Search Results (16,849)

In the context of sustainable logistics planning, carbon emission costs have become a critical factor influencing distribution decisions. Meanwhile, the time-dependent characteristics of urban road networks and simultaneous pickup–delivery operations present significant challenges to vehicle routing problems (VRPs). This study addresses a time-dependent vehicle routing problem with simultaneous pickup–delivery and time windows (TDVRPSPDTW). Fuel consumption and carbon emission costs are quantified using a comprehensive emission model, while time-dependent network conditions, simultaneous pickup–delivery demands, and time window constraints are integrated into a unified modeling framework. To solve this NP-hard problem, an improved ant colony optimization (IACO) algorithm is developed by incorporating adaptive large neighborhood search to enhance solution diversity and convergence efficiency. Computational experiments are conducted using internationally recognized VRPSPDTW benchmark datasets and newly constructed TDVRPSPDTW instances, together with sensitivity analyses under varying traffic conditions, time window flexibility, and delivery strategies. The results indicate that the proposed IACO effectively addresses the TDVRPSPDTW. Comparing ant colony optimization with local search (ACO-LS), the IACO achieves a maximum reduction of 11.78% in total distribution cost. Furthermore, relative to the conventional separate pickup–delivery strategy, the simultaneous pickup–delivery mode reduces total distribution cost and carbon emission cost by 49.96% and 53.48%, respectively. Full article

Cancer is one of the leading causes of mortality worldwide, with breast and colon cancers being among the most common neoplasms in men and women, respectively. Despite significant advancements in treatment, there is a pressing need to enhance specificity and reduce systemic side effects. Importantly, a distinctive feature of cancer cells is their acidic extracellular environment, which profoundly influences cancer progression. In this study, we evaluated the anticancer activity of a pH-sensitive nanocomposite based on silver nanoparticles and pegylated carboxymethyl chitosan (AgNPs-CMC-PEG) in breast cancer (MCF-7) and colon cancer (HCT 116) cell lines. To achieve this, we synthesized and characterized the nanocomposite using UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (STEM-in-SEM). Furthermore, we assessed cytotoxic effects, apoptosis, and reactive oxygen species (ROS) generation using MTT, DAPI, and H2DCFDA assays. Additionally, we analyzed the expression of DNA methyltransferases (DNMT3a) and histone acetyltransferases (MYST4, GCN5) at the mRNA level using RT-qPCR, along with the acetylation and methylation of H3K9ac and H3K9me2 through Western blot analysis. The synthesized nanocomposite demonstrated an average hydrodynamic diameter of approximately 175.4 nm. In contrast, STEM-in-SEM analyses revealed well-dispersed nanoparticles with an average core size of about 14 nm. Additionally, Fourier-transform infrared (FTIR) spectroscopy verified the successful surface functionalization of the nanocomposite with polyethylene glycol (PEG), indicating effective conjugation and structural stability. The nanocomposite exhibited a pH and concentration dependent cytotoxic effect, with enhanced activity observed at an acidic pH 6.5 and at concentrations of 150 µg/ml, 75 µg/ml, and 37.5 µg/ml for both cell lines. Notably, the nanocomposite preferentially induced apoptosis accompanied by ROS generation. Moreover, expression analysis revealed a decrease in H3K9me2 and H3K9ac in both cell lines, with a more pronounced effect in MCF-7 at an acidic pH. Furthermore, the expression of DNMT3a at the mRNA level significantly decreased, particularly at acidic pH. Regarding histone acetyltransferases, GCN5 expression decreased in the HCT 116 line, while MYST4 expression increased in the MCF-7 line. These findings demonstrate that the AgNPs-CMC-PEG nanocomposite has therapeutic potential as a pH-responsive nanocomposite, capable of inducing significant cytotoxic effects and altering epigenetic markers, particularly under the acidic conditions of the tumor microenvironment. Overall, this study highlights the advantages of utilizing pH-sensitive materials in cancer therapy, paving the way for more effective and targeted treatment strategies. Full article

