This study aimed to clarify the relationship between the joint and ligament structures of the subtalar joint and degeneration of the subtalar articular facet. We examined 50 feet from 25 Japanese cadavers. The number of articular facets, joint congruence, and intersecting angle were measured for the joint structure of the subtalar joint, and the footprint areas of the ligament attachments of the cervical ligament, interosseous talocalcaneal ligament (ITCL), and anterior capsular ligament were measured for the ligament structure. Also, subtalar joint facets were classified into Degeneration (+) and (-) groups according to degeneration of the talus and calcaneus. No significant relationship was identified between the joint structure of the subtalar joint and degeneration of the subtalar articular facet. In contrast, footprint area of the ITCL was significantly higher in the Degeneration (+) group than in the Degeneration (-) group for the subtalar joint facet. These results suggest that the joint structure of the subtalar joint may not affect degeneration of the subtalar articular facet. Degeneration of the subtalar articular facet may be related to the size of the ITCL.

The purpose of this study was to determine changes in the mechanical properties of the thigh and lower leg musculature during the early follicular and ovulatory phases. Subjects were 15 female university students with normal menstrual cycles. The early follicular and ovulatory phases were estimated by the basal body temperature method, ovulation kits, and salivary estradiol concentration measurement. The MyotonPRO digital palpation device (Myoton AS, Tallinn, Estonia) was used to measure muscle and tendon stiffness in the early follicular and ovulatory phases. Measurement sites were the rectus femoris (RF), vastus medialis (VM), patellar tendon (PT), medial head of gastrocnemius, soleus, and Achilles tendon. No significant differences in stiffness of all muscle tendons were identified between the early follicular and ovulatory phases. In the ovulatory phase, a significant positive correlation was seen between stiffness of RF and PT, and between stiffness of VM and PT. These results suggest that the stiffness of muscles and tendons of anterior sites of the thigh and posterior sites of the lower leg may not change between the early follicular and ovulatory phases. During the ovulatory phase, tendons may also be stiffer in individuals with stiffer anterior thigh muscles.

Neonicotinoids, such as dinotefuran (DF), have caused a variety of problems, such as massive loss and winter failure of the bee colony, as a price for the benefit of reducing farm work, because it continues to maintain a high insecticide activity over a long period of time. In this study, a field experiment was conducted for about six months to investigate the effects of DF on bee colonies damaged by Varroa mites. This study examined the long-term changes in such as the size of bee colonies, the intake of sugar syrup (SS), intake of pollen paste (PP), which is a vehicle for administering DF, the intake of DF, the mite-prevalence of bees and the inside and outside temperatures of hive-boxes. The variation width of the inner temperature of the hive-box is less than that of the ambient temperature (Ta). The inner temperature of the hive-box is adjusted with about 30 ℃ of Ta as the boundary. If Ta is lower than 30 ℃, the inner temperature of the box is higher than Ta, and if Ta is higher than 30 ℃, it is lower than Ta. The temperature variation width of the DF-exposed colony is greater than that of the control colony. The average intake of SS per bee per day of the DF-exposed colony is more than that of the control colony. The average intake of PP per bee per day of the DF-exposed colony is almost equal to that of the control colony. These results suggest that bees do not avoid DF, and ingest PP without distinction between toxic and pesticide-free. In the period from the start of DF administration to the colony extinction, the intake of DF per colony is about 865 µg/colony, the intake per bee is 14 ng/bee, and the intake per bee per day is less than 0.1 ng/bee/day in this work. These intakes are much lower than the previous ones (60-65 ng/bee, 0.27-2.32 ng/bee/day). These discrepancies may be because attacks of mites and Japanese giant hornets hastened the colony collapse. Seasonal changes in mite-prevalence of honeybees is approximately the same regardless of the bee colonies. At the end of August (the start of attacks by Japanese giant hornets), the mite-prevalence will increase rapidly. Even if the number of bees damaged by mites turns to decrease, the mite-prevalence will continue to increase, with approaching 100% before bee colonies become extinct. In this study, it was found that the bee colony was collapsed by the intake of a smaller amount of DF due to the synergistic effect of DF and mite-damage. To prevent a bee colony collapse, not only to make an effort to minimalize the adverse effect on the bee colony of neonicotinoids such as DF with long-term residual effect and high insecticide properties, it is necessary to reduce the damage of mites as much as possible, while considering the synergistically adverse effects of neonicotinoids and miticides.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

A novel nor-phragmalin-type limonoid, named carapanosin D (1), and two novel mexicanolide-type limonoids, carapanosins E (2) and F (3), were isolated from the seeds oil of Carapa guianensis AUBLET (andiroba), a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and HRFABMS. Compounds 1—3 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. The NO inhibitory assay suggested that compound 2 may be valuable as potential inhibitors of macrophage activation.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

This paper briefly reviews the state of the art in artificial intelligence including inductive and deductive methods. Deep learning and ensemble machine learning lie in inductive methods while automated reasoning implemented in deductive computer languages (Prolog, Otter, and Z3) is based on deductive methods. In the inductive methods, intelligence is inferred by pseudorandom number for creating the sophisticated decision trees in Go (game), Shogi (game), and quiz bowl questions. This paper demonstrates how to wisely use the pseudorandom number for solving coin-weighing puzzles with the deductive method. Monte Carlo approach is a general purpose problem-solving method using random number. The proposed method using pseudorandom number lies in one of Monte Carlo methods. In the proposed method, pseudorandom number plays a key role in generating constrained solution candidates for coin-weighing puzzles. This may be the first attempt that every solution candidate is solely generated by pseudorandom number while deductive rules are used for verifying solution candidates. In this paper, the performance of the proposed method was measured by comparing with the existing open source codes by solving 12-coin and 24-coin puzzles respectively.

Seventy-three male specimens of ”Platorchestia platensis”from Japan were inspected on 13 morphological characters. Most characters revealed high variation. The coxa and propodus of gnathopod 2 and the carpus of pereopod 7 indicated that the specimens comprised two species: Platorchestia pacifica Miyamoto and Morino, 2004 and Demaorchestia joi (Stock and Biernbaum, 1994) sensu lato. Both species were rediagnosed.　Demaorchestia hatakejima Lowry and Myers, 2022 was synonymized to P. pacifica. A key to allied species in Platorchestia and Demaorchestia from Japan and the surrounding countries was given.

More than 3 years have passed since the emergence of COVID-19. On May 8, 2023, COVID-19 in Japan was downgraded to Category 5 by the Infectious Disease Control Law. In Japan, at the beginning of the COVID-19 pandemic in 2020, cases of infection and deaths from severe disease were few compared with those of Western countries. However, in the medical field, screening for COVID-19 was given top priority, resulting in confusion and proving disadvantageous for many patients, also the overreaction to COVID-19 as the most important issue in society can be attributed largely to statements by infectious disease experts. In addition, the mRNA vaccine emerged in 2021, and most of the population was vaccinated up to two times within a short period of less than 1 year because infectious disease experts strongly promoted vaccination. After 2022, when vaccination progressed, and the Omicron strain, which is an attenuated strain, became the mainstay of the SARS-CoV-2, the number of severe cases of COVID-19 decreased significantly; however, the number of infected people increased dramatically instead. A significant portion of the population is thought to have hybrid immunity due to vaccination plus natural infection and maintains high antibody titers. Henceforth, additional vaccination should be given preferentially to those who will benefit most from it. Conversely, measures against COVID-19 caused serious damage to the economy and society. Policies that not only address countermeasures against infection, but also those that encompass the economy and society as a whole are necessary.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines.

In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published. Several tools exist to create, simulate, or visualize models encoded in SBML. However, setting up and establishing analysis environments is a crucial hurdle for non-modelers. Therefore, easy access to perform fundamental analyses of ODE models is a significant challenge. We developed SBMLWebApp, a web-based service to execute SBML-based simulations, steady-state analysis, and parameter estimation directly in the browser without the need for any setup or prior knowledge to address this issue. SBMLWebApp visualizes the result and numerical table of each analysis and provides a download of the results. SBMLWebApp allows users to select and analyze SBML models directly from the BioModels Database. Taken together, SBMLWebApp provides barrier-free access to an SBML analysis environment for simulation, steady-state analysis, and parameter estimation for SBML models. SBMLWebApp is implemented in Java™ based on an Apache Tomcat® web server using COPASI, the SBSCL, and LibSBMLSim as simulation engines. SBMLWebApp is licensed under MIT with source code available from https://github.com/TakahiroYamada/SBMLWebApp. The program runs online at http://simulate-biology.org.

