Two-dimensional molybdenum disulfide (2D MoS) nanomaterials are seeing increased use in several areas, and this will lead to their inevitable release into soils. Surface defects can occur on MoS nanosheets during synthesis or during environmental aging processes. The mechanisms of MoS nanosheet toxicity to soil invertebrates and the role of surface defects in that toxicity have not been fully elucidated. We integrated traditional toxicity end points, targeted energy metabolomics, and transcriptomics to compare the mechanistic differences in the toxicity of defect-free and defect-rich MoS nanosheets (DF-MoS and DR-MoS) to using a coelomocyte-based assessment model. After organism-level exposure to DF-MoS for 96 h at 10 and 100 mg Mo/L, cellular reactive oxygen species (ROS) levels were elevated by 25.6-96.6% and the activity of mitochondrial respiratory electron transport chain (Mito-RETC) complex III was inhibited by 9.7-19.4%. The tricarboxylic acid cycling and glycolysis were also disrupted. DF-MoS preferentially up-regulated subcellular component motility processes related to microtubules and caused mitochondrial fission. Unlike DF-MoS, DR-MoS triggered an increased degree of mitochondrial fusion, as well as more severe oxidative stress. The activities of Mito-RETC complexes (I, III, IV, V) associated with oxidative phosphorylation were significantly inhibited by 22.8-68.6%. Meanwhile, apoptotic pathways were activated upon DR-MoS exposure, which together with the depolarization of mitochondrial membrane potential, mediated significant apoptosis. In turn, genes related to cellular homeostasis and energy release were up-regulated to compensate for DR-MoS-induced energy deprivation. Our study indicates that MoS nanosheets have nanospecific effects on and also that the role of surface defects from synthesis or that accumulate from environmental impacts needs to be fully considered when evaluating the toxicity of these 2D materials.
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http://dx.doi.org/10.1021/acsnano.2c10623 | DOI Listing |
PLoS One
January 2025
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.
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January 2025
Internal Medicine Division, Federal University of Parana (UFPR), Curitiba, PR, Brazil.
Patients with radiographic axial spondyloarthritis (r-axSpA) experience a higher prevalence of fragility fractures, though the pathophysiology of osteoporosis associated with this disease remains poorly understood. The objective of this study was to evaluate the histomorphometric data in r-axSpA patients. Male r-axSpA patients up to 55 years old were enrolled in this cross-sectional study.
View Article and Find Full Text PDFCalcif Tissue Int
January 2025
Orthopaedic Research Laboratory, Department of Orthopedic Surgery and Traumatology, Odense University Hospital & Department of Clinical Research, University of Southern Denmark, V18-812B-1, Etage 1, Bygning 45.4, Nyt Sund, SDU Campus 5230, Odense, Denmark.
There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan, Ann Arbor, MI, USA.
Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background: While disease-modifying treatments that reduce Aβ have been recently approved by the FDA, the identification of novel therapeutic targets and strategies that target underlying mechanisms to delay the AD development are still needed. Abnormal brain energy homeostasis and mitochondria dysfunction are observed early in AD. Therefore, the development of treatments to restore these defects could be beneficial.
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