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The majority of chemical experiments conducted during educational programs are carried out in laboratories because they require instructors with special skills, in addition to large, expensive instruments. Recently, there has been an increasing demand for chemical experiments that can be carried out anywhere. Herein, we propose a novel type of paper-based analytical device (PAD) for enabling quantitative analysis without the requirement for a micropipette, since the PAD features a large sample loading zone and a waste zone, enabling accurate volume control of a liquid sample. We initially employed a micropipette to evaluate the PAD and demonstrate the quantitative analysis of ascorbic acid (AA) and pH using different loading volumes. Finally, we determined the AA concentrations and pH values of commercially available beverages using disposable plastic droppers, and the obtained results were in good agreement with those obtained through conventional methods. This PAD format can therefore be used as a novel educational tool for conducting certain chemical analyses in remote learning environments.

Abstract The fluoride ion‐catalyzed selective O‐acylation of enol silyl ethers with acyl fluorides using KF and 18‐Crown‐6 is described herein. This catalytic system facilitated the practical and facile reaction of a variety of enol silyl ethers derived from aromatic/aliphatic ketones and aldehydes with acyl fluorides to afford useful and valuable enol esters.

Abstract Developing compounds with novel structures is important for the production of new drugs. From an intellectual perspective, confirming the patent status of newly developed compounds is essential, particularly for pharmaceutical companies. The generation of a large number of compounds has been made possible because of the recent advances in artificial intelligence (AI). However, confirming the patent status of these generated molecules has been a challenge because there are no free and easy-to-use tools that can be used to determine the novelty of the generated compounds in terms of patents in a timely manner; additionally, there are no appropriate reference databases for pharmaceutical patents in the world. In this study, two public databases, SureChEMBL and Google Patents Public Datasets, were used to create a reference database of drug-related patented compounds using international patent classification. An exact structure search system was constructed using InChIKey and a relational database system to rapidly search for compounds in the reference database. Because drug-related patented compounds are a good source for generative AI to learn useful chemical structures, they were used as the training data. Furthermore, molecule generation was successfully directed by increasing and decreasing the number of generated patented compounds through incorporation of patent status (i.e., patented or not) into learning. The use of patent status enabled generation of novel molecules with high drug-likeness. The generation using generative AI with patent information would help efficiently propose novel compounds in terms of pharmaceutical patents. Scientific contribution: In this study, a new molecule-generation method that takes into account the patent status of molecules, which has rarely been considered but is an important feature in drug discovery, was developed. The method enables the generation of novel molecules based on pharmaceutical patents with high drug-likeness and will help in the efficient development of effective drug compounds.

Abstract Production of D-amino acids (D-AAs) on a large-scale enables to provide precursors of peptide therapeutics. In this study, we designed a novel L-amino acid oxidase, HTAncLAAO2, by ancestral sequence reconstruction, exhibiting high thermostability and long-term stability. The crystal structure of HTAncLAAO2 was determined at 2.2 Å by X-ray crystallography, revealing that the enzyme has an octameric form like a “ninja-star” feature. Enzymatic property analysis demonstrated that HTAncLAAO2 exhibits three-order larger k cat/K m values towards four L-AAs (L-Phe, L-Leu, L-Met, and L-Ile) than that of L-Trp. Through screening the variants, we obtained the HTAncLAAO2(W220A) variant, which shows a > 6-fold increase in k cat value toward L-Trp compared to the original enzyme. This variant applies to synthesizing enantio-pure D-Trp derivatives from L- or rac-forms at a preparative scale. Given its excellent properties, HTAncLAAO2 would be a starting point for designing novel oxidases with high activity toward various amines and AAs.

Upon degranulation, basophils and mast cells secrete an array of inflammatory mediators, including histamine, which leads to not only allergic inflammation but also other inflammatory diseases. We previously reported that an aqueous extract from enzyme-treated, dried sardine inhibits the degranulation of RBL-2H3 cells and attenuates the symptoms of Japanese cedar pollinosis in mice. This study evaluated an antiallergic effect of dipeptides containing acidic amino acid residue in an antigen-induced degranulation assay using RBL-2H3 cells. The result showed that acidic amino acid residue-containing dipeptides inhibit the degranulation of RBL-2H3 cells without cytotoxicity. Additionally, L-histidyl-L-glutamic acid (His-Glu), one of the acidic amino acid residue-containing dipeptides tested in this study, inhibited calcium ionophore-induced degranulation. We also found that His-Glu suppressed microtubule reorganization in RBL-2H3 cells after antigen stimulation. His-Glu slightly, but not significantly, suppressed the elevation of cytosolic calcium ion concentration leading to degranulation. Immunoblot analysis revealed that His-Glu significantly suppressed the phosphorylation of phosphoinositide 3-kinase and Akt, but not that of Syk or phospholipase Cγ. Overall results suggest that acidic amino acid residue-containing dipeptides can be used as food ingredients with an antiallergic effect.

