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Find video protocols related to scientific articles indexed in Pubmed.
A novel fluorene-based aggregation-induced emission (AIE)-active gold(i) complex with crystallization-induced emission enhancement (CIEE) and reversible mechanochromism characteristics.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A new fluorene-based AIE-active gold(i) complex was designed and synthesized. The novel luminogen exhibits a crystallization-induced emission enhancement (CIEE) effect and reversible mechanochromic behavior with fluorescence changes between green and yellow emissions.
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[Preventive effect of behavioral therapy plus flunarizine in children with migraine.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To investigate the preventive effect of behavioral therapy plus flunarizine in children with migraine.
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Developing a Two-Step Heat Treatment for Inactivating Desiccation-Adapted Salmonella spp. in Aged Chicken Litter.
Foodborne Pathog. Dis.
PUBLISHED: 11-19-2014
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Abstract The effectiveness of a two-step heat treatment for eliminating desiccation-adapted Salmonella spp. in aged chicken litter was evaluated. The aged chicken litter with 20, 30, 40, and 50% moisture contents was inoculated with a mixture of four Salmonella serotypes for a 24-h adaptation. Afterwards, the inoculated chicken litter was added into the chicken litter with the adjusted moisture content for a 1-h moist-heat treatment at 65°C and 100% relative humidity inside a water bath, followed by a dry-heat treatment in a convection oven at 85°C for 1?h to the desired moisture level (<10-12%). After moist-heat treatment, the populations of Salmonella in aged chicken litter at 20 and 30% moisture contents declined from ?6.70 log colony-forming units (CFU)/g to 3.31 and 3.00 log CFU/g, respectively. After subsequent 1-h dry-heat treatment, the populations further decreased to 2.97 and 2.57 log CFU/g, respectively. Salmonella cells in chicken litter with 40% and 50% moisture contents were only detectable by enrichment after 40 and 20?min of moist-heat treatment, respectively. Moisture contents in all samples were reduced to <10% after a 1-h dry-heat process. Our results demonstrated that the two-step heat treatment was effective in reducing >5.5 logs of desiccation-adapted Salmonella in aged chicken litter with moisture content at or above 40%. Clearly, the findings from this study may provide the chicken litter processing industry with an effective heat treatment method for producing Salmonella-free chicken litter.
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Biocompatible ionic liquid-biopolymer electrolyte enabled thin and compact magnesium air batteries.
ACS Appl Mater Interfaces
PUBLISHED: 11-08-2014
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With the surge of interest in miniaturized implanted medical devices (IMDs), implantable power sources with small dimensions and biocompatibility are in high demand. Implanted battery/supercapacitor devices are commonly packaged within a case that occupies a large volume making miniaturization difficult. In this study, we demonstrate a polymer electrolyte enabled biocompatible magnesium-air battery device with a total thickness of approximately 300 µm. It consists of a biocompatible polypyrrole-para(toluene sulfonic acid) cathode and a bioresorbable magnesium alloy anode. The biocompatible electrolyte used is made of choline nitrate (ionic liquid) embedded in a biopolymer, chitosan. This polymer electrolyte is mechanically robust and offers a high ionic conductivity of 8.9×10-3 S cm-1. The assembled battery delivers a maximum volumetric power density of 3.9 W L-1, which is sufficient to drive some types of IMDs such as cardiac pacemakers or bio-monitoring systems. This miniaturized, biocompatible magnesium-air battery may pave a way to the future generation of implantable power sources.
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High Expression of Bcl-2 Protein Predicts Favorable Outcome in Non-small Cell Lung Cancer: Evidence from a Systematic Review and Meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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The prognostic value of Bcl-2 protein expression in non-small cell lung cancer (NSCLC) is under debate. We therefore systematically reviewed the evidence for Bcl-2 protein effects on NSCLC survival to elucidate this issue.
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First Genome Sequence of Potential Mycotoxin-Degrading Bacterium Devosia nanyangense DDB001.
Genome Announc
PUBLISHED: 10-25-2014
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Devosia sp. nov. DDB001, isolated from mycotoxin-contaminated soil, is a potential mycotoxin-degrading alphaproteobacterium. To our knowledge, this is the first draft genome announcement of a Devosia species.
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[Clinical application of the adjacent horn shaped perforator fasciocutaneous flap in the trunk area].
Zhonghua Zheng Xing Wai Ke Za Zhi
PUBLISHED: 10-18-2014
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To study the anatomy basis for the clinical application of the adjacent horn shaped perforator fasciocutaneous flap for the reconstruction of small and medium-sized defects in the trunk area.
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Imides modified benzopicenes: synthesis, solid structure and optoelectronic properties.
Org. Biomol. Chem.
PUBLISHED: 09-30-2014
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Imide-modified polycyclic aromatic hydrocarbons can be widely applied in the field of optoelectronic materials. In this work, we have synthesized four novel functionalized benzopicenes and characterized their solid structures and optoelectronic properties. The fluorescence of the four functionalized benzopicenes showed red shifts with increasing solvent polarity; the quantum yields are high in the solution state and moderate in the solid state. The single crystal structures show that the benzopicenes adopt a lamellar motif ?-stacking. Their good solubility and optoelectronic properties make them potential solution-processable candidates for organic devices, bioimaging and biolabeling.
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Nucleophilic Substitution Catalyzed by a Supramolecular Cavity Proceeds with Retention of Absolute Stereochemistry.
J. Am. Chem. Soc.
PUBLISHED: 09-30-2014
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While the reactive pocket of many enzymes has been shown to modify reactions of substrates by changing their chemical properties, examples of reactions whose stereochemical course is completely reversed are exceedingly rare. We report herein a class of water-soluble host assemblies that is capable of catalyzing the substitution reaction at a secondary benzylic carbon center to give products with overall stereochemical retention, while reaction of the same substrates in bulk solution gives products with stereochemical inversion. Such ability of a biomimetic synthetic host assembly to reverse the stereochemical outcome of a nucleophilic substitution reaction is unprecedented in the field of supramolecular host-guest catalysis.
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Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-29-2014
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Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-? and PDGFR-?, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
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Optimal SVM parameter selection for non-separable and unbalanced datasets.
