Genre
EnzyControl: Adding Functional and Substrate-Specific Control for Enzyme Backbone Generation
Designing enzyme backbones with substrate-specific functionality is a critical challenge in computational protein engineering. Current generative models excel in protein design but face limitations in binding data, substrate-specific control, and flexibility for de novo enzyme backbone generation. To address this, we introduce EnzyBind, a dataset with 11,100 experimentally validated enzyme-substrate pairs specifically curated from PDBbind. Building on this, we propose EnzyControl, a method that enables functional and substrate-specific control in enzyme backbone generation. Our approach generates enzyme backbones conditioned on MSAannotated catalytic sites and their corresponding substrates, which are automatically extracted from curated enzyme-substrate data. At the core of EnzyControl is EnzyAdapter, a lightweight, modular component integrated into a pretrained motifscaffolding model, allowing it to become substrate-aware. A two-stage training paradigm further refines the model's ability to generate accurate and functional enzyme structures. Experiments show that our EnzyControl achieves the best performance across structural and functional metrics on EnzyBind and EnzyBench benchmarks, with particularly notable improvements of 13% in designability and 13% in catalytic efficiency compared to the baseline models.
Beyond Chemical QA: Evaluating LLM's Chemical Reasoning with Modular Chemical Operations
While large language models (LLMs) with Chain-of-Thought (CoT) reasoning excel in mathematics and coding, their potential for systematic reasoning in chemistry, a domain demanding rigorous structural analysis for real-world tasks like drug design and reaction engineering, remains untapped. Current benchmarks focus on simple knowledge retrieval, neglecting step-by-step reasoning required for complex tasks such as molecular optimization and reaction prediction. To address this, we introduce ChemCoTBench, a reasoning framework that bridges molecular structure understanding with arithmetic-inspired operations, including addition, deletion, and substitution, to formalize chemical problem-solving into transparent, step-by-step workflows. By treating molecular transformations as modular "chemical operations", the framework enables slow-thinking reasoning, mirroring the logic of mathematical proofs while grounding solutions in real-world chemical constraints. We evaluate models on two high-impact tasks: Molecular Property Optimization and Chemical Reaction Prediction. These tasks mirror real-world challenges while providing structured evaluability. We further provide ChemCoTDataset, a pioneering 22,000-instance chemical reasoning dataset with expert-annotated chains of thought to facilitate LLM fine-tuning.
ForgerySleuth: Empowering Multimodal Large Language Models for Image Manipulation Detection
Multimodal large language models have unlocked new possibilities for various multimodal tasks. However, their potential in image manipulation detection remains unexplored. When directly applied to the IMD task, M-LLMs often produce reasoning texts that suffer from hallucinations and overthinking. To address this, we propose ForgerySleuth, which leverages M-LLMs to perform comprehensive clue fusion and generate segmentation outputs indicating specific regions that are tampered with. Moreover, we construct the ForgeryAnalysis dataset through the Chain-of-Clues prompt, which includes analysis and reasoning text to upgrade the image manipulation detection task. A data engine is also introduced to build a largerscale dataset for the pre-training phase. Our extensive experiments demonstrate the effectiveness of ForgeryAnalysis and show that ForgerySleuth significantly outperforms existing methods in generalization, robustness, and explainability.
PRIMT: Preference-based Reinforcement Learning with Multimodal Feedback and Trajectory Synthesis from Foundation Models
Preference-based reinforcement learning (PbRL) has emerged as a promising paradigm for teaching robots complex behaviors without reward engineering. However, its effectiveness is often limited by two critical challenges: the reliance on extensive human input and the inherent difficulties in resolving query ambiguity and credit assignment during reward learning. In this paper, we introduce PRIMT, a PbRL framework designed to overcome these challenges by leveraging foundation models (FMs) for multimodal synthetic feedback and trajectory synthesis. Unlike prior approaches that rely on single-modality FM evaluations, PRIMT employs a hierarchical neuro-symbolic fusion strategy, integrating the complementary strengths of large language models and vision-language models in evaluating robot behaviors for more reliable and comprehensive feedback. PRIMT also incorporates foresight trajectory generation, which reduces early-stage query ambiguity by warm-starting the trajectory buffer with bootstrapped samples, and hindsight trajectory augmentation, which enables counterfactual reasoning with a causal auxiliary loss to improve credit assignment. We evaluate PRIMT on 2 locomotion and 6 manipulation tasks on various benchmarks, demonstrating superior performance over FM-based and scripted baselines.
