Friction is an important subject for sustainability due to problems associated with energy loss. Recent years, surface micro- and nanostructures have attracted much attention to reduce friction; however, suitable structures are still under consideration. Many functional surfaces are present in nature, such as the friction reduction surfaces of snake skins. In this study, we focused on firebrats, Thermobia domestica, living in narrow spaces such as under bark, so their surface frequently contacts with surrounding surfaces. We speculate that their body surface would be adapted to reduce friction. To investigate the firebrat surface functions, firebrat surfaces were observed by using a field-emission scanning electron microscope (FE-SEM) and a colloidal probe atomic force microscope (AFM), respectively. Results of surface observations by the FE-SEM revealed that firebrats are entirely covered with scales, whose surfaces have micro groove structures. Scale groove periods around the firebrat's head are almost uniform within a scale but vary between scales. AFM friction force measurements revealed that firebrat scale reduces friction by decreasing contact area between scales and a colloidal probe. The heterogeneity of groove periods of the scales suggest that it is difficult to fix the whole body in particular rough surfaces and that lead to be "fail-safe".

Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, DAPK, miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.

Artifact metrics is a technology for authenticating artifacts based on their unique characteristics. The artifact-metric system offers "clone resistance," i.e., it makes it highly improbable to create another object exhibiting the same measured values as a genuine artifact. However, determined adversaries may still attempt to create imitations or clones with close physical characteristics to those of registered products, even if they cannot perfectly replicate the genuine product. Such clones serve to deceive users into believing they are genuine rather than counterfeits. Thus, in this study, we consider a scenario in which we measure raster-scanning-generated clones via a non-raster scanning method. Further, we employ image processing techniques to generate image data representing the clones and theoretically assess the filtering effects on these images. Our findings reveal that applying filters to specific frequency components in the spatial frequency domain can effectively highlight differences between raster-scanning-created clones and the corresponding genuine artifacts. Thus, we demonstrate directional emphasis filtering in artifact metrics as an effective approach for rejecting raster-scanning-created clones.

The realization of a perfect absorber A = 1 with transmittance and reflectance T=R=0 by a thin metasurface is one of the hot topics in recent nanophotonics prompted by energy harvesting and sensor applications (A + R + T =1 is the energy conservation). Here we tested optical properties of over 400 structures of metal-insulator-metal (MIM) metasurfaces for a range of variation in thickness of insulator, the diameter of a disc and intra-disc distance experimentally and numerically. Conditions of a near-perfect absorption A > 95% with simultaneously occurring anti-reflection property (R < 5%) were experimentally determined. Differences between the bulk vs. nano-thin film properties at mid-IR of the used materials can be of interest for plasmonic multi-metal alloys and high entropy metals.

Background and Objectives: Although adult spinal deformity (ASD) surgery brought about the improvement of quality of life in patients, it accompanied with a high invasiveness of surgery and several complications. Specifically, mechanical complications of rod fracture, instrumentation failures, and pseudarthrosis are still unsolved issues. To better improve these problems, the oblique lateral interbody fusion at L5/S1 (OLIF51) was introduced since 2015 in my institution. The objective of this study was to compare the clinical and radiographic outcomes of anterior-posterior combined surgery for ASD between the use of OLIF51 versus transforaminal interbody fusion (TLIF) at L5/S1. Materials and Methods :A total of 117 ASD patients received anterior-posterior correction surgeries either use of OLIF51 (35 patients) or L5/S1 TLIF (82 patients). In both groups, L1-5 OLIF and minimally invasive posterior procedures of hybrid or circumferential MIS were employed. The sagittal and coronal spinal alignment and spino-pelvic parameters are recorded preoperatively and at follow-up. The quality of life parameters and visual analogue scale were evaluated as well as surgical complications at follow-up. Results: The average follow-up period was thirty months (13-84). The average fused segments were eight (4-12). The operation time and estimated blood loss were significantly smaller in OLIF51 that those in TLIF. The PI-LL mismatch, LLL, L5/S1 segmental lordosis, and L5 coronal tilt were significantly better in OLIF51 than TLIF. The complication rate was statistically equivalent between two groups. Conclusion: The introduction of OLIF51 for adult spine deformity surgery led to the decrease of operation time and estimated blood loss as well as the improvement of sagittal and coronal correction when compared to TLIF.

In many developed countries, mental health disorders have become problematic, and the economic loss due to treatment costs and interference with work is immeasurable. Therefore, we developed a method to assess individuals’ mental health using emotional components contained in their voice. We propose two indices of mental health: vitality, a short-term index, and mental activity, a long-term index capturing the trends in vitality. To evaluate our method, we used the voices of healthy individuals (n = 14) and patients with major depression (n = 30). The patients were also assessed by specialists using the Hamilton Rating Scale for Depression (HAM-D). A significant negative correlation existed between the vitality extracted from the voices and HAM-D scores (r = -0.33, p &lt; .05). We could discriminate the voice data of healthy individuals and patients having depression with a high accuracy using the vitality (p = .0085, area under the curve = 0.76). Further, we developed a method to estimate stress through emotion instead of analyzing stress directly from voice data. By daily monitoring of vitality using smartphones, we can encourage hospital visits for people before they become depressed or during the early stages of depression, to prevent adverse consequences of depression.

Background and objectives: As the oblique lateral interbody fusion at L5/S1 (OLIF51) and lateral corridor approach (LCA) have gained popularity, the understanding of precise vascular structure at L5/S1 level is indispensable. The objectives of this study were to investigate the vascular anatomy at L5/S1 level, and to compare the movement of vascular tissue between supine and lateral decubitus position using the intraoperative enhanced CT and MRI. Materials and Methods: A total of 43 patients who underwent either OLIF51 or LCA were investigated with the average age at surgery of 60.4 (37-80) years old. The preoperative MRI was taken to observe axial and sagittal anatomy of vascular position under supine position. The intraoperative vein-enhanced CT was taken just before incision in the right decubitus position, and compared to supine MRI anatomy. The iliolumbar vein appearance and its types were also classified. Results: The average vascular window allowed for OLIF51 was 22.8 mm and 34.1 mm at either L5 caudal endplate or S1 cephalad endplate level, respectively. It allowed for LCA was 14.2 mm and 12.6 mm at either level, respectively. The left common iliac vein moved 3.8 mm and 6.9 mm to right direction at either level from supine to right decubitus position, respectively. The bifurcation moved 6.3 mm to caudal direction from supine to right decubitus. The iliolumbar vein was located at 31 mm lateral from midline, and MRI detection rate was 52%. Conclusions: The precise measurement of vascular anatomy indicated that OLIF51 approach was the standard minimally invasive anterior approach for L5/S1 disc level compared to LCA, however, there were many variations in quantitative anatomy as well as significant vascular movements between supine and right decubitus position. In the clinical setting of OLIF51 and LCA surgeries, the careful preoperative evaluation and intraoperative 3D imaging are recommended for the safe and accurate surgery.

It has been demonstrated that cancer cells that have survived cancer treatment may be more malignant than the original cancer cells. These cells are considered to be the main cause of metastasis in prognosis. A Nanog-overexpressing colon-26 (Nanog+colon26) was generated and its metastatic potential was confirmed to be enhanced, indicating higher malignancy. Extracellular vesicles (EVs) secreted from the cell line (Nanog+colon26EVs) were administered to mice at 5 μg nine times (three times per week for three weeks) via the tail vein (PBS was used as a control). Subsequently, Nanog+colon26 cells were administered to mice via the spleen, and the quantity of metastatic colonies in the liver was analyzed two weeks later. The results demonstrated that the administration of EVs suppressed metastasis. The enhanced phagocytic activity of macrophages observed in the group treated with Nanog+colon26EVs indicated the involvement of the immune system in the observed metastasis-suppressing effect. Small RNA sequencing was conducted to identify Nanog-dependent miRNAs that exhibited significant changes (Fc>=1.5 or Fc

High-performance properties of interpenetration polymer network (IPN) hydrogels, based on physically crosslinked chitosan (CS) and chemically crosslinked poly(N-isopropylacrylamide) (PNiPAM), have been successfully developed. The IPN of CS/PNiPAM is proposed to overcome the limited mechanical properties of the single CS network. In this study, the viscoelastic behaviors of prepared materials in both solution and gel states have been extensively examined, considering the UV exposure time and crosslinker concentration as key factors. The effect of these factors on gel formation, hydrogel structures, thermal stabilities of networks, and HeLa cell adhesion were studied sequentially. The sol-gel transition was effectively demonstrated through the scaling law, which agrees well with Winter and Chambon's theory. By subjecting the CS hydrogel to the process operation in an ethanol solution, its properties can be significantly enhanced with increased crosslinker concentration, including the shear modulus, crosslinking degree, gel strength, and thermal stability in its swollen state. The IPN samples exhibit a smooth and dense surface with irregular pores, allowing for much water absorption. The HeLa cells were adhered to and killed using the CS surface cationic derivative, then released through hydrolysis by utilizing the hydrophilic/hydrophobic switchable property or thermo-reversible gelation of the PNiPAM network. The results demonstrated that IPN is a highly attractive candidate for anti-fouling materials.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

