Search Results (17,129)

Targeted down-modulation of monocytes and macrophages is a promising strategy for controlling excessive inflammatory processes. Bacterial protein toxins are attractive pharmacological modulation tools for this purpose because of their potency and specificity. Here, we combined the specific properties of the two protein toxins C3lim from Clostridium limosum and CyaA from Bordetella pertussis in the preferentially monocyte/macrophage-targeting bioconjugate C2IN-C3lim_E174Q-Cys_His-AC. The enzymatically inactive and monocytic cell-targeting transporter C2IN-C3lim_E174Q-Cys was recombinantly produced and chemically coupled to the isolated adenylate cyclase (AC) domain of CyaA, which mediates down-modulation of monocytic cell functions through intracellular cAMP accumulation Within 1 h, the bioconjugate showed preferential cell association with monocytic cells relative to HeLa cells, which served as the non-target cell model, without impairing overall cellular viability. Intracellular enzymatic activity was successfully confirmed by significantly elevated cAMP levels in all target cell types. Moreover, in migration assays with primary human monocytes, the bioconjugate markedly reduced both general motility and targeted chemotaxis, demonstrating that the delivery of the enzyme moiety translates into a measurable functional response. Therefore, we conclude that the novel bioconjugate C2IN-C3lim_E174Q-Cys_His-AC enables preferential targeting of monocytes and macrophages under the experimental conditions investigated here and provides proof-of-concept for a targeted protein delivery platform for functional modulation of monocytic cells. Full article

Reliable emergency supply systems are particularly vulnerable when a supply interruption coincides with a surge in demand. This study examines a single-period procurement problem involving a lower-cost primary supplier that may be completely disrupted and a more reliable but higher-priced backup supplier. A joint emergency event simultaneously disrupts the primary supplier and generates additional emergency demand. Routine demand is represented by a random variable, whereas additional emergency demand is modeled as a nonnegative uncertain variable. Chance theory combines these two types of demand information and provides a unified basis for evaluating expected profit. The retailer chooses among primary supplier single sourcing, backup supplier single sourcing, and dual sourcing. The analysis derives the expected profit functions, optimal order quantities, and conditional switching thresholds for the three sourcing modes. Under the analytical conditions of the benchmark model—complete primary-supplier disruption, unconstrained backup capacity, and an interior dual-sourcing solution—dual sourcing reallocates a fixed optimal total order between the two suppliers rather than changing the total quantity. Subject to the derived threshold conditions, an increase in the probability of the joint emergency event may shift the preferred mode from primary supplier single sourcing to dual sourcing and eventually to backup supplier single sourcing. Numerical comparisons using zero-truncated normal and zigzag uncertainty distributions preserve this qualitative sourcing sequence under the tested parameter settings, although the resulting profits, order allocations, and switching thresholds remain distribution-dependent. The extensions show that partial primary-supplier fulfillment may change the optimal total order, whereas a binding backup-capacity constraint limits the feasible allocation to the backup supplier. These findings provide conditional implications for sourcing-mode selection and backup-capacity planning during the initial emergency response period. Full article

