Results 81 to 90 of about 232,598 (258)

Lactate‐Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo‐Immunotherapy by Suppressing Tumor PANoptosis

Advanced Science, EarlyView.
Tumor‐derived lactate establishes a metabolic lock that drives chemo‐immunotherapy resistance by suppressing PANoptosis. Mechanistically, KAT8 lactylates the mitochondrial translocator ANT2, which recruits PGAM5 to dephosphorylate CypD. This cascade restricts mitochondrial permeability transition pore opening, preventing pro‐inflammatory mtDNA leakage.
Sen Zhong, Wenlong Chen, Fanglong Liu, Shengyi Zhou, Bolin Yu, Yuying Wang, Xiqian Zhou, Xuehui Wang, Diya Liu, Zhuoyu Zhang, Xinran Wang, Mounia Lalouly, Yiwen Li, Zhefei Du, Tao Yan, Zhihui Xiao, Zhou Zhou, Huanhuan Zhu, Fengyuan Qian, Bowen Zheng, Lin Fang   +20 more
wiley   +1 more source

CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation

EMBO Reports
While cancer cells overexpress lactate dehydrogenase A (LDHA) to support glycolytic flux and lactate production, the role of LDHB—which preferentially catalyzes lactate oxidation—remains unclear. Here, we demonstrate that LDHB, but not LDHA, is essential
Mengting Liu, Aoxing Cheng, Weiyi You, Jiaxin Wu, Chenxu Dai, Ting Wang, Ying Wu, Fumei Zhong, Jue Shi, Yingying Du, Zhonghuai Hou, Ping Gao, Ke Ruan, Yi Yang, Yuzheng Zhao, Kaiguang Zhang, Zhenye Yang, Jing Guo   +17 more
doaj   +1 more source

Slc44a2 Deficiency Unveils an IFN‐I–Dependent Feedback Control of pDC Egress

Advanced Science, EarlyView.
Working model of SLC44A2‐mediated maintenance of pDC homeostasis. This model illustrates two central mechanisms by which SLC44A2 regulates pDC homeostasis: (1) SLC44A2 limits IFN‐I production by exporting amino acids (T, N, Q), thereby preventing spontaneous pDC activation.
Ruiqun Chen, Tao Wu, Zhen Shi, Ravi Kumar Verma, Linlin Sheng, Lei Tao, Mingming Yang, Yuchen Wang, Conggang Zhang, Hao Fan, Li Wu, Ligong Chen   +11 more
wiley   +1 more source

Fatty Acid Binding Protein 5 Mediates Astrocytic Pyroptosis and Neuroinflammation in Epilepsy via cGAS/STING Pathway

Advanced Science, EarlyView.
Astrocytic FABP5 promotes mitochondrial stress, cGAS‐STING pathway activation, pyroptosis, and neuroinflammation in epilepsy, contributing to seizure pathology. Genetic targeting of FABP5 or pharmacological inhibition of STING alleviates epileptic phenotypes, highlighting a potential therapeutic strategy for epilepsy.
Chen Chen, Yao Zhao, Yangye Lian, Yifei Hou, Lifen Gong, Tingting Wu, Yulin Yang, Jiaqi Zhu, Xin Wang, Kaihua Zhang, Jing Ding   +10 more
wiley   +1 more source

Porcine Deltacoronavirus M Protein Binds NLRP3 to Promote Inflammasome Assembly via Competition with TRIM31

Advanced Science, EarlyView.
Porcine deltacoronavirus (PDCoV) infection induces severe intestinal inflammation and acute diarrhea in piglets, yet the molecular mechanism remains incompletely understood. The M protein activates NLRP3 inflammasome through dual mechanisms: direct binding to the NLRP3 LRR domain and disruption of TRIM31‐mediated K48‐linked ubiquitination.
Jinhui Hou, Fangfang Han, Anqi Liu, Yang Yu, Rui Zhao, Zhengting Shi, Yanrong Lv, Jinli Liu, Shaopo Zu, Zhanyong Wei, Jin Yuan, Hui Hu   +11 more
wiley   +1 more source

