Impaired T lymphopoiesis is associated with immunosuppression of the adaptive immune response and plays a role in the morbidity and mortality of patients and animal models of sepsis. Although previous studies examined several intrathymic mechanisms that negatively affect T lymphopoiesis, the extrathymic mechanisms remain poorly understood. Here, we report a dramatic decrease in the percentage of early T lineage progenitors (ETPs) in three models of sepsis in mice (cecal ligation and puncture, lipopolysaccharide continuous injection, and poly I:C continuous injection). However, septic mice did not show a decrease in the number of bone marrow (BM) precursor cells. Instead, the BM progenitors for ETPs expressed reduced mRNA levels of CC chemokine receptor (CCR) 7, CCR9 and P-selectin glycoprotein ligand 1, and exhibited impaired homing capacity in vitro and in vivo. Furthermore, RNA-Seq analysis and real-time PCR showed a marked downregulation of several lymphoid-related genes in hematopoietic stem and progenitor cells. Hematopoietic stem and progenitor cells differentiated into myeloid cells but failed to generate T lymphocytes in vitro and in vivo. Our results indicate that the depletion of ETPs in septic mice might be a consequence of an impaired migration of BM progenitors to the thymus, as well as a defect in lymphoid lineage commitment. Stem Cells 2016;34:2902-2915.

Micro/nanoplastics have emerged as global contaminants of serious concern to human and ecosystem health. However, identification and visualization of microplastics and particularly nanoplastics have remained elusive due to the lack of feasible and reliable analytical approaches, particularly for trace nanoplastics. Here, an efficient surface-enhanced Raman spectroscopy (SERS)-active substrate with triangular cavity arrays is reported. The fabricated substrate exhibited high SERS performance for standard polystyrene (PS) nanoplastic detection with size down to 50 nm and a detection limit of 0.001% (1.5 × 1011 particles/mL). Poly(ethylene terephthalate) (PET) nanoplastics collected from commercially bottled drinking water were detected with an average mean size of ∼88.2 nm. Furthermore, the concentration of the collected sample was estimated to be about 108 particles/mL by nanoparticle tracking analysis (NTA), and the annual nanoplastic consumption of human beings through bottled drinking water was also estimated to be about 1014 particles, assuming water consumption of 2 L/day for adults. The facile and highly sensitive SERS substrate provides more possibilities for detecting trace nanoplastics in an aquatic environment with high sensitivity and reliability.

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