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Advanced Science (Weinheim,... Apr 2024Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation...
Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation of TAMs or reprogram TAMs into the tumor-suppressive type. To gain insight into the mechanisms of macrophage polarization, a designed co-culture system is established, allowing for the education of macrophages in a manner that closely mimics the intricacies of TAMs in the tumor immune microenvironment (TIME). Through database mining, exosomal miR-1246 is identified and is then validated. Exosomal miR-1246-driven polarization of TAMs disrupts the infiltration and function of CD8 T cells. Mechanically, the amassment of exosomal miR-1246 stems from TUT7-mediated degradation of small noncoding RNA, a process stabilized by SNRPB, but not the precursor of miR-1246. Moreover, an Exo-motif is present in the exosomal miR-1246 sequence, enabling it to bind with the exosomal sorting protein hnRNPA2B1. RNA-seq analysis reveals that exogenous miR-1246 modulates the polarization of TAMs at a post-transcriptional level, emphasizing the pivotal role of the NLRP3 in macrophage polarization. In conclusion, the findings underscore the importance of exosomal miR-1246 as a trigger of macrophage reprogramming and uncover a novel mechanism for its enhanced presence in the TIME.
Topics: Tumor-Associated Macrophages; Menogaril; CD8-Positive T-Lymphocytes; MicroRNAs; Macrophages
PubMed: 38342611
DOI: 10.1002/advs.202304222 -
Oxidative Medicine and Cellular... 2020This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating,...
This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating, rat heart myocytes. Doxorubicin produced a dose-dependent increase in the rate of cyanide-resistant respiration by beating myocytes. The anthracycline analogs 4-demethoxydaunorubicin, 4'-epidoxorubicin, 4'-deoxydoxorubicin, and menogaril, as well as the anticancer quinones mitomycin C and menadione, also significantly increased oxygen consumption by cardiac myocytes. However, 5-iminodaunorubicin (which has a substituted quinone group) and mitoxantrone (which is not easily reduced by flavin dehydrogenases) had no effect on cardiac respiration. Both catalase (43%) and acetylated cytochrome c (19%) significantly decreased oxygen consumption that had been stimulated by doxorubicin; furthermore, extracellular hydrogen peroxide production was increased from undetectable control levels to 1.30 ± 0.02 nmol/min/10 myocytes ( = 4, < 0.01) in the presence of 400 M doxorubicin. These experiments suggest that the anthracycline antibiotics and other anticancer quinones stimulate cardiac oxygen radical production in intact heart myocytes; such a free radical cascade could contribute to the cardiac toxicity of these drugs.
Topics: Aging; Animals; Antineoplastic Agents; Benzoquinones; Cell Respiration; Cyanides; Doxorubicin; Free Radical Scavengers; Hydrogen Peroxide; Male; Myocytes, Cardiac; Oxygen Consumption; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 33144915
DOI: 10.1155/2020/8877100 -
RNA (New York, N.Y.) Nov 2022Metazoan histone mRNAs are the only cellular eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. SLBP is bound to the 3' end of...
Metazoan histone mRNAs are the only cellular eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. SLBP is bound to the 3' end of histone mRNAs and is required for translation of histone mRNA. The expression of histone mRNAs is tightly cell-cycle regulated. A major regulatory step is rapid degradation of histone mRNA at the end of S-phase or when DNA synthesis is inhibited in S-phase. 3'hExo, a 3' to 5' exonuclease, binds to the SLBP/SL complex and trims histone mRNA to 3 nt after the stem-loop. Together with a terminal uridyl transferase, 3'hExo maintains the length of the histone mRNA during S-phase. 3'hExo is essential for initiating histone mRNA degradation on polyribosomes, initiating degradation into the 3' side of the stem-loop. There is extensive uridylation of degradation intermediates in the 3' side of the stem when histone mRNA is degraded. Here, we knocked out TUT7 and 3'hExo and we show that both modification of histone mRNA during S-phase and degradation of histone mRNA involve the interaction of 3'hExo, and a specific TUTase, TENT3B (TUT7, ZCCHC6). Knockout of 3'hExo prevents the initiation of 3' to 5' degradation, stabilizing histone mRNA, whereas knockout of TUT7 prevents uridylation of the mRNA degradation intermediates, slowing the rate of degradation. In synchronized 3'hExo KO cells, histone mRNA degradation is delayed, but the histone mRNA is degraded prior to mitosis by a different pathway.
Topics: Animals; Humans; Histones; Menogaril; HeLa Cells; RNA Stability; RNA, Messenger; mRNA Cleavage and Polyadenylation Factors
PubMed: 36041871
DOI: 10.1261/rna.079233.122 -
Sensors (Basel, Switzerland) Jan 2023Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications....
Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications. However, since the imaging mode of SAR is side-by-side, the TomoSAR point cloud of a single orbit cannot achieve a complete observation of buildings. It is difficult for existing methods to extract the same features, as well as to use the overlap rate to achieve the alignment of the homologous TomoSAR point cloud and the cross-source TomoSAR point cloud. Therefore, this paper proposes a robust alignment method for TomoSAR point clouds in urban areas. First, noise points and outlier points are filtered by statistical filtering, and density of projection point (DoPP)-based projection is used to extract TomoSAR building point clouds and obtain the facade points for subsequent calculations based on density clustering. Subsequently, coarse alignment of source and target point clouds was performed using principal component analysis (PCA). Lastly, the rotation and translation coefficients were calculated using the angle of the normal vector of the opposite facade of the building and the distance of the outer end of the facade projection. The experimental results verify the feasibility and robustness of the proposed method. For the homologous TomoSAR point cloud, the experimental results show that the average rotation error of the proposed method was less than 0.1°, and the average translation error was less than 0.25 m. The alignment accuracy of the cross-source TomoSAR point cloud was evaluated for the defined angle and distance, whose values were less than 0.2° and 0.25 m.
Topics: Menogaril; Tomography, X-Ray Computed; City Planning; Cluster Analysis; Principal Component Analysis
PubMed: 36679649
DOI: 10.3390/s23020852 -
Sensors (Basel, Switzerland) Jun 2021Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture...
Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture radar tomography (TomoSAR) can achieve the three-dimensional imaging of forests, it has been widely used in underlying topography estimation. At present, there are two kinds of TomoSAR based on the applied datasets: single polarimetric TomoSAR (SP-TomoSAR) and fully polarimetric TomoSAR (FP-TomoSAR). However, SP-TomoSAR cannot obtain the underlying topography accurately due to the lack of enough observations. FP-TomoSAR can improve the estimation accuracy of underlying topography. However, it requires high-cost data acquisition for the large-scale application. Thus, this paper proposes the dual polarimetric TomoSAR (DP-TomoSAR) as another suitable candidate to estimate the underlying topography because of its wide swath and multiple polarimetric observations. Moreover, three frequently used spectral estimation algorithms, namely, Beamforming, Capon and MUSIC, are used in DP-TomoSAR. For validation, a series of simulated experiments was carried out, and the airborne P-band multiple polarimetric SAR data over the Lope, Gabon was also acquired to estimate the underlying topography. The results suggest that DP-TomoSAR in HH & HV combination is more suitable to estimate underlying topography over forest areas than other DP combinations. Moreover, the estimation accuracy of DP-TomoSAR is slightly lower than that of FP-TomoSAR but is higher than that of SP-TomoSAR.
Topics: Environmental Monitoring; Forests; Menogaril; Radar; Tomography
PubMed: 34203846
DOI: 10.3390/s21124117 -
Sensors (Basel, Switzerland) Oct 2021Synthetic aperture radar (SAR) tomography (TomoSAR) can obtain 3D imaging models of observed urban areas and can also discriminate different scatters in an azimuth-range...
Synthetic aperture radar (SAR) tomography (TomoSAR) can obtain 3D imaging models of observed urban areas and can also discriminate different scatters in an azimuth-range pixel unit. Recently, compressive sensing (CS) has been applied to TomoSAR imaging with the use of very-high-resolution (VHR) SAR images delivered by modern SAR systems, such as TerraSAR-X and TanDEM-X. Compared with the traditional Fourier transform and spectrum estimation methods, using sparse information for TomoSAR imaging can obtain super-resolution power and robustness and is only minorly impacted by the sidelobe effect. However, due to the tight control of SAR satellite orbit, the number of acquisitions is usually too low to form a synthetic aperture in the elevation direction, and the baseline distribution of acquisitions is also uneven. In addition, artificial outliers may easily be generated in later TomoSAR processing, leading to a poor mapping product. Focusing on these problems, by synthesizing the opinions of various experts and scholarly works, this paper briefly reviews the research status of sparse TomoSAR imaging. Then, a joint sparse imaging algorithm, based on the building points of interest (POIs) and maximum likelihood estimation, is proposed to reduce the number of acquisitions required and reject the scatterer outliers. Moreover, we adopted the proposed novel workflow in the TerraSAR-X datasets in staring spotlight (ST) work mode. The experiments on simulation data and TerraSAR-X data stacks not only indicated the effectiveness of the proposed approach, but also proved the great potential of producing a high-precision dense point cloud from staring spotlight (ST) data.
Topics: Algorithms; Menogaril; Radar; Tomography; Tomography, X-Ray Computed
PubMed: 34696097
DOI: 10.3390/s21206888