Ultra-small bimetallic phosphides for dual-modal MRI imaging guided photothermal ablation of tumors.

Metal phosphides have been proved to be potential theranostic agents of tumors. However, the limitations of single-modal imaging or the treatment effect of such materials need to be further improved. Here, we successfully prepared polyvinylpyrrolidone-modified bimetallic nickel cobalt phosphide (NiCoP/PVP) nanoparticles as a theranostic agent of tumors. Owing to the different types of magnetic properties of Ni and Co components, T1- and T2-weighted magnetic resonance imaging (MRI) could be simultaneously achieved to compensate the low accuracy brought about by single-modal MRI. In addition, NiCoP/PVP possesses excellent photothermal properties owing to its obvious absorption in the near-infrared (NIR) region, which endows NiCoP/PVP with high photothermal conversion efficiency (PCE) to serve as a photothermal agent for tumor ablation. Therefore, NiCoP/PVP is a promising theranostic agent for accurate diagnosis and effective treatment of tumors.

A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABA(A) Receptors and Synaptic Inhibition.

Exogenously expressed opsins are valuable tools for optogenetic control of neurons in circuits. A deeper understanding of neural function can be gained by bringing control to endogenous neurotransmitter receptors that mediate synaptic transmission. Here we introduce a comprehensive optogenetic toolkit for controlling GABA(A) receptor-mediated inhibition in the brain. We developed a series of photoswitch ligands and the complementary genetically modified GABA(A) receptor subunits. By conjugating the two components, we generated light-sensitive versions of the entire GABA(A) receptor family. We validated these light-sensitive receptors for applications across a broad range of spatial scales, from subcellular receptor mapping to in vivo photo-control of visual responses in the cerebral cortex. Finally, we generated a knockin mouse in which the "photoswitch-ready" version of a GABA(A) receptor subunit genomically replaces its wild-type counterpart, ensuring normal receptor expression. This optogenetic pharmacology toolkit allows scalable interrogation of endogenous GABA(A) receptor function with high spatial, temporal, and biochemical precision.

Oxygenated Phosphine Fumigation for Control of Light Brown Apple Moth (Lepidoptera: Tortricidae) Eggs on Cut-Flowers.

Light brown apple moth, Epiphyas postvittana (Walker), eggs were subjected to oxygenated phosphine fumigation treatments under 70% oxygen on cut flowers to determine efficacy and safety. Five cut flower species: roses, lilies, tulips, gerbera daisy, and pompon chrysanthemums, were fumigated in separate groups with 2,500 ppm phosphine for 72 h at 5°C. Egg mortality and postharvest quality of cut flowers were determined after fumigation. Egg mortalities of 99.7-100% were achieved among the cut flower species. The treatment was safe to all cut flowers except gerbera daisy. A 96-h fumigation treatment with 2,200 ppm phosphine of eggs on chrysanthemums cut flowers also did not achieve complete control of light brown apple moth eggs. A simulation of fumigation in hermetically sealed fumigation chambers with gerbera daisy showed significant accumulations of carbon dioxide and ethylene by the end of 72-h sealing. However, oxygenated phosphine fumigations with carbon dioxide and ethylene absorbents did not reduce the injury to gerbera daisy, indicating that it is likely that phosphine may directly cause the injury to gerbera daisy cut flowers. The study demonstrated that oxygenated phosphine fumigation is effective against light brown apple moth eggs. However, it may not be able to achieve the probit9 quarantine level of control and the treatment was safe to most of the cut flower species.

Acaricidal activity against Tetranychus urticae and chemical composition of peel essential oils of three Citrus species cultivated in NE Brazil.

