Results 141 to 150 of about 484,668 (274)

BCR::ABL1‐Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B‐ALL Cells to Enhancer‐Targeting Drugs

Advanced Science, EarlyView.
Ng et al. show that the BCR::ABL1 kinase that drives the lymphoid leukemia Ph+B‐ALL modulates enhancer function by coopting signaling‐inducible transcription factors such as MYC, STAT5, and ETV5. BCR::ABL1 thereby promotes the transcriptional program driving and defining this leukemia and renders Ph+B‐ALL cells hypersensitive to enhancer‐inhibiting ...
Han Leng Ng, Trudy Lee Glaser, Jintao Zhu, Mark E. Robinson, Kadriye N. Cosgun, Valeriya Malysheva, Ozgen Deniz, Nicholas T. Crump, Kaiyue Helian, Andrew J. Innes, Richard Burt, Li Sun, George John, Haibin Zhou, Atsunori Kaneshige, Longchuan Bai, Shaomeng Wang, Mikhail Spivakov, Markus Müschen, Niklas Feldhahn   +19 more
wiley   +1 more source

Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes

Advanced Science, EarlyView.
This review synthesizes advances in bone organoid engineering and evaluates their potential to model diabetic bone fragility. Current in vitro and animal models do not fully recapitulate diabetes‐associated skeletal phenotypes. Cell‐based and scaffold‐based bone organoids are discussed as complementary approaches to reconstruct multicellular bone ...
Shuangzhe Lin, Karthikeyan Narayanan, Deepak Vashishth   +2 more
wiley   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

Advanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao, Yaxian Liao, Pengyun Li, Regina Stasser de Gonzalez, Xuankun Chen, Nicholas S. Nieto, Florence M. Brunel, Nick Cox, Joseph Stock, Matthew McHenry, Guangsen Fu, Penghsuan Huang, Wenxin Wu, Deqin Cai, Lingjun Li, Alexander N. Zaykov, Weiping Tang   +16 more
wiley   +1 more source

Targeting PRKCN, an Essential Driver Orchestrating mTOR‐IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma

Advanced Science, EarlyView.
Constitutive PRKCN expression is driven by super‐enhancers and modulated by NF‐κB signaling in multiple myeloma (MM). PRKCN activates mTORC1/2‐IRF4 signaling axis and favors tumor cell growth independently of its kinase activity. IRF4 reciprocally promotes PRKCN transcription, creating a feed‐forward loop.
Koukou Tang, Dongpeng Jiang, Peng Ke, Xiaosen Bian, Lili Zhang, Ying Zhang, Tingting Zhu, Weiwei Qu, Wenhui Qi, Yang Xu, Chengcheng Fu, Depei Wu, Jianhong Chu   +12 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

Macrophage Extracellular Traps in Immunity and Cancer

Advanced Science, EarlyView.
As a macrophage‐mediated innate defense mechanism, the dysregulated release of METs drives chronic inflammation and influences tumor progression. Furthermore, METs exhibit a functional duality within the tumor microenvironment, capable of both promoting and suppressing tumor development.
Junyao Li, Eugenie Nepovimova, Adam Grundel, Lukas Peter, Qinghua Wu, Kamil Kuca   +5 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

TGM2 Aggravates Acute Pancreatitis by Impairing Macrophage Efferocytosis Through Inhibition of the STAT6–GAS6 Axis

Advanced Science, EarlyView.
This study shows TGM2 is upregulated in AP, impairing macrophage efferocytosis by inhibiting the STAT6–GAS6 axis. The lactoferrin‐modified, ROS‐responsive LF‐LNP@si‐TGM2 targets pancreatic macrophages, silences TGM2, restores the axis, and alleviates AP.
Xuxu Liu, Zhiwei Du, Liyi Wang, Zhihong Xie, Ziang Meng, Yi Zheng, Heming Wang, Yuanhang He, Dongbo Xue   +8 more
wiley   +1 more source

Beden erk ilişkisi

, 2020
Bu araştırma; siyasi iktidar dönemlerinde uygulanan devlet politikalarının ideolojik aygıtlarını (sürekli gözetim, tahakküm ve tecrit gibi) merkeze alıp bu olguların beden kavramı üzerine olan yansımalarını araştırmak ile `Beden- Erk ` ilişkilerine tarihsel bilgiler, farklı disiplinler (Resim, Heykel, Edebiyat, Sinema) ve sanatçıların çalışmaları baz ...
openaire   +1 more source

Persistently Increased Expression of PKMzeta and Unbiased Gene Expression Profiles Identify Hippocampal Molecular Traces of a Long‐Term Active Place Avoidance Memory and “Shadow” Proteins

Advanced Science, EarlyView.
Protein complexes like KIBRA‐PKMζ are crucial for maintaining memories, forming month‐long protein traces in memory‐tagged neurons, but conventional RNA‐seq analysis fails to detect their transcript changes, leaving memory molecules undetected in the shadows of abundantly‐expressed genes.
Jiyeon Han, Alejandro Grau‐Perales, Rayna M. Harris, Edith Lesburguères, Hsin‐Yi Kao, Asit Pal, Juan Marcos Alarcon, Todd C. Sacktor, Stefano Martiniani, Hans A. Hofmann, André A. Fenton   +10 more
wiley   +1 more source