Search Results (268)

The effect of high-gravity fields, generated by rapid rotation, on CO₂ adsorption in activated carbon beds is examined. Adsorption-desorption kinetics is monitored before, during, and after short rotation periods at up to 5000 rpm. Rotation induced a reproducible transient bump in headspace pressure, quantitatively attributed to a centrifugal free energy shift (~12.2 J/mol) that overfilled weak adsorption sites beyond their static equilibrium. The bump mechanism is described by fold catastrophe theory, with a critical angular velocity (ω_c = 3500 rpm) triggering a sudden transition to a high-occupancy branch. Post-rotation, constant-rate zero-order desorption from shallow sites overlapped with a slower pseudo-first-order adsorption process as deep, previously inaccessible pores became available, increasing CO₂ capacity by 2.5%. Kinetic modeling produced an apparent diffusivity of 1.2 × 10⁻⁵ m²/s and a structural accessibility time constant of ~25 h. Thermodynamic analysis showed that rotation improved the overall free energy of adsorption and altered entropy in a manner consistent with the observed adsorption-desorption sequence. These results demonstrate that rotational fields can enhance CO₂ uptake, modify kinetic pathways, and trigger threshold phenomena in porous adsorbents. Full article

To explore the strong coupling between surface phonon polaritons (SPhPs) and quantum dots in one-dimensional periodic microstructures for quantum information processing, we establish a comprehensive theoretical model for SPhPs at air–polar dielectric interfaces. By rigorously deriving the dispersion relations, we reveal the decisive role of scale effects on bandgap formation: continuous spectra without bandgaps emerge at the nanoscale ($d\sim 10$–100 nm), whereas periodic modulation induces significant Bloch mode folding and tunable bandgaps (0.5–5 $\mathsf{\mu }\mathrm{m}$ width) at the microscale ($d\sim 1$–10 $\mathsf{\mu }\mathrm{m}$). Based on Fourier bandwidth limitations, we determine optimal channel widths ($L_y\ge 10 \mathsf{\mu }\mathrm{m}$) for maintaining low-loss modes with energy deviations below 1%. Through electromagnetic field quantization, we obtain analytical expressions for SPhP mode amplitudes and quantum dot transition rates. Calculations demonstrate that in micrometer-scale CsI structures, spontaneous emission rates can be modulated significantly: suppressed to <0.1 times the free-space values within bandgaps (excited-state lifetimes extended to ∼10 ns) and enhanced 5–8 times at conduction band edges. Leveraging these characteristics, we propose a scheme for batch quantum state manipulation of ${10}^2$–${10}^3$ arrayed quantum dots via selective excitation of specific Bloch modes using controlled laser frequency and angle, enabling parallel single-qubit gates with theoretical fidelity > 99%. Compared with surface plasmon polariton schemes, our approach utilizes the low-loss infrared characteristics of SPhPs ($Q\sim 100$–1000, 1–2 orders higher) to reduce decoherence rates, offering a new pathway for room-temperature solid-state quantum computing and on-chip multi-node entanglement distribution. Full article

Hyperdimensional computing (HDC) provides a highly efficient alternative to neural networks for intracranial electroencephalography (iEEG) seizure detection on edge devices with strict resource limits. While sparse HDC can significantly reduce energy use, current hardware fails to capitalize on this for two reasons. First, existing designs do not optimize the encoding architecture specifically for sparse execution, leaving potential energy savings on the table. Second, researchers often ignore the “area” problem, the large physical space high-dimensional vectors take up on a chip, which must be solved to make these devices small enough for practical edge use. This work presents a sparse HDC accelerator that bridges these gaps through three key contributions. First, we streamline the sparse encoding architecture to improve energy and area efficiency by integrating a compressed item memory (CompIM) and simplified spatial bundling. Second, to address the area bottleneck and enable true edge deployment, we systematically explore area trade-offs via sequentialization techniques, evaluating both channel folding (CF) and vector folding (VF). Third, we push efficiency even further by proposing an item-memory-free (IM-free) architecture. By replacing the baseline segmented shift binding with a standard shift binding scheme, and gracefully utilizing raw local binary pattern (LBP) codes directly as shift amounts, we completely bypass the CompIM for simultaneous area and energy savings. However, this optimization incurs a drop in detection accuracy; hence, we ultimately present two tailored configurations. First, our energy-optimized IM-free design achieves a 5.55× area and 3.08× energy improvement over the sparse HDC baseline, alongside 8.20× and 13.37× improvements over the dense baseline. Second, to prioritize clinical performance, our balanced streamlined design utilizes a channel folding factor (CFF) of 4 to preserve higher accuracy. This balanced approach achieves a 5.97× area and a 4.66× energy improvement over the dense baseline, with a 4× latency increase. Full article

