Search Results (167)

Alkaptonuria (AKU) is a rare metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency, leading to homogentisic acid (HGA) accumulation and ochronotic pigment deposition, which drug therapy cannot reverse. The process of pigment formation and deposition is still unclear. This study offers molecular insights into the polymeric structure, with the goal of developing future adjuvant strategies that can inhibit or reverse pigment formation, thereby complementing drug therapy in AKU. HGA polymerisation was examined under physiological, acidic, and alkaline conditions using liquid and solid phase nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and polyacrylamide gel electrophoresis. At physiological pH, HGA polymerised slowly, while alkaline catalysis accelerated pigment formation while retaining the HGA aromatic scaffold. During the process, EPR detected a semiquinone radical intermediate, consistent with an oxidative coupling mechanism. Reactivity profiling showed the diphenol ring was essential for polymerisation, while –CH₂COOH modifications did not impair reactivity. Pigments displayed a polydisperse molecular weight range (11–50 kDa) and a strong negative charge. Solid-state NMR has revealed the presence of phenolic ether and biphenyl linkages. Collectively, these identified structural motifs can serve as a foundation for future molecular targeting related to pigment formation. Full article

Background/Objectives: Cancer progression is characterized by the suppression of apoptosis, activation of metastatic processes, and dysregulation of cell proliferation. The proper functioning of these mechanisms relies on critical signaling pathways, including Phosphoinositide 3-kinase/Protein kinase B/mammalian Target of Rapamycin (PI3K/Akt/mTOR), Mitogen-Activated Protein Kinase (MAPK), and Signal Transducer and Activator of Transcription 3 (STAT3). Although curcumin and resveratrol exhibit anticancer properties and affect these pathways, their pharmacokinetic limitations, including poor bioavailability and low solubility, restrict their clinical application. The aim of our study was to evaluate the synergistic anticancer potential of curcumin and resveratrol through hybrid molecules rationally designed from these compounds to mitigate their pharmacokinetic limitations. Furthermore, we analyzed the multi-target anticancer effects of these hybrids on the AKT serine/threonine kinase 1 (AKT1), MAPK, and STAT3 pathways using in silico molecular modeling approaches. Methods: Three hybrid molecules, including a long-chain (ELRC-LC) and a short-chain (ELRC-SC) hybrid, an ester-linked hybrid, and an ether-linked hybrid (EtLRC), were designed using the Avogadro software (v1.2.0), and their geometry optimization was carried out using Density Functional Theory (DFT). The electronic properties of the structures were characterized through Frontier Molecular Orbital (FMO), Molecular Electrostatic Potential (MEP), and Fourier Transform Infrared (FTIR) analyses. The binding energies of the hybrid molecules, curcumin, resveratrol, their analogs, and the reference inhibitor were calculated against the AKT1, MAPK, and STAT3 receptors using molecular docking. The stabilities of the best-fitting complexes were evaluated through 100 ns molecular dynamics (MD) simulations, and their binding free energies were estimated using the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Results: DFT analyses demonstrated stable electronic characteristics for the hybrids. Molecular docking analyses revealed that the hybrids exhibited stronger binding compared to curcumin and resveratrol. The binding energy of −11.4 kcal/mol obtained for the ELRC-LC hybrid against AKT1 was particularly remarkable. Analysis of 100 ns MD simulations confirmed the conformational stability of the hybrids. Conclusions: Hybrid molecules have been shown to exert multi-target mechanisms of action on the AKT1, MAPK, and STAT3 pathways, and to represent potential anticancer candidates capable of overcoming pharmacokinetic limitations. Our in silico-based study provides data that will guide future in vitro and in vivo studies. These rationally designed hybrid molecules, owing to their receptor affinity, may serve as de novo hybrid inhibitors. Full article

