Search Results (14,292)

A novel composite adhesive for lacquer film restoration was developed by modifying natural lacquer with Tween-20, soy protein isolate (SPI), and nano-SiO₂ to address the bonding failure and interfacial instability of glyoxal-dehydrated lacquerware. The optimal formulation (70% lacquer, 10% Tween-20, 15% SPI, 5% nano-SiO₂) achieved a shear bond strength of 3.8 ± 0.3 MPa, corresponding to a 58% increase compared with pure lacquer (2.4 ± 0.2 MPa). After 30 days of immersion in a pH 4.0 acidic solution, the adhesive retained 91 ± 3% of its initial shear strength, significantly higher than that of pure lacquer (65 ± 5%). Under accelerated aging conditions (50 °C and 95% relative humidity), the composite adhesive exhibited minimal weight gain (1.0 ± 0.2%) and no visible mold growth, whereas pure lacquer showed greater moisture uptake (3.0 ± 0.4%) accompanied by evident fungal colonization. The cured film displayed good color compatibility (ΔE ≈ 2.0) and improved flexibility (elongation at break: 12.5% vs. 4.2%). XPS and FTIR analyses suggested enhanced interfacial bonding through hydrogen-bond interactions and possible Si–O–C linkages at the wood–lacquer interface. Practical restoration of a Warring States period lacquer ear cup (China) demonstrated effective and stable reattachment of detached fragments with satisfactory visual integration and long-term durability. Overall, this work provides a compatible and durable material strategy for the conservation of glyoxal-dehydrated lacquerware. Full article

Metabolomics and lipidomics enable comprehensive profiling of metabolic states across diverse diseases and have generated a vast number of candidate biomarkers. Despite this progress, only a small fraction of metabolite-based biomarkers have achieved durable clinical translation. While this gap is often attributed to biological complexity or limited cohort size, increasing evidence suggests that failure more commonly reflects systematic misalignment between analytical measurement, biological interpretation, and clinical decision-making requirements. In this review, we argue that metabolites are not intrinsically unreliable biomarkers but are frequently overinterpreted as disease-specific indicators despite being highly context-dependent reporters of physiological state. We synthesize recurrent failure modes across the translational pipeline—including pre-analytical instability, ionization bias and semi-quantitative measurement, structural and annotation ambiguity, statistical overfitting, loss of disease specificity under systemic stress, and cohort-dependent performance collapse. Building on these insights, we propose a structured roadmap for the clinical translation of metabolite and lipid biomarkers. Rather than emphasizing further discovery, this framework prioritizes decision-oriented eligibility criteria encompassing pre-analytical robustness, analytical validity, molecular definition, biological interpretability, validation under real-world heterogeneity, and alignment with clinical utility and regulatory expectations. By reframing metabolic biomarkers as context-sensitive measurements embedded within clinical decision systems, this review provides practical guidance for investigators, clinicians, and regulators seeking to translate metabolomics and lipidomics into reliable tools for clinical practice. Full article

Background/Objectives: In metastatic colorectal cancer (mCRC) the evaluation of mismatch repair (MMR) and microsatellite instability (MSI) status is essential to identify patients eligible for treatment with immune-checkpoint inhibitors (ICI). This study aims to evaluate the potential utility of Comprehensive Genomic Profiling (CGP) in assessing MSI status, in addition to other immunotherapy-predictive biomarkers such as high tumor molecular burden (TMB) and the POLE and POLD1 mutations. Methods: A total of 138 mCRC tumor samples underwent a first-level molecular test (MMR status by immunohistochemistry, MSI by a melting-based PCR approach and RAS/BRAF mutational status by a small next-generation sequencing (NGS) panel) and second-level CGP analysis by the FoundationOne CDx assay. The prevalence of dMMR and MSI tumors was reported. Moreover, the concordance between the MMR and MSI status was determined, and discordant cases were discussed. Results: Twelve cases (8.7%) were MMR-deficient (dMMR); 10 showed high MSI and TMB (>10 mut/Mb). MSI status assessed by CGP and PCR was concordant in all cases except one MSH6-deficient tumor. Two dMMR cases were stable with low TMB. Moreover, in two MLH1/PMS2-deficient cases CGP revealed pathogenic alterations in the MSH2 and MSH6 genes; in both cases, the MLH1 promoter was hypermethylated. A high TMB was the only positive biomarker in 11 cases with a proficient MMR system and no MSI. Conclusions: MSI assessment by CGP analysis showed high concordance (98%) with MMR and was helpful in evaluating ICI eligibility in three out of twelve dMMR cases. Overall, compared to standard methods, analyzing a broader range of microsatellite loci and the simultaneous assessment of multiple predictive biomarkers by CGP may increase diagnostic accuracy and improve therapeutic assessment. Full article

