Publications by authors named "Lingyun Long"

Metastasis is the main cause of colorectal cancer (CRC)-related death, and the 5-year relative survival rate for CRC patients with distant metastasis is only 14%. X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a zinc-rich protein belonging to the interferon (IFN)-induced gene family. Here, we report a metastasis-promoting role of XAF1 in CRC by acting as a novel adaptor of valosin-containing protein (VCP).

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The importance of adequate sleep for good health cannot be overstated. Excessive light exposure at night disrupts sleep, therefore, it is important to find more healthy drinks that can promote sleep under sleep-disturbed conditions. The present study investigated the use of (Lour.

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Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8 T cells expressing SPRY1 (CD8 Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8 Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8 T cells enforces Tpex phenotype and enhances ICB efficacy.

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Article Synopsis
  • Nutrients play a significant role in regulating adaptive immunity by activating mTORC1, a critical factor for cell metabolism, but the integration of these signals is not fully understood.
  • Researchers used CRISPR screening and protein interaction networks to uncover how immune signals and nutrients affect mTORC1 in mouse regulatory T cells, identifying SEC31A as a key player in promoting mTORC1 activation.
  • The study found that mechanisms like the SWI/SNF complex and the SAGA complex regulate mTORC1 activity, influencing T cell priming, inflammation, and antitumor immunity.
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Photoactivated phytochrome B (PHYB) binds to antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to regulate hundreds of light responsive genes in Arabidopsis by promoting PIF degradation. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (AD) consisting of a hydrophobic activator motif flanked by acidic residues.

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Article Synopsis
  • T follicular helper (T) cells play an essential role in supporting B cell function and the immune response, with transcription factors like BCL6 driving their development.
  • This study uncovers the importance of the CDP-ethanolamine pathway and specific enzymes (ETNK1, PCYT2, SELENOI) for promoting T cell differentiation by regulating the expression of the CXCR5 protein, critical for T cell response.
  • The research shows that lipid metabolism, particularly through the synthesis of phosphatidylethanolamine (PE), is vital in maintaining CXCR5's presence on T cells and ensuring effective humoral immunity, indicating a link between metabolic processes and immune cell signaling.
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Chimeric antigen receptor (CAR)-T-cell therapeutic efficacy is associated with long-term T-cell persistence and acquisition of memory. Memory-subset formation requires T-cell factor 1 (TCF-1), a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B-cell acute lymphoblastic leukemia (ALL; B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR-T-cell expansion and memory-like cell formation.

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Article Synopsis
  • - The study explores how metabolic factors influence the development and responses of effector T cells (Teff) and memory T cells (Tm) through a systematic analysis using CRISPR screening, focusing on negative regulators.
  • - Researchers found that certain amino acid transporters, Slc7a1 and Slc38a2, reduce T cell differentiation by affecting mTORC1 signaling and that different T cell types exhibit diverse metabolic characteristics.
  • - The investigation also revealed that the availability of GDP-fucose and its impact on Notch signaling is crucial for T cell fate, revealing the importance of nutrient uptake and signaling in shaping T cell responses.
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Regulatory T cells (T cells) are essential for immune tolerance, but also drive immunosuppression in the tumour microenvironment. Therapeutic targeting of T cells in cancer will therefore require the identification of context-specific mechanisms that affect their function. Here we show that inhibiting lipid synthesis and metabolic signalling that are dependent on sterol-regulatory-element-binding proteins (SREBPs) in T cells unleashes effective antitumour immune responses without autoimmune toxicity.

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Effector regulatory T (eT) cells are essential for immune tolerance and depend upon T cell receptor (TCR) signals for generation. The immunometabolic signaling mechanisms that promote the differentiation and maintenance of eT cells remain unclear. Here, we show that isoprenoid-dependent posttranslational lipid modifications dictate eT cell accumulation and function by intersecting with TCR-induced intracellular signaling.

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Sisal (Agave sisalana Perrine) is an important hard fiber crop that is widely planted in Guangxi, Guangdong, Hainan, Yunnan, and Fujian provinces, China. In July 2019, a new leaf disease of sisal with a disease incident of about 36% was found in Guangxi (Fig.1a~d).

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The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR.

