Search Results (3,284)

Background: Inhibition of histone deacetylase is a highly sought-after objective in the fight against cancer. Thus, the development of innovative HDAC inhibitors with significantly higher potency than SAHA against specific cancer cell types represents complex and demanding work. Method: The utilization of the underexplored and privileged scaffold 4-chlorothieno[2,3-b]pyridine as a cap tethering diverse aliphatic and aromatic linkers, followed by the screening of both cellular and enzymatic activities, is undertaken in this study. Results: Compounds 7a and 9a demonstrated impressive mean GI₅₀ values of 2.15 µM and 1.89 µM, respectively. Both compounds reduced caspase-3 levels in RPMI-8226 cells, suggesting induction of apoptosis. Compound 7a showed remarkable IC₅₀ values of 0.37 µM, 0.58 µM, and 0.70 µM against HDACs 1, 4, and 6, respectively, consistent with the cellular assay. Additionally, compound 7a exhibited a selectivity index of 11 for RPMI-8226 cells over PBMCs, reflecting its high selectivity and potential safety. Moreover, ADMET prediction tools indicated that compounds 7a and 9b may have more favorable pharmacokinetic properties than the gold-standard HDAC inhibitor, SAHA. Conclusion: Further study and exploration of the derivatives of compounds 7a and 9a can lead to further advancement in the development of potent HDAC inhibitor anticancer drugs. Full article

Hepatic encephalopathy is a severe complication of liver failure, traditionally investigated through brain–liver interactions; however, the involvement of extrahepatic organs remains poorly understood. This study examined splenic histopathological changes in a mouse model of acute hepatic encephalopathy induced by ammonium acetate administration, focusing on iron metabolism and macrophage activation. Although conventional hematoxylin and eosin staining revealed no overt structural abnormalities, unstained spleen sections demonstrated abundant black deposits, predominantly in the red pulp. Prussian blue staining confirmed a significant increase in hemosiderin-positive cells; however, a subset of black deposits was iron-negative. Immunohistochemical analyses revealed that these iron-negative pigments were localized within F4/80-positive macrophages and colocalized with heme oxygenase-1 (HO-1), suggesting enhanced heme degradation. Ultrastructural observations further identified electron-dense granules consistent with hematin accumulation in splenic macrophages. Hematological analyses revealed significant reductions in red blood cell count and hemoglobin levels, indicating accelerated erythrocyte destruction. Collectively, these findings demonstrate that acute hepatic encephalopathy induces splenic macrophage activation, accompanied by disordered iron metabolism and hematin accumulation. This study highlights the spleen as a previously underappreciated extrahepatic organ involved in the pathophysiology of hepatic encephalopathy and suggests that splenic heme–iron handling may represent a novel therapeutic target. Full article

Facial aging is primarily characterized by the loss and disorganization of the dermal extracellular matrix (ECM), particularly collagen. Injectable biostimulators, such as calcium hydroxyapatite (CaHA), represent a vital non-surgical strategy to counteract these changes by inducing neocollagenesis. This 90-day clinical trial was designed to comparatively evaluate the efficacy of a novel regenerative solution (RS) diluent, formulated to potentially enhance the biostimulatory effects of standard CaHA (STIIM product), against a conventional diluent (control) for the treatment of facial laxity. Twenty-one subjects (N = 21) were randomized to receive CaHA diluted with either RS or control formulation. Efficacy was assessed using histological analysis (collagen I area percentage), ultrasound (US) for dermal density, and clinical laxity scoring. Histological analysis, although limited by a small subsample size (N = 3), showed qualitative and exploratory evidence of collagen remodeling in both groups. However, the RS group showed enhanced dermal thickening via US (15% increase vs. 5% control, p-value = 0.012), and improvement in clinical laxity. Furthermore, histological findings, including Picrosirius red staining, indicated that the RS group resulted in qualitatively greater ECM organization and more robust type I collagen fibers compared to the control. The novel regenerative solution is safe and demonstrates enhanced neocollagenesis and clinical efficacy over the conventional formulation, validating its potential as a diluent for CaHA for optimized facial rejuvenation. Full article

