Hansen Chen

Yao Pu, Yiming Shi, Zhenxi Zhang et al.

Magnetic resonance imaging (MRI) is essential for nasopharyngeal carcinoma (NPC) radiotherapy (RT), but practical constraints, such as patient discomfort, long scan times, and high costs often lead to incomplete modalities in clinical practice, compromising RT planning accuracy. Traditional MRI synthesis methods are modality-specific, limited in anatomical adaptability, and lack clinical interpretability-failing to meet NPC's RT needs. Here, we developed a unified foundation model integrating contrastive visual representation learning and vision-language alignment (VLA) to enable any-to-all MRI synthesis. The model uses a contrastive encoder for modality-invariant representations and a CLIP-based text-informed decoder for semantically consistent synthesis, supporting any-to-all MRI synthesis via one unified foundation model. Trained on 40,825 images from 13 institutions, it achieves consistently high performance (average SSIM 0.90, PSNR 27) across 26 internal/external validation sites (15,748 images), with superior synthesis fidelity and robustness to noise and domain shifts. Meanwhile, its unified representation enhances downstream RT-relevant tasks (e.g., segmentation). This work advances digital medicine solutions for NPC care by leveraging foundation models to bridge technical synthesis and clinical utility.

Jing Lan, Hexiao Ding, Hongzhao Chen et al.

Accurate identification of drug-target interactions (DTI) remains a central challenge in computational pharmacology, where sequence-based methods offer scalability. This work introduces a sequence-based drug-target interaction framework that integrates structural priors into protein representations while maintaining high-throughput screening capability. Evaluated across multiple benchmarks, the model achieves state-of-the-art performance on Human and BioSNAP datasets and remains competitive on BindingDB. In virtual screening tasks, it surpasses prior methods on LIT-PCBA, yielding substantial gains in AUROC and BEDROC. Ablation studies confirm the critical role of learned aggregation, bilinear attention, and contrastive alignment in enhancing predictive robustness. Embedding visualizations reveal improved spatial correspondence with known binding pockets and highlight interpretable attention patterns over ligand-residue contacts. These results validate the framework's utility for scalable and structure-aware DTI prediction.

Jing Lan, Hexiao Ding, Hongzhao Chen et al.

Accurate prediction of protein-ligand interactions is essential for computer-aided drug discovery. However, existing methods often fail to capture solvent-dependent conformational changes and lack the ability to jointly learn multiple related tasks. To address these limitations, we introduce a pre-training method that incorporates ligand conformational ensembles generated under diverse solvent conditions as augmented input. This design enables the model to learn both structural flexibility and environmental context in a unified manner. The training process integrates molecular reconstruction to capture local geometry, interatomic distance prediction to model spatial relationships, and contrastive learning to build solvent-invariant molecular representations. Together, these components lead to significant improvements, including a 3.7% gain in binding affinity prediction, an 82% success rate on the PoseBusters Astex docking benchmarks, and an area under the curve of 97.1% in virtual screening. The framework supports solvent-aware, multi-task modeling and produces consistent results across benchmarks. A case study further demonstrates sub-angstrom docking accuracy with a root-mean-square deviation of 0.157 angstroms, offering atomic-level insight into binding mechanisms and advancing structure-based drug design.

Yujia Ding, Qidi Peng, Zhengming Song et al.

We introduce the arbitrary rectangle-range generalized elastic net penalty method, abbreviated to ARGEN, for performing constrained variable selection and regularization in high-dimensional sparse linear models. As a natural extension of the nonnegative elastic net penalty method, ARGEN is proved to have variable selection consistency and estimation consistency under some conditions. The asymptotic behavior in distribution of the ARGEN estimators have been studied. We also propose an algorithm called MU-QP-RR-W-$l_1$ to efficiently solve ARGEN. By conducting simulation study we show that ARGEN outperforms the elastic net in a number of settings. Finally an application of S&P 500 index tracking with constraints on the stock allocations is performed to provide general guidance for adapting ARGEN to solve real-world problems.