Analysis of the 2p-manifold population distribution in a diode-pumped metastable Ar laser.

The complex excited energy levels in the diode-pumped metastable Ar laser may induce harmful effects in laser cycling. Significantly, the influence of the population distribution in 2p energy levels on the laser performance is unclear yet. In this work, the absolute populations in all the 2p states were measured online by the simultaneous applications of tunable diode laser absorption spectroscopy and optical emission spectroscopy. The results showed that most atoms were populated to the 2p8, 2p9, and 2p10 levels while lasing, and the majority of the 2p9 population was efficiently transferred to the 2p10 level with the aid of helium, which was beneficial for the laser performance.

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. To comprehensively address this question, we used a haplo-MHC-matched transplantation aGVHD murine model and performed single-cell RNA-Seq of nonhematopoietic BM cells. Transcriptional analysis showed that BM mesenchymal stromal cells (BMSCs) were severely affected, with a reduction in cell ratio, abnormal metabolism, compromised differentiation potential, and defective hematopoiesis-supportive function, all of which were validated by functional assays. We found that ruxolitinib, a selective JAK1/2 inhibitor, ameliorated aGVHD-related hematopoietic dysfunction through a direct effect on recipient BMSCs, resulting in improved proliferation ability, adipogenesis/osteogenesis potential, mitochondria metabolism capacity, and crosstalk with donor-derived hematopoietic stem/progenitor cells. By inhibiting the JAK2/STAT1 pathway, ruxolitinib maintained long-term improvement of aGVHD BMSC function. Additionally, ruxolitinib pretreatment in vitro primed BMSCs to better support donor-derived hematopoiesis in vivo. These observations in the murine model were validated in patient samples. Overall, our findings suggest that ruxolitinib can directly restore BMSC function via the JAK2/STAT1 pathway and, in turn, improve the hematopoietic dysfunction caused by aGVHD.

Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100Ahigh immunoregulatory neutrophil progenitors, immunophenotyped as Lin-CD34+CD66b+CD177+, than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.

Uncovering the emergence of HSCs in the human fetal bone marrow by single-cell RNA-seq analysis.

During fetal development, human hematopoietic stem cells (HSCs) colonize the bone marrow (BM), where they self-renew and sustain hematopoiesis throughout life; however, the precise timepoint at which HSCs seed the BM is unclear. We used single-cell RNA-sequencing to map the transcriptomic landscape of human fetal BM and spleen hematopoietic stem/progenitor cells (HSPCs) and their microenvironment from 10 to 14 post-conception weeks (PCWs). We further demonstrated that functional HSCs capable of reconstituting long-term multi-lineage hematopoiesis in adult NOG mice do not emerge in the BM until 12 PCWs. In contrast, functional HSCs were not detected in the spleen by 14 PCWs. By comparing the niche-HSPC interactions between BM and spleen, we identified ligand-receptor pairs likely to be involved in fetal HSC migration and maintenance. Our work paves the way for research into the mechanisms underlying HSC colonization in human fetal BM and provides invaluable resources for future studies on HSC development.

Polarization insensitive efficient ultra-narrow diode laser strictly locked by a Faraday filter.

A Faraday anomalous dispersion optical filter (FADOF) could lock high-power diode lasers to atomic resonance lines with ultra-narrow bandwidth. However, the polarization sensitivity of the Faraday filter limits its applications since the standard diode module often employs polarization combination to increase pumping brightness. We proposed a polarization-insensitive mutual injection configuration to solve this problem and locked a standard polarization combined diode module to Rb D2-line. The laser bandwidth was narrowed from 4 nm to 0.005 nm (2.6 GHz, FWHM) with 38.3 W output and an external cavity efficiency of 80%. This FADOF-based polarization-insensitive external-cavity scheme would find many applications, such as high energy atomic gas laser pumping (alkali lasers, metastable rare gas lasers) and quantum optics, etc.

Simultaneous Observation of Visible Upconversion and Near-Infrared Downconversion in SrF2:Nd3+/Yb3+/Er3+ Nanocrystals and Their Application for Detecting Metal Ions under Dual-Wavelength Excitation.

In this work, a sequence of Nd3+, Yb3+, and Er3+ tridoped SrF2 nanocrystals (NCs) is synthesized by a hydrothermal method. Both the efficient near-infrared downconversion luminescence (DCL) and visible upconversion luminescence (UCL) of the Er3+ and Nd3+ ions are simultaneously observed and systematically demonstrated under dual-wavelength excitation (808 and 980 nm continuous-wave lasers). Subsequently, the SrF2:Nd3+/Yb3+/Er3+ (15/4/0.2 mol %) NCs with the strongest luminescence were utilized for detecting the metal ion concentrations under 808 nm excitation. The results reveal that both the UCL and DCL gradually decrease as the metal ion concentrations increase, and high sensitivity is obtained for Cu2+ ions with a detection limit of 0.22 nM (∼650 nm) and 0.63 nM (∼976 nm). In addition, these SrF2:Nd3+/Yb3+/Er3+ NCs are further demonstrated to achieve a solid-state display under 980 nm excitation, exhibiting obvious "red" and "green" patterns by varying the doping rare earth ion concentrations.