Background/Objectives: With increasing life expectancy, interest in healthy aging has grown substantially. Dietary habits are among the key factors that contribute to achieving healthy aging. This study analyzes the relationship between dietary habits and the age–health association in older adults, using the first two years of data from an ongoing annual cohort study conducted in a region of Japan. Methods: We used observational data from approximately 1200 community-dwelling males and females aged 55 to 75 at baseline, drawing on the first two years of a ten-year annual cohort study conducted from 2023 to 2032. First, dietary habits were classified using an ordinal latent block model (OLBM), a model-based clustering approach applied to food frequency questionnaire (FFQ) data. We then examined whether the age–health gradient—measured across 33 indicators—differed significantly across the derived dietary habit types, using random effects models. Results: Dietary habits in the analyzed sample were categorized into six distinct types. Parameter estimates from the model suggest that the extracted patterns represent a continuum ranging from low to high dietary diversity. Regression analyses indicated that, in females, a negative association between age and LDL-C levels was observed among those with highly diverse dietary habits. Conclusions: The data-driven classification of dietary habits based on FFQ responses highlights the potential importance of dietary diversity. Full article

Postbiotics produced by beneficial bacteria are emerging as safe dietary approaches to intestinal inflammation. We evaluated intestinal bacterial metabolites (IBM), a cell-free fermented soybean extract generated by co-culturing 31 Lactobacillus/Bifidobacterium-related strains, for prophylactic protection in 3% dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6NJ mice received oral IBM (0.4 or 2 mL/kg/day) or vehicle for 7 days before and during 7 days of DSS. Disease activity index (DAI), colon length, and histopathology were assessed, and endpoint serum cytokines were quantified by a multiplex bead assay. DSS-independent responses were examined in healthy mice after 7 days of IBM by rectal RNA sequencing and cecal 16S rDNA profiling, and direct epithelial effects were tested in HCT-116 and DLD-1 cells treated with 2% IBM. IBM attenuated colitis, improving DAI, preventing colon shortening, and ameliorating histopathology, with decreased IL-23 and IL-17A and increased IFN-β and GM-CSF. Rectal transcriptomics showed modulation of circadian programs, upregulation of mucosal/barrier genes, and reduced extracellular-matrix remodeling signatures. IBM increased junctional proteins and barrier-related transcripts in vitro and shifted the microbiota, increasing Lactobacillus and Roseburia while decreasing Streptococcus and Staphylococcus. These coordinated clinical, immunological, transcriptomic, epithelial, and microbiome changes support prophylactic protection by IBM against DSS colitis. Full article

Salinity is a major abiotic stress limiting rice production worldwide. This study aims to elucidate the effects of heading date on salt tolerance in rice. Five near-isogenic lines (NILs) developed from the SL2038/Koshihikari backcross population were grown with or without salt stress. SL2038 is a salt-tolerant line with delayed heading (~18 days) compared to the salt-sensitive background Koshihikari. The results showed that late-heading NILs produced significantly higher plant dry weight, panicle weight, percentage of filled grains, and grain weight (p < 0.05) under long-term salt stress. In Koshihikari, which exhibited delayed heading due to long-day treatment, the percentage of white heads was low, and panicle and grain weights were significantly higher under salt stress. Experiments with different sowing times indicated that late heading, such as sowing in June, resulted in higher grain weights. This is the first report to assess the impact of heading date on agronomic and yield-related traits under salt stress. In conclusion, even with a prolonged salt treatment period, heading during periods of low temperature and solar radiation results in higher grain weight under salt stress. This is proposed as one of the strategies for salt escape. These findings can be used to improve rice yield and implement crop management in salt-affected regions. Full article

Recently, piecewise differential operators have been introduced to capture crossover dynamics in physical systems. In the evolution of corruption, the underlying dynamics can shift across different regimes. These crossovers occur due to policy changes, economic shocks, or shifts in social behavior. To demonstrate the crossover dynamics of a corruption mathematical system, we use a piecewise operator. The piecewise operator is divided into three pieces: a classic or integer order operator, a fractional operator, and a stochastic operator. For the fractional order case, we use the constant proportional Caputo (CPC) operator, which is a straightforward linear combination of the Riemann–Liouville (RL) integral and the Caputo derivative. Theoretical analysis such as existence and uniqueness of solutions for the fractional case under CPC derivative, is elucidated via notions of fixed point theory, specifically the implication of Perov’s fixed point result and for the stochastic model using Ito calculus. Numerical results are presented for the proposed model. Graphical analysis of the corruption model is performed using PW operators across three distinct intervals to portray the crossover dynamics of the considered system. Also, the influence of various parameters on the crossover dynamics of the corruption model is illustrated via numerical simulations. Sensitivity of parameters is demonstrated via some statistical experiments, such as scatter plots and Pearson correlation coefficients, quantifying the relationship between key parameters of the system. The validity of the result is verified by comparing the system dynamics with real data dynamics via 2D graphs. Full article

