Search Results (1,061)

This paper introduces a novel fractional-order model using the Caputo derivative operator to investigate the virus dynamics of adaptive immune responses. Two infection routes, namely cell-to-cell and virus-to-cell transmissions, are incorporated into the dynamics. Our research establishes the existence and uniqueness of positive and bounded solutions through the application of the generalized mean-value theorem and Banach fixed-point theory methods. The fractional-order model is shown to be Ulam–Hyers stable, ensuring the model’s resilience to small errors. By employing the normalized forward sensitivity method, we identify critical parameters that profoundly influence the transmission dynamics of the fractional-order virus model. Additionally, the framework of optimal control theory is used to explore the characterization of optimal adaptive immune responses, encompassing antibodies and cytotoxic T lymphocytes (CTL). To assess the influence of memory effects, we utilize the generalized forward–backward sweep technique to simulate the fractional-order virus dynamics. This study contributes to the existing body of knowledge by providing insights into how the interaction between virus-to-cell and cell-to-cell dynamics within the host is affected by memory effects in the presence of optimal control, reinforcing the invaluable synergy between fractional calculus and optimal control theory in modeling within-host virus dynamics, and paving the way for potential control strategies rooted in adaptive immunity and fractional-order modeling. Full article

Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon complexation with a DNA-based nanostructure. Upon localized plasma exposure, DNA masking was disrupted, restoring the biological functions of the peptides. Transmission electron microscopy revealed that the synthesized DNA nanoflower structures were approximately 150–250 nm in size. Structural and functional analyses confirmed that the system remained inert under physiological conditions and was rapidly activated by plasma treatment. Fluorescence recovery, cellular uptake assays, and cytotoxicity measurements demonstrated that the peptide activity could be precisely controlled in both monolayer and three-dimensional spheroid models. This externally activatable nanomaterial-based system enables the spatial and temporal regulation of peptide function without requiring biochemical triggers or permanent chemical modifications. This platform provides a modular strategy for the development of potential peptide therapeutics that require precise control of activation in complex biological environments. Full article

Accurate peak detection in the frequency domain is fundamental to reliable range estimation in Frequency-Modulated Continuous-Wave (FMCW) radar systems, particularly in challenging conditions characterized by a low signal-to-noise ratio (SNR) and phase noise impairments. This paper presents a comprehensive comparative analysis of five peak detection algorithms: FFT thresholding, Cell-Averaging Constant False Alarm Rate (CA-CFAR), a simplified Matrix Pencil Method (MPM), SVD-based detection, and a novel Learned Thresholded Subspace Projection (LTSP) approach. The proposed LTSP method leverages singular value decomposition (SVD) to extract the dominant signal subspace, followed by signal reconstruction and spectral peak analysis, enabling robust detection in noisy and spectrally distorted environments. Each technique was analytically modeled and extensively evaluated through Monte Carlo simulations across a wide range of SNRs and oscillator phase noise levels, from $-100$ dBc/Hz to $-70$ dBc/Hz. Additionally, real-world validation was performed using a custom-built harmonic FMCW radar prototype operating in the 2.4–2.5 GHz transmission band and 4.8–5.0 GHz harmonic reception band. Results show that CA-CFAR offers the highest resilience to phase noise, while the proposed LTSP method delivers competitive detection performance with improved robustness over conventional FFT and MPM techniques. Furthermore, the hardware feasibility of each algorithm is assessed for implementation on a Xilinx FPGA platform, highlighting practical trade-offs between detection performance, computational complexity, and resource utilization. These findings provide valuable guidance for the design of real-time, embedded FMCW radar systems operating under adverse conditions. Full article

The application of cellular spheroids in bone tissue engineering research has gained significant interest in the last decade. Compared to monolayer cell cultures, the 3D architecture allows for more physiological cell–cell and cell–extracellular matrix (ECM) interactions that make cellular spheroids a suitable model system to investigate the bone ECM in vitro. The use of 3D model systems requires fine-tuning of the experimental methods used to study cell morphology, ECM deposition and mineralization, and cell–ECM interactions. In this study, we use a construct made of MC3T3-E1 cellular spheroids encapsulated in an alginate hydrogel to study and characterize the deposited ECM. Spheroid shape and structure were evaluated using confocal microscopy. The deposited collagenous ECM was characterized using Second Harmonic Imaging Microscopy (SHIM), quantitative hydroxyproline (HYP) assay, and Transmission Electron Microscopy (TEM). The use of hydrogel constructs enabled easy handling and imaging of the samples, while also helping to preserve the spheroid’s stability by preventing cells from adhering to the culture dish surface. We used a non-modified alginate hydrogel that did not facilitate cell attachment and therefore functioned as an inert encapsulating scaffold. Constructs were cultured for up to 4 weeks. SHIM, HYP assay, and TEM confirmed the deposition of a collagenous matrix. We demonstrated that alginate-encapsulated bone spheroids are a convenient and promising model for studying the bone ECM in vitro. Full article

