Simulation-to-real transfer learning for infrared spectroscopic chemical sensing and analysis from molecules to complex samples

Infrared (IR) spectroscopy is widely used for chemical sensing, but extracting reliable chemical information from spectra remains challenging. Conventional interpretation is labor-intensive, relies on prior knowledge and reference spectra, and is difficult to scale, whereas most machine-learning methods are tailored to individual tasks or datasets, require large labeled training sets, and transfer poorly across analytical objectives and experimental datasets. Here we introduce UltraIR, a foundation model for IR spectroscopy with more than 100 million parameters that enables simulation-to-real transfer learning for chemical sensing and analysis from molecules to complex samples. UltraIR is pretrained on approximately 60 million simulated IR spectra using spectral reconstruction, molecular fingerprint similarity alignment, and functional-group prediction, then adapted to downstream objectives with task-specific labels or targets. Across functional-group prediction, molecular structure elucidation, physicochemical property prediction, mixture-component identification and quantification, bacterial classification, medicinal-herb geographic origin traceability and constituent quantification, microplastics classification, and soil property prediction, UltraIR outperforms conventional machine-learning and task-specific deep-learning baselines. It performs strongly with limited labeled experimental spectra and in zero-shot inference for the same analytical task across Fourier-transform infrared spectrometers and laboratories, providing a route to adaptable, data-efficient chemical sensing from complex real-world samples.

scMIR: a vision-language foundation model for single-cell light microscopy image representation

Single-cell light microscopy images have become an important data source for characterizing cell phenotypes, but their complexity and heterogeneity pose challenges to high-throughput automated analysis. Existing representation learning methods mostly rely on task-oriented modeling, which is limited by specific datasets and predefined tasks, making them difficult to generalize across different cell types and microscopy modalities, and experimental conditions. Although general-purpose methods have improved the generalization ability of image representation in recent years, their limited utilization of experimental background and biological context information still poses challenges in complex phenotypic analysis. Here, we propose scMIR, a vision-language foundation model for single-cell light microscopy image representation. By synergistically combining self-supervised image reconstruction with text-guided cross-modal alignment, scMIR can simultaneously encode morphological and biological semantic information in a unified representation space. scMIR is pre-trained on 207,957 image-text pairs, covering various cell types, microscopy modalities, and perturbation conditions. scMIR outperforms existing general models and task-oriented methods as systematically evaluated on various complex tasks using 16 benchmark datasets, including cell classification, clustering, phenotype inference, and batch effect correction tasks. Furthermore, scMIR shows a strong generalization ability across various tasks without requiring task-specific fine-tuning. With its unique advantages, we envision scMIR may promote the standardization and automation of high-throughput phenotyping workflows through supporting various downstream analysis tasks.

A large-scale foundation model enables simulation-to-real adaptation for nuclear magnetic resonance-based molecular structure analysis

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for molecular structure analysis, and spectral artificial intelligence offers great potential for its rapid and automated interpretation. However, the scarcity of experimental NMR datasets has constrained deep learning in this domain to narrow, task-specific applications that lack broad generalization. Here, we introduce UltraNMR, a large-scale foundation model for NMR that leverages the intrinsic properties of NMR spectra to learn generalizable spectral representations. We collected 158 million paired simulated $^{1}$H and $^{13}$C NMR spectra to train UltraNMR, employing multiple domain-specific pre-training objectives. UltraNMR captures both intra-spectral and inter-spectral dependencies, enabling seamless simulation-to-real adaptation. We demonstrate that adapting UltraNMR to a range of molecular structure analysis tasks on experimental NMR spectra consistently yields state-of-the-art performance and clearly outperforms UltraNMR variants trained directly on downstream data without simulation pre-training. We also construct a large-scale NMR spectral vector library by encoding simulated NMR spectra using UltraNMR, covering 94 million unique molecules and enabling effective structure-aware retrieval. In real-world applications, UltraNMR facilitates the structural elucidation of two previously unknown natural products from Chinese herbal medicines recorded in the Chinese Pharmacopoeia. These results suggest that large-scale simulation pre-training can effectively bridge the simulation-to-real gap, enabling robust and generalizable molecular structure analysis of real-world NMR spectra.

