Despite many efforts to develop hormone therapy and chemotherapy, no effective strategy to suppress prostate cancer metastasis has been established because the metastasis is not well understood. We ...here investigate a role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis. CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival. The CITED2 gene is highly activated by ETS-related gene that is overexpressed due to chromosomal translocation. CITED2 acts as a molecular chaperone to guide PRMT5 and p300 to nucleolin, thereby activating nucleolin. Informatics and experimental data suggest that the CITED2-nucleolin axis is involved in prostate cancer metastasis. This axis stimulates cell migration through the epithelial-mesenchymal transition and promotes cancer metastasis in a xenograft mouse model. Our results suggest that CITED2 plays a metastasis-promoting role in prostate cancer and thus could be a target for preventing prostate cancer metastasis.
Current‐induced control of magnetization in ferromagnets using spin–orbit torque (SOT) has drawn attention as a new mechanism for fast and energy efficient magnetic memory devices. Energy‐efficient ...spintronic devices require a spin‐current source with a large SOT efficiency (ξ) and electrical conductivity (σ), and an efficient spin injection across a transparent interface. Herein, single crystals of the van der Waals (vdW) topological semimetal WTe2 and vdW ferromagnet Fe3GeTe2 are used to satisfy the requirements in their all‐vdW‐heterostructure with an atomically sharp interface. The results exhibit values of ξ ≈ 4.6 and σ ≈ 2.25 × 105 Ω‐1 m‐1 for WTe2. Moreover, the significantly reduced switching current density of 3.90 × 106 A cm−2 at 150 K is obtained, which is an order of magnitude smaller than those of conventional heavy‐metal/ferromagnet thin films. These findings highlight that engineering vdW‐type topological materials and magnets offers a promising route to energy‐efficient magnetization control in SOT‐based spintronics.
All‐van der Waals (vdW) heterostructure with an atomically sharp interface based on topological semimetal shows spin–orbit torque (SOT)‐driven magnetization switching. These findings highlight that engineering vdW‐type topological materials and magnets offers a promising route to energy‐efficient magnetization control in SOT‐based spintronics.
A polar conductor, where inversion symmetry is broken, may exhibit directional propagation of itinerant electrons, i.e., the rightward and leftward currents differ from each other, when time-reversal ...symmetry is also broken. This potential rectification effect was shown to be very weak due to the fact that the kinetic energy is much higher than the energies associated with symmetry breaking, producing weak perturbations. Here we demonstrate the appearance of giant nonreciprocal charge transport in the conductive oxide interface, LaAlO
/SrTiO
, where the electrons are confined to two-dimensions with low Fermi energy. In addition, the Rashba spin-orbit interaction correlated with the sub-band hierarchy of this system enables a strongly tunable nonreciprocal response by applying a gate voltage. The observed behavior of directional response in LaAlO
/SrTiO
is associated with comparable energy scales among kinetic energy, spin-orbit interaction, and magnetic field, which inspires a promising route to enhance nonreciprocal response and its functionalities in spin orbitronics.
Controlling magnetic states by a small current is essential for the next‐generation of energy‐efficient spintronic devices. However, it invariably requires considerable energy to change a magnetic ...ground state of intrinsically quantum nature governed by fundamental Hamiltonian, once stabilized below a phase‐transition temperature. Here, it is reported that, surprisingly, an in‐plane current can tune the magnetic state of the nanometer‐thin van der Waals ferromagnet Fe3GeTe2 from a hard magnetic state to a soft magnetic state. It is a direct demonstration of the current‐induced substantial reduction of the coercive field. This surprising finding is possible because the in‐plane current produces a highly unusual type of gigantic spin–orbit torque for Fe3GeTe2. In addition, a working model of a new nonvolatile magnetic memory based on the principle of the discovery in Fe3GeTe2, controlled by a tiny current, is further demonstrated. The findings open up a new window of exciting opportunities for magnetic van der Waals materials with potentially huge impact on the future development of spintronic and magnetic memory.
Substantial coercivity reduction by the current, larger at least by two orders of magnitude than those in previous reports, is found in the van der Waals ferromagnet Fe3GeTe2. It is theoretically shown to arise from an unusual type of gigantic spin–orbit torque, which itself is directly related to its special symmetries, large Berry curvature, and band topology. A working model of a new robust nonvolatile magnetic memory based on Fe3GeTe2, controlled by a much smaller current, is also produced.
