N 6 -methyladenosine (m 6 A) is a well-known post-transcriptional modification that is the most common type of methylation in eukaryotic mRNAs. The regulation of m 6 A is dynamic and reversible, which is erected by m 6 A methyltransferases ("writers") and removed by m 6 A demethylases ("erasers"). Notably, the effects on targeted mRNAs resulted by m 6 A predominantly depend on the functions of different m 6 A-binding proteins ("readers") including YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs). Indeed, m 6 A readers not only participate in multiple procedures of RNA metabolism, but also are involved in a variety of biological processes. In this review, we summarized the specific functions and underlying mechanisms of m 6 A-binding proteins in tumorigenesis, hematopoiesis, virus replication, immune response, and adipogenesis.
Key Points• We developed an approach of T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin.• Outcomes of suitably matched URD-HSCT and HRD-HSCT are similar, and HRD-HSCT improves outcomes of patients with high-risk leukemia.We developed an approach of T-cell-replete haploidentical hematopoietic stem cell transplantation (HSCT) with low-dose anti-T-lymphocyte globulin and prospectively compared outcomes of all contemporaneous T-cell-replete HSCT performed at our center using matched sibling donors (MSDs), unrelated donors (URDs), and haploidentical related donors (HRDs). From 2008 to 2013, 90 patients underwent MSD-HSCT, 116 underwent URD-HSCT, and 99 underwent HRD-HSCT. HRDs were associated with higher incidences of grades 2 to 4 (42.4%) and severe acute graft-versus-host disease (17.2%) and nonrelapse mortality (30.5%), compared with MSDs (15.6%, 5.6%, and 4.7%, respectively; P < .05), but were similar to URDs, even fully 10/10 HLA-matched URDs. For high-risk patients, a superior graft-versus-leukemia effect was observed in HRD-HSCT, with 5-year relapse rates of 15.4% in HRD-HSCT, 28.2% in URD-HSCT (P 5 .07), and 49.9% in MSD-HSCT (P 5 .002). Furthermore, 5-year disease-free survival rates were not significantly different for patients undergoing transplantation using 3 types of donors, with 63.6%, 58.4%, and 58.3% for MSD, URD, and HRD transplantation, respectively (P 5 .574). Our data indicate that outcomes after HSCT from suitably matched URDs and HRDs with low-dose anti-Tlymphocyte globulin are similar and that HRD improves outcomes of patients with high-risk leukemia. This trial was registered at www.chictr.org (Chinese Clinical Trial Registry) as #ChiCTR
Wild emmer, Triticum dicoccoides, the progenitor of cultivated wheat, harbors rich genetic resources for wheat improvement. They include many agronomic traits such as abiotic stress tolerances (salt, drought and heat), biotic stress tolerances (powdery mildew, rusts, and Fusarium head blight), grain protein quality and quantity, and micronutrient concentrations (Zn, Fe, and Mn). In this review, we summarize (1) traits and controlling genes identiWed and mapped in T. dicoccoides; and (2) the genes transferred to cultivated wheat from T. dicoccoides. These genes, controlling important agronomic traits such as disease resistance, high protein and micronutrient content, should contribute to wheat production and food nutrition. However, most of the rich genetic reservoir in wild emmer remains untapped, highlighting the need for further exploration and utilization for long-term wheat breeding programs.
The synthesis and biological efficacy of novel nanomicelles that rapidly disassemble and release their encapsulated payload intracellularly under tumor-relevant glutathione (GSH) levels are reported. The unique design includes a PEG-sheddable shell and poly(ε-benzyloxycarbonyl-l-lysine) core with a redox-sensitive disulfide linkage.
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