Search Results (1,249)

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin–diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein–ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin–diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin–diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac–heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex–COX assemblies. These findings indicate that heparin–diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo. Full article

Solidification cracking is a critical defect in Cu–steel dissimilar laser welding for cylindrical lithium-ion battery busbar assembly, yet the metallurgical role of phosphorus (P) in crack formation has not been quantitatively established. In this study, the influence of phosphorus in the coating layer on weld solidification behavior was clarified by preparing Cu substrates with four different coating conditions—Ni–P-coated Cu (10 and 50 μm) and pure Ni-coated Cu (10 and 50 μm)—and performing high-speed single-mode fiber-laser welding under identical heat-input conditions. Shear-tensile testing, EPMA-based microstructural analysis, and Thermo-Calc solidification calculations were combined to correlate P segregation with solidification cracking susceptibility. The Ni–P 10 μm coating generated severe solidification cracking compared with the pure Ni 50 μm coating, which was attributed to excessive P enrichment in the terminal liquid phase (up to 8.8 mass%). This enrichment significantly expanded the mushy-zone width to approximately 869 K, yielding a highly solidification crack-susceptible fusion zone. In contrast, 50 μm pure Ni coatings produced narrow mushy-zone widths (200–400 K) and extremely low residual P levels (~0.1 mass%), resulting in fully crack-free microstructures. The 50 μm Ni coating exhibited the highest shear-tensile strength and largest rupture displacement among all conditions, confirming that suppression of P segregation directly improves both structural integrity and mechanical performance. Overall, this study demonstrates that phosphorus enrichment critically governs the solidification-cracking susceptibility of Cu–steel dissimilar welds by widening the solidification temperature range. Eliminating P from the coating layer and applying an adequately thick pure Ni coating constitute highly effective strategies for achieving crack-free, mechanically robust welds in lithium-ion battery busbar manufacturing. Full article

This study presents a strategy for enhancing hydrogel formation through SpyCatcher-mediated conjugation of nanoscale scaffold proteins. We demonstrate that SpyCatcher can facilitate hydrogel assembly with various nano-scaffolds of diverse structural configurations. By conjugating one, two, or three SpyCatcher units to the P9 protein nanoscaffold, hydrogel yield was substantially increased, allowing for the simultaneous co-immobilization of a larger number of enzymes. Characterization using cell-free biosynthesis, electron microscopy, and rheological analysis revealed that the resulting SpyCatcher-mediated nanoscaffold hydrogels exhibit soft solid-like behavior, high elasticity, and an “ink-bottle” pore morphology, which collectively promote and regulate enzymatic activity. Notably, hydrogels crosslinked via the P9 scaffold with two SpyCatcher units showed the most balanced properties, leading to a 149% increase in pyruvic acid production. These findings not only advance the efficient design of hydrogels for enzyme co-immobilization but also provide a foundation for developing more sophisticated models and expanding the scope of biocatalytic systems. Full article

Alterations in the expression of the Klotho gene have been associated with chronic kidney disease (CKD), and its potential as an early diagnostic biomarker is currently under active investigation. In this work, we report the development of a highly sensitive, label-free electrochemical DNA-based biosensor for the detection of a 100 mer DNA fragment corresponding to a partial region of Klotho mRNA. The proposed bioplatform integrates mixed self-assembled monolayers (SAMs) and gold nanoparticles for efficient DNA immobilization within a sandwich-type configuration, coupled with impedimetric detection. Different SAM architectures were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy, with the binary monolayer composed of 1-hexadecanethiol (HDT) and the capture probe (CP) exhibiting the best analytical performance. The use of gold nanoparticle-modified screen-printed carbon electrodes (AuNPs–SPCEs) resulted in a 1.4-fold increase in the signal-to-noise ratio compared to screen-printed gold electrodes. Additionally, the incorporation of a blocking step using bovine serum albumin (BSA–HDT–CP–AuNPs–SPCE) enhanced the sensitivity by 1.6-fold compared to the unblocked system. The genosensor displayed a linear response in the concentration range of 3 × 10⁻¹⁰ to 7.5 × 10⁻⁸ M, achieving a detection limit of 0.09 nM. Relative standard deviations below 7.5% were obtained for different Klotho concentrations, confirming high intra-assay and intermediary precision. Selectivity assays demonstrated negligible signals for non-complementary sequences, while recovery experiments in spiked human serum samples yielded satisfactory values between 96.5% and 103.4%. Full article

