Objective To explore the efficacy and adverse events of antibody-drug conjugate(ADC)combined with PD-1 inhibitors in neoadjuvant therapy for muscle-invasive bladder cancer.Methods A retrospective study included 22 patients with bladder cancer who received neoadjuvant therapy with ADC combined with PD-1 inhibitors and gemcitabine+cisplatin(GC)regimen combined with PD-1 inhibitors in the Department of Urology,Cancer Hospital,Chinese Academy of Medical Sciences from Nov.2020 to Jan.2025.The patients were divided into the vedotinumab combined with toripalimab group and the GC combined with toripalimab group.The clinical complete response rate(cCR)of the two groups of patients was compared and analyzed,and the adverse events(AEs)that occurred during the medication period were evaluated simultaneously.Results The cCR in the vedotinmab combined with toripalimab group was higher than that in the GC combined with toripalimab group(54.5％vs.27.3％),but the difference was not statistically significant(P=0.387).In the vedotinumab combined with toripalimab group,one patient(9.1％)developed grade 3-4 AEs,presenting with peripheral sensory nerve function decline,nausea,loss of appetite and fatigue.Two patients(18.2％)in the GC combined with toripalimab group developed grade 3-4 AEs,presenting with leukopenia and nausea.Conclusion In neoadjuvant therapy for bladder cancer,ADC(vedotinumab)combined with PD-1 inhibitors(toripalimab)has better clinical complete remission and adverse events compared with the traditional GC combined with PD-1 inhibitors regimen.

Objective To explore the efficacy and adverse events of antibody-drug conjugate(ADC)combined with PD-1 inhibitors in neoadjuvant therapy for muscle-invasive bladder cancer.Methods A retrospective study included 22 patients with bladder cancer who received neoadjuvant therapy with ADC combined with PD-1 inhibitors and gemcitabine+cisplatin(GC)regimen combined with PD-1 inhibitors in the Department of Urology,Cancer Hospital,Chinese Academy of Medical Sciences from Nov.2020 to Jan.2025.The patients were divided into the vedotinumab combined with toripalimab group and the GC combined with toripalimab group.The clinical complete response rate(cCR)of the two groups of patients was compared and analyzed,and the adverse events(AEs)that occurred during the medication period were evaluated simultaneously.Results The cCR in the vedotinmab combined with toripalimab group was higher than that in the GC combined with toripalimab group(54.5％vs.27.3％),but the difference was not statistically significant(P=0.387).In the vedotinumab combined with toripalimab group,one patient(9.1％)developed grade 3-4 AEs,presenting with peripheral sensory nerve function decline,nausea,loss of appetite and fatigue.Two patients(18.2％)in the GC combined with toripalimab group developed grade 3-4 AEs,presenting with leukopenia and nausea.Conclusion In neoadjuvant therapy for bladder cancer,ADC(vedotinumab)combined with PD-1 inhibitors(toripalimab)has better clinical complete remission and adverse events compared with the traditional GC combined with PD-1 inhibitors regimen.

The structures and activities of enzymes are influenced by pH of the environment. Understanding and distinguishing the adaptation mechanisms of enzymes to extreme pH values is of great significance for elucidating the molecular mechanisms and promoting the industrial applications of enzymes. In this study, the ESM-2 protein language model was used to encode the secreted microbial proteins with the optimal performance above pH 9 and below pH 5, which yielded 47 725 high-pH protein sequences and 66 079 low-pH protein sequences, respectively. A deep learning model was constructed to identify protein acid-base tolerance based on amino acid sequences. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 94.8%, precision of 91.8%, and a recall rate of 93.4% on the test set. Furthermore, we built a website (https://enzymepred.biodesign.ac.cn), which enabled users to predict the acid-base tolerance by submitting the protein sequences of enzymes. This study has accelerated the application of enzymes in various fields, including biotechnology, pharmaceuticals, and chemicals. It provides a powerful tool for the rapid screening and optimization of industrial enzymes.
Deep Learning ; Hydrogen-Ion Concentration ; Amino Acid Sequence ; Enzymes/metabolism* ; Sequence Analysis, Protein ; Proteins/metabolism* ; Bacterial Proteins/metabolism*