Leveraging generative hallucination and biophysics-informed modeling for unified biomolecular sequence-structure co-design

Biomolecular design underpins applications from molecular recognition to therapeutics and synthetic biology, yet de novo interaction design remains challenging-especially for DNA/RNA, underexplored non-protein modalities with scarce, heterogeneous complex data and sharper geometric and chemical constraints. We introduce MCTH (Monte Carlo Tree Hallucination), an inference-only framework that casts all-atom sequence-structure co-design as uncertainty-aware planning over hallucinated states from pretrained folding and inverse-folding models, with optional biophysical control within the same decision loop. MCTH treats these models as frozen black-box operators and uses Monte Carlo Tree Search to allocate a fixed inference budget across competing design trajectories, incorporating model confidence and uncertainty, as well as cross-expert consensus/disagreement when multiple predictors are available. Across protein-RNA, protein-DNA, protein-protein, and protein-ligand design, matched-budget experiments show that adaptive search improves over simpler sampling and cycling strategies, while held-out AlphaFold3 and Chai-1 evaluations demonstrate transfer beyond the search-time oracle. MCTH provides a shared planning layer across modalities while allowing task-specific folding, inverse-folding, and biophysical modules, requiring no fine-tuning or backpropagation through component models.

Retrieval-guided Twin Fusion with Similarity-aware Contrast for Molecule-Text Alignment

This paper studies the problem of molecule-text alignment, which aims to project molecules and their textual descriptions into a joint latent space for downstream tasks including molecule search and molecular property prediction. Previous approaches typically combine graph structure mining with contrastive learning to enhance joint representation learning. However, they typically neglect fine-grained semantic relationships between substructures and texts, leading to suboptimal performance on downstream tasks. Towards this end, we propose a novel approach named Retrieval-guided Twin Fusion with Similarity-aware Contrast (RISEN) for molecule-text alignment. The core idea of RISEN is to construct a latent twin molecule for each substructure with cross-modal retrieval for semantic enhancement. In particular, for each substructure query, we retrieve relevant textual descriptions and sample several molecules that share similar descriptions of substructures. Then, we aggregate their representations via attention pooling for a twin latent representation, which would be further fused with the original substructure for representation enrichment. In addition, we measure the similarity across substructures and texts, which would further guide cross-modal contrastive learning with soft thresholding. Extensive experiments on benchmark datasets validate the superiority of the proposed RISEN in comparison with existing baselines.

ROAD: Reciprocal-Objective Alignment of Discriminative Semantics for 3D Shape Generation

High-fidelity 3D generation predominantly relies on scaling model capacity and data, which incurs prohibitive computational costs. This paradigm typically requires learning geometry from scratch and overlooks the rich semantic and structural priors already encapsulated in discriminative 3D foundation models. We contend that leveraging the profound understanding of the 3D world possessed by these discriminative models can significantly reduce generative cost. To this end, we propose ROAD, a framework that reduces the training cost of 3D generation by transferring these rich discriminative priors into diffusion transformers. To address the inherent semantic-structural heterogeneity between generative and discriminative latents, we introduce a reciprocal-objective alignment strategy. This method synergizes Holistic Semantic Condensing to enforce global semantic coherence and Structural Optimal Alignment, which is formulated as a bipartite matching problem to rigorously align microscopic geometric details between disparate latent spaces. The 3D foundation model is only used for training-time supervision of alignment and is not used at inference, incurring no additional inference cost. Compared with the industrial baseline Step1X-3D, the proposed ROAD achieves highly competitive generation performance with only 1.5% of the training data and significantly reduces training costs, effectively reducing the computational overhead of high-fidelity 3D generation. Code is available at https://github.com/H-EmbodVis/ROAD.

Von Mises-Fisher Mixture Model with Dynamic Shrinkage for Realistic Test-Time Transduction