Shortcutting Pre-trained Flow Matching Diffusion Models is Almost Free Lunch
We present an ultra-efficient post-training method for shortcutting large-scale pretrained flow matching diffusion models into efficient few-step samplers, enabled by novel velocity field self-distillation. While shortcutting in flow matching, originally introduced by shortcut models, offers flexible trajectory-skipping capabilities, it requires a specialized step-size embedding incompatible with existing models unless retraining from scratch--a process nearly as costly as pretraining itself. Our key contribution is thus imparting a more aggressive shortcut mechanism to standard flow matching models (e.g., Flux), leveraging a unique distillation principle that obviates the need for step-size embedding.
FLOWING: Implicit Neural Flows for Structure-Preserving Morphing
Morphing is a long-standing problem in vision and computer graphics, requiring a time-dependent warping for feature alignment and a blending for smooth interpolation. Recently, multilayer perceptrons (MLPs) have been explored as implicit neural representations (INRs) for modeling such deformations, due to their meshlessness and differentiability; however, extracting coherent and accurate morphings from standard MLPs typically relies on costly regularizations, which often lead to unstable training and prevent effective feature alignment. To overcome these limitations, we propose FLOWING (FLOW morphING), a framework that recasts warping as the construction of a differential vector flow, naturally ensuring continuity, invertibility, and temporal coherence by encoding structural flow properties directly into the network architectures.
SPICED: ASynaptic Homeostasis-Inspired Framework for Unsupervised Continual EEG Decoding
Human brain achieves dynamic stability-plasticity balance through synaptic homeostasis, a self-regulatory mechanism that stabilizes critical memory traces while preserving optimal learning capacities. Inspired by this biological principle, we propose SPICED: a neuromorphic framework that integrates the synaptic homeostasis mechanism for unsupervised continual EEG decoding, particularly addressing practical scenarios where new individuals with inter-individual variability emerge continually. SPICED comprises a novel synaptic network that enables dynamic expansion during continual adaptation through three bio-inspired neural mechanisms: (1) critical memory reactivation, which mimics brain functional specificity, selectively activates task-relevant memories to facilitate adaptation; (2) synaptic consolidation, which strengthens these reactivated critical memory traces and enhances their replay prioritizations for further adaptations and (3) synaptic renormalization, which are periodically triggered to weaken global memory traces to preserve learning capacities. The interplay within synaptic homeostasis dynamically strengthens task-discriminative memory traces and weakens detrimental memories.
Training-Free Test-Time Adaptation via Shape and Style Guidance for Vision-Language Models
Test-time adaptation with pre-trained vision-language models shows impressive zero-shot classification abilities, and training-free methods further improve the performance without any optimization burden. However, existing training-free test-time adaptation methods typically rely on entropy criteria to select the visual features and update the visual caches, while ignoring the generalizable factors, such as shape-sensitive and style-insensitive factors. In this paper, we propose a novel shape and style guidance method (SSG) for training-free test-time adaptation in vision-language models, aiming to highlight the shape-sensitive (SHS) and styleinsensitive (STI) factors. Specifically, SSG perturbs the raw test image with shape and style corruption operations, and measures the prediction difference between the raw and corrupted ones as perturbed prediction difference (PPD). Based on the PPD measurement, SSG reweights the high-confidence visual features and corresponding predictions, aiming to highlight the effect of SHS and STI factors during the test-time procedure. Furthermore, SSG takes both PPD and entropy into consideration to update the visual cache, aiming to maintain the stored sample with high entropy and generalizable factors. Extensive experimental results on out-of-distribution and cross-domain benchmark datasets demonstrate that our proposed SSG consistently outperforms previous state-of-the-art methods while also exhibiting promising computational efficiency.
Offline Actor-Critic for Average Reward MDPs
We study offline policy optimization for infinite-horizon average-reward Markov decision processes (MDPs) with large or infinite state spaces. Specifically, we propose a pessimistic version of actor-critic methods using a computationally efficient linear function class for value function estimation. At the core of our method is a critic that computes a pessimistic estimate of the average reward under the current policy, as well as the corresponding policy gradient, by solving a fixedpoint Bellman equation, rather than solving a successive sequence of regression problems as in finite horizon settings. Due to the nature of our policy-based method, the critic only needs to solve a linear optimization problem with convex quadratic constraints. We show that a very mild data coverage requirement is sufficient for our algorithm to achieve O(ε 2) sample complexity for learning a near-optimal policy up to model misspecification errors. To our knowledge, this is the first result with optimal εdependence in the offline average reward setting.