Retinol dehydrogenase 12 (RDH12) knock out may cause hyperuricemia phenotype in mice.

Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. And several gene loci and transporter proteins that associated with uric acid transport functions have been identified. Retinol Dehydrogenase 12 (RDH12), recognized for its role in safeguarding photoreceptors, and our study investigated the potential impact of Rdh12 mutations on other organs and diseases, particularly hyperuricemia. We assessed Rdh12 mRNA expression levels in various tissues and conducted serum biochemical analyses in Rdh12-/- mice. Compared with the wild type, significant alterations in serum uric acid levels and kidney-related biochemical indicators have been revealed. Then further analysis, including quantitative RT-PCR of gene expression in the liver and kidney, highlighted variations in the expression levels of specific genes linked to hyperuricemia. And renal histology assessment exposed mild pathological lesions in the kidneys of Rdh12-/- mice. In summary, our study suggests that Rdh12 mutations impact not only retinal function but also contribute to hyperuricemia and renal disease phenotypes in mice. Our finding implies that individuals with Rdh12 mutations may be prone to hyperuricemia and gout, emphasizing the significance of preventive measures and regular examinations in daily life.

Predicting mine water inflow volumes using a decomposition-optimization algorithm-machine learning approach.

Disasters caused by mine water inflows significantly threaten the safety of coal mining operations. Deep mining complicates the acquisition of hydrogeological parameters, the mechanics of water inrush, and the prediction of sudden changes in mine water inflow. Traditional models and singular machine learning approaches often fail to accurately forecast abrupt shifts in mine water inflows. This study introduces a novel coupled decomposition-optimization-deep learning model that integrates Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN), Northern Goshawk Optimization (NGO), and Long Short-Term Memory (LSTM) networks. We evaluate three types of mine water inflow forecasting methods: a singular time series prediction model, a decomposition-prediction coupled model, and a decomposition-optimization-prediction coupled model, assessing their ability to capture sudden changes in data trends and their prediction accuracy. Results show that the singular prediction model is optimal with a sliding input step of 3 and a maximum of 400 epochs. Compared to the CEEMDAN-LSTM model, the CEEMDAN-NGO-LSTM model demonstrates superior performance in predicting local extreme shifts in mine water inflow volumes. Specifically, the CEEMDAN-NGO-LSTM model achieves scores of 96.578 in MAE, 1.471% in MAPE, 122.143 in RMSE, and 0.958 in NSE, representing average performance improvements of 44.950% and 19.400% over the LSTM model and CEEMDAN-LSTM model, respectively. Additionally, this model provides the most accurate predictions of mine water inflow volumes over the next five days. Therefore, the decomposition-optimization-prediction coupled model presents a novel technical solution for the safety monitoring of smart mines, offering significant theoretical and practical value for ensuring safe mining operations.

Cascaded Antitumor Therapy Excited by Dual Nanozymes Based on Energy Restriction and Photocatalysis.

In nanocatalytic medicine, drugs can be transformed into toxic components through highly selective and highly specific catalytic reactions in the tumor microenvironment, avoiding toxic side effects on normal tissues. Due to the coexistence of Ce3+ and Ce4+, CeO2 is endowed with dual nanozyme activities. Herein, CeO2 nanoparticles served as templates to construct a biomimetic nanodrug delivery system (C/CeO2@M) by electrostatic adsorption of carbon quantum dots (CQDs) and coating a homologous tumor cytomembrane. After homologous targeting to tumors, the CQDs emitted 350-600 nm light under 660 nm laser irradiation by upconversion luminescence, which caused a CeO2-mediated photocatalytic reaction to generate reactive oxygen species. The catalase-like activity of CeO2-enabled converting excess H2O2 to O2, which not only alleviated tumor hypoxia and promoted intratumor drug delivery but also provided substrates for subsequent catalytic reactions. Meanwhile, the phosphatase activity of CeO2 could consume adenosine triphosphate (ATP) to block the energy supply for tumor cells, thus limiting cell proliferation and metastasis. The strategy of energy restriction and photocatalysis of dual nanozyme stimulation offers great potentials in enhancing drug penetration and eradicating solid tumors.

Gene Therapy for Rdh12-Associated Retinal Diseases Helps to Delay Retinal Degeneration and Vision Loss.

PURPOSE: The aim of study was to establish Rdh12-associated inherited retinal disease (Rdh12-IRD) mouse model and to identify the best timepoint for gene therapy. METHODS: We induced retinal degeneration in Rdh12-/- mice using a bright light. We clarified the establishment of Rdh12-IRD mouse model by analyzing the thickness of retinal layers and electroretinography (ERG). Rdh12-IRD mice received a subretinal injection of adeno-associated virus 2/8-packaged Rdh12 cDNA for treatment. We evaluated the visual function and retinal structure in the treated and untreated eyes to identify the best timepoint for gene therapy. RESULTS: Rdh12-IRD mice showed significant differences in ERG amplitudes and photoreceptor survival compared to Rdh12+/+ mice. Preventive gene therapy not only maintained normal visual function but also prevented photoreceptor loss. Salvage gene therapy could not reverse the retinal degeneration phenotype of Rdh12-IRD mice, but it could slow down the loss of visual function. CONCLUSION: The light-induced retinal degeneration in our Rdh12-/- mice indicated that a defect in Rdh12 alone was sufficient to cause visual dysfunction and photoreceptor degeneration, which reproduced the phenotypes observed in RDH12-IRD patients. This model is suitable for gene therapy studies. Early treatment of the primary Rdh12 defect helps to delay the later onset of photoreceptor degeneration and maintains visual function in Rdh12-IRD mice.

A magnetically responsive drug-loaded nanocatalyst with cobalt-involved redox for the enhancement of tumor ferrotherapy.

Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(iii) to Fe(ii) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an "all in one" strategy: (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.