International Journal of Biological Macromolecules最新文献

Multifunctional green-engineered nanomaterials with high catalytic efficiency and environmental safety are highly desired for effective wastewater treatment. In the present work, for the first time, we have synthesized a ternary nanocomposite of Ag, Co, and V₂O₅ using cinnamon extract as a green medium with high catalytic efficiency and environmental safety. The synthesized nanocomposites have a defect-rich, mesoporous, highly crystalline system with enhanced colloidal stability and synergistic adsorption-degradation performance. The procedure leverages the reducing/catalytic chelation properties offered by phytoconstitients derived from plants and the biopolymer capping agent AG to form a stable organic-inorganic nanocomposite material incorporating Ag, Co, V₂O₅, and AG. Extensive material analysis using several techniques, namely, XPS, FTIR, UV-Vis spectroscopy, XRD, BET analysis, zeta potential measurement, SEM, TEM, SAED, and element mapping analysis, has verified the successful formation of a defect-rich, mesoporous, and highly crystalline Ag/Co/V₂O₅/AG system with enhanced surface functionality and colloidal stability. The AG-functionalized nanocomposite exhibited a high BET surface area of 115.4 m² g^-1, mesoporous architecture, and improved surface charge (-26.10 mV), directly correlating with superior adsorption-catalytic performance. The material demonstrated efficient crystal violet (CV) removal exceeding 93%, governed by pseudo-second-order kinetics (R² = 0.994) and predominantly monolayer adsorption behavior (Langmuir R² = 0.992, q_max = 66.7 mg g^-1). These thermodynamic studies have further affirmed its spontaneity (ΔG° = -3.39 to -8.59 kJ/mol), endothermic nature (ΔH° = +48.3 kJ/mol), and entropy-driven phenomena. More importantly, eco-safe analysis showed negligible Ag leaching of less than 0.24% and controlled release of cobalt, and its pH-dependent stability analysis proved its sustainability at all ranges of pH values. The improved decolorization efficiency is primarily related to its synergistic adsorption-degradation ability through electrostatic forces, π-π interaction, surface complexation, and reactive oxygen species (ROS) assays on Ag/Co/V₂O₅ active sites. This work introduces a biopolymer-stabilized, eco-safe, and high-performance nanocomposite platform, offering a sustainable and scalable solution for dye-contaminated wastewater remediation.

Friedelin, a unique friedelane-type pentacyclic triterpenoid, exhibits diverse pharmacological activities and serves as a key biosynthetic precursor for bioactive compounds such as anti-obesity agent celastrol. However, its structural complexity, arising from the extensive carbocation rearrangement cascade catalyzed by 2,3-oxidosqualene cyclases (OSCs), along with its low abundance in plants, poses significant challenges for sustainable production. Advances in multi-omics integration technologies have facilitated the identification and characterization of friedelane-type OSCs, with 18 such enzymes identified to date. Seminal structural studies, including the first cryogenic electron microscopy (cryo-EM) structure of a plant OSC, have elucidated the unique "cation shuttle-run" mechanism, providing valuable insights into the structure-function relationships governing catalytic specificity and efficiency. Concurrently, synthetic biology strategies have enabled the reconstruction of the friedelin biosynthetic pathway in engineered Saccharomyces cerevisiae. This review comprehensively synthesizes research progress, from the functional characterization and structure-function relationships of friedelane-type OSCs, to the development of integrated biotechnology strategies, including metabolic pathway engineering, protein engineering, and subcellular compartmentalization, which have enabled high-yield de novo production of friedelin. We also discuss future prospects for exploring OSC diversity and integrating systems biology, synthetic biology, and computational design to achieve sustainable biomanufacturing of friedelin and its high-value derivatives, while also addressing potential challenges in industrial applications.

