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In swash plate type axial piston pumps, slipper/swash plate sliding surfaces is subject to high fluctuating load. Therefore, the slippers are required to provide stable operation and reduce losses due to sliding. The behavior of the slipper fluctuates in a complex manner due to changes in the hydraulic pressure in the cylinder and inertial forces caused by the reciprocating motion of the piston. However, the time variation of the oil film thickness distribution of the slipper has not been measured. Furthermore, there are no measurements of the movement of the spherical joint connecting the slipper and piston, which affects the slipper behavior. In this study, the visualized sliding test rig with a sapphire glass swash plate was developed. The oil film thickness distribution of the slipper and the rotation of the slipper and the piston were measured continuously during one rotation of the pump.

Abstract Photolysis is an attractive method in organic synthesis to produce free radicals through direct bond cleavage. However, in this method, specific irradiation wavelengths of light have been considered indispensable for excitation through S0–Sn or S0–Tn transitions. Here we report the photoinduced homolysis of electronegative interelement bonds using light at wavelengths much longer than theoretically and spectroscopically predicted for the S0–Sn or S0–Tn transitions. This long-wavelength photolysis proceeds in N–Cl, N–F, and O–Cl bonds at room temperature under blue, green, and red LED irradiation, initiating diverse radical reactions. Through experimental, spectroscopic, and computational studies, we propose that this “hidden” absorption is accessible via electronic excitations from naturally occurring vibrationally excited ground states to unbonded excited states and is due to the electron-pair repulsion between electronegative atoms.

The emergence of aerosol reanalyses in recent years has facilitated a comprehensive and systematic evaluation of aerosol optical depth (AOD) trends and attribution over multi-decadal timescales. Notable multi-year aerosol reanalyses currently available include NAAPS-RA from the US Naval Research Laboratory, the NASA MERRA-2, JRAero from the Japan Meteorological Agency (JMA), and CAMSRA from Copernicus/ECMWF. These aerosol reanalyses are based on differing underlying meteorology models, representations of aerosol processes, as well as data assimilation methods and treatment of AOD observations. This study presents the basic verification characteristics of these four reanalyses versus both AERONET and MODIS retrievals in monthly AOD properties and identifies the strength of each reanalysis and the regions where divergence and challenges are prominent. Regions with high pollution and often mixed fine-mode and coarse-mode aerosol environments, such as South Asia, East Asia, Southeast Asia, and the Maritime Continent, pose significant challenges, as indicated by higher monthly AOD root mean square error. Moreover, regions that are distant from major aerosol source areas, including the polar regions and remote oceans, exhibit large relative differences in speciated AODs and fine-mode versus coarse-mode AODs among the four reanalyses. To ensure consistency across the globe, a multi-reanalysis consensus (MRC, i.e., ensemble mean) approach was developed similarly to the International Cooperative for Aerosol Prediction Multi-Model Ensemble (ICAP-MME). Like the ICAP-MME, while the MRC does not consistently rank first among the reanalyses for individual regions, it performs well by ranking first or second globally in AOD correlation and RMSE, making it a suitable candidate for climate studies that require robust and consistent assessments.

The 9th International Tribology Conference, Fukuoka 2023 was held on 25–30 September 2023 at Fukuoka International Congress Center in Fukuoka City, Japan. The number of participants was 975 from 30 countries and regions, and the number of papers presented was 676. We thank all the people who joined and contributed to ITC. Papers submitted to this special issue went through peer-review process. Twenty papers were already published in Part 1, and 19 papers were accepted for publication in this Part 2. On behalf of the Organizing Committee, we would like to thank all the authors for their contributions, and also thank the editors, reviewers and the editorial office of Tribology Online for their efforts. Taking this opportunity, we would like to include in the next page the manuscript of the congratulatory speech delivered by Professor Masato Tanaka in Banquet on Thursday, 28 September, 2023