Dynamic stretching (DS) is performed as a warm-up to improve the range of motion and athletic performance. However, the effect of different amounts of DS on muscle performance remains unclear. This study investigated the effects of DS repetitions with one or four sets of 30 s on musculotendinous extensibility and muscle strength. Fourteen healthy men (23.6 ± 1.5 years) underwent DS to ankle plantar flexors for one set (fifteen repetitions) or four sets after warm-up. The maximal ankle dorsiflexion angle, musculotendinous stiffness (MTS), passive torque, peak plantarflexion torque during maximal isometric contraction, and muscle temperature were measured before and after stretching. A significant effect of time was observed on the maximal ankle dorsiflexion angle, MTS, passive torque, and muscle temperature (p < 0.001). However, no interactions or effects between the conditions were observed. After DS, the maximal ankle dorsiflexion angle and muscle temperature significantly increased (p < 0.01), while the MTS and passive torque significantly decreased (p < 0.01). The maximal muscle strength showed no significant effects or interactions (p = 0.198−0.439). These results indicated that one and four sets of DS effectively increased musculotendinous extensibility. Thus, one set of DS may have similar effects as a warm-up before four sets of DS.

This study aimed to analyze the relationship between bone density, habitual chewing side (HCS), and mini-screw stability to investigate the intra-individual factors contributing to mini-screw failure. This retrospective study included 86 sides in 43 adults, who underwent bilateral maxillary mini-screw placement with subsequent unilateral failure of the mini-screw. Pre-treatment cone-beam computed tomography was used to measure the buccal cortical bone thickness and bone density on the failed and successful sides. Pre-treatment mandibular kinesiographic records were used to determine the HCS. Paired t-tests, one-proportion z-tests, and multivariable multilevel Poisson regression were used to examine the statistical significance. The buccal cortical bone thicknesses were 0.93 ± 0.27 mm (unsuccessful side) and 1.01 ± 0.27 mm (successful side), with no significant difference. The bone density on the unsuccessful side (1059.64 ± 202.64 mg/cm3) was significantly lower than the success side (1317.89 ± 332.23 mg/cm3). Regarding HCS, 27.9% of failures occurred on the preferred side, and 62.8% occurred on the non-preferred side. After adjusting for all factors, the non-preferred side showed a 2.22 times higher prevalence ratio for mini-screw failure than the preferred side. HCS is significantly related to mini-screw stability, while the cortical bone thickness, bone density, and site of mini-screw implantation were not correlated.

Our laboratory has been studying the strong enhancement in the fluorescence quantum yield and an excited lifetime of the organic dye molecules on the clay nanosheets and refer to as “Surface-Fixation Induced Emission”. In this study, Safranine-O which is a mono-cationic phenazine-based dye molecule, was used as the organic dye. It has fluorescence enhancement properties on the clay surface due to the suppression of the non-radiative deactivation rate constant (knr) on the clay nanosheets. While Safranine-O in water in the absence of clay nanosheets exhibited the values as 0.068 and 1.09 × 10−9 s for ϕf and τ, those on the clay surface are 0.121 and 1.96 × 10−9 s. knr values in water and on the clay were calculated to be 8.6 × 108 s − 1 and 4.5 × 108 s − 1, respectively. These results can be explained well by the structure fixing and structure resembling effect. This study helps to explore the possibility of utilizing mono-cationic dye molecules for the realization of desired photo-functional materials and photochemical reactions.

The progress in artificial bone research is crucial for addressing fractures and bone defects in the aging population. However, challenges persist in terms of biocompatibility and structural complexity. Nanotechnology provides a promising avenue by which to overcome these challenges, with nano-ferrite particles (NFPs) exhibiting superparamagnetic properties. The ability to control cell positioning using a magnetic field opens up new possibilities for customizing artificial bones with specific shapes. This study explores the biological effects of NFPs on osteoblast-like cell lines (MC3T3-E1), including key analyses, such as cell viability, cellular uptake of NFPs, calcification processes, cell migration under external magnetic field conditions, and three-dimensional modeling. The results indicate that the impact of NFPs on cell proliferation is negligible. Fluorescence and transmission electron microscopy validated the cellular uptake of NFPs, demonstrating the potential for precise cell positioning through an external magnetic field. Under calcification-inducing conditions, the cells exhibited sustained calcification ability even in the presence of NFPs. The cell movement analysis observed the controlled movement of NFP-absorbing cells under an external magnetic field. Applying a magnetic field along the z-axis induced the three-dimensional shaping of cells incorporating NFPs, resulting in well-arranged z-axis directional patterns. In this study, NFPs demonstrated excellent biocompatibility and controllability under an external magnetic field, laying the foundation for innovative treatment strategies for customizing artificial bones.

