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Find video protocols related to scientific articles indexed in Pubmed.
Long-term thiol monitoring in living cells using bioorthogonal chemistry.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Intracellular thiols play vital roles in living systems, and their in situ monitoring is of great importance. Here, we report on a bioorthogonal chemistry based fluorescent probe, which is capable of monitoring intracellular thiols in living cells for up to 36 hours with an obvious blue-to-green fluorescence change.
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Formation of polyphenyl chains through hierarchical reactions: Ullmann coupling followed by cross-dehydrogenative coupling.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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From an interplay of UHV-STM imaging and DFT calculations, we have illustrated on-surface formation of polyphenyl chains through a hierarchical reaction pathway involving two different kinds of reactions (Ullmann coupling and cross-dehydrogenative coupling), which will provide a deeper understanding of on-surface chemical reactions and an alternative and efficient strategy to fabricate desired surface molecular nanostructures.
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[Effect of hypothermia on TLR2/MyD88 signal pathway in lung tissue in rats with acute lung injury induced by lipopolysaccharide].
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 11-18-2014
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To investigate the effect of hypothermia on the expression Toll-like receptor 2 (TLR2), myeloid differentiation factor 88 (MyD88), nuclear factor-?Bp65 (NF-?Bp65), plasminogen activator inhibitor-1 (PAI-1) in the TLR2/MyD88 pathway in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS) inhalation.
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On-surface synthesis of organometallic complex via metal-alkene interactions.
Chem. Commun. (Camb.)
PUBLISHED: 11-10-2014
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From the interplay of high-resolution scanning tunneling microscopy (STM) imaging/manipulation and density functional theory (DFT) calculations, we have shown that the spontaneous formation of an organometallic complex by copper-alkene interactions can be successfully achieved, where the specific molecular adsorption geometry is revealed to be the key for facilitating such interaction.
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Natural Gradient Learning Algorithms for RBF Networks.
Neural Comput
PUBLISHED: 11-08-2014
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Radial basis function (RBF) networks are one of the most widely used models for function approximation and classification. There are many strange behaviors in the learning process of RBF networks, such as slow learning speed and the existence of the plateaus. The natural gradient learning method can overcome these disadvantages effectively. It can accelerate the dynamics of learning and avoid plateaus. In this letter, we assume that the probability density function (pdf) of the input and the activation function are gaussian. First, we introduce natural gradient learning to the RBF networks and give the explicit forms of the Fisher information matrix and its inverse. Second, since it is difficult to calculate the Fisher information matrix and its inverse when the numbers of the hidden units and the dimensions of the input are large, we introduce the adaptive method to the natural gradient learning algorithms. Finally, we give an explicit form of the adaptive natural gradient learning algorithm and compare it to the conventional gradient descent method. Simulations show that the proposed adaptive natural gradient method, which can avoid the plateaus effectively, has a good performance when RBF networks are used for nonlinear functions approximation.
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Broadband fiber-optical parametric amplification for ultrafast time-stretch imaging at 1.0???m.
Opt Lett
PUBLISHED: 11-01-2014
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We demonstrate a broadband all-fiber-optical parametric amplifier for ultrafast time-stretch imaging at 1.0 ?m, featured by its compact design, alignment-free, high efficiency, and flexible gain spectrum through fiber nonlinearity- and dispersion-engineering: specifically on a dispersion-stabilized photonic-crystal fiber (PCF) to achieve a net gain over 20 THz (75 nm) and a highest gain of ?6000 (37.5 dB). Another unique feature of the parametric amplifier, over other optical amplifiers, is the coherent generation of a synchronized signal replica (called idler) that can be exploited to offer an extra 3-dB gain by optically superposing the signal and idler. It further enhances signal contrast and temporal stability. For proof-of-concept purpose, ultrahigh speed and diffraction-limited time-stretch microscopy is demonstrated with a single-shot line-scan rate of 13 MHz based on the dual-band (signal and idler) detection. Our scheme can be extended to other established bioimaging modalities, such as optical coherence tomography, near infrared fluorescence, and photoacoustic imaging, where weak signal detection at high speed is required.
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Formation of a G-Quartet-Fe Complex and Modulation of Electronic and Magnetic Properties of the Fe Center.
ACS Nano
PUBLISHED: 10-28-2014
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Although the G-quartet structure has been extensively investigated due to its biological importance, the formation mechanism, in particular, the necessity of metal centers, of an isolated G-quartet on solid surfaces remains ambiguous. Here, by using scanning tunneling microscopy under well-controlled ultra-high-vacuum conditions and density functional theory calculations we have been able to clarify that besides the intraquartet hydrogen bonding a metal center is mandatory for the formation of an isolated G-quartet. Furthermore, by subtly perturbing the local coordination bonding schemes within the formed G-quartet complex via local nanoscale scanning tunneling microscopy manipulations, we succeed in modulating the d orbitals and the accompanying magnetic properties of the metal center. Our results demonstrate the feasibility of forming an isolated G-quartet complex on a solid surface and that the strategy of modulating electronic and magnetic properties of the metal center can be extended to other related systems such as molecular spintronics.
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[Influencing factors of sludge liquor treatment in UASBB].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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The effect of ammonia nitrogen concentration, temperature, pH, HRT and C/N ratio on ANAMMOX was studied. The reactor was fed with sludge liquor. The efficiency of nitrogen removal for the UASBB was researched under different ammonia nitrogen concentration, HRT, temperature, pH and C/N ratio when the influent rho(NH4(+) -N)/rho(NO2(-) -N) was controlled at 1:1.32. The results showed that the nitrogen removal rate for the ANANMMOX reactors was optimal when the influent NH4(+) -N and NO2(-) -N concentrations were 200 mg x L(-1) and 264 mg x L(-1), HRT was 24 h, temperature was in the range of 30-35 degrees C, pH was at 7.5-8.5 and the C/N ratio was 0.5. The average removal rates of NH4(+) -N, NO2(-) -N and TN were 75.72%, 76.36% and 70.19%, respectivley, the average TN was 0.464 kg x (m3 x d)(-1) and the removal rate of COD was 30%. The efficiency of nitrogen removal for the ANAMMOX reactors could be enhanced by controlling ammonia nitrogen concentration and HRT. The efficiency of ANAMMOX bacteria was optimal when temperature and pH were suitable. The denitrification occurred in the ANAMMOX reactors when the influent contained organics. The inhibition of denitrification bacteria on the ANAMMOX increased with rising concentration of organics.
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Creating SERS Hot Spots on MoS2 Nanosheets with in Situ Grown Gold Nanoparticles.
ACS Appl Mater Interfaces
PUBLISHED: 10-23-2014
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Herein, a reliable surface-enhanced Raman scattering (SERS)-active substrate has been prepared by synthesizing gold nanoparticles (AuNPs)-decorated MoS2 nanocomposite. The AuNPs grew in situ on the surface of MoS2 nanosheet to form efficient SERS hot spots by a spontaneous redox reaction with tetrachloroauric acid (HAuCl4) without any reducing agent. The morphologies of MoS2 and AuNPs-decorated MoS2 nanosheet were characterized by TEM, HRTEM, and AFM. The formation of hot spots greatly depended on the ratio of MoS2 and HAuCl4. When the concentration of HAuCl4 was 2.4 mM, the as-prepared AuNPs@MoS2-3 nanocomposite exhibited a high-quality SERS activity toward probe molecule due to the generated hot spots. The spot-to-spot SERS signals showed that the relative standard deviation (RSD) in the intensity of the main Raman vibration modes (1362, 1511, and 1652 cm(-1)) of Rhodamine 6G were about 20%, which displayed good uniformity and reproducibility. The AuNPs@MoS2-based substrate was reliable, sensitive, and reproducible, which showed great potential to be an excellent SERS substrate for biological and chemical detection.
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Damping of Confined Modes in a Ferromagnetic Thin Insulating Film: Angular Momentum Transfer across a Nanoscale Field-Defined Interface.
Phys. Rev. Lett.
PUBLISHED: 10-21-2014
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We observe a dependence of the damping of a confined mode of precessing ferromagnetic magnetization on the size of the mode. The micron-scale mode is created within an extended, unpatterned yttrium iron garnet film by means of the intense local dipolar field of a micromagnetic tip. We find that the damping of the confined mode scales like the surface-to-volume ratio of the mode, indicating an interfacial damping effect (similar to spin pumping) due to the transfer of angular momentum from the confined mode to the spin sink of ferromagnetic material in the surrounding film. Though unexpected for insulating systems, the measured intralayer spin-mixing conductance g_{??}=5.3×10^{19}??m^{-2} demonstrates efficient intralayer angular momentum transfer.
