Solvent-Free Reaction for Unsymmetrical Organodisulfides with High Purity and Application as Cathode-Active Materials.

Unsymmetrical disulfides, in which different organic groups are bonded to disulfide bonds, have been synthesized by cross-coupling reactions using thiols as substrates. However, due to the low-binding energy of unsymmetrical disulfides, its disproportionation occurs based on the side reactions with nucleophilic thiols, resulting in the impurity of symmetric disulfides. In this study, we developed a solvent-free synthesis method for unsymmetrical disulfides using thiosulfonates, thiols, and a base. This synthetic method enabled us to obtain highly pure diaryl-substituted unsymmetrical disulfides with particularly low-binding energy without control over the nucleophilicity and elimination properties of the substrate. Furthermore, it was observed that the disproportionation of unsymmetrical disulfides occurred in the solvent. This means that solvent-free condition is one of the factors to obtain unsymmetrical disulfides. As a new application of unsymmetrical disulfides, we applied unsymmetrical disulfides to cathode active materials of lithium batteries based on the reversible multi-electron redox activity of S-S bonds. The batteries using unsymmetrical disulfide cathode-active materials with a carbon nanotube exhibited initial capacities of 127 and 158 Ah/kg, equal to 42 and 53% of their theoretical ones. We demonstrated that unsymmetrical disulfides could be used as cathode-active materials for rechargeable batteries.

Formation of octacalcium phosphate with incorporated dicarboxylate ions containing disulfide bonds.

Octacalcium phosphate (OCP) is a layered compound capable of incorporating carboxylate ions within its interlayer structure. In this study, we successfully synthesised OCP with incorporated 3,3'-dithiodipropionate ions. Our finding is beneficial for the development of novel OCP-based materials with dynamic properties derived from disulfide bonds.

Development of bioinspired damage-tolerant calcium phosphate bulk materials.

Improving the damage tolerance and reliability of ceramic artificial bone materials, such as sintered bodies of hydroxyapatite (HAp), that remain in vivo for long periods of time is of utmost importance. However, the intrinsic brittleness and low damage tolerance of ceramics make this challenging. This paper reports the synthesis of highly damage tolerant calcium phosphate-based materials with a bioinspired design for novel artificial bones. The heat treatment of isophthalate ion-containing octacalcium phosphate compacts in a nitrogen atmosphere at 1000°C for 24 h produced an HAp/ß-tricalcium phosphate/pyrolytic carbon composite with a brick-and-mortar structure (similar to that of the nacreous layer). This composite exhibited excellent damage tolerance, with no brittle fracture upon nailing, likely attributable to the specific mechanical properties derived from its unique microstructure. Its maximum bending stress, maximum bending strain, Young's modulus, and Vickers hardness were 11.7 MPa, 2.8 × 10‒2, 5.3 GPa, and 11.7 kgf/mm2, respectively. The material exhibited a lower Young's modulus and higher fracture strain than that of HAp-sintered bodies and sintered-body samples prepared from pure octacalcium phosphate compacts. Additionally, the apatite-forming ability of the obtained material was confirmed in vitro, using a simulated body fluid. The proposed bioinspired material design could enable the fabrication of highly damage tolerant artificial bones that remain in vivo for long durations of time.

Ultra-High-Capacity Lithium Metal Batteries Based on Multi-Electron Redox Reaction of Organopolysulfides including Conductive Organic Moieties.

Recently, organic polysulfides have been synthesized as cathode active materials exceeding the battery performance of sulfur. However, the conventional organic polysulfides have exhibited capacities lower than the theoretical capacity of sulfur because the π-organic moieties do not conjugate with the sulfur chains. In this work, the organopolysulfides, synthesized via inverse vulcanization using disulfide compounds, exhibited higher capacities equal to the theoretical capacity of sulfur because of enhanced electronic conductivity based on the conjugation between organic moieties and sulfur chains. Furthermore, the organopolysulfide including 1,3-dhitiol-2-thione moiety exhibited the highest capacity because of the enhanced electronic conductivity. This finding will pave the way to develop next-generation rechargeable batteries.

Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low-Dose/High-Frequency and High-Dose/Low-Frequency Regimens in a Late-Stage Chronic Kidney Disease Rat Model.

