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The challenge in photothermal therapy (PTT) is to develop biocompatible photothermal transducers that can absorb and convert near-infrared (NIR) light into heat with high efficiency. Herein, we report salt-induced aggregation of gold nanoparticles (GNPs) in biological media to form highly efficient and biocompatible NIR photothermal transducers for PTT and photothermal/photoacoustic (PT/PA) imaging of cancer. The GNP depots in situ formed by salt-induced aggregation of GNPs show strong NIR absorption induced by plasmonic coupling between adjacent GNPs and very high photothermal conversion efficiency (52%), enabling photothermal destruction of tumor cells. More interestingly, GNPs in situ aggregate in tumors to form GNP depots, enabling simultaneous PT/PA imaging and PTT of the tumors. These findings may provide a simple and effective way to develop a new class of intelligent and biocompatible NIR photothermal transducers with high efficiency for PT/PA imaging and PTT.

Ontology search interfaces can benefit from the latest information retrieval advances. This paper introduces a Conjunctive Ontology Browser and Explorer (COBE) for searching and exploring SNOMED CT concepts and visualizing SNOMED CT fragments. COBE combines navigational exploration (NE) with direct lookup (DL) as two complementary modes for finding specific SNOMED CT concepts. The NE mode allows a user to interactively and incrementally narrow down (hence conjunctive) the search space by adding word stems, one at a time. Such word stems serve as attribute constraints, or "attributes" in Formal Concept Analysis, which allows the user to navigate to specific SNOMED CT concept clusters. The DL mode represents the common search mechanism by using a collection of key words, as well as concept identifiers. With respect to the DL mode, evaluation against manually created reference standard showed that COBE attains an example-based precision of 0.958, recall of 0.917, and F1 measure of 0.875. With respect to the NE mode, COBE leverages 28,371 concepts in non-lattice fragments to construct the stem cloud. With merely 9.37% of the total SNOMED CT stem cloud, our navigational exploration mode covers 98.97% of the entire concept collection.

A rapid, sensitive, selective and periodic polarity-switching liquid chromatography-tandem mass spectrometry(LC-MS-MS) method was developed for the simultaneous determination of eight components in an important traditional Chinese medicinal capsule, Fufang Xueshuantong. LC analysis was carried out on a Kinetex 2.6 µm XB-C18 column by gradient elution. The detection was performed by multiple reaction monitoring (MRM) with a periodic polarity-switching electrospray ionization (ESI) source across five periods of switching between positive and negative mode. Periodic polarity-switching was used to acquire maximal responses and to simultaneously detect eight constituents in one analysis run lasting 8 min. All of the analytes showed good linearity (r > 0.9947) in the tested ranges. The average recoveries were in the range of 95.4-103.9% with relative standard deviations ≤6.3%, and the intra- and inter-day variations were ≤3.7%. The developed method was successfully employed to analyze three batches of Fufang Xueshuantong capsule samples. The results showed that the levels of notoginsenoside R1, ginsenoside Rb1 and salvianolic acid B were clearly different in different batches of Fufang Xueshuantong capsules. Furthermore, the new established periodic polarity-switching LC-MS-MS method was proven to be highly sensitive and effective in evaluating the quality of Fufang Xueshuantong capsules., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Tumor-homing and pH-responsive polypeptide-drug nanoparticles for targeted cancer therapy are precisely designed by site-specific drug conjugation to a bioactive and well-defined elastin-like polypeptide through an acid-labile linker. In a murine cancer model, these nanoparticles show significantly better anti-tumor efficacy and less systemic toxicity than not only free drugs, but also polypeptide-drug nanoparticles without the tumor-homing function.