Recently, some facilities have utilized the dual-energy subtraction (DES) technique for chest radiography to increase pulmonary lesion detectability. However, the availability of the technique is limited to certain facilities, in addition to other limitations, such as increased noise in high-energy images and motion artifacts with the one-shot and two-shot methods, respectively. The aim of this study was to develop artificial intelligence-based DES (AI–DES) technology for chest radiography to overcome these limitations. Using a trained pix2pix model on clinically acquired chest radiograph pairs, we successfully converted 130 kV images into virtual 60 kV images that closely resemble the real images. The averaged peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) between virtual and real 60 kV images were 33.8 dB and 0.984, respectively. We also achieved the production of soft-tissue- and bone-enhanced images using a weighted image subtraction process with the virtual 60 kV images. The soft-tissue-enhanced images exhibited sufficient bone suppression, particularly within lung fields. Although the bone-enhanced images contained artifacts on and around the lower thoracic and lumbar spines, superior sharpness and noise characteristics were presented. The main contribution of our development is its ability to provide selectively enhanced images for specific tissues using only high-energy images obtained via routine chest radiography. This suggests the potential to improve the detectability of pulmonary lesions while addressing challenges associated with the existing DES technique. However, further improvements are necessary to improve the image quality.

Glutathione (GSH) is present in almost all human cells and has a beneficial effect on human skin brightness. Cysteinylglycine (Cys-Gly) and γ-glutamylcysteine (γ-Glu-Cys) are GSH synthesis components. In this study, we defined glutathione (GSH), cysteinylglycine (Cys-Gly), and γ-glutamylcysteine (γ-Glu-Cys) as cysteine peptide and performed a randomized, double-blind, placebo-controlled study to investigate the effects of orally administered cysteine peptide on human skin brightness using a CM-26d portable spectrophotometer in healthy males and females aged between 20 and 65 years old. Eligible participants were randomly allocated into three groups (cysteine peptide 45 mg: n = 16, 90 mg: n = 15, and placebo: n = 16). Each subject ingested six tablets every day for 12 weeks, and skin brightness was measured at 0, 4, 8, and 12 weeks. As a result, the 45 mg group exhibited arm brightening in a time-dependent manner, and a significant difference was observed compared to the placebo at week 12 (p = 0.028). Moreover, no serious adverse events and changes related to 270 mg study food were observed in the safety trial. Here, we suggest that cysteine peptide is a promising and safe compound for human skin brightness.

Amino acids are involved in various chemical reactions in vivo, and changes in several amino acids in urine are related to certain disease states. Therefore, developing an efficient method to analyze the amino acids in urine is useful in the timely diagnosis of diseases. In this study, we developed a high-performance liquid chromatography (HPLC) fluorescence method for the quantitative analysis of urinary amino acids using the fluorescence derivatization reagent 2,3-naphthalenedicarboxaldehyde (NDA). NDA was selected because it does not require heating for the reaction and can react within a short time, rendering its use in clinical settings feasible. The reaction temperature, reaction time, and other derivatization conditions were optimized, and the reaction was found to be completed in 5 min at 25 °C. The separation of NDA–amino acids was investigated on an octadecylsilyl (ODS) column under gradient conditions. The mobile phase was a mixture of water–acetonitrile–trifluoroacetic acid. Eighteen NDA–amino acids (histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), citrulline (Cit), serine (Ser), aspartic acid (Asp), threonine (Thr), glutamic acid (Glu), glycine (Gly), tyrosine (Tyr), alanine (Ala), tryptophan (Trp), valine (Val), phenylalanine (Phe), isoleucine (Ile), leucine (Leu), and 5-aminovaleric acid (internal standard)) were separated within 100 min under optimal conditions. The calibration curves showed good linearity in the range of 0.25–25 pmol per injection with correlation coefficients of >0.998. The limits of quantification for NDA–amino acids were 16.7–74.7 fmol. The developed analytical method was applied to a human urine sample and 16 amino acids (His, Arg, Asn, Gln, Cit, Ser, Thr, Glu, Gly, Tyr, Ala, Trp, Val, Phe, Ile, and Leu) were quantified. The urinary amino acid concentrations were 5–960 μM. Urinary amino acid analysis using this method is expected to be clinically applicable as a novel biomarker for diseases affecting the bladder, urinary tract, and kidneys.

