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Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer

Oncogene, Published online: 04 April 2026; doi:10.1038/s41388-026-03764-2

Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer

Isobavachalcone exerts anti-gastric cancer effects by targeting dihydroorotate dehydrogenase to induce ROS release and activating the STING pathway

Phytomedicine. 2026 Mar 27;155:158126. doi: 10.1016/j.phymed.2026.158126. Online ahead of print.

ABSTRACT

BACKGROUND: Mitochondrial damage can induce the release of mitochondrial DNA (mtDNA), leading to oxidative stress and activation of immune responses. Targeting mitochondrial dysfunction may thus represent a therapeutic strategy for gastric cancer. Isobavachalcone (IBC), a prenylated chalcone derived from Psoralea corylifolia L., has demonstrated antitumor activity, but its mechanism of action remains unclear, limiting its clinical application.

PURPOSE: This study aimed to investigate the antitumor effects of IBC in gastric cancer and to elucidate the underlying molecular mechanisms, with a focus on mitochondrial damage and immune activation.

STUDY DESIGN: The study combined in vitro and in vivo assays with multi-omics sequencing and network pharmacology to identify IBC's therapeutic target and downstream signaling pathways.

METHODS: Gastric cancer cells and mouse models were treated with IBC to assess its inhibitory effects. Multi-omics approaches and network pharmacology were used to identify potential targets. ROS production, mitochondrial membrane integrity, and immune pathway activation were evaluated via biochemical and molecular assays.

RESULTS: IBC significantly suppresses gastric cancer growth both in vitro and in vivo. Integrated analysis identifies dihydroorotate dehydrogenase (DHODH) as a direct target of IBC. DHODH deficiency can induce mitochondrial membrane remodeling and STING pathway activation. Inhibition of DHODH by IBC induces ROS accumulation, mitochondrial membrane remodeling, and activation of the STING pathway, promoting antitumor immune responses. This study demonstrates that IBC enhances antitumor immunity in gastric cancer through mitochondrial damage-mediated mechanisms.

CONCLUSION: IBC exerts dual antitumor and immunostimulatory effects in gastric cancer by targeting DHODH, inducing mitochondrial damage, and activating the STING pathway, highlighting its promising therapeutic potential in gastric cancer.

PMID:41931998 | DOI:10.1016/j.phymed.2026.158126

Isobavachalcone exerts anti-gastric cancer effects by targeting dihydroorotate dehydrogenase to induce ROS release and activating the STING pathway

Phytomedicine. 2026 Mar 27;155:158126. doi: 10.1016/j.phymed.2026.158126. Online ahead of print.

ABSTRACT

BACKGROUND: Mitochondrial damage can induce the release of mitochondrial DNA (mtDNA), leading to oxidative stress and activation of immune responses. Targeting mitochondrial dysfunction may thus represent a therapeutic strategy for gastric cancer. Isobavachalcone (IBC), a prenylated chalcone derived from Psoralea corylifolia L., has demonstrated antitumor activity, but its mechanism of action remains unclear, limiting its clinical application.

PURPOSE: This study aimed to investigate the antitumor effects of IBC in gastric cancer and to elucidate the underlying molecular mechanisms, with a focus on mitochondrial damage and immune activation.

STUDY DESIGN: The study combined in vitro and in vivo assays with multi-omics sequencing and network pharmacology to identify IBC's therapeutic target and downstream signaling pathways.

METHODS: Gastric cancer cells and mouse models were treated with IBC to assess its inhibitory effects. Multi-omics approaches and network pharmacology were used to identify potential targets. ROS production, mitochondrial membrane integrity, and immune pathway activation were evaluated via biochemical and molecular assays.

RESULTS: IBC significantly suppresses gastric cancer growth both in vitro and in vivo. Integrated analysis identifies dihydroorotate dehydrogenase (DHODH) as a direct target of IBC. DHODH deficiency can induce mitochondrial membrane remodeling and STING pathway activation. Inhibition of DHODH by IBC induces ROS accumulation, mitochondrial membrane remodeling, and activation of the STING pathway, promoting antitumor immune responses. This study demonstrates that IBC enhances antitumor immunity in gastric cancer through mitochondrial damage-mediated mechanisms.