Boltzmann- and Non-Boltzmann-Based Thermometers in the First, Second and Third Biological Windows for the SrF2:Yb3+, Ho3+ Nanocrystals Under 980, 940 and 915 nm Excitations.

Spectrally determination of temperature based on the lanthanide-doped nanocrystals (NCs) is a vital strategy to noninvasively measure the temperature in practical applications. Here, we synthesized a series of SrF2:Yb3+/Ho3+ NCs and simultaneously observed the efficient visible upconversion luminescence (UCL) and near-infrared (NIR) downconversion luminescence (DCL) under 980, 940 and 915 nm excitations. Subsequently, these NCs were further utilized for thermometers based on the Boltzmann (thermally coupled levels, TCLs) and non-Boltzmann (non-thermally coupled levels, NTCLs) of Ho3+ ions in the first (~ 650 nm), second (~ 1012 nm) and third (~ 2020 nm) biological windows (BW-I, BW-II and BW-III) under tri-wavelength excitations. The thermometric parameters including the relative sensitivity ([Formula: see text]) and temperature uncertainty ([Formula: see text]) are quantitatively determined on the I648/I541 (BW-I), I1186/I1012 (BW-II), and I1950/I2020 (BW-III) transitions of Ho3+ ions in the temperature range of 303-573 K. Comparative experimental results demonstrated that the thermometer has superior performances.

Demonstration of a diode-pumped plasma jet-type rare gas laser.

The diode-pumped metastable rare gas laser (DPRGL) is showing potential for high-power operation. A key issue in developing this concept is to produce high-density metastables in a large volume. To achieve this goal, we propose a new, to the best of our knowledge, architecture by extracting laser power from a diode-pumped plasma jet. In this scheme, the discharge and gain regions are separated, avoiding the negative effects of discharges in confined regions. A diode-pumped plasma jet-type Ar laser is demonstrated with 466-mW output and 33% slope efficiency. The gain volume can be increased with multi-jets, providing a better scaling potential for the DPRGL system.

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. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript that has not been reported before. lncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat-containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.

Excitation-Power-Dependent Upconversion Luminescence Competition in Single ß-NaYbF4:Er Microcrystal Pumped at 808 nm.

Controlling the upconversion luminescence (UCL) intensity ratio, especially pumped at 808 nm, is of fundamental importance in biological applications due to the water molecules exhibiting low absorption at this excitation wavelength. In this work, a series of ß-NaYbF4:Er microrods were synthesized by a simple one-pot hydrothermal method and their intense green (545 nm) and red (650 nm) UCL were experimentally investigated based on the single-particle level under the excitation of 808 nm continuous-wave (CW) laser. Interestingly, the competition between the green and red UCL can be observed in highly Yb3+-doped microcrystals as the excitation intensity gradually increases, which leads to the UCL color changing from green to orange. However, the microcrystals doped with low Yb3+ concentration keep green color which is independent of the excitation power. Further investigations demonstrate that the cross-relaxation (CR) processes between Yb3+ and Er3+ ions result in the UCL competition.

Fast on-line rubidium DPAL atomic concentration measurement by 420 nm probe laser: erratum.

We present an erratum to our recent work [Appl. Opt.60, 10862 (2021)APOPAI0003-693510.1364/AO.440435] that corrects errors in Fig. 4 and the body of the paper. The corrections do not affect the results and conclusions of the original paper.

Revealing kinetics of a diode-pumped metastable Ar laser in pulsed and CW lasing.

We have experimentally investigated the kinetics of a diode-pumped metastable Ar laser by simultaneously monitoring the population evolution of 1s5 and 1s4 states during lasing. A comparison between the two cases with the pump laser on and off revealed the cause for the transition from pulsed to CW lasing. The depletion of 1s5 atoms was responsible for the pulsed lasing phenomenon, while increasing the duration and density of 1s5 atoms resulted in CW lasing. Furthermore, population accumulation of the 1s4 state was observed.

18W ultra-narrow diode laser absolutely locked to the Rb D2 line.

We described a wavelength locked and spectral narrowed high-power diode laser with a Faraday anomalous dispersion optical filter (FADOF). By an external cavity with a 85Rb FADOF, the central wavelength of the diode laser was precisely locked to the Rb resonance D2 line. The bandwidth was narrowed from the free-running 4 nm to 0.002 nm (1.2 GHz, FWHM). At 4.9 A maximal driven current, the laser produced a continuous wave (CW) output of 18 W with an external cavity efficiency of 80%, either the current or the temperature had no impact on the central wavelength of the diode laser. The Rb cell works well without any damage under a long-time running. This ultra-stable and extreme-narrowed high power diode laser would find many applications in alkali lasers pumping, metastable rare gas laser pumping, spin-exchange optical pumping, and quantum optics.