Background/Objectives: Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is intended to restore reparative signaling in diabetic wounds, yet its efficacy and the contribution of delivery systems remain uncertain. This systematic review evaluated its preclinical efficacy, mechanistic responses, safety, risk of bias, certainty, and attribution of effects. Methods: Following PRISMA 2020 and an OSF-registered protocol, PubMed, Embase, Scopus, Web of Science, and ScienceDirect were searched from inception to 29 July 2026 for controlled in vivo diabetic wound studies. Compatible outcomes were pooled using random-effects models with restricted maximum-likelihood estimation and Hartung–Knapp adjustment. Non-poolable findings were synthesized using attribution-specific effect direction maps. Risk of bias and certainty were assessed with SYRCLE and preclinical GRADE, respectively. Results: Twenty-nine studies were included from 3844 records. For percentage wound closure at days 10–12, three studies comprising 113 animals yielded a favorable but imprecise pooled estimate (mean difference: 12.94 percentage points; 95% CI: −0.34 to 26.23; p = 0.052; I² = 54.6%). Two studies comprising 45 animals suggested a non-significant 4.28-day reduction in time to complete closure (95% CI: −27.98 to 19.42). In the exploratory effect direction synthesis, directly attributable macroscopic healing showed a favorable direction in 17 of 22 studies and was the only domain meeting the prespecified 70% concordance threshold; four of these studies had confirmed unit-of-analysis concerns, and other reparative domains were heterogeneous. Formulation-level comparisons met the same exploratory threshold across four reparative domains, but the isolated contribution of rhPDGF-BB could not be determined. Safety reporting was sparse. Certainty for the primary outcome was very low. Conclusions: Directly attributable comparisons showed a predominantly favorable study-level pattern for macroscopic wound healing in the exploratory synthesis, but the pooled effects were imprecise and inconclusive. Formulation-level comparisons suggested broader reparative activity, although the independent contribution of rhPDGF-BB could not be isolated. Better controlled and clinically representative studies are required before confident translation. Full article

Creativity is a critical higher-order cognitive capacity for college students in the age of artificial intelligence. This study examined the relationship between AI dependence and self-reported creativity among Chinese college students, the mediating roles of motivation for AI use and the moderating role of AI literacy. A total of 5764 valid responses were collected from university students across multiple regions of China. Participants completed measures of AI dependence, perceived AI literacy, motivation for AI use, and self-reported creativity. The results showed that AI dependence was negatively associated with self-reported creativity. Parallel mediation analysis indicated significant negative indirect associations through escape and social motivation, whereas the indirect associations through instrumental and entertainment motivation were positive. In the primary moderated mediation analysis, perceived AI literacy significantly moderated the associations of AI dependence with escape, social, and entertainment motivation, but not with instrumental motivation. The interaction between AI dependence and perceived AI literacy in predicting self-reported creativity was not significant. The study contributes to research on AI use in higher education by identifying differentiated motivational pathways and clarifying the pathway-specific moderating role of perceived AI literacy. Full article

Protoporphyrin IX (PpIX) occupies a unique nexus in photodynamic therapy (PDT) by bridging the endogenous metabolism of heme biosynthesis with highly efficient, light-induced cytotoxicity. Administered via its precursor 5-aminolevulinic acid (5-ALA) or its derivatives, intracellularly generated PpIX undergoes intersystem crossing upon irradiation to predominantly initiate Type II photochemistry. This process yields singlet oxygen and ancillary reactive oxygen species (ROS) characterized by a strict, nanometer-scale radius of molecular attack. Consequently, the spatiotemporal kinetics of PDT are dictated by the precise subcellular compartmentalization of PpIX within the mitochondria, mitochondrial-associated membranes (MAMs), endoplasmic reticulum, lysosomes, and plasma membrane. Beyond inducing direct biomolecular damage, PpIX-PDT operates as a localized selector of complex signaling networks, orchestrating organelle communication, redox-mediated pathways, and cell fate adaptations. This comprehensive review systematically delineates the metabolic parameters governing intracellular PpIX accumulation, the biophysical mechanisms driving its excitation, and the subsequent cascade from primary oxidative stress to downstream signaling responses. Crucially, we present a novel, integrated framework that seamlessly connects upstream transporter kinetics and metabolic flux directly to downstream immunogenic and therapeutic outcomes. Ultimately, these multifaceted properties establish 5-ALA-mediated PpIX-PDT as a powerful theranostic platform, advancing pathway-oriented and personalized strategies to optimize modern anticancer interventions. Full article

