Results 11 to 20 of about 136,524 (172)

Innate Immunocompetent hiPSC‐Derived Neurospheroids Capture Early CNS Responses to rAAV

Advanced Science, EarlyView.
Knowledge of human CNS immune responses to AAV‐based gene therapies remains limited due to the lack of immune‐competent human models. Here, a hiPSC‐derived 3D neuroimmune platform integrating neurospheroids and microglia is established using stirred‐tank bioreactors.
Catarina M. Gomes, Gabriela Silva, Mafalda Aleixo, Marta Gomes, Daniel Simão, Stephan J. Holtkamp, Diana D. Lobo, Pradeep Harish, Rosalind Jenkins, Lekh N. Dahal, Rui J. Nobre, Luís de Pereira de Almeida, Mark Trautwein, Paula M. Alves, Catarina Brito   +14 more
wiley   +1 more source

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2‐Mediated Glycolysis in Keratinocytes

Advanced Science, EarlyView.
In this study, we identify TOLLIP as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. Our findings establish the TOLLIP‐PKM2‐glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.
Xiuhuan Jiang, Guoying Miao, Na Shen, Qingxia Han, Xiaoru Han, Zichang Qiao, Kexin Feng, Zhuo Tan, Yaguang Wang, Xiuhua Liu, Chen Wu, Zhenzhen Yan   +11 more
wiley   +1 more source

MAM‐Localized MANF Counteracts Microinflammatory Stress to Attenuate Mitochondrial Dysfunction and Cataractogenesis in High Myopia

Advanced Science, EarlyView.
Chronic microinflammation in high myopia suppresses MANF in lens epithelial cells. MANF normally resides within MAMs and promotes ubiquitin‐mediated degradation of the ER Ca2+ pump SERCA2. MANF loss causes pathological SERCA2 accumulation, MAM hyperassembly, and disrupted ER‐to‐mitochondria Ca2+ transfer, leading to mitochondrial failure, oxidative ...
Xin Liu, Hao Li, Ching Kang, Dongling Guo, Shuyu Liu, Jiaqi Meng, Zhiqian Huang, Yu Du, Xiangjia Zhu   +8 more
wiley   +1 more source

Targeting p21‐High Senescent Kupffer Cells Nanotherapeutically Potentiates Antitumor Immunity in Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Advanced Science, EarlyView.
Schematic illustration of a biomimetic SKEV@AAV platform targeting p21‐high senescent Kupffer cells (sKCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). p21‐high sKCs accumulate in the PVTT microenvironment and establish an immunosuppressive, SASP‐rich environment that facilitates tumor cell proliferation and immune evasion.
Na Ta, Shuyi Wang, Boyan Zhang, Ning Liu, Yingchen Han, Aoran Liu, Ying Xu, Tingsong Chen, Ye Zhang, Qiuhua Luo, Tao Han   +10 more
wiley   +1 more source

CXCL10/SLC11A1 Axis Exacerbates Septic Liver Injury by Regulating Neutrophil Extracellular Traps Formation to Drive Macrophage Pro‑Inflammatory Polarization

Advanced Science, EarlyView.
In sepsis‐induced liver injury, marked neutrophil infiltration correlates with disease severity. Neutrophil SLC11A1 drives intracellular Fe2+ and ROS via the Fenton reaction, promoting NETs formation. Hepatocyte‐derived CXCL10 recruits neutrophils and activates the JAK/STAT1/SLC11A1 axis, enhancing NETs‐mediated inflammation.
Haiping Lin, Shicong Zheng, Pei Song, Jie Chang, Zewei Chen, Cang Li, Min Yu, Lude Wang, Shian Yu   +8 more
wiley   +1 more source

HMGCR‐Driven Cholesterol Metabolism Promotes Osteoarthritis Progression by Accelerating Synovial Fibroblast Senescence