We investigated the structural evolution of the two-phase blends of polycarbonate (PC) and poly(methyl methacrylate) (PMMA) at various blend compositions by simultaneous biaxial stretching using optical microscopy and SEM observation. The spherical PMMA domains and PC matrix in 30/70 PC/PMMA were enlarged uniformly at all in-plane direction, while the anisotropic-shaped co-continuous structure in 50/50 PC/PMMA was deformed to crosshatched one by in-plane bimodal orientation. In 70/30 PC/PMMA, the phase inversion was found to occur by simultaneous biaxial stretching; i.e., the spherical PMMA domains were changed to crosshatched matrix by in-plane bimodal orientation due to coalescence of the PMMA domains during the stretching. Owing to the phase inversion, the surface hardness estimated by pencil hardness test became harder from 2B to 2H with increasing the strain from 1.0 to 2.0.

In this study, based on our previous study, we examined the mathematical properties, especially the stability of the equilibrium for our proposed mathematical model. By means of the results of the stability in this study, we also used actual data representing transient booms and resurgent booms, and conducted parameter estimation for our proposed model using Bayesian inference. In addition, we conducted a model fitting to five actual data. By this study, we reconfirmed that we can express the resurgences or minute vibrations of actual data by means of our proposed model.

This manuscript reviews three case studies from Brazil, Panama, and Portugal that illustrate Nature-based Solutions. The Tijuca Forest in Rio de Janeiro is a remarkable story of centuries of forest management that today is recognized as a UNESCO World Heritage Site. The Panama Canal Watershed produces water for Canal operations, electricity generation, and drinking water for half the country´s population. Traditional windmills and weirs near streams in the Alentejo Region, Portugal, have largely been abandoned due to the damming of the Guadiana River. Yet today, weirs are increasingly recognized for their important contribution to water provisioning in this dry region. All have a primary goal related to water provisioning, yet their ecosystem benefits are multiple. The cases offer important lessons for adaptation to climate change, cultural benefits from traditional human activities, and concerns about social equity.

With the progression of AI, embedding advanced AI technologies into small robotics and mobile devices has become essential, driving research towards lightweighting AI models. Our study enhances the EPINET depth estimation model for light field images, aiming for compactness and faster inference while preserving accuracy. We conducted two-step experiments aimed at enhancing inference efficiency: Initially, by adjusting input streams and convolution layers, we simplified the CNN model, achieving faster inference times at the cost of reduced accuracy. To address this reduction in accuracy, we then applied knowledge distillation, allowing the simplified model to learn from the original model’s more complex patterns. In our quantitative experiments using two error metrics, MSE (Mean Squared Error) and BadPix, we identified optimal knowledge positions and evaluated the required complexity for the student model. As a result, our method improved MSE by 21% and BadPix by 14% compared to training without it. Furthermore, the student model achieved an inference speed 13% faster than the teacher model and surpassed its accuracy by 10% in MSE. Additionally, we demonstrated that repeatedly applying our approach could further enhance both model compactness and accuracy.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines TNF- and IL-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-17, IL-23, GM-CSF, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

Keywords: Y RNA; Canine hepatocellular carcinoma, canine hepatocellular adenoma

Glaucoma secondary to Peters' anomaly (PA) is an important factor affecting visual prognosis, but there are few reports on it. This study aimed to investigate the characteristics of glaucoma asso-ciated with PA and glaucoma surgery outcomes. This retrospective study included 31 eyes of 20 patients with PA. PA was classified into three stages: Stage 1, with a posterior corneal defect only; Stage 2, a corneal defect with iridocorneal adhesion; and Stage 3, a corneal defect with lens ab-normalities. The associations between glaucoma and anterior segment dysgenesis severity, visual prognosis, and glaucoma surgery outcomes were analyzed. Sixteen eyes of 10 patients developed glaucoma. Stage 1 PA had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Of the 16 eyes with glaucoma, 11 underwent surgery. Eight of these 11 eyes achieved intraocular pressure (IOP) control. Five of the nine eyes that underwent trabeculotomy (TLO) succeeded, and none had corneal staphyloma. Three of the four eyes for which TLO was ineffective had corneal staphyloma (P=0.0331). Patients with PA are more likely to develop glaucoma as anterior segment dysgenesis progresses, and the effect of TLO is limited if corneal staphyloma is present.

Global concerns of decreasing water availability and food security are being exacerbated by the increasing demand for food, water quality degradation, and climate change impacts. Rice is an essential crop for food security with paddy rice cultivation largely practiced using traditional flooding conditions. Water regimes and components of the soil water balance in paddy rice catchments affect uptake of water by rice roots. Paddy management, especially puddling, significantly affects soil hydrological properties, such as hydraulic conductivity, percolation, and seepage in the paddy rhizosphere. Improved knowledge of these interactions is vital for developing sustainable water management strategies in paddy fields. Alternate Wetting and Drying (AWD) practice contributes to sustainable water management, but little is known about effects of soil wetting and drying duration on gravitational soil water flow, moisture dynamics, and hydraulic conductivity in the rice paddy rhizosphere. These factors depend on soil type, rice variety, rooting conditions, and environmental factors, such as solar radiation and temperature. Here we examine the paddy cultivation environment and soil properties under traditional continuous flooding and AWD practice. Some studies indicate that the duration and frequency of wetting and soil drying under AWD practice in paddy fields affects soil hydraulic conductivity that alters the next cycle of water application. During droughts and short rainy seasons, rainfall, soil properties, and atmospheric conditions control soil moisture dynamics in paddy fields. Limitations and challenges of applying AWD in paddy soils, including the variation of hydrological properties and the need for frequent field manual monitoring of water level (WL) head, are discussed. Implications of AWD practice on yield, water use efficiency, soil hydrology, and reduction of methane emissions, are outlined along with opportunities to improve AWD integration within government policies, irrigation schemes, and adoption by farmers. Coupled crop models can provide important insights for sustainable agricultural water management.

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.

Formation of Fe- and Mg-rich smectite and zeolite under alkaline conditions is concerned as secondary minerals after alkaline alteration of bentonite in a repository of radioactive wastes. It might be crucial for safety assessment whether smectite will be formed or not as secondary minerals after alkaline alteration of bentonite. In present paper, Fe- and Mg-rich smectite which are currently interacting with hyperalkaline groundwater was found at Narra in Palawan, Philippines. Mineralogical and geochemical investigation was conducted to understand formation process of smectite and factors determined secondary mineral species. Our study revealed a certain amount of smectite may have been produced under hyperalkaline conditions, altered from amorphous or poorly crystalline material such as M-S-H and F-S-H. Key factor which decides smectite or zeolite as secondary minerals after alkaline alteration of bentonite might be whether nuclei of M-S-H and/or F-S-H will be formed or not. This might be decided by the presence of dissolved Mg2+ and Fe2+ in the system. Our suggested formation process of smectite under alkaline conditions is analogue with generally-accepted model of smectite formation that might have been occurred on early Mars.

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

Long-term care (LTC) settings are increasingly used for palliative care in Japan. This study aimed to assess the proportion of LTC settings that provide palliative care services for older clients with advanced dementia in Japan and the trends across the types of settings. A nationwide questionnaire survey was conducted between November 2022 and January 2023, targeting 1,000 geriatric hospitals (GHs), 1,000 geriatric health services facilities (GHSFs), and 1,000 home nursing care stations (HNCSs). The palliative care practices for older patients with advanced dementia and their families in the agencies were assessed. Less than half of the GHs supported family participation or the spiritual needs of their older clients with dementia, while many had access to pain and symptom assessments and analgesic prescriptions by physicians. Less than half the GHSFs used pain assessment tools, assessed and supported family caregivers' pain and distress, and supported family participation in palliative care. More than 80% of the HNCSs practiced most of the listed palliative care. Current palliative care practices for older adults with dementia vary among GHs, GHSFs, and HNCSs. This emphasizes the need for targeted approaches to improve the provision of palliative care for patients with dementia across LTC settings in Japan.