Cultured meat has progressed from early in vitro cell culture concepts to regulatory approvals and preliminary commercialization, with recent advancements propelled by interdisciplinary innovations in cell line engineering, serum-free media, bioreactor design, and three-dimensional (3D) assembly technologies. This review synthesizes recent developments from 2023 to 2025, utilizing peer-reviewed publications, patent analyses, regulatory frameworks, and media reports to assess global preparedness for large-scale production. Asia has emerged as a leading hub, with China, Japan, South Korea, and Singapore focusing on scaffold-based 3D cultures, bioinks, and serum-free strategies, complemented by national centers and pilot facilities. The United States leverages its technological advancements and established regulatory framework, as evidenced by recent Food and Drug Administration and United States Department of Agriculture approvals. However, potential complications related to political regional bans and legislation may arise. Europe and the UK prioritize defined media, cell optimization, and structured novel-food regulations, with early commercialization primarily in pet food. Looking ahead, the industrialization of cultured meat is anticipated to be driven by process engineering and hybrid product strategies, with initial pilot-to-demonstration facilities established in countries open to alternative food products. Premium and hybrid cultured meat products are expected to enter the market first, while whole-cut cultured meat is likely to remain a premium offering into the early 2030s. Full article

The synthesis of biocidal peptide materials using simple, low-cost, solvent-free methods is a crucial challenge for developing new antimicrobial approaches. In this study, we produced proteinoid nanostructures through simple, inexpensive, and environmentally friendly thermal reactions between glutamic acid (Glu) and tyrosine (Tyr) in various molar ratios. Mechanistically, the thermal cyclization of glutamic acid into pyroglutamic acid (pGlu) facilitated the formation of short peptide chains containing pGlu as the N-terminus moiety and subsequent L-tyrosine or glutamic acid residues, which self-assembled into nanometric spheroidal structures that exhibit blue emission. Spectroscopic (FTIR, UV-Vis, photoluminescence) and mass (LC-MS) analyses confirmed the formation of mixed pGlu-/Tyr/Glu peptides. All products exhibit dose-dependent antimicrobial activity against Methicillin-Resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 mg mL⁻¹ for the GluTyr 1:1 and 2:1 proteinoids. The outcomes observed following 24 h exposure of the HEK293 cell line to the materials indicate their suitability for integration into hybrid systems for antimicrobial surfaces. This work is the first to demonstrate a direct antibacterial activity of proteinoids obtained by thermal condensation, opening up the possibility of designing a new class of synthetic antimicrobial peptides. Full article

Background/Objectives: A carrier-free self-assembled nanomedicine delivery system refers to a high drug-loading nanomedicine delivery system prepared by one or more active drug ingredients through supramolecular self-assembly, which has the advantages of high drug-loading and a simple preparation process, enabling multidrug synergistic therapy. 10-hydroxycamptothecin (HCPT) have active antitumor effects. Pentacyclic triterpenes are natural active components with a wide range of pharmacological activities. This study aimed to investigate the impact of structural types on the self-assembly of pentacyclic triterpenes and HCPT. Methods: Molecular docking studies were performed. Self-assembled nanoparticles were designed by co-assembling ursolic acid (UA), asiatic acid (AA), oleanic acid (OA), and betulinic acid (BA) with HCPT via anti-solvent precipitation combined with ultrasonication, followed by characterization. Cytotoxicity assays using the CCK-8 method revealed that the prepared self-assembled nanoparticles exhibited concentration-dependent inhibitory effects against A375, AGS, HCT-116, and HepG2 tumor cells. Confocal laser scanning microscopy (CLSM) indicated that UA/HCPT nanoparticles (UA/HCPT-NPs) were more efficiently internalized and accumulated in cells compared with the UA + HCPT physical mixture. Results: Both in vitro and in vivo results demonstrated that the self-assembled nanoparticles significantly enhanced antitumor efficacy while exerting minimal toxicity on major organs within the tested dose range. Conclusions: In summary, these findings highlight that pentacyclic triterpenoids components possess significant self-assembly potential, and that dual-drug co-delivery via self-assembled nanoparticles represents as a promising strategy for cancer therapy. Full article

