Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective: To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening (microstomia) due to systemic scleroderma. Methods: This study followed medical ethics, and informed consent has been obtained from patients. A case of Ken's Type I mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression. Individual trays were made based on the patient's left and right mandibular dentition, and segmented molds were obtained. Simultaneously, intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles. After each part of the model was obtained, the mandibular model was scanned and digitally aligned to form the final denture model, and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing (CAD/CAM) technology. At the same time, combined with the literature, the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed. Results: The denture was well retained and achieved a good repair effect. The patients expressed satisfaction with the mastication efficiency and other functions of the denture. The findings of the literature review show that the integration of digital technology with the traditional impression method, along with computer fitting, can accurately obtain the patient's oral model and facilitate successful follow-up repairs. However, when the anterior mandibular dentition of the patient is absent, the margin of error is increased in this procedure, which deserves further exploration. Conclusion Utilizing digital technology as the leading method, combined with the traditional impression method of segmental impression, for the repair of dental defects in patients with limited mouth opening, has proven to be effective. Thus, patients report a positive medical experience with high satisfaction, indicating that this approach is worthy of clinical promotion.

Objective:To investigate the relationship between the LAMA2 gene expression and the survival time of cancer patients, tumor microenvironment, tumor immune cell infiltration, and the immunotherapy responsiveness in pan-cancer. Methods:Download the expression data matrix and the clinical data from TCGA and IMvigor210, furthermore analyze the correlation between the expression level of LAMA2 and survival time, tumor microenvironment, and immunotherapy responsiveness by R and perform the gene set enrichment analysis of LAMA2 in pan-cancer to explore the related pathways. The Wilcoxon test was used to compare the expression difference of LAMA2 between tumor tissues and normal tissues. Kaplan-Meier method was used for survival analysis, and univariate COX regression analysis was used to evaluate the risk ratio relationship of LAMA2 in various tumors. Spearman correlation analysis was used to evaluate the correlation between the expression level of LAMA2 and tumor microenvironment immune score, as well as immune cell infiltration. Pearson correlation analysis was used to evaluate the correlation between the immunotherapy responsiveness and the expression level of LAMA2. Results:Compared with normal tissues, the expression level of LAMA2 was significantly decreased in most cancer types. In addition, the up-regulation or down-regulationand of LAMA2 expression may indicate the prognosis of patients. Univariate COX regression analysis showed that LAMA2 was significantly associated with prognosis in bladder cancer, renal papillary cell carcinoma, adrenocortical carcinoma, and so on. LAMA2 expression level was also significantly correlated with tumor microenvironment score, immune score and stromal score. Furthermore, the expression level of LAMA2 was correlated with the infiltration of tumor immune cells, including B cell, CD8 + T cell, regulatory T cell, mast cell, and so on. The results of gene set enrichment analysis show that the LAMA2 was mostly involved in the biological process of ion channels, gene expression, and skeletal muscle movement. LAMA2 expression was also associated with tumor mutation burden, microsatellite instability, and cell programmed death-ligand 1 immunotherapy responsiveness. Conclusions:LAMA2 has predictive value for survival and prognosis of patients in tumors, and is significantly correlated with tumor microenvironment, immune cell infiltration, tumor microenvironment, immunotherapy responsiveness, etc. As a potential tumor marker, LAMA2 provides a new direction for tumor prognosis judgment and treatment selection.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.

Objective To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening(microstomia)due to systemic scleroderma.Methods This study followed medical ethics,and informed consent has been obtained from patients.A case of Ken's Type Ⅰ mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression.Individual trays were made based on the patient's left and right mandibular dentition,and segmented molds were obtained.Simultaneously,intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles.After each part of the model was obtained,the man-dibular model was scanned and digitally aligned to form the final denture model,and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing(CAD/CAM)technology.At the same time,combined with the literature,the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.Results The denture was well retained and achieved a good repair ef-fect.The patients expressed satisfaction with the mastication efficiency and other functions of the denture.The findings of the literature review show that the integration of digital technology with the traditional impression method,along with computer fitting,can accurately obtain the patient's oral model and facilitate successful follow-up repairs.However,when the anterior mandibular dentition of the patient is absent,the margin of error is increased in this procedure,which deserves further exploration.Conclusion Utilizing digital technology as the leading method,combined with the tradi-tional impression method of segmental impression,for the repair of dental defects in patients with limited mouth open-ing,has proven to be effective.Thus,patients report a positive medical experience with high satisfaction,indicating that this approach is worthy of clinical promotion.