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

Hydrogen gas (H2) has attracted attention as a next-generation clean energy source. Its efficient and safe preparation and utilization are crucial in both industry and organic chemistry. In this study, a Pt/CB-catalyzed MW-mediated continuous-flow hydrogenation reaction was developed using methylcyclohexane (MCH) as the reducing agent (hydrogen carrier). Alkynes, alkenes, nitro groups, benzyl esters, and aromatic chlorides were chemoselectively hydrogenated using Pt/CB under MW-assisted continuous-flow conditions. This methodology represents a safe and energy-efficient hydrogenation process, as it eliminates the need for an external hydrogen gas supply or heating jackets as a heat medium. Further application of MW-mediated continuous-flow hydrogenation reactions is a viable method for the efficient generation and utilization of sustainable energy.

The environmental pollution by microplastics (MPs) has become a growing concern, and measures are being taken in many countries. Long-term and extensive MPs investigations involving not only professional researchers but also the citizenry are needed to understand the pollution situation and to confirm the decreasing trend of MPs pollution as a result of pollution control measures. In this study, the author evaluated the accuracy of a simple method of investigating MPs on sandy beaches that can be conducted even by high school students. In a land survey using such simple tools as a tape measure and cardboard, 70% of the deviations were within approximately 20 cm when multiple surveys of approximately 20 m distance were performed. Even without heavy liquid, 89% of MPs could be recovered using only seawater. An investigation of MPs content by sampling 0.5 cm of the surface layer of sand could explain more than half of the MPs content when the sand was sampled to a depth of approximately 50 cm below the surface layer. A method in which the recovered MPs are not visually sorted but floating matter after boiling is considered as MPs is acceptable. If there was no concern about pumice contamination, the overestimation was within approximately 1.5 times. Simple laboratory equipment such as buckets, sieves, seawater, hot plates, dryers, and electronic balances could achieve lower limits of quantification of MPs of 13 mg-MPs/m2-sand and 2 mg-MPs/kg-sand.

In 2011, by 1.3 mm wavelength VLBI radio wave observations of the SgrA*, Fish, V. L. et al showed that the emissions tightly related to the formation of a black hole shadow have a remarkably large time-varying feature within a region of less than 50 μas. The present paper suggests that the origin of the time variation in the observed emission is due to effects of the orbital motion of the existing super-massive black hole binary orbiting at SgrA* with a period of 2150±2.5 s. This suggestion is based on observations of decameter radio wave pulses from SgrA*. We show a good correlation between the time variation in the coherent flux density of the VLBI results and the time variation model of estimated emission intensities based on the periodic motion of the super-massive black hole binary by applying parameters deduced from the decameter radio wave pulse observation model (DRWP-Model). With further confirmation by Fourier analyses of the potential periodicity of the VLBI data that show the same periods of DRWP Model, we conclude that the time variation detected by the 1.3 mm wavelength radio wave VLBI is evidence of an existing super-massive black hole at Sgr A*.

Clarifying hydrologic behavior, especially behavior related to extreme events such as flash floods, is vital for flood mitigation and management. However, discharge and rainfall measurement data are scarce, which is a major obstacle to flood mitigation. This study (i) simulated flash floods on a regional scale using three types of rainfall forcing implemented in a land surface model and (ii) evaluated and compared simulated flash floods with the observed discharge. The three types of rainfall forcing were those observed by the Automated Meteorological Data Acquisition System (AMeDAS) (Simulation I), the observed rainfall from the Ministry of Land, Infrastructure and Transportation (MLIT) (Simulation II), and the estimated rainfall from the Multi-purpose Transport Satellite (MTSAT), which was downscaled by AMeDAS rainfall (Simulation III). MLIT rainfall observations have a denser station network over the Ishikari River basin (spacing of approximately 10 km) compared with AMeDAS (spacing of approximately 20 km), so they are expected to capture the rainfall spatial distribution more accurately. A land surface model, Minimal Advance Treatments of Surface Interaction and Runoff (MATSIRO), was implemented for the flash flood simulation. The river flow simulations were run over the Ishikari river basin at a 1-km grid resolution and a 1-h temporal resolution during August 2010. The statistical performance of the river flow simulations demonstrated that Simulation I was reasonable compared with Simulation III. The findings also suggest that the advantage of the MTSAT-based estimated rainfall (i.e., good spatial distribution) can be coupled with the benefit of direct AMeDAS observations (i.e., representation of the true rainfall).

Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms uses one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such as a comprehensive knowledge-integrated model of a target phenomenon, for example a whole-cell model, the variation of analyses is limited to particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we developed a hybrid method that combines both approaches. To construct a mathematical model, we extracted network motifs, subgraph structures that recur more often in a metabolic network or gene regulatory network than in a random network, from a large-scale regulatory network, detected regulatory motifs among them, and combined these motifs. We confirmed that the model reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop which has not been focused on. The model extracted by our hybrid method has the potential to reveal the critical mechanisms of neural differentiation. The hybrid method is applicable to other biological events.

Achieving the thermal conductivity required for efficient heat management in semiconductors and other devices requires the integration of thermally conductive ceramic fillers at concentrations of 60 vol% or higher. However, the increased filler content often negatively affects the mechanical properties of the composite matrix, limiting its practical applicability. To address this issue, in this paper, we present a new strategy to reduce the required ceramic filler content: the use of a thermally conductive ceramic composite filler with carbon nanotubes (CNT) grown on aluminum nitride (AlN). We have combined catalyst coating technology with vacuum filtration to ensure that the catalyst is uniformly applied to micrometer-sized AlN particles, followed by efficient and uniform synthesis of CNTs using a water-assisted process in a vertical furnace. By carefully controlling the number of vacuum filtration cycles and the growth time of the CNTs, we demonstrate precise control over the number and length of the CNT layers, thereby adjusting the properties of the composite to the intended specifications. When AlN/CNT hybrid fillers are incorporated into silicone rubber, while maintaining the mechanical properties of rubber, the thermal diffusivity achieved at reduced filler levels exceeds that of composites using AlN-only or simultaneous AlN and CNTs formulations. This demonstrates the critical role of CNTs on AlN surfaces. Our study represents a significant advancement in the design of thermally conductive materials with potential implications for a wide range of applications.

The authors recently proposed a method for on-site dosimetry by a combination of radiochromic film and portable colorimeter. To test and expand the applicability of this method, dosimetric properties of radiochromic reactions were examined for six combinations of two popular Gafchromic films (EBT3 and EBT-XD) and three commercially-available portable colorimeters (nix pro2, nix spectro2 and Spectro1 Pro; abbreviated to “NixP”, “NixS” and “SpoP”, respectively). EBT3 and EBT-XD were irradiated with 160 kV X-rays at 0.3 to 40Gy and 1 to 80 Gy, respectively, and the radiation-induced color levels of RGB and CMMK components were measured with the three colorimeters. Angle dependence was examined by reading at 15° intervals. As results, it was judged that all combinations would work effectively as tools for on-site dosimetry. NixP and NixS showed advantages that they were applicable to a wider dose range for both films, while Spo1 worked better in a lower dose range. On the other hand, Spo1 had an advantageous feature of no angular dependence in reading films, while NixP and NixS showed significant angle-dependent changes. These differences were presumed to attribute to the different geometries of LED light emission; it came from all directions (ring-shape source) in Spo1, 4 directions in NixP, and 8 directions in NixS. These findings would expand the applicability of the proposed on-site dosimetry method to various occasions.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was screened using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir, and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.

Kluyveromyces marxianus is an attractive thermotolerant yeast species for ethanol production because of its ability to utilize various carbon sources as a fermentation substrate. The use of thermotolerant microbes enables performance of high-temperature ethanol fermentation, which has several advantages including reduction of cooling costs and minimization of contamination risk. To improve K. marxianus for ethanol fermentation under stress conditions, two strains, DMKU 3-1042 and DMKU 3-118, were adapted for heat resistance and toxic substances in pulp wastewater from a paper mill, respectively, resulting in the generation of KMR1042 and KMR118, respectively. Both adapted mutants exhibited clumpy clusters of cells as pseudohyphae and altered colony morphology, and their sedimentation speeds were much faster than those of the corresponding parent strains. The two mutants showed stronger tolerance to various stresses and higher performance for ethanol production than those of the corresponding parent strains at high temperatures or in the presence of toxic substances. Genome sequencing analysis revealed that both mutants had disruption of the same gene, SWI5, despite adaptation under different stress conditions, suggesting that the formation of pseudohyphae is a common strategy of K. marxianus for coping with stresses.