Background: Prone positioning and lung-protective ventilation are key components of the management of moderate-to-severe acute respiratory distress syndrome (ARDS). However, protective ventilation may be limited by refractory hypercapnia, acidosis, and hemodynamic instability. Whether extracorporeal multiorgan support can complement prone positioning by alleviating these physiologic constraints remains unknown. Methods: We conducted a retrospective physiologic cohort study of adult patients with severe ARDS treated with prone positioning combined with extracorporeal multiorgan support using the ADVOS system. The cohort represented a highly selected population with bacterial pneumonia-associated ARDS, sepsis, acute kidney injury, and vasopressor dependence. Physiologic variables were recorded from baseline to the end of the first (t16) and second (t40) prone sessions. The primary objective was to assess short-term changes in arterial pH, PaCO₂, PaO₂/FiO₂ ratio, driving pressure, and respiratory system compliance. Results: Fifteen patients were included. Median baseline PaCO₂ was 68.1 mmHg and pH was 7.22. By t16, PaCO₂ decreased to 42.6 mmHg (p = 0.001) and pH increased to 7.41 (p = 0.001). The PaO₂/FiO₂ ratio increased from 82 to 146 (p = 0.001), and driving pressure decreased from 20 to 17 cmH₂O (p = 0.003). Mechanical power decreased from 28.5 to 25.9 J/min (p = 0.033), whereas respiratory rate and respiratory system compliance did not reach statistical significance at t16. Vasopressor requirements also decreased during the observation period. Extracorporeal support was maintained throughout prone positioning in all patients. Conclusions: In this highly selected cohort, combined prone positioning and extracorporeal multiorgan support was associated with rapid correction of hypercapnic acidosis, improved oxygenation, and favorable changes in selected measures of ventilatory load. These findings describe the integrated physiologic response to the combined strategy and warrant evaluation in prospective controlled studies. Full article

Pyrazines are the key odorants in food contributing to baked and nutty aromas. In order to improve practicality, a novel electrochemical olfactory biosensor for pyrazine analysis was developed using an olfactory receptor (OR5K1) as the recognition element and AuNPs-PB/ZIF-8@SWCNT/Ti₃C₂ MXene as the sensing matrix. The sensing application and molecular recognition mechanism of OR5K1 toward pyrazines were explored using molecular docking and in silico site-directed mutagenesis. We explored the sensing application and molecular recognition mechanism of OR5K1 toward pyrazines using molecular docking and in silico site-directed mutagenesis. The sensor achieved a linear detection range of 10⁻¹⁴ to 10⁻⁹ M with a low detection limit of 10⁻¹⁴ M. The biosensor exhibited significantly higher current responses toward pyrazine compounds compared to interfering substances, including ethanol, hexanal, acetone, and phenol, demonstrating excellent selectivity, and retained 79% of its initial signal after 12 days of storage, indicating good stability. The change in the reduction peak current (ΔI) in the presence of pyrazine was used as an analytical signal. When applied to four malt samples (pilsner, munich, crystal, and caramel malts), the biosensor showed ΔI responses ranging from 4.6 ± 0.2 µA to 108 ± 6 µA, which corresponded well with the total pyrazine contents determined by GC-TOF/MS (0.092–0.391 mg/kg), with a correlation coefficient of 0.96. Molecular docking revealed binding energies ranging from −3.9 to −6.0 kcal/mol, suggesting spontaneous interactions between OR5K1 and pyrazines, with Leu14, Met81, Asn84, Phe17, Phe85, and Lys90 identified as potential key residues and hydrogen bonds, hydrophobic interactions, and π−π stacking as primary driving forces. This work provides a sensitive and selective biosensor for pyrazine detection, and the elucidated recognition mechanism offers a molecular basis for understanding roasted aroma perception, supporting applications in food quality control and flavor analysis. Collectively, this study offers new insights for designing olfactory receptor-based electrochemical biosensors and facilitates future exploration of food aroma–receptor interaction mechanisms. Full article