Metal-organic frameworks (MOFs) represent the largest class of materials among the crystalline porous materials ever developed and have attracted attention as core materials for separation technology. Their extremely uniform pore aperture and nearly unlimited structural and chemical characteristics have attracted great interest and promise in applying MOFs to adsorptive and membrane–based separations. This paper reviews the recent research and development of MOF membranes for gas separation. Strategies for polycrystalline membranes and mixed matrix membranes are discussed, with a focus on separation systems involving hydrocarbon separation and CO2 capture. Challenges and opportunities for the industrial deployment of MOF membranes are also be discussed, providing guidance for the design and fabrication of future high-performance membranes. The contributions of the underlying mechanism to separation performances, and the adopted strategies and membrane processing technologies for breaking the selectivity/permeability trade–off are discussed.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD such that AD may be a form of brain insulin resistance. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Agricultural drainage canals that connect upstream fish spawning areas to downstream rivers and lakes serve as crucial habitats for migrating fish. However, disconnections, such as drops and chutes, have been constructed in these canals due to agricultural modernization and flood control measures, hindering the movement of fish with limited swimming abilities. Portable fishways offer a promising solution to reconnect water bodies in agricultural canals, as they can be easily removed during high water discharges to avoid impeding the canals' drainage function. In addition to experimental assessments of fishway functionality, employing a hydrodynamic model to explore effective placement strategies for portable fishways is essential to maximize their effectiveness. This study presents a method to determine the best horizontal location of a portable fishway in an agricultural drainage canal using two-dimensional hydrodynamic simulations within the specified cases. The applicability of this method is demonstrated by addressing the positioning challenge of a portable fishway on a chute in an agricultural drainage canal in Japan. Results indicate that the proposed method allows for the selection of a suitable location, considering preferable hydraulic conditions both within the portable fishway and around its entrance.

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. Cell detachment from the primary tumor and subsequent invasion are considered to be early phase of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phase. The assay system for late phase was set up with intra-portal-vein injection of pancreatic cancer cells. Administration of DHMEQ was found to inhibit the liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also when the pancreatic cancer cells treated with DHMEQ was inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis. DHMEQ inhibited the 3D invasion of breast cancer cells without toxicity. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

Patients with neurodegenerative diseases (NDDs) are rapidly increasing all over the world. Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease (HD), frontotemporal lobar degeneration (FTLD) and many other diseases are classified as NDDs, however, no therapeutic drugs have been developed against NDDs yet. As common phenomenon, protein oligomers and aggregates (inclusion bodies) are formed in neurons, and they trigger neuronal cell death and/or axonal degeneration. We have investigated the mechanisms of NDDs, and discovered several chemicals and peptides have potential to cure NDDs. Here, we show phorbol 12-myristate 13-acetate (PMA) significantly inhibits aggregate formation and promotes neurite regeneration in human neuronal cell culture model of NDDs, FTLD and AD. We expressed R406W mutant tau protein found in FTLD patients in human neuroblastoma SH-SY5Y cells as FTLD cell culture model. These FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA to culture medium 60% suppressed aggregate formation. PMA also enhanced neurite growth to the normal level at nanomolar concentration. We cultured SH-SY5Y cells in the medium containing -amyloid (1-42) as AD cell culture model. In these cells, neurite growth was limited to less than 50% of controls by the treatment of -amyloid (1-42). Surprisingly, addition of PMA increased the number of cells with >10-fold neurite extension to seven times even in -amyloid (1-42) contained medium. Also, PMA increased the expression of several genes and proteins important for cell survival in both cell culture models. These results suggest PMA has unexpected potential for the drug development against NDDs.

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.

Staphylococcus aureus, found in the oral cavity as an opportunistic bacterium, has been reported as a cause of infective endocarditis and pneumonia. Salt is an essential mineral component for maintaining human body cells and has attracted attention as a promoter of S. aureus biofilms. This study was conducted to clarify how salt affects biofilm formation by S. aureus and S. mutans, which is a pathogen implicated in the dental caries. Bacteria were cultivated with various concentration of sodium chloride (NaCl) in Toryptic Soy Broth with 0.25% sucrose and 0.25% glucose (TSBs and TSBg) for 16 hours. Contribution of GTF on the membrane vesicles (MVs) from S. mutans and extracellular DNA (eDNA) was also analyzed in the biofilm formation. S. aureus biofilms were induced by the addition of 0.004–0.25 M NaCl but decreased by NaCl concentrations greater than 0.25 M, in TSBs. The biofilm formation of mixed bacteria (S. aureus and S. mutans) gradually increased in a NaCl concentration-dependent manner in TSBs and TSBg. Moreover, the biofilm was dependent on glucan formation by GTF in MVs at high salinity. The mixed-species biofilm of S. aureus and S. mutans was upregulated by the collaboration of eDNA and MVs. Therefore, eDNA and MVs are developmental factors for S. aureus biofilm formation under harsh conditions. The intake of sucrose and glucose may be a risk factor for infection by opportunistic pathogens such as S. aureus in persons who consume high concentrations of salt in foods and drinks in custom-type foods.

Considering the health benefits of the kombucha, already widely studied, the objective of the study was to development of the beverage with the addition of infusion of special arabica coffee from the first fermentation varying the proportion of special coffee (2% a 13%) and evaluate the pH, volatile acidity, degree of alcohol, centesimal composition, sodium contents, colour parameters as like acceptability of the beverages. With respect to the pH, all the formulations conformed with the kombucha identity standard, but K3 and K4 were below the established minimum for volatile acidity. Except for K4, all the other formulations were classified as alcoholic kombuchas, although the values were very close to the limit for non-alcoholic. The formulations presented low sugar and sodium content, which corroborated the low caloric value. Therefore, coffee-flavored kombucha fermented for 18 days becomes an option for consumers looking for low-calorie, refreshing and healthy drinks. The luminosity of the beverages decreased as the proportion of coffee increased, and consequently the values for a* and b* increased, indicating a strong tendency for a yellowish red colour. Sensorially, the formulations K4 and K3 were the most well accepted in all respects and can therefore be considered formulations with high commercialization potential.

Hypoxia contributes to tumor progression and metastasis, and hypoxically dysregulated RNA molecules may thus be implicated in poor outcomes. Canine oral melanoma (COM) has a par-ticularly poor prognosis, and some hypoxia-mediated miRNAs are known to exist in this cancer; however, equivalent data on hypoxically dysregulated other non-coding RNAs (ncRNAs) are lacking. Accordingly, we aimed to elucidate non-miRNA ncRNAs that may be mediated by hy-poxia, targeting primary-site and metastatic COM cell lines and clinical COM tissue samples in next generation sequencing (NGS), with subsequent qPCR validation and quantification in COM primary and metastatic cells, plasma and extracellular vesicles (EVs) for any identified ncRNA of interest. Findings suggested that a number of non-miRNA ncRNA species are hypoxically up- or downregulated in COM. We identified one ncRNA, the long ncRNA fragment EN-SCAFT00000084705.1, as a molecule of interest due to its consistent downregulation in COM tissues, hypoxically and normoxically cultured primary and metastatic cell lines, when compared to the oral tissues from healthy dogs. However, this molecule was undetectable in plasma and plasma EVs, suggesting that its expression may be tumor tissue-specific and it has little potential as a biomarker. Here, we provide evidence of hypoxic transcriptional dysregulation for ncRNAs other than miRNA in COM for the first time, and suggest that ncRNA ENSCAFT00000084705.1 is a molecule of interest for future research on the role of the transcriptome in hypoxia-mediated progression of this aggressive cancer.

Screen-printed carbon electrode (SPCE) is a useful technique that has been widely used in the practical application of biosensors oriented to point-of-care testing (POCT) due to its characteristics of cost-effectiveness, disposability, miniaturization, wide potential window, and easy of electrode design. Compared with gold or platinum electrodes, surface modification is difficult because the carbon surface is chemically or physically stable. Oxygen plasma can easily produce carboxyl groups on the carbon surface, which act as scaffolds for covalent bonds. However, the effect of O2-plasma treatment on electrode performance remains to be investigated from an electrochemical perspective, and sensor performance can be improved by clarifying the surface conditions of plasma treated biosensors. In this research, we compared antibody modification by plasma treated and physical adsorption, using our original immunosensor based on gold nanoparticles (AuNPs). Consequently, the O2-plasma treatment produced carboxyl groups on the electrode surface, which changed the electrochemical properties owing to electrostatic interactions. It was also found that the surface became hydrophilic, inhibiting non-specific antigen adsorption. The sensitivity was 6.5 times higher than the Limit of Detection (LOD) using physical adsorption.

