Current cyanide antidotes have limitations including delayed onset, methemoglobinemia, or the need for multiple agents. We developed Sodasulphanecobalamin (SSC), a cobalt‑sulfur complex integrating rapid cyanide chelation with sulfur-donor detoxification. SSC was synthesized from hydroxocobalamin and sulfur-based precursors, characterized by HPLC, HR-MS, NMR, IR, and elemental analysis, with the coordination geometry pending X-ray crystallography. In rats, SSC given 1 or 5 min after intravenous KCN (2.5 mg/kg) restored mean arterial pressure (MAP) within 5 ± 1 and 9 ± 2 min, respectively, with 100% survival in both groups (n = 9). At a higher cyanide dose (3.5 mg/kg, ~1.7× LD₅₀), SSC given after 5 min maintained 100% survival (n = 6), whereas hydroxocobalamin resulted in 83% survival. SSC (78% yield, >98% purity) restored MAP significantly faster than hydroxocobalamin (11 ± 2 min, p = 0.032) and standard nitrite-thiosulfate therapy (28 ± 3 min, p = 0.0004). At 3.5 mg/kg, SSC achieved 100% survival vs. 83% for hydroxocobalamin and 67% for standard therapy. Blood cyanide declined 85% within 5 min with corresponding thiocyanate rise, and methemoglobin remained below 3% (p > 0.05 vs. controls). Naive rats showed no toxicity over 28 days. Pharmacokinetics revealed a half-life of 4.2 ± 0.6 h. SSC is a fast-acting, well-tolerated cyanide antidote outperforming current therapies. Further studies are needed for dosing optimization and intramuscular administration.
Tungsten (W) and molybdenum disulphide (MoS₂) particles are increasingly used industrially, but may pose potential health risks, particularly following inhalation in occupational settings. Existing data is inconsistent but there is evidence that these particles are genotoxic. Therefore, there is a need to further increase our understanding on their toxicity and underlying mechanisms. To this end, we tested W and MoS2 particles in two human cell models, in vitro bronchial epithelial cells (BEAS-2B) and monocyte-derived macrophages (dTHP-1) after acute exposure (24 h), but we also investigated effects after subacute (2-week) exposure of BEAS-2B cells. We evaluated cellular metal content (by ICP-MS), cytotoxicity (by Alamar Blue and Trypan Blue), DNA damage (by alkaline comet assay) and secretion of pro-inflammatory cytokines (IL-6, IL-8/CXCL8, IL-1ß, TNF-α by multiplex electrochemiluminescence) into cell media. After acute exposure, both particles induced dose-dependent DNA damage in BEAS-2B and dTHP-1 cells. In addition, W particles also increased secretion of cytokines from dTHP1, while none were significantly increased in BEAS-2B cells. After subacute exposure both particles increased IL-6 secretion from BEAS-2B cells and induced dose-dependent DNA damage, which remained persistent at 1 week of recovery. Overall, our data indicate that MoS2 and W are genotoxic, likely via different mechanisms. The data suggest that exposure duration did not influence genotoxicity in BEAS-2B, but was important for inflammatory responses. When compared with in vivo data, our cell models predicted genotoxicity in bronchoalveolar lavage cells well and, to some extent, also lung inflammation. Finally, these findings stress the importance of limiting occupational exposure to W and MoS2 to protect workers' health.
Lapatinib is an important targeted drug used to treat HER2-positive breast cancer. However, its hepatotoxicity restricts its clinical efficacy. This study aims to elucidate the molecular mechanism of lapatinib's hepatotoxicity. Through in vivo models, we found that lapatinib treatment led to significant increases in serum ALT/AST levels and pathological damage to liver tissue in mice. It also induced a decrease in mitochondrial membrane potential and cell apoptosis in AML12 liver cells in vitro. Furthermore, this study revealed that lapatinib causes damage to both the mitochondria and the lysosomes. This led to lysosomal membrane permeabilization (LMP) and blocked mitochondrial autophagy, resulting in cathepsin leakage into the cytoplasm. Based on these findings, we discovered that the FDA-approved food additive tannic acid (TA) as a cathepsin inhibitor can effectively protect liver cells and alleviate liver damage in mice without affecting lapatinib's ability to kill SKBR3 breast cancer cells. This study has revealed a new mechanism of lapatinib hepatotoxicity involving the lysosome for the first time, providing a new target and an experimental basis for developing selective liver protection strategies in clinical practice.
