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Biomedical subjects

Jun Yang

Publications and source records attributed to Jun Yang.

6 recordsLinked to original sources

The complete sequence of chloroplast genome of an important medicinal plant, Chamaemelum nobile Linaeus 1785 (Asteraceae).

Chamaemelum nobile L. (Asteraceae), commonly known as Roman chamomile, is a perennial herb with branched rhizomes and multiple leafy stems. The length of the complete cp genome is 149,827 bp, and it comprises 128 genes, including 83 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. By conducting phylogenetic analyses based on chloroplast genomes, we found that C. nobile was more closely related to Matricaria chamomilla var. recutita within the chamomile species. This finding contributes to a better understanding of the phylogenetic relationship between C. nobile and other species.

Asteraceae

Single-Cell Proteomics Reveals Proteome Remodeling and Cellular Heterogeneity During NGF-Induced PC12 Neuronal Differentiation.

Single-cell proteomics enables direct measurement of cellular heterogeneity during dynamic biological processes, but its application to fragile and highly adherent neuronal models remains challenging. Here, we developed and applied an optimized single-cell proteomics workflow to characterize proteome remodeling during nerve growth factor (NGF)-induced differentiation of PC12 cells. To enable reliable single-cell analysis, we implemented gentle dissociation, antiaggregation strategies, and thermal inkjet-based cell dispensing, achieving high accuracy in single-cell isolation. Inclusion of n-dodecyl-β-d-maltoside (DDM) improved recovery of membrane-associated and low-solubility proteins. Coupled with LC-ion mobility-mass spectrometry, this workflow enabled quantification of 2,000-3,000 proteins per cell across the differentiation time course. Single-cell proteomic analysis revealed progressive and heterogeneous proteome remodeling during differentiation. While undifferentiated cells formed a relatively homogeneous population, later stages (Days 4-6) exhibited increased variability, including multimodal protein abundance distributions and separation into distinct subpopulations. Dimensionality reduction, clustering, and non-negative matrix factorization identified multiple coexisting proteomic states within the same time points, reflecting asynchronous differentiation trajectories. These subpopulations were characterized by coordinated differences in pathways related to intracellular trafficking, protein translation, cytoskeletal organization, and neuronal maturation. Comparison with bulk proteomics demonstrated that proteins associated with differentiated neuronal states, including those involved in neurite formation and structural remodeling, are underrepresented in population-averaged measurements but are enriched within specific single-cell subpopulations. Temporal and cluster-resolved analyses further revealed distinct protein expression trajectories, including early decreases in cell cycle and metabolic pathways and later increases in neuronal structural and regulatory proteins. Together, this study establishes an optimized workflow for single-cell proteomics of neuronal systems and demonstrates that NGF-induced PC12 differentiation proceeds through heterogeneous and divergent proteomic states that are not resolved by bulk analysis.

Animals

In vitro and in vivo studies on the impact of the familial adenomatous polyposis heterogeneous mutation MUC20-S671C on colorectal carcinogenesis and progression.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer (CRC). We performed genetic testing on nine FAP patients and identified a recurrent mutation at the 671st site of the MUC20 gene-MUC20-S671C. This mutation has a detection frequency of zero in the 1000 Genomes Project database. Previous studies have demonstrated that MUC20 can promote CRC progression through epithelial-mesenchymal transition (EMT). We conducted a series of experiments to analyze the impact of this mutation on CRC cells, aiming to infer its potential role and significance in CRC patients. METHODS: We introduced the MUC20-S671C mutation into the CRC SW480 cell line using the CRISPR-Cas9 technique and established a stable cell line carrying this mutation. We then conducted various experiments to assess the effects of this mutation. The Transwell assay was used to evaluate cell invasion and migration. We also examined cell proliferation, cell cycle progression, and apoptosis rate. Furthermore, we tested the tumorigenic ability of these cells in NOD-scid IL2Rγ[null] (NSG) mice. Additionally, transcriptome sequencing was performed on both cell lines and mouse tumor tissues to obtain molecular regulatory network data, and key molecules were further validated. RESULTS: The results of Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays indicated that the proliferation ability of mutant cells was significantly reduced. The Transwell assay demonstrated a marked decline in the invasion and migration capabilities of mutant cells. Flow cytometry analysis revealed that the mutation increased the apoptosis rate of CRC cells and might have caused S-phase arrest. The tumor formation assay in nude mice showed that the tumorigenic ability of mutant cells was weakened. Transcriptome sequencing of both the cells and tumor tissues suggested that the mutation altered the expression of apoptosis- and cell cycle-related molecules and also affected EMT. Further experiments confirmed that key molecules involved in the EMT process, such as E-cadherin, were upregulated, while Vimentin, MMP9, and MMP14 were significantly downregulated, indicating that the mutation weakened the EMT capability of CRC cells. CONCLUSIONS: We have identified a novel mutation, MUC20-S671C, in patients with FAP. Our study demonstrates that this mutation exerts its tumor-suppressive effect by reversing the EMT process.