Ixabepilone (IXA) is a potent antineoplastic agent capable of overcoming tumor resistance in breast cancer; however, its clinical utility is limited by systemic toxicity and off-target effects. To address these limitations, IXA-loaded blend nanoparticles combining the advantages of targeted FACS and FAALG polymer systems (FACS-FAALG blend NPs) were developed and comprehensively characterized. The nanoparticles exhibited a mean size of 218.17 ± 6.9 nm and an encapsulation efficiency of 53.7 ± 7.7%. In vitro release studies conducted at pH 5.5, 6.5, and 7.4 demonstrated pH-responsive behavior, with the highest cumulative release (85.0%) observed at pH 5.5. Cytotoxicity assays performed on MCF-7 and MDA-MB-231 cells revealed that IXA-loaded blend NPs induced greater reductions in cell viability and enhanced cellular uptake in MDA-MB-231 cells compared to the free drug. In vivo antitumor studies in nude mice bearing MDA-MB-231 tumors showed that IXA/FACS-FAALG blend NPs significantly inhibited tumor growth compared to non-targeted CS-ALG blend NPs. Folic acid-mediated targeting improved tumor accumulation, biodistribution, and therapeutic efficacy, as supported by IVIS imaging. Overall, this blended nanoparticle platform represents a formulation approach for targeted IXA delivery and shows potential for further investigation in breast cancer models.

In conventional co-delivered chemotherapeutic strategies, the disparity in physicochemical properties and non-coordinated pharmacokinetic profile is largely overlooked. To overcome these long-standing challenges, we prepared a Palbociclib (PAL) and Tamoxifen citrate (TC) co-loaded in a synergetic fashion into a Human serum albumin nanoparticle (PAL/TC-HSA-NPs). It was optimised through Box-Behnken design of experiment and had a Particle size, Polydispersity index, and zeta potential of 155.7 ± 8.12 nm, 0.15 ± 0.01, and - 19.52 ± 2.04 mV. At both pH conditions of 5.5 and 7.4, it displayed a prolonged release profile over 48 h. The molecular dynamics and simulation study confirmed an energetically stable protein-ligand interaction and well-submerged active moieties in the binding pockets of HSA. The maximal in vitro cytotoxicity caused by PAL/TC-HSA-NPs is attributed to a synergistic effect, along with active targeting achieved via the gp60 and SPARC proteins. In a flow cytometry study, PAL/TC-HSA-NPs showed maximal apoptosis and G0/G1 phase arrest in MDA-MB-231 cells. The AUC_0-t for PAL and TC in PAL/TC-HSA-NPs were found to be 26.16 ± 4.2 ppm*h and 18.25 ± 2.5 ppm*h, respectively, which were 1.17-fold and 1.44-fold higher than PAL and TC in PAL-TC (1:1) solution. The final tumour weight was found to be 2.62-fold reduced in comparison to the free PAL-TC group. In in vivo bioimaging, after a 24 h study, FITC-HSA-NP showed a pronounced fluorescence signal at the tumour site that remained detectable over an extended period. Overall, PAL/TC-HSA-NPs showed excellent tumour targeting, efficacy and biosafety.

Polyethylene terephthalate (PET) pollution poses a global environmental challenge, and enzymatic degradation represents a promising eco-friendly solution. The BhrPETase mutant Bhr6M demonstrated high degradation efficiency, showing considerable potential for PET biodegradation. To facilitate its practical application, we scaled up recombinant Bhr6M production in Escherichia coli via a 3-L bioreactor and identified optimal induction conditions of 30 °C and lactose feeding at 0.3 g·L^-1·h^-1. However, the enzyme solution exhibited limited stability, with a half-life (t_1/2) of approximately four days at 30 °C and four hours at 70 °C, hindering its broader application. To address this issue, we rationally designed via AlphaFold3, PROSS and combinatorial mutagenesis, obtaining the double mutant Bhr-S184H/M57I with synergistic performance improvements. This mutant achieved a yield of 3.17 g·L^-1 in approximately 31 h of fermentation, representing the highest productivity reported for PET hydrolases. Its stability was enhanced with a 66-fold longer t_1/2 at 70 °C than Bhr6M, and over 90% residual activity after 30 days at 30 °C. In addition, the mutant degraded 97% of amorphous PET at 70 °C within 48 h, a process that required 96 h for Bhr6M at its optimal temperature of 60 °C. After that, we further validated its practical utility by achieving over 95% degradation of pretreated PET bottles. Molecular dynamics (MD) simulations revealed the enhanced stability originates from new hydrogen-bonding networks and reduced conformational flexibility in key regions. This study provides a scalable strategy to simultaneously improve enzyme yield and stability, laying a foundation for industrial PET biodegradation.