Nickel is a transition metal that is widely distributed in the environment. Nickel compounds are classified as Group 1 carcinogens (human carcinogens) by the International Agency for Research on Cancer (IARC). Despite extensive studies, the molecular mechanisms underlying nickel-induced carcinogenesis remain incompletely understood. Maternally Expressed Gene 3 (MEG3) is the first long non-coding RNA (lncRNA) identified as a tumor suppressor. Previous studies have shown that downregulation of MEG3 increases HIF-1α expression in human bronchial epithelial BEAS-2B cells chronically exposed to nickel. In the present study, we observed that MEG3 expression is markedly reduced in nickel-transformed cells. Dysregulation of Runt-Related Transcription Factor 2 (RUNX2) has also been implicated in multiple cancer types. Previous studies have demonstrated that RUNX2 is upregulated in nickel-induced malignantly transformed BEAS-2B cells. Consistent with these findings, we observed that chronic exposure of BEAS-2B cells to low-dose nickel increases both RUNX2 mRNA and protein expression, accompanied by elevated expression of mesenchymal markers and enhanced migratory and invasive capacities. Overexpression of MEG3 in nickel-transformed cells reduces RUNX2 protein levels and reverses the alterations of epithelial-mesenchymal transition (EMT) markers, resulting in decreased cell migration and invasion in nickel-transformed cells. Similarly, silencing RUNX2 reverses the expression of EMT markers and suppresses the migratory and invasive capacities of nickel-transformed cells. Notably, shRNA-mediated RUNX2 knockdown increases MEG3 expression, indicating reciprocal regulation between MEG3 and RUNX2 in nickel-transformed cells. Collectively, our findings demonstrate that MEG3 and RUNX2 form a reciprocally regulated signaling axis that contributes to EMT, thereby promoting migration and invasion in nickel-transformed cells. These results identify MEG3 and RUNX2 as interconnected biomarkers and potential therapeutic targets for cancer prevention and treatment, warranting further mechanistic investigation.
Titanium dioxide nanoparticles (TiO₂ NPs) are extensively utilized in biomedical and pharmacological sectors; however, they may interact with biological systems causing various risks. Therefore, the present study assessed the role of surface modification by either chitosan (CS) or silica (Si) in mitigating TiO₂ NPs-induced neurotoxicity in rats. A total of twenty adult male rats were randomly distributed into 4 experimental groups (n = 5) as follows: control; uncoated TiO₂ NPs (100 mg/kg bwt); CS/TiO₂ NPs (100 mg/kg bwt), and Si/TiO₂ NPs (100 mg/kg bwt). All rats received daily treatments via oral gavage for a period of 2 months. The uncoated TiO₂ NPs elicited pronounced neurobehavioral disturbances, including cognitive disruption, memory impairment, and heightened anxiety, associated with increased acetylcholinesterase (AChE) activity, malondialdehyde (MDA), and nitric oxide (NO) levels, while reduced antioxidant activity. A pronounced upregulation of caspase-3 with downregulation of Nrf2 and Bdnf genes was also observed alongside strong immunoreactivity of caspase-3, iNOS, and GFAP in many brain areas, indicating neurodegenerative and inflammatory responses. In contrast, the encapsulation of TiO₂ NPs with either CS or Si significantly mitigated the biochemical, molecular, histopathological, and behavioral alterations compared to the uncoated TiO2 NPs.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, typically associated with poor clinical outcomes. Recently, ferroptosis has emerged as a promising therapeutic target for TNBC. ΔA146Ply, a novel pneumolysin variant, has demonstrated potential as an anti-tumor agent; however, its role in regulating ferroptosis remains unclear. This study investigates whether ΔA146Ply exerts anti-TNBC effects by promoting ferroptosis via the CYP24A1-mediated Calcitriol/vitamin D receptor (VDR) pathway. Our in vitro results reveal that ΔA146Ply inhibits MDA-MB-231 cells by inducing ferroptosis. Mechanistically, we demonstrate that CYP24A1 negatively regulates the Calcitriol-VDR pathway and serves as a critical mediator of ferroptosis. In vivo, ΔA146Ply suppresses TNBC tumor growth by downregulating CYP24A1 and promoting ferroptosis. In conclusion, ΔA146Ply exerts anti-TNBC effects by activating ferroptosis through the regulation of the CYP24A1-mediated Calcitriol-VDR pathway.