Struct Multidiscipl Optim
PUBLISHED: 09-27-2014
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This article presents a study of three validation metrics used for the selection of optimal parameters of a support vector machine (SVM) classifier in the case of non-separable and unbalanced datasets. This situation is often encountered when the data is obtained experimentally or clinically. The three metrics selected in this work are the area under the ROC curve (AUC), accuracy, and balanced accuracy. These validation metrics are tested using computational data only, which enables the creation of fully separable sets of data. This way, non-separable datasets, representative of a real-world problem, can be created by projection onto a lower dimensional sub-space. The knowledge of the separable dataset, unknown in real-world problems, provides a reference to compare the three validation metrics using a quantity referred to as the "weighted likelihood". As an application example, the study investigates a classification model for hip fracture prediction. The data is obtained from a parameterized finite element model of a femur. The performance of the various validation metrics is studied for several levels of separability, ratios of unbalance, and training set sizes.
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Universal predictability of mobility patterns in cities.
J R Soc Interface
PUBLISHED: 09-19-2014
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Despite the long history of modelling human mobility, we continue to lack a highly accurate approach with low data requirements for predicting mobility patterns in cities. Here, we present a population-weighted opportunities model without any adjustable parameters to capture the underlying driving force accounting for human mobility patterns at the city scale. We use various mobility data collected from a number of cities with different characteristics to demonstrate the predictive power of our model. We find that insofar as the spatial distribution of population is available, our model offers universal prediction of mobility patterns in good agreement with real observations, including distance distribution, destination travel constraints and flux. By contrast, the models that succeed in modelling mobility patterns in countries are not applicable in cities, which suggests that there is a diversity of human mobility at different spatial scales. Our model has potential applications in many fields relevant to mobility behaviour in cities, without relying on previous mobility measurements.
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[Clinical features and risk factors of co-morbid tic disorder in children with attention deficit hyperactivity disorder].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 09-18-2014
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To study the clinical features and risk factors of co-morbid tic disorder (TD) in children with attention deficit hyperactivity disorder (ADHD).
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A novel mutant of human papillomavirus type 18 E6E7 fusion gene and its transforming activity.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer.
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One-step synthesis of graphene/polypyrrole nanofiber composites as cathode material for a biocompatible zinc/polymer battery.
ACS Appl Mater Interfaces
PUBLISHED: 09-18-2014
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The significance of developing implantable, biocompatible, miniature power sources operated in a low current range has become manifest in recent years to meet the demands of the fast-growing market for biomedical microdevices. In this work, we focus on developing high-performance cathode material for biocompatible zinc/polymer batteries utilizing biofluids as electrolyte. Conductive polymers and graphene are generally considered to be biocompatible and suitable for bioengineering applications. To harness the high electrical conductivity of graphene and the redox capability of polypyrrole (PPy), a polypyrrole fiber/graphene composite has been synthesized via a simple one-step route. This composite is highly conductive (141 S cm(-1)) and has a large specific surface area (561 m(2) g(-1)). It performs more effectively as the cathode material than pure polypyrrole fibers. The battery constructed with PPy fiber/reduced graphene oxide cathode and Zn anode delivered an energy density of 264 mWh g(-1) in 0.1 M phosphate-buffer saline.
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[Assessment on the effect of joint effort for schistosomiasis control in Hubei Province].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 09-17-2014
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To analyze the progress of implementation of integrated strategy with emphasis on the control of infectious sources and effectiveness for joint-project of schistosomiasis control in Hubei province.
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Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R.
Clin. Cancer Res.
PUBLISHED: 09-03-2014
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Activating mutations in the RAS oncogene occur frequently in human leukemias. Direct targeting of RAS has proven to be challenging, although targeting of downstream RAS mediators, such as MEK, is currently being tested clinically. Given the complexity of RAS signaling, it is likely that combinations of targeted agents will be more effective than single agents.
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A portable lab-on-a-chip system for gold-nanoparticle-based colorimetric detection of metal ions in water.
Biomicrofluidics
PUBLISHED: 09-01-2014
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Heavy metal ions released into various water systems have a severe impact on the environment and human beings, and excess exposure to toxic metal ions through drinking water poses high risks to human health and causes life-threatening diseases. Thus, there is high demand for the development of a rapid, low-cost, and sensitive method for detection of metal ions in water. We present a portable analytical system for colorimetric detection of lead (Pb(2+)) and aluminum (Al(3+)) ions in water based on gold nanoparticle probes and lab-on-a-chip instrumentation. The colorimetric detection of metal ions is conducted via single-step assays with low limits of detection (LODs) and high selectivity. We design a custom-made microwell plate and a handheld colorimetric reader for implementing the assays and quantifying the signal readout. The calibration experiments demonstrate that this portable system provides LODs of 30?ppb for Pb(2+) and 89?ppb for Al(3+), both comparable to bench-top analytical spectrometers. It promises an effective platform for metal ion analysis in a more economical and convenient way, which is particularly useful for water quality monitoring in field and resource-poor settings.
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Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.
Nat. Med.
PUBLISHED: 08-31-2014
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Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the clinical observation of a patient with ALK fusion-positive lung cancer who had an exceptional response to an insulin-like growth factor 1 receptor (IGF-1R)-specific antibody, we define a therapeutic synergism between ALK and IGF-1R inhibitors. Similar to IGF-1R, ALK fusion proteins bind to the adaptor insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effects of ALK inhibitors. In models of ALK TKI resistance, the IGF-1R pathway is activated, and combined ALK and IGF-1R inhibition improves therapeutic efficacy. Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy. Collectively these data support a role for the IGF-1R-IRS-1 pathway in both ALK TKI-sensitive and ALK TKI-resistant states and provide a biological rationale for further clinical development of dual ALK and IGF-1R inhibitors.
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Functional features of crossmodal mismatch responses.
Exp Brain Res
PUBLISHED: 08-20-2014
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Research on brain mechanisms of deviance detection and sensory memory trace formation, best indexed by the mismatch negativity, mainly relied on the investigation of responses elicited by auditory stimuli. However, comparable less research reported the mismatch negativity elicited by somatosensory stimuli. More importantly, little is known on the functional features of mismatch deviant and standard responses across different sensory modalities. To directly compare different sensory modalities, we adopted a crossmodal roving paradigm and collected event-related potentials elicited by auditory, non-nociceptive somatosensory, and nociceptive trains of stimuli, during Active and Passive attentional conditions. We applied a topographical segmentation analysis to cluster successive scalp topographies with quasi-stable landscape of significant differences to extract crossmodal mismatch responses. We obtained three main findings. First, across different sensory modalities and attentional conditions, the formation of a standard sensory trace became robust mainly after the second stimulus repetition. Second, the neural representation of a modality deviant stimulus was influenced by the preceding sensory modality. Third, the mismatch negativity significantly covaried between Active and Passive attentional conditions within the same sensory modality, but not between different sensory modalities. These findings provide robust evidence that, while different modalities share a similar process of standard trace formation, the process of deviance detection is largely modality dependent.
