Ultrathin Organic Electrochemical Transistor with Nonvolatile and Thin Gel Electrolyte for Long‐Term Electrophysiological Monitoring

Skin‐based electrical‐signal monitoring is one of the basic and noninvasive diagnostic methods for observing vital signals that contain valuable information about the dynamic status of the inner body. Soft bioelectronic devices are developed for the acquisition of high‐quality biosignals by taking advantage of their inherent thin and soft bodies. Among these devices, the organic electrochemical transistor (OECT) is a promising local transducing amplifier because of its key advantages, such as low operating voltage, high transconductance, and biocompatibility. However, the transistor's direct electrolyte‐gated operation limits its ability to measure biosignals only when the electrolyte exists. Here, an ultrathin OECT‐based wearable electrophysiological sensor based on a thin (≈6 µm) and nonvolatile gel electrolyte is reported, which can operate on dry biological surfaces. This sensor can measure biopotentials with a high mechanical stability and high signal‐to‐noise ratio (24 dB) even from dry surfaces of the human body and also shows stable performance during long‐term continuous monitoring and multiple reuse in a test that lasted more than a week.     

Oxygen doped Ge crystals Czochralski-grown from the B2O3-fully-covered melt

Local vibrations of oxygen in Ge crystals grown from a melt fully covered by B₂O₃ were evaluated by Fourier-transform infrared spectroscopy. Ge single crystals containing oxygen were grown by the Czochralski method under various growth conditions. Oxygen concentrations in the crystals were determined to be in the range between 8.5 × 10¹⁵ and 5.5 × 10¹⁷ cm⁻³ from the infrared absorption at 855 cm⁻¹ originating in local vibration of Ge-O_i-Ge quasi-molecules. Absorption peaks relating to GeO_x, SiO_x and Si-O_i-Si were not detected in the as-grown crystals. The calibration coefficient for determining oxygen concentration in Ge crystals from the absorption peak intensity at 1264 cm⁻¹ was estimated to be 1.15 × 10¹⁹ cm⁻².     

Energy‐Dissipative Matrices Enable Synergistic Toughening in Fiber Reinforced Soft Composites

Tough hydrogels have shown strong potential as structural biomaterials. These hydrogels alone, however, possess limited mechanical properties (such as low modulus) when compared to some load‐bearing tissues, e.g., ligaments and tendons. Developing both strong and tough soft materials is still a challenge. To overcome this obstacle, a new material design strategy has been recently introduced by combining tough hydrogels with woven fiber fabric to create fiber reinforced soft composites (FRSCs). The new FRSCs exhibit extremely high toughness and tensile properties, far superior to those of the neat components, indicating a synergistic effect. Here, focus is on understanding the role of energy dissipation of the soft matrix in the synergistic toughening of FRSCs. By selecting a range of soft matrix materials, from tough hydrogels to weak hydrogels and even a commercially available elastomer, the toughness of the matrix is determined to play a critical role in achieving extremely tough FRSCs. This work provides a good guide toward the universal design of soft composites with extraordinary fracture resistance capacity.     

Oxidation and stress relief in air at room temperature of amorphous silicon hydrogenated in a glow discharge

Glow-discharge-hydrogenated amorphous silicon (a-Si : H) was found to be oxidized in the following two ways after exposing to air at room temperature; first, thin oxide films grew uniformly on the a-Si : H, slowly with increase of exposure time; secondly, oxide with a columnar morphology grew rapidly with the increase of exposure time and the cross section of the columnar oxide was small. Mechanical stress caused by the differences of the thermal expansion coefficient and the crystallographical structure between the a-Si : H and substrates was relieved with the increase in the amount of the columnar oxide.     