Background/Objectives: We conducted this study to develop a generic amiodarone tablet pharmaceutically equivalent to the reference drug. This development is crucial for securing a stable supply chain for this orphan drug, which currently faces domestic market instability. Amiodarone, a national essential medicine, often experiences unstable supply due to its limited profitability. Methods: To secure this stable supply chain, we employed a factorial design, utilizing a Quality by Design (QbD) approach, to create the most suitable formulation. Initially, we observed a limitation where the formulation exhibited a flowability of 25% based on the Carr’s Index, which exceeded the target of 20%. To address this challenge, we incorporated lactose monohydrate during the pre-mixing stage rather than the post-mixing stage. Subsequently, we identified the binder content and the amount of granulation solvent as Critical Material Attributes (CMAs), and we performed a Design of Experiments (DoE). Result: Based on these investigations, we determined that the optimal prescription utilizes 5.71% povidone K25 and 40 mg/T of purified water. The final formulation successfully achieved an excellent flowability of 15.8%. Furthermore, this formulation showed a dissolution and bioequivalence PK profile equivalent to the reference drug in pH 1.2, 4.0, and 6.8 buffer solutions, each containing 1% Tween 80. Conclusion: Ultimately, the developed formulation is anticipated to establish a stable domestic supply chain and concurrently reduce national healthcare costs. These research findings also establish the groundwork for future continuous manufacturing implementation. Full article

This work presents a high-performance piezoelectric MEMS yaw gyroscope fabricated on a single-crystal silicon platform, which achieves a quality factor of 75 k—the highest reported to date among silicon-based piezoelectric gyroscopes. The device employs a wide annular resonator that operates at 132 kHz in the in-plane wineglass mode. To maximize transduction efficiency, we develop an analytical model that relates output charge to the area-integrated in-plane stress under modal deformation, and we use this model to guide parametric optimization of the annular width. The resulting geometry simultaneously enhances the mechanical quality factor and the piezoelectric coupling. A back-etching fabrication process is used to eliminate front-side release holes, thereby preserving structural continuity and suppressing thermoelastic damping. In open-loop rate mode operation with a native frequency split of 28 Hz, the gyroscope demonstrates an angle random walk of 0.34°/√h and a bias instability of 8.19°/h. These performance metrics are comparable to those of state-of-the-art lead zirconate titanate (PZT)-based annular gyroscopes, while the use of lead-free aluminum nitride as the transduction material ensures compliance with RoHS environmental regulations. Full article

Land-use and land-cover change plays a critical role in shaping urban expansion patterns and modifying near-surface soil conditions, hydrological behaviour, and geomorphological stability in rapidly developing regions. This study presents a comparative modelling framework to analyze long-term land-use change and its implications for regional-scale geotechnical risk screening by integrating historical land-use classification, Markov transition analysis, and machine learning–based spatial simulation. Landsat imagery from 1985 and 2024 was classified using a Support Vector Machine approach, and future land-use projections for 2063 were generated using both the TerrSet Land Change Modeler (LCM) and the GeoFLUS model under identical transition demands. Spatial driving variables included topographic, hydrological, and accessibility-related factors that influence soil behaviour and urban suitability. The results reveal sustained urban expansion primarily driven by the systematic conversion of agricultural land into built-up surfaces, while forested areas and water bodies exhibit high class persistence, as indicated by dominant diagonal values in the Markov transition matrix. Although both models reproduce consistent directional trends, they generate distinct spatial allocation patterns, with LCM producing compact and centralized growth and GeoFLUS generating more spatially dispersed expansion. These differences lead to contrasting implications for potential settlement, flooding, and slope instability zones. By treating future land-use maps as alternative geotechnical screening scenarios rather than fixed predictions, this study demonstrates how model uncertainty can be incorporated into hazard-sensitive planning. The proposed framework supports preliminary geotechnical zoning and infrastructure planning by identifying robust development corridors and spatial uncertainty zones where detailed site investigations may be prioritized. The methodology is transferable to other rapidly urbanizing regions facing complex soil and geomorphological constraints. Full article