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Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro.
Sci China Life Sci
PUBLISHED: 08-16-2014
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Ebola virus (EBOV) causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein (GP) mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs (miRNAs) in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we report that the mi-RNAs hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells (HUVECs) following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor (TFPI), dystroglycan1 (DAG1) and the caspase 8 and FADD-like apoptosis regulator (CFLAR) were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.
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Inhibiting CCN1 blocks AML cell growth by disrupting the MEK/ERK pathway.
Cancer Cell Int.
PUBLISHED: 08-16-2014
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CCN1 plays distinct roles in various tumor types, but little is known regarding the role of CCN1 in leukemia.
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Hawaiinolides E-G, cytotoxic cassane and cleistanthane diterpenoids from the entomogenous fungus Paraconiothyrium hawaiiense.
Fitoterapia
PUBLISHED: 08-13-2014
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Hawaiinolides E-G (1-3), three additional new secondary metabolites including two cassane (1 and 2) types of diterpene lactones and one cleistanthane (3) diterpenoid, were isolated from the scale-up fermentation extract of Paraconiothyrium hawaiiense, an entomogenous fungus isolated from the Septobasidium-infected insect Diaspidiotus sp. The structures of 1-3 were elucidated by nuclear magnetic resonance experiments, and 1 and 3 were further confirmed by X-ray crystallography. The absolute configurations of 1 and 3 were assigned by single-crystal X-ray diffraction analysis using Cu K? radiation, whereas that of 2 was deduced via the circular dichroism data. Compound 1 showed significant cytotoxic effects against the human tumor cell line T24, with an IC50 value (9.32?M) comparable to that of the positive control cisplatin.
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Designing of a "cheap to run" fermentation platform for an enhanced production of single cell oil from Yarrowia lipolytica DSM3286 as a potential feedstock for biodiesel.
Bioresour. Technol.
PUBLISHED: 08-08-2014
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In this study, the culture medium components screening and filtering were undertaken in order to set up efficient and cost effective minimal culture media for lipid production from Yarrowia lipolytica DSM3286. The basal minimal culture medium (S2) designed yielded lipid content up to 35% of the microbial dry cell weight. A set of fermentation strategies based on this minimal medium was developed and the lipid content was raised to 51%. The scale-up under different fermentation conditions based on S2 medium led to a maximum lipid content of 65%. The produced microbial oils displayed interesting properties to be used as a feedstock for high quality biodiesel production. The minimal media and operable cultivation strategies devised in this study, in association with the works done so far by other authors, could enable fast, massive, viable and more economical production of single cell oils and smooth biodiesel manufacture.
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A novel fluorene-based gold(I) complex with aggregate fluorescence change: a single-component white light-emitting luminophor.
Chem. Commun. (Camb.)
PUBLISHED: 08-07-2014
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A new fluorene-based white light-emitting gold(I) complex with aggregate fluorescence change is reported. The novel luminogen emits direct white light in the solid state without involving complex doping/mixing procedures.
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Dithienylethene-based rotaxanes: synthesis, characterization and properties.
Org. Biomol. Chem.
PUBLISHED: 08-01-2014
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The photochromic materials have been widely applied in many fields. In this article, we report a class of photochromic ammoniums with a dithienylethene backbone. They were utilized as templates to construct mechanically interlocked rotaxanes and pseudorotaxanes showing photo-responsive behavior by template-directed clipping reaction and the threading approach. The structures of novel rotaxanes were well defined. It is worth mentioning that the single crystal structure of [3]rotaxane containing two N-hetero crown ether units was obtained. Their photoisomerization behavior was investigated. These N-hetero crown ether-based rotaxanes displayed good reversibility and similar photochromic behaviors to their corresponding ammoniums when they underwent UV/vis photoirradiation. Interestingly, the cucurbit[6]uril-based pseudorotaxane showed better photoisomerization than its corresponding ammonium and those of N-hetero crown ether-based rotaxanes.
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Non-small-cell lung cancers: a heterogeneous set of diseases.
Nat. Rev. Cancer
PUBLISHED: 07-25-2014
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Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been developed with compelling clinical proofs of concept; however, treatment responses are typically short-lived. Further studies of the tumour microenvironment have uncovered new possible avenues to control this deadly disease, including immunotherapy.
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Novel role of resveratrol: suppression of high-mobility group protein box 1 nucleocytoplasmic translocation by the upregulation of sirtuin 1 in sepsis-induced liver injury.
Shock
PUBLISHED: 07-09-2014
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High-mobility group protein box 1 (HMGB1) is essential in the response to injury during sepsis. We hypothesized that resveratrol (RESV) administration would inhibit nuclear-cytoplasmic HMGB1 translocation in hepatocytes, which is associated with sirtuin 1 (SIRT1) upregulation. We investigated the regulatory role of SIRT1 in HMGB1 nucleocytoplasmic translocation and its effect on sepsis-induced liver injury.
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Visualization of the ocular pulse in the anterior chamber of the mouse eye in vivo using phase-sensitive optical coherence tomography.
J Biomed Opt
PUBLISHED: 07-03-2014
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We report on a phase-based method for accurately measuring the ocular pulse in the anterior chamber in vivo. Using phase-sensitive optical coherence tomography with optimized scanning protocols and equations for compensating bulk motion and environmental vibrations, a high sensitivity of 0.9 ?m/s minimal velocity is demonstrated at a wide detection band of 0 to 380 Hz. The pulsatile relative motion between cornea and crystalline lens in rodents is visualized and quantified. The relative motion is most likely caused by respiration (1.6 Hz) and heartbeat (6.6 Hz). The velocity amplitude of the relative motion is 10.3 ± 2.4 ?m/s. The displacement amplitudes at the respiratory and cardiac frequencies are 202.5 ± 64.9 and 179.9 ± 49.4 nm, respectively. The potential applications the measurement technique can be found in the evaluation of intraocular pressure and the measurement of biomechanical properties of the ocular tissue, which are important in several ocular diseases.