Human cytomegalovirus (HCMV) remains a significant cause of morbidity in immunocompromised patients, necessitating the development of improved antivirals. Using an integrated in silico and in vitro approach, we identified a novel ligand (NL) as a letermovir analog with enhanced binding affinity and reduced cytotoxicity. A pUL56 terminase subunit model generated with AlphaFold 3 was used for the virtual screening of a 15,000-compound library. Among the 73 candidates with structural similarity to letermovir (Tanimoto ≥ 0.6), NL exhibited superior predicted binding affinity (ΔG_bind = −10.7 kcal/mol). In silico toxicity prediction (ProTox 3.0) classified NL as having low toxicity (class 4, LD50 ≈ 1000 mg/kg), which was confirmed in vitro, where NL demonstrated 158-fold less toxic (CC50 = 2.69 mg/mL) in MRC-5 cells than letermovir (0.017 mg/mL). Molecular dynamics simulations over 500 ns revealed that the pUL56-NL complex forms a more thermodynamically stable interaction, with a lower calculated free energy of binding (MMGBSA: −40.89 ± 7.40 kcal/mol vs. −32.76 ± 4.96 kcal/mol) and a narrower free energy landscape. These results establish NL as a promising, low-cytotoxicity candidate with enhanced target engagement, warranting further investigation as a potential anti-HCMV therapeutic. Full article

Aflatoxin B1 (AFB1) poses a serious threat to global food and feed safety. Laccase-based enzymatic degradation represents a promising green strategy for AFB1 removal; however, its industrial application is severely limited by the rapid thermal inactivation of wild-type enzymes under high-temperature processing conditions (>70 °C). Here, we engineered the thermal stability of a laccase from Bacillus amyloliquefaciens B10 through an integrated strategy combining computational structural biology with semi-rational design. By coupling molecular dynamics (MD) simulations with folding free-energy (ΔΔG) calculations, we identified key flexible regions associated with thermal instability and subsequently implemented iterative saturation mutagenesis. The best single mutant, R196C, retained more than 96% relative activity after heat treatment at 80 °C for 10 min. Further iterative mutational stacking progressively enhanced thermostability: the R90E/R196C double mutant showed 1.25-fold higher activity at 80 °C than R196C, and the R90E/R196C/H54F triple mutant showed a further 1.16-fold increase over the double mutant. The final quadruple mutant, R90E/R196C/H54F/R253I, achieved 86.9% AFB1 degradation at 80 °C after 24 h. High-temperature MD simulations (100 ns at 353.15 K) indicated that the enhanced thermostability was associated with reduced conformational flexibility, lower radius of gyration (Rg) and solvent-accessible surface area (SASA), and a coil-to-β-sheet transition that contributed to stabilization of the protein core. In addition, efficient secretory expression of the engineered enzyme was achieved in Pichia pastoris, reaching 3.0 U/mL, while the crude enzyme maintained more than 70% activity at 80 °C. Collectively, these results provide a practical basis for the rational engineering and scalable production of thermostable biocatalysts for AFB1 detoxification-related applications of AFB1 control, and offer broader insights into the targeted enhancement of thermal stability in industrial enzymes. Full article

Trichothecene mycotoxins, especially T-2 toxin, represent a significant threat to food safety and public health. Although the enzymatic degradation of deoxynivalenol has been extensively investigated, there are few reports of enzymes capable of efficiently degrading T-2 toxin. This study identified that the aldo-keto reductase AKR13B3 from Devosia A6-243 exhibits 3-keto-DON-degrading and a little T-2 toxin-degrading activity. To address this limitation, a rational design strategy targeting the substrate-binding pocket was employed to enhance its activity. Utilizing site-directed and combinatorial mutagenesis, a double mutant R134F/D217A was successfully screened. R134F/D217A retains catalytic activity towards 3-keto-DON while significantly enhancing its catalytic capacity for T-2. Specifically, the R134F/D217A variant exhibited a 2.88-fold increase in catalytic activity and a 3.15-fold enhancement in catalytic efficiency (k_cat/K_m) relative to the wild type enzyme. Notably, a substantial improvement in thermal stability was also observed. After incubation at 55 °C, the residual activity of the R134F/D217A mutant was 2.63 times that of the wild type. Molecular dynamics (MD) simulations and three-dimensional structural modeling suggested the mechanistic basis for the enhanced performance of the R134F/D217A double mutant. Catalytic enhancement stems from a shortened nucleophilic attack distance, a positively biased electrostatic environment, combined with an enlarged pocket and reduced binding free energy. Concurrently, the increased thermal stability results from decreased flexibility and a more rigid structural architecture. This work presents the first report of AKR13B3 as an effective enzyme for T-2 toxin transformation, and its catalytic activity was significantly enhanced through rational design. Thus, a novel enzymatic strategy was proposed, and could inform future approaches to study issues related to T-2 toxin contamination. Full article