Protein-based parenteral drug products processed in a filling line can be exposed to shear stress of varying magnitude depending on the operation. These shear stresses and other factors, such as interfacial stress, have been the focus of many studies in recent years on the cause of product degradation. Estimating shear stress in individual operating units represents the first step towards a more in-depth study of the shear-induced product instability. In this frame, the present manuscript shows an innovative workflow to obtain a computational model of a peristaltic pump and evaluate the exposure of the product to shear stresses. This was accomplished through Computational Fluid Dynamics simulations combined with Lagrangian Particle Tracking techniques. In this way, the shear stress history of each individual product particle passing through the peristaltic pump was taken into account. The results provide insight into shear stress dynamics within a peristaltic pump and show potential for future applications. Full article

This study addresses the problem of traffic congestion in large cities caused by long-term repairs of underground utility networks. An innovative mobile overpass is considered, which combines the functions of a vehicle and a temporary bridge, allowing passenger cars up to 3.5 t to pass directly over repair trenches without detours. The research focuses on optimizing the placement of overpass supports relative to the trench edge to reduce soil deformation and prevent trench wall instability. A numerical methodology is developed in ANSYS Workbench that integrates finite element analysis of the soil-support system with parametric optimization using the nonlinear Drucker–Prager elastoplastic model. The soil parameters are obtained from oedometer compression tests (KPr-1M) and direct shear tests (PSG-2M) on clayey soils and then used to calibrate the numerical model. The optimization results show that the optimal distance from the trench wall to the overpass support is L_min = 2.78 m, which is 13.5% greater than the initial design value. This modification reduces the maximum horizontal displacement of the trench wall by more than a factor of two and ensures compliance with the displacement criteria. Comparison between experimental and numerical compression curves yields an average deviation of 37.55%, with errors below 5% at higher stress levels, confirming that the Drucker–Prager model is suitable for engineering optimization of mobile overpass support placement on similar soils. The proposed methodology can be applied to the design and verification of temporary bridge systems operating above utility trenches in urban environments. Full article

To investigate the heat-generation mechanisms of journal bearings under different whirl motion and to clarify the corresponding temperature distribution characteristics, a computational fluid dynamics-based method was developed. The model incorporates temperature-dependent lubricant viscosity and employs an unsteady dynamic-mesh updating approach based on structured grids, enabling the automatic iterative tracking of the journal center during whirl motion. A thermal-effect analysis model that accounts for journal whirl trajectories was thereby established. The whirl orbit shape is characterized using elliptical eccentricity, and the effects of whirl direction, elliptical eccentricity, and whirl frequency on the circumferential temperature and pressure distributions of the journal are examined. Results show that under forward whirl, increasing whirl frequency and elliptical eccentricity initially enhances and then weakens local hydrodynamic pressure and viscous shear dissipation in the oil-film convergent region, producing pronounced first-order circumferential temperature nonuniformity and a high risk of thermal bending at intermediate frequencies. Under backward whirl, hydrodynamic effects are reduced and heat generation shifts from localized concentration to global shear dissipation, forming a relatively uniform second-order circumferential temperature field. Increasing elliptical eccentricity causes the whirl orbit to become more linear, improving load-carrying capacity and heat-transfer performance and thereby mitigating thermally induced vibration and oil-film whirl instability. Full article

