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The increasing demand for sustainable machining necessitates the development and toxicological evaluation of environmentally friendly alternatives to conventional metalworking fluids (MWFs). This study investigated the respiratory and systemic effects of a nanoparticle-enhanced vegetable oil-based MWF (NPVO-MWF) using a whole-body inhalation exposure model in male C57BL/6 mice. Both sub-acute (4-week) and sub-chronic (13-week) exposures were performed, followed by detailed bioanalytical and histopathological assessments. Cytokine analyses (IL-1β, TNF-α, IL-6) via ELISA and RT-PCR revealed no significant pro-inflammatory responses. Reactive oxygen species (ROS) levels in blood, bronchoalveolar lavage fluid, and lung homogenates remained unchanged, indicating an absence of oxidative stress. Histopathological analysis using hematoxylin and eosin staining showed mild epithelial hyperplasia in sub-chronic exposures. Sirius Red staining revealed minimal collagen deposition and slight reductions in pulmonary airspace. No substantial evidence of lung injury, pulmonary toxicity, or carcinogenicity was observed. This study represents one of the first applications of a whole-body inhalation model for evaluating NPVO-MWFs, addressing a critical gap in occupational health risk assessment. The findings indicate that NPVO-MWFs present low toxicological risk under the tested conditions and offer a viable, sustainable alternative to conventional MWFs. Additional chronic exposure studies are recommended to further establish their occupational safety.

The advent of long-term implants has increased the urgent need for self-powered biomedical devices. Utilize enzymes to expedite the process of biofuel oxidation. These systems frequently make use of glucose oxidase. A possible solution involves glucose biofuel cells powered by the glucose found in physiological fluids. Biocompatible substances like carbon electrode designs help to transport electrons from the biological reactions to the external circuit as efficiently as possible while maximizing surface area. Despite advances in implantable electrodes, developing miniaturized and flexible electrodes remains challenging. In this work, a metal-coated flexible carbon thread and foam bioelectrode are fabricated and successfully implanted inside a living and freely moving rat. These electrodes are prepared using gold nanostructures as electron enhancers, a negatively charged conducting polymer, a biocompatible redox mediator, and enzymes as biocatalysts. The carbon foam-based enzymatic biofuel cell produces in vitro and in vivo settings, generates a power density of 165 µW/cm 2 and 285 µW/cm 2 , and the carbon thread-based fuel cell produces a power density of 98 µW/cm 2 and 180 µW/cm 2 in vitro and in vivo environments, respectively. This work paves the way for the possible use of inexpensive electrodes for subdermal implantable microsystems.

Objective and designTo understand the expression of dsRNA-dependent protein kinase R (PKR) in impaired diabetic wounds, hyperglycemia was induced in C57/BL6 mice with streptozotocin. Murine macrophage cell line, Raw 264.7, stimulated with high glucose and LPS was used to mimic diabetic wound environment in in-vitro.MaterialsMacrophages stimulated with HG + LPS, in presence and absence of PKR inhibitor (C16) and wound tissue samples from topically treated mice with C16, were analyzed for the expression of PKR, NALP3, active caspase-1, mature IL-1β and phosphorylation of PKR and eIF2α. Wounds tissues were also analyzed for inflammatory cell infiltration by immunohistochemistry, angiogenesis by CD31 staining, collagen expression by western blotting, expression of CD206+ macrophages by flow cytometry and wound strength by texture analyzer.ResultsPKR and NALP3 were found to be upregulated in macrophages stimulated with HG + LPS as well as in impaired diabetic wounds. PKR inhibition using C16 ameliorated expression of NALP3, caspase-1, IL-1β and phosphorylation of PKR and eIF2α, in macrophages and also in diabetic wounds. Treatment with C16 promoted the wound healing in diabetic mice by increasing collagen synthesis, reducing infiltration of F4/80+ macrophages and MPO+ neutrophil cells, increased angiogenesis, and increased number of M2 macrophages.ConclusionPKR inhibition using C16 accelerates the wound healing process in diabetic mice by decreasing NALP3-mediated IL-1β maturation.

Human immunodeficiency virus (HIV) mainly attacks lymphocytes of the human immune system. The untreated infection leads to acquired immune deficiency syndrome (AIDS). Ritonavir (RTV) belongs to protease inhibitors (PIs), the crucial contributors of the combination therapy used in the treatment of HIV that is called highly active antiretroviral therapy (HAART). Formulations targeting the lymphatic system (LS) play a key role in delivering and maintaining therapeutic drug concentrations in HIV reservoirs. In our previous study, we developed RTV-loaded nanostructured lipid carriers (NLCs), which contain the natural antioxidant alpha-tocopherol (AT). In the current study, the cytotoxicity of the formulation was studied in HepG2, MEK293, and H9C2 cell lines. The formulation efficacy to reach the LS was evaluated through a cycloheximide-injected chylomicron flow blockade model in Wistar rats. Biodistribution and toxicity studies were conducted in rodents to understand drug distribution patterns in various organs and to establish the safety profile of the optimized formulation (RTV-NLCs). From the MTT assay, it was found that the cell viability of the formulation is comparable with the pure drug (RTV-API). More than 2.5-folds difference in AUC was observed in animals treated with RTV-NLCs with and without cycloheximide injection. Biodistribution studies revealed higher drug exposure in the lymphoidal organs with the RTV-NLCs. No significant increase in serum biomarkers for hepatotoxicity was observed in rats dosed with the RTV-NLCs. The current study reveals the lymphatic uptake of the RTV-NLCs and their safety in rodents. As the tissue distribution of RTV-NLCs is high, hence re-adjusting the RTV-NLCs dose to get the response equivalent to RTV-API may be more beneficial with respect to its safety and efficacy. Graphical Abstract