Sertraline, a widely used antidepressant, has shown emerging anticancer activity, but its metabolic mechanism in colorectal cancer (CRC) remains unclear. In this study, we evaluated the in vivo antitumor effect of sertraline using a CT26 tumor-bearing BALB/c mouse model, and performed UPLC-MS-based untargeted metabolomics to characterize serum metabolic alterations. Our results found that sertraline significantly inhibited tumor growth in BALB/c mice and partially reversed tumor-associated metabolic disturbances. Notably, levels of arachidonic acid (AA), 11,12-epoxyeicosatrienoic acid (11,12-EET), and 12-KETE were markedly elevated in the tumor model group but shifted toward normal levels after sertraline treatment. Pathway analysis identified arachidonic acid metabolism as the most significantly affected pathway, and Western blot confirmed that sertraline downregulated ALOXE3 expression in both tumor tissues and CT26 cells. ROC analysis revealed that a panel of only two metabolites achieved an AUC of 0.845, demonstrating good discriminatory ability between the tumor model and sertraline-treated groups, while expanding to ten metabolites further improved the AUC to 0.975 (95% CI: 0.800-1.000). These findings suggest that sertraline exerts antitumor effects in CRC associated with metabolic remodeling of arachidonic acid metabolism and altered ALOXE3 expression, providing preclinical evidence supporting further investigation of sertraline as a potential drug-repurposing candidate for CRC.
Environmental nanoplastics are increasingly prevalent in global environments and represent an emerging systemic health risk, yet the mechanistic links between nanoplastic exposure and multi-organ dysfunction in mammals remain incompletely characterized. We integrated phenotypic assessments, gut shotgun metagenomics, and dual-organ transcriptomics to investigate the toxic effects of 28-day oral exposure to polystyrene nanoplastics (PS-NPs) in male CD-1 mice. PS-NPs induced a non-monotonic dose-dependent response, characterized by significant body weight loss at high doses, severe impairment of sperm motility, and progressive epididymal histopathological lesions. Gut metagenomics revealed significant microbiota dysbiosis, including an elevated Firmicutes/Bacteroidota ratio and marked depletion of beneficial commensal bacteria such as Ligilactobacillus murinus. Hepatic transcriptomics identified dysregulation of metabolic, detoxification, and circadian rhythm pathways, while testicular transcriptomics identified sustained transcriptional downregulation of genes annotated to steroid hormone biosynthesis and alterations in FoxO and apoptosis-related signaling. Spearman correlation network analysis identified associations between specific microbial shifts and organ-specific transcriptional alterations, providing a hypothesis-generating framework for the proposed gut-liver/testis axis. Together, these findings indicate that, under the present experimental conditions, oral PS-NPs exposure was associated with gut microbial dysbiosis, hepatic transcriptional perturbations, reduced sperm motility, and epididymal histopathological alterations, while the mechanistic relationships among these changes require further experimental validation.
Increasing evidence suggests that Ras-related protein RAB17 plays a crucial role in tumor progression. Our preliminary data demonstrated that RAB17 is overexpressed in prostate cancer; however, its specific function in this malignancy is still poorly understood. This study sought to systematically clarify the functional role of RAB17 in prostate cancer, delineate its underlying molecular mechanisms, and evaluates its therapeutic potential. Analysis of clinical samples revealed that elevated RAB17 levels correlate with poorer overall survival in prostate cancer patients. Gene knockdown experiments demonstrated that silencing RAB17 exhibited notable tumor-suppressive effects in prostate cancer cells. Further investigations revealed that RAB17 knockdown increased intracellular iron concentrations and elevated lipid peroxidation levels, thereby triggering ferroptosis. Inhibiting ferroptosis significantly rescued the cancer-inhibiting impact elicited by RAB17 depletion. Notably, RAB17 was identified to interact with the iron uptake receptor transferrin receptor 1 (TfR1), promoting its degradation. Consequently, RAB17 knockdown increased TfR1 protein levels, enhancing iron influx and leading to iron overload and ferroptosis. Silencing TfR1 in RAB17 knockdown cells significantly reversed the tumor-suppressive and ferroptosis-inducing effects. In vivo experiments demonstrated that targeting RAB17 significantly delayed xenograft tumor growth associated with the induction of ferroptotic changes in tumor tissues. In conclusion, RAB17 is overexpressed in prostate cancer and exerts a tumor-promoting function. Silencing RAB17 induces ferroptosis through TfR1-mediated iron overload, thereby exerting tumor-suppressive effects. The RAB17-TfR1-ferroptosis axis may represent a pivotal modulator of prostate cancer and a promising candidate for targeted therapeutic intervention.
