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AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PM(2.5) exposure

Nat Commun. 2026 Mar 30. doi: 10.1038/s41467-026-71196-3. Online ahead of print.

ABSTRACT

Exposure to airborne fine particulate matter (PM2.5) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we uncover shared transcriptional signatures between PM2.5 exposure and SARS-CoV-2 infection. We further validate this association using population-level epidemiological analyses and perform genome-wide association studies (GWAS) to identify genetic variants that modulate infection risk under PM2.5 exposure. In addition, we identify NPC1 as a key modulator involved in SARS-CoV-2 infection efficiency under virus-laden PM2.5 exposure through integrative functional genomic analyses and in vitro experiments. Our findings suggest that PM2.5 facilitates viral entry through an NPC1-modulated endo-lysosomal pathway, providing a mechanistic explanation for observed pollution-related susceptibility. By integrating artificial intelligence (AI)-guided transcriptomics, epidemiology, GWAS, functional genomics, and in vitro verification, our study elucidates how environmental and genetic factors jointly influence SARS-CoV-2 susceptibility. This work highlights how AI-assisted multi-omics integration systematically decodes the health impacts of environmental exposures from molecular to population levels and informs air quality policy and infectious disease preparedness.

PMID:41912520 | DOI:10.1038/s41467-026-71196-3

Real-Time Aligned Reward Model beyond Semantics

arXiv:2601.22664v3 Announce Type: replace Abstract: Reinforcement Learning from Human Feedback (RLHF) is a pivotal technique for aligning large language models (LLMs) with human preferences, yet it is susceptible to reward overoptimization, in which policy models overfit to the reward model, exploit spurious reward patterns instead of faithfully capturing human intent. Prior mitigations primarily relies on surface semantic information and fails to efficiently address the misalignment between the reward model (RM) and the policy model caused by continuous policy distribution shifts. This inevitably leads to an increasing reward discrepancy, exacerbating reward overoptimization. To address these limitations, we introduce R2M (Real-Time Aligned Reward Model), a novel lightweight RLHF framework. R2M goes beyond vanilla reward models that solely depend on the semantic representations of a pretrained LLM. Instead, it leverages the evolving hidden states of the policy (namely policy feedback) to align with the real-time distribution shift of the policy during the RL process. This work points to a promising new direction for improving the performance of reward models through real-time utilization of feedback from policy models.

GraphMERT: Efficient and Scalable Distillation of Reliable Knowledge Graphs from Unstructured Data

arXiv:2510.09580v2 Announce Type: replace Abstract: Researchers have pursued neurosymbolic artificial intelligence (AI) applications for nearly three decades. A marriage of the neural and symbolic components can lead to rapid advancements in AI. Yet, the field has not realized this promise since most neurosymbolic AI frameworks fail to scale. In addition, the implicit representations and approximate reasoning of purely neural approaches limit interpretability and trust. Knowledge graphs (KGs), a gold-standard representation of explicit semantic knowledge, can address the symbolic side of the problem. However, automatically deriving reliable KGs from text corpora remains an open problem. We address these challenges by introducing GraphMERT, a tiny graphical encoder-only model that distills high-quality KGs from unstructured text corpora and its own internal representations. GraphMERT and its equivalent KG form a modular neurosymbolic stack: neural learning of abstractions; symbolic KGs for verifiable reasoning. GraphMERT + KG is the first efficient and scalable neurosymbolic model to achieve state-of-the-art benchmark accuracy along with superior symbolic representations relative to baselines. Concretely, we target reliable domain-specific KGs that are both (1) factual (with provenance) and (2) valid (ontology-consistent relations with domain-appropriate semantics). When a large language model (LLM), e.g., Qwen3-32B, generates domain-specific KGs, it falls short on reliability due to prompt sensitivity, shallow domain expertise, and hallucinated relations. On text obtained from PubMed papers on diabetes, our 80M-parameter GraphMERT yields a KG with a 69.8% FActScore; a 32B-parameter baseline LLM yields a KG that achieves only 40.2% FActScore. The GraphMERT KG also attains a higher ValidityScore of 68.8%, versus 43.0% for the LLM baseline.

Does Your Reasoning Model Implicitly Know When to Stop Thinking?

arXiv:2602.08354v2 Announce Type: replace Abstract: Recent advancements in large reasoning models (LRMs) have greatly improved their capabilities on complex reasoning tasks through Long Chains of Thought (CoTs). However, this approach often results in substantial redundancy, impairing computational efficiency and causing significant delays in real-time applications. Recent studies show that longer reasoning chains are frequently uncorrelated with correctness and can even be detrimental to accuracy. In a further in-depth analysis of this phenomenon, we surprisingly uncover and empirically verify that LRMs implicitly know the appropriate time to stop thinking, while this capability is obscured by current sampling paradigms. Motivated by this, we introduce SAGE (Self-Aware Guided Efficient Reasoning), a novel sampling paradigm that unleashes this efficient reasoning potential. Furthermore, integrating SAGE as mixed sampling into group-based reinforcement learning (SAGE-RL) enables SAGE-RL to effectively incorporate SAGE-discovered efficient reasoning patterns into standard pass@1 inference, markedly enhancing both the reasoning accuracy and efficiency of LRMs across multiple challenging mathematical benchmarks.
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