A5071618218- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Hearing, Cochlea, Tinnitus, Genetics
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Vestibular and auditory disorders
- Biochemical effects in animals
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Heme Oxygenase-1 and Carbon Monoxide
- Neuroscience and Neuropharmacology Research
- HIV/AIDS Research and Interventions
- Traditional Chinese Medicine Analysis
- Natural product bioactivities and synthesis
- Biochemical and Molecular Research
- Computational Drug Discovery Methods
- Hepatitis B Virus Studies
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- S100 Proteins and Annexins
- Hemoglobin structure and function
- Protein Kinase Regulation and GTPase Signaling
- Cancer Research and Treatments
- Inorganic Chemistry and Materials
- Plant-based Medicinal Research
United States Military Academy
2020-2025
Inner Mongolia Medical University
2019-2025
Institute of Laboratory Animal Science
2020-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2020-2024
Buchang Pharma (China)
2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2009-2024
Shanghai Jiao Tong University
2017-2024
Shandong Normal University
2024
Vrije Universiteit Amsterdam
2024
Wuchang University of Technology
2024
We developed a transgenic mouse to permit conditional and selective ablation of hair cells in the adult utricle by inserting human diphtheria toxin receptor ( DTR ) gene into Pou4f3 gene, which encodes cell-specific transcription factor. In wild-type mice, administration (DT) caused no significant cell loss. +/ DT treatment reduced numbers 6% normal 14 days post-DT. Remaining were located primarily lateral extrastriola. Over time, increased these regions, reaching 17% untreated mice 60...
Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but nature of interaction between macrophages and sensory structures inner ear remains unclear. The present study examined role fractalkine signaling regulating injury-evoked behavior following selective ablation cochlear hair cells. We used a novel transgenic mouse model which human diphtheria toxin receptor (huDTR) is selectively expressed under control Pou4f3 , cell-specific...
Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, learning has yet to well established a laboratory mammal. Mice are potentially an excellent model organism studying mechanisms underlying communication. vocalize different social contexts, whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship emitted by...
During nervous system development, critical periods are usually defined as early during which manipulations dramatically change neuronal structure or function, whereas the same in mature animals have little no effect on property. Neurons ventral cochlear nucleus (CN) dependent excitatory afferent input for survival a period of development. Cochlear removal young mammals and birds results rapid death target neurons CN. older neuron death. However, extent to hair-cell-specific activity...
Abstract Breast cancer patients often have recurrence and metastasis after surgery. Predicting the risk of for a breast patient is essential development precision treatment. In this study, we proposed novel multi-modal deep learning prediction model by integrating hematoxylin & eosin (H&E)-stained histopathological images, clinical information gene expression data. Specifically, segmented tumor regions in H&E into image blocks (256 × 256 pixels) encoded each block 1D feature...
Abstract Background Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric Methods Human cell lines SGC-7901 MKN-45 were treated with diverse concentrations MJ. Cell viability, proliferation, capabilities cells measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel tube...
Abstract The inferior colliculus (IC) is a major center of integration in the ascending as well descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play key role. When normal input to system decreased, balance between excitation inhibition IC disturbed. We examined global changes gene expression rat 3 21 days following bilateral deafening, using Affymetrix GeneChip arrays focused our analysis on neurotransmission‐related genes. Over 1400 probe sets...
We describe the research that led to discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with "flat" GT1 mutant profile. This NS5A contains unique tetracyclic indole core while maintaining imidazole-proline-valine Moc motifs our previous inhibitors. Compound is currently in early clinical trials and under evaluation as part an all-oral DAA regimen for treatment chronic infection.
The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development CNS directed therapeutics. We others have investigated muscarinic acetylcholine 4 (M4) positive allosteric modulators (PAMs) for the treatment symptoms associated with neuropsychiatric disorders. In this article, we describe synthesis, vitro, vivo characterization a series central pyridine-related M4 PAMs that can be conveniently radiolabeled...
Acinetobacter baumannii is a Gram-negative pathogen responsible for pneumonia and wound, bloodstream, urinary tract infections, particularly patients in intensive care units. Using phenotypic screening we have identified novel class of small molecule inhibitors that potent highly selective antibacterial activity against baumannii. Resistance selection the molecular target as MsbA, an essential ABC transporter functions by flipping lipid A across inner membrane most gram-negative bacteria....
Background: Cisplatin is an extensively used anti-neoplastic agent for the treatment of various solid tumors. However, a high incidence severe ototoxicity accompanied by its use in clinic. Currently, no drugs or therapeutic strategies have been approved cisplatin-induced FDA. Purpose: The purpose this study was to investigate otoprotective effects dexamethasone (DEX)-loaded silk-polyethylene hydrogel (DEX-SILK) following round window membrane administration mouse model. Methods: morphology,...
The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes mutants, lacking models inhibitor/protein complexes for rational inhibitor design. As part ongoing efforts inhibition at Merck, we now describe a novel series chromane containing inhibitors. SAR studies around "Z" group tetracyclic...
Abstract Background Ototoxicity is one of the major side effects platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, generally believed be produced by excessive generation reactive oxygen species (ROS) in inner ear, thus leading development various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) an interesting candidate new therapies for preventing and treating oxidative...
[ 11 C]MK-6884 is an M4R-specific PET tracer for quantifying target engagement in brain and providing insights into AD neuropathology.