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Grueneisen relaxation photoacoustic microscopy.
Phys. Rev. Lett.
PUBLISHED: 10-20-2014
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The temperature-dependent property of the Grueneisen parameter has been employed in photoacoustic imaging mainly to measure tissue temperature. Here we explore this property using a different approach and develop Grueneisen relaxation photoacoustic microscopy (GR-PAM), a technique that images nonradiative absorption with confocal optical resolution. GR-PAM sequentially delivers two identical laser pulses with a microsecond-scale time delay. The first laser pulse generates a photoacoustic signal and thermally tags the in-focus absorbers. When the second laser pulse excites the tagged absorbers within the thermal relaxation time, a photoacoustic signal stronger than the first one is produced, owing to the temperature dependence of the Grueneisen parameter. GR-PAM detects the amplitude difference between the two colocated photoacoustic signals, confocally imaging the nonradiative absorption. We greatly improved axial resolution from 45???m to 2.3???m and, at the same time, slightly improved lateral resolution from 0.63???m to 0.41???m. In addition, the optical sectioning capability facilitates the measurement of the absolute absorption coefficient without fluence calibration.
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Performance of megahertz amplified optical time-stretch optical coherence tomography (AOT-OCT).
Opt Express
PUBLISHED: 10-17-2014
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Enabled by the ultrahigh-speed all-optical wavelength-swept mechanism and broadband optical amplification, amplified optical time-stretch optical coherence tomography (AOT-OCT) has recently been demonstrated as a practical alternative to achieve ultrafast A-scan rate of multi-MHz in OCT. With the aim of identifying the optimal scenarios for MHz operation in AOT-OCT, we here present a theoretical framework to evaluate its performance metric. In particular, the analysis discusses the unique features of AOT-OCT, such as its superior coherence length, and the relationship between the optical gain and the A-scan rate. More importantly, we evaluate the sensitivity of AOT-OCT in the MHz regime under the influence of the amplifier noise. Notably, the model shows that AOT-OCT is particularly promising when operated at the A-scan rate well beyond multi-MHz - not trivially achievable by any existing swept-source OCT platform. A sensitivity beyond 90 dB, close to the shot-noise limit, can be maintained in the range of 2 - 10 MHz with an optical net gain of ~10dB. Experimental measurement also shows excellent agreement with the theoretical prediction. While distributed fiber Raman amplification is mainly considered in this paper, the theoretical model is generally applicable to any type of amplification schemes. As a result, our analysis serves as a useful tool for further optimization of AOT-OCT system - as a practical alternative to enable MHz OCT operation.
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Molecular Behavior at Buried Epoxy/Poly(ethylene terephthalate) Interface.
Langmuir
PUBLISHED: 10-17-2014
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Epoxies are widely used as main components in packaging underfills for microelectronics. Their strong adhesion to different substrate materials is an important factor for the functioning of electronic devices. Amines are commonly used cross-linking agents for epoxides. However, the molecular mechanisms of epoxide-amine mixture adhesion to substrate materials remain unclear. In this research we investigated the adhesion mechanism of epoxide-amine mixtures at poly(ethylene terephthalate) (PET) interfaces using attenuated total-internal reflection Fourier transform infrared (ATR-FTIR) spectroscopy and sum frequency generation (SFG) vibrational spectroscopy. Results show that both epoxide and amine could diffuse into the PET film. They could also dissolve or modify the PET film at the interphase region. In the process of epoxy curing on PET, epoxide molecules could cross-link with the modified PET film, providing strong adhesion. This hypothesis was further confirmed by adding reactive and nonreactive silanes to the epoxies and measuring the adhesion strengths of such mixtures to PET. The reactive silanes could cross-link with the system, showing good adhesion, while the nonreactive silane prevented sufficient cross-linking, showing poor adhesion. This research developed an in-depth insight for molecular behaviors at the epoxy/PET interface which helped clarify the related adhesion mechanism.
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Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex.
J. Exp. Med.
PUBLISHED: 10-06-2014
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Genetic studies have shown that the tuberous sclerosis complex (TSC) 1-TSC2-mammalian target of Rapamycin (mTOR) and the Hippo-Yes-associated protein 1 (YAP) pathways are master regulators of organ size, which are often involved in tumorigenesis. The crosstalk between these signal transduction pathways in coordinating environmental cues, such as nutritional status and mechanical constraints, is crucial for tissue growth. Whether and how mTOR regulates YAP remains elusive. Here we describe a novel mouse model of TSC which develops renal mesenchymal lesions recapitulating human perivascular epithelioid cell tumors (PEComas) from patients with TSC. We identify that YAP is up-regulated by mTOR in mouse and human PEComas. YAP inhibition blunts abnormal proliferation and induces apoptosis of TSC1-TSC2-deficient cells, both in culture and in mosaic Tsc1 mutant mice. We further delineate that YAP accumulation in TSC1/TSC2-deficient cells is due to impaired degradation of the protein by the autophagosome/lysosome system. Thus, the regulation of YAP by mTOR and autophagy is a novel mechanism of growth control, matching YAP activity with nutrient availability under growth-permissive conditions. YAP may serve as a potential therapeutic target for TSC and other diseases with dysregulated mTOR activity.
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Hyperspectral imaging and characterization of live cells by broadband coherent anti-Stokes Raman scattering (CARS) microscopy with singular value decomposition (SVD) analysis.
Appl Spectrosc
PUBLISHED: 10-01-2014
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Coherent anti-Stokes Raman scattering (CARS) microscopy can be used as a powerful imaging technique to identify chemical compositions of complex samples in biology, biophysics, medicine, and materials science. In this work we developed a CARS microscopic system capable of hyperspectral imaging. By employing an ultrafast laser source, a photonic crystal fiber, and a scanning laser microscope together with spectral detection by a highly sensitive back-illuminated cooled charge-coupled device (CCD) camera, we were able to rapidly acquire and process hyperspectral images of live cells with chemical selectivity. We discuss various aspects of hyperspectral CARS image analysis and demonstrate the use of singular value decomposition methods to characterize the cellular lipid content.
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Percutaneous drainage of Morel-Lavallée lesions when the diagnosis is delayed.
Can J Surg
PUBLISHED: 09-30-2014
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Morel-Lavallée lesions are a closed internal degloving, and open débridement can damage the only remaining blood supply to the skin. We performed percutaneous draining and débridement to treat 8 patients in whom the diagnosis of Morel-Lavallée lesions was delayed more than 1 week. Here we discuss our treatment procedures and the outcomes in these 8 patients. We consider percutaneous drainage to be an effective treatment for patients with delayed diagnosis of Morel-Lavallée lesions.
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Adeno-Associated Virus-RNAi of GlyR?1 and Characterization of Its Synapse-specific Inhibition in OFF alpha Transient Retinal Ganglion Cells.
J. Neurophysiol.
PUBLISHED: 09-19-2014
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In the central nervous system, inhibition shapes neuronal excitation. In spinal cord glycinergic inhibition predominates, whereas GABAergic inhibition predominates in the brain. The retina uses GABA and glycine in approximately equal proportions. Glycinergic crossover inhibition, initiated in the On retinal pathway, controls glutamate release from presynaptic OFF cone bipolar cells (CBCs) and directly shapes temporal response properties of OFF retinal ganglion cells (RGCs). In the retina, four glycine receptor (GlyR) ? subunit isoforms are expressed in different sublaminae and their synaptic currents differ in decay kinetics. GlyR?1, expressed in both On and Off sublaminae of the inner plexiform layer, could be the glycinergic isoform that mediates On-to-Off crossover inhibition. However, subunit selective glycine contributions remain unknown because we lack selective antagonists or cell class specific subunit knockouts. To examine the role of GlyR?1 in direct inhibition in mature RGCs, we used retrogradely transported adeno-associated virus (AAV) that performed RNAi and eliminated almost all glycinergic spontaneous and visually evoked responses in PV5 (OFF?Transient) RGCs. Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV-Glra1-shRNA confirm a role for GlyR?1 in crossover inhibition in cone driven circuits. Our results also define a role for direct GlyR?1 inhibition in setting resting membrane potential of PV5 RGCs. The absence of GlyR?1 input unmasked a serial and a direct feedforward GABAAergic modulation in PV5 RGCs, reflecting a complex interaction between glycinergic and GABAAergic inhibition.