The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular interface between gene-specific transcription factors and RNA polymerase II (Pol II). Although its overall architecture and general role in transcription have been extensively reviewed, accumulating genetic, genomic, and clinical evidence indicates that individual Mediator subunits make distinct and non-redundant contributions to human physiology and disease. In this review, we move beyond a generic description of Mediator function and present a subunit-resolved synthesis of Mediator biology with an emphasis on disease pathogenesis. A key feature of this review is a comprehensive table integrating disease associations and molecular functions of individual human Mediator subunits, enabling rapid assessment of functional specialization across the complex. We further discuss chromatin-based mechanisms of Mediator action, including cooperation with cohesin and architectural factors to regulate enhancer-promoter communication and higher-order genome organization. By organizing recent structural, mechanistic, and pathological findings into a unified framework, this review highlights how disruption of specific Mediator subunits contributes to cancer, developmental disorders, and metabolic disease, and outlines emerging opportunities for therapeutic intervention. Full article

Background: Osteotomy around the knee (OAK) is a joint-preserving surgery for knee osteoarthritis, yet some patients experience suboptimal outcomes. Preoperative identification of high-risk patients remains challenging. This study aimed to develop a machine learning model to predict clinical outcomes after OAK using preoperative gait acceleration data from inertial measurement units (IMUs). Methods: This multicenter prospective study enrolled patients undergoing OAK. Preoperative gait was recorded using synchronized IMUs placed on the lumbar spine and tibia. Lumbar and tibial signals were used for gait-cycle segmentation, while wavelet-based time–frequency features were extracted from tibial acceleration only. Outcomes were defined by achievement of the minimal clinically important difference in ≥3 KOOS subscales at 2-year follow-up (Good vs. Poor). Continuous wavelet transform features (5–20 Hz) were summarized as mean and standard deviation across six stance subphases. A Random Undersampling Boost classifier was trained and evaluated using nested leave-one-subject-out cross-validation. A sensitivity analysis using logistic regression confirmed that the IMU-based prediction score was independently associated with outcome after adjustment for baseline KOOS (p = 0.047). Results: Of 67 enrolled patients, 37 were classified as Good and 30 as Poor outcome. For machine learning analysis, 1173 tibial acceleration gait-cycle waveforms were usable. The model achieved an AUC of 0.744 (95% CI, 0.610–0.860) using a median of 15 features (range, 5–25) with sensitivity of 0.69 and specificity of 0.72. The most informative predictors were the mean magnitude in the 5–8 Hz band during loading response (0–17%) and variability in the 5–8 Hz band during late stance (67–83%). No significant differences in baseline demographics or radiographic parameters were found between outcome groups. Conclusions: Preoperative IMU-derived gait acceleration features showed moderate-to-good discrimination between outcome groups and may support preoperative risk stratification and individualized perioperative management. Full article

In response to the significant challenges posed by the rapid progress of multi-spectral detection technologies to traditional stealth techniques, this paper presents a flexible transparent metasurface structure that is compatible with radar and infrared stealth. It consists of multi-layer functional patterned indium tin oxide (ITO) films and a flexible polydimethylsiloxane (PDMS) substrate. The metasurface uses a high-duty-cycle multi-scale circular ring to achieve a microwave absorption bandwidth of 30 GHz and low infrared emissivity of 0.33 in an optimized ultra-thin 2.65 mm thickness system. The simulation results show that the metasurface achieves absorption exceeding 90% in the frequency range of 10.8–40.8 GHz, which covers common radar bands like X, Ku, K, and Ka. Furthermore, the structure exhibits polarization insensitivity and sustains stable absorption in a wide range of 60 degrees of transverse magnetic (TM) fields. Meanwhile, it decreases the radar cross-section (RCS) by more than 10 dB over a wide angular range even when bent. This study presents a feasible metasurface with ultra-thin, flexible, transparent, and multi-spectral compatibility for the next generation of stealth systems. Full article

