g(-1), showing a significant cyclability enhancement. It is believed that under the collective effect of hierarchical architecture, as well as the existence of carboxyl functional groups, sulfur/carbon materials with large pores could also exhibit an excellent electrochemical performance. The synthesis process introduced here is simple and broadly applicable, which would not only be beneficial to design new materials for lithium sulfur batteries but can also be extended to many different electrode materials for lithium ion batteries.

Traumatic Aortic Injuries Associated with Major Visceral Vascular Injuries in Major Blunt Trauma Patients

World Journal of Surgery. Mar, 2012  |  Pubmed ID: 22382770

BACKGROUND: The objectives of this study were to report the clinical and radiological characteristics and outcomes of a series of acute traumatic aortic injuries (ATAIs) with associated injury to major aortic abdominal visceral branches (MAAVBs). METHODS: From January 2000 to August 2011, 10 consecutive major blunt trauma patients with associated ATAI and injury to MAAVBs (group A) and 42 major blunt trauma patients presenting only an ATAI without MAAVB injuries (group B) were admitted to our institution. RESULTS: Overall in-hospital mortality was 32.7%. In-hospital mortality in group A was 40% and in group B it was 31% (p = 0.86). Observed in-hospital mortality was slightly lower than the expected in-hospital mortality in both groups. Mean peak creatine phosphokinase was significantly higher in group A than in group B patients (23,008 ± 33,400 vs. 3,970 ± 3,495 IU/L; p < 0.001). Acute renal injury occurred in 50% of group A and in 26.2% of group B patients. Hemodiafiltration was required in 30% of group A and in 9.5% of group B patients. Median follow-up time was 64 months (range = 1-130 months). Group A survival was 60% at 1, 5 and 10 years. Group B survival was 69% at 1 year and 63.3% at 5 and 10 years (p = 0.15). CONCLUSIONS: Aortic injuries associated with MAAVB injuries in major trauma patients seem to present in a different clinical scenario. These patients present increased risk of rhabdomyolysis, visceral ischemia, and acute renal failure, as well as higher in-hospital mortality. A multidisciplinary approach combining endovascular and open surgical techniques for a staged treatment of these life-threatening aortic and MAAVB injuries is mandatory in this critical subset of trauma patients.

Newly Diagnosed Acute Lymphoblastic Leukemia in China (I): Abnormal Genetic Patterns in 1346 Childhood and Adult Cases and Their Comparison with the Reports from Western Countries

Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. Feb, 2012  |  Pubmed ID: 22382891

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically correlated (P<0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20-38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4-11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.Leukemia advance online publication 2 March 2012; doi:10.1038/leu.2012.26.

Aspartic Acid Substitutions in Monoamine Oxidase-A Reveal Both Catalytic-dependent and -independent Influences on Cell Viability and Proliferation

Journal of Neural Transmission (Vienna, Austria : 1996). Mar, 2012  |  Pubmed ID: 22382901

Post-translational influences could underlie the ambiguous roles of monoamine oxidase-A (MAO-A) in pathologies such as depression, cancer and Alzheimer disease. In support of this, we recently demonstrated that the Ca(2+)-sensitive component of MAO-A catalytic activity is inhibited by a pro-survival p38 (MAPK)-dependent mechanism. We substituted three aspartic acid (D) residues in human MAO-A that reside in putative Ca(2+)-binding motifs and overexpressed the individual proteins in the human HEK293 cell line. We assayed the overexpressed proteins for catalytic activity and for their influence on cell viability (using MTT conversion and trypan blue exclusion) and proliferation/DNA synthesis [using bromodeoxyuridine (BrdU) incorporation]. Innate MAO-A catalytic activity (and the capacity for generating hydrogen peroxide) was unaffected by the D61A substitution, but inhibited moderately or completely by the D248A and D328G substitutions, respectively. The Ca(2+)-sensitive activities of wild-type and D248A MAO-A proteins were enhanced by treatment with the selective p38(MAPK) inhibitor, SB203580, but was completely abrogated by the D61A substitution. Monoamine oxidase-A(D61A) was toxic to cells and exerted no effect on cell proliferation, while MAO-A(D248A) was generally comparable to wild-type MAO-A. As expected, the catalytic-dead MAO-A(D328G) was not cytotoxic, but unexpectedly enhanced both MTT conversion and BrdU staining. Variant-dependent changes in Bax and Bcl-2/Bcl-XL protein expression were observed. A different pattern of effects in N2-a cells suggests cell line-dependent roles for MAO-A. A catalytic-dependent mechanism influences MAO-A-mediated cytotoxicity, whereas a catalytic-independent mechanism contributes to proliferation. Context-dependent inputs by either mechanism could underlie the ambiguous pathological contributions of MAO-A.