Objective: To assess the association of neural precursor cell expressed developmentally down-regulated 4 (NEDD4) with schizophrenia., Methods: Five single nucleotide polymorphisms (SNPs) of the NEDD4 gene were genotyped by TaqMan SNP genotyping assay in an independent sample of 464 individuals with schizophrenia and 487 healthy controls from eastern Han Chinese population. Clinical data were collected with a general information questionnaire and Positive and Negative Syndrome Scale (PANSS)., Results: Frequencies of rs3088077 (allelic: χ2=18.024, P=0.000; genotypic: χ2=16.634, P=0.000), rs7162435 (allelic: χ2=6.771, P=0.009; genotypic: χ2=7.352, P=0.025) and rs2303579 (allelic: χ2=11.253, P=0.001; genotypic: χ2=12.248, P=0.002) were found to be significant different between the two groups. Moreover, TT of rs7162435 was significantly correlated with scores of factors of excitement and hostility (14.53±3.925, F=3.551, P=0.029)., Conclusion: rs3088077, rs7162435 and rs2303579 of the NEDD4 gene may be associated with schizophrenia. Moreover, the TT genotype of rs7162435 may increase the severity of excitement and hostility. Our results may provide a clue for delineating the connection between the glutamate hypothesis of schizophrenia and ubiquitination.

A major disadvantage of therapeutic proteins is their instability to external stressors during storage, transport and use. Here, we report site-specific in situ growth of a cyclized protein-polymer conjugate with improved in vitro and in vivo stability. Green fluorescence protein (GFP) was genetically fused at its N- and C-termini with two sortase recognition sequences pentaglycine and LPETG, respectively to yield a linear GFP (l-GFP). A cyclized GFP (c-GFP) was generated from the l-GFP by sortase-catalyzed cyclization. A maleimide-functionalized atom transfer radical polymerization (ATRP) initiator was selectively attached to a free cysteine residue genetically engineered at the C-terminus of GFP to form a macroinitiator (c-GFP-Br). Subsequent in situ ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) from the c-GFP-Br generated a site-specific (C-terminal) and stoichiometric (1:1) c-GFP-POEGMA conjugate with almost quantitative conversion and highly retained activity. Notably, the c-GFP-POEGMA conjugate showed 9- and 310-fold increases in thermal stability as compared to the l-GFP and its counterpart l-GFP-POEGMA, respectively. Additionally, the conjugate displayed significantly improved tumor retention relative to the l-GFP and l-GFP-POEGMA. The method developed may be applicable to a variety of therapeutic proteins to improve their in vitro and in vivo stability., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A structural disparity of the subsumption relationship between FMA and SNOMED CT's Body Structure sub-hierarchy is that while the is-a relation in FMA has a tree structure, the corresponding relation in Body Structure is not even a lattice. This paper introduces a method called NEO, for non-lattice embedding of FMA fragments into the Body Structure sub-hierarchy to understand (1) this structural disparity, and (2) its potential utility in analyzing non-lattice fragments in SNOMED CT. NEO consists of four steps. First, transitive, upper- and down-closures are computed for FMA and SNOMED CT using MapReduce, a modern scalable distributed computing technique. Secondly, UMLS mappings between FMA and SNOMED CT concepts are used to identify equivalent concepts in non-lattice fragments from Body Structure. Then, non-lattice fragments in the Body Structure sub-hierarchy are extracted, and FMA concepts matching those in the non-lattice fragments are used as the seeds to generate the corresponding FMA fragments. Lastly, the corresponding FMA fragments are embedded to the non-lattice fragments for comparative visualization and analysis. After identifying 8,428 equivalent concepts between the collection of over 30,000 concepts in Body Structure and the collection of over 83,000 concepts in FMA using UMLS equivalent concept mappings, 2,117 shared is-a relations and 5,715 mismatched relations were found. Among Body Structure's 90,465 non-lattice fragments, 65,968 (73%) contained one or more is-a relations that are in SNOMED CT but not in FMA, even though they have equivalent source and target concepts. This shows that SNOMED CT may be more liberal in classifying a relation as is-a, a potential explanation for the fragments not conforming to the lattice property.

