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"Li, Chan"
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Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations
The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR). Recently, a considerable number of studies have provided robust statistical evidence suggesting that the TyG index is associated with the development and prognosis of cardiovascular disease (CVD). Nevertheless, the application of the TyG index as a marker of CVD has not systemically been evaluated, and even less information exists regarding the underlying mechanisms associated with CVD. To this end, in this review, we summarize the history of the use of the TyG index as a surrogate marker for IR. We aimed to highlight the application value of the TyG index for a variety of CVD types and to explore the potential limitations of using this index as a predictor for cardiovascular events to improve its application value for CVD and provide more extensive and precise supporting evidence.
Journal Article
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial–mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal–epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
PD-L1 accumulates on cancer stem cells and favours immune evasion but the mechanism underlying this accumulation are unknown. Here the authors show that epithelial-mesenchymal transition induces glycosylation and stabilisation of PD-L1; antagonising this process renders cancer cells sensitive to anti-Tim3-therapy.
Journal Article
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Major depressive disorder (MDD) is associated with alterations of GABAergic interneurons, notably somatostatin (Sst) as well as parvalbumin (Pvalb), in cortical brain areas. In addition, the antidepressant effects of rapid-acting drugs are thought to occur via inhibition of GABA interneurons. However, the impact of these interneuron subtypes in affective behaviors as well as in the effects of rapid-acting antidepressants remains to be determined. Here, we used a Cre-dependent DREADD-chemogenetic approach to determine if inhibition of GABA interneurons in the mPFC of male mice is sufficient to produce antidepressant actions, and conversely if activation of these interneurons blocks the rapid and sustained antidepressant effects of scopolamine, a nonselective acetylcholine muscarinic receptor antagonist. Chemogenetic inhibition of all GABA interneurons (Gad1+), as well as Sst+ and Pvalb+ subtypes in the mPFC produced dose and time-dependent antidepressant effects in the forced swim and novelty suppressed feeding tests, and increased synaptic plasticity. In contrast, stimulation of Gad1, Sst, or Pvalb interneurons in mPFC abolished the effects of scopolamine and prevented scopolamine induction of synaptic plasticity. The results demonstrate that transient inhibition of GABA interneurons promotes synaptic plasticity that underlies rapid antidepressant responses.
Journal Article
A Deep Learning-Based Piano Music Notation Recognition Method
In the era of rapid development of computer technology, piano music notation and electronic synthesis system can be established using computer technology, and the basic laws of music score can be analyzed from the perspective of image processing, which is of a great significance in promoting piano improvement and research and development, etc. In this paper, the Beaulieu analysis method is used to analyze the piano music notation and electronic synthesis system module. For piano sheet music, sheet music recognition is the main problem in the whole system. Through the digital recognition method, the piano sheet music feature matrix is extracted to get the piano sheet music multiplication frequency points and the envelope function needs to be extracted for better electronic synthesis of piano sheet music. The envelope function can represent the relationship between piano sound intensity and time change and finally achieve the recognition of the piano score. We extract the music information from the digital score, thus converting the music information into MIDI files, reconstructing the score, and providing an audio carrier for the score transmission. The experimental results show that the system has a correct rate of 94.4% in extracting music information from piano scores, which can meet the needs of practical applications and provide a new way for music digital libraries, music education, and music theory analysis.
Journal Article