A5024486204- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cancer, Hypoxia, and Metabolism
- Fluid Dynamics and Turbulent Flows
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- Advancements in Solid Oxide Fuel Cells
- Gut microbiota and health
- Particle Dynamics in Fluid Flows
- Immunotherapy and Immune Responses
- Fluid Dynamics and Vibration Analysis
- Histone Deacetylase Inhibitors Research
- Aeolian processes and effects
- Chemical Looping and Thermochemical Processes
- Computational Drug Discovery Methods
- Natural product bioactivities and synthesis
- Mesenchymal stem cell research
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Cancer-related molecular mechanisms research
- Lattice Boltzmann Simulation Studies
- Inflammatory Bowel Disease
- ATP Synthase and ATPases Research
- Amino Acid Enzymes and Metabolism
Shanghai University
2016-2025
Army Medical University
2013-2025
Southwest Hospital
2013-2025
Shandong University
2023-2024
Shanghai Institute of Materia Medica
2015-2024
Chinese Academy of Sciences
2015-2024
Tianjin Third Central Hospital
2019-2024
Tianjin Medical University
2019-2024
Chinese PLA General Hospital
2021-2024
Changchun Institute of Applied Chemistry
2024
Abstract One of the biggest hurdles for development metabolism-targeted therapies is to identify responsive tumor subsets. However, metabolic vulnerabilities most human cancers remain unclear. Establishing link between signatures and oncogenic alterations receptor tyrosine kinases (RTK), well-defined cancer genotypes, may precisely direct intervention a broad patient population. By integrating metabolomics transcriptomics, we herein show that RTK activation causes distinct preference....
An efficient one-pot chemoenzymatic glycoengineering technology introduced reactive functional groups (azido <italic>etc.</italic>) onto IgG Fc <italic>N</italic>-glycans for preparation of novel glycosite-specific ADCs as anticancer reagents.
Nanozymes, exemplified by metal nanoparticles, have shown promise in the fields of biological diagnostics and therapeutics. However, their practical application is often hindered aggregation or deactivation complex systems. Here, we develop a DNA-engineered nanozyme coating to preserve peroxidase-like catalytic activity platinum nanoparticles environments. We employed thiol-modified single-stranded DNA coat through metal–sulfur interaction. found that negatively charged prevents high-salt...
Abstract Pyruvate dehydrogenase kinase PDK1 is a metabolic enzyme responsible for switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells, general hallmark of malignancy termed the Warburg effect. Herein we report identification JX06 as selective covalent inhibitor cells. forms disulfide bond with thiol group conserved cysteine residue (C240) based on recognition hydrophobic pocket adjacent ATP enzyme. Our investigations mechanism suggested that...
Concurrent inhibition of Janus kinase (JAK) and histone deacetylase (HDAC) could potentially improve the efficacy HDAC inhibitors in treatment cancers resolve problem inhibitor resistance some tumors. Here, a novel series pyrimidin-2-amino-pyrazol hydroxamate derivatives as JAK dual was designed, synthesized, evaluated, among which 8m possessed potent balanced activities against both JAK2 HDAC6 with half-maximal inhibitory concentration at nanomolar level. exhibited improved...
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on basis scaffold 16, we identify two novel types disulfide-based PDK1 inhibitors. The potent analogue, 3a, effectively inhibits both at molecular (kinact/Ki = 4.17 × 103 M-1 s-1) cellular level (down to 0.1 μM). In contrast 3a is a...
It remains a big challenge to develop HDAC inhibitors effective for solid tumors. Previous studies have suggested that the feedback activation of JAK-STAT3 pathway represents key mechanism leading resistance in breast cancer, suggesting therapeutic promise JAK/HDAC dual inhibitors. In this work, we discovered series pyrrolo[2,3-d]pyrimidine-based derivatives as potent JAK and Especially, compounds 15d 15h potently inhibited JAK1/2/3 HDAC1/6 displayed antiproliferative proapoptotic activities...
Abstract Although androgen ablation therapy is effective in treating primary prostate cancers, a significant number of patients develop incurable castration-resistant disease. Recent studies have suggested potential synergy between vaccination and ablation, yet the enhanced T-cell function transient. Using defined tumor antigen model, UV-8101-RE, we found that concomitant castration significantly increased frequency antigen-specific CD8+ T cells early after immunization wild-type mice....
Targeting metabolic enzymes is believed to provide new therapeutic opportunities for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) a glycolytic enzyme that importantly coordinates glycolysis, pentose phosphate pathway (PPP) flux and serine biosynthesis in cells hence gains increasing interest of inhibitor discovery. Only few PGAM1 inhibitors have been reported the molecular potency remains very limited. In an effort discover inhibitors, we carried out biochemical assay-based screen was...
Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses treatment. However, in human cancers with diverse oncogenic activation, how pathways cooperate modifiers regulate the mark is poorly understood. We herein discover hedgehog (Hh) pathway reprograms methylation landscape breast cancer, especially triple-negative cancer (TNBC). This facilitates...
Abstract Intervention of the gut microbiome is a promising adjuvant strategy in cancer immunotherapy. Chemotherapeutic agents are recognized for their substantial impacts on microbiome, yet therapeutic potential as modulators remains uncertain, due to complexity microbiome‐host‐drug interactions. Here, it showed that low‐dose chemotherapy preferentially shapes ileal augment extraintestinal immune response anti‐programmed death‐1 (anti‐PD‐1) therapy without causing intestinal toxicity....
This study investigates the effects of wave coupling on oceanic and atmospheric responses to Tropical Storm Choi-wan (2021) using a coupled ocean-atmosphere model. Modeled tropical cyclone metrics ocean are compared with without waves. A dependent surface roughness scheme is evaluated understand influence induced changes in sea temperature (SST), currents, fields. The results reveal that significantly improves representation SST cooling vertical thermal structures. outperforms capturing...
Phytochemical investigation of the 70% acetone extract Croton crassifolius roots afforded eight new diterpenoids, crassins A–H (1–8), and 19 known compounds. The structures compounds were determined by spectroscopic methods, their absolute configurations electronic circular dichroism, single-crystal X-ray diffraction analysis, comparison with literature data, biogenetic considerations. Crassins A (1) B (2) are ring B-rearranged whereas crassin C (3) is a A-rearranged diterpenoid. Crassin H...
Being the rate-limiting enzyme within serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH) is abnormally overexpressed in numerous malignant tumor cells and a promising target for cancer treatment. Here, we report series of novel PHGDH inhibitors using focused compound screening structural optimization approach. The lead D8 displayed good enzymatic inhibitory activity (IC50 = 2.8 ± 0.1 μM), high binding affinity (Kd 2.33 sensitivity to cell lines with gene amplification or...