Eudragit nanofibers are smart and pH-sensitive materials that experience extensive structural changes with pH variations. In the present study, a new solvent system was developed for electrospinning of Eudragit and the physicochemical properties of the resulting nanofibers were compared with those produced from conventional solvents used for electrospinning. Electrospinning with an acidic mixed solvent produced fibers with minimal structural and dimensional changes at both acidic and neutral pH and enabled the combination of a natural polymer, chitosan, with Eudragit. Then, chitosan was added to Eudragit and Eudragit/chitosan blended nanofibers with different blending ratios were prepared. Chemical, morphological, thermal and mechanical properties of the fibers, as well as their stability in aqueous media, were evaluated by various analyses. Morphological evaluation showed that increasing chitosan ratio in blended nanofibers decreased the fiber diameter. Shrinkage measurement revealed that increasing chitosan ratio did not significantly change the structural and dimensional stability of the fibers, however, morphological observation following shrinkage measurement corroborated the better stability of the fibers with 10% chitosan ratio at both acidic and neutral pH. Swelling and contact angle measurements verified that bulk and surface hydrophilicity increased proportionally with the chitosan ratio. Mechanical assay confirmed that nanofibers with 10% chitosan had higher strength and modulus compared to other formulations. Therefore, it can be said that fibers with 10% chitosan have better wettability and mechanical properties, while experiencing less structural changes and shrinkage than pure Eudragit fibers, and are considered an ideal choice as a pH-sensitive material.

Ovalbumin (OVA), the major protein in egg white, has attracted attention for its gel-forming properties. pH and temperature are the key parameters regulating protein conformational changes and gel formation. At present, there have been many studies on the structure and gelation mechanism of OVA under thermal and acidic conditions, but there is still a lack of systematic elaboration on how the combination of alkaline-thermal treatment affects the structural changes and gelation process of OVA. To address this issue, spectroscopy, molecular dynamics (MD) simulation, small-angle X-ray scattering (SAXS), and atomic force microscopy (AFM) were used to elucidate the mechanism of alkaline-thermal-induced OVA gelation at multiple scales. The results showed that OVA transitioned from the native state to a molten globule (MG) state under alkaline-thermal induction. In the secondary structures, the α-helix decreases with the enhancement of residue deprotonation and electrostatic repulsion, the β-sheet becomes a relatively stable structural skeleton, and the tertiary structure is partially unfolded. The MG state of OVA resembles a "Janus-like" particle, with ordered regions providing electrostatic repulsion and steric hindrance, while disordered regions mediate attraction. Under the balance between electrostatic repulsion and attraction, proteins were driven to self-assemble into "beaded" oligomeric fibers to form transparent gels. The above findings can provide theoretical guidance for the development of new gel foods and the industrial production of traditional gel foods.

Zygotic genome activation (ZGA) is crucial and indispensable for early embryonic development, marking the process in which the embryonic genome awakens from silence and begins to direct development. Owing to a lack of robust tools, the key transcription factors governing ZGA in species beyond mouse, such as pigs and humans, remain poorly defined. Here, we established an efficient gene inactivation system using the cytosine base editor miniSdd7-BE4max-SpG, which introduces premature termination codons and achieves high efficiency in porcine embryonic fibroblast cells (PEFs), approaching 100% in the embryos. Applying this approach, we demonstrated that zinc finger and SCAN domain-containing 4 (ZSCAN4) is critical for porcine early embryo development, as its knockout caused severe developmental arrest. Transcriptome profiling of ZSCAN4 knockout (KO) four-cell (4C) stage embryos revealed broad downregulation of ZGA genes, particularly enriching key embryonic development pathways, including RNA processing and translation. Mechanistically, ZSCAN4 KO elevated DNA methylation and H3K9me3 levels, alongside reduced H3K27ac and H3K4me3 levels, establishing a repressive chromatin state that ultimately impedes ZGA. Taken together, we present miniSdd7-BE4max-SpG as a highly efficient base-editing system that enables complete gene inactivation in porcine embryos, offering a definitive approach to study the function of ZGA regulators in early mammalian embryogenesis.