Abstract Although anion‐exchange membranes (AEMs) are commonly used in fuel cells and water electrolyzers, their widespread commercialization is hindered by problems such as low anion conductivity and durability. Moreover, the development of high‐performance AEMs remains complex and time consuming. Here, we address these challenges by proposing an innovative approach for the efficient design and screening of AEM polymers using unsupervised machine learning. Our model, which combines principal component analysis with uniform manifold approximation and projection, generates an intuitive map that clusters AEM polymers based on structural similarities without any predefined knowledge regarding anion conductivity or other experimentally derived variables. As a powerful navigation tool, this map provides insights into promising main‐chain structures, such as poly(arylene alkylene)s with consistently high conductivity and polyolefins with exceptional performance depending on the substituent. Furthermore, assisted by key molecular descriptors, inverse analysis with this model allows targeted design and property prediction before synthesis, which will significantly accelerate the discovery of novel AEM polymers. This work represents a paradigm shift not only in AEM research but also generally in materials research, moving from black‐box predictions toward interpretable guidelines that foster collaboration between researchers and machine learning for efficient and informed material development.

Abstract Supramolecular liquid crystals (SLCs) are attractive materials for fabricating devices with new optoelectronic functions. Conventional SLCs are made from hydrogen‐bonded mesogens. However, these mesogens suffer from high melting points, and the types of formable aggregates are limited owing to the directionality of the hydrogen bonding. Therefore, to fabricate non‐hydrogen‐bonded SLCs, we hypothesized that the introduction of tertiary amide groups into calamitic molecules would be advantageous because they have an L‐shaped structure with N‐ or C‐alkyl side chains not aligned along the long axis and the flexibility to undergo cis–trans isomerization. In this study, we developed a novel non‐hydrogen‐bonded SLC by assembling an L‐shaped dimer composed of calamitic molecules (phenyltolanes) with tertiary amides at their ends. These molecules exhibited a smectic B phase. The phase transition temperature of the SLCs from crystal to liquid crystal phase was low despite the long π‐conjugated core. Wide‐angle X‐ray diffraction and variable‐temperature Fourier‐transform infrared measurements revealed dimer formation by weak intermolecular interactions, that is, the molecular recognition of L‐shaped molecules, and mobility of the alkyl groups attached to amide driven by cis–trans isomerization in the liquid crystal phase. Thus, cis–trans isomerization of tertiary amides contributed enormously to the formation and lower clearing points of this SLC. The developed method can be used not only to develop non‐hydrogen‐bonded SLCs but also to develop novel soft matter with controlled properties by incorporating the SLCs, as the aggregates can be controlled to impart desired functionalities.

Abstract Cylinder‐shaped macrocycles composed of π‐panels have attracted special attention as one of the best platforms for the development of organic molecule‐based chiroptical materials. Pillar[n]arenes are a class of macrocycles with the advantage of easy preparation but have not been extensively investigated from the perspective of luminescent molecules. However, common alkoxy pillar[n]arenes are fluorescent in non‐haloalkane solvents, showing potential to be used for molecule‐based chiroptical materials. In this work, circularly polarized luminescence (CPL) spectra are reported for a pillar[5]arene with stable planar chirality using tetrahydrofuran (THF) and cyclohexane as solvents, which has been missing for many years. The pillar[5]arene also forms co‐aggregates with 1,4‐bis(phenylethynyl)benzene and 1,4‐bis[(pentafluorophenyl)ethynyl]benzene in THF/H2O mixtures, owing to a hydrophobic effect. The co‐aggregates with the fluorinated π‐rod display a new low‐energy absorption peak and broad emission band as well as intense circular dichroism and CPL signals. Chiral information from the enantiopure pillar[5]arene core is efficiently transmitted to the co‐aggregates with the π‐conjugated rod, leading to the highest dissymmetry factor for CPL (2.9 × 10−2 at 472 nm) among pillar[n]arene‐based CPL materials.

Abstract Copper (Cu) nanoparticles (NPs) loaded on titanium(IV) oxide (TiO2) exhibit an extinction at about λ=580 nm because of surface plasmon resonance (SPR); however, they rapidly lose their its SPR when exposed to air. In order to stabilize the Cu NPs, a multi‐step photodeposition method was used to introduce chromium, which resulted in successful synthesis of a Cr2O3/Cu/TiO2 sample that exhibited extinction even when exposed to air. Transmission electron microscopy, scanning transmission electron microscopy, X‐ray photoelectron spectroscopy and UV‐vis spectroscopy were utilized to analyze the Cu/TiO2 and Cr2O3/Cu/TiO2 samples with a focus on SPR of the nanoparticles and state of the Cu species. The prepared Cr2O3/Cu/TiO2 samples acted as plasmonic photocatalysts in oxidation of 2‐propanol under aerated conditions and visible light irradiation. Expandability of the Cr2O3/Cu/TiO2 plasmonic photocatalyst was also investigated, and the results suggested the potential of a Cu‐based plasmonic photocatalyst working under irradiation of visible light.

