- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Protein Structure and Dynamics
- Protein Degradation and Inhibitors
- Microbial Natural Products and Biosynthesis
- Acute Ischemic Stroke Management
- Epigenetics and DNA Methylation
- Chemical Synthesis and Analysis
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Lung Cancer Treatments and Mutations
- Influenza Virus Research Studies
- Click Chemistry and Applications
- Oral Health Pathology and Treatment
- Enzyme Structure and Function
- Genomics, phytochemicals, and oxidative stress
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Signaling Pathways in Disease
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Cholinesterase and Neurodegenerative Diseases
- Autophagy in Disease and Therapy
Taipei Medical University
2016-2025
Wan Fang Hospital
2020-2025
China Medical University Hospital
2021-2025
China Medical University
2021-2025
Academia Sinica
2014-2024
National Yang Ming Chiao Tung University
2006-2023
Drug Discovery Laboratory (Norway)
2016-2023
National Institute of Neurological Disorders and Stroke
2020-2022
Institute of Biological Chemistry, Academia Sinica
2022
National Institutes of Health
2020-2022
Abstract Background Pharmacological interactions are useful for understanding ligand binding mechanisms of a therapeutic target. These often inferred from set active compounds that were acquired experimentally. Moreover, most docking programs loosely coupled the stages (binding-site and preparations, virtual screening, post-screening analysis) structure-based screening (VS). An integrated VS environment, which provides friendly interface to seamlessly combine these identify pharmacological...
An overview on the electrostatic discharge (ESD) protection circuits by using silicon controlled rectifier (SCR)-based devices in CMOS ICs is presented. The history and evolution of SCR device used for on-chip ESD introduced. Moreover, two practical problems (higher switching voltage transient-induced latchup issue) limiting use SCR-based are reported. Some modified structures trigger-assist circuit techniques to reduce discussed. solutions overcome issue also discussed safely apply IC products.
Abstract This study aimed to evaluate the sensitivity of AI in screening acute leukemia and its capability classify either physiological or pathological cells. Utilizing an orientation tube (ALOT), one protocols Euroflow, flow cytometry efficiently identifies various forms leukemia. However, analysis can be time-consuming work. retrospective included 241 patients who underwent examination using ALOT between 2017 2022. The collected data were used train artificial intelligence deep learning....
The KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A-KDM4D), which selectively remove the methyl group(s) from tri/dimethylated 9/36 of H3, modulate transcriptional activation and genome stability. overexpression KDM4A/KDM4B in prostate cancer their association with androgen receptor suggest that are potential progression factors for cancer. Here, we report crystal structure KDM4B·pyridine 2,4-dicarboxylic acid·H3K9me3 ternary complex, revealing core active-site region a...
This paper reports the development of a series 5-aroylindolyl-substituted hydroxamic acids. N-Hydroxy-4-((5-(4-methoxybenzoyl)-1H-indol-1-yl)methyl)benzamide (6) has potent inhibitory selectivity against histone deacetylase 6 (HDAC6) with an IC50 value 3.92 nM. It decreases not only level phosphorylation tau proteins but also aggregation proteins. Compound shows neuroprotective activity by triggering ubiquitination. In animal models, compound is able to ameliorate impaired learning and...
The clinical dementia rating (CDR) scale is commonly used to diagnose due Alzheimer's disease (AD). sum of boxes the CDR (CDR-SB) has recently been emphasized and applied interventional trials for tracing progression cognitive impairment (CI) in early stages AD. We aimed study influence baseline CDR-SB on or reversion normal cognition (NC).
Abstract Regulation of CO 2 fixation in cyanobacteria is important both for the organism and global carbon balance. Here we show that phosphoketolase Synechococcus elongatus PCC7942 ( Se XPK) possesses a distinct ATP-sensing mechanism, where drop ATP level allows XPK to divert precursors RuBisCO substrate away from Calvin–Benson–Bassham cycle. Deleting gene increased particularly during light–dark transitions. In high-density cultures, Δxpk strain showed 60% increase unexpectedly resulted...
Alzheimer's disease (AD) is a devastating neurodegenerative with more than 50 million people suffer from it. Unfortunately, none of the currently available drugs able to improve cognitive impairment in AD patients. Urolithin A (UA) metabolite obtained ellagic acid and ellagitannin through intestinal flora, it has antioxidant anti-inflammatory properties. Previous reports found that UA had neuroprotective effects an animal model, but detailed mechanism still needs be elucidated. In this...
Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue important and urgent. In study, we found that targeting USP24 by specific inhibitors, USP24-i its analogues, dramatically activated autophagy interphase mitotic periods of lung cells inhibiting E2F4 TRAF6, respectively. functional knockout,
Purpose: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms.Experimental Design: Autophagy flux, morphology, intracellular organelles were evaluated by Western blotting, transmission electron microscope, fluorescence microscope. Molecular docking surface plasmon resonance assay performed identify drug-protein interaction....
Prostate cancer is a prevalent malignancy among men globally, and androgen deprivation therapy the conventional first-line treatment for metastatic prostate cancer. While efficacious in castration-sensitive cancer, it remains less effective castration-resistant cases. Transcriptional dysregulation well-established hallmark of targeting proteins involved transcriptional regulation, such as cyclin-dependent kinase 8 (CDK8), has become an attractive therapeutic strategy. CDK8, nuclear...
Abstract Crown ethers are small, cyclic polyethers that have found wide‐spread use in phase‐transfer catalysis and, to a certain degree, protein chemistry. readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein‐crown ether co‐crystals grown presence 18‐crown‐6. then employed biophysical methods molecular dynamics simulations compare these complexes with corresponding apoproteins similar...
Abstract Histone deacetylases (HDAC) contain eighteen isoforms that can be divided into four classes. Of these isoform enzymes, class IIa (containing HDAC4, 5, 7 and 9) target unique substrates, some of which are client proteins associated with epigenetic control. Class HDACs reportedly neuronal disorders, making therapeutic targets for treating neurodegenerative diseases. Additionally, reported HDAC inhibitors hydroxamate moiety chelates zinc ion to become the cofactor enzymes. However,...