Comprehensive transcriptomic analysis of VISTA in acute myeloid leukemia: Insights into its prognostic value

The V-domain Ig suppressor of T-cell activation (VISTA) has been recognized as a critical negative regulator of antitumor immune response and is gaining growing interest as a potential pharmacological target in immunotherapy. This molecule is highly expressed in hematopoietic stem cells and myeloid compartment, and it has been found upmodulated in acute myeloid leukemia (AML). However, VISTA-associated immune features are relatively unexplored in myeloid malignancies. Herein, we aimed to explore whether this immune checkpoint regulator could play a role in the generation of an immune escape environment in AML patients. We characterized VISTA mRNA expression levels in leukemia cell lines and in large publicly available cohorts of specimens from bone marrow of healthy individuals and AML patients at diagnosis by deploying bulk and single-cell RNA sequencing. We also defined the correlations with leukemia-associated burden using results of whole-exome sequencing of AML samples at disease onset. We showed that VISTA expression linearly increased across the myeloid differentiation tree in normal hematopoiesis. Accordingly, its transcript was highly enriched in AML cell lines as well as in AML patients at diagnosis presenting with myelomonocytic and monocytic differentiation. A strong correlation was seen wit

Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment

The acquisition of stemness in colorectal cancer (CRC) attributed to the recurrence and metastasis in CRC treatment. Therefore, targeting the stemness of CRC forms a basis for the development of novel therapeutic approaches. However, the pain and systemic side effect from long-term of venipuncture injection remain great challenges to neoplastic treatment. Here, we introduce an oral drug delivery system for sustained release of BMI-1 inhibitor (PTC209) that reverse the stemness of CRC to over-come these obstacles. In this system, nanoparticles modified with hyaluronic acid (HA) showed high-affinity to CD44 / CD168 overexpressed-CRC cells, and efficiently targeted to tumor site in a metastatic orthotropic colon cancer mouse model by oral administration. Significantly, the observed tumor growth inhibition is accompanied by decreased expression of stemness markers in the tumor tissues. Furthermore, HA-NPs-PTC209 also significantly prevented metastasis to the gastrointestinal system, while failing to exhibit acute side effects. In summary, we have developed an orally active, easily synthesized nanomedicine that shows promise for the treatment of colon cancer

Government decentralization as a disincentive for transnational terror? : an empirical analysis

Using panel data for a maximum of 109 countries over the years 1976-2000, we empirically analyze the impact of decentralization on the occurrence of transnational terror. Our results show that expenditure decentralization reduces the number of transnational terror events in a country, while political decentralization has no impact. These results are robust to the choice of control variables and method of estimation

29 m 6 A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation - 102 Transcriptomic Dataset Analyses

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m6A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers

Decentralization as a Disincentive for Transnational Terror? An Empirical Test

Using panel data for a maximum of 109 countries over the years 1976-2000, we empirically analyze the impact of decentralization on the occurrence of transnational terror. Taking account of the potential simultaneity between terror and decentralization, our results show that expenditure decentralization robustly reduces the number of terror events in a country, while political decentralization has no impact

Interleukin 35 Delays Hindlimb Ischemia-Induced Angiogenesis Through Regulating ROS-Extracellular Matrix but Spares Later Regenerative Angiogenesis.

Interleukin (IL) 35 is a novel immunosuppressive heterodimeric cytokine in IL-12 family. Whether and how IL-35 regulates ischemia-induced angiogenesis in peripheral artery diseases are unrevealed. To fill this important knowledge gap, we used loss-of-function, gain-of-function, omics data analysis, RNA-Seq, in vivo and in vitro experiments, and we have made the following significant findings: i) IL-35 and its receptor subunit IL-12RB2, but not IL-6ST, are induced in the muscle after hindlimb ischemia (HLI); ii) HLI-induced angiogenesis is improved in Il12rb2-/- mice, in ApoE-/-/Il12rb2-/- mice compared to WT and ApoE-/- controls, respectively, where hyperlipidemia inhibits angiogenesis in vivo and in vitro; iii) IL-35 cytokine injection as a gain-of-function approach delays blood perfusion recovery at day 14 after HLI; iv) IL-35 spares regenerative angiogenesis at the late phase of HLI recovery after day 14 of HLI; v) Transcriptome analysis of endothelial cells (ECs) at 14 days post-HLI reveals a disturbed extracellular matrix re-organization in IL-35-injected mice; vi) IL-35 downregulates three reactive oxygen species (ROS) promoters and upregulates one ROS attenuator, which may functionally mediate IL-35 upregulation of anti-angiogenic extracellular matrix proteins in ECs; and vii) IL-35 inhibits human microvascular EC migration and tube formation in vitro mainly through upregulating anti-angiogenic extracellular matrix-remodeling proteins. These findings provide a novel insight on the future therapeutic potential of IL-35 in suppressing ischemia/inflammation-triggered inflammatory angiogenesis at early phase but sparing regenerative angiogenesis at late phase