This meta-analysis explored the relationship of palm kernel cake inclusion level (PKC_Inclusion) with nutrient utilization and performance in cattle, goats and sheep under confinement. For this purpose, a dataset with 51 studies was constructed by using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) Protocol. Relationships of PKC_Inclusion with dry matter (DM), crude protein (CP), EE (ether extract), NDF (neutral detergent fiber) and TDN (total digestible nutrients) intake and digestibility, as well as with ADG (average daily gain) and FE (feed efficiency), were explored under a mixed model approach, considering the species and study as fixed and random effects, respectively. Data revealed independent (p < 0.075) relationships of EE and TDN intake and digestibility with PKC_Inclusion for cattle, goats and sheep. However, the relationship of CP intake and digestibility with PKC_Inclusion did not differ (p > 0.114) between ruminant species. Goats and sheep demonstrated similar quantitative patterns for DM and NDF intake but different quantitative patterns (p < 0.037) from those observed for cattle with the increase in PKC_Inclusion in the diet. Regarding performance, FE responses were similar between cattle and sheep but differed (p < 0.001) from those observed for goats; however, ADG demonstrated similar (p = 0.243) decreasing rates among ruminant species in function of dietary PKC_Inclusion. In conclusion, PKC_Inclusion has differential effects on the intake and digestibility of DM and most of the nutritional components in confined cattle, goats and sheep, except for CP. The data reported herein could be used in future nutritional models to allow for the better use of alternative feedstuffs, such as PKC in productive ruminants under confinement. Full article

Fungi are a prolific source of diverse bioactive metabolites, yet many remain unexplored. Among these, depsidones are a rare class of compounds with significant biological potential, but they are seldom reported in mushrooms. This study investigated the medicinal fungus Ganoderma lucidum, known for its extensive therapeutic use in traditional medicine. Fruiting bodies were extracted using petroleum ether, ethyl acetate, n-butanol, and methanol. Extracts were screened phytochemically and assessed for total phenolic content and antioxidant activity using the DPPH assay. Ethyl acetate extract exhibited the highest phenolic yield and antioxidant potential and was subsequently evaluated for cytotoxicity against HepG2, HCT116, MCF7, and A549 cancer cell lines. It showed notable anticancer activity with minimal toxicity to normal Vero cells. UHPLC/Q-TOF-MS/MS analysis of G. lucidum ethyl acetate extract tentatively identified nine minor depsidones including mollicellin G, simplicildone I, mollicellin B, talaromyone B, simplicildone A, purpactin C, emeguisin B, mollicellin E, and simplicildone D on the basis of high-resolution negative-mode detection and characteristic MS/MS fragmentation patterns. Molecular docking revealed strong binding affinities between these compounds and cancer-related targets (AKT1, CDK2, ERK1, TNFα), with simplicildone D and mollicellin G demonstrating particularly high interactions. These findings provide mechanistic insights into the observed bioactivity and highlight G. lucidum as a promising source of therapeutic depsidones for future anticancer drug development. Full article

Hemorrhagic stroke is a severe cerebrovascular disease with a high rate of disability and mortality. Its complex pathological mechanisms, such as blood–brain barrier damage, neuroinflammation, and oxidative stress, along with the restrictive nature of the blood–brain barrier, have restricted the clinical therapeutic effects of drugs. Nanotechnology, with its advantages of targeting ability, biocompatibility, and multifunctionality, has provided a new approach for the precise diagnosis and treatment of hemorrhagic stroke. In terms of diagnosis, imaging technology enhanced by magnetic nanoparticles can achieve real-time bedside monitoring of hematoma dynamics and cerebral perfusion, significantly improving the timeliness compared with traditional imaging methods. In the field of treatment, the nanodrug delivery system can remarkably improve the bioavailability and brain targeting of clinical drugs and herbal medicines by enhancing drug solubility, crossing the blood–brain barrier, and responsive and targeting drug release. Multifunctional inorganic nanomaterials, such as cerium oxide nanoparticles, graphene, and perfluorooctyl octyl ether nanoparticles, can alleviate brain edema and neuronal damage through antioxidant and anti-inflammatory effects, and the scavenging of free radicals. Moreover, gene delivery mediated by nanocarriers and stem cell transplantation protection strategies have provided innovative solutions for regulating molecular pathways and promoting nerve repair. Although nanotechnology has shown great potential in the diagnosis and treatment of hemorrhagic stroke, its clinical translation still faces challenges such as the evaluation of biosafety, standardization of formulations, and verification of long-term efficacy. In the future, it is necessary to further optimize material design and combine multimodal treatment strategies to promote a substantial breakthrough in this field from basic research to clinical application. Full article