Developing efficient Artificial Intelligence (AI)-enabled system to substitute human role in non-destructive testing is an emerging topic of considerable interest. In this study, we propose a novel impact-echo analysis system using online machine learning, which aims at achieving near-human performance for assessment of concrete structures. Current computerized impact-echo systems commonly employ lab-scale data to validate the models. In practice, however, the echo patterns can be far more complicated due to varying geometric shapes and materials of structures. To deal with a large variety of unseen data, we propose a sequential treatment for echo characterization. More specifically, the proposed system can adaptively update itself to approaching human performance in impact-echo data interpretation. To this end, a two-stage framework has been introduced, including echo feature extraction and the model updating scheme. Various state-of-the-art online learning algorithms have been reviewed and evaluated for the task. To conduct experimental validation, we collected 10,940 echo instances from multiple inspection sites with each sample had been annotated by human experts with healthy/defective condition labels. The results demonstrated that the proposed scheme achieved favorable echo pattern classification accuracy with high efficiency and low computation load.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

To understand functions of biomolecules such as proteins, not only structures but their conformational change and kinetics are important to be characterized but its atomistic details are hard to obtain both experimentally and computationally. We review our recent computational studies using novel enhanced sampling techniques for conformational sampling of biomolecules and calculations of their kinetics. For efficiently characterizing the free energy landscape of a biomolecule, we introduce the multiscale enhanced sampling method, which uses a combined system of atomistic and coarse-grained models. Based on the idea of Hamiltonian replica exchange, we can recover the statistical properties of the atomistic model without any biases. We next introduce the string method as a path search method to calculate the minimum free energy pathways along a multidimensional curve in high dimensional space. Finally we introduce novel methods to calculate kinetics of biomolecules based on the ideas of path sampling: One is the Onsager-Machlup action method, and the other is the weighted ensemble method. Some applications of above methods to biomolecular systems are also discussed and illustrated.

Nonlinear rheological properties of chiral crystal cholesteryl oleyl carbonate (COC) in blue phase III are investigated under different shear deformations; large amplitude oscillatory shear, step shear deformation, and continuous shear flow. Rheology of the liquid crystal is significantly affected by structural rearrangement of defects under shear flow. One of the examples on the defect-mediated rheology is the blue phase rheology. Blue phase is characterized by three dimensional network structure of the disclination lines. It has been numerically studied that the rheological behavior of the blue phase is dominated by destruction and creation of the disclination networks. In this study, we find that the nonlinear viscoelasticity of BPIII is characterized by the fracture of the disclination networks. Depending on the degree of the fracture, the nonlinear viscoelasticity is divided into two regimes; the weak nonlinear regime where the disclination network locally fractures but still show elastic response, and the strong nonlinear regime where the shear deformation breaks up the networks, which results in a loss of the elasticity. Continuous shear deformation reveals that a series of the fracture process delays with shear rate. The shear rate dependence suggests that force balance between the elastic force acting on the disclination lines and the viscous force determines the fracture behavior.

Kawasaki disease is a form of acute febrile multisystem vasculitis. In Japan, the Kobayashi score is used to predict intravenous immunoglobulin resistance and subsequent complications, including coronary artery abnormalities, in children with Kawasaki disease. If the score is high, it is standard practice to use steroids in the initial treatment of the disease. In this study, we describe a pediatric case of coronary artery abnormality formation after acute steroid treatment for Kawasaki disease, despite the lack of an inflammatory response and Kawasaki disease symptoms. The use of steroids with acute Kawasaki disease patients can mask laboratory findings and clinical symptoms. Echocardiogram should be considered an equivalent technique to physical examination.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4⁺ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

Background: The dietary factors and nutrients contributing to the prevention of microalbuminuria in type 2 diabetic nephropathy is unclear, so we investigated dietary factors affecting urinary albumin excretion in patients with type 2 diabetes. Methods: 42 patients with type 2 diabetes were participated, the subjects were divided to a normal albuminuria group (urinary albumin / creatinine ratio of less than 30 mg / g Cr) and a microalbuminuria group of 30 mg / g to 299 mg / g Cr. We performed casual blood sampling and conducted a food frequency questionnaire survey. Results: There were no significant differences in age, BMI and other physiological and biochemical data, the average daily intake of energy and many of nutrients, while β-cryptoxanthin was significantly lower in the microalbuminuria group than in the normal group (506.4 ± 793.9 μg/day vs. 715.3 ± 500.3 μg/day, p <0.05). The intake of 17 food groups per day showed that the intakes of fruits were significantly lower in the microalbuminuria group than in the normal group (76.9 ± 134.1 g vs. 111.9 ± 84.5 g, p <0.05). Conclusion: These results suggest that fruits and foods rich in β-cryptoxanthin would make it possible to prevent diabetic nephropathy progression.

Cancer invasion through basement membranes represents the initial step of tumor dissemination and metastasis. However, little is known about how human cancer cells breach basement membranes. Here, we used a 3-dimensional in vitro invasion model consisting of cancer spheroids encapsulated by a basement membrane and embedded in 3D collagen gels to visualize the early events of cancer invasion by confocal microscopy and live-cell imaging. Human breast cancer cells generated large numbers of basement membrane perforations, or holes, of varying sizes that expanded over time during cell invasion. We used a wide variety of small molecule inhibitors to probe the mechanisms of basement membrane perforation and hole expansion. Protease inhibitor treatment (BB94), led to a 63% decrease in perforation size. After myosin II inhibition (blebbistatin), basement membrane perforation area decreased by only 15%. These treatments produced correspondingly decreased cellular breaching events. Interestingly, inhibition of actin polymerization dramatically decreased basement membrane perforation by 80% and blocked invasion. Our findings suggest that human cancer cells can primarily use proteolysis and actin polymerization to perforate the BM and to expand perforations for basement membrane breaching, with a relatively small contribution from myosin II contractility.

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. Recently, we generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.

We numerically study surface models defined on hexagonal disks with a free boundary. 2D surface models for planer surfaces have recently attracted interest due to the engineering applications of functional materials such as graphene and its composite with polymers. These 2D composite meta-materials are strongly influenced by external stimuli such as thermal fluctuations if they are sufficiently thin. For this reason, it is very interesting to study the shape stability/instability of thin 2D materials against thermal fluctuations. In this paper, we study three types of surface models including Landau-Ginzburg (LG) and Helfirch-Polyakov models defined on triangulated hexagonal disks using the parallel tempering Monte Carlo simulation technique. We find that the planer surfaces undergo a first-order transition between the smooth and crumpled phases in the LG model and continuous transitions in the other two models. The first-order transition is relatively weaker compared to the transition on spherical surfaces already reported. The continuous nature of the transition is consistent with the reported results, although the transitions are stronger than that of the reported ones.

The interlaminar shear behavior of a [±45°] laminated carbon fiber reinforced plastic (CFRP) specimen was investigated utilizing microscale strain mapping in a wide field of view. A three-point bending device was developed under a laser scanning microscope, and the full-field strain distributions including normal, shear and principal strains of CFRP in a three-point bending test were measured using a developed sampling Moire technique. The microscale shear strain concentrations at interfaces between each two adjacent layers were successfully detected and found to be positive-negative alternately distributed before damage occurrence. The 45° layers slipped to the right relative to the -45° layers, visualized from the revised Moire phases and shear strain distributions of the angle-ply CFRP under different loads. The absolute values of the shear strain at interfaces gradually rose with the increase of the bending load, and the sudden decrease of the shear strain peak value implied the occurrence of interlaminar damage. The evolution of the shear strain concentrations is useful in the quantitative evaluation of the potential interlaminar shear failure.

The aim of this study was to investigate the effect of laser irradiation to computer-aided de-sign/computer-aided fabrication (CAD/CAM) resin blocks coated with a silane coupling agent on the bond strength between the resin blocks and composite resin. The CAD/CAM resin blocks used in this study were Cerasmart 300 (GC) and Vita Enamic (Vita); they were cut into plates and then subjected to a series of treatments. After processing with a silane coupling agent, treatment with a semiconductor laser was performed at 3.0, 5.0, and 7.0 W, followed by the bonding procedures. The control group included those exposed to silane and bonded without laser application. After bonding, a mold with a simulated cavity was formed on the specimen and filled with flowable composite resin, and they were stored for 24 h or stressed by thermal cycling for subsequent testing that assessed the shear bond strength (n = 10). The results revealed that the bond strength was significantly enhanced by laser irradiation after applying a silane coupling agent, whereas significant effect was not detected between the materials. Particularly, 7 W laser irradiation had a significant effect on the bond strength between the composite resin and Cerasmart block after thermal cycling.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

This study proposed the combination system consisting of biogas dry reforming reactor and solid oxide fuel cell (SOFC). Since a biogas dry reforming is an endothermic reaction, this study adopted a membrane reactor operated due to the non-equilibrium state with H2 separation from the reaction space. This study aimed to clarify the characteristics of Ni/Cr/Ru catalyst using for a biogas dry reforming membrane reactor. Additionally, this study also investigated the comparison of the characteristics of Ni/Cr/Ru catalyst with that of Ni/Cr catalyst. The impact of operation temperature, the molar ratio of CH4 : CO2, the differential pressure between the reaction chamber and the sweep chamber and the introduction of sweep gas on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr/Ru catalyst was examined. The concentration of H2 using Ni/Cr/Ru catalyst was larger than that using Ni/Cr catalyst by 2871 ppmV for the molar ratio of CH4 : CO2 = 1.5 : 1 at the reaction temperature of 600 ℃ and the differential pressure of 0 MPa without a sweep gas, especially. Under this condition, CH4 conversion, H2 yield and thermal efficiency were 67.4 %, 1.77×10-2 % and 0.241 %, respectively.

