Biology subjects

Liu, Y.-G.

Publications and source records attributed to Liu, Y.-G..

5 recordsLinked to original sources

bioRxiv2026

Nanotherapy-mediated biased antigen-presenting cell reprogramming supports T cell anergy to prevent type 1 diabetes

Engineering immune tolerance using endogenously expressed autoantigens could enable early intervention in autoimmune disease. Present therapies suppress T cells to slow disease progression. Here, we develop rapamycin-loaded poly(ethylene glycol)-b-poly(propylene sulfide) polymersomes (rPS) to modulate antigen-presenting cells (APCs) during disease-associated antigen presentation. The rPS morphology enables lymphatic drainage following subcutaneous administration to access APCs in draining lymph nodes. Treatment reduced APC costimulatory marker coexpression and shifted CD4+ T cells toward an FR4hi CD73hi anergic phenotype. In a type 1 diabetes (T1D) nonobese diabetic (NOD) mouse model, rPS significantly delayed disease onset relative to the standard of care and selectively prevented hyperglycemia. Mediation via APCs, rPS avoids adverse effects including transient lymphopenia. These findings demonstrate how biomaterial-directed drug delivery can reshape APC--T cell interactions, supporting an antigen-agnostic strategy for delaying autoimmune diabetes without systemic lymphocyte depletion.

bioengineering↗

bioRxiv2024

Moderate Cold Stress Enhance Drought Resistance through CCA1 via -an ABA- independent Pathway

In nature, plants frequently encounter concurrent stresses, particularly the simultaneous occurrence of cold and drought stress poses a challenge to plants in middle and high latitudes. However, the molecular mechanisms underlying the plants response to this double-stress scenario remain unclear. Although some responses suggest that drought stress can improve cold resistance in plants, through ABA signaling pathways. In our study, we discovered that moderate low temperature treatment significantly enhanced Arabidopsis drought tolerance. Low temperature rapidly triggers the transcription factor CCA1, a prototypical response to cold stress, which inturn directly regulates the expression of OST1 and P5CS1 by binding to their promoters. This leads to the premature closure of stomata and accumulation of proline through a non-ABA-dependent pathway even before plants experience drought stress, ultimately improving plant resistance against drought and cold. Moreover, this mechanism is conserved across plant species, and the synergistic resistance mechanism enables perennial plants to survive winter conditions and annual plants to withstand multi-stresses.

cell biology↗

bioRxiv2023

Functional characterization of the disease-associated CCL2 rs1024611G-rs13900T haplotype: The role of the RNA-binding protein HuR

CC-chemokine ligand 2 (CCL2) is involved in the pathogenesis of several diseases associated with monocyte/macrophage recruitment, such as HIV-associated neurocognitive disorder (HAND), tuberculosis, and atherosclerosis. The rs1024611 (alleles: A>G; G is the risk allele) polymorphism in the CCL2 cis-regulatory region is associated with increased CCL2 expression in vitro and ex vivo, leukocyte mobilization in vivo, and deleterious disease outcomes. However, the molecular basis for the rs1024611-associated differential CCL2 expression remains poorly characterized. It is conceivable that genetic variant(s) in linkage disequilibrium (LD) with rs1024611 could mediate such effects. Previously, we used rs13900 (alleles: C>T) in the CCL2 3 untranslated region (3 UTR) that is in perfect LD with rs1024611 to demonstrate allelic expression imbalance (AEI) of CCL2 in heterozygous individuals. Here we tested the hypothesis that the rs13900 could modulate CCL2 expression by altering mRNA turnover and/or translatability. The rs13900 T allele conferred greater stability to the CCL2 transcript when compared to the rs13900 C allele. The rs13900 T allele also had increased binding to Human Antigen R (HuR), an RNA-binding protein, in vitro and ex vivo. The rs13900 alleles imparted differential activity to reporter vectors and influenced the translatability of the reporter transcript. We further demonstrated the role of HuR in mediating allele-specific effects on CCL2 expression in overexpression and silencing studies. Our studies suggest that the differential interactions of HuR with rs13900 could modulate CCL2 expression and could in part explain the interindividual differences in CCL2-mediated disease susceptibility.