Gene Correction Enhances Dopaminergic Cell Therapy in a Nonhuman Primate Model of Parkinson's Disease

Advanced Science, EarlyView.
LRRK2‐mutant induced pluripotent stem cells (iPSCs) were derived from a patient with Parkinson's disease (PD). Using CRISPR/Cas9–mediated gene editing, the pathogenic LRRK2 mutations were precisely corrected, and isogenic dopaminergic neural progenitor cells (DA‐NPCs) were subsequently generated.
Qing Yan, Chongchong Xu, Jiangmei Gao, Pu Wang, Qingling Wu, Ying Jin, Binyan Lu, Mu Li, Mingting Shao, Bihai Li, Zhenghui Su, Yijng Zhang, Jianhuan Chen, Haojie An, Mengyao Huang, Xiaoji Zhuang, Yuhui Shen, Fenglin Wang, Nana Xu, Yiyan Liu, Lei Tang, Xiuling Zhong, Minyan Zhong, Jiecong Chen, Zhenhuang Wang, Xingrong Luo, Sheng Liu, RuiFeng Liu, Ling Zhang, Junhua Rao   +29 more
wiley   +1 more source

ANXA2+ Small Extracellular Vesicles Drive Chemoresistance in Anaplastic Thyroid Cancer by Promoting XRCC5 Lactylation and Enhancing Non‐Homologous End‐Joining Repair

Advanced Science, EarlyView.
ANXA2+ sEVs promote cisplatin resistance in ATC by stabilizing the SRC/LDHA interaction, increasing LDHA phosphorylation and activity, and lactate production. Elevated lactate levels promote KAT5‐mediated lactylation of XRCC5 at lysine 265, enhancing its binding to XRCC6.
Shanshan Su, YiShan Xiong, Yuxuan Liang, Xiang Min, Daofeng Dai   +4 more
wiley   +1 more source

Penfluridol Triggers GSDME‐Mediated Immunogenic Pyroptosis to Potentiate Antitumor Immunotherapy

Advanced Science, EarlyView.
A high‐throughput screen of FDA‐approved antipsychotics identifies penfluridol as a potent pyroptosis inducer acting via direct TTI1 inhibition. This triggers TNFA‐NFKB signaling and caspase‐8/‐3‐dependent GSDME cleavage. The compound stimulates antitumor immunity alone and synergizes with anti‐PD‐1 therapy, while low TTI1 expression emerges as a ...
Linfeng Li, Daishi Li, Danyao Chen, Yating Dian, Lei Yao, Hui Su, Ziyu Guo, Deze Zhao, Zihua Wu, Furong Zeng, Chunfang Zhang, Guangtong Deng   +11 more
wiley   +1 more source

Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice

Fundamental Research
The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and ...
Xiaqing Ma, Qi Qi, Wenying Wang, Min Huang, Haiyan Wang, Limin Luo, Xiaotao Xu, Tifei Yuan, Haibo Shi, Wei Jiang, Tao Xu   +10 more
doaj   +1 more source

Biomimetic Nanoplatform for Dual Target Nano‐Metabolic Therapy in Diabetes‐Associated Biofilm Infections

Advanced Science, EarlyView.
A biomimetic GOx/Arg‐loaded nanoplatform produces nitric oxide through an in situ catalytic cascade reaction, enabling dual‐target metabolic regulation in diabetes‐associated biofilm infections. Bacterial metabolism is disrupted, and macrophage immunometabolism is reprogrammed, resulting in biofilm eradication, immune restoration, and enhanced ...
Mingzhang Li, Yonglong Li, Jiren Yan, Changming Wang, Jinlong Yu, Feng Jiang, Boyong Wang, Yi Yang, Deyi Ding, Jin Tang, Pei Han, Botao Song, Geyong Guo, Hao Shen   +13 more
wiley   +1 more source