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Clostridium huakuii sp. nov., a novel anaerobic acetogenic bacterium isolated from methanogenic consortia.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 09-19-2014
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A Gram-staining-positive, spore-forming, obligate anaerobic acetogenic bacterium, designated LAM1030 (T), was isolated from methanogenic consortia enriched from biogas slurry collected from the large-scale anaerobic digester of Modern Farming Corporation in Hebei Province, China. Cells of strain LAM1030(T) were motile, straight or spiral-rod-shaped. Strain LAM1030(T) could utilize glucose, fructose, maltose, galacatose, lactose, sucrose, cellobiose?mannitol, pyruvate, succinic acid, tryptophan as sole carbon source. Acetic acid, isovaleric acid and butanoic acid were the main productions of glucose fermentation. Sodium sulfite was used as electron acceptor. Growth of strain LAM1030(T) was completely inhibited by the addition of 20 ?g/ml of ampicillin, tetracycline, gentamicin and erythromycin. The main polar lipids of strain LAM1030(T) were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and eleven unknown glycolipids and two unknown phospholipids. No respiratory quinone was detected. The major fatty acids of strain LAM1030(T) were C16:0 (21.1%), C14:0 (10.3%) and iso-C15:0 (6.6%). The analysis on the 16S rRNA gene sequence indicated that strain LAM1030(T) belonged to the genus Clostridium and was most closely related to C. subterminale DSM 6970(T), C. thiosulfatireducens DSM 13105(T) and C. sulfidigenes DSM 18982(T), with 97.0%, 96.9% and 96.8% similarity, respectively. The G+C content of the genomic DNA of strain LAM1030(T) was 31.2±0.3 mol%. On the basis of its phenotypic, phylogenetic and chemotaxonomic characterization, strain LAM1030(T) was suggested to represent a novel species of the genus Clostridium , for which the name Clostridium huakuii sp. nov. is proposed. The type strain is LAM1030(T) (=ACCC 00698(T) = JCM 19186(T)).
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The effect of anatomic variations of circle of Willis on cerebral blood distribution during posture change from supination to standing: a model study.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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The anatomic variation of Circle of Willis (CoW) has great impact on its compensatory capacity during stroke and cerebral ischemia. In the present study, a series of lumped parameter models were developed and used to simulate the effect of postural changes on the cerebral blood flow in ICA stenosis patients with different anatomic variants of the CoW. The results showed that the asymmetric distribution of cerebral blood flow caused by stenosis was attenuated in standing position in complete and half-complete CoW. However, in incomplete CoW, the decrease in blood flow in the ipsilateral cerebral arteries caused by unilateral ICA stenosis was dramatic in both supine and standing positions, a likely result of inadequate collateral circulation within the CoW. In conclusion, the anatomic variation of CoW plays a significant role in maintaining the balance of cerebral blood supply in patients with ICA stenosis, especially during postural change.
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PTK7 regulates Id1 expression in CD44-high glioma cells.
Neuro-oncology
PUBLISHED: 09-11-2014
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CD44 is a molecular marker associated with molecular subtype and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting the CD44-high gliomas.
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Progress and perspectives of biomarker discovery in Chinese medicine research.
Chin J Integr Med
PUBLISHED: 09-02-2014
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Biomarker discovery in Chinese medicine (CM) has recently attracted a great deal of attention, owing to the promise of high-throughput technologies development and the potential of Chinese herbal medicine. Furthermore, it seems that pattern classification in CM might be serving as inspirational analogy and a practical guide, which might contribute to biomarkers discovery rather than just being used as diagnostic method. Although much work is still needed to identify markers, efforts are now being directed towards discovering biomarkers or biomarkers based network that could target herbal formulae. In this article, we review progress in biomarker discovery development, discuss current biomarker discovery in CM highlighting challenges and opportunities of pattern classification and presenting a perspective of the future integrative modeling approaches as an emerging trend in biomarker discovery.
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Oxygen-induced self-assembly of quaterphenyl molecules on metal surfaces.
Chem. Commun. (Camb.)
PUBLISHED: 08-30-2014
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From high-resolution UHV-STM imaging and DFT calculations we have demonstrated a novel method to construct well-ordered molecular nanostructures of an unfunctionalized aromatic molecule (4Ph) on both Ag(110) and Cu(110) by introducing oxygen molecules.
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Fenofibrate increases radiosensitivity in head and neck squamous cell carcinoma via inducing G2/M arrest and apoptosis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-30-2014
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Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.
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Up-regulation of 14-3-3? expression in intrahepatic cholangiocarcinoma and its clinical implications.
Tumour Biol.
PUBLISHED: 08-29-2014
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The 14-3-3 proteins are highly conserved molecules that are involved in many vital biologic processes and are associated with the progression of cancer. The role of 14-3-3?, a dimeric isoform of 14-3-3, in intrahepatic cholangiocarcinoma (ICC) was investigated in this study. The expression of 14-3-3? in tumour samples from patients with ICC was examined by Western blot and immunohistochemistry, and the correlation between its expression and various clinicopathological features was determined. Then, the capacity for invasion, migration and proliferation as well as the expression of epithelial-mesenchymal transition (EMT)-related markers in ICC cells were assessed after 14-3-3? depletion. Finally, the prognostic significance of 14-3-3? in patients with ICC was further evaluated by Kaplan-Meier and Cox regression analyses. The expression of 14-3-3? was significantly higher in ICC tissues compared to peritumoural tissues. High expression of 14-3-3? positively correlated with lymphatic metastasis and tumour-node-metastasis (TNM) stage. The inhibition of 14-3-3? expression was able to impair the invasion, migration and proliferation of ICC cells in vitro. The expression of 14-3-3? was significantly correlated with the expression of the EMT-related markers snail and E-cadherin in ICC samples. Moreover, the down-regulation of 14-3-3? also decreased the phosphorylation of extracellular signal-regulated kinase (ERK) in ICC cells. Clinically, patients with ICC with high 14-3-3? expression demonstrated a poor prognosis in terms of a short overall survival and a high recurrence rate of the disease. A multivariate analysis revealed that 14-3-3? overexpression was an independent prognostic indicator for patients with ICC. 14-3-3? may enhance the invasive and proliferative capacity of tumour cells and thus prompt the progression of ICC via the activation of ERK signalling and the induction of EMT. The overexpression of 14-3-3? may be used as a prognostic biomarker and therapeutic target in patients with ICC.
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AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells.
J. Pharmacol. Sci.
PUBLISHED: 08-27-2014
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IAP antagonists increased the antitumor efficacy of X-irradiation in some types of cancers, but their effects on hypoxic cancer cells remain unclarified. We aims to investigate the radiosensitizing effect of an IAP inhibitor AT-406 on cervical cancer cell lines under both normoxia and hypoxia conditions. Hela and Siha cells were treated to investigate the effects of drug administration on cell proliferation, apoptosis, and radiosensitivity. Western blot analysis was used to determine the role of AT-406 in inhibition of IAPs. The pathway of apoptosis was characterized by caspases activity assay. AT-406 potently sensitized Hela cells but not Siha cells to radiation under normoxia. Notably, the radiosensitizing effect of AT-406 on hypoxic cells was more evident than on normoxic cells in both cell lines. Further mechanism studies by western blot showed that under normoxia AT-406 decreased the level of cIAP1 in Hela cells in a dose-dependent manner; while additional downregulation of XIAP expression was induced by AT-406 treatment under hypoxia in both cell lines. Finally, AT-406 works on both extrinsic death receptor and intrinsic mitochondrial apoptosis pathways to activate apoptosis. Totally, AT-406 acts as a strong radiosensitizer in human cervical cancer cells, especially in hypoxic condition.
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On-surface aryl-aryl coupling via selective C-H activation.
Chem. Commun. (Camb.)
PUBLISHED: 08-27-2014
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Through the interplay of high-resolution scanning tunneling microscopy (STM) imaging/manipulation and density functional theory (DFT) calculations, we have demonstrated that an unprecedented selective aryl-aryl coupling via direct C-H bond activation can be successfully achieved on Cu(110). These findings present a simple and generalized route for preparing low dimensional carbon nanomaterials.
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Adsorption-geometry induced transformation of self-assembled nanostructures of an aldehyde molecule on Cu(110).
