In vitro nematicidal activity of two ferrocenyl chalcones against larvae of Haemonchus contortus (L3) and Nacobbus aberrans (J2).

The main goal of this work was to evaluate the in vitro biological activity of two ferrocenyl chalcones (FcC-1 and FcC-2) against Haemonchus contortus (third-stage larvae (L3)) and Nacobbus aberrans (second-stage juveniles (J2)). Both compounds were synthesized and characterized by usual spectroscopic methods and their molecular structures were confirmed by single-crystal X-ray diffractometry. Nematode strains were examined in terms of percentage mortality of H. contortus (L3) by the action of FcC-1, which showed an effectivity of 100% at a concentration of 342 µM in 24 h, with EC50 = 20.33 µM and EC90 = 162.76 µM, whereas FcC-2 had an effectivity of 72% at a concentration of 342 µM in 24 h, with EC50 = 167.39 µM and EC90 = 316.21 µM. The effect of FcC-1 against nematode phytoparasite N. aberrans showed a better percentage of 95% at a concentration of 342 µM, with EC50 = 7.18 µM and EC90 = 79.25 µM, whereas the effect of FcC-2 was 87% at 342 µM, with EC50 = 168 µM and EC90 = 319.56 µM at 36 h. After treatment, the scanning electron micrographs revealed deformities in the dorsal flank and posterior part close to the tail of H. contortus L3. They showed moderate in vitro nematicidal activity against H. contortus L3 and N. aberrans J2.

Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by flufenamic acid.

In this work, we report the synthesis of novel fluorescent molecules, based on 1,8-naphthalimide thio- and amino-derivatives, designed to display an OFF-ON and ON-OFF photoelectron transfer fluorescence switch upon interaction with a proton-donor drug. We have functionalized the new probes to allow easy formation of a covalent link to polymer matrices, for future applications as drug delivery sensors. We have investigated the fluorescent switch of the new probes using flufenamic acid (FA, pKa 3.65), a water insoluble, non-steroidal anti-inflammatory drug, as a model drug and proton source. The rapid interaction of the new probes with FA resulted in fluorescence enhancement or decrease and a large Stokes shift, all of which allowed the detection of the drug in the nanomolar range. The new 1,8-naphthalimide fluorescent dyes reported in this work are interesting tools for the detection and quantification of acidic drugs and biomolecules.

Quantum spin liquids unveil the genuine Mott state.

The localization of charge carriers by electronic repulsion was suggested by Mott in the 1930s to explain the insulating state observed in supposedly metallic NiO. The Mott metal-insulator transition has been subject of intense investigations ever since1-3-not least for its relation to high-temperature superconductivity4. A detailed comparison to real materials, however, is lacking because the pristine Mott state is commonly obscured by antiferromagnetism and a complicated band structure. Here we study organic quantum spin liquids, prototype realizations of the single-band Hubbard model in the absence of magnetic order. Mapping the Hubbard bands by optical spectroscopy provides an absolute measure of the interaction strength and bandwidth-the crucial parameters that enter calculations. In this way, we advance beyond conventional temperature-pressure plots and quantitatively compose a generic phase diagram for all genuine Mott insulators based on the absolute strength of the electronic correlations. We also identify metallic quantum fluctuations as a precursor of the Mott insulator-metal transition, previously predicted but never observed. Our results suggest that all relevant phenomena in the phase diagram scale with the Coulomb repulsion U, which provides a direct link to unconventional superconductivity in cuprates and other strongly correlated materials.

Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. RESULTS: A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. CONCLUSION: Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Screening out the non-Arrhenius behaviour of nematic-isotropic transition by room temperature ionic liquid.

Differential Scanning Calorimetry (DSC) and optical polarization microscopy of a mixture of the liquid crystalline material (N-(4-methoxybenzylidene)-4-butylaniline, MBBA) and a Fe-based room temperature ionic liquid 1-ethyl-3-methylimidazolium tetrachloroferrate ([Emim](+) [FeCl4](-), EMIF) indicate a decrease in the nematic-isotropic (N-I) phase transition temperature (T(NI)) with an increase in EMIF concentration, explained by a proposed model of Coulomb "screening" of MBBA quadrupoles by the EMIF ions along with ionic "self screening." DSC studies of EMIF-MBBA and pure EMIF and comparison with pure MBBA results show that the major transitions in pure EMIF have Arrhenius behaviour, but more importantly the previously found convex Arrhenius behaviour of the pristine MBBA [K. Dan et al., Europhys. Lett. 108, 36007 (2014)] becomes Arrhenius in the mixture, indicating a conversion of the entropic N-I activation barrier to an enthalpic one. In presence of EMIF, a drastic decrease in the intensity of out-of-plane distortions of benzene rings in MBBA is found from Fourier transform infrared spectroscopy, consistent with significant reduction in the conformational states of MBBA. This suppression of large amplitude motion is again consistent with a Coulomb screening and gives a molecular basis for the entropic-to-enthalpic conversion of the N-I activation barrier.

Magnetic and non-magnetic phases of a quantum spin liquid.

