Input: Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB: AII TRLs can contribute to decrease LCAT mass in Tx patients.


Input: Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases.

statin

triglycerides

cholesterol

cholesterol


Input: Quercetin mitochondriotropic derivatives antagonize nitrate tolerance and endothelial dysfunction of isolated rat aorta rings.

Quercetin

nitrate


Input: Chronic use of glyceryl trinitrate is limited by serious side effects, inter alia tolerance and endothelial dysfunction of coronary and resistance arteries.

glyceryl trinitrate


Input: The natural flavonoid quercetin has been shown to counteract the development of glyceryl trinitrate tolerance in vitro.

quercetin

glyceryl trinitrate


Input: Two mitochondriotropic, 4-O-triphenylphosphoniumbutyl derivatives of quercetin (QTA-3BTPI and Q-3BTPI) were compared to quercetin for protection against glyceryl trinitrate-induced tolerance and endothelial dysfunction of isolated rat aorta rings.

quercetin

quercetin

glyceryl trinitrate


Input: Both QTA-3BTPI and Q-3BTPI significantly counteracted the reduced vascular responsiveness to both glyceryl trinitrate and acetylcholine caused by prolonged exposure of the vessel to glyceryl trinitrate itself, their potency being much greater than that of quercetin.

glyceryl trinitrate

acetylcholine

glyceryl trinitrate

quercetin


Input: QTA-3BTPI, however, turned out to cause endothelial dysfunction per se.


Input: Since Q-3BTPI antagonized in vitro nitrate tolerance and endothelial dysfunction of vessels, this encourages assessing whether this effect is displayed also in vivo during long-term glyceryl trinitrate treatment.

nitrate

glyceryl trinitrate


Input: Cytotoxic pentacyclic triterpenoids from Prinsepia utilis.

pentacyclic triterpenoids


Input: Phytochemical investigation of the aerial parts of Prinsepia utilis Royle resulted in the isolation and identification of ten pentacyclic triterpenoids, including two new triterpenoids, 2 alpha-O-trans-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid (1) and 2 alpha-O-cis-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid (2), along with eight known pentacyclic triterpenoids (3-10).

pentacyclic triterpenoids

triterpenoids

2 alpha-O-trans-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid

2 alpha-O-cis-p-coumaroyl-3 beta, 19 alpha-dihydroxy-urs-12-en-28-oic acid

pentacyclic triterpenoids


Input: The structures were elucidated by extensive spectroscopic methods and by comparison to previously reported spectroscopic data.


Input: Most of these compounds showed significant cytotoxic activities against four human cancer cell lines (A549, HCT116, MDA-MB-231, and CCRF-CEM), and the structure-activity relationships are also discussed.


Input: New Concepts, Experimental Approaches, and Dereplication Strategies for the Discovery of Novel Phytoestrogens from Natural Sources.


Input: Phytoestrogens constitute an attractive research topic due to their estrogenic profile and their biological involvement in woman' s health.


Input: Therefore, numerous studies are currently performed in natural products chemistry area aiming at the discovery of novel phytoestrogens.


Input: The main classes of phytoestrogens are flavonoids (flavonols, flavanones), isoflavonoids (isoflavones, coumestans), lignans, stilbenoids as well as miscellaneous chemical groups abundant in several edible and/or medicinal plants, belonging mostly to the Leguminosae family.

flavonoids

flavonols

flavanones

isoflavonoids

isoflavones

coumestans

lignans

stilbenoids


Input: As for other bioactives, the detection of new structures and more potent plant-derived phytoestrogens typically follows the general approaches currently available in the natural product discovery process.


Input: Plant-based approaches selected from traditional medicine knowledge and bioguided concepts are routinely employed.


Input: However, these approaches are associated with serious disadvantages such as time-consuming, repeated, and labor intensive processes as well as lack of specificity and reproducibility.


Input: In recent years, the natural products chemistry became more technology-driven, and several different strategies have been developed.


Input: Structure-oriented procedures and miniaturized approaches employing advanced hyphenated analytical platforms have recently emerged.


Input: They facilitate significantly not only the discovery of novel phytoestrogens but also the dereplication procedure leading to the anticipation of major drawbacks in natural products discovery.


Input: In this review, apart from the traditional concepts followed in phytochemistry for the discovery of novel biologically active compounds, recent applications in the field of extraction, analysis, fractionation, and identification of phytoestrogens will be discussed.


Input: Moreover, specific methodologies combining identification of actives and biological evaluation in parallel, such as liquid chromatography-biochemical detection, frontal affinity chromatography-mass spectrometry and pulsed ultrafiltration-MS will also be presented.


Input: Finally, miniaturized methods (microchip and biosensor) will be also discussed. With the current review, we attempt to give a wide and holistic overview of the different approaches which could be employed in the discovery of new phytoestrogens.


Input: On the other hand, we anticipate to attract more scientists to the area of phytoestrogens and to indicate the need of multidisciplinary concepts.


Input: Structural Units Important for Activity of a Novel-type Phosphoserine Phosphatase from Hydrogenobacter thermophilus TK-6 Revealed by Crystal Structure Analysis.

Phosphoserine


Input: Novel-type serine-synthesizing enzymes, termed metal-independent phosphoserine phosphatases (iPSPs), were recently identified and characterized from Hydrogenobacter thermophilus, a chemolithoautotrophic bacterium belonging to the order Aquificales.

serine

phosphoserine


Input: iPSPs are cofactor-dependent phosphoglycerate mutase (dPGM)-like phosphatases that have significant amino acid sequence similarity to dPGMs but lack phosphoglycerate mutase activity.

phosphoglycerate

amino acid

phosphoglycerate


Input: Genes coding dPGM-like phosphatases have been identified in a broad range of organisms; however, predicting the function of the corresponding proteins based on sequence information alone is difficult due to their diverse substrate preferences.


Input: Here, we determined the crystal structure of iPSP1 from H. thermophilus in the apo-form and in complex with its substrate l-phosphoserine to find structural units important for its phosphatase activity toward l-phosphoserine.

l-phosphoserine

l-phosphoserine


Input: Structural and biochemical characterization of iPSP1 revealed that the side chains of His (85) and C-terminal region characteristic of iPSP1 are responsible for the PSP activity.

His

C


Input: The importance of these structural units for PSP activity was confirmed by high PSP activity observed in two novel dPGM-like proteins from Cyanobacteria and Chloroflexus in which the two structural units were conserved.


Input: We anticipate that our present findings will facilitate understanding of the serine biosynthesis pathways of organisms that lack gene (s) encoding conventional PSPs, as the structural information revealed here will help to identify iPSP from sequence databases.

serine


Input: N-[9-(ortho-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides as Potent and Selective Ligands for A1 Adenosine Receptors.

N-[9-(ortho-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides

Adenosine


Input: A series of N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides were synthesised and tested for their affinity toward A1, A2A and A3 adenosine receptor subtypes.

N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides

adenosine


Input: Biological results demonstrated that the introduction of a fluorine atom at the ortho position of the 9-benzyl group generally enhanced affinity toward A1 subtype and did not significantly affect A2A and A3 affinity.

fluorine


Input: Very interesting is the compound bearing a meta-fluorophenyl substituent on the carbonyl carbon of the amide group, which shows significantly high A1/A2A-A3 selectivity.

meta-fluorophenyl

carbonyl carbon

amide


Input: Compounds of this new series, together with the previously published analogs without the fluorine atom on the 9-benzyl group, constituted the starting dataset for the development of QSAR models.

fluorine


Input: The models obtained were able to rationally describe the affinity trends resulting from biological testing, and to enable investigation of the role of different substituents on the 8-azapurine scaffold, as well as the influence of the newly introduced fluorine atom on the benzyl moiety.

fluorine

benzyl


Input: The said QSAR models can also assist in the design of new compounds selectively active on A1 adenosine receptors.

adenosine


Input: Furthermore, a molecular docking study was carried out in order to assess hypothetical binding mode of N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides to A1 adenosine receptors.

N-[9-(ortho-fluorobenzyl)-2-phenyl-8-azapurin-6-yl]-amides

adenosine


Input: (c) 2013 John Wiley & Sons A/S.


Input: Physicochemical Properties and Supernucleophilicity of Oxime-Functionalized Surfactants: Hydrolytic Catalysts toward Dephosphorylation of Di-and Triphosphate Esters.

Oxime

Di-and Triphosphate Esters


Input: Aggregation and kinetic studies have been performed to understand the hydrolytic potencies of the series of oxime-functionalized surfactants, viz., 3-hydroxyiminomethyl-1-alkylpyridinium bromide (alkyl = CnH2n + 1, n = 10, 12, 14, 16, 18) in the cleavage of phosphate esters, p-nitrophenyl diphenyl phosphate (PNPDPP) and bis (2, 4-dinitrophenyl) phosphate (BNDPP), in mixed micelles with cetylpyridinium bromide (CPB).

oxime

3-hydroxyiminomethyl-1-alkylpyridinium bromide

alkyl

CnH2n + 1

phosphate esters

p-nitrophenyl diphenyl phosphate

PNPDPP

bis (2, 4-dinitrophenyl) phosphate

BNDPP

cetylpyridinium bromide

CPB


Input: Micellization and surface properties of mixed micelles functional surfactants with CPB were studied by conductivity and surface tension measurements.

CPB


Input: Acid dissociation constants (pKa) were determined, the effect of functional surfactant alkyl chain length and pH on the observed rate constant (kobs) for phosphate ester cleavage has been discussed, and the effect of substrate on the supernucleophilicities of the studied oximes was monitored.

alkyl

phosphate ester

oximes


Input: Functionalized oxime-based surfactants were proved to be supernucleophiles to attack on the P = O center of tri-and diphosphate esters.

oxime

P = O

tri-and diphosphate esters


Input: Oximes with hexadecyl alkyl chain length (3-C16) showed maximum micellar effect on the rate constants toward PNPDPP.

Oximes

hexadecyl alkyl

PNPDPP


Input: Micellar effects were analyzed in terms of the pseudophase model.


Input: A concise total synthesis of the natural carbazole clauraila A.

carbazole


Input: A short and efficient total synthesis of naturally occurring carbazole clauraila A (1) is described.

carbazole clauraila A


Input: The approach is designed on the basis of the key regioselective Diels-Alder reaction of the properly substituted exo-2-oxazolidinone diene 3 with acrolein (4) to give the corresponding adduct 2.

exo-2-oxazolidinone diene

acrolein


Input: The latter is converted to functionalised diarylamine 8, which is cyclised to the desired carbazole 1 through a Pd-promoted or-catalysed double C-H bond activation process in a fairly good overall yield.

diarylamine

carbazole

Pd

C-H


Input: Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies.

fatty acid

retinol

simvastatin

metformin


Input: Abstract Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome.

fatty acid

retinol


Input: We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS).


