Transfusion-dependent non-severe aplastic anemia: characteristics and outcomes in the clinic

Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic anemia (SAA). Little is known about the clinical and laboratory characteristics, and disease prognosis and outcomes in TD-NSAA patients. The clinical and laboratory data of 124 consecutive TD-NSAA patients in the Chinese Eastern Collaboration Group of Anemia from December 2013 and January 2017 were analyzed retrospectively. In 124 TD-NSAA patients, the median age was 32 years (range: 3-80) and the median disease course was 38 months (range: 3-363). Common complications were iron overload (53/101, 52.5%), liver and kidney dysfunction (42/124, 33.9%), diabetes mellitus/impaired glucose tolerance (24/124, 19.4%), and severe infection (29 cases, 23.4%). 58% of patients (57/124) developed severe aplastic anemia with a median progression time of 24 months (range: 3-216). Patients with absolute neutrophil count (ANC) <0.5×109/L, severe infection, or iron overload had a higher probability of progression to SAA (P=0.022, P=0.025, P=0.001). Patients receiving antithymocyte globulin (ATG) plus Cyclosporin A (CsA) had a higher overall response rate compared to those receiving CsA alone (56.7% vs 19.3%, P < 0.001). The addition of ATG was the favorable factor for efficacy (P=0.003). Fourteen patients developed secondary clonal hematologic disease: eleven patients with paroxysmal nocturnal hemoglobinuria, two patients with myelodysplastic syndromes, and one patient with acute myeloid leukemia, respectively. Ten patients (8.1%) died with a median follow-up of 12 months (range: 3- 36 months). Patients with TD-NSAA usually have a prolonged course of disease, and are prone to be complicated with important organ damage and disease progression to SAA. Intensive immunosuppressive therapy based on ATG might be an appropriate approach for TD-NSAA.Clinical trial registration:http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895

Enhanced cryogenic mechanical properties of heterostructured CrCoNi multicomponent alloy:Insights from <i>in-situ</i> neutron diffraction

Heterostructured materials (HSMs) has been shown to improve the strength-ductility trade-off of conventional alloys but their cryogenic performance has not been studied during real-time deformation. We investigated heterostructured CrCoNi medium-entropy alloy by in-situ neutron diffraction at cryogenic (77 K) and room (293 K) temperatures. The significant mechanical mismatch at interfaces between fine and coarse grains, due to pronounced grain size disparity, resulted in exceptional yield strength of 918 MPa at 293 K. The yield strength further increased to 1244 MPa at 77 K with an excellent uniform elongation of 34 %. The exceptional strength–ductility combination at 77 K can be attributed to enhanced geometrically necessary dislocation pile-up density boosted from high-mechanical mismatch interfaces, as well as higher planar faults, and martensitic phase transformation. Comparison with homogenous counterparts demonstrates the potential of HSMs as a new strategy to improve the mechanical performance of different materials, including medium-/high-entropy alloys for cryogenic applications.</p

Bone marrow endothelial cell-derived interleukin-4 contributes to thrombocytopenia in acute myeloid leukemia

Normal hematopoiesis can be disrupted by the leukemic bone marrow microenvironment, which leads to cytopenia-associated symptoms including anemia, hemorrhage and infection. Thrombocytopenia is a major and sometimes fatal complication in patients with acute leukemia. However, the mechanisms underlying defective thrombopoiesis in leukemia have not been fully elucidated. In the steady state, platelets are continuously produced by megakaryocytes. Using an MLL-AF9-induced acute myeloid leukemia mouse model, we demonstrated a preserved number and proportion of megakaryocyte-primed hematopoietic stem cell subsets, but weakened megakaryocytic differentiation via both canonical and non-canonical routes. This primarily accounted for the dramatic reduction of megakaryocytic progenitors observed in acute myeloid leukemia bone marrow and a severe disruption of the maturation of megakaryocytes. Additionally, we discovered overproduction of interleukin-4 from bone marrow endothelial cells in acute myeloid leukemia and observed inhibitory effects of interleukin-4 throughout the process of megakaryopoiesis in vivo. Furthermore, we observed that inhibition of interleukin-4 in combination with induction chemotherapy not only promoted recovery of platelet counts, but also prolonged the duration of remission in our acute myeloid leukemia mouse model. Our study elucidates a new link between interleukin-4 signaling and defective megakaryopoiesis in acute myeloid leukemia bone marrow, thereby offering a potential therapeutic target in acute myeloid leukemia