Quantitative Trait Loci Identification by Estimating the Genetic Model based on the Extremal Samples.

Background: In genetic association studies with quantitative trait loci (QTL), the association between a candidate genetic marker and the trait of interest is commonly examined by the omnibus F test or by the t-test corresponding to a given genetic model or mode of inheritance. It is known that the t-test with a correct model specification is more powerful than the F test. However, since the underlying genetic model is rarely known in practice, the use of a model-specific t-test may incur substantial power loss. Robust-efficient tests, such as the Maximin Efficiency Robust Test (MERT) and MAX3 have been proposed in the literature. Methods: In this paper, we propose a novel two-step robust-efficient approach, namely, the genetic model selection (GMS) method for quantitative trait analysis. GMS selects a genetic model by testing Hardy-Weinberg disequilibrium (HWD) with extremal samples of the population in the first step and then applies the corresponding genetic model-specific t-test in the second step. Results: Simulations show that GMS is not only more efficient than MERT and MAX3, but also has comparable power to the optimal t-test when the genetic model is known. Conclusion: Application to the data from Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort demonstrates that the proposed approach can identify meaningful biological SNPs on chromosome 19.

Fast online rubidium DPAL atomic concentration measurement by 420 nm probe laser.

The alkali atom concentration plays an important role in the performance of a diode pumped alkali vapor laser (DPAL). At the rubidium DPAL operational region, the alkali concentration is as high as 1013-1014cm-3, which is "optically thick," or opaque, for the 780 nm or 795 nm doublet D lines when the traditional scanning absorption spectrum method is used for concentration measurement. To solve this problem, we propose the use of a probe laser of 420 nm, which corresponds to the 52S1/2 to 62P3/2 transition and has a lower absorption cross section compared to the D-line doublet. Due to the moderate absorption strength at a fixed 420 nm probe wavelength, we realized fast, online measurement of the Rb concentration in a real-world DPAL. By combining it with the quasi-two-level model, we further provided the population distribution in the lower three energy levels. This fast, online diagnostic method could be well applied in DPAL concentration measurement, and could show the dynamics of a laser's performance.

Dual-Wavelength Excited Intense Red Upconversion Luminescence from Er3+-Sensitized Y2O3 Nanocrystals Fabricated by Spray Flame Synthesis.

Er3+-sensitized upconversion nanoparticles (UCNPs) have attracted great attention due to their tunable upconversion (UC) emissions, low cytotoxicity, high resistance to photobleaching and especially multiple effective excitation wavelengths. However, detailed energy conversion between Er3+ and Tm3+ ions in Y2O3 UCNPs is still a problem, especially under multi-wavelength and variable pulse width excitation. In this work, we successfully fabricated a series of Er3+-sensitized Y2O3 nanocrystals by a spray flame synthesis method with a production rate of 40.5 g h-1. The as-prepared UCNPs are a pure cubic phase with a mean size of 14 nm. Excited by both 980 and 808 nm lasers, the tunable upconversion luminescence (UCL) from Er3+ ions was achieved by increasing the Er3+ doping concentration, co-doping Tm3+ ions and extending excitation pulse-width. The investigations of the lifetimes and the laser power dependence of UC emissions further support the proposed mechanism, which provides guidance for achieving effective color control in anticounterfeiting and multiplexed labeling applications. In addition, the red UC emission at about 5 mm beneath the tissue surface was observed in an ex vivo imaging experiment under the excitation of 808 nm laser, indicating that the Y2O3:Er3+/Tm3+ UCNPs have great prospects in further biological applications.

Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis.

How transplanted haematopoietic stem cells (HSCs) behave soon after they reside in a preconditioned host has not been studied due to technical limitations. Here, using single-cell RNA sequencing, we first obtained the transcriptome-based classifications of 28 haematopoietic cell types. We then applied them in conjunction with functional assays to track the dynamic changes of immunophenotypically purified HSCs in irradiated recipients within the first week after transplantation. Based on our transcriptional classifications, most homed HSCs in bone marrow and spleen became multipotent progenitors and, occasionally, some HSCs gave rise to megakaryocytic-erythroid or myeloid precursors. Parallel in vitro and in vivo functional experiments supported the paradigm of robust differentiation without substantial HSC expansion during the first week. Therefore, this study uncovers the previously inaccessible kinetics and fate choices of transplanted HSCs in myeloablated recipients at early stage, with implications for clinical applications of HSCs and other stem cells.

[Dynamics of Proliferation and Differentiation after Transplantation of Hematopoietic Cells in Mouse].

