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Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and contributes to high morbidity and mortality. However, our current understanding of the development and progression of aGVHD after allo-HSCT remains limited. To identify the potential biomarkers for the prevention and treatment of aGVHD during the early hematopoietic reconstruction after transplantation, we meticulously performed a comparative analysis of single-cell RNA sequencing data from post-transplant patients with or without aGVHD. Prior to the onset of aGVHD, monocytes in the peripheral blood of patients with aGVHD experienced a dramatic rise and activation on day 21 post-transplantation. This phenomenon is closely aligned with clinical cohort results obtained from blood routine examinations. Furthermore, in vitro co-culture experiments showed that peripheral blood monocytes extracted from patients with aGVHD approximately 21 days post-transplantation induced a significantly higher proliferation rate of allogeneic T cells compared to those from patients without aGVHD. Our study indicates that monocytes could be a crucial early clinical risk factor for the development of aGVHD, and this insight could potentially guide the timing of monitoring efforts, recommending assessments at the pivotal juncture of approximately day 21 post-transplantation, shedding fresh light on the significance of early hematopoietic regeneration in relation to the onset of aGVHD.

Fully reduced polyoxometalates are predicted to give rise to a broad and strong absorption spectrum, suitable energy levels, and unparalleled electronic and optical properties. However, they are not available to date. Here, an unprecedented fully reduced polyoxomolybdate cluster, namely Na8[MoV 60O140(OH)28]·19H2O {MoV 60}, was successfully designed and obtained under hydrothermal conditions, which is rare and is the largest fully reduced polyoxometalate reported so far. The MoV 60 molecule describes one Keggin {ε-Mo12} encapsulated in an unprecedented {Mo24} cage, giving rise to a double truncated tetrahedron quasi-nesting architecture, which is further face-capped by another four {Mo6} tripods. Its crystalline stability in air, solvent tolerance, and photosensitivity were all shown. As a cheap and robust molecular light-absorber model possessing wide light absorption, MoV 60 was applied to build a co-sensitized solar cell photoelectronic device along with N719 dyes and the optimal power conversion efficiency was 28% higher than that of single-dye sensitization. These results show that MoV 60 polyoxometalate could serve as an ideal model for the design and synthesis of all-inorganic molecular light-absorbers for other light-driven processes in the future.

Abstract Thrombocytopenia is a major and fatal complication in patients with acute myeloid leukemia (AML), which results from disrupted megakaryopoiesis by leukemic niche and blasts. Our previous research revealed that elevated interleukin-4 (IL-4) in AML bone marrow had adverse impact on multiple stages throughout megakaryopoiesis including hematopoietic stem cells (HSCs), but the specific mechanism remains unknown. In the present study, we performed single-cell transcriptome analysis and discovered activated oxidative stress pathway and apoptosis pathway in IL-4Rαhigh versus IL-4Rαlow HSCs. IL-4 stimulation in vitro led to apoptosis of HSCs and down-regulation of megakaryocyte-associated transcription factors. Functional assays displayed higher susceptibility of IL-4Rαhigh HSCs to tunicamycin and irradiation-induced apoptosis, demonstrating their vulnerability to endoplasmic reticulum (ER) stress injury. To clarify the downstream signaling of IL-4, we analyzed the transcriptomes of HSCs from AML bone marrow and found a remarkable down-regulation of the proteasome component Psmd13, whose expression was required for megakaryocytic-erythroid development but could be inhibited by IL-4 in vitro. We knocked down Psmd13 by shRNA in HSCs, and found their repopulating capacity and megakaryocytic differentiation were severely compromised, with increased apoptosis in vivo. In summary, our study uncovered a previous unrecognized regulatory role of IL-4-Psmd13 signaling in anti-stress and megakaryocytic differentiation capability of HSCs.

