Results 161 to 170 of about 248,807 (309)

Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition

Advanced Science, EarlyView.
The authors engineer colorectal cancer cells with reduced redundancy of UHRF1 and DNMT1, key DNA methylation maintenance factors, lowering the maintenance threshold and sensitizing cells to inhibition. They develop reporter assays driven by endogenous tumor‐suppressor gene promoters with enhanced sensitivity and dynamic range to demethylating drugs ...
Cuicui Xia, Ying Cui, Jiongliang Wang, Wenjing Bai, Danyang Wang, Yao Chen, Huahui Guo, Liangyi Zong, Bing Qin, Xintong Cai, Jie Wang, Jing Huang, Scott B. Rothbart, Zufeng Guo, Stephen B. Baylin, Xiangqian Kong   +15 more
wiley   +1 more source

Humanized and Charge‐Optimized CSPG4‐Specific CAR‐T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma

Advanced Science, EarlyView.
CSPG4 is identified as a high‐value, stemness‐associated target in HPV‐negative HNSCC. By implementing rational biophysical engineering, a humanized and charge‐optimized CAR is developed to overcome tonic signaling‐induced exhaustion. This strategy induces a profound transcriptomic shift toward a rejuvenated, stem‐like memory state, significantly ...
Xiang Xu, Shizhen Qiu, Zhitong Wang, Dan Li, Min Chen, Yinying Chu, Guangfei Li, Yi Fang, Changjiang Li, Fang Shi, Peijie He, Haitao Wu, Haopeng Wang, Jian Chen   +13 more
wiley   +1 more source

Design of Safe and Efficient Adenine Base Editors via Protein Language Model Screening for Osteoarthritis Treatment

Advanced Science, EarlyView.
ABSTRACT Base editors enable precise genome modification and have emerged as a promising therapeutic approach for correcting diseases caused by single‐nucleotide variants. While the current efficient version of adenine base editors (ABEs), such as ABE8e, exhibits exceptional efficiency for A‐to‐G conversions, their clinical translation is hindered by ...
Jiawei Yao, Dalin Chen, Ziyi Zhang, Jingxuan Ren, Chengcheng Zhao, Shengfang Wang, Mengyu Shang, Dawei Jiang, Yinuo Li, Su'an Tang, Kai Li, Xiaohui Zhang, Xiaogang Wang   +12 more
wiley   +1 more source

Inhibition of SIRT7 Overcomes Radioresistance in Pancreatic Neuroendocrine Tumors by Reactivating MEN1 Expression

Advanced Science, EarlyView.
Pancreatic neuroendocrine tumors frequently silence MEN1 through epigenetic mechanisms. Here, SIRT7 recruits DNMT1 to the MEN1 promoter, drives hypermethylation, and enhances DNA repair. Inhibiting SIRT7 restores MEN1, reduces MRN complex abundance, impairs double‐strand break repair, and sensitizes PanNET models to radiation, supporting SIRT7 as a ...
Jianyun Jiang, Yan Wang, Yi Qin, Luohai Chen, Xiaowu Xu, Guixiong Fan, Desheng Jing, Miaoyan Wei, Xianjun Yu, Junfeng Xu, Shunrong Ji, Jie Chen   +11 more
wiley   +1 more source

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

Advanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng, Jieyan Wang, Meiyu Jin, Xu Chen, Hui Liang, Jiaxing Zhang, Junhang Luo   +15 more
wiley   +1 more source

PSMA8‐Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility

Advanced Science, EarlyView.
PSMA8 assembles s20S proteasome that degrades specific substrates in elongating spermatids. Degradation of s20S‐substrates activates translation of FXR1‐target mRNAs, which are essential for mitochondrial sheath formation and sperm morphogenesis.
Huiwen Cao, Qianting Zhang, Wei Xu, Anxuan Fang, Haomang Xu, Cheng Qiu, Lugeng He, Chao Yu   +7 more
wiley   +1 more source

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics. [PDF]

Cells
Rutkowska A, Strózik T, Wasiak T, Ciunowicz D, Kapelan N, Szczepaniak N, Sosnowski J, Goślińska W, Bartkowiak J, Budny-Lewandowska A, Antończyk P, Markiewicz M, Gustaw P, Filiks K, Jaskólska M, Stoczyńska-Fidelus E.   +15 more
europepmc   +1 more source

Integration of Spatiotemporal Multi‐Omics in Peach Fruit Unravels a Metabolic Niche and the Genetic Basis of Trichome‐Mediated Stress Adaptation

Advanced Science, EarlyView.
This study constructed the first spatiotemporal multi‐omics map of peach fruit and discovered a key candidate gene that synergistically regulates trichome development and drought tolerance through the jasmonic acid signaling pathway, providing insights into the coupling mechanism between development and stress resistance.
Zhixin Liu, Ke Cao, Liping Guan, Aizhi Qin, Yong Li, Zihao Zhao, Yinpeng Zhang, Yaping Zhou, Lirong Wang, Xuwu Sun   +9 more
wiley   +1 more source

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

Advanced Science, EarlyView.
T cell exhaustion limits immunotherapy efficacy. This article delineates its progression from stem‐like to terminally exhausted states, governed by persistent antigen, transcription factors, epigenetics, and metabolism. It maps the exhaustion landscape in the TME and proposes integrated reversal strategies, providing a translational roadmap to overcome
Yang Yu, Xiaoyu Yao, Qingyang Wang, Mengrui Yang, Runze Li, Jiangjiang Qin, Jing Zhuang, Changgang Sun   +7 more
wiley   +1 more source

Understanding the public's intention to adopt CRISPR-Cas9: the effect of beliefs, knowledge, and innovativeness. [PDF]

Hum Genet
Melamed J, Barnoy S.
europepmc   +1 more source