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Find video protocols related to scientific articles indexed in Pubmed.
Intra-arterial delivery of human bone marrow mesenchymal stem cells is a safe and effective way to treat cerebral ischemia in rats.
Cell Transplant
PUBLISHED: 11-06-2014
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Cerebral ischemic stroke is a very common condition that can cause death and disability. Studies have confirmed that stem cells have therapeutic effects if administered after stroke. There is still a great deal of debate regarding the best route for cell transplantation. Intravascular delivery is the most commonly used one. In this study, the therapeutic effects of bone marrow stem cells (BMSCs) delivered by intra-arterial (IA) and intravenous (IV) injection in a rat transient middle cerebral artery occlusion model (MCAO) are compared. Histological analysis demonstrated that the IA route bypasses the pulmonary system and directs the cells to the ischemic parts of the brain more efficiently. The BMSCs delivered via the IA route promoted angiogenesis and improved functional recovery. The cerebral blood flow (CBF) of the rats was monitored during the IA injection process. No reduction in CBF or microstrokes was detected. Brain perfusion and metabolism, as evaluated by SPECT and PET, were better in rats treated with cells delivered via IA. Results showed that the IA route is a safe and effective way to transplant hBMSCs.This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
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[NK4 growth inhibition of human Raji lymphoma xenografts by competitive interrupting HGF/Met signal pathway].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 10-28-2014
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To observe the inhibition of NK4 protein in the proliferation of human Raji lymphoma xenografts in nude mice, and to explore its molecular mechanism.
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Superlattice assembly of graphene oxide (GO) and titania nanosheets: fabrication, in situ photocatalytic reduction of GO and highly improved carrier transport.
Nanoscale
PUBLISHED: 10-24-2014
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Two different kinds of two-dimensional (2D) materials, graphene oxide (GO) and titanium oxide nanosheets (Ti0.87O2(0.52-)), were self-assembled layer-by-layer using a polycation as a linker into a superlattice film. Successful construction of an alternate molecular assembly was confirmed by atomic force microscopy and UV-visible absorption spectroscopy as well as X-ray diffraction analysis. Exposure of the resulting film to UV light effectively promoted photocatalytic reduction of GO as well as decomposition of the polycation, which are due to their intimate molecular-level contact. The reduction completed within 3 hours, bringing about a decrease of the sheet resistance by ?10(6). This process provides a clean and mild route to reduced graphene oxide (rGO), showing advantages over other chemical and thermal reduction processes. A field-effect-transistor device was fabricated using the resulting superlattice assembly of rGO/Ti0.87O2(0.52-) as a channel material. The rGO in the film was found to work as a unipolar n-type conductor, which is in contrast to ambipolar or unipolar p-type behavior mostly reported for rGO films. This unique property may be associated with the electron doping effect from Ti0.87O2(0.52-) nanosheets. A significant improvement in the conductance and electron carrier mobility by more than one order of magnitude was revealed, which may be accounted for by the heteroassembly with Ti0.87O2(0.52-) nanosheets with a high dielectric constant as well as the better 2D structure of rGO produced via the soft photocatalytic reduction.
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Layered zinc hydroxide nanocones: synthesis, facile morphological and structural modification, and properties.
Nanoscale
PUBLISHED: 10-14-2014
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Layered zinc hydroxide nanocones intercalated with DS(-) have been synthesized for the first time via a convenient synthetic approach, using homogeneous precipitation in the presence of urea and sodium dodecyl sulfate (SDS). SDS plays a significant role in controlling the morphologies of as-synthesized samples. Conical samples intercalated with various anions were transformed through an anion-exchange route in ethanol solution, and the original conical structure was perfectly maintained. Additionally, these DS(-)-inserted nanocones can be transformed into square-like nanoplates in aqueous solution at room temperature, fulfilling the need for different morphology-dependent properties. Corresponding ZnO nanocones and nanoplates have been further obtained through the thermal calcination of NO3(-)-intercalating zinc hydroxide nanocones/nanoplates. These ZnO nanostructures with different morphologies exhibit promising photocatalytic properties.
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Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas.
Oncotarget
PUBLISHED: 10-04-2014
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The intrinsic signaling cascades and cell states associated with the Glioma CpG Island Methylator Phenotype (G-CIMP) remain poorly understood. Using published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling using three independent datasets, including the Chinese Glioma Genome Atlas(CGGA; n=155), the REMBRANDT dataset (n=288), and The Cancer Genome Atlas (TCGA; n=406). Additionally, an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (p<0.001), indicating suppressed EGFR signaling. Analysis of TCGA glioblastomas revealed that G-CIMP+ glioblastomas harbored lowered mRNA levels for EGFR and H-Ras. Induction of G-CIMP+ state by exogenous expression of a mutated isocitrate dehydrogenase 1, IDH1-R132H, suppressed EGFR and H-Ras protein expression as well as pERK accumulation in independent glioblastoma models. These suppressions were associated with increased deposition of the repressive histone markers, H3K9me3 and H3K27me3, in the EGFR and H-Ras promoter regions. The IDH1-R132H expression-induced pERK suppression can be reversed by exogenous expression of H-RasG12V. Finally, the G-CIMP+ Ink4a-Arf-/- EGFRvIII glioblastoma line was more resistant to the EGFR inhibitor, Gefitinib, relative to its isogenic G-CIMP- counterpart. These results suggest that G-CIMP epigenetically regulates EGFR signaling and serves as a predictive biomarker for EGFR inhibitors in glioblastoma patients.
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[Pathological mechanisms of chronic insomnia: Evidence from neuro-electrophysiology and neuroimaging research].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-02-2014
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As a widely recognized public health problem as well as prevalent and challenging to modern society, chronic insomnia is involved in wide brain areas (such as prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and thalamus) and emotion-cognition neuro-circuit. It is closely related to the conditioned hyperarousal and the increased information process and/or the impaired inhibitory ability to withdraw from awaking state. Thus, some specific abnormal mode may exist in the emotion-cognition circuit, which is associated with abnormal cognition load, such as repeated retrieval/intrusion of aversive memories during night. Studies through the combination of multiple techniques including psychology, electrophysiology and neuroimaging methods are needed to further enhance the understanding of chronic insomnia.
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Cerebral infarction caused by pituitary apoplexy: case report and review of literature.
Turk Neurosurg
PUBLISHED: 10-01-2014
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Pituitary apoplexy followed by cerebral infarction is rare. In this report, we present a 42-year-old man who had been diagnosed of pituitary adenoma presented with a sudden onset of unconsciousness, left hemiplegia and right ptosis. Investigations revealed the development of pituitary apoplexy. The extension of tumor mass compressed the supraclinoid portion of the right internal carotid artery, resulting in the cerebral infarction in the right anterior and middle cerebral artery territory. Left anterior cerebral artery territory infarction was also found, which could be caused by vasospasm provoked by pituitary apoplexy. The patient underwent decompression surgery via transsphenoidal approach after four weeks' conservative treatment, and pathological examination revealed hemorrhage and necrosis of the pituitary adenoma. His symptoms improved within five months' follow-up. Since pituitary apoplexy producing cerebral infarction is rare, clinicians should be alert to that possibility, and delayed transsphenoidal surgery following conservative management with steroids is the appropriate management of such an occurrence.
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Nuclear Protein C23 on the Cell Surface Plays an Important Role in Activation of CXCR4 Signaling in Glioblastoma.
Mol. Neurobiol.
PUBLISHED: 09-29-2014
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The chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 (SDF-1) plays an important role in tumor progression and are associated with angiogenesis. Meanwhile, the implications of C23 in multiple signaling pathways have been also investigated. However, the effects of C23 on CXCR4 pathway in glioblastoma are not fully characterized. In the present study, C23 and CXCR4 of U87 cell line were inhibited by anti-C23 and anti-CXCR4 antibodies, respectively; and then C23 and CXCR4 siRNAs were used to knock down endogenous C23 and CXCR4, respectively. In addition, MTT assay was also introduced. Our data showed that either anti-C23 or anti-CXCR4 antibodies efficaciously repressed the phosphorylation levels of ERK (p?
