Biology subjects

Li, C. Y.

Publications and source records attributed to Li, C. Y..

5 recordsLinked to original sources

bioRxiv2026

Structural insight into sodium-dependent bile acid transport by members of the SLC10 family

ASBT and NTCP are sodium-coupled secondary transporters of the SLC10 family that play critical roles in the enterohepatic recycling of bile acids. Secondary transporters generally function through the alternating access mechanism. However, in outward-facing structures of NTCP this mechanism is violated with a pore running through the protein. No such pore is observed in previously reported structures of bacterial ASBT homologues, but these proteins have an additional transmembrane-helix adjacent to the binding site. Here we investigate another homologue of ASBT without this extra helix. We solve the crystal structure of the inward-facing state in multiple conformations and a humanised version in the outward-facing state, with and without bile acid bound. Unlike for NTCP there is no pore through the protein as the exit is blocked by the flexible TM6. Consequently, the presence of the pore is not necessarily common to the family. Molecular dynamics simulations of both bacterial and human proteins highlight that while the bile acid substrate is anchored to residues at the centre of the transporter, lipids from the surrounding membrane interact with the hydrophobic sterol group. Incorporating lipids into the transport mechanism can explain how bile acids modified by large hydrophobic groups can bind and be transported.

biochemistry↗

bioRxiv2024

ABA increases fatty acids levels in apple roots to boost colonization by arbuscular mycorrhizal fungi

The roots of most land plants are in symbiosis with arbuscular mycorrhizal (AM) fungi. The fungus promotes nutrient uptake from the soil while receiving plant photosynthate as lipids and sugars. Nutrient exchange must be regulated by both partners, but the mechanisms underlying the regulation of lipid supplement from the plant to the AM fungus remain elusive. Here, we conducted a molecular study on the role of increased abscisic acid (ABA) levels during AM fungus infection in the roots of apple (Malus spp.). AM fungus induced the expression of two ABA synthesis genes, MdNCED3.1 and 3.2, in apple roots and increased the ABA content, which promoted the growth of the AM fungus. The effect of ABA on symbiosis was confirmed in transgenic apple roots either overexpressing or silencing MdNCED3.1 or MdNCED3.2. Transcriptome analysis and transgenic manipulation revealed that the transcription factor MdABF2 played a key role in the ABA-mediated formation of symbiosis during AM infection and that MdABF2 could regulate the expression levels of genes related to fatty acid (FA) synthesis (e.g., MdKASIII) and translocation (such as MdSTR2) in apple roots. Activation of these genes boosted the levels of available fatty acids in the roots and increased the AM fungal colonization and arbuscule development in the roots. These results revealed a molecular pathway in which positive regulation of FA synthesis and transport by the ABA signaling pathway increases supplementation to AM fungi and promotes AM symbiosis.

molecular biology↗

bioRxiv2024

Biomimetic fractal topography enhances podocyte maturation in vitro

Cells and tissues in their native environment are organized into intricate fractal structures, which are rarely recapitulated in their culture in vitro. The extent to which fractal patterns that resemble complex topography in vivo influence cell maturation, and the cellular responses to such shape stimulation remain inadequately elucidated. Yet, the application of fractal cues (topographical stimulation via self-similar patterns) as an external input may offer a much-needed solution to the challenge of improving the differentiated cell phenotype in vitro. Here, we established fractality in podocytes, branching highly differentiated kidney cells, and glomerulus structure. Biomimetic fractal patterns derived from glomerular histology were used to generate topographical (2.5-D) substrates for cell culture. Podocytes grown on fractal topography were found to express higher levels of functional markers and exhibit enhanced cell polarity. To track morphological complexities of differentiated podocytes, we employed a fluorescent labelling assay where labelled individual cells are tracked within otherwise optically silent confluent cell monolayer to reveal cell-cell interdigitation. RNAseq analysis suggests enhanced ECM deposition and remodeling in podocytes grown on fractal topography compared to flat surface or non-fractal microcurvature, mediated by YAP signaling. The incorporation of fractal topography into standard tissue culture well plates as demonstrated here may serve as a user-friendly bioengineered platform for high-fidelity cell culture.

bioengineering↗

bioRxiv2023

Novel gut microbiota and microbiota-metabolites signatures in gliomas and its predictive/prognosis functions

Gliomas are the most common malignant tumors in the central nervous system. Host genetic and environmental factors have been implicated as the causes and regulators of gliomas. Evidence shows that alterations of the gut microbiome play an important role in multiple diseases including central nervous system disorders. However, the influence of gut microbiome to the epigenesis of gliomas remains largely unknown. Here we profiled the gut microbiome and metabolome in fecal samples from healthy volunteers and the patients with gliomas through the 16S rRNA gene sequencing and LC-MS analyses. The fecal samples from primary glioma patients (n=51), recurrent glioma patients (n=11), patients who underwent TMZ radio-chemotherapy (n=16) and healthy volunteers (n=37) were collected. 56 discriminatory OTUs and 144 metabolites were observed in gliomas compared to those in healthy volunteers, and some species were correlated with clinical parameters, such as tumor grade, IDH-1 and MGMT status. Moreover, the gliomas group showed increased activity in pathways associated with ectoine biosynthesis, fatty acid elongation (saturated), and protocatechuate degradation. At the same time, we revealed 4 fatty-acid metabolites(palmitic acid, oleic acid, DL-beta-Hydroxypalmitic acid, 4-(Methylamino)-4-(3-pyridyl)butyric acid) as possibly interacting with glioma growth. Random forest modeling indicated that a model involving 8 genera and 10 metabolite biomarkers achieved a high accuracy in gliomas prediction (AUC=94.4%). We investigated interassociations between the microbial genera in glioblastoma multiforme (GBM) and progression-free survival (PFS) and overall survival (OS) by Spearmans correlation analysis. Patients with high proportions of fecal Faecalibacterium had significantly better median PFS or OS than those with low proportions (mPFS 495 vs. 281 days, p=0.005; mOS 604 vs. 395 days, p=0.044). Moreover, animal experiments have verified the causal relationship between the structural changes of gut microbiome and glioma growth. Our current study comprehensively characterizes the perturbed interface of gut microbiome and metabolites in glioma patients, which may be used as diagnostic and prognostic biomarkers of gliomas.

neuroscience↗

bioRxiv2019

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Polybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act in cis to perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are human-derived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 M for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and PPAR-RXR activation but also regulate distinctive pathways involved in intermediary metabolism. BDE-47 uniquely regulated signaling by Rho Family GTPases and PBDE-99 uniquely regulates JAK/Stat signaling, bile acid biosynthesis, sirtuin signaling pathway, and autophagy. In conclusion, lncRNAs play essential roles in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism.

pharmacology and toxicology↗