genomics↗

bioRxiv2020

Co-administration of macropinocytosis inhibitory nanoparticles (MiNP) for enhanced nanoparticle circulation time and target tissue accumulation following subcutaneous injection

A signficant barrier to the application of nanoparticles for precision medicine is the mononuclear phagocyte system (MPS), a diverse population of phagocytic cells primarily located within the liver, spleen and lymph nodes. The majority of nanoparticles are indiscriminantly cleared by the MPS via macropinocytosis before reaching their intended targets, resulting in side effects and decreased efficacy. This work demonstrates that the biodistribution and desired tissue accumulation of targeted nanoparticles can be significantly enhanced by co-injection with polymeric micelles containing the actin depolymerizing agent latrunculin A. These macropinocytosis inhibitory nanoparticles (MiNP) were found to selectively inhibit non-specific uptake of a second "effector" nanoparticle in vitro without impeding receptor-mediated endocytosis. In tumor bearing mice, co-injection with MiNP in a single multi-nanoparticle formulation significantly increased the accumulation of folate-receptor targeted nanoparticles within tumors. Furthermore, subcutaneous co-administration with MiNP allowed effector nanoparticles to achieve serum levels that rivaled a standard intravenous injection. This effect was only observed if the effector nanoparticles were injected within 24 h following MiNP administration, indicating a temporary avoidance of MPS cells. Co-injection with MiNP therefore allows reversible evasion of the MPS for targeted nanoparticles and presents a previously unexplored method of modulating and improving nanoparticle biodstribution following subcutaneous administration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/267054v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@e2e675org.highwire.dtl.DTLVardef@883af7org.highwire.dtl.DTLVardef@1d74912org.highwire.dtl.DTLVardef@fe6bd9_HPS_FORMAT_FIGEXP M_FIG C_FIG TOC Text: Polymeric macropinocytosis inhibiting nanoparticles reduce non-specific uptake of an "effector" nanoparticle by cells of the mononuclear phagocyte system. This macropinocytosis specific inhibition allows for greater accumulation and uptake of targeted nanoparticles in tissues of interest thereby increasing their efficacy and reducing side effects.

bioengineering↗

bioRxiv2018

Alternative splicing and translation play important roles in parallel with transcriptional regulation during rice hypoxic germination

Post-transcriptional mechanisms, including alternative splicing (AS) and alternative translation initiation (ATI), have been used to explain the protein diversity involved in plant developmental processes and stress responses. Rice germination under hypoxia conditions is a classical model system for the study of low oxygen stress. It is known that there is transcriptional regulation during rice hypoxic germination, but the potential roles of AS and ATI in this process are not well understood. In this study, a proteogenomic approach was used to integrate the data from RNA sequencing, qualitative and quantitative proteomics to discover new players or pathways in the response to hypoxia stress. The improved analytical pipeline of proteogenomics led to the identification of 10,253 intron-containing genes, 1,729 of which were not present in the current annotation. Approximately 1,741 differentially expressed AS (DAS) events from 811 genes were identified in hypoxia-treated seeds in comparison to controls. Over 95% of these were not present in the list of differentially expressed genes (DEG). In particular, regulatory pathways such as spliceosome, ribosome, ER protein processing and export, proteasome, phagosome, oxidative phosphorylation and mRNA surveillance showed substantial AS changes under hypoxia, suggesting that AS responses are largely independent of traditional transcriptional regulation. Massive AS changes were identified, including the preference usage of certain non-conventional splice sites and enrichment of splicing factors in the DAS datasets. In addition, using self-constructed protein libraries by 6-frame translation, thousands of novel proteins/peptides contributed by ATI were identified. In summary, these results provide deeper insights towards understanding the underlying mechanisms of AS and ATI during rice hypoxic germination.

plant biology↗