CONCLUSION: IBC exerts dual antitumor and immunostimulatory effects in gastric cancer by targeting DHODH, inducing mitochondrial damage, and activating the STING pathway, highlighting its promising therapeutic potential in gastric cancer.

PMID:41931998 | DOI:10.1016/j.phymed.2026.158126

The Latent Space: Foundation, Evolution, Mechanism, Ability, and Outlook

arXiv:2604.02029v1 Announce Type: new Abstract: Latent space is rapidly emerging as a native substrate for language-based models. While modern systems are still commonly understood through explicit token-level generation, an increasing body of work shows that many critical internal processes are more naturally carried out in continuous latent space than in human-readable verbal traces. This shift is driven by the structural limitations of explicit-space computation, including linguistic redundancy, discretization bottlenecks, sequential inefficiency, and semantic loss. This survey aims to provide a unified and up-to-date landscape of latent space in language-based models. We organize the survey into five sequential perspectives: Foundation, Evolution, Mechanism, Ability, and Outlook. We begin by delineating the scope of latent space, distinguishing it from explicit or verbal space and from the latent spaces commonly studied in generative visual models. We then trace the field's evolution from early exploratory efforts to the current large-scale expansion. To organize the technical landscape, we examine existing work through the complementary lenses of mechanism and ability. From the perspective of Mechanism, we identify four major lines of development: Architecture, Representation, Computation, and Optimization. From the perspective of Ability, we show how latent space supports a broad capability spectrum spanning Reasoning, Planning, Modeling, Perception, Memory, Collaboration, and Embodiment. Beyond consolidation, we discuss the key open challenges, and outline promising directions for future research. We hope this survey serves not only as a reference for existing work, but also as a foundation for understanding latent space as a general computational and systems paradigm for next-generation intelligence.

DR-LoRA: Dynamic Rank LoRA for Fine-Tuning Mixture-of-Experts Models

arXiv:2601.04823v5 Announce Type: replace Abstract: Mixture-of-Experts (MoE) has become a prominent paradigm for scaling Large Language Models (LLMs). Parameter-efficient fine-tuning methods, such as LoRA, are widely adopted to adapt pretrained MoE LLMs to downstream tasks. However, existing approaches typically assign identical LoRA ranks to all expert modules, ignoring the heterogeneous specialization of pretrained experts. This uniform allocation leads to a resource mismatch: task-relevant experts are under-provisioned, while less relevant ones receive redundant parameters. To address this, we propose DR-LoRA, a Dynamic Rank LoRA framework for fine-tuning pretrained MoE models. Specifically, DR-LoRA initializes all expert LoRA modules with a small active rank and uses an expert saliency score, which combines routing frequency and gradient-based rank importance, to identify which experts would benefit most from additional capacity. It then periodically expands the active ranks of the task-critical expert LoRA, progressively constructing a heterogeneous rank distribution tailored to the target task. Experiments on three MoE models across six tasks show that DR-LoRA consistently outperforms LoRA and other strong baselines, demonstrating that task-adaptive heterogeneous rank allocation is an effective strategy to improve active capacity utilization in MoE fine-tuning.

Bias Is a Subspace, Not a Coordinate: A Geometric Rethinking of Post-hoc Debiasing in Vision-Language Models