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Blockade of PKC? protects against remote organ injury induced by intestinal ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway.
Apoptosis
PUBLISHED: 06-16-2014
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Intestinal ischemia-reperfusion (I/R) is a serious clinical dilemma with high morbidity and mortality. Remote organ damage, especially acute lung injury and liver injury are common complications that contribute to the high mortality rate. We previously demonstrated that activation of PKC?II is specifically involved in the primary injury of intestinal I/R. Considering the tissue-specific features of PKC activation, we hypothesized that some kind of PKC isoform may play important roles in the progression of secondary injury in the remote organ. Mice were studied in in vivo model of intestinal I/R. The activation of PKC isoforms were screened in the lung and liver. Interestingly, we found that PKC?II was also activated exclusively in the lung and liver after intestinal I/R. PKC?II suppression by a specific inhibitor, LY333531, significantly attenuated I/R-induced histologic damage, inflammatory cell infiltration, oxidative stress, and apoptosis in these organs, and also alleviated systemic inflammation. In addition, LY333531 markedly restrained p66shc activation, mitochondrial translocation, and binding to cytochrome-c. These resulted in the decrease of cytochrome-c release and caspase-3 cleavage, and an increase in glutathione and glutathione peroxidase. These data indicated that activated PKC isoform in the remote organ, specifically PKC?II, is the same as that in the intestine after intestinal I/R. PKC?II suppression protects against remote organ injury, which may be partially attributed to the p66shc-cytochrome-c axis. Combined with our previous study, the development of a specific inhibitor for prophylaxis against intestinal I/R is promising, to prevent multiple organ injury.
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Enhanced electroluminescence using Ta?O?/ZnO/HfO? asymmetric double heterostructure in ZnO/GaN-based light emitting diodes.
Opt Express
PUBLISHED: 06-13-2014
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ZnO/GaN-based light-emitting diodes (LEDs) with improved asymmetric double heterostructure of Ta?O?/ZnO/HfO? have been fabricated. Electroluminescence (EL) performance has been enhanced by the HfO? electron blocking layer and further improved by continuing inserting the Ta?O? hole blocking layer. The origins of the emission have been identified, which indicated that the Ta?O?/ZnO/HfO? asymmetric structure could more effectively confine carriers in the active i-ZnO layer and meanwhile suppresses of radiation from GaN. This device exhibits superior stability in long-time running. It's hoped that the asymmetric double heterostructure may be helpful for the development of the future ZnO-based LEDs.
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Vitreous seeding from a large optic disc melanocytoma.
J Neuroophthalmol
PUBLISHED: 06-05-2014
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We report the case of a 17 year-old man with a large optic disc melanocytoma that underwent spontaneous rupture and seeding of the vitreous with pigmented cells. Potential pathogenic mechanisms and visual prognosis of this rare event are discussed.
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Measurement of genome-wide DNA methylation predicts survival benefits from chemotherapy in non-small cell lung cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 05-26-2014
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Novel molecular predictive biomarkers for chemotherapy have been screened and validated in non-small cell lung cancer (NSCLC). However, there was no report on the correlation of genome-wide DNA methylation with survival benefit from chemotherapy in NSCLC.
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Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.
Diabetologia
PUBLISHED: 05-21-2014
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We examined whether or not the association of physical activity with type 2 diabetes incidence differs according to several types of genetic susceptibility.
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Risk score to predict mortality in continuous ambulatory peritoneal dialysis patients.
Eur. J. Clin. Invest.
PUBLISHED: 05-15-2014
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Patients with continuous ambulatory peritoneal dialysis (CAPD) have high all-cause mortality risk that varies extensively among different conditions. The objective of this study was to develop and validate risk models to predict the 2-year all-cause mortality risks of CAPD patients.
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Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate.
Nat. Cell Biol.
PUBLISHED: 05-03-2014
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Branching morphogenesis is thought to be governed by epithelial-stromal interactions, but the mechanisms underlying specification of branch location remain largely unknown. Prompted by the striking absence of Hedgehog (Hh) response at the sites of nascent buds in regenerating tubules of the adult prostate, we investigated the role of Hh signalling in adult prostate branching morphogenesis. We find that pathway activity is localized to stromal cells, and that its attenuation by genetic or pharmacologic manipulation leads to increased branching. Decreased pathway activity correlates with increased stromal production of hepatocyte growth factor (Hgf), and we show that Hgf induces epithelial tubule branching. Regulation of Hgf expression by Hh signalling is indirect, mediated by Hh-induced expression of the microRNAs miR-26a and miR-26b, which in turn downregulate expression of Hgf. Prostate tubule branching thus may be initiated from regions of low Hh pathway activity, with implications for the prostatic hyperplasia commonly observed in late adulthood.
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Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.
Cancer Cell
PUBLISHED: 05-02-2014
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Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or accelerate progression in treatment of endodermally derived colon and pancreatic cancers. In bladder, another organ of endodermal origin, we find that despite its initial presence in the cancer cell of origin Sonic hedgehog (Shh) expression is invariably lost during progression to invasive urothelial carcinoma. Genetic blockade of stromal response to Shh furthermore dramatically accelerates progression and decreases survival time. This cancer-restraining effect of Hh pathway activity is associated with stromal expression of BMP signals, which stimulate urothelial differentiation. Progression is dramatically reduced by pharmacological activation of BMP pathway activity with low-dose FK506, suggesting an approach to management of human bladder cancer.
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Comparison of contrast-enhanced ultrasonography and contrast-enhanced MRI for the assessment of vascularization of hydroxyapatite orbital implants.
Clin Imaging
PUBLISHED: 04-24-2014
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To compare contrast-enhanced ultrasound and contrast-enhanced magnetic resonance imaging for the assessment of vascularization of hydroxyapatite orbital implants.
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Unusual electroluminescence from n-ZnO@i-MgO core-shell nanowire color-tunable light-emitting diode at reverse bias.
