PubMed HealthSearch

Biomedical subjects

Liang Ma

Publications and source records attributed to Liang Ma.

3 recordsLinked to original sources

Bayesian inference of lineage trees by joint analysis of single-cell multimodal lineage-tracing data with BiLinT.

The advent of single-cell lineage-tracing technologies has enabled the simultaneous profiling of gene expression and lineage barcodes. However, accurate, high-resolution reconstruction of cell lineage trees remains challenging because most existing approaches treat these modalities separately and therefore fail to fully exploit their complementary information. Here we present BiLinT, a Bayesian framework that jointly models multimodal single-cell lineage-tracing data for lineage tree reconstruction. BiLinT integrates barcode evolution (a continuous-time Markov chain) with gene expression dynamics (an Ornstein-Uhlenbeck process) within a unified probabilistic model. Across synthetic and real data sets, BiLinT provides accurate lineage-tree reconstruction and reveals differentiation-associated clonal structure and developmental fate biases.

Journal Article

Characteristics of Protein Profiling and Biomarkers in Aortic Regurgitation With Heart Failure.

BACKGROUND: Valvular heart disease, particularly aortic valve disease including stenosis and regurgitation, is a common heart disease. This study aimed to explore the protein profiling and the biomarkers in severe aortic valve disease and to provide new insights into the therapeutic strategy. METHODS: Blood samples from 80 subjects were collected and analyzed by data independent acquisition technique in 3 comparisons (mild/moderate-control, severe-control, and severe-mild/moderate) and validated by ELISA. The diagnostic value of differentially expressed proteins associated with severe valvular heart disease was also evaluated by the receiver operating characteristic curve. RESULTS: A total of 9976 peptides and 451 proteins were identified through liquid chromatography-tandem mass spectrometry analysis. From these, 64 in mild/moderate-control, 50 in severe-control, and 50 in severe-mild/moderate comparisons were identified as differentially expressed proteins. IGFBP7 (insulin-like growth factor-binding protein 7; 5581.0&#xb1;697.0&#x2009;ng/mL), DSG1 (desmoglein-1; 21.0&#xb1;2.0 pg/mL), ADIPOQ (adiponectin; 26&#x2009;686.0&#xb1;3730&#x2009;ng/mL), and JUP (junction plakoglobin; 10.2&#xb1;0.6&#x2009;ng/mL) levels in the severe group were significantly higher than that in the mild/moderate (P<0.05) group. Additionally, ADIPOQ and JUP levels in the severe group were also higher than that in control (P<0.001). Receiver operating characteristic curve analysis showed that IGFBP7, DSG1, JUP, and ADIPOQ had strong potential value to be associated with severe aortic valve disease. CONCLUSIONS: By constructing proteomics profile to identify the protein characteristics this study found that increased IGFBP7, DSG1, JUP, and ADIPOQ are the characteristics of proteins in patients with severe valvular heart disease. These findings provide new insight into the diagnosis and pathogenesis of valvular heart disease, particularly aortic valve disease.

Humans

Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.

Humans