Renewable-powered electric vehicle charging can support sustainable transport electrification by coupling low-carbon electricity generation with charging demand. Autonomous microgrids (MGs) combining wind, solar, and energy storage offer a pathway to this integration, including at locations with limited grid access. However, it can be challenging to monitor and manage the energy of standalone microgrids because they are time-varying and nonlinear. Solar and wind energy were the main sources of power for the microgrid. A microgrid’s primary load is thought to be an electric vehicle charging station (EVCS). The EVCS can charge quickly and uses a lot of power. Additionally, an energy storage system (ESS) is incorporated into the microgrid. This research evaluates a fractional-order-super-twisting sliding mode controller (FOSTSMC) for DC-bus regulation and ESS-assisted power balancing to support reliable renewable-powered fast EV charging. The FOSTSMC scheme includes three key parameters that are optimally tuned using the starfish optimization algorithm (SFOA). Regarding changes in wind velocity and solar irradiance, the response of the FOSTSMC was contrasted to that of a conventional proportional-integral (PI), super-twisting sliding mode controller (STSMC), and the fractional-order-PI (FOPI) regulators. MATLAB/Simulink (R2023a version 9.14) was used to simulate and model the MG. The findings show that the introduced FOSTSMC enhanced the MG’s transient response when compared to the other controllers. The proposed optimal FOSTSMC provides an improvement in the peak overshoot of 41.8% and 47.6% in the settling times over the best values of the other controllers. Moreover, simulation-based evaluation using NASA POWER weather profiles for solar irradiance and wind speed are applied to the proposed system to validate energy management effectiveness. Despite changes in wind velocity, solar intensity, and other parameters, the EVCS charging process and the DC-bus voltage tracked the set point with the least amount of disruption. To prove the effectiveness of SFOA, it is compared to particle swarm optimization (PSO). Full article

Child Sexual Abuse Material (CSAM) constitutes one of the most serious forms of child sexual abuse in the digital environment, causing not only primary harm at the moment of abuse but also prolonged and repeated victimization due to the continued storage, dissemination, and accessibility of such material. Although international and European Union legal frameworks provide extensive mechanisms for the protection of children and the prosecution of offenders, questions remain regarding the effectiveness of these mechanisms in preventing the repeated digital victimization of child victims. The aim of this study is to evaluate the criminal justice response to CSAM and to analyse the implementation of the best interests of the child principle in the protection of children who are victims of online sexual abuse. This article argues that the prevention of digital re-victimization should be recognised as an integral component of the best interests of the child principle in CSAM cases. The research employs doctrinal legal analysis, comparative legal methods, and normative analysis, examining the United Nations Convention on the Rights of the Child, European Union legal instruments, the case law of the European Court of Human Rights, and recent academic literature. The analysis indicates that substantial emphasis within the existing criminal justice framework remains on the investigation of offences and the punishment of offenders, while the continuing digital harm that may persist after the conclusion of criminal proceedings requires broader child-protection measures. The article concludes that, in CSAM cases, the best interests of the child principle should be interpreted as imposing a state obligation not only to ensure child-friendly criminal proceedings but also to establish effective mechanisms for the identification, removal, and prevention of the further dissemination of child sexual abuse material, thereby reducing the risk of repeated digital victimization. Full article

Near-infrared (NIR)-responsive nanocarriers offer spatially and temporally controlled heating, drug release, and imaging for biomedical applications. Gold nanorods (AuNRs) and polydopamine (PDA) are two widely investigated platforms with complementary properties: AuNRs provide spectrally tunable plasmonic heating and strong optical imaging capability, whereas PDA offers broadband absorption, adhesive surface chemistry, high cargo-loading capacity, and compatibility with hydrogels and regenerative matrices. Polysaccharide modification can improve physiological stability, reduce nonspecific biological interactions, and introduce receptor targeting, mucoadhesion, or microenvironment responsiveness. This review compares the conjugation chemistry, therapeutic mechanisms, pharmacokinetics, biosafety, and biomedical applications of polysaccharide-modified AuNR and PDA systems, with emphasis on tumor therapy, antibacterial treatment, wound repair, and local drug delivery. AuNR-based platforms are most suitable when rapid wavelength-selective heating and image guidance are primary requirements, whereas PDA-based systems are generally better suited to sustained delivery, tissue adhesion, and long-term local integration. We further discuss AuNR–PDA hybrid architectures and identify key translational barriers, including inconsistent characterization, uncertain long-term fate, nonstandardized photothermal dosimetry, and limited manufacturing reproducibility. This function-oriented comparison provides a practical framework for selecting polysaccharides and carrier platforms according to administration route, biological barrier, therapeutic objective, and safety requirements. Full article