Phys Chem Chem Phys
PUBLISHED: 04-10-2014
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Light-emitting diodes (LEDs) based on n-ZnO@i-MgO core-shell (CS) nanowires (NWs) are herein demonstrated and characterized. MgO insulating layers were rationally introduced as shells to modify/passivate the surface defects of ZnO NWs. A high-quality ZnO/MgO interface was attained and the optically pumped near-band-edge emission of the bare ZnO NWs was greatly enhanced after cladding i-MgO shells. Electroluminescence (EL) spectra measured in the whole UV-visible range revealed that light emission can only be detected when LEDs were applied with reverse bias. Moreover, the emission color can be tuned from orange to bright white with increasing reverse bias. We explored these interesting results tentatively in terms of the energy-band diagram of the heterojunction and it was found that the interfacial i-MgO shells not only acted as an insulator to prevent a short circuit between the two electrodes, but also offered a potential energy difference so that electron tunneling was energetically possible, both of which were essential to generate the reverse-bias EL. The dipole-forbidden d-d transitions by the Laporte selection rule in the p-NiO might be the reason to why there is no light being detected from the CS NW LED under forward bias. It is hoped that this simple and facile route may provide an effective approach in designing low-cost CS NW LEDs.
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Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.
Cancer Res.
PUBLISHED: 03-27-2014
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Although several groups have demonstrated that concomitant use of MEK and phosphoinositide 3-kinase (PI3K) inhibitors (MEKi/PI3Ki) can induce dramatic tumor regressions in mouse models of KRAS-mutant non-small cell lung cancer (NSCLC), ongoing clinical trials investigating this strategy have been underwhelming to date. While efficacy may be hampered by a narrow therapeutic index, the contribution of biologic heterogeneity in the response of KRAS-mutant NSCLCs to MEKi/PI3Ki has been largely unexplored. In this study, we find that most human KRAS-mutant NSCLC cell lines fail to undergo marked apoptosis in response to MEKi/PI3Ki, which is key for tumor responsiveness in vivo. This heterogeneity of apoptotic response occurs despite relatively uniform induction of growth arrest. Using a targeted short hairpin RNA screen of BCL-2 family members, we identify BIM, PUMA, and BCL-XL as key regulators of the apoptotic response induced by MEKi/PI3Ki, with decreased expression of BIM and PUMA relative to BCL-XL in cell lines with intrinsic resistance. In addition, by modeling adaptive resistance to MEKi/PI3Ki both in vitro and in vivo, we find that, upon the development of resistance, tumors have a diminished apoptotic response due to downregulation of BIM and PUMA. These results suggest that the inability to induce apoptosis may limit the effectiveness of MEKi/PI3Ki for KRAS-mutant NSCLCs by contributing to intrinsic and adaptive resistance to this therapy.
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The homeobox gene EMX2 is a prognostic and predictive marker in malignant pleural mesothelioma.
Lung Cancer
PUBLISHED: 03-08-2014
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Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm with a poor prognosis and limited treatment options. EMX2 is a homeobox transcription factor that may regulate key developmental pathways known to promote tumorigenesis. In this study, we evaluated the prognostic and predictive significance of EMX2 expression in MPM.
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The APOE ?2 allele may decrease the age at onset in patients with spinocerebellar ataxia type 3 or Machado-Joseph disease from the Chinese Han population.
Neurobiol. Aging
PUBLISHED: 02-16-2014
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Polymorphism of the apolipoprotein E (APOE) gene has been defined as a modifying factor for age at onset (AO) in neurodegenerative disorders. The AO of spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3 or MJD) is inversely correlated with expanded CAG repeat lengths in the ATXN3 gene; however, AO is only partially explained by the expanded CAG repeats. We performed a case-control study to explore whether APOE genotypes play a role in AO of SCA3 or MJD from the Chinese Han population. The APOE genotypes were analyzed in an independent cohort of 155 patients with SCA3 or MJD and 191 controls both from Mainland China. Our study demonstrated that SCA3 or MJD patients experienced an earlier onset if they were carriers of APOE ?2 allele, which decreased the AO by nearly 4 years. This study may also reconfirm the effect of the APOE gene on SCA3 or MJD patients from different races and indicated that certain APOE alleles might be genetic modifiers for AO in SCA3 or MJD.
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Predicting the human epigenome from DNA motifs.
Nat. Methods
PUBLISHED: 02-10-2014
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The epigenome is established and maintained by the site-specific recruitment of chromatin-modifying enzymes and their cofactors. Identifying the cis elements that regulate epigenomic modification is critical for understanding the regulatory mechanisms that control gene expression patterns. We present Epigram, an analysis pipeline that predicts histone modification and DNA methylation patterns from DNA motifs. The identified cis elements represent interactions with the site-specific DNA-binding factors that establish and maintain epigenomic modifications. We cataloged the cis elements in embryonic stem cells and four derived lineages and found numerous motifs that have location preference, such as at the center of H3K27ac or at the edges of H3K4me3 and H3K9me3, which provides mechanistic insight about the shaping of the epigenome. The Epigram pipeline and predictive motifs are at http://wanglab.ucsd.edu/star/epigram/.
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Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study.
Am. J. Clin. Nutr.
PUBLISHED: 02-05-2014
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Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear.
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Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.
Cancer Cell
PUBLISHED: 01-29-2014
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Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, gene expression, and microenvironment found in human disease. Lkb1;Pten null (LP) tumors expressed the squamous markers KRT5, p63 and SOX2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. SCA1(+)NGFR(+) fractions were enriched for tumor-propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and NGFR(+) cells in human SCCs highly expressed Pd-ligand-1 (PD-L1), suggesting a mechanism of immune escape for TPCs.
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Xenogenic (porcine) acellular dermal matrix is useful for the wound healing of severely damaged extremities.
Exp Ther Med
PUBLISHED: 01-20-2014
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This study was conducted to investigate the possibility of improving the success rate of patient treatment and promoting wound healing by utilizing xenogenic (porcine) acellular dermal matrix (XADM) to cover large areas of severely damaged wounds. Patients with severely damaged large-area wounds (56 cases) were enrolled in the study from May 2002 to May 2012. All patients admitted to hospital received a rapid infusion via intravenous access to maintain an effective circulating blood volume and to correct disorders of water and electrolytes. The wounds were exposed and covered with XADM during the initial surgery. All patients subsequently received secondary stage surgery. Of the patients, 47 cases received an autologous skin graft for wound closure, six cases underwent wound repair with a local flap and three cases underwent wound repair with an axial flap. There were two cases of amputation and three cases of mortality. The cases of two of the patients are described in detail. XADM was demonstrated to reduce the risk of emergency during surgery and improve the success rate of wound healing and patient treatment.
