Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Aiming at the human-computer interaction problem during the movement of the rehabilitation exoskeleton robot, this paper proposes an adaptive human-computer interaction control method based on real-time monitoring of human muscle state. Considering the efficiency of patient health monitoring and rehabilitation training, a new fatigue assessment algorithm was proposed. The method fully combined the human neuromuscular model, and used the relationship between the model parameter changes and the muscle state to achieve the classification of muscle fatigue state on the premise of ensuring the accuracy of the fatigue trend. In order to ensure the safety of human-computer interaction, a variable impedance control algorithm with this algorithm as the supervision link was proposed. On the basis of not adding redundant sensors, the evaluation algorithm was used as the perceptual decision-making link of the control system to monitor the muscle state in real time and carry out the robot control of fault-tolerant mechanism decision-making, so as to achieve the purpose of improving wearing comfort and improving the efficiency of rehabilitation training. Experiments show that the proposed human-computer interaction control method is effective and universal, and has broad application prospects.
Humans ; Exoskeleton Device ; Muscle Fatigue ; Muscles ; Algorithms ; Electric Impedance

Objective To explore the value of iDose4 iterative reconstruction for coronary CT angiography (CCTA).Methods Totally 124 coronary heart disease patients underwent iDose4 iterative reconstruction and filtered back projection (FBP) reconstruction,of whom,56 ones with BMI not less than 20 kg/m2 were put into No.1 iteration group using 135 kV tube voltage and 68 ones with BMI less than 20 kg/m2 were into No.2 iteration group using 110 kV tube voltage.FBP reconstruction was executed with 110 kV tube voltage.Comparison analyses were carried out on signal noise ratio (SNR),contrast to noise ratio (CNR) and image quality.Results There were significant differences between the values of SNR,radiation dose and image quality in No.1 iteration group and FBP group (P＜0.05).Statistical differences were also found between the values of CNR and radiation dose in No.2 iteration group and FBP group,while there were no obvious differences between the values of SNR and image quality in the above two groups (P＜0.05).Conclusion Low-voltage iDose reconstruction gains advantages in radiation dose and image quality during 64-slice CCTA,and thus is worthy promoting clinically.