arXiv:2511.18123v2 Announce Type: replace-cross Abstract: Vision-Language Models (VLMs) have become indispensable for multimodal reasoning, yet their representations often encode and amplify demographic biases, resulting in biased associations and misaligned predictions in downstream tasks. Such behavior undermines fairness and distorts the intended alignment between vision and language. Recent post-hoc approaches attempt to mitigate bias by replacing the most attribute-correlated embedding coordinates with neutral values. However, our systematic analysis reveals three critical limitations of this coordinate-wise approach: feature entanglement, poor cross-dataset generalization, and incomplete bias removal. We find that bias is not localized to a few coordinates but is instead distributed across a few linear subspaces. To address these limitations, we propose $\textbf{S}$ubspace $\textbf{P}$rojection $\textbf{D}$ebiasing ($\textbf{SPD}$), a geometrically principled framework that identifies and removes the entire subspace of linearly decodable bias while reinserting a neutral mean component to preserve semantic fidelity. Extensive experiments across zero-shot classification, text-to-image retrieval, and image generation validate the effectiveness of SPD: our method achieves more robust debiasing with an average improvement of $18.5\%$ across four fairness metrics, while maintaining minimal loss in task performance compared to the best debiasing baseline.

Scaling the Long Video Understanding of Multimodal Large Language Models via Visual Memory Mechanism

arXiv:2603.29252v1 Announce Type: cross Abstract: Long video understanding is a key challenge that plagues the advancement of \emph{Multimodal Large language Models} (MLLMs). In this paper, we study this problem from the perspective of visual memory mechanism, and proposed a novel and training-free approach, termed \emph{Flexible Memory} (\textbf{FlexMem}). In principle, FlexMem aims to mimic human behavior of video watching, \emph{i.e.}, continually watching video content and recalling the most relevant memory fragments to answer the question. In this way, FlexMem can help MLLMs achieve video understanding of infinite lengths, unlike previous methods that process all video information at once and have input upper-limit. Concretely, FlexMem first consider the visual KV caches as the memory sources, and realize the effective memory transfer and writing via a dual-pathway compression design. Afterwards, FlexMem also explores different memory reading strategies for the diverse video understanding tasks, including the popular streaming one. To validate FlexMem, we apply it to two popular video-MLLMs, and conduct extensive experiments on five long video and one streaming video task. The experimental results show that on \textbf{a single 3090 GPU}, our FlexMem can achieve obvious improvements than existing efficient video understanding methods and process more than \textbf{1k frames}, which also helps the base MLLMs achieve comparable or even better performance than SOTA MLLMs on some benchmarks, \emph{e.g.} , GPT-4o and Gemini-1.5 Pro.

6GAgentGym: Tool Use, Data Synthesis, and Agentic Learning for Network Management

arXiv:2603.29656v1 Announce Type: cross Abstract: Autonomous 6G network management requires agents that can execute tools, observe the resulting state changes, and adapt their decisions accordingly. Existing benchmarks based on static questions or scripted episode replay, however, do not support such closed-loop interaction, limiting agents to passive evaluation without the ability to learn from environmental feedback. This paper presents 6GAgentGym to provide closed-loop capability. The framework provides an interactive environment with 42 typed tools whose effect classification distinguishes read-only observation from state-mutating configuration, backed by a learned Experiment Model calibrated on NS-3 simulation data. 6G-Forge bootstraps closed-loop training trajectories from NS-3 seeds via iterative Self-Instruct generation with execution verification against the Experiment Model. Supervised fine-tuning on the resulting corpus followed by reinforcement learning with online closed-loop interaction enables an 8B open-source model to achieve comparable overall success rate to GPT-5 on the accompanying 6GAgentBench, with stronger performance on long-horizon tasks. Together, these components provide a viable path toward autonomous, closed-loop network management.

The 1000 Chinese Pangenome empowers medical and population genetics

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10315-y

Development of the pangenome-informed genome assembly (PIGA) workflow enabled the generation of 1,116 diploid genome assemblies (55 de novo and 1,061 pangenome-informed), representing an extensive resource of medically relevant genic variations.

PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments

arXiv:2603.23231v1 Announce Type: new Abstract: Empowering large language models with long-term memory is crucial for building agents that adapt to users' evolving needs. However, prior evaluations typically interleave preference-related dialogues with irrelevant conversations, reducing the task to needle-in-a-haystack retrieval while ignoring relationships between events that drive the evolution of user preferences. Such settings overlook a fundamental characteristic of real-world personalization: preferences emerge gradually and accumulate across interactions within noisy contexts. To bridge this gap, we introduce PERMA, a benchmark designed to evaluate persona consistency over time beyond static preference recall. Additionally, we incorporate (1) text variability and (2) linguistic alignment to simulate erratic user inputs and individual idiolects in real-world data. PERMA consists of temporally ordered interaction events spanning multiple sessions and domains, with preference-related queries inserted over time. We design both multiple-choice and interactive tasks to probe the model's understanding of persona along the interaction timeline. Experiments demonstrate that by linking related interactions, advanced memory systems can extract more precise preferences and reduce token consumption, outperforming traditional semantic retrieval of raw dialogues. Nevertheless, they still struggle to maintain a coherent persona across temporal depth and cross-domain interference, highlighting the need for more robust personalized memory management in agents. Our code and data are open-sourced at https://github.com/PolarisLiu1/PERMA.

ForestPrune: High-ratio Visual Token Compression for Video Multimodal Large Language Models via Spatial-Temporal Forest Modeling

arXiv:2603.22911v1 Announce Type: cross Abstract: Due to the great saving of computation and memory overhead, token compression has become a research hot-spot for MLLMs and achieved remarkable progress in image-language tasks. However, for the video, existing methods still fall short of high-ratio token compression. We attribute this shortcoming to the insufficient modeling of temporal and continual video content, and propose a novel and training-free token pruning method for video MLLMs, termed ForestPrune, which achieves effective and high-ratio pruning via Spatial-temporal Forest Modeling. In practice, ForestPrune construct token forests across video frames based on the semantic, spatial and temporal constraints, making an overall comprehension of videos. Afterwards, ForestPrune evaluates the importance of token trees and nodes based on tree depth and node roles, thereby obtaining a globally optimal pruning decision. To validate ForestPrune, we apply it to two representative video MLLMs, namely LLaVA-Video and LLaVA-OneVision, and conduct extensive experiments on a bunch of video benchmarks. The experimental results not only show the great effectiveness for video MLLMs, e.g., retaining 95.8% average accuracy while reducing 90% tokens for LLaVA-OneVision, but also show its superior performance and efficiency than the compared token compression methods, e.g., +10.1% accuracy on MLVU and -81.4% pruning time than FrameFusion on LLaVA-Video.

ImplicitRM: Unbiased Reward Modeling from Implicit Preference Data for LLM alignment

arXiv:2603.23184v1 Announce Type: cross Abstract: Reward modeling represents a long-standing challenge in reinforcement learning from human feedback (RLHF) for aligning language models. Current reward modeling is heavily contingent upon experimental feedback data with high collection costs. In this work, we study \textit{implicit reward modeling} -- learning reward models from implicit human feedback (e.g., clicks and copies) -- as a cost-effective alternative. We identify two fundamental challenges in implicit reward modeling: (1) Implicit preference data lacks definitive negative samples, which makes standard positive-negative classification methods inapplicable; (2) Implicit preference data suffers from user preference bias, where different responses have different propensities to elicit user feedback actions, which exacerbates the difficulty of distinguishing definitive negative samples. To address these challenges, we propose ImplicitRM, which aims to learn unbiased reward models from implicit preference data. ImplicitRM stratifies training samples into four latent groups via a stratification model. Building on this, it derives a learning objective through likelihood maximization, which we prove is theoretically unbiased, effectively resolving both challenges. Experiments demonstrate that ImplicitRM learns accurate reward models across implicit preference datasets. Code is available on our project website.

