Structurally Dynamic Gelatin-Based Hydrogels with Self-Healing, Shape Memory, and Cytocompatible Properties for 4D Printing.

Three-dimensional (3D) printable hydrogels with a shape memory effect have emerged as a new class of 4D printing materials recently and found wide applications in various fields. However, synergistically endowing such materials with good mechanical strength and biocompatibility for biomedical uses remains challenging. In this study, a series of multiresponsive hydrogels have been prepared through a dynamic covalent imine/Diels-Alder network from biocompatible starting materials of modified gelatin and poly(ethylene glycol)-based polymers. By further secondary crosslinking with a hyperbranched triethoxysilane reagent (HPASi) that contains multiple supramolecular hydrogen bonding, the hydrogels presented a strengthened self-healing and temperature-responsive shape memory effect. With the additional features of superior stretchability (elongation at break up to 523%), good cytocompatibility, and 3D printable properties, these multifunctional hydrogels showed great potential for broad biomedical applications.

Inhaled polystyrene microplastics impaired lung function through pulmonary flora/TLR4-mediated iron homeostasis imbalance.

Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 µm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.

Nanocellulose from agro-industrial wastes: A review on sources, production, applications, and current challenges.

Significant volumes of agricultural and industrial waste are produced annually. With the global focus shifting towards sustainable and environmentally friendly practices, there is growing emphasis on recycling and utilizing materials derived from such waste, such as cellulose and lignin. In response to this imperative situation, nanocellulose materials have surfaced attracting heightened attention and research interest owing to their superior properties in terms of strength, stiffness, biodegradability, and water resistance. The current manuscript provided a comprehensive review encompassing the resources of nanocellulose, detailed pretreatment and extraction methods, and present applications of nanocellulose. More importantly, it highlighted the challenges related to its processing and utilization, along with potential solutions. After evaluating the benefits and drawbacks of different methods for producing nanocellulose, ultrasound combined with acid hydrolysis emerges as the most promising approach for large-scale production. While nanocellulose has established applications in water treatment, its potential within the food industry appears even more encouraging. Despite the numerous potential applications across various sectors, challenges persist regarding its modification, characterization, industrial-scale manufacturing, and regulatory policies. Overcoming these obstacles requires the development of new technologies and assessment tools aligned with policy. In essence, nanocellulose presents itself as an eco-friendly material with extensive application possibilities, prompting the need for additional research into its extraction, application suitability, and performance enhancement. This review focused on the wide application scenarios of nanocellulose, the challenges of nanocellulose application, and the possible solutions.

The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways.

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 µg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

Preclinical evaluation of recombinant HFMD vaccine based on enterovirus 71 (EV71) virus-like particles (VLP): Immunogenicity, efficacy and toxicology.

Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in children. Currently, three inactivated EV71 vaccines have been approved by Chinese government. We previously demonstrated that recombinant EV71 virus-like particles (VLP) produced in Pichia pastoris can be produced at a high yield with a simple manufacturing process, and the candidate vaccine elicited protective humoral immune responses in mice. In present study, the nonclinical immunogenicity, efficacy and toxicity of the EV71 vaccine was comprehensively evaluated in rodents and non-human primates. The immunogenicity assessment showed that EV71 VLPs vaccine elicited high and persistent neutralizing antibody responses, which could be comparable with a licensed inactivated vaccine in animals. The immune sera of vaccinated mice also exhibited cross-neutralization activities to the heterologous subtypes of EV71. Both passive and maternal antigen specific antibodies protected the neonatal mice against the lethal EV71 challenge. Furthermore, nonclinical safety assessment of EV71 VLP vaccine showed no signs of systemic toxicity in animals. Therefore, the excellent immunogenicity, efficacy and toxicology data supported further evaluation of the VLP-based EV71 vaccine in humans.