Search Results (6,245)

In this paper, we study a nonlinear system of sequential Caputo fractional differential equations equipped with coupled mixed multi-point boundary conditions. In particular, the boundary conditions involve the values of the unknown functions at the endpoints expressed as linear combinations of their values at several interior points, forming a closed system of relations. The existence of solutions is established by applying the Leray–Schauder alternative, while uniqueness is proved using Banach’s contraction principle. In addition, we investigate the Hyers–Ulam stability of the proposed system. Several examples are included to demonstrate the applicability of the theoretical results. Some special cases of the general problem are also discussed. Full article

This paper develops a unified analytical framework for pricing discretely sampled volatility-average swaps under the 4/2 stochastic volatility model. The model accommodates a broad range of volatility dynamics by combining affine and inverse-affine components in the instantaneous volatility specification, thereby unifying and extending the structural features of the classical Heston and 3/2 stochastic volatility models. Closed-form expressions for the conditional complex moments of the asset price are derived and serve as the fundamental building blocks for obtaining explicit analytical pricing formulas for volatility-average swaps under discrete sampling. The validity of the proposed pricing formulas is rigorously established within the admissible parameter space of the model. Extensive numerical experiments verify the accuracy and computational efficiency of the analytical results when compared with Monte Carlo simulations. The numerical analysis further reveals that discretely sampled volatility swap prices converge to their continuous-time counterparts in a manner that may be monotonic or non-monotonic, depending on the interaction between the volatility and inverse-volatility components of the 4/2 model, thereby emphasizing the importance of sampling effects in volatility derivative valuation. A detailed sensitivity analysis demonstrates how variations in the parameters governing the volatility and inverse-volatility components influence the fair strike prices, underscoring the structural flexibility of the 4/2 stochastic volatility model. Overall, the proposed framework provides an analytically tractable and computationally efficient approach for pricing volatility-linked derivatives under discrete sampling, offering valuable insights for both theoretical research and practical applications in volatility markets. Full article

Background: The efficacy of pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) has been confirmed in numerous controlled studies. However, in clinical practice, pharmacological treatment is heavily dependent upon the parents or guardians of patients. Parental attitudes are shaped not only by medical knowledge but also by parental beliefs about the use of pharmacotherapy and psychoactive substances, including ADHD pharmacotherapy. Parental beliefs about the safety and possible side effects of pharmacotherapy significantly influence their decision to accept or reject pharmacotherapy. This study aimed to explore parental beliefs and attitudes toward ADHD pharmacotherapy and their association with parental treatment acceptance and treatment-related decision-making. Methods: The cross-sectional online survey included 506 parents of children diagnosed with ADHD, recruited through closed social media groups. Parental treatment acceptance and decisions regarding initiation of pharmacotherapy were examined. Results: Parents of children with experience of pharmacotherapy more frequently considered pharmacotherapy safe (83.4% vs. 39.7%, p < 0.001) and expressed readiness to start treatment immediately (73.8% vs. 32.5%, p < 0.001). In this group, 72.6% of parents indicated that the benefits of pharmacotherapy outweigh potential risks. However, concerns about addiction were similar in both groups (49.4% vs. 45.3%, p = 0.400). In a gendered analysis, fathers were more likely than mothers to consider pharmacotherapy unnecessary for treating ADHD (35.3–22.4%; p = 0.002; V = 0.142) or disbelieve in ADHD treatment (25.7–15.1%; p = 0.005; V = 0.132). Furthermore, fathers were more likely than mothers to support limiting the use of pharmacotherapy for treating ADHD to those over 18 (41.3% vs. 26.5%; p < 0.001; V = 0.156), and to report parental opposition (28% vs. 8.1%; p < 0.001; V = 0.264), with a minimal to moderate effect size. Conclusions: Parental treatment acceptance decisions were associated with more favorable parental beliefs, although subjective concerns about addiction remained. Given the study’s cross-sectional and exploratory nature, causal interpretations should be avoided. Parental gender was associated with differences in beliefs and attitudes toward the use of pharmacotherapy for treating children diagnosed with ADHD, especially regarding necessity, consent and age-specificity. In our surveyed sample, fathers tended to be more restrictive or cautious than mothers. The findings also highlight the importance of psychoeducation and partnership-based communication between clinicians and families as key factors that may help support treatment acceptance-related decision-making in ADHD. Full article