Input: Sixty-two healthy, untreated women with PCOS (age 25. 1 +/- 3. 6 years, BMI: 24. 0 +/- 4. 7 kg/m (2)) were randomized to metformin (n = 24), simvastatin (n = 20) or metformin plus simvastatin (n = 18) for 3 months.

metformin

simvastatin

metformin

simvastatin


Input: Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end.

glucose


Input: At the baseline serum FABP4 correlated with obesity (BMI: r = 0. 63, p < 0. 001), insulin resistance (fasting insulin: r = 0. 44, p = 0. 0002; QUICKI: r =-0. 30, p = 0. 02; OGTT-insulin sensitivity index: r =-0. 27, p = 0. 04), dyslipidemia (HDL: r =-0. 26, p = 0. 03) and hyperandrogenemia (free-testosterone: r = 0. 23, p = 0. 03; SHBG: r =-0. 28, p = 0. 03); while RBP4 correlated with total-cholesterol (r = 0. 33, p = 0. 009).

cholesterol


Input: Multiple regression analysis indicated that t best predictors of serum FABP4 and RBP4 were BMI (beta = 1. 02, p = 0. 0003) and total cholesterol (beta = 2326, p = 0. 01), respectively.

cholesterol


Input: Simvastatin, alone or with metformin did not affect serum FABP4 or RBP4.

Simvastatin

metformin


Input: Serum FABP4 related to the obesity, insulin resistance and inflammation while RBP4 related to lipids.


Input: Insulin sensitizing and lipid lowering therapies did not affect FABP4 or RBP4 levels in PCOS.


Input: Temperature-Dependent Conformations of a Membrane Supported Zinc Porphyrin Tweezer by 2D Fluorescence Spectroscopy.

Zinc Porphyrin


Input: We studied the equilibrium conformations of a zinc porphyrin tweezer composed of two carboxylphenyl-functionalized zinc tetraphenyl porphyrin subunits connected by a 1, 4-butyndiol spacer, which was suspended inside the amphiphilic regions of 1, 2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes.

zinc porphyrin

carboxylphenyl

zinc tetraphenyl porphyrin

1, 4-butyndiol

1, 2-distearoyl-sn-glycero-3-phosphocholine

DSPC


Input: By combining phase-modulation two-dimensional fluorescence spectroscopy (2D FS) with linear absorbance and fluorimetry, we determined that the zinc porphyrin tweezer adopts a mixture of folded and extended conformations in the membrane.

zinc porphyrin


Input: By fitting an exciton-coupling model to a series of data sets recorded over a range of temperatures (17-85 degrees C) and at different laser center wavelengths, we determined that the folded form of the tweezer is stabilized by a favorable change in the entropy of the local membrane environment.


Input: Our results provide insights toward understanding the balance of thermodynamic factors that govern molecular assembly in membranes.


Input: Efficient MRI labeling of endothelial progenitor cells: Design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles.

iron oxide


Input: The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity.

iron oxide


Input: TSS-SPIONs were developed by chelation between thiolated chitosan-thioglycolic acid (chitosan-TGA) hydrogel and iron ions (Fe (2 +)/Fe (3 +)).

thioglycolic acid

TGA

iron

Fe (2 +)

Fe (3 +)


Input: Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control.


Input: Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization.

iron

iron


Input: TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3. 1 +/- 0. 02nm, a hydrodynamic diameter of 94 +/- 20nm, a zeta potential of + 21 +/- 5mV, and an iron content of 3. 6 +/- 0. 9mg/mL.

iron oxide

iron


Input: In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively.


Input: With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist (R).

iron


Input: Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24h.


Input: The molar MR relaxivities (r2) value at 1. 5T was threefold higher than that of Resovist (R) and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent.


Input: According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking.


Input: Rules for the recognition of dilysine retrieval motifs by coatomer.

dilysine


Input: Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer alpha-COP and beta'-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval.

dilysine


Input: Numerous ER/Golgi proteins contain K (x) Kxx motifs, but the rules for their recognition are unclear.


Input: We present crystal structures of alpha-COP and beta'-COP bound to a series of naturally occurring retrieval motifs-encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences.


Input: Binding experiments show that alpha-COP and beta'-COP have generally the same specificity for KKxx and KxKxx, but only beta'-COP recognizes the RKxx signal.


Input: Dilysine motif recognition involves lysine side-chain interactions with two acidic patches.

Dilysine

lysine


Input: Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches.

lysine


Input: We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.

C

carboxylate

lysine

lysine


Input: First report on predictive chemometric modeling, 3D-toxicophore mapping and in silico screening of in vitro basal cytotoxicity of diverse organic chemicals.


Input: Classification and regression based quantitative structure-toxicity relationship (QSTR) as well as toxicophore models were developed for the first time on basal cytotoxicity data (in vitro 3T3 neutral red uptake data) of a diverse series of chemicals (including drugs and environmental pollutants) collected from the ACuteTox database (http://www. acutetox. eu/).


Input: Statistically significant QSTR models were obtained using linear discriminant analysis (classification) and partial least squares (regression) methodologies.


Input: Generated toxicophore models showed four important features responsible for basal cytotoxicity: (i) two hydrophobic aliphatic groups (HYD Aliphatic), (ii) ring aromatic group (RA) and (iii) hydrogen bond donor (HBD).

hydrogen


Input: The most predictive hypothesis (Hypo 1) had a correlation coefficient of 0. 932 for the training set, a low rms deviation of 1. 105, and an acceptable cost difference of 62. 8 bits, which represents a true correlation and a good predictivity.


Input: QSTR and toxicophore models were rigorously validated internally as well as externally along with the randomization test to nullify the possibilities of chance correlation.


Input: Our in silico models enable to identify the essential structural attributes and quantify the prime molecular pre-requisites which were chiefly responsible for in vitro basal cytotoxicity.


Input: The developed models were also implemented to screen basal cytotoxicity for huge number DrugBank database (http://www. drugbank. ca/) compounds.


Input: Testosterone modulates spatial recognition memory in male rats.

Testosterone


Input: A growing body of research indicates that testosterone influences spatial cognition in male rats; however, the overwhelming majority of studies have been conducted on tasks motivated by either food deprivation or water escape.

testosterone


Input: The hippocampus-dependent version of the Y-maze task, which characterizes spatial recognition memory, capitalizes on the propensity of rats to gravitate toward novel spatial environments and is not contingent upon either appetite or the stress associated with water escape, two factors also affected by testosterone.

testosterone


Input: Accordingly, the aim of the current study was to examine the effects of orchidectomy and subsequent testosterone treatment on spatial recognition memory.

testosterone


Input: Orchidectomy did not impact spatial recognition memory when the delay between the information and retention trials of the Y-maze task was 24h.


Input: Alternatively, on the second Y-maze task, which featured a 48-h delay between trials, orchidectomy reduced, and treatments that produced higher levels of testosterone restored, preference for the arm associated with the novel spatial environment.

testosterone


Input: Importantly, there were no differences in activity levels as a function of orchidectomy or testosterone treatment on either of the two tasks.

testosterone


Input: Consistent with previous findings, orchidectomy attenuated, and testosterone treatment restored, both body weight gain and the relative weight of the androgen-sensitive ischiocavernosus muscle, which confirmed the efficacy of orchidectomy and testosterone treatments on physiological outcomes.

testosterone

androgen

testosterone


Input: Therefore, testosterone influenced spatial cognition on a task that minimized the influence of non-mnemonic factors and took advantage of the innate preference of rodents to seek out novel spatial environments.

testosterone


Input: Identification of mRNAs bound and regulated by human LIN28 proteins and molecular requirements for RNA recognition.


Input: Human LIN28A and LIN28B are RNA-binding proteins (RBPs) conserved in animals with important roles during development and stem cell reprogramming.


Input: We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HEK293 cells and identified a largely overlapping set of ~ 3000 mRNAs at ~ 9500 sites located in the 3' UTR and CDS.

Ribonucleoside


Input: In vitro and in vivo, LIN28 preferentially bound single-stranded RNA containing a uridine-rich element and one or more flanking guanosines and appeared to be able to disrupt base-pairing to access these elements when embedded in predicted secondary structure.

uridine

guanosines


Input: In HEK293 cells, LIN28 protein binding mildly stabilized target mRNAs and increased protein abundance.


Input: The top targets were its own mRNAs and those of other RBPs and cell cycle regulators.


Input: Alteration of LIN28 protein levels also negatively regulated the abundance of some but not all let-7 miRNA family members, indicating sequence-specific binding of let-7 precursors to LIN28 proteins and competition with cytoplasmic miRNA biogenesis factors.


Input: Novel tacrine-related drugs as potential candidates for the treatment of Alzheimer' s disease.

tacrine


Input: A summary of the recently published efforts on tacrine derivatives as a renewed potential therapeutic approach for the treatment of Alzheimer' s disease is presented.

tacrine


Input: The mammalian clock and chronopharmacology.


Input: Increases in our understanding of the molecular control of circadian rhythms and subsequent signaling pathways has allowed for new therapeutic drug targets to be identified as well as for a better understanding of how to more efficaciously and safely utilize current drugs.


Input: Here, we review recent advances in targeting components of the molecular clock in mammals for the development of novel therapeutics as well as describe the impact of the circadian rhythm on drug efficacy and toxicity.


Input: Synthesis, receptor binding and activity of iso and azakainoids.

iso and azakainoids


Input: Two syntheses for the production of an unsubstituted azakainoid are described.

azakainoid


Input: The 1, 3-dipolar cycloaddition of diazomethane with trans-dibenzyl glutaconate yields a 1-pyrazoline, which may be reduced directly to the pyrazolidine.

diazomethane

trans-dibenzyl glutaconate

pyrazolidine


Input: An unexpected trans-cis isomerization is observed during Hg/Al reduction of the 1-pyrazoline NN bond.

Hg

Al

1-pyrazoline NN


Input: Alternatively, when TMS diazomethane is used as the dipole, the resulting 2-pyrazoline obtained after desilylation may be reduced with NaCNBH3 to provide the trans azakainate analog exclusively.

