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.

In patients with sepsis and AKI, increasing the intensity of renal replacement therapy from 50 (HVHF) to 85 mL/kg/h (EHVHF) had no effect on survival at 28 and 90 days.

Donor cell leukemia after allogeneic hematopoietic stem cell transplantation might provide a unique human model for our understanding of leukemogenesis in vivo. We hypothesized that the "2-genetic-hits model" may contribute to the "leukemization" of donor cells and first evaluated these genetic mutations that are implicated in the development of acute myeloid leukemia in a donor cell leukemia patient and donor. The patient and his donor-sister both harbored a germline mutation in CEBPA (584_589dup). Susceptible donor hematopoietic cells evolved to overt acute myeloid leukemia by developing 2 somatic CEBPA mutations (247dupC and 914_916dup) in the patient's microenvironment. These were identical to the acquired mutations identified in leukemic cells that originated from the patient during de novo acute myeloid leukemia. Our results provide the first report of multiple mutations of CEBPA contributing to the transformation of donor cells to the leukemic phenotype and provide clues to support the multiplegenetic-hits mechanism of donor cell leukemia. (Blood. 2011;117(19):5257-5260) IntroductionLeukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that arises in cells of donor origin in the transplant recipient, so-called donor cell leukemia (DCL), is a rare disease entity, and only 51 cases were reported since 1971. [1][2][3][4] The precise etiologic mechanisms of DCL remain unknown, and no common mechanism can be identified in most of the cases reported in the literature. Careful analysis of the mechanisms with respect to the oncogenic transformation of donor-derived cells might provide a unique human model for our understanding of leukemogenesis in vivo.According to the "2-genetic-hits model," cooperation between 2 classes of genetic mutations contributes to leukemogenesis. 5 One group (class 1) comprises mutations in the fms-related tyrosine kinase 3 gene (FLT3) or the neuroblastoma RAS viral oncogene homolog gene (NRAS), which increase the proliferation and/or survival of hematopoietic stem/progenitor cells. 6,7 The other complementation group (class 2) comprises mutations in CEBPA, the gene that encodes the CCAAT enhancer-binding protein␣ (C/EBP␣); the myeloid-lymphoid or mixed-lineage leukemia gene (MLL); or the nucleophosmin gene (NPM1), which cause impaired differentiation. [8][9][10] The most common mutations, which include internal tandem duplications restricted to exons 14 and 15 and point mutation of Asp 835 within the TK domain of FLT3, codon 12/13 in exon 1 and codon 61 in exon 2 of NRAS, the entire coding region of CEBPA, partial tandem duplications that span exons 2-6 or exons 2-8 of MLL, and mutations in exon 12 of NPM1, have been described extensively in acute myeloid leukemia (AML). [11][12][13][14] We hypothesized that the 2-genetic-hits model may contribute to the "leukemization" of donor cells in DCL. We screened these genetic mutations implicated in the development of common forms of AML in a DCL patient and donor. MethodsThe study was approved by the Zhejiang U...

Xie (2019) Risk factors of early death in adult patients with secondary hemophagocytic lymphohistiocytosis: a single-institution study of 171 Chinese patients, Hematology, 24:1, 606-612, ABSTRACT Background: Adult secondary hemophagocytic lymphohistiocytosis (HLH) is a potentially lifethreatening syndrome characterized by excessive activation of mononuclear-phagocytic system resulting in hyperinflammatory response. To date, the factors influencing early death of HLH are still not fully elucidated. Patients and Methods: We did a retrospective study of 171 adult patients with newly diagnosed HLH at our institution from January 2012 to April 2018. All patients' clinical features, laboratory findings, treatments and prognosis were reviewed. Results: The median age was 49 years (range, 18-88 years), and 110 (64.3%) were male. The major underlying trigger of HLH was malignancy (88/171, 51.5%), especially non-Hodgkin lymphoma. In a multivariate analysis, age ≥54 years (P = 0.002), platelet ≤39.5 × 10 9 /L (P = 0.028), activated partial thromboplastin time (APTT) ≥54 sec (P = 0.048), triglyceride ≥3.23 mmol/L (P < 0.001), lactate dehydrogenase (LDH) ≥1300 U/L (P = 0.012) and malignancy (P = 0.001) were significantly associated with early death in HLH. Then, patients were classified into four groups according to the number of risk factors at the time of diagnosis: low risk (zero, one or two risk factors), low intermediate risk (three risk factors), high intermediate risk (four risk factors) and high risk (at least five risk factors), with the 30day overall survival (OS) of 92.4%, 58.8%, 30.0% and 4.8%, respectively (P < 0.001). Conclusions: Patients with old age, thrombocytopenia, prolonged APTT, hypertriglyceridemia, elevated LDH and malignancy had inferior survival. It is important to identify those patients at risk of early death, which may guide treatment and reduce mortality.

The gene-pool of wild emmer wheat, Triticum turgidum ssp. dicoccoides, harbors a rich allelic repertoire for disease resistance. In the current study, we made use of tetraploid wheat mapping populations derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16) to identify and map a new powdery mildew resistance gene derived from wild emmer wheat. Initially, the two parental lines were screened with a collection of 42 isolates of Blumeria graminis f. sp. tritici (Bgt) from Israel and 5 isolates from Switzerland. While G18-16 was resistant to 34 isolates, Langdon was resistant only to 5 isolates and susceptible to 42 isolates. Isolate Bgt#15 was selected to differentiate between the disease reactions of the two genotypes. Segregation ratio of F(2-3) and recombinant inbreed line (F(7)) populations to inoculation with isolate Bgt#15 indicated the role of a single dominant gene in conferring resistance to Bgt#15. This gene, temporarily designated PmG16, was located on the distal region of chromosome arm 7AL. Genetic map of PmG16 region was assembled with 32 simple sequence repeat (SSR), sequence tag site (STS), Diversity array technology (DArT) and cleaved amplified polymorphic sequence (CAPS) markers and assigned to the 7AL physical bin map (7AL-16). Using four DNA markers we established colinearity between the genomic region spanning the PmG16 locus within the distal region of chromosome arm 7AL and the genomic regions on rice chromosome 6 and Brachypodium Bd1. A comparative analysis was carried out between PmG16 and other known Pm genes located on chromosome arm 7AL. The identified PmG16 may facilitate the use of wild alleles for improvement of powdery mildew resistance in elite wheat cultivars via marker-assisted selection.