Inhalation of crystalline silica (CS) is linked to pulmonary silicosis, fibrosis, and cancer in exposed workers, but the underlying molecular mechanisms are obscure. We obtained publicly available datasets in the NCBI Gene Expression Omnibus for CS-induced gene expression changes in the rat lung. Seven datasets were identified via a PRISMA-guided systematic search using predefined databases, search terms, and eligibility criteria. Data from seven datasets, in total 194 rats and 5726 genes were classified for responses after equivalent to acute (≤2days), sub-acute (3days to 1month), and sub-chronic exposures (1 to 6months). Following normalization and batch correction, transcriptomic datasets were subjected to temporal clustering, pathway-level gene set enrichment analysis, immune cell deconvolution, and machine-learning-based feature selection to identify key molecular signatures associated with crystalline silica exposure. The temporal clustering revealed eight distinct gene clusters. Acute responses were marked by macrophage-driven proinflammatory cytokines (TNF/NF-κB, Il1b signaling) and neutrophil-recruiting chemokines (Cxcl2). The sub-acute responses showed transient suppression of interferon signaling, while later responses were dominated by persistent inflammatory and fibrosis-related programs reflected by Spp1, TGF-β signaling, and glycolytic metabolic reprogramming. Immune cell deconvolution indicated a neutrophil influx in the sub-acute time points, followed by progressive macrophage accumulation throughout exposure. ML analyses highlighted Chi3l1, Mt1, Phka1, and Sod2 as top predictive biomarkers, which were consistently changed across all time points, enriched in immune and fibrotic pathways, and strongly correlated with macrophage subtypes. Verification using transcriptomic profiles from chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis lungs further supported their predictive value. This integrative approach revealed temporal gene expression patterns and indicated both known and novel mechanisms and lung cell dynamics underlying CS-lung pathogenesis.

Micro- and nano-plastics (MNPs) have become ubiquitous environmental pollutants. Extensive toxicological studies of MNPs have been conducted in recent years. However, because of the difficulties involved in extraction and collection of MNPs from environmental media, most of these studies have employed simplistic, pristine, spherical, micro- or nano-sized commercial MNPs, whose properties, including morphology, surface chemistry, and size, do not adequately approximate those of environmentally relevant MNPs. Here, we describe the development and use of methods for the synthesis of well characterized, environmentally relevant MNPs across the life cycle of a plastic material, in a property-controlled manner. Multiple degradation scenarios, including mechanical fragmentation (cryogenic milling), UV weathering, and thermal disintegration (incineration) were applied to virgin plastic materials (polyvinyl chloride, PVC; polyethylene terephthalate, PET; High density polyethylene, HDPE; Acrylonitrile butadiene styrene, ABS; polycarbonate, PC; and polypropylene, PP) to simulate the life cycle pathways that likely occur in the environment over time. The MNPs generated from these degradation processes were size fractionated using both "dry" and "wet" separation methods. Detailed physicochemical characterization of the size fractionated reference MNPs was performed to determine size, morphology, chemical and elemental compositions, and hydrophobicity. Microbiological sterility and endotoxin content of reference MNPs were also assessed. Protocols for storage of reference MNPs in controlled oxygen and moisture conditions for future use in toxicological studies are also described. The methodology developed in this study can be used to synthesize environmentally relevant reference MNPs across the life cycle of plastic materials for use in risk assessment studies.

Titanium dioxide nanoparticles (TiO2 NPs) have promising applications in food additives and pharmaceutical dressings, raising concerns about their oral safety. The current studies mainly focus on healthy groups, and the effect of TiO2 NPs on the patient population is rarely known. Here, a comprehensive toxicity study of TiO2 NPs (75±15nm, anatase) in gastric ulcer rats (male 8-week old Sprague-Dawley rats) is reported following oral exposure at dose of 0, 10, 50, 200mg/kg body weight per day for 30days. The gastric ulcer rats were produced by submucosal injection of acetic acid solution into the rat stomach. The healthy rats were used as the normal control. We evaluated nanoparticle biodistribution, systemic toxicity, and gastrointestinal function indices in the rats. Our findings indicate that oral administration of TiO2 NPs resulted in minimal intestinal absorption and transport with limited systemic organ toxicity. The internalization of TiO2 NPs and activation of mast cells in the stomach tissues, along with the low serum levels of histamine and IgE, suggest a localized allergic reaction rather than a systemic one. Furthermore, the notably reduced plasma levels of D-lactate and the activity of diamine oxidase (DAO) indicated the upregulation of intestinal barrier function. These statistically significant results indicated that gastrointestinal dysfunction was the main performance of the oral toxicity of TiO2 NPs on gastric ulcer rats, emphasizing the importance of controlling the intake of TiO2 NPs in patients with gastric ulcers.