P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3

Nucleotides mediate intercellular communication by activating purinergic receptors and take part in various physiological and pathological processes. Abnormal purinergic signaling plays important roles in malignant progression. P2X7, which belongs to the P2X family of purinergic receptors, is abnormally expressed in various types of malignancies including leukemia. However, its role and molecular mechanism in leukemia have not been elucidated. Here, we analyzed the correlation between P2X7 expression and AML clinical outcome; explored the role and mechanism of P2X7 in AML progression by using mouse acute myeloid leukemia (AML), nude mouse xenograft and patient-derived xenograft models. High levels of P2X7 expression were correlated with worse survival in AML. P2X7 was highly expressed in MLL-rearranged AML. Furthermore, P2X7 accelerated the progression of MLL-rearranged AML by both promoting cell proliferation and increasing leukemia stem cell (LSC) levels. Moreover, P2X7 caused upregulation of Pbx3 accounts for its pro-leukemic effects. The P2X7-Pbx3 pathway might also contribute to the progression of other types of leukemia as well as solid tumors with high levels of P2X7 expression. Our study provides new insights into the malignant progression caused by abnormal purinergic signaling

The Overseeing Mother: Revisiting the Frontal-Pose Lady in the Wu Family Shrines in Second Century China

Located in present-day Jiaxiang in Shandong province, the Wu family shrines built during the second century in the Eastern Han dynasty (25–220) were among the best-known works in Chinese art history. Although for centuries scholars have exhaustively studied the pictorial programs, the frontal-pose female image situated on the second floor of the central pavilion carved at the rear wall of the shrines has remained a question. Beginning with the woman’s eyes, this article demonstrates that the image is more than a generic portrait (“hard motif ”), but rather represents “feminine overseeing from above” (“soft motif ”). This synthetic motif combines three different earlier motifs – the frontal-pose hostess enjoying entertainment, the elevated spectator, and the Queen Mother of the West. By creatively fusing the three motifs into one unity, the Jiaxiang artists lent to the frontal-pose lady a unique power: she not only dominated the center of the composition, but also, like a divine being, commanded a unified view of the surroundings on the lofty building, hence echoing the political reality of the empress mother’s “overseeing the court” in the second century during Eastern Han dynasty

Optimizing Painting Sequence Scheduling Based on Adaptive Partheno-Genetic Algorithm

In this paper, we formulate and solve a novel real-life large-scale automotive parts paint shop scheduling problem, which contains color arrangement restrictions, part arrangement restrictions, bracket restrictions, and multi-objectives. Based on these restrictions, we construct exact constraints and two objective functions to form a large-scale multi-objective mixed-integer linear programming problem. To reduce this scheduling problem’s complexity, we converted the multi-objective model into a multi-level objective programming problem by combining the rule-based scheduling algorithm and the adaptive Partheno-Genetic algorithm. The rule-based scheduling algorithm is adopted to optimize color changes horizontally and bracket replacements vertically. The adaptive Partheno-Genetic algorithm is designed to optimize production based on the rule-based scheduling algorithm. Finally, we apply the model to the actual optimization problem that contained 829,684 variables and 137,319 constraints, and solved this problem by Python. The proposed method solves the optimal solution, consuming 575 s

Thermal Resistance Analysis of Power MOSFETs using Creo/ANSYS Software Versus Physical Measurements

High requirement of power electronic converters in power density makes heat dissipation issue critical caused by the packaging of power electronic devices and modules. Compared with the wire bond process, the clip bond process shows excellent thermal performance, which is widely used in the packaging of power MOSFETs. However, due to the complicated structure of the copper bridge in the clip bond process, the thermal resistance cannot be easily evaluated according to mathematical models. A generic method is proposed to evaluate the thermal resistance of power MOSFETs, which is verified by a PDFN5 76 plastic-packaged power MOSFET. According to the physical structure of the selected MOSFET, the finite element model is established using combined Creo and ANSYS software. The thermal resistance from the PN junction to the case and the one from the junction to the PCB board can be accurately simulated from the developed model. The simulation results show very small errors compared with the physical measurements based on the JESD51 standard. The proposed method can replace the thermal resistance test to some extent, which can save time and cost in the early stage of the design and development of power electronic devices and modules

Electroclinical characteristics of seizures arising from the precuneus based on stereoelectroencephalography (SEEG)