CryoProt: A Protein Pretraining Framework with Cross-Box Interactions on Cryo-EM Density Maps

Despite the growing availability of cryo-electron microscopy (cryo-EM) density maps, effectively leveraging them for protein representation remains challenging. First, current methods lack a general-purpose protein pretraining framework tailored for cryo-EM density maps, designed for protein-related property prediction. Second, existing approaches typically partition density maps into local box regions and model them independently, overlooking interactions across boxes which are essential for capturing global structural context in cryo-EM density map. To address these challenges, we propose CryoProt, a protein pretraining framework designed for cryo-EM density maps. CryoProt introduces a Map Encoder based on multi-head latent attention (MLA), where box-level representations interact through a shared latent space, enabling explicit modeling of cross-box dependencies within the density map. Furthermore, we adopt a multi-task pretraining strategy to learn generalizable representations that can be effectively transferred to diverse downstream tasks, such as protein flexibility prediction, where cryo-EM density maps are not required and can be inferred implicitly by the pretrained model. Experimental results demonstrate that CryoProt consistently outperforms existing state-of-the-art methods across multiple benchmarks, achieving up to 12% improvement over the best-performing baselines, highlighting the importance of modeling cross-box interactions in cryo-EM data. The source code is publicly available at https://anonymous.4open.science/r/CryoProt.

CaptchaMind: Training CAPTCHA Solvers via Reinforcement Learning with Explicit Reasoning Supervision

CAPTCHAs are widely deployed as human verification mechanisms and frequently block intelligent agents from completing end-to-end automation in real-world web environments. Solving modern CAPTCHAs requires robust multi-step visual reasoning and interaction capabilities, yet training-based approaches have remained absent due to the lack of large-scale training data and process-level annotations. We introduce CaptchaBench, the first CAPTCHA benchmark designed to support large-scale training, comprising 16,000 programmatically generated samples across eight task categories with detailed region and process-level annotations. Systematic evaluation on CaptchaBench reveals that existing methods fail consistently on tasks requiring fine-grained visual detail capture and region-level comparison. We therefore present CaptchaMind, an RL-based solver trained with explicit reasoning process supervision, achieving 82.9% average success rate across eight tasks and 71.0% on real-world instances, substantially outperforming all existing methods without closed-source APIs.

Sparse Task Vector Mixup with Hypernetworks for Efficient Knowledge Transfer in Whole-Slide Image Prognosis

Whole-Slide Images (WSIs) are widely used for estimating the prognosis of cancer patients. Current studies generally follow a cancer-specific learning paradigm. However, the available training samples for one cancer type are usually scarce in pathology. Consequently, the model often struggles to learn generalizable knowledge, thus performing worse on the tumor samples with inherent high heterogeneity. Although multi-cancer joint learning and knowledge transfer approaches have been explored recently to address it, they either rely on large-scale joint training or extensive inference across multiple models, posing new challenges in computational efficiency. To this end, this paper proposes a new scheme, Sparse Task Vector Mixup with Hypernetworks (STEPH). Unlike previous ones, it efficiently absorbs generalizable knowledge from other cancers for the target via model merging: i) applying task vector mixup to each source-target pair and then ii) sparsely aggregating task vector mixtures to obtain an improved target model, driven by hypernetworks. Extensive experiments on 13 cancer datasets show that STEPH improves over cancer-specific learning and an existing knowledge transfer baseline by 5.14% and 2.01%, respectively. Moreover, it is a more efficient solution for learning prognostic knowledge from other cancers, without requiring large-scale joint training or extensive multi-model inference. Code is publicly available at https://github.com/liupei101/STEPH.