Chronic unpredictable stress (CUS) is a significant contributor to male reproductive dysfunction; however, no effective clinical therapies are available, highlighting the need to explore novel preclinical interventions with translational potential. CUS disrupts testicular metabolic homeostasis, however the metabolic mechanisms underlying spermatogenic dysfunction remain poorly understood. Irisin is an exerkine with recognized metabolic functions and may counteract stress-induced testicular injury. In the present study, we investigated whether Irisin restores stress-induced metabolic remodeling in the testis using 1H NMR-based metabolomics together with molecular and histological analyses. The study demonstrated for the first time that Irisin (100 ng/kg/day, s.c., for 4 weeks) exerts protective effects in a CUS-induced adult male rat model. CUS elevated corticosterone, anxiety-like behaviour, decreased sperm count, viability, chromatin integrity, and circulating Irisin, luteinizing hormone, testosterone, and follicle-stimulating hormone, which were restored by Irisin. Irisin also restored testicular histoarchitecture, increased the Johnsen score and seminiferous tubule diameter, thereby improving spermatogenesis impaired by CUS. At the molecular level, Irisin suppressed NF-κB signaling, enhanced Nrf2/HO-1 antioxidant defense, and restored blood-testis barrier (BTB) integrity and ectoplasmic specialization (ES) proteins disrupted by CUS. Further, metabolomic profiling identified significant alterations in lactate, pyruvate, citrate, succinate, glutamate, betaine, glycerol, and choline, reflecting impaired glycolysis, tricarboxylic acid cycle activity, antioxidant metabolism, and membrane homeostasis in the testis. Pathway analysis further identified disruptions in alanine, aspartate, and glutamate; glycine, serine, and threonine; phenylalanine; and taurine and hypotaurine metabolism. Collectively, Irisin preserved testicular function by restoring metabolic homeostasis, redox balance, and BTB integrity under chronic stress.
Propofol is a widely used intravenous (IV) anesthetic primarily eliminated through hepatic metabolism. However, quantitative prediction of pharmacokinetic (PK) alterations and dose adjustment requirements in patients with liver cirrhosis remains limited. This study aimed to develop a physiologically-based-pharmacokinetic (PBPK) model of propofol and evaluate impact of liver cirrhosis on systemic exposure and dosing requirements according to Child-Pugh (CP) classification. A PBPK model was developed using published clinical PK data from healthy adults and implemented in PK-Sim®. Drug-specific physicochemical properties and CYP2B6-, CYP2C9-, and UGT1A9-mediated metabolic pathways were incorporated into model. Subsequently, disease-specific physiological and biochemical changes associated with CP-A, CP-B, and CP-C cirrhosis were integrated to construct cirrhosis PBPK models. Healthy PBPK model adequately reproduced observed plasma concentration-time profiles across multiple IV dosing scenarios. Predicted-to-observed ratios ranged from 0.77 to 1.80 for AUCall and 0.51-1.31 for Cmax, with all datasets meeting conventional two-fold acceptance criterion. Cirrhosis PBPK models also demonstrated acceptable predictive performance, with AUCall and Cmax fold-errors ranging from 0.65 to 1.27 and 0.54-0.87, respectively. Simulations indicated progressive increases in propofol exposure with worsening liver cirrhosis severity. Simulation-based exposure matching predicted no maintenance infusion adjustment for CP-A, whereas reductions of approximately 6-7% and 12-14% were estimated for CP-B and CP-C, respectively, to approximate exposure in healthy subjects. Developed PBPK model characterized propofol PK in healthy and cirrhotic populations and provides a quantitative framework for simulation-based, exposure-matching dose adjustment according to CP classification. Prospective clinical validation is required before these model-derived dosing strategies can inform clinical practice.