Background/Objectives: Integrating technology with caring is essential in modern healthcare, yet the clinical applicability of nursing theories remains underexplored. Locsin’s Technological Competency as Caring in Nursing (TCCN) theory emphasizes the competent use of technology to address patients holistically, rather than focusing solely on health concerns. Here, we explored the interpretive clarity of the TCCN Instrument–Revised for Practice (TCCNI-RePract) items and identified the conceptual barriers encountered by psychiatric nurses when engaging with its theoretical constructs. Methods: This concurrent mixed-methods study surveyed 291 psychiatric nurses across five large hospitals in the Kansai region of Japan. Quantitative data on the TCCNI-RePract perception dimension were examined using descriptive statistics and normality testing. Qualitative open-ended responses were analyzed using reflexive thematic analysis. To ensure rigor and integration, a joint display was utilized to bridge both data strands. Results: Quantitative findings indicated that nurses strongly endorsed core values of caring (high agreement) but perceived theoretical constructs (wholeness and technological knowing) as significantly more difficult to interpret than concrete, behavior-oriented items. Qualitative analysis revealed four major themes: (1) fragmented understanding of “technology and caring,” (2) struggles with abstract and philosophical language, (3) moral and emotional tensions in caring relationships, and (4) contextual barriers to integrating caring and technology. We found a “semantic gap,” where the professional endorsement of caring values was not automatically translated into the mastery of theoretical lexicon. Conclusions: While psychiatric nurses identify with the moral core of TCCN, a substantial gap exists between abstract theory and clinical practice. For effectiveness, middle-range theories require “clinical translation” that resonates with the moral, emotional, and organizational realities of psychiatric settings. Full article

Polytetrafluoroethylene (PTFE) is attractive for high-frequency communications but adheres very poorly to other materials due to its very low surface energy. Conventionally, surface treatments of PTFE are used to increase the polarity of the PTFE surface and enable bonding to materials with increased surface free energy. However, surface treatments are difficult to scale, can damage surfaces, and often lack reproducibility. Therefore, developing a material that can make PTFE adhere well to other materials without surface treatment is highly desirable. In this study, we aimed to develop a new material with strong adhesion to PTFE. We synthesized three polymer gels from dodecyl acrylate (DA) and 2-(dimethylamino) ethyl acrylate (DMAE): the homopolymer gels PDEAE and PDA, and the copolymer gel P(DEAE-co-DA). The copolymer gel P(DEAE-co-DA) exhibited high pressure-sensitive adhesion to PTFE, recording the highest adhesive strength (F = 430.0 N/m) and the highest peel energy (G = 713.4 J/m²) compared to the homopolymer gels PDEAE and PDA. Mechanical testing showed PDEAE had the greatest strength and toughness, PDA balanced stiffness and extensibility, and P(DEAE-co-DA) was the most flexible and extensible. The P(DEAE-co-DA) with the smoothest surface (Sz ≈ 0.176 µm) showed the highest F and G, implying that surface roughness did not contribute significantly to the interfacial adhesion between the gels and the PTFE. Based on the surface free energy ${\sigma }_s$ and work of adhesion $W_a$ values, the adhesive strength to PTFE was predicted to be PDEAE > P(DEAE-co-DA) > PDA, but the measured G in peel tests contradicted this, indicating that the gels’ viscoelastic deformation and energy dissipation dominate the measured F and G. The frequency-dependent viscoelastic data and relaxation times τ and activation energies $E_a$ suggested optimal adhesion requires a balance of adhesion (mobility for energy dissipation (short τ, low $E_a$)) and sufficient cohesion (high G′). P(DEAE-co-DA) achieved this balance, explaining its high measured F and G. With precise control of polymer chain mobility, the adhesion of P(DEAE-co-DA) gels can likely be improved further. Future work will employ block copolymerization and monomer-ratio control to tune molecular motion and enhance adhesion to PTFE. Full article

