Although biological scaffolds containing bone morphogenetic protein-2 (BMP-2) have been widely used for osteogenic therapy, achieving stable and controlled release of BMP-2 remains a challenge. Herein, a novel BMP-2 sustained-release system composed of carboxymethyl chitosan (CMCS)/polyethylene glycol (PEG)/heparin sulfate (HS) (CMCS/PEG/HS) was constructed with a Schiff base reaction, yielding an injectable hydrogel for the release of BMP-2 in a controlled manner. For the CMCS/PEG/HS/BMP-2 hydrogel, the HS component had a negatively charged structure, which can bind to positively charged growth factors and prevent early hydrolytic metabolism of growth factors, thus achieving sustainable release of BMP-2. Notably, the release of BMP-2 in hydrogels was dependent mainly on degradation of the hydrogel matrix rather than simple diffusion. Generally, the CMCS/PEG/HS/BMP-2 hydrogel scaffold demonstrated excellent recoverability, good injectability, excellent biocompatibility and high adaptability, as well as efficient self-healing features to occupy irregularly shaped bone marrow cavities. The in vitro results revealed that the CMCS/PEG/HS/BMP-2 hydrogel promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, the in vivo results suggest that the hydrogel has promising osteogenic effects that promote bone regeneration in a skull bone defect model. The injectable hydrogel scaffold shows great promise for bone treatment in the future.
Derivatives of chitosan-ethyl formate polymers (Chs-EF) show promise as biologically relevant materials. The novelty of this study lies in the innovative use of Chs-EF doped with zinc oxide nanoparticles and beta-cyclodextrin, which significantly enhances the polymers' protective activities against Alternaria early blight disease in Vicia faba by improving both disease resistance and plant health. After doping Chs-EF with zinc oxide nanoparticles (ZnONPs) and inserting it into the beta-cyclodextrin (CD), two products emerged: Chs-EF/ZnONPs and Chs-EF/CD. Using βCD and ZnONPs to modify the Chs-EF polymer improves the optical properties of the generated polymers. Also, the energy gab values of the modified polymers (Chs-EF/ZnONPs and Chs-EF/βCD) were 3.3 and 3.7 eV, respectively, while energy gab value of the Chs-EF polymer was 3.9 eV. In this study, the effects of ZnONPs, chitosan, β-CD, and Chs-EF/ZnONPs on Alternaria solani early blight disease in Vicia faba plants were investigated. The treatments were evaluated based on disease symptoms and a disease index (DI) to assess their ability to protect against Alternaria early blight disease blight. The results show that the modified polymer with ZnONPs and beta-cyclodextrin (β-CD) and the modified polymer with ZnONPs (Chs-EF/ZnO NPs) provided the best protection, with DI values of 25 % and 12.5 %, respectively. Furthermore, it was discovered that the levels of carotenoids, chlorophyll a, and chlorophyll b in the infected plants had dropped by 52.6 %, 69.2 %, and 36.1 %, respectively. Chs-EF/ZnONPs were the most effective treatment, showing significant increases in the contents of chlorophyll a and b in infected plants by 120.8 % and 225.4 %, respectively. The study revealed that Chs-EF/ZnONPs exhibited a 131 % increase in the total phenolic content of plants, peroxidase (POD) activity (110.6 %), and a 347 % increase in polyphenol oxidase (PPO) activity, respectively, compared to healthy plants. Malondialdhyde (MDA) decreased by 50.7 %, 49.7 %, 43.4 %, 36.6 %, 31.7 %, and 7.5 % in response to Chs-EF/ZnONPs, Chs-EF/β-CD, Chs-EF, ZnONPs, Chitosan, and β-CD, respectively. Also, application of Chs-EF/ZnONPs, Chs-EF/β-CD, Chs-EF, ZnONPs, Chitosan, and β-CD reduced the production of H2O2 by 77.5 %, 62.8 %, 62.5 %, 39.6 %, 22 %, and 15.1 %, respectively, compared to infected controls. We recommend considering these substances as promising candidates for agricultural use, as they may effectively serve as control agents against early blight caused by Alternaria solani.
Nanocellulose-graphene hybrid composites for high-performance uses have been the focus of recent research. In contrast to graphene, which has great conductivity and mechanical strength, nanocellulose possesses special qualities like renewability and biocompatibility but lacks electrical conductivity. Since graphene-nanocellulose has such promising features, efforts to make flexible electronic composites employing them have accelerated. However, the environmental impacts are needed to be addressed prior to the applications of these hybrid composites. This review article explores environmental aspects for nanocellulose-graphene hybrid composites because of their sustainability, which is a major step in the right direction. The article also emphasizes how these composites have the potential to transform several industries and open the door to a more environmentally friendly future. This paper explores into the most recent developments in nanocellulose-graphene hybrid composites, highlighting its environmental benefits and adaptability. These composites offer remarkable performance by combining the strength and conductivity of graphene with the mechanical, electrical, and thermal capabilities of nanocellulose.
Purpose: Using clinical information and transcriptomic sequencing data from glioblastoma (GBM) patients in the TCGA database to perform gene-by-gene analysis that is aligned with individual patient characteristics and develop an optimal prognostic index of survival-related variables (OPISV) through iterative machine learning techniques to predict the prognosis of GBM patients.