Background and Aim: Zinc plays a pivotal role in various zinc enzymes, resulting in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. It remains unknown whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development. Patients and Methods: Two hundred sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients) were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Results: Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p<0.001). According to the serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dl (p<0.001). Conclusion: Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dl.

Extruded polystyrene (XPS) is frequently used in the construction of many different structures. It is therefore necessary to appropriately characterize its mechanical properties to ensure the safety of said structures. Among the available characterization tests, static bending tests are simple and easy to perform; owing to these characteristics, they should be performed more frequently than other tests. However, in static bending tests on XPS, there are several challenges owing to the high flexibility of XPS, and the chosen testing method and sample configuration affect the accuracy of characterization. In this study, three bending properties (Young’s modulus, proportional limit stress, and bending strength) of samples cut from an XPS panel were determined using three-point bending (TPB), four-point bending (FPB), and compression bending (CB) tests with varying sample span/depth ratios, and statistical analyses were performed to determine the relevance of the tests. The experimental results suggest that the TPB and CB tests were more feasible than the FPB test when the span/depth ratio was appropriately determined. However, clear differences were observed in the sample bending properties determined in these tests. In light of these findings, further studies should be conducted to elucidate these differences.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

Room-temperature phosphorescent (RTP) materials have been attracted tremendous interest owing to their unique material characteristics and potential applications for state-of-the-art optoelectronic devices. Recently, we have reported a synthesis and fundamental photophysical properties of new RTP materials based on benzil, i.e., fluorinated monobenzil derivative and fluorinated and non-fluorinated bisbenzil derivative analogues [Yamada, S. et al, Beilstein J. Org. Chem. 2020, 16, 1154–1162.]. To further understand their RTP properties, here we investigated the excited-state dynamics and photostability of the derivatives by means of time-resolved and steady-state photoluminescence spectroscopies. For these derivatives, clear RTP emissions with lifetimes on the microsecond timescale were identified. Among them, the monobenzil derivative was found to be the most efficient RTP material, showing both the longest lifetime and highest amplitude RTP emission. Time-resolved photoluminescence spectra measured at 77 K and density functional theory calculations revealed the existence of a second excited triplet state in the vicinity of the first excited singlet state for the monobenzil derivative, indicative of the presence of a fast intersystem crossing pathway. A discussion of the correlation between the excited state dynamics, emission properties, and conformational flexibility of the three derivatives is presented.

The purpose of this study was to investigate the horizontal force and contribution of shoulder horizontal adductor and elbow extensor muscles activity during wide and narrow grip bench press (BP) in various conditions, such as resistance trained/non-trained, concentric/eccentric and muscle fatigue/non-fatigue.　We measured the horizontal force on the bar and the electromyographic (EMG) muscle activity of pectoralis major (PM) and triceps brachii (TB) during 10RM BP with wide grip (81cm) and narrow grip (40cm)　in 7　resistance trained men and 7 non-trained men. The all-reps average of the horizontal to vertical force ratio both in resistance trained and non-trained subjects was about 30% outward for the wide grip, and about 10% inward for the narrow grip. The EMG contribution ratio PM/TB shows no significant differences between narrow and wide grip in all evaluated conditions except in non-trained subjects muscle fatigue eccentric phase. Both resistance trained and non-trained subjects did not push the bar straight upward, and the EMG PM/TB was almost unchanged by hand width. The direction adjustment of the force on the bar that achieves almost the same muscle activity degree of the shoulder and elbow joints might be optimal BP kinetics.

Papain-like lysosomal cysteine proteases include 11 human cysteine cathepsins which act as endopeptidases and/or exopeptidases. They are involved in numerous physiological and pathological processes. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Their activities are tightly regulated in various ways to prevent potentially hazardous effects on the cell. In this review, we focus on the structural and functional aspects of these four cysteine cathepsins and their role in neurodegeneration and cancer. Neurodegenerative disorders of aging share an endolysosomal dysfunction and accumulation and spread of oligomeric forms of neurotoxic proteins. The accumulation of various protein aggregates activates the microglia, thus inducing the activation and release of cysteine cathepsins and proinflammatory cytokines, leading to neurodegeneration. In cancer, cysteine cathepsins participate in tumor progression and metastasis. Tumor–stromal crosstalk leads to activation of the stroma and overexpression and secretion of proteolytic enzymes, triggering extracellular matrix degradation and the release of soluble factors. Activated stromal cells (i.e., macrophages, fibroblasts, mast cells) secrete additional growth factors, cytokines, and chemokines that are responsible for the regulation of processes leading to tumor progression and metastasis. Therefore, a better understanding of the role of cysteine cathepsins in neurodegeneration and cancer could lead to novel targeted therapeutic approaches.

African trypanosomes are an early branch in eukaryotic evolution and developed a unique endomembrane system as an adaptation to their parasitic life style. The key virulence mechanism of many pathogens is successful immune evasion to enable survival within the host, which is a feature requiring both genetic events and membrane transport in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unravelled some of the connections between these processes and highlighted how immune evasion mechanisms associated with adaptations in membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purpose.

Japan has the world’s largest old population ratio, and aging is an urgent societal issue. As global trends seem to be following Japan’s social changes, there is an emphasis on municipalities becoming more age-friendly. Hence, we examine the age-friendliness of 135 Japanese municipalities, selecting 240 resident architectural designers and constructors to assess their municipalities, using the Age-Friendly Cities and Communities Questionnaire (AFCCQ). The findings indicate that Japan lacks “outdoor spaces and buildings.” Additionally, the evaluation of “housing,” “community support and health services,” and “transportation” in populated municipalities in the past five years is significantly higher than those in depopulated ones. Age-friendliness is significantly affected in the AFCCQ total score (hereafter, Score) based on “housing,” “social participation,” “community support and health services,” “transportation” and “financial situation” evaluations. High specificity (0.939) was found when the Score was treated as a marker of depopulation and, therefore, an age-friendly approach is a necessary condition to prevent depopulation. Furthermore, a lack of “communication and information” is observed in municipalities with a higher rate of single-person households aged 65 years and above. Therefore, resident architectural designers’ and constructors’ assessments, combined with the AFCCQ can be a powerful tool in evaluating the age-friendliness of municipalities.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

Adequate energy intake is critical for the healthy longevity of older adults, and the estimated energy requirement is determined by total energy expenditure (TEE). We aimed to identify the relationship between measured aerobic capacity and TEE, activity energy expenditure (AEE) or physical activity level (PAL) with the doubly labeled water (DLW) methods in the advanced older adults. A total of 12 physically independent older adults (10 males and 2 females) aged between 81 to 94 years participated in this study. Aerobic capacity was evaluated according to the lactate threshold (LT). TEE under free-living conditions was assessed using the DLW method, and self-reported physical activity was obtained through the Japanese version of the International Physical Activity Questionnaire (IPAQ). LT was significantly positively correlated with TEE, AEE, and PAL after adjustment for age and sex (ρ= 0.77 (P<0.01), 0.86 (p<0.01), and 0.86 (p<0.01), respectively). We found the LT as an aerobic capacity is positively and independently correlated with TEE, AEE or PAL. The present results suggest that maintaining aerobic capacity is an important factor for preventing frailty, although further research is needed to multisite studies and many samples.

The poor solvent crystallization of carbapenem CS-023 has been performed at 25 °C. The following results have been obtained: 1) A solvate crystal Form A (5/2 Ethanol·1/2 H2O) is recovered from 80 v/v% ethanol solution, 2) Form A transforms to Form H (4H2O) by the solid-phase transition through the solvate-free polymorph, Form A-2, and Form A also transformed to Form C (1Ethanol·3H2O) by the solvent-mediated transformation. In the present study, we found that Form C also transforms to Form H by the solid-phase transition through the solvate-free polymorph, Form C-2. The three polymorphs, Form A, H, and C, were composed of the helical-chain structures, respectively. However, there was an incomprehensible affair in the solid phase transition among the three polymorphs. Namely, Form A comprised a left-handed helix.On the other hand, Form C and Form H’s helix chains were in a left- and right-handed helix complex. The solid-phase transition of Form A into Form H suggested the switch of helicity in the solid. We attempted to explain the helicity change in the solid phase transition. As a result, it was suggested that the over-absorption of water of Form A-2 at high humidity plays a vital role in the helicity change.