A range of methods aim to enhance the performance of vision-language models (VLMs) at test time. Among them, transduction has emerged as a promising paradigm due to its strong compatibility and efficiency. However, realistic evaluations often involve highly imbalanced class distributions, which cause performance degradation or even collapse. In this work, we systematically revisit transduction from the perspective of penalized likelihood estimation (PLE), showing that PLE with a KL-divergence anchor term naturally yields an adaptive shrinkage behavior between prior anchors and empirical estimates. From this viewpoint, the brittleness of transductive methods can be attributed to the absence of anchoring mechanism and static modeling of the shrinkage strength. Therefore, we propose Mixture of Von Mises-Fisher Models with Dynamic Shrinkage (MOON). MOON is built upon a mixture of von Mises-Fisher distributions to model feature representations on the unit hypersphere. To handle imbalance, MOON dynamically adjusts the shrinkage strength using zero-shot priors at both instance and class levels. Thus, it suppresses unreliable assignments and prevents harmful updates from outlier classes, thereby mitigating negative transfer. MOON is model-agnostic, training-free, and requires no task-specific hyperparameter tuning. Extensive experiments further validate the advantage of MOON in both performance and efficiency. Our code is available at https://github.com/walawalagoose/MOON

Skill-Conditioned Gated Self-Distillation for LLM Reasoning

On-policy self-distillation (SD) improves LLM reasoning by using teacher-side privileged information (PI) to turn sparse verifier outcomes into dense token-level supervision. Existing methods usually assume trusted PI, such as reference answers or successful traces. We ask whether PI can instead come from an experience-derived skill bank, where retrieved skills are compact and reusable but may also be irrelevant or misleading. We propose Skill-Conditioned Gated Self-Distillation (SGSD), which formulates skill-based SD as teacher hypothesis validation rather than unconditional imitation. SGSD retrieves skill-mistake pairs, constructs a multi-teacher pool, and lets all skill-conditioned teachers score the same plain-prompt student rollout. The verifier validates each teacher's polarity: supporting a success or suppressing a failure gives positive supervision, while the opposite stance is reversed. A robust gated objective then distills informative teacher-student disagreements while suppressing uncertain or extreme signals. Experiments on multiple mathematical reasoning benchmarks show that SGSD consistently improves over GRPO and remains competitive with answer-conditioned OPSD under a weaker PI assumption. For example, on Qwen3-1.7B, SGSD outperforms GRPO by 6.2% and OPSD by 1.7% on average on AIME24, AIME25, and HMMT25. Our code is available at https://github.com/walawalagoose/SGSD.

Computational Modeling of Antibody-Antigen Complexes: PLM-Based and MSA-Based Approaches

Antibodies play a central role in the immune response by specifically recognizing and neutralizing antigens, and therapeutic antibodies have become major drugs for cancer and autoimmune diseases. However, their discovery still relies on extensive in vitro screening, and accurate computational modeling of antibody structures and antibody-antigen interactions can prioritize candidates, reduce experimental burden, and accelerate rational design. Despite recent advances in high-accuracy protein and complex prediction, a persistent performance gap remains for antibody-related tasks compared with general protein-protein interactions, limiting downstream design. This thesis investigates why antibody-related tasks are harder and proposes improvements along two complementary directions. First, we investigate protein language model (PLM)-based methods for antibody and antibody-antigen structure prediction. Using embeddings from multiple PLMs, our approach achieves the best CDR-H3 accuracy among compared PLM-based methods on antibody monomer prediction. Extending it to complex prediction does not generalize: without co-evolutionary signals between antibody and antigen, single-sequence PLM representations do not reliably identify binding interfaces. Second, we develop two MSA-based interventions for antibody-antigen complex prediction: MSA refinement, which combines CDR-focused filtering with depth recovery from a larger sequence database, and convergence-aware recycling, which selects a stable intermediate recycle state for final diffusion sampling. Together, these interventions provide consistent gains over the AlphaFold3 baseline on a held-out antibody-antigen test set. Because the methods modify MSA construction and recycling behavior rather than model parameters, they apply without retraining or weight access.

The MiniMax-M2 Series: Mini Activations Unleashing Max Real-World Intelligence

We introduce the MiniMax-M2 series, a family of Mixture-of-Experts language models built around the principle that mini activations can unleash maximum real-world intelligence. The flagship M2 contains 229.9B total parameters with only 9.8B activated per token. Designed end-to-end for agentic deployment, the M2 series rests on three components: (i) agent-driven data pipelines producing large-scale, verifiable trajectories across agentic coding and agentic cowork, each grounded in an executable workspace and an artifact-aligned reward; (ii) Forge, a scalable agent-native RL system that adapts to long-horizon agent trajectories, paired with windowed-FIFO scheduling, prefix-tree merging, inference optimization, and a clean training-inference-agent decoupling that supports both white-box and black-box agents; (iii) the latest M2.7 checkpoint takes an early step toward self-evolution -- autonomously debugging training runs and modifying its own scaffold. Across M2 through M2.7, this combination translates a mini-activation footprint into frontier-tier performance on agentic coding, deep search, office-task, and reasoning benchmarks.