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Highly efficient genome editing via 2A-coupled co-expression of two TALEN monomers.
BMC Res Notes
PUBLISHED: 09-04-2014
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Transcription activator-like effector nucleases (TALENs) are a useful tool for targeted gene editing. TALEN monomers are traditionally expressed from two different plasmids. Each encodes a different TALEN arm that binds to a user-defined sequence and mediates gene editing. Expression of TALEN monomers in two separate plasmids requires co-delivery of each plasmid to the cell. Efficacy of gene editing may be increased if each monomer was transcribed from the same reading frame.
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The Downregulation of MicroRNA-146a Modulates TGF-? Signaling Pathways Activity in Glioblastoma.
Mol. Neurobiol.
PUBLISHED: 08-24-2014
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Transforming growth factor-? (TGF-?) is considered to be one of the main factors responsible for glioblastoma tumorigenesis. MicroRNAs have recently been shown to regulate cell proliferation, differentiation, and apoptosis. However, the involvement of miRNA-146a in TGF-?1-induced glioblastoma development remains largely unknown. Here, miRNA-164a transfection was used to overexpress miRNA-164a in U87, and then real-time quantitative PCR and Western blot were applied to detect the gene transcription and protein expression. In addition, MTT and wound healing assay were also used to observe cell proliferation and migration. Our data revealed that miRNA-146a was downregulated by TGF-?1 treatment, but upregulated by miRNA-164a transfection. MiRNA-146a overexpression significantly reduced SMAD4 protein expression instead of p-SMAD2. Besides, miRNA-146a overexpression also decreased the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9 as well as the p-ERK1/2 level. Furthermore, the upregulation of miRNA-146a suppressed TGF-?1-mediated U87 proliferation and migration. These results demonstrate that miRNA-146a acts as a novel regulator to modulate the activity and transduction of TGF-? signaling pathways in glioblastoma, and the downregulation of miRNA-146a is required for overexpression of EGFR and MMP9, which can be considered an efficiently therapeutic target and a better understanding of glioblastoma pathogenesis.
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The Clinical Implications of Chemokine Receptor CXCR4 in Grade and Prognosis of Glioma Patients: A Meta-Analysis.
Mol. Neurobiol.
PUBLISHED: 08-20-2014
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Chemokine receptor CXCR4 has been identified to affect glioma progression by dominating cancer cell survival, proliferation, and migration in vitro recently. However, the implications and utilities of CXCR4 in clinical grade and prognosis were rarely reported. Thus, it is essential to carry out a meta-analysis to draw a convincing conclusion. The relevant articles were included through careful assessment, and then, odds ratios (ORs), standard mean differences (SMDs), and hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were estimated. Heterogeneity and funnel plots evaluation were conducted. In this meta-analysis, all 13 eligible studies involving 785 patients were included and conducted in China. Ten studies revealed altered CXCR4 expression in glioma tissues was closely associated with high WHO grade (III?+?IV) (n?=?10, OR 5.46, 95 % CI 3.81-7.84; p?=?0.000); besides, six studies also demonstrated CXCR4 expression intensity extremely correlated to high grade (n?=?6, SMD -2.45, 95 % CI -2.78, -2.12; p?=?0.000). Most importantly, three articles identified that CXCR4 expression significantly correlated to 3-year overall survival (OS) (HR 7.32, 95 % CI 4.16-12.90; p?=?0.000) in glioma patients. No heterogeneity and publication bias were observed across all studies. Taken together, this meta-analysis suggests CXCR4 expression in gliomas can be recommended as evidence of WHO grade and indeed predict 3-year overall survival. We also provided a scientific rationale for clinically pathological detection of CXCR4 that is required for treatment of glioma patients.
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Identifying the Association Between Alzheimer's Disease and Parkinson's Disease Using Genome-Wide Association Studies and Protein-Protein Interaction Network.
Mol. Neurobiol.
PUBLISHED: 08-18-2014
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Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative diseases in the elderly. Shared clinical and pathological features have been reported. Recent large-scale genome-wide association studies (GWAS) have been conducted and reported a number of AD and PD variants. Until now, the underlying genetic mechanisms for all these newly identified PD variants as well as the association between AD and PD are still unclear exactly. We think that PD variants may contribute to AD and PD by influence on brain gene expression. Here, we conducted a systems analysis using (1) AD and PD variants (P?
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Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates.
Int. J. Toxicol.
PUBLISHED: 08-17-2014
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The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.
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Fabrication of nickel-foam-supported layered zinc-cobalt hydroxide nanoflakes for high electrochemical performance in supercapacitors.
Chem. Commun. (Camb.)
PUBLISHED: 08-12-2014
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Nickel foam supported Zn-Co hydroxide nanoflakes were fabricated by a facile solvothermal method. Benefited from the unique structure of Zn-Co hydroxide nanoflakes on a nickel foam substrate, the as prepared materials exhibited an excellent specific capacitance of 901 F g(-1) at 5 A g(-1) and remarkable cycling stability as electrode materials in supercapacitors.
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Electron-Acceptor-Dependent Light Absorption, Excited-State Relaxation, and Charge Generation in Triphenylamine Dye-Sensitized Solar Cells.
ChemSusChem
PUBLISHED: 08-07-2014
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By choosing a simple triphenylamine electron donor, we herein compare the influence of electron acceptors benzothiadiazole benzoic acid (BTBA) and cyanoacrylic acid (CA), on energy levels, light absorption, and dynamics of excited-state evolution and electron injection. DFT and time-dependent DFT calculations disclosed remarkable intramolecular conformational changes for the excited states of these two donor-acceptor dyes. Photoinduced dihedral angle variation occurs to the triphenylamine unit in the CA dye and backbone planarization happens to conjugated aromatic blocks in the BTBA dye. Femtosecond spectroscopic measurements suggested the crucial role of having a long excited-state lifetime in maintaining a high electron-injection yield because a reduced driving force for a low energy-gap dye can result in slower electron-injection dynamics.
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Tetrabutylphosphonium ions as a new swelling/delamination agent for layered compounds.
Chem. Commun. (Camb.)
PUBLISHED: 07-19-2014
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The swelling and exfoliation behavior of protonated layered oxides using an organo-phosphonium base, tetrabutylphosphonium hydroxide (TBPOH), was examined for the first time. The action of the aqueous solution induced massive interlayer expansion up to ~100-fold. The swollen crystals were immediately broken and completely exfoliated into unilamellar nanosheets in 1-2 h by shaking.
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The Impact of Survivin on Prognosis and Clinicopathology of Glioma Patients: A Systematic Meta-Analysis.
Mol. Neurobiol.
PUBLISHED: 06-26-2014
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Up to now, survivin has been recommended as a prognostic and diagnostic indicator in glioma patients. However, there are still many controversies. Here, a meta-analysis was conducted to draw a more definitive conclusion on the correlation of survivin with overall survival (OS), age, gender, and WHO grade. Eligible studies were available through careful assessment, and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots were introduced to evaluate the publication bias. Additionally, heterogeneity and sensitivity were also evaluated. In the present meta-analysis, 15 eligible studies with a total of 1,089 patients were incorporated. Survivin expression in gliomas correlated with 2-year OS (n?=?8; HR 0.17, 95 % CI 0.11-0.26) and 5-year OS (n?=?7; HR 0.12, 95 % CI 0.07-0.22) in patients. In addition, a fixed-effect model revealed a significant association between survivin and age (male/+; OR 2.10, 95 % CI 1.44-3.05) and survivin and WHO grade (I+II/+; OR 0.27, 95 % CI 0.19-0.38). No heterogeneity was observed across all studies. According to Begg's and Egger's test and funnel plot, no publication bias was reported. Taken together, our meta-analysis suggests that survivin expression is associated with poor survival, older age, and higher WHO grade and could be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target.
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Cell Surface Protein C23 Affects EGF-EGFR Induced Activation of ERK and PI3K-AKT Pathways.