Abstract During the long-term storage of cells, it is necessary to inhibit ice crystal formation by adding cryoprotectants. Non-cell-permeable cryoprotectants have high osmotic pressure which dehydrates cells, indirectly suppressing intracellular ice crystal formation. However, the high osmotic pressure and dehydration often damage cells. Emerging polymer-type non-cell-permeable cryoprotectants form matrices surrounding cells. These matrices inhibit the influx of extracellular ice nuclei that trigger intracellular ice crystal formation. However, these polymer-type cryoprotectants also require high osmotic pressure to exert an effective cryoprotecting effect. In this study, we designed a poly(zwitterion) (polyZI) that forms firm matrices around cells based on their high affinity to cell membranes. The polyZI successfully cryopreserved freeze-vulnerable cells under isotonic conditions. These matrices also controlled osmotic pressure by adsorbing and desorbing NaCl depending on the temperature, which is a suitable feature for isotonic cryopreservation. Although cell proliferation was delayed by the cellular matrices, washing with a sucrose solution improved proliferation.

The effects of enhanced late INa, a persistent component of the Na+ channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late INa, caused increases in the basal Na+ and Ca2+ concentrations, increases in the number of Ca2+ sparks and Ca2+ waves, and the generation of repetitive Ca2+ transients. These phenomena were inhibited by eleclazine, a blocker of the late INa; SEA0400, an inhibitor of the Na+/Ca2+ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late INa in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca2+-dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.

Galectins are β-galactoside-binding animal lectins involved in various biological functions, such as host defense. Galectin-2 and -3 are members of the galectin family that are expressed in the stomach, including the gastric mucosa and surface mucous cells. Galectin-3 exhibits aggregation and bactericidal activity against Helicobacter pylori in a β-galactoside-dependent manner. We previously reported that galectin-2 has the same activity under neutral pH conditions. In this study, the H. pylori aggregation activity of galectin-2 was examined under weakly acidic conditions, in which H. pylori survived. Galectin-2 agglutinated H. pylori even at pH 6.0, but not at pH 5.0, correlating with its structural stability, as determined using circular dichroism. Additionally, galectin-2 binding to the lipopolysaccharide (LPS) of H. pylori cultured under weakly acidic conditions was investigated using affinity chromatography and Western blotting. Galectin-2 could bind to H. pylori LPS containing H type I, a Lewis antigen, in a β-galactoside-dependent manner. In contrast, galectin-3 was structurally more stable than galectin-2 under acidic conditions and bound to H. pylori LPS containing H type I and Lewis X. In conclusion, galectin-2 and -3 might function cooperatively in the defense against H. pylori in the stomach under different pH conditions.

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.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody (mAb), H2Mab-250/H2CasMab-2. In flow cytometry and immunohistochemistry, H2Mab-250 reacted with HER2-positive breast cancer cells but did not show reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG1 version of H2Mab-250 (H2Mab-250-hG1) possesses compatible in vivo antitumor effects against breast cancer xenografts to trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H2Mab-250-hG1 and trastuzumab. Both H2Mab-250-hG1 and trastuzumab showed ADCC activity against HER2-overexpressed Chinese hamster ovary -K1 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed where trastuzumab showed a more significant ADCC effect compared to H2Mab-250-hG1. Importantly, H2Mab-250-hG1 exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in the mouse IgG2a types of both H2Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H2Mab-250-hG1 and trastuzumab, and indicate a future direction for the clinical development of H2Mab-250-hG1 against HER2-positive tumors.

Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13—a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content—against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.

