Search

To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis.20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated.The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.CD47分子在初诊成人急性髓系白血病患者中的表达及与临床预后的相关性.探讨CD47分子在初诊成人急性髓系白血病（AML）患者中的表达及其与临床预后的相关性.选择2020年4月-2021年10月上海市奉贤区中心医院诊断明确的AML患者20例，另5例非恶性血液病患者作为对照组。实时荧光定量聚合酶链式反应（qPCR）检测骨髓、外周血单个核细胞CD47的表达。结合患者初诊时血象、骨髓涂片、流式细胞术、染色体及基因检测、ECOG评分等情况，评价患者预后与CD47表达的关系.与对照组比较，初诊AML患者骨髓（P=0.0115）及外周血单个核细胞（P=0.0069）中CD47表达明显升高。在骨髓单个核细胞中，CD47高表达患者总的生存时间短于CD47 低表达患者（P=0.036），不同危险分层患者的生存率差异有统计学意义（P=0.012），但在外周血单个核细胞中CD47表达高、低的患者生存时间比较差异无统计学意义（P=0.116）。骨髓单个核细胞CD47表达高低组在白血病相关基因突变、存在融合基因、CD34骨髓单个核细胞CD47在AML患者中表达升高，提示更差的生存和更高的复发风险.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully establishes infection in macrophages with functional SAMHD1 remains unclear. Here, we demonstrate that while equine SAMDH1 can limit EIAV replication in equine macrophages at the reverse transcription stage, the antiviral effect is counteracted by the well-known transcriptional regulator Rev, which downregulates equine SAMHD1 through the lysosomal pathway. Remarkably, Rev hijacks BECN1 (beclin 1) and PIK3C3 to mediate SAMHD1 degradation in a canonical macroautophagy/autophagy-independent pathway. Our study illustrates that equine lentiviral Rev possesses important functions in evading cellular innate immunity in addition to its RNA regulatory function, and may provide new insights into the co-evolutionary arms race between SAMHD1 and lentiviruses. Abbreviations:3-MA: 3-methyladenine; AA: amino acid; ACTB: actin beta; AD: activation domain; ATG: autophagy related; Baf A1: bafilomycin A1; BD: binding domain; BECN1: beclin 1; BH3: BCL2-homology-3 domain; BiFC: bimolecular fluorescence complementation; CCD: coiled-coil domain; class III PtdIns3K: class III phosphatidylinositol 3-kinase; CQ: chloroquine; Co-IP: co-immunoprecipitation; dNTPase: dGTP-stimulated deoxynucleoside triphosphate triphosphohydrolase; ECD: evolutionarily conserved domain; EIAV: equine infectious anemia virus; eMDMs: equine monocyte-derived macrophages; GFP: green fluorescent protein; HD: histidine-aspartic; HIV-1: human immunodeficiency virus-1; hpi: hours post infection; hpt: hours post transfection; KO: knockout; LAMP2: lysosomal associated membrane protein 2; LMB: leptomycin B; PMA: phorbol 12-myristate 13-acetate; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ND: unknown non-essential domain; NES: nuclear export signal; NLS: localization signal; NS: statistically non-significant; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RBD: RNA binding domain; RT: reverse transcriptase; siRNAs: small interfering RNAs; SAMHD1: SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1; SIV: simian immunodeficiency virus; VN: C-terminal residues of Venus 174 to 238; VC: N-terminal residues 2 to 173 of Venus

In the maintenance work of tunnels, images are often used to detect diseases, but collections of tunnel images are limited by the tunnel environment and working time. Three-dimensional laser scanning technology can acquire high-precision tunnel information efficiently, and the main problem to be solved by using this technology to collect tunnel inner wall images is the dimensionality reduction of the laser tunnel point cloud data. This letter proposes a tunnel surface parameterization algorithm based on a harmonic map, where a 3-D tunnel point cloud is used as a data source to reconstruct a triangle mesh model of the tunnel and then generate a harmonic map depth map of the tunnel inner wall on the triangle mesh. We can obtain the spatial distribution and position information of the appendages and detect whether there are cracks, water leakage, falling pieces, and other diseases by the depth images. The results of this study indicate that the proposed algorithm is suitable for tunnels of various shapes and has low area distortion, which can better avoid the loss of information during dimensionality reduction. Compared with other existing methods, the algorithm has higher efficiency and applicability.