J. Mol. Neurosci.
PUBLISHED: 06-26-2014
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The epidermal growth factor (EGF) pathway has been reported as canonical causes in cancer development. Meanwhile, the involvement of C23 in multiple signaling pathways has been also investigated (Lv et al., 2014). However, the effect of C23 on EGF pathway in glioblastoma is not fully characterized. In the present study, C23 and the epidermal growth factor receptor (EGFR) of U251 cell line were inhibited by C23 and EGFR antibodies, respectively; and then C23 and EGFR siRNAs were used to knock down endogenous C23 and EGFR, respectively. In addition, soft-agar and MTT assay were also introduced. Compared with control, either C23 or EGFR antibodies efficiently repressed the phosphorylation levels of ERK1/2 (p?
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Nerve Regeneration and Functional Recovery by Collagen-Binding Brain-Derived Neurotrophic Factor in an Intracerebral Hemorrhage Model.
Tissue Eng Part A
PUBLISHED: 06-20-2014
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Brain-derived neurotrophic factor (BDNF) exerts therapeutic effects following intracerebral hemorrhage (ICH). However, it is difficult to maintain sufficient concentrations in the hemorrhage hemisphere. We demonstrated previously that BDNF fused to a collagen-binding domain (CBD) could bind to collagen in the ventricular ependyma and stimulate cell proliferation in the subventricular zone (SVZ). In this study, we verified the therapeutic effects of CBD-BDNF in the rat ICH model induced by bacterial collagenase by injecting CBD-BDNF into the lateral ventricle of ICH rats. The results demonstrated that CBD-BDNF was retained at high levels in the hemorrhage hemisphere, where it promoted neural regeneration and angiogenesis, reduced tissue loss, and improved functional recovery.
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Improvement in Diagnosis of Metastatic Pituitary Carcinoma by 68Ga DOTATATE PET/CT.
Clin Nucl Med
PUBLISHED: 05-31-2014
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Pituitary carcinoma is a rare disease with a challenge in both diagnosis and treatment. A 50-year-old female patient who underwent transsphenoidal resection of a pituitary tumor experienced progressive headache. For the evaluation, Ga DOTATATE PET/CT was used and compared with F-FDG PET/CT and enhanced MRI. Multiple lesions were detected by Ga DOTATATE PET/CT at the cerebral cortex, cerebellum, and cerebellopontine angle with a higher contrast than F-FDG PET/CT and enhanced MRI. With a biopsy, the patient was diagnosed as metastatic pituitary carcinoma. Moreover, it thus presents potential therapeutic implications on molecular-targeted therapy using somatostatin analogs and peptide receptor radionuclide therapy targeting the somatostatin receptors.
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Comparison of (68)Ga DOTATATE to 18F-FDG uptake is useful in the differentiation of residual or recurrent pituitary adenoma from the remaining pituitary tissue after transsphenoidal adenomectomy.
Clin Nucl Med
PUBLISHED: 05-31-2014
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The evaluation of the remaining pituitary tissue and recurrent or residual tumor after the pituitary adenoma resection is difficult. However, it is essential to assess the size of the recurrent tumor and remaining pituitary reserve before resurgery. This study aimed to distinguish the remaining pituitary tissue from pituitary adenoma with Ga 1,4,7,10-tetraazacyclododecane-N,N',N?,N?'-tetraacetic acid-D-Phe,Tyr3-octreotate (DOTATATE) and F-FDG PET imaging in patients status post transsphenoidal adenomectomy.
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Land-use suitability analysis for urban development in Beijing.
J. Environ. Manage.
PUBLISHED: 05-29-2014
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Land-use suitability analyses are of considerable use in the planning of mega-cities. An Urban Development Land-use Suitability Mapping (UDLSM) approach has been constructed, based on opportunity and constraint criteria. Two Multi-criteria Evaluation (MCE) methods, the Ideal Point Method (IPM) and Ordered Weighted Averaging (OWA), were used to generate the opportunity map. The protection map was obtained by means of constraint criteria, utilizing the Boolean union operator. A suitability map was then generated by overlaying the opportunity and protection maps. By applying the UDLSM approach to Beijing, its urban development land-use suitability was mapped, and a sensitivity analysis undertaken to examine the robustness of the proposed approach. Indirect validation was achieved by mutual comparisons of suitability maps resulting from the two MCE methods, where the overall agreement of 91% and kappa coefficient of 0.78 indicated that both methods provide very similar spatial land-use suitability distributions. The suitability level decreases from central Beijing to its periphery, and the area classed as suitable amounts to 28% of the total area. Leading attributes of each opportunity factor for suitability were revealed, with 2256 km(2), i.e. 70%, of existing development land being overlaid by suitable areas in Beijing. Conflicting parcels of land were identified by overlaying the resultant map with two previous development blueprints for Beijing. The paper includes several recommendations aimed at improving the long-term urban development plans for Beijing.
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[Expression level of SET gene in acute myeloid leukemia and its clinical significance].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-27-2014
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To investigate the expression level of SET gene in patients with acute myeloid leukemia (AML) and evaluate its significance.
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The complete mitochondrial genome of the Vibrissaphora boringii (Anura: Megophryidae).
Mitochondrial DNA
PUBLISHED: 05-21-2014
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Abstract Vibrissaphora boringii (Anura: Megophryidae) is an endemic precious species of China. In this paper, we determined the complete nucleotide sequence of the mitochondrial genome of the V. boringii. The entire mtDNA sequence was 17,085?bp in length, which contained 13 protein-coding genes, 2 rRNA genes, 23 tRNA genes and 1 displacement loop (D-loop). The base composition was 27.7% A, 25.5% C, 15.4% G and 31.5% T, with a much higher A?+?T content. Except for eight tRNAs and nd6 genes, all other mitochondrial genes were encoded on the heavy strand (H-strand). Molecular data presented here provide a useful tool for resolving phylogenetic and genetic problems related to this species.
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Intramedullary spinal cord metastasis of renal cell carcinoma 6 years following the nephrectomy.
Turk Neurosurg
PUBLISHED: 05-17-2014
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Intramedullary spinal cord metastasis is an uncommon manifestation of systemic tumor. We present a case of metastatic mass inside the thoracic spinal cord 6 years after nephrectomy because of renal cell carcinoma. The parenchymal lesion was resected totally and the histologic examination confirmed it as renal cell carcinoma metastasis. The patient's neurological function improved apparently until the intramedullary spinal cord metastasis recurred in situ later. The case shows that renal cell carcinoma has the possibility of metastasis into spinal cord even several years after nephrectomy. Any symptom of neurological deficit should alert to a possible intramedullary spinal cord metastasis.
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Layered rare earth hydroxides (LREHs): synthesis and structure characterization towards multifunctionality.
Dalton Trans
PUBLISHED: 05-14-2014
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Layered rare earth hydroxides (LREHs) represent a new family of layered host compounds that integrate attractive physicochemical properties of rare earth elements with the wide tunability of guest anions. The compounds have attracted significant research attention, and potential applications have been found in various fields such as optics, catalysis, bio-medicine and so on. In this perspective, we describe our recent progress in the synthesis, structure characterization, and development of functionalities of the LREH compounds. A unique homogeneous alkalization method, in which RE ions are precipitated from a solution containing RE salt, concentrated target anions and hexamethylenetetramine, has been employed to effectively produce highly crystalline LREH samples. A range of anionic forms including chloride-, nitrate-, sulfate- and organodisulfonate-series, have been synthesized and structurally characterized. Two types of cationic rare earth hydroxide layers, {[RE2(OH)5(H2O)2](+)}? for the chloride- and nitrate-series and {[RE(OH)2(H2O)](+)}? for the sulfate- and organodisulfonate-series, are classified. Unique dehydration/rehydration behaviors or thermal phase evolution of the LREH compounds have been revealed and discussed in relation to the crystal structures. An outlook for potential applications of LREH compounds as anion exchangers, precursors to unique functional oxides, and optical phosphors is described.
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SMOQ: a tool for predicting the absolute residue-specific quality of a single protein model with support vector machines.
BMC Bioinformatics
PUBLISHED: 04-15-2014
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It is important to predict the quality of a protein structural model before its native structure is known. The method that can predict the absolute local quality of individual residues in a single protein model is rare, yet particularly needed for using, ranking and refining protein models.
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Designing and evaluating the MULTICOM protein local and global model quality prediction methods in the CASP10 experiment.