This paper presents a comprehensive framework for the identification, state estimation, and robust control of a bistable Duffing–Holmes oscillator, validated through an experimental setup. First, to address parametric uncertainty, a Recursive Least Squares Method (RLSM) with a forgetting factor is applied to a filtered model representation, enabling accurate parameter convergence from noisy measurements. Subsequently, a Nonlinear Integral Extended State Observer (NIESO) is designed to reconstruct unmeasured states and estimate total disturbances. A key theoretical contribution is the derivation of explicit gain conditions that guarantee the observer’s stability, overcoming limitations of previous designs. For trajectory tracking, an observer-based backstepping controller is synthesized. Crucially, to bridge the gap between theory and practice, a drift-free integration scheme is implemented to generate feasible position commands for the shake table, preventing actuator saturation. Experimental results confirm the framework’s effectiveness, achieving a 3.7-fold reduction in RMS tracking error compared to open-loop operation, with the tracking error rapidly converging to a small neighborhood within approximately $0.2$ $\mathrm{s}$. Furthermore, the closed-loop system demonstrates superior energy efficiency, requiring significantly lower actuator voltage to sustain stable interwell oscillations. Full article

Cell-free protein synthesis has become a powerful tool for producing functional proteins, circumventing many limitations of live-cell systems. Platforms based on wheat germ extract are favored for their high efficiency in translating and folding complex eukaryotic proteins. To overcome the energy limitation common in such systems, we engineered an Escherichia coli strain to function as a self-renewing ATP source. This strain co-expresses a three-enzyme cascade—adenosine kinase, adenylate kinase, and acetate kinase—that efficiently converts adenosine and acetyl phosphate into ATP. Using the lysate from this biocatalyst to energize an optimized wheat germ extract, we established a high-performance cell-free synthesis platform. This integrated system supported the robust production of multiple recombinant proteins. As a key demonstration, we synthesized human vascular endothelial growth factor 165, which exhibited full biological activity. The cell-free-produced VEGF₁₆₅ significantly stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). It also potently induced angiogenic responses, including the formation of extensive, interconnected capillary-like networks by HUVECs in vitro and accelerated cell migration in scratch-wound assays. Our work establishes a scalable and efficient platform for on-demand production of bioactive eukaryotic proteins, highlighting its considerable potential for advancing regenerative medicine and related therapeutic applications. Full article

Deciphering the coupling mechanisms between post-harvest precursor shaping and roasting thermochemistry is pivotal for precise coffee flavor modulation. This study aimed to investigate the regulation mechanisms of in vitro biomimetic fermentation (BF) on the precursor-roasting reaction network. Integrated multi-omics characterization and sensory evaluation reveal that the BF protocol achieves targeted substrate enrichment, notably amplifying free amino acids—particularly leucine and phenylalanine—by 1.89-fold while accumulating lactate and succinate buffering salt systems. This reconfiguration constructs a matrix with superior thermal buffering capacity (ΔpH 0.17), which optimizes the thermal reaction kinetic window during roasting. Consequently, BF drives a 3.08-fold surge in esterification flux, significantly increasing the abundance of key fruity markers such as ethyl acetate and ethyl isovalerate. It also enhances the diversity of Maillard products, specifically elevating nutty-associated alkylpyrazines (e.g., 2,3,5-trimethylpyrazine). Concurrently, BF improves the thermal stability of bioactive compounds, including 5-caffeoylquinic acid (5-CQA) and trigonelline. Multi-scale molecular dynamics and quantum chemical calculations elucidate that BF-derived organic acid–salt complexes exert a ‘pseudo-catalytic effect,’ lowering activation free energy barriers for critical aroma-generating reactions by approximately 8.5 kcal/mol. This study demonstrates high sensory predictability (predictive model R² = 0.98) and provides a quantitative theoretical framework to advance coffee processing from empirical observation to rational flavor design. Full article

