Nobuo Iyi

Crush syndrome (CS) is characterised by ischaemia/reperfusion-induced rhabdomyolysis, leading to systemic inflammation and high mortality. Building on our previous findings that intravenous nitric oxide (NO) donors improve survival in this condition, we investigated the therapeutic efficacy of inhaled NO delivered via a portable, controlled-release device in an experimental rat model of CS. Anaesthetised rats underwent bilateral hindlimb compression using rubber tourniquets for 5 h, followed by reperfusion. Among the various inhalation conditions tested, administration of NO (160 parts per million) for 2 h after reperfusion significantly increased survival rate from 20 to 90%. Improvements in haemodynamic parameters, biochemical markers, and histopathological findings correlated with enhanced survival outcomes. These results suggest that on-site NO inhalation therapy may serve as an effective first-line, emergency intervention for CS, particularly in disaster settings. Graphical

Protonic layered transition metal oxides readily undergo significant swelling and exfoliation into unilamellar nanosheets upon contact with aqueous solutions of amines and other basic compounds. Despite the crucial importance of this reactivity, it often degrades over time, leading to a loss of swelling and exfoliation capabilities. However, the cause of this degradation has remained unclear. In this study, we systematically investigated the conditions that lead to the loss of swelling ability, using protonic layered perovskite crystals of HCa₂Nb₃O₁₀·1.5H₂O as a representative example. The crystals were stored under various conditions, including ambient air, sealed environments, and dry/humid conditions, both in the dark and under light. Their reactivity with dimethylaminoethanol (DMAE) was then examined. We found that only the crystals exposed to ambient air for more than 10 days lost their swelling ability, whereas those stored under other conditions retained their reactivity. Based on these results, we speculated that ammonia, the most abundant alkaline component in the atmosphere, is absorbed from the air via an acid-base interaction. This hypothesis was confirmed through XRD and FTIR characterization. We conclude that trace amounts of ammonia (0.02-0.12 ppm) in the atmosphere intercalate into the acidic interlayer galleries and are responsible for the degradation in reactivity. Furthermore, the original reactivity can be easily restored by acid treatment, which replaces the intercalated ammonium ions with protons, thereby recovering the swelling capability. These findings resolve a long-standing question regarding the degradation of protonic layered metal oxides and provide a practical method for restoring their native properties.

The inhalation of nitric oxide (NO), which acts as a selective vasodilator of pulmonary blood vessels, is an established medical treatment. However, its wide adoption has been limited by the lack of a convenient delivery technique of this unstable gas. Here we report that a solid mixture of Fe^IISO₄·7H₂O and a layered double hydroxide (LDH) containing nitrite (NO₂^–) in the interlayer spaces (NLDH) stably generates NO at a therapeutic level (∼40 ppm over 12 h from freshly mixed solids; ∼80 ppm for 5–10 h from premixed solids) under air flow (0.25 L min^–1) if the NLDH has been prepared by using a reconstruction method. Mg/Al-type LDH was calcined at 550 °C to remove interlayer CO₃^2– and then treated with NaNO₂ in water to reconstruct the NLDH. This one-pot, organic solvent-free process can be performed at large scales and is suitable for mass production. Humid air promotes anion exchange between NO₂^– and SO₄^2– in the solid mixture, resulting in persistent interactions of NO₂^– and Fe²⁺, generating NO. In contrast to the previously reported NLDH prepared using an anion-exchange method, the reconstructed NLDH exhibits stable and persistent generation of NO because of partial deformation of the layered structures (e.g., particle aggregation, reduced crystallinity, and enhanced basicity). Degradation of the solid mixture is suppressed under dry conditions, so that a portable cartridge column that is readily available as an NO source for emergency situations can be prepared. This work demonstrates that the interlayer nanospace of LDH serves as a reaction mediator for excellent controllability of solid-state reactions. This inexpensive and disposable NO generator will facilitate NO inhalation therapy in developing countries and nonhospital locations.

Difficulties related to handling gases are a common bottleneck for applications. Although solid materials that release gas molecules under external stimuli exist, they require an external energy or a device for reliable operation. Herein, we report a CO₂ stimulus for controlled release of p.p.m.-level functional gases from solid materials. A CO₂-preferential anion-exchange property of layered double hydroxides and redox reactions in gas molecules are combined to release various gases (including H₂S and NO) under ambient air from HS⁻ and NO₂⁻-incorporated layered double hydroxides, respectively. The profiles of gas release are mainly governed by the difference of pK_a between H₂CO₃ and resulting acids (formed through protonation of interlayer anions), and are not so susceptible to the variation of relative humidity in air. Moreover, structural modulation of solid materials enables fine control of the gas release profiles. The use of safe, ubiquitous, and nearly constant (~400 p.p.m. in atmosphere) CO₂ stimulus offers broad applications for functional gases.