BMC Struct. Biol.
PUBLISHED: 04-01-2014
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Protein model quality assessment is an essential component of generating and using protein structural models. During the Tenth Critical Assessment of Techniques for Protein Structure Prediction (CASP10), we developed and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM-NOVEL, and MULTICOM-CONSTRUCT) that predicted both local and global quality of protein structural models.
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Gigantic swelling of inorganic layered materials: a bridge to molecularly thin two-dimensional nanosheets.
J. Am. Chem. Soc.
PUBLISHED: 03-31-2014
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Platy microcrystals of a typical layered material, protonated titanate, have been shown to undergo an enormous degree of swelling in aqueous solutions of various amines, including tertiary amines, quaternary ammonium hydroxides, and primary amines. Introducing these solutions expanded the crystal gallery height by up to ~100-fold. Through systematic analysis, we determined that ammonium ion intercalation is predominantly affected by the acid-base equilibrium and that the degree of swelling or inflow of H2O is controlled by the osmotic pressure balance between the gallery and the solution environment, both of which are relatively independent of electrolyte identity but substantially dependent on molarity. In solutions of tertiary amines and quaternary ammonium hydroxides, the uptake of ammonium ions increases nearly linearly with increasing external concentration before reaching a saturation plateau, i.e., ~40% relative to the cation-exchange capacity of the crystals used. The only exception is tetrabutylammonium ions, which yield a lower saturation value, ~30%, owing to steric effects. The swelling behaviors in some primary amine solutions differ as a result of the effect of attractive forces between amine solute molecules on the solution osmotic pressure. Although the swelling is essentially colligative in nature, the stability of the resultant swollen structure is heavily dependent on the chemical nature of the guest ions. Intercalated ions of higher polarity and smaller size help stabilize the swollen structure, whereas ions of lower polarity and larger size lead readily to exfoliation. The insight gained from this study sheds new light on both the incorporation of guest molecules into a gallery of layered structures in general and the exfoliation of materials into elementary single-layer nanosheets.
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The distribution of transplanted human mesenchymal stem cells in the CNS of young Macaca fascicularis.
Brain Res.
PUBLISHED: 03-14-2014
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Mesenchymal stem cell (MSC)-based therapies have generated much hope and promise as a potential source of cells for cell-based therapeutic strategies in pediatric degenerative diseases. However, the distribution and migratory routes of MSCs are unknown. Here, real-time PCR and microscopy were used to observe the migration and distribution of labeled human MSCs (hMSCs) transplanted into the striatum of young Macaca fascicularis. Moreover, the differentiation of hMSCs was also detected using immunofluorescence. We found that hMSCs were mainly located near the injection site in the brain and in the anterior brain after 2 weeks. After 4 weeks, the hMSCs had dispersed and could be detected in each brain slice and were more uniformly distributed than after 2 weeks. The hMSCs showed a preference for migration towards blood vessels, which may be one of the migratory routes used by hMSCs. Additionally, hMSCs could be observed to give rise to NeuN- and GFAP-positive cells. Transplanted hMSCs also increased the expression levels of N-cadherin in the host brain tissue, which may be one factor that drives the migration and differentiation of hMSCs after transplantation. These results provide preclinical evidence that MSC-based therapies may represent an efficacious alternative to more conventional treatment regimens for a variety of pediatric neurologic disorders.
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The intracellular Ca(2+) channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy.
Nat. Med.
PUBLISHED: 03-05-2014
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The integrity of the plasma membrane is maintained through an active repair process, especially in skeletal and cardiac muscle cells, in which contraction-induced mechanical damage frequently occurs in vivo. Muscular dystrophies (MDs) are a group of muscle diseases characterized by skeletal muscle wasting and weakness. An important cause of these group of diseases is defective repair of sarcolemmal injuries, which normally requires Ca(2+) sensor proteins and Ca(2+)-dependent delivery of intracellular vesicles to the sites of injury. MCOLN1 (also known as TRPML1, ML1) is an endosomal and lysosomal Ca(2+) channel whose human mutations cause mucolipidosis IV (ML4), a neurodegenerative disease with motor disabilities. Here we report that ML1-null mice develop a primary, early-onset MD independent of neural degeneration. Although the dystrophin-glycoprotein complex and the known membrane repair proteins are expressed normally, membrane resealing was defective in ML1-null muscle fibers and also upon acute and pharmacological inhibition of ML1 channel activity or vesicular Ca(2+) release. Injury facilitated the trafficking and exocytosis of vesicles by upmodulating ML1 channel activity. In the dystrophic mdx mouse model, overexpression of ML1 decreased muscle pathology. Collectively, our data have identified an intracellular Ca(2+) channel that regulates membrane repair in skeletal muscle via Ca(2+)-dependent vesicle exocytosis.
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The MULTICOM protein tertiary structure prediction system.
Methods Mol. Biol.
PUBLISHED: 02-28-2014
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With the expansion of genomics and proteomics data aided by the rapid progress of next-generation sequencing technologies, computational prediction of protein three-dimensional structure is an essential part of modern structural genomics initiatives. Prediction of protein structure through understanding of the theories behind protein sequence-structure relationship, however, remains one of the most challenging problems in contemporary life sciences. Here, we describe MULTICOM, a multi-level combination technique, intended to predict moderate- to high-resolution structure of a protein through a novel approach of combining multiple sources of complementary information derived from the experimentally solved protein structures in the Protein Data Bank. The MULTICOM web server is freely available at http://sysbio.rnet.missouri.edu/multicom_toolbox/.
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All-nanosheet ultrathin capacitors assembled layer-by-layer via solution-based processes.
ACS Nano
PUBLISHED: 02-19-2014
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All-nanosheet ultrathin capacitors of Ru0.95O20.2-/Ca2Nb3O10-/Ru0.95O20.2- were successfully assembled through facile room-temperature solution-based processes. As a bottom electrode, conductive Ru0.95O20.2- nanosheets were first assembled on a quartz glass substrate through a sequential adsorption process with polycations. On top of the Ru0.95O20.2- nanosheet film, Ca2Nb3O10- nanosheets were deposited by the Langmuir-Blodgett technique to serve as a dielectric layer. Deposition parameters were optimized for each process to construct a densely packed multilayer structure. The multilayer buildup process was monitored by various characterizations such as atomic force microscopy (AFM), ultraviolet-visible absorption spectra, and X-ray diffraction data, which provided compelling evidence for regular growth of Ru0.95O20.2- and Ca2Nb3O10- nanosheet films with the designed multilayer structures. Finally, an array of circular films (50 ?m ?) of Ru0.95O20.2- nanosheets was fabricated as top electrodes on the as-deposited nanosheet films by combining the standard photolithography and sequential adsorption processes. Microscopic observations by AFM and cross-sectional transmission electron microscopy, as well as nanoscopic elemental analysis, visualized the sandwich metal-insulator-metal structure of Ru0.95O20.2-/Ca2Nb3O10-/Ru0.95O20.2- with a total thickness less than 30 nm. Electrical measurements indicate that the system really works as an ultrathin capacitor, achieving a capacitance density of ?27.5 ?F cm(-2), which is far superior to currently available commercial capacitor devices. This work demonstrates the great potential of functional oxide nanosheets as components for nanoelectronics, thus contributing to the development of next-generation high-performance electronic devices.
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The complete mitochondrial genome of the Elaphe perlacea (Squamata: Colubridae).
Mitochondrial DNA
PUBLISHED: 01-21-2014
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Abstract The Pearl-banded rat-snake Elaphe perlacea (recently renamed Euprepiophis perlacea) belongs to the family Colubridae, and is only distributed in western Sichuan Province, China. In this study, the whole mitochondrial genome of E. perlacea was first sequenced. It was determined to be 17,160?bp and included 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 control regions (D-loop). Except for eight tRNAs and nd6 genes, all other mitochondrial genes were encoded on the heavy strand (H strand). Molecular data presented here provide a useful tool for helping set the stage for further studies and the molecular evolution of the mitochondrial genome.
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The association of CXCR4 expression with prognosis and clinicopathological indicators in colorectal carcinoma patients: a meta-analysis.