Allergic rhinitis (AR) is a prevalent inflammatory disorder of the upper airways, and exposure to environmental endocrine-disrupting chemicals such as bisphenol A (BPA) and bisphenol F (BPF) has been implicated in its pathogenesis, yet the underlying molecular mechanisms remain poorly understood. We integrated network toxicology, bioinformatics, and machine learning approaches to identify key target genes linking BPA/BPF exposure to AR, followed by molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) to evaluate binding affinities. In vitro experiments using human nasal epithelial cells (HNEpC) were conducted to validate the effects of BPA/BPF on cell viability, apoptosis, inflammatory cytokines, senescence-associated secretory phenotype (SASP), and the NF-κB signaling pathway, with further functional assessment via MMP9 overexpression. Four common genes (MAPT, MMP9, CHRM3, ESR2) were identified for BPA and three (MMP9, CHRM3, ESR2) for BPF. SPR confirmed direct binding of both bisphenols to MMP9 with KD values of 3.46 μM (BPA) and 9.47 μM (BPF). BPA/BPF treatment inhibited cell viability, suppressed MMP9, promoted apoptosis, upregulated IL-4, IL-6, IL-8, IL-13, CCL2, TNF-α, and IL-1β, downregulated MMP1, and suppressed the NF-κB pathway. MMP9 overexpression reversed these effects. Our findings demonstrate that BPA and BPF promote AR pathogenesis through MMP9 suppression, SASP activation, and NF-κB inhibition, identifying MMP9 as a potential therapeutic target for pollutant-exacerbated AR.
Doxorubicin (Dox), a widely applied anthracycline antitumor agent, exhibits severe dose-dependent cardiotoxicity that greatly restricts its clinical utilization, yet the molecular mechanism linking Calpain-1 to cardiomyocyte ferroptosis in doxorubicin-induced cardiotoxicity (DIC) remains poorly clarified. This study aimed to explore how Calpain-1 regulates cardiomyocyte ferroptosis in DIC. Differentially expressed proteins from Dox-treated H9c2 cells were screened by proteomics, stable Calpain-1 knockdown cell lines were generated to detect cell viability and ferroptosis indicators through CCK-8, FerroOrange staining, biochemical kits and western blotting, and PPI network, co-IP and cycloheximide chase assays were performed to confirm Calpain-1-p53 binding and p53 protein stability regulation, with p53 rescue tests further verifying their functional relationship. In vivo, Calpain-1 expression was detected in Dox-exposed mouse hearts, and AAV9-driven myocardial Calpain-1 knockdown was established in DIC mice, where myocardial injury and ferroptosis were evaluated by HE staining, serum CK-MB/LDH and protein detection. Calpain-1 was significantly upregulated in Dox-stimulated cardiomyocytes and cardiac tissue. Calpain-1 silencing alleviated Dox-induced ferroptosis in vitro, with decreased Fe2+, MDA, LPO and ACSL4, elevated GSH and SLC7A11; co-IP verified direct Calpain-1-p53 interaction, and cycloheximide assays proved Calpain-1 inhibits p53 degradation to accumulate p53 protein, whereas p53 overexpression completely abolished the protective effect of Calpain-1 knockdown. Consistent with cellular results, cardiac-specific Calpain-1 knockdown mitigated myocardial damage and suppressed ferroptosis in DIC mice. These findings suggest that Calpain-1 exacerbates DIC by stabilizing p53 to initiate p53-dependent cardiomyocyte ferroptosis, offering a novel therapeutic target and theoretical basis for DIC intervention.
BACKGROUND:Sevoflurane (Sevo) is widely applied in clinical anesthesia practice, and exposure to this agent has been linked to cognitive impairment. PURPOSE:This study aimed to explore how microRNA-519a-3p (miR-519a-3p) contributes to Sevo-induced cognitive impairment and the molecular mechanisms involved. METHODS:A Sevo-induced anesthesia injury model was established by exposing rats to 2.5% Sevo for 6 h, and spatial learning and memory were subsequently evaluated using the Morris water maze (MWM). The expression level of miR-519a-3p was determined by RT-qPCR. CCK-8 assay, RT-qPCR, ELISA, and Western blot were respectively applied to evaluate cell viability, apoptotic gene expression, inflammatory cytokine levels, as well as protein levels of key mitochondrial dynamics and endoplasmic reticulum stress markers. A dual-luciferase reporter assay further verified the direct binding interaction between miR-519a-3p and estrogen receptor 1 (ESR1). RESULTS:Sevo exposure caused marked impairments in spatial learning and memory in rats, manifested as prolonged escape latency, reduced dwell time in the target quadrant, and fewer platform crossings. In vitro assays demonstrated that Sevo treatment significantly elevated miR-519a-3p expression in SH-SY5Y cells, while suppressing cell viability, accelerating apoptosis, and boosting the release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Knockdown of miR-519a-3p markedly reversed these aberrant phenotypes both in vivo and in vitro. MiR-519a-3p inhibition restored ESR1 expression. Rescue experiments further confirmed that ESR1 knockdown attenuated the protective effects of miR-519a-3p silencing against Sevo-induced cellular damage. CONCLUSIONS:MiR-519a-3p contributed to Sevo-induced cognitive dysfunction and cellular injury via negatively targeting ESR1.
