Deciphering cell states and genealogies of human haematopoiesis.

The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived haematopoietic stem cells (HSCs)1. Perturbations to this process underlie diverse diseases, but the clonal contributions to human haematopoiesis and how this changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems2-5, simultaneous detection of cell states and phylogenies from natural barcodes in humans remains challenging. Here we introduce an improved, single-cell lineage-tracing system based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs and map the physiological state and output of clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as both differences in total HSC output and biases towards the production of different mature cell types. We also find that the diversity of HSC clones decreases markedly with age, leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides a clonally resolved and cell-state-aware atlas of human haematopoiesis at single-cell resolution, showing an unappreciated functional diversity of human HSC clones and, more broadly, paving the way for refined studies of clonal dynamics across a range of tissues in human health and disease.

Graphite-N reinforced sludge biochar electrode: A experimental and DFT theoretical analysis of efficient evolution and in-situ utilization of H2O2.

Rational reuse of municipal sludge to produce electro-Fenton electrode can not only save resources, but also produce superior peroxide and degradation pollutants simultaneously. Herein, a novel electro-Fenton electrode derived from sludge biochar loaded on Ni foam (SBC@Ni) was constructed via high temperature pyrolysis and chemical coating for efficient H2O2 evolution and pollutant degradation. Systematic experiments and density functional theory calculations (DFT calculation) explained that the production of graphite C and graphite N during high-temperature pyrolysis of municipal sludge can greatly enhance the oxygen reduction reaction of SBC@Ni electrode and promote the evolution of H2O2. And the hybrid heterojunctions, such as FeP, also played a key role in electrocatalytic processes. Notably, the electrode still exhibited excellent performance after 1000 linear scans and 12 h of continuous current stimulation, which demonstrated the excellent stability of the electrode. Moreover, SBC@Ni electrode can not only effectively oxidize 4-chlorophenol through the electro-Fenton effect, but also fully mineralize organic matter, indicating promising environmental application. The free radical quenching experiment also revealed that the ·OH is the main active species for 4-CP degradation in SBC@Ni electro-Fenton system.