Histopathology
PUBLISHED: 01-15-2014
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The clinical relevance of expression of chemokine receptor 4 (CXCR4) in colorectal carcinoma (CRC) remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features.
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Pituitary abscess following transsphenoidal surgery: the experience of 12 cases from a single institution.
Clin Neurol Neurosurg
PUBLISHED: 01-06-2014
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To explore possible reasons for the incidence of a pituitary abscess following transsphenoidal surgery and determine the most effective treatment.
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Molecular-scale heteroassembly of redoxable hydroxide nanosheets and conductive graphene into superlattice composites for high-performance supercapacitors.
Adv. Mater. Weinheim
PUBLISHED: 01-05-2014
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Artificial superlattice nanocomposites are successfully prepared by electrostatic heteroassembly of redoxable Co-Al or Co-Ni layered double hydroxide (LDH) nanosheets with graphene. The superlattice electrodes exhibit a high capacity up to ca. 650 F/g, which is approximately 6 times that of pure graphene. The composites are found to be capable of superfast charging and discharging, up to ca. 100 Hz, comparable with the high-power performance of graphene electrodes.
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Application of (68)Ga-PRGD2 PET/CT for ?v?3-integrin imaging of myocardial infarction and stroke.
Theranostics
PUBLISHED: 01-01-2014
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Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of ?v?3-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed (68)Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 ((68)Ga-PRGD2) to evaluate the ?v?3-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT).
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Anoctamin 6 regulates C2C12 myoblast proliferation.
PLoS ONE
PUBLISHED: 01-01-2014
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Anoctamin 6 (Ano6) belongs to a conserved gene family (TMEM16) predicted to code for eight transmembrane proteins with putative Ca2+-activated chloride channel (CaCC) activity. Recent work revealed that disruption of ANO6 leads to a blood coagulation defect and impaired skeletal development. However, its function in skeletal muscle cells remains to be determined. By using a RNA interference mediated (RNAi) loss-of-function approach, we show that Ano6 regulates C2C12 myoblast proliferation. Ano6 is highly expressed in C2C12 myoblasts and its expression decreases upon differentiation. Knocking down Ano6 significantly reduces C2C12 myoblast proliferation but has minimal effect on differentiation. Ano6 deficiency significantly reduces ERK/AKT phosphorylation, which has been shown to be involved in regulation of cancer cell proliferation by another Anoctamin member. Taken together, our data demonstrate for the first time that Ano6 plays an essential role in C2C12 myoblast proliferation, likely via regulating the ERK/AKT signaling pathway.
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Anatomical analysis on the lateral bone window of the sella turcica: a study on 530 adult dry skull base specimens.
Int J Med Sci
PUBLISHED: 01-01-2014
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To investigate the morphometric characteristics of the lateral bone window (LBW) of the sella turica.
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Transsphenoidal approach for pituitary adenomas in patients with McCune-Albright syndrome.
Pituitary
PUBLISHED: 12-25-2013
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The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.
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N-Annulated Perylene as An Efficient Electron Donor for Porphyrin-Based Dyes: Enhanced Light-Harvesting Ability and High-Efficiency Co(II/III)-Based Dye-Sensitized Solar Cells.
J. Am. Chem. Soc.
PUBLISHED: 12-24-2013
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Porphyrin-based dyes recently have become good candidates for dye-sensitized solar cells (DSCs). However, the bottleneck is how to further improve their light-harvesting ability. In this work, N-annulated perylene (NP) was used to functionalize the Zn-porphyrin, and four "push-pull"-type NP-substituted and fused porphyrin dyes with intense absorption in the visible and even in the near-infrared (NIR) region were synthesized. Co(II/III)-based DSC device characterizations revealed that dyes WW-5 and WW-6, in which an ethynylene spacer is incorporated between the NP and porphyrin core, showed pantochromatic photon-to-current conversion efficiency action spectra in the visible and NIR region, with a further red-shift of about 90 and 60 nm, respectively, compared to the benchmark molecule YD2-o-C8. As a result, the short-circuit current density was largely increased, and the devices displayed power conversion efficiencies as high as 10.3% and 10.5%, respectively, which is comparable to that of the YD2-o-C8 cell (? = 10.5%) under the same conditions. On the other hand, the dye WW-3 in which the NP unit is directly attached to the porphyrin core showed a moderate power conversion efficiency (? = 5.6%) due to the inefficient ?-conjugation, and the NP-fused dye WW-4 exhibited even poorer performance due to its low-lying LUMO energy level and nondisjointed HOMO/LUMO profile. Our detailed physical measurements (optical and electrochemical), density functional theory calculations, and photovoltaic characterizations disclosed that the energy level alignment, the molecular orbital profile, and dye aggregation all played very important roles on the interface electron transfer and charge recombination kinetics.
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Altering the Self-organization of Dyes on Titania with Dyeing Solvents to Tune the Charge-transfer Dynamics of Sensitized Solar Cells.
Chemphyschem
PUBLISHED: 10-31-2013
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Herein we selected the model organic donor-acceptor dye C218 and modulated the self-organization of dye molecules on the surface of titania by changing the dyeing solvent from chlorobenzene to a mixture of acetonitrile and tert-butanol. We further unveiled the relationship between the microstructure of a dye layer and the multichannel charge-transfer dynamics that underlie the photovoltaic performance of dye-sensitized solar cells.
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Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities.
Peptides
PUBLISHED: 10-04-2013
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In view of the recent findings of stimulatory effects of GHRH analogs, JI-34, JI-36 and JI-38, on cardiomyocytes, pancreatic islets and wound healing, three series of new analogs of GHRH(1-29) have been synthesized and evaluated biologically in an endeavor to produce more potent compounds. "Agmatine analogs", MR-356 (N-Me-Tyr(1)-JI-38), MR-361(N-Me-Tyr(1), D-Ala(2)-JI-38) and MR-367(N-Me-Tyr(1), D-Ala(2), Asn(8)-JI-38), in which Dat in JI-38 is replaced by N-Me-Tyr(1), showed improved relative potencies on GH release upon subcutaneous administration in vivo and binding in vitro. Modification with N-Me-Tyr(1) and Arg(29)-NHCH3 as in MR-403 (N-Me-Tyr(1), D-Ala(2), Arg(29)-NHCH3- JI-38), MR-406 (N-Me-Tyr(1), Arg(29)-NHCH3- JI-38) and MR-409 (N-Me-Tyr(1), D-Ala(2), Asn(8), Arg(29)-NHCH3- JI-38), and MR-410 (N-Me-Tyr(1), D-Ala(2), Thr(8), Arg(29)-NHCH3- JI-38) resulted in dramatically increased endocrine activities. These appear to be the most potent GHRH agonistic analogs so far developed. Analogs with Apa(30)-NH2 such as MR-326 (N-Me-Tyr(1), D-Ala(2), Arg(29), Apa(30)-NH2-JI-38), and with Gab(30)-NH2, as MR-502 (D-Ala(2), 5F-Phe(6), Ser(28), Arg(29),Gab(30)-NH2-JI-38) also exhibited much higher potency than JI-38 upon i.v. administration. The relationship between the GH-releasing potency and the analog structure is discussed. Fourteen GHRH agonists with the highest endocrine potencies were subjected to cardiologic tests. MR-409 and MR-356 exhibited higher potency than JI-38 in activating myocardial repair in rats with induced myocardial infarction. As the previous class of analogs, exemplified by JI-38, had shown promising results in multiple fields including cardiology, diabetes and wound healing, our new, more potent, GHRH agonists should manifest additional efficacy for possible medical applications.
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Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury.
J Transl Med
PUBLISHED: 09-15-2013
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This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation).
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Visual field improvement after pituitary tumor surgery in patients with McCune-Albright syndrome.
J Neuroophthalmol
PUBLISHED: 08-10-2013
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McCune-Albright syndrome (MAS) is a rare, sporadic congenital disorder, in which optic neuropathy may cause devastating visual consequences. Pituitary adenoma with overproduction of growth hormone (GH) is present in approximately two-thirds of MAS patients, and its role in the pathogenesis of MAS-associated optic neuropathy has not been studied.