Elastomer-based nanocomposites combining polymer flexibility with conductive nanofillers provide lightweight, stretchable systems with tunable electromechanical properties for wearable electronics, soft robotics, and self-powered sensors. However, predicting their nonlinear response remains challenging because the observed piezoelectric-like response arises from strain-dependent interfacial polarization and evolving piezoresistive conduction pathways within heterogeneous microstructures. We introduce a continuum electro-hyperelastic framework combining the Mooney–Rivlin model for large-strain elasticity with a Helmholtz free-energy approach for electrostatic coupling. Analytical expressions for stress, electric displacement, and apparent piezoelectric coefficients are derived and implemented in finite element simulations. The model accurately reproduces the experimental mechanical, dielectric, and electromechanical behaviour of polydimethylsiloxane (PDMS) nanocomposites with 0.1–1 wt% graphene. These show increased stiffness, relative permittivity (from 3.4 to 4.0, ≈18%), and quasi-static d₃₃ coefficients (from −5.6 to −10.0 pC N⁻¹, ≈80% enhancement). Analytical and finite element method (FEM) results show consistent trends across the full deformation range, with Maxwell stress agreement within 10% at lower deformation levels, while deviations of 33–40% for coupled electromechanical quantities at an axial displacement u_z = ~−1 mm (~16.7% compressive strain) are attributable to three-dimensional shear effects absent from the uniaxial analytical assumption. Simulations reveal that graphene boosts Maxwell stress, yielding a four-fold increase at lower stretch ratios. This reframes PDMS–graphene composites as electro-hyperelastic materials, offering a predictive, extensible framework. It highlights apparent piezoelectricity as an emergent, tunable effect from charge redistribution in a compliant hyperelastic matrix—guiding the design of next-generation flexible devices leveraging field-induced coupling over intrinsic polarization. Full article

Ketone bodies (KBs) are the only energy substrates oxidized by the brain, whose concentration in the circulation can greatly increase when a physiological situation requires it. For example, when an adult human fasts for two days, circulating KBs rise twenty-fold from ~0.1 to ~2 mM. As a fuel, KBs provide the brain with acetyl-CoA that produces ATP or glutamate, notably in certain brain regions. Remarkably, KBs activate the expression of their own cerebral transporters and KB-utilizing enzymes so that circulating levels determine cerebral utilization of KBs. Throughout evolution, the energetic role of KBs has been crucial for the metabolic homeostasis of humans endowed with a large brain and facing unpredictable periods of food shortage. Paradoxically, the brain of modern, regularly fed humans whose ordinary blood KBs are ~0.1 mM, has access to much fewer circulating sources of energy than that of their distant ancestors. KBs can modify certain proteins post-translationally, for example, histones through lysine-butyrylation. KBs could act as short- or long-term epigenetic messengers. These properties of KBs might allow a fetus to directly sense maternal starvation and adapt their cerebral metabolism to this situation, possibly preparing for nutritional constraints in extra-uterine life. KB transcriptional and epigenetic properties could also enable the postnatal organism to retain a molecular memory of its own starvation episodes. No other energy substrate, such as glucose or lactate, has such capacities. Medicine turned its attention to KBs a century ago. Indeed, KBs are the only energy substrates whose circulating levels can be increased, and nutritional interventions can alter them under free-living conditions. This property opens broad prospects for ketogenic diets (KDs) to prevent or rescue neurodegenerative diseases characterized by glucose hypometabolism, notably Alzheimer’s disease (AD). However, KDs have not yet found real medical applications, for reasons that are discussed. Full article

The emergence of drug-resistant strains of Plasmodium falciparum continues to challenge global malaria control efforts, underscoring the urgent need for novel therapeutic strategies. In this study, we present an integrative computational framework that combines ensemble machine learning, molecular docking, and molecular dynamics simulations to predict and characterize the antimalarial activity of compounds from the Malaria Box database. Initially, topographical and quantum mechanical descriptors were used to construct regression models for predicting pEC₅₀ values, but due to the limited predictive performance in the global regression, a classification strategy was adopted, categorizing compounds into “active” and “very active” classes. The best ensemble classifier achieved robust performance (Acc₁₀-fold = 0.738, Acc_ext = 0.675), with good sensitivity and specificity over individual models. Subsequent regression modeling within each class yielded high predictive accuracy, with ensemble models reaching Q²10-fold values of 0.810 and 0.793 for the very active and active classes, respectively. To explore potential mechanisms of action, molecular docking was performed against P. falciparum Cytochrome B, revealing strong binding affinities for most compounds, particularly those forming π–π stacking and hydrogen bonds with Glu272. Molecular dynamics simulations over 200 ns confirmed the stability of several ligand–protein complexes, including unexpected behavior from compound M31, which demonstrated stable binding despite poor docking scores, suggesting a possible competitive inhibition mechanism. Binding free energy calculations further validated these findings, highlighting several promising candidates for future experimental evaluation. This integrative approach offers a powerful platform for accelerating antimalarial drug discovery by combining predictive modeling with mechanistic insights. Full article

