A5051730015- Hearing, Cochlea, Tinnitus, Genetics
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Muscle Physiology and Disorders
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Ocular Diseases and Behçet’s Syndrome
- Cellular Mechanics and Interactions
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Neurological Disease Mechanisms and Treatments
- Cytomegalovirus and herpesvirus research
- Cellular transport and secretion
- Cancer Mechanisms and Therapy
- Ion channel regulation and function
- Corneal Surgery and Treatments
- Herpesvirus Infections and Treatments
- RNA regulation and disease
- Connexins and lens biology
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Synthetic Aperture Radar (SAR) Applications and Techniques
Shanghai Jiao Tong University
2017-2025
Shanghai Ninth People's Hospital
2022-2025
State Key Laboratory of Pollution Control and Resource Reuse
2025
Tongji University
2024-2025
First People's Hospital of Chongqing
2024
Zhejiang University
2008-2024
University of Shanghai for Science and Technology
2024
Shanghai East Hospital
2023
Shanghai Sixth People's Hospital
2023
Shanghai Clinical Research Center
2023
We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, marmoset. identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes 136,932 regulatory elements, including most complete set human-specific differences. estimate that 819.47 Mbp or ∼27% genome has been affected by SVs across primate evolution. identify 1,607 structurally divergent...
Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are interest as potential treatments for cancer. A new class small molecule reversible inhibitors hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor cobalt-activated hMetAP2, also inhibits mouse endothelial cell growth. Using matrigel model, this shown to inhibit angiogenesis in vivo.
Interstitial fluid pressure (IFP) in tumor is much higher than that normal tissue, and it constitutes a great obstacle for the delivery of antitumor drugs, thus becoming potential target cancer therapy. In this study, cationic nanostructured lipid carriers (NLCs) were modified by low molecular weight gelatin to achieve desirable reduction IFP improve drug delivery. way, chemotherapy formulations on proliferation pulmonary metastasis was further improved. The nanoparticles used load three...
Myosin X (MyoX), encoded by Myo10 , is a representative member of the MyTH4–FERM domain-containing myosins, and this family unconventional myosins shares common functions in promoting formation filopodia/stereocilia structures many cell types with unknown mechanisms. Here, we present structure MyoX tandem complex cytoplasmic tail P3 domain netrin receptor DCC. The structure, together biochemical studies, reveals that MyTH4 FERM domains interact each other, forming structural functional...
Processive movements of unconventional myosins on actin filaments generally require motor dimerization. A commonly accepted myosin dimerization mechanism is via formation a parallel coiled-coil dimer by stretch amino acid residues immediately carboxyl-terminal to the motor's lever-arm domain. Here, we discover that predicted region X forms highly stable, antiparallel (anti-CC). Disruption anti-CC either single-point mutations or replacement with coiled coil similar length compromised...
Abstract The molecular mechanisms driving metastatic progression in triple-negative breast cancer (TNBC) patients are poorly understood. In this study, we demonstrate that epidermal growth factor-like 9 (EGFL9) is significantly upregulated basal-like cells and associated with tumor samples. Functionally, EGFL9 both necessary sufficient to enhance cell migration invasion, as well distant metastasis. Mechanistically, binds cMET, activating cMET-mediated downstream signaling. cMET co-localize...
Atherosclerosis (AS) is a chronic inflammatory disease involving blood vessels. Inflammation affects different cells and increases the expression of adhesion molecules. Morin hydrate (MO) naturally occurring bioflavonoid with anti-inflammatory anti-oxidant effects. Although exact mechanism has not been fully elucidated, MO possibly influences autophagy pathways in immunity inflammation. In this study, showed potential to inhibit atherosclerotic promote vascular endothelial apolipoprotein E...
The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in genomics. T2T-CHM13 extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. current reference (GRCh38) has been widely used various genomic studies. However, the large-scale differences between these two important assemblies are not characterized detail yet.Here, addition to previously reported "non-syntenic" regions, we find 67 additional discrepant...
