An enzymatically activated fluorescence probe for targeted tumor imaging

Beta-galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-betaGal (J. Am. Chem. Soc. 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-betaGal, provides a dramatic fluorescence enhancement upon reaction with beta-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM-TG-betaGal, after confirming that tumors in the model could be labeled with an avidin-beta-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-betaGal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 microm. This strategy has potential clinical application, for example, in video-assisted laparoscopic tumor resection.     

Solid-state low-temperature extrusion of P3HT ribbons

Ribbons of poly(3-hexylthiophene) (P3HT) 0.15 and 0.30 mm thickness were extruded at the temperatures of 200 and 250 °C, i.e., below and above the melting temperature of P3HT (～240 °C), using a small home-made extrusion device. The ribbons produced by this method are continuous and freestanding. WAXS results show that all the extruded samples are more crystalline than the original powder, and the different processing conditions cause different variations in the crystal unit cell dimensions of P3HT. In terms of the degree of orientation, the ribbons extruded in the solid state (T < T _m ) show significant degrees of anisotropy in opposition to the sample extruded in the molten state (T > T _m ), which is fully isotropic.     

Interaction of thorium(IV) with nitrate in aqueous solution: medium effect or weak complexation?

Microcalorimetric titrations were performed to study the Th(IV)/nitrate interaction in aqueous solution. The results show the formation of a weak mononuclear complex of Th(IV) with nitrate and allow the determination of the complexation thermodynamic parameters at 298 K and ionic strength 1.0 mol dm(-3). The reaction is endothermic and entropy driven. Data and comparison with similar actinide(IV) complexes allow to confirm the inner-sphere nature of the Th(NO(3))(3+) complex.     

Electrochemical Behavior of Gold Nanoparticles Generated In Situ on 3‐(1‐Imidazolyl)propyl‐silsesquioxane

Gold nanoparticles of different morphologies have been synthesized on a silica‐based organic‐inorganic hybrid material for catalytic applications. The gold nanoparticles formations proceed through in situ chemical reduction of the AuCl₄^? anions previously adsorbed on 3‐(1‐imidazolyl)propyl‐silsesquioxane, which plays the role of substrate and stabilizer. Two distinct reducing agents, sodium citrate and sodium borohydride, were employed to generate gold nanoparticles of different sizes. UV‐vis diffuse reflectance as well as transmission electron microscopy were employed to evaluate the particle’s morphology. Modified carbon paste electrodes were prepared from these materials and their electrochemical behavior investigated using potassium ferrocyanide and 4‐nitrophenol as redox model compounds. Both AuNPs‐modified electrodes decreased the overpotential of 4‐nitrophenol reduction by around 90 mV compared to the unmodified electrode as evidenced by cyclic voltammetry experiment. However, the smaller diameter particles (borohydride‐reduced) produced more significant catalytic effect as a consequence of their large surface area. Regarding the sensing parameters, the sensitivity is higher for the borohydride‐reduced AuNPs while the values of limit of detection are of the same order of magnitude. Thus, the detection limit and sensitivity are 70.0±0.6 nM and 187 µA/mM for the citrate‐reduced AuNPs; and 75.0±2.2 nM and 238 µA/mM for the borohydride‐reduced AuNPs.     

New Complexes of Ditopic Ligands with “d” and/or “s” Metal Ions

Abstract

The asymmetric compartmental macrocycles containing one N₂O₂ or N₃O₂ Schiff base and one O₂O₃ or O₂O₄ crown-ether like chamber, have been obtained by condensation reaction of the formyl precursors 3,3′-(3-oxapentane-1, 5-diyldioxy) bis (2-hydroxybenzaldehyde) or 3,3′-(3,6-dioxaoctane-1,8-diyldioxy)-bis(2-hydroxybenzaldehyde) with ethyl ethylenediamine (H₂L_A, H₂L_C), 1,5-diamino-3-azamethylpentane(H₂L_B, H₂L_D), also in the presence of metal ions as templating agents. These ditopic ligands, with dissimilar coordination sites, have been designed and used for the selective complexation of “d” and/or “s” metal ions, respectively into the Schiff base and the crown ether chamber. The selectivity of these processes strongly depends on the size and on the donor atom sets of the sites. The possibility to obtain mononuclear M(L)·nH₂O (M = Ni²⁺, Cu²⁺, Co²⁺), Mn(L)(CH₃COO)·nH₂O or Na(L) and hetero-dinuclear MNa(L)(CH₃COO) (M = Ni²⁺, Cu²⁺, Co²⁺) and MnNa(L)(CH₃COO)₂·nH₂O complexes has been successfully tested. The ligands and complexes have been characterized by ir, nmr, mass spectrometry and magnetic susceptibility measurements.

