Search Results (1,433)

Large-scale computer simulations were employed to investigate the conformational response of the spike protein components S1 and S2 using a coarse-grained model. Temperature was systematically varied to assess the balance between stabilizing residue–residue interactions and thermal fluctuations. The resulting contact profiles reveal distinct segmental reorganization and self-assembly behaviors between S1 and S2. At lower, thermoresponsive temperatures, pronounced segmental globularization occurs in the N-terminal domain (NTD; M153–K202) and receptor-binding domain (RBD; E406–E471) of S1, whereas S2 exhibits alternating regions of high and low contact density. Increasing temperature reduces this segmental globularization, leaving only minor persistence at elevated temperatures. The temperature dependence of the radius of gyration (R_g) further demonstrates the contrasting thermal behaviors of S1 and S2. For S1, R_g increases continuously and monotonically with temperature, reaching a steady-state value approximately 50% higher than that at low temperature. In contrast, S2 displays a non-monotonic response: R_g initially rises to a maximum nearly sevenfold higher than its low-temperature value, then decreases with further temperature increase. Scaling analysis of the structure factor reveals that the globularity of S1 diminishes significantly upon heating, while S2 becomes modestly more compact yet retains its predominantly fibrous character. Full article

Background/Objectives: Non-syndromic tooth agenesis (NSTA) is a congenital condition that causes the absence of one or more teeth without accompanying systemic abnormalities, which significantly affects quality of life. Genetic factors, including mutations in several specific genes, contribute to the pathogenesis of NSTA. This study investigates a novel EVC2 mutation in a patient with NSTA and explores its potential pathogenic mechanism, with the aim of enriching the spectrum of pathogenic genes. Methods: Whole-exome sequencing (WES) was performed on peripheral blood samples from a patient diagnosed with NSTA. Bioinformatics analysis was utilized to identify the mutation and assess its potential impact on protein structure and function. Molecular dynamics simulations were conducted to analyze structural alterations in the EVC2 protein. The binding affinity between EVC2, EVC, and Smoothened (SMO) was to determine the effect of mutation on protein–protein interaction. Protein localization and expression were analyzed using immunofluorescence and Western blotting. Reverse transcription quantitative PCR (RT-qPCR) was employed to evaluate downstream signaling pathway alterations. Results: A novel EVC2 mutation (c.1657_1660delinsA, p.Glu553_leu554delinsMet) was identified in the proband, and the mutation was maternally inherited. Molecular dynamics simulations revealed that the mutation resulted in a decrease in α-helical content and significant conformational changes in the protein structure. This led to reduced binding affinity between EVC2 and its ligands EVC and SMO, destabilizing the structural integrity of the protein complex. Despite these structural changes, EVC2 protein localization and expression were unaffected. Furthermore, a downregulation of GLI1 and SHH expression was observed, indicating impaired Hedgehog (Hh) signaling. The downregulation of the Hh signaling pathway impairs the tooth development process and may lead to the occurrence of tooth agenesis. Conclusions: A novel EVC2 mutation was identified in a patient with NSTA. Based on molecular dynamics simulations, it is hypothesized that this EVC2 variant could contribute to the pathogenesis of NSTA by impairing the EVC2-EVC-SMO complex formation, which may lead to downregulation of downstream GLI1 and SHH. These findings provide new insights into the molecular mechanisms underlying EVC2-mediated NSTA, suggesting that disruption of Hh signaling may represent a critical pathogenic mechanism. Full article