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

Background: Exposure to environmental pollutants, especially endocrine-disrupting chemicals, disproportionately affects vulnerable populations like pregnant women, lactating mothers, and preterm infants. This study aimed to assess the detection patterns of DiNP-, DEP-, and DEHP-related metabolites in maternal urine and breast milk, examine agreement between matrices, and explore maternal factors associated with phthalate exposure. Methods: Fifty-five mothers who delivered at ≤32 gestational weeks and whose infants were hospitalized in the Neonatal Intensive Care Unit (NICU) were enrolled. Breast milk and urine samples were analyzed using a validated isotope-dilution LC–MS/MS method. Urinary phthalate metabolite concentrations were adjusted for specific gravity. Linear mixed-effects models with a random intercept for mother were used to examine associations between urinary and breast milk phthalate metabolite concentrations, assess temporal changes, and evaluate the influence of breast milk lipid content. Results: DEHP and DiNP metabolites were detected in nearly all maternal urine samples. Breast milk contained predominantly primary metabolites (MEHP and MiNP), while secondary oxidative metabolites were rarely detected. Urine concentrations consistently exceeded breast milk concentrations. Urinary and breast milk phthalate concentrations were not correlated across sampling periods, indicating limited matrix concordance. Conclusions: Mothers of very preterm infants experience sustained phthalate exposure in the postpartum period; however, limited metabolite transfer to breast milk indicates that maternal urine remains the preferred biomonitoring matrix for assessing systemic phthalate exposure. Breast milk phthalate profiles exhibit compound-specific temporal changes and appear largely independent of concurrent urinary exposure biomarkers. Full article

The application of zinc oxide nanoparticles (ZnONPs) in agriculture is expanding due to their biostimulant potential; however, their influence on plant chemical communication and associated microbial communities remains not fully characterized. This study presents a multi-perspective analysis contrasting the effects of ZnONPs with those of conventional microparticulate ZnO (Bulk) on Capsicum annuum seedlings grown in substrate at 50 and 500 mg kg⁻¹. Results indicate that, at high doses, the bulk material (B500) led to higher foliar zinc accumulation (128.7 mg kg⁻¹) compared to ZnONPs (NP500, 119.7 mg kg⁻¹), a difference potentially linked to nanoparticle aggregation in the soil matrix limiting root uptake. At the physiological level, a distinct response was observed: while Bulk ZnO stimulated superoxide dismutase (SOD) activity, ZnONPs resulted in a marked reduction (93%), suggesting a shift in the antioxidant strategy toward non-enzymatic mechanisms, such as increased total phenol content. Regarding the volatilomic profile, ZnONPs induced specific metabolic alterations in the green leaf volatile (GLV) pathway, characterized by hexanal accumulation and reduced levels of hexanol and hexyl acetate. Additionally, ZnONPs were associated with lower methyl salicylate (MeSA) emissions, whereas the Bulk treatment increased its relative abundance to 41.7%. Finally, metagenomic analysis revealed that zinc treatments modulated the phyllosphere microbiota, favoring the proliferation of Actinobacteria while decreasing the abundance of sensitive taxa, such as Spirochaetes. Taken together, these findings suggest that ZnONPs act as a distinct metabolic modulator, altering internal physiology and chemical signaling. Full article

As a contribution to automated set-theoretic inferencing, a translation is proposed of conjunctions of literals of the forms $x=y\setminus z$, $x\ne y\setminus z$, and $z=\left\{x\right\}$, where $x,y,z$ stand for variables ranging over the von Neumann universe of sets, into quantifier-free Boolean formulae of a rather simple conjunctive normal form. The formulae in the target language involve variables ranging over a Boolean ring of sets, along with a difference operator and relators designating equality, non-disjointness, and inclusion. Moreover, the result of each translation is a conjunction of literals of the forms $x=y\setminus z$ and $x\ne y\setminus z$ and of implications whose antecedents are isolated literals and whose consequents are either inclusions (strict or non-strict) between variables, or equalities between variables. Besides reflecting a simple and natural semantics, which ensures satisfiability preservation, the proposed translation has quadratic algorithmic time complexity and bridges two languages, both of which are known to have an $\mathsf{NP}$-complete satisfiability problem. Full article