The efficacy and renal safety of low-dose/high-frequency (LDHF) dosing and high-dose/low-frequency (HDLF) dosing of bisphosphonates (BPs) are comparable in patients with normal kidney function but might be different in patients with late-stage chronic kidney disease (CKD). This study aimed to compare the efficacy and renal safety of two different dosage regimens of a BP, alendronate (ALN), in stage 4 CKD using a rat model. Male, 10-week-old Sprague-Dawley rats were subjected to either 5/6 nephrectomy or sham surgery. The animals received subcutaneous administration of vehicle (daily) or ALN in LDHF dosage regimen (LDHF-ALN: 0.05 mg/kg/day) or HDLF dosage regimen (HDLF-ALN: 0.70 mg/kg/2 weeks). Medications commenced at 20 weeks of age and continued for 10 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum and urine assays were performed to examine the efficacy and renal safety of the ALN regimens. Both LDHF-ALN and HDLF-ALN increased bone mass, improved micro-structure, and enhanced mechanical properties, without causing further renal impairment in CKD rats. Histologically, however, HDLF-ALN more efficiently suppressed bone turnover, leading to more mineralized trabecular bone, than LDHF-ALN in CKD rats, whereas such differences between LDHF-ALN and HDLF-ALN were not observed in sham rats. Both LDHF-ALN and HDLF-ALN showed therapeutic effects on high bone turnover osteoporosis in CKD stage 4 rats without causing further renal impairment. However, as HDLF-ALN more efficiently suppressed bone turnover than LDHF-ALN in late-stage CKD, HDLF-ALN might be more appropriate than LDHF-ALN for fracture prevention in high bone turnover osteoporosis patients with late-stage CKD.

Environmentally Benign Strategy for Arylation of Nitronyl Nitroxide Using a Non-Transition Metal Nucleophile.

We have developed a method for the arylation of nitronyl nitroxide without using its transition metal complex as a nucleophile. Various nitronyl nitroxide-substituted π-electronic compounds can be obtained from the parent nitronyl nitroxide and the corresponding aryl iodides using a combination of zero-valent palladium catalysts and a 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl ligand in the presence of sodium tert-butoxide. The utility of the method has been demonstrated by the direct synthesis of open-shell compounds with giant π-electronic systems, such as 10P.

Determination of Dipicolinic Acid in "Natto" by High-Performance Liquid Chromatography Coupled With Postcolumn Photoirradiation With Zinc Acetate.

A system was developed for determining dipicolinic acid in "natto" using liquid chromatography with fluorometric detection. The compound was separated by reversed-phase chromatography using a mobile phase of 0.1 mol/L disodium hydrogen phosphate, 0.05 mol/L citric acid buffer (adjusted to pH 3.0) containing 3.0 mmol/L zinc acetate and 35 mmol/L perchloric acid. The compound in the column effluent was irradiated with ultraviolet light to produce fluorescence. This fluorescence was monitored at an excitation at 336 nm and an emission at 448 nm. The calibration curve for dipicolinic acid was observed to be linear in a range of 0.2 to 112 ng. The dipicolinic acid content of natto was 7.24 ± 0.54 mg/100 g (wet weight, mean ± standard deviation [SD], n = 6).

Possibility of chest wall dose reduction using volumetric-modulated arc therapy (VMAT) in radiation-induced rib fracture cases: comparison with stereotactic body radiation therapy (SBRT).

The present study compares dosimetric parameters between volumetric-modulated arc therapy (VMAT) and 3D conformal radiation therapy (3D-CRT) in lung tumors adjacent to the chest wall treated with stereotactic body radiation therapy (SBRT). The study focused on the radiation dose to the chest wall of 16 patients who had developed radiation-induced rib fractures (RIRF) after SBRT using 3D-CRT. The targets in all patients were partially overlapping with the fractured ribs, and the median overlapping rib-PTV distance was 0.4 cm. Stereotactic body radiation therapy was re-planned for all patients. The prescribed dose was 48 Gy in four fractions to cover at least 95% of the planning target volume (PTV). Evaluated dosimetric factors included D98% and the conformation number (CN) of the PTV, the D2cm3, V40 and V30 of the fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung. A comparison of 3D-CRT with the VMAT plan for PTV revealed that CN was significantly improved in the VMAT plan, whereas D98% did not significantly differ between the two plans. Regarding organs at risk (OARs), the D2cm3, V40 and V30 of fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung, were significantly decreased in the VMAT plan. We concluded that the dose to OARs such as ribs and chest wall could be reduced with improved target conformity using VMAT instead of 3D-CRT for SBRT to treat peripheral lung tumors.

