HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells.

BACKGROUND: A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection. RESULTS: In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs. CONCLUSIONS: Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.

HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into T lymphoid cells.

OBJECTIVE: Despite successful antiviral therapy, the recovery of CD4+ T cells may not be complete in certain HIV-1-infected individuals. In our previous work with humanized mice infected with CXCR4-tropic HIV-1LAI (LAI), viral protein Nef was found the major factor determining rapid loss of both CD4+ T cells and CD4+CD8+ thymocytes but its effect on early T-cell development is unknown. The objective of this study is to investigate the influence of LAI Nef on the development of hematopoietic stem/progenitor cells (HSPCs) into T lymphoid cells. DESIGN: HSPC-OP9-DL1 cell co-culture and humanized mouse model was used to investigate the objective of our study in vitro and in vivo. RNA-seq was exploited to study the change of gene expression signature after nef expression in HSPCs. RESULTS: Nef expression in HSPCs was found to block their development into T lymphoid cells both in vitro and in the mice reconstituted with nef-expressing HSPCs derived from human cord blood. More surprisingly, in humanized mice nef expression preferentially suppressed the production of CD4+ T cells. This developmental defect was not the result of CD34+ cell loss. RNA-seq analysis revealed that Nef affected the expression of 176 genes in HSPCs, including those involved in tumor necrosis factor, Toll-like receptor, and nucleotide-binding oligomerization domain-like receptor signaling pathways that are important for hematopoietic cell development. CONCLUSION: Our results demonstrate that Nef compromises the development of HSPCs into T lymphoid cells, especially CD4+ T cells. This observation suggests that therapeutics targeting Nef may correct HIV-1-associated hematopoietic abnormalities, especially defects in T-cell development.

Management of Delayed Fluorophor-Sensitized Exciton Harvesting for Stable and Efficient All-Fluorescent White Organic Light-Emitting Diodes.

White organic light-emitting diodes (WOLEDs) using thermally activated delayed fluorescence (TADF)-based single emissive layer (SEL) have attracted enormous attention because of their simple device structure and full exciton utilization potential for high efficiency. However, WOLEDs made of an all-TADF SEL usually exhibit serious efficiency roll-off and poor color stability due to serious exciton-annihilation and unbalanced radiative decays of different TADF emitters. Herein, a new strategy is proposed to manipulate the TADF-sensitized fluorescence process by combining dual-host systems of high triplet energy with a conventional fluorescent emitter of complementary color. The multiple energy-funneling paths are modulated and short-range Dexter energy transfer is largely suppressed due to the steric effect of peripheral tert-butyl group in the blue TADF sensitizer. The resulting all-fluorescent WOLEDs achieve an unprecedentedly high external quantum efficiency of 21.8% with balanced white emission of Commission Internationale de l'Eclairage coordinate of (0.292, 0.343), accompanied with good color stability, reduced efficiency roll-off, and prolonged operational lifetime. These findings demonstrate the validity of this strategy for precisely allocating the exciton harvesting in SEL WOLEDs.

High-Performance Nondoped Blue Delayed Fluorescence Organic Light-Emitting Diodes Featuring Low Driving Voltage and High Brightness.

Thermally activated delayed fluorescence (TADF) provides great potential for the realization of efficient and stable organic light-emitting diodes (OLEDs). However, it is still challenging for blue TADF emitters to simultaneously achieve high efficiency, high brightness, and low Commission Internationale de l'Eclairage (CIE) y coordinate (CIEy) value. Here, the design and synthesis of two new benzonitrile-based TADF emitters (namely 2,6-di(9H-carbazol-9-yl)-3,5-bis(3,6-diphenyl-9H-carbazol-9-yl)benzonitrile (2PhCz2CzBn) and 2,6-di(9H-carbazol-9-yl)-3,5-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)benzonitrile (2tCz2CzBn)) with a symmetrical and rigid heterodonor configuration are reported. The TADF OLEDs doped with both the emitters can achieve a high external quantum efficiency (EQE) over 20% and narrowband blue emission of 464 nm with a CIEy < 0.2. Moreover, the incorporation of a terminal tert-butyl group can weaken the intermolecular π-π stacking in the nondoped TADF emitter, and thus significantly suppress self-aggregation-caused emission quenching for enhanced delayed fluorescence. A peak EQE of 21.6% is realized in the 2tCz2CzBn-based nondoped device with an extremely low turn-on voltage of 2.7 V, high color stability, a high brightness over 20 000 cd m-2, a narrow full-width at half-maximum of 70 nm, and CIE color coordinates of (0.167, 0.248).

Highly efficient organic light-emitting devices based on multifunctional nanoparticles.

We have constructed a new approach to realize the light extraction enhancement in organic light-emitting diodes (OLEDs) by using Fe3O4@Au nanoparticles (FOA NPs). The current efficiency of 97.8 cd/A at a luminance of 500 cd/m2 can be obtained for the FOA-NP-based device, while it is only 61 cd/A for the control device without FOA NPs, corresponding a 60% enhancement in efficiency. The time-resolved photoluminescence and optical haze characterizations were performed to study the influence of FOA NPs on the lifetime of excitons and the light-scattering effect, respectively. These results reveal that the enhanced radical efficiency of an FOA-NP-based device is mainly ascribed to the localized surface plasmonic effects induced by Au NPs and the strong light-scattering effect related to FOA NPs, thereby achieving a double enhancement in light extraction, which paves a new way in realizing high-efficiency and controllable OLEDs.

High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing.

BACKGROUND: The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species. RESULTS: The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels. CONCLUSIONS: We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.