TMS diazomethane

trans azakainate


Input: The synthesis of an unsubstituted isokainoid via Michael addition is also described.

isokainoid


Input: Glutamate receptor binding assays revealed that the azakaniod has a moderate affinity for unspecified glutamate receptors.

Glutamate

azakaniod

glutamate


Input: Membrane depolarization of Aplysia neurons upon application of the azakainoid demonstrates that it is an ionotropic glutamate receptor agonist.

azakainoid

glutamate


Input: Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract.

sucrose


Input: A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper (I)-catalyzed azide-alkyne cycloaddition.

alkyne

sucrose

azide

Gd-DOTA

copper (I)

azide-alkyne


Input: The resulting contrast agent (CA) was administered by gavage to C3H mice.


Input: Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 47h, by which time the CA had exited the GI tract.


Input: No evidence for leakage of the CA from the GI tract was observed.


Input: Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated.


Input: Cytotoxic and Anti-Inflammatory Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi.

Eunicellin

Diterpenoids


Input: Five new eunicellin-based diterpenoids, krempfielins E-I (1-5) and seven known compounds (6-12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi.

eunicellin

diterpenoids

krempfielins E-I


Input: The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis.


Input: Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines.


Input: Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264. 7 macrophage cells.


Input: New Azalomycin F Analogs from Mangrove Streptomyces sp.

Azalomycin F


Input: 211726 with Activity against Microbes and Cancer Cells.


Input: Seven new azalomycin F analogs (1-7) were isolated from the broth of mangrove Streptomyces sp.

azalomycin F


Input: 211726, and respectively identified as 25-malonyl demalonylazalomycin F5a monoester (1), 23-valine demalonylazalomycin F5a ester (2), 23-(6-methyl) heptanoic acid demalonylazalomycins F3a ester (3), F4a ester (4) and F5a ester (5), 23-(9-methyl) decanoic acid demalonylazalomycin F4a ester (6) and 23-(10-methyl) undecanoic acid demalony lazalomycin F4a ester (7).

25-malonyl demalonylazalomycin F5a monoester

23-valine demalonylazalomycin F5a ester

23-(6-methyl) heptanoic acid demalonylazalomycins F3a ester

F4a ester

F5a ester

23-(9-methyl) decanoic acid demalonylazalomycin F4a ester

23-(10-methyl) undecanoic acid demalony lazalomycin F4a ester


Input: Their structures were established by their spectroscopic data and by comparing with those of azalomycins F3a, F4a and F5a.

azalomycins F3a, F4a and F5a


Input: Biological assays exhibited that 1-7 showed broad-spectrum antimicrobial and anti HCT-116 activities.


Input: Comparative annotation of functional regions in the human genome using epigenomic data.


Input: Epigenetic regulation is dynamic and cell-type dependent.


Input: The recently available epigenomic data in multiple cell types provide an unprecedented opportunity for a comparative study of epigenetic landscape.


Input: We developed a machine-learning method called ChroModule to annotate the epigenetic states in eight ENCyclopedia Of DNA Elements cell types.


Input: The trained model successfully captured the characteristic histone-modification patterns associated with regulatory elements, such as promoters and enhancers, and showed superior performance on identifying enhancers compared with the state-of-art methods.


Input: In addition, given the fixed number of epigenetic states in the model, ChroModule allows straightforward illustration of epigenetic variability in multiple cell types.


Input: Using this feature, we found that invariable and variable epigenetic states across cell types correspond to housekeeping functions and stimulus response, respectively.


Input: Especially, we observed that enhancers, but not the other regulatory elements, dictate cell specificity, as similar cell types share common enhancers, and cell-type-specific enhancers are often bound by transcription factors playing critical roles in that cell type.


Input: More interestingly, we found some genomic regions are dormant in cell type but primed to become active in other cell types.


Input: These observations highlight the usefulness of ChroModule in comparative analysis and interpretation of multiple epigenomes.


Input: Sorafenib Hepatobiliary Disposition: Mechanisms of Hepatic Uptake and Disposition of Generated Metabolites.

Sorafenib


Input: Sorafenib is an orally active tyrosine kinase inhibitor used in the treatment of renal and hepatocellular carcinoma.

Sorafenib

tyrosine


Input: This study was designed to establish whether transport proteins are involved in the hepatic uptake of sorafenib, and to determine the extent of biliary excretion of sorafenib/metabolites in human hepatocytes.

sorafenib

sorafenib


Input: Initial uptake was assessed in freshly isolated, suspended human hepatocytes in the presence of inhibitors and modulators.


Input: [(14) C] Sorafenib (1 mu M) uptake at 4 degrees C was ~ 61-63% of the uptake at 37 degrees C, suggesting a high degree of passive diffusion.

[(14) C] Sorafenib


Input: Hepatocyte uptake of [(14) C] sorafenib was not Na (+)-dependent or influenced by the organic anion transporter 2 (OAT2) inhibitor ketoprofen.

[(14) C] sorafenib

Na (+)

ketoprofen


Input: However, initial [(14) C] sorafenib hepatocyte uptake was reduced by 46 and 30% compared to control values in the presence of the organic anion transporting polypeptide (OATP) inhibitor rifamycin SV, and the organic cation transporter (OCT) inhibitor decynium 22, respectively.

[(14) C] sorafenib

rifamycin SV

decynium 22


Input: [(14) C] Sorafenib (0. 5 to 5 mu M) uptake was significantly higher in hOCT1-transfected CHO cells compared to mock cells, and inhibited by the general OCT inhibitor, MPP (+).

[(14) C] Sorafenib

MPP (+)


Input: OCT1-mediated uptake was saturable with a Km of 3. 80 +/- 2. 53 mu M and Vmax of 116 +/- 42 pmol/mg/min.


Input: The biliary excretion index (BEI) and in vitro biliary clearance (Clbiliary) of sorafenib (1 mu M) in sandwich-cultured human hepatocytes were low (~ 11% and 11 ml/min/kg, respectively).

sorafenib


Input: Results suggest that sorafenib uptake in human hepatocytes occurs via passive diffusion, and by OCT1 and a rifamycin-sensitive transporter.

sorafenib

rifamycin


Input: Sorafenib undergoes modest biliary excretion, predominantly as glucuronide conjugate (s).

Sorafenib


Input: Enhanced photovoltaic performance of a dye-sensitized solar cell using graphene-TiO2 photoanode prepared by a novel in situ simultaneous reduction-hydrolysis technique.

graphene


Input: Enhanced photovoltaic performance of a DSSC using graphene-TiO2 photoelectrodes prepared by our recent in situ simultaneous reduction-hydrolysis technique (Adv. Funct. Mater., 2012, DOI: 10. 1002/adfm. 201202349, in press) was achieved.

graphene


Input: The DSSCs based on the G-TiO2 nanocomposites improved their overall energy conversion efficiency to 7. 1%.


Input: The results prove that the promoting effect of graphene is strongly dependent on its content; namely, the efficiency of DSSCs increases and then decreases with increasing graphene content in TiO2-graphene composites.

graphene

graphene

graphene


Input: Excessive graphene in the nanocomposite leads to a decrease of the light harvest of dye molecules and thus a negative effect on the power conversion efficiency of DSSCs.

graphene


Input: Effects of treatment with a carbon monoxide-releasing molecule and a heme oxygenase 1 inducer in the antinociceptive effects of morphine in different models of acute and chronic pain in mice.

carbon monoxide

morphine


Input: RATIONALE: Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium (II) dimer, CORM-2) or a classical heme oxygenase 1 inducer (cobalt protoporphyrin IX, CoPP) has potent anti-inflammatory effects, but the role played by these treatments in the antinociceptive effects of morphine during acute and chronic pain was not evaluated.

carbon monoxide

tricarbonyldichlororuthenium (II)

cobalt protoporphyrin IX

CoPP

morphine


Input: OBJECTIVES: In wild type (WT), neuronal (NOS1-KO), or inducible (NOS2-KO) nitric oxide synthases knockout mice, we evaluated the effects of CORM-2 and CoPP treatments in the antinociceptive actions of morphine and their interaction with nitric oxide during acute, visceral, and chronic inflammatory or neuropathic pain.

nitric oxide

CoPP

morphine

nitric oxide


Input: METHODS: Acute and visceral pain was assessed through formalin and acid acetic writhing tests.

formalin

acid acetic


Input: Chronic inflammatory pain induced by the intra-articular administration of complete Freund' s adjuvant and neuropathic pain by partial ligation of sciatic nerve were evaluated by measuring allodynia and hyperalgesia using the von Frey filaments, plantar, or cold plate tests.


Input: RESULTS: While nitric oxide, synthetized by NOS1 and/or NOS2, increased the local antinociceptive effects of morphine during acute and chronic pain, it decreased the inhibitory effects of morphine after visceral pain.

nitric oxide

morphine

morphine


Input: Moreover, while CORM-2 or CoPP treatments did not alter or reduced the antinociceptive effects of morphine during acute and visceral pain, both treatments improved the local antiallodynic and antihyperalgesic effects of morphine after chronic inflammatory or neuropathic pain in WT, but not in KO mice.

CoPP

morphine

morphine


Input: CONCLUSIONS: CORM-2 and CoPP treatments improved the local antinociceptive effects of morphine during chronic inflammatory and neuropathic pain by interaction with nitric oxide synthetized by NOS1 and NOS2 isoforms.

CoPP

morphine

nitric oxide


Input: Liquid-Crystalline Blue Phase Laser with Widely Tunable Wavelength.


Input: A lasing peak shift of more than 100 nm is realized due to the large shift of a photonic bandgap of a liquid-crystalline blue phase.


Input: Protein-protein nanoimprinting of silk fibroin films.


Input: Protein-protein imprinting of silk fibroin is introduced as a rapid, high-throughput method for the fabrication of nanoscale structures in silk films, through the application of heat and pressure.


Input: Imprinting on conformal surfaces is demonstrated with minor adjustments to the system, at resolutions comparable to other currently available nonplanar nanoimprint lithography techniques.


Input: Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype a.

Paclitaxel

boron dipyrromethene


Input: We have successfully identified one new inhibitor and one new fluorescent recognition agent for the botulinum neurotoxin subtype A (BoNT/A) using the virtual screening protocol " protein scanning with virtual ligand screening " (PSVLS).


Input: Hit selection used an in-house developed holistic binding scoring method.


Input: Selected hits were tested experimentally for inhibitory activity using fluorescence resonance energy transfer (FRET) assays against the light chain (catalytic domain) of BoNT/A.