Proprioceptive deficits accompanied with motor paresis after stroke, namely sensory ataxic motor paresis has a poorer prognosis of recovery than pure motor deficit. We aimed to investigate the effects of repetitive peripheral magnetic stimulation (rPMS) on sensory ataxic upper extremity (UE) paresis at acute stroke. Eighteen stroke participants with sensory ataxic UE paresis were randomized. rPMS group received five sessions of intervention per week, where 20 minutes of rPMS prior to 20 minutes of physical therapy (PT) every other day, alternating with 40 minutes of PT. The control group received five sessions of 40 minutes of PT/week. Outcome measures were Wolf motor function test (WMFT), UE motor section of Fugl-Meyer Motor Assessment Scale (FMA-UE), and Thumb localizing test (TLT). All assessments were compared before and after intervention. rPMS group received mean 6.5 sessions and the control group received 12.8 sessions, showing significantly imbalanced intervention due to different timing of hospital discharge. The imbalance was corrected by calculating gains of motor scores divided by sessions as Progress Rate (PR). Corrected gains (PR) of rPMS group was more significantly enhanced in WMFT and FMA-UE than control groups. rPMS group tended to improve TLT more than control one. rPMS might improve sensory ataxic UE paresis after stroke and proprioceptive deficit.

Yerba maté, an herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole body metabolism, were explored in healthy adult mice. Yerba maté treatment increased mitochondrial oxygen consumption in adipose, but not in other tissues examined. Yerba maté increased ATP concentration in skeletal muscle and decreased ATP concentration in adipose. Combined with observed changes in oxygen consumption, these data yielded a significantly higher ATP:O2, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O2 in adipose, which were consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting potential protective effects against oxidative stress and preservation of cellular function. Together, these data indicate beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity.

This study characterizes the microstructure and its associated crystallographic features of bulk maraging steels fabricated by selective laser melting (SLM) combined with a powder bed technique. The fabricated sample exhibited characteristic melt pools in which the regions had locally melted and rapidly solidified. A major part of these melt pools corresponded with the ferrite (alpha) matrix, which exhibited a lath martensite structure with a high density of dislocations. A number of fine retained austenite (gamma) with a <001> orientation along the build direction was often localized around the melt pool boundaries. The orientation relationship of these fine gamma grains with respect to the adjacent alpha grains in the martensite structure was (111) gamma // (011) alpha and [-101] gamma // [-1-11] apha (Kurdjumov–Sachs orientation relationship). Using the obtained results, we inferred the microstructure development of maraging steels during the SLM process. The results depict that new and diverse high-strength materials can be used to develop industrial molds and dies.

Considering tumors from an evolucionary perspective, successive tumor cells undergo turnover in response to stressful conditions which pressures tumor cells to adapt to a new environment. Tumor cells uses parts of themselves to communicate and share biological information, known as extracellular vesicles (EV) secretion to promote their survival and “survive to each and every metabolic cost”. Tumor microenvironment (TME) is a miscellaneous of cells, factors, extracellular matrix proteins and EVs. EVs include smalls (<160nm, exosomes) and larger (100-1,000nm, microvesicles) lipid bilayer enclosed packages of biomolecules that are shed by tumors to TME. Tumor-derived extracellular vesicles transfer adaptative stress signaling to recipient cells, reprograming these cells. Heat Shock Proteins (HSP) are more prominent stress response regulators found in exosomes. HSP-loaded exosomes actively reprogram tumor and TME cells to acquire mechanisms that contribute to tumor progression and therapy resistance. The intercellular communication mediated by HSP-loaded EVs favors the escape of tumor cells from, endoplasmic reticulum (ER) stress, hypoxia, apoptosis and anti-cancer therapies. Extracellular HSPs activate and deactivate immune response, induce cell differentiation, changes vascular homeostasis, and help to augment the pre-metastatic niche formation. Here we will explore the EV mechanism of HSP transmission among TME cells and the relevance of these intercellular communications for resistance to therapies in cancer.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

With a large number of annotated non-coding RNAs (ncRNAs), repetitive sequences are found to constitute functional components (termed as repetitive elements) in ncRNAs that perform specific biological functions. Bioinformatics analysis is a powerful tool for improving our understanding of the role of repetitive elements in ncRNAs. This chapter summarizes recent findings that reveal the role of repetitive elements in ncRNAs. Furthermore, relevant bioinformatics approaches are systematically reviewed, which promises to provide valuable resources for studying the functional impact of repetitive elements on ncRNAs.

We summarize how to obtain protein crystals from which better diffraction images can be obtained. In particular, we describe in detail the quality evaluation of the protein sample, the crystallization methods and crystallization conditions, the flash-cooling protection of the crystal, and the crystallization under a microgravity environment.

Background: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: A retrospective analysis was done on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM). Results: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance (PD), longer whole eye movement, and longer whole eye movement time than patients with POAG. Highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL. Conclusions: Biomechanical properties of the cornea differed between PACG and POAG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

This study aimed to describe the injury profiles of young Korean baseball players according to position and age as the proportion and distribution of injuries based on playing position and age remains unclear. A total of 271 elite youth baseball players aged 8 to 16 years were divided into two groups: elementary school (ES) (n=135) and middle school (MS) (n=136). The participants' basic, baseball practice, and injury information were collected. Injuries in the MS group were not limited to the elbow and shoulder, and the injury prevalence varied by age group and baseball position. The most injured body region in the ES group was the elbow joint, regardless of the position. In contrast, the most injured body region in the MS group was the lower back, except for infielders whose elbows were the most injured. Additionally, the MS group was more likely to experience injuries of the lower back (OR=4.27, 95% CI=2.47–7.40), shoulder (OR=1.93, 95% CI=1.08–3.43; P=0.024), and knee (OR=2.15, 95% CI=1.17–3.94; P=0.012). Our findings indicate that excessive practice and lack of rest during MS (growth spurt period) can significantly increase the risk of lower back problems in young baseball players.

Background: It is not clear whether rehabilitation after surgery for trigger finger is effective. The aim of this study was to reveal the effectiveness for trigger finger. Methods: This study was a randomized, controlled trial that included patients who underwent operations for trigger fingers. The patients in the rehabilitation group had postoperative occupational therapy (OT) for 3 months, while the patients in the control group were not referred for rehabilitation but received advice for a range of motion exercise. We evaluated the severity of trigger finger, Disability of Arm-Shoulder-Hand (DASH) score, pain-visual analogue scale (VAS), grip strength, whether they gained a full range of motion (ROM), and complications before and after surgery. Results: Finally, 29 and 28 patients were included in the control and rehabilitation groups, respectively. DASH score, grip strength, and ROM were significantly improved in the rehabilitation group from that preoperatively at final follow-up. Pain was significantly improved in both groups from that preoperatively at final follow-up. Subgroup analysis showed that there is a significant difference in the DASH score of patients doing housework or light work and those with a duration of symptoms &gt; 12 months between the control and rehabilitation groups at the final follow-up.

: We evaluated the pharmaceutical properties of levofloxacin (LV) in the form of an orally disintegrating tablet (LVODT) to find a new usefulness of low frequency (LF) Raman spectroscopy. LVODT contained dispersed granules with diameters in the order of several hundred micrometers, which were composed of the active pharmaceutical ingredient (API), as confirmed by infrared (IR) microspectroscopy. On the contrary, the API and inactive pharmaceutical ingredients (non-APIs) were homogeneously distributed in LV tablet (LVT) formulations. Microscopic IR spectroscopy and thermal analyses showed that LVODT and LVT contained the API in different crystalline forms or environment around the API each other. Furthermore, powder X-ray diffraction showed that LVT contained a hemihydrate of the API, while LVODT showed a partial transition to the monohydrate form. This result was confirmed by microscopic LF Raman spectroscopy. Moreover, this method confirmed the presence of thin layers coating the outer edges of the granules that contained the API. Spectra obtained from these thin layers indicated the presence of titanium dioxide, suggesting that the layers coexisted with a polymer that masks the bitterness of API. The microscopic LF Raman spectroscopy results in this study indicated new applications of this method in pharmaceutical science.

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations at one side of the mandible and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close at the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ±9.3%) compared to the onlay (10.4 ±7.4%) groups (p=0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ±1.05% at the onlay group and 0.78 ±0.71% at the inlay group (p=0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay grafts possibly due to the defect conformation that presented more sources for bone formation. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in growth of bone on the graft trabeculae toward the most superior regions in both groups, and in the closure of the coronal entrance of the defects in the inlay group.

Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by RT-PCR using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

Background: In schizophrenia (SZ), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. Methods: Using data obtained through an internet survey, 210 patients with SZ or MDD were selected using propensity score matching based on their demographic information and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each disease group. Invariances of the mediation model across the two groups were then analyzed. Results: The SZ and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. Conclusion: The role of social cognition in patients with chronic depression was similar to that in schizophrenia. Social cognition could be a common endophenotype for various psychiatric disorders.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 hrs. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNA upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

We report a case in which a 74-year-old man suffering from esophageal achalasia complicated with epiphrenic esophageal diverticulum was successfully treated with a simultaneous laparoscopic surgery. The gentleman was referred with symptoms suggestive of a passage disorder in lower esophagus from 5 years. Esophagogastroduodenoscopy demonstrated an epiphrenic diverticulum at the left wall of the lower esophagus, and esophagography led to the suspicion of a combined esophageal achalasia. A simultaneous laparoscopic surgery, with an abdominal approach was performed in which, following the opening of the esophageal hiatus, the diverticular wall was separated from the mediastinal organs and diverticulectomy was performed with linear staplers. After Heller’s myotomy, Dor’s fundoplication was subsequently performed in which both incisional line of muscle layer and the suturing line of diverticulectomy were wrapped by the fornix of stomach to make up for the wall strength and avoid the suture leakage. It was theoretically considered logical and effective to reinforce this vulnerable site with Dor’s fundoplication. He had an uneventful recovery and a rapid relief from symptoms following surgery.

Quartz Crystal Microbalance (QCM) is a well-known method to measure the mass of ligands bound to receptor-covered surfaces in various fields, ranging from materials science to biology. Actin molecule is essential in various cellular processes through its function of monomer-to-filament polymerization, forming a double-stranded filament with a 75 nm pitch. In this study, QCM was applied to measure the physical properties of actin, finding that the frequency shifted negatively when monomeric actin bound to the QCM surface, whereas the frequency shifted positively when filaments bound. Using fluorescence light microscopic observations, we have examined whether negative and positive frequency shifts originated from their length. In order to control this process, a severing protein, fragmin was used to change the length of actin filament. When the average length of filaments shortened, the magnitude of positive shift decreased in a concentration-dependent manner. However, shorter filaments showed a negative frequency shift depending on their concentration, showing that the weight derived from the loaded concentration and the function derived from actin polymerization dynamics are detectable. Interestingly, the transition from positive to negative occurred when the average length of actin was ~33 nm, or approximately equal to the half-pitch of filaments. Thus, actin filaments can serve as an excellent standard to measure the mechanical properties of biopolymers. Our results show that the QCM sensor could be both a "weight" and a "function" sensor of biomolecules in vitro.

The effects of statin use for primary prevention in reducing mortality among older adults in Asian populations are unknown. This study aimed to determine whether use of statins for primary prevention was associated with a decreased risk of all-cause mortality in a Japanese older adult population. A regional, population-based, longitudinal cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33–0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group (7.9%) compared with that in the control group (92.1%) was 0.05 (95% CI, 0.04–0.06), and the number needed to treat was 21.20 (95% CI, 18.10–24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to &lt;85 years and in patients with comorbidities such as diabetes, or dementia.

Zika virus (ZIKV) outbreaks in Central and South America caused severe public health problems in 2015 and 2016. These outbreaks were finally contained through several methods, including mosquito control using insecticides and repellents. Additionally, the development of herd immunity in these countries might have contributed to containing the epidemic. While ZIKV is mainly transmitted by mosquito bites, mucosal transmission via bodily fluids, including the semen of infected individuals, has also been reported. We evaluated the effect of mucosal ZIKV infection on continuous subcutaneous challenges in a cynomolgus monkey model. Repeated intravaginal inoculations of ZIKV did not induce detectable viremia or clinical symptoms, and all animals developed a potent neutralizing antibody, protecting animals from the subsequent subcutaneous superchallenge. These results suggest that viral replication at mucosal sites can induce protective immunity without causing systemic viremia or symptoms.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Advances in diagnostic procedures have led to an increasing rate of diagnosis of autoimmune encephalitis or paraneoplastic neurological syndrome (AE/PNS) among patients with progressive supranuclear palsy (PSP)-like manifestations. The antibodies involved in these conditions include anti-IgLON5, -Ma2, and -Ri antibodies, each of which has a characteristic clinical presentation. The steps in the diagnosis of AE/PNS in patients with PSP-like manifestations include (i) suspicion of AE/PNS based on clinical presentations atypical of PSP and (ii) antibody detection measures. Methods used to identify antibodies include a combination of tissue-based assays and confirmatory tests. The primary confirmatory tests include cell-based assays and immunoblotting (line or western blot). Treatments can be divided into immunotherapy and tumor therapies, the former of which includes acute and maintenance therapies comprising corticosteroids, intravenous immunoglobulins, plasmapheresis, rituximab, and cyclophosphamide. One of the major challenges of diagnosis is that existing reports on PSP-like patients with AE/PNS include only case reports, with the majority discussing antibodies other than anti-IgLON5 antibody. As such, more patients need to be evaluated to establish the relationship between antibodies and PSP-like manifestations.

The purpose of the present study was to investigate the effect of the laterally moving tactile stimuli to the sole on the anticipatory postural adjustment (APA) of the gait initiation. Thirteen healthy males participated in this study. A sound cue was provided at the beginning of each trial. The moving tactile stimuli were delivered to the sole after the start cue. The loci of the tactile stimuli moved from the left to right most side of the sole, and then moved from the right to left most side of that in a stimuli cycle. The duration of one stimuli cycle was 960 ms, and this cycle repeated 16 times in a trial. The participants made three steps forward from quiet stance at the participants' preferred time after the start cue. The APA did not onset at the specific direction or phase of the moving tactile stimuli, indicating that they did not use the stimuli as a trigger for initiating the gait. The moving tactile stimuli decreased the amplitude and increased the duration of the APA. The moving tactile stimuli increased the time between the APA onset and toe-off of the initial support leg, indicating that they moved slower when initiating gait during the moving tactile stimuli. Those findings are explained by the view that suppression of the APA induced by the moving tactile stimuli to the sole is caused by the decrease in the velocity of the gait initiation, and the slower velocity of the gait initiation is caused by masking tactile sensation of the sole.

Geometrical assessments of human skull have been done based on the anatomical landmarks. Automatic detection of the landmarks, if developed, will be a great help not only medically, but also anthropologically. An automated system with multi-phased deep learning networks to predict three-dimensional coordinate values of cranio-facial landmarks, was developed. From a publicly available database, computed tomography images of craniofacial area were obtained. They were digitally reconstructed into three-dimensional models. Sixteen anatomical landmarks were plotted on each of the models and coordinate values of them were recorded. Three-phased regression deep learning networks were trained respectively with 90 training datasets. For evaluation, 30 testing datasets were employed. Three-dimensional error for the first phase, testing 30 data, was 11.60 pixels in average. (1 pixel = 500 / 512 mm) For the second phase, it was significantly improved to 4.66 pixels. For the third phase, it was significantly progressed to 2.88. This was comparable to the gaps between the landmarks, plotted by two experienced practitioners. Our proposing method of multi-phased prediction, coarse detection first and narrowing down the detection area, may be a possible solution, within the physical limitation of memory and computation.

1) Background: Capturing patients’ medical histories significantly influences clinical decisions. Errors in this process lead to clinical errors, increase costs and dissatisfaction among physicians and patients. Physicians in developing countries are overloaded with patients and cannot always follow the proper history-taking procedure. The challenges are acknowledged; however, a comprehensive understanding of the status and the remedies remained unexplored. 2) Objective: This paper aims to investigate the workload, history-taking challenges, and the willingness of the physicians to accept digital solutions. 3) Methods: A cross-sectional online survey was conducted on 104 physicians across Bangladesh, featuring 22 questions regarding their professional environment, workload, digitization status of health records, challenges in history-taking, and attitudes toward adopting digital solutions for managing patient histories; 4) Results: 92.67% of the physicians face workloads, 88.46% struggle in medical history-taking, and only 4.81% use digital medical records. About 70% struggle to complete the necessary history-taking steps, emphasizing the urgent need for solutions. An AI-based Smart Health Gantt Chart (SHGC) system has been introduced for their instant feedback. 93.27% of physicians expressed their willingness to use such a system. 5) Conclusions: The proposed SHGC has the potential to enhance healthcare efficiency in developing nations, benefit physicians, and improve patient-centered care.