TRACE: A Multi-Agent System for Autonomous Physical Reasoning in Seismological

arXiv:2603.21152v2 Announce Type: replace-cross Abstract: Inferring the physical mechanisms that govern earthquake sequences from indirect geophysical observations remains difficult, particularly across tectonically distinct environments where similar seismic patterns can reflect different underlying processes. Current interpretations rely heavily on the expert synthesis of catalogs, spatiotemporal statistics, and candidate physical models, limiting reproducibility and the systematic transfer of insight across settings. Here we present TRACE (Trans-perspective Reasoning and Automated Comprehensive Evaluator), a multi-agent system that combines large language model planning with formal seismological constraints to derive auditable, physically grounded mechanistic inference from raw observations. Applied to the 2019 Ridgecrest sequence, TRACE autonomously identifies stress-perturbation-induced delayed triggering, resolving the cascading interaction between the Mw 6.4 and Mw 7.1 mainshocks; in the Santorini-Kolumbo case, the system identifies a structurally guided intrusion model, distinguishing fault-channeled episodic migration from the continuous propagation expected in homogeneous crustal failure. By providing a generalizable logical infrastructure for interpreting heterogeneous seismic phenomena, TRACE advances the field from expert-dependent analysis toward knowledge-guided autonomous discovery in Earth sciences.

Deciphering lung adenocarcinoma heterogeneity: a multi-omics approach reveals nuclear division fibroblasts as prognosticators and therapeutic targets

J Transl Med. 2026 Mar 20. doi: 10.1186/s12967-026-08022-3. Online ahead of print.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is a predominant contributor to cancer‑related mortality globally. Lung‑associated fibroblasts (LAFs) are intricately linked to tumorigenesis and the tumor microenvironment (TME), but their heterogeneity and prognostic relevance in LUAD remain incompletely understood. This study aimed to systematically characterize LAF subsets across the spectrum of pulmonary disease, identify LAF subpopulations associated with LUAD prognosis, and construct a robust LAF‑based prognostic signature.

METHODS: We employed a multi-omics approach, leveraging bulk RNA data of 2719 patients from 19 LUAD cohorts, single-cell RNA (scRNA) sequencing data of 368,904 cells from 93 samples, and spatial transcriptomics data of 15,673 spots from 6 samples to characterize the landscape of LAFs across various stages of pulmonary disease. We employed multiple advanced machine learning algorithms to construct and validate a robust nuclear division LAFs (nLAFs) risk score (nLRS) prediction model.

RESULTS: We observed a dynamic and gradual increase in the proportion of LAFs during the progression of LUAD. Throughout this process, we identified nine LAFs subtypes and found nLAFs are significantly associated with the prognosis of LUAD. Utilizing 100 machine learning algorithm combinations and integrating nLAFs marker genes, we developed a five gene based nLRS model, which demonstrated superior performance than other 49 published models in predicting clinical outcomes for LUAD. Additionally, we observed distinct biological functions and immune cell infiltration in the TME between high and low nLRS groups. Exploratory analysis of pan-cancer immunotherapy cohorts suggested that patients with high nLRS scores may exhibit resistance to immunotherapy in some cancer types, but prospective validation in LUAD-specific cohorts is required. Conversely, high nLRS patients displayed increased sensitivity to chemotherapeutic and targeted therapies in preclinical models.

CONCLUSION: Our study introduces a candidate five-gene signature derived from nLAFs that may serve as a robust prognostic biomarker pending prospective validation, offering insights into personalized therapeutic strategies for LUAD patients.

PMID:41862916 | DOI:10.1186/s12967-026-08022-3

One-Step Flow Policy: Self-Distillation for Fast Visuomotor Policies

arXiv:2603.12480v1 Announce Type: cross Abstract: Generative flow and diffusion models provide the continuous, multimodal action distributions needed for high-precision robotic policies. However, their reliance on iterative sampling introduces severe inference latency, degrading control frequency and harming performance in time-sensitive manipulation. To address this problem, we propose the One-Step Flow Policy (OFP), a from-scratch self-distillation framework for high-fidelity, single-step action generation without a pre-trained teacher. OFP unifies a self-consistency loss to enforce coherent transport across time intervals, and a self-guided regularization to sharpen predictions toward high-density expert modes. In addition, a warm-start mechanism leverages temporal action correlations to minimize the generative transport distance. Evaluations across 56 diverse simulated manipulation tasks demonstrate that a one-step OFP achieves state-of-the-art results, outperforming 100-step diffusion and flow policies while accelerating action generation by over $100\times$. We further integrate OFP into the $\pi_{0.5}$ model on RoboTwin 2.0, where one-step OFP surpasses the original 10-step policy. These results establish OFP as a practical, scalable solution for highly accurate and low-latency robot control.