Input: Ligand binding was determined against the light and heavy chain BoNT/A complex through either radiolabeled ligand binding assays (nonfluorescent ligands) or fluorescence intensity assays (fluorescent ligands).


Input: These experimental assays have confirmed one compound (paclitaxel) to inhibit BoNT/A' s proteolytic activity experimentally with an IC50 of 5. 2 mu M.


Input: A fluorescent derivative was also confirmed to bind to the toxin and therefore is a suitable candidate for the rational design of new detection agents and for the development of fluorescence-based multiprobe detection assays.


Input: Embellicines A and B: Absolute Configuration and NF-kappa B Transcriptional Inhibitory Activity.

Embellicines A and B


Input: Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae).

embellicines A and B

EtOAc


Input: The structures of these new compounds were determined on the basis of extensive one-and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry.


Input: The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1.

embellicine A

embellicine B


Input: Both embellicines (1 and 2) are cytostatic, cytotoxic, and inhibit NF-kappa B transcriptional activity, indicating that inhibition of NF-kappa B may be a possible mechanism of action of these compounds.

embellicines


Input: Embellicine B (2) was the most active compound encountered in this study and acts at nanomolar concentrations without affecting tumor microenvironment.

Embellicine B


Input: Tin-coated viral nanoforests as sodium-ion battery anodes.

Tin

sodium


Input: Designed as a high-capacity alloy host for Na-ion chemistry, a forest of Sn nanorods with a unique core-shell structure was synthesized on viral scaffolds, which were genetically engineered to ensure a nearly vertical alignment upon self-assembly onto a metal substrate.

Sn


Input: The interdigital spaces thus formed between individual rods effectively accommodated the volume expansion and contraction of the alloy upon sodiation/desodiation, while additional carbon-coating engineered over these nanorods further suppressed Sn aggregation during extended electrochemical cycling.

carbon

Sn


Input: Due to the unique nanohierarchy of multiple functional layers, the resultant 3D nanoforest of C/Sn/Ni/TMV1cys, binder-free composite electrode already and evenly assembled on a stainless steel current collector, exhibited supreme capacity utilization and cycling stability toward Na-ion storage and release.

C

Sn

Ni

steel


Input: An initial capacity of 722 mA. h (g Sn) (-1) along with 405 mA. h (g Sn) (-1) retained after 150 deep cycles demonstrates the longest-cycling nano-Sn anode material for Na-ion batteries reported in the literature to date and marks a significant performance improvement for neat Sn material as alloy host for Na-ion chemistry.

Sn

Sn

Sn

Sn


Input: Direct modulation of microtubule stability contributes to anthracene general anesthesia.

anthracene


Input: Recently, we identified 1-aminoanthracene as a fluorescent general anesthetic.


Input: To investigate the mechanism of action, a photoactive analogue, 1-azidoanthracene, was synthesized.


Input: Administration of 1-azidoanthracene to albino stage 40-47 tadpoles was found to immobilize animals upon near-UV irradiation of the forebrain region.


Input: The immobilization was often reversible, but it was characterized by a longer duration consistent with covalent attachment of the ligand to functionally important targets.


Input: IEF/SDS-PAGE examination of irradiated tadpole brain homogenate revealed labeled protein, identified by mass spectrometry as beta-tubulin.


Input: In vitro assays with aminoanthracene-cross-linked tubulin indicated inhibition of microtubule polymerization, similar to colchicine.

aminoanthracene

colchicine


Input: Tandem mass spectrometry confirmed anthracene binding near the colchicine site.

anthracene

colchicine


Input: Stage 40-47 tadpoles were also incubated 1 h with microtubule stabilizing agents, epothilone D or discodermolide, followed by dosing with 1-aminoanthracene.

epothilone D

discodermolide


Input: The effective concentration of 1-aminoanthracene required to immobilize the tadpoles was significantly increased in the presence of either microtubule stabilizing agent.


Input: Epothilone D similarly mitigated the effects of a clinical neurosteroid general anesthetic, allopregnanolone, believed to occupy the colchicine site in tubulin.

Epothilone D

allopregnanolone

colchicine


Input: We conclude that neuronal microtubules are " on-pathway " targets for anthracene general anesthetics and may also represent functional targets for some neurosteroid general anesthetics.

anthracene


Input: Unraveling the Role of the Protein Environment for [FeFe]-Hydrogenase: A New Application of Coarse-Graining.

[FeFe]


Input: Hydrogenase enzymes are natural biocatalysts that might be harnessed to reduce the cost of hydrogen gas production.

hydrogen


Input: [FeFe]-hydrogenases are the most effective of three such enzymes at catalyzing H (+) reduction.

[FeFe]

H (+)


Input: In this study, we develop and apply a novel combination of all-atom molecular dynamics and coarse-grained (CG) analysis to characterize two important steps of the catalytic cycle of [FeFe]-hydrogenase.

[FeFe]


Input: The first is the electron transport through FeS clusters to the active site.

FeS


Input: We use a Marcus formulation to compute the free energy and the reorganization energy of three electron transport steps and decompose these values into contributions from the CG protein sites and the solvent.


Input: The three-step transport process is found to be downhill with relative free energies of-11. 7 for the first step,-14. 8 for the second step, and-17. 1 kcal/mol for the third step.


Input: The electron-transport process is also found to activate a water channel suggesting a coupled mechanism for proton and electron transport to the active site.


Input: The channel opening is orchestrated by three CG sites located in the active-site domain of the protein with one of the sites also contributing a strong attractive electrostatic potential (ESP) to help shuttle protons to the active site.


Input: Overall, our CG analysis points to a concerted mechanism of electron and proton delivery to the active site in these proteins thus providing important insight for the development of biomimetic devices.


Input: Therapeutic effectiveness of botulinum neurotoxin A: Potent blockade of autonomic transmission by targeted cleavage of only the pertinent SNAP-25.


Input: In search of a basis for the impressive potency of an endoprotease that cleaves SNAP-25, botulinum neurotoxin type A (BoNT/A), in treating numerous diseases due to hyper-active autonomic nerves, truncation of its target and inhibition of neurotransmission were studied in rat sympathetic neurons.


Input: Tetrodotoxin-sensitive spontaneous cholinergic neurotransmission was blocked > 80% by 1 pM BoNT/A despite cleaving < 20% of the SNAP-25.

Tetrodotoxin


Input: A maximum cleavage of ~ 60% SNAP-25 could be achieved with > 1 nM BoNT/A, despite an absence of non-cleavable SNAP-25 in the detergent-solubilised neurons.


Input: In contrast, BoNT/E (100 nM) truncated nearly all the SNAP-25 in the intact cells, but was unable to block neurotransmission at low concentrations like BoNT/A.


Input: Chimeras created by inserting the acceptor-binding HC domain of BoNT/A into BoNT/E still cleaved all the SNAP-25, indicating ubiquitous expression of BoNT/A acceptors.


Input: Accordingly, SV2 and SNAP-25 were found to be co-expressed and broadly co-localised in neurons, but absent from non-neuronal cells.


Input: On the other hand, partial cleavage by the BoNT/A protease persisted upon replacing its HC with counterparts from BoNT/E or BoNT/B.


Input: Moreover, limited cleavage of SNAP-25 was conferred onto the protease from BoNT/E when fused to the N-terminus of BoNT/A.


Input: Thus, the BoNT/A protease is uniquely well-adapted for selectively inactivating the SNAP-25 directly involved in neurotransmission; this together with the toxin' s acceptor and its target being localised on the peri-somatic boutons likely contribute to its exceptional therapeutic utility in the clinic.


Input: Structural modifications of polymethacrylates: Impact on thermal behavior and release characteristics of glassy solid solutions.

polymethacrylates


Input: Polymethacrylates such as Eudragit (R) polymers are well established as drug delivery matrix.

Polymethacrylates

Eudragit


Input: Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization.

Eudragit E PO

n-butyl

dimethylaminoethyl

methyl-methacrylate

terpolymer


Input: These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets.


Input: Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit.

n-butyl

t-butyl

dimethylaminoethyl methacrylate

DMAEMA

isobornyl


Input: These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties.


Input: The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics.

DMAEMA


Input: Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding.

methacrylate


Input: Mercury in fishes from Augusta Bay (southern Italy): Risk assessment and health implication.

Mercury


Input: Our study reports on the total mercury (HgT) concentrations measured in the muscles and livers of several benthic, demersal and pelagic fish species caught inside and outside of Augusta Bay (southern Italy), a semi-enclosed marine area, highly contaminated by the uncontrolled (since the 1950s to 1978s) discharge of the largest European petrochemical plant.

mercury


Input: Mercury levels in fish tissues are discussed with regard to specific habitat, size and/or age of the specimens and HgT distribution in the bottom sediments.

Mercury


Input: Results suggest a still active Hg release mechanism from the polluted sediments to the marine environment.

Hg


Input: Also, the high HgT concentrations measured in fishes caught in the external area of the bay imply a potential role of Augusta Bay as a pollutant source for the Mediterranean ecosystem.


Input: Finally, values of hazard target quotient (THQ) and estimated weekly intake (EWI) demonstrate that consumption of fishes caught inside the bay represents a serious risk for human health.


Input: Also, data indicate that intake of fishes caught from the external area of the bay, especially for that concern demersal and benthic species, could be represent a significant component of risk for the local population.


Input: 1-Methylimidazolium hydrogen sulfate catalyzed convenient synthesis of 2, 5-dimethyl-N-substituted pyrroles under ultrasonic irradiation.

1-Methylimidazolium hydrogen sulfate

2, 5-dimethyl-N-substituted pyrroles


Input: Ionic liquid [HMIM] HSO4 was found to be an efficient catalyst for the synthesis of N-substituted pyrroles through the reaction of 2, 5-hexanedione with amines under ultrasonic irradiation at room temperature.

[HMIM] HSO4

N-substituted pyrroles

2, 5-hexanedione

amines


Input: These reactions proceed with good yields under short reaction time.


Input: Furthermore, the green catalytic system can be recycled specific times with no decreases in yields and reaction rates.


Input: Platycodi Radix attenuates dimethylnitrosamine-induced liver fibrosis in rats by inducing Nrf2-mediated antioxidant enzymes.

dimethylnitrosamine


Input: The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats.

dimethylnitrosamine

DMN


Input: DMN treatment for 4weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content.

DMN


Input: CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content.

