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

Quark clustering could occur in cold quark matter because of the strong coupling between quarks at realistic baryon densities of compact stars. Although one may still not be able to calculate this conjectured matter from first principles, the inter-cluster interaction might be analogized to the interaction between inert molecules. Cold quark matter would then crystallize in a solid state if the inter-cluster potential is deep enough to trap the clusters in the wells. We apply the Lennard-Jones potential to describe the inter-cluster potential, and derive the equations of state, which are stiffer than that derived in conventional models (e.g., MIT bag model). If quark stars are composed of Lennard-Jones matter, they could have high maximum masses ($>2M_{\odot}$) as well as very low masses ($<10^{-3}M_{\odot}$). These features could be tested by observations.Comment: 5 pages, 2 figures. Accepted by MNRAS (Letters

In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Science, the eXTP mission is expected to be launched in the mid 2020s.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for both malignant and nonmalignant hematologic disorders. However, primary poor graft function (PGF) is a serious early complication of allo-HSCT that leads to a poor outcome. Little is known about the characteristics, incidence, and risk factors of primary PGF occurring after allo-HSCT. Here we performed a 1:4 ratio nested case-control study in 830 patients who underwent allo-HSCT between April 2013 and November 2018 at our center. Twenty-four patients (14 males and 10 females; average age, 35.79 years; range, 17 to 53 years) developed primary PGF. On univariate and multivariate analyses, a CD34 + cell dose <5 £ 10 6 /kg (P = .003), a serum ferritin (SF) level >2000 ng/mL (P = .008), and splenomegaly (P = .039) were identified as 3 independent risk factors for primary PGF. After a median follow-up of 7.5 months (range, 1 to 48 months), only 5 patients (20.8%) survived. The survival rate of patients with primary PGF was significantly lower than that of patients with good graft function (GGF) (1-year overall survival, 25.0% versus 90.6%; P < .001). Cox regression analysis suggested that PGF and high SF level were strongly associated with rapid death in these patients. In conclusion, allo-HSCT recipients with a low CD34 + cell dose in their graft and exhibiting a high SF level and splenomegaly should be monitored for the development of primary PGF after allo-HSCT, and effective therapies need to be explored.

Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.

Mobilization of mesenchymal stem cells (MSCs) is a promising strategy for tissue repair and regenerative medicine. The establishment of an appropriate animal model and clarification of the underlying mechanisms are beneficial to develop the mobilization regimens for therapeutic use. In this study, we therefore established a rat MSC mobilization model and investigated the related mechanisms, using continuous hypoxia as the mobilizing stimulus. We found that MSCs could be mobilized into peripheral blood of rats exposed to short-term hypoxia (2 days) and the mobilization efficiency increased in a time-dependent manner (2-14 days). Hypoxia-inducible factor-1α (HIF-1α) was upregulated during hypoxic exposure and was expressed continuously in bone marrow. Inhibition of HIF-1α expression by YC-1 remarkably reduced the number of mobilized MSCs, suggesting that HIF-1α is essential for hypoxia-induced MSC mobilization. Further, we investigated the potential role of HIF-1α target genes, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α). VEGF expression was elevated from day 2 to day 7 of hypoxia, stimulating an increase in bone marrow sinusoidal vessels and possibly facilitating the egress of MSCs. SDF-1α protein levels were increased in the peripheral blood of rats during MSC mobilization and promoted the migration of MSCs under hypoxic conditions in vitro. These results suggest that HIF-1α plays a pivotal role in hypoxia-induced MSC mobilization, possibly acting via its downstream genes VEGF and SDF-1α. These data provide a novel insight into the mechanisms responsible for MSC mobilization and may help in the development of clinically useful therapeutic agents.

Background: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy.Methods: A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. Results: Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pretransplant MRD-negative recipients (MRD− group) had a lower cumulative incidence of relapse (17.3%) than those

A corresponding-state approach to quark-cluster matter * GUO Yan-Jun( ) 1;1) LAI Xiao-Yu( ) 2;2) XU Ren-Xin( ) 1,3;3)