From Snapshots to Trajectories: Learning Single-Cell Gene Expression Dynamics via Conditional Flow Matching

Single-cell RNA sequencing (scRNA-seq) provides high-dimensional profiles of cellular states, enabling data-driven modeling of cellular dynamics over time. In practice, time-resolved scRNA-seq is collected at only a few discrete time points as unpaired snapshot populations, leaving substantial temporal gaps. This motivates trajectory inference at unmeasured time points. Existing methods mainly follow two directions, optimal-transport (OT) alignment provides distribution-level matching between observed snapshots, while continuous-time generative models support forecasting via learned dynamics. However, two challenges remain: (i) unpaired snapshots render local transitions between adjacent time points ambiguous, leading to unstable supervision; and (ii) long-horizon prediction relies on repeated integration, where small modeling errors compound and cause distribution drift. To address these challenges, we propose single-cell Flow Matching (scFM), a latent generative framework based on coupling-conditioned flow matching. First, we compute entropically regularized OT couplings between adjacent snapshots and use them to construct soft, weighted flow-matching targets for learning time-dependent velocity fields. Second, we learn bidirectional velocity fields and leverage their consistency to refine couplings and improve temporal coherence under sparse supervision. Third, we introduce distribution-level alignment and latent dynamic regularization to anchor long rollouts and mitigate drift. Experiments on real-world time-series scRNA-seq datasets show that scFM consistently improves distributional prediction performance for both temporal interpolation and extrapolation. Moreover, scFM yields more accurate trajectory reconstruction and temporally coherent visualizations where intermediate time points are absent, indicating a more faithful recovery of underlying temporal gene expression dynamics.

SciCustom: A Framework for Custom Evaluation of Scientific Capabilities in Large Language Models

Large language models (LLMs) are increasingly applied to scientific research, yet existing evaluations often fail to reflect the fine-grained capabilities required in practice. Most benchmarks are manually curated or domain-generic, limiting scalability and alignment with real scientific use cases. In this paper, we propose a new framework named SciCustom to address the problem. It enables the custom construction of benchmarks from large-scale scientific data to evaluate application-specific scientific capabilities in LLMs. SciCustom first organizes scientific knowledge into ontology-grounded knowledge units with controlled granularity and trains a tagger to map large-scale data instances into this knowledge space. Given a custom requirement, relevant knowledge units are identified via voting-based multi-model consensus. These units enable relevance-aware benchmark retrieval via binary search, followed by proxy subset selection and data-grounded benchmark generation for efficient evaluation. Experiments in chemistry and healthcare demonstrate that SciCustom reveals fine-grained differences in LLM scientific capabilities that standard benchmarks overlook, while requiring neither expert annotation nor synthetic question generation. This work provides a scalable and application-aware foundation for benchmarking scientific capabilities in LLMs. The source code is available at https://github.com/yjwtheonly/SciCustom.

UNSEEN: A Cross-Stack LLM Unlearning Defense against AR-LLM Social Engineering Attacks

Emerging AR-LLM-based Social Engineering attack (e.g., SEAR) is at the edge of posing great threats to real-world social life. In such AR-LLM-SE attack, the attacker can leverage AR (Augmented Reality) glass to capture the image and vocal information of the target, using the LLM to identify the target and generate the social profile, using the LLM agents to apply social engineering strategies for conversation suggestion to win the target trust and perform phishing afterwards. Current defensive approaches, such as role-based access control or data flow tracking, are not directly applicable to the convergent AR-LLM ecosystem (considering embedded AR device and opaque LLM inference), leaving an emerging and potent social engineering threat that existing privacy paradigms are ill-equipped to address. This necessitates a shift beyond solely human-centric measures like legislation and user education toward enforceable vendor policies and platform-level restrictions. Realizing this vision, however, faces significant technical challenges: securing resource-constrained AR-embedded devices, implementing fine-grained access control within opaque LLM inferences, and governing adaptive interactive agents. To address these challenges, we present UNSEEN, a coordinated cross-stack defense that combines an AR ACL (Access Control Layer) for identity-gated sensing, F-RMU-based LLM unlearning for sensitive profile suppression, and runtime agent guardrails for adaptive interaction control. We evaluate UNSEEN in an IRB-approved user study with 60 participants and a dataset of 360 annotated conversations across realistic social scenarios.