Relation reversals in ontological systems refer to such patterns as a path from concept A to concept B in one version becoming a path with the position of A and B switched in another version. We present a scalable approach, using cloud computing, to systematically extract all hierarchical relation reversals among 8 SNOMED CT versions from 2009 to 2014. Taking advantage of our MapReduce algorithms for computing transitive closure and large-scale set operations, 48 reversals were found through 28 pairwise comparison of the 8 versions in 18 minutes using a 30-node local cloud, to completely cover all possible scenarios. Except for one, all such reversals occurred in three sub-hierarchies: Body Structure, Clinical Finding, and Procedure. Two (2) reversal pairs involved an uncoupling of the pair before the is-a coupling is reversed. Twelve (12) reversal pairs involved paths of length-two, and none (0) involved paths beyond length-two. Such reversals not only represent areas of potential need for additional modeling work, but also are important for identifying and handling cycles for comparative visualization of ontological evolution.

In this study, a liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine naproxcinod and naproxen concentrations in rat plasma for the first time. Plasma samples were prepared by simple one-step extraction with methanol for protein precipitation using only 50 μL plasma. Separation was performed on a Synergi Fusion-RP C18 column with a run time of 4 min. Naproxcinod, naproxen and internal standard concentrations were detected in the positive ion mode using multiple reaction monitoring (MRM) of the transitions at m/z 348.2→302.2, 231.1→185.1 and 271.2→203.1, respectively. The calibration curves were linear, with all correlation coefficients being ≥0.9952, in the range of 1.00-400 ng/mL for naproxcinod and 20.0-8000 ng/mL for naproxen. Their accuracy was in the range of -8.1% to 8.7%, and the intra- and inter-day variations were ≤4.53%. The mean extraction recovery of all analytes was more than 93.1% efficient. Stability testing showed that naproxcinod and naproxen remained stable during the whole analytical procedure. After validation, the method was successfully applied to a pharmacokinetic study of naproxcinod and naproxen in rats. The AUC0-∞ of naproxen was 74.6 times larger than that of naproxcinod, which indicated that naproxcinod was rapidly metabolized into naproxen in rats., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Non-lattice fragments are often indicative of structural anomalies in ontological systems and, as such, represent possible areas of focus for subsequent quality assurance work. However, extracting the non-lattice fragments in large ontological systems is computationally expensive if not prohibitive, using a traditional sequential approach. In this paper we present a general MapReduce pipeline, called MaPLE (MapReduce Pipeline for Lattice-based Evaluation), for extracting non-lattice fragments in large partially ordered sets and demonstrate its applicability in ontology quality assurance. Using MaPLE in a 30-node Hadoop local cloud, we systematically extracted non-lattice fragments in 8 SNOMED CT versions from 2009 to 2014 (each containing over 300k concepts), with an average total computing time of less than 3 hours per version. With dramatically reduced time, MaPLE makes it feasible not only to perform exhaustive structural analysis of large ontological hierarchies, but also to systematically track structural changes between versions. Our change analysis showed that the average change rates on the non-lattice pairs are up to 38.6 times higher than the change rates of the background structure (concept nodes). This demonstrates that fragments around non-lattice pairs exhibit significantly higher rates of change in the process of ontological evolution.

In order to investigate the effect of sodium ferulate (SF) on voltage-activated K + channels, the delayed rectifier K + current (Ik) in PC12 rat pheochromocytoma cells was recorded using the automated patch-clamp method. The results indicated that following the application of SF, the Ik in PC12 cells was significantly decreased in a concentration-dependent manner. The analysis of activation kinetic curves and inactivation kinetic curves of Ik showed that SF had an effect on the activation and inactivation kinetics. Following the application of 15.3 μM SF, the activation curve of the Ik of PC12 cells was shifted to positive potentials and the inactivation curve of the Ik of PC12 cells was shifted to negative potentials. This study revealed that the delayed rectifier K + currents of PC12 cells were inhibited following SF treatment in a concentration-dependent manner. The mechanism may be associated with the delayed activation and enhanced inactivation of Ik-associated channels.