4',6-Dimethoxyisoflavone-7-O-ß-D-glucopyranoside (wistin) is a peroxisome proliferator-activated receptor α (PPARα) agonist in mouse hepatocytes.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that regulate lipid and glucose metabolism. PPARα mainly affects fatty acid metabolism, and its activation lowers lipid levels. PPARγ is involved in the regulation of adipogenesis, insulin sensitivity, energy balance, and lipid biosynthesis. We have previously reported that 4',6-dimethoxyisoflavone-7-O-ß-D-glucopyranoside (wistin) can activate PPARγ. The purpose of the present study is to investigate the PPARα agonist activity of wistin. Using a luciferase reporter assay system of PPARα in monkey COS7 kidney cells, we showed that wistin could activate PPARα (P < 0.01 at 10 µg/mL) in a dose-dependent manner. Moreover, the addition of wistin upregulated the expression of PPARα (P < 0.01 at 10 µg/mL) and PPARα target genes including carnitine palmitoyltransferase 1a (P < 0.05 at 10 µg/mL), acyl-CoA oxidase (P < 0.01 at 10 µg/mL), acyl-CoA synthase (P < 0.05 at 10 µg/mL), PPARγ coactivator 1α (P < 0.05 at 10 µg/mL), uncoupling protein 2 (P < 0.05 at 1 µg/mL), and uncoupling protein 3 (P < 0.05 at 10 µg/mL), which are genes involved in lipid efflux and energy expenditure, in mouse primary hepatocytes. Furthermore, wistin inhibited cellular triglyceride accumulation in hepatocytes (P < 0.05 at 10 µg/mL) in a dose-dependent manner. These results indicate that wistin could suppress lipid accumulation through PPARα activation. The action of wistin on PPARα could be of interest for the amelioration of lipid metabolic disorders. To the best of our knowledge, wistin is the first reported isoflavonoid O-glycoside with PPARα agonist activity.

Lactobacillus helveticus-fermented milk containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) improves cognitive function in healthy middle-aged adults: a randomised, double-blind, placebo-controlled trial.

This study aimed to determine the effects of a Lactobacillus helveticus-fermented milk drink containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) on the cognitive function of healthy middle-aged adults. A randomised, double-blind controlled study was conducted in healthy participants who were randomly assigned to receive a L. helveticus-fermented milk drink (190 g/day) or the equivalent amount of a placebo drink once a day for eight weeks. Cognitive function was evaluated using the Japanese version of the repeatable battery for the assessment of neuropsychological status (RBANS) test. There was a statistically significant improvement in the total score, attention score, and delayed memory score of participants who received the L. helveticus-fermented milk drink. There was also a significant difference in the attention score between the placebo and test groups after eight weeks (p = .028). Therefore, supplementation of healthy middle-aged adults with a L. helveticus-fermented milk drink for eight weeks improved both attention and delayed memory.

4',6-dimethoxyisoflavone-7-O-ß-D-glucopyranoside (wistin) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist that stimulates adipocyte differentiation.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor that directly activates the expression of adipocyte-specific genes, and is universally accepted as the master regulator for adipocyte differentiation. Using a PPARγ luciferase reporter assay system, we showed that 4',6-dimethoxyisoflavone-7-O-ß-D-glucopyranoside (wistin) dose-dependently activates PPARγ. Treatment with wistin enhanced the marker of adipocyte differentiation, such as triglyceride accumulation in 3T3-L1 cells. Real-time quantitative polymerase chain reaction showed that wistin increased the expression of PPARγ2 messenger RNA. Moreover, the addition of wistin upregulated the expression of PPARγ-target genes, aP2 and adiponectin in 3T3-L1 cells. To our knowledge, wistin is the first isoflavonoid O-glycoside that exhibits PPARγ agonist activity.

Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans.

