Multiscale Cross-Modal Mapping of Molecular, Pathologic, and Radiologic Phenotypes in Lipid-Deficient Clear Cell Renal CellCarcinoma

Clear cell renal cell carcinoma (ccRCC) exhibits extensive intratumoral heterogeneity on multiple biological scales, contributing to variable clinical outcomes and limiting the effectiveness of conventional TNM staging, which highlights the urgent need for multiscale integrative analytic frameworks. The lipid-deficient de-clear cell differentiated (DCCD) ccRCC subtype, defined by multi-omics analyses, is associated with adverse outcomes even in early-stage disease. Here, we establish a hierarchical cross-scale framework for the preoperative identification of DCCD-ccRCC. At the highest layer, cross-modal mapping transferred molecular signatures to histological and CT phenotypes, establishing a molecular-to-pathology-to-radiology supervisory bridge. Within this framework, each modality-specific model is designed to mirror the inherent hierarchical structure of tumor biology. PathoDCCD captured multi-scale microscopic features, from cellular morphology and tissue architecture to meso-regional organization. RadioDCCD integrated complementary macroscopic information by combining whole-tumor and its habitat-subregions radiomics with a 2D maximal-section heterogeneity metric. These nested models enabled integrated molecular subtype prediction and clinical risk stratification. Across five cohorts totaling 1,659 patients, PathoDCCD reliably recapitulated molecular subtypes, while RadioDCCD provided reliable preoperative prediction. The consistent predictions identified patients with the poorest clinical outcomes. This cross-scale paradigm unifies molecular biology, computational pathology, and quantitative radiology into a biologically grounded strategy for preoperative noninvasive molecular phenotyping of ccRCC.

Thinker: Training LLMs in Hierarchical Thinking for Deep Search via Multi-Turn Interaction

Efficient retrieval of external knowledge bases and web pages is crucial for enhancing the reasoning abilities of LLMs. Previous works on training LLMs to leverage external retrievers for solving complex problems have predominantly employed end-to-end reinforcement learning. However, these approaches neglect supervision over the reasoning process, making it difficult to guarantee logical coherence and rigor. To address these limitations, we propose Thinker, a hierarchical thinking model for deep search through multi-turn interaction, making the reasoning process supervisable and verifiable. It decomposes complex problems into independently solvable sub-problems, each dually represented in both natural language and an equivalent logical function to support knowledge base and web searches. Concurrently, dependencies between sub-problems are passed as parameters via these logical functions, enhancing the logical coherence of the problem-solving process. To avoid unnecessary external searches, we perform knowledge boundary determination to check if a sub-problem is within the LLM's intrinsic knowledge, allowing it to answer directly. Experimental results indicate that with as few as several hundred training samples, the performance of Thinker is competitive with established baselines. Furthermore, when scaled to the full training set, Thinker significantly outperforms these methods across various datasets and model sizes. The source code is available at https://github.com/OpenSPG/KAG-Thinker.

DualSG: A Dual-Stream Explicit Semantic-Guided Multivariate Time Series Forecasting Framework

Multivariate Time Series Forecasting plays a key role in many applications. Recent works have explored using Large Language Models for MTSF to take advantage of their reasoning abilities. However, many methods treat LLMs as end-to-end forecasters, which often leads to a loss of numerical precision and forces LLMs to handle patterns beyond their intended design. Alternatively, methods that attempt to align textual and time series modalities within latent space frequently encounter alignment difficulty. In this paper, we propose to treat LLMs not as standalone forecasters, but as semantic guidance modules within a dual-stream framework. We propose DualSG, a dual-stream framework that provides explicit semantic guidance, where LLMs act as Semantic Guides to refine rather than replace traditional predictions. As part of DualSG, we introduce Time Series Caption, an explicit prompt format that summarizes trend patterns in natural language and provides interpretable context for LLMs, rather than relying on implicit alignment between text and time series in the latent space. We also design a caption-guided fusion module that explicitly models inter-variable relationships while reducing noise and computation. Experiments on real-world datasets from diverse domains show that DualSG consistently outperforms 15 state-of-the-art baselines, demonstrating the value of explicitly combining numerical forecasting with semantic guidance.

Test-Time Scaling with Reflective Generative Model

We introduce our first reflective generative model MetaStone-S1, which obtains OpenAI o3's performance via the self-supervised process reward model (SPRM). Through sharing the backbone network and using task-specific heads for next token prediction and process scoring respectively, SPRM successfully integrates the policy model and process reward model(PRM) into a unified interface without extra process annotation, reducing over 99% PRM parameters for efficient reasoning. Equipped with SPRM, MetaStone-S1 is naturally suitable for test time scaling (TTS), and we provide three reasoning effort modes (low, medium, and high), based on the controllable thinking length. Moreover, we empirically establish a scaling law that reveals the relationship between total thinking computation and TTS performance. Experiments demonstrate that our MetaStone-S1 achieves comparable performance to OpenAI-o3-mini's series with only 32B parameter size. To support the research community, we have open-sourced MetaStone-S1 at https://github.com/MetaStone-AI/MetaStone-S1.

DeepResearch Bench: A Comprehensive Benchmark for Deep Research Agents

Deep Research Agents are a prominent category of LLM-based agents. By autonomously orchestrating multistep web exploration, targeted retrieval, and higher-order synthesis, they transform vast amounts of online information into analyst-grade, citation-rich reports--compressing hours of manual desk research into minutes. However, a comprehensive benchmark for systematically evaluating the capabilities of these agents remains absent. To bridge this gap, we present DeepResearch Bench, a benchmark consisting of 100 PhD-level research tasks, each meticulously crafted by domain experts across 22 distinct fields. Evaluating DRAs is inherently complex and labor-intensive. We therefore propose two novel methodologies that achieve strong alignment with human judgment. The first is a reference-based method with adaptive criteria to assess the quality of generated research reports. The other framework is introduced to evaluate DRA's information retrieval and collection capabilities by assessing its effective citation count and overall citation accuracy. We have open-sourced DeepResearch Bench and key components of these frameworks at https://github.com/Ayanami0730/deep_research_bench to accelerate the development of practical LLM-based agents.