Nucleotide sequences of alcohol acetyltransferase genes from lager brewing yeast,Saccharomyces carlsbergensis

The nucleotide sequences of alcohol acetyltransferase genes isolated from lager brewing yeast, Saccharomyces carlsbergensis have been determined. S. carlsbergensis has one ATF1 gene and another homologous gene, the Lg-ATF1 gene. There was a high degree of homology between the amino acid sequences deduced for the ATF1 protein and the Lg-ATF1 protein (75·7%), but the N-terminal region has a relatively low degree of homology. Southern analysis and contour-clamped homogeneous electric field analysis of Saccharomyces strains suggest that the ATF1 gene is located on chromosome XV in S. cerevisiae and that the Lg-ATF1 gene might originate from the ‘non-S. cerevisiae’ genome of S. carlsbergensis, which is similar to that of S. bayanus and S. pastorianus. The nucleotide sequence data reported in this paper will appear in the DDBJ, EMBL and GenBank data banks with the Accession Numbers D63449 (ATF1) and D63450 (Lg-ATF1).     

CRISPR Therapeutics for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder with a prevalence of approximately 1 in 3500–5000 males. DMD manifests as childhood-onset muscle degeneration, followed by loss of ambulation, cardiomyopathy, and death in early adulthood due to a lack of functional dystrophin protein. Out-of-frame mutations in the dystrophin gene are the most common underlying cause of DMD. Gene editing via the clustered regularly interspaced short palindromic repeats (CRISPR) system is a promising therapeutic for DMD, as it can permanently correct DMD mutations and thus restore the reading frame, allowing for the production of functional dystrophin. The specific mechanism of gene editing can vary based on a variety of factors such as the number of cuts generated by CRISPR, the presence of an exogenous DNA template, or the current cell cycle stage. CRISPR-mediated gene editing for DMD has been tested both in vitro and in vivo, with many of these studies discussed herein. Additionally, novel modifications to the CRISPR system such as base or prime editors allow for more precise gene editing. Despite recent advances, limitations remain including delivery efficiency, off-target mutagenesis, and long-term maintenance of dystrophin. Further studies focusing on safety and accuracy of the CRISPR system are necessary prior to clinical translation.     

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.     

Quantitative Visualization of the Interaction between Complement Component C1 and Immunoglobulin G: The Effect of CH1 Domain Deletion

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component C1q. In order to provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for the quantitative visualization of the interaction between mouse IgG and the C1 complex composed of C1q, C1r, and C1s. The results showed that the C1q in the C1 complex is restricted regarding internal motion, and that it has a stronger binding affinity for on-membrane IgG2b assemblages than C1q alone, presumably because of the lower conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG2a variant that lacks the entire C_H1 domain in the absence of an antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the C_L domain that is cryptic in the presence of the C_H1 domain. Our findings offer clues for novel-modality therapeutic antibodies.     

Deformation of Alumina/Titanium Carbide Composite at Elevated Temperatures

The deformation behavior of an Al₂O₃/30 wt% TIC composite in uniaxial tension was evaluated under vacuum over the temperature range of 1300° to 1550°C. The Al₂0₃/TiC composite exhibited the maximum elongation of 66% at an initial strain rate of 1.19 X l0^-4 s^-1 at 1550°C. The stress exponent calculated from peak stresses of true stress-true strain curves at 1500^OC was 3.8, which was in good agreement with that obtained by changing the crosshead speed during the tension test. The apparent activation energy at 20 MPa was 853 kJ/mol. In addition the deformation of the Al₂O³/TiC composite in uniaxial tension at elevated temperature was accompanied by cavitation.     

Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. Herein, we examined for the first time the synthetic docosahexaenoic acid esters of 12-hydroxy stearic acid (12-DHAHSA) or oleic acid (12-DHAHOA) against NRF2 activation in cultured human hepatoma-derived cells (C3A). The effect of DHA-derived FAHFAs on lipid metabolism was explored by the nontargeted lipidomic analysis using liquid chromatography-mass spectrometry. Furthermore, their action on lipid droplet (LD) oxidation was investigated by the fluorescence imaging technique. The DHA-derived FAHFAs showed less cytotoxicity compared to their native fatty acids and activated the NRF2 in a dose-dependent pattern. Treatment of 12-DHAHOA with C3A cells upregulated the cellular triacylglycerol levels by 17-fold compared to the untreated group. Fluorescence imaging analysis also revealed the suppression of the degree of LDs oxidation upon treatment with 12-DHAHSA. Overall, these results suggest that DHA-derived FAHFAs as novel and potent activators of NRF2 with plausible antioxidant function.