Using nanocellulose to improve heat-induced cull cow meat myofibrillar protein gels: effects of particle morphology and content.

BACKGROUND: Enhancing protein gel properties is essential to improve the texture of meat products. In this study, the improvement effects of three types of nanocellulose, i.e. rod-like cellulose nanocrystals (CNC), long-chain cellulose nanofibers (CNF) and spherical cellulose nanospheres (CNS) with different concentrations (1, 3, 5, 10, 15 and 20 g kg-1 ), on cull cow meat myofibrillar protein (MP) gel were investigated. RESULTS: Compared with needle-shaped CNC and spherical CNS, the addition of 10 and 20 g kg-1 long-chain CNF had the most significant improvement effect on gel hardness and water-holding capacity, respectively (P < 0.05), increasing to 160.1 g and 97.8%, respectively. In addition, the incorporation of long-chain CNF shortened the T2 relaxation time and induced the formation of the densest network structure and promoted the phase transition of the gel. However, excessive filling of nanocellulose would destroy the structure of the gel, which was not conducive to the improvement of gel properties. Fourier transform infrared results showed that there was no chemical reaction between the three nanocellulose types and MP, but the addition of nanocellulose was conducive to gel formation. CONCLUSION: The improvement of MP gel properties by adding nanocellulose mainly depends on its morphology and concentration. Nanocellulose with higher aspect ratio is more beneficial to the improvement of gel properties. For each nanocellulose type, there is an optimal addition amount for MP gel improvement. © 2023 Society of Chemical Industry.

Structure-based antigenic epitope and PEGylation improve the efficacy of staphylokinase.

Staphylokinase (Sak) holds promise for use in thrombolytic therapy for acute myocardial infarction. However, its immunogenicity is a major disadvantage under clinical conditions. PEGylation has become a sophisticated method to decrease that immunogenicity. In this report, according predicted epitope from the active center, five residues, including Gly79, Leu82, Lys84, Ala97, and Arg104 have been mutant as cysteine for mono PEGylation, respectively. According to the relative immunogenicity of Sak or its PEGylation derivatives, the amount of specific anti-Sak IgG antibodies elicited by PEGylation proteins, including C79G, C82L, C84K, C97A, and C104R in BALB/c mice decreased by approximately 15-75% each. PEGylated Sak derivatives showed a decrease of up to 75% in the immune reactivity in PEG-Sak-C104R. Thrombelastography experiments showed that two PEG-conjugated derivatives, PEG-Sak-C97A (Ly30, 68.14 ± 2.51%) and PEG-Sak-C104R (Ly30, 66.49 ± 5.97%), the LY30 of PEG-Sak-C97A, and PEG-Sak-C104R produced values very similar to those of wild-type Sak. The fibrin plate assays showed the bioactivity of PEG-Sak-C104R to exhibit the most activity approximately as much as urokinase (diameter of halo pattern, 18.6 ± 1.06 mm) and tPA (diameter of halo pattern, 17.2 ± 0.49 mm). The Sak PEGylation derivative PEG-Sak-C104R was also selected for further in vivo activity experimentation. The thrombolytic ability of PEG-Sak-C104R is a little lower than wild-type Sak, whereas, this PEGylated protein retained high activity suitable for thrombolytic therapy. Collectively, with the in vivo and in vitro experiments, the present study suggests that site mutant PEGylation, PEG-Sak-C104R, is a suitable type of PEGylation for clinical applications. Further optimization would help maintain the bioactivity and decrease the immunogenicity of staphylokinase.

Engineered Polymer Nanoplatforms for Targeted Tumor Cells and Controlled Release Cargos to Enhance Cancer Treatment.

Cancer is composed of a series of uncontrollable cells, which finally form tumors to negatively impact the functions of the body and induce other serious diseases, even leading to death. During the last decades, scientists have devoted great efforts to study cancer; however, there are no effective diagnoses and treatments. Nanomaterials have attracted great attention in the biomedical field in recent years, which are widely used as optical imaging probes and delivery systems for cancer therapy. Among the numerous nanomaterials, polymeric nanoparticles occupy a prominent position because of their tunable micro-size, multifunctional surface, prominent biocompatibility and high drug-carrying capacity. These significant advantages of polymeric nanomaterials have significance over the traditional nanomaterials and have become a potential therapy for cancer. In this review, we focus on the applications of polymeric nanoparticles in cancer theranostics, especially as the drug delivery systems for cancer treatment. This review provides an overview on the advancement of synthesis, application of polymeric nanoparticles- based drug delivery systems and highlights the evaluation for cancer therapy.

UBQLN2-HSP70 axis reduces poly-Gly-Ala aggregates and alleviates behavioral defects in the C9ORF72 animal model.

