Search Results (168)

To enhance the bioavailability of hydrophobic nobiletin (NOB), this study constructed nanoparticles (LT-NOB) via self-assembly of lysozyme and tannic acid (TA). The multivalent weak interaction network between TA and lysozyme effectively encapsulated amorphous NOB, inhibiting crystallization. The optimized LT-NOB exhibited a size of 212 nm, high encapsulation efficiency (89.5%), and drug loading (47.25%). Cellular uptake was significantly improved, primarily through macropinocytosis, followed by lysosomal escape and endoplasmic reticulum targeting. In Caco-2 and co-culture models, LT-NOB enhanced mucosal permeation by 75% and 50%, respectively, compared to free NOB. This work elucidates a robust strategy for stabilizing amorphous drugs and promoting their intestinal absorption, providing a foundation for advanced nanodrug delivery. Full article

HIV-1 entry into host cells culminates in integration of the reverse transcribed double-stranded viral DNA into host genes. Several lines of evidence suggest that intact, or nearly intact, HIV-1 cores—large, ~60 nm-wide structures—pass through the nuclear pore complex (NPC), and that this passage is associated with pore remodeling. Cryo-electron tomography studies support the dynamic nature of NPCs and their regulation by cytoskeleton and ATP-dependent processes. To explore NPC remodeling, we used super-resolution Stochastic Optical Reconstruction Microscopy (STORM) of U2OS cells endogenously expressing nucleoporin 96 tagged with SNAP. Single-molecule localization imaging and computational averaging resolved 8-fold symmetric nuclear pores with an average radius of ~51 nm. Depletion of cellular ATP using sodium azide or antimycin A, previously reported to reduce the size of yeast NPCs, did not significantly alter the nuclear pore radius in U2OS cells. Similarly, stressing the nuclear envelope by hypotonic or hypertonic conditions failed to induce detectable expansion or contraction of NPCs. These results indicate that the NPCs in U2OS cells do not respond to ATP depletion nor mechanical stresses on changes in pore morphology that can be resolved by STORM. Since these cells are infectable by HIV-1, we surmise that direct multivalent interactions between HIV-1 capsid and phenylalanine-glycine nucleoporins lining the pore’s interior drive the core penetration into the nucleus and the associated changes in the pore structure. Full article

Magnesium–sulfur (Mg-S) batteries represent a novel category of multivalent energy storage systems, characterised by enhanced theoretical energy density, material availability, and ecological compatibility. Notwithstanding these benefits, the practical implementation of this approach continues to be hindered by ongoing issues, such as polysulfide shuttle effects, slow Mg²⁺ transport, and significant interfacial instability. This study emphasises recent progress in utilising transition metal chalcogenides (TMCs) as cathode materials and modifiers to overcome these challenges. We assess the structural, electrical, and catalytic characteristics of TMCs such as MoS₂, CoSe₂, WS₂, and TiS₂, highlighting their contributions to improving redox kinetics, retaining polysulfides, and enabling reversible Mg²⁺ intercalation. The review synthesises results from experimental and theoretical studies to offer a thorough comprehension of structure–function interactions. Particular emphasis is placed on morphological engineering, modulation of electronic conductivity, and techniques for surface functionalisation. Furthermore, we examine insights from density functional theory (DFT) simulations that corroborate the observed enhancements in electrochemical performance and offer predictive direction for material optimisation. This paper delineates nascent opportunities in Artificial Intelligence (AI)-enhanced materials discovery and hybrid system design, proposing future trajectories to realise the potential of TMC-based Mg-S battery systems fully. Full article

