The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis.

BACKGROUND: Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. RESULTS: In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson's disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. CONCLUSION: These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

Putative Adverse Outcome Pathway for Parkinson's Disease-like Symptoms Induced by Silicon Quantum Dots based on In Vivo/Vitro Approaches.

Given the commercial proliferation of silicon quantum dots (SiQDs) and their inevitable environmental dispersal, this study critically examines their biological and public health implications, specifically regarding Parkinson's disease. The study investigated the toxicological impact of SiQDs on the onset and development of PD-like symptoms through the induction of ferroptosis, utilizing both in vivo [Caenorhabditis elegans (C. elegans)] and in vitro (SH-SY5Y neuroblastoma cell line) models. Our findings demonstrated that SiQDs, characterized by their stable and water-soluble physicochemical properties, tended to accumulate in neuronal tissues. This accumulation precipitated dopaminergic neurodegeneration, manifested as diminished dopamine-dependent behaviors, and escalated the expression of PD-specific genes in C. elegans. Importantly, the results revealed that SiQDs induced ferritinophagy, a selective autophagy pathway that triggered ferroptosis and resulted in PD-like symptoms, even exacerbating disease progression in biological models. These insights were incorporated into a putatively qualitative and quantitative adverse outcome pathway framework, highlighting the serious neurodegenerative risks posed by SiQDs through ferroptosis pathways. This study provides a multidisciplinary analysis critical for informing policy on the regulation of SiQDs exposure to safeguard susceptible populations and guiding the responsible development of nanotechnologies impacting environmental and public health.

Minodronate in the treatment of osteoporosis: A systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD: The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT: Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION: Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).