Molecular Cloning and Functional Characterization of a Novel Apple MdCIPK6L Gene Reveals Its Involvement in Multiple Abiotic Stress Tolerance in Transgenic Plants

Plant Molecular Biology. Mar, 2012  |  Pubmed ID: 22382993

CBL-interacting protein kinases (CIPKs) are involved in many aspects of plant responses to abiotic stresses. However, their functions are poorly understood in fruit trees. In this study, a salt-induced MdCIPK6L gene was isolated from apple. Its expression was positively induced by abiotic stresses, stress-related hormones and exogenous Ca(2+). MdCIPK6L was not homologous to AtSOS2, however, its ectopic expression functionally complemented Arabidopsis sos2 mutant. Furthermore, yeast two-hybrid assay showed that MdCIPK6L protein interacted with AtSOS3, indicating that it functions in salt tolerance partially like AtSOS2 through SOS pathway. As a result, the overexpression of both MdCIPK6L and MdCIPK6LT175D remarkably enhanced the tolerance to salt, osmotic/drought and chilling stresses, but did not affect root growth, in transgenic Arabidopsis and apple. Also, T-to-D mutation to MdCIPK6L at Thr175 did not affect its function. These differences between MdCIPK6L and other CIPKs, especially CIPK6s, indicate that MdCIPK6L encodes a novel CIPK in apple. Finally, MdCIPK6L overexpression also conferred tolerance to salt, drought and chilling stresses in transgenic tomatoes. Therefore, MdCIPK6L functions in stress tolerance crossing the species barriers, and is supposed to be a potential candidate gene to improve stress tolerance by genetic manipulation in apple and other crops.

Cold-induced Activation of Brown Adipose Tissue and Adipose Angiogenesis in Mice

Nature Protocols. 2012  |  Pubmed ID: 22383039

Exposure of humans and rodents to cold activates thermogenic activity in brown adipose tissue (BAT). This protocol describes a mouse model to study the activation of BAT and angiogenesis in adipose tissues by cold acclimation. After a 1-week exposure to 4 °C, adult C57BL/6 mice show an obvious transition from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the end of week 5 BRITE contains a high number of uncoupling protein-1-positive mitochondria, a characteristic feature of BAT. During the transition from WAT into BRITE, the vascular density is markedly increased owing to the activation of angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the mitochondrial content and metabolic rate. BAT and the increased metabolic rate result in a lean phenotype. This protocol provides an outstanding opportunity to study the molecular mechanisms that control adipose mass.

Nerve Sprouting Contributes to Increased Severity of Ventricular Tachyarrhythmias by Upregulating IGluRs in Rats with Healed Myocardial Necrotic Injury

Journal of Molecular Neuroscience : MN. Mar, 2012  |  Pubmed ID: 22383217

Sympathetic nerve sprouting in healed myocardial infarction (MI) has been associated with high incidences of lethal arrhythmias, but the underlying mechanisms are largely unknown. This study sought to test that sympathetic hyperinnervation and/or MI remodels the myocardial glutamate signaling and ultimately increases the severity of ventricular tachyarrhythmias. Myocardial necrotic injury (MNI) was created by liquid nitrogen freeze-thawing across an intact diaphragm to mimic MI. Cardiac sympathetic hyperinnervation was induced by chronic subcutaneous injection of 4-methylcatechol, a potent stimulator of nerve growth factor expression. The results showed that sympathetic hyperinnervation with or without MNI upregulated the myocardial expression of ionotropic glutamate receptors (iGluRs), including NMDA receptor (NMDAR) and AMPA receptor (AMPAR), and induced cardiomyocyte apoptosis. Intravenous infusion with either NMDA (12 mg/kg) or AMPA (15 mg/kg) triggered ventricular tachycardia and ventricular fibrillation in rats with healed MNI plus sympathetic hyperinnervation; these arrhythmias were prevented by respective antagonist of NMDAR or AMPAR. We conclude that MNI with sympathetic nerve sprouting upregulates the expression of NMDAR and AMPAR in the myocardium and this impact in turn enhances cardiac responses to stimulations of iGluRs and thus increases the incidence of ventricular tachyarrhythmias.