Abstract Background Seizures arising from the precuneus are rare, and few studies have aimed at characterizing the clinical presentation of such seizures within the anatomic context of the frontoparietal circuits. We aimed to characterize the electrophysiological properties and clinical features of seizures arising from the precuneus based on data from stereoelectroencephalography (SEEG). Methods The present retrospective study included 10 patients with medically intractable epilepsy, all of whom were diagnosed with precuneal epilepsy via stereoelectroencephalography (SEEG) at Yuquan Hospital and Xuan Wu Hospital between 2014 and 2016. Clinical semiology, scalp electroencephalography (EEG) findings, magnetic resonance images (MRI), and positron emission tomography (PET) images were analyzed during phase I preoperative evaluations. Following electrode implantation, the semiological sequence, ictal SEEG evolution, and anatomy of the relevant brain structures were analyzed for each seizure. Results Seven of ten patients reported auras, including body image disturbance (2/7), vestibular responses (2/7), somatosensory auras (1/7), visual auras (1/7), and non-specific auras (1/7). Primary motor manifestations included bilateral asymmetric tonic seizures (BATS) (7/10) and hypermotor seizures (HMS) (3/10). In one patient, epileptiform discharge on interictal EEG occurred ipsilateral to the side of the epileptogenic zone (EZ). Discharge was non-lateralized in the remaining nine patients. In six patients, interictal EEG signals were primarily localized in the temporal–parietal–occipital area. In two patients, ictal onset occurred ipsilateral to the EZ, which was mainly located in the temporal–parietal–occipital area. Two patterns of seizure spread were observed. The first pattern was characterized by BATS activity with ictal spread to the supplementary motor area (SMA), paracentral lobule (PCL), precentral gyrus (PrCG), or postcentral gyrus (PoCG). The second pattern was characterized by HMS activity with ictal spread to middle cingulate cortex (MCC) and posterior cingulate cortex (PCC). Conclusion Aura type (e.g., body image disturbance and vestibular response), BATS, and HMS are the main indicators of precuneal epilepsy. Scalp EEG is of little use when attempting to localize precuneal seizures. Our findings indicate that the clinical characteristics of precuneal epilepsy vary among patients, and that the final electro–clinical phenotype depends on the pattern of seizure spread

Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia

Abstract Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the survival, differentiation and function of monocytic lineage cells and plays pathologic roles in a broad range of diseases. However, the role of IL-34 in leukemia has not been established. Here MLL-AF9 induced mouse acute myeloid leukemia (AML) model overexpressing IL-34 (MA9-IL-34) was used to explore its role in AML. MA9-IL-34 mice exhibited accelerated disease progression and short survival time with significant subcutaneous infiltration of AML cells. MA9-IL-34 cells showed increased proliferation. In vitro colony forming assays and limiting dilution transplantation experiments demonstrated that MA9-IL-34 cells had elevated leukemia stem cell (LSC) levels. Gene expression microarray analysis revealed a panel of differential expressed genes including Sex-determining region Y (SRY)-box 13 (Sox13). Furthermore, a positive correlation between the expressions of IL-34 and Sox13 was detected human datasets. Knockdown of Sox13 rescued the enhanced proliferation, high LSC level and subcutaneous infiltration in MA9-IL-34 cells. Moreover, more leukemia-associated macrophages (LAMs) were detected in MA9-IL-34 microenvironment. Additionally, those LAMs showed M2-like phenotype since they expressed high level of M2-associated genes and had attenuated phagocytic potential, suggesting that LAMs should also contribute to IL-34 caused adverse phenotypes. Therefore, our findings uncover the intrinsic and microenvironmental mechanisms of IL-34 in AML and broadens the knowledge of M-CSF/IL-34-CSF-1R axis in malignancies

Proteomics analysis of rice proteins up-regulated in response to bacterial leaf streak disease

Bacterial leaf streak (BLS), caused by the pathogen Xanthomonas campestris pv. Oryzicola, is a major rice disease in tropical and subtropical regions of Asia. Rice proteins responsive to BLS are still not well characterized. We took a proteomics approach to identify the proteins that are up-regulated in rice leaves after infection. Approximately 1,500 protein spots were detected on each 2-D gel after silver-staining; those with increased protein levels were selected for MALDI-TOF-MS analysis. We identified 32 up-regulated proteins that might be involved in disease resistance signal transduction, pathogenesis, and regulation of cell metabolism. By using publicly available microarray data, we determined the mRNA transcripts of 23 proteins expressed in the leaves. Seven genes were analyzed by northern blots, which demonstrated that transcript levels were increased after bacterial infection. Our findings help elucidate the molecular mechanisms underlying BLS and provide a solid foundation for further research on the functions of relevant genes.National 863 Project; National Program of Transgenic Variety Development of China [2009ZX08009-045B, 2007AA10Z132, 2011ZX08001-001