Non-small cell lung cancers (NSCLCs), most notably adenocarcinoma and large cell carcinoma, have been the most frequently diagnosed lung cancer and continue to represent a leading cause of cancer-related mortality worldwide, largely due to its aggressive growth and limited therapeutic responsiveness. Natural products derived from traditional medicinal plants remain a valuable source for the discovery of novel anti-cancer agents. In this study, the anti-cancer potential of Angiopteris evecta (G. Forst.) Hoffm., a medicinal fern widely used in Thai traditional medicine, was investigated in human NSCLC, A549 and H1299 cells. Subsequential solvent extraction yielded hexane, ethyl acetate, and ethanol fractions, among which the ethyl acetate extract (AE-EA) exhibited the strongest growth inhibitory activity. Bioactivity-guided fractionation of AE-EA by thin-layer chromatography generated an (-)-epi-osmundalactone-rich fraction (OLRF), which contained three closely related lactone/furanone derivatives, with (-)-epi-osmundalactone as the predominant constituent, as determined by NMR analysis. AE-EA and OLRF significantly suppressed NSCLC cell viability and clonogenic survival and induced G0/G1 cell cycle arrest, accompanied by downregulation of cyclin D1, cyclin E1, CDK-2, and CDK-4 (p < 0.05). Both treatments also triggered intrinsic apoptosis, as evidenced by mitochondrial membrane depolarization, reduced expression of Bcl-2, and Bcl-xL, and survivin, and activation of cleaved caspase-9 and caspase-3. Mechanistically, AE-EA and OLRF significantly suppressed mitogen-activated protein kinase (MAPK) signaling through inhibition of ERK1/2, JNK1/2, and p38 phosphorylation in both NSCLC cells (p < 0.05). Collectively, these findings demonstrate that AE-EA and OLRF exert pronounced anti-cancer effects in both NSCLC cells through coordinated inhibition of MAPK signaling, induction of cell-cycle arrest, and activation of intrinsic apoptosis, supporting their potential for further development as plant-derived anti-cancer agents. Full article

This paper details the design of a guidance architecture, in the form of a layered, finite state machine, meant to enable safe and autonomous rendezvous operations. The onboard software uses relative state parametrization based on relative orbital elements which provide significant geometrical insight into the shape of the relative orbit. The development is structured in two main steps: first, novel closed-form impulsive control schemes, derived from the Gauss Variational Equations expressed in a velocity-aligned frame, are formulated. These complement available strategies from the literature and generalize them for arbitrarily eccentric reference orbits. Secondly, the definition of the guidance layer provides the chaser spacecraft with the capability to select, schedule, and execute the proper maneuvers to complete a given rendezvous scenario, ensuring operational safety and predictability. The functionality and performance of the implemented architecture are analyzed through numerical tests in a linear propagator and a high-fidelity non-linear simulator. The results provide validation of the developed maneuvers’ strategies, as well as demonstrating how the proposed guidance architecture can be used in a straightforward fashion across different target orbit scenarios, while guaranteeing the same level of passive safety. Full article

Membrane lipid remodeling plays a pivotal role in regulating plant growth, reproductive development, and adaptive responses to environmental stress. However, several lipid-modifying enzymes remain uncharacterized in Arabidopsis thaliana. Here, we provide the first comprehensive in silico functional characterization of the unannotated gene AT5G35460, integrating domain architecture, AlphaFold-supported structural validation, and phylogenetic, expression, and regulatory analyses. Domain architecture and conserved DUF2838 signatures, together with transmembrane topology and validation using AlphaFold-predicted structural data, support its identity as a glycerophosphocholine acyltransferase (GPCAT1). Phylogenetic reconstruction showed that GPCAT1 clustered closely with its orthologs of major angiosperms, suggesting deep evolutionary preservation. Expression profiling revealed over a tenfold higher transcript abundance in mature pollen, detected 6–8 times more than during leaf senescence, indicating strong developmental control. Co-expression network analysis revealed links to the lipid metabolism genes (CDS2, LACS8, and SBH1) as well as factors involved in response to stress, indicating that AT5G35460 may act at the level of phosphatidylcholine remodeling, membrane resistance and stress response. Analysis of the promoter sequences showed AACTAAA, ABRE and G-box elements (pollen-specific, ABA-responsive and stress-inducible motif respectively), suggesting appropriate transcriptional regulation consistent with its expression profile. As a whole, the findings revealed that AT5G35460 is an unexplored membrane-localized acyltransferase involved in lipid maintenance during reproductive development and environmental responses. This study serves as a basis for subsequent functional characterization and identifies AT5G35460 as a potential target for modifying pollen viability, senescence kinetics and stress tolerance in plants. Full article