Electric vehicle (EV) wireless power transfer (WPT) systems face two fundamental challenges that hinder their widespread adoption: sensitivity to coil misalignment and the need for battery-friendly fast charging protocols. This paper presents a comprehensive and integrated framework that addresses both challenges through a three-pronged approach combining advanced coil geometry optimization, multi-stage current method (MSCM) charging, and reinforcement learning (RL)-based adaptive control. First, a memetic algorithm hybridizing global exploration and local refinement is employed to design coil geometries that are inherently resilient to misalignment. The optimized coils maintain strong magnetic coupling under lateral displacements up to ±75 mm by strategically sizing the secondary coil’s outer diameter to be smaller than the primary coil’s, ensuring it remains within the optimal magnetic flux region. Second, an MSCM charging protocol is developed and optimized with the objective of balancing charging speed against battery thermal stability and state of health (SoH). The proposed strategy determines optimal current levels for each charging stage, reducing temperature rise compared to conventional CC-CV charging. Third, a novel Deep Q-Network (DQN) RL agent is implemented for real-time adaptive control of the WPT system. The RL controller dynamically adjusts phase shift in response to varying coupling conditions, load disturbances, and battery state, outperforming traditional PI controllers with 23% faster settling time and improved efficiency under dynamic misalignment scenarios. Finite element analysis (FEA) simulations validate the electromagnetic performance of the optimized coils, while an experimental prototype demonstrates the integrated system’s performance. Results show that the combined approach achieves 91.2% DC-DC efficiency under nominal conditions and maintains over 83% efficiency under lateral misalignments up to ±75 mm, fully complying with SAE J2954 alignment tolerance requirements. The MSCM charging protocol, guided by the memetic algorithm, limits battery temperature rise during a full charge cycle, while the RL controller ensures stable power delivery under real-world dynamic conditions. This work establishes a new paradigm for holistic WPT system design, demonstrating that synergistic optimization of magnetic structures, charging protocols, and intelligent control can simultaneously achieve misalignment resilience, fast charging, and adaptive robustness. Full article

In deep-water environments, the combined effects of hydrostatic pressure, explosion-induced shock waves, and bubble pulsation can produce complex nonlinear dynamic responses and instability in stiffened cylindrical shells. Clarifying these response mechanisms is critical for the safety assessment and blast-resistant design of deep-sea equipment. In this study, an acoustic–structural coupled numerical method was developed for stiffened cylindrical shells subjected to underwater explosion loading and validated using deep-water explosion tests conducted in a pressure vessel. The numerical results show that the relative error between the numerical and experimental wall-pressure impulses on the blast-facing surface is 3.6%, while the relative error in the maximum compressive strain at a representative measurement point on the blast-facing surface is 15.6%, indicating that the established numerical model can reasonably reproduce the pressure impulse and the primary dynamic response of the structure. Based on this validated model, a systematic investigation was conducted to evaluate the effects of hydrostatic pressure, stand-off distance, shell-plate thickness, and stiffener number on the deep-water explosion response of stiffened cylindrical shells. With increasing water depth, the structural deformation mode transitions from localized plastic indentation to global instability and crushing. The findings provide practical guidance for blast-resistant design and parameter optimization of deep-water stiffened cylindrical shells. Full article