DMN

alanine

aspartate

malondialdehyde


Input: CK also inhibited DMN-induced reductions in rat body and liver weights.

DMN


Input: Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-alpha) mRNA, and collagen type I and alpha-smooth muscle actin protein.

DMN


Input: DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-kappa B) activation was reduced by CK treatment.

DMN


Input: Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as gamma-glutamylcysteine synthetase (gamma-GCS), heme oxygenase-1 (HO-1), NAD (P) H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells.

gamma-glutamylcysteine

heme

NAD (P) H quinone

glutathione

S


Input: These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes.

DMN


Input: Subchronic and reproductive toxicity of whole dried Hoodia parviflora aerial parts in the rat.


Input: Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products.


Input: As part of the safety assessment process for H. parviflora, a freeze dried powder preparation was tested in a 90-day oral toxicity study with reproductive/recovery component in rats.


Input: Groups of 10 male and female Sprague-Dawley rats were administered H. parviflora dried powder at doses of 0, 100, 250, and 350mg/kg body weight/day by gavage for an 11-week pre-mating period and a 14-day co-habitation period, and for females, through lactation day 4.


Input: An additional 5 rats/sex/group received 0 or 350mg/kg bw/day for 90days and were sacrificed 28days after cessation of treatment.


Input: Statistically significant, non-adverse reductions in body weight, body weight gain, food consumption and food efficiency were observed at 250 and 350mg/kg/day in females.


Input: Food consumption was reduced in high-dose males.


Input: There were no adverse effects on hematological, blood biochemical, coagulation or urinalysis parameters or on the results of the functional observational battery and histopathological examinations.


Input: No evidence of any effect was noted on reproductive or developmental parameters.


Input: The NOAEL for dried H. parviflora powder was 350mg/kg bw/day, the highest permissible dose tested, for both male and female rats.


Input: Migrants determination and bioaccessibility study of ethyl lauroyl arginate (LAE) from a LAE based antimicrobial food packaging material.

ethyl lauroyl arginate

LAE

LAE


Input: Ethyl lauroyl arginate (LAE, ethyl-N-dodecanoyl-L-arginate hydrochloride) is a strong antimicrobial agent that was included as an active compound in an antimicrobial food packaging material.

Ethyl lauroyl arginate

LAE

ethyl-N-dodecanoyl-L-arginate hydrochloride


Input: The potential existence of non-intentionally added substances (NIASs) such as impurities must therefore be checked before launching any food contact material onto the market.


Input: For this reason, an untargeted analysis of the migration was performed in both food simulants and fresh chicken breast fillets wrapped with the active material.


Input: The analysis was performed by liquid chromatography coupled to mass spectrometry detection with a quadrupole-time-of-flight analyzer, LC-MS (QTOF), for the identification of nonvolatile substances.


Input: The migration values found for LAE were 0. 94 +/- 0. 14 and 1. 62 +/- 0. 70 mu g/g in ethanol 10% v/v (simulant A) and in ethanol 95% v/v (simulant D), respectively, and 0. 93 +/- 0. 17 mu g/g in chicken.

LAE

ethanol

ethanol


Input: Other migrants such as dipropylene glycol methyl ether or tributyl-o-acetylcitrate, both coming from the coating were also found, but none of them have potential adverse effects.

dipropylene glycol methyl ether

tributyl-o-acetylcitrate


Input: Bioaccessibility studies showed that after a simulated gastrointestinal digestion, LAE was not available anymore for subsequent intestinal absorption and new toxic compounds were not formed.

LAE


Input: Cadmium telluride quantum dots cause oxidative stress leading to extrinsic and intrinsic apoptosis in hepatocellular carcinoma HepG2 cells.

Cadmium telluride


Input: The mechanisms of toxicity related to human hepatocellular carcinoma HepG2 cell exposures to cadmium telluride quantum dots (CdTe-QDs) were investigated.

cadmium telluride

CdTe


Input: CdTe-QDs caused cytotoxicity in HepG2 cells in a dose-and time-dependent manner.

CdTe


Input: Treated cells showed an increase in reactive oxygen species (ROS).

oxygen


Input: Altered antioxidant levels were demonstrated by depletion of reduced glutathione (GSH), a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and an increased NF-E2-related Factor 2 (Nrf2) activation.

reduced glutathione

GSH

glutathione

oxidized glutathione

GSH

GSSG


Input: Enzyme assays showed that superoxide dismutase (SOD) activity was elevated whereas catalase (CAT) and glutathione-S-transferase (GST) activities were depressed.

superoxide

glutathione

S


Input: Further analyses revealed that CdTe-QD exposure resulted in apoptosis, indicated by changes in levels of caspase-3 activity, poly ADP-ribose polymerase (PARP) cleavage and phosphatidylserine externalization.

CdTe

poly ADP-ribose

phosphatidylserine


Input: Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure.

CdTe


Input: Involvement of the intrinsic/mitochondrial apoptotic pathway was indicated by decreased levels of B-cell lymphoma 2 (Bcl2) protein and mitochondrial cytochrome c, and by increased levels of mitochondrial Bcl-2-associated X protein (Bax) and cytosolic cytochrome c.


Input: Further, mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (Erk1/2), and p38 were all activated.

N


Input: Our findings reveal that CdTe-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein kinases, leading to apoptosis via both extrinsic and intrinsic pathways.

CdTe


Input: Since the effects of CdTe-QDs on selected biomarkers were similar or greater compared to those of CdCl2 at equivalent concentrations of cadmium, the study suggests that the toxicity of CdTe-QDs arises from a combination of the effects of cadmium and ROS generated from the NPs.

CdTe

cadmium

CdTe


Input: Stimulation of rat liver branched-chain alpha-keto acid dehydrogenase activity by low doses of bezafibrate.

alpha-keto acid

bezafibrate


Input: Multienzyme branched-chain alpha-ketoacid dehydrogenase complex (BCKDH) catalyzes the regulatory step of oxidative catabolism of indispensable branched-chain amino acids (BCAA).

alpha-ketoacid

amino acids


Input: The activity of the BCKDH complex is regulated by a reversible phosphorylation, end-product inhibition and by changes in the gene expression of BCKDH component enzymes.


Input: It has been shown previously that a high dose of bezafibrate (an agent added to rat chow at final concentration of 0. 5%) changes mRNA levels of BCKDH-related enzymes and increases dephosphorylation of the complex leading to stimulation of liver BCKDH activity and the enhanced BCAA catabolism.

bezafibrate


Input: The aim of the present study was to determine an in vivo effect of low, clinically relevant doses of bezafibrate on BCKDH activity in rat liver.

bezafibrate


Input: Bezafibrate was administrated for 14 days by gastric gavage to Wistar male rats (fed low-protein chow; 8% protein) at one of the following daily doses of 5, 10 and 20mg/kgb. wt.

Bezafibrate


Input: The control group was given the vehicle (0. 3% methylcellulose) only.


Input: The actual BCKDH and total BCKDH activities were assayed spectrophotometrically before and after incubation with a broad-specificity phosphatase, respectively.


Input: The mRNA levels of the selected genes (BCKDH catalytic subunits and regulatory enzymes) were quantified by means of semi-quantitative RT-PCR.


Input: Current catalytic activity of BCKDH (described as BCKDH activity state-the proportion of the BCKDH complex in its active dephosphorylated form) increased by 2. 1 +/- 0. 2, 2. 3 +/- 0. 2 and 2. 7 +/- 0. 2 fold (p < 0. 01).


Input: Changes in BCKDH activity did not correspond with changes in mRNA levels of the complex catalytic subunits.


Input: Moreover, mRNA levels of regulatory enzymes remained unaltered.


Input: Initially bezafibrate caused a transient insignificant reduction in body weight, but it had no effect on the final body weight.

bezafibrate


Input: The highest dose of bezafibrate induced hepatomegaly.

bezafibrate


Input: In conclusion, these data indicate that under conditions of dietary protein restriction low, clinically relevant doses of bezafibrate have a similar adverse effect on rat liver BCKDH activity and BCAA degradation rate as the high experimental dose.

bezafibrate


Input: Up-regulation of liver BCKDH activity by low doses of bezafibrate appears to result mainly from changes in phosphorylation status of the complex (increased dephosphorylation) and is not associated with elevations in mRNA levels of BCKDH enzymatic components.

bezafibrate


Input: Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants.


Input: Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes.


Input: Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites.

Amitriptyline

clomipramine

doxepin

imipramine

trimipramine


Input: These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites.

desipramine

nortriptyline


Input: Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.


Input: Structural Explanation for Allolactose (lac Operon Inducer) Synthesis by lacZ beta-Galactosidase and the Evolutionary Relationship between Allolactose Synthesis and the lac Repressor.

Allolactose

Allolactose


Input: beta-Galactosidase (lacZ) has bifunctional activity.


Input: It hydrolyzes lactose to galactose and glucose and catalyzes the intramolecular isomerization of lactose to allolactose, the lac operon inducer.

lactose

galactose

glucose

lactose

allolactose


Input: beta-Galactosidase promotes the isomerization by means of an acceptor site that binds glucose after its cleavage from lactose and thus delays its exit from the site.

glucose

lactose


Input: However, because of its relatively low affinity for glucose, details of this site have remained elusive.

glucose


Input: We present structural data mapping the glucose site based on a substituted enzyme (G794A-beta-galactosidase) that traps allolactose.

glucose

allolactose


Input: Various lines of evidence indicate that the glucose of the trapped allolactose is in the acceptor position.

glucose

allolactose


Input: The evidence includes structures with Bis-Tris (2, 2-bis (hydroxymethyl)-2, 2', 2''-nitrilotriethanol) and l-ribose in the site and kinetic binding studies with substituted beta-galactosidases.

Bis-Tris (2, 2-bis (hydroxymethyl)-2, 2', 2''-nitrilotriethanol)

l-ribose


Input: The site is composed of Asn-102, His-418, Lys-517, Ser-796, Glu-797, and Trp-999.

Asn

His

Lys

Ser

Glu

Trp


Input: Ser-796 and Glu-797 are part of a loop (residues 795-803) that closes over the active site.

Ser

Glu


Input: This loop appears essential for the bifunctional nature of the enzyme because it helps form the glucose binding site.

glucose


Input: In addition, because the loop is mobile, glucose binding is transient, allowing the release of some glucose.

glucose

glucose


Input: Bioinformatics studies showed that the residues important for interacting with glucose are only conserved in a subset of related enzymes.

glucose


Input: Thus, intramolecular isomerization is not a universal feature of beta-galactosidases.