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Nickel Dichalcogenide Hollow Spheres: Controllable Fabrication, Structural Modification, and Magnetic Properties.
Chemistry
PUBLISHED: 07-12-2013
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Magnetize your chemistry! A facile hydrothermal synthetic route was developed for the synthesis of uniform NiS2 hollow spheres, which could be transformed into NiSe2 and NiTe2 hollow spheres through a chemical conversion process. Furthermore, NiS and NiO hollow spheres could be selectively obtained by calcination of NiS2 hollow spheres at different temperatures.
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siRNA-mediated knockdown of SMC1A expression suppresses the proliferation of glioblastoma cells.
Mol. Cell. Biochem.
PUBLISHED: 05-24-2013
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SMC1A is a member of cohesin complex which has essential functions in cell cycle progression and DNA repair. Therefore, we choose SMC1A as a target gene therapy of glioblastoma. It is well known that glioblastoma has very low survival rate because of ineffectiveness of conventional treatments. This study was designed to explore the possibilities of small interfering RNA (siRNA)-mediated SMC1A silencing as alternative method of treatment. We found that the lentivirus-mediated RNAi system efficiently decreased the expression level of SMC1A. Inhibiting SMC1A expression efficiently (P < 0.001) resulted in inhibiting the proliferation and colony formation of U251 and U87MG cells. Moreover, we found that SMC1A silencing led to S cell-cycle arresting. Collectively, these results demonstrated the possibility of siRNA-mediated silencing of SMC1A as a therapeutic tool for the treatment of glioblastoma.
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Combined 18F-FDG PET/CT and 99mTc 3PRGD2 SPECT/CT imaging in a case of pituitary metastases.
Clin Nucl Med
PUBLISHED: 05-10-2013
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We compare F-FDG PET/CT and 99mTc 3PRGD2 SPECT/CT scans in a case of histologically proved pituitary metastases. The ratio of tumor to cerebellum (T/C) of 99mTc 3PRGD2 SPECT is much higher than that for 18F-FDG PET. We then conduct the same scans for a pituitary adenoma patient for better comparison. The T/C of 18F-FDG is not able to differentiate pituitary metastases from pituitary adenoma. However, The T/C of 99mTc 3PRGD2 observed in pituitary metastases was higher than that in pituitary adenoma.
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Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation.
Immunity
PUBLISHED: 05-03-2013
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Nlrp3 inflammasome activation occurs in response to numerous agonists but the specific mechanism by which this takes place remains unclear. All previously evaluated activators of the Nlrp3 inflammasome induce the generation of mitochondrial reactive oxygen species (ROS), suggesting a model in which ROS is a required upstream mediator of Nlrp3 inflammasome activation. Here we have identified the oxazolidinone antibiotic linezolid as a Nlrp3 agonist that activates the Nlrp3 inflammasome independently of ROS. The pathways for ROS-dependent and ROS-independent Nlrp3 activation converged upon mitochondrial dysfunction and specifically the mitochondrial lipid cardiolipin. Cardiolipin bound to Nlrp3 directly and interference with cardiolipin synthesis specifically inhibited Nlrp3 inflammasome activation. Together these data suggest that mitochondria play a critical role in the activation of the Nlrp3 inflammasome through the direct binding of Nlrp3 to cardiolipin.
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Suppression of STIM1 inhibits human glioblastoma cell proliferation and induces G0/G1 phase arrest.
J. Exp. Clin. Cancer Res.
PUBLISHED: 04-02-2013
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Depletion of calcium (Ca2+) from the endoplasmic reticulum (ER) activates the ubiquitous store-operated Ca2+ entry (SOCE) pathway which sustains long-term Ca2+ signals and is critical for cellular functions. Stromal interacting molecule 1 (STIM1) serves a dual role as an ER Ca2+ sensor and activator of SOCE. Aberrant expression of STIM1 could be observed in several human cancer cells. However, the role of STIM1 in regulating tumorigenesis of human glioblastoma still remains unclear.
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Pyrimethamine sensitizes pituitary adenomas cells to temozolomide through cathepsin B-dependent and caspase-dependent apoptotic pathways.
Int. J. Cancer
PUBLISHED: 03-19-2013
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Invasive pituitary adenomas (PAs) are generally refractory to conventional therapy and salvage treatment with temozolomide (TMZ). In addition to antiprotozoan effects, pyrimethamine (PYR) has recently shown its strong antitumor activity as an antineoplastic agent or in combination with TMZ in metastatic melanoma cells. In this study, the effects of TMZ, PYR or TMZ/PYR combination on rat/mouse PA cell lines ?T3-1, GH3, MMQ and ATt-20 as well as GH3 xenograft tumor model were evaluated. TMZ/PYR combination synergistically inhibited proliferation, invasion and induced apoptosis of these PA cell lines in vitro. Strikingly, combination treatment with TMZ and PYR produced synergistic antitumor activity and enhanced the survival rate of GH3 xenograft tumor models without increasing systemic side effects. In addition, TMZ/PYR induced cell cycle arrest, increased DNA damage, upregulated the expression of cathepsin B, BAX, cleaved PARP and phosphorylated histone H2AX as well as elevated caspase3/7, 8 and 9 activities. The decreased expression of Bcl-2, MMP-2 and MMP-9 alone with cytochrome c release from mitochondria into the cytosol was also observed in the TMZ/PYR combination group. The increase in cell apoptosis due to combination with PYR was rescued by leucovorin. These data suggest that PYR may enhance the efficacy of TMZ via triggering both cathepsin B-dependent and caspase-dependent apoptotic pathways. Therefore, combination of PYR and TMZ may provide a novel regimen for invasive PAs refractory to standard therapy and TMZ.
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Direct conversion of fibroblasts into neural progenitor-like cells by forced growth into 3D spheres on low attachment surfaces.
Biomaterials
PUBLISHED: 03-17-2013
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Many stem cells grow into three-dimensional (3D) spheres or colonies, such as neural progenitor cells (NPCs) and embryonic stem cells (ESCs). Sphere morphology helps maintaining the stemness of stem cells. Our previous study demonstrated that forced growth of RT4 and HEK293 cells into 3D sphere on low attachment surface could induce stem cell properties. The close relationship between 3D sphere morphology and stem cell stemness drives us to hypothesize that 3D sphere formation induces fibroblasts reprogramming. The key gene Sox2 for reprogramming fibroblasts into NPCs was found to be overexpressed in 3D sphere cultured mouse fibroblasts. These cells exhibited similar morphological and molecular features to NPCs in vitro, were capable of differentiating into neurons, astrocytes and oligodendrocytes, and could generate long-term expandable neurospheres while maintaining differentiation capability. When engrafted into hippocampus of adult rat brain, the 3D sphere cells differentiated into neural cells. Thus, NPCs can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.
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Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor ?-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells.
Endocrinology
PUBLISHED: 03-05-2013
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There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)? is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FR?-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FR? and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FR? plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FR?.
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Three-level prediction of protein function by combining profile-sequence search, profile-profile search, and domain co-occurrence networks.
BMC Bioinformatics
PUBLISHED: 02-28-2013
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Predicting protein function from sequence is useful for biochemical experiment design, mutagenesis analysis, protein engineering, protein design, biological pathway analysis, drug design, disease diagnosis, and genome annotation as a vast number of protein sequences with unknown function are routinely being generated by DNA, RNA and protein sequencing in the genomic era. However, despite significant progresses in the last several years, the accuracy of protein function prediction still needs to be improved in order to be used effectively in practice, particularly when little or no homology exists between a target protein and proteins with annotated function. Here, we developed a method that integrated profile-sequence alignment, profile-profile alignment, and Domain Co-Occurrence Networks (DCN) to predict protein function at different levels of complexity, ranging from obvious homology, to remote homology, to no homology. We tested the method blindingly in the 2011 Critical Assessment of Function Annotation (CAFA). Our experiments demonstrated that our three-level prediction method effectively increased the recall of function prediction while maintaining a reasonable precision. Particularly, our method can predict function terms defined by the Gene Ontology more accurately than three standard baseline methods in most situations, handle multi-domain proteins naturally, and make ab initio function prediction when no homology exists. These results show that our approach can combine complementary strengths of most widely used BLAST-based function prediction methods, rarely used in function prediction but more sensitive profile-profile comparison-based homology detection methods, and non-homology-based domain co-occurrence networks, to effectively extend the power of function prediction from high homology, to low homology, to no homology (ab initio cases).
