Yongrui Hai
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View article: An immunometabolic prodrug strategy overcomes DHODH inhibitor resistance in refractory melanoma
An immunometabolic prodrug strategy overcomes DHODH inhibitor resistance in refractory melanoma Open
Background Metabolic reprogramming, particularly upregulated de novo pyrimidine biosynthesis, drives cancer progression and immune evasion. Dihydroorotate dehydrogenase (DHODH), a key enzyme in this pathway, is a promising therapeutic targ…
View article: Immunometabolic Rewiring of Dendritic Cells to Overcome Glutamine‐Driven Immune Suppression in Colorectal Cancer
Immunometabolic Rewiring of Dendritic Cells to Overcome Glutamine‐Driven Immune Suppression in Colorectal Cancer Open
The immunosuppressive tumor microenvironment imposes significant metabolic constraints that impair dendritic cell (DC) maturation and antigen presentation, ultimately undermining antitumor immunity. In colorectal cancer (CRC), elevated glu…
View article: Dihydroorotate dehydrogenase inhibition activates STING pathway and pyroptosis to enhance NK cell-dependent tumor immunotherapy
Dihydroorotate dehydrogenase inhibition activates STING pathway and pyroptosis to enhance NK cell-dependent tumor immunotherapy Open
View article: Neuroimmune circuit mediates apathy in cancer cachexia
Neuroimmune circuit mediates apathy in cancer cachexia Open
View article: Innovative PDK1‐Degrading PROTACs Transform Cancer Aerobic Glycolysis and Induce Immunogenic Cell Death in Breast Cancer
Innovative PDK1‐Degrading PROTACs Transform Cancer Aerobic Glycolysis and Induce Immunogenic Cell Death in Breast Cancer Open
Cancer cells are characterized by the Warburg effect, which hijacks glycolysis and hinders OXPHOS. Pyruvate dehydrogenase kinase 1 (PDK1) is a key modulator in the Warburg effect and is highly expressed in tumor cells. We utilize PROTAC te…
View article: Inhibition of DHODH Activates Pyroptosis and cGAS-STING Pathways to Enhance NK cell Infiltration Mediated Anti-tumor Immunity in Melanoma
Inhibition of DHODH Activates Pyroptosis and cGAS-STING Pathways to Enhance NK cell Infiltration Mediated Anti-tumor Immunity in Melanoma Open
Cancer cells are heavily reliant on de novo pyrimidine synthesis. Suppression of pyrimidine metabolism directly inhibits tumor growth and fosters immune activation within the tumor microenvironment. Dihydroorotate dehydrogenase (DHODH), a …
View article: A Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy
A Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy Open
Sepsis, a life-threatening inflammatory disorder characterized by multiorgan failure, arises from a dysregulated immune response to infection. Modulating macrophage polarization has emerged as a promising strategy to control sepsis-associa…
View article: A STING agonist prodrug reprograms tumor-associated macrophage to boost colorectal cancer immunotherapy
A STING agonist prodrug reprograms tumor-associated macrophage to boost colorectal cancer immunotherapy Open
Rationale: Tumor-associated macrophages (TAMs) are abundant in colorectal cancer (CRC), correlating with immunosuppression and disease progression. Activation of the stimulator of interferon gene (STING) signaling pathway in TAMs of…
View article: A platinum(IV)–artesunate complex triggers ferroptosis by boosting cytoplasmic and mitochondrial lipid peroxidation to enhance tumor immunotherapy
A platinum(IV)–artesunate complex triggers ferroptosis by boosting cytoplasmic and mitochondrial lipid peroxidation to enhance tumor immunotherapy Open
Ferroptosis is an iron‐dependent cell death form that initiates lipid peroxidation (LPO) in tumors. In recent years, there has been growing interest on ferroptosis, but how to propel it forward translational medicine remains in mist. Altho…
View article: A novel mitochondria-targeting DHODH inhibitor induces robust ferroptosis and alleviates immune suppression
A novel mitochondria-targeting DHODH inhibitor induces robust ferroptosis and alleviates immune suppression Open
Dihydroorotate dehydrogenase (DHODH)-mediated ferroptosis defense is a targetable vulnerability in cancer. Currently, only a few DHODH inhibitors have been utilized in clinical practice. To further enhance DHODH targeting, we introduced th…
View article: Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy
Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy Open