A quantum spin-liquid phase is an intriguing possibility for a system of strongly interacting magnetic units in which the usual magnetically ordered ground state is avoided owing to strong quantum fluctuations. It was first predicted theoretically for a triangular-lattice model with antiferromagnetically coupled S = 1/2 spins. Recently, materials have become available showing persuasive experimental evidence for such a state. Although many studies show that the ideal triangular lattice of S = 1/2 Heisenberg spins actually orders magnetically into a three-sublattice, non-collinear 120° arrangement, quantum fluctuations significantly reduce the size of the ordered moment. This residual ordering can be completely suppressed when higher-order ring-exchange magnetic interactions are significant, as found in nearly metallic Mott insulators. The layered molecular system κ-(BEDT-TTF)(2)Cu(2)(CN)(3) is a Mott insulator with an almost isotropic, triangular magnetic lattice of spin-1/2 BEDT-TTF dimers that provides a prime example of a spin liquid formed in this way. Despite a high-temperature exchange coupling, J, of 250 K (ref. 6), no obvious signature of conventional magnetic ordering is seen down to 20 mK (refs 7, 8). Here we show, using muon spin rotation, that applying a small magnetic field to this system produces a quantum phase transition between the spin-liquid phase and an antiferromagnetic phase with a strongly suppressed moment. This can be described as Bose-Einstein condensation of spin excitations with an extremely small spin gap. At higher fields, a second transition is found that suggests a threshold for deconfinement of the spin excitations. Our studies reveal the low-temperature magnetic phase diagram and enable us to measure characteristic critical properties. We compare our results closely with current theoretical models, and this gives some further insight into the nature of the spin-liquid phase.

[Acute pulmonary embolism following lung resection: report of two cases].

We reported 2 cases of acute pulmonary embolism after resection for lung cancer. A 47-year-old male was admitted to our hospital with ground-glass opacity (GGO) on a chest computed tomography (CT). We performed a right upper lobectomy and node dissection (ND) 2a dissection. Two days after the operation, he developed hypotension and hypoxemia. He was diagnosed as acute pulmonary embolism by chest CT and lung scintigram. A 68-year-old women was performed right S6 segmentectomy for lung cancer. The next day, she complained of sudden chest discomfort and dyspnea. She was diagnosed as acute pulmonary embolism by chest CT. Immediately, we started anticoagration therapy with heparin and their condition were improved. It was very important to early diagnose and start anticoagration therapy immediately for acute pulumonary embolism.

Mott transition from a spin liquid to a Fermi liquid in the spin-frustrated organic conductor kappa-(ET)2Cu2(CN)3.

The pressure-temperature phase diagram of the organic Mott insulator kappa-(ET)2Cu2(CN)3, a model system of the spin liquid on triangular lattice, has been investigated by 1H NMR and resistivity measurements. The spin-liquid phase is persistent before the Mott transition to the metal or superconducting phase under pressure. At the Mott transition, the spin fluctuations are rapidly suppressed and the Fermi-liquid features are observed in the temperature dependence of the spin-lattice relaxation rate and resistivity. The characteristic curvature of the Mott boundary in the phase diagram highlights a crucial effect of the spin frustration on the Mott transition.

Spin liquid state in an organic Mott insulator with a triangular lattice.

1H NMR and static susceptibility measurements have been performed in an organic Mott insulator with a nearly isotropic triangular lattice, kappa-(BEDT-TTF)2Cu2(CN)(3), which is a model system of frustrated quantum spins. The static susceptibility is described by the spin S=1/2 antiferromagnetic triangular-lattice Heisenberg model with the exchange constant J approximately 250 K. Regardless of the large magnetic interactions, the 1H NMR spectra show no indication of long-range magnetic ordering down to 32 mK, which is 4 orders of magnitude smaller than J. These results suggest that a quantum spin liquid state is realized in the close proximity of the superconducting state appearing under pressure.

Enhanced cytosolic delivery of plasmid DNA by a sulfhydryl-activatable listeriolysin O/protamine conjugate utilizing cellular reducing potential.

Listeriolysin O (LLO), a sulfhydryl-activated pore-forming protein from Listeria monocytogenes, was tested and utilized for promoting plasmid DNA (pDNA) delivery into the cytosol of cells in culture. To render pDNA-complexing capability to LLO, the unique cysteine 484 of LLO was conjugated to polycationic peptide protamine (PN) at a 1:1 molar ratio through a reversible, endosome-labile disulfide bond. The sulfhydryl-oxidized LLO construct, LLO-s-s-PN, completely lacked its pore-forming activity, yet regained its original activity upon reduction. The enhanced cytosolic delivery using this construct therefore relies on the requisite reduction of the disulfide bond in LLO-s-s-PN by endogenous cellular reducing capacity. Condensed PN/pDNA complexes incorporating LLO-s-s-PN were tested for their enhanced gene delivery capability monitoring reporter gene expression in HEK293, RAW264.7, P388D1 cell lines and bone-marrow-derived macrophages in the presence of serum. Dramatic enhancement was observed for all tested complexes with varying weight ratios. The effect was most prominent at 0.64-0.80 (w/w) of PN/pDNA upon replacing 1-4% of PN with LLO-s-s-PN, resulting in approximately three orders of magnitude higher luciferase expression compared to PN/pDNA without apparent toxicity. These results demonstrate that incorporation of endosomolytic LLO into pDNA delivery systems in a controlled fashion is a promising approach of enhancing delivery into the cytosol of target cells in gene delivery strategies.