Ocean waves constitute a vast renewable resource, yet most linear generator-based wave energy converters (WECs) rely on single-degree-of-freedom (SDOF) linear oscillators that exhibit narrow resonance bandwidths and utilise sliding components prone to wear. To address these limitations, this paper presents a nonlinear three-degree-of-freedom (3DOF) magnetic spring power-take-off (PTO) system for broadband wave energy harvesting. The device comprises three axially levitated NdFeB permanent magnets, each coupled to an independent copper coil, forming a compact, friction-free generator column. A coupled electromechanical state-space model was developed and experimentally validated on a laboratory-scale test rig. The 3DOF PTO exhibited three distinct resonance modes at approximately 35, 48, and 69 rad s⁻¹, enabling multi-mode energy capture across a broad frequency range. Under identical excitation (6.5 N amplitude and 3.13 Hz excitation force), the 3DOF configuration achieved a 114.5% increase in RMS voltage compared with the SDOF design and a 44.10% improvement over the 2DOF benchmark, confirming the effectiveness of the coupled resonance mechanism. The levitated magnetic architecture eliminates mechanical contact and lubrication, reducing wear and maintenance while improving long-term reliability in marine environments. A preliminary life-cycle assessment estimated a cradle-to-gate carbon intensity of 40–80 g CO₂-eq kWh⁻¹, significantly lower than that of conventional hydraulic PTOs, owing to reduced steel use and recyclable magnet assemblies. The proposed 3DOF magnetic spring PTO thus offers a sustainable, low-maintenance, and high-efficiency solution for next-generation ocean-energy converters. Full article

This work develops a novel Ni-Co nanoparticles coupled with Ni₃S₂ and Co₉S₈ phases on nickel foam (denoted as Ni-Co NPS@Ni₃S₂/Co₉S₈/NF) hybrid structure material as a bifunctional water electrolysis catalyst. The self-assembly Ni-Co alloy phases enhance electrical conductivity, while the synergistic interactions among the three components (Ni-Co, Ni₃S₂ and Co₉S₈) optimize the lattice parameters and electronic environment for boosting both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The catalyst achieves low overpotentials of 106 mV for HER and 185 mV for OER at 10 mA·cm⁻² in 1M KOH, along with a very low charge-transfer resistance. Density functional theory (DFT) calculations reveal that the multi-component interaction narrows the band gap and optimizes the hydrogen adsorption free energy (ΔG_H*) as well as the adsorption free energies of OER intermediates (ΔG_OH*). This work identifies the hybrid structure as the key to the enhanced activity and offers a promising strategy for designing efficient nickel–cobalt-based electrocatalysts. Full article

Free/Libre and Open-Source Hardware requires documentation that ensures replicability and accessibility for both experts and non-experts. Existing tools for generating assembly animations are often difficult to use, require specialized knowledge, and are poorly suited for instructional or workshop contexts. This paper addresses this gap by proposing a method for generating implosion-style CAD animations that separates transformation logic from geometry. The method enables fast, low-effort creation of animations through either manual grouping or large language model (LLM) automation. The approach is validated through a web-based implementation that can produce complete animations within minutes using mesh or boundary-representation input. The system supports step-wise playback, interactive part grouping, and export of vector-based views for technical documentation. Evaluation includes nine models ranging from simple parts to assemblies with over 1400 components. The system successfully generated animations for all models, with the LLM-based schema generation achieving high sequence coherence and coverage in most cases. The proposed method enables scalable, reusable, and version-controlled animation workflows that are particularly suited for open-source documentation, manufacturing education, and distributed design environments. Full article