Strigolactones (SLs), a group of plant hormones, induce germination of root-parasitic plants and inhibit shoot branching in many plants. Shoot branching is an important trait that affects the number and quality of flowers and fruits. Root-parasitic plants such as Phelipanche spp. infect tomato roots and cause economic damage in Europe and North Africa. Thus, resistant tomato cultivars are needed. In this study, we found carotenoid cleavage dioxygenase 8-defective mutants of Micro-Tom tomato (slccd8) by the “targeting induced local lesions in genomes” (TILLING) method. The mutants showed excess branching, which was suppressed by exogenously applied SL. Grafting shoot scions of the slccd8 mutants onto wild-type (WT) rootstocks restored normal branching in the scions. The levels of endogenous orobanchol and solanacol in WT were enough detectable, whereas that in the slccd8 mutants were below the detection limit of quantification analysis. Accordingly, root exudates of the slccd8 mutants hardly stimulated seed germination of root parasitic plants. In addition, SL deficiency did not critically affect the fruit traits of Micro-Tom. Using a rhizotron system, we also found that Phelipanche aegyptiaca infection was lower in the slccd8 mutants than in wild-type Micro-Tom because of the low germination. We propose that the slccd8 mutants might be useful as new tomato lines resistant to P. aegyptiaca.

In this paper, we synthesized MC(BeA-co-MMA) copolymer microcapsules through suspension polymerization. The pendent n-behenyl group of BeA is highly crystalline, and it acts as the side-chain in the structure of BeA-co-MMA copolymer. The highly crystalline n-behenyl side-chain provides BeA-co-MMA copolymer thermal-energy-storage capacity. In order to investigate the correlation between thermal properties and crystal structure of BeA-co-MMA copolymer, the effects of monomer ratio, temperature changing and changing rate, as well as synthesis method were discussed. The monomer ratio influenced crystal transition behavior and thermal properties greatly. The DSC results proved that when the monomer ratio of BeA and MMA was 3:1, MC(BeA-co-MMA)3 showed the highest average phase change enthalpy ΔH (105.1 J·g–1). It indicated that the n-behenyl side-chain formed relatively perfect crystal region, which ensured a high energy storage capacity of copolymer. All the DSC and SAXS results proved that the amount of BeA had a strong effect on the thermal-energy-storage capacity of copolymer and the long spacing of crystals, but barely on the crystal lamella. It was found that MMA units worked like defects in the n-behenyl side-chain crystal structure of BeA-co-MMA copolymer. Therefore, a lower fraction of MMA, that is, a higher fraction of BeA contributed to a higher crystallinity of BeA-co-MMA copolymer for providing a better energy storage capacity and thermoregulation property. ST(BeA-co-MMA) copolymer sheets with the same ingredients as microcapsules were also prepared through light-induced polymerization aiming at clarifying the effect of synthesis method. The results proved that synthesis method mainly influenced the copolymer chemical component, but lightly on the crystal packing of n-behenyl side-chain.

A nonlinear MEMS multimass sensor is investigated. The MEMS design consists of an array of nonlinear microcantilevers clamped to a shuttle mass which, in turn, is attached to a linear spring and a dashpot. The microcantilevers are made of a polymeric hosting matrix reinforced by aligned carbon nanotubes (CNT) with different CNT volume fractions in each cantilever so as to suitably tune the frequency bandwidth of the device. The advantages of a single input-single output (SISO) system are here exploited for the design, actuation and detection principles as in previous literature.

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have favorable prognosis and quality of life with preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting clinical outcomes of chemoradiation-based BPT. Biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both chemoradiation response and prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an ametabolic state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

Despite extensive investigations of the Depression Anxiety Stress Scales-21 (DASS-21) since its development in 1995, its factor structure and other psychometric properties still need to be firmly established, with several calls for revising its item structure. Employing confirmatory factor analysis (CFA), this study examined the factor structure of the DASS-21 and five shortened versions of the DASS-21 among psychiatric patients (N = 168) and the general public (N = 992) during the COVID-19 confinement period in Saudi Arabia. Multigroup CFA, Mann Whitney W test, Spearman’s correlation, and coefficient alpha were used to examine the shortened versions of the DASS-21 (DASS-13, DASS-12, DASS-9 (two versions), and DASS-8) for invariance across age and gender groups, discriminant validity, predictive validity, item coverage, and internal consistency, respectively. Compared with the DASS-21, all three-factor structures of the shortened versions expressed good fit, with the DASS-8 demonstrating the best fit and highest item loadings on the corresponding factors in both samples (χ2(16, 15) = 16.5, 67.0; p = 0.420, 0.000; CFI= 1.000, 0.998; TLI = 0.999, 0.997; RMSEA = 0.013, 0.059, SRMR = 0.0186, 0.0203). It expressed configural, metric, and scalar invariance across age and gender groups. Its internal consistency was comparable to other versions (α = 0.94). Strong positive correlations of the DASS-8 and its subscales with the DASS-21 and its subscales (r = 0.97 to 0.81) suggest adequate item coverage and good predictive validity of this version. The DASS-8 and its subscales distinguished the clinical sample from the general public at the same level of significance expressed by the DASS-21 and other shortened versions, supporting its discriminant validity. Neither the DASS-21 nor the shortened versions distinguished patients diagnosed with depression and anxiety from other conditions. The DASS-8 represents a valid short version of the DASS-21, which may be useful in research and clinical practice for quick identification of individuals with potential psychopathologies. Diagnosing depression/anxiety disorders may be further confirmed in a next step by clinician-facilitated examinations. Brevity of the DASS-21 would save time and effort used for filling the questionnaire and support comprehensive assessments by allowing the inclusion of more measures on test batteries.

The theory that an itch inhibits pain has been refuted; however, previous research did not investigate this theory for interleukin-31 (IL-31)-induced itch. Previously, we have found that morphine-induced antinociception was partially reduced in IL-31 receptor A (IL-31RA)-deficient (IL-31RAKI) mice, indicating that IL-31RA may play an important role in morphine-induced peripheral antinociception. In the present study, we evaluated the effect of IL-31-induced analgesia on a 2,4,6-trinitrochlorobenzene (TNCB)-sensitized mice using a hot-plate test. This test evaluated the antinociceptive activity of morphine, and non-steroidal anti-inflammatory drugs (NSAIDs). Repeated pretreatment with IL-31 showed significant antinociceptive action. Furthermore, its combination with morphine, but not with NSAIDs, increased the analgesic action. In contrast, treatment with TNCB and capsaicin decreased antinociception. Moreover, TNCB increased IL-31RA expression in the dorsal root ganglia at 24 h, whereas capsaicin inhibited it. The comparative action of several analgesics on TNCB or capsaicin was evaluated using a hot-plate test, which revealed that the antinociceptive activity was decreased or disappeared in response to capsaicin-induced pain and in IL-31RAKI mice. These results indicate that the analgesic action of IL-31 involves the peripheral nervous system, which affects sensory nerve. These results provide a basis for developing novel analgesics using this mechanism.

In this paper, a novel pendulum-type accelerometer based on hetero-core fiber optics has been proposed for structural health monitoring targeting large-scale civil infrastructures. Vibration measurement is a non-destructive method for diagnosing the failure of structures by assessing natural frequencies and other vibration patterns. The hetero-core fiber optic sensor utilized in the proposed accelerometer can serve as a displacement sensor with robustness to temperature changes in addition to immunity to electromagnetic interference and chemical corrosions. Thus the hetero-core sensor inside the accelerometer measures applied acceleration by detecting the rotation of an internal pendulum. A series of experiments showed that the hetero-core fiber sensor linearly responded to the rotation angle of the pendulum ranging within ±5°, and furthermore the proposed accelerometer could reproduce the waveform of input vibration in a frequency band of several Hz order.

Background. Many anticancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (compound B) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds, in comparison with 4 popular anticancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one-order of magnitude higher TSM as compared with newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two order of magnitude lower TSE than compounds A and B. Compounds A and B showed higher TSM, TSE and TSN values than doxorubicin, 5-FU and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long-term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyse the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in germination rate and RNA integrity number (RIN) after long-term storage, or CDT. The RIN value was obtained by electrophoresis of total RNA extracted from seed embryos. Seeds of ‘Vandaran (Indica)’, ‘Tupa 729 (Japonica)’, and ‘Badari Dhan (Indica)’ consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions, regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between germination rates and RIN values of the seeds after long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials, including both Japonica and Indica cultivars, for improving rice seed longevity.

