A5084130569- CRISPR and Genetic Engineering
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- GaN-based semiconductor devices and materials
- Advanced biosensing and bioanalysis techniques
- Semiconductor materials and devices
- Melanoma and MAPK Pathways
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Immune cells in cancer
- Virus-based gene therapy research
- Ga2O3 and related materials
- Ubiquitin and proteasome pathways
- Sleep and related disorders
- Semiconductor Quantum Structures and Devices
- Semiconductor materials and interfaces
- RNA modifications and cancer
- Cellular transport and secretion
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Reproductive Biology and Fertility
- Child Nutrition and Feeding Issues
Model Animal Research Center
2015-2025
Nanjing University
2016-2025
State Key Laboratory of Pharmaceutical Biotechnology
2017-2024
Yancheng First People's Hospital
2023
Nantong University
2023
Shanghai Stomatological Hospital
2023
Nanjing Drum Tower Hospital
2019
University of Pennsylvania
1998-2018
Wenzhou Medical University
2011-2016
Boston University
2003
The prime editors (PEs) have shown great promise for precise genome modification. However, their suboptimal efficiencies present a significant technical challenge. Here, by appending viral exoribonuclease-resistant RNA motif (xrRNA) to the 3'-extended portion of pegRNAs increased resistance against degradation, we develop an upgraded PE platform (xrPE) with substantially enhanced editing in multiple cell lines. A pan-target average enhancement up 3.1-, 4.5- and 2.5-fold given types is...
Abstract Signaling by viral nucleic acids and subsequently type I IFN is central to antiviral innate immunity. These signaling events are also likely engage metabolic changes in immune nonimmune cells support defense. In this study, we show that cytosolic recognition, way of secondary signaling, leads upregulation glycolysis preferentially macrophages. This switch involves induction glycolytic activator 6-phosphofructose-2-kinase fructose-2,6-bisphosphatase (PFKFB3). Using a genetic...
Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent cell signaling. Along with linear endocytic motifs that recruit adaptin protein complex 2 (AP2)-clathrin molecules, monoubiquitination has emerged as a major signal. By investigating ubiquitin-dependent interferon (IFN)-alpha/beta receptor 1 (IFNAR1) subunit type I IFN receptor, we reveal IFNAR1 is polyubiquitinated via both Lys48- Lys63-linked chains. The SCF(betaTrcp) (Skp1-Cullin1-F-box complex)...
Perfluorooctanesulfonic acid (PFOS), a ubiquitous contaminant, has been used in various industrial applications. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially aquatic organisms. The present study defined to low level metabolism F0 adult zebrafish and F1 offspring. Our findings revealed severe fatty degeneration liver males treated with 0.5 μM significant ultrastructure changes associated substance transport or intestines (abnormal...
Abstract The applicability of nuclease-based form prime editor (PEn) has been hindered by its complexed editing outcomes. A chemical inhibitor against DNA-PK, which mediates the nonhomologous end joining (NHEJ) pathway, was recently shown to promote precise insertions PEn. Nevertheless, intrinsic issues specificity and toxicity for such a approach necessitate development alternative strategies. Here, we find that co-introduction PEn NHEJ-restraining, 53BP1-inhibitory ubiquitin variant...
Phosphorylation of the degron IFNAR1 chain type I interferon (IFN) receptor triggers ubiquitination and degradation this and, therefore, plays a crucial role in negative regulation IFN-alpha/beta signaling. Besides IFN-stimulated Jak activity-dependent pathways, basal ligand-independent phosphorylation has been described implicated downregulating response to virus-induced endoplasmic reticulum (ER) stress. Here we report purification characterization casein kinase 1alpha (CK1alpha) as bona...
Short-chain fatty acids (SCFAs) with the anti-inflammatory capacity are produced by intestinal bacteria; however, their effect on acute systematical inflammation remains unclear. This study aimed to investigate effects of SCFAs, acetate, propionate and butyrate, septic shock underlying mechanism. The LPS-induced model was used evaluate function SCFAs survival rate observation. Only but not acetate or propionate, significantly decrease mortality mice. At 2 h 6 LPS administration, levels...