Background: Whole-body computed tomography (WBCT) is commonly employed for primary screening in pediatric patients experiencing out-of-hospital cardiac arrest (OHCA) without prehospital return of spontaneous circulation (ROSC). This study aimed to evaluate the cause of OHCA on WBCT and compare WBCT findings between ROSC and non-ROSC groups in non-traumatic pediatric OHCA cases in an emergency department (ED) setting. Methods: A retrospective analysis was conducted on 27 pediatric patients (mean age: 32.4 months; median age: 10 months) who experienced non-traumatic OHCA without prehospital ROSC and were transported to our tertiary care hospital between January 2013 and December 2023. WBCT scans were performed to investigate the cause of OHCA, with recorded findings in the head, chest, abdomen, and subcutaneous tissues. Results: In all cases, the direct causes of OHCA were undetermined, and WBCT identified no fatal findings. Statistical comparisons of CT findings between the ROSC and non-ROSC groups revealed significant differences. The non-ROSC group had a higher incidence of brain swelling, loss of cerebral gray-white matter differentiation, symmetrical lung consolidation/ground-glass opacity, cardiomegaly, hyperdense aortic walls, narrowed aorta, gas in the mediastinum, and hepatomegaly compared to the ROSC group. Conclusions: Although WBCT did not provide the direct cause of OHCA, it clarified several indicative findings for non-ROSC. These imaging findings could support clinical decision-making, offering objective criteria for discontinuing resuscitation in pediatric OHCA cases where prehospital ROSC is absent.

Quarry waste fines and eggshells are unavoidable wastes which relentlessly contribute to environmental load and pollution. Although a number of studies have suggested various methods for recycling, these wastes remain underutilized due to some technical constraints. In addition, no study has yet been explored on the possibility of combining quarry waste fines (QWF) and eggshell powder (ESP) for tobermorite synthesis. Tobermorite is the main component which primarily provides strength to the autoclaved aerated concrete products. For this purpose, this study seeks to evaluate the potential of QWF- ESP mix at 10%, 15% and 20% amounts of cement, respectively. The XRF, XRD, and TGA–DTA techniques were used to characterize the waste materials while physical and mechanical property tests and XRD analysis were performed on the autoclaved samples. It was found that QWF contains 53.77% SiO2, while ESP contains 97.8% CaO which are key components for tobermorite synthesis. This study also revealed that the mixture with only 10% cement has the highest compressive strength among the QWF-ESP samples. Furthermore, the formation of tobermorite in the samples was confirmed through XRD analysis. Hence, the hydrothermal curing of QWF –ESP can be further developed to produce functional tobermorite – bearing materials.

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.

Reactive oxygen species and reactive nitrogen species in semen are both essential for fertilization process; however, they become harmful at excessive levels, causing oxidative stress and nitrosative stress, respectively. Recently, oxidation–reduction potential (ORP) has been used as a marker for measuring oxidative stress, and this study investigated the possibility of comprehensively evaluating nitrosative stress. The correlation between standardized ORP (sORP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and NOx per unit sperm was tested. Based on the previously reported cutoff value, samples were classified into oxidative stress-positive and negative groups. Thereafter, a receiver operating characteristic curve was drawn on 8-OHdG and NOx, and each optimal cutoff value was determined. Both standardized 8-OHdG and NOx significantly correlated with sORP. Although both correlated significantly with sORP in the oxidative stress group, no correlation was found in the nonoxidative stress group. The optimal standardized 8-OHdG level to determine oxidative stress status was 0.52 ng/106 spermatozoa, and the standardized NOx was 0.17 µM/106 spermatozoa/mL. The ORP is a simpler and quicker assay that can comprehensively assess oxidative and nitrosative stresses. Optimal cutoff values for both stresses were established in this study.

Synthetic bone made of calcium phosphate is widely used for the clinical treatment of bone defects caused by trauma and bone tumors. Although synthetic bone is easy to use, its effects are only partial depending on the size and location of the bone defect, and there are many treatment options other than the use of synthetic bone. Various biodegradable polymers that are being considered for use as scaffolds for regenerative medicine are also being considered for use as synthetic bones; however, commercial synthetic bone products with performance comparable to that of calcium phosphate bioceramics have not yet been clinically applied. This review introduces the practice of bone regeneration therapy with synthetic bone and recent research on bone regeneration therapy with biodegradable polymers.

To reduce the cost of small wind turbines, a prototype of a butterfly wind turbine (6.92 m in diameter), a small vertical-axis type, was developed with many parts made of extruded aluminum suitable for mass production. An over-speed control system with movable arms that operated using centrifugal and aerodynamic forces was installed for further cost reduction. Introducing this mechanism eliminates the need for large active brakes and expands the operating wind speed range of the wind turbine. However, although the mechanism involving the use of only bearings is simple, the violent movement of the movable arms can be a challenge. To address this in the present study, dampers were introduced on the movable arm rotation axes to improve the movement of the movable arms. To predict the behavior of a movable arm and the performance of the wind turbine with the mechanism, a simulation method was developed based on the blade element momentum theory and the equation of motion of the movable arm system. Comparison of experiments and predictions with and without dampers demonstrated qualitative agreement. In the case with dampers, measurements confirmed the predicted increase in the rotor rotational speed when the shorter ailerons installed perpendicularly to the movable arms were used to achieve the inclination. The movable arm system with dampers is expected to be a useful device for vertical-axis wind turbines that are difficult to control.

With the inclusion of Internet Gaming Disorder (IGD) in both the DSM-5 and ICD-11, understanding the prevalence and diagnostic discrepancies is crucial for developing appropriate interventions. This study presents a meta-analysis of the prevalence of IGD based on two diagnostic criteria. We systematically searched PubMed, Web of Science databases. 17 studies were included in the final analysis, The analysis incorporated studies employing the DSM-5 and ICD-11 criteria and focused on the impact of various factors, including study location, sample size, and quality score, on the reported prevalence rates using a random-effects model. Heterogeneity and publication bias were analyzed using an I2 test and Galbraith plots , The prevalence of IGD varied among the selected studies, with a general pooled prevalence of 5% (95% CI: 3%–7%). Subgroup analysis indicated that the prevalence rates of IGD (DSM-5 criteria) and GD (ICD-11 criteria) do not show significant differences. DSM-5-based scales yielded varied results, while heterogeneity among the studies was high (I2 = 98.50). In contrast, ICD-11-based scales produced more consistent and less variable findings. Our findings highlight that assessment scales, not diagnostic criteria, impact IGD prevalence. This underscores the importance of adopting standardized methodologies to guide public health interventions. However, given the limited research based on ICD-11 diagnostic criteria, further investigation is necessary to determine the variations in prevalence rates of IGD under different diagnostic standards.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

To cope the high glycemic variability (GV) is crucial in the management of multiple daily insulin (MDI) in diabetes. We compared the effect of low dose metformin 750mg/d adding vildagliptin 100mg/d (DPP4+LMET) or the high dose metformin 1500mg/d (HMET), in type 2 diabetes (T2D) with MDI, evaluating GV by continuous glucose monitoring (CGM). Single center, open-label, 12 weeks - 2 period crossover design. Twenty T2D with inadequately controlled (7.0% <HbA1c ≦9.0%) with MDI + LMET were enrolled. Primary endpoints were GV and hypoglycemia derived from CGM performed after each 12 weeks treatment periods. There was no significant difference in HbA1c, body weight changes, total daily dose of insulin. DPP4+LMET compared to the HMET, significantly reduced the calculated GV value, mean (7.15±1.3 vs 7.82±1.6, p<0.05), standard deviation (1.78±0.55 vs 2.27±1.11, p=0.03), continuous overlapping net glycemic action (6.44±1.28 vs 7.12±1.69, p<0.05), J-Index (26.7±11.0 vs 34.9±19.8, p<0.05), high blood glucose index (3.01±1.96 vs. 6.73±4.85, p=0.02), and mean amplitude of glycemic excursions (4.53±1.35 vs 5.50±2.34, p=0.03). The GV metrics with hypoglycemia and nocturnal hypoglycemia were not significantly different. DPP4+LMET decreased GV associated with hyperglycemia. Adding DPP4 inhibitor to the lower dose of metformin is an alternative approach to the stable GV in MDI.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

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.

Abstract: Physicians, physical therapists, and occupational therapists have traditionally assessed hand motor function in hemiplegic patients but often struggle to evaluate complex hand move-ments. To address this issue, in 2019, we developed Fahrenheit, a device and algorithm that uses infrared camera image processing to estimate hand paralysis. However, due to Fahrenheit's de-pendency on specialized equipment, we conceived a simpler solution: developing a smartphone app that integrates MediaPipe. The objective of this study was to measure hand movements in stroke patients using both MediaPipe and Fahrenheit and to assess their criterion-related validity. The analysis revealed moderate-to-high correlations between the two methods. Consistent results were also observed in the peak angle and velocity comparisons across severity stages. Because Fahrenheit determines finger recovery status based on these measures, it has the potential to transfer this function to MediaPipe. This study highlighted the potential use of MediaPipe in pa-ralysis estimation applications.

