Biology subjects

liang, s.

Publications and source records attributed to liang, s..

3 recordsLinked to original sources

bioRxiv2026

Phosphoinositide Variant Fuels 53BP1 Oligomerization and Higher-Order Assembly in the DNA Damage Response

53BP1 nuclear bodies are dynamic structures with properties resembling biomolecular condensates, but the molecular determinants that govern 53BP1 higher-order assembly at DNA double-strand breaks (DSBs) remain to be established. Here, we show that 53BP1 condensation is stimulated by phosphatidylinositol 3-phosphate (PI(3)P) in vitro through a highly specific interaction with its C-terminal tandem BRCT domain (tBRCT). Consequently, mutational inactivation of the 53BP1 tBRCT domain compromised PI(3)P binding and suppressed 53BP1 optodroplet formation in vivo. We further show that rapid 53BP1 clustering following DNA damage precedes its stable assembly on DSB-flanking chromatin, requires its tBRCT, and is suppressed by sequestration of nuclear PI(3)P. Taken together, our findings identify PI(3)P binding as a mechanism that promotes the formation and maturation of 53BP1 condensate-like assemblies on damaged chromatin.

cell biology↗

bioRxiv2021

Single-shot rAAV5-based Vaccine Provides Long-term Protective Immunity against SARS-CoV-2 and Its Variants

The COVID-19 pandemic and the SARS-CoV-2 with its variants have posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against the SARS-CoV-2 variants. Therefore, novel vaccines to match current mutated viral lineages with long-term protective immunity are urgently in demand. In the current study, we for the first time designed a recombinant Adeno-Associated Virus 5 (rAAV5)-based vaccine named as rAAV-COVID-19 vaccine (Covacinplus) by using RBD-plus of spike protein with both the single-stranded and the self-complementary AAV5 delivering vectors (ssAAV5 and scAAAV5), which provides excellent protection from SARS-CoV-2 infection. A single dose vaccination induced the strong immune response against SARS-CoV-2. The induced neutralizing antibodies (NAs) titers were maintained at a high peak level of over 1:1024 even after more than one year of injection and accompanied with functional T-cells responses in mice. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines exhibited high levels of serum NAs against current circulating variants including variants Alpha, Beta, Gamma and Delta. SARS-CoV-2 virus challenge test showed that ssAAV5-RBD-plus vaccine protected both young and old age mice from SARS-CoV-2 infection in the upper and the lower respiratory tracts. Moreover, whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genome of the vaccinated mice after one year vaccination, demonstrating excellent safety of the vaccine. Taken together, this study suggests that rAAV5-based vaccine is powerful against SARS-CoV-2 and its variants with long-term protective immunity and excellent safety, which has great potential for development into prophylactic vaccination in human to end this global pandemic.

immunology↗

bioRxiv2020

Identification of key candidate genes and pathways in axial Spondyloarthritis through integrated bioinformatics analysis

BackgroundRadiographic axial Spondyloarthritis (r-axSpA) is the prototypic form of seronegative spondyloarthritis (SpA). In the present study, we evaluated the key genes related with r-axSpA, and then elucidated the possible molecular mechanisms of r-axSpA. Material/MethodsThe gene expression GSE13782 was downloaded from the GEO database contained five proteoglycan-induced spondylitis mice and three naive controls. The differentially expressed genes (DEGs) were identified with the Bioconductor affy package in R. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were built with the DAVID program followed by construction of a protein-protein interaction (PPI) network performed with Cytoscape. WebGestalt was performed to construct transcriptional regulatory network and microRNAs-target regulatory networks. RT-PCR and immunohistochemical staining were performed to testify the expression of hub genes, transcription factors (TFs) and microRNAs. ResultsA total of 230 DEGs were identified. PPI networks were constructed by mapping DEGs into STRING, in which 20 hub proteins were identified. KEGG pathway analyses revealed that the chemokine, NOD-like receptor, IL-17, and TNF signalling pathways were altered. GO analyses revealed that DEGs were extensively involved in the regulation of cytokine production, the immune response, the external side of the plasma membrane, and G-protein coupled chemoattractant receptor activity. The results of RT-PCR and immunohistochemical staining demonstrated that the expression of DEGs, TFs and microRNAs in our experiment were basically consistent with the predictions. ConclusionsThe results of this study offer insight into the pathomechanisms of r-axSpA and provide potential research directions.

molecular biology↗