The principal challenge in the development of efficient porphyrin-based photosensitizers is the intrinsic aggregation-induced quenching effect, which significantly impairs the generation efficiency of singlet oxygen (¹O₂) in photodynamic therapy (PDT). This study addresses this limitation through a supramolecular approach grounded in host-guest chemistry. Partially methyl-substituted cucurbit[6]uril (HMeQ[6]) was selected as the macrocyclic host owing to its smaller portal size and larger outer diameter, features that facilitate both strong binding affinity and effective spatial isolation. A porphyrin derivative functionalized with two cationic arms (DPPY) was designed and synthesized as the guest molecule. The results derived from ¹H NMR titration and UV spectroscopy analyses demonstrate that, in aqueous solution, these components self-assemble via host-guest interactions to form a 2:1 stoichiometric supramolecular complex (DPPY@HMeQ[6]) with a binding constant of 2.11 × 10⁵ M⁻¹. TEM, AFM, and DLS analyses indicate that this complex further assembles into nanosheet structures with dimensions of approximately 100 nm. Spectroscopic analyses reveal that encapsulation by HMeQ[6] effectively inhibits π-π stacking aggregation of DPPY molecules, resulting in an approximate threefold increase in fluorescence intensity and an extension of fluorescence lifetime from 3.2 ns to 6.2 ns. Relative to free DPPY, the complex demonstrates a sixfold enhancement in ¹O₂ generation efficiency. Subsequently, 4T1 cells, derived from mouse triple-negative breast tumors, were selected as the experimental model. These cells exhibit high invasiveness and metastatic potential, thereby effectively recapitulating the pathological progression of human triple-negative breast cancer. In vitro cellular assays indicate efficient internalization of the complex by 4T1 cells, inducing a concentration-dependent increase in reactive oxygen species (ROS) and oxidative stress following light irradiation. The in vitro cytotoxicity of the supramolecular photosensitizer was assessed employing the CCK-8 assay and flow cytometry techniques. The half-maximal inhibitory concentration (IC₅₀) against cancer cells is 1.8 μM, with apoptosis rates reaching up to 65.3%, while exhibiting minimal dark toxicity. This study expands the potential applications of methyl-substituted cucurbiturils within functional supramolecular assemblies and proposes a viable approach for the development of efficient and activatable supramolecular photosensitizers. Full article

Reference intervals for clinical chemistry blood parameters are valuable for both individual diagnostics for animals in managed or veterinary care, and for evaluating wild population health. However, for marine mammals obtaining sufficient data from suitable groups or populations is logistically difficult. Here, we have assembled a large dataset of clinical chemistry results from free-living adult UK harbour seals (Phoca vitulina), analysed in the same commercial laboratory. We applied an open-source algorithm (available as the R package refineR, R version 4.5.2, refineR version 2.0.0) to produce robust reference intervals from these Real-World Data. This novel approach resulted in the generation of 95% reference intervals with 90% confidence bounds for 18 key chemistry parameters indicative of a range of physiological processes including, inflammation, nutritional status, kidney function and liver function. Reference intervals were also generated for triiodothyronine, the active thyroid hormone important in the regulation of metabolism. These intervals will provide critical baseline data for the assessment of harbour seal health as, to our knowledge, this is the largest dataset on which clinical chemistry reference intervals from wild-caught adult harbour seals have been based. Full article