Background/Objectives: Melanoma, characterized by high rates of metastasis and recurrence, is a particularly aggressive malignant tumor. The underlying mechanisms driving its progression remain enigmatic. The close interplay between tumor and non-tumor cells is pivotal, significantly shaping the tumor microenvironment. Extracellular vesicles emerge as a crucial vector influencing this environment, as they can modulate cellular mechanisms and biological functions—marking a key frontier in tumor mechanism research. However, the potential impact of intercellular communication on tumor cell biology remains largely unexplored. Methods: In the study, we employed a pair of cell lines derived from melanoma M14 cells, designated as highly metastatic cells (POL cells) and the low metastatic cells (OL cells), and elucidate their characteristics. Results: Our findings revealed that POL cells can potentiate the metastatic potential of OL cells through the transfer of extracellular vesicles, which harbor functional microRNAs, specifically miR-23a-5p in this context. Upon entering OL cells, the EV-miR-23a-5p orchestrates changes in the m6A modification levels of the mRNA of tumor suppressor genes Mtus1 and Prrg4. Conclusions: This modulation subsequently influences the expression of these genes and, in turn, the invasive behavior of OL cells. Full article

This paper presents an orthogonal-heading wavelength-resolution SAR (WRSAR) target detection framework that fuses multi-heading image stacks for foliage-penetrating (FOPEN) vehicle detection. First, a low-rank–sparse decomposition is applied to very-high-frequency (VHF), ultra-wideband (UWB) WRSAR stacks to suppress vegetation clutter and enhance target contrast. The clutter-suppressed sparse stacks acquired from orthogonal headings are then fused to enrich target scattering characteristics. Finally, a Rayleigh-entropy statistic computed on the fused sparse stack is used to represent discontinuous positional changes. Based on the non-negative nature of WRSAR amplitudes for both clutter and FOPEN targets, we introduce a non-negative constrained tensor robust principal component analysis (NCTRPCA) to improve sparsity in the stack components. Furthermore, since Shannon differential entropy has no tunable parameter, we replace Shannon entropy with RE in this work and derive its closed-form expression for the proposed detector. Experiments on the publicly available multi-heading, multi-temporal CARABAS II dataset show that the proposed orthogonal-heading WRSAR fusion achieves higher FOPEN vehicle detection performance than recent state-of-the-art methods while maintaining moderate computational cost. Full article

Flemingia philippinensis Merr. et Rolfe (F. philippinensis) is a Chinese herbal medicine rich in polyphenols, especially isoflavone derivatives. It exhibits potent anti-inflammatory properties and is widely used in the treatment of various diseases. In this study, we aim to sequence, assemble, and analyze the mitogenome of F. philippinensis in detail to understand the genetic structure of their organelles and their gene expression. The results showed that the mitogenome of F. philippinensis possesses a circular architecture with a total length of 427,353 bp and a GC content of 44.90%. Annotation results revealed 33 unique protein-coding genes (PCGs), 16 transfer RNA (tRNA), and 3 ribosomal RNA (rRNA) genes in the mitogenome. Furthermore, comparative analysis of mitogenome andchloroplast gemone (cpgemone) sequences identified six mitochondrial plastid sequences (MTPTs), including one partial PCG and five complete tRNA genes. Subsequent collinearity analysis indicated that numerous homologous collinear blocks were detected between F. philippinensis and its closely related species, and have undergone a large number of genomic rearrangements in the F. philippinensis mitogenome. Finally, RNA editing analysis identified 498 C -to- U editing sites, notably enriched in nad4 (44 sites) and ccmB (33 sites). Codon usage bias analysis indicated that leucine (Leu 10.66%) and serine (Ser 9.19%) were the most frequently used amino acids. This study lays a theoretical foundation for further elucidating the structural characteristics and understanding the evolution, classification, and identification of F. philippinensis. Full article

The Asian migratory locust (Oedaleus decorus asiaticus) is a major grassland pest in northern China, with outbreak dynamics closely linked to phase transition mediated by chemical communication. This study focused on a chemosensory protein, OasiCSP12, to explore its potential role in this process. We analyzed its expression patterns via qRT-PCR, purified the recombinant protein, and identified potential ligands through fluorescence competitive binding assays. Structural insights were gained through homology modeling, molecular docking, and molecular dynamics simulations, with binding energetics assessed using MM/PBSA. Results showed that OasiCSP12 expression is phase- and sex-specific, being significantly upregulated in gregarious adult antennae. The protein bound selectively to 15 locust body-surface volatiles, including aldehydes and esters. Its structure features a hydrophobic binding cavity where van der Waals interactions, primarily predicted to be mediated by residues Val86, Leu71, and Trp101, likely stabilize ligand complexes. These findings indicate that OasiCSP12 is potentially associated with both chemical perception and phase regulation in O. d. asiaticus, providing a candidate target for developing behavior-based green control strategies against this pest. Full article

Tachykinins (TKs), a conserved family of neuropeptides, play critical roles in regulating multiple physiological processes such as feeding and energy metabolism in insects. This study identified the TK gene (ApTK) from the Chinese oak silkworm, Antheraea pernyi, an economically important insect species. Bioinformatic analysis showed that ApTK possesses four FX₁GX₂R motifs (X₁ and X₂ represent variable amino acid residues), comprising FMGVR, FYGVR, FIGVR, and FFGMR, in the C-terminus and shares a close phylogenetic relationship with TKs from Bombyx mori and Manduca sexta. Tissue-specific expression profiling demonstrated that ApTK was mainly expressed in the brain and midgut. Starvation–refeeding experiments showed that the expression of ApTK was significantly upregulated during food deprivation and returned to baseline after refeeding, evincing its involvement in hunger signaling. RNA interference (RNAi)-mediated knockdown of ApTK led to a significant increase in larval body weight and increased levels of triglyceride, glycogen, and trehalose, indicating enhanced energy storage. Collectively, these results demonstrate that ApTK acts as a key regulator in restraining feeding and modulating energy homeostasis in A. pernyi. Our findings provide insights into the neuroendocrine mechanisms underlying feeding behavior and energy metabolism in A. pernyi. Full article

This study aimed to qualitatively analyze the identified use of dusty construction products in relation to hazard characteristics, occupational exposure limits, Safety Data Sheet features, and material composition. The secondary aim of the study was to explore the relationship between sustainability, expressed as Portland clinker percentage, and health-related indicators. A total of 283 Safety Data Sheets (SDSs) from six large construction companies operating in central Italy were analyzed. Data were extracted on identified use, risk classification, hazard score (H-score), occupational exposure limits (TLVs), composition, SDS update status, and clinker content. Associations between identified use and qualitative variables were explored, while differences in hazard score and clinker percentage were assessed across product categories. Univariate regression analyses were conducted to evaluate predictors of clinker content. The results show marked differences among construction products in terms of hazard profiles, exposure limits, and composition, closely linked to their intended use. Cement-containing products were predominant and associated with higher hazard scores and lower TLVs. Clinker percentage increased with product hazardousness and H-score, indicating a link between sustainability indicators and occupational risk. This study provides the first identified-use–based analysis of powdery construction materials. Overall, these findings emphasize the importance of use-specific risk assessment and targeted safety training in the construction sector. Full article