Two of the ligands used for the preparation of the solid samples, i.e., to H₂L_A and H₂L_B, have been employed to study complexation reactions of Co(II) and Na(I) in solution. In order to obtain information on the ligand preorganization effect toward the complex stabilities, a simpler open chain parent compound of H₂L_B (H₂L_E) has been also prepared and studied. FT-IR spectra show that H₂L_A is unable to complex Na⁺ in DMSO while the complexation reactions of Na⁺ by H₂L_B and of Co²⁺ by H₂L_A take place with slow kinetics. Therefore, thermodynamic data have been obtained only for the systems Co²⁺/H₂L_B and Co²⁺/H₂L_E. The thermodynamic parameters obtained for the complexation reactions show that the pre-organization of the donor atoms in H₂L_B does not add a significant contribution to the stabilities of the complexes. Both H₂L_B and H₂L_E form in DMSO 1:1, 1:2 and 1:3 = M:L complexes with very similar stabilities and almost equal enthalpies of formation. Physico-chemical studies suggest besides that the slow reaction of Na⁺ with H₂L_B is probably due to the formation of a 1:1 complex where the metal cation, initially occupying the O₃ cage of the ligand, slowly binds also the oxygens of the phenolic moieties. Spectral and calorimetric data on solutions containing H₂L_B and different Co²⁺: Na⁺ ratios evidence that in DMSO no stable heterodinuclear complexes form when the neutral ligand is considered.     

Influence of Feedstock Particle Size on Lignocellulose Conversion—A Review

Feedstock particle sizing can impact the economics of cellulosic ethanol commercialization through its effects on conversion yield and energy cost. Past studies demonstrated that particle size influences biomass enzyme digestibility to a limited extent. Physical size reduction was able to increase conversion rates to maximum of ≈50%, whereas chemical modification achieved conversions of >70% regardless of biomass particle size. This suggests that (1) mechanical pretreatment by itself is insufficient to attain economically feasible biomass conversion, and, therefore, (2) necessary particle sizing needs to be determined in the context of thermochemical pretreatment employed for lignocellulose conversion. Studies of thermochemical pretreatments that have taken into account particle size as a factor have exhibited a wide range of maximal sizes (i.e., particle sizes below which no increase in pretreatment effectiveness, measured in terms of the enzymatic conversion resulting from the pretreatment, were observed) from <0.15 to 50 mm. Maximal sizes as defined above were dependent on the pretreatment employed, with maximal size range decreasing as follows: steam explosion > liquid hot water > dilute acid and base pretreatments. Maximal sizes also appeared dependent on feedstock, with herbaceous or grassy biomass exhibiting lower maximal size range (<3 mm) than woody biomass (>3 mm). Such trends, considered alongside the intensive energy requirement of size reduction processes, warrant a more systematic study of particle size effects across different pretreatment technologies and feedstock, as a requisite for optimizing the feedstock supply system.     

Hydrolysis of plutonium(VI) at variable temperatures (283-343 K)