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Background: The aim of this study was to demonstrate involvement of whole-body compensatory alignment in different conditions of spinopelvic sagittal balance (compensated/decompensated). Methods: We enrolled 330 healthy subjects and divided them according to sagittal vertical axis (SVA): the compensated group, < 4 cm, (group C) and the decompensated group, ≥ 4 cm, (group D). The correlation between lack of ideal lumbar lordosis (iLL), which is calculated by using the Schwab formula, and the compensatory radiographic parameters in each group were analyzed. The threshold value of KF angle that indicates a spinopelvic sagittal imbalance (SVA ≥ 4) was determined by ROC curve analysis. Results: Correlation analysis of lack of iLL and each com-pensatory parameter showed a strong correlation for pelvic tilt (PT) (r = -.723), and a weak cor-relation for thoracic kyphosis (TK) (r = 275) in Group C. In Group D, the correlations were strong for PT (r = -.796), moderate for TK (r = .462), and KF (r = -.415). The optimal cutoff value for KF angle was determined to be 8.4 degrees (sensitivity 89%, specificity 46%). Conclusions: The pre-sent study showed differences between compensated/decompensated spinopelvic sagittal balance in the correlation strength between lack of iLL and whole-body compensatory parameters.

Objective: Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection (“hybrid immunity”). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan.Methods: We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization.Results: The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately one year after coronavirus disease 2019 (COVID-19 diagnosis), even without booster vaccination.Conclusions: Most Japanese patients naturally infected with COVID-19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid-immunized cases is highly questionable regarding cost-effectiveness and risk-benefit.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

A change in the wettability of liquid sodium due to sodium implantation was evaluated theoretically. Interface models between sodium and a sodium-implanted substrate metal were created, and their electronic states were calculated. The discrete variational Xα cluster method was used in the calculations. The calculations show that the bond order, indicating the strength of the covalent bonds between atoms, decreases within the substrate metal and increases at the interface between sodium and the substrate metal due to sodium implantation. Their ratio, the bond order ratio, increased with the increasing sodium implantation. Previous studies have shown that wettability is better as the bond order ratio increases. Therefore, from the calculations results, wettability improves with increasing sodium implantation. The wettability of sodium-implanted metals was experimentally evaluated using the contact angle of the sodium droplets. The contact angle decreased, and the wettability improved due to sodium implantation. The change rate in the contact angle increased with the bond order ratio. The experimental and calculation results correlate well, without contradiction. In conclusion, sodium implantation changes the electronic state of the interface, affecting the wettability of liquid sodium.

Lung adenocarcinoma with EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) resistance was reported to harbor higher ability of invasion and migration than those sensitive to EGFR-TKI, but the function of MMPs (matrix metalloproteinases) has not been explored in EGFR-TKI resistant lung adenocarcinoma. In this study, the correlation between immunohistochemical status of MMP-1 and clinicopathological factors were analyzed in 89 lung adenocarcinoma. We performed microarray, migration assay and invasion assay using EGFR-TKI sensitive cell lines and EGFR-TKI resistant cell lines. To clarify the mechanism of MMP-1 induction, we treated lung adenocarcinoma cells with EGF and rapamycin, performed phosphorylation antibody array and analyzed the correlation between MMP-1 expression and EGFR or mTOR (mammalian target of rapamycin) pathway. As a result, we firstly demonstrated that MMP-1 played an important role in migration and invasion abilities of EGFR-TKI resistant lung adenocarcinoma, and that mTOR pathway could be associated with an induction of MMP-1. We demonstrated the significant positive correlation between MMP-1 status in lung adenocarcinoma cells and the history of smoking, and the subtype of invasive mucinous adenocarcinoma. In conclusion, This study provides insights into the development of a possible alternative therapy manipulating MMP-1 and mTOR signaling pathway in EGFR-TKI resistant lung adenocarcinoma.

For the diagnosis of disease, the ability to quantitatively detect trace amounts of the causal proteins from bacteria/viruses as biomarkers in patient specimens is highly desirable. Here we introduce a simple, rapid, and colorimetric assay as a de novo, ultrasensitive detection method. This ultrasensitive assay consists of sandwich enzyme-linked immunosorbent assay (ELISA) and thionicotinamide-adenine dinucleotide (thio-NAD) cycling, forming an ultrasensitive ELISA, in which the signal substrate (i.e., thio-NADH) accumulates in a triangular manner, and the accumulated thio-NADH is measured at its maximum absorption wavelength of 400 nm. We have successfully achieved a limit of detection of ca. 10–18 moles/assay for a target protein. As an example of infectious disease detection, HIV-1 p24 could be measured at 0.0065 IU/assay (i.e., 10⁻¹⁸ moles/assay), and as a marker for a lifestyle-related disease, adiponectin could be detected at 2.3 × 10⁻¹⁹ moles/assay. In particular, despite the long-held belief that the trace amounts of adiponectin in urine can only be detected using a radioisotope, our ultrasensitive ELISA was able to detect urinary adiponectin. This method is highly versatile, because simply changing the antibody enables the detection of various proteins. This assay system requires only the measurement of absorbance, thus it requires equipment that is easily obtained by medical facilities, which facilitates diagnosis in hospitals and clinics. Moreover, we describe an expansion of our ultrasensitive ELISA to a non-amplification nucleic acid detection method for nucleic acids using hybridization. These de novo methods will enable simple, rapid, and accurate diagnosis.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, QOL survey is difficult using patients. We created cancer scenarios and investigated QOL utility values among the general public using vignette-based methods. On the other hand, some scenarios may have been difficult for the general public to image and understand. Therefore, we conducted a QOL survey among physicians. This survey was conducted by interviewing physicians adminis-tering chemotherapy to patients for recurrent/metastatic pancreatic cancer. Responses were eval-uated using Composite Time Trade-Off (cTTO) and Visual Analog Scale (VAS) for 11 pancreatic cancer status scenarios to be evaluated (survey scenarios). Survey scenarios consisted of health state, type and Grade of adverse events. Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). Twenty responders answered in this survey, however two responses were excluded because of inconsistent responses. The stable disease had the highest QOL value for both assessment method. Whereas progression disease (PD) had the lowest QOL value. The physicians scored higher QOL values on VAS and cTTO than the general public in all survey scenarios. The QOL values obtained by physicians were consistent with the degree of sta-tus in any assessment scenarios.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

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.

MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dog is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MicroRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor microRNAs (miRNAs), we report 30 oncogenic miRNAs in COM. Expression of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had significant negative co-relation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors in respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA’s profile in COM which will be a useful resource for developing therapeutic interventions in both species.

Observation of the ambient aerosol surface area concentrations is important to understand the aerosol toxicity because an increased surface area may be able to act as an enhanced reaction interface for certain reactions between aerosol particles and biological cells, as well as an augmented carrier surface for co-pollutants. In this study, the concentration of aerosol surface area was measured from April 2015 to March 2016 in Fukuoka, Japan. We investigated the monthly and diurnal variations in the correlations between the aerosol surface area and black carbon (BC) and sulfate concentrations. Throughout the year, aerosol surface area concentration was strongly correlated with the concentrations of BC, which has relatively large surface area since BC particles are usually submicron agglomerates consisting of much smaller (tens of nanometers) sized primary soot particles. The slopes of the regression between the aerosol surface area and BC concentrations was highest in August and September 2015. This appears to have been the results of an increase in the proportion of the airmass that originated on the main islands of Japan. This may enhance the introduction of the BC from the main islands of Japan that is relatively fresh (or “uncoated”), thereby maintaining its larger surface area.