Derivatization Followed by Gas Chromatography-mass Spectrometry for Quantification of Ethyl Carbamate in Alcoholic Beverages

Journal of Separation Science. Mar, 2012  |  Pubmed ID: 22383421

A sensitive and rapid analytical methodology based on derivatization followed by gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC, urethane, C(2) H(5) OCONH(2) ) in alcoholic samples. EC was extracted using liquid-liquid extraction technique, and then silylated with bis-(trimethylsilyl)trifluoroacetamide, analysed finally by GC-MS. The isopropyl carbamate was used as the internal standard for quantitative analysis of EC in alcoholic samples. In this work, the sample extraction and derivatization reaction conditions were investigated, and the optimal extraction conditions obtained were: pH of 9 and solvent of ethyl acetate, and the derivatization conditions were: derivatization reaction temperature of 80°C and time duration of 30 min. With the optimal conditions, the method validations were also studied. In the validation studies, EC exhibited good linearity with a regression coefficient of 0.9999. The limit of detection and limit of quantification were 0.30 and 5.0 μg/kg, respectively. The precision was less than 8.4%. Finally, the proposed technique was successfully applied to the analysis of EC in 35 kinds of alcoholic samples. The experimental results have demonstrated that the proposed technique is a fast, reliable and low-cost method for determination of EC in alcoholic samples.

Prognostic and Predictive Significance of Plasma HGF and IL-8 in a Phase III Trial of Chemoradiation with or Without Tirapazamine in Locoregionally Advanced Head and Neck Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Mar, 2012  |  Pubmed ID: 22383739

Hepatocyte growth factor (HGF) is a hypoxia-induced secreted protein that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the role of circulating HGF and IL-8 as prognostic and predictive factors for efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin.

Identification of Genome-Wide Variations Among Three Elite Restorer Lines for Hybrid-Rice

PloS One. 2012  |  Pubmed ID: 22383984

Rice restorer lines play an important role in three-line hybrid rice production. Previous research based on molecular tagging has suggested that the restorer lines used widely today have narrow genetic backgrounds. However, patterns of genetic variation at a genome-wide scale in these restorer lines remain largely unknown. The present study performed re-sequencing and genome-wide variation analysis of three important representative restorer lines, namely, IR24, MH63, and SH527, using the Solexa sequencing technology. With the genomic sequence of the Indica cultivar 9311 as the reference, the following genetic features were identified: 267,383 single-nucleotide polymorphisms (SNPs), 52,847 insertion/deletion polymorphisms (InDels), and 3,286 structural variations (SVs) in the genome of IR24; 288,764 SNPs, 59,658 InDels, and 3,226 SVs in MH63; and 259,862 SNPs, 55,500 InDels, and 3,127 SVs in SH527. Variations between samples were also determined by comparative analysis of authentic collections of SNPs, InDels, and SVs, and were functionally annotated. Furthermore, variations in several important genes were also surveyed by alignment analysis in these lines. Our results suggest that genetic variations among these lines, although far lower than those reported in the landrace population, are greater than expected, indicating a complicated genetic basis for the phenotypic diversity of the restorer lines. Identification of genome-wide variation and pattern analysis among the restorer lines will facilitate future genetic studies and the molecular improvement of hybrid rice.

GSK3 Inhibitor-BIO Regulates Proliferation of Immortalized Pancreatic Mesenchymal Stem Cells (iPMSCs)

PloS One. 2012  |  Pubmed ID: 22384031

The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present.

Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Multi-ethnic Region, Xinjiang Uygur Autonomous Region, China

PloS One. 2012  |  Pubmed ID: 22384153

The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic region and suffered second highest incidence of TB in China. However, epidemiological information on MDR and XDR TB is scarcely investigated.