A lunar landing pad (LLP) represents essential initial infrastructure for establishing sustainable lunar settlements. This study investigates the feasibility of constructing LLPs through in situ resource utilization (ISRU), focusing on an innovative composite material comprising lunar regolith and the high-performance thermoplastic Polyether Ether Ketone (PEEK). The proposed manufacturing approach involves mechanically blending regolith with PEEK granules, compacting the mixture in a mold, and thermally processing it to induce polymer melting and binding. Experimental analysis indicates that a modest binder fraction (15 wt. % PEEK) yields a robust composite with a flexural strength of 14.6 MPa, although exhibiting inherently brittle characteristics. Compaction pressure emerges as a crucial factor influencing material performance. Utilizing these findings, hexagonal modular tiles were designed as the fundamental LLP elements, specifically engineered to optimize manufacturing simplicity, mechanical robustness, stackability for redundancy, and ease of replacement or repair. The tile geometry strategically mitigates brittleness-induced vulnerabilities by avoiding stress concentrations. Explicit finite element analyses validated tile performance under simulated lunar landing conditions corresponding to the European Large Logistic Lander specifications. Results demonstrated safe landing velocities between 0.1 and 0.7 m/s, governed by the binder content and compaction pressure. A clearly identified linear correlation between the binder fraction and permissible impact velocity enables predictive tailoring of the material composition, confirming the suitability and scalability of thermoplastic–regolith composites for future lunar infrastructure development. Full article

Fiber-reinforced composites (FRCs) have emerged as transformative alternatives to traditional marine construction materials, owing to their superior corrosion resistance, design flexibility, and strength-to-weight ratio. This review comprehensively examines the current state of FRC technologies in marine deck and underwater applications, with a focus on manufacturing methods, durability challenges, and future innovations. Thermoset polymer composites, particularly those with epoxy and vinyl ester matrices, continue to dominate marine applications due to their mechanical robustness and processing maturity. In contrast, thermoplastic composites such as Polyether Ether Ketone (PEEK) and Polyether Ketone Ketone (PEKK) offer advantages in recyclability and hydrothermal performance but are hindered by higher processing costs. The review evaluates the performance of various fiber types, including glass, carbon, basalt, and aramid, highlighting the trade-offs between cost, mechanical properties, and environmental resistance. Manufacturing processes such as vacuum-assisted resin transfer molding (VARTM) and automated fiber placement (AFP) enable efficient production but face limitations in scalability and in-field repair. Key durability concerns include seawater-induced degradation, moisture absorption, interfacial debonding, galvanic corrosion in FRP–metal hybrids, and biofouling. The paper also explores emerging strategies such as self-healing polymers, nano-enhanced coatings, and hybrid fiber architectures that aim to improve long-term reliability. Finally, it outlines future research directions, including the development of smart composites with embedded structural health monitoring (SHM), bio-based resin systems, and standardized certification protocols to support broader industry adoption. This review aims to guide ongoing research and development efforts toward more sustainable, high-performance marine composite systems. Full article

Polymer inclusion membranes (PIMs) have undergone substantial advancements in their selectivity and efficiency, driven by their increasing deployment in separation processes, environmental remediation, and sensing applications. This review presents recent progress in the development of PIMs, focusing on strategies to enhance ion and molecule selectivity through the incorporation of novel carriers, including ionic liquids and task-specific extractants, as well as through polymer functionalization techniques. Improvements in mechanical and chemical stability, achieved via the utilization of high-performance polymers such as polyvinylidene fluoride (PVDF) and polyether ether ketone (PEEK), as well as cross-linking approaches, are critically analyzed. The expanded application of PIMs in the removal of heavy metals, organic micropollutants, and gas separation, particularly for carbon dioxide capture, is discussed with an emphasis on efficiency and operational robustness. The integration of PIMs with electrochemical and optical transduction platforms for sensor development is also reviewed, highlighting enhancements in sensitivity, selectivity, and response time. Furthermore, emerging trends towards the fabrication of sustainable PIMs using biodegradable polymers and green solvents are evaluated. Advances in scalable manufacturing techniques, including phase inversion and electrospinning, are addressed, outlining pathways for the industrial translation of PIM technologies. The review concludes by identifying current limitations and proposing future research directions necessary to fully exploit the potential of PIMs in industrial and environmental sectors. Full article