Microwave heating is a method with a uniform heating effect and environmental friendliness in in-place hot recycling, but the microwave absorption capacity of traditional asphalt mixtures is still insufficient. As an excellent microwave-absorbing material, magnetite powder has the characteristics of high temperature resistance, corrosion resistance, and good thermodynamic stability. This study selects it as the microwave-absorbing material, prepares AC (Asphalt Concrete) type and SMA (Stone Mastic Asphalt) type microwave asphalt mixtures by adjusting its content, and investigates its influence on the microwave-heating characteristics and pavement performance of the mixtures. Simulations of the microwave-heating process of AC-type mixtures using COMSOL software (COMSOL Multiphysics 6.2) show that magnetite powder achieves optimal performance in terms of heating effect and economic efficiency when its content is 0.5%. Subsequently, laboratory tests are conducted to study the wave absorption and temperature rise performance of AC and SMA microwave asphalt mixtures; combined with economic factors, the optimal contents of magnetite powder for the two types of mixtures are determined to be 0.5% and 1%, respectively, and at the same time, these results are explained based on multiple physical theories. Furthermore, pavement performance is investigated through laboratory tests, including high-temperature rutting tests, low-temperature bending tests, immersed Marshall tests, and freeze–thaw cycle durability tests, and the results indicate that the high-temperature performance, low-temperature performance, and water stability of the microwave asphalt mixtures all meet the specification requirements for pavement performance. Subsequently, after 15 freeze–thaw cycles, the splitting tensile strength retention rate and stiffness modulus of the two types of mixtures show minimal differences from those of ordinary mixtures, and there is no durability degradation caused by the incorporation of magnetite powder. Finally, outdoor environment verification is carried out, and the results show that under complex conditions such as environmental factors, the wave absorption and temperature rise rates of AC and SMA mixtures at optimal contents are 52.2% and 14.6% higher than those of ordinary AC and SMA asphalt mixtures, respectively. In addition, these microwave asphalt mixtures have the advantages of both sustainability and reduced carbon emissions. By combining simulation methods and experimental verification, this study finally prepared two types of microwave asphalt mixtures with excellent performance, not only improving the microwave absorption and heating performance of asphalt mixtures, but also reducing environmental pollution and energy consumption, which conforms to the development of green transportation. Full article

Pseudomonas aeruginosa (P. aeruginosa) is a high-priority opportunistic pathogen responsible for severe healthcare-associated infections exhibiting multidrug resistance, emphasizing the urgent need for alternative therapeutic strategies. Monoclonal antibodies (mAbs) targeting the highly conserved outer membrane protein OprF represent a promising approach to mitigate its infectivity. OprF, the major and highly conserved outer membrane protein of P. aeruginosa, plays key roles in the pathogenesis of this bacterium, including biofilm formation, host cell adhesion, immune sensing, and resistance to macrophage clearance, making it a crucial factor in virulence and a promising immunotherapeutic target. Here, we report the preclinical evaluation of EPY001, an anti-OprF mAb generated by immunization of a macaque with OprF-containing proteoliposomes. EPY001 exhibited strong nanomolar binding to OprF. Epitope mapping suggests recognition of a conformational epitope, underscoring the value of proteoliposome-based immunization for membrane protein targets. Functional assays provide insights into OprF’s role in biofilm formation, pyocyanin production, and antibiotic resistance. However, in vivo studies revealed that targeting OprF alone is insufficient to protect mice from lethal infection. These findings contribute to ongoing efforts to develop effective alternatives to conventional antibiotics against this resilient pathogen. Full article

This review explores the transformative potential of graphene-based, non-invasive biochemical sensors in the context of real-time health monitoring and personalised medicine. Traditional diagnostic methods often involve invasive procedures that can be uncomfortable, pose risks, and limit the frequency of monitoring. In contrast, wearable sensors incorporating graphene offer a compelling alternative by enabling continuous, real-time tracking of physiological and biochemical signals with minimal intrusion. Graphene’s exceptional electrical conductivity, mechanical flexibility, biocompatibility, and high surface-area-to-volume ratio make it ideally suited for integration into skin-conformal sensor platforms. These properties not only enhance sensitivity and signal fidelity but also promote user comfort and long-term wearability, critical factors for the adoption of wearable health technologies. The discussion evaluates current developments in the design and deployment of graphene-based biosensors, with particular attention given to their role in managing chronic conditions, supporting preventative healthcare, and facilitating decentralised diagnostics. By bridging materials science and biomedical engineering, this review positions graphene as a key enabler in the shift towards more proactive, patient-centred healthcare models. The text also identifies ongoing challenges and future directions in sensor design, aiming to inform researchers working at the intersection of advanced materials and medical technology. Full article

