Ruxolitinib improves hematopoietic regeneration by restoring mesenchymal stromal cell function in acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. Hematopoietic dysfunction accompanied by severe aGVHD, which may be caused by niche impairment, is a long-standing clinical problem. However, how the bone marrow (BM) niche is damaged in aGVHD hosts is poorly defined.

WDR82-binding long noncoding RNA lncEry controls mouse erythroid differentiation and maturation.

Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long noncoding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes.

Enantioselective Construction of Tertiary α-Alkyl Fluoride via BTM-Catalyzed Fluorination of α-Alkynyl-Substituted Acetic Acids.

The isothiourea-catalyzed enantioselective construction of tertiary α-fluoro stereogenic centers has been demonstrated by using branched alkynyl-substituted acetic acids as starting materials, providing a broad range of optically active tertiary α-alkyl fluorides in high enantioselectivity (up to 97% ). Furthermore, this methodology was proven to be scaled up to a Gram scale without loss of enantioselectivity.

Understanding the "SMART" features of hematopoietic stem cells and beyond.

Since the huge success of bone marrow transplantation technology in clinical practice, hematopoietic stem cells (HSCs) have become the gold standard for defining the properties of adult stem cells (ASCs). Here, we describe the "self-renewal, multi-lineage differentiation, apoptosis, rest, and trafficking" or "SMART" model, which has been developed based on data derived from studies of HSCs as the most well-characterized stem cell type. Given the potential therapeutic applications of ASCs, we delineate the key characteristics of HSCs using this model and speculate on the physiological relevance of stem cells identified in other tissues.

[2.2]Paracyclophane-Based Isothiourea-Catalyzed Highly Enantioselective α-Fluorination of Carboxylic Acids.

Planar chiral [2.2]paracyclophane-based isothiourea catalysts have been prepared over a few simple steps in high yields. In the presence of these catalysts, highly efficient catalytic enantioselective fluorination of carboxylic acids has been accomplished, providing a broad range of optically active α-fluoroesters in high yield and excellent enantioselectivity.

Oxidative Asymmetric [2 + 3] Annulation of Aldehydes with Azomethine Imines Enabled by N-Heterocyclic Carbene Catalysis.

An efficient asymmetric [2 + 3] annulation of simple aldehydes with N,N'-cyclic azomethine imines via oxidative N-heterocyclic carbene (NHC) catalysis is disclosed, affording bicyclic pyrazolidinones bearing two vicinal tertiary stereogenic centers with moderate to good yields (56-84% for 19 examples), good to excellent diastereoselectivities (>20:1 for 17 examples), and good to excellent enantioselectivities (66-98% for 19 examples). This direct α-carbon functionalization reaction of aldehyde can be readily performed on gram scale under mild conditions, and a five-membered transition state is proposed to rationalize the stereochemical outcome.

Base-mediated diastereoselective [4 + 3] annulation of in situ generated ortho-quinone methides with C,N-cyclic azomethine imines.

An efficient [4 + 3] annulation of 2-(1-tosylalkyl)phenols with C,N-cyclic azomethine imines via in situ generation of ortho-quinone methides (o-QMs) under mild basic reaction conditions is disclosed, furnishing biologically interesting seven-membered heterocyclic compounds with moderate to good yields and excellent diastereoselectivities. A gram-scale reaction is performed to demonstrate the potential in industrial application and two transition states are proposed to rationalize the outstanding diastereoselectivity.

Enantioselective [2+2] annulation of simple aldehydes with isatin-derived ketimines via oxidative N-heterocyclic carbene catalysis.

An asymmetric [2+2] annulation reaction through direct α-carbon functionalization of simple aldehydes via oxidative N-heterocyclic carbene catalysis is disclosed. These in situ generated triazolium enolate intermediates undergo a highly stereoselective Mannich reaction with isatin-derived ketimines followed by intramolecular lactamization to afford enantioenriched spirooxindole β-lactams bearing two vicinal stereogenic centers.

1-Hydroxybenzotriazole-Assisted, N-Heterocyclic Carbene Catalyzed β-Functionalization of Saturated Carboxylic Esters: Access to Spirooxindole Lactones.

A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct β-functionalization of saturated carboxylic esters is disclosed. This formal [3 + 2] annulation reaction of carboxylic esters with isatins affords optically pure spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A dual role of HOBt is proposed based on controlled experiments to rationalize the enhancement of diastereoselectivity and enantioselectivity.

N-Heterocyclic Carbene Catalyzed [4 + 2] Annulation Reactions with in Situ Generated Heterocyclic ortho-Quinodimethanes.

An efficient strategy for the in situ generation of heterocyclic ortho-quinodimethanes (oQDMs) from 2-methyl-heteroarene-3-carboxylic esters by N-heterocyclic carbene (NHC) catalysis is disclosed. These heterocyclic oQDMs undergo highly enantioselective [4 + 2] annulation reactions with isatin-derived ketimines to afford optically pure heteroarene-fused δ-lactams bearing a quaternary stereogenic center. The main features of this reaction include challenging direct C(sp(3))-H bond functionalizations, excellent enantioselectivities, readily available starting materials, mild reaction conditions, high efficiency, and operational simplicity.