Background Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone with aging, and is associated with various symptoms, including lower urinary tract symptoms (LUTS). Although some reports have shown that testosterone replacement treatment for LOH improved LUTS, no large study has revealed a correlation between LUTS and LOH. This study investigated the correlation between the severity of LOH and LUTS in Asian Japanese males of >40 years of age using a web-based questionnaire. Methods We asked a total of 2,000 Japanese male individuals to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2,000 individuals, 500 individuals were assigned to each of the following age groups: 40-49, 50-59, 60-69, and ≥70 years. LOH symptoms were assessed by AMS score as no/little (17-26 points), mild (27-36 points), moderate (37-49 points), and severe (≥50 points). To compare the risk of voiding and storage dysfunction according to the severity of AMS, voiding dysfunction was assessed by the sum of IPSS Q1, Q3, Q5, and Q6, while storage dysfunction was assessed by the sum of IPSS Q2, Q4, and Q7. Results The IPSS total score was positively correlated with the severity of AMS (shown as median [mean±SD]): no/little group, 2 (3.67±5.36); mild group, 6 (7.98±6.91); moderate group, 11 (12.49±8.63); and severe group, 16 (14.83±9.24) (p<0.0001). The prevalence of an IPSS total score of ≥8 in the AMS severity groups was as follows: no/little group, 13.3% (111 of 834); mild group, 38.3% (225 of 587); moderate group, 64.2% (244 of 380); severe group, 72.4% (144/199). The prevalence of nocturia in the AMS severity groups was as follows: no/little group, 19.8% (165 of 834); mild group, 31.5% (185 of 587); moderate group, 43.9% (167 of 380); and severe group, 50.8% (101 of 199). Conclusions Individuals with higher AMS values, which represents severe LOH symptoms, showed a higher risk of nocturia and LUTS.

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adult, it is rare in early infant. Methods: Clinical testing was performed as part of medical evaluation and management. Next gene se-quencing (NGS) was performed for a patient with TIC. Literature review about TIC was con-ducted. Results: The case was a 5-month-old infant referred the hospital due to symptoms with heart failure at least lasting two months. Heart rate was 200 beats per minute, left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardiover-sion, there was no recurrence of atrial flutter, and cardiac function was improved at 98 days after tachycardia arrest. There were no pathogenic variants identified according to NGS. Literature review identified 8 early infantile cases with TIC reported. However, there were no previous re-ports such as our case with longer duration of TIC. Conclusions: Improvement of cardiac function depends on the duration of TIC. TIC should be considered in all patients with a dilated cardiomyopathy of uncertain origin and who have tachycardias such as atrial flutter.

This study examined the patterns of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between histopathological severity of EFEMP1 deposition and constipation and determine if amyloid transthyretin (ATTR) and EFEMP1 deposits can colocalize. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage); progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage); and finally, spreading diffusely to areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. We identified a subgroup of cases in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings emphasize that EFEMP1 deposits may be associated with lower gastrointestinal pathological conditions. Given the challenges of histopathological diagnosis on Congo red-stained specimens, we recommend the combined use of elastic fiber staining and immunohistochemistry for EFEMP1 to prevent overlooking this deposition.

Deep-ultraviolet (UV) light-emitting diodes (LEDs) based on AlGaN crystals have low light-emission efficiency; therefore, there is a need to improve this light-emission efficiency for a wide range of applications such as water and air sterilizations. UV-light-transparent device structures are considered one of the many solutions toward increasing light output power. To this end, the present study focused on developing a transparent AlGaN-based tunnel junction (TJ) as the anode of a deep-UV LED. Deep-UV LEDs composed of n+/p+-type AlGaN TJs were fabricated under the growth condition that reduced the carrier compensation in the n+-type AlGaN layers. The operating voltage was 10.8 V under the direct current (DC) operation of 63 A/cm2. In addition, magnesium zinc oxide (MgZnO)/Al reflective electrodes were fabricated to enhance the output power of the AlGaN homoepitaxial TJ LED. The output power was 57.3 mW under a DC operation of 63 A/cm2, and it was 1.7 times higher than that realized using the conventional Ti/Al electrodes. The combination of the AlGaN-based TJ and MgZnO/Al reflective contact allows further improvement of the light output power. This study confirms that the AlGaN TJ is a promising UV-transmittance structure that can obtain a high light-extraction efficiency.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

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.

The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells (CD8+ T cells, NK cells, etc.) are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in the offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that MBW of &lt;2,500 g (low MBW) was associated with increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while MBW of ≥4,000 g (high MBW) with congenital anomalies of the urinary tract (2.194, [1.261–3.819]), and arrhythmia (1.775, [1.157–2.725]), compared with those with MBW of 3,000-3,499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs(1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease(1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Clupeiformes, such as sardines and herrings, represent an important share of worldwide fisheries. Among those, the European sardine (Sardina pilchardus, Walbaum 1792) exhibits significant commercial relevance. While the last decade showed a steady and sharp decline in capture levels, recent advances in culture husbandry represent promising research avenues. Yet, the complete absence of genomic resources from sardine imposes a severe bottleneck to understand its physiological and ecological requirements. We generated 69 Gbp of paired-end reads using Illumina HiSeq X Ten and assembled a draft genome assembly with an N50 scaffold length of 25579 bp and BUSCO completeness of 82.1% (Actinopterygii). The estimated size of the genome ranges between 655 and 850 Mb. Additionally, we generated a relatively high-level liver transcriptome. To deliver a proof of principle of the value of this dataset, we established the presence and function of enzymes (elovl2, elovl5 and fads2) that have pivotal roles in the biosynthesis of long chain polyunsaturated fatty acids, essential nutrients particularly abundant in oily fish such as sardines. Our study provides the first omics dataset from a valuable economic marine teleost species, the European sardine, an essential resource for their effective conservation, management and sustainable exploitation.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

Arterivirus can establish persistent infection in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some Arterivirus can even cause overt and severe diseases such as Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs, leading to huge economic losses. Arterivirus have evolved viral proteins to antagonize the host cell’s innate immune responses by inhibiting type I interferon (IFN) signaling, assisting viral evasion and persistent infection. So far, the role of the Arterivirus glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 Arterivirus GP5 proteins derived from various hosts. We demonstrated that all GP5 proteins showed conserved activity for antagonizing TIR-domain-containing adapter protein inducing interferon-β (TRIF)-mediated IFN- signaling through TRIF degradation. In addition, Arterivirus GP5 proteins showed conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain Arterivirus GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of Arterivirus GP5 proteins in supporting persistent infection.

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (9 males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p &lt; 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibres of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasise that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection.

Background: We investigated the tumor immune response in gastric cancer patients receiving third line nivolumab monotherapy to identify immune-related biomarkers for better patient se-lection. Methods: Nineteen patients (10 males, median age 67 years) who received nivolumab as a third or later line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. Results: DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR, OS, PFS) to previous trials. Individual immunograms showed no significant changes before and ear-ly-on-treatment, nor consistent alterations among DCB cases. The intratumoral immune response was suppressed by previous treatments in most third or later line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in on-treatment tumors, but clonal re-placement did not impact efficacy. High T cells/Tregs ratios and a low UV radiation response gene signature were linked to DCB and treatment response. Conclusions: This study emphasizes the tumor immune response's importance in nivolumab ef-ficacy for gastric cancer. High T cells/Tregs ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. Larger cohort validation is crucial to optimize immune checkpoint inhibitors in gastric cancer treatment.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic [GTC] and National Defense Medical College hospital [NDMC]) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D&lt;8) and a depression group (HAM-D≥8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at GTC and 1% (p = 0.0038) at NDMC was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for GTC, and the AUC for NDMC was 0.70. The relationship between arousal level and depression severity was indirectly suggested via ALVI.

Background: A challenge in locally advanced, unresectable pancreatic cancer treatment is to achieve both survival benefits and a safe margin-negative resection. There is no robust evidence regarding the treatment of patients with unresectable pancreatic cancer. Methods: We conducted a prospective, single-arm, phase II trial in patients with unresectable pancreatic cancer using the FOLFIRINOX regimen. After completing 4–8 cycles, patients underwent surgical resection when feasible. The primary endpoint was the R0 resection rate. Results: Fifteen patients were enrolled in this study. This study was terminated without reaching the prespecified accrual target due to low accrual rate. A median of six courses of FOLFIRINOX chemotherapy was administered, and a partial response or R0 resection was achieved in 26.7% or 33% of the patients, respectively. Se-vere adverse events due to chemotherapy and major surgical complications were observed in 33.3% and 6.7% of patients, respectively. The median overall survival rate of patients who un-derwent R0 resection or with R1 or unresectable disease was 47.8 months (95% CI, 22.5–73.1) or 14.5 months (95% CI, 11.8–17.2), respectively (P=0.031). Conclusions: Well-selected patients with URLA-PC treated with FOLFIRINOX achieved a relatively high rate of R0 resection and had pro-longed survival. Therefore, induction FOLFIRINOX is feasible and well-tolerated for locally ad-vanced, initially unresectable pancreatic cancer, and may be effective in facilitating R0 resection and prolonging survival. This should be further assessed in future randomized multicenter trials.