Chasing the precursor of functional hematopoietic stem cells at the single cell levels in mouse embryos

Abstract Background Adult hematopoietic stem cells (HSCs), the ideal system for regenerative research, were isolated at single cell levels decades ago, whereas studies on embryonic HSCs are much more difficult. Methods Zhou et al identified a new pre-HSC cell surface marker, CD201, by which they isolated pre-HSCs at single cell levels for further analyses. Results The novel expression pattern of HSC development is revealed, including the fundamental role of mammalian targets of rapamycin (mTOR) signaling pathway in HSCs emergence, and the repopulation potential of S/G2/M phase pre-HSCs. Conclusions Deeper understandings of the cellular origin and developmental regulatory network of HSCs are essential to develop new strategies of generating HSCs in vitro for clinical application

Resolution Enhancement Method of L(0,2) Ultrasonic Guided Wave Signal Based on Variational Mode Decomposition, Wavelet Transform and Improved Split Spectrum Processing

Pipeline systems are prone to defects due to the harsh service conditions, which may induce catastrophic failure if found not in time. Ultrasonic guided wave (UGW) testing provides a convenient option for pipeline detection, showing high-efficiency, non-contact, long-distance and large-scale capabilities. To address the problem that UGW signals suffer from poor signal resolution that is mainly related to the coherent noise caused by the dispersion, multi-mode and mode conversion, an advanced signal processing method called VWISSP, based on variational mode decomposition (VMD), wavelet transform (WT), and improved split spectrum processing (ISSP) was proposed, of which SSP was improved by replacing the Gaussian filter bank with cosine filters of constant frequency-to-bandwidth and frequency-to-filter spacing ratios. Compared with ISSP, VWISSP shows better higher accuracy and resolution processing effects to noisy multi-defect UGW signals, which is manifested through the improvement of both the signal-to-noise ratio gain and the defect-to-noise gain. Only feature signals (defects and pipe end) are retained, whereas noise signals are eliminated completely

Resolution Enhancement Method of L(0,2) Ultrasonic Guided Wave Signal Based on Variational Mode Decomposition, Wavelet Transform and Improved Split Spectrum Processing

Pipeline systems are prone to defects due to the harsh service conditions, which may induce catastrophic failure if found not in time. Ultrasonic guided wave (UGW) testing provides a convenient option for pipeline detection, showing high-efficiency, non-contact, long-distance and large-scale capabilities. To address the problem that UGW signals suffer from poor signal resolution that is mainly related to the coherent noise caused by the dispersion, multi-mode and mode conversion, an advanced signal processing method called VWISSP, based on variational mode decomposition (VMD), wavelet transform (WT), and improved split spectrum processing (ISSP) was proposed, of which SSP was improved by replacing the Gaussian filter bank with cosine filters of constant frequency-to-bandwidth and frequency-to-filter spacing ratios. Compared with ISSP, VWISSP shows better higher accuracy and resolution processing effects to noisy multi-defect UGW signals, which is manifested through the improvement of both the signal-to-noise ratio gain and the defect-to-noise gain. Only feature signals (defects and pipe end) are retained, whereas noise signals are eliminated completely

Multi-Objective Parameter Optimization Dynamic Model of Grinding Processes for Promoting Low-Carbon and Low-Cost Production

Grinding is widely used in mechanical manufacturing to obtain both precision and part requirements. In order to achieve carbon efficiency improvement and save costs, carbon emission and processing cost models of the grinding process are established in this study. In the modeling process, a speed-change-based adjustment function was introduced to dynamically derive the change of the target model. The carbon emission model was derived from the grinding force using regression. Considering the constraints of machine tool equipment performance and processing quality requirements, the grinding wheel&rsquo;s linear velocity, cutting feed rate, and the rotation speed of the workpiece were selected as the optimization variables, and the improved NSGA-II algorithm was applied to solve the optimization model. Finally, fuzzy matter element analysis was used to evaluate the most optimal processing plan