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Dysregulation of JAM-A plays an important role in human tumor progression.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Junctional adhesion molecule A (JAM-A) is a transmembrane protein that belongs to the immunoglobulin (Ig) superfamily. Evidence determines that JAM-A plays a role in numerous cellular processes, including tight junction assembly, leukocyte migration, platelet activation, angiogenesis and virus binding. Recent research suggests that JAM-A is dysregulated in various cancers and is vital for tumor progression. JAM-A is implicated in carcinogenesis via different signal pathways such as TGF-?1 signaling. Furthermore, JAM-A expression in cancers is usually associated with certain outcome of patients and might be a prognostic indicator. In this review, the correlation between JAM-A expression and human cancers will be described.
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Diabetes mellitus and risk of age-related macular degeneration: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00-1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00-1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44-1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13-1.49) and late AMD (OR, 1.16; 95% CI, 1.11-1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96-1.26), 1.48 (95% CI, 1.44-1.51), and 1.15 (95% CI, 1.11-1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.
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BRCA1 silencing is associated with failure of DNA repairing in retinal neurocytes.
PLoS ONE
PUBLISHED: 01-01-2014
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Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes.
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Modulating the p66shc signaling pathway with protocatechuic acid protects the intestine from ischemia-reperfusion injury and alleviates secondary liver damage.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Intestinal ischemia-reperfusion (I/R) injury is a serious clinical pathophysiological process that may result in acute local intestine and remote liver injury. Protocatechuic acid (PCA), which has been widely studied as a polyphenolic compound, induces expression of antioxidative genes that combat oxidative stress and cell apoptosis. In this study, we investigated the effect of PCA pretreatment for protecting intestinal I/R-induced local intestine and remote liver injury in mice. Intestinal I/R was established by superior mesenteric artery occlusion for 45 min followed by reperfusion for 90 min. After the reperfusion period, PCA pretreatment markedly alleviated intestine and liver injury induced by intestinal I/R as indicated by histological alterations, decreases in serological damage parameters and nuclear factor-kappa B and phospho-foxo3a protein expression levels, and increases in glutathione, glutathione peroxidase, manganese superoxide dismutase protein expression, and Bcl-xL protein expression in the intestine and liver. These parameters were accompanied by PCA-induced adaptor protein p66shc suppression. These results suggest that PCA has a significant protective effect in the intestine and liver following injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the regulation of p66shc-related antioxidative and antiapoptotic factors.
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Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
PLoS ONE
PUBLISHED: 01-01-2014
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Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation.
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Ligand-Based Carbon-Nitrogen Bond Forming Reactions of Metal Dinitrosyl Complexes with Alkenes and Their Application to C-H Bond Functionalization.
Acc. Chem. Res.
PUBLISHED: 12-23-2013
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Over the past few decades, researchers have made substantial progress in the development of transition metal complexes that activate and functionalize C-H bonds. For the most part, chemists have focused on aliphatic and aromatic C-H bonds and have put less effort into complexes that activate and functionalize vinylic C-H bonds. Our groups have recently developed a novel method to functionalize vinylic C-H bonds that takes advantage of the unique ligand-based reactivity of a rare class of metal dinitrosyl complexes. In this Account, we compare and discuss the chemistry of cobalt and ruthenium dinitrosyl complexes, emphasizing alkene binding, C-H functionalization, and catalysis. Initially discovered in the early 1970s by Brunner and studied more extensively in the 1980s by the Bergman group, the cyclopentadienylcobalt dinitrosyl complex CpCo(NO)2 reacts reversibly with alkenes to give, in many cases, stable and isolable cobalt dinitrosoalkane complexes. More recently, we found that treatment with strong bases, such as lithium hexamethyldisilazide, Verkades base, and phosphazene bases, deprotonates these complexes and renders them nucleophilic at the carbon ? to the nitroso group. This conjugate anion of metal dinitrosoalkanes can participate in conjugate addition to Michael acceptors to form new carbon-carbon bonds. These functionalized cobalt complexes can further react through alkene exchange to furnish the overall vinylic C-H functionalized organic product. This stepwise sequence of alkene binding, functionalization, and retrocycloaddition represents an overall vinylic C-H functionalization reaction of simple alkenes and does not require directing groups. We have also developed an asymmetric variant of this reaction sequence and have used this method to synthesize C1- and C2-symmetric diene ligands with high enantioinduction. Building upon these stepwise reactions, we eventually developed a simple one-pot procedure that uses stoichiometric amounts of a cobalt dinitrosoalkane complex for both inter- and intramolecular C-H functionalization. We can achieve catalysis in one-pot intramolecular reactions with a limited range of substrates. Our groups have also reported an analogous ruthenium dinitrosyl complex. In analogy to the cobalt complex, this ruthenium complex reacts with alkenes in the presence of neutral bidentate ligands, such as TMEDA, to give octahedral dinitrosoalkane complexes. Intramolecular functionalization or cyclization of numerous ruthenium dinitrosoalkane complexes proceeds under mild reaction conditions to give the functionalized organic products in excellent yields. However, despite extensive efforts, so far we have not been able to carry out intermolecular reactions of these complexes with a variety of electrophiles or C-H functionalization reactions. Although additional work is necessary to further boost the catalytic capabilities of both cobalt and ruthenium dinitrosyl complexes for vinylic C-H functionalization of simple alkenes, we believe this ligand-based vinylic C-H functionalization reaction has provided chemists with a useful set of tools for organic synthesis.
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Biomarker-calibrated protein intake and physical function in the Womens Health Initiative.
J Am Geriatr Soc
PUBLISHED: 10-28-2013
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To determine whether preservation of physical function with aging may be partially met through modification in dietary protein intake.
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Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer.
Clin. Cancer Res.
PUBLISHED: 09-17-2013
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Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non-small cell lung cancer (NSCLC) with BET inhibition.
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Predicting enhancer transcription and activity from chromatin modifications.
Nucleic Acids Res.