Advanced Science, EarlyView.
In the pathological context of osteoarthritis (OA), the phosphorylation of AKT1 at Ser473 enhances its binding to Lys140 of Insig1, which facilitates the formation of AKT1–Insig1 complex. Subsequently, the activation of AKT1 promotes the phosphorylation of Insig1 at Ser189, potentially enhancing the dissociation of Insig1 from sterol regulatory element‑
Xiaoqi Zhang, Siru Zhou, Xi Liu, Wei Xiang, Xiuqin Peng, Yu Tian, Song Li, Hailin Wang, Bo Liao, Shunzheng Fang, Runze Jin, Jinhui Wu, Chuanqing Bai, Wei Zhang, Bo Huang, Bingfei Li, Lifeng Chen, Lin Chen, Bin Zhang, Zhenhong Ni   +19 more
wiley   +1 more source

PEAR1 Promotes Glucose Metabolism Reprogramming in Sepsis‐Associated Acute Lung Injury via AARS1‐Mediated HIF‐1α Lactylation

Advanced Science, EarlyView.
This study revealed that a PEAR1/HIF‐1α/ glycolysis/lactate/H3K18la positive feedback loop in PMVECs that drives the development of S‐ALI. Mechanistically, PEAR1 mediates the binding of HIF‐1α to AARS1, leading to the lactylation of HIF‐1α, the primary lactylation site of which is K172.
Shuai Li, Zongqing Lu, Pu Fang, Qingqing Pang, Xianghui Wu, Bo Wang, Min Liang, Jingjing Pan, Haobo Kong, Haijian Cai, Juanjuan Li, Jiaying Kang, Dongsheng Wang, Dunling Xia, Mengmeng Xu, Qinghai You   +15 more
wiley   +1 more source

Structural Polymorphism of polyG Inclusions Revealed by In Situ Cryo‐Electron Tomography

Advanced Science, EarlyView.
Correlative cryo‐electron tomography in primary cortical neurons and NIID mouse brain tissue reveals that polyG inclusions are interconnected ribbon‐like assemblies rather than canonical amyloid fibrils. Multiple compartment‐specific ribbon states show distinct 26S proteasome accessibility, while cytoplasmic ribbons contact and deform ER‐like ...
Yunwen Qian, Yalan Wan, Chen Chen, Xiaoyu Zheng, Wenjing Du, Junhan Yang, Zhihao Quan, Biyu Yang, Jiaxi Yu, Jie Zheng, Zhaoxia Wang, Jianwen Deng, Qiang Guo   +12 more
wiley   +1 more source

SOX5 Orchestrates Malignant Evolution via Promoter‐Centric Chromatin Remodeling in MYC‐Driven B‐Cell Lymphoma

Advanced Science, EarlyView.
In MYC‐enforced B‐cell lymphoma, SOX5 occupies promoter‐proximal regulatory regions and is associated with reduced chromatin accessibility at the PCNP locus. PCNP repression promotes proliferative remodeling by limiting apoptosis and cell‐cycle restraint.
Yiyou Mao, Zhenyuan Jia, Xiao‐Qin Mu, Ruilin Wang, Jianli Ma, Qingyuan Zhang, Yuwei Deng   +6 more
wiley   +1 more source

Computation and Structure‐Guided Arginine Scanning Engineers a Hyperactive AP Endonuclease for Multiplex Viral RNA Sensing

Advanced Science, EarlyView.
Computational and structure‐guided arginine scanning rewires the DNA‐binding interface of APE1 to create APE1‐Evo, a hyperactive yet specific AP endonuclease. Integrated into the NAPTUNE‐V2.0 cascade, APE1‐Evo enables amplification‐free, multiplex viral RNA sensing for dengue virus and influenza A/B, highlighting a general strategy for engineering ...
Junlan Wang, Ting Wu, Feizuo Wang, Boyang Wang, Xin Yu Wong, Senfeng Zhang, Shengsheng Ma, Yao Liu, Fangyao Yao, Zhifeng Zeng, Siyuan Yang, Kunming Liu, Qi Wang, Yilong Wang, Yunxiang Zang, Xiaolong Wang, Xingxu Huang, Shao Li, Quanquan Ji, Tao Hu, Chunyi Hu   +20 more
wiley   +1 more source