Nanoscale
PUBLISHED: 08-23-2014
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From an interplay of high-resolution STM imaging/manipulation and DFT calculations, we have revealed that different self-assembled nanostructures of BA molecules on Cu(110) are attributable to specific molecular adsorption geometries, and thus the corresponding intermolecular hydrogen bonding patterns. The STM manipulations demonstrate the feasibility of switching such weak-hydrogen-bonding patterns.
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Reaction-based fluorescent probe for detection of endogenous cyanide in real biological samples.
Chem Asian J
PUBLISHED: 08-22-2014
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Herein, two compounds (1?a and 1?b) were rationally constructed as novel reaction-based fluorescent probes for CN(-) by making use of the electron-withdrawing ability of the cyano group that was formed from the sensing reaction. Notably, this design strategy was first employed for the development of fluorescent CN(-) probes. The experimental details showed that probe 1?a exhibited a fluorescence turn-on response to CN(-) , whereas other anions, biological thiols, and hydrogen sulfide gave almost no interference. The detection limit of probe 1?a for CN(-) was found to be 0.12??M. The sensing reaction product of 1?a with CN(-) was characterized by NMR spectroscopy and mass spectrometry. TD-DFT calculations demonstrated that the formed cyano group drives the intramolecular charge transfer (ICT) process from coumarin dye to the cyano group and thus the original strong ICT from the coumarin dye to the 3-position pyridyl vinyl ketone substituent is weakened, which results in recovery of coumarin fluorescence. The practical utility of 1?a was also examined. By fabricating paper strips, probe 1?a can be used as a simple tool to detect CN(-) in field measurements. Moreover, probe 1?a has been successfully applied for quantitative detection of endogenous CN(-) from cassava root.
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Broadband focusing and collimation of water waves by zero refractive index.
Sci Rep
PUBLISHED: 08-21-2014
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It is always a challenge to realize extreme and unusual values of refractive index for a broad range of frequencies. We show that when water is covered by a thick, rigid and unmovable plate, it behaves like a medium with zero refractive index for water waves at any frequency. Hence, by covering water with a plate of a concave or rectangular shape, water waves can be focused or collimated in a broad range of frequencies. Experiments were conducted to demonstrate these effects and results are in excellent agreement with numerical simulations.
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Cancer risks and long-term community-level exposure to pentachlorophenol in contaminated areas, China.
Environ Sci Pollut Res Int
PUBLISHED: 08-21-2014
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Widespread use of pentachlorophenol (PCP) in schistosomiasis endemic areas had led to ubiquitous exposure to PCP and its residues. Numerous studies had revealed that occupational PCP exposure probably increased risk of cancers, but whether long-term community-level exposure to PCP generates the similarly carcinogenic effect, seldom studies focused on it. This study was to explore the cancer risks of long-term community-level PCP exposure from drinking water in a Chinese general population. Incident (2009-2012) cancer records were identified by local government national registry. And PCP concentration of raw drinking water samples in each district was measured by GC-MS/MS analysis for further division of three PCP exposure categories by interquartile range (high vs. medium vs. low). Internal comparisons were performed, and standard rate ratio was calculated to describe the relationship between PCP exposure and cancer risks by using low-exposure group as the reference group. PCP was detected in all 27 raw drinking water samples ranging from 11.21 to 684.00 ng/L. A total of 6,750 cases (4,409 male and 2,341 female cases) were identified, and age-standardized rate (world) was 154.95 per 100,000 person-years. The cancer incidence for the high-exposure group was remarkably high. Internal comparisons indicated that high PCP exposure might be positively associated with high cancer risks in the community population, particularly for leukemia (SRR?=?5.93, 95 % CI?=?5.24-6.71), maligant lymphoma (SRR?=?2.27, 95 % CI?=?2.10-2.54), and esophageal cancer (SRR?=?2.42, 95 % CI?=?2.35-2.50). Long-term community-level exposure to PCP was probably associated with hemolymph neoplasm, neurologic tumors, and digestive system neoplasm.
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Changes of serum parameters of TiO? nanoparticle-induced atherosclerosis in mice.
J. Hazard. Mater.
PUBLISHED: 08-20-2014
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The evaluation of toxicological effects of nanoparticulate matter is increasingly important due to their growing occupational use and presence as compounds in consumer products. Numerous studies have shown that exposure to nanosized particles lead to systemic inflammation in experimental animals, but whether long-term exposure to nanosized particles induces atherogenesis is rarely evaluated. In the current study, mice were continuously exposed to TiO2 nanoparticles (NPs) at 1.25, 2.5, or 5mg/kg body weight, administered by nasal instillation for nine consecutive months, and the association between serum parameter changes and atherosclerosis in mice were investigated. The present findings suggested that chronic exposure to TiO2 NPs resulted in atherogenesis coupling with pulmonary inflammation, increased levels of serum triglycerides, glucose, total cholesterol, low-density lipoprotein cholesterol, advanced glycation end products, reactive oxygen species, NAD(P)H oxidases 4, C-reaction protein, E-selectin, endothelin-1, tissue factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and reduced levels of serum high-density lipoprotein cholesterol, nitric oxide and tissue plasminogen activator. Our study suggests an association of long-term exposure to TiO2 NPs with atherosclerosis and pulmonary inflammation. This finding demonstrates the hypothesized role of TiO2 NPs as a risk factor for atherogenesis.
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H2S, a novel therapeutic target in renal-associated diseases?
Clin. Chim. Acta
PUBLISHED: 08-20-2014
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For more than a century, hydrogen sulfide (H2S) has been regarded as a toxic gas. Recently, the understanding of the biological effects of H2S has been changed. This review surveys the growing recognition of H2S as an endogenous signaling molecule in mammals, with emphasis on its physiological and pathological pathways in the urinary system. This article reviews recent progress of basic and pharmacological researches related to endogenous H2S in urinary system, including the regulatory effects of H2S in the process of antioxidant, inflammation, cellular matrix remodeling and ion channels, and the role of endogenous H2S pathway in the pathogenesis of renal and urogenital disorders.
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Comparison of five chromogenic media for recovery of vancomycin-resistant enterococci from fecal samples.
J. Clin. Microbiol.
PUBLISHED: 08-20-2014
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Five chromogenic agars, evaluated using 400 stool specimens, were found to be superior in sensitivity (range, 89.9 to 93.9%) to bile esculin azide agar with vancomycin (BEAV) agar (84.8%) for detecting vancomycin-resistant enterococci (VRE), and the results were available 24 to 48 h sooner. The time to detection, need for supplemental testing, color distinction, and breakthrough of non-VRE organisms vary among the chromogenic media tested and may factor into the decision to use a particular medium.
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Mipu1 Overexpression Protects Macrophages from oxLDL-Induced Foam Cell Formation and Cell Apoptosis.
DNA Cell Biol.
PUBLISHED: 08-20-2014
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Mipu1 (myocardial ischemic preconditioning upregulated protein 1) is a novel N-terminal Kruppel-associated box (KRAB)/C2H2 zinc finger superfamily protein, that displays a powerful effect in protecting H9c2 cells from oxidative stress-induced cell apoptosis. The present study aims to investigate the effect of Mipu1 overexpression on oxidized low-density lipoprotein (oxLDL)-induced foam cell formation, cell apoptosis, and its possible mechanisms. New Zealand healthy rabbits were used to establish atherosclerosis model, and serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were detected by an automatic biochemical analyzer. Sudan IV staining was used to detect atherosclerotic lesions. The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining, high-performance liquid chromatography, and Dil-labeled lipoprotein were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to determine cell apoptosis. Real-time quantitative PCR was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as ABCA1, ABCG1, SR-BI, and CD36. Western blot analysis was used to detect the protein expression of Mipu1. There were atherosclerotic lesions in the high-fat diet group with Sudan IV staining. High-fat diet decreased Mipu1 expression and increased CD36 expression significantly at the 10th week compared with standard-diet rabbits. Mipu1 overexpression decreased oxLDL-induced cholesterol accumulation, oxLDL uptake, cell apoptosis, and cleaved caspase-3. Mipu1 overexpression inhibited the oxLDL-induced CD36 mRNA and protein expression, but it did not significantly inhibit the mRNA expression of ABCA1, ABCG1, and SR-BI. Mipu1 overexpression inhibits oxLDL-induced foam cell formation and cell apoptosis. Mipu1 overexpression reduces the lipid intake of macrophages and might be associated with the downregulation of CD36 expression in the presence of oxLDL.
