Structure-based drug discovery (SBDD) is a systematic scientific process that develops new drugs by leveraging the detailed physical structure of the target protein. Recent advancements in pre-trained models for biomolecules have demonstrated remarkable success across various biochemical applications, including drug discovery and protein engineering. However, in most approaches, the pre-trained models primarily focus on the characteristics of either small molecules or proteins, without delving into their binding interactions which are essential cross-domain relationships pivotal to SBDD. To fill this gap, we propose a general-purpose foundation model named BIT (an abbreviation for Biomolecular Interaction Transformer), which is capable of encoding a range of biochemical entities, including small molecules, proteins, and protein-ligand complexes, as well as various data formats, encompassing both 2D and 3D structures. Specifically, we introduce Mixture-of-Domain-Experts (MoDE) to handle the biomolecules from diverse biochemical domains and Mixture-of-Structure-Experts (MoSE) to capture positional dependencies in the molecular structures. The proposed mixture-of-experts approach enables BIT to achieve both deep fusion and domain-specific encoding, effectively capturing fine-grained molecular interactions within protein-ligand complexes. Then, we perform cross-domain pre-training on the shared Transformer backbone via several unified self-supervised denoising tasks. Experimental results on various benchmarks demonstrate that BIT achieves exceptional performance in downstream tasks, including binding affinity prediction, structure-based virtual screening, and molecular property prediction.

Information theft attacks pose a significant risk to Large Language Model (LLM) tool-learning systems. Adversaries can inject malicious commands through compromised tools, manipulating LLMs to send sensitive information to these tools, which leads to potential privacy breaches. However, existing attack approaches are black-box oriented and rely on static commands that cannot adapt flexibly to the changes in user queries and the invocation chain of tools. It makes malicious commands more likely to be detected by LLM and leads to attack failure. In this paper, we propose AutoCMD, a dynamic attack comment generation approach for information theft attacks in LLM tool-learning systems. Inspired by the concept of mimicking the familiar, AutoCMD is capable of inferring the information utilized by upstream tools in the toolchain through learning on open-source systems and reinforcement with target system examples, thereby generating more targeted commands for information theft. The evaluation results show that AutoCMD outperforms the baselines with +13.2% $ASR_{Theft}$, and can be generalized to new tool-learning systems to expose their information leakage risks. We also design four defense methods to effectively protect tool-learning systems from the attack.

Advancements in DNA sequencing technologies have significantly improved our ability to decode genomic sequences. However, the prediction and interpretation of these sequences remain challenging due to the intricate nature of genetic material. Large language models (LLMs) have introduced new opportunities for biological sequence analysis. Recent developments in genomic language models have underscored the potential of LLMs in deciphering DNA sequences. Nonetheless, existing models often face limitations in robustness and application scope, primarily due to constraints in model structure and training data scale. To address these limitations, we present GENERator, a generative genomic foundation model featuring a context length of 98k base pairs (bp) and 1.2B parameters. Trained on an expansive dataset comprising 386B bp of eukaryotic DNA, the GENERator demonstrates state-of-the-art performance across both established and newly proposed benchmarks. The model adheres to the central dogma of molecular biology, accurately generating protein-coding sequences that translate into proteins structurally analogous to known families. It also shows significant promise in sequence optimization, particularly through the prompt-responsive generation of promoter sequences with specific activity profiles. These capabilities position the GENERator as a pivotal tool for genomic research and biotechnological advancement, enhancing our ability to interpret and predict complex biological systems and enabling precise genomic interventions.

Modeling detector response is a key challenge in time projection chambers. We cast this problem as an unpaired point cloud translation task, between data collected from simulations and from experimental runs. Effective translation can assist with both noise rejection and the construction of high-fidelity simulators. Building on recent work in diffusion probabilistic models, we present a novel framework for performing this mapping. We demonstrate the success of our approach in both synthetic domains and in data sourced from the Active-Target Time Projection Chamber.

Multi-modality pre-training paradigm that aligns protein sequences and biological descriptions has learned general protein representations and achieved promising performance in various downstream applications. However, these works were still unable to replicate the extraordinary success of language-supervised visual foundation models due to the ineffective usage of aligned protein-text paired data and the lack of an effective function-informed pre-training paradigm. To address these issues, this paper curates a large-scale protein-text paired dataset called ProtAnno with a property-driven sampling strategy, and introduces a novel function-informed protein pre-training paradigm. Specifically, the sampling strategy determines selecting probability based on the sample confidence and property coverage, balancing the data quality and data quantity in face of large-scale noisy data. Furthermore, motivated by significance of the protein specific functional mechanism, the proposed paradigm explicitly model protein static and dynamic functional segments by two segment-wise pre-training objectives, injecting fine-grained information in a function-informed manner. Leveraging all these innovations, we develop ProtCLIP, a multi-modality foundation model that comprehensively represents function-aware protein embeddings. On 22 different protein benchmarks within 5 types, including protein functionality classification, mutation effect prediction, cross-modal transformation, semantic similarity inference and protein-protein interaction prediction, our ProtCLIP consistently achieves SOTA performance, with remarkable improvements of 75% on average in five cross-modal transformation benchmarks, 59.9% in GO-CC and 39.7% in GO-BP protein function prediction. The experimental results verify the extraordinary potential of ProtCLIP serving as the protein multi-modality foundation model.