Nitrogen-doped carbon dots (NCDs) have been recognized as a promising supporting material for stabilizing metal nanoparticles. In this study, copper nanoparticles (CuNPs) decorated onto NCDs were easily prepared under mild conditions. Two types of Cu fabricated NCDs were prepared by using different Cu precursors – CuCl2 and N,N-dimethylformamide (DMF)-protected CuNPs, where DMF was employed as a multifunctional reagent serving as a reducing agent, stabilizer, and solvent for the synthesis of the CuNPs. The resulting NCDs with Cu species were characterized using ICP-AES, FT-IR, XPS, XRD, and STEM. We found that the Cu precursor greatly influence the fabrication of Cu species on NCDs, with the Cu content of the CuNPs/NCDs being almost twice that of CuCl2/NCDs. Furthermore, when DMF-protected CuNPs were used, nano-sized Cu particles ranging from 4 to 11 nm were immobilized on NCDs surface, whereas single-atom Cu were observed when using CuCl2. This indicates that DMF-protected CuNPs are a suitable source of Cu for the preparation of nano-sized Cu on NCDs.

Collagen-binding proteins (CBP), Cnm and Cbm, from Streptococcus mutans are involved in infective endocarditis caused by S. mutans because of their collagen-binding ability. In this study, we focused on the collagen-binding domain (CBD), which is responsible for the collagen-binding ability of CBP, and analyzed its structure, binding activity, and stability using CBD domain variants. The CBD consists of the N1 domain, linker, N2 domain, and latch (N1-N2~) as predicted from the amino acid sequences. The crystal structure of the Cnm/CBD was determined at a 1.81 Å resolution. N1_linker_N2 forms a ring structure that can enfold collagen molecules, and the latch interacts with N1 to form a ring clasp. N1 and N2 have similar immunoglobulin folds. The collagen-binding activities of Cbm/CBD and its domain variants were examined using ELISA. N1-N2~ bound to collagen with KD = 2.8 μM, and the latch-deleted variant (N1-N2) showed weaker binding (KD = 28 μM). The linker-deleted variant (N1N2~) and single-domain variants (N1 and N2) showed no binding activity, whereas the domain-swapped variant (N2-N1~) showed binding ability, indicating that the two N-domains and the linker are important for collagen binding. Thermal denaturation experiments showed that N1-N2 was slightly less stable than N1-N2~, and that N2 was more stable than N1. The results of this study provide a basis for the development of CBD inhibitors and applied research utilizing their collagen-binding ability.

Whereas the cationic homopolymerization of β-pinene and isobutene (IB) have been extensively studied, their copolymerization is still very scarce, and the conditions under which copolymerization can occur are limited to extremely low temperatures. Moreover, the application of the copolymer has not been reported. Here, a series of room-temperature copolymerizations of β-pinene and IB, using group 13 compounds as catalysts, were conducted. The copolymerizations yielded a low molecular weight (Mn ~ 103) and a narrow molecular weight distribution (Mw/Mn < 2.0) copolymer, with a satisfactory yield at various comonomer feeds, and their glass transition temperature was predictable from the comonomer composition. Furthermore, the tackifying property of the obtained copolymer was investigated using a 180° peel adhesion test. A blend polymer of the copolymer and a styrene-isoprene triblock copolymer showed a high peeling force (0.58 ± 0.14 N/10 mm) and a glass transition temperature low enough for its application as a pressure-sensitive adhesive.

Potato mop-top virus (PMTV) is an emerging viral pathogen that causes tuber necrosis in potatoes. PMTV is composed of three single-stranded RNA segments: RNA1 encodes RNA-dependent RNA polymerase, RNA2 contains the coat protein (CP), and RNA3 harbors a triple gene block (TGB 1, TGB2, and TGB3). CP plays a role in viral transmission, while TGB is known to facilitate cell-to-cell and long-distance systemic movement. The role of CP in symptom development, specifically in the presence of TGB genes, was investigated using potato virus X (PVX) as a delivery vehicle to express PMTV genes in the model plant Nicotiana benthamiana. Plants expressing individual genes showed mild symptoms that included leaf curling and crumpling. Interestingly, symptom severity varied among plants infected with three different combinations: CP with TGB1, CP with TGB2, and CP with TGB3. Notably, the combination of CP and TGB3 induced a hypersensitive response, accompanied by stunted growth and downward curling and crumpling. These results suggest the potential role of TGB co-expressed with CP in symptom development during PMTV infection. Additionally, this study demonstrates the use of the PVX-based expression system as a valuable platform for assessing the role of unknown genes in viral pathogenicity.