A fluorescent polyvinylpyrrolidone (PVP) film with assembled nanostructures is successfully prepared in one pot by using perylene-3,4,9,10-tetracarboxylic acid dianhydride (PDA) as the fluorophore. The reactive anhydride groups in PDA play an important role in the covalent bonding of fluorescent molecules in the fluorescent PVP film, which has been demonstrated by a small-molecule model reaction. Interestingly, rod-like structures are found on the surface of the fluorescent film, which is attributed to the π-π interaction of PDA that occurred in the crosslinked PVP film. Further polarized optical microscopy (POM), X-ray diffraction (XRD) and optical analyses demonstrate the stable existence of π-conjugated nanostructures in the fluorescent PDA-based PVP film. The reactive anhydrides and the π-π interaction of perylene molecules are essential for the fabrication of the fluorescent perylene-assembled PVP film. This method could be extended to the preparation of the fluorescent PVP film with self-assembled nanostructures.

The aim of this study was to investigate the effects of the combination of SF and OMT on ethanol-induced liver damage in mice. The animal liver wet/dry weight (W/D) ratio and liver tissue histopathology, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), superoxidase dismutase (SOD), C-reactive protein (CRP), interleukin-6 (IL-6), and nuclear factor κB (NF-κB) levels were measured. The data indicated that the levels of ALT, AST, TG, CRP, IL-6, NF-κB and MDA significantly decreased and that SOD activity improved after treatment with the combination of SF and OMT; the same effects were not observed with the same dose of SF or OMT when used alone. These results indicated that the combination of SF and OMT had a protective effect on ethanol-induced liver damage in mice and that antioxidation and anti-inflammatory effects might be involved in this protective mechanism., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Human serum albumin (HSA) nanometer or micron particles represent promising drug-carrier systems. The azimuthal and radial variations of a linear polarization-sensitive backscattering Mueller matrix were experimentally studied in two cases: the scattering particle was smaller or larger in size to the probing wavelength of 780 nm. The results show that the twofold and fourfold structures are characteristic of small particle size suspension, whereas the eightfold structure is characteristic of large particle size suspension. Moreover, for both particle size suspensions, the element patterns have strong radial dependence when the suspension concentration and the incident power of laser change. In addition, for both particle size suspensions, the rotational symmetry of each element is lost in the case of oblique incidence but the multifold structure is maintained. Some suggestions for applications of Mueller matrix imaging in biomedical optics are provided.

A polyvinylpyrrolidone (PVP)-based fluorescent film with stable optical properties is successfully prepared in one pot without any additive. The reaction mechanism of ring-opening and self-crosslinking of linear PVP is proposed and demonstrated. The morphologies and the nanostructures of the fluorescent film as well as the unmodified film are investigated. The dye is incorporated into the film networks via covalent linkages, thus leading to the highly stable optical properties. The facile and effective synthesis approach opens a new way for the design of other multi-functional composite materials based on linear PVP., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel and sensitive method utilizing high performance liquid chromatography coupled with electrospray ionization source tandem mass spectrometry (LC-ESI-MS(3)) was developed for the first time in order to analyze nitrendipine in human plasma samples. Human plasma samples were prepared by protein precipitation with acetonitrile and well resolved on a 100 mm reversed-phase column in gradient elution with 0.05% (v/v) formic acid in acetonitrile as the mobile phase. Determination was performed in MS(3) scan mode for nitrendipine and in the multiple reaction monitoring (MRM) mode for nimodipine (internal standard). This method, having a lower limit of quantification (LLOQ) of 0.05 ng/mL when using a 100 μL sample aliquot (5 pg/sample), is acceptable for calibration of the linearity and repeatability and is of better sensitivity than the reported methods (>0.25 ng/mL). The major advantages of the method are that small sample volume (100 μL) is required, simple sample processing technique, high sensitivity and excellent selectivity is guaranteed by the MS(3) detection. The proposed validated method has been successfully applied to a clinical study on nitrendipine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD., Methods: We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression., Results: The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events., Limitations: Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships., Conclusions: The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We compared the European and eastern Chinese waterbird assemblages and checked whether the effects of human disturbance could be detected in the assemblages' composition. For the different Chinese provinces, we expected to find a negative effect of economic development on the mean bird species mass and on the proportion of bentivorous, piscivorous and insectivorous bird species. We also expected to find relatively fewer large species in the Chinese assemblage. Species rank-abundance curves were relatively similar, but China had significantly more species with smaller body masses. The China assemblage was characterized by relatively higher abundance of heavy-bodied species, contrary to our expectations. Mean bird body mass decreased in China with increasing disturbance and increasing gross domestic product (GDP). For coastal provinces in China the percentage of bentivorous, piscivorous and insectivorous bird species declined with increasing GDP, maybe through the increased use of pesticides or fertilizer.