The hydrolysis of Pu^VI was studied at variable temperatures (283–343 K) by potentiometry, microcalorimetry, and spectrophotometry. Three hydrolysis reactions, mPuO₂²⁺+nH₂O=(PuO₂)_m(OH)_n+nH⁺), in which (n,m)=(1,1), (2,2), and (5,3), were invoked to describe the potentiometric and calorimetric data. The equilibrium constants (*β_n,m) were determined by potentiometry at 283, 298, 313, 328, and 343 K. As the temperature was increased from 283 to 343 K, *β_1,1, *β_2,2, and *β_5,3, increased by 1, 1.5, and 4 orders of magnitude, respectively. The enhancement of hydrolysis at elevated temperatures is mainly due to the significant increase of the degree of ionization of water as the temperature increases. Measurements by microcalorimetry indicate that the three hydrolysis reactions are all endothermic at 298.15 K, with enthalpies of (35.0±3.4) kJ mol^?1, (65.4±1.0) kJ mol^?1, and (127.7±1.7) kJ mol^?1 for ΔH_1,1, ΔH_2,2, and ΔH_5,3, respectively. The hydrolysis constants at infinite dilution have been obtained with the Specific Ion Interaction approach. The applicability of three approaches for estimating the equilibrium constants at different temperatures, including the constant enthalpy approach, the DQUANT equation, and the Ryzhenko–Bryzgalin model, were evaluated with the data from this work.     

Constrained information minority game: How was the night at El Farol?

We introduce a variation of the El Farol Game in which the only players who surely know the outcome of the last turn of the game are those who actually attended the bar. Other players may receive this information with reduced probability. This information can be transmitted by another player who actually attended the bar in the last turn of the game or from the media. We show that since this game is not organized around the socially optimal point, arbitrage opportunities may arise. Therefore, we study how these opportunities can be exploited by an agent. An interesting application of this model is the market of goods being auctioned, such as cars being repossessed. The results obtained here seem to closely reflect the dynamics of this market in Brazil.     

Camel Grass Phenolic Compounds: Targeting Inflammation and Neurologically Related Conditions

Background: The use of plants for therapeutic purposes has been supported by growing scientific evidence. Methods: This work consisted of (i) characterizing the phenolic compounds present in both aqueous and hydroethanol (1:1, v/v) extracts of camel grass, by hyphenated liquid chromatographic techniques, (ii) evaluating their anti-inflammatory, antioxidant, and neuromodulation potential, through in vitro cell and cell-free models, and (iii) establishing a relationship between the chemical profiles of the extracts and their biological activities. Results: Several caffeic acid and flavonoid derivatives were determined in both extracts. The extracts displayed scavenging capacity against the physiologically relevant nitric oxide (^•NO) and superoxide anion (O₂^•−) radicals, significantly reduced NO production in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7), and inhibited the activity of hyaluronidase (HAase), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some of these bioactivities were found to be related with the chemical profile of the extracts, namely with 3-caffeoylquinic, 4-caffeoylquinic, chlorogenic, and p-coumaric acids, as well as with luteolin and apigenin derivatives. Conclusions: This study reports, for the first time, the potential medicinal properties of aqueous and hydroethanol extracts of camel grass in the RAW 264.7 cell model of inflammation, and in neurologically related conditions.     

Effects of the Seed Oil of Carica papaya Linn on Food Consumption,Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet

Background: Studies indicate that different parts of Carica papaya Linn have nutritional properties that mean it can be used as an adjuvant for the treatment of various pathologies. Methods: The fatty acid composition of the oil extracted from the seeds of Carica papaya Linn was evaluated by gas chromatography, and an acute toxicity test was performed. For the experiment, Swiss mice were fed a balanced or high-fat diet and supplemented with saline, soybean oil, olive oil, or papaya seed oil. Oral glucose tolerance and insulin sensitivity tests were performed. After euthanasia, adiposity, glycemia, total cholesterol and fractions, insulin, resistin, leptin, MCP-1, TNF-α, and IL-6 and the histology of the liver, pancreas, and adipose tissue were evaluated. Results: Papaya seed oil showed predominance of monounsaturated fatty acids in its composition. No changes were observed in the acute toxicity test. Had lower food intake in grams, and caloric intake and in the area of adipocytes without minimizing weight gain or adiposity and impacting the liver or pancreas. Reductions in total and non-HDL-c, LDL-c, and VLDL-c were also observed. The treatment had a hypoglycemic and protective effect on insulin resistance. Supplementation also resulted in higher leptin and lower insulin and cytokine resistance. Conclusions: Under these experimental conditions, papaya seed oil led to higher amounts of monounsaturated fatty acids and had hypocholesterolemic, hypotriglyceridemic, and hypoglycemic effects.