The Rift Valley fever virus (RVFV) is a highly pathogenic, mosquito-borne zoonotic virus that poses a significant risk to livestock, human health, and global public health security. Although RVFV is classified by the World Health Organization (WHO) as a priority pathogen with epidemic potential, no licensed vaccines or effective antiviral therapies are currently available. A limited understanding of the molecular mechanisms of RVFV entry has hindered therapeutic development. Here, we elucidate the molecular basis by which the RVFV envelope glycoprotein Gn recognizes its receptor, low-density lipoprotein receptor-related protein 1 (LRP1). Bio-layer interferometry (BLI) demonstrates that full-length LRP1 directly binds the head domain of Gn with nanomolar affinity in a Ca²⁺-dependent manner. Both LRP1 clusters II (CL II) and IV (CL IV) independently interact with Gn, with CL IV exhibiting stronger affinity, indicating a multivalent recognition mode. Structural modeling using AlphaFold 3 reveals pronounced charge complementarity between basic residues on Gn and acidic, Ca²⁺-coordinated pockets within LRP1. Mutations in key acidic residues in CL IV greatly reduced Gn binding, confirming the essential roles of Ca²⁺ coordination and electrostatic interactions. Collectively, our findings define a Ca²⁺-stabilized, electrostatically driven mechanism for RVFV Gn recognition by LRP1, providing molecular insight into viral entry and a structural framework for the rational design of vaccines and antiviral therapeutics. Full article

CRISPR/Cas12a systems coupled with lateral flow tests (LFTs) are a promising route to rapid, instrument-free nucleic acid diagnostics due to conversion target recognition into a simple visual readout via cleavage of dual-labeled single-stranded DNA reporters. However, the conventional CRISPR/Cas12a–LFT system is constructed in a format where the intact reporter should block nanoparticle conjugate migration and can produce false-positive signals and shows strong dependence on component stoichiometry and kinetics. Here, we present the first combined experimental and theoretical analysis quantifying these limitations and defining practical solutions. The experimental evaluation included 480 variants of LFT configuration with reporters differing in the concentration of interacting components and the kinetic conditions of the interactions. The most influential factor leading to 100% false-positive results was insufficient interaction time between the components; pre-incubation of the conjugate with the reporter for 5 min eliminated these artifacts. Theoretical analysis of the LFT kinetics based on a mathematical model confirmed kinetic constraints at interaction times below a few minutes, which affect the detectable signal. Reporter concentration and conjugate architecture represented the second major factors: lowering reporter concentration to 20 nM and using smaller gold nanoparticles with multivalent fluorescent reporters markedly improved sensitivity. The difference in sensitivity between various LFT configurations exceeded 50-fold. The combination of identified strategies eliminated false-positive reactions and enabled the detection of up to 20 pM of DNA target (the hisZ gene of Erwinia amylovora, a bacterial phytopathogen). The strategies reported here are general and readily transferable to other DNA targets and CRISPR/Cas12a amplification-free diagnostics. Full article

Phosphate pollution caused by human activities has become a pressing environmental issue, leading to eutrophication and severe ecological risks. In this study, artificial humic acid (HA) and fulvic acid (FA) were synthesized from tung fruit and glucose, respectively, and further composited with ferrihydrite (Fh) to prepare HA/Fh and FA/Fh adsorbents for phosphate removal. The structural and morphological characteristics of the composites were confirmed by SEM, XRD, FTIR, and XPS analyses, which indicated successful complexation of HA or FA with Fh through ligand exchange and surface interactions. Batch adsorption experiments revealed that HA/Fh and FA/Fh exhibited significantly enhanced adsorption capacities compared to pristine Fh, with maximum Langmuir adsorption capacities of 33.67 mg g⁻¹ and 37.06 mg g⁻¹, respectively. The adsorption behavior was well described by the pseudo-second-order kinetic model and the Langmuir isotherm, suggesting a chemisorption-dominated process involving ligand exchange between surface –OH groups of Fh and phosphate ions, supplemented by electrostatic attraction. Coexisting ion studies demonstrated that Cl⁻ and SO₄²⁻ slightly promoted phosphate adsorption, while NO₃⁻ and CO₃²⁻ strongly inhibited it, highlighting the competition of multivalent anions with phosphate for Fe³⁺ active sites. Importantly, the phosphate-enriched adsorbents can be directly recycled as phosphorus fertilizers, providing a sustainable pathway for both environmental remediation and phosphorus resource recovery. Full article

