Results 101 to 110 of about 197 (188)

Discriminator‐Guided Inverse Folding for Multi‐Property Protein Design

open access: yesAdvanced Science, EarlyView.
Discriminator‐Guided Inverse Folding (DGIF) integrates multiple property predictors trained from single‐property datasets to guide protein sequence generation from a backbone structure. DGIF enables simultaneous improvement of thermostability and solubility without requiring multi‐property annotated datasets and generates designs that move toward the ...
Yuchuan Zheng   +7 more
wiley   +1 more source

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

open access: yesAdvanced Science, EarlyView.
Tumor‐derived lactate activates PSCs through MCT1‐mediated Vps34 lactylation and autophagy. These activated PSCs secrete CXCL9/10, upregulating PD‐1 on CD8+ T cells via the CXCR3/STAT3 axis to foster immunosuppression. Disrupting this metabolic crosstalk by targeting MCT1 effectively sensitizes pancreatic cancer to PD‐1 blockade, presenting a promising
Wenfeng Zhuo   +14 more
wiley   +1 more source

PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction

open access: yesAdvanced Science, EarlyView.
In the pathological state of PD induced by MPP+, the upregulated PRMT9 in dopaminergic neurons translocates into mitochondrion and interacts with DUSP26 and catalyzes its arginine methylation, leading to the ubiquitin‐proteasomal degradation of DUSP26 mediated by Trim32.
Tengfei Liu   +13 more
wiley   +1 more source

Targeting DNGR‐1 with Fangchinoline Elevates Dendritic Cell Antigen Cross‐Presentation‐Mediated Antitumor Immunity in Melanoma

open access: yesAdvanced Science, EarlyView.
Fangchinoline is identified as a small‐molecule DNGR‐1 modulator that enhances dendritic‐cell cross‐presentation of tumor antigens. By engaging DNGR‐1 and activating Syk–Nox2 signaling, it promotes phagosomal ROS, antigen escape, MHC‐I presentation, and CD8+ T‐cell priming, thereby strengthening antitumor immunity and sensitizing tumors to PD‐1 ...
Yuan Liao   +19 more
wiley   +1 more source

Circulating Amino Acid Network Remodeling Reveals Systemic Metabolic Reprogramming Predictive of Colorectal Cancer Recurrence and Metastasis

open access: yesAdvanced Science, EarlyView.
Blood‐based amino acid patterns measured by 19F NMR reveal hidden metabolic changes in colorectal cancer. By analyzing how these amino acids interact as a network, machine learning models identify patients at higher risk of recurrence and metastasis.
Ji‐Yeon Lee   +9 more
wiley   +1 more source

Single‐Cell Reveal GALNT7‐Dependent Ferroptosis Suppression as a Mechanism of Immunotherapy Resistance in Non‐Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Integrated clinical and mechanistic analyses identify GALNT7 as a ferroptosis‐suppressive regulator associated with immunotherapy resistance in non‐small cell lung cancer. GALNT7 depletion promotes lipid peroxidation, mitochondrial dysfunction, and ferroptosis, enhances CD8+ T‐cell activation and IFN‐γ production, and sensitizes tumors to PD‐1 blockade,
Jiadi Gan   +11 more
wiley   +1 more source

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing

open access: yesAdvanced Science, EarlyView.
Excessive mechanical stress activates Piezo1, triggering Ca2+‐dependent cytoskeletal forces that deform the nucleus and reduce H3K4me3. Kdm5c demethylates H3K4me3 at Col2a1 and Runx3 promoters. Kdm5c knockout rescues degradation. Repurposed telmisartan directly inhibits Kdm5c, blocking this axis and showing disease‐modifying efficacy in mouse OA models
Tianyou Kan   +13 more
wiley   +1 more source

p300 Degradation by the p53‐SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity

open access: yesAdvanced Science, EarlyView.
This study identifies p300 as the acetyltransferase that acetylates TBK1 and inhibits its phosphorylation. Activation of the p53‐SIAH1 axis by immune response downregulates p300 expression to sustain innate antiviral immunity. Conditional p300 knockout in alveolar epithelial cells in vivo promotes antiviral responses and suppresses virus replication ...
Huidi Yu   +6 more
wiley   +1 more source

A Modular PLUG‐IN Photosynthetic Chassis With Tunable Thermal Control for Mammalian Systems

open access: yesAdvanced Science, EarlyView.
This work establishes a “plug‐in” chassis compatible with mammalian systems that synchronizes growth, production, and cell‐wall re‐configuration, providing a versatile platform for photosynthetic bioproduction and microalgal synthetic biology. ABSTRACT Microalgae are promising photosynthetic platforms for high‐value compounds, yet their industrial use ...
Qinhua Gan   +13 more
wiley   +1 more source

A Phase‐Resolved Geometric Deep Learning Framework Maps Structural Determinants of Disease‐Associated Protein Aggregation and Guides Suppressor Design

open access: yesAdvanced Science, EarlyView.
SKALE 2.0 maps disease‐associated protein aggregation as a phase‐resolved structural process, linking mutation‐induced geometric perturbations to nucleation, elongation, and suppressor design. Across neurodegenerative proteins, the framework reveals cryptic aggregation vulnerabilities, separates phase‐concordant and phase‐switching mutations, and ...
Jia Shen Sio   +6 more
wiley   +1 more source

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