Background/Objectives: Comprehensive Geriatric Assessment (CGA) is essential for maintaining quality of life (QOL) and independence in older adults. Still, its implementation is labor-intensive and difficult to sustain in aging societies such as Japan. Digital technologies may enable continuous, scalable CGA in daily living environments. This study aimed to develop and preliminarily evaluate a digital CGA (D-CGA) framework by integrating data from multiple monitoring devices, as a preparatory step toward Artificial Intelligence (AI)-supported personalized care planning. Methods: Four devices (Handy, Apple Watch, Withings Sleep, and Vieureka) were selected. Due to ethical constraints in Japan, a pilot study was conducted with graduate students. Participants underwent continuous monitoring for five weekdays. Common and device-specific measurement items were extracted, visualized, and compared across devices. Heart rate data were examined using correlation-based analyses. Baseline CGA was conducted before monitoring. Results: Distributional and temporal characteristics of physiological measures were explored separately for daytime and nocturnal periods. Continuous heart rate and respiratory rate data were successfully collected across monitoring days, demonstrating the feasibility of real-life data acquisition using the selected devices. Heart and respiratory rates showed distinct distributional patterns between daytime and nocturnal periods, supporting context-specific physiological characterization. Conclusions: This pilot study demonstrates the feasibility of integrating multi-device data for D-CGA and provides foundational reference data for future studies of older adults. The results support the potential of D-CGA to inform personalized care and guide subsequent large-scale and clinical investigations. Full article

Observations of photoelectric conversion in Fe- and Mn-rich semiconductor mineral coatings highlight their potential role in the origin of life and the evolution of environmental conditions. However, natural silicate minerals, which make up most of the Earth’s crust, are generally considered wide-bandgap insulators and are not expected to exhibit a photoelectric effect. In this study, we experimentally confirm measurable impurity-like photoelectron activity in natural silicate minerals and explore possible regulatory mechanisms. We show that electron-active elements (e.g., structural Fe and Ti) and lattice defects in minerals such as pyroxene and mica can reduce the optical gap (E_opt) to below ~4.13 eV, producing small photocurrents ranging from 0.010 to 0.114 μA/cm² on ITO substrates (background signal excluded). The structural types of these minerals—chain, island, layer, and framework—may influence their photoelectric responses by affecting electron transport pathways. Notably, light wavelength strongly controls both the photoelectric relative activity (PRA = 3–10 for silicates) and the decay kinetics (0.002–0.021 s⁻¹) of minerals. Visible light (400–800 nm) markedly enhances photocurrent densities in low-bandgap minerals such as limonite (E_opt = 2.11 eV). In contrast, ultraviolet light (UVB, 300 nm) enhances photoelectric responses in high-bandgap minerals, including feldspar and quartz (E_opt = 4.31 and 6.08 eV, respectively). Multivariate statistical analysis further indicates that elemental composition governs spectroscopic features that influence photoelectric behavior. Among these, Fe, Al, Si, and Ti are identified as key regulatory elements. These results provide new insights into the role of natural silicates in photoelectron-driven environmental and geological processes and highlight the potential of silicate-based materials for solar energy conversion applications. Full article

Background/Objectives: Clinical remission (CR) is an ambitious and attainable treatment goal for asthma; however, CR definitions vary. Evidence of CR in Japanese patients with moderate-to-severe asthma on inhaled therapies is lacking and was evaluated based on three guideline definitions: the United States Workgroup consensus statement, Japanese Guidelines for adult asthma (JGL), and Practical Guidelines for Asthma Management (PGAM). Methods: Post hoc analysis of Phase III studies including Japanese participants: Japanese subpopulation of CAPTAIN (NCT02924688) and a 52-week Japanese long-term safety study (NCT03184987). CAPTAIN randomized participants to once-daily fluticasone furoate/vilanterol (FF/VI) regimens ± umeclidinium (UMEC). The long-term safety study allocated participants to once-daily FF/UMEC/VI based on asthma control status. All three CR definitions assessed systemic corticosteroid use, severe exacerbations, and asthma control (Asthma Control Questionnaire-5 <1.5 [Workgroup] or ≤0.75 [JGL/PGAM]); Workgroup and JGL also assessed lung function (change from baseline in trough forced expiratory volume in 1 s of ≥0 [stabilized] or ≥100 mL [optimized]). Results: CR attainability varied on definition and thresholds used. At Week 24 in the CAPTAIN Japanese subpopulation, 34–59% and 18–45% of participants (Workgroup; stabilized and optimized), and 21–34% and 8–24% (JGL; stabilized and optimized) met CR criteria across treatment arms. At Week 52 in the long-term safety study, equivalent figures for CR achievement were 33–60%, 22–45%, 11–28%, and 11–23%. Conclusions: This analysis demonstrates that CR, using different definitions and criteria, is an attainable treatment goal with inhaled therapy in Japanese patients with moderate-to-severe asthma not yet eligible for biologics. Full article