•High-speed camera technique is applied to investigate the spark-charge bubble behaviors.•High-speed jet is proved to be the one of most important factors to cause cavitation erosion.•The effect of ...boundary conditions on the bubble dynamics is systematically investigated.
The objective of this paper is to apply experimental methods to investigate the dynamics of spark-induced bubbles in the vicinity of the elastic and rigid boundary. In the experiment, the temporal evolution of the bubble is recorded by the high-speed camera at the 25,000 frames per second, as well as corresponding data such as normalized collapse position, the time of bubble collapse, and the velocity of the high-speed liquid jet. Results are presented for a single bubble generated over the elastic and rigid plates, under a wide range of normalized standoff distance from 0.5 to 3.0. The results show that the high-speed jet emitted by non-spherical bubble collapse near the boundary is one of the important factors to cause the destructive erosion pit. With the increase of the standoff distance, the expansion, shrink, jet formation, and rebound of the bubbles vary evidently adjacent to the different boundary conditions. Compared with the rigid boundary cases, the normalized first collapsed position and the time of bubble collapse are much smaller near the elastic boundary. The formation of the high-speed liquid jet in the neighborhood of the elastic/rigid boundary is founded in two different mechanisms. Furthermore, the normalized maximum velocity near the rigid plate is always larger than that near the elastic plate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS ...patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.
Shallow water passive source localization is an essential problem in underwater detection and localization. Traditional matched-field processing (MFP) methods are sensitive to environment mismatches. ...Many neural network localization methods still have room for improvement in accuracy if they are further adjusted to underwater acoustic characteristics. To address these problems, we propose a deep learning localization method via improved input features and network structure, which can effectively estimate the depth and the closest point of approach (CPA) range of the acoustic source. Firstly, we put forward a feature preprocessing scheme to enhance the localization accuracy and robustness. Secondly, we design a deep learning network structure to improve the localization accuracy further. Finally, we propose a method of visualizing the network to optimize the estimated localization results. Simulations show that the accuracy of the proposed method is better than other compared features and network structures, and the robustness is significantly better than that of the MFP methods. Experimental results further prove the effectiveness of the proposed method.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Telitacicept is a novel humanized, recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor and the Fc portion (TACI-Fc) fusion protein, designed to neutralize the ...activity of both B-cell lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). On March 9, 2021, telitacicept received its first approval in China for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE). Additionally, on April 15, 2020, the U.S. Food and Drug Administration (FDA) granted fast track designation to telitacicept for the treatment of SLE. Clinical studies of telitacicept in several other indications, including IgA nephropathy, multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorders, rheumatoid arthritis and Sjögren’s syndrome are underway in China. This is the first case that reports telitacicept successfully treated a SLE patient with refractory cutaneous involvement, which provides a potential therapeutic option for recalcitrant cutaneous manifestations of SLE. Furthermore, we review reported studies of BLyS targeted treatments for mucocutaneous lupus. Telitacicept appears to have activity in refractory cutaneous involvement of SLE and clinical trials are warranted to further assess this potential therapy.
Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have ...established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3Kγ inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3Kγ, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and ...heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl
2
. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl
2
, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl
2
induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34
+
and c-kit
+
was immunologically detected in the presence of CoCl
2
. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Simple translocations and complex rearrangements are formed through illegitimate ligations of double-strand breaks of fusion partners and lead to generation of oncogenic fusion ...genes that affect cellular function. The contact first hypothesis states that fusion partners tend to colocalize prior to fusion in normal cells. Here we test this hypothesis at the single-cell level and explore the underlying mechanism.
Results
By analyzing published single-cell diploid Hi-C datasets, we find partner genes fused in leukemia exhibit smaller spatial distances than those fused in solid tumor and control gene pairs. Intriguingly, multiple partners tend to colocalize with KMT2A in the same cell. 3D genome architecture has little association with lineage decision of KMT2A fusion types in leukemia. Besides simple translocations, complex rearrangement-related KMT2A fusion genes (CRGs) also show closer proximity and belong to a genome-wide mutual proximity network. We find CRGs are co-expressed, co-localized, and enriched in the targets of the transcriptional factor RUNX1, suggesting they may be involved in RUNX1-mediated transcription factories. Knockdown of RUNX1 leads to significantly fewer contacts among CRGs. We also find CRGs are enriched in active transcriptional regions and loop anchors, and exhibit high levels of TOP2-mediated DNA breakages. Inhibition of transcription leads to reduced DNA breakages of CRGs.
Conclusions
Our results demonstrate KMT2A partners and CRGs may form dynamic and multipartite spatial clusters in individual cells that may be involved in RUNX1-mediated transcription factories, wherein massive DNA damages and illegitimate ligations of genes may occur, leading to complex rearrangements and KMT2A fusions in leukemia.
SUMMARY
Knowledge about the spatial contact relationship between the Yangtze Plate and the eastern Qinling-Dabie orogenic belt can not only provide a scientific basis for the exploration of mineral ...resources, disaster prevention and earthquake prediction in the region, but also play an important role in reconstructing the geological process of the central orogenic belt. Hence, high-resolution lithospheric velocity model is essential to address these geological problems. In this study, using waveform data from 48 stations in Hubei Province and adjacent regions, central China, we invert for a 3-D S-wave velocity structure model of the crust and upper mantle from Rayleigh wave tomography. Our model reveals the complex subduction pattern of the Yangtze Plate to the north and the thrust-nappe tectonics of the Qinling-Dabie orogenic belt along the Mianlue suture with different scales and different deformation strengths. In addition, in the central part of Hubei Province, the local Yangtze slab has been broken into several pieces, among which the upwelling low-velocity anomalies appear. Moreover, the southern margin of the Dabie orogenic belt has undergone thrusting-nappe movement, and a series of associated structures are formed in the northern margin of the middle Yangtze platform. The contact zone between the two blocks in this area is composed of a series of thrust faults with dextrorotation slip component. Finally, based on the 3-D S-wave velocity image of Hubei Province and its vertical cross-section profiles along three different directions, three dynamic models are proposed to explain the spatial contact relationship between the Yangtze Plate and the eastern Qinling-Dabie orogenic belt in different regions.
The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor ...development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Our previous result indicated that memory-like human natural killer (NK) cells from TB pleural fluid cells (PFCs) produced large amounts of IFN-γ in response to Bacille Calmette Guerin (BCG). ...Furthermore, recent studies have shown that human lymphoid tissues harbored a unique NK cell subset that specialized in production of interleukin (IL)-22, a proinflammatory cytokine that mediates host defense against pathogens. Yet little information was available with regard to the properties of IL-22 production by memory-like human NK cells. In the present study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL-22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the subset of specific IL-22-producing NK cells were distinct from IFN-γ-producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured with autologous monocytes and stimulated with BCG for the production of IL-22. The result demonstrated that CD45RO+ but not CD45RO- NK cells produced significantly higher level of IL-22. Anti-IL-12Rβ1 mAbs (2B10) partially inhibit the expression of IL-22 by NK cells under the culture with BCG. Consistently, BCG specific IL-22-producing NK cells from PFCs expressed CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that memory-like antigen-specific CD45RO+ NK cells might participate in the recall immune response for M. tb infection via producing IL-22, which display a critical role to fight against M. tb.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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