Kudzu (Pueraria spp.) starch, valued for its transparency, viscosity, and stability, has broad potential in functional and instant food applications. However, its limited cold-water solubility and inconsistent functional performance across cultivars hinder wider utilization. To improve its processability and nutritional functionality, this study aimed to elucidate how the degree of gelatinization (DG)—a structural indicator of starch transformation—can be precisely controlled and used to modulate starch properties. Starches from two typical kudzu cultivars, K10 (Pueraria thomsonii) and K27 (Pueraria lobata), were subjected to hydrothermal treatment (45–95 °C) to obtain samples with defined DG levels. DG was quantitatively determined by enzymatic assay, differential scanning calorimetry (DSC), and iodine-binding analysis, enabling method cross-validation. Increasing DG enhanced iodine complexation capacity, elevated gelatinization temperatures, and reduced enthalpy change and crystallinity. K27 exhibited more pronounced physicochemical transitions at lower DG than K10, indicating cultivar-specific sensitivity. In vitro digestion revealed that hydrolysis kinetics gradually approached and eventually conformed to a first-order model as DG increased, confirming a DG-dependent shift in digestibility. These results establish DG—rather than processing temperature—as the primary factor governing kudzu starch functionality and provide a methodological basis for designing starch-based foods with tailored glycemic and textural properties. Full article

Background: Despite guidelines recommending lower alcohol limits for individuals who flush, some still drink at unhealthy levels. This study investigates whether drinking motives are differentially associated with alcohol consumption based on self-reported flushing status among U.S. Asian young adults. Asian American youth report alcohol use at rates comparable to other high-risk groups, identifying the need to understand factors shaping these behaviors. Methods: The current analysis drew participants from a longitudinal multi-cohort study examining the emotional and behavioral health of college students. Freshmen were recruited, all aged 18 years and older, to complete a baseline survey and follow up surveys over a four-year period. The analytic sample (Mean age = 19.4; 70.5% female) included 244 students who self-identified as Asian. Participants self-reported whether they experience facial flush when consuming alcohol and rated their endorsement of various drinking motives. Negative binomial regression models tested main effects and interaction effects between flushing status (flushers, non-flushers) and drinking motives (coping, enhancement, conformity, social). Results: Facial flushing moderated enhancement, conformity, and social drinking motives, but not coping. Among flushers, enhancement and social motives were more strongly associated with greater alcohol consumption. Among non-flushers, conformity motives were stronger and associated with greater drinking, at a trend level. Overall, flushing or higher coping motives were associated with lower alcohol consumption. Peer drinking was associated with higher consumption in both flushing-status groups. Conclusions: The current study extends prior international research on drinking motives and flushing status to U.S. Asian young adults. Findings support the need for prevention strategies that address individual drinking motives and the modeling of alcohol use by peers. Reducing alcohol use among individuals who experience alcohol-induced flushing is a public health priority, given their heightened risk for alcohol-related cancers and other negative health outcomes. Full article

Adjuvant radiotherapy improves local cancer control and the overall survival of women with breast cancer. However, it is unclear what the ideal radiotherapy (RT) planning technique is for these patients. The aim was to perform a synopsis of the literature comparing RT techniques to treat early-stage left breast tumours. A PRISMA guideline was used on this systematic review and registered in PROSPERO (CRD420251168901). For all the investigations, the Open-field technique (OF) showed worse results for the Planning Target Volume (PTV), lung and heart. Field-in-Field stood out in low doses and mean doses in OARs. IMRT distinguished itself in Homogeneity Index. VMAT provides higher Conformity Index results and thus an advantage in high and mean doses of OARs. Hybrid-IMRT and Hybrid-VMAT combine the advantages of two techniques; however, few studies have included them in their research. There is not a clear “gold-standard” technique, and the results depend heavily on many factors which affect the quality of the plans and the priorities of the departments. However, OF is no longer recommended. An international framework should be developed to allow for a standardisation of the plans, improving inter-departmental comparisons. And each department should perform their own comparison between the techniques available to them. Full article

