A5014668342- Advanced Neuroimaging Techniques and Applications
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Advanced MRI Techniques and Applications
- Cancer-related Molecular Pathways
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Memory and Neural Mechanisms
- Cerebral Palsy and Movement Disorders
- interferon and immune responses
- Functional Brain Connectivity Studies
- Immune Response and Inflammation
- Memory Processes and Influences
- RNA and protein synthesis mechanisms
- Psychosomatic Disorders and Their Treatments
- COVID-19 Clinical Research Studies
- Click Chemistry and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Lung Cancer Treatments and Mutations
- MRI in cancer diagnosis
- HER2/EGFR in Cancer Research
- Viral gastroenteritis research and epidemiology
- Cancer, Hypoxia, and Metabolism
Duke University
2024
National Health Research Institutes
2011-2021
Massachusetts General Hospital
2021
Harvard University
2021
McLean Hospital
2021
National Yang Ming Chiao Tung University
2009-2020
Johns Hopkins Medicine
2013-2019
Johns Hopkins University
2009-2019
National Tsing Hua University
2006-2008
George Washington University
2004-2006
SARS‐CoV is the causative agent of severe acute respiratory syndrome (SARS). The virally encoded 3C‐like protease (3CLPro) has been presumed critical for viral replication in infected host cells. In this study, we screened a natural product library consisting 720 compounds inhibitory activity against 3CLPro. Two were found to be inhibitive: tannic acid (IC50 = 3 µM) and 3‐isotheaflavin‐3‐gallate (TF2B) 7 µM). These two belong group polyphenols tea. We further investigated 3CLPro‐inhibitory...
Functional imaging studies of healthy participants and previous lesion have provided evidence that empathy involves dissociable cognitive functions rely on at least partially distinct neural networks can be individually impaired by brain damage. These converge in support the proposal affective empathy—making inferences about how another person feels—engages following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, cingulate temporal pole, amygdala temporoparietal junction. We...
The Asp-Phe-Gly (DFG) motif plays an important role in the regulation of kinase activity. Structure-based drug design was performed to compounds able interact with DFG motif; epidermal growth factor receptor (EGFR) selected as example. Structural insights obtained from EGFR/2a complex suggested that extension meta-position on phenyl group (ring-5) would improve interactions motif. Indeed, introduction N,N-dimethylamino tail resulted 4b, which showed almost 50-fold improvement inhibition...
Objective Common neurological diseases or injuries that can affect the right hemisphere, including stroke, traumatic brain injury, and frontotemporal dementia, disrupt emotional empathy—the ability to share in make inferences about how other people feel. This impairment negatively impacts social interactions relationships. Accumulating evidence indicates empathy depends on coordinated functions of orbitofrontal cortex, anterior insula, cingulate, temporal pole, amygdala, but few studies have...
The coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is a health threat worldwide. Viral main protease (M pro , also called 3C‐like [3CL ]) therapeutic target for drug discovery. Herein, we report that GC376, broad-spectrum inhibitor targeting M in the picornavirus-like supercluster, potent encoded SARS-CoV-2, with half-maximum inhibitory concentration (IC 50 ) of 26.
Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s (AD), major form dementia, β-amyloid (Aβ) levels in blood increased; however, impact elevated Aβ on progression COVID-19 remains largely unknown. Here, our findings demonstrate Aβ1-42, but not Aβ1-40, bound various viral proteins a preferentially high affinity for spike protein S1 subunit (S1) acute respiratory syndrome 2 (SARS-CoV-2)...
3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting 960 commercially available drugs biologically active substances was screened inhibition SARS-CoV 3CL protease. Potent achieved using mercury-containing compounds thimerosal phenylmercuric acetate, as well hexachlorophene. As well, 1-10 microM each inhibited viral replication in Vero E6 cell culture....
Aurora kinases have emerged as attractive targets for the design of anticancer drugs. Through structure-based virtual screening, novel pyrazole hit 8a was identified kinase A inhibitor (IC50 = 15.1 μM). X-ray cocrystal structure in complex with protein revealed C-4 position ethyl carboxylate side chain a possible modification site improving potency. On basis this insight, bioisosteric replacement ester amide linkage and changing substituent to hydrophobic 3-acetamidophenyl ring led...
In this paper, we propose a novel method for parcellating the human brain into 193 anatomical structures based on diffusion tensor images (DTIs). This was accomplished in setting of multi-contrast diffeomorphic likelihood fusion using multiple DTI atlases. are modeled as high dimensional fields, with each voxel exhibiting vector valued feature comprising mean diffusivity (MD), fractional anisotropy (FA), and fiber angle. For structure, probability distribution element is mixture Gaussians,...
A structure-based virtual screening strategy, comprising homology modeling, ligand–support binding site optimization, screening, and structure clustering analysis, was developed used to identify novel tryptophan 2,3-dioxygenase (TDO) inhibitors. Compound 1 (IC50 = 711 nM), selected by showed inhibitory activity toward TDO subjected structural modifications molecular docking studies. This resulted in the identification of a potent selective inhibitor (11e, IC50 30 making it potential compound...
Enterovirus 71 (EV71) causes serious diseases in humans. The aim of this study was to examine the effects aurintricarboxylic acid (ATA) on EV71 replication and explore underlying mechanism. To measure activity ATA inhibiting cytopathic effect (CPE) EV71, a cell-based neutralization (inhibition virus-induced CPE) assay performed. further confirmed using plaque reduction viral yield assays. A time addition performed identify mechanisms ATA's anti-EV71 activity. We examined following key steps...
One goal of computational anatomy (CA) is to develop tools accurately segment brain structures in healthy and diseased subjects. In this paper, we examine the performance complexity such segmentation framework large deformation diffeomorphic metric mapping (LDDMM) registration method with reference atlases parameters. First report application a multi-atlas approach define basal ganglia kids' brains. The accuracy compared single atlas LDDMM implementation two state-of-the-art...
The overexpression of HER2/neu and EGFR receptors plays important roles in tumorigenesis tumor progression.Targeting these two simultaneously can have a more widespread application early diagnosis cancers.In this study, new multifunctional nanoparticles (MnMEIO-CyTE777-(Bis)-mPEG NPs) comprising manganese-doped iron oxide nanoparticle core (MnMEIO), silane-amino functionalized poly(ethylene glycol) copolymer shell, near infrared fluorescence dye (CyTE777), covalently conjugated anti-HER2/neu...
ABSTRACT Epstein-Barr virus (EBV) lytic replication involves complex processes, including DNA synthesis, cleavage and packaging, virion egress. These processes require many different gene products, but the mechanisms of their actions remain unclear, especially for packaging. According to sequence homology analysis, EBV BALF3, encoded by third leftward open reading frame BamHI-A fragment in viral genome, is a homologue herpes simplex type 1 UL28. This product believed possess properties...
Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed lives of 900 victims. The high mortality rate resulted, at least in part, from absence definitive treatment protocols or therapeutic agents. Although virus spreading has been contained, due preparedness planning, including successful development antiviral drugs against SARS-CoV, necessary for possible reappearance...