Input: Genomic analyses indicated that lac repressors were co-selected only within the conserved subset.


Input: This shows that the glucose binding site of beta-galactosidase played an important role in lac operon evolution.

glucose


Input: Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay.


Input: Haploinsufficiency of the gene encoding the insulin-like growth factor 1 receptor (IGF1R), either caused by telomeric 15q26 deletions, or by heterozygous point mutations in IGF1R, segregate with short stature and various other phenotypes, including microcephaly and dysmorphic facial features.


Input: Psychomotor retardation and behavioral anomalies have been seen in some cases.


Input: Here we report small, intragenic deletions of IGF1R, identified by chromosome microarray analysis in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/autoaggressive behaviors.


Input: The deletions are in frame, and both wild-type and mutant mRNAs are expressed as measured by quantitative real-time PCR.


Input: While short stature is considered a phenotypic hallmark of IGF1R haploinsufficiency, the present report suggests that in frame exon deletions of IGF1R present predominantly with cognitive and neuropsychiatric phenotypes. European Journal of Human Genetics advance online publication, 13 March 2013; doi: 10. 1038/ejhg. 2013. 42.


Input: A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists.


Input: Angiotensin II type 1 receptor antagonists (ARBs) have become an important drug class in the treatment of hypertension and heart failure and the protection from diabetic nephropathy.


Input: Eight ARBs are clinically available [azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan].

azilsartan

candesartan

eprosartan

irbesartan

losartan

olmesartan

telmisartan

valsartan


Input: Azilsartan (in some countries), candesartan, and olmesartan are orally administered as prodrugs, whereas the blocking action of some is mediated through active metabolites.

Azilsartan

candesartan

olmesartan


Input: On the basis of their chemical structures, ARBs use different binding pockets in the receptor, which are associated with differences in dissociation times and, in most cases, apparently insurmountable antagonism.


Input: The physicochemical differences between ARBs also manifest in different tissue penetration, including passage through the blood-brain barrier.


Input: Differences in binding mode and tissue penetration are also associated with differences in pharmacokinetic profile, particularly duration of action.


Input: Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly telmisartan, are partial agonists at peroxisome proliferator-activated receptor-gamma.

telmisartan


Input: All of these properties are comprehensively reviewed in this article.


Input: Although there is general consensus that a continuous receptor blockade over a 24-hour period is desirable, the clinical relevance of other pharmacological differences between individual ARBs remains to be assessed.


Input: Understanding multi-quantum NMR through secular approximation.


Input: With the development of technology and improved understanding of nuclear spin-spin interactions and their behavior in static/oscillating magnetic fields, NMR spectroscopy has emerged as a powerful tool for characterizing molecular structure in a wide range of systems of chemical, physical and biological relevance.


Input: Here in this article, we revisit the important connection between " Secular-Approximation " (a well-known fundamental concept) and NMR spectroscopy.


Input: Employing recent experimental results as the background, an alternate interpretation of the secular approximation is presented for describing and understanding the nuances of Multi-Quantum (MQ) NMR spectroscopy of quadrupolar nuclei.


Input: Since MQ NMR spectroscopy of quadrupolar nuclei forms the basis of the structural characterization of inorganic solids and clusters, we believe that the analytic theory presented herein would be beneficial both in the understanding and design of MQ NMR experiments.


Input: Additionally, the analytic results are corroborated with rigorous numerical simulations and could be employed in the quantitative interpretation of experimental results.


Input: Heterogeneous OH oxidation of biomass burning organic aerosol surrogate compounds: assessment of volatilisation products and the role of OH concentration on the reactive uptake kinetics.

OH

OH


Input: The reactive uptake coefficients (gamma) of OH by levoglucosan, abietic acid, and nitroguaiacol serving as surrogate compounds for biomass burning aerosol have been determined employing a chemical ionisation mass spectrometer coupled to a rotating-wall flow-tube reactor over a wide range of [OH] ~ 10 (7)-10 (11) molecule cm (-3).

OH

levoglucosan

abietic acid

nitroguaiacol

OH


Input: Volatilisation products of these organic substrates due to heterogeneous oxidation by OH have been determined at 1 atm using a high resolution proton transfer reaction time-of-flight mass spectrometer (HR-PTR-ToF-MS).

OH


Input: gamma range within 0. 05-1 for [OH] = 2. 6 x 10 (7)-3 x 10 (9) molecule cm (-3) for all investigated organic compounds, but decrease to 0. 008-0. 034 for [OH] = 4. 1 x 10 (10)-6. 7 x 10 (10) molecule cm (-3).

OH

OH


Input: gamma as a function of [OH] can be described by a Langmuir-Hinshelwood model, neglecting bulk processes, suggesting that despite its strong reactivity, OH is mobile on surfaces prior to reaction.

OH

OH


Input: The best fit Langmuir-Hinshelwood parameters on average are K (OH) = 3. 81 x 10 (-10) cm (3) molecule (-1) and k (s) = 9. 71 x 10 (-17) cm (2) molecule (-1) s (-1) for all of the investigated organic compounds.

OH


Input: Volatilised products have been identified indicating enhancements over background of 50% up to a factor of 15.


Input: Amongst the common volatile organic compounds (VOCs) identified between levoglucosan, abietic acid, and nitroguaiacol were methanol, acetaldehyde, formic acid, and acetic acid.

levoglucosan

abietic acid

nitroguaiacol

methanol

acetaldehyde

formic acid

acetic acid


Input: VOCs having the greatest enhancement over background were glucic acid from levoglucosan, glycolic acid from abietic acid, and methanol and nitric acid from nitroguaiacol.

glucic acid

levoglucosan

glycolic acid

abietic acid

methanol

nitric acid

nitroguaiacol


Input: Reaction mechanisms leading to the formation of glucic acid, glycolic acid, methanol, and nitric acid are proposed.

glucic acid

glycolic acid

methanol

nitric acid


Input: Estimated lower limits of atmospheric lifetimes of biomass burning aerosol particles, 200 nm in diameter, by heterogeneous OH oxidation under fresh biomass burning plume conditions are ~ 2 days and up to ~ 2 weeks for atmospheric background conditions.

OH


Input: However, estimated lifetimes depend crucially on [OH] and corresponding gamma, emphasising the need to determine gamma under relevant conditions.

OH


Input: Baseline HbA1c predicts attainment of 7. 0% HbA1c target with structured titration of insulin glargine in type 2 diabetes: a patient-level analysis of 12 studies.


Input: AIMS: To determine whether baseline characteristics, especially haemoglobin A1c (HbA1c), predict the likelihood of reaching HbA1c <= 7. 0% or the risk of experiencing hypoglycaemia after the addition of insulin glargine to oral therapy in type 2 diabetes.


Input: METHODS: Pooled patient-level data from 12 prospective, randomized, controlled studies that used insulin glargine in a treat-to-target titration regimen seeking fasting glucose levels <= 5. 5 mmol/l (100 mg/dl) were analysed.

glucose


Input: Baseline characteristics were evaluated by logistic regression models as predictors of reaching a target HbA1c <= 7. 0% or experiencing confirmed hypoglycaemia.


Input: The effect of prior glycaemic control was further explored by analysis of categorical ranges of baseline HbA1c.


Input: RESULTS: Of 2312 participants, 95% completed 24 weeks of treatment.


Input: Lower HbA1c at baseline was independently associated with reaching HbA1c target [adjusted odds ratio (OR) for 1% difference: 0. 538, p < 0. 0001] and also with likelihood of experiencing confirmed hypoglycaemic events (adjusted OR: 0. 835, p < 0. 0001) at week 24.


Input: In an unadjusted analysis by baseline HbA1c range, the strong association between baseline control and attaining target HbA1c was confirmed (75% with baseline HbA1c < 8. 0%, 60% with baseline HbA1c >= 8. 0 and < 9. 0% and 38% with baseline HbA1c >= 9. 0% attained HbA1c <= 7. 0%).


Input: The incidence of hypoglycaemia confirmed < 3. 9 mmol/l (70 mg/dl) was higher in the lower baseline HbA1c ranges but severe hypoglycaemia was infrequent at all baseline HbA1c levels.


Input: CONCLUSIONS: Systematically titrated insulin glargine, added to oral agents, was effective over a wide range of baseline HbA1c.


Input: Lower baseline HbA1c was the best clinical predictor of achieving HbA1c <= 7. 0% and also associated with higher risk of glucose-confirmed hypoglycaemia.

glucose


Input: Severe hypoglycaemia was infrequent using this treatment approach.


Input: Synthesis, crystal structure and biological evaluation of a main group seven-coordinated bismuth (III) complex with 2-acetylpyridine N4-phenylthiosemicarbazone.

bismuth (III)

2-acetylpyridine N4-phenylthiosemicarbazone


Input: Up to now, bismuth (III) complexes with thiosemicarbazones have been comparatively rare.

bismuth (III)

thiosemicarbazones


Input: Here, a main group seven-coordinated bismuth (III) complex [Bi (L) (NO3) 2 (CH3CH2OH)] (1) (HL = 2-acetylpyridine N (4)-phenylthiosemicarbazone) has been synthesized and characterized by elemental analysis, IR, (1) H NMR and single-crystal X-ray diffraction studies.

bismuth (III)

Bi (L) (NO3) 2 (CH3CH2OH)

2-acetylpyridine N (4)-phenylthiosemicarbazone

(1) H


Input: The cytotoxicity data suggest that 1 exhibits higher in vitro antiproliferative activity in four human cancer cells tested.


Input: Its possible apoptotic mechanism has been evaluated in HepG2 cells.


Input: Compound 1 promotes a dose-dependent apoptosis in HepG2 cells and the apoptosis is associated with an increase in intracellular reactive oxygen species (ROS) production and reduction of mitochondrial membrane potential (MMP).

oxygen


Input: Identification and synthesis of N-(thiophen-2-yl) benzamide derivatives as BRAF (V600E) inhibitors.

N-(thiophen-2-yl) benzamide


Input: The V600E BRAF kinase mutation, which activates the downstream MAPK signaling pathway, commonly occurs in about 8% of all human malignancies and about 50% of all melanomas.


Input: In this study, we employed virtual screening and chemical synthesis to identify a series of N-(thiophen-2-yl) benzamide derivatives as potent BRAF (V600E) inhibitors.

