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At least 325 records · Page 18

Migration-inducing gene-7 independently predicts poor prognosis of human osteosarcoma and is associated with vasculogenic mimicry

Highlights: • MIG-7 expression is associated with VM formation. • MIG-7 is an independent indicator of both overall and metastasis-free survival. • MIG-7 knockdown reduces osteosarcoma cells migration, invasion and VM formation. • MIG-7 knockdown didn’t affect osteosarcoma cell apoptosis or proliferation. • MIG-7 knockdown exhibits potent antimetastasis and anti-VM effects in vivo. Vasculogenic mimicry (VM) is a special type of vascular channel formed by tumor cells without endothelial cell participation. Migration-inducing gene 7 (MIG-7) plays an important role in regulating VM. In this study, immunohistochemical staining was used to detect MIG-7 in tissue specimens from 141 primary osteosarcoma patients, and the relationship between MIG-7 and VM was examined. Survival analysis were performed to evaluate the prognoses. MIG-7 knockdown osteosarcoma cells were used for cell proliferation, apoptosis, migration, invasiveness and VM formation assays. A spontaneously metastasizing cell line-derived orthotopic xenograft mouse model was established to evaluate the effect of MIG-7 knockdown on tumorigenesis, VM formation and lung metastasis. MIG-7 expression was associated with VM formation. There were significant differences in overall and metastasis-free survival between the MIG-7-positive and MIG-7-negative groups. The MIG-7 expression was shown to be an independent indicator of both overall and metastasis-free survival. In vitro knockdown of MIG-7 dramatically reduced migration, invasion and VM formation in osteosarcoma cells without any significant effect on cell proliferation and apoptosis. MIG-7 knockdown also exhibited potent antitumor, antimetastasis and anti-VM effects in the orthotopic mouse model of 143B osteosarcoma. Therefore, MIG-7 serves as an independent unfavorable prognostic indicator in osteosarcoma patients and MIG-7 is an important mediator of osteosarcoma VM formation.

60 APPLIED LIFE SCIENCES↗

Desmoglein 3 – Influence on oral carcinoma cell migration and invasion

Desmoglein 3 (Dsg3) is an adhesion receptor in desmosomes, but its role in carcinoma cell migration and invasion is mostly unknown. Our aim was to quantitatively analyse the motion of Dsg3-modified carcinoma cells in 2D settings and in 3D within tumour microenvironment mimicking (TMEM) matrices. We tested mutant constructs of C-terminally truncated Dsg3 (∆238 and ∆560), overexpressed full-length (FL) Dsg3, and empty vector control (Ct) of buccal mucosa squamous cell carcinoma (SqCC/Y1) cells. We captured live cell images and analysed migration velocities and accumulated and Euclidean distances. We compared rodent collagen and Matrigel{sup ®} with human Myogel TMEM matrices for these parameters in 3D sandwich, in which we also tested the effects of monoclonal antibody AK23, which targets the EC1 domain of Dsg3. In monolayer culture, FL and both truncated constructs migrated faster and had higher accumulated distances than Ct cells. However, in the 3D assays, only the mutants invaded faster relative to Ct cells. Of the mutants, the shorter form (Δ238) exhibited faster migration and invasion than Δ560 cells. In the Transwell, all of the cells invaded faster through Myogel than Matrigel{sup ®} coated wells. In 3D sandwich, AK23 antibody inhibited only the invasion of FL cells. We conclude that different experimental 2D and 3D settings can markedly influence the movement of oral carcinoma cells with various Dsg3 modifications.

60 APPLIED LIFE SCIENCES↗

Talin is a substrate for SUMOylation in migrating cancer cells

Highlights: • Talin is SUMOylated in cancer cells. • SUMOylation may regulate focal adhesion disassembly and cell migration. • SUMOylation may also regulate cleavage of talin. • Other focal adhesion proteins have been identified as potential SUMO targets including filamin-A and vinculin. Focal adhesions (FAs) play an important role in cancer cell migration and metastasis by linking the actin cytoskeleton to the extracellular matrix, allowing the cell to generate traction. SUMOylation is a post-translational modification of proteins on lysine residues that can affect protein localisation, turnover and protein-protein interactions. In this study, we demonstrate that talin, a key component of FAs, can be post-translationally modified by SUMOylation in MDA-MB-231 breast cancer cells and U2OS osteosarcoma cells. Furthermore we demonstrate that SUMOylation regulates the dynamic activities of FAs including their number, size and turnover rate. Inhibiting SUMOylation significantly reduced the speed of cell migration. The identification of talin as a SUMO target provides insight into the mechanisms regulating focal adhesion formation and turnover and potentially identifies a novel mechanism underlying cell migration.