When designing rule-based dialogue systems, the need for elaborate design by the designer is a challenge for dialogue systems. One way to reduce the cost of creating content is to generate utterances from data collected in an objective and reproducible manner. This study focuses on rule-based dialogue systems using survey data, and more specifically on opinion dialogue where the system models the user. In opinion dialogue, there has not been much study of topic transition methods for modeling users while maintaining their motivation for dialogue. To model them, we adopted information content. Our contribution includes the design of a rule-based dialogue system that does not require elaborate design. We also reported an appropriate topic transition method based on information content. This is confirmed by the influence of the user's personality characteristics. The content of questions can give the user a sense of the system's intention to understand them. We also reported the possibility that the system's rational intention contributes to the user's motivation for dialogue with the system.

Photosynthetic activities of the sago palm (Metroxylon sagu Rottb.) were studied to find out its sensitivity to changes in ambient air temperature. The minimum ambient air temperature designed for the experiment was 25–29⁰C, while the higher end was 29–33⁰C. Several photosynthetic parameters were studied to support our analysis in sago photosynthetic activity, including diurnal leaf gas exchange, assimilation rate vs. CO₂ concentration, leaf greenness, leaf chlorophyll content, and photosynthetic rate vs. irradiance. We found that sago palm photosynthetic activity tends to be more sensitive to minimum than to maximum ambient air temperature. The plants exposed to higher air temperatures had dark green leaf color associated with higher rates of diurnal photosynthesis, chlorophyll content, and rubisco limited photosynthetic activity. They also exhibited higher trend in optimum irradiance absorption level. Consequently, maximum light energy dissipation occurred at higher temperatures.

This paper presents a novel approach for individual design perception modeling using the YUKI-trained Fuzzy Inference System. The study focuses on understanding how individuals perceive design based on personality traits, particularly openness to experience. The proposed YUKI algorithm optimizes the FCM clustering algorithm, enhancing its ability to handle uncertain and imprecise data. The YUKI-trained FIS generates several Sugeno-type FIS models to predict design perception, to minimize the Root Mean Squared Error between the model prediction and the actual design perception of participants. The results demonstrate that the YUKI-trained FIS offers more accurate predictions compared to the traditional FCM-trained FIS, and the RMSE values for individual design perceptions fall within a satisfactory range of 0.84 to 1.32. The YUKI-trained FIS proves effective in clustering individuals based on their level of openness, providing insights into how personality traits influence design perception.

(1)Background：To date, no studies have epidemiologically examined whether the concentration of particulate matter (PM) 2.5 and its ionic components is related to the prevalence of skin symptoms. Therefore, this study aimed to clarify this association in patients with allergic diseases. (2)Methods: From February 1 to May 31, 2020, we evaluated the daily prevalence of skin symptoms in outpatients with allergic diseases being treated at Fukuoka Hospital, Fukuoka, Japan, and measured the concentration of PM2.5 and its ionic components. （3）Results: Univariate analysis showed a statistically significant association between skin symptoms and the concentration of PM2.5 and the ionic components SO42-, NH4+, K+, and Mg2+, and multivariate analysis showed a statistically significant association between the daily prevalence of skin symptoms and the concentration of the ionic components SO42- or Mg2+. (4)Conclusions: Our findings indicate that the concentration of some PM2.5 ionic components may affect skin symptoms in patients with allergic diseases.

The expedited development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our comprehension of type 2 diabetes mellitus (T2DM). The virtual screening based on a three-dimensional (3D) protein structure has been expected as potential technique to accelerate a development of molecular target drugs. Among the targets implicated in insulin resistance, genetic characterization and protein function of Grb14 have been clarified without contradiction. The Grb14 gene displays notable variations in T2DM, and its gene product known to inhibit the function of the insulin receptor (IR) by directly binding to the tyrosine kinase domain. In the present study, a virtual screening, based on 3D structure of IR tyrosine kinase domain (IRβ) in complex with part of Grb14, was conducted to find compounds that can disrupt the complex formation between Grb14 and IRβ. First, ten compounds were selected from 154,118 compounds via hierarchical in silico structure-based drug screening, composed of grid docking-based and genetic algorithm-based programs. The experimental validations suggested that the one compound can affect blood glucose level. The molecular dynamics simulations and co-immunoprecipitation analysis showed that the compound did not completely suppress the protein–protein interaction between Grb14 and IR, though competitively bound to IR with the tyrosine kinase pseudosubstrate region in Grb14.

Techniques have been developed to determine whether a horse is in resting or running mode by measuring at least one of the following: the horse's body temperature, heart rate, oxygen saturation, and exercise level. However, the existing technology has not reached a level where a trainer can accurately assess a horse's running conditions, such as speed, acceleration, stride, limb rotation, ground impact, and frontal balance, during the training of racehorses. In addition, data is needed to quickly detect abnormalities during training and provide a basis for changing the intensity of training or deciding to give a rest to the horse. Devices that detect abnormalities in equine gait with high sensitivity will contribute to animal welfare and increase the athletic longevity of horses. This paper reports the development results of a new IoT device that acquires, processes, and analyzes information such as heart rate, position, speed, acceleration, pitch, stride, and ground contact during a training of racehorses. The purpose of this development is to provide an information on a novel processing system, device, method, and program that can analyze training condition of racehorses from multiple angles.

A relatively loud sound is audible when a vibrator is attached to the aural cartilage. This form of conduction is referred to as cartilage conduction (CC). In Japan, a new type of hearing aid has been developed using CC and is available in clinical practice since 2017. A clinical study conducted prior to its launch demonstrated its benefits, particularly in patients with aural atresia who were unable to use air-conduction hearing aids. Several studies have been published on the benefits of CC hearing aids since their introduction in clinical practice. Most of the patients included in these studies had canal stenosis or aural atresia, and the purchase rates of CC hearing aids in these patients were relatively high. However, the number of patients with open ears was small, with overall poor results in the trials, with the exception in patients with continuous otorrhea. CC hearing aids are considered a good option for compensating hearing loss in ears with canal stenosis or atresia in both bilateral and unilateral cases. However, CC hearing aids are not currently considered the first choice for patients with an open ear,.

The use of interspecific hybrids during the industrial fermentation process has been well established, positioning the frontier of advancement in brewing to capitalize on the potential of Saccharomyces hybridization. Interspecific yeast hybrids used in modern monoculture inoculations benefit from a wide range of volatile metabolites that broaden the organoleptic complexity. This is the first report of sake brewing by Saccharomyces arboricola and its hybrids. S. arboricola x S. cerevisiae direct-mating generated cryotolerant interspecific hybrids which increased yields of ethanol and ethyl hexanoate compared to parental strains, important flavor attributes of fine Japanese ginjo sake rice wine. We used hierarchical clustering heatmapping with principal component analysis for metabolic profiling and found that the low levels of endogenous amino/organic acids clustered S. arboricola apart from the S. cerevisiae industrial strains. In sake fermentations, hybrid strains showed a mosaic profile of parental strains, while metabolic analysis suggested S. arboricola had a lower amino acid net uptake than S. cerevisiae. Additionally, we found an increase in ethanolic fermentation from pyruvate and increased sulfur metabolism. Together, our results suggest S. arboricola is poised for in-depth metabolomic exploration in sake fermentation.

Urban floods are typical urban disasters that threaten the economy and development of cities. Sponge cities can improve the flood resistance ability and reduce the floods by setting low-impact development measures (LID). Evaluating the floods reduction benefits is the basic link in the construction of sponge cities. Therefore, it is of great significance to evaluate the benefits of sponge cities from the perspective of different rain patterns. In this study, we investigated the urban runoff of various rainfall patterns in Mianyang city using the Strom Water Management Model (SWMM). We employed 2–100-year return periods and three different temporal rainfall downscaling methods to evaluate rain patterns and simulate urban runoff in Mianyang, with and without the implementation of sponge city measures. After calibration, model performance was validated using multi-source data concerning flood peaks and inter-annual variations in flood magnitude. Notably, the effects of peak rainfall patterns on historical floods were generally greater than the effects of synthetic rainfalls generated by temporal downscaling. Compared to the rainfall patterns of historical flood events, the flood protection capacities of sponge cities tended to be overestimated when using the synthetic rainfall patterns generated by temporal downscaling. Overall, an earlier flood peak was associated with better flood sponge city protection capacity.