Background: Rapid Sequence Induction (RSI) is a widely used method for emergency airway management in critically ill and clinically unstable patients. Beyond the risks inherent to the procedure itself, RSI is almost exclusively performed in emergency settings where patients present with severe physiological derangement and a high risk of aspiration. In postmortem examinations, forensic toxicology results may be influenced by the patient’s clinical condition, the sampling site, the postmortem interval (PMI), and postmortem drug redistribution (PMR). This review aims to evaluate the existing literature regarding PMR of drugs commonly used during RSI. Methods: PubMed/MEDLINE, Embase and the Cochrane Library were searched for studies on PMR of drugs used in intravenous (IV) RSI (up to November 2025). Human and animal studies, patient populations comparable to critically ill individuals requiring RSI, and forensic case reports of exclusively IV drug administration were included. Studies on recreational use, overdose and non-IV administration were excluded. Results: Data on the PMR of IV-administered RSI drugs remain limited. Most available studies involve Intensive Care Unit (ICU) patients or individuals who underwent RSI in emergency settings. Fentanyl and midazolam appear to demonstrate notable PMR. Several factors influencing postmortem drug concentrations were identified. Although these findings are consistent with the existing literature, the small number of studies and the heterogeneity of data preclude definitive conclusions. Conclusions: Critical patient condition, including frailty due to advanced age, hemodynamic instability (particularly in ICU patients), hypoalbuminemia, body mass index (BMI), and injury and/or trauma, as well as the interval between IV drug administration and death, appear to affect postmortem concentrations of drugs used during RSI. The potential for PMR of certain agents, such as fentanyl and midazolam, adds further complexity. Given the scarcity of consolidated evidence and until further research provides more robust data, postmortem drug levels should not be interpreted as directly reflective of antemortem concentrations. Full article

This study presents the electrochemical characterization of a novel, binder-free, plasma-treated aluminum/carbon electrode (“Surge”) using lithium metal half-cells. The low operating potential near 0 V vs. Li/Li${}^{+}$ enables the investigation of the electrode’s charge storage mechanisms and stability limits. We compare its electrochemical behavior in coin cells (CR2032) against two reference configurations: (i) the Surge electrode with a thin copper backer (Surge + Cu-backer) and (ii) a commercial graphite electrode on an aluminum current collector (C-REF). The Surge electrode demonstrated ultra-high initial specific capacities of up to approximately 4500 mAh/g (cycle 1) with Coulombic efficiencies exceeding 85% after the formation cycle. The observed capacity significantly exceeds the theoretical value for Li-Al alloying (993 mAh/g), indicating that lithium plating within the porous carbon scaffold contributes substantially to the total charge storage. However, this high performance was limited to approximately 8 to 9 stable cycles. Post-cycling analysis via scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM/EDX) revealed a dominant failure mechanism: partial dissolution and consumption of the Al current collector leading to material redistribution. Quantitative EDX analysis showed a decrease in Al content from 45 at.% to 12 at.% alongside an increase in oxygen content from 8 at.% to 38 at.%, suggesting extensive Al-oxide formation. Critically, in the absence of a backer, Al-containing material deposited onto the stainless-steel cell components. The Cu backer served to redirect these deposits, improving current collection and modestly extending the short-term durability to approximately 1800 mAh/g at cycle 14 (approximately 75% capacity retention). In contrast, the C-REF control cell reached only approximately 1000 mAh/g (cycle 4) before failing within 5 to 6 cycles, underscoring the inherent instability of bare Al at low potentials. This characterization study establishes the Surge architecture as a successful proof-of-concept for ultra-high capacity charge storage and identifies Al dissolution as the dominant degradation mechanism. Future optimization must focus on stabilizing the Al substrate through protective interphases, alloying, or electrolyte engineering. Full article

Heterogeneous ion-exchange membranes (IEMs) are cost-effective but suffer from low electrochemical efficiency due to surface inhomogeneities. While surface coating with homogeneous ionomers is a known modification strategy, its direct impact on electro-hydrodynamic behavior and desalination performance has rarely been visually verified. In this study, we employed a microfluidic platform to visualize and quantify the performance enhancement of Nafion-coated heterogeneous cation exchange membranes (CEMs). Contrary to conventional theories linking electro-convection (EC) to surface hydrophobicity, our results show that the hydrophilic Nafion coating significantly amplifies EC vortices. Direct visualization revealed that the coating layer acts as an electrical nozzle, inducing intense electric field focusing that triggers macroscopic vortex growth. Furthermore, we visually confirmed that the coating layer physically seals catalytic sites, effectively suppressing parasitic water-splitting reactions. In continuous desalination experiments, this hydrodynamic synergy led to a 32% increase in current efficiency (CE: 1.23) and an 18% increase in salt removal ratio (SRR: 79.4%) compared to bare membranes in the over-limiting regime. These findings demonstrate that inducing controlled hydrodynamic instability via surface modification is a dominant factor for high-efficiency desalination. Full article