In complex neural circuits of the brain, massive information is processed with neuronal communication through synaptic transmissions. It is thus fundamental to delineate information flows encoded by various kinds of transmissions. Here, we show that glutamate signals from two distinct sensory neurons bidirectionally affect the same postsynaptic interneuron, thereby producing the opposite behaviours. EAT-4/VGLUT (vesicular glutamate transporter)-dependent glutamate signals from AFD thermosensory neurons inhibit the postsynaptic AIY interneurons through activation of GLC-3/GluCl inhibitory glutamate receptor and behaviourally drive migration towards colder temperature. By contrast, EAT-4-dependent glutamate signals from AWC thermosensory neurons stimulate the AIY neurons to induce migration towards warmer temperature. Alteration of the strength of AFD and AWC signals led to significant changes of AIY activity, resulting in drastic modulation of behaviour. We thus provide an important insight on information processing, in which two glutamate transmissions encoding opposite information flows regulate neural activities to produce a large spectrum of behavioural outputs.

Miscibility and multilayer formation of fluoroalkane-α,ω-diol mixtures at the air/water interface.

The surface tension γ of the aqueous solution of 1H,1H,6H,6H-perfluorohexane-1,6-diol (FC6diol) and 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8diol) mixtures was measured as a function of total molality m and composition of FC8diol in the mixture X2 at 293.15 K under atmospheric pressure. The γ vs m curves except at X2 = 0 and 0.05 have a distinct break point due to a phase transition in the adsorbed film. The surface pressure π vs mean area per adsorbed molecule A curves consist of two parts connected by a discontinuous change. The curve was almost vertical just below the phase transition, and the variation of the A value with film composition X(2)(H) was linear corresponding to the fact that FC6diol and FC8diol molecules orient parallel to the surface and are densely packed with the same areas of individual condensed films. Above the phase transition, the A value further decreases to around 0.12-0.19 nm² which is much smaller than the cross-sectional area of the fluorocarbon chain, indicating the multilayer formation at the surface. The phase diagram of adsorption (PDA) in the condensed film showed that the m vs film composition X(2)(H) curve is almost linear and the excess Gibbs energy of adsorption g(HE)/RT is at most 0.01, manifesting the ideal mixing of molecules. This is in contrast to a positive deviation (g(HE)/RT ~0.12) observed in the condensed film of the mixture of 1H,1H,2H,2H-perfluorodecanol (FC10OH) and 1H,1H,2H,2H-perfluorododecanol (FC12OH) with perpendicular molecular orientation. The loss of dispersion interaction between different species having different chain lengths is more appreciable in the perpendicular condensed films and thus leads to less miscibility of FC10OH and FC12OH. In the parallel condensed film, on the other hand, FC6diol and FC8diol molecules can arrange their position as close as possible to minimize the loss of dispersion interaction. The X(2)(H) value in the multilayer is close to unity, and thus, the multilayer consists of almost FC8diol molecules which form a multilayer in the single-component system. Furthermore, the condensed monolayer-multilayer phase transition was accompanied by a large increase in surface density of FC8diol and a small decrease in that of FC6diol, indicating that FC8diol molecules pile preferentially to form a multilayer.

Molecular orientation and multilayer formation of 1H,1H,8H,8H-perfluorooctane-1,8-diol at the air/water interface.

The surface tension of the aqueous solution of 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC(8)diol) was measured as a function of temperature and concentration under atmospheric pressure. The interfacial density and the entropy and energy of adsorption were evaluated and compared to those obtained for the adsorption of 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC(10)diol) at the hexane solution/water interface. The surface tension curves show a break point corresponding to a phase transition of the adsorbed FC(8)diol film. The value of mean area per adsorbed molecule A just below the phase transition indicated the formation of a parallel condensed monolayer, and that above the phase transition suggested the spontaneous formation of a multilayer. The multilayer of FC(8)diol is less compressible and shows a smaller increase in layering with pi compared to FC(10)diol. This is probably because the surface force is repulsive for the hexane/FC/water interface, while it is attractive for the air/FC/water interface. The partial molar entropy change of adsorption is positive in the condensed FC(8)diol film, while it is negative in the condensed FC(10)diol film, which is reasonably explained in terms of the difference in entropy change accompanied by desolvation around the hydrophobic chain. From the viewpoints of the energetic stabilization accompanied by adsorption for the FC(8)diol system, the contribution from the replacement of air/water contact with air/fluorocarbon and fluorocarbon/water contacts and that from the molecular ordering in the adsorbed film is almost equal in case of the condensed monolayer, while in the multilayer the latter is comparatively larger than the former due to the hydrogen bonding between hydroxyl groups and the dispersion interaction among the ordered hydrophobic chains.