Estrogen suppress food intake, and soy isoflavones exhibit estrogen-like activities. However, the specific isoflavone components responsible for appetite regulation and their underlying neuroendocrine mechanisms remain unclear. We investigated whether the major soy isoflavones daidzein and genistein differentially influence feeding behavior and hypothalamic appetite-regulating neuropeptides in female rats. Ovariectomized (OVX) and sham-operated female rats were fed a control diet or diets supplemented with daidzein or genistein (150 mg/kg diet) for one or two weeks under ad libitum conditions. A separate OVX group received subcutaneous estradiol. Hypothalamic expression of orexigenic and anorexigenic neuropeptides was quantified during the dark (active) and light (inactive) phases. Daidzein, but not genistein, significantly reduced food intake, body weight gain, and body fat in both OVX and intact females, whereas estradiol decreased these parameters only in OVX rats. Among all hypothalamic neuropeptides examined, urocortin was the only gene that responded to dietary daidzein, showing a significant increase exclusively during the light phase of Week 1. Neither NPY nor CRH expression was altered by daidzein. The temporal pattern of urocortin induction closely paralleled the reduction in food intake, suggesting a potential mechanistic link. Daidzein exerts a female-specific anorectic effect that cannot be explained solely by estrogenic activity. The selective upregulation of hypothalamic urocortin during the light phase represents a novel neuroendocrine response to dietary daidzein and may contribute to its suppression of food intake. These findings provide new insight into the sex-specific metabolic actions of dietary isoflavones. Full article

Analytical models of transdermal drug delivery (TDD) often represent deeper skin layers using ideal sink assumptions or phenomenological interfacial resistances. While mathematically convenient, these approaches obscure the physical role of the dermis and hypodermis in controlling molecular transport. Here, we develop an impedance-based analytical model for diffusion across multilayer skin membranes, in which the epidermal barrier is dynamically coupled to a finite diffusive backing layer representing the dermis–hypodermis composite. Diffusion impedance links transport conductivity, storage capacity, and layer thickness, while preserving continuity of concentration and flux at all interfaces. Closed-form expressions in the Laplace domain describe concentration fields and interfacial fluxes, and cumulative drug uptake is computed in the time domain via inverse Laplace transformation. The model identifies distinct short- and long-time transport regimes. Commonly used Dirichlet and Robin boundary conditions emerge as limiting cases but cannot reproduce the regime-dependent behavior of a backing layer. In particular, Robin formulations reduce the backing layer to a constant effective resistance, neglecting its storage capacity and time-dependent impedance. By replacing ad hoc boundary conditions with a physically grounded impedance framework, this approach provides a unified and extensible method for analyzing multilayer transport systems, including extensions to anomalous or memory-dependent diffusion. Full article

Background: Prostate cancer (PCa) shows a marked biological heterogeneity that is closely associated with tumor aggressiveness. A substantial proportion of clinically significant tumors remain undetected by multiparametric magnetic resonance imaging (mpMRI). Elucidating the molecular basis of MRI visibility and identifying non-invasive biomarkers could improve the risk stratification and clinical management of patients. Accordingly, this study aimed to assess tissue and urine proteomic signatures associated with PCa aggressiveness and mpMRI visibility. Methods: In this exploratory study, we performed an integrated proteomic analysis of prostate tissue and preoperative urine samples from 24 patients stratified into four groups: benign prostatic hyperplasia (BPH), indolent PCa (Gleason 6), clinically significant PCa with MRI-visible lesions, and clinically significant PCa with MRI-non-visible lesions. Data-independent acquisition mass spectrometry (DIA workflows) was used to identify differentially expressed proteins associated with malignancy, tumor aggressiveness, and MRI visibility. Results: Pairwise proteomic analyses revealed significant molecular differences between BPH and all PCa groups, identifying 694 non-redundant proteins differentially expressed in tissue and 482 in preoperative urine, showing molecular features associated with both disease presence and progression. Comparative tissue and urine analyses identified 82 proteins, reflecting shared biological pathways in metabolism, cytoskeletal organization, immune processes, and extracellular matrix remodeling. Finally, a direct comparison of MRI-visible and MRI-non-visible clinically significant PCa identified a panel of differentially expressed proteins, including LCN2/NGAL, S100A9, and AOC1/DAO, that showed differential urinary abundance and prognostic relevance in the TCGA-PRAD cohort. Conclusion: Our results suggest that proteomic alterations in PCa are associated with disease progression and aggressiveness and capture biologically relevant differences between tissue and urinary proteomes. These differences are also observed between MRI-visible and MRI-non-visible clinically significant prostate cancers, supporting the potential of urinary proteomics as a non-invasive complement to imaging-based diagnostics. Full article