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Demystifying the Roles of LLM Layers in Retrieval, Knowledge, and Reasoning

arXiv:2510.02091v2 Announce Type: replace Abstract: Recent studies suggest that the deeper layers of Large Language Models (LLMs) contribute little to representation learning and can often be removed without significant performance loss. However, such claims are typically drawn from narrow evaluations and may overlook important aspects of model behavior. In this work, we present a systematic study of depth utilization across diverse dimensions, including evaluation protocols, task categories, and model architectures. Our analysis confirms that very deep layers are generally less effective than earlier ones, but their contributions vary substantially with the evaluation setting. Under likelihood-based metrics without generation, pruning most layers preserves performance, with only the initial few being critical. By contrast, generation-based evaluation uncovers indispensable roles for middle and deeper layers in enabling reasoning and maintaining long-range coherence. We further find that knowledge and retrieval are concentrated in shallow components, whereas reasoning accuracy relies heavily on deeper layers -- yet can be reshaped through distillation. These results highlight that depth usage in LLMs is highly heterogeneous and context-dependent, underscoring the need for task-, metric-, and model-aware perspectives in both interpreting and compressing large models.

A Definition of AGI

arXiv:2510.18212v2 Announce Type: replace Abstract: The lack of a concrete definition for Artificial General Intelligence (AGI) obscures the gap between today's specialized AI and human-level cognition. This paper introduces a quantifiable framework to address this, defining AGI as matching the cognitive versatility and proficiency of a well-educated adult. To operationalize this, we ground our methodology in Cattell-Horn-Carroll theory, the most empirically validated model of human cognition. The framework dissects general intelligence into ten core cognitive domains-including reasoning, memory, and perception-and adapts established human psychometric batteries to evaluate AI systems. Application of this framework reveals a highly "jagged" cognitive profile in contemporary models. While proficient in knowledge-intensive domains, current AI systems have critical deficits in foundational cognitive machinery, particularly long-term memory storage. The resulting AGI scores (e.g., GPT-4 at 27%, GPT-5 at 57%) concretely quantify both rapid progress and the substantial gap remaining before AGI.

R-loops in hepatocellular carcinoma: Bridging genomic instability and therapeutic opportunity (Review)

Mol Med Rep. 2026 Jan;33(1):6. doi: 10.3892/mmr.2025.13716. Epub 2025 Oct 17.

ABSTRACT

R‑loops, three‑stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced single‑stranded DNA, have emerged as important regulators of gene expression and genome maintenance. Although physiological R‑loops participate in normal cellular processes, their dysregulation can threaten genomic integrity by inducing DNA damage and replication stress. The present review explores the role of R‑loops in hepatocellular carcinoma (HCC), a malignancy characterized by marked genomic instability. In the present review, the formation mechanisms of R‑loops, their dual functions in transcriptional regulation and DNA damage, and their specific implications for HCC pathophysiology were discussed. HCC cells exhibit altered R‑loop homeostasis with aberrant accumulation linked to hepatitis B virus infection, inflammatory signaling and oncogene activation. The present review highlighted how HCC cells exploit or manage R‑loops to promote tumor progression, particularly through the epigenetic silencing of differentiation genes and modulation of replication stress responses. Furthermore, emerging therapeutic strategies targeting R‑loop biology were examined, including small molecules that induce synthetic lethality, gene‑based interventions and combination approaches that exploit R‑loop vulnerabilities. Challenges in targeting R‑loops and future directions, including multi‑omics profiling and biomarker development, were also addressed. Understanding the complex interplay between R‑loops and HCC offers promising avenues for novel diagnostic and therapeutic approaches for this malignancy.

PMID:41104860 | DOI:10.3892/mmr.2025.13716

Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution

Cell. 2025 Aug 22:S0092-8674(25)00922-5. doi: 10.1016/j.cell.2025.08.008. Online ahead of print.

ABSTRACT

Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage. We demonstrated the robust performance of Stereo-seq V2 on clinical FFPE samples using triple-negative breast cancer (TNBC) sections and identified tumor-specific alternative splicing events. In a Mycobacterium tuberculosis (Mtb)-infected mouse model, we monitored gene expression dynamics of host and pathogen transcriptomes simultaneously by utilizing Stereo-seq V2. We also assembled immune repertoires and identified Mtb-specific BCR clones, which could also be observed in human tuberculous lung samples. These results highlight Stereo-seq V2's potential in biomedical research and personalized medicine.

PMID:40882628 | DOI:10.1016/j.cell.2025.08.008

OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death

Cell Death Discovery, Published online: 23 April 2024; doi:10.1038/s41420-024-01948-x

OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death

Nuclear export of circular RNA

Nature, Published online: 14 February 2024; doi:10.1038/s41586-024-07060-5

Circular RNAs are exported from the nucleus by Ran-GTP, exportin-2 and IGF2BP1 in a mechanism analogous to protein export rather than mRNA export.
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