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Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of homologous recombination repair.
J Hematol Oncol
PUBLISHED: 08-20-2014
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Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC).
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Preventive effect of non-mitogenic acidic fibroblast growth factor on diabetes-induced testicular cell death.
Reprod. Toxicol.
PUBLISHED: 08-19-2014
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Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). Whether the nmFGF-1 protects male germ cells from diabetes-induced apoptotic death was examined in diabetic mice induced with multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated the diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 may alleviate diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio and endoplasmic reticulum stress as well as associated cell death, which is associated with Nrf-2 activation.
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Contact electrification field-effect transistor.
ACS Nano
PUBLISHED: 08-15-2014
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Utilizing the coupled metal oxide semiconductor field-effect transistor and triboelectric nanogenerator, we demonstrate an external force triggered/controlled contact electrification field-effect transistor (CE-FET), in which an electrostatic potential across the gate and source is created by a vertical contact electrification between the gate material and a “foreign” object, and the carrier transport between drain and source can be tuned/controlled by the contact-induced electrostatic potential instead of the traditional gate voltage. With the two contacted frictional layers vertically separated by 80 ?m, the drain current is decreased from 13.4 to 1.9 ?A in depletion mode and increased from 2.4 to 12.1 ?A in enhancement mode at a drain voltage of 5 V. Compared with the piezotronic devices that are controlled by the strain-induced piezoelectric polarization charged at an interface/junction, the CE-FET has greatly expanded the sensing range and choices of materials in conjunction with semiconductors. The CE-FET is likely to have important applications in sensors, human–silicon technology interfacing, MEMS, nanorobotics, and active flexible electronics. Based on the basic principle of the CE-FET, a field of tribotronics is proposed for devices fabricated using the electrostatic potential created by triboelectrification as a “gate” voltage to tune/control charge carrier transport in conventional semiconductor devices. By the three-way coupling among triboelectricity, semiconductor, and photoexcitation, plenty of potentially important research fields are expected to be explored in the near future.
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Virus-host mucosal interactions during early SIV rectal transmission.
Virology
PUBLISHED: 08-14-2014
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To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggest that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into mucosa; and a high-level expression of SIV accessory genes, which are known to be able to counter and evade host restriction factors and innate immune responses. This study provides new insights into the mechanism of rectal transmission.
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The effect of nC?? on tissue distribution of ibuprofen in Cyprinus carpio.
Sci. Total Environ.
PUBLISHED: 08-07-2014
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The potential transfer of fullerene aqueous suspension (nC??) associated contaminants in vivo is one of the most significant and currently not well-understood environmental risks. In this study, the carrier function of nC?? for ibuprofen (IBU) was examined through whole-body and tissue distribution determination of nC?? and IBU in Cyprinus carpio. The results showed that the presence of nC?? only slightly increased the whole-body burden of IBU, because the amount of soluble IBU far exceeds that of nC?? associated form of IBU; while the presence of nC?? activated the catalase activity and enhanced the lipid peroxidation in the liver, suggesting an obviously induced oxidative damage to fish. With the presence of nC??, the uptake of IBU in both gill and digestive tract tissues increased obviously: the uptake of IBU in the gill was mainly from the desorption of nC?? associated IBU, and that in the digestive tract was both from nC?? associated IBU and soluble IBU. On the contrary, the nC?? reduced IBU uptake in the brain, probably due to the high accumulation of nC?? which blocked the blood brain barrier. Moreover, there was no significant increase in the muscle, which implies that the soluble form should be the main source of IBU accumulation in the muscle. The carrier function of nC?? observed in the present study indicates the potential transportation of other contaminants and the subsequently enhanced environmental risks.
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Woven structured triboelectric nanogenerator for wearable devices.
ACS Appl Mater Interfaces
PUBLISHED: 08-07-2014
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To date, quite a few wearable electronics have entered the market, which are changing the life pattern of consumers. However, the limited lifetime and energy storage capacity have made rechargeable batteries the bottleneck in wearable technology, especially with the increase of number of wearable devices and their large distribution. To solve this problem, we demonstrate a woven-structured triboelectric nanogenerator (W-TENG) using commodity nylon fabric, polyester fabric, and conductive silver fiber fabric. With the advantage of being flexible, washable, breathable, wearable, and able to be triggered by a freestanding triboelectric layer, this W-TENG can move freely without any constraint and is suitable for wearable electronics. To demonstrate the potential applications of the W-TENG, the W-TENG is integrated into shoes, coats, and trousers to harvest different kinds of mechanical energy from human motion. This work presents a new approach in applying triboelectric nanogenerator to wearable devices.
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Substituent-enabled oxidative dehydrogenative cross-coupling of 1,4-naphthoquinones with alkenes.
J. Org. Chem.
PUBLISHED: 08-05-2014
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A Rh-catalyzed oxidative dehydrogenative cross-coupling of 1,4-naphthquinones with alkenes was achieved by using a substituent-enabled C(sp(2))-H functionalization (SEF) strategy. The method shows high functional group tolerance, broad substrate scope, and great potential for further functional transformations.
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Austenite layer and precipitation in high Co-Ni maraging steel.
Micron
PUBLISHED: 08-04-2014
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In high Co-Ni maraging steel, austenite has a great effect on the fracture toughness of the steel and the precipitated carbides are the main strengthening phase. In this study, both austenite layers and precipitation were observed and their formation theory was analyzed by Thermo-Calc simulation and several reported results. TEM and HRTEM observation results showed that the thickness of the austenite layers was about 5-10 nm and the length of the needle-like precipitated carbides was less than 10nm. The carbides maintained coherent or semi-coherent relation with the matrix.
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The potential use of H102 peptide-loaded dual-functional nanoparticles in the treatment of Alzheimer's disease.
J Control Release
PUBLISHED: 08-04-2014
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Alzheimer's disease (AD) is a complex neurodegenerative disease with few effective treatments. The non-targeted distribution of drugs decreases drug efficiency and cause side effects. The cascade targeting strategy has been suggested for precise drug delivery. We developed a dual-functional nanoparticle drug delivery system loaded with ?-sheet breaker peptide H102 (TQNP/H102). Two targeting peptides, TGN and QSH, were conjugated to the surface of the nanoparticles for blood-brain barrier transport and A?42 targeting, respectively. The prepared nanoparticles were spherical and uniform. The brain distribution study of H102 was conducted with the HPLC-mass spectrometry method to evaluate whether this nano-carrier could achieve increased AD-lesion delivery. The highest uptake of H102 was observed in the hippocampi of the TQNP/H102 group mice 1h after administration, which was 2.62 and 1.86 times the level of non-modified nanoparticles (NP/H102) and TGN modified nanoparticles (TNP/H102), respectively. The neuroprotective effects of H102 preparations were evaluated using Morris water maze experiment, biochemical indexes assay and tissue histology. The spatial learning and memory of the AD model mice in the TQNP/H102 group were significantly improved compared with the AD control group, and were also better than other preparations at the same dosage, even the TNP/H102 group. These results were consistent with the values of biochemical indexes in mouse hippocampi as well as the histological observations. The results demonstrate that TQNP is a promising carrier for peptide or protein drugs, such as H102, for entry into the central nervous system (CNS) and subsequent location of brain AD lesions, thus offering a highly-specific method for AD therapy.
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The role of transmembrane proteins on force transmission in skeletal muscle.
J Biomech
PUBLISHED: 07-30-2014
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Lateral transmission of force from myofibers laterally to the surrounding extracellular matrix (ECM) via the transmembrane proteins between them is impaired in old muscles. Changes in geometrical and mechanical properties of ECM of skeletal muscle do not fully explain the impaired lateral transmission with aging. The objective of this study was to determine the role of transmembrane proteins on force transmission in skeletal muscle. In this study, a 2D finite element model of single muscle fiber composed of myofiber, ECM, and the transmembrane proteins between them was developed to determine how changes in spatial density and mechanical properties of transmembrane proteins affect the force transmission in skeletal muscle. We found that force transmission and stress distribution are not affected by mechanical stiffness of the transmembrane proteins due to its non-linear stress-strain relationship. Results also showed that the muscle fiber with insufficient transmembrane proteins near the end of muscle fiber transmitted less force than that with more proteins does. Higher stress was observed in myofiber, ECM, and proteins in the muscle fiber with fewer proteins.
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Ni12P5 nanoparticles as an efficient catalyst for hydrogen generation via electrolysis and photoelectrolysis.