This work reports an enhanced flexible vacuum-ultraviolet (VUV) photodetector on a polyimide (PI) substrate based on hexagonal boron nitride nanosheets (BNNSs) with Al nanoparticles (Al NPs). The BNNS film were prepared via liquid-phase exfoliation combined with a self-assembly process, and size-controllable Al NPs were constructed on the BNNS’s surface by electron-beam evaporation followed by thermal annealing. When the Al film thickness was 15 nm, the annealed Al NPs exhibited a pronounced enhancement of photoelectric effects at a wavelength of 185 nm. Combined with finite-difference time-domain (FDTD) simulations, it was confirmed that the localized surface plasmon resonance (LSPR) generated by Al NPs significantly enhanced the local electromagnetic field and effectively coupled into the interior of BNNSs. These exhibited a strong plasmon-enhanced absorption effect and thereby improved light absorption and carrier generation efficiency. The flexible photodetector based on this structure showed an increase in the photo-to-dark current ratio from 110.17 to 527.79 under a bias voltage of 20 V, while maintaining fast response and recovery times of 79.79 ms and 82.38 ms, respectively. In addition, the device demonstrated good stability under multiple bending angles and cyclic bending conditions, highlighting its potential applications in flexible solar-blind VUV photo ultraviolet. Full article

Silver nanoparticles (AgNPs) have been studied extensively in recent years due to their biological activities. In addition to their well-known antibacterial, antioxidant, and anti-inflammatory properties, AgNPs also exhibit anticancer properties. Increasing evidence from in vivo and in vitro studies demonstrates that AgNPs exert significant anticancer effects through multiple mechanisms, including oxidative stress, mitochondrial dysfunction, DNA damage, cell cycle arrest, and apoptosis. In addition to these mechanisms, inhibition of certain pathways is also an important mechanism that enables AgNPs to exhibit anticancer activity. Furthermore, green-synthesized AgNPs often exhibit enhanced biocompatibility and improved selective cytotoxicity against cancer cells. Despite these promising findings, concerns regarding AgNP-associated toxicity, non-specific cellular damage, and long-term safety remain major challenges limiting their clinical translation. Strategies such as size and shape optimization, surface functionalization, and combination therapies have been recommended to enhance anticancer efficacy while minimizing adverse effects on healthy cells. This review brings together recent studies, offers a broad perspective, and aims to present an objective viewpoint to fully explain the anticancer potential and current challenges of AgNPs. Full article

Quantitative evaluations in 3D images acquired via Cone-Beam Computed Tomography (CBCT) are limited by the scatter abundance and cone-beam artifacts. This work investigates benefits in using an innovative scanning geometry in CBCT (eCT), which replaces each projection of the conventional scanning protocol with a series of collimated projections (Np) acquired over an oscillating trajectory, realized either with an oscillating source or a multi-spot array. In silico tests employed a cylindrical water phantom embodying inserts of four biological materials. 1 mm-thick bone slabs were sandwiched between 9 mm water slabs to evaluate the image conspicuity. eCT improved the Hounsfield Unit (HU) accuracy, with a direct relation with Np. eCT with Np = 10 reduced the bias of the estimated HU more than two times when compared to CBCT. Increasing the Np presented a large impact on the image conspicuity for portions of the FOV distant from the central axial plane, with the signal-to-noise ratio between water and bone slabs increasing by a factor of 18 for Np = 10 compared to CBCT. The proposed eCT configuration is expected to be adopted in applications without strict demand for scanning time and projection number, such as dentomaxillofacial and intrasurgical imaging, imaging of the extremities, and image-guided radiotherapy. Full article