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous researches have shown OXT properties to reduce self-administration, alleviate motor impairment in rodents, and reduce craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to increased drug incentive, remains unexplored. OXT is also associated with modulating the Hypothalamic-Pituitary-Adrenal (HPA) axis, with corticosterone well-known as a significant factor in behavioral sensitization development. This study aimed to investigate the effects of Carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and drinking in the dark (DID) methodology. For the sensitization study, mice received either ethanol (1.8 g/kg, ip) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, ip) or a vehicle for 6 days. Subsequently, on day 22, all animals underwent an ethanol challenge to assess the expression of behavioral sensitization. Plasma corticosterone levels were measured on days 21 and 22. CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations detected in corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, mice underwent a 6-day treatment with CBT i.p or saline before being reexposed to ethanol. We also found a reduction in ethanol consumption due to CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention in mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

The relationship between city size, coastal land use and air temperature rise with distance from coast during summer day is analyzed using the meso-scale Weather Research & Forecasting (WRF) model in five coastal cities in Japan with different sizes and coastal land use (Tokyo, Osaka, Nagoya, Hiroshima and Sendai) and inland cities in Germany (Berlin, Essen and Karlsruhe). Air temperature increased as distance from the coast increased, reached its maximum, and then decreased slightly. In Nagoya and Sendai, the number of urban land use in coastal areas is less than the other three cities, where air temperature is a little lower. As a result, air temperature difference between coastal and inland urban area is small and the curve of air temperature rise is smaller than those in Tokyo and Osaka. In Sendai, air temperature in the inland urban area is the same as in the other cities, but air temperature in the coastal urban area is a little lower than the other cities, due to about one degree lower sea surface temperature influenced by the latitude. In three German cities, the urban boundary layer may not develop sufficiently because the fetch distance is not enough.

The availability of sufficient amounts of form I of benzocaine has led to the investigation of its phase relationships with the other two existing forms II and III using adiabatic calorimetry, powder X-ray diffraction, and high-pressure differential thermal analysis. The latter two forms were known to have an enantiotropic phase relationship with form III stable at low-temperature and high-pressure, while form II is stable at room temperature. Using adiabatic calorimetry data, it can be concluded, that form I is the stable low-temperature, high-pressure form, which also happens to be stable at room temperature; however, form II, due to its persistence at room temperature, is still the most convenient polymorph to use in formulations. Form III presents a case of overall monotropy and does not possess any stability domain in the pressure-temperature phase diagram. Heat capacity data for benzocaine have been obtained by adiabatic calorimetry from 11 K up to 369 K above its melting point, which can be used to compare to results from in-silico crystal structure prediction.

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interplays the contraction of actin-containing thin filaments and myosin-containing thick filaments. The breakdown product of titin has been measurable in urine as urinary titin N-fragments. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

Background/Objectives: Postoperative intraocular lens (IOL) is a risk associated with IOL scleral fixation. However, the cause of IOL tilt during IOL suturing remains unclear. Therefore, this study aimed to evaluate the surgical outcomes of a modified IOL suturing technique and investigate the factors contributing to postoperative IOL tilt and decentration. Methods: We included 25 eyes of 22 patients who underwent IOL suturing between April 2018 and February 2020. A modified IOL suturing technique that decreased the need for intraocular suture manipulation was used. Factors contributing to IOL tilt and decentration were investigated using an intraoperative optical coherence tomography (iOCT) system. Results: The mean postoperative best-corrected visual acuity improved from 0.15 ± 0.45 to -0.02 ± 0.19 (p = 0.02). The mean IOL tilt angle at the last visit after surgery was 1.84 ± 1.28 degrees. The study revealed that the distance of the scleral puncture site from the corneal limbus had a stronger effect on IOL tilt; while, the suture position of the haptics had a greater effect on IOL decentration. Conclusions: The modified IOL suturing technique, which avoids intraocular suture handling, had favorable surgical outcomes with improved postoperative visual acuity and controlled IOL tilt and decentration. Accurate surgical techniques and careful measurement of distances during surgery are crucial for preventing postoperative IOL tilt and decentration.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

The development of non-destructive testing (NDT) methods for infrastructure facilities and residential buildings that may affect human life is urgent to prevent collapse due to aging or damage in the event of earthquakes and other events. In this study, we developed a single-input and multiple-output (SIMO) synthetic aperture radar (SAR) imaging system using a high-sensitivity millimeter-wave (MM-wave) array antenna module with high directivity and absolute gains of 13.5 dB and 14.5 dB for the transmit and receive antennas, respectively. After various performance evaluations, we successfully demonstrated the usefulness of this system in NDT. Specifically, we observed cracks hidden by fiberglass tape and black acrylic paint during measurements on concrete materials. In addition, we demonstrated the transmission performance of the MM-wave against a thin concrete plate and obtained the attenuation distance Λ_exp=6.0 mm. Furthermore, in the experiment using composite materials consisting of ceramic tiles and a refractory board bonded together, and another experiment using composite plywood which is used in ordinary residential construction materials in Japan, we were able to observe defects in the internal structure that are invisible to the human eye through a perspective view.

Ecological and environmental damage caused by oil spillage has attracted great attention. Used cigarette filter (CF) has also caused negative environmental consequences. Converting CF to economical materials is a feasible way to address these problems. In this study, we demonstrate a simple method for production of a highly hydrophobic absorbent from CF. CF was modified by using different volume ratios of octadecyltrichlorosilane and methyltrimethoxysilane. When the volume ratio was 3:2, the modified CF had the high water contact angle of 155°. It could selectively and completely absorb silicone oil from an oil-water mixture and showed a good absorption capacity of 38.3 g/g. The absorbed oil was readily and rapidly recovered by simple mechanical squeezing, and it could be reused immediately without any additional treatments. The as-obtained superhydrophobic modified CF retained an absorption capacity of 80% for pump oil and 82% for silicone oil after 10 cycles. The modified CF showed good elasticity in the test of repeated use. The present study provides novel design of a functional material for development of hydrophobic absorbents from used CF via a facile method toward oil spillage cleanup as well as a new recycling method of CF to alleviate the environmental impact.

Gradient based methods are popularly used in training neural networks and can be broadly categorized into first and second order methods. Second order methods have shown to have better convergence compared to first order methods, especially in solving highly nonlinear problems. The BFGS quasi-Newton method is the most commonly studied second order method for neural network training. Recent methods have shown to speed up the convergence of the BFGS method using the Nesterov’s acclerated gradient and momentum terms. The SR1 quasi-Newton method though less commonly used in training neural networks, are known to have interesting properties and provide good Hessian approximations when used with a trust-region approach. Thus, this paper aims to investigate accelerating the Symmetric Rank-1 (SR1) quasi-Newton method with the Nesterov’s gradient for training neural networks and briefly discuss its convergence. The performance of the proposed method is evaluated on a function approximation and image classification problem.

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

Keywords: Endodontic microsurgery; Root canal treatment; Isthmus preparation; Short-term outcomes

Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.

The purpose of this study was to investigate the changes in anterior knee laxity (AKL), stiffness, general joint laxity (GJL), and genu recurvatum (GR) during the menstrual cycle in female non-athletes and female athletes with normal and irregular menstrual cycles. Participants were 19 female non-athletes (eumenorrhea, n=11; oligomenorrhea, n=8) and 15 female athletes (eumenorrhea, n=8; oligomenorrhea, n=7). AKL was measured as the amount of anterior tibial displacement at 67 N - 133 N. Stiffness was calculated as change in (Δ)force/Δ anterior displacement. The Beighton method was used to evaluate the GJL. The GR was measured as the maximum angle of passive knee joint extension. AKL, stiffness, GJL, and GR were measured twice in four phases during the menstrual cycle. Stiffness was significantly higher in oligomenorrhea groups than in eumenorrhea groups, although no significant differences between menstrual cycle phases were evident in female non-athletes. GR was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase, although no significant differences between groups were seen in female athletes. Estradiol may affect the stiffness of the periarticular muscles in the knee, suggesting that GR in female athletes may change during the menstrual cycle.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Most of the phase change materials (PCMs) have been limited to use as functional additions or sealed in containers, and extra auxiliary equipment or supporting matrix is needed. The emergence of 3D printing technique has dramatically advanced the developments of materials and simplified production processes. This study focuses on a novel strategy to model thermal energy storage crystalline gels with three-dimensional architecture directly from liquid resin without supporting materials through light-induced polymerization 3D printing technique. A mask-projection stereolithography printer was used to measure the 3D printing test, and the printable characters of crystalline thermal energy storage P(SA-DMAA) gels with different molar ratios were evaluated. For the P(SA-DMMA) gels with small fraction of SA, the 3D fabrication was realized with higher printing precision both on mili- and micro-meter scales. As a comparison of 3D printed samples, P(SA-DMAA) gels made by other two methods, post-UV curing treatment after 3D printing and UV curing using conventional mold, were prepared. The 3D printed P(SA-DMAA) gels shown high crystallinity. Post–UV curing treatment was beneficial to full curing of 3D printed gels, but did not lead to the further improvement of crystal structure to get higher crystallinity. The P(SA-DMAA) crystalline gel having the highest energy storage enthalpy that reached 69.6 J·g⁻¹ was developed. Its good thermoregulation property in the temperature range from 25 to 40 °C was proved. The P(SA-DMAA) gels are feasible for practical applications as one kind of 3D printing material with thermal energy storage and thermoregulation functionality.

