Biology subjects

xie, j.

Publications and source records attributed to xie, j..

4 recordsLinked to original sources

bioRxiv2025

FGF8 promotes lipid droplet accumulation via the FGFR1/p-p38 axis in chondrocytes

Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes, and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aimed to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results showed that FGF8 promoted LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirmed the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. These results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.

cell biology↗

bioRxiv2024

CellFM: a large-scale foundation model pre-trained on transcriptomics of 100 million human cells

The rapid evolution of single-cell sequencing technologies has facilitated precise transcriptomics profiling at the single-cell level, shedding light on the intricate heterogeneity within cellular populations. Despite these advances, the inherent diversity of cells and data challenges such as noise, batch effects, and sparsity, underscores the pressing need for a unified model to learn and represent cellular states effectively. Single-cell Large Language Models (LLMs) have been crafted to bridge this gap yet exhibit limited performance on human cells. This short-fall may stem from the confounding effects of training data from diverse species, partly because of limited cells for the single species. Here, we have compiled a dataset of approximately 100 million human cells sequenced by multiple technolo-gies from human single-cell datasets with various file types deposited in public databases and websites. Leveraging these extensive data cohorts, we developed CellFM, a robust single-cell foundation model with an impressive 800 million parameters, marking an eight-fold increase over the current largest single-species model. To ensure the training of CellFM on the MindSpore AI framework from Huawei, we have integrated RetNet, a Transformer architecture variant with lin-ear complexity for a balance between efficiency and performance, serving as the backbone of our model. Our comprehensive experiments have shown that CellFM outperforms existing models across diverse applications, such as cell annotation, perturbation prediction, and gene function prediction.

bioinformatics↗

bioRxiv2022

Effect of Puerarin on PI3K-AKT Signaling Pathway in OsteoclastEffect of Puerarin on PI3K-AKT Signaling Pathway in Osteoclast

objectiveThis study intends to explore the role of PI3K-AKT signaling pathway in the effect of Puerarin on the proliferation, activity, and function of osteoclasts from the perspective of antioxidation. MethodsRAW264. 7 cells were divided into control group, induction group treated with 20ng/mL M-CSF and 50ng/mL RANKL, puerarin group treated with 20ng/mL M-CSF, 50ng/mL RANKL, and 50mol/L puerarin. The staining of osteoclasts before and after puerarin intervention was measured by TRAP staining and cell count. The changes of related molecules before and after puerarin intervention in osteoclasts were detected by real-time fluorescence quantitative PCR and Western Blot, including TRAP, MMP-9, Cathepsin K, NFATc1, PTEN, Catalase, PI3K, AKT, P-AKT(ser473), FoxO1, P-FoxO1. ResultsTRAP staining showed that puerarin inhibited the proliferation and differentiation of RAW264.7 cells into osteoclasts. The results of qRT-PCR and WB showed that compared with the control group, the gene expression of TRAP, MMP-9, cathepsin K and NFATc1 in the induction group was up-regulated, while the gene expression of Catalase was down-regulated. PTEN gene had no significant changes before and after puerarin intervention. The expression of P-AKT (ser473) and NFATc1 protein was up-regulated, while the expression of PI3K and AKT protein had no change. Compared with the induction group, the gene expression of TRAP, MMP-9, Cathepsin K, and NFATc1 in the puerarin group decreased, the gene expression of Catalase increased, the protein expression of PI3K and AKT remained unchanged, the protein expression of P-AKT (ser473), P-FoxO1 and NFATc1 decreased, and the protein expression of FoxO1 and Catalase increased. ConclusionPuerarin may promote the transcriptional activity of FoxO1, increase the expression of catalase protein and exert its antioxidant activity by regulating the PI3K-AKT signal pathway, so as to inhibit the proliferation and differentiation of osteoclasts.

cell biology↗

bioRxiv2019

Respiratory syncytial virus activates Rab5a to suppress IRF1-dependent IFN-{lambda} production, subverting the antiviral defense of airway epithelial cells

Human respiratory syncytial virus (RSV) is a negative-strand RNA virus that causes severe acute pediatric respiratory tract infections worldwide. The limited effective antiviral options and lack of an effective vaccine against RSV highlight the need for a novel anti-viral therapy. One alternative is to identify and target the host factors required for viral infection. All viruses, including RSV, utilize cellular trafficking machinery to fulfill their life cycle in the infected host cells. Rab proteins mediate specific steps in intracellular membrane trafficking through the recruitment and tethering of fusion factors, and docking with actin- or microtubule-based motor proteins. Using RNA interference to knock down Rab proteins, we document that the micropinocytosis-associated Rab5a is required for RSV infection. RSV infection itself induces activation of Rab5a, and inhibition of this activation reduces RSV infection, but the mechanism for this effect remains unknown. Interferon (IFN) signaling plays an important role in innate immunity, and recent studies have identified IFN-{lambda} (lambda), a type III IFN, as the most important IFN for antiviral immune in response to RSV infection of mucosal epithelium. However, how the RSV-induced Rab5a suppresses airway epithelial antiviral immunity has not been unraveled. Here, we show that activated Rab5a inhibits IRF1-induced IFN-{lambda} production and IFN-{lambda}-mediated signal transduction via JAK-STAT1, thereby increasing viral replication. Rab5a knockdown by siRNA resulted in stimulation of IRF1, IFN-{lambda} and JAK-STAT1 expression, and suppressed viral growth. Our results highlight new role for Rab5a in RSV infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity, which suggests that Rab5a is a potential target for novel therapeutics against RSV infection. Author summaryRSV is the leading cause of lower respiratory tract infection in under 5 years old children. Worldwide. We identified Rab5a as a host factor involved in RSV infection via RNA interference to knock down familiar Rab proteins in human lung epithelial A549 cells infected with RSV. Rab5a belongs to Rab GTPases subfamily, which contributes to intracellular trafficking to promote virus infection. Knockdown or inactive (GDP-bound) Rab5a results in low infection and replication through stimulating IRF1, IFN-{lambda} and JAK-STAT1 expression, and suppressed viral growth. Besides, we propose that the regulation of Rab5a expression during RSV infection might be a viral strategy to promote its infectivity.

immunology↗