PUBLISHED: 09-12-2013
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Enhancers play a pivotal role in regulating the transcription of distal genes. Although certain chromatin features, such as the histone acetyltransferase P300 and the histone modification H3K4me1, indicate the presence of enhancers, only a fraction of enhancers are functionally active. Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers. However, the systematic identification of the most informative single modification, or combination thereof, is still lacking. Furthermore, the discovery of enhancer RNAs (eRNAs) provides an alternative approach to directly predicting enhancer activity. However, it remains challenging to link chromatin modifications to eRNA transcription. Herein, we develop a logistic regression model to unravel the relationship between chromatin modifications and eRNA synthesis. We perform a systematic assessment of 24 chromatin modifications in fetal lung fibroblast and demonstrate that a combination of four modifications is sufficient to accurately predict eRNA transcription. Furthermore, we compare the ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate that eRNA is more indicative of enhancer activity. Finally, we apply our fibroblast trained model to six other cell-types and successfully predict eRNA synthesis. Thus, we demonstrate the learned relationships are general and independent of cell-type. We provided a powerful tool to identify active enhancers and reveal the relationship between chromatin modifications, eRNA production and enhancer activity.
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Thermal inactivation of desiccation-adapted Salmonella spp. in aged chicken litter.
Appl. Environ. Microbiol.
PUBLISHED: 09-06-2013
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Thermal inactivation of desiccation-adapted Salmonella spp. in aged chicken litter was investigated in comparison with that in a nonadapted control to examine potential cross-tolerance of desiccation-adapted cells to heat treatment. A mixture of four Salmonella serovars was inoculated into the finished compost with 20, 30, 40, and 50% moisture contents for a 24-h desiccation adaptation. Afterwards, the compost with desiccation-adapted cells was inoculated into the aged chicken litter with the same moisture content for heat treatments at 70, 75, 80, 85, and 150°C. Recovery media were used to allow heat-injured cells to resuscitate. A 5-log reduction in the number of the desiccation-adapted cells in aged chicken litter with a 20% moisture content required >6, >6, ?4 to 5, and ?3 to 4 h of exposure at 70, 75, 80, and 85°C, respectively. As a comparison, a 5-log reduction in the number of nonadapted control cells in the same chicken litter was achieved within ?1.5 to 2, ?1 to 1.5, ?0.5 to 1, and <0.5 h at 70, 75, 80, and 85°C, respectively. The exposure time required to obtain a 5-log reduction in the number of desiccation-adapted cells gradually became shorter as temperature and moisture content were increased. At 150°C, desiccation-adapted Salmonella cells survived for 50 min in chicken litter with a 20% moisture content, whereas control cells were detectable by enrichment for only 10 min. Our results demonstrated that the thermal resistance of Salmonella in aged chicken litter was increased significantly when the cells were adapted to desiccation. This study also validated the effectiveness of thermal processing being used for producing chicken litter free of Salmonella contamination.
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Targeted surface-functionalized gold nanoclusters for mitochondrial imaging.
Biosens Bioelectron
PUBLISHED: 09-05-2013
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Due to mitochondria involved in both apoptotic and necrotic cell death, labeling and imaging mitochondria has attracted considerable interest. However, conventional organic dyes used for mitochondrial imaging are limited because of their poor photostability. Considering that gold nanoclusters (AuNCs) possess some advantages over considerable interest, such as excellent photostability and strong fluorescence emission, we herein prepared a mitochondria-targeted fluorescent probe, AuNCs@CS-TPP, based on a covalent link between triphenylphosphonium (TPP) cations and chitosan-coated AuNCs (AuNCs@CS). The as-prepared AuNCs@CS-TPP exhibited a bluish fluorescence emission at 440nm with a quantum yield of 8.5%. Meanwhile, the fluorescence intensity of AuNCs@CS-TPP labeled HeLa cells did not show apparent decrease after 8min irradiation. Cytotoxicity assay showed that AuNCs@CS-TPP did not display any appreciable cytotoxicity on cells even at a concentration of 60?gmL(-1). In addition, the result of fluorescence co-localization imaging in vitro indicated that AuNCs@CS-TPP could selectively accumulate into mitochondria of HeLa cells and HepG2 cells. These findings demonstrated that AuNCs@CS-TPP possessed superior photostability, low cytotoxicity, high sensitivity and target-specificity to mitochondria, allowing labeling and imaging of the mitochondria in living cells.
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Uremic anorexia and gastrointestinal motility dysfunction correlate with the changes of ghrelin system in hypothalamus.
Nephrology (Carlton)
PUBLISHED: 07-03-2013
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Ghrelin can act as a signal for meal initiation and play a role in the regulation of gastrointestinal (GI) motility via hypothalamic circuit. This study investigated the correlation between changes of hypothalamic ghrelin system and GI motility dysfunction and anorexia in rats with chronic renal failure (CRF).
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Lithium chloride alleviates neurodegeneration partly by inhibiting activity of GSK3? in a SCA3 Drosophila model.
Cerebellum
PUBLISHED: 07-02-2013
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Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucelotide repeat that encodes an abnormal polyglutamine (PolyQ) tract in the disease protein, ataxin-3. The formation of neuronal intranuclear inclusions in the specific brain regions is one of the pathological hallmarks of SCA3. Acceleration of the degradation of the mutant protein aggregates is proven to produce beneficial effects in SCA3 and other PolyQ diseases. Lithium is known to be neuroprotective in various models of neurodegenerative disease and can reduce the mutant protein aggregates by inducing autophagy. In this study, we explored the therapeutic potential of lithium in a SCA3 Drosophila model. We showed that chronic treatment with lithium chloride at specific doses notably prevented eye depigmentation, alleviated locomotor disability, and extended the median life spans of SCA3 transgenic Drosophila. By means of genetic approaches, we showed that co-expressing the mutant S9E, which mimicked the phosphorylated S9 state of Shaggy as done by lithium, also partly decreased toxicity of gmr-SCA3tr-Q78. Taken together, our findings suggest that lithium is a promising therapeutic agent for the treatment of SCA3 and other PolyQ diseases.
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Enhanced Sensitivity for Detection of Low-Level Germline Mosaic RB1 Mutations in Sporadic Retinoblastoma Cases Using Deep Semiconductor Sequencing.
Hum. Mutat.