Collagen is a family of large, fibrous biomacromolecules common in animals, distinguished by unique molecular, structural, and functional properties. Despite the relatively low complexity of their sequences and the repetitive conformation of the triple helix, which is the defining feature of this family, unraveling sequence–stability and structure–function relationships in this group of proteins remains a challenging task. Considering the importance of the structural aspects in collagen chain recognition and selection, we reviewed our current knowledge of the heterotrimeric structures of non-collagenous (NC) regions that lack the triple helix sequence motif, Gly-X-Y, and are crucial for the correct folding of the functional states of these proteins. This study was conducted by simultaneously surveying the current literature, mining the structural database, and making predictions of the three-dimensional structure of these domains using highly reliable approaches based on machine learning techniques, such as AlphaFold. The combination of experimental structural data and predictive analyses offers some interesting clues about the structural features of heterotrimers formed by collagen NC regions. Structural studies carried out in the last decade show that for fibrillar collagens (types I, V, XI, and mixed V/XI), key factors include the formation of specific disulfide bridges and electrostatic interaction patterns. In the subgroup of collagens whose heterotrimers create supramolecular networks (types IV and VIII), available structural information provides a solid ground for the definition of the basis of the molecular and supramolecular organization. Very recent AlphaFold predictions and structural analyses of type VI collagen offer strong evidence of the specific domains in the NC region of the protein that are involved in chain selection and their staggering. Insightful crystallographic studies have also revealed some fundamental elements of the chain selection process in type IX collagen. Collectively, the data reported here indicate that, although some aspects (particularly the quantification of the relative contribution of the NC and triple helix regions to correct collagen folding) are yet to be fully understood, the available structural information provides a solid foundation for future studies aimed at precisely defining sequence–structure–function relationships in collagens. Full article

The digitization of healthcare has enabled the application of advanced analytics, such as process mining and machine learning, to electronic health records (EHRs). This study aims to identify workflow inefficiencies, temporal bottlenecks, and risk factors for delayed recovery in surgical pathways using the open-access MOVER dataset. A multi-stage framework was implemented, including heuristic control-flow discovery, Petri net-based conformance checking, temporal performance analysis, unsupervised clustering, and Random Forest-based classification. All analyses were simulated on pre-discharge (“preliminary”) patient records to enhance real-time applicability. Control-flow models revealed deviations from expected pathways and issues with data quality. Conformance checking yielded perfect fitness (1.0) and moderate precision (0.46), indicating that the model generalizes despite clinical variability. Stratified performance analysis exposed duration differences across ASA scores and age groups. Clustering revealed latent patient subgroups with distinct perioperative timelines. The predictive model achieved 90.33% accuracy, though recall for delayed recovery cases was limited (24.23%), reflecting class imbalance challenges. Key features included procedural delays, ICU status, and ASA classification. This study highlights the translational potential of integrating process mining and predictive modeling to optimize perioperative workflows, stratify recovery risk, and plan resources. Full article

Achieving a best-fit prosthetic socket is essential to comfort, functional performance, and long-term residual limb health in lower-limb amputees. To our knowledge, no previous study has quantitatively compared in vivo residual limb geometry under vacuum versus non-vacuum conditions using high-resolution computed tomography (CT). In this patient-specific case study of a bilateral knee-disarticulation (KD) amputee, both residual limbs were scanned under standardized conditions: one enclosed in a vacuum-compressed sleeve and the contralateral limb untreated as a natural control, thereby minimizing inter-subject variability. CT-based 3D reconstructions enabled volumetric and cross-sectional quantification, including symmetry/asymmetry analysis of paired limbs, while finite element analysis (FEA) assessed the biomechanical consequences for socket performance. Vacuum application resulted in a 4.1% reduction in total limb volume and a 5.3% reduction in mid-thigh cross-sectional area, with regionally asymmetric displacement of soft tissues. FEA demonstrated that vacuum-induced geometry reduced peak Von Mises stresses (27.43 MPa to 15.83 MPa), minimized maximum displacement (1.72 mm to 0.88 mm), and improved minimum factor of safety (~2.0 to ~3.0), while homogenizing contact pressure distribution (peak fell from 2.42 to 1.28 N/mm²). These findings provide preliminary CT-based evidence that vacuum application induces measurable morphological adaptations with implications for socket conformity, comfort, and load transfer. While limited to a single patient, this study highlights the potential of vacuum-induced modeling to inform personalized prosthetic socket design. Full article

Additive manufacturing offers significant design freedom for injection mold tooling, particularly in optimizing cooling performance and reducing mass. This study presents a holistic framework for the topology optimization of mold inserts considering design for additive manufacturing principles, integrating essential boundary conditions from the mold making, injection molding process, and post-processing operations. A slider component with conformal cooling channels serves as the case study. Using simulation-driven design and finite element analysis, two design variants, based on conventional and modified design spaces, were evaluated. Mechanical loads from clamping and the injection process were considered, with safety factors applied to reflect industrial misuse scenarios. The topology optimization process was implemented using Altair OptiStruct and validated through displacement and stress analyses. The results show savings in both mass and costs of up to 60% while maintaining structural integrity under operational and misuse conditions. The maximum displacements—only a 4 µm increase compared to the reference—remained within DIN ISO 20457 tolerances, and stresses did not exceed 170 MPa under operational conditions, confirming industrial applicability. This study concludes with a proposed framework for integrating topology optimization into mold design workflows. Full article