ACS Nano
PUBLISHED: 07-30-2014
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The exploitation of a low-cost catalyst is desirable for hydrogen generation from electrolysis or photoelectrolysis. In this study we have demonstrated that nickel phosphide (Ni12P5) nanoparticles have efficient and stable catalytic activity for the hydrogen evolution reaction. The catalytic performance of Ni12P5 nanoparticles is favorably comparable to those of recently reported efficient nonprecious catalysts. The optimal overpotential required for 20 mA/cm(2) current density is 143 ± 3 mV in acidic solution (H2SO4, 0.5 M). The catalytic activity of Ni12P5 is likely to be correlated with the charged natures of Ni and P. Ni12P5 nanoparticles were introduced to silicon nanowires, and the power conversion efficiency of the resulting composite is larger than that of silicon nanowires decorated with platinum particles. This result demonstrates the promising application potential of metal phosphide in photoelectrochemical hydrogen generation.
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Eukaryotic elongation factor 2 kinase confers tolerance to stress conditions in cancer cells.
Cell Stress Chaperones
PUBLISHED: 07-19-2014
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Eukaryotic elongation factor 2 (eEF2) is a member of the GTP-binding translation elongation factor family that is essential for protein synthesis. eEF2 kinase (eEF2K) is a structurally and functionally unique protein kinase in the calmodulin-mediated signaling pathway. eEF2K phosphorylates eEF2, thereby inhibiting eEF2 function under stressful conditions. eEF2K regulates numerous processes, such as protein synthesis, cell cycle progression, and induction of autophagy and apoptosis in cancer cells. This review will demonstrate the mechanisms underlying eEF2K activity in cancer cells under different stresses, such as nutrient deprivation, hypoxia, and DNA damage via eEF2 regulation. In vivo, in vitro, and clinical studies indicated that eEF2K may be a novel biomarker and therapeutic target for cancer.
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Repeated doses of intravenous tranexamic acid are effective and safe at reducing perioperative blood loss in total knee arthroplasty.
Biosci Trends
PUBLISHED: 07-18-2014
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Fibrin sealant (FS) and tranexamic acid (TXA) have been used in total knee arthroplasty (TKA) to minimize perioperative blood loss. The efficacy of FS has been debated, and few studies have looked into the effects of FS and TXA on perioperative coagulability. The current study retrospectively reviewed 100 cases of unilateral primary TKA. Twenty-five cases served as blank controls, FS was used without TXA in 23, TXA was used without FS in 20, and both FS and TXA (FS + TXA) were used in 32. FS was sprayed before wound closure whereas 1 g of TXA was intravenously administered before incision and 1 g was administered 15 min before tourniquet release. Hematocrit and hemoglobin levels and thromboelastography (TEG) parameters were assessed pre-operatively and on day 1, 4, and 9 post-operatively. Blood transfusions were noted and the incidence of symptomatic DVT/PE was determined. Hematocrit and hemoglobin levels were significantly higher in the TXA and FS + TXA groups compared to the control and FS groups on day 1, 4, and 9 post-operatively. Hematocrit and hemoglobin levels in the control group were similar to those in the FS group and hematocrit and hemoglobin levels in the TXA group were similar to those in the FS + TXA group. TEG parameters (R, K, ?, MA, and CI) remained within normal ranges. Mean CI was less than +3 in all four groups, suggesting that hypercoagulation was not promoted. One patient in the FS group received an allogeneic transfusion. Incidence of symptomatic DVT/PE was not noted. Intravenous TXA significantly reduced perioperative blood loss in patients undergoing a TKA but FS did not. Administration of FS in addition to TXA was not superior to TXA alone. FS and/or TXA did not increase the risk of hypercoagulation according to TEG parameters. Intravenous administration of 1 g of TXA pre-operatively and administration of 1 g before tourniquet release is an effective and safe method of reducing blood loss in TKA.
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A novel human interleukin-24 peptide created by computer-guided design contributes to suppression of proliferation in esophageal squamous cell carcinoma Eca-109 cells.
Oncol. Rep.
PUBLISHED: 07-10-2014
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Based on the three-dimensional modeling structure of human interleukin-24 (hIL-24) and its most likely active position predicted by solvent accessibility and apparent electrostatic properties, a novel hIL-24 peptide M1 was created by computer-guided molecular design. The cytotoxicity and cell selectivity of M1 were examined in three human carcinoma cell lines and one normal human embryo lung fibroblast cell line (HEL). MTT assay showed that M1 induced growth arrest in two IL-20 receptor complex-positive cancer cell lines (the esophageal squamous cell carcinoma cell line Eca-109 and the melanoma cell line A375), and antibodies against IL-24 or IL-20 receptor complexes significantly neutralized the inhibitory activity. Moreover, M1 had almost no cytotoxicity on the lung cancer A549 cell line, which lacks a full complement of the IL-20 receptor complexes, or on HEL cells that express the IL-20 receptor complexes. These findings demonstrate that M1 could act as an excellent candidate for the induction of growth arrest on receptor complex-positive cancer cells. In summary, the M1 peptide may represent a novel anticancer agent for esophageal squamous cell carcinoma therapy due to its cancer cell selectivity and its relatively low cytotoxicity to normal cells.
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Molecular interactions between amantadine and model cell membranes.
Langmuir
PUBLISHED: 07-10-2014
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Sum frequency generation (SFG) vibrational spectroscopy was applied to study molecular interactions between amantadine and substrate supported lipid bilayers serving as model cell membranes. Both isotopically asymmetric and symmetric lipid bilayers were used in the research. SFG results elucidated how the water-soluble drug, amantadine, influenced the packing state of each leaflet of a lipid bilayer and how the drugs affected the lipid flip-flop process. It is difficult to achieve such detailed molecular-level information using other analytical techniques. Especially, from the flip-flop rate change of isotopically asymmetric lipid bilayer induced by amantadine, important information on the drug-membrane interaction mechanism can be derived. The results show that amantadine can be associated with zwitterionic PC bilayers but has a negligible influence on the flip-flop behavior of PC molecules unless at high concentrations. Different effects of amantadine on the lipid bilayer were observed for the negatively charged DPPG bilayer; low concentration amantadine (e.g., 0.20 mM) in the subphase could immediately disturb the outer lipid leaflet and then the lipid associated amantadine molecules gradually reorganize to cause the outer leaflet to return to the original orderly packed state. Higher concentration amantadine (e.g., 5.0 mM) immediately disordered the packing state of the outer lipid leaflet. For both the high and low concentration cases, amantadine molecules only bind to the outer PG leaflet and cannot translocate to the inner layer. The presence of amantadine within the negatively charged lipid layers has certain implications for using liposomes as drug delivery carriers for amantadine. Besides, by using PC or PG bilayers with both leaflets deuterated, we were able to examine how amantadine is distributed and/or oriented within the lipid bilayer. The present work demonstrates that SFG results can provide an in-depth understanding of the molecular mechanisms of interactions between water-soluble drugs and model cell membranes.
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Enzyme-catalyzed macrocyclization of long unprotected peptides.
Org. Lett.
PUBLISHED: 07-08-2014
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A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective S(N)Ar reaction between an N-terminal glutathione (GSH, ?-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quantitatively produced within 2 h in aqueous pH = 8 buffer at room temperature. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chemical ligation to generate a large 40-residue peptide macrocycle.
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Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris.
Mol. Biol. Rep.
PUBLISHED: 07-05-2014
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Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case-control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (?25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12-2.37), 2.09(95 % CI; 1.44-3.03) and 1.65(95 % CI; 1.15-2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (?25) increased risk of PV (OR = 2.09; 95 % CI, 1.02-4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37-7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09-6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10-1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.
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The functional significance of common polymorphisms in zinc finger transcription factors.