Abstract Type I interferons (IFN-Is) have been harnessed for cancer therapies due to their immunostimulatory functions. However, certain tumor-tolerating activities by IFN-Is also exist, and may potentially thwart therapeutic effects. In this respect, our previous studies demonstrated a monocyte-orchestrated, IFN-I-to-IL-4 cytokine axis, which can subsequently drive M2-skewed pro-tumoral polarization of macrophages. Whether other IFN-dependent signals contribute such an unconventional...
Abstract Base editors (BEs) are a recent generation of genome editing tools that couple cytidine or adenosine deaminase activity to catalytically impaired Cas9 moiety (nCas9) enable specific base conversions at the targeted genomic loci. Given their strong application potential, BEs under active developments toward greater levels efficiency and safety. Here, previously overlooked nCas9‐centric strategy is explored for enhancement BE. Based on cytosine BE (CBE), 20 point mutations associated...
An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays central role in host's defenses. Activation these through stimulation pathogen-recognition receptors induces production cytokines Type I interferons (IFNs) that mediate diverse mechanisms innate immunity. IFNs interact with IFN receptor, composed IFNAR1 and IFNAR2 chains, mount host defense responses. However, at same time, elicit potent anti-proliferative pro-apoptotic effects could be...
Phosphorylation-dependent ubiquitination and ensuing down-regulation lysosomal degradation of the interferon alpha/beta receptor chain 1 (IFNAR1) for Type I interferons play important roles in limiting cellular responses to these cytokines. These events could be stimulated either by ligands (in a Janus kinase-dependent manner) or unfolded protein response (UPR) inducers including viral infection manner dependent on activity pancreatic endoplasmic reticulum kinase). Both ligand-dependent...
In mammals, resting female oocytes reside in primordial ovarian follicles. An individual follicle may stay quiescent for a protracted period of time before initiating follicular growth, which is also termed “activation.” Female reproductive capacity sustained by the gradual, streamlined activation entire population follicles, but this process results senescence older animals. Based on recent findings that genetically triggered, excessive mammalian target rapamycin complex 1 (mTORC1) mouse...
Granulosa cells (GCs) are tightly associated with fertility and the fate of ovarian follicles. Mitochondria central executers apoptosis. However, genetic basis underlying mitochondrial modulation in GCs during development is poorly understood. Here, CRISPR/Cas9-mediated screening was used to identify genes conferring metabolism human GCs. The results uncovered roles for several tumor suppressors, including HBP1, augmentation function. Focused analysis revealed that high-mobility group...
Neurite outgrowth requires coordinated cytoskeletal rearrangements in the growth cone and directional membrane delivery from neuronal soma. As an essential Rho guanine nucleotide exchange factor (GEF), TRIO is necessary for dynamics during neurite outgrowth, but its participation unclear. Using co-localization studies, live-cell imaging, fluorescence recovery after photobleaching analysis, along with assay various biochemical approaches, we here report that mouse cerebellar granule neurons,...
While negative effect of smoking on the resistance to viral infections was known, underlying mechanisms remained unclear. Here we report that products cigarette compromise cellular anti‐viral defenses by inhibiting signaling induced Type I interferon (IFN). Cigarette condensate (but not pure nicotine) stimulated specific serine phosphorylation‐dependent ubiquitination and degradation IFNAR1 subunit IFN receptor leading attenuation decreased infection. This restored in cells where is...
BackgroundType I IFN-based therapies against solid malignancies have yielded only limited success. How IFN affects tumor-associated macrophage (TAM) compartment to impact the therapeutic outcomes are not well understood.MethodsThe effect of an IFN-inducer poly(I:C) on tumor-infiltrating monocytes and TAMs were analyzed using a transplantable mouse tumor model (LLC). In vitro culture systems utilized study direct actions by poly(I:C)-IFN differentiating monocytes.ResultsWe found that...