N-(thiophen-2-yl) benzamide


Input: Structure-activity relationship studies of these derivatives revealed that compounds b40 and b47 are the two most potent BRAF (V600E) inhibitors in this series.


Input: Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype: A cohort study.


Input: OBJECTIVESTo determine the correlates of the " metabolically healthy obese " (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this phenotype. RESEARCH DESIGN AND METHODSThe North West Adelaide Health Study is a prospective cohort study of 4, 056 randomly selected adults aged >= 18 years.


Input: Participants free of CVD/stroke and not underweight (n = 3, 743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. RESULTSCorrelates of the MHO (n = 454 [12. 1%]) included smoking, socioeconomic disadvantage, and physical inactivity.


Input: Compared with metabolically healthy normal-weight subjects (n = 1, 172 [31. 3%]), the MHO were more likely to develop metabolic risk (15. 5 vs. 33. 1%, P < 0. 001) and incident diabetes (odds ratio 2. 09 [95% CI 0. 87-5. 03]) but not CVD/stroke (1. 16 [0. 58-2. 29]) during 5. 5-10. 3 years of follow-up.


Input: These risks were not seen in MHO subjects maintaining metabolic health (n = 188 [67%]).


Input: Sustained metabolic health in obese participants was associated with age <= 40 years and lower waist circumference.


Input: Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean [SE]) percentage of leg fat (49. 9 [0. 5] vs. 53. 2 [0. 7]) and lower waist circumference (104 [0. 6] vs. 101 cm [0. 8]), despite no significant differences in overall adiposity. CONCLUSIONS " Healthy " obesity was a transient state for one-third of subjects.


Input: Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution.


Input: The MHO phenotype may be sustained by promoting lower waist circumferences.


Input: Blocking IL-1 beta Induces a Healing-associated Wound Macrophage Phenotype and Improves Healing in Type-2 Diabetes.


Input: Diabetes is associated with persistent inflammation and defective tissue repair responses.


Input: The hypothesis of this study was that IL-1 beta is part of a pro-inflammatory positive feedback loop that sustains a persistent pro-inflammatory wound macrophage phenotype which contributes to impaired healing in diabetes.


Input: Macrophages isolated from wounds in diabetic humans and mice exhibited a pro-inflammatory phenotype, including expression and secretion of IL-1 beta.


Input: The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena as in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of pro-inflammatory genes and downregulates expression of pro-healing factors in cultured macrophages.


Input: Furthermore, inhibiting the IL-1 beta pathway using a neutralizing antibody and macrophages from IL1 receptor knockout mice blocked the conditioned medium-induced upregulation of pro-inflammatory genes and downregulation of pro-healing factors.


Input: Importantly, inhibiting the IL-1 beta pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from pro-inflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors and improved healing of these wounds.


Input: Our findings indicate that targeting the IL-1 beta pathway represents a new therapeutic approach for improving the healing of diabetic wounds.


Input: Atmospheric chemistry of CF3O2: a theoretical study on mechanisms and pathways of the CF3O2 + IO reaction.

IO


Input: The mechanisms and reaction pathways for the CF3O2 + IO reaction have been investigated by quantum chemistry methods.

IO


Input: It has been found that the title reaction takes place on both the singlet and triplet potential energy surfaces (PES).


Input: On the singlet PES, the most important products include CF3OOOI, CF3OOIO, CF3OIO2, and CF2O + FIO2, while other products such as CF2O + FOIO, CF2O + FOOI, CF3OOI + O ((3) P), CF3OI + O2 ((1) Delta and (3) Sigma), and CF3O + OIO are negligible due to high barriers or unstable formations.

FOIO

FOOI

O

OIO


Input: On the triplet PES, CF3O + OIO is the dominant product with a lower barrier.

OIO


Input: As for FIO2 and it isomers, the most stable one is FIO2.


Input: TDDFT (Time Dependent Density Functional Theory) calculation indicates that CF3OOOI, CF3OOIO and CF3OIO2 undergo photolysis easily under sunlight.


Input: Moreover, a minor contribution relative to hydrogen is found in the CX3O2 + IO (X = H and F) reactions.

hydrogen

IO

H

F


Input: Optically healable polymers.


Input: Polymers that can easily be repaired after being damaged are attractive as this characteristic can improve the reliability, functionality, and lifetime of many products.


Input: In the last decade, researchers have thus developed new approaches to create stimuli-responsive polymer systems, which have the ability to autonomously heal or can be repaired upon exposure to an external stimulus.


Input: This review summarizes the current knowledge of optically healable or photo-healable polymers.


Input: The use of light as a stimulus for healing offers several attractive features, including the ability to deliver the stimulus locally, which opens up the possibility of healing the material under load, as well as the ability to tailor the wavelength of light to selectively address a specific component of the material, e. g. only the damaged parts.


Input: So far, two main classes of optically healable polymers have been explored, which are structurally dynamic polymers and mechanically activated reactive systems.


Input: Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.

nicotine


Input: RATIONALE: Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established.

acetylcholine


Input: OBJECTIVE: Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids.


Input: METHODS: Separate groups of male C57BL/6J mice discriminated 0. 56, 1, or 1. 78 mg/kg of nicotine base.

nicotine


Input: Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-beta-erythroidine (DH beta E).

Nicotine

varenicline

cytisine

mecamylamine

dihydro-beta-erythroidine

DH beta E


Input: Midazolam and morphine were tested to examine sensitivity to non-nicotinics.

Midazolam

morphine


Input: RESULTS: The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased.

nicotine


Input: Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose.

Varenicline

cytisine

nicotine

nicotine

nicotine


Input: Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine.

Morphine

nicotine

midazolam

nicotine


Input: As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased.

mecamylamine


Input: DH beta E antagonized nicotine in animals discriminating the smallest dose of nicotine.

DH beta E

nicotine

nicotine


Input: Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine.

Varenicline

nicotine

cytisine

nicotine


Input: CONCLUSIONS: These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.

nicotine

varenicline

cytisine

acetylcholine


Input: Reinforcement enhancing effects of nicotine via smoking.

nicotine


Input: RATIONALE: In animals, nicotine enhances reinforcement from stimuli unrelated to nicotine intake.

nicotine

nicotine


Input: Human research is suggestive but has not clearly shown a similar influence of nicotine.

nicotine


Input: OBJECTIVES: We assessed acute effects of nicotine via smoking on enhancement of positive (money, music) or negative (termination of noise) reinforcers, or no " reward " (control).

nicotine


Input: These different rewards determined the generalizability of nicotine effects.

nicotine


Input: MATERIALS AND METHODS: Dependent (n = 25) and nondependent (n = 27) smokers participated in three sessions, each after overnight abstinence.


Input: Using a within-subjects design, sessions involved no smoking or smoking denicotinized (0. 05 mg) or nicotine (0. 6 mg) Quest (R) brand cigarettes.

nicotine


Input: For comparison, a fourth session involved no abstinence prior to smoking one' s own brand to gauge responses under typical nicotine satiation.

nicotine


Input: Reinforcement was assessed by responses on a simple operant computer task for the rewards, each available singly on a progressive ratio schedule during separate trials.


Input: RESULTS: The reinforcing effect of music, but not other rewards, was greater due to the nicotine cigarette, compared to the denicotinized cigarette or no smoking.

nicotine


Input: Reinforcement enhancing effects of nicotine did not differ between dependent and nondependent groups, indicating no influence of withdrawal relief.

nicotine


Input: Responding due to acute nicotine after abstinence was very similar to responding to one' s own brand after no abstinence.

nicotine


Input: CONCLUSIONS: Acute nicotine intake per se from smoking after abstinence enhances the reinforcing value of rewards unassociated with smoking, perhaps in a manner comparable to ad lib smoking after no abstinence.

nicotine


Input: Nicotine' s reinforcement enhancing effects may be specific to certain rewards, perhaps those sensory in nature.

Nicotine


Input: Evaporation-Induced Coating of Hydrous Ruthenium Oxide on Mesoporous Silica Nanoparticles to Develop High-Performance Supercapacitors.

Hydrous Ruthenium Oxide

Silica


Input: An efficient evaporation-induced coating method combining microwave-assisted hydrothermal transformation and annealing is developed to fabricate an ideal electrode material from composites with a layer of hydrous RuO2 on mesoporous silica nanoparticles (MSNs), for a high-performance supercapacitor.

hydrous RuO2

silica


Input: Total and RuO2-based specific capacitances are as high as 1125 and 2000 F g (-1), respectively.


Input: Anti-biofilm Effects of Honey Against Wound Pathogens Proteus mirabilis and Enterobacter cloacae.


Input: Biofilm growth and its persistence within wounds have recently been suggested as contributing factors to impaired healing.


Input: The goal of this study was to investigate the anti-biofilm effects of several honey samples of different botanical origin, including manuka honey against Proteus mirabilis and Enterobacter cloacae wound isolates.


Input: Quantification of biofilm formation was carried out using a microtiter plate assay.


Input: All honeys at a sub-inhibitory concentration of 10% (w/v) significantly reduced the biofilm development of both isolates.


Input: Similarly, at a concentration of 50% (w/v), each of the honeys caused significant partial detachment of Pr. mirabilis biofilm after 24 h.


Input: On the other hand, no honey was able to significantly detach Ent. cloacae biofilm.


Input: In addition, treatment of Ent. cloacae and Pr. mirabilis biofilms with all honeys resulted in a significant decrease in colony-forming units per well values in a range of 0. 35-1. 16 and 1. 2-7. 5 log units, respectively.


Input: Of the tested honeys, manuka honey possessed the most potent anti-biofilm properties.


Input: Furthermore, methylglyoxal, an antibacterial compound of manuka honey, was shown to be responsible for killing biofilm-embedded wound bacteria.

methylglyoxal


Input: These findings suggest that manuka honey could be used as a potential therapy for the treatment of wounds containing Pr. mirabilis or Ent. cloacae.


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Solution-processible highly conducting fullerenes.

fullerenes


Input: n-Doping of solution-processible organic semiconductors: highly conductive fullerenes are demonstrated through solution-processed fulleropyrrolidinium iodide (FPI) and FPI-doped PCBM to reach a high conductivity (3. 2 S/m).

fullerenes

fulleropyrrolidinium iodide

FPI

FPI

PCBM


Input: The n-doping proceeds via anion-induced electron transfer between the iodide on FPI and the fullerene in the solid state.

iodide

FPI

fullerene


Input: Influence of the Green Tea Leaf Extract on Neurotoxicity of Aluminium Chloride in Rats.