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Transplantation of human mesenchymal stem cells loaded on collagen scaffolds for the treatment of traumatic brain injury in rats.
Biomaterials
PUBLISHED: 02-27-2013
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Studies have suggested that mesenchymal stem cells (MSCs) have therapeutic effects following traumatic brain injury (TBI). However, cell distribution and survival rate are two major barriers to their success as therapeutic treatment. The improvement of cell therapy using collagen delivery matrices had been reported. However, we know very little about the mechanisms. We labeled human bone marrow-derived mesenchymal stem cells (hMSCs) with a positron emission tomography (PET) tracer, 18F-fluoro-2-deoxy-D-glucose (FDG). hMSCs were transplanted with or without collagen scaffolds into rats with experimental TBI and the whole-body nuclear images were compared. Collagen scaffolds increased the retention of hBMSC in the lesion site and limited its distribution at the transplanted region. Significantly more hMSCs were detected in the brain when transplanted with collagen scaffolds. The results showed collagen scaffolds also efficiently improved cell survival and neurite outgrowth in vivo, resulting in better neural functional recovery. In addition, brain metabolism also improved in the collagen scaffold implanted group, as evaluated by PET. We speculated that collagen scaffolds would improve early engraftment and support the survival of grafted cells post-transplantation.
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Unusually stable ~100-fold reversible and instantaneous swelling of inorganic layered materials.
Nat Commun
PUBLISHED: 02-25-2013
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Cells can swell or shrink in certain solutions; however, no equivalent activity has been observed in inorganic materials. Although lamellar materials exhibit increased volume with increase in the lamellar period, the interlamellar expansion is usually limited to a few nanometres, with a simultaneous partial or complete exfoliation into individual atomic layers. Here we demonstrate a large monolithic crystalline swelling of layered materials. The gallery spacing can be instantly increased ~100-fold in one direction to ~90 nm, with the neighbouring layers separated primarily by H2O. The layers remain strongly held without peeling or translational shifts, maintaining a nearly perfect three-dimensional lattice structure of >3,000 layers. First-principle calculations yield a long-range directional structuring of the H2O molecules that may help to stabilize the highly swollen structure. The crystals can also instantaneously shrink back to their original sizes. These findings provide a benchmark for understanding the exfoliating layered materials.
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TRPM2 links oxidative stress to NLRP3 inflammasome activation.
Nat Commun
PUBLISHED: 02-14-2013
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Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin-1? secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactive oxygen species have a central role in NLRP3 inflammasome activation, how reactive oxygen species signal assembly of the NLRP3 inflammasome remains elusive. Here, we identify liposomes as novel activators of the NLRP3 inflammasome and further demonstrate that liposome-induced inflammasome activation also requires mitochondrial reactive oxygen species. Moreover, we find that stimulation with liposomes/crystals induced reactive oxygen species-dependent calcium influx via the TRPM2 channel and that macrophages deficient in TRPM2 display drastically impaired NLRP3 inflammasome activation and interleukin-1? secretion. Consistently, Trpm2(-/-) mice are resistant to crystal-/liposome-induced interleukin-1?-mediated peritonitis in vivo. Together, these results identify TRPM2 as a key factor that links oxidative stress to the NLRP3 inflammasome activation. Therefore, targeting TRPM2 may be effective for the treatment of NLRP3 inflammasome-associated inflammatory disorders.
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New family of lanthanide-based inorganic-organic hybrid frameworks: Ln2(OH)4[O3S(CH2)nSO3]·2H2O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4) and their derivatives.
Inorg Chem
PUBLISHED: 02-07-2013
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We report the synthesis and structure characterization of a new family of lanthanide-based inorganic-organic hybrid frameworks, Ln(2)(OH)(4)[O(3)S(CH(2))(n)SO(3)]·2H(2)O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4), and their oxide derivatives. Highly crystallized samples were synthesized by homogeneous precipitation of Ln(3+) ions from a solution containing ?,?-organodisulfonate salts promoted by slow hydrolysis of hexamethylenetetramine. The crystal structure solved from powder X-ray diffraction data revealed that this material comprises two-dimensional cationic lanthanide hydroxide {[Ln(OH)(2)(H(2)O)](+)}(?) layers, which are cross-linked by ?,?-organodisulfonate ligands into a three-dimensional pillared framework. This hybrid framework can be regarded as a derivative of UCl(3)-type Ln(OH)(3) involving penetration of organic chains into two {LnO(9)} polyhedra. Substitutional modification of the lanthanide coordination promotes a 2D arrangement of the {LnO(9)} polyhedra. A new hybrid oxide, Ln(2)O(2)[O(3)S(CH(2))(n)SO(3)], which is supposed to consist of alternating {[Ln(2)O(2)](2+)}(?) layers and ?,?-organodisulfonate ligands, can be derived from the hydroxide form upon dehydration/dehydroxylation. These hybrid frameworks provide new opportunities to engineer the interlayer chemistry of layered structures and achieve advanced functionalities coupled with the advantages of lanthanide elements.
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The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.
PLoS ONE
PUBLISHED: 02-06-2013
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The spatial conformation of a genome plays an important role in the long-range regulation of genome-wide gene expression and methylation, but has not been extensively studied due to lack of genome conformation data. The recently developed chromosome conformation capturing techniques such as the Hi-C method empowered by next generation sequencing can generate unbiased, large-scale, high-resolution chromosomal interaction (contact) data, providing an unprecedented opportunity to investigate the spatial structure of a genome and its applications in gene regulation, genomics, epigenetics, and cell biology. In this work, we conducted a comprehensive, large-scale computational analysis of this new stream of genome conformation data generated for three different human leukemia cells or cell lines by the Hi-C technique. We developed and applied a set of bioinformatics methods to reliably generate spatial chromosomal contacts from high-throughput sequencing data and to effectively use them to study the properties of the genome structures in one-dimension (1D) and two-dimension (2D). Our analysis demonstrates that Hi-C data can be effectively applied to study tissue-specific genome conformation, chromosome-chromosome interaction, chromosomal translocations, and spatial gene-gene interaction and regulation in a three-dimensional genome of primary tumor cells. Particularly, for the first time, we constructed genome-scale spatial gene-gene interaction network, transcription factor binding site (TFBS) - TFBS interaction network, and TFBS-gene interaction network from chromosomal contact information. Remarkably, all these networks possess the properties of scale-free modular networks.
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Inhibition of PI3K/AKT/mTOR pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice.
Endocrinology
PUBLISHED: 02-05-2013
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Invasive pituitary adenomas (PAs) are often refractory to standard therapy and salvage treatment with temozolomide (TMZ). Hyperactivation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway contributes to chemotherapy resistance in many cancers. XL765, a novel dual-PI3K/mTOR inhibitor, has recently shown its efficacy as a monotherapy and in combination with conventional therapeutics in many cancers. The hyperactive PI3K/AKT/mTOR pathway frequently occurs in invasive PAs. In this study, we investigated whether XL765 sensitizes PA cells to TMZ in vitro and in vivo. Experiments were carried out to evaluate the effect of XL765 and TMZ alone or in combination on cell proliferation and apoptosis of PA cell lines (?T3-1, GH3, and MMQ) in vitro as well as the tumor growth and serum GH and prolactin secretions in a GH3 xenograft tumor model of female nude mice. XL765 and TMZ synergistically inhibited the growth of PA cell lines and induced apoptosis. Combination of XL765 and TMZ synergistically inhibited tumor growth, decreased serum GH and prolactin levels, and reduced the sacrifice rate of GH3 xenograft tumor models without increased systemic side effects. In addition, XL765 in combination with TMZ dramatically decreased phosphorylation of AKT and mTOR as well as the expression of Bcl-2. The increased expression of cleaved poly (ADP-ribose) polymerase and Bcl-2-associated X protein along with elevated caspase-3/7 activity were also observed in the combination group. Therefore, dual inhibitors of PI3K and mTOR may enhance alkylating agent-mediated cytotoxicity and provide a novel regimen in the treatment of invasive PAs.