Incorporating external knowledge into large language models (LLMs) has emerged as a promising approach to mitigate outdated knowledge and hallucination in LLMs. However, external knowledge is often imperfect. In addition to useful knowledge, external knowledge is rich in irrelevant or misinformation in the context that can impair the reliability of LLM responses. This paper focuses on LLMs' preferred external knowledge in imperfect contexts when handling multi-hop QA. Inspired by criminal procedural law's Chain of Evidence (CoE), we characterize that knowledge preferred by LLMs should maintain both relevance to the question and mutual support among knowledge pieces. Accordingly, we propose an automated CoE discrimination approach and explore LLMs' preferences from their effectiveness, faithfulness and robustness, as well as CoE's usability in a naive Retrieval-Augmented Generation (RAG) case. The evaluation on five LLMs reveals that CoE enhances LLMs through more accurate generation, stronger answer faithfulness, better robustness against knowledge conflict, and improved performance in a popular RAG case.

Tool-calling has changed Large Language Model (LLM) applications by integrating external tools, significantly enhancing their functionality across diverse tasks. However, this integration also introduces new security vulnerabilities, particularly in the tool scheduling mechanisms of LLM, which have not been extensively studied. To fill this gap, we present ToolCommander, a novel framework designed to exploit vulnerabilities in LLM tool-calling systems through adversarial tool injection. Our framework employs a well-designed two-stage attack strategy. Firstly, it injects malicious tools to collect user queries, then dynamically updates the injected tools based on the stolen information to enhance subsequent attacks. These stages enable ToolCommander to execute privacy theft, launch denial-of-service attacks, and even manipulate business competition by triggering unscheduled tool-calling. Notably, the ASR reaches 91.67% for privacy theft and hits 100% for denial-of-service and unscheduled tool calling in certain cases. Our work demonstrates that these vulnerabilities can lead to severe consequences beyond simple misuse of tool-calling systems, underscoring the urgent need for robust defensive strategies to secure LLM Tool-calling systems.

Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has seen significant success, the prevailing approaches, which predominantly employ a discriminative formulation, frequently encounter the error accumulation issue and often fail to capture the extensive variety of plausible sequences. To fill these gaps, we propose Bridge-IF, a generative diffusion bridge model for inverse folding, which is designed to learn the probabilistic dependency between the distributions of backbone structures and protein sequences. Specifically, we harness an expressive structure encoder to propose a discrete, informative prior derived from structures, and establish a Markov bridge to connect this prior with native sequences. During the inference stage, Bridge-IF progressively refines the prior sequence, culminating in a more plausible design. Moreover, we introduce a reparameterization perspective on Markov bridge models, from which we derive a simplified loss function that facilitates more effective training. We also modulate protein language models (PLMs) with structural conditions to precisely approximate the Markov bridge process, thereby significantly enhancing generation performance while maintaining parameter-efficient training. Extensive experiments on well-established benchmarks demonstrate that Bridge-IF predominantly surpasses existing baselines in sequence recovery and excels in the design of plausible proteins with high foldability. The code is available at https://github.com/violet-sto/Bridge-IF.

Neural code models have found widespread success in tasks pertaining to code intelligence, yet they are vulnerable to backdoor attacks, where an adversary can manipulate the victim model's behavior by inserting triggers into the source code. Recent studies indicate that advanced backdoor attacks can achieve nearly 100% attack success rates on many software engineering tasks. However, effective defense techniques against such attacks remain insufficiently explored. In this study, we propose CodePurify, a novel defense against backdoor attacks on code models through entropy-based purification. Entropy-based purification involves the process of precisely detecting and eliminating the possible triggers in the source code while preserving its semantic information. Within this process, CodePurify first develops a confidence-driven entropy-based measurement to determine whether a code snippet is poisoned and, if so, locates the triggers. Subsequently, it purifies the code by substituting the triggers with benign tokens using a masked language model. We extensively evaluate CodePurify against four advanced backdoor attacks across three representative tasks and two popular code models. The results show that CodePurify significantly outperforms four commonly used defense baselines, improving average defense performance by at least 40%, 40%, and 12% across the three tasks, respectively. These findings highlight the potential of CodePurify to serve as a robust defense against backdoor attacks on neural code models.

In this paper, we present our solutions for emotion recognition in the sub-challenges of Multimodal Emotion Recognition Challenge (MER2024). To mitigate the modal competition issue between audio and text, we adopt an early fusion strategy based on a large language model, where joint training of audio and text is conducted initially. And the joint Audio-Text modal feature will be late-fused with other unimodal features. In order to solve the problems of data insufficiency and class imbalance, We use multiple turns of multi-model voting for data mining. Moreover, to enhance the quality of audio features, we employ speech source separation to preprocess audios. Our model ranks \textbf{2nd} in both MER2024-SEMI and MER2024-NOISE, validating our method's effectiveness.