Results 151 to 160 of about 579,314 (305)

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

open access: yesAdvanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel   +16 more
wiley   +1 more source

Improved Systemic Immunochemotherapy Employing an Oxaliplatin‐TLR7/8 Agonist Prodrug Strategy

open access: yesAdvanced Science, EarlyView.
A platinum(IV) prodrug is developed to systemically deliver the TLR7/8 agonist gardiquimod. Tumor‐targeting is mediated by an albumin‐binding maleimide, which limits premature complex activation. Ox‐Gardi‐Mal accumulates specifically in the tumor, where it activates the immune system.
Michael Gutmann   +15 more
wiley   +1 more source

BGN/MDK Axis in the Melanoma Tumor Microenvironment Strengthens Tumor Malignancy by Modulating Cancer Cells and Cancer‐Associated Fibroblasts Crosstalk

open access: yesAdvanced Science, EarlyView.
This study reveals that m6A regulators cooperatively upregulate BGN in melanoma, promoting malignancy. Within the tumor microenvironment, CAFs show highest BGN expression. The BGN/MDK axis mediates cancer‐stroma crosstalk, driving normal fibroblast (NF) activation and enhancing the pro‐tumor effect of CAFs, highlighting a promising therapeutic target ...
Hao‐ze Shi   +16 more
wiley   +1 more source

Endogenous “Time Bomb” – Mislocalized Phospholipase A2 as a Critical Mediator of Ultra‐Rapid Mortality in Sepsis and Acute Lung Injury

open access: yesAdvanced Science, EarlyView.
Phospholipase A2 (PLA2), a dormant enzyme, becomes lethal when activated—collapsing lungs in minutes. Our dual therapy (DOPS + varespladib) boosts survival from 0% to >90% in sepsis/ALI. A breakthrough for acute lung injury treatment. ABSTRACT This study reveals that phospholipase A2 (PLA2), normally stable and nontoxic, can be activated specifically ...
Jianyu Wang   +7 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

open access: yesAdvanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong   +5 more
wiley   +1 more source

Mechanostimulatory Cues Determine Intestinal Fibroblast Fate and Profibrotic Remodeling in a Physiodynamic Human Gut‐on‐a‐Chip

open access: yesAdvanced Science, EarlyView.
A healthy gut barrier shields underlying fibroblasts from luminal shear forces, illustrating that “good fences make good neighbors.” Barrier damage exposes fibroblasts to shear stress, inducing cell death and the emergence of stress‐adapted, profibrotic fibroblasts. Sustained shear exposure promotes the formation of stiff aggregates of mechanoadapative
Soyoun Min   +6 more
wiley   +1 more source

CRP Deficiency Rescues Periodontitis‐Induced Hippocampal Neurogenesis Impairment by Suppressing OPC‐Derived BMP4 Signaling in Rats

open access: yesAdvanced Science, EarlyView.
Chronic periodontitis elevates circulating CRP, which enters the hippocampus to upregulate BMP4 in oligodendrocyte precursor cells (OPCs), thereby impairing neurogenesis and inducing anxiety/depression‐like behaviors in rats. Counteracting this pathway, CRP deficiency helps confer functional resilience to OPCs.
Lingjie Li   +9 more
wiley   +1 more source

Hierarchical Targeting of TREM2+ Myeloid Cells via Acid‐Triggered OMVs Reprogram Immunosuppression and Suppress Osteolysis in Bone‐Metastatic TNBC

open access: yesAdvanced Science, EarlyView.
This study developed a hierarchical targeting nanoplatform, siTREM2@ETP‐PEOz‐OMVs, against triple‐negative breast cancer (TNBC) bone metastasis. It precisely delivers therapeutic siTREM2 to monocytes/macrophages within the metastatic niche. This intervention dually regulates cell fate: reprogramming immunosuppressive macrophages and inhibiting ...
Fanglu Chen   +12 more
wiley   +1 more source

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