G3 (Bethesda)
PUBLISHED: 06-28-2014
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Variants that alter the DNA-binding specificity of transcription factors could affect the specificity for and expression of potentially many target genes, as has been observed in several tumor-derived mutations. Here we examined if such trans expression quantitative trait loci (trans-eQTLs) could similarly result from common genetic variants. We chose to focus on the Cys2-His2 class of zinc finger transcription factors because they are the most abundant superfamily of transcription factors in human and have well-characterized DNA binding interactions. We identified 430 SNPs that cause missense substitutions in the DNA-contacting residues. Fewer common missense SNPs were found at DNA-contacting residues compared with non-DNA-contacting residues (P = 0.00006), consistent with possible functional selection against SNPs at DNA-contacting positions. Functional predictions based on zinc finger transcription factor (ZNF) DNA binding preferences also suggested that many common substitutions could potentially alter binding specificity. However, Hardy-Weinberg Equilibrium analysis and examination of seven orthologs within the primate lineage failed to find evidence of trans-eQTLs associated with the DNA-contacting positions or evidence of a different selection pressure on a contemporary and evolutionary timescales. The overall conclusion was that common SNPs that alter the DNA-contacting residues of these factors are unlikely to produce strong trans-eQTLs, consistent with the observations by others that trans-eQTLs in humans tend to be few and weak. Some rare SNPs might alter specificity and remained rare due to purifying selection. The study also underscores the need for large-scale eQTLs mapping efforts that might provide experimental evidence for SNPs that alter the choice of transcription factor binding sites.
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The safety and efficacy of daptomycin versus other antibiotics for skin and soft-tissue infections: a meta-analysis of randomised controlled trials.
BMJ Open
PUBLISHED: 06-26-2014
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Daptomycin, a cyclic lipopeptide that exhibits rapid, concentration-dependent bactericidal activity in vitro against a broad spectrum of Gram-positive pathogens, has now, since 2003, been approved in more than 70 countries and regions to treat skin and soft-tissue infections (SSTIs). The purpose of this meta-analysis was to compare the safety and efficacy of daptomycin with other antibiotics, especially with vancomycin which has long been considered the standard therapy for complicated SSTIs.
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Genome Sequence of the ?-Poly-l-Lysine-Producing Strain Streptomyces albulus NK660, Isolated from Soil in Gutian, Fujian Province, China.
Genome Announc
PUBLISHED: 06-14-2014
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We determined the complete genome sequence of a soil bacterium, Streptomyces albulus NK660. It can produce ?-poly-l-lysine, which has antimicrobial activity against a spectrum of microorganisms. The genome of S. albulus NK660 contains a 9,360,281-bp linear chromosome and a 12,120-bp linear plasmid.
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Comparison of transverse and modified subtrochanteric femoral shortening osteotomy in total hip arthroplasty for developmental dysplasia of hip: a meta-analysis.
BMC Musculoskelet Disord
PUBLISHED: 06-11-2014
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Subtrochanteric femoral shortening osteotomy is a crucial procedure to prevent nerve injury in total hip arthroplasty for severe developmental dysplasia of the hip. Transverse osteotomy was first applied, and other modified methods have also been reported. Each has its own advantages and limitations, but no definitive conclusions regarding differences in outcomes have been reached to date.
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Ultrafast and versatile spectroscopy by temporal Fourier transform.
Sci Rep
PUBLISHED: 06-02-2014
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One of the most remarkable and useful properties of a spatially converging lens system is its inherent ability to perform the Fourier transform; the same applies for the time-lens system. At the back focal plane of the time-lens, the spectral information can be instantaneously obtained in the time axis. By implementing temporal Fourier transform for spectroscopy applications, this time-lens-based architecture can provide orders of magnitude improvement over the state-of-art spatial-dispersion-based spectroscopy in terms of the frame rate. On the other hand, in addition to the single-lens structure, the multi-lens structures (e.g. telescope or wide-angle scope) will provide very versatile operating conditions. Leveraging the merit of instantaneous response, as well as the flexible lens structure, here we present a 100-MHz frame rate spectroscopy system - the parametric spectro-temporal analyzer (PASTA), which achieves 17 times zoom in/out ratio for different observation ranges.
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Mechanisms of TiO2 nanoparticle-induced neuronal apoptosis in rat primary cultured hippocampal neurons.
J Biomed Mater Res A
PUBLISHED: 06-01-2014
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Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to decrease learning and memory of animals. However, whether the impacts of these NPs on the recognition function are involved in hippocamal neuron damages is poorly understood. In this study, primary cultured hippocampal neurons from one-day-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 ?g/mL TiO2 NPs for 24 h, we investigated cell viability, ultrastructure, and mitochondrial membrane potential (MMP), calcium homeostasis, oxidative stress, antioxidant capacity, apoptotic signaling pathway associated with the primary cultured hippocamal neuron apoptosis. Our findings showed that TiO2 NP treatment resulted in reduction of cell viability, promoted lactate dehydrogenase release, apoptosis and increased neuron apoptotic rate in a dose-dependent manner. Furthermore, TiO2 NPs led to [Ca(2+) ]i elevation, and mitochondrial membrane potential reduction, up-regulated protein expression of cytochrome c, Bax, caspase-3, glucose-regulate protein 78, C/EBP homologous protein and caspase-12, and down-regulated bcl-2 expression in the primary cultured hippocampal neurons. These findings suggested that hippocampal neuron apoptosis caused by TiO2 NPs may be associated with mitochondria-mediated signal pathway and endoplasmic reticulum-mediated signal pathway.
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Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women.
Endocrine
PUBLISHED: 05-30-2014
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We investigated whether thyroid autoantibody status influences pregnancy outcomes in euthyroid women, by comparing abnormal pregnancy outcome rates between those who tested positive for thyroid autoantibodies (Ab(+)) and those who tested autoantibody-negative (Ab(-)). Euthyroid pregnant women (n = 7,641) underwent tests for serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The subjects were divided into 4 groups according to thyroid antibody status: TPOAb(-)/TgAb(-) (92.9 %); TPOAb(+)/TgAb(-) (3.2 %); TPOAb(-)/TgAb(+) (2.0 %); and TPOAb(+)/TgAb(+) (1.9 %). The incidence rates of the following abnormal pregnancy outcomes were compared among the 4 groups and analyzed by Fisher's exact test: gestational diabetes, gestational hypertension, placenta previa, placental abruption, premature rupture of fetal membrane (PROM), intrauterine growth restriction, fetal distress, fetal anomalies, stillbirth, preterm birth, and low birth weight. Among the 4 groups, there were no significant differences in age, gestational age, or in the incidence rates of abnormal pregnancy outcomes, except for PROM and low birth weight. The highest incidence rates for PROM and low birth weight were in the TPOAb(-)/TgAb(+) and TPOAb(+)/TgAb(+) subjects, respectively. TgAb positivity and TPOAb positivity were associated with PROM and low birth weight, respectively. Underlying factors that govern the association between thyroid autoantibodies and PROM and low birth weight require further investigation.
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Spatial and seasonal distribution of organochlorine pesticides in the sediments of the Yangtze Estuary.
Chemosphere
PUBLISHED: 05-29-2014
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The spatial and seasonal distribution of organochlorine pesticides (OCPs) in the sediments of the Yangtze Estuary was investigated. The total concentration of 19 OCPs (?OCPs), including ?-HCH, ?-HCH, ?-HCH, ?-HCH, o, p'-DDE, p, p'-DDE, o, p'-DDD, p, p'-DDD, o, p'-DDT, p, p'-DDT, heptachlor, aldrin, heptachlor epoxide (Isomer B, Isomer A), endosulfan I, dieldrin, endrin, endosulfan II and methoxychlor, in the surface sediments ranged from 0.4 to 82.1 ng g(-1) d.w. The mean values of the ?OCPs were 8.5 ± 8.3 ng g(-1) d.w., 26.7 ± 12.1 ng g(-1) d.w., 40.5 ± 18.2 ng g(-1) d.w., and 13.0 ± 11.2 ng g(-1) d.w. for August 2010, November 2010, February 2011 and May 2011, respectively. The highest concentration of OCPs was detected at the river-sea boundary because of the intense resuspension and redeposition of sediments in this area. The OCPs preferred to accumulate in the inner estuary, rather than in the offshore area in the dry season, whereas the opposite occurred in the flood season. This phenomenon was related to the seasonal changes of the Changjiang diluted water (CDW). OCPs in the offshore area were controlled by the ocean currents and the monsoon. There was a southward increase for the OCP deposition in the offshore area in the winter. This increase resulted from the influences of the southward Yellow Sea coastal current and the East China Sea coastal current, as well as the northwest wind in winter. The Three Gorges Dam had an impact on HCH composition by changing the sediment redistribution during the deposition process.
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Melittin enhances radiosensitivity of hypoxic head and neck squamous cell carcinoma by suppressing HIF-1?.
Tumour Biol.