The picornavirus 3CD protein is a precursor to the 3C main protease and the 3D RNA-dependent RNA polymerase. In addition to its functions in proteolytic processing of the virus polyprotein and cleavage of key host factors, the 3C domain interacts with cis-acting replication elements (CREs) within the viral genome to regulate replication and translation events. We investigated the molecular determinants of RNA binding to 3C using a wide range of biophysical and computational methods. These studies showed that 3C binds to a broad spectrum of RNA oligonucleotides, displaying minimal sequence and structure dependence, at least for these shorter RNAs. However, they also uncovered a novel aspect of these interactions, that is, 3C-RNA binding can induce liquid–liquid phase separation (LLPS), with 3CD–RNA interactions likewise leading to LLPS. This may be a general phenomenon for other 3C and 3C-like proteases and polyproteins incorporating 3C domains. These findings have potential implications in understanding virally induced apoptosis and the control of stress granules, which involve LLPS and include other proteins with known interactions with 3C/3CD. Full article

The increasing demand for sustainable and high-performance energy storage underscores the limitations of lithium-ion batteries (LIBs), notably in terms of finite resources, safety issues, and rising costs. Multivalent metal-ion batteries (MMIBs)—employing Zn²⁺, Mg²⁺, Ca²⁺, and Al³⁺ ions—represent promising alternatives, as their multivalent charge carriers facilitate higher energy densities and greater electron transfer per ion. The widespread availability, lower cost, and favorable safety profiles of these metals further enhance MMIB suitability for large-scale deployment. However, MMIBs encounter significant obstacles, including slow ion diffusion, strong Coulombic interactions, electrolyte instability, and challenging interfacial compatibility. This review provides a systematic overview of recent advancements in MMIB research. Key developments are discussed for each system: electrode synthesis and flexible architectures for zinc-ion batteries; anode and cathode innovation alongside electrolyte optimization for magnesium-ion systems; improvements in anode engineering and solvation strategies for calcium-ion batteries; and progress in electrolyte formulation and cathode design for aluminum-ion batteries. The review concludes by identifying persistent challenges and future directions, with particular attention to material innovation, electrolyte chemistry, interfacial engineering, and the adoption of data-driven approaches, thereby informing the advancement of next-generation MMIB technologies. Full article

Chitosan is a promising biopolymer for drug delivery due to its biocompatibility, biodegradability, and low toxicity. However, its limited dispersibility in water restricts applications, which can be improved through organic acid salts. This study examined how acetic, lactic, glutamic, and citric acids influence the physicochemical, rheological, swelling, bioadhesive, stability, and cytotoxicity properties of chitosan hydrogels. Gels were prepared using varying chitosan-to-acid molar ratios (1:1; 1:1.2 for citrate) and characterized by NMR, FTIR, TGA, and XRD. Despite identical chitosan concentrations (2%, 3%, 3.5%), gels displayed distinct viscosity, swelling, and adhesion profiles depending on the acid. Lactate gels exhibited the most favorable overall performance, combining high viscosity (1555–6665 mPa·s), structural stability, and strong bioadhesion. Citrate gels showed the lowest viscosity (825–3550 mPa·s), cell viability, and stability but the highest bioadhesiveness, likely due to multivalent ionic interactions. Short-term stability tests revealed that low pH accelerated chitosan degradation, leading to viscosity loss up to ~90–95% within 30 days, particularly in citrate hydrogels. Cytotoxicity tests confirmed high biocompatibility, with all formulations maintaining cell viability above 80%. Overall, the findings highlight that organic acid selection is a critical determinant of chitosan gel behavior, offering guidance for tailoring safe, stable, and bioadhesive drug delivery systems. Full article

Enargite (Cu₃AsS₄), a copper–arsenic sulfosalt, represents a critical challenge in copper mineral processing due to its high arsenic content, which poses significant environmental, metallurgical, and economic issues. Its flotation behavior closely resembles that of other copper sulfides such as chalcopyrite and chalcocite, complicating selective separation at early beneficiation stages. This review presents a comprehensive examination of enargite’s surface chemistry and electrochemical behavior, focusing on the influence of oxidation, pH, and pulp potential on surface reactivity, charge distribution (zeta potential), and hydrophobicity. Detailed insights into the formation of surface oxidation layers, passivation mechanisms, and contact angle variations are provided to elucidate collector-mineral interactions. Advances in selective flotation techniques are also discussed, including the use of depressant reagents, controlled redox environments, and reagent conditioning strategies. Special attention is given to flotation in seawater, where ionic strength and multivalent ions significantly influence mineral-reagent interactions and flotation outcomes. Galvanic interactions between enargite and other sulfide minerals are identified as critical factors affecting floatability and selectivity. The review consolidates findings from recent experimental and electrochemical studies, highlighting promising approaches to enhance enargite rejection and copper concentrate purity. It concludes with perspectives on future research aimed at optimizing flotation processes and developing sustainable solutions for processing arsenic-bearing copper ores. Full article