Epigallocatechin-3-gallate (EGCG) is a major component of green tea polyphenols which displays potential properties of anticancer and neuroprotection. Here we show that protection of motor neuron by EGCG is associated with regulating glutamate level in organotypic culture of rat spinal cord. In this model, EGCG blocked glutamate excitotoxicity caused by threohydroxyaspartate, an inhibitor of glutamate transporter. This property of EGCG may be not due to its intrinsic antioxidative activity, because another antioxidant could not regulate glutamate level under the same condition. These results show that EGCG may be a potential therapeutic candidate for neurodegenerative diseases involving glutamate excitotoxicity such as ALS., (Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

A novel micro-mesopores composite material has successfully been synthesized at basic hydrothermal conditions using natural mineral montmorillonite (MMT) and tetraethoxysilane (TEOS). Two surfactants, cetyltrimethyl ammonium bromide (CTAB) and polyethylene glycol (PEG), have been employed in order to shape the pores in the composite. The resultant silica-clay has large surface area (472m(2)/g) and high hydrothermal stability, which makes it a potentially host-material for catalyst. The molecular size of different surfactant leads to the multi-peak distribution of pore size, and the surfactant of larger size (PEG) corresponds to the formation of larger pores. Moreover, the photocatalytic results show that, comparing with pure TiO(2) particles, the loaded TiO(2) on such silica-clay shows higher photodegradation rate of methyl orange (MO) in aqueous. And another porous aluminosilicate host, zeolite, was also discussed for comparison.

Threohydroxyaspartate (THA)-induced glutamate excitotoxicity in organotypic culture of rat spinal cord is a well-known model of motor neuron degeneration. THA causes accumulation of synaptic glutamate and over stimulation of the postsynaptic receptor by inhibiting glutamate uptake. This model has also been used to identify agents that inhibit glutamate excitotoxicity by increasing the expression of glutamate transporter. We now show that THA also increases iron level in rat spinal cord tissue, with concomitant modulation of key iron transport and storage proteins, including transferrin receptor, divalent metal-ion transporter 1 and ferritin. More significantly, iron chelator deferoxamine (DFO) was able to completely prevent THA-induced motor neuron degeneration. The protective effect of DFO did not involve enhancing glutamate uptake. These data provide new mechanistic insight into THA-induced glutamate excitotoxicity and suggest that blocking THA-induced iron rise alone may be sufficient for prevention of glutamate excitotoxicity.

Natural mordenite, replacing the synthetic zeolites, has been employed as the support of TiO2, and its photocatalytic activity has been examined in methyl orange (MO) aqueous under UV light. AFM, TEM, XRD, FTIR and fluorescence spectra have been used to reveal the loading effects of TiO2 on mordenite. The results show that the photocatalytic degradation (PCD) reaction rates are sharply increased by natural zeolite supports. Since mordenite is photo-inert, the PCD-enhancement is mostly caused by the bonding effects of Ti-O-Si and Ti-O-Al. Moreover, another two distinct natural zeolites have been employed as the supports of TiO2, in order to check the universality of PCD-enhancement effect of natural zeolites on TiO2. And the factors of PCD reaction on TiO2-zeolite, such as pH and catalyst dose, have been investigated.