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Biology subjects

Zhang, Y. H.

Publications and source records attributed to Zhang, Y. H..

4 recordsLinked to original sources

Proteome-wide Mapping of Cysteine Persulfidation in Deep-Sea Hyperthermophilic Archaea

Protein persulfidation, a primary post-translational modification mediated by the gaseous signaling molecule hydrogen sulfide (H2S), regulates diverse physiological processes in eukaryotes and bacteria. However, its existence and functional roles in archaea, the third domain of life, remain completely unexplored. Here, we investigate this in the deep-sea hyperthermophilic archaeon Thermococcus aciditolerans SY113, which thrives in sulfur rich hydrothermal vents and endogenously produces substantial H2S. Our profiling not only delineated the unique reactivity landscape of these modifications but also enabled quantitative analysis of its dynamic regulation by H2S. A total of 204 persulfidation sites on 171 proteins were identified, over 65% of which were dynamically regulated by H2S. Further functional analysis suggests that persulfidation represents an ancient and conserved regulatory mechanism in primordial life including the regulation of catalytic activity, maintenance of protein conformation, and mediation of protein-protein interactions. Our findings provide a valuable dataset and theoretical foundation for understanding the role of persulfidation in the physiological regulation of deep-sea hyperthermophilic archaea.

microbiology↗

Human umbilical mesenchymal stem cell-derived mitochondria ameliorate maternal phenotype by improving placental mitochondria and vascular function in angiotensin II-induced preeclampsia rat

BackgroundMitochondrial transplantation (Mito-T) is a novel therapeutic strategy targeting ischemic cardiovascular diseases. Here, we tested the efficacy of human umbilical mesenchymal stem cell-derived mitochondria transplantation (Mito-T) on a rat model of PE. MethodsPE was induced by infusing angiotensin II (Ang II) to SD pregnancy rats on gestation day 8 (GD 8). Mito-T (100 g/l) was injected via jugular vein on GD 14. FindingsOn GD 20, PE rats showed high blood pressure, kidney and placental vascular abnormalities, reduced placental and fetal weights. Injected Mito-T was distributed intensively in the kidney, uterus and placenta of PE rats. Importantly, Mito-T reversed clinical manifestations of PE, restored placental abnormalities and reduced serum sFLT-1 levels and sFLT-1/PlGF ratio. In the placental mitochondria, Mito-T increased ETC complexes (complex I-V), improved mitochondrial membrane potential, ATP synthase and citrate synthase activities and biogenesis markers (PGC-1, TFAM, NRF1) and reduced ROS production. Mito-T increased mitochondrial fusion proteins (OPA1, MFN1 and MFN2), reduced mitochondrial fission proteins (DRP1 and FIS1) and mitophagy proteins (PINK, BNIP3, BNIP3L, FUNDC1), restored sFLT-1 regulating calcineurin-NFAT-dependent pathways in the placental tissue, primary trophoblast cells and Bewo cell line. Furthermore, eNOS, nNOS and AT2R mRNA and protein expressions were restored in placenta and trophoblast cells after Mito-T. InterpretationThis is the first study of PE treatment with Mito-T. Mito-T reverses pathological phenotypes of PE rats by improving placental mitochondrial and vascular function. The results provide proofs of concept of Mito-T as a potential therapeutic strategy for reducing maternal and fetal risks in PE patients. FundingThis work is supported by Korean National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2019R1A2C1005720, NRF-2023R1A2C1005720), BK21 FOUR education program, Korean Society of Hypertension (Grant number KSH-R-2020), National Natural Science Foundation of China (NSFC 31660284, NSFC31860288).

pathology↗

Brain Data Standards Ontology: A data-driven ontology of transcriptomically defined cell types in the primary motor cortex

Large-scale single-cell omics profiling is revolutionising our understanding of cell types in complex organs like the brain, where it is being used to define a complete catalogue of cell types, something that traditional methods struggle with due to the diversity and complexity of the brain. But this poses a problem. How do we organise such a catalogue - providing a standard way to refer to the cell types discovered, linking their classification and properties to supporting data? Cell ontologies provide a solution to recording definitions, classifications, and properties of cell types and provide standard identifiers for annotation, but they currently do not support the data driven cell type definitions and classifications needed for multi-modal single cell omics profiling. Here we describe the construction and application of a semi-automated, data-linked extension to the Cell Ontology that represents cell types in the Primary Motor Cortex of humans, mice and marmosets. The methods and resulting ontology are designed to be scalable and applicable to similar whole brain atlases currently in preparation.

neuroscience↗

NS-Forest: A machine learning method for the objective identification of minimum marker gene combinations for cell type determination from single cell RNA sequencing

Single cell genomics is rapidly advancing our knowledge of cell phenotypic types and states. Driven by single cell/nucleus RNA sequencing (scRNA-seq) data, comprehensive atlas projects covering a wide range of organisms and tissues are currently underway. As a result, it is critical that the cell transcriptional phenotypes discovered are defined and disseminated in a consistent and concise manner. Molecular biomarkers have historically played an important role in biological research, from defining immune cell-types by surface protein expression to defining diseases by molecular drivers. Here we describe a machine learning-based marker gene selection algorithm, NS-Forest version 2.0, which leverages the non-linear attributes of random forest feature selection and a binary expression scoring approach to discover the minimal marker gene expression combinations that precisely captures the cell type identity represented in the complete scRNA-seq transcriptional profiles. The marker genes selected provide a barcode of the necessary and sufficient characteristics for semantic cell type definition and serve as useful tools for downstream biological investigation. The use of NS-Forest to identify marker genes for human brain middle temporal gyrus cell types reveals the importance of cell signaling and non-coding RNAs in neuronal cell type identity.

bioinformatics↗