OBJECTIVE: To observe the dynamic changes of hematopoietic reconstitution and multiple lineages differentiation at early phase after transplantation. METHODS: Whole bone marrow mononuclear cells (wBMMNC, 5×106) and enriched c-Kit+ hematopoietic stem/progenitor cells (HSPC, 3×105) from the BM of B6-Ly5.1 mice were transplanted into lethally irradiated B6-Ly5.2 mice, the frequencies and absolute numbers of donor-derived cells (including LKS- and LKS+) were detected by flow cytometry. The multiple lineages differentiation of donor-derived cells was also monitored by flow cytometry. The homing and early phase proliferations of donor-derived cells were observed by two-photon microscope. RESULTS: The donor-derived cells started to proliferation from 5-7 days after transplantation and reached the peak value at 2-3 weeks after wBMMNC transplantation. The donor-derived cells proliferated from 1-2 weeks and maintained until 4 weeks after c-kit+HSPC transplantation. At 1 week after transplantation, the donor-derived cells mainly differentiated into myeloid cells with a few lymphoid cells production (B cells) but the production of T cells was not observed at most in wBMMNC transplanted group, while myeloid cells occupied the majority of donor-derived cells at 2-4 weeks; donor-derived cells almost totally differentiated into myeloid cells at 1-3 weeks after transplantation in c-Kit+ transplanted group and donor-derived B cells appeared at 4 weeks. The absolute number of donor-derived LKS- and LKS+ cells in the BM of c-Kit+ transplanted group were much higher than that of wBMMNC group (P＜0.001) at 2 weeks respectively. The clustering proliferation of cKit+ cells at 4-5 days after transplantation was observed by two photon microscope. CONCLUSION: The dynamical rate of proliferation and reconstitution of donor-derived cells are much earlier and quicker in c-Kit+ group than those of wBMMNC group. c-Kit+ cells mainly differentiate into myeloid cells within 1-3 weeks and the lymphoid cell differentiation starts at 4 weeks after transplantation. The immediate proliferation and differentiation of c-Kit+ cells within 1 week maybe due to the urgent needs of hematopoietic regeneration under the myeloablated hosts.

Revisiting the Enhanced Red Upconversion Emission from a Single ß-NaYF4:Yb/Er Microcrystal By Doping with Mn2+ Ions.

The presence of manganese ions (Mn2+) in Yb/Er-co-doped nanomaterials results in suppressing green (545 nm) and enhancing red (650 nm) upconversion (UC) emission, which can achieve single-red-band emission to enable applications in bioimaging and drug delivery. Here, we revisit the tunable multicolor UC emission in a single Mn2+-doped ß-NaYF4:Yb/Er microcrystal which is synthesized by a simple one-pot hydrothermal method. Excited by a 980 nm continuous wave (CW) laser, the color of the single ß-NaYF4:Yb/Er/Mn microrod can be tuned from green to red as the doping Mn2+ ions increase from 0 to 30 mol%. Notably, under a relatively high excitation intensity, a newly emerged emission band at 560 nm (2H9/2 → 4I13/2) becomes significant and further exceeds the traditional green (545 nm) emission. Therefore, the red-to-green (R/G) emission intensity ratio is subdivided into traditional (650 to 545 nm) and new (650 to 560 nm) R/G ones. As the doped Mn2+ ions increase, these two R/G ratios are in lockstep with the same tunable trends at low excitation intensity, but the tunable regions become different at high excitation intensity. Moreover, we demonstrate that the energy transfer (ET) between Mn2+ and Er3+ contributes to the adjustment of R/G ratio and leads to tunable multicolor of the single microrod. The spectroscopic properties and tunable color from the single microrod can be potentially utilized in color display and micro-optoelectronic devices.

Simultaneous size manipulation and red upconversion luminescence enhancement of CaF2:Yb3+/Ho3+ nanoparticles by doping with Ce3+ ions.

Harnessing the color tuning capability of upconversion nanoparticles (UCNPs) is of great significance in the field of advanced bioimaging and color display. Here, we report the tunable size and upconversion luminescence (UCL) multicolor in CaF2:Yb3+/Ho3+/Ce3+ UCNPs, which were synthesized by a facile hydrothermal method. It was found that the size of these UCNPs could be controlled (from 600 to 30 nm) by varying the concentration of Ce3+ ions. Under the excitation of a 980 nm continuous-wave (CW) laser, the UCL color of these UCNPs can be tuned from green to red as the doped Ce3+ ions gradually increase from 0 to 10 mol% and the red-to-green (R/G) ratio is enhanced remarkably. It is suggested that the cross-relaxation (CR) processes between Ho3+ and Ce3+ ions contribute to the tunable multicolor and enhancement of the R/G ratio. The mechanism of these processes is well supported by the time-resolved decay and near infrared (NIR) emission measurements.