Expansion of a hexanucleotide repeat GGGGCC (G4C2) in the intron of the C9ORF72 gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Transcripts carrying G4C2 repeat expansions generate neurotoxic dipeptide repeat (DPR) proteins, including poly-Gly-Ala (poly-GA), which tends to form protein aggregates. Here, we demonstrate that UBQLN2, another ALS/FTD risk factor, is recruited to reduce poly-GA aggregates and alleviate poly-GA-induced neurotoxicity. UBQLN2 could recognize HSP70 ubiquitination, which facilitates the UBQLN2-HSP70-GA complex formation and promotes poly-GA degradation. ALS/FTD-related UBQLN2 mutants fail to bind HSP70 and clear poly-GA aggregates. Disruption of the interaction between UBQLN2 and HSP70 inhibits poly-GA aggregation in C9-ALS/FTD iPSC-derived neurons. Finally, enhancing HSP70 by the chemical compound 17AAG at the adult stage mitigates behavioral defects in poly-GA animals. Our findings suggest a critical role of the UBQLN2-HSP70 axis in protein aggregate clearance in C9-ALS/FTD.

Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer.

Cancer is a leading cause of human mortality. Given that it is difficult for conventional therapeutic approaches to effectively eradicate tumors and inhibit their recurrence and metastasis, new therapeutic strategies for solving this problem are urgently needed. In this work, we report the development of a two-dimensional titanium carbide nanocomposite drug delivery system. The system can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system. A surface modification engineering strategy has been elaborately designed to realize the multifunctionalization of an MXene, Ti3C2. In this strategy, the nanocomposite drug delivery system (Ti3C2@Met@CP) was established via layer by layer adsorption of metformin (Met) and compound polysaccharide (CP) on the surface of Ti3C2 nanosheets. Among these materials, the synthesized (AlOH)4--functionalized Ti3C2 nanosheets possess strong near-infrared absorption (extinction coefficient of 36.2 L g-1 cm-1), high photothermal conversion efficiency (∼59.6%) and effective singlet oxygen generation (1O2). Compound polysaccharide (CP) is a new immunomodulator formed by mixing lentinan, pachymaran and tremella polysaccharides in optimal proportions. Especially, the decoration of CP onto the Ti3C2 nanosheets endows Ti3C2 with a well-defined shell, improves its tumor site aggregation and biocompatibility, and activates the host's immune functions. The synergistic eradication and inhibition of tumor recurrence and metastasis have been systematically evaluated by in vivo and in vitro experiments.

Novel aza-BODIPY based small molecular NIR-II fluorophores for in vivo imaging.

The development of new NIR-II fluorophores, particularly those with facile syntheses, high fluorescence quantum yields, and stable and tunable photophysical properties, is challenging. Herein, we report a new class of small molecular NIR-II fluorophores based on aza-dipyrromethene boron difluoride (aza-BODIPY) dyes. We demonstrate promising photophysical properties of these dyes, such as large Stokes shift, superior photostability, and good fluorescence brightness as nanoparticles in aqueous solution. Because of these properties and high resolution and deep penetration NIR-II imaging ability, the aza-BODIPY based dyes show great potential as NIR-II imaging agents.

Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery.

Sustained-release systems made by biodegradable polymers for protein and peptide drug delivery have received considerable attention by academic researchers and major pharmaceutical companies around the world. Various types of biodegradable materials, including natural and synthetic polymers, have been applied to form protein and peptide drug carriers. Among these material candidates, poly lactic acid (PLA) and poly lactic-co-glycolic acid (PLGA) are the most commonly used biodegradable materials in the development of protein and peptide microspheres. In addition, many microsphere preparation technologies, including spray drying, coacervation, multiple emulsion solvent evaporation method and microporous membrane emulsification have been developed for microspheres preparation. In this review, we particularly summarize and briefly introduce the materials and methods that are used to fabricate microspheres as protein delivery systems. The existing opportunities and challenges for successful protein delivery are also discussed.

Maximizing Aggregation of Organic Fluorophores to Prolong Fluorescence Lifetime for Two-Photon Fluorescence Lifetime Imaging.

Two-photon fluorescence lifetime imaging (TP-FLIM) not only permits imaging deep inside the tissues with precise spatial manipulation but also circumvents tissue autofluorescence, holding tremendous promise in molecular imaging. However, the serious lack of suitable contrast agents with long fluorescence lifetime and efficient two-photon absorption (TPA) greatly limits the advance of TP-FLIM. This study reports a simple approach to fabricate water-soluble organic semiconducting nanoparticles [thioxanthone (TXO) NPs] with ultralong fluorescence lifetime and efficient TPA for in vivo TP-FLIM. The approach utilizes the aggregation of a specifically selected thermally activated delayed fluorescence (TADF) fluorophore to prolong its fluorescence lifetime. Encapsulating the TADF fluorophore within an amphiphilic copolymer not only maximizes its aggregation but also obtains TXO NPs with efficient TPA. Importantly, as-prepared TXO NPs exhibit a considerably long fluorescence lifetime at a magnitude of 4.2 µs, which is almost 1000 times larger than that of existing organic contrast agents. Moreover, such long fluorescence lifetime is almost oxygen-inert, readily realizing both in vitro and in vivo TP-FLIM. This work may set valuable guidance for designing organic semiconducting materials with ultralong fluorescence lifetimes to fulfill the potential of FLIM.