Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma.

Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 µg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.

Genomic and vaccine preclinical studies reveal a novel mouse-adapted Helicobacter pylori model for the hpEastAsia genotype in Southeast Asia.

Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential.Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance.Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies.Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model.Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model.Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.

Synthesis, Characteristics, Oil Adsorption, and Thermal Insulation Performance of Cellulosic Aerogel Derived from Water Hyacinth.

Cellulosic aerogel from water hyacinth (WH) was synthesized to address the dual environmental issues of water hyacinth pollution and the production of a green material. Raw WH was treated with sodium hydroxide (NaOH) with microwave assistance and in combination with hydrogen peroxide (H2O2). The results from X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) showed that lignin and hemicellulose were markedly decreased after treatment, reducing from 24.02% hemicellulose and 5.67% lignin in raw WH to 8.32 and 1.92%, respectively. Cellulose aerogel from the pretreated WH had a high porosity of 98.8% with a density of 0.0162 g·cm-3 and a low thermal conductivity of 0.030 W·m-1·K-1. After modification with methyl trimethoxysilane (MTMS) to produce a highly hydrophobic material, WH aerogel exhibited high stability for oil absorption at a capacity of 43.3, 43.15, 40.40, and 41.88 (g·g-1) with diesel oil (DO), motor oil (MO), and their mixture with water (DO + W and MO + W), respectively. The adsorption remained stable after 10 cycles.

Novel compound heterozygous stop-gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency.

BACKGROUND: Lipopolysaccharide-responsive and beige-like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000-1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. METHODS: We report a 16-year-old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. RESULTS: Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop-gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. CONCLUSION: This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting.

Cross-dehydrogenative coupling of coumarins with Csp3-H bonds using an iron-organic framework as a productive heterogeneous catalyst.

The iron-organic framework VNU-20 was utilized as an active heterogeneous catalyst for the cross-dehydrogenative coupling of coumarins with Csp3-H bonds in alkylbenzenes, cyclohexanes, ethers, and formamides. The combination of DTBP as the oxidant and DABCO as the additive led to high yields of coumarin derivatives. The VNU-20 was more active towards this reaction than numerous other homogeneous and heterogeneous catalysts. Heterogeneous catalysis was confirmed for the cross-dehydrogenative coupling transformation utilizing the VNU-20 catalyst, and the contribution of active iron species in the liquid phase was insignificant. The iron-based framework was reutilized many times for the functionalization of coumarins without a remarkable decline in catalytic efficiency. To the best of our knowledge, these reactions of coumarins have not previously been conducted using heterogeneous catalysts.