This paper investigated the tunnel slags generated from a specific tunnel project to systematically assess their environmental risk through phase composition, chemical composition, acidification potential, and heavy metal speciation. Leaching experiments were conducted under various influencing factors, including particle size, time, liquid-to-solid ratio, pH, temperature. The release concentration of heavy metals from the tunnel slag particles follows the following order: Zn > Cu > Cr. This is primarily attributed to the preferential release of Zn under acidic conditions due to its high acid-soluble state, while Cr, which is predominantly present in the residual state, exhibits very low mobility. Furthermore, decreased particle sizes, increased liquid-to-solid ratios, elevated leaching temperatures, extended leaching times, and lower pH values can effectively promote the dissolution of heavy metals from the tunnel slag. The cumulative leaching curves of Cr, Cu, and Zn from the three types of tunnel slags conform to the Elovich equation (R² > 0.88), indicating that the release process of heavy metals is primarily controlled by diffusion mechanisms. The S- and Fe/Mg-rich characteristics of D3 confers a high acidification risk, accompanied by a rapid and persistent heavy metal release rate. In contrast, D2, which is influenced by the neutralizing effect of carbonate dissolution, releases heavy metals at a steady rate, while D1, which is dominated by inert minerals like quartz and muscovite, exhibits the slowest release rate. It is recommended that waste management engineering prioritize controlling S- and Fe/Mg-rich tunnel slags (D3) and mitigating risks of elements like Zn and Cu under acidic conditions. This study provides a scientific basis and technical support for the environmentally safe disposal and resource utilization of tunnel slag. Full article

In this paper, we study the thermodynamic behavior of charged AdS black holes in higher-dimensional spacetimes within the framework of conformal holographic extended thermodynamics. This formalism is based on a novel AdS/CFT dictionary in which the conformal rescaling factor of the boundary conformal field theory (CFT) is treated as a thermodynamic parameter, while Newton’s constant is held fixed and the AdS radius is allowed to vary. We explore how variations in the CFT state, represented by its central charge, influence the bulk thermodynamics, phase structure, and stability of black holes in five and six dimensions. Our analysis reveals the emergence of Van der Waals-like phase transitions, critical phenomena governed by the central charge. Additionally, we find that the thermodynamic behavior of AdS black holes is affected by the dimensionality of the bulk spacetime, as we compare higher-dimensional black holes to lower-dimensional ones, such as the BTZ black holes. These findings provide new insights into the role of boundary degrees of freedom in shaping the thermodynamics of gravitational systems via holography. Full article

Offshore reservoirs in the high water-cut stage present significant development challenges, including declining production, complex remaining oil distribution, and the inadequacy of conventional evaluation methods to capture intricate flow dynamics. To overcome these limitations, this study introduces a novel approach based on flow diagnostics for performance evaluation and potential adjustment. The method integrates key metrics such as time-of-flight (TOF) and the dynamic Lorenz coefficient, supported by reservoir engineering principles and numerical simulation, to construct a multi-parameter evaluation system. This system, which also incorporates injection–production communication volume and inter-well fluid allocation factors, precisely quantifies and visualizes waterflood displacement processes and sweep efficiency. Applied to the QHD32 oilfield, this framework was used to establish specific thresholds for operational adjustments. These include criteria for infill drilling (waterflooded ratio < 45%, remaining oil thickness > 6 m, TOF > 200 days), conformance control (TOF < 50 days, dynamic Lorenz coefficient > 0.5), and artificial lift optimization (remaining oil thickness ratio > 2/3, TOF > 200 days). Field validation confirmed the efficacy of this approach: an additional cumulative oil production of 165,600 m³ was achieved from infill drilling in the C29 well group, while displacement adjustments in the B03 well group increased oil production by 2.2–3.8 tons/day, demonstrating a significant enhancement in waterflooding performance. This research provides a theoretical foundation and a technical pathway for the refined development of offshore heavy oil reservoirs at the ultra-high water-cut stage, offering a robust framework for the sustainable management of analogous reservoirs worldwide. Full article