H2S and NO are gas molecules with physiological activities; solid materials that release these gases under safe and ubiquitous stimuli offer broad medical applications. Herein, we report solid materials that autonomously release ppm-level H2S or NO under air. HS− or NO2− incorporated in the interlayer of layered double hydroxide (LDH), a clay mineral, is protonated by CO2 and H2O, yielding H2S or HNO2. HNO2 generates NO through disproportionation or reduction. Moreover, another NO-release method employs solid mixtures of NO2−-incorporated LDH and FeSO4, wherein wet air triggers NO2− reduction with Fe2+ through anion exchange between NO2− and SO42−. A potential application of the air-stimulated gas release system is demonstrated by creating a portable and battery-free NO inhaler for emergency treatment of respiratory distress.

Osmotic swelling behaviors in layered perovskite niobate were examined in aqueous solutions containing three types of amine-related agents including quaternary ammonium hydroxides and tertiary aminoethanol. Platelet microcrystals of a protonated layered perovskite niobate, HCa₂Nb₃O₁₀·1.5H₂O, were found to show enormous swelling in the aqueous solutions, which was clearly recognized by the noticeable expansion of the sample volume over 100-fold. Optical microscopy observations revealed that the crystals underwent accordion-like elongation in the layer-stacking direction up to several ten-fold the initial thickness. Small-angle X-ray scattering measurements of swollen samples indicate the expansion of interlayer separation ranging from ∼20 nm to over 100 nm, which is primarily governed by the concentrations of the amine-related agents. The magnitudes of the interlayer separation were comparable to those of the macroscopic swelling. The degree of swelling was progressively suppressed with further increasing concentration, and this suppression trend was related to the amines.

Through various in situ analyses, we have revealed the structural changes that occur during the reversible melting–solidification process of layered alkylsiloxanes (C_nLSiloxanes) with carbon numbers (n) of 18 and 16. In situ high-resolution solid-state ¹³C nuclear magnetic resonance (NMR) analysis at controlled temperatures indicates drastic conformational changes of the long alkyl chains during the melting–solidification process. A ¹³C NMR signal at 33 ppm, which shows the highest intensity at room temperature (RT), is assigned to an inner methylene group with an all-trans conformation. As the temperature increases, the 33-ppm signal intensity decreases while the signal intensity at 30.5 ppm simultaneously increases. The 30.5 ppm signal is assigned to an inner methylene group with a trans–gauche conformation. Subsequently, upon cooling, the signal at 33 ppm recovers, even after C_nLSiloxanes have melted. In situ X-ray diffraction measurements at controlled temperatures reveal that the ordered arrangement of the long alkyl chains becomes disordered with elevating temperatures and reordered upon cooling to RT. In situ high-resolution solid-state ²⁹Si NMR analysis shows that the melting–solidification process progresses without any structural change in siloxane sheets of the C_nLSiloxanes. Thus, the in situ analyses show that disordering of the long alkyl chains causes the C_nLSiloxanes to melt. Because the majority of long alkyl chains are packed again in the ordered arrangement with the all-trans conformation upon cooling, the C_nLSiloxanes are reversibly solidified and the C_nLSiloxane structure is recovered.

Rodlike polysilsesquioxanes forming regular higher-ordered nanostructure such as hexagonal phase were prepared by sol-gel reaction of organotrimethoxysilanes having amino groups in aqueous solutions of inorganic strong acids. The XRD profiles of the resulting polysilsesquioxanes showed three peaks with the d-value ratio of 1:1/3:12, indicating that these polysilsesquioxanes have hexagonal phase. The diffraction peaks shifted by changing the humidity. In addition, the d-values of diffraction peaks increased by ion-exchange reaction with organic compounds such as fatty acid salt and anionic polymer. Therefore, this hexagonal phase originated from the stacking of rodlike polysilsesquioxanes with Si–O–Si framework at the core and ammonium groups extruding outside. This Si–O–Si framework probably formed a ladder or ladder-related structure, which was characterized by solid-state 29Si NMR and IR spectrometries.

Platelet crystals of a layered perovskite enormously swelled in a tetrabutylammonium hydroxide solution, producing unique columnar shaped crystals with a water content of >90 wt%.