Sichuan-style black soybean soy sauce is a traditional fermented condiment renowned for its complex and regionally distinctive flavor profile. This study systematically investigated the physicochemical properties, flavor compounds, and microbial succession during six months of natural fermentation to elucidate the mechanisms underlying its unique flavor formation. Results showed that the amino acid nitrogen level increased to a peak of 1.37 g/100 mL before stabilizing at 1.01 g/100 mL, accompanied by a continuous rise in total acidity (0.69–2.75 g/100 mL). A total of 132 volatile compounds were identified, with esters (e.g., hexanoic acid, methyl ester, hexadecanoic acid, and methyl ester), alcohols (e.g., (E)-2-hepten-1-ol and trans-2-undecen-1-ol), and aldehydes (e.g., benzaldehyde and benzeneacetaldehyde) serving as key differentiating components. Nine taste-active (TAV ≥ 1) and 22 odor-active (ROAV ≥ 1) compounds were recognized as major flavor determinants, among which methional (ROAV = 4.77–119.05), 1-octen-3-ol (ROAV = 40.68–149.35), and 4-ethyl-2-methoxyphenol (ROAV = 4.70–36.26) were dominant contributors imparting sauce-like, mushroom-like, and smoky-clove notes, respectively. Microbial succession revealed a transition from Weissella and Aspergillus dominance in the early stage to salt-tolerant Tetragenococcus and aroma-producing yeasts (Kodamaea and Zygosaccharomyces) in later phases. Beyond organic acids and fermentation parameters (e.g., pH and salinity), microbial interactions were identified as critical drivers shaping community assembly and succession. Metabolic pathway analysis revealed a stage-dependent mechanism of flavor formation. During the initial stage (0–2 months), Aspergillus-mediated proteolysis released free amino acids as key taste precursors. In the later stages (3–6 months), Tetragenococcus and aroma-producing yeasts dominated, synthesizing characteristic esters (e.g., benzoic acid and methyl ester, correlated with Tetragenococcus; r = 0.71, p < 0.05), phenolics (e.g., 4-ethyl-2-methoxyphenol, correlated with Wickerhamomyces; r = 0.89, p < 0.05), and sulfur-containing compounds (e.g., methional, correlated with Wickerhamomyces; r = 0.83, p < 0.05). Full article

Selective Laser Sintering (SLS) is an Additive Manufacturing (AM) technology that is receiving considerable attention in the scientific and industrial communities due to its great ability to efficiently produce functional and complex parts. The present work aims to fabricate a real prototype via SLS, such as a hose reel for industrial applications, using polyamide 11 (PA11) as a starting material. Characterization of the PA11 powder properties was first carried out from a thermal and morphological viewpoint to determine the powder’s thermal stability by TGA, the sintering window and degree of crystallinity by DSC, and the microstructure by SEM, PSD, and XRD analyses. The results revealed that PA11 has a 45-micron average particle size, circularity close to 1, and a Hausner ratio of 1.17. Together, these parameters ensure that PA11 powder flows smoothly, packs uniformly, and forms dense and defect-free layers during the SLS process, directly contributing to high part quality, dimensional precision, and stable process performance. The printability of the PA11 was optimized for the realization of 3D-printed parts for industrial applications. Finally, the quality of the printed samples and the mechanical and thermal performance were investigated. Several PA11-based parts were fabricated via SLS, showing a high level of complexity and definition, ideal for industrial applications, as confirmed by the predominantly green areas of the colored maps of X-CT. A complete prototypal case for a hose reel was assembled by using the parts realized, and it was chosen as a technological demonstrator to verify the feasibility of PA11 powder in the production of industrial professional components. Full article

MXene–polymer hybrids combine the high in-plane conductivity and rich surface chemistry of MXenes with the processability and mechanical tunability of polymers for lithium-metal and lithium–sulfur batteries. Most reported systems still rely on HF-etched MXenes, introducing F-rich terminations, safety and waste issues, and poorly controlled surfaces. This review instead centers on fluoride-free synthesis routes, benchmarks them against HF methods, and translates route–termination relationships into practical rules for choosing polymer backbones. We track the evolution from early linear hosts such as PEO- and PVDF-type polymers to polar nitrile or carbonyl matrices, crosslinked and ionogel networks, and emerging biopolymers and COF-type porous frameworks that are co-designed with MXene terminations to regulate ion transport, interfacial chemistry, and mechanical robustness. These chemistry–backbone pairings are linked to five scalable fabrication modes, including solution blending and film casting, in situ polymerization, surface grafting, layer-by-layer assembly, and electrospinning, and to roles as solid or quasi-solid electrolytes, artificial interphases, separator-like coatings, and electrode-facing architectures. Finally, we highlight key evidence gaps and reporting standards needed to de-risk scale-up of green MXene–polymer batteries. Full article