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in Japanese healthy older volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥ 65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL).

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

Wasted Green tuff powder produced by cutting Towada stone is recycled as environmental cleaning material. The optimum temperature for green tuff powder calcination to reduce the hydroxyl radical produced in hydrogen peroxide decomposition with ultraviolet light (UV) and no light. The green tuff calcined at 800 °C shows the large decomposition rate of hydrogen peroxide with no UV light when measured by using ESR. With UV light, the optimum temperature for calcinating the green tuff powder in order to reduce hydroxyl radical is also 800 °C. Next, the powder calcined at 800 °C is used to produce the tile by compression and heating, and then the formaldehyde adsorption rate was measured. The green tuff powder calcined at 800 °C showed a high adsorption rate, similar to that of the activated carbon. The tiles formed at 40 MPa and heated st 1100 °C were the strongest and also adsorbed formaldehyde. The adsorbed formaldehyde on the green tuff tile and powder might have a possibility to decompose by photocatalytic.

The black soldier larvae meal (BSFLM) has been the most extensively studied insect protein source in shrimp nutrition. However, both the availability and prices of BSFLM are still a constraint for its widespread use as an ingredient in animal feeds. The present study investigated the growth and economic performance of post-larval (PL) P. vannamei fed nursery diets with a progressive replacement of fish meal (FML) for BSFLM at 0, 25, 50, 75 and 100%. These replacements corresponded to a dietary inclusion (% of the diet, as-is) of FML and BSFLM of 16.50 and 6.33%, 11.00 and 13.04%, 5.50 and 19.74%, and 0 and 26.46%, respectively. A total of 102,647 shrimp at the age of PL15 with 2.7 ± 0.2 mg body weight (BW) were stocked in fifty 1.5-m3 tanks under 1,369 PLs/m3 (2,053 ± 33 PLs/tank) and reared for 42 days. Final shrimp survival (90.5 ± 7.6%), daily weight gain (14.7 ± 1.1 mg/day), and apparent feed intake (0.67 ± 0.03 g of feed per stocked shrimp) were unaffected by dietary treatment. The highest gained yield (791 ± 52 and 776 ± 38 g/m3) and final BW (621 ± 7.2 and 632 ± 7.2 mg) were attained when FML was replaced for BSFLM at 50 and 75% with the lowest at 0% (726 ± 34 g/m3 and 598 ± 8.1 mg, respectively). Shrimp fed diets with 0 and 100% replacement of FML exhibited the highest feed conversion ratio (1.25 ± 0.04 and 1.24 ± 0.08) compared to those fed a diet with 50% (1.16 ± 0.06). At a price of USD 2.00/kg, BSFLM demonstrated a favorable ROI (Return of Investment) when compared to FML, irrespective of the replacement level. With 25 and 50% replacement, BSFLM remained cost-competitive up to 3.50 USD/kg. At 75% FML replacement, there were no significant differences in ROI with a price range of 2.00 up to 3.04 USD/kg. At full replacement, ROI dropped significantly at a BSFLM price of 2.50 USD/kg and beyond. It can be concluded that FML can be fully replaced for BSFLM in well-balanced nursery diets for P. vannamei. While the full replacement of FML for BSFLM was successfully accomplished, the competitive ROI was sustained only when the price of BSFLM did not exceed 3.04 USD/kg at its dietary highest inclusion of 19.74%. Further research may be necessary to fine-tune cost-effective inclusion levels of BSFLM to optimize the economic outcomes while considering the fluctuating prices of FML.

Hydroxyapatite and b-tricalcium phosphate have been clinically applied as artificial bone materials due to their high biocompatibility. The development of artificial bones requires the verification of safety and efficacy through animal experiments; however, from the viewpoint of animal welfare, there is necessary to reduce the number of animal experiments. In this study, we utilized machine learning to construct a model that estimates the bone-forming ability of bioceramics from material fabrication conditions, material properties, and in vivo experimental conditions. We succeeded in constructing the two models as follows: ‘Model 1’, which predicts material properties from their fabrication conditions, and ‘Model 2’, which predicts the bone-formation rate from material properties and in vivo experimental conditions. By an inverse analysis of the two models, we proposed candidates for material fabrication conditions to achieve target values of bone-formation rate. Under the proposed conditions, the material properties of the fabricated material were consistent with the estimated material properties. Furthermore, a comparison between bone-formation rates after 12 weeks of implantation in the porcine tibia and the estimated bone-formation rate. This result showed that the actual bone-formation rates existed within the error range of the estimated bone-formation rates, indicating that machine learning consistently predicts the results of animal experiments using material fabrication conditions. We believe that these findings will lead to the establishment of alternative animal experiments to replace animal experiments in the development of artificial bones.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate expression of differentiated phenotype of chondrocytes. We also found that cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2 and chondroitin sulfate biosynthetic enzymes. Blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

The molecular mechanisms underlying insect gall formation remain unclear. A major reason for the inability to identify the responsible genes is that most insect galls are produced on woody plants and therefore cannot be experimentally validated in the laboratory. To overcome these problems, we established a new galling insect model, Smicronyx madaranus. Our manipulation experiments using nail polish sealing and insecticide treatment revealed an age-dependent change in gall formation during S. madaranus; adult females and larvae are responsible for gall induction and enlargement, respectively. Furthermore, it has been suggested that substances released during oviposition and larval feeding are involved in each process. Phylogenetic analysis showed that most gall-forming weevils, including S. madaranus, belong to a single lineage, suggesting that gall-forming traits evolved in a specific lineage within Smicronyx. The efficacy of RNA interference (RNAi) in S. madaranus was confirmed by targeting multicopper oxidase 2 gene. It is expected that the mechanisms of gall formation will be elucidated by a comprehensive functional analysis of candidate genes using RNAi and the S.madaranus galling system in the near future.

Ultrasound has become widely used as a mean to measure the rectus femoris muscle in the acute and chronic phase of critical illness. Despite its noninvasiveness and accessibility, its accuracy highly depends on the skills of the technician. However, few ultrasound phantoms for the confirmation of its accuracy or to improve technical skills exist. In this study, we created a novel phantom model and used it for investigating the accuracy of measurements and for training. Study 1 investigated how various conditions affect ultrasound measurements such as thickness, cross-sectional area, and echogenicity. Study 2 investigated if the phantom can be used for training of various health care providers in vitro and vivo. Study 1 showed that thickness, cross-sectional area, and echogenicity were affected by probe compression strength, probe angle, phantom compression, and varying equipment. Study 2 in vitro showed that using the phantom for training improved the accuracy of the measurements taken within phantom, and Study 2 in vivo showed the phantom training had a short-term effect on improving the measurement accuracy in a human volunteer. The new ultrasound phantom model revealed that various conditions affected ultrasound measurements, and phantom training improved the measurement accuracy.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

Tertiary lymphoid structures (TLSs) have become the focus of antitumor immunity. However, the prognostic significance of TLSs in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unelucidated. This retrospective study examined the prognostic value of TLSs in tumor tissues obtained during PDS and IDS. Pathological specimens were collected from patients with EOC who underwent PDS or IDS between 2017 and 2020 at the National Cancer Center Hospital East. The correlation of tumor-infiltrating lymphocyte frequency, TLS presence, and PD-L1 expression with progression-free survival (PFS) and overall survival (OS) and the correlation between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS in patients who underwent PDS but not in patients who underwent IDS. No correlation was identified between TLS and PFS in patients with PDS or with IDS. However, TLS was positively correlated with PD-L1 positivity. The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive correlation between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Self-assembly membranes, composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), were characterized at the total lipid concentration below 20 mM. The sizes of the assemblies varied depending on the molar ratio of DMPC and DHPC (q = [DMPC]/[DHPC]). The small assemblies with diameter of ca. 10 nm were formed at q ≤ 2.0 at 20 ºC (below phase transition temperature of DMPC). The physicochemical membrane properties were then studied using fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene and 6-dodecanoyl-N,N-dimethyl-2-naphthylamine, upon the dilution. DHPC micelle showed a higher membrane fluidity, while the DMPC/DHPC membranes at q ≥ 0.5 showed lower membrane fluidities as well as DMPC vesicle in gel (ordered) phase. Upon dilution, the ordered membrane properties were maintained while the solution turbidities increased, implying the morphological change of the self-assembly, bicelle to the vesicle in gel phase. Based on the obtained results, a phase diagram of DMPC/DHPC binary system (at 20 ºC) is described: (i) the bicelle suspension is transparent and the membrane is in ordered state, (ii) the micelle suspension is transparent and the membrane is in disordered state, (iii) the vesicle suspension is turbid and the membrane is in ordered state.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.