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.

Increased human T-cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is a significant risk factor for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is controversy surrounding whether HTLV-1-specific cytotoxic T lymphocytes (CTLs) are beneficial or harmful to HAM/TSP patients. Recently, HTLV-1 Tax 301–309 has been identified as an immunodominant epitope restricted to HLA-A*2402. We investigated whether HLA-A*24 reduces HTLV-1 PVL and the risk of HAM/TSP using blood samples from 152 HAM/TSP patients and 155 asymptomatic HTLV-1 carriers. The allele frequency of HLA-A*24 was higher in HAM/TSP patients than in asymptomatic HTLV-1 carriers (72.4% vs. 58.7%, odds ratio 1.84), and HLA-A*24-positive patients showed a 42% reduction in HTLV-1 PVL compared to negative patients. Furthermore, the PVL negatively correlated with the frequency of Tax 301–309-specific CTLs. These findings are opposite to the effects of HLA-A*02, which reduces HTLV-1 PVL and the risk of HAM/TSP. Therefore, we compared the functions of CTLs specific to Tax 11–19 or Tax 301–309, which are immunodominant epitopes restricted to HLA-A*0201 or HLA-A*2402, respectively. The maximum responses of these CTLs were not different in the production of IFN-γ and MIP-1β or in the expression of CD107a—a marker for the degranulation of cytotoxic molecules. However, Tax 301–309-specific CTLs demonstrated 50-fold higher T-cell avidity than Tax 11–19-specific CTLs, suggesting better antigen recognition at low expression levels of the antigens. These findings suggest that HLA-A*24, which induces sensitive HTLV-1-specific CTLs, increases the risk of HAM/TSP despite reducing HTLV-1 PVL.

Various metabolites, including phytohormones, phytoalexins, and amino acids, take part in the plant immune system. Herein, we analyzed the effects of L-methionine (Met), a sulfur-containing amino acid, on the plant immune system in tomato. Treatment with low concentrations of Met enhanced the resistance of tomato to a broad range of diseases caused by the hemi-biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) and the necrotrophic fungal pathogen Botrytis cinerea (Bc), although it did not induce the production of any antimicrobial substances against these pathogens in tomato leaf tissues. Analyses of gene expression and phytohormone accumulation indicated that Met treatment alone did not activate the defense signals mediated by salicylic acid, jasmonic acid, and ethylene. However, the salicylic acid-responsive defense gene and the jasmonic acid-responsive gene were induced more rapidly in Met-treated plants after infection with Pst and Bc, respectively. These findings suggest that low concentrations of Met have a priming effect on the phytohormone-mediated immune system in tomato.

Dielectric barrier discharge plasma actuators (DBD-PAs) have the potential to improve the performance of fluid machineries such as aircrafts and wind turbines by preventing flow separation. In this study, to identify the multiple flow control mechanisms in high Reynolds number flow, parametric experiments for an actuation parameter F+ with a wide range of Re values (105–106) for NACA0015 airfoil was conducted. We conducted wind tunnel tests by applying a DBD-PA to the flow field around a wing model at the leading edge. Lift characteristics, turbulent kinetic energy in the flow field, shear layer height, and the separation point of the boundary layer were evaluated based on pressure distributions on the wing surface and velocity of the flow field, with the effect of DBD-PA on the post-stall flow around the wing and the mechanism behind the increase in the lift coefficient CL analyzed based on these evaluation results. The following phenomena contributed to the increase in CL: (1) increase in turbulent kinetic energy; (2) increase in circulation; and (3) acceleration of the flow near the leading edge. Thus, this study effectively investigated the dependence of the increase in lift on F+ and the lift-increasing mechanism for a wide range of Re values.

