International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis

122 type pnictide superconductors are of particular interest for high-field applications because of their large upper critical fields H c2 (> 100 T) and low anisotropy γ (<2). Successful magnet applications require fabrication of polycrystalline superconducting wires that exhibit large critical current density J c , which is limited by poor grain coupling and weak-link behavior at grain boundaries.Here we report our recent achievement in the developing Sr 0.6 K 0.4 Fe 2 As 2 tapes with transport J c up to 0.1 MA/cm 2 at 10 T and 4.2 K. This value is by far the highest ever recorded for iron based superconducting wires and has surpassed the threshold for practical application. The synergy effects of enhanced grain connectivity, alleviation of the weak-link behavior at grain boundaries, and the strong intrinsic pinning characteristics led to the superior J c performance exhibited in our samples. This advanced J c result opens up the possibility for iron-pnictide superconducting wires to win the race in high-field magnet applications.

V␣14i natural killer T (NKT)-cell function has been implicated in a number of disease conditions. The molecular events that drive V␣14i NKT-cell development remain elusive. We recently showed that T-bet is required for the terminal maturation of these cells. Here we identify some of the genetic targets of T-bet during V␣14i NKT-cell lineage development. Microarray gene-expression analyses on developing V␣14i NKT cells were performed and provide a molecular framework to study these maturation events. In vitro ectopic expression of T-bet in immature V␣14i NKT cells, which do not yet express T-bet, was sufficient to promote V␣14i NKT-cell maturation, driving the expression of multiple genes, including those that participate in migration, survival, and effector func- IntroductionNatural killer T (NKT) cells are a unique lymphocyte lineage that coexpresses a rearranged T-cell receptor (TCR) in association with the CD3 complex as well as several receptors first identified on bona fide NK cells, such as NK1.1, the interleukin-2 (IL-2)/15R␤ chain (CD122) and various Ly49 molecules. 1 Most NKT cells in the mouse express a semi-invariant TCR composed of a V␣14-J␣18 rearrangement that preferentially associates with either V␤8, V␤7, or V␤2, 2 and are positively selected by CD1d, a nonclassical major histocompatibility (MHC) class I molecule. We refer to this CD1d reactive subgroup as V␣14 invariant (V␣14i) NKT cells to distinguish them from other populations of NKT cells that have been defined. 3,4 The early and potent cytokine secretion by V␣14i NKT cells following TCR stimulation may provide an important link between the innate and adaptive immune systems. 3,5 Consistent with this, V␣14i NKT cells appear to be important for responses to tumors, infectious agents, the maintenance of self tolerance, and the prevention of autoimmunity. 1,3 Recent progress has been made in identifying V␣14i NKT-cell developmental intermediates. [6][7][8][9] V␣14i NKT cells develop from CD4 ϩ CD8 ϩ double-positive (DP) V␣14-J␣18 TCR ϩ thymocyte precursors. 6,[10][11][12] Following positive selection by CD1d molecules, V␣14i NKT cells undergo a maturation process defined by the sequential up-regulation of diverse markers and the late fate specification of the NKT-cell lineage. 6-9 NKT-cell precursors can be identified on the basis of TCR specificity in the thymus of young mice using the CD1d tetramer. These cells are phenotypically indistinguishable from conventional mature lymphocytes, being HSA low , CD44 low , and NK1.1 Ϫ . 7 This phenotype is defined as stage 1. 13 Ontogeny and transfer studies defined a developmental sequence from CD44 low NK1.1 -(stage 1) to CD44 high NK1.1 -(stage 2). At this latter stage, V␣14i NKT cells are still considered immature but can leave the thymus and colonize peripheral organs. 7,8 A final maturation step that occurs either in the thymus or in the peripheral organs is accompanied by the expression of NK1.1, Ly49 receptors and CD122 (stage 3). 7,8,14 Interestingly, these 3 developmental intermediates each ha...

High-performance Sr0.6K0.4Fe2As2 (Sr-122) tapes have been successfully fabricated using hot pressing (HP) process. The effect of HP temperatures (850–925°C) on the c-axis texture, resistivity, Vickers micro-hardness, microstructure and critical current properties has been systematically studied. Taking advantage of high degree of c-axis texture, well grain connectivity and large concentration of strong-pinning defects, we are able to obtain an excellent Jc of 1.2 × 105 A/cm2 at 4.2 K and 10 T for Sr-122 tapes. More importantly, the field dependence of Jc turns out to be very weak, such that in 14 T the Jc still remains ~ 1.0 × 105 A/cm2. These Jc values are the highest ever reported so far for iron-pnictide wires and tapes, achieving the level desired for practical applications. Our results clearly strengthen the position of iron-pnictide conductors as a competitor to the conventional and MgB2 superconductors for high field applications.

Improving transport current has been the primary topic for practical application of superconducting wires and tapes. However, the porous nature of powder-in-tube (PIT) processed iron-based tapes is one of the important reasons for low critical current density (Jc) values. In this work, the superconducting core density of ex-situ Sr0.6K0.4Fe2As2 + Sn tapes, prepared from optimized precursors, was significantly improved by employing a simple hot pressing as an alternative route for final sintering. The resulting samples exhibited optimal critical temperature (Tc), sharp resistive transition, small resistivity and high Vickers hardness (Hv) value. Consequently, the transport Jc reached excellent values of 5.1 × 104 A/cm2 in 10 T and 4.3 × 104 A/cm2 in 14 T at 4.2 K, respectively. Our tapes also exhibited high upper critical field Hc2 and almost field-independent Jc. These results clearly demonstrate that PIT pnictide wire conductors are very promising for high-field magnet applications.

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

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