Study design: The TCGA dataset was utilized as the training dataset, while two GEO datasets served as independent validation cohorts. Initially, survival analysis (p < 0.001***), differential gene expression analysis (p < 0.05*), and univariate Cox regression analysis (p < 0.05*) were employed to identify genes that are highly correlated with patient prognosis and exhibit significant differences in survival status. Subsequently, incorporating the non-excludable variable of age, a multivariate Cox regression analysis was performed in a stepwise manner to construct the OPISV. Finally, logistic and LASSO regressions were used to validate the association between the identified genes and patient survival. The OPISV performance is evaluated and its potential mechanisms are explored.
Results: Age, CTSD, PTPRN, PTPRN2, NSUN5, DNAJC30 and SOX21 emerged as the optimal variables through multivariate Cox regression iterations. Further analysis characterized Age, PTPRN and DNAJC30 as independent prognostic risk factors for constructing OPISV, which is validated with external GEO datasets and GEPIA database. In OPISV_high populations, significantly upregulated GABAergic synapse function was exposed. Differential genes identified from gene clustering of the GABAergic synapse pathway and gene module highly correlated with GABAergic synapse in the WGCNA analysis are pointing unequivocally to the glioma progress.
Conclusion: OPISV is feasible for predicting patient survival, as it may serve as a potential mechanism underlying the involvement of GABAergic synapses in the progression of GBM.
The study demonstrates the preparation of active edible biocomposites using Pullulan (PUL) and Gum Arabic (GA), functionalized with Chitosan Nanoparticles (NCS) and Neem Essential Oil (NEO). These biocomposites addressed the issues of high hydrophilicity and poor barrier properties in packaging. The effects of varying NCS concentrations (1 %, 2 %, and 3 %) on various film properties were studied, while keeping PUL, GA, and NEO concentrations constant. The biocomposite containing NEO and 3 % NCS (PUL/GA/NCS3/NEO), significantly improved surface properties, transforming it from hydrophilic (water contact angle 55.49 ± 2.31°) to hydrophobic (115.01 ± 1.86°). Additionally, tensile strength increased by ~12.77 MPa, elongation at break by ~6.26 %, thermal stability (Toffset) by ~22.49 °C, and water vapour barrier by ~45.95 %, alongside enhanced UV-shielding, antimicrobial and antioxidant properties. The EDX analysis confirmed the biocomposite safety, with 55.7 % carbon (C), 3.6 % nitrogen (N), and 40.8 % oxygen (O). Moreover, in vitro biocompatibility tests on Human Embryonic Kidney (HEK-293) cells indicated non-cytotoxicity, with 86.82 ± 2.28 % viability after 72 h. Furthermore, the practical application of PUL/GA/NCS3/NEO solution was tested as an edible coating material for fresh-cut guava preservation. The coated guava better maintained storage quality parameters in terms of colour, weight loss, firmness, microbiological shelf-life and antioxidant activity, under both ambient and refrigerated conditions.
Deoxynivalenol (DON) is a widely distributed mycotoxin that is severely cytotoxic and genotoxic to animals and humans. The gut is the initial site of DON exposure and absorption, which can cause severe intestinal damage. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the study indicated that DON exposure caused significant DNA damage in intestinal porcine epithelial cells (IPEC-J2), enhanced significantly the expression of γ-H2AX and 8-hydroxy-2'-deoxyguanosine, and altered the mRNA expression of key genes in the DNA repair pathway. Among them, ligases3 (LIG3) is the key DNA damage/repair gene and the only ligase responsible for the replication and maintenance of mitochondrial DNA. The expression of LIG3 was significantly decreased after DON exposure and showed a dose-dependent effect, decreased expression of LIG3 exacerbates DON-induced cytotoxicity and genotoxicity, decreased cell viability, induced apoptosis and cell cycle arrest, activation of inflammatory factors and MAPK pathway. Furthermore, LIG3 directly binds and regulates PCNA and play a positive regulatory role in the cellular cytotoxicity and genotoxicity upon DON exposure. Collectively, the findings elucidate the regulatory function of LIG3 in DON-induced DNA damage, providing valuable insights into identifying molecular targets for the comprehensive prevention and control of DON contamination.
Adequate vascularization essential for delivering nutrients critical to wound healing, yet impaired angiogenesis is a major barrier in diabetic wound repair. This study investigates the impact of hyaluronic acid on interpenetrating network sponge scaffolds derived from an acellular dermal matrix, with the aim of enhancing vascularization and healing of diabetic wounds via photothermal warm bath therapy. We prepared three-dimensional porous sponges (H1P4D2@DFO) using molecular interpenetration and ion crosslinking of porcine acellular dermal matrix (PADM), hyaluronic acid, and polydopamine nanoparticles loaded with deferoxamine mesylate (PDA@DFO). This resulting extracellular matrix-based sponge demonstrated properties suitable for wound repair, including high cell adhesion, biocompatibility, bioactivity, porosity (85 %), and water absorption (4500 %). The near-infrared (NIR) photothermal effect of PDA@DFO and the sustained release of deferoxamine mesylate (DFO) enhanced wound vascularization within the wound site. These findings suggest that our sponge scaffold can simulate skin-like structures and establish a supportive microenvironment conducive to microvascular reconstruction. By combining the photothermal warm bath approach with the scaffold's tailored 3D structure, we observed enhanced angiogenesis and accelerated diabetic wound healing, indicating potential clinical applications of these scaffolds in chronic wound management.