Abstract In computer-assisted synthesis planning (CASP) programs, providing as many chemical synthetic routes as possible is essential for considering optimal and alternative routes in a chemical reaction network. As the majority of CASP programs have been designed to provide one or a few optimal routes, it is likely that the desired one will not be included. To avoid this, an exact algorithm that lists possible synthetic routes within the chemical reaction network is required, alongside a recommendation of synthetic routes that meet specified criteria based on the chemist’s objectives. Herein, we propose a chemical-reaction-network-based synthetic route recommendation framework called “CompRet” with a mathematically guaranteed enumeration algorithm. In a preliminary experiment, CompRet was shown to successfully provide alternative routes for a known antihistaminic drug, cetirizine. CompRet is expected to promote desirable enumeration-based chemical synthesis searches and aid the development of an interactive CASP framework for chemists.

Abstract Deep learning is developing as an important technology to perform various tasks in cheminformatics. In particular, graph convolutional neural networks (GCNs) have been reported to perform well in many types of prediction tasks related to molecules. Although GCN exhibits considerable potential in various applications, appropriate utilization of this resource for obtaining reasonable and reliable prediction results requires thorough understanding of GCN and programming. To leverage the power of GCN to benefit various users from chemists to cheminformaticians, an open-source GCN tool, kGCN, is introduced. To support the users with various levels of programming skills, kGCN includes three interfaces: a graphical user interface (GUI) employing KNIME for users with limited programming skills such as chemists, as well as command-line and Python library interfaces for users with advanced programming skills such as cheminformaticians. To support the three steps required for building a prediction model, i.e., pre-processing, model tuning, and interpretation of results, kGCN includes functions of typical pre-processing, Bayesian optimization for automatic model tuning, and visualization of the atomic contribution to prediction for interpretation of results. kGCN supports three types of approaches, single-task, multi-task, and multi-modal predictions. The prediction of compound-protein interaction for four matrixmetalloproteases, MMP-3, -9, -12 and -13, in the inhibition assays is performed as a representative case study using kGCN. Additionally, kGCN provides the visualization of atomic contributions to the prediction. Such visualization is useful for the validation of the prediction models and the design of molecules based on the prediction model, realizing “explainable AI” for understanding the factors affecting AI prediction. kGCN is available at https://github.com/clinfo .

With the advent of nanotechnology, the use of nanoparticles as drug delivery system (DDS) has attracted great interest. We aimed to apply carbon nanohorns (CNHs) as DDS in the development of new treatments for bone diseases. We evaluated the in vitro and in vivo cellular responses of CNHs in bone-related cells compared with carbon blacks (CBs), which are similar in particle size but differ in surface and structural morphologies. Although in vitro experiments revealed that both CNHs and CBs were incorporated into the lysosomes of RAW264-induced osteoclast-like cells (OCs) and MC3T3-E1 osteoblast-like cells (OBs), no severe cytotoxicity was observed. CNHs reduced the tartrate-resistant acid phosphatase activity and expression of the differentiation marker genes in OCs at noncytotoxic concentrations, whereas the alkaline phosphatase activity and differentiation of OBs increased. Under calcification of OBs, CNHs increased the number of calcified nodules and were intra- and extracellularly incorporated into calcified vesicles to form crystal nuclei. The in vivo experiments showed significant promotion of bone regeneration in the CNH group alone, with localized CNHs being found in the bone matrix and lacunae. The suppression of OCs and promotion of OBs suggested that CNHs may be effective against bone diseases and could be applied as DDS.

A studio arson attack in Japan caused 36 deaths. Dentists obtained dental findings from 33 unidentified bodies immediately after the attack and autopsy. The dental findings before autopsy were obtained on the day of the incident and the next day. Dental findings after autopsy were obtained at 1 week from the day after the incident. We examined issues associated with collecting these dental findings. Other findings recorded were CT images, autopsy findings, and various blood and pathological examinations. Among the 33 unidentified bodies, for 30 bodies, the number of teeth from which the dental findings were obtained was significantly higher after autopsy than before autopsy. The dental findings of the remaining three bodies were not obtained before or after the autopsy. Five percent of anterior teeth and 28.7% of molars had differing pre-autopsy and post-autopsy findings. This discrepancy can be attributed to various factors. One of the major influencing factors was the carbonization of the facial surface muscles and skin along with limited mouth opening due to thermocoagulation. For the scientific identification of an individual based on dental findings, it is mandatory to examine the teeth in all quadrants. The collection of dental findings solely from anterior teeth may not be adequate to establish identity. The present article describes the challenges faced by the dentists while identifying charred bodies in an arson attack.