Norovirus is a major cause of acute viral gastroenteritis in humans. Molecular biology-based detection methods play a pivotal role in ensuring accurate and specific diagnosis. The inclusion of Qβ phage particles as armored positive controls in these assays can further enhance their reliability and specificity. Herein, we discuss rational design strategies to improve the stability of Qβ bacteriophage capsid proteins armored with RNA using Discovery Studio 2019 protein design software. Amino acid mutation sites were deter-mined based on changes in folding free energy differences (ΔΔGmut). These single-site mutations were subsequently evaluated using molecular dynamics simulations. Wild-type and mutant recombinant expression plasmids were constructed and transformed into Escherichia coli BL21 (DE3) for cloning and expression. The stability of Qβ virus-like particles (VLPs) was assessed using real-time fluorescence RT-qPCR. The results showed that structurally intact and uniformly distributed wild-type and single-site mutant VLPs were successfully obtained. Stability analyses indicated that at 4 °C, 25 °C, 37 °C, 45 °C, and 60 °C, the single-site mutant exhibited a significantly lower rate of degradation than the wild-type. In conclusion, rational design enables the generation of single-site mutant VLPs with enhanced stability, providing a safer and more stable standard reference material for the molecular detection of foodborne viruses. Full article

The performance of Gas Metal Arc-Directed Energy Deposition (GMA-DED) strongly depends on efficient path-planning strategies that balance trajectory quality and computational cost. With the purpose of developing a computationally faster and more scalable path-planning approach, this study introduces the Fast Advanced-Pixel strategy by integrating the K-means clustering algorithm into to the Advanced Pixel strategy version to reduce the dimensionality of an optimization problem. Computational validation was conducted on four geometrically distinct parts using different clustering configurations. Statistical analysis (ANOVA) was applied to assess the significance of the results. The findings revealed that by increasing the number of clusters, computational time is substantially reduced, achieving up to a twenty-fold improvement compared with the former strategy, while maintaining consistent trajectory quality. Experimental validation using complex parts, such as a “Jaw Gripper” and a “C-frame” of a resistance spot welding gun, confirmed defect-free deposition and dimensional agreement with the CAD models. Accordingly, within the scope of GMA-DED technology and pixel-based path-planning strategies, the Fast Advanced-Pixel approach demonstrates a significant improvement in computational efficiency while preserving trajectory quality, enabling the accurate and reliable fabrication of geometrically complex metallic parts. Full article

Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear. Methods: In this study, we performed a comparative computational analysis of norovirus–glycan interactions by integrating AlphaFold3-based structure prediction, molecular docking, and molecular dynamics simulations. A total of 182 P-domain models representing all genotypes across five human norovirus genogroups (GI, GII, GIV, GVIII, and GIX) were predicted and docked with a lettuce-derived core-fucosylated hexasaccharide (H₂N₂F₂) previously identified by our group. The three complexes exhibiting the most favorable docking energies were further examined using 40 ns molecular dynamics simulations, followed by MM/GBSA binding free energy calculations and per-residue decomposition analyses. Results: Docking results indicated that the majority of modeled P proteins were able to adopt energetically favorable interaction poses with H₂N₂F₂, with predicted binding energies ranging from −3.7 to −7.2 kcal·mol⁻¹. The most favorable docking energies were observed for GII.6_S9c_KC576910 (−7.2 kcal·mol⁻¹), GII.3_MX_U22498 (−7.1 kcal·mol⁻¹), and GII.4_CARGDS11182_OR700741 (−6.8 kcal·mol⁻¹). Molecular dynamics simulations suggested stable ligand engagement within canonical HBGA-binding pockets, with recurrent residues such as Asp374, Gln393, and Arg345 contributing to electrostatic and hydrophobic interactions, consistent with previously reported HBGA-binding motifs. MM/GBSA analyses revealed comparatively favorable binding tendencies among these complexes, particularly for globally prevalent genotypes including GII.3, GII.4, and GII.6. Conclusions: This work provides a large-scale structural and energetic assessment of the potential interactions between a naturally occurring lettuce-derived fucosylated hexasaccharide and human norovirus P domains. The results support the notion that core-fucosylated food-associated glycans can serve as interaction partners for diverse norovirus genotypes and offer comparative molecular insights into glycan recognition patterns relevant to foodborne transmission. The integrative AlphaFold3–docking–dynamics framework presented here may facilitate future investigations of virus–glycan interactions within food matrices. Full article