The repellency and fumigant toxicities of the peel essential oils of Citrus sinensis var. pêra (LP), C. sinensis var. mimo (LM), and C. aurantium (LL) cultivated in northeast Brazil were evaluated against Tetranychus urticae. Analysis of the oils by GC and GC/MS led to the identification of twenty-eight components, which represented 99.9%, 99.7% and 99.3% of the total constituents of the LP, LM and LL oils, respectively. Limonene was the main component found in all three oils. Other main components were alpha-pinene (1.5% in LP; 1.4% in LM), myrcene (5.7% in LP; 5.9% in LM and 5.6% in LL) and linalool (2.4% in LP; 2.3% in LM and 3.9% in LL). The best repellency action was observed for LM at 2.0%, followed by LL oil and eugenol, both of them at 2.5%. The Citrus oils were less active than eugenol (LC50 = 0.004 microL/L air) and phosphine, which revealed 100% mortality at 2 x 10(-3) g/L (66.7% of the recommended dose). However, the most potent fumigant toxicity was found with LL oil, with an LC50 value of 1.63 microL/L air, followed by the oils from LM and LP with LC50 values of 2.22 microL/L air and 4.63 microL/L air, respectively. The associated fumigant and repellent properties of these Citrus peel oils, particularly those of C. aurantium and C. senensis var. mimo, could be used to advantage for the control of T. urticae.

Synthesis and characterization of a novel class of reducing agents that are highly neuroprotective for retinal ganglion cells.

Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury, in part regulated by an intracellular superoxide anion burst, for which the target(s) are unknown. Shifting the RGC redox state towards reduction and preventing sulfhydryl oxidation is neuroprotective in vitro and in vivo, implying that one or more sulfhydryls on one or more critical proteins may be involved. We synthesized novel borane-protected analogues of the reductant tris(2-carboxyethyl)phosphine (TCEP) with the intent of increasing cell permeability and improving chemical stability, and tested their ability to increase RGC survival in vitro. Retinal ganglion cells of postnatal day 2-4 Long-Evans rats were retrogradely labeled with 4',6-diamidino-2-phenylindole (DAPI). At postnatal days 11-13 the animals were sacrificed, the retinas enzymatically dissociated and plated on poly-L-lysine-coated 96-well flat-bottomed tissue culture plates for 72 h in Neurobasal-A, B27 supplement lacking antioxidants, and TCEP, bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1), (3-propionic acid methyl ester)diphenylphosphine borane complex (PB2), or three commercially available phosphines. Viable DAPI-positive RGCs were identified by calcein-AM staining. At 72 h, PB1 was effective at rescuing acutely axotomized RGCs at concentrations from 1 nM to 100 microM. RGC survival with 1 nM PB1 was 174+/-12% of control (p=0.002). Another compound, PB2, rescued RGCs at 10 pM (177+/-24%; p=0.006) and 10 nM (251+/-34%; p=0.004) at 72 h. A PAMPA assay demonstrated that PB1 and PB2 were substantially more permeable than TCEP. These data demonstrate that modified reductants are effective RGC neuroprotectants at picomolar-nanomolar concentrations. We propose that these novel molecules may act by inhibiting the sulfhydryl oxidation effect of an intracellular superoxide burst.

Comparative toxicity of fumigants and a phosphine synergist using a novel containment chamber for the safe generation of concentrated phosphine gas.

BACKGROUND: With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments. PRINCIPAL FINDINGS: Here we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20 degrees C has been determined with an LC(50) of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20 degrees C is 600 times more potent than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm,

[Preclinical pharmacological study of a novel myocardial perfusion agent: 99mTc-Q3].

In order to provide an experimental foundation for clinical study, we made a preclinical pharmacological investigation of 99mTc-Q3, a novel myocardial perfusion imaging agent, technetium-99m-N,N'-ethylenebis (acetylace-toneiminato) bis (tris (3-methoxy-1-proply) phosphine). After the preparation of this compound, the kinetics of blood clearance in rabbits, biodistribution in mice, measurement of plasma protein binding rate, and myocardial perfusion imaging in dog were carried out. The labelling efficiency and radiochemical purity measured were over 99%, and the stability (in vitro) was good and stable up to 6 hr of testing at room temperature. The pharmacokinetics met the two-compartment model with 0.23 +/- 0.09 ml/min of excellent blood clearance, an initial half-time of 1.5979 +/- 0.4182 min, and a late half-time of 203 +/- 25.83 min. The biodistribution as shown in myocardial accumulation was earlier, the radioactive value was higher, and once extracted, it remained relatively constant in the myocardium for at least 4 hr. The tracer was rapidly cleared from the blood, lung and the liver. The scintigraphy imaging in dog demonstrated that it was rapidly cleared from the lung, and the radioactive concentration approached that of background 1 hr after injection. At 15 min after injection, the myocardial imaging displayed clearly up to 3 hr. In vitro protein binding rate was low (7.13 +/- 0.42%). The tolerance of this drug in mice was 500 times as much as in humans. In conclusion, 99mTc-Q3 exhibits favorable stability, biological property and safety, so clinical study of this preparation as a myocardial perfusion imaging agent is worthwhile.