60 APPLIED LIFE SCIENCES↗

Glioblastoma cell migration is directed by electrical signals

Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signalling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on primary differentiated and glioma stem cell (GSCs) migration, finding opposing preferences for anodal and cathodal migration, respectively. We next sought to determine whether chemically disrupting Akt through PTEN upregulation with the PPARγ agonist, pioglitazone, would modulate electrotaxis of these cells. We found that directed cell migration was significantly inhibited with the addition of pioglitazone in both differentiated GBM and GSCs subtypes. Western blot analysis did not demonstrate any change in PPARγ expression with and without exposure to EF. In summary we demonstrate opposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.

60 APPLIED LIFE SCIENCES↗

Enhancing Chemical Stability and Suppressing Ion Migration in CH 3 NH 3 PbI 3 Perovskite Solar Cells via Direct Backbone Attachment of Polyesters on Grain Boundaries

Organic–inorganic halide perovskites feature excellent optoelectronic properties but poor chemical stability. While passivating perovskite grain boundary (GB) by polymers shows prospects on long-term performance of perovskite solar cells (PSCs), its detailed impact on the ion migration phenomenon, which largely deteriorates the PSC stability, remains less probed. In this work, we introduce a new polar polymer, polycaprolactone (PCL), to passivate GBs of methylammonium lead triiodide (MAPbI 3 ) perovskite with only 1–2 polymer monolayers via direct backbone attachment. The PSCs with passivated MAPbI 3 , using a classic but less stable Spiro-OMeTAD (2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene) hole transport layer (HTL), exhibit improved power conversion efficiencies up to 20.1%, with 90% of the initial PCE being preserved after 400 h ambient storage, and 80% even after 100 h, 85 °C aging. The improved PSC stability indicates critical roles of PCL GB passivation in retarding moisture-induced decomposition and suppressing ion migration within the perovskite. Furthermore, time-of-flight secondary ion mass spectrometry reveals that I– ions can actively migrate into the electrode, HTL, and their interface in nonpassivated PSCs, even without an externally applied electric field, while such migration is significantly mitigated in PCL-passivated PSCs. This effective GB passivation by PCL suggests an important potential of polymer additives toward the development of stable high-performance PSCs.

36 MATERIALS SCIENCE↗

Unlocking the Dynamics of Ion Migration and Voltage Bias Stress Effects through Crystallite Engineering in Metal Halide Perovskites

Understanding the interplay between crystal engineering and the coupled electronic-ionic charge transport properties of metal halide perovskites remains a critical issue in the field. In this work, we developed an experimental approach to tune the crystallite orientation of methylammonium lead iodide (CH 3 NH 3 PbI 3 ) while maintaining their overall crystal structure. This approach allows us to selectively manipulate crystallite orientations to control out-ofplane ion migration and mitigate voltage bias stress effects in CH 3 NH 3 PbI 3 thin films. By employing advanced diffraction and spectroscopic techniques, we achieved a comprehensive characterization of the anisotropic crystallite properties in CH 3 NH 3 PbI 3 thin films with distinct preferred orientations. Our findings reveal that specific crystallite orientations, particularly those that limit halide ion migration pathways along the (200) crystallographic plane, significantly suppress out-of-plane ion migration. This suppression reduces hysteresis and alleviates voltage bias stress effects in CH 3 NH 3 PbI 3 solar cells, ultimately enhancing device stability and performance. These insights not only deepen our understanding of the relationship between crystallite orientation and device functionality but also highlight a promising strategy for regulating ion migration in MHP-based devices. This approach holds significant potential for advancing the stability and efficiency of perovskite solar cells and extending its applicability to other optoelectronic devices.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Imine Reductase-Catalyzed, Radical-Mediated Asymmetric Cyano Group Migration

Functional group migration (FGM) reactions represent a fundamental class of transformations in organic chemistry, enabling the repositioning of functional moieties in nonobvious ways. However, catalytic asymmetric radical-mediated FGMs remain rare due to the inherent challenges of achieving catalyst-controlled enantioselectivity over free radical intermediates. Herein, we repurpose imine reductases (IREDs), a class of biotechnologically important enzymes known for their substrate promiscuity, to enable the first examples of catalytic asymmetric cyano group migration via a radical mechanism. An orthogonal set of radical enzymes, including PbaIREDCym and SmiIREDCym, was engineered, allowing both 1,4- and 1,5-cyano group migration reactions to occur in an enantiodivergent fashion. The use of the nonionic surfactant TPGS-1000 was found to improve both the yield and enantioselectivity of these cyano migration reactions. Furthermore, this biocatalytic process exhibited a broad substrate scope and is readily scalable, affording a rare example of chiral nonamine product assembly with imine reductases. More broadly, stereoselective radical biocatalysis with engineered IREDs and other versatile enzymes provides a potentially general solution to challenging asymmetric FGM reactions.