Summary: Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e− cells. CD66e+CD34+CD90+CD45RA− cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e−CD34+CD90+CD45RA−cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA− population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Despite eye-opening advances in developing novel therapeutics for hard-to-treat diseases, treatment of Alzheimer's disease (AD) is still known as the challenge of generations. By the way, scrutinizing and shedding light on a major cause of AD, i.e., fibrillation of β amyloid (Aβ) peptides, have paved the way to find an effective therapy for this life-threatening disease in the foreseeable future. In this study, we endeavored to push forward with research on AD therapy, even as much as an inch, by fabricating and evaluating a theranostic system based on iron oxide nanoparticles-loaded hyaluronic acid nanogels (Fe3O4-HyA NGs). Fe3O4 nanoparticles were fabricated via a facile co-precipitation method and were loaded in HyA NGs in situ by formation of NGs using a thiolated HyA (HyA-SH) precursor. Standard structural analysis was performed on Fe3O4-HyA NGs, and the results revealed the NGs were negatively charged, which led to relatively poor adsorption of plasma proteins, and sized at the range of 120–150 nm. Also, Fe3O4-HyA NGs showed a superparamagnetic property with a magnetic saturation of about 62.8 emu/g indicating the successful loading of Fe3O4 nanoparticles. Besides, findings of the cytotoxicity analysis could primarily show the NGs did not pose a noticeable risk to normal astrocyte cells (i.e., 96.7% cell viability at 100 µg/ml after 48 h treatment). Moreover, in vitro magnetic resonance imaging (MRI) analysis could reveal the noticeable potential ability of the Fe3O4-HyA NGs to generate negative contrast by reducing both T2-weighted and T2*-weighted MR signal intensities with a relaxation rate (r2) of about 120.87 (1/mM.sec). Finally, Fe3O4-HyA NGs exhibited a potential ability to impede Aβ aggregation by around 44% at 10 µM; also, they could induce disaggregation of Aβ fibrils by about 13% at 10 µM. Hence, Fe3O4-HyA NGs could be a promising choice for AD theranostics and could be further scrutinized in vitro and in vivo.

Abstract. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China led to a public health emergency of international concern, putting all health organizations on high alert in the beginning of 2020. Corona virus disease 2019 (COVID-19) is highly infectious and has resulted in thousands of deaths which exceeded that of the SARS coronavirus (SARS-CoV) outbreak back in 2002 and 2003 in China. Besides, the number of diagnosed patients, patients who are suspected to have contracted the disease, and deaths are increasing worldwide. Unfortunately, effective drugs and vaccines to combat SARS-CoV-2 are still lacking. Convalescent plasma, a seemingly successful treatment for COVID-19 patients, proved to be of huge value in terms of saving severely ill patients. This review introduces the reported effects, potential mechanisms, and future uncertainties of convalescent plasma therapy in the treatment of COVID-19 patients, in the hopes that it will provide useful information for relevant physicians and researchers.

Shotcrete spray is an indispensable process in tunnel construction. At present, the construction of tunnels in China is mainly depend on labor or mobile concrete sprayer, which has lots problems like time-consuming, low precision, and labor intensive. An intelligent detection method for tunnel shotcrete spraying is proposed in this article. There are two main issues need to be solved, one is the modeling of tunnel in real-time to monitor the thickness of shotcrete and other is the detection of spraying area in the tunnel. The LiDAR can obtain a 3D model of tunnel after performing necessary preprocess on it in real-time. On the other hand, the spraying areas are usually divided by arches in the tunnel, so we can detect the position of arches to determine the spraying areas. Inspired by the YOLO algorithm, we proposed a novel neural network structure to detect the approximate bounding boxes of the arches and a line-detection algorithm is used to determine the final positions of the spraying area in the image. The size of the weight file of our neural network is only 2.57 MB after the use of some deep compression tricks, which means our model is device friendly. After that, the object detection results in the image will be projected to the point cloud data. The experimental results suggest that our method performed well in the detection for tunnel shotcrete spraying, and the mAP for spraying area detection was found to be 91.4%.

Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

Hematopoietic stem cells (HSC) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSC are poised to be immediately activated in certain conditions and can return to quiescence after homeostasis has been regained. At present, the molecular networks of regulating the threshold of HSC dormancy, if existing, remain largely unknown. Here, we show that deletion of Nupr1, a gene preferentially expressed in HSC, activated quiescent HSC under homeostasis, which conferred a competitive engraftment advantage for these HSC without compromising their stemness or multi-lineage differentiation capacity in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSC proliferated more robustly than their wild-type counterparts in vitro. Nupr1 inhibits the expression of p53 and rescue of this inhibition offsets the engraftment advantage. Our data reveal a new role for Nupr1 as a regulator of HSC quiescence, which provides insights for accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.