(1) Background: The tongue plays a key role in the stomatognathic system in carrying out oral functions. The aim of this study was to identify the association between tongue pressure and orthodontic parameters. (2) Methods: This study is a cross-sectional multicentered cohort study with IRB approval. During routine orthodontic initial examinations, the following data were recorded: age, sex, angle classification, overjet (OJ), overbite (OB), arch sizes, tongue width, and maximum tongue pressure (MTP). The association between MTP and orthodontic parameters was analyzed using Pearson’s correlation analysis and the Student’s t-test. (3) Results: There is a positive correlation between MTP and age between ages 10 and 20 (R = 0.47, p < 0.01). There is a negative correlation with MTP and age between 20 and 40 (R = −0.30, p < 0.05). There are negative correlations between MTP and OJ (R = −0.278, p < 0.01)) and OB (R = −0.374, p < 0.01). While there is no statistical significance between MTP and tongue width, there is a statistically significant difference between age and tongue width (R = 0.22482, p < 0.05). There is no statistical significance between MTP and sex, angle classification, arch length, intercanine width, and intermolar width. (4) Conclusion: An earlier decline in MTP is observed with patients with malocclusion. This implies that patients with malocclusion should seek early treatment for the malocclusion.

Scientists, curators, historians and archaeologists are always looking for new techniques for the study of archaeological artefacts, especially if they are non-destructive. With most non-destructive investigations, it is challenging to measure beneath the surface. Among the vast board of techniques used for cultural heritage studies, it is difficult to find one able to give information about the bulk and the compositional variations, along with the depth. In addition, most other techniques have self-absorption issues (i.e., only surface sensitive) and limited sensitivity to low Z atoms. In recent years, more and more interest has been growing around large-scale facility-based techniques, thanks to the possibility of adding new and different insights to the study of material in a non-destructive way. Among them, muonic X-ray spectroscopy is a very powerful technique for material characterization. By using negative muons, scientists are able to perform elemental characterization and depth profile studies. In this work, we give an overview of the technique and review the latest applications in the field of cultural heritage.

The fundamental characteristics of nanoparticle (NP) deposition of the fluoropolymer CYTOP using a femtosecond (fs) laser were investigated. In previous studies, we have demonstrated the microfluidic fabrication of CYTOP, which enables clear microscopic observation of the fluid boundary because of its low refractive index, as well as that of water. In the present work, we generated CYTOP NPs using holographic fs laser processing with a spatial light modulator to demonstrate the capabilities of this functional polymer. We established a deposition technique via five-dot parallel fs laser beam irradiation for fibrous network and monolayer structures composed of CYTOP NPs on the surface of glass slides by manipulating the various fundamental laser processing parameters. The network structure on the glass surface exhibits superhydrophobic behavior, while the monolayer structure performs almost the same wettability as that of CYTOP thin film. After an investigation of the surface features of the NPs deposited onto the glass, the combination of the holographic fs laser deposition and the removal of CYTOP NPs was used to selectively pattern CYTOP NPs on the glass slide for HeLa cell culturing. Consequently, cells were selectively cultured on the glass surface where the laser removal of deposited NPs was carried out.

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.

Pneumatic servo valves are key components of pneumatic servo systems. Multi-degree-of-freedom systems, such as robot systems, utilize many servo valves to control their actuators. However, conventional servo valves always consume air due to leakage even when the pneumatic actuator is not moving. Hence, the consumption flow rate of the entire system corresponds to a heavy load on the air compressor. Reduction in the leakage of servo valves contributes to lower requirements for the air compressor and saves energy. In this study, we develop a four-way pinch- type pneumatic servo valve that controls flow rates by pinching air tubes to realize a leak-free servo valve. A cam to control the aperture of the flow channel is newly designed, and a control system is established. Measurement results indicate high linearity in static flow characteristics and high dynamic characteristics corresponding to 30 Hz. We experimentally confirm a good position tracking property in the position control of a pneumatic cylinder by using the developed valve. Finally, evaluation results of air consumption in a robotic control application indicate that the developed valve contributes to a significant reduction in air consumption compared to that of a conventional spool-type valve.