Significance MyTH4-FERM myosins (Myo7a, Myo7b, and Myo15a) regulate actin-bundle protrusion structures in various tissues, including brush border microvilli of intestines stereocilia inner ear hair cells. Mutations the cargo binding tandems these are frequently associated with human diseases, hearing loss, vision defects, digestive disorders, but poorly understood mechanisms. In this work, we present high-resolution crystal structure Myo7b C-terminal tandem (CMF) complex USH1C PDZ3 domain....
Sodium tanshinone IIA sulfonate (STS) has been reported to protect organ function in sepsis. However, the attenuation of sepsis-associated brain injury and its underlying mechanisms by STS not established.C57BL/6 mice were used establish cecal ligation perforation (CLP) model, was injected intraperitoneally 30 min before surgery. The BV2 cells stimulated lipopolysaccharide after being pre-treated with for 4 h. protective effects against vivo anti-neuroinflammatory investigated using 48-hour...
ABSTRACT The crab-eating macaques ( Macaca fascicularis ) and rhesus M. mulatta are widely studied nonhuman primates in biomedical evolutionary research. Despite their significance, the current understanding of complex genomic structure differences between species requires substantial improvement. Here, we present a complete genome assembly macaque 20 haplotype-resolved assemblies to investigate regions major species. Segmental duplication is ∼42% lower, while centromeres ∼3.7 times longer...
Myosin X (MyoX) is an unconventional myosin that known to induce the formation and elongation of filopodia in many cell types. MyoX-induced filopodial induction requires three PH domains its tail region, although with unknown underlying molecular mechanisms. MyoX's first domain split into halves by second domain. We show here PH1 N -PH2-PH1 C tandem allows MyoX bind phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P 3 ] high specificity cooperativity. further PH2 responsible for...
Stereocilia, the mechanosensory organelles on apical surface of hair cells, are necessary to detect sound and carry out mechano-electrical transduction. An electron-dense matrix is located at distal tips stereocilia plays crucial roles in regulation morphology. Mutations components this tip complex density (TCD) have been associated with profound deafness. However, mechanism underlying formation TCD largely unknown. Here, we discover that specific multivalent interactions among...
Abstract Isoforms of a gene may contribute to diverse biological functions. In the cochlea, repertoire alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques identified 236,012 transcripts, 126,612 which were unannotated in GENCODE database. Then we analyzed verified transcripts using RNA-seq, RT-PCR, Sanger sequencing, MS-based proteomics approaches. To illustrate importance identifying spliced isoforms, investigated otoferlin,...
Abstract Stereocilia are actin-based cell protrusions of inner ear hair cells and indispensable for mechanotransduction. Ankle links connect the ankle region developing stereocilia, playing an essential role in stereocilia development. WHRN, PDZD7, ADGRV1 USH2A have been identified to form so-called link complex (ALC); however, detailed mechanism underlying temporal emergence degeneration remains elusive. Here we show that WHRN PDZD7 orchestrate assemble ALC through liquid-liquid phase...
Cucurbitacin B (CuB) is a potent but toxic anticancer natural product. Herein, we designed and synthesized 2-OH- 16-OH-modified CuB derivatives to improve their antitumor efficacy reduce toxicity. Among them, derivative A11 had the most antiproliferative activity against A549 lung cancer cells (IC50 = 0.009 μM) was approximately 10-fold more than CuB, while cytotoxicity of toward normal L02 about less potent, indicating much wider therapeutic window CuB. Derivative directly binds...
Abstract EphrinB2 (erythropoietin-producing hepatoma interactor B2) is a key Eph/ephrin family member, promoting angiogenesis, vasculogenesis, and lymphangiogenesis during embryonic development. However, the role of in cardiac following myocardial infarction (MI) potential molecular mechanism remains to be demonstrated. This study revealed that prevented ischemic heart post-MI from remodeling dysfunction by activating signaling pathway. Deletion impaired aggravated adverse ventricular...