An error concealment algorithm for entire frame loss in video transmission

In video transmission over the Internet, the quality of service is usually not guaranteed. The loss of a packet may result in the loss of a whole video frame. While most of the current error concealment techniques can only deal with the loss of macroblocks, our bi-directional temporal error concealment method can recover a whole missing frame. For each pixel in the lost frame, the proposed algorithm extrapolates two motion vectors from the motion vectors of the previous reconstructed frame and the next frame. The lost pixel is then reconstructed using multi-hypothesis motion compensation. Experiments are carried with an H.263 video codec. The results show that our algorithm obviously outperforms the existing methods on both the PSNR and visual quality. Moreover, our method is efficient in stopping error propagation. 1

A method to calculate reasonable water injection rate for M oilfield

Abstract In recent years, M oilfield has entered into high water cut stage. Two main problems are imposed in the process of development including sharp water cut rising rate and rapid oil production decline. These problems are difficult to solve, which may bring other problems. In order to slow down production decline rate and control the rising rate of water cut, it is necessary to control water injection rate. However, oil production rate can be affected if water injection rate is too low to provide enough water volume for maintaining reservoir pressure. A method to calculate reasonable injection–production ratio and predict water cut is provided in this paper. Its main mechanism is to resolve above contradictions by calculating reasonable water injection rate. Firstly, an equation to calculate reasonable injection–production ratio is deduced by material balance equation. It considers several parameters including rate of pressure recovery, water cut and other production indexes. Secondly, reasonable oil production rates and water cut of future 10 years are predicted. Oil production is predicted by the law of production decline, and water cut is predicted by regression equation of water drive characteristic curve. Lastly, reasonable water injection rates of next 10 years are calculated through predicted injection–production ratios and liquid production rates. Taking M oilfield as an example, this paper presents a method to determine reasonable water injection rate of multilayer sandstone water drive reservoir

Simulation Experiment and Analysis of GNSS/INS/LEO/5G Integrated Navigation Based on Federated Filtering Algorithm

This article examines the positioning effect of integrated navigation after adding an LEO constellation signal source and a 5G ranging signal source in the context of China’s new infrastructure construction. The tightly coupled Kalman federal filters are used as the algorithm framework. Each signal source required for integrated navigation is simulated in this article. At the same time, by limiting the range of the azimuth angle and visible height angle, different experimental scenes are simulated to verify the contribution of the new signal source to the traditional satellite navigation, and the positioning results are analyzed. Finally, the article compares the distribution of different federal filtering information factors and reveals the method of assigning information factors when combining navigation with sensors with different precision. The experimental results show that the addition of LEO constellation and 5G ranging signals improves the positioning accuracy of the original INS/GNSS by an order of magnitude and ensures a high degree of positioning continuity. Moreover, the experiment shows that the federated filtering algorithm can adapt to the combined navigation mode in different scenarios by combining different precision sensors for navigation positioning

Bi-level Video: Video Communication at Very Low Bit Rates

The rapid development of wired and wireless networks tremendously facilitates communications between people. However, most of the current wireless networks still work in low bandwidths, and mobile devices still suffer from weak computational power, short battery lifetime and limited display capability. We developed a very low bit-rate bi-level video coding technique, which can be used in video communications almost anywhere, anytime on any device. The spirit of this method is that rather than giving highest priority to the “basic colors ” of an image as in conventional DCT-based compression methods, we give preference to the outline features of scenes when we have limited bandwidths. These features can be represented by bi-level image sequences that are converted from gray-scale image sequences. By analyzing the temporal correlation betwee