LatentChem: From Textual CoT to Latent Thinking in Chemical Reasoning

Chemical large language models (LLMs) predominantly rely on explicit Chain-of-Thought (CoT) in natural language to perform complex reasoning. However, chemical reasoning is inherently continuous and structural, and forcing it into discrete linguistic tokens introduces a fundamental representation mismatch that constrains both efficiency and performance. We introduce LatentChem, a latent reasoning interface that decouples chemical computation from textual generation, enabling models to perform multi-step reasoning directly in continuous latent space while emitting language only for final outputs. Remarkably, we observe a consistent emergent behavior: when optimized solely for task success, models spontaneously internalize reasoning, progressively abandoning verbose textual derivations in favor of implicit latent computation. This shift is not merely stylistic but computationally advantageous. Across diverse chemical reasoning benchmarks, LatentChem achieves a 59.88\% non-tie win rate over strong CoT-based baselines on ChemCoTBench, while delivering a 10.84$\times$ average inference speedup. Our results provide empirical evidence that chemical reasoning is more naturally and effectively realized as continuous latent dynamics rather than discretized linguistic trajectories.

Rethinking Genomic Modeling Through Optical Character Recognition

Recent genomic foundation models largely adopt large language model architectures that treat DNA as a one-dimensional token sequence. However, exhaustive sequential reading is structurally misaligned with sparse and discontinuous genomic semantics, leading to wasted computation on low-information background and preventing understanding-driven compression for long contexts. Here, we present OpticalDNA, a vision-based framework that reframes genomic modeling as Optical Character Recognition (OCR)-style document understanding. OpticalDNA renders DNA into structured visual layouts and trains an OCR-capable vision--language model with a \emph{visual DNA encoder} and a \emph{document decoder}, where the encoder produces compact, reconstructible visual tokens for high-fidelity compression. Building on this representation, OpticalDNA defines prompt-conditioned objectives over core genomic primitives-reading, region grounding, subsequence retrieval, and masked span completion-thereby learning layout-aware DNA representations that retain fine-grained genomic information under a reduced effective token budget. Across diverse genomic benchmarks, OpticalDNA consistently outperforms recent baselines; on sequences up to 450k bases, it achieves the best overall performance with nearly $20\times$ fewer effective tokens, and surpasses models with up to $985\times$ more activated parameters while tuning only 256k \emph{trainable} parameters.

Surface-based Molecular Design with Multi-modal Flow Matching

Therapeutic peptides show promise in targeting previously undruggable binding sites, with recent advancements in deep generative models enabling full-atom peptide co-design for specific protein receptors. However, the critical role of molecular surfaces in protein-protein interactions (PPIs) has been underexplored. To bridge this gap, we propose an omni-design peptides generation paradigm, called SurfFlow, a novel surface-based generative algorithm that enables comprehensive co-design of sequence, structure, and surface for peptides. SurfFlow employs a multi-modality conditional flow matching (CFM) architecture to learn distributions of surface geometries and biochemical properties, enhancing peptide binding accuracy. Evaluated on the comprehensive PepMerge benchmark, SurfFlow consistently outperforms full-atom baselines across all metrics. These results highlight the advantages of considering molecular surfaces in de novo peptide discovery and demonstrate the potential of integrating multiple protein modalities for more effective therapeutic peptide discovery.

DeepDR: an integrated deep-learning model web server for drug repositioning

Background: Identifying new indications for approved drugs is a complex and time-consuming process that requires extensive knowledge of pharmacology, clinical data, and advanced computational methods. Recently, deep learning (DL) methods have shown their capability for the accurate prediction of drug repositioning. However, implementing DL-based modeling requires in-depth domain knowledge and proficient programming skills. Results: In this application, we introduce DeepDR, the first integrated platform that combines a variety of established DL-based models for disease- and target-specific drug repositioning tasks. DeepDR leverages invaluable experience to recommend candidate drugs, which covers more than 15 networks and a comprehensive knowledge graph that includes 5.9 million edges across 107 types of relationships connecting drugs, diseases, proteins/genes, pathways, and expression from six existing databases and a large scientific corpus of 24 million PubMed publications. Additionally, the recommended results include detailed descriptions of the recommended drugs and visualize key patterns with interpretability through a knowledge graph. Conclusion: DeepDR is free and open to all users without the requirement of registration. We believe it can provide an easy-to-use, systematic, highly accurate, and computationally automated platform for both experimental and computational scientists.