Abstract
Imaging X-ray Polarimetry Explorer (IXPE) is a Small Explorer mission by NASA and Agenzia Spaziale Italiana, launched on 2021 December 9, dedicated to investigating X-ray polarimetry ...allowing angular-, time-, and energy-resolved observations in the 2–8 keV energy band. IXPE is in the science observation phase since 2022 January; it is comprised of three identical telescopes with grazing-incidence mirrors, each one having in the focal plane a gas pixel detector. In this paper, we present a possible guideline to obtain an optimal background selection in polarimetric analysis, and a rejection strategy to remove instrumental background. This work is based on the analysis of IXPE observations, aiming to improve as much as possible the polarimetric sensitivity. In particular, the developed strategies have been applied
as a case study
to the IXPE observation of the 4U 0142+61 magnetar.
Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. ...Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.
As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently ...suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.
Abstract
We present new results of a
12
CO(
J
= 1–0) imaging survey using the Atacama Compact Array (ACA) for 31 H
i
detected galaxies in the IC 1459 and NGC 4636 groups. This is the first CO imaging ...survey for loose galaxy groups. We obtained well-resolved CO data (∼0.7–1.5 kpc) for a total of 16 galaxies in two environments. By comparing our ACA CO data with the H
i
and UV data, we probe the impacts of the group environment on the cold gas components (CO and H
i
gas) and star formation activity. We find that CO and/or H
i
morphologies are disturbed in our group members, some of which show highly asymmetric CO distributions (e.g., IC 5264, NGC 7421, and NGC 7418). In comparison with isolated galaxies in the xCOLD GASS sample, our group galaxies tend to have low star formation rates and low H
2
gas fractions. Our findings suggest that the group environment can change the distribution of cold gas components, including the molecular gas and star formation properties of galaxies. This is supporting evidence that preprocessing in the group-like environment can play an important role in galaxy evolution.
The expression of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) has been reported in Parkinson's disease; however, its role in other ...diseases is unknown. Gastric cancer is the second leading cause of cancer death. Cancer stem cells (CSC) are a subpopulation of cancer cells that contribute to the initiation and invasion of cancer. We identified LINGO2 as a CSC-associated protein in gastric cancers both in vitro and in patient-derived tissues. We studied the effect of LINGO2 on cell motility, stemness, tumorigenicity, and angiogenic capacity using cells sorted based on LINGO2 expression and LINGO2-silenced cells. Tissue microarray analysis showed that LINGO2 expression was significantly elevated in advanced gastric cancers. The overall survival of patients expressing high LINGO2 was significantly shorter than that of patients with low LINGO2. Cells expressing high LINGO2 showed elevated cell motility, angiogenic capacity, and tumorigenicity, while LINGO2 silencing reversed these properties. Silencing LINGO2 reduced kinase B (AKT)/extracellular signal-regulated kinase (ERK)/ERK kinase (MEK) phosphorylation and decreased epithelial-mesenchymal transition (EMT)-associated markers-N-Cadherin and Vimentin and stemness-associated markers- POU class 5 homeobox 1 (OCT4) and Indian hedgehog (IHH), and markedly decreased the CD44⁺ population. These indicate the involvement of LINGO2 in gastric cancer initiation and progression by altering cell motility, stemness, and tumorigenicity, suggesting LINGO2 as a putative target for gastric cancer treatment.
Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their ...function and mechanism remain unclear.
In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication.
PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery.
Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.
Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel ...histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.
Particle acceleration mechanisms in supermassive black hole jets, such as shock acceleration, magnetic reconnection, and turbulence, are expected to have observable signatures in the multiwavelength ...polarization properties of blazars. The recent launch of the Imaging X-Ray Polarimetry Explorer (IXPE) enables us, for the first time, to use polarization in the X-ray band (2–8 keV) to probe the properties of the jet synchrotron emission in high-synchrotron-peaked BL Lac objects (HSPs). We report the discovery of X-ray linear polarization (degree Πx = 15% ± 2% and electric vector position angle ψx = 35° ± 4°) from the jet of the HSP Mrk 421 in an average X-ray flux state. At the same time, the degree of polarization at optical, infrared, and millimeter wavelengths was found to be lower by at least a factor of 3. During the IXPE pointing, the X-ray flux of the source increased by a factor of 2.2, while the polarization behavior was consistent with no variability. The higher level of Πx compared to longer wavelengths, and the absence of significant polarization variability, suggest a shock is the most likely X-ray emission site in the jet of Mrk 421 during the observation. The multiwavelength polarization properties are consistent with an energy-stratified electron population, where the particles emitting at longer wavelengths are located farther from the acceleration site, where they experience a more disordered magnetic field.
Iroquois homeobox 1 (IRX1) belongs to the Iroquois homeobox family known to play an important role during embryonic development. Interestingly, however, recent studies have suggested that IRX1 also ...acts as a tumor suppressor. Here, we use homozygous knockout mutants of zebrafish to demonstrate that the IRX1 gene is a true tumor suppressor gene and mechanism of the tumor suppression is mediated by repressing cell cycle progression. In this study, we found that knockout of zebrafish Irx1 gene induced hyperplasia and tumorigenesis in the multiple organs where the gene was expressed. On the other hands, overexpression of the IRX1 gene in human tumor cell lines showed delayed cell proliferation of the tumor cells. These results suggest that the IRX1 gene is truly involved in tumor suppression. In an attempt to identify the genes regulated by the transcription factor IRX1, we performed microarray assay using the cRNA obtained from the knockout mutants. Our result indicated that the highest fold change of the differential genes fell into the gene category of cell cycle regulation, suggesting that the significant canonical pathway of IRX1 in antitumorigenesis is done by regulating cell cycle. Experiment with cell cycle blockers treated to IRX1 overexpressing tumor cells showed that the IRX1 overexpression actually delayed the cell cycle. Furthermore, Western blot analysis with cyclin antibodies showed that IRX1 overexpression induced decrease of cyclin production in the cancer cells. In conclusion, our in vivo and in vitro studies revealed that IRX1 gene functionally acts as a true tumor suppressor, inhibiting tumor cell growth by regulating cell cycle.
Abstract
The lower-energy peak of the spectral energy distribution of blazars has commonly been ascribed to synchrotron radiation from relativistic particles in the jets. Despite the consensus ...regarding jet emission processes, the particle acceleration mechanism is still debated. Here, we present the first X-ray polarization observations of PG 1553+113, a high-synchrotron-peak blazar observed by the Imaging X-ray Polarimetry Explorer (IXPE). We detect an X-ray polarization degree of (10 ± 2)% along an electric-vector position angle of
ψ
X
= 86° ± 8°. At the same time, the radio and optical polarization degrees are lower by a factor of ∼3. During our IXPE pointing, we observed the first orphan optical polarization swing of the IXPE era, as the optical angle of PG 1553+113 underwent a smooth monotonic rotation by about 125°, with a rate of ∼17° day
–1
. We do not find evidence of a similar rotation in either radio or X-rays, which suggests that the X-ray and optically emitting regions are separate or, at most, partially cospatial. Our spectropolarimetric results provide further evidence that the steady-state X-ray emission in blazars originates in a shock-accelerated and energy-stratified electron population.
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