While research has identified several inhibitors of the main protease (Mpro) of SARS-CoV-2, a significant portion of these compounds exhibit reduced activity in the presence of reducing agents, raising concerns about their effectiveness in vivo. Furthermore, the conventional biosafety level 3 (BSL-3) for cellular assays using viral particles poses a limitation for the widespread evaluation of Mpro inhibitor efficacy in a cell-based assay. Here, we established a BSL-1 compatible cellular assay to evaluate the in vivo potential of Mpro inhibitors. This assay utilizes mammalian cells expressing a tagged Mpro construct containing N-terminal glutathione S-transferase (GST) and C-terminal hemagglutinin (HA) tags and monitors Mpro autodigestion. Using this method, GC376 and boceprevir effectively inhibited Mpro autodigestion, suggesting their potential in vivo activity. Conversely, carmofur and ebselen did not exhibit significant inhibitory effects in this assay. We further investigated the inhibitory potential of selenoneine on Mpro using this approach. Computational analyses of binding energies suggest that noncovalent interactions play a critical role in facilitating the covalent modification of the C145 residue, leading to Mpro inhibition. Our method is straightforward, cost-effective, and readily applicable in standard laboratories, making it accessible to researchers with varying levels of expertise in infectious diseases.

The PAX8/PPARγ rearrangement, producing the PAX8–PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble-docking-based compound screening. Specifically, we investigated the pocket structure that should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand-binding pocket on the PPARγ side of the PPFP is similar to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to the PPFP for 97 drug or drug-like compounds registered in the DrugBank database with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics Poisson–Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

The human genome encodes at least 500 protein kinases, and among them, there are at least 90 tyrosine kinases [...]

Porous metallic nanomaterials exhibit interesting physical and chemical properties, and are widely used in various fields. Traditional fabrication techniques are limited to metallurgy, sintering, electrodeposition, etc., which limit the control of pore size and distribution, and make it difficult to achieve materials with high surface areas. On the other hand, the chemical preparation of metallic nanoparticles is usually carried out with strong reducing agents or at high temperature, resulting in the formation of dispersed particles which cannot evolve into porous metal. In this study, we reported the simple fabrication of coral-like mesoporous Pd nanomaterial (Pd NC) with a ligament size of 4.1 nm. The fabrication was carried out by simple solvothermal reduction at a mild temperature of 135 °C, without using any templates. The control experiments suggested that tetrabutylammonium bromide (TBAB) played a critical role in the Pd(II) reduction into Pd nanoclusters and their subsequent aggregation to form Pd NC, and another key point for the formation of Pd NC is not to use a strong reducing agent. In alkaline water electrolysis, the Pd NC outperforms the monodisperse Pd NPs and the state-of-the-art Pt (under large potentials) for H2 evolution reaction, probably due to its mesoporous structure and large surface area. This work reports a simple and novel method for producing porous metallic nanomaterials with a high utilization efficiency of metal atoms, and it is expected to contribute to the practical preparation of porous metallic nanomaterials by solvothermal reductions.

The trichothecene biosynthesis in Fusarium begins with the cyclization of farnesyl pyrophosphate to trichodiene, followed by subsequent oxygenation to isotrichotriol. This initial bicyclic intermediate is further cyclized to isotrichodermol (ITDmol), a tricyclic precursor with a toxic trichothecene skeleton. Although the first cyclization and subsequent oxygenation are catalyzed by enzymes encoded by Tri5 and Tri4, the second cyclization occurs non-enzymatically. Following ITDmol formation, the enzymes encoded by Tri101, Tri11, Tri3, and Tri1 catalyze 3-O-acetylation, 15-hydroxylation, 15-O-acetylation, and A-ring oxygenation, respectively. In this study, we extensively analyzed the metabolites of the corresponding pathway-blocked mutants of Fusarium graminearum. The disruption of these Tri genes, except Tri3, led to the accumulation of tricyclic trichothecenes as the main products: ITDmol due to Tri101 disruption; a mixture of isotrichodermin (ITD), 7-hydroxyisotrichodermin (7-HIT), and 8-hydroxyisotrichodermin (8-HIT) due to Tri11 disruption; and a mixture of calonectrin and 3-deacetylcalonectrin due to Tri1 disruption. However, the ΔFgtri3 mutant accumulated substantial amounts of bicyclic metabolites, isotrichotriol and trichotriol, in addition to tricyclic 15-deacetylcalonectrin (15-deCAL). The ΔFgtri5ΔFgtri3 double gene disruptant transformed ITD into 7-HIT, 8-HIT, and 15-deCAL. The deletion of FgTri3 and overexpression of Tri6 and Tri10 trichothecene regulatory genes did not result in the accumulation of 15-deCAL in the transgenic strain. Thus, the absence of Tri3p and/or the presence of a small amount of 15-deCAL adversely affected the non-enzymatic second cyclization and C-15 hydroxylation steps.