MUC20-S671C

Microbial DNA analysis of paired blood-bronchoalveolar lavage fluid in post-HSCT patients with pneumonia implying application conditions of blood as a surrogate in pathogen detection.

BACKGROUND: Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing's simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens. RESULTS: Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients' BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients' blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with > 70% certainty. CONCLUSION: Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.

Humans

Perirenal Adipose Tissue and Hypertension: Observational and Genetic Analyses.

BACKGROUND: Perirenal adipose tissue (PRAT) consists of white and brown adipocytes with good vascularization and dense innervation, which could influence the blood pressure. We aim to investigate the association of PRAT thickness with risks of overall and specific forms of hypertension. METHODS: We measured PRAT thickness in the UK Biobank and CONPASS (Chongqing Primary Aldosteronism Study). We prospectively examined the correlation between PRAT thickness and incident hypertension in the UK Biobank. We cross-sectionally explored associations between PRAT thickness and common forms of hypertension in CONPASS. Integrating data from GWAS (Genome-Wide Association Study), we investigated the potential causal relationship between PRAT and hypertension forms by 2-sample Mendelian randomization analyses. RESULTS: In the prospective analysis of the UK Biobank, participants whose PRAT thickness was &#x2265;46.1 mm showed a higher risk of developing hypertension than participants whose PRAT thickness was <16.4 mm (hazard ratio, 2.91 [95% CI, 1.97-4.32]). In the cross-sectional analysis of CONPASS, a 1 SD increment in PRAT thickness was associated with a 2.77-fold higher adjusted odds of low-renin essential hypertension and a 3.89-fold higher adjusted odds of idiopathic hyperaldosteronism. PRAT thickness was not significantly associated with other forms of hypertension, such as aldosterone-producing adenoma and obstructive sleep apnea. In 2-sample Mendelian randomization analyses, PRAT thickness was only significantly associated with a higher risk of idiopathic hyperaldosteronism (inverse variance weighted odds ratio, 1.33 [95% CI, 1.09-1.62]), with no evidence of significant heterogeneity or substantial directional pleiotropy. CONCLUSIONS: PRAT is causally associated with idiopathic hyperaldosteronism rather than essential hypertension and other forms of secondary hypertension.

Humans

Genome sequencing and population genomics provide insights into the demographic history, genetic load, and local adaptation of an endangered Tertiary relict.

Endangered Tertiary relict trees represent an exceptional evolutionary heritage with small and isolated populations, yet little is known about how demographic history, local adaptation, and genetic load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Ulmus elongata L. K. Fu & C. S. Ding, an endangered Tertiary relict tree endemic to East Asia. By integrating genomes from U. elongata and seven other endangered trees from public databases, we identified rate-decelerated genes across endangered trees and genes under positive selection of U. elongata associated with tissue development, detoxification, and immune response, and signal transduction and regulation mechanisms potentially leading to endangered status. Demographic analyses revealed continuous population decline from the late Miocene to present, especially during the last glacial maximum (LGM) and last 10&#x2009;000&#x2009;years. Spearman correlation indicated a strong negative relationship between effective population size and human population density (rpopulation density&#x2009;=&#x2009;-0.90, P&#x2009;<&#x2009;0.001) as well as cropland use (rcropland use&#x2009;=&#x2009;-0.89, P&#x2009;<&#x2009;0.001). Genotype-environment association (GEA) analyses identified a set of candidate genes associated with temperature and precipitation, supporting a polygenic adaptation model in U. elongata. Overall, our findings underscore the severe population bottlenecks that have led to the fixation of strongly deleterious mutations and inbreeding, further compromising the adaptive potential and long-term viability of U. elongata. Furthermore, assessments of genomic vulnerability under future climate scenarios revealed higher genetic offsets in northern region of Fujian and Jiangxi populations, suggesting these regions require prioritized conservation efforts due to reduced adaptive capacity.

Endangered Species