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Received — 10 September 2026 ⏭

A complement C5-targeted GalNAc-conjugated siRNA with sustained efficacy in a non-human primate model of IgA nephropathy

✇Molecular Therapy
By: Xueyan Zhang · Xue Zhang · Qiuyu Yang · Bin Kang · Mo Dan · Chunlei Li · Yan Chen · Jianhua Gan · Xiaoye Su
13 August 2026 at 08:00
This study characterizes a GalNAc-C5 small interfering RNA with potent in vitro and in vivo activity. Single subcutaneous dosing sustains long-term C5 suppression in cynomolgus monkeys with IgA nephropathy, outperforming Nefecon in blocking glomerular complement deposition, supporting its standalone or combinational clinical application.

A helicase-fused Cas9 improves large-size fragment knockin

✇Molecular Therapy
By: Duowei Zhao · Xiangjie Zhao · Yuhang Gao · Sujie Yang · Xiaochen Guo · Caiyan Zhang · Chuanpei Li · Chengda Zhang · Huan Tian · Qianqian Xu · Zhi Yin · Zhonghua Liu · Jun Song
29 July 2026 at 08:00
By fusing MCM5, a subunit of the eukaryotic MCM2–7 helicase complex, to the N terminus of spCas9 (MCCas), the MCCas fusion protein enhances large-size fragment knockin via homologous recombination, reduces insertions and deletions (indels), and enables efficient large-size fragment insertions in human cells and rabbit embryos.

Efficient Diversity-based Experience Replay for Deep Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Kaiyan Zhao · Yiming Wang · Yuyang Chen · Yan Li · Leong Hou U · Xiaoguang Niu
10 September 2026 at 12:00
arXiv:2410.20487v5 Announce Type: replace-cross Abstract: Experience replay is widely used to improve learning efficiency in reinforcement learning by leveraging past experiences. However, existing experience replay methods, whether based on uniform or prioritized sampling, often suffer from low efficiency, particularly in real-world scenarios with high-dimensional state spaces. To address this limitation, we propose a novel approach, Efficient Diversity-based Experience Replay (EDER). EDER employs a determinantal point process to model the diversity between samples and prioritizes replay based on the diversity between samples. To further enhance learning efficiency, we incorporate Cholesky decomposition for handling large state spaces in realistic environments. Additionally, rejection sampling is applied to select samples with higher diversity, thereby improving overall learning efficacy. Extensive experiments are conducted on robotic manipulation tasks in MuJoCo, Atari games, and realistic indoor environments in Habitat. The results demonstrate that our approach not only significantly improves learning efficiency but also achieves superior performance in high-dimensional, realistic environments.

G9a-mediated cholesterol metabolism triggers cuproptosis to promote alcohol-related liver disease

✇Cell Death Discovery nature.com science feeds
By: Rong Dong · Jing Yuan · Jingzhou Chen · Yi Zhu · Yurong Zhao · Chi Luo · Jinghao Sheng · Yan Zha
7 September 2026 at 08:00

Cell Death Discovery, Published online: 07 September 2026; doi:10.1038/s41420-026-03299-1

G9a-mediated cholesterol metabolism triggers cuproptosis to promote alcohol-related liver disease

Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma

✇Omics in Hepatocellular
By: Ze-Kai Li · Min-Rui Luo · Shu-Jie Fang · Yi-Da Wu · Quan-Hui Hu · Dong-Yan Zhang
1 September 2026 at 18:00

Anal Cell Pathol (Amst). 2026;2026(1):e1554526. doi: 10.1155/ancp/1554526.

ABSTRACT

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.

PMID:42678131 | PMC:PMC13532061 | DOI:10.1155/ancp/1554526

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