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1.
Sci Adv ; 10(25): eadk8501, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905342

ABSTRACT

Single-cell technology has allowed researchers to probe tissue complexity and dynamics at unprecedented depth in health and disease. However, the generation of high-dimensionality single-cell atlases and virtual three-dimensional tissues requires integrated reference maps that harmonize disparate experimental designs, analytical pipelines, and taxonomies. Here, we present a comprehensive single-cell transcriptome integration map of cardiac fibrosis, which underpins pathophysiology in most cardiovascular diseases. Our findings reveal similarity between cardiac fibroblast (CF) identities and dynamics in ischemic versus pressure overload models of cardiomyopathy. We also describe timelines for commitment of activated CFs to proliferation and myofibrogenesis, profibrotic and antifibrotic polarization of myofibroblasts and matrifibrocytes, and CF conservation across mouse and human healthy and diseased hearts. These insights have the potential to inform knowledge-based therapies.


Subject(s)
Fibroblasts , Fibrosis , Single-Cell Analysis , Transcriptome , Animals , Single-Cell Analysis/methods , Humans , Fibroblasts/metabolism , Mice , Myocardium/metabolism , Myocardium/pathology , Myofibroblasts/metabolism , Myofibroblasts/pathology , Gene Expression Profiling
2.
Nat Metab ; 6(5): 847-860, 2024 May.
Article in English | MEDLINE | ID: mdl-38811804

ABSTRACT

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.


Subject(s)
Adaptor Proteins, Signal Transducing , Adipocytes , Adipose Tissue , Energy Metabolism , Hippo Signaling Pathway , Leptin , Protein Serine-Threonine Kinases , Signal Transduction , YAP-Signaling Proteins , Animals , Leptin/metabolism , Protein Serine-Threonine Kinases/metabolism , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , YAP-Signaling Proteins/metabolism , Adipose Tissue/metabolism , Adipocytes/metabolism , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism , Phosphoproteins/metabolism , Phosphoproteins/genetics , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Trans-Activators/metabolism , Trans-Activators/genetics
3.
Environ Sci Pollut Res Int ; 29(28): 42074-42089, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35129745

ABSTRACT

Single-use plastic waste is gradually considered a potential material for circular economy. Ion exchange resin obtained from polystyrene waste by sulfonating with H2SO4 was used for heavy metal removal from electroplating wastewater. Batch mode experiments of Cu2+, Zn2+, and Cd2+ were carried out to determine effect of pH, initial concentration, equilibrium time, and the isotherm and kinetic parameters; the stability of the resin in continuous operation was then evaluated. Finally, the longevity of the resin after being exhausted was explored. The results indicated that at pH 6, a pseudo-second-order kinetic model was applicable to describe adsorption of studied heavy metals by sulfonated polystyrene with adsorption capacities of 7.48 mg Cu2+/g, 7.23 mg Zn2+/g, and 6.50 mg Cd2+/g, respectively. Moreover, the ion exchange process between sulfonated polystyrene resin and Cu2+, Zn2+, Cd2+ ions followed the Langmuir isotherm adsorption model with R2 higher than 96%. The continuous fixed-bed column in conditions of a sulfonated polystyrene mass of 500 g, and a flow rate of 2.2 L/h was investigated for an influent solution with known initial concentration of 20 mg/L. Thomas and Yoon-Nelson models were tested with regression analysis. When being exhausted, the sulfonated polystyrene was regenerated by NaCl in 10 min with ratio 5 mL of NaCl 2 M per 1 g saturated resins. After 4 times regeneration, the heavy metal removal efficiency of sulfonated polystyrene was reduced to 50%. These aforementioned results can figure out that by sulfonating polystyrene waste to synthesize ion exchanging materials, this method is technically efficient and environmentally friendly to achieve sustainability.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Adsorption , Cadmium/analysis , Hydrogen-Ion Concentration , Kinetics , Metals, Heavy/analysis , Plastics , Polystyrenes/analysis , Sodium Chloride , Wastewater/analysis , Water Pollutants, Chemical/analysis
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