Protein ubiquitination is involved in nearly all biological processes in Eukaryotes. To gain precise insights into the function of ubiquitination in these processes, researchers frequently employ ubiquitinated protein probes with well-defined structures. While chemical protein synthesis has afforded a variety of ubiquitinated protein probes, there remains a demand for efficient synthesis methods for complex probes, such as ubiquitinated glycoproteins and ubiquitinated cysteine-containing proteins. In this study, we introduce a new method to obtain ubiquitinated proteins through isopeptide bond formation mediated by δ-selenolysine residues. We synthesized δ-selenolysine derivatives in both L- and D-forms starting from DL-δ-hydroxy-DL-lysine, accomplished by substituting the δ-mesylate with KSeCN and by enzymatic optical resolution with L- and D-aminoacylase. We synthesized ubiquitin (46–76)-α-hydrazide with a δ-seleno-L-lysine residue at position 48, as well as ubiquitin (46–76)-α-thioester, using solid-phase peptide synthesis. Subsequently, the δ-selenolysine-mediated ligation of these peptides, followed by one-pot deselenization, provided the desired isopeptide-linked ubiquitin peptide. The new δ-selenolysine-mediated isopeptide bond formation offers an alternative method to obtain complex ubiquitin- and ubiquitin-like probes with multiple post-translational modifications. These probes hold promise for advancing our understanding of ubiquitin biology.

Food is a complex soft matter, because various components, such as proteins, lipids, and carbohydrates, are self-assembled via non-covalent, colloidal interactions and form hierarchical structures at multiple length scales. Soft matter scientists have shown an increasing interest in understanding the general principles governing the food structure formation. During the last several decades, an increasing number of studies have shown that the maintenance of healthy gastrointestinal tract and its microbiome is essential for human health and wellbeing. The realization of the importance of the gastrointestinal microbiome has led to the development of probiotics, which are defined as living bacteria that confer a health benefit on the host. Probiotic bacteria and enzymes can be delivered to the intestinal system by formulating appropriate carriers and including these into food ingested by humans. Despite this simple statement, it involves many challenges in the field of soft matter science. This review aims to highlight how the key concepts in soft matter science can be used to design, characterize, and evaluate self-assembled formulations of probiotics and enzymes based on lipids and biopolymers. The topics covered in this review includes the emulsification of oil-water mixtures, the self-assembly of lipids and polymers at interfaces, the electrostatics and viscoelasticity of interfaces, and the wetting/adhesion of colloidal particles.

To investigate the regulation of soluble very low-density lipoprotein receptor (sVLDL-R), which is cleaved mostly from the extracellular domain of VLDL-R II, we generated two rat monoclonal antibodies (mAbs) against human sVLDL-R, and used them to develop a sandwich enzyme-linked immunosorbent assay (ELISA) to measure sVLDL-R levels in human serum or plasma. The ELISA had a linear range from 0.20 ng/mL to 13.02 ng/mL and allowed for the quantification of sVLDL-R in serum and culture cell medium. The coefficient of variation (CV) was less than 10% for both the intra- and inter-assays. The bililubin F, and C, triglyceride (TG), and hemoglobin levels did not affect assay precision. The sVLDL-R concentration was negatively associated with body fat percentage, TG, and HbA1c, suggesting the possibility of obesity and diabetes in middle-aged Japanese women.

As a novel anode material for Na-ion battery, we evaluated rutile-type TiNbO4 synthesized by a sol−gel method. It was revealed for the first time that TiNbO4 showed reversible reactions of Na+-insertion and Na+-extraction in the potential ranges of 0.005–1.0 and 0.6–1.6 V vs. Na+/Na, respectively. TiNbO4 maintained its rutile structure even after charge−discharge cycling. The size of Na+ diffusion path along its c-axis was broadened with increasing Nb amount in TiNbO4, leading to the improvement in the reversible capacity. The TiNbO4 electrode with Nb 48 at.% exhibited a high capacity of 360 mA h g−1. The long-term cyclability and rate capability were also improved by increasing Nb amount. We consider that the wider space in the diffusion path increases the degree of freedom of Na+ occupancy position, which weakens the electrostatic repulsion between Na+ and Na+ to increase Na storage capacity. These results clearly demonstrate that TiNbO4 can be applied as a promising anode material.