The escalating challenges of greenhouse gas emissions, coupled with the severe depletion of oil reserves and the surging global energy demand, have emerged as critical concerns requiring urgent attention. Against this backdrop, biodiesel has been recognized as a viable alternative fuel for compression ignition (CI) engines. The primary objective of this research is to review the application of biodiesel in CI engines, with a focus on enhancing fuel properties and improving atomization performance. This article examines the spray and atomization characteristics of biodiesel fuels and conducts a comparative analysis with diesel fuel. The results show that biodiesel has a longer spray tip penetration, smaller spray cone angle, larger Sauter mean diameter (SMD) and faster droplet velocity due to its higher viscosity and surface tension. Blending with other fuels, such as ethanol, butanol, dimethyl ether (DME) and di-n-butyl ether, results in reduced viscosity and surface tension in these mixed fuels, representing a simple and effective approach for improving biodiesel atomization performance. A comprehensive analysis of spray and droplet impingement is also conducted. The findings reveal that biodiesel exhibits a higher probability of fuel–wall impingement, suggesting that future research should focus on two key directions: first, developing combined strategies to enhance impact-induced secondary atomization while minimizing fuel deposition; and second, investigating single-droplet impingement, specifically that of microscale biodiesel droplets and blended fuel droplets under real engine operating conditions. This paper also presents several advanced techniques, including air-assisted atomization, dual-fuel impingement, nano-biodiesel, and water-emulsified biodiesel, aimed at mitigating the atomization limitations of biodiesel, thereby facilitating the broader adoption of biodiesel in compression ignition engines. Full article

Some propylene glycol ethers (PGEs) have been associated with reproductive toxicity. Ethoxypropanol (PGEE) and propoxypropanol (PGPE) are two common PGEs found in many commercial products. Although skin exposure is frequent when handling such products, no studies have investigated their skin absorption. Neat or aqueous concentrations of PGEs were applied with different concentrations on previously frozen human skin according to OECD guidelines. We also explored the use of frozen skin for skin irritation screening. Our results show that both PGEs readily permeate human skin (permeation coefficients: Kp_PGEE = 0.0005–0.002 cm/h; Kp_PGPE = 0.0002–0.002 cm/h; rates: J_PGEE = 447.5–1075.2 µg/cm²/h; J_PGPE = 193.9–826.1 µg/cm²/h; and time lag: 2–5 h). The permeability rate was four times greater for PGPE diluted in water compared to neat, and double for PGEE. Increasing the water content increased PGEE skin permeation but had no effect on PGPE. Cleaning products contain 1–5% PGEs, and water-based paints 10–50%, thus increasing the potential for skin uptake in consumers. Our skin irritation results were inconsistent, so we conclude that skin irritation cannot be assessed with previously frozen human skin. Future studies should assess the irritation using fresh skin and investigate the risk of health effects from PGEs exposures. Full article

The optimum degree of sulfonation (DS) for sulfonated poly(ether ether ketone) (SPEEK) membranes is determined by comprehensive characterization results, including proton conductivity, swelling ratio, water uptake, chemical stability, thermal stability, mechanical indicators, and proton exchange membrane fuel cell (PEMFC) performance. The PEMFC with a membrane electrode assembly containing a SPEEK-62 (DS = 62%) membrane realizes the power density of 482.08 mW/cm², surpassing that of commercial Nafion-212 under identical conditions. In the crucial Fenton test for durability, the SPEEK-51 membrane demonstrated outstanding dimensional and chemical stability, with a decomposition time of up to 137 min, far surpassing the durability of SPEEK-62 or other membranes with a higher DS. The results indicate that in comparison to the SPEEK-67 membrane as reported in the literature, SPEEK membranes with a DS = 51~62% hold great potential for future applications in PEMFC, and further modifications of these membranes can be a promising approach to enhance the conductivity while maintaining good chemical stability. Full article