PUBLISHED: 05-22-2014
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Hypoxia is a widespread phenomenon present in many human solid tumors and is associated with a poor prognosis and therapy resistance. Here, we tested the feasibility of melittin, a major component of bee venom, on radiosensitization of hypoxic head and neck squamous cell carcinoma (HNSCC). CNE-2 and KB cells were treated with melittin and radiation response was determined. Cell viability, cytotoxicity and apoptosis induction were examined by CCK-8 assay, colony formation assay, and flow cytometry. Expression of hypoxia-inducible factor 1-alpha (HIF-1?) and vascular endothelial growth factor (VEGF) proteins were assessed using western blotting. Additionally, we also examined the effect of melittin on tumor growth and radiosensitivity in vivo using a xenograft model of HNSCC. Treatment with melittin resulted in cell growth inhibition, induction of cell apoptosis, and reduction of HIF-1? and VEGF expression, which has been linked to hypoxia cell radioresistance. In addition, intraperitoneal injection of melittin significantly reduced the growth of HNSCC tumors in CNE-2 tumor-bearing mice. These data suggest that melittin enhances radiosensitivity of HNSCC under hypoxia condition, and this is associated with the suppression of HIF-1? expression. Melittin appears to be a potential radiotherapy sensitization agent due to its significant antihypoxia activity.
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SIRT1 in cardiovascular aging.
Clin. Chim. Acta
PUBLISHED: 05-10-2014
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Cardiovascular disease (CVD) is the leading cause of death worldwide, with aging as the key independent risk factor. Effective interventions are necessary to delay aging. Sirtuin1 (SIRT1), a NAD(+)-dependent histone deacetylase, is closely related to lifespan extension. SIRT1 exerts beneficial effects on aging and age-related diseases, such as atherosclerosis. In this review, we summarize the current knowledge on the functions of SIRT1 in cardiovascular aging, focusing on the underlying molecular mechanisms, including inhibition of oxidative stress and inflammation, and induction of autophagy. We also demonstrate that moderate up-regulation or activation of SIRT1 in cardiovascular aging and age-related CVD may confer important application values.
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Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies.
Eur. J. Epidemiol.
PUBLISHED: 05-05-2014
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Studies that investigated the association between tea consumption and the risk of major cardiovascular events have reported inconsistent results. We conducted a meta-analysis of prospective observational studies in order to summarize the evidence regarding the association between tea consumption and major cardiovascular outcomes or total mortality. In July 2014, we performed electronic searches in PubMed, EmBase, and the Cochrane Library, followed by manual searches of reference lists from the resulting articles to identify other relevant studies. Prospective observational studies that reported effect estimates, with 95 % confidence intervals (CIs), for coronary heart disease (CHD), stroke, cardiac death, stroke death, or total mortality for more than two dosages of tea consumption were included. A random-effects meta-analysis was performed to determine the risk of major cardiovascular outcomes associated with an increase in tea consumption by 3 cups per day. Of the 736 citations identified from database searches, we included 22 prospective studies from 24 articles reporting data on 856,206 individuals, and including 8,459 cases of CHD, 10,572 of stroke, 5,798 cardiac deaths, 2,350 stroke deaths, and 13,722 total deaths. Overall, an increase in tea consumption by 3 cups per day was associated with a reduced risk of CHD (relative risk [RR], 0.73; 95 % CI: 0.53-0.99; P = 0.045), cardiac death (RR, 0.74; 95 % CI: 0.63-0.86; P < 0.001), stroke (RR, 0.82; 95 % CI: 0.73-0.92; P = 0.001), total mortality (RR, 0.76; 95 % CI: 0.63-0.91; P = 0.003), cerebral infarction (RR, 0.84; 95 % CI: 0.72-0.98; P = 0.023), and intracerebral hemorrhage (RR, 0.79; 95 % CI: 0.72-0.87; P < 0.001), but had little or no effect on stroke mortality (RR, 0.93; 95 % CI: 0.83-1.05; P = 0.260). The findings from this meta-analysis indicate that increased tea consumption is associated with a reduced risk of CHD, cardiac death, stroke, cerebral infarction, and intracerebral hemorrhage, as well as total mortality.
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STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1?.
Tumour Biol.
PUBLISHED: 04-27-2014
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Radiotherapy is the main therapy for inoperable and locally advanced esophageal squamous cell carcinoma (ESCC). However, radioresistance in ESCC remains a challenge. The aim of this study is to investigate the radiosensitizing effects of STAT3 inhibitor NSC74859 on ESCC and explore the underlying mechanisms. ECA109 and TE13 cells were exposed to hypoxia, and treated with NSC74859 or radiation, alone or in combination. Cell proliferation, survival, apoptosis, and double-stranded DNA breaks (DSBs) were examined. Nude mice model of ECA109 xenograft was treated with radiation and/or NSC74859. The levels of STAT3, p-STAT3, HIF-1?, and VEGF were detected by Western blot analysis. NSC74859 efficiently radiosensitized ESCC cells and xenografts in nude mice, and inhibited hypoxia-/radiation-induced activation of STAT3 and upregulation of HIF-1? and VEGF expression. NSC74859 confers radiosensitivity in ESCC via the inhibition of STAT3 activation and the downregulation of HIF-1? and VEGF expression. NSC74859 may become a promising radiosensitizer for ESCC radiotherapy.
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Role of surgery in the treatment of patients with high-risk neuroblastoma who have a poor response to induction chemotherapy.
J. Pediatr. Surg.
PUBLISHED: 04-15-2014
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In instances of high-risk neuroblastoma that do not show a clinical response to induction therapy, whether it is worth performing surgical resection or not and whether gross total resection (GTR) is more important than subtotal resection (STR) remain controversial.
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Optical-resolution photoacoustic microscopy for volumetric and spectral analysis of histological and immunochemical samples.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-28-2014
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Optical-resolution photoacoustic microscopy (OR-PAM) is an imaging modality with superb penetration depth and excellent absorption contrast. Here we demonstrate, for the first time, that this technique can advance quantitative analysis of conventional chromogenic histochemistry. Because OR-PAM can quantify the absorption contrast at different wavelengths, it is feasible to spectrally resolve the specific biomolecules involved in a staining color. Furthermore, the tomographic capability of OR-PAM allows for noninvasive volumetric imaging of a thick sample without microtoming it. By immunostaining the sample with different chromogenic agents, we further demonstrated the ability of OR-PAM to resolve different types of cells in a coculture sample with imaging depths up to 1?mm. Taken together, the integration of OR-PAM with (immuno)histochemistry offers a simple and versatile technique with broad applications in cell biology, pathology, tissue engineering, and related biomedical studies.
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A new approach to light up the application of semiconductor nanomaterials for photoelectrochemical biosensors: using self-operating photocathode as a highly selective enzyme sensor.
Biosens Bioelectron
PUBLISHED: 03-22-2014
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Due to the intrinsic hole oxidation reaction occurred on the photoanode surface, currently developed photoelectrochemical biosensors suffer from the interference from coexisting reductive species (acting as electron donor) and a novel design strategy of photoelectrode for photoelectrochemical detection is urgently required. In this paper, a self-operating photocathode based on CdS quantum dots sensitized three-dimensional (3D) nanoporous NiO was designed and created, which showed highly selective and reversible response to dissolved oxygen (acting as electron acceptor) in the electrolyte solution. Using glucose oxidase (GOD) as a biocatalyst, a novel photoelectrochemical sensor for glucose was developed. The commonly encountered interferents such as H2O2, ascorbic acid (AA), cysteine (Cys), dopamine (DA), etc., almost had no effect for the cathodic photocurrent of the 3D NiO/CdS electrode, though these substances were proved to greatly influence the photocurrent of photoanodes, which indicated greatly improved selectivity of the method. The method was applied to detect glucose in real samples including serum and glucose injections with satisfactory results. This study could provide a new train of thought on designing of self-operating photocathode in photoelectrochemical sensing, promoting the application of semiconductor nanomaterials in photoelectrochemistry.
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The complex jujube genome provides insights into fruit tree biology.
Nat Commun
PUBLISHED: 03-21-2014
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The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65?Mb (98.6% of the estimated) with 321.45?Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.
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Report of China's innovation increase and research growth in radiation oncology.
Chin. J. Cancer Res.
PUBLISHED: 03-19-2014
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To investigate the research status of radiation oncology in China through survey of literature in international radiation oncology journals and retrospectively compare the outputs of radiation oncology articles of the three major regions of China-Mainland (ML), Taiwan (TW) and Hong Kong (HK).
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Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration.
Pharm. Res.
PUBLISHED: 03-09-2014
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Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal immunization.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.