Disruption of Membrane Integrity as a Molecular Initiating Event Determines the Toxicity of Polyhexamethylene Guanidine Phosphate Depending on the Routes of Exposure.

Polyhexamethylene guanidine phosphate (PHMG-P), a cationic biocide, is widely used in household products due to its strong bactericidal activity and low toxicity. However, it causes fatal lung damage when inhaled. In this study, we investigated why PHMG-P causes fatal lung injury when inhaled, and demonstrated that the disruption of membrane integrity through ionic interaction-a molecular initiating event of PHMG-P-determines toxicity. Mice were injected intravenously with 0.9 or 7.2 mg/kg PHMG-P (IV group), or instilled intratracheally with 0.9 mg/kg PHMG-P (ITI group); they were euthanatized at 4 h and on days 1 and 7 after treatment. Increased total BAL cell count and proinflammatory cytokine production, along with fibrotic changes in the lungs, were detected in the ITI group only. Levels of hepatic enzymes and hepatic serum amyloid A mRNA expression were markedly upregulated in the 7.2 mg/kg IV and ITI groups at 4 h or day 1 after treatment, but returned to baseline. No pathological findings were detected in the heart, liver, or kidneys. To simulate the IV injection, A549, THP-1, and HepG2 cells were treated with PHMG-P in cell culture media supplemented with different serum concentrations. Increased serum concentration was associated with an increase in cell viability. These results support the idea that direct contact between PHMG-P and cell membranes is necessary for PHMG-induced toxicity.

Preparation and Characterization of Gas-Forming Polyacrylonitrile/Polymethylmethacrylate/Methylcyclohexane Nanocapsules for the Desorption of Optical Adhesive Films.

We herein report a simple approach to the preparation of gas-forming polyacrylonitrile/polymethyl-methacrylate/methylcyclohexane core-shell nanocapsules for the desorption of optical adhesive films. The proposed gas-forming core-shell nanocapsules are based on a shell structure composed of a polyacrylonitrile/polymethylmethacrylate copolymer, where the core contains vaporizable cyclic hydrocarbons (i.e., methylcyclohexane). These stable functional nanocapsules were spherical in shape, with an average particle size of ~110 nm. Interestingly, using the proposed synthetic method, it was also possible to prepare nanoparticles with varying particle sizes and copolymer ratios through a simple pre-emulsification stage and careful control of the monomer ratio employed. Upon mixing the resulting core-shell nanocapsules uniformly with the optical adhesive films, desorption was observed between layers following heat treatment. Furthermore, the high optical transmittance of the optical adhesive film was retained due to the small size of the core-shell nanoparticles. It was therefore apparent that the proposed method should be applicable for the preparation of future optical films where functional core-shell nanocapsules are required.

Microbubble-Triggered Spontaneous Separation of Transparent Thin Films from Substrates Using Evaporable Core-Shell Nanocapsules.

The spontaneous separation of a polymer thin film from a substrate is an innovative technology that will enable material recycling and reduce manufacturing cost in the film industry, and this can be applied in a wide range of applications, from optical films to wearable devices. Here, we present an unprecedented spontaneous strategy for separating transparent polymer films from substrates on the basis of microbubble generation using nanocapsules containing an evaporable material. The core-shell nanocapsules are prepared from poly(methyl methacrylate)-polyethyleneimine nanoparticles via the encapsulation of methylcyclohexane (MCH). A spherical nanostructure with a vaporizable core is obtained, with the heat-triggered gas release ability leading to the formation of microbubbles. Our separation method applied to transparent polymer films doped with a small amount of the nanocapsules encapsulating evaporable MCH enables spontaneous detachment of thin films from substrates via vacuum-assisted rapid vaporization of MCH over a short separation time, and clear detachment of the film is achieved with no deterioration of the inherent optical transparency and adhesive property compared to a pristine film.

The critical warning sign of real-time brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm.

OBJECTIVE: The aim of this study was to define the critical warning sign of real-time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL) after microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: Nine hundred and thirty-two patients with HFS who underwent MVD with intraoperative monitoring (IOM) of BAEP were analyzed. We used a 43.9 Hz/s stimulation rate and 400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and speech discrimination scoring were performed before and one week after surgery. We analyzed the incidence for postoperative HL according to BAEP changes and calculated the diagnostic accuracy of significant warning criteria. RESULTS: Only 11 (1.2%) patients experienced postoperative HL. The group showing permanent loss of wave V showed the largest percentage of postoperative HL (p < 0.001). No patient who experienced only latency prolongation (≥1 ms) had postoperative HL. Loss of wave V and latency prolongation (≥1 ms) with amplitude decrement (≥50%) were highly associated with postoperative HL. CONCLUSIONS: Loss of wave V and latency prolongation of 1 ms with amplitude decrement ≥50% were the critical warning signs of BAEP for predicting postoperative HL. SIGNIFICANCE: These findings elucidate the critical warning sign of real-time BAEP.

Induced neural stem cells from distinct genetic backgrounds exhibit different reprogramming status.

Somatic cells could be directly converted into induced neural stem cells (iNSCs) by ectopic expression of defined transcription factors. However, the underlying mechanism of direct lineage transition into iNSCs is largely unknown. In this study, we examined the effect of genetic background on the direct conversion process into an iNSC state. The iNSCs from two different mouse strains exhibited the distinct efficiency of lineage conversion as well as clonal expansion. Furthermore, the expression levels of endogenous NSC markers, silencing of transgenes, and in vitro differentiation potential were also different between iNSC lines from different strains. Therefore, our data suggest that the genetic background of starting cells influences the conversion efficiency as well as reprogramming status of directly converted iNSCs.