This work aimed to advance the knowledge in the field of eco-friendly dielectrics with applicative relevance for future energy-related technologies. New multicomponent composites were prepared by using a cellulose ether/citric acid mixture as the matrix, which was gradually filled with strontium titanate nanoparticles (5–20 wt%). In this case, citric acid can act as a crosslinking agent for the polymer but also can react differently with the other counterparts from the composite as a function of the solvent used (H₂O and H₂O₂). This led to considerable differences in the morphological, thermal, optical, and electrical characteristics due to distinct solvent-driven interactions, as revealed by the infrared spectroscopy investigation. Hence, in contrast to H₂O, the oxidizing activity of H₂O₂ led to changes in the surface morphology, a greater transparency, a greater yellowness, an enhanced refractive index, and higher permittivity. These data provide new pathways to advance the optical and dielectric behavior of eco-compatible materials for energy devices by the careful selection of the composite’s components and the modulation of the molecular interactions via solvent features. Full article

This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SO_x emissions. Conventional hydrodesulfurization (HDS) operates under severe temperature–pressure conditions and displays limited efficacy toward sterically hindered thiophenic compounds, motivating the exploration of non-hydrogen routes such as oxidative desulfurization (ODS). Within ODS, PTC offers distinctive benefits by shuttling reactants across immiscible phases, thereby enhancing reaction rates and selectivity. In particular, PTC enables efficient migration of organosulfur substrates from the hydrocarbon matrix into an aqueous phase where they are oxidized and subsequently extracted. The review first summarizes the deployment of classic PTC systems—quaternary ammonium salts, crown ethers, and related agents—in ODS operations and then delineates the underlying phase-transfer mechanisms, encompassing reaction-controlled, thermally triggered, photo-responsive, and pH-sensitive cycles. Attention is next directed to a new generation of catalysts, including quaternary-ammonium polyoxometalates, imidazolium-substituted polyoxometalates, and ionic-liquid-based hybrids. Their tailored architectures, catalytic performance, and mechanistic attributes are analyzed comprehensively. By incorporating multifunctional supports or rational structural modifications, these systems deliver superior desulfurization efficiency, product selectivity, and recyclability. Despite such progress, commercial deployment is hindered by the following outstanding issues: long-term catalyst durability, continuous-flow reactor design, and full life-cycle cost optimization. Future research should, therefore, focus on elucidating structure–performance relationships, translating batch protocols into robust continuous processes, and performing rigorous environmental and techno-economic assessments to accelerate the industrial adoption of PTC-enabled desulfurization. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Per- and polyfluoroalkyl substances (PFAS) are of concern because of their potential thyroid hormone system disruption by binding to human transthyretin (hTTR). However, the amount of experimental data is scarce. In this work, new classification and regression QSARs were developed to predict the hTTR disruption based on experimental data measured for 134 PFAS. Bootstrapping, randomization procedures, and external validation were used to check for overfitting, to avoid random correlations, and to evaluate the predictivity of the QSARs, respectively. The best QSARs were characterized by good performances (e.g., training and test accuracies in classification of 0.89 and 0.85, respectively; R², Q²_loo, and Q²_F3 in regression of 0.81, 0.77, and 0.82, respectively) and significantly broader domains compared to the few existing similar models. The application of QSARs application to the OECD List of PFAS allowed for the identification of structural categories of major concern, such as per- and polyfluoroalkyl ether-based, perfluoroalkyl carbonyl, and perfluoroalkane sulfonyl compounds. Forty-nine PFAS showed a stronger binding affinity to hTTR than the natural ligand T4. Uncertainty quantification for each model and prediction further enhanced the reliability assessment of predictions. The implementation of the new QSARs in non-commercial software facilitates their application to support future research efforts and regulatory actions. Full article