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Received β€” 13 April 2026 ⏭

Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis

βœ‡Omics In Lung
By: Zhaoqi Li Β· Luna Hong Β· Xingyu Lv Β· Shuangyu Yang Β· Fengzhan Ye Β· Linjie Huang Β· Shanping Jiang Β· Huiying Zhao
11 April 2026 at 18:00

Commun Biol. 2026 Apr 11. doi: 10.1038/s42003-026-10033-1. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a complex disease without clear etiology or effective therapy. While DNA methylation has been implicated in IPF pathogenesis, the tissue-specific causal effects of the epigenetic factors on IPF remain undetermined. Here, we perform epigenome-wide Mendelian randomization using blood-based methylation quantitative trait loci of 420,509 CpG sites and genome-wide association study for IPF to elucidate the causal effects of the CpG sites on IPF. Totally, 452 CpG sites has shown putative causal effects on IPF risk after Bonferroni correction. Among them, 13 CpG sites have shown strong colocalization evidence with genetic factors associated with IPF. Specifically, DNA methylation at CpG sites within MAN2A2 and TRIM27 shows significant differences between IPF lungs and controls, correlating with altered mRNA expressions of these genes in lung tissues. The CpG site in MAN2A2 is a binding site of ZNF384 according to transcription factor databases. RNA sequencing in the TGFΞ²1-induced alveolar epithelia confirms significantly reduced expression of MAN2A2 and ZNF384 comparing to the controls. Collectively, our study suggests a putative causal link between DNA methylation within MAN2A2 and IPF risk, wherein lung-specific DNA methylation in MAN2A2 may perturb the interaction between ZNF384 and MAN2A2, revealing novel roles for these genes in IPF pathogenesis.

PMID:41965819 | DOI:10.1038/s42003-026-10033-1

Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis

βœ‡(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Zhaoqi Li Β· Luna Hong Β· Xingyu Lv Β· Shuangyu Yang Β· Fengzhan Ye Β· Linjie Huang Β· Shanping Jiang Β· Huiying Zhao
11 April 2026 at 18:00

Commun Biol. 2026 Apr 11. doi: 10.1038/s42003-026-10033-1. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a complex disease without clear etiology or effective therapy. While DNA methylation has been implicated in IPF pathogenesis, the tissue-specific causal effects of the epigenetic factors on IPF remain undetermined. Here, we perform epigenome-wide Mendelian randomization using blood-based methylation quantitative trait loci of 420,509 CpG sites and genome-wide association study for IPF to elucidate the causal effects of the CpG sites on IPF. Totally, 452 CpG sites has shown putative causal effects on IPF risk after Bonferroni correction. Among them, 13 CpG sites have shown strong colocalization evidence with genetic factors associated with IPF. Specifically, DNA methylation at CpG sites within MAN2A2 and TRIM27 shows significant differences between IPF lungs and controls, correlating with altered mRNA expressions of these genes in lung tissues. The CpG site in MAN2A2 is a binding site of ZNF384 according to transcription factor databases. RNA sequencing in the TGFΞ²1-induced alveolar epithelia confirms significantly reduced expression of MAN2A2 and ZNF384 comparing to the controls. Collectively, our study suggests a putative causal link between DNA methylation within MAN2A2 and IPF risk, wherein lung-specific DNA methylation in MAN2A2 may perturb the interaction between ZNF384 and MAN2A2, revealing novel roles for these genes in IPF pathogenesis.

PMID:41965819 | DOI:10.1038/s42003-026-10033-1

Received β€” 14 March 2026 ⏭

The Struggle Between Continuation and Refusal: A Mechanistic Analysis of the Continuation-Triggered Jailbreak in LLMs

βœ‡cs.AI, q-bio.NC updates on arXiv.org
By: Yonghong Deng Β· Zhen Yang Β· Ping Jian Β· Xinyue Zhang Β· Zhongbin Guo Β· Chengzhi Li
10 March 2026 at 12:00
arXiv:2603.08234v1 Announce Type: new Abstract: With the rapid advancement of large language models (LLMs), the safety of LLMs has become a critical concern. Despite significant efforts in safety alignment, current LLMs remain vulnerable to jailbreaking attacks. However, the root causes of such vulnerabilities are still poorly understood, necessitating a rigorous investigation into jailbreak mechanisms across both academic and industrial communities. In this work, we focus on a continuation-triggered jailbreak phenomenon, whereby simply relocating a continuation-triggered instruction suffix can substantially increase jailbreak success rates. To uncover the intrinsic mechanisms of this phenomenon, we conduct a comprehensive mechanistic interpretability analysis at the level of attention heads. Through causal interventions and activation scaling, we show that this jailbreak behavior primarily arises from an inherent competition between the model's intrinsic continuation drive and the safety defenses acquired through alignment training. Furthermore, we perform a detailed behavioral analysis of the identified safety-critical attention heads, revealing notable differences in the functions and behaviors of safety heads across different model architectures. These findings provide a novel mechanistic perspective for understanding and interpreting jailbreak behaviors in LLMs, offering both theoretical insights and practical implications for improving model safety.
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