PUBLISHED: 07-01-2013
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Sporadic retinoblastoma (RB) is caused by de novo mutations in the RB1 gene. Often, these mutations are present as mosaic mutations that cannot be detected by Sanger sequencing. Next-generation deep sequencing allows unambiguous detection of the mosaic mutations in lymphocyte DNA. Deep sequencing of the RB1 gene on lymphocyte DNA from 20 bilateral and 70 unilateral RB cases was performed, where Sanger sequencing excluded the presence of mutations. The individual exons of the RB1 gene from each sample were amplified, pooled, ligated to barcoded adapters, and sequenced using semiconductor sequencing on an Ion Torrent Personal Genome Machine. Six low-level mosaic mutations were identified in bilateral RB and four in unilateral RB cases. The incidence of low-level mosaic mutation was estimated to be 30% and 6%, respectively, in sporadic bilateral and unilateral RB cases, previously classified as mutation negative. The frequency of point mutations detectable in lymphocyte DNA increased from 96% to 97% for bilateral RB and from 13% to 18% for unilateral RB. The use of deep sequencing technology increased the sensitivity of the detection of low-level germline mosaic mutations in the RB1 gene. This finding has significant implications for improved clinical diagnosis, genetic counseling, surveillance, and management of RB.
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Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer.
Cancer Discov
PUBLISHED: 05-28-2013
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The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling showed that Lkb1-null cells had a striking decrease in multiple nucleotide metabolites as compared with the Lkb1-wild-type cells. Thus, LKB1-mutant lung cancers have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors.
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OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Womens Health Initiative Observational Study.
Bone
PUBLISHED: 05-16-2013
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The osteoprotogerin/receptor activator of NF-kappa ?/receptor activator of NF-kappa ? ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture.
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A deletion mutation of the VHL gene associated with a patient with sporadic von Hippel-Lindau disease.
J Clin Neurosci
PUBLISHED: 04-28-2013
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Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited familial cancer syndrome resulting from mutations in the VHL tumor suppressor gene, which leads to the development of a variety of benign and malignant tumors, especially central nervous system hemangioblastomas, retinal angiomas, clear-cell renal cell carcinomas and pheochromocytomas, with age-dependent penetrance. To date, nearly 400 germline mutations have been found to be involved in VHL disease according to the public Human Gene Mutation Database (HGMD). Although most index cases have a positive family history of VHL, some do not and may represent de novo cases. Patients diagnosed without family histories of VHL have been reported in as many as 23% of affected individuals with VHL. In this paper, we report the presence of a heterozygous deletion mutation of c.227_229delTCT in the VHL gene, causing the deletion of phenylalanine at codon 76 (p.Phe76del) of the VHL protein in a patient with sporadic VHL with a benign prognosis. The mutation involved may be de novo or the seemingly unaffected parent may be mosaic for the disease.
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Optimal extraction and fingerprint analysis of Cnidii fructus by accelerated solvent extraction and high performance liquid chromatographic analysis with photodiode array and mass spectrometry detections.
Food Chem
PUBLISHED: 04-20-2013
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A confirmatory and reliable procedure has been developed for extraction and determination of Cnidii fructus by accelerated solvent extraction (ASE) and high-performance liquid chromatography coupled with photodiode array, electrospray ionisation ion trap tandem mass spectrometry and time of flight mass spectrometry (HPLC-PDA-ESI-ITMS(n)/TOF-MS). The determination method enabled the characterisation of sixteen bioactive components in C. fructus and quantification of three major coumarins, namely osthole, imperatorin and isopimpinellin. Response surface methodology (RSM) was employed to optimise the extraction parameters yielding the optimum conditions of ASE (extraction temperature 122 °C, extraction time 5 min and two static cycles). And the total contents of three major coumarins extracted by ASE under the optimum conditions was significantly higher than those by reflux and ultrasonic extraction (P<0.05) with better reproducibility. At last, the proposed method coupled with pattern recognition was applied to analysis of C. fructus from eight different regions in China.
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Using next-generation sequencing as a genetic diagnostic tool in rare autosomal recessive neurologic Mendelian disorders.
Neurobiol. Aging
PUBLISHED: 04-18-2013
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Next-generation sequencing was used to investigate 9 rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. Five probands with ataxia-telangectasia and 1 proband with chorea-acanthocytosis were analyzed by targeted gene sequencing. Whole-exome sequencing was used to investigate 3 affected individuals with Joubert syndrome, nemaline myopathy, or spastic ataxia Charlevoix-Saguenay type. A list of known and novel candidate variants was identified for each causative gene. All variants were genetically verified by Sanger sequencing or quantitative polymerase chain reaction with the strategy of disease segregation in related pedigrees and healthy controls. The advantages of using next-generation sequencing to diagnose rare autosomal recessive neurologic Mendelian disorders characterized by genetic and phenotypic heterogeneity are demonstrated. A genetic diagnostic strategy combining the use of targeted gene sequencing and whole-exome sequencing with the aid of next-generation sequencing platforms has shown great promise for improving the diagnosis of neurologic Mendelian disorders.
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Genome-wide association study of age at menarche in African-American women.
Hum. Mol. Genet.
PUBLISHED: 04-17-2013
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African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P < 5 × 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.
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Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-28-2013
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Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-?) and tumor necrosis factor-alpha (TNF-?). Moreover, the SalA pretreatment ameliorated the increases in NF-?B and in cleaved caspase-3 caused by ConA exposure. Whereas, the pretreatment completely reversed expression of the B-cell lymphoma-extra large (Bcl-xL). More importantly, the SalA pretreatment significantly increased the expression of SIRT1, a NAD(+)-dependent deacetylase, which was known to attenuate acute hypoxia damage and metabolic liver diseases. In our study, the increase in SIRT1 was closely associated with down-regulation of the p66 isoform (p66shc) of growth factor adapter Shc at both protein and mRNA levels. In HepG2 cell culture, SalA pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly reversed the decreased expression of p66shc, and attenuated SalA-induced p66shc down-regulation. Collectively, the present study indicated that SalA may be a potent activator of SIRT and that SalA can alleviate ConA-induced hepatitis through SIRT1-mediated repression of the p66shc pathway.
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Aggregation-induced emission (AIE) behavior and thermochromic luminescence properties of a new gold(I) complex.
Chem. Commun. (Camb.)
PUBLISHED: 03-26-2013
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A new gold complex that shows the AIE effect as well as the thermochromic fluorescence switch is reported. This interesting phenomenon is attributed to changes in the intermolecular Au???Au interactions and the formation of nano-aggregates.
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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.