Gathering public consensus about long-term urban open space development is more difficult than ever, even though public engagement is crucial for sustainable long-term policymaking. Routine ...evaluation of public awareness is important for retaining project momentum and designing appropriate public engagement processes for the future. This study focuses on the Yongsan Park Development Project, which has been in progress for more than three decades. An online survey of 2,000 respondents was conducted and analyzed to evaluate the current public awareness and ask questions about respondents' expectations for public engagement. The results of this study reveal that 1) a hybrid methodology is needed to effectively approach different age groups; 2) an online survey can offer new insights for projects that repurpose U.S. army base and military sites into urban open spaces; 3) the survey results will enable us to design a better public participation process that is appropriate for post-pandemic society, in which virtual meetings and socially distanced communications are part of the new norm.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen (1O2) and superoxide radical (O2 •–) is considered to trigger cell death pathways associated with protein dysfunction; ...however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm–2) because of the relatively high 1O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with tissue remodeling. Epithelial-to-mesenchymal transition (EMT), a process of tissue remodeling, can be a therapeutic target ...of CRSwNP. Glucocorticoids are a type of steroid hormone that is used primarily in medical therapy for patients with CRSwNP; however, their effects on EMT in the airway epithelium remain unknown. To investigate the effects of dexamethasone and fluticasone propionate, a class of glucocorticoids, on transforming growth factor-β1 (TGF-β1) -induced EMT, we used A549 cells, human primary nasal epithelial cells (hPNECs) and ex vivo organ culture of the inferior turbinate. TGF-β1 induced changes in cell morphology, suppressed the expression of E-cadherin and enhanced the expression of a-smooth muscle actin, vimentin and fibronectin in A549 cells. However, glucocorticoids inhibited EMT, migration and invasion enhancement by TGF-β1. We found that the induction of phosphorylated ERK, p38 and the activity of Snail and Slug transcription factors by TGF-β1 were suppressed by glucocorticoids. Glucocorticoids also had a similar effect in hPNECs and ex vivo organ cultures of the inferior turbinate. These findings suggest that glucocorticoids might be a useful therapy for preventing tissue remodeling by blocking the EMT initiated by TGF-β1-induced MAPK and Snail/Slug signaling pathways in CRSwNP.
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via ...activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells. Astrocyte-derived chemokine C-C motif ligand 20 (CCL20) was identified using cytokine arrays, and its role in glioblastoma development was evaluated in orthotopic xenografts. Astrocytes augmented HIF-1α expression in glioblastoma cells under hypoxia. The expression of HIF-1 downstream genes, cancer colony formation, and Matrigel invasion of glioblastoma cells were stimulated by conditioned medium from astrocytes pre-exposed to hypoxia. CCL20 was secreted in a hypoxia-dependent manner from astrocytes and busted the hypoxic induction of HIF-1α in glioblastoma cells. Mechanistically, the CCL20/CCR6 signaling pathway upregulates HIF-1α by stimulating nuclear factor kappa B-driven transactivation of the HIF1A gene. Compared with the control tumors, CCR6-deficient glioblastoma xenografts grew more slowly, with poor vascularization, and expressed lower levels of HIF-1α and its downstream proteins. Furthermore, CCR6 expression was correlated with HIF-1α expression in GEO and TCGA datasets from human glioblastoma tissues. These results suggest that glioblastoma cells adapt well to hypoxic stress by virtue of CCL20 derived from neighboring astrocytes.
Abstract
Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell ...and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe
i
SLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate
i
SLET in a whole-body system, we express
i
SLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver
i
SLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together,
i
SLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.
Objective
Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disease. In particular, CRS with eosinophilic features and/or nasal polyps (NPs) is often recalcitrant to current treatment; ...thus, appropriate animal models are mandatory to elucidate the pathogenesis of CRS and develop novel and efficient treatment modalities. The author reviewed the recently proposed animal models in CRS and discussed the pathophysiologic insights gained.
Data Sources: Articles in the English language referenced in MEDLINE/PubMed from the year 2006 onward (for last 10 years).
Review Methods: Review of the literature regarding animal models and related pathologic insights in CRS.
Results
Mouse, rabbit, and sheep models of CRS have been used for studying the pathogenesis of CRS. Most of researchers adopted animal models of CRS to prove any molecular mechanisms or therapeutic efficacy. In vitro or human findings and related hypothesis were evaluated in vivo using these models. In addition, novel therapeutic candidates for CRS with or without NP have been applied to animal models.
Conclusion
Animal models have elicited insights into the pathogenesis of CRS and also have been useful in testing new treatment modalities. Although there are still clear limitations in the animal studies, newly proposed or revised animal models would be helpful to understand the exact pathophysiology of CRS
PDF