Discussed is the preparation of synthetic brochantite from solution and a thermogravimetric-differential thermal analysis study of the thermal decomposition of this compound. Other analyses included are chemical analysis and IR spectroscopy. Experimental procedures and results are presented. (CW)

Alkyl chlorides are robust precursors to carbon radicals; however, their relative inertness has hampered their practical use. Although modern photochemical strategies have greatly enhanced the utility of alkyl chlorides as radical precursors, these methods often depend on strongly reducing conditions leading to unproductive side reactions. Here, we report a catalytic radical generation from 1°, 2°, and 3° unactivated alkyl chlorides with zirconocene and photoredox catalysis, which enables both hydrogenation and borylation on a range of structurally complex molecules. This mild zirconocene-catalyzed protocol shows that zirconium can render the C–Cl bond cleavage more exergonic and can lower the activation energy of the transition state, amplifying the ability of metallocenes toward halogen atom transfer.

The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer’s disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation.

The bone healing process is influenced by various physiological factors. Fracture fixation traditionally relied on rigid metallic implants. However, excessively rigid constructs can lead to complications, necessitating revision surgery. This review focuses on approaches to improve bone healing by introducing adequate interfragmentary movement (IFM) at the fracture site. IFM promotes secondary fracture healing and callus formation. Studies suggest that rigid fixation may impair fracture healing by inhibiting callus formation and causing stress shielding. Titanium alloy locking plates have been shown to be biomechanically superior to stainless steel. Flexible fixation and techniques to regulate implant stiffness are crucial for managing fractures with bridge plating. Materials with a lower Young’s modulus balance biomechanical properties. A novel TiNbSn alloy with a low Young’s modulus has been developed to address stress shielding issues. It is effective in promoting osteosynthesis, bone healing, and superior mechanical properties compared with materials with higher Young’s moduli. The enhanced formation of bone and callus associated with TiNbSn alloy suggests its promise for use in fracture treatment plates. Understanding the biomechanics of fracture healing, optimizing fixation stiffness, and exploring innovative materials like TiNbSn alloys, are crucial for advancing approaches to accelerate and enhance bone healing.

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (

The central nervous system (CNS) is the final frontier in drug delivery because of the blood–brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis. Since platelets have been reported to modulate immune responses, we aimed to determine the role of platelets in TMEV infection. In transcriptome analyses of platelets, distinct sets of immune-related genes, including major histocompatibility complex (MHC) class I, were up- or downregulated in TMEV-infected mice at different time points. We depleted platelets from TMEV-infected mice by injecting them with platelet-specific antibodies. The platelet-depleted mice had significantly fewer viral antigen-positive cells in the CNS. Platelet depletion reduced the severities of TMEV-IDD and myocarditis, although the pathology scores did not reach statistical significance. Immunologically, the platelet-depleted mice had an increase in interferon (IFN)-γ production with a higher anti-TMEV IgG2a/IgG1 ratio. Thus, platelets may play roles in TMEV infection, such as gene expression, viral clearance, and anti-viral antibody isotype responses.

The perivascular space has been proposed as a clearance pathway for degradation products in the brain, including amyloid β, the accumulation of which may induce Alzheimer’s disease. Live images were acquired using a two-photon microscope through a closed cranial window in mice. In topical application experiments, the dynamics of FITC-dextran were evaluated from 30 to 150 min after the application and closure of the window. In continuous injection experiments, image acquisition began before the continuous injection of FITC-dextran. The transport of dextran molecules of different sizes was evaluated. In topical application experiments, circumferential accumulation around the penetrating arteries, veins, and capillaries was observed, even at the beginning of the observation period. No further increases were detected. In continuous injection experiments, a time-dependent increase in the fluorescence intensity was observed around the penetrating arteries and veins. Lower-molecular-weight dextran was transported more rapidly than higher-molecular-weight dextran, especially around the arteries. The largest dextran molecules were not transported significantly during the observation period. The size-dependent transport of dextran observed in the present study strongly suggests that diffusion is the main mechanism mediating substance transport in the perivascular space.

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC