Search Results (452)

This work proposes the study of light-sensitive resistive sensors composed of dispersed heterojunctions (BHJs) in a poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) matrix, fabricated from cobalt and palladium porphyrins (CoOEP and PdOEP), and mixed with ethylanthraquinone (EAQ). Topographical characterization was performed using atomic force microscopy. In addition, the BHJs were characterized by their transmittance and fluorescence, and their band gap of 3.6 eV was similar for both heterojunctions and independent of the metal in the porphyrin. However, transmittance and fluorescence are more strongly correlated with the metal of the macrocycle. With PdOEP-EAQ/PEDOT:PSS and CoOEP-EAQ/PEDOT:PSS films as active layers, sensitive resistive sensors were fabricated and optimized by embedding SnO₂ and ZnO nanoparticles in PEDOT:PSS, as well as aluminum hydroxyquinoline, within the same polymer matrix. The devices fabricated on Tetra Pak and glass substrates were electrically characterized over a voltage range of −1.1 to 1.1 V under both white illumination and darkness. The results show that glass devices deposited with SnO₂-PEDOT:PSS and ZnO-PEDOT:PSS exhibit improved linearity of electrical conduction under dark conditions. Furthermore, for the SnO₂-PEDOT:PSS/CoOEP-EAQ device, the electron mobility and free carrier density were estimated, yielding values of ${\mu }_n=2.495\times {10}^{-3}{\displaystyle \frac{\mathrm{c}{\mathrm{m}}^2}{\mathrm{V}\mathrm{s}}}$ and $n_0=8.69\times {10}^{20}{\displaystyle \frac{1}{\mathrm{c}{\mathrm{m}}^3}}$, respectively. The manufactured devices exhibited a light-dependent resistive response, suggesting their suitability for light-sensing applications. Full article

Prolactin (PRL) is a hormone synthesized by lactotrophs in the anterior pituitary gland. It is also produced by extrapituitary glands such as the prostate and breast, where it promotes growth. Notably, PRL also contributes to cancer development in these glands. PRL is known to stimulate cancer cell migration, suggesting its possible involvement in metastasis, for which cell migration is a critical step. However, the role and mechanisms by which PRL induces cancer cell migration are not yet fully understood. One well-studied mechanism involves its receptor, the prolactin receptor (PRLR). After PRL binds to its receptor, PRLR dimerizes and induces transphosphorylation of Janus kinase 2 (JAK2), which subsequently phosphorylates p21-activated kinase 1 (PAK1), leading to increased cell migration. Although the PRL-JAK2-PAK1 pathway in cancer cell migration has been investigated, the molecular mechanism remains incompletely understood. Additionally, other PRL-activated pathways are implicated in migration, but their roles remain debated. This narrative review examines and discusses the main findings on the involvement of PRL in the migration of cancerous and non-cancerous cells, as well as the molecular mechanisms involved. We conclude that PRL promotes the migration of both cancerous and non-cancerous cell lines and should, therefore, be taken into account in future cancer research. Full article

Background/Objectives: To evaluate the impact of dental laboratory material overlays on metal artifact reduction in multidetector computed tomography (MDCT) of the oral cavity across different CT protocols and reconstruction algorithms. Methods: An anthropomorphic mandible phantom was constructed using extracted human teeth, metal-ceramic restorations, and ballistic gelatin as a soft-tissue analog. Six dental materials (Elite HD+, Vonflex S Putty, Tropicalgin, MB Wax 1, Zetaplus, and COE-PAK) were tested as overlays. MDCT imaging was performed following low-dose and standard protocols with primary and O-MAR reconstructions, yielding 28 datasets. Two radiologists independently assessed artifact indices (AIs), overall image quality (OIQ), and spherical marker visibility (SMV), with excellent inter-observer agreement (ICC = 0.985). Results: Vonflex S Putty model consistently demonstrated the lowest AIs and highest OIQ scores, while maintaining stable performance across both protocols and reconstructions. Elite HD+ and Zetaplus also showed favorable results, while COE-PAK and MB Wax 1 frequently underperformed. Tropicalgin exhibited high AIs with primary reconstruction but improved markedly with O-MAR. SMV analysis confirmed Vonflex S Putty as the only material to consistently outperform the control under low-dose conditions. Conclusions: Silicone-based overlays, particularly Vonflex S Putty, are effective in reducing metal artifacts and improving image quality in MDCT. Overlay selection, combined with MAR algorithms such as O-MAR, represents a complementary strategy for optimizing diagnostic accuracy in patients with metallic restorations. Full article

This paper presents the strain-smoothed element (SSE) method applied to the 4-node tetrahedral finite element. The unique characteristic of the SSE method represents constructing a smoothed strain field for the elements, rather than for the smoothing domains, whereby the constant strains of all adjacent elements are fully utilized for the strain smoothing of the target element. Consequently, a linear strain field within the 4-node tetrahedral finite element is constructed through four Gauss integration points. The method does not require any additional creation of the mesh, and a standard isoparametric formulation of the 4-node tetrahedral finite element is used to formulate it. A numerical example was used to demonstrate the stress prediction improvement achieved as regards the corrected element, as taken from Chaemin Lee and Phill-Seung Lee’s publication of the method itself, compared with the linear and quadratic tetrahedral finite elements, which are implemented within the PAK and Simcenter Nastran software packages. The numerical results show that stresses predicted by the strain-smoothed 4-node tetrahedral finite element are comparable to that of a 10-node tetrahedral finite element that incorporates an extrapolation process for the determination of nodal stress values. Full article

This paper presents an analytical and numerical benchmark verification framework for explicit time integration procedures applied to the one-dimensional wave equation. The study combines an exact analytical solution, a closed-form discrete central-difference solution, and explicit finite element models implemented in LS-DYNA and in the in-house academic FEM code PAK-Multiphysics. Two benchmark problems with the same first sinusoidal spatial mode and homogeneous Dirichlet boundary conditions are considered. The first problem, defined by sinusoidal initial displacement and zero initial velocity, is used to analyse the central-difference discretization and its convergence behaviour. The closed-form discrete response enables direct comparison with the analytical solution and confirms the expected second-order accuracy under coupled mesh and time-step refinement at a fixed Courant number. The second problem, defined by zero initial displacement and sinusoidal initial velocity, introduces a phase-shifted temporal response suitable for explicit finite element verification. Four meshes are analysed over five periods of the first longitudinal mode. The numerical responses are assessed using displacement histories, maximum absolute errors, RMS errors, relative RMS errors, amplitude errors, and an energy check. The PAK-Multiphysics results show very close agreement with the analytical solution and a systematic reduction of the error measures, consistent with the lumped-mass central-difference formulation. The LS-DYNA results provide an independent commercial-code comparison, showing decreasing displacement errors under refinement and bounded total-energy variation. The proposed framework provides a transparent and reproducible benchmark for verifying one-dimensional explicit wave propagation models. Full article

Dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising therapeutic strategy due to its ability to simultaneously target oncogenic signaling and cellular metabolism in cancer. While existing inhibitors such as KPT9274 and PF-3758309 have demonstrated preclinical activity, their clinical translation has been limited by poor selectivity, suboptimal efficacy, and dose-limiting toxicities. Reliance on a small number of available compounds is therefore insufficient, highlighting the need for systematic optimization to identify candidates with improved therapeutic profiles. Although several dual PAK4 and NAMPT inhibitors such as GNE2861, LCH7749944, and PF3758309 have been identified in our previous study, the number of compounds available is limited. Identification of new candidate compounds would allow researchers to identify those that are the most efficient, those that are the most potent and selective, and those that have optimal pharmacokinetics. In this study, we performed additional large-scale drug screening to identify new candidate dual PAK4 and NAMPT inhibitors and expand the diversity of this inhibitor class. Computational molecular docking was used to evaluate binding affinities toward both targets, followed by drug–protein interaction analyses to assess binding stability and interaction patterns at the molecular level. Several new candidate compounds demonstrated favorable predicted binding to both PAK4 and NAMPT, with distinct interaction profiles compared to previously reported inhibitors. Biochemical assays further demonstrated inhibitory activity against both PAK4 and NAMPT among several selected compounds, supporting their potential as dual-target inhibitors. These findings provide mechanistic insight into dual-target engagement and highlight structural features associated with improved binding behavior. Expanding the pool of dual inhibitors enhances opportunities for preclinical development, supports optimization of pharmacokinetic and safety profiles, and strengthens datasets for drug discovery. Collectively, this work broadens the landscape of dual PAK4 and NAMPT inhibitors and supports their potential application across multiple cancer types beyond triple-negative breast cancer. Full article

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article

Functional fermented foods are increasingly recognized as sources of microbial metabolites with potential biological activity. In this study, MRK2-3, a protease-sensitive anti-Helicobacter pylori component produced by Lactiplantibacillus pentosus MRK2-3 isolated from fermented mushroom sausage, was enriched and preliminarily characterized for in vitro anti-H. pylori activity. Activity appeared during the stationary phase. Sequential ethyl acetate extraction, Sep-Pak C18 chromatography, and reverse-phase HPLC increased specific activity, although the final activity recovery was 0.72%. MALDI-TOF analysis of the active fraction showed a dominant ion at approximately m/z 1848 together with several lower-intensity ions; therefore, chemical homogeneity and sequence identity were not established. The MRK2-3 fraction retained activity after incubation at pH 2–6 and after heating at 80 °C and 100 °C for 30 min, whereas activity decreased under alkaline conditions and after treatment at 121 °C for 15 min. Trypsin, α-chymotrypsin, pepsin and proteinase K reduced activity. The fraction inhibited all tested H. pylori strains (agar-dilution MIC ranged from 12.5 to 100 μg/mL). In a simulated gastric fluid, higher concentrations produced a rapid reduction in viable H. pylori 3949 counts. These findings support MRK2-3 as a fermentation-derived putative antimicrobial peptide candidate with anti-H. pylori activity under gastric-like conditions. However, its amino acid sequence, structural identity, and novelty require confirmation. Antimicrobial mechanism, cytotoxicity, and in vivo efficacy also remain to be established. Full article

Water hyacinth has become a major environmental problem in aquatic ecosystems worldwide, including Indonesia, due to its rapid growth and extensive surface coverage. Transforming this invasive biomass into high-quality compost offers a sustainable solution for biomass management and agricultural utilization. However, information regarding the combined effects of decomposer selection and the compost aeration process on compost quality, nutrient transformation, and agronomic performance remains limited. This study was conducted in Rawa Pening, Central Java, Indonesia, to determine how decomposer type and turning regime (specifically the frequency and method of mechanically aerating the compost pile) influence the quality of water hyacinth compost and to identify the most suitable formulation for pak choi (Brassica rapa L.) growing media. The experiment consisted of four sequential stages: composting, compost quality assessment, compost selection, and plant growth bioassay. Three decomposers (EM4™, cow dung, and Stardec™) were evaluated under turning and no-turning conditions using a factorial completely randomized design. Compost quality was assessed based on physicochemical characteristics, nutrient composition, compost yield, and correlation analysis. The best compost treatment was subsequently evaluated in different soil–compost mixtures using ANOVA, PCA, and correlation analysis. The results demonstrated that turning and decomposer selection acted synergistically to determine compost performance. Cow dung consistently produced the highest compost yield, whereas Stardec™ combined with turning generated the most mature compost, characterized by the lowest C/N ratio and the highest nitrogen and phosphorus contents. Plant bioassay confirmed that the optimal growing medium consisted of 50% soil and 50% compost, which maximized vegetative growth by balancing nutrient availability with physical support for root development. No toxicity symptoms were observed, indicating that mature water hyacinth compost is safe for agricultural use. These findings provide practical guidance for selecting decomposers based on compost production objectives and promote the sustainable utilization of invasive water hyacinth. Full article

Agrarian cultural landscapes depend not only on the symbolic value of place but also on the viability of the producers who sustain landscape-bearing practices. This study asks which indigenous rice value-chain pathway is most supportable in the near term under current production, post-harvest, market, and coordination conditions, and what this implies for conservation planning. Using the Pak Phanang Basin, Thailand, as an area-based case, the study integrates evidence from 52 indigenous rice-farming households in four subdistricts, farmer meetings and focus group discussions, value-chain actors, relevant agencies, spatial and documentary sources, and a consumer survey used as supplementary demand-side evidence. Seven value-chain pathways were compared qualitatively using six criteria: downstream demand or final use, quality requirements, post-harvest burden, investment needs, coordination burden, and producer readiness. The findings show that farmer participation remains concentrated in low-risk channels, especially household consumption and mill sales. Paddy rice for game fowl and native chicken feed emerged as the most territorially supportable near-term pathway because it showed the strongest practical fit among identifiable downstream buyers and final-use clarity, moderate quality requirements, manageable post-harvest and investment burdens, coordination requirements, and producer readiness. Its feasibility, however, depends on reducing post-harvest bottlenecks, improving aggregation, managing quality, and coordinating with downstream buyers. The study concludes that feasible value-chain upgrading should be planned as conservation-enabling support for custodian viability, rather than as a simple shift toward higher-value markets. Full article

This study investigated the effects of far-red (FR, 740 nm) and ultraviolet-A (UV-A, 370 nm) supplementation on the growth and nutritional quality of pak choi (Brassica rapa ssp. chinensis ‘Xiawang’) under different light intensities. Plants were grown under a white LED background light (6500 K) at two light intensities (100 and 400 μmol·m⁻²·s⁻¹) either without (T100 and T400) or with an additional 40 μmol·m⁻²·s⁻¹ of FR or UV-A radiation (T100FR, T100UV-A, T400FR, and T400UV-A). The results demonstrated a significant interactive effect between light intensity and FR/UV-A supplementation. Under low light intensity (T100), both FR and UV-A significantly enhanced biomass accumulation, the net photosynthetic rate, and the content of soluble proteins, soluble sugars, and cellulose. Under a high light intensity (T400), FR and UV-A primarily promoted morphological development (leaf expansion and thickening), photosynthetic performance, and carbohydrate accumulation. Specifically, FR notably promoted petiole elongation while reducing photosynthetic pigment content, whereas UV-A markedly increased the vitamin C content while decreasing nitrate accumulation. In conclusion, both FR and UV-A supplementation effectively improve the growth and quality of pak choi, but, through light-intensity-dependent mechanisms. FR acts mainly via morphological and photosynthetic optimization, whereas UV-A acts as a physiological and nutritional regulator. These findings highlight the complementary roles of FR and UV-A, providing practical guidance for optimizing spectral strategies in controlled environment agriculture (CEA). Full article

Phosphorus scarcity and inefficient fertilizer utilization highlight the need for sustainable phosphorus recovery and reuse strategies. In this study, a Zn/Fe-layered double hydroxide (Zn/Fe-LDH)-kelp-derived biochar (KBC) composite (Zn/Fe-LDH@0.5KBC) was synthesized via co-precipitation for phosphate capture and subsequent reutilization as a slow-release fertilizer. The incorporation of KBC improved the dispersion of LDH nanosheets and generated a hierarchical porous structure with a specific surface area of 122.13 m²/g. As a result, Zn/Fe-LDH@0.5KBC exhibited a high phosphate adsorption capacity of 132.52 mg P/g and reached adsorption equilibrium within 240 min. Kinetic and isotherm analyses indicated that phosphate adsorption was dominated by chemisorption and was best described by the Sips model. Comprehensive scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analyses revealed that phosphate removal occurred through synergistic mechanisms, including electrostatic attraction, interlayer anion exchange, surface complexation, and metal phosphate precipitation. The P-loaded composite exhibited diffusion-dominated phosphorus release in soil and significantly enhanced pak choi growth. Compared with the control, labile phosphorus increased from 2.8% to 6.8%, while moderately labile phosphorus increased from 6.3% to 14.1%, indicating improved phosphorus availability. These findings demonstrate an effective strategy for integrating phosphate recovery from wastewater with agricultural reuse and provide insights into the development of multifunctional adsorbent-fertilizer systems for circular phosphorus management. Full article

