Predicting the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small molecules remains a major challenge in drug discovery. Here, we present MEGA-CL, a foundation graph neural network framework for universal molecular ADMET prediction. MEGA-CL integrates self-supervised contrastive learning with a multi-head external attention mechanism and an enhanced message-passing architecture, enabling simultaneous modeling of local chemical substructures and global inter-graph relationships while mitigating over-smoothing effects commonly observed in deep graph networks. Across 13 benchmark datasets and 21 downstream ADMET tasks, MEGA-CL consistently outperforms state-of-the-art baseline models. In particular, the framework demonstrates robust performance on challenging regression tasks, including clearance (CL) and steady-state volume of distribution (VDss), while maintaining strong generalization ability in independent external validation. Clinically relevant predictive accuracy was achieved, with more than 75% of predictions falling within a 3-fold error range. In an external evaluation on 18 novel compounds derived from recently approved FDA drugs, over 50% of human liver microsome clearance (HLMC) predictions were within a 2-fold error range. To further assess its practical applicability, MEGA-CL was prospectively evaluated on three preclinical drug candidates using in vitro hepatic microsomal metabolism assays and CYP450 inhibition assays guided by model predictions. The predicted HLMC values for all candidates were within 2.5-fold of the experimentally measured values, and 73.3% of CYP450 inhibition endpoints (11/15) were correctly classified. These results demonstrate the potential of MEGA-CL as a generalizable framework for accelerating in silico ADMET evaluation and early-stage drug candidate optimization.
Multivariate time series forecasting plays a pivotal role in numerous real-world applications, including financial analysis, energy management, and traffic planning. While Transformer-based architectures have gained popularity for this task, recent studies reveal that simpler MLP-based models can achieve competitive or superior performance with significantly reduced computational cost. In this paper, we propose ITS-Mina, a novel all-MLP framework for multivariate time series forecasting that integrates three key innovations: (1) an iterative refinement mechanism that progressively enhances temporal representations by repeatedly applying a shared-parameter residual mixer stack, effectively deepening the model's computational capacity without multiplying the number of distinct parameters; (2) an external attention module that replaces traditional self-attention with learnable memory units, capturing cross-sample global dependencies at linear computational complexity; and (3) a Harris Hawks Optimization (HHO) algorithm for automatic dropout rate tuning, enabling adaptive regularization tailored to each dataset. Extensive experiments on six widely-used benchmark datasets demonstrate that ITS-Mina achieves state-of-the-art or highly competitive performance compared to eleven baseline models across multiple forecasting horizons.