METHODS AND RESULTS: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-β1, α-SMA, IL-1β, and TGF-β1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-β1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-β1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-β1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-β1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-β1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis.
CONCLUSION: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-β1/LIMK1 signaling pathway in this process.
OBJECTIVES: By leveraging the power of advanced machine learning schemes and experimental approaches, this research aims to provide valuable insights into CO2 flux prediction in coal fire areas and inform environmental monitoring and management strategies.
METHODS: The study involves the collection of an experimental dataset specific to underground coal fire areas, encompassing various parameters related to CO2 flux and underground coal fire characteristics. Innovative feature engineering techniques are applied to capture the unique characteristics of underground coal fire areas and their impact on CO2 flux. Different machine learning algorithms, including Natural gradient boosting regression (NGRB), Extreme gradient boosting (XGboost), Light gradient boosting (LGRB), and random forest (RF), are evaluated and compared for their predictive capabilities. The models are trained, optimized, and assessed using appropriate performance metrics.
RESULTS: The NGRB model yields the best predictive performances with R2 of 0.967 and MAE of 0.234. The novel contributions of this study include the development of accurate prediction models tailored to underground coal fire areas, shedding light on the underlying factors driving CO2 flux. The findings have practical implications for delineating the spontaneous combustion zone and mitigating CO2 emissions from underground coal fires, contributing to global efforts in combating climate change.