Background/Objectives: Nanoparticles (NPs) were previously explored as enhancers in electroporation due to their potential to locally amplify electric fields near cell membranes, with gold nanoparticles (AuNPs) in particular showing promise in improving membrane permeability and gene electrotransfer (GET). In this study, we systematically investigated the influence of NP properties—including size, shape, surface functionalization, and material—on electroporation efficacy. Methods: A combined approach using theoretical modeling and experimental validation was employed, encompassing numerical simulations, membrane permeabilization assays, transmission electron microscopy, and GET efficiency measurements. Results: Numerical results revealed that the presence of NPs alters local electric field distributions, but the amplification is highly localized, regardless of NP conductivity or geometry. Experimentally, only two out of six tested NP types produced a statistically significant, yet modest, increase in membrane permeability at one electric field intensity. Similarly, GET improvement was observed with only one NP type, with no dependence on concentration or functionalization. Conclusions: Overall, our findings demonstrate that NPs, under tested conditions, do not substantially enhance cell membrane permeability or GET efficacy. These conclusions are supported by both computational modeling and in vitro experiments. Full article

Background: As a well-known environmental hazard, ambient fine particulate matter (PM_2.5, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM_2.5 exposure has been shown to alter microbiota composition and diversity in human and animal models. However, its impact on goblet cells and gut mucus barrier integrity remains unclear. Methods: To address this, 8-week-old male and female interleukin-10 knockout (IL10^−/−) mice, serving as a spontaneous colitis model, were exposed to concentrated ambient PM_2.5 or filtered air (FA) in a whole-body exposure system for 17 weeks. Colon tissues from the PM_2.5-exposed mice and LS174T goblet cells were analyzed using H&E staining, transmission electron microscopy (TEM), and transcriptomic profiling. Results: The average PM_2.5 concentration in the exposure chamber was 100.20 ± 13.79 µg/m³. PM_2.5 exposure in the IL10^−/− mice led to pronounced colon shortening, increased inflammatory infiltration, ragged villi brush borders, dense goblet cells with sparse enterocytes, and lipid droplet accumulation in mitochondria. Similar ultrastructure changes were exhibited in the LS174T goblet cells after PM_2.5 exposure. Transcriptomic analysis revealed a predominantly upregulated gene expression spectrum, indicating an overall enhancement rather than suppression of metabolic activity after PM_2.5 exposure. Integrated enrichment analyses, including GO, KEGG, and GSEA, showed enrichment in pathways related to oxidative stress, xenobiotic (exogenous compound) metabolism, and energy metabolism. METAFlux, a metabolic activity analysis, further substantiated that PM_2.5 exposure induces a shift in cellular energy metabolism preference and disrupts redox homeostasis. Conclusions: The findings of exacerbated gut barrier impairment and goblet cell dysfunction following PM_2.5 exposure provide new evidence of environmental factors contributing to colitis, highlighting new perspectives on its role in the pathogenesis of colitis. Full article

Background: Toxoplasma gondii (T. gondii) causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of T. gondii plays a key role in parasitic cyst formation. Methods: This study evaluated the protective immune responses induced by a virus-like particle (VLP) vaccine expressing the T. gondii-derived antigen GRA5 in a mouse model challenged with the ME49 strain of T. gondii. GRA5 VLPs were generated using a baculovirus expression system, and VLP formation was confirmed by Western blotting and visualized using transmission electron microscopy. Mice were intranasally immunized with GRA5 VLPs three times at 4-week intervals to induce immune responses, followed by infection with T. gondii ME49. Results: Intranasal immunization with GRA5 VLPs induced parasite-specific IgG antibody responses in the serum and both IgG and IgA antibody responses in the brain. Compared to the non-immunized group, immunized mice exhibited significantly higher levels of germinal center B cells and antibody-secreting cell responses. Moreover, the VLP vaccine suppressed the production of IFN-γ and IL-6 cytokines, leading to a significant reduction in brain inflammation and decreased cyst counts following lethal challenge with T. gondii ME49 infection. Conclusion: These findings suggest that the GRA5 VLP vaccine derived from T. gondii elicits a protective immune response, highlighting its potential as an effective vaccine candidate against toxoplasmosis. Full article