Optimal transportation finds the most economical way to transport one probability measure to another, and it plays an important role in geometric modeling and processing. In this paper, we propose a moving mesh method to generate adaptive meshes by optimal transport. Given an initial mesh and a scalar density function defined on the mesh domain, our method will redistribute the mesh nodes such that they are adapted to the density function. Based on the Brenier theorem, solving an optimal transportation problem is reduced to solving a Monge-Ampère equation, which is difficult to compute due to the high non-linearity. On the other hand, the optimal transportation problem is equivalent to the Alexandrov problem, which can finally induce an effective variational algorithm. Experiments show that our proposed method finds the adaptive mesh quickly and efficiently.

Optimal transportation (OT) finds the most economical way to transport one measure to another and plays an important role in geometric modeling and processing. Based on the Brenier theorem, the OT problem is equivalent to the Alexandrov problem, which is the dual to the Pogorelov problem. Although solving the Alexandrov/Pogorelov problem are both equivalent to solving the Monge-Ampère equation, the former requires second type boundary condition and the latter requires much simpler Dirichlet boundary condition. Hence, we propose to use the Pogorelov map to approximate the OT map. The Pogorelov problem can be solved by a convex geometric optimization framework, in which we need to ensure the searching inside the admissible space. In this work, we prove the discrete Alexandrov maximum principle, which gives an apriori estimate of the searching. Our experimental results demonstrate that the Pogorelov map does approximate the OT map well with much more efficient computation.

Quadrilateral meshes generated for the industrial applications have to meet some special quality demands and it remains a tricky problem. We propose a novel method for high quality quad mesh generation based on the equivalence relation between quadrilateral meshes and meromorphic quartic differentials[1]. As long as more than one meromorphic quartic differential were obtained, the linear space extended by them is also available for us according to the meromorphic quartic differentials space theory. We can search the space for better quadrilateral mesh and the high quality mesh construction problem becomes a optimization problem. This paper gives the algorithm and carries out experiments under two different mesh quality constrains including mesh cell size constrain and feature lines constrain. The experimental results demonstrate the efficiency and efficacy of the algorithm.

The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection.

The nuclear export receptor CRM1 is an important regulator involved in the shuttling of various cellular and viral RNAs between the nucleus and the cytoplasm. HIV-1 Rev interacts with CRM1 in the late phase of HIV-1 replication to promote nuclear export of unspliced and single spliced HIV-1 transcripts. However, the knowledge of cellular factors that are involved in the CRM1-dependent viral RNA nuclear export remains inadequate. Here, we identified that ANP32A and ANP32B mediate the export of unspliced or partially spliced viral mRNA via interacting with Rev and CRM1. We found that double, but not single, knockout of ANP32A and ANP32B, significantly decreased the expression of gag protein. Reconstitution of either ANP32A or ANP32B restored the viral production equally. Disruption of both ANP32A and ANP32B expression led to a dramatic accumulation of unspliced viral mRNA in the nucleus. We further identified that ANP32A and ANP32B interact with both Rev and CRM1 to promote RNA transport and that this function is Rev/RRE-dependent, but not CTE-dependent. Together our data suggests that ANP32A and ANP32B are required for HIV-1 unspliced RNA export in the Rev-CRM1 pathway.Author summaryPosttranscriptional regulation of HIV-1 genome is very important for viral protein expression and viral replication. HIV-1 Rev protein bind to RRE structure of viral RNA and interacts with the mammalian nuclear export factor Chromosomal Maintenance 1 (CRM1) in the late phase of HIV-1 replication to promote nuclear export of unspliced and single spliced HIV-1 transcripts. The REV/RRE-CRM1 pathway has been investigated for years and many host factors have been reported to be involved, but the complicated complex and procedure remain largely unknown. Here the authors report that two host proteins, ANP32A and ANP32B, are novel key factors that support export of unspliced and partial spliced viral RNA from the nucleus to the cytosol. ANP32A/B can interact with both Rev and CRM1, and this interaction is necessary for Rev/RRE-CRM1 dependent viral RNA export. These results suggest that ANP32A and ANP32B are important in viral replication and could be potential targets for novel antiviral strategy.