Drug-induced liver injury (DILI) remains an issue in clinical and drug development settings causing large financial and health issues. This is in part due to the poor specificity and sensitivity of current standard circulating liver enzyme biomarkers, and research is ongoing to characterize more suitable novel candidates. Despite accounting for a small proportion of total liver cells, biliary epithelial cholangiocytes are vital to hepatic homeostasis due to their role in exporting toxic bile acids. Up to 40% of DILI cases can involve the biliary tract, yet much of the research for novel biomarkers has focused on hepatocellular injury, with miR-122 especially showing promise. We aimed to investigate novel microRNA (miR) biomarkers for cholangiocyte DILI. Characterization of basal murine hepatocyte and cholangiocyte miR profiles showed distinct expressions, which led to selection of a panel of cholangiocyte-enriched biomarker candidates, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-141-3p and miR-429-3p. This panel was then evaluated in an α-Naphthyl isocyanate (ANIT) CD-1 mouse in vivo model of biliary toxicity. Liver phenotype and serum enzymes indicated that ANIT initially caused biliary perturbation before later progressing into wider hepatic injury. At 24-h following ANIT administration, during the biliary damage phase, miR-200a-3p showed the most consistent elevations in serum as per liquid biopsy vs controls, indicating a large dynamic range. No meaningful changes in serum miR-122-5p were evident until 48-h post-dose, once hepatocellular damage was taking place. miR expression differences were incorporated into a miR ratio calculation previously reported in a clinical DILI cohort, and results were able to successfully distinguish cholestatic or hepatocellular patterns of injury. This novel panel of cholangiocyte-selective miR-200 family members should be further investigated in larger cholestatic DILI cohorts, with miR-200a-3p in particular showing potential as a sensitive circulating marker of biliary toxicity with serum increases that precede miR-122-5p and hepatocellular damage.
Diquat (DQ) has emerged as an important cause of herbicide poisoning following restrictions on paraquat (PQ) and is associated with multi-organ injury involving the liver, kidneys, and brain. Acute DQ poisoning is characterized by marked lipid metabolic dysregulation, including elevated free fatty acids (FFA) and reduced triglycerides (TG). Nevertheless, the mechanisms responsible for these lipid abnormalities remain unclear. To further characterize the lipidomic landscape of acute DQ poisoning, we performed untargeted serum lipidomics using ultra-high-performance liquid chromatography in combination with high-resolution mass spectrometry in 52 confirmed bipyridyl poisoning cases (32 DQ and 20 PQ). KEGG pathway enrichment analysis revealed significant perturbations in glycerophospholipid, glycerolipid, linoleic acid, α-linolenic acid, and arachidonic acid metabolism following DQ exposure. Within 6 h after ingestion, several O-acylhydroxy fatty acids and fatty acids (20:4) tended to increase, and these lipid alterations appeared earlier than laboratory parameters. Triglyceride (26:0/18:2/18:2) and sphingomyelin (d42:8) were independently associated with 28-day mortality. Compared with DQ poisoning, PQ poisoning exhibited a more pronounced depletion of plasmalogen-phosphatidylethanolamines despite broadly similar overall lipidomic profiles. The observed lipidomic alterations suggest that acute DQ poisoning may promote excessive lipolysis, disrupt glycerophospholipid homeostasis, and impair mitochondria-associated membrane function, thereby potentially contributing to oxidative stress and organ dysfunction. These findings demonstrate substantial lipid metabolic disturbances following acute DQ poisoning and identify candidate lipid markers that warrant further evaluation for diagnosis and prognosis.