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Adoptive cell therapy represents a new paradigm in cancer immunotherapy, but it can be limited by the poor persistence and function of transferred T cells. Here we use an in vivo pooled CRISPR-Cas9 mutagenesis screening approach to demonstrate that, by targeting REGNASE-1, CD8 T cells are reprogrammed to long-lived effector cells with extensive accumulation, better persistence and robust effector function in tumours. REGNASE-1-deficient CD8 T cells show markedly improved therapeutic efficacy against mouse models of melanoma and leukaemia.

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Regulatory T (Treg) cells are critical mediators of immune tolerance whose activity depends upon T cell receptor (TCR) and mTORC1 kinase signaling, but the mechanisms that dictate functional activation of these pathways are incompletely understood. Here, we showed that amino acids license Treg cell function by priming and sustaining TCR-induced mTORC1 activity. mTORC1 activation was induced by amino acids, especially arginine and leucine, accompanied by the dynamic lysosomal localization of the mTOR and Tsc complexes.

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Dendritic cells (DCs) play a pivotal role in priming adaptive immunity. However, the involvement of DCs in controlling excessive and deleterious T cell responses remains poorly defined. Moreover, the metabolic dependence and regulation of DC function are unclear.

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A method was developed for the determination of 42 glucocorticoids in infant eczema products by auto-solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (ASPE-UHPLC-MS/MS).The analytes were extracted by acetonitrile after dispersing in saturated sodium chloride solution.Macromolecules matrix were precipitated by adding potassium and zinc acetate, and then purified by HLB SPE column.

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Regulatory T cells (T cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of T cells in the prevention of diverse types of inflammatory responses. It remains unclear how T cells orchestrate their homeostasis and interplay with environmental signals.

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Myelopoiesis is necessary for the generation of mature myeloid cells during homeostatic turnover and immunological insults; however, the metabolic requirements for this process remain poorly defined. Here, we demonstrate that myelopoiesis, including monocyte and macrophage differentiation, requires mechanistic target of rapamycin complex 1 (mTORC1) signaling and anabolic metabolism. Loss of mTORC1 impaired myelopoiesis under steady state and dampened innate immune responses against infection.

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Article Synopsis
  • Eph receptors, particularly EphB3, are important transmembrane proteins linked to cancer development, especially in papillary thyroid cancer (PTC).
  • This study demonstrated that higher levels of EphB3 in PTC cells promote cell migration and metastasis, while reducing its expression or function inhibits these processes.
  • The research revealed that EphB3 influences the activity of specific proteins (Rac1 and RhoA) through the activation of Vav2, suggesting that EphB3 acts as a tumor promoter in PTC by regulating cell movement.
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Background & Aims: Iron is an essential metal for fundamental metabolic processes, but little is known regarding the involvement of iron in other nutritional disorders. In the present study, we investigated disordered iron metabolism in a murine model of hereditary tyrosinemia type I (HT1), a disease of the tyrosine degradation pathway.

Methods: We analysed the status of iron accumulation following NTBC withdrawal from Fah(-/-) mice, a murine model for HT1.

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Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell-specific deletion of Atg7 or Atg5, two essential genes in autophagy, leads to loss of Treg cells, greater tumor resistance and development of inflammatory disorders.

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Unlabelled: Sorafenib is a specific adenosine triphosphate-competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line-derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule-positive cells, which may be tumor initiating cells in HCC.

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Phytochromes (phys) are red and far-red photoreceptors that control plant development and growth by promoting the proteolysis of a family of antagonistically acting basic helix-loop-helix transcription factors, the PHYTOCHROME-INTERACTING FACTORs (PIFs). We have previously shown that the degradation of PIF1 and PIF3 requires HEMERA (HMR). However, the biochemical function of HMR and the mechanism by which it mediates PIF degradation remain unclear.

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The transcription factor IRF3 is a central regulator of type I interferon (IFN) signaling. The mechanisms underlying deactivation of IRF3 are poorly understood although many studies suggest that IRF3 activity is terminated through degradation after viral infection. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1.

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The transcription factor NF-κB plays a pivotal role in innate immunity in response to a variety of stimuli, and the coordinated regulation of this pathway determines the proper host responses to extracellular signals. In this study, we identified RACK1 as a novel negative regulator of NF-κB signaling, NF-κB-mediated cytokine induction and inflammatory reactions. RACK1 physically associates with the IKK complex in a TNF-triggered manner.

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