Acoustic tweezers, as advanced micro/nano manipulation tools, play a pivotal role in biomedical engineering, microfluidics, and precision manufacturing. However, piezoelectric-based acoustic tweezers face performance limitations due to multi-physical coupling effects during microfabrication. This study proposes a novel approach using injection molding with embedded electronics (IMEs) technology to fabricate piezoelectric micro-ultrasonic transducers with micron-scale precision, addressing the critical issue of acoustic node displacement caused by thermal–mechanical coupling in injection molding—a problem that impairs wave transmission efficiency and operational stability. To optimize the IME process parameters, a hybrid multi-objective optimization framework integrating NSGA-II and MOPSO is developed, aiming to simultaneously minimize acoustic node displacement, volumetric shrinkage, and residual stress distribution. Key process variables—packing pressure (80–120 MPa), melt temperature (230–280 °C), and packing time (15–30 s)—are analyzed via finite element modeling (FEM) and validated through in situ tie bar elongation measurements. The results show a 27.3% reduction in node displacement amplitude and a 19.6% improvement in wave transmission uniformity compared to conventional methods. This methodology enhances acoustic tweezers’ operational stability and provides a generalizable framework for multi-physics optimization in MEMS manufacturing, laying a foundation for next-generation applications in single-cell manipulation, lab-on-a-chip systems, and nanomaterial assembly. Full article

Energy storage plays an essential role in stabilizing fluctuations in renewable energy sources such as wind and solar, enabling surplus electricity retention, and delivering dynamic frequency regulation. However, relying solely on a single form of storage often proves insufficient due to constraints in performance, capacity, and cost-effectiveness. To tackle frequency regulation challenges in remote desert-based renewable energy hubs—where traditional power infrastructure is unavailable—this study introduces a planning framework for an electro-hydrogen energy storage system with grid-forming capabilities, designed to supply both inertia and frequency response. At the system design stage, a direct current (DC) transmission network is modeled, integrating battery and hydrogen storage technologies. Using this configuration, the capacity settings for both grid-forming batteries and hydrogen units are optimized. This study then explores how hydrogen systems—comprising electrolyzers, storage tanks, and fuel cells—and grid-forming batteries contribute to inertial support. Virtual inertia models are established for each technology, enabling precise estimation of the total synthetic inertia provided. At the operational level, this study addresses stability concerns stemming from renewable generation variability by introducing three security indices. A joint optimization is performed for virtual inertia constants, which define the virtual inertia provided by energy storage systems to assist in frequency regulation, and primary frequency response parameters within the proposed storage scheme are optimized in this model. This enhances the frequency modulation potential of both systems and confirms the robustness of the proposed approach. Lastly, a real-world case study involving a 13 GW renewable energy base in Northwest China, connected via a ±10 GW HVDC export corridor, demonstrates the practical effectiveness of the optimization strategy and system configuration. Full article

Perovskite solar cells (PSCs) leverage the exceptional photoelectric properties of perovskite materials, yet interfacial energy level mismatches limit carrier extraction efficiency. In this work, energy level alignment was exploited to reduce the charge transport barrier, which can be conducive to the transmission of photo-generated carriers and reduce the probability of electron–hole recombination. We designed a dual-transition perovskite solar cell (PSC) with the structure of FTO/TiO₂/Nb₂O₅/CH₃NH₃PbI₃/MoO₃/Spiro-OMeTAD/Au by finite element analysis methods. Compared with the pristine device (FTO/TiO₂/CH₃NH₃PbI₃/Spiro-OMeTAD/Au), the open-circuit voltage of the optimized cell increases from 0.98 V to 1.06 V. Furthermore, the design of a circular platform light-trapping structure makes up for the light loss caused by the transition at the interface. The short-circuit current density of the optimized device increases from 19.81 mA/cm² to 20.36 mA/cm², and the champion device’s power conversion efficiency (PCE) reaches 17.83%, which is an 18.47% improvement over the planar device. This model provides new insight for the optimization of perovskite devices. Full article

Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF. Full article

Purpose: Collagen membranes with biomimetic mineralization are emerging as promising materials for bone regeneration, owing to their high biocompatibility. In this study, we developed a biogenic collagen membrane by combining citrate (C) pretreatment and carboxymethyl chitosan (CMC)-mediated mineralization and further evaluated its bone healing potential. Methods: C-CMC collagen membranes were prepared by lyophilization. The mineral composition and content were tested through X-ray diffraction (XRD), Fourier transform infrared (FTIR), and thermogravimetric analysis (TGA). The micromorphology was observed using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and scanning probe microscopy (SPM). Physical and mechanical properties, including the swelling rate, porosity, hydrophilicity, tensile strength, Young’s modulus, degradation, and barrier function, were also evaluated. Bone mesenchymal stem cells (BMSCs) were cultured in vitro to observe their behavior. An in vivo critical-size rat calvarial defect model was used to validate the effects of the membrane on bone regeneration. Results: The C-CMC collagen membrane was successfully synthesized as a collagen–hydroxyapatite complex with intrafibrillar mineralization, exhibiting improved mechanical properties and an optimal swelling rate, porosity, hydrophilicity, and degradation rate. Additionally, the C-CMC collagen membrane promoted BMSC proliferation, adhesion, and osteogenesis while preventing epithelial cell infiltration. In vivo experiments indicated that C-CMC collagen membranes significantly stimulated bone regeneration without causing systemic toxicity. Conclusions: Our findings suggest that the C-CMC collagen membrane possesses satisfactory physical and mechanical properties, along with good biocompatibility and efficacy in bone defect regeneration, making it a potential candidate for a bioactive guided bone regeneration membrane in clinical applications. Full article

Recently, there has been a rise in skin cancer cases, for which early detection is highly relevant, as it increases the likelihood of a cure. In this context, this work presents a benchmarking study of standard Convolutional Neural Network (CNN) architectures for automated skin lesion classification. A total of 38 CNN architectures from ten families (ConvNeXt, DenseNet, EfficientNet, Inception, InceptionResNet, MobileNet, NASNet, ResNet, VGG, and Xception) were evaluated using transfer learning on the HAM10000 dataset for seven-class skin lesion classification, namely, actinic keratoses, basal cell carcinoma, benign keratosis-like lesions, dermatofibroma, melanoma, melanocytic nevi, and vascular lesions. The comparative analysis used standardized training conditions, with all models utilizing frozen pre-trained weights. Cross-database validation was then conducted using the ISIC 2019 dataset to assess generalizability across different data distributions. The ConvNeXtXLarge architecture achieved the best performance, despite having one of the lowest performance-to-number-of-parameters ratios, with 87.62% overall accuracy and 76.15% F1 score on the test set, demonstrating competitive results within the established performance range of existing HAM10000-based studies. A proof-of-concept multiplatform mobile application was also implemented using a client–server architecture with encrypted image transmission, demonstrating the viability of integrating high-performing models into healthcare screening tools. Full article

With the vigorous development of Internet of Things technologies, Cell-Free Radio Access Network (CF-RAN), leveraging its distributed coverage and single/multi-antenna Access Point (AP) coordination advantages, has become a key technology for supporting massive Machine-Type Communication (mMTC). However, under the grant-free random access mechanism, this network architecture faces the problem of information freshness degradation due to channel congestion. To address this issue, a joint decoding model based on logical grouping architecture is introduced to analyze the correlation between the successful packet transmission probability and the Peak Age of Information (PAoI) in both single-AP and multi-AP scenarios. On this basis, a global Particle Swarm Optimization (PSO) algorithm is designed to dynamically adjust the channel access probability to minimize the average PAoI across the network. To reduce signaling overhead, a PSO algorithm based on local topology information is further proposed to achieve collaborative optimization among neighboring APs. Simulation results demonstrate that the global PSO algorithm can achieve performance closely approximating the optimum, while the local PSO algorithm maintains similar performance without the need for global information. It is especially suitable for large-scale access scenarios with wide area coverage, providing an efficient solution for optimizing information freshness in CF-RAN. Full article

In the environment, plastic waste degrades into small particles known as microplastics and nanoplastics (MNPLs), depending on their size. Given the potential harmful effects associated with MNPL exposure, it is crucial to develop environmentally representative particles for hazard assessment. These so-called true-to-life MNPLs are generated through in-house degradation of real-world plastic products. In this study, we produced titanium-doped nanoplastics (NPLs) from opaque polyethylene terephthalate (PET) milk bottles, which contain titanium dioxide as a filler. The resulting PET(Ti)-NPLs were thoroughly characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), mass spectrometry (MS), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. Human-derived THP-1 monocytes were employed to investigate particle uptake kinetics, dosimetry, and genotoxicity. A combination of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) enabled the quantification of internalized particles, while the comet assay assessed DNA damage. The results revealed dose- and time-dependent effects of PET(Ti)-NPLs on THP-1 cells, particularly in terms of internalization. Titanium doping facilitated detection and influenced genotoxic outcomes. This study demonstrates the relevance of using environmentally representative nanoplastic models for evaluating human health risks and underscores the importance of further mechanistic research. Full article