Emerging from millions of years of evolutionary optimization, Natural products (NPs) remain unique, unparalleled sources of bioactive scaffolds. Unlike synthetic molecules engineered around single therapeutic targets, NPs often exhibit multi-target, system-level bioactivity, aligned with the principles of network pharmacology, which modulates pathways in a coordinated, non-disruptive manner. This approach reduces resistance, buffers compensatory feedback loops, and enhances therapeutic resilience. Fungal endophytes represent one of the most chemically diverse and biologically sophisticated NP reservoirs known, producing polyketides, alkaloids, terpenoids, and peptides with intricate three-dimensional architectures and emergent bioactivity patterns that remain exceptionally difficult to design de novo. Advances in artificial intelligence (AI), machine learning, deep learning, and multi-omics integration have redefined the discovery landscape, transforming previously intractable fungal metabolomes and cryptic biosynthetic gene clusters (BGCs) into tractable, predictable, and engineerable systems. AI accelerates genome mining, metabolomic annotation, BGC-metabolite linking, structure prediction, and activation of silent pathways. Generative AI and diffusion models now enable de novo design of NP-inspired scaffolds while preserving biosynthetic feasibility, opening new opportunities for direct evolution, pathway refactoring, and precision biomanufacturing. This review synthesizes the chemical and biosynthetic diversity of major NP classes from fungal endophytes and maps them onto the rapidly expanding ecosystem of AI-driven tools. We outline how AI transforms NP discovery from empirical screening into a predictive, hypothesis-driven discipline with direct industrial implications for drug discovery and synthetic biology. By coupling evolutionarily refined chemistry with modern computational intelligence, the field is poised for a new era in which natural-product leads are not only rediscovered but systematically expanded, engineered, and industrialized to address urgent biomedical and sustainability challenges. Full article

The Profitable Tour Problem is a well-known NP-hard optimization challenge central to tourism planning, aiming to maximize collected profit while minimizing travel costs. While classical heuristics provide approximate solutions, they often struggle with finding globally optimal routes. This paper explores the application of near-term quantum computing to this problem. We propose a framework based on the Variational Quantum Eigensolver to find high-quality solutions for the Profitable Tour Problem. The core of our contribution is a novel methodology for constructing a constraint-aware variational ansatz that directly encodes the problem’s hard constraints. This approach circumvents the need for large penalty terms in the Hamiltonian problem, which are often a source of optimization challenges. We validate our method through numerical simulations on a representative tourism scenario of up to 25 qubits. The results demonstrate the viability of the approach, achieving high solution accuracy consistent with brute-force enumeration for smaller instances. This work serves as a proof-of-concept for applying Variational Quantum Eigensolver to complex tourism optimization problems and provides a basis for future exploration on real quantum hardware. Full article

Over the past few decades, the production and application of nanoparticle-contained products have been increasing. With increasing production, nanoparticles (NPs) entered water and terrestrial environments, posing a threat to living organisms because their ecotoxicological characteristics are not yet fully understood. Upon entering the marine environment, NPs are subjected to various factors that can alter their properties. This could lead to changes in their toxic effects on marine organisms. One potential physical factor that affects NPs is UV radiation. The toxicity of different concentrations of UV-pre-irradiated TiO₂ NPs on dollars Scaphechinus mirabilis sperm was studied, which allowed comparison of the effects of UV-activated and non-activated NPs. According to the resazurin and comet assays, a significant toxic effect is observed at lower concentrations for pre-irradiated TiO₂ NPs compared to non-irradiated ones. Additionally, high concentrations of pre-irradiated TiO₂ resulted in a significant increase in levels of malondialdehyde (MDA) compared to non-irradiated. Thus, it was demonstrated that the UV pre-irradiation NPs caused a more pronounced toxic effect than the non-irradiated TiO₂ NPs. Full article