Aluminium Chloride


Input: Aluminium may have an important role in the aetiology/pathogenesis/precipitation of Alzheimer' s disease.

Aluminium


Input: Because green tea (Camellia sinensis L.) reportedly has health-promoting effects in the central nervous system, we evaluated the effects of green tea leaf extract (GTLE) on aluminium chloride (AlCl3) neurotoxicity in rats.

aluminium chloride


Input: All solutions were injected into the cornu ammonis region 1 hippocampal region.


Input: We measured the performance of active avoidance (AA) tasks, various enzyme activities and total glutathione content (TGC) in the forebrain cortex (FbC), striatum, basal forebrain (BFb), hippocampus, brain stem and cerebellum.

glutathione


Input: AlCl3 markedly reduced AA performance and activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE) in all regions.


Input: It decreased TGC in the FbC, striatum, BFb, hippocampus, brain stem and cerebellum, and increased superoxide dismutase activity in the FbC, cerebellum and BFb.

superoxide


Input: GTLE pretreatment completely reversed the damaging effects of AlCl3 on AA and superoxide dismutase activity, markedly corrected COX and AChE activities, and moderately improved TGC.

superoxide


Input: GTLE alone increased COX and AChE activities in almost all regions.


Input: GTLE reduces AlCl3 neurotoxicity probably via antioxidative effects and improves mitochondrial and cholinergic synaptic functions through the actions of (-)-epigallocatechin gallate and (-)-epicatechin, compounds most abundantly found in GTLE.

(-)-epigallocatechin gallate

(-)-epicatechin


Input: Our results suggest that green tea might be beneficial in Alzheimer' s disease.


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Towards squalamine mimics: synthesis and antibacterial activities of head-to-tail dimeric sterol-polyamine conjugates.

sterol

polyamine


Input: Four dimeric sterol-polyamine conjugates have been synthesized from the homo-and hetero-connection of monomeric sterol-polyamine analogs in a head-to-tail manner.

sterol

polyamine

sterol

polyamine


Input: These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate.


Input: Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs.

cholic acid

deoxycholic acid


Input: This is in contrast to the finding that a monomeric deoxycholic acid-spermine conjugate was more active than the corresponding cholic acid-derived analog.

deoxycholic acid

spermine

cholic acid


Input: Synthesis and Structure-Activity Relationship Studies of Derivatives of the Dual Aromatase-Sulfatase Inhibitor 4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate.

4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate


Input: 4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs).

4-{[(4-Cyanophenyl) (4H-1, 2, 4-triazol-4-yl) amino] methyl} phenyl sulfamate

F

Cl

Br


Input: Structure-activity relationship studies were performed on these compounds, and various modifications were made to their structures involving relocation of the halogen atom, introduction of more halogen atoms, replacement of the halogen with another group, replacement of the methylene linker with a difluoromethylene linker, replacement of the para-cyanophenyl ring with other ring structures, and replacement of the triazolyl group with an imidazolyl group.

halogen

halogen

halogen

methylene

difluoromethylene

para-cyanophenyl

triazolyl

imidazolyl


Input: The most potent in vitro DASI discovered is an imidazole derivative with IC50 values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0. 2 and 2. 5 nM, respectively.

imidazole

steroid


Input: The parent phenol of this compound inhibits aromatase with an IC50 value of 0. 028 nM in the same assay.

phenol


Input: P2X and P2Y nucleotide receptors as targets in cardiovascular disease.

nucleotide


Input: Endogenous nucleotides have widespread actions in the cardiovascular system, but it is only recently that the P2X and P2Y receptor subtypes, at which they act, have been identified and subtype-selective agonists and antagonists developed.

nucleotides


Input: These advances have greatly increased our understanding of the physiological and pathophysiological functions of P2X and P2Y receptors, but investigation of the clinical usefulness of selective ligands is at an early stage.


Input: Nonetheless, the evidence considered in this review demonstrates clearly that various cardiovascular disorders, including vasospasm, hypertension, congestive heart failure and cardiac damage during ischemic episodes, may be viable targets.


Input: With further development of novel, selective agonists and antagonists, our understanding will continue to improve and further therapeutic applications are likely to be discovered.


Input: Therapeutic applications of PI3K inhibitors in cardiovascular diseases.


Input: PI3Ks are signaling enzymes engaged by different types of membrane receptors and activated in cardiovascular diseases such as hypertension, atherosclerosis, thrombosis and heart failure.


Input: Studies performed on genetically modified animals have provided proof-of-concept that general or isoform-specific blockade of these enzymes can modify disease development and progression.


Input: Hence, therapeutic inhibition of PI3Ks with novel pharmacological compounds constitutes a promising area of drug development.


Input: In particular, inhibitors of PI3Ks have the potential to reduce blood pressure, restrain the development of atherosclerosis and/or stabilize atherosclerotic plaques, blunt platelet aggregation, prevent left ventricular remodeling and preserve myocardial contractility in heart failure.


Input: This review summarizes the rationale of PI3K inhibition in the most prevalent cardiovascular diseases, and the available data on the therapeutic effects of PI3K inhibitors in their preclinical models.


Input: Implications for future drug development and human therapy are also discussed.


Input: Design of UCST Polymers for Chilling Capture of Proteins.


Input: Ureido-derivatized polymers, such as poly (allylurea) (PU) and poly (L-citrulline) derivatives, exhibited upper critical solution temperature (UCST) behavior under physiological buffer conditions as we previously reported.

poly (allylurea)

poly (L-citrulline)


Input: The PU derivatives having amino groups (PU-Am) also showed UCST behavior.

amino

PU-Am


Input: In this study, we modified the amino groups of the polymer with succinyl anhydride (PU-Su) or acetyl anhydride (PU-Ac) to determine the effects of these ionic groups on the UCST behavior and to control interactions between the PU derivatives and biocomponents such as proteins and cells.

amino

succinyl anhydride

PU-Su

acetyl anhydride

PU-Ac


Input: Succinylation of PU-Am resulted in a significant decrease in phase separation temperature (Tp), whereas acetylation of PU-Am resulted in an increase in Tp.

PU-Am

PU-Am


Input: As expected, the Tp of PU-Am and PU-Su changed when the pH of the solution was changed.

PU-Am

PU-Su


Input: The Tp of PU-Am increased at higher pH, whereas that of PU-Su increased at lower pH, indicating that ionic charge decreases Tp of PU derivatives by increasing osmotic pressure and by increasing hydrophilicity of the polymer chains.

PU-Am

PU-Su


Input: Interestingly, these groups did not significantly change UCST when these groups were nonionic.


Input: We then examined capture and separation of particular proteins from a protein mixture by cooling-induced phase separation.


Input: Selective and rapid capture of particular proteins from protein mixture by PU derivatives was shown, indicating that the ureido-derivatized polymers are potential media for bioseparation under biofriendly conditions.


Input: Self-assembly of elastin-mimetic double hydrophobic polypeptides.


Input: We have constructed a novel class of " double-hydrophobic " block polypeptides based on the hydrophobic domains found in native elastin, an extracellular matrix protein responsible for the elasticity and resilience of tissues.


Input: The block polypeptides comprise proline-rich poly (VPGXG) and glycine-rich poly (VGGVG), both of which dehydrate at higher temperature but form distinct secondary structures, beta-turn and beta-sheet respectively.

proline

glycine


Input: In water at 45 degrees C, the block polypeptides initially assemble into nanoparticles rich in beta-turn structures, which further connect into long (> 10 mu m), beaded nanofibers along with the increase in the beta-sheet content.


Input: The nanofibers obtained are well-dispersed in water, and show thermoresponsive properties.


Input: Polypeptides comprising each block component assemble into different morphologies, showing that the conjugation of poly (VPGXG) and poly (VGGVG) plays a role for beaded fiber formation.


Input: These results may provide innovative ideas for designing peptide-based materials but also opportunities for developing novel materials useful for tissue engineering and drug delivery systems.


Input: Extraction of the volatile oil from Carum carvi of Tunisia and Lithuania by supercritical carbon dioxide: chemical composition and antiulcerogenic activity.

carbon dioxide


Input: This study investigates whether the essential oil prepared from Carum carvi seeds exhibits antiulcerogenic activity.


Input: Its volatile oil was obtained by supercritical fluid extraction (SFE) and by hydrodistillation.


Input: The essential oils were analysed by GC-MS to monitor their composition.


Input: The chemical analysis revealed that the essential oils extracted under SFE conditions had high carvone and limonene contents.

carvone

limonene


Input: The antiulcerogenic activity was evaluated by the HCl/ethanol method, which causes injury to the gastric mucosa.

HCl

ethanol


Input: Three treated groups received the essential oil (100-300 mg/kg).


Input: The reference group received omeprazole (30 mg/kg) and the control group received NaCl.

omeprazole

NaCl


Input: After 30 min, all groups were treated with HCl/EtOH for gastric ulcer induction.

HCl

EtOH


Input: The results show C. carvi essential oil enhanced a significant inhibition of 47%, 81% and 88%, respectively, for three doses of essential oil used, which was similar to that induced by omeprazole (95%) (p < 0. 005).

omeprazole


Input: Creating " Living " Polymer Surfaces to Pattern Biomolecules and Cells on Common Plastics.


Input: Creating patterns of biomolecules and cells has been applied widely in many fields associated with the life sciences, including diagnostics.


Input: In these applications it has become increasingly apparent that the spatiotemporal arrangement of biological molecules in vitro is important for the investigation of the cellular functions found in vivo.


Input: However, the cell patterning techniques often used are limited to creating 2D functional surfaces on glass and silicon.

silicon


Input: In addition, in general, these procedures are not easy to implement in conventional biological laboratories.


Input: Here, we show the formation of a living poly (ethylene glycol) (PEG) layer that can be patterned with visible light on plastic surfaces.

poly (ethylene glycol)

PEG


Input: This new and simple method can be expanded to pattern multiple types of biomolecule on either a previously formed PEG layer or a plastic substrate.

PEG


Input: Using common plastic wares (i. e., polyethylene films and polystyrene cell culture Petri-dishes), we demonstrate that these PEG-modified surfaces have a high resistance to protein adsorption and cell adhesion, while at the same time, being capable of undergoing further molecular grafting with bioactive motifs.

polyethylene

polystyrene

PEG


Input: With a photomask and a fluid delivery system, we illustrate a flexible way to immobilize biological functions with a high degree of 2D and 3D spatial control.