Neural-Quantum-States Impurity Solver for Quantum Embedding Problems

arXiv:2509.12431v2 Announce Type: replace-cross Abstract: Neural quantum states (NQS) have emerged as a promising approach to solve second-quantized Hamiltonians, because of their scalability and flexibility. In this work, we design and benchmark an NQS impurity solver for the quantum embedding (QE) methods, focusing on the ghost Gutzwiller Approximation (gGA) framework. We introduce a graph transformer-based NQS framework able to represent arbitrarily connected impurity orbitals of the embedding Hamiltonian (EH) and develop an error control mechanism to stabilize iterative updates throughout the QE loops. We validate the accuracy of our approach with benchmark gGA calculations of the Anderson Lattice Model, yielding results in excellent agreement with the exact diagonalisation impurity solver. Finally, our analysis of the computational budget reveals the method's principal bottleneck to be the high-accuracy sampling of physical observables required by the embedding loop, rather than the NQS variational optimization, directly highlighting the critical need for more efficient inference techniques.

FCMBench: The First Large-scale Financial Credit Multimodal Benchmark for Real-world Applications

arXiv:2601.00150v3 Announce Type: replace-cross Abstract: FCMBench is the first large-scale and privacy-compliant multimodal benchmark for real-world financial credit applications, covering tasks and robustness challenges from domain specific workflows and constraints. The current version of FCMBench covers 26 certificate types, with 5198 privacy-compliant images and 13806 paired VQA samples. It evaluates models on Perception and Reasoning tasks under real-world Robustness interferences, including 3 foundational perception tasks, 4 credit-specific reasoning tasks demanding decision-oriented visual evidence interpretation, and 10 real-world challenges for rigorous robustness stress testing. Moreover, FCMBench offers privacy-compliant realism with minimal leakage risk through in-house scenario-aware captures of manually synthesized templates, without any publicly released images. We conduct extensive evaluations of 28 state-of-the-art vision-language models spanning 14 AI companies and research institutes. Among them, Gemini 3 Pro achieves the best F1 score as a commercial model (65.16), Kimi-K2.5 achieves the best score as an open-source baseline (60.58). The mean and the std. of all tested models is 44.8 and 10.3 respectively, indicating that FCMBench is non-trivial and provides strong resolution for separating modern vision-language model capabilities. Robustness evaluations reveal that even top-performing models experience notable performance degradation under the designed challenges. We have open-sourced this benchmark to advance AI research in the credit domain and provide a domain-specific task for real-world AI applications.

BitDance: Scaling Autoregressive Generative Models with Binary Tokens

arXiv:2602.14041v2 Announce Type: replace-cross Abstract: We present BitDance, a scalable autoregressive (AR) image generator that predicts binary visual tokens instead of codebook indices. With high-entropy binary latents, BitDance lets each token represent up to $2^{256}$ states, yielding a compact yet highly expressive discrete representation. Sampling from such a huge token space is difficult with standard classification. To resolve this, BitDance uses a binary diffusion head: instead of predicting an index with softmax, it employs continuous-space diffusion to generate the binary tokens. Furthermore, we propose next-patch diffusion, a new decoding method that predicts multiple tokens in parallel with high accuracy, greatly speeding up inference. On ImageNet 256x256, BitDance achieves an FID of 1.24, the best among AR models. With next-patch diffusion, BitDance beats state-of-the-art parallel AR models that use 1.4B parameters, while using 5.4x fewer parameters (260M) and achieving 8.7x speedup. For text-to-image generation, BitDance trains on large-scale multimodal tokens and generates high-resolution, photorealistic images efficiently, showing strong performance and favorable scaling. When generating 1024x1024 images, BitDance achieves a speedup of over 30x compared to prior AR models. We release code and models to facilitate further research on AR foundation models. Code and models are available at: https://github.com/shallowdream204/BitDance.
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