[ Dynamics of NAD-dependent isocitrate dehydrogenase activity in homogenized rat liver exposed to toxic products of the phosphorus industry]. / Dinamika akivnosti NAD-zavisimoi izotsitratdegidrogenazy v gomogenatakh pecheni krys pod deistviem vrednykh veshchestv fosfornogo proizvodstva.

Dynamic studies showed that the combined action of phosphine and hydrofluoric acid damages the Krebs cycle reactions, dehydrogenization of isocitrate and synthesis of citrate in homogenized rat liver. Yellow phosphorus harmed the citrate synthetic reaction of citric acid cycle in homogenized rat liver as well. That activated the alternative action principles in the cycle. The main cause of such disorders in the Krebs cycle in likely to be the abnormal fat metabolism induced by toxic products of phosphorus industry.

Characterization of transmembrane chemical shift differences in the 31P NMR spectra of various phosphoryl compounds added to erythrocyte suspensions.

Trimethyl phosphate, dimethyl methylphosphonate, diethyl methylphosphonate, trimethylphosphine oxide, and the hypophosphite, phenylphosphinate, and diphenylphosphinate ions all contain the phosphoryl functional group. When added to an intact erythrocyte suspension at 20 degrees C, each of the compounds gave rise to separate intra- and extracellular 31P NMR resonances, and the separation between the two resonances of each compound varied with the mean cell volume. The differences between the intra- and extracellular chemical shifts were shown to be primarily attributable to the effects of hemoglobin. The presence of hemoglobin inside the cell gave rise to a significant difference in the magnetic susceptibilities of the two compartments. In addition, it exerted a large susceptibility-independent chemical shift effect, the magnitude of which was dependent upon the chemical structure of the phosphoryl compound involved. A number of other intra- and extracellular components were also shown to cause chemical shift variations, smaller than those arising from hemoglobin but nonetheless significant. The cell volume dependence of the transmembrane chemical shift differences therefore reflected not only the cell volume dependence of the intracellular hemoglobin concentration but also the changing concentration of the other solutes in the two compartments. In addition to their cell volume dependence, the transmembrane chemical shift differences varied with temperature. In the case of the nonelectrolytes this reflected not only the temperature dependence of the mechanism(s) responsible for the susceptibility-independent shift effects but also the temperature dependence of the rates at which the compounds traversed the cell membrane.

Physical basis of the effect of hemoglobin on the 31P NMR chemical shifts of various phosphoryl compounds.

The marked difference between the intra- and extracellular 31P NMR chemical shifts of various phosphoryl compounds when added to a red cell suspension may be largely understood in terms of the effects of hemoglobin on the 31P NMR chemical shifts. The presence of [oxy- or (carbonmonoxy)-] hemoglobin inside the red cell causes the bulk magnetic susceptibility of the cell cytoplasm to be significantly less than that of the external solution. This difference is sufficient to account for the difference in the intra- and extracellular chemical shifts of the two phosphate esters trimethyl phosphate and triethyl phosphate. However, in the case of the compounds dimethyl methylphosphonate, diethyl methylphosphonate, and trimethyl-phosphine oxide as well as the hypophosphite, phenylphosphinate, and diphenylphosphinate ions, hemoglobin exerts an additional, much larger, effect, causing the 31P NMR resonances to shift to lower frequency in a manner that cannot be accounted for in terms of magnetic susceptibility. Lysozyme is a protein structurally unrelated to hemoglobin and was shown to cause similar shifts to lower frequency of the resonances of these six compounds; this suggests that the mechanism may involve a property of proteins in general and not a specific property of hemoglobin. The effect of different solvents on the chemical shifts of the eight phosphoryl compounds provided an insight into the possible physical basis of the effect.(ABSTRACT TRUNCATED AT 250 WORDS)