Background/Objectives: Docetaxel is a frontline chemotherapeutic agent for breast cancer; however, therapeutic resistance remains a major clinical challenge. Emerging evidence suggests that chemotherapy-induced adaptive phosphorylation events can promote survival signaling and contribute to drug resistance. However, the phosphoproteomic mechanisms underlying docetaxel-induced adaptive responses remain poorly characterized. Methods: We performed integrated quantitative proteomic and phosphoproteomic profiling in breast cancer cells following docetaxel exposure. Candidate kinases associated with phosphorylation remodeling were identified and validated using TCGA-BRCA and CPTAC clinical datasets. The functional significance of PAK4 phosphorylation was validated using phosphomimetic and phospho-deficient mutants, pharmacological inhibition, and assessment of microtubule stabilization. Results: Integrated phosphoproteomic analysis revealed extensive phosphorylation remodeling following docetaxel treatment and identified PAK4 as a candidate kinase associated with the adaptive response. Analysis of the CPTAC phosphoproteomic dataset showed that phosphorylation of PAK4 at S474 was elevated in breast cancer tissues, increased with tumor stage, and was associated with poorer overall survival. In breast cancer cells, docetaxel induced phosphorylation of PAK4 at S474 without altering total PAK4 expression. Functionally, phosphomimetic PAK4 (S474D) reduced docetaxel sensitivity, whereas phospho-deficient PAK4 (S474A) enhanced drug sensitivity. Pharmacological inhibition of PAK4 using LCH-7749944 significantly enhanced the inhibitory effect of docetaxel on cell viability and increased apoptosis in breast cancer cells. Mechanistically, PAK4 inhibition enhanced docetaxel-induced microtubule stabilization, as evidenced by increased α-tubulin acetylation and accumulation of stabilized microtubule structures. Conclusions: Our study demonstrates that docetaxel induces global phosphorylation network reprogramming in breast cancer cells and identifies PAK4 S474 phosphorylation as a key determinant of docetaxel sensitivity. Inhibition of PAK4 enhances microtubule stabilization and improves the efficacy of docetaxel, providing a potential combinatorial strategy to overcome taxane resistance. Full article

KIF21A, a member of the Kinesin-4 family of motor proteins, is involved in the regulation of microtubule dynamics and intracellular transport, with emerging evidence suggesting its potential role in cancer progression. In this study, we performed an integrative analysis of over 3825 human phosphoproteomics studies to characterize site-specific phosphorylation of KIF21A. Three predominant phosphosites were identified in KIF21A (S853, S1212, and S1239) with the highest detection frequency across phosphoproteomics studies, and were analyzed for co-regulation patterns to identify potential kinase associations and functional networks. Phosphosite S853 showed a strong association with cytoskeletal organization and cortical microtubule stabilization complexes (CMSCs) components, including KANK1 (S186), PHLDB2 (S513, S42) and CLASP1 (S600, S572, S646), indicating its role in cytoskeletal organization. Upstream kinase analysis identified potential regulators, such as PAK2, RPS6KA1/A3, RPS6KB1, CHEK1/2 and CDK18/16 with site-specific variability in their associations with KIF21A predominant sites. Interestingly, phosphosite-specific correlation analysis between KIF21A and candidate kinases revealed that the KIF21A S1239 phosphosite exhibited tumor-specific correlations with CDK18 across multiple cancer types. Functional enrichment revealed that co-regulated phosphoproteins were involved in cytoskeleton regulation, cell cycle regulation, and carcinogenesis. Pan-cancer analysis demonstrated dysregulated expression of KIF21A in multiple tumor types, with stage-associated upregulation in selected cancers. Gene-level validation further supported these findings, showing consistent positive correlations between KIF21A and key regulators such as CTNND1 and PTK2, as well as other cytoskeleton and cancer-associated genes. Overall, this study highlights site-specific phosphorylation as a key regulatory mechanism of KIF21A and suggests its involvement in cytoskeleton-associated signaling networks in cancer. Full article

Background/Objectives: To determine the association between post-pancreas transplantation weight gain and graft dysfunction. Methods: Retrospective analysis of pancreas transplantation from 1 August 2008 to 1 November 2022. All patients > 18 years old who underwent simultaneous kidney pancreas transplant (SPK), pancreas after kidney transplant (PAK), and pancreas transplant alone (PTA) with at least one year of follow up were included. The association between post-transplant weight gain and graft dysfunction was assessed. Graft dysfunction was defined as HbA1c > 6.5% or use of antihyperglycemic medication. Results: Twenty-five percent of recipients had substantial weight gain (SWG), defined as >7% weight increase, by 1 year post-transplant. Recipients with T2D and SPK recipients were more likely to gain weight. SWG within the first year was significantly associated with the development of graft dysfunction at most recent follow up (Cox HR = 3.3, p = 0.005), but not at 1 year. Recipients with SWG in the first year had significantly higher HbA1C at most recent follow up (5.3 ± 0.7% vs. 5.9 ± 0.9%, p = 0.009), but not at 1 year. Among recipients with SWG occurring after 1 year, there were no differences in graft dysfunction or HbA1C at 1 year and no difference in graft dysfunction or HbA1C at most recent follow up. Conclusions: In this single-center study, SWG at 1 year post-transplant was associated with the development of graft dysfunction and elevated HbA1C in the long term. Full article