To investigate drug delivery in cancer therapy, we integrate fluorescence lifetime measurements, microspectrometry, and confocal laser scanning microscopy to track the uptake of inorganic–organic hybrid nanoparticles (IOH-NPs) by breast cancer cells over incubation periods ranging from 2 to 24 h. Non-radiative energy transfer (FRET) from the LysoTracker Green to the IOH-NPs confirms their lysosomal localization and possibly improves their optical excitation. Beyond the resolution limits of light and electron microscopy, fluorescence lifetime kinetics—including FRET—can thus reveal the nanoscale cellular localization of IOH-NPs and guide the optimization of fluorescence excitation. Here, we extend optical microscopy into a fifth dimension—picosecond fluorescence decay times—complementing 3D spatial and spectral information, establishing lifetime measurements as a versatile tool to study nanoparticle uptake in cancer therapy. Full article

Increasingly frequent extreme droughts threaten forest vegetation and highlight the need to identify drought-tolerant germplasm. To support conservation and cultivation of Illicium lanceolatum, we investigated ecotypic differences in photosynthetic responses to short-term drought and rewatering under varying light intensity. One-year-old seedlings from four I. lanceolatum ecotypes originating from the Zhejiang (Lin’an, LA; Kaihua, KH), Jiangxi (Wu’ning, WN), and Fujian (Nan’ping, NP) provinces in China were subjected to drought stress by withholding irrigation and subsequent rewatering. Photosynthesis–light response curves were measured before drought; 2, 4, and 7 days after the last watering; and following rewatering. Short-term drought significantly affected photosynthetic traits in an ecotype-dependent manner. Maximum net photosynthetic rate, light saturation point, light compensation point, and apparent quantum yield increased during drought, indicating enhanced utilization of both high and low light. After rewatering, stomatal conductance increased significantly in the WN and KH ecotypes but declined in the NP ecotype when compared with those under the initial water supply. Instantaneous water use efficiency (A/E) recovered rapidly in all ecotypes and exceeded pre-drought levels. Under light intensity above 1500 µmol·m⁻²·s⁻¹, stomatal conductance exhibited a significant nonlinear relationship with water use efficiency. Overall, these physiological responses indicate that I. lanceolatum is moderately drought-tolerant and exhibits mild sensitivity to soil water variation. The WN and KH ecotypes showed superior improvement in water use efficiency under drought and high light, suggesting their potential for breeding drought-resistant cultivars and for afforestation in drought-prone environments. Full article

This study examined the effects of applying silver nanoparticles (AgNPs; 0, 5 and 10 mg L⁻¹) in a hydroponic system for seven days on growth parameters and on nutrient and phytohormone concentrations in two tomato cultivars, Vengador and Rio Grande. The results indicated that AgNPs at concentrations of 5 and 10 mg L⁻¹ did not change leaf number, stem length, or fresh/dry biomass weight. In leaves of Vengador, P and K concentrations decreased, while Mg and S increased in response to AgNPs. In stems and roots, both P and K decreased. Zn concentrations increased in leaves, Mn in stems and roots. In leaves of Rio Grande, K, Mg, S, Cu and Mn concentrations increased, while P decreased in AgNP-treated plants, as compared to the control. In stems, N, S and Mn concentrations increased, but P, K, Ca, Mg and B decreased. In roots, P, K, Ca, Mg, Cu, Zn, Mn and B decreased, whereas S increased. Silver was only detected in roots of plants treated with AgNPs in both cultivars under study. In leaves of Rio Grande plants, kinetin concentrations decreased with AgNPs applications. In roots of Vengador, indole-acetic acid concentrations increased with 10 mg AgNP L⁻¹; in Rio Grande, roots exhibited an increased concentration of gibberellic acid and abscisic acid in plants exposed to 5 mg AgNP L⁻¹. The evidence retrieved from this work unveils the impact of metal-based NMs on the modulation of nutrient and phytohormone concentrations in a so important food crop such as tomato. Full article