Reliable classification of brain sequence cases is a challenging problem due to signal ambiguity and noise. Personal concentration is primarily determined by the base frequency of electroencephalogram (EEG) waves, i.e., the task rests on appropriate modelling and recognition of patterns in the corresponding human (in)activity (e.g., reading, relaxation, solving maths problems, etc.). Five underlying types of frequency (alpha, beta, gamma, delta, and theta) were considered as secondary input wave parameters in complex-valued node extensions to the prime amplitude in processing signals. Self-optimisable Artificial Intelligence (AI) methods can process, statistically analyse, and model the series-specific character and time behaviour to recognise untrained session assigned labels. This procedure involves signal pre-processing (transformation) and feature extraction to enhance the representation in time variability, eliminate uncertain cases, and reduce the unacceptable large raw format of data in detailed frequency band recording. This study focuses on improving AI modelling through brain-inspired doubled amplitude/frequency signal processing. This extended concept is based on an analogy with neural activity that generates dynamic frequency pulses as the main information holder in response to time excitations. The model is obtained in partial differential equation (PDE) solutions of evolutionary tree structure nodes—self-computational terms, using the optimal sine/cosine or rational expression. It enables the representation of periodic patterns in their intrinsic form related to primary wave characteristics. Two different machine learning methodologies were compared: the first evolutionary PDE transform and deep learning-based recurrent processing applied to all session records in bloc, assessing only one final class assessment, achieving predictive accuracy above 90% on untrained 1/3 data. The second group of regular modelling techniques evaluates each data row separately to compute its bound-label output in a time-lagged frame, reaching accuracy above 70%. An executable parametric software with a link to the public EEG data repository is available. Full article

The growth of the plant-based dairy alternatives market and consumers’ diverse preferences and expectations prompted an evaluation of plant-based yogurt alternatives based on coconut, oat, soy, and cashew nut compared with dairy yogurt. Consumers’ responses were assessed under blind, expected, and informed conditions using hedonic evaluation, the Check-All-That-Apply (CATA) questionnaire, and purchase intention measurement. The type of raw material significantly influenced the physicochemical properties, sensory profile, and consumer perception of fermented products. Dairy yogurt achieved the highest overall liking, while the coconut-based yogurt alternative was the most preferred plant-based product and showed sensory characteristics closest to dairy yogurt. Taste was identified as the main driver of overall liking, followed by creaminess, thickness, and light color. Conversely, artificial flavor notes, blandness, gray appearance, and thin texture were the main negative drivers of overall liking. The integration of physicochemical, sensory, and hedonic data confirmed that consumer responses are shaped through sensory perception rather than direct evaluation of instrumental quality parameters. Product information positively influenced consumer expectations, but its effect on final acceptance depended on whether sensory quality met those expectations. Higher overall liking consistently predicted higher purchase intention, indicating that sensory acceptance remained the primary determinant of consumers’ willingness to buy plant-based yogurt alternatives. Full article

Background/Objectives: Hospital malnutrition is a prevalent and clinically significant issue associated with prolonged hospital stays, increased complications, and mortality. Although nurses play a key role in monitoring nutritional status and delivering nutrition care, many lack confidence and do not perceive nutrition care as part of their primary responsibilities. This study assessed nurses’ self-perceived nutrition care competence, identified associated factors, and examined their objectively scored nutrition knowledge alongside self-reported nutrition care competence. Methods: A cross-sectional study was conducted among unit nurses providing direct patient care at a tertiary hospital in Korea. Data were collected using a structured questionnaire assessing participant characteristics, nutrition education–related characteristics, nutrition knowledge, and self-perceived nutrition care competence. Data were analyzed using descriptive statistics, group comparisons, correlation analyses, and multiple linear regression analyses. Results: Among 206 recruited nurses, data from 185 were analyzed. The mean self-perceived nutrition care competence score was 72.24 ± 12.48 (possible range: 24–120). Greater clinical experience, pediatric unit practice, previous nutrition-related education, and higher nutrition knowledge were independently associated with self-perceive nutrition care competence. The mean nutrition knowledge score was 13.81 ± 2.69 (69.1% correct). Notably, although nurses recognized the importance of nutrition care and expressed willingness to receive education, participation in nutrition-related training was limited. Conclusions: Self-perceived nutrition care competence was associated with both individual and practice environment factors. Despite the high perceived need for and willingness to participate in nutrition education, previous participation in nutrition-related education was limited. These findings support consideration of educational and organizational strategies to facilitate nutrition care in nursing practice. Full article