This paper critically examines Charles Taylor’s analysis in A Secular Age, with a focus on the concepts of authenticity, fragilization and cross-pressure. I explore the ethic of authenticity in relation to the ontological instability produced by exclusive humanism and consider how fragilization and cross-pressure reflect the fragmentation of our relation to the spiritual. At the same time, I engage with critical responses to Taylor that challenge his claims about authenticity and question the coherence and universality of fragilization and cross-pressure as social and cultural phenomena. I conclude that Taylor’s account of authenticity is fundamentally ambivalent, as it reproduces the rigid distinction between immanence and transcendence that the ethic of authenticity itself seeks ostensibly to destabilize. Full article

Background: Chromosome 3p (chr3p) is frequently deleted in multiple cancers, indicating the presence of shared tumor suppressors. In aggressive uveal melanomas (UVM), this deletion often co-occurs with chr8q amplification (8q+), suggesting strong selection pressure during UVM evolution. Methods: To understand the pattern of genomic alterations mediated by chr3p deletion, we have developed an algorithm for detecting isochromosomes in 10,632 TCGA cancer patients. We further perform integrative genomics analysis to investigate how chr3p deletion could affect subsequent cancer genome evolution and synthetic lethality in UVM. Results: Analysis of genomic alterations in 33 different cancer types implicates the deletion or deleterious mutations of SET-domain-containing 2 (SETD2) at chr3p21 in significantly facilitating the formation of isochromosomes, thereby promoting genomic instability conducive to rapid cancer genome evolution. Fracturing of dicentric isochromosomes during cell division is pervasive and follows the dynamic fragmentation pattern of solids under impulse. In the most aggressive UVM subtype, chr3 deletion includes MITF, a master regulator of melanocyte survival and differentiation, and co-occurs with 8q+. We demonstrate that MITF is a master transcriptional regulator of GNAQ/GNA11 and associated synthetic-lethal genes in UVM. MITF maintains MAPK and calcium homeostasis in UVM, and its hemizygous deletion is thus accidental, likely creating an early crisis during oncogenesis. We further show that MITF, MYC, and GNAQ/GNA11 form coupled regulatory feedback loops in the melanocyte lineage, and MITF deletion in UVM creates acute dependency on MYC-mediated rescue via 8q+. The discovered feedback loops predict both overall and relapse-free patient survival within the most aggressive UVM subtype, explain sensitivity to therapeutic gene perturbations, and inform effective combinatorial therapies. Conclusions: SETD2 deletion potentiates isochromosome formation across diverse cancers. Combinatorial targeting of MITF together with a previously identified synthetic lethal gene may benefit UVM patients harboring both chr3 deletion and 8q+. Full article

Shear slip along structural planes in jointed rock masses is the primary trigger for rock slope instability, threatening geotechnical engineering safety. Direct shear tests were conducted on prefabricated granite specimens with regular sawtooth structural planes (undulation angles: 15°, 30°, 45°; tooth spacing: 10 mm) under 2, 4 and 6 MPa normal stresses, with synchronous acquisition of acoustic emission (AE) and infrasonic signals to explore shear failure characteristics, acoustic spectral features and instability precursors. Results show (1) peak shear stress and stiffness rise significantly with increasing undulation angle and normal stress, and failure modes evolve from sliding friction-dominated to asperity shearing-dominated, finally to composite asperity shearing and compressive crushing. (2) The spectral characteristics of both acoustic emission (AE) and infrasonic signals are closely related to the shear fracture mechanism. (3) Approaching peak shear stress, dominant frequency ratio correlation dimension drops to a minimum and the ib-value rises to a pre-sudden-drop critical point; higher undulation angles align these values with stress closer to the peak, valid as instability precursors. (4) A two-level early warning model (early to imminent warning) is proposed via cross-frequency band AE-infrasonic monitoring, providing a fundamental basis for rock slope stability monitoring using these signals. Full article