Biomolecular condensates (BCs), formed through liquid–liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies. Full article

Tungsten disulfide (WS₂), a two-dimensional layered material with favorable electronic properties, has been explored as a promising negative electrode material for calcium-ion batteries (CIBs). Despite its use in monovalent systems, its performance in divalent Ca²⁺ intercalation remains poorly understood. Herein, a combined theoretical and experimental framework is used to elucidate the electronic mechanisms underlying Ca²⁺ intercalation. Theoretical insights were obtained through density functional theory calculations, incorporating periodic simulations using the Vienna Ab initio Simulation Package, and localized orbital-level analysis using the discrete variational Xα method. These approaches reveal that Ca²⁺ insertion induces significant interlayer expansion, lowers diffusion barriers, and narrows the bandgap compared to Li⁺. Orbital analysis revealed strengthened W–S bonding and diminished antibonding interactions, which may contribute to the improved structural resilience. Electrochemical tests validated these predictions; the CaWS₂ electrode delivered an initial discharge capacity of 208 mAh·g⁻¹ at 0.1C, with 61% retention after 50 cycles at 1C. The voltage profile exhibits a distinct plateau near 0.7 V, consistent with a two-phase-like intercalation mechanism, contrasting with the gradual slope observed for Li⁺. These findings suggest that Ca²⁺ intercalation facilitates both rapid ion transport and enhanced structural robustness. This study offers mechanistic insights into multivalent-ion storage and supports the design of high-performance CIB electrodes. Full article

Background/Objectives: To design the pDNA delivery carrier for delivery into skeletal muscle, a total of twelve terminal-alkylated PEGs (Cx-I-PEGy) with four alkyl groups of different carbon numbers (Cx: x = 4, 8, 12, 16) modified via an imine spacer at the ends of three methoxy PEGs of different molecular weights (PEGy: y = 500, 2k, 5k) have been synthesized. Methods: Among them, four Cx-I-PEG5k formed an imine-mediated complex formation with pDNA, as assessed by agarose gel electrophoresis, defined as an iminium mono-ion complex (I-MIC) without multivalent electrostatic interaction by minimizing potential toxic cations. Results: Most resulting I-MICs maintained the flexible structure of pDNA and promoted the binding to pDNA. The expression of pDNA by intramuscular injection with the resulting I-MICs was the highest by using I-MICs with C4-I-PEG5k and was observed extensively by the in vivo imaging system (IVIS). Conclusions: These results suggest that the I-MICs with C4-I-PEG5k are promising for pDNA transfection into skeletal muscle, offering the alkyl iminium for the pDNA binding group to demonstrate the factor of pDNA’s flexible structure as one of the key parameters for in vivo local pDNA transfection. Full article

This review aims to advance quartz processing technology by examining the surface properties, flotation behavior, and selective flotation mechanisms of quartz mineral. Characterized by a strong negative charge over a wide pH range and an isoelectric point around pH 2, quartz surfaces allow physical adsorption of cationic collectors, particularly amines, which render the quartz surface hydrophobic and enhance bubble–particle interactions. In contrast, flotation with anionic collectors requires prior surface activation via multivalent metal cations such as Ca²⁺. The pH value of the medium plays a critical role in both collector adsorption and flotation selectivity. Both direct and reverse flotation strategies can be used, depending on whether quartz is targeted as a valuable mineral or a gangue mineral. In direct flotation, depressants like carboxymethyl cellulose and starch are used to depress gangue minerals, while in reverse flotation, quartz is depressed using chemicals such as fluoride ions and cationic polymers. To improve the efficiency and selectivity of quartz flotation, further research is needed on surface chemistry, collector adsorption mechanisms, and the transition from laboratory-scale experiments to industrial applications. Full article

Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC₅₀. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article