Graph Neural Networks in Modern AI-aided Drug Discovery

Graph neural networks (GNNs), as topology/structure-aware models within deep learning, have emerged as powerful tools for AI-aided drug discovery (AIDD). By directly operating on molecular graphs, GNNs offer an intuitive and expressive framework for learning the complex topological and geometric features of drug-like molecules, cementing their role in modern molecular modeling. This review provides a comprehensive overview of the methodological foundations and representative applications of GNNs in drug discovery, spanning tasks such as molecular property prediction, virtual screening, molecular generation, biomedical knowledge graph construction, and synthesis planning. Particular attention is given to recent methodological advances, including geometric GNNs, interpretable models, uncertainty quantification, scalable graph architectures, and graph generative frameworks. We also discuss how these models integrate with modern deep learning approaches, such as self-supervised learning, multi-task learning, meta-learning and pre-training. Throughout this review, we highlight the practical challenges and methodological bottlenecks encountered when applying GNNs to real-world drug discovery pipelines, and conclude with a discussion on future directions.

From Real to Synthetic: Synthesizing Millions of Diversified and Complicated User Instructions with Attributed Grounding

The pursuit of diverse, complex, and large-scale instruction data is crucial for automatically aligning large language models (LLMs). While there are methods capable of generating synthetic instructions at scale, they either suffer from limited grounding sources, leading to a narrow distribution, or rely on trivial extensions that fail to produce meaningful trajectories in terms of complexity. In contrast, instructions that benefit efficient alignment are typically crafted with cognitive insights and grounded in real-world use cases. In this paper, we synthesize such instructions using attributed grounding, which involves 1) a top-down attribution process that grounds a selective set of real instructions to situated users, and 2) a bottom-up synthesis process that leverages web documents to first generate a situation, then a meaningful instruction. This framework allows us to harvest diverse and complex instructions at scale, utilizing the vast range of web documents. Specifically, we construct a dataset of 1 million instructions, called SynthQuestions, and demonstrate that models trained on it achieve leading performance on several common benchmarks, with improvements that continually scale with more web corpora. Data, models and codes will be available at https://github.com/Ignoramus0817/SynthQuestions.

MIRROR: Multi-agent Intra- and Inter-Reflection for Optimized Reasoning in Tool Learning

Complex tasks involving tool integration pose significant challenges for Large Language Models (LLMs), leading to the emergence of multi-agent workflows as a promising solution. Reflection has emerged as an effective strategy for correcting erroneous trajectories in agentic workflows. However, existing approaches only exploit such capability in the post-action stage, where the agent observes the execution outcomes. We argue that, like humans, LLMs can also engage in reflection before action execution: the agent can anticipate undesirable outcomes from its own decisions, which not only provides a necessarily complementary perspective to evaluate the decision but also prevents the propagation of errors throughout the trajectory. In this paper, we propose MIRROR, a framework that consists of both intra-reflection, which critically assesses intended actions before execution, and inter-reflection, which further adjusts the trajectory based on observations. This design systematically leverages LLM reflection capabilities to eliminate and rectify erroneous actions on a more comprehensive scope. Evaluations on both the StableToolBench and TravelPlanner benchmarks demonstrate MIRROR's superior performance, achieving state-of-the-art results compared to existing approaches.

Training LLM-Based Agents with Synthetic Self-Reflected Trajectories and Partial Masking

Autonomous agents, which perceive environments and take actions to achieve goals, have become increasingly feasible with the advancements in large language models (LLMs). However, current powerful agents often depend on sophisticated prompt engineering combined with closed-source LLMs like GPT-4. Although training open-source LLMs using expert trajectories from teacher models has yielded some improvements in agent capabilities, this approach still faces limitations such as performance plateauing and error propagation. To mitigate these challenges, we propose STeP, a novel method for improving LLM-based agent training. We synthesize self-reflected trajectories that include reflections and corrections of error steps, which enhance the effectiveness of LLM agents in learning from teacher models, enabling them to become agents capable of self-reflecting and correcting. We also introduce partial masking strategy that prevents the LLM from internalizing incorrect or suboptimal steps. Experiments demonstrate that our method improves agent performance across three representative tasks: ALFWorld, WebShop, and SciWorld. For the open-source model LLaMA2-7B-Chat, when trained using self-reflected trajectories constructed with Qwen1.5-110B-Chat as the teacher model, it achieves comprehensive improvements with less training data compared to agents trained exclusively on expert trajectories.

Automated Creativity Evaluation for Large Language Models: A Reference-Based Approach

Creative writing is a key capability of Large Language Models (LLMs), with potential applications in literature, storytelling, and various creative domains. However, evaluating the creativity of machine-generated texts remains a significant challenge, as existing methods either rely on costly manual annotations or fail to align closely with human assessments. In this paper, we propose an effective automated evaluation method based on the Torrance Test of Creative Writing (TTCW), which evaluates creativity as product. Our method employs a reference-based Likert-style approach, scoring generated creative texts relative to high-quality reference texts across various tests. Experimental results demonstrate that our method significantly improves the alignment between LLM evaluations and human assessments, achieving a pairwise accuracy of 0.75 (+15\%).