Extended resection of the pulmonary artery and the aorta for primary lung cancer. Report of a case.

We report a case of squamous cell carcinoma of the lung in which a left pneumonectomy combined resection of the pulmonary artery and aorta was performed using a cardiopulmonary bypass. The bifurcation of the pulmonary artery was repaired with a pericardial patch and the descending aorta was replaced with an artificial vessel Eleven months later, the patient underwent dissection of the contralateral mediastinal lymph nodes because of a recurrence of the disease. Even though pulmonary metastases have again recently appeared, he is alive and doing well two years after operation. To obtain a better prognosis in cases demonstrating an involvement of the bifurcation of pulmonary artery, more effective combined treatment still needs to be developed.

Large-Scale Mapping Observations of the C i (3P1-3P0) and CO (J = 3-2) Lines toward the Orion A Molecular Cloud.

Large-scale mapping observations of the 3P1-3P0 fine-structure transition of atomic carbon (C i, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mount Fuji submillimeter-wave telescope. The observations cover 9 deg2 and include the Orion Nebula M42 and the L1641 dark cloud complex. The C i emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO (J=1-0). The CO (J=3-2) emission shows a more featureless and extended distribution than C i. The C i/CO (J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the C i/13CO (J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the C i and 13CO (J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.

CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs.

The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO-K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. Vmax in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO-K1 cells, while Km values were similar in all cases. The uptake of beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO-K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter.

Pulmonary blastoma in an adult. A case with rapid progression.

A case of biphasic type pulmonary blastoma in a 59-year-old man is reported. Although the tumour was radically resected, there was rapid metastasization to the neck, mediastinum, liver and multiple bones. Despite radiotherapy, the patient died about 14 months postoperatively. Close follow-up and aggressive chemotherapy should be considered for such tumours.

A sweat-gland tumor metastasizing to the axilla: report of a case.

Sclerosing sweat-duct carcinoma is a rare malignancy of the skin. We herein present the case of a 68-year-old Japanese man who developed sclerosing sweat-duct carcinoma 2 years after undergoing local excision of a primary tumor in his right arm. Firm nodules appeared in the right axilla, which were revealed by surgical resection to be metastases. This rare tumor grows slowly but usually metastasizes to the regional lymph nodes, whereupon they are often associated with a poor prognosis. As the effectiveness of chemotherapy and radiotherapy against this neoplasm remains unclear, we recommend that the disease should initially be aggressively treated by surgery, which would also be indicated for any metastatic lesions.

Inhibition of IL-1-induced IL-6 production by synthetic retinoids.

The effects of retinoids and retinoid antagonists on IL-6 production in MC3T3-E1 cells were investigated. None of the synthetic retinoids examined stimulated IL-6 production, but all of them strongly inhibited IL-6 production induced by mouse IL-1 alpha. Their inhibitory activities correlated well with their differentiation-inducing activities in HL-60 assay or their binding affinities to nuclear retinoic acid receptors (RARs). Among three retinoid antagonists, two weak antagonists exhibited similar inhibition of mouse IL-1 alpha-induced IL-6 production, whereas a potent retinoid antagonist, 4-(13H-10,11,12,13-tetrahydro-10,10,13,13,15-pentamethyl-dinaph tho[2,3-b] [1,2-e]diazepin-7-yl)benzoic acid (LE540, 14), enhanced IL-6 production under the same conditions.

Effect of vapor pressure deficit on spinach growth under hypobaric conditions.

The effect of vapor pressure deficit (VPD) of air during photoperiod on spinach growth under low total pressure was examined. Spinach plants grown under atmospheric pressure were transplanted into a pressure-reduced growth chamber and cultured hydroponically for eight days. The air temperature in the growth chamber was kept at 25 degrees C during the light period and 20 degrees C during the dark period. In the control, the total pressure was 101 kPa and the VPD was 0.95 kPa. The low pressure treatment had a total pressure of 25 kPa and a VPD of 0.95 kPa. The low pressure and high humidity treatment had a total pressure of 25 kPa, and a VPD of 0.48 kPa. The VPD during the dark period was consistent for all treatments at 0.44 kPa. O2 and CO2 partial pressures were constant at 21 kPa and 40 Pa, respectively. The photosynthetic photon flux density (PPFD) on a plant bed inside the growth chamber was 250 micromoles m-2 s-1 on a plant bed. Relative growth rate (RGR) of spinach in the low pressure and high humidity treatment was significantly greater than in the control. There was no significant difference in RGR between the control and the low pressure treatment. The low pressure and high humidity treatment also had increased leaf area. These results showed that the effect of pressure alone was not significant on RGR, but the combination of low pressure with high humidity was important.