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Suppression of the coffee-ring effect by self-assembling graphene oxide and monolayer titania.
Nanotechnology
PUBLISHED: 01-28-2013
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The in situ self-assembly of two types of typical two-dimensional (2D) nanomaterials (i.e., graphene oxide (GO) and monolayer titania (TO)) is realized using a simple drop-casting method. Within the as-prepared hybrid films, the GO and TO nanosheets arrange alternately into a lamellar structure. Notably, the hybridization of GO and TO suppresses the formation of coffee-rings when drop-cast, which is attributed to the strong interactions between the GO and TO nanosheets. Finally, the mechanism for the in situ hybridization of these two types of nanosheets into heterogeneous lamellar films and the suppression of the coffee-ring effect are discussed. These results demonstrate the potential applications of drop-cast hybrid films for high-quality membrane deposition from liquid phases.
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New emerging recombinant HIV-1 strains and close transmission linkage of HIV-1 strains in the Chinese MSM population indicate a new epidemic risk.
PLoS ONE
PUBLISHED: 01-23-2013
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In recent years, the population of men who have sex with men (MSM) have become the most significant increasing group of HIV-1 transmission in China. To identify new recombinant strains and transmission patterns of HIV-1 in Chinese MSM population, a cross-sectional investigation of MSM in Anhui Province (in south-eastern China) was performed in 2011. The diagnosed AIDS case rate, CD4 T-cell counts, HIV subtypes, and origin of the recombinant strains were investigated in 138 collected samples. The phylogenetic and bootscan analyses demonstrated that, apart from three previously reported circulating strains (CRF07_BC, CRF01_AE, subtype B), various recombinant strains among subtype B, subtype C, CRF01_AE, and CRF07_BC were simultaneously identified in Chinese MSM for the first time. The introducing time of B subtype in Chinese MSM populations was estimated in 1985, CRF01_AE in 2000, and CRF07_BC in 2003; the latter two account for more than 85% of MSM infections. Notably, in comparison with B subtype infections in Anhui MSM, CRF01_AE, with the highest prevalence rate, may accelerate AIDS progression. Over half of patients (56%) infected with new recombinant strains infection are diagnosed as progression into AIDS. Both Bayes and phylogenetic analyses indicated that there was active HIV transmission among MSM nationwide, which may facilitate the transmission of the new 01B recombinant strains in MSM. In conclusion, new recombinant strains and active transmission were identified in the Chinese MSM population, which may lead to a new alarming HIV pandemic in this population due to the increased pathogenesis of the newly emerging strains.
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Targeted Myostatin Gene Editing in Multiple Mammalian Species Directed by a Single Pair of TALE Nucleases.
Mol Ther Nucleic Acids
PUBLISHED: 01-18-2013
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Myostatin (MSTN) is a negative regulator of skeletal muscle mass. Strategies to block myostatin signaling pathway have been extensively pursued to increase muscle mass in various disease settings including muscular dystrophy. Here, we report a new class of reagents based on transcription activator-like effector nucleases (TALENs) to disrupt myostatin expression at the genome level. We designed a pair of MSTN TALENs to target a highly conserved sequence in the coding region of the myostatin gene. We demonstrate that codelivery of these MSTN TALENs induce highly specific and efficient gene disruption in a variety of human, cattle, and mouse cells. Based upon sequence analysis, this pair of TALENs is expected to be functional in many other mammalian species. Moreover, we demonstrate that these MSTN TALENs can facilitate targeted integration of a mCherry expression cassette or a larger muscular dystrophy gene (dysferlin) expression cassette into the MSTN locus in mouse or human cells. Therefore, targeted editing of the myostatin gene using our highly specific and efficient TALEN pair would facilitate cell engineering, allowing potential use in translational research for cell-based therapy.Molecular Therapy-Nucleic Acids (2013) 2, e112; doi:10.1038/mtna.2013.39; published online 30 July 2013.
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Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.
Sci China Life Sci
PUBLISHED: 01-18-2013
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Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.
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Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study.
Cytotherapy
PUBLISHED: 01-11-2013
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Pre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders.
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Dysferlin-deficient muscular dystrophy and innate immune activation.
FEBS J.
PUBLISHED: 01-02-2013
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Cells encounter many physical, chemical and biological stresses that perturb plasma membrane integrity, warranting an immediate membrane repair response to regain cell homeostasis. Failure to respond properly to such perturbation leads to individual cell death, which may also produce systemic influence by triggering sterile immunological responses. In this review, we discuss recent progress on understanding the mechanisms underlying muscle cell membrane repair and the potential mediators of innate immune activation when the membrane repair system is defective, specifically focusing on pathology associated with dysferlin deficiency.
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Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function.
PLoS ONE
PUBLISHED: 01-01-2013
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Myosin binding protein-C (MyBP-C) exists in three major isoforms: slow skeletal, fast skeletal, and cardiac. While cardiac MyBP-C (cMyBP-C) expression is restricted to the heart in the adult, it is transiently expressed in neonatal stages of some skeletal muscles. However, it is unclear whether this expression is necessary for the proper development and function of skeletal muscle. Our aim was to determine whether the absence of cMyBP-C alters the structure, function, or MyBP-C isoform expression in adult skeletal muscle using a cMyBP-C null mouse model (cMyBP-C((t/t))). Slow MyBP-C was expressed in both slow and fast skeletal muscles, whereas fast MyBP-C was mostly restricted to fast skeletal muscles. Expression of these isoforms was unaffected in skeletal muscle from cMyBP-C((t/t)) mice. Slow and fast skeletal muscles in cMyBP-C((t/t)) mice showed no histological or ultrastructural changes in comparison to the wild-type control. In addition, slow muscle twitch, tetanus tension, and susceptibility to injury were all similar to the wild-type controls. Interestingly, fMyBP-C expression was significantly increased in the cMyBP-C((t/t)) hearts undergoing severe dilated cardiomyopathy, though this does not seem to prevent dysfunction. Additionally, expression of both slow and fast isoforms was increased in myopathic skeletal muscles. Our data demonstrate that i) MyBP-C isoforms are differentially regulated in both cardiac and skeletal muscles, ii) cMyBP-C is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and iii) skeletal isoforms can transcomplement in the heart in the absence of cMyBP-C.
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The effects of Gd3+ substitution on the crystal structure, site symmetry, and photoluminescence of Y/Eu layered rare-earth hydroxide (LRH) nanoplates.
Dalton Trans
PUBLISHED: 12-14-2011
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Well crystallized nanoplates of the (Y(0.95-x)Gd(x)Eu(0.05))(2)(OH)(5)NO(3)·nH(2)O ternary layered rare-earth hydroxides (LRHs), synthesized hydrothermally, have been investigated with emphasis on the effects of Gd(3+) substitution for Y(3+) on the structural features and optical properties. Characterizations of the materials were achieved by the combined techniques of XRD, FT-IR, TEM, DTA/TG, and optical spectroscopies. The results showed that Gd(3+) substitution leads to linearly expanded ab plane, shortened interlayer distance (c/2), and reduced hydration (smaller n value) of the crystal structure. As a consequence, the Ln(3+) partially shifts from the C(4v) to C(1) site symmetries and thus leads to systematically altered photoluminescence behaviors. Under the (7)F(0)?(5)L(6) transition excitation of Eu(3+) at 394 nm, both the (5)D(0)?(7)F(2) to (5)D(0)?(7)F(4) and the 595 nm (5)D(0)?(7)F(1) to 590 nm (5)D(0)?(7)F(1) intensity ratios linearly increase towards a higher Gd(3+) content. The incorporated Gd(3+) cations selectively sensitize emission from the C(1)-site Eu(3+) and produce a new charge transfer (CT) excitation band at ?254 nm. With this, the desired 615-nm red emission is obtainable either under intra-4f(6) transition excitation of Eu(3+) or by exciting the CT band. The materials have similar fluorescence lifetimes of 0.85 ± 0.05 ms for the 615-nm emission, irrespective of the Gd(3+) content and excitation wavelength.
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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.