Biocatalysis↗

The Role of Capillary Hysteresis and Pore-Scale Heterogeneity in Limiting the Migration of Buoyant Immiscible Fluids in Porous Media

Understanding the main mechanisms affecting long-term migration and redistribution of injected CO 2 in geological carbon storage is needed for developing predictive models to assess environmental risks and designing monitoring schemes. Preparation of a postinjection site care plan is required for CO 2 injection wells, including monitoring of pressure changes and injected CO 2 plume. Knowledge gaps exist regarding assessment of postinjection monitoring timeframes for the CO 2 plume because the processes driving long-term CO 2 plume migration and trapping are not fully understood. In the postinjection stage of geological carbon storage, redistribution of CO 2 occurs mainly due to buoyancy and capillary forces. This work presents experimental and modeling studies to investigate processes contributing to postinjection plume distribution and stabilization. We conducted a flow cell experiments (0.5 m × 0.05 m × 0.01 m) with two immiscible fluid phases in a glass bead porous medium to study postinjection plume behavior. We employed a hysteretic macroscopic two-phase flow model to interpret the experimental results and to understand main processes leading to plume stabilization. Our findings show that capillary pressure hysteresis explains the experimentally observed plume shape and redistribution at early postinjection stages; however, the long-term plume migration and eventual plume stabilization can only be represented when in addition microscale heterogeneity is accounted for. Results also show that plume stabilization can be extremely slow and that the migration of the plume front can occur through multiple intermittent bursts over long times. Here, further studies are needed to understand implications of the results for more realistic porous media and large-scale storage reservoirs.

58 GEOSCIENCES↗

A Mixed Length Scale Model for Migrating Fluvial Bedforms

With the expansion of hydropower, in-stream converters, flood-protection infrastructures, and growing concerns on deltas fragile ecosystems, there is a pressing need to evaluate and monitor bedform sediment mass flux. It is critical to estimate real-time bedform size and migration velocity and provide a theoretical framework to convert easily accessible time histories of bed elevations into spatially evolving patterns. In this study, we collected spatiotemporally resolved bathymetries from laboratory flumes and the Colorado River in statistically steady, homogeneous, subcritical flow conditions. Wave number and frequency spectra of bed elevations show compelling evidence of scale-dependent velocity for the hierarchy of migrating bedforms observed in the laboratory and field. New scaling laws were applied to describe the full range of migration velocities as function of two dimensionless groups based on the bed shear velocity, sediment diameter, and water depth. Further simplification resulted in a mixed length scale model estimating scale-dependent migration velocities, without requiring bedform classification or identification.

58 GEOSCIENCES↗

The Mechanism of Methane Gas Migration Through the Gas Hydrate Stability Zone: Insights From Numerical Simulations

Free gas migration through the gas hydrate stability zone (GHSZ) and subsequent gas seepage at the seabed are characteristic features in marine gas hydrate provinces worldwide. The biogenic or thermogenic gas is typically transported along faults from deeper sediment strata to the GHSZ. Several mechanisms have been proposed to explain free gas transport through the GHSZ. While inhibition of hydrate formation by elevated salinities and temperatures have been addressed previously in studies simulating unfocused, area-wide upward advection of gas, which is not adequately supported by field observations, the role of focused gas flow through chimney-like structures has been underappreciated in this context. Our simulations suggest that gas migration through the GHSZ is, fundamentally, a result of methane gas supply in excess of its consumption by hydrate formation. The required high gas flux is driven by local overpressure, built up from gas accumulating below the base of the GHSZ that fractures the overburden when exceeding a critical pressure, thereby creating the chimney-like migration pathway. Initially rapid hydrate formation raises the temperature in the chimney structure, thereby facilitating further gas transport through the GHSZ. As a consequence, high hydrate saturations form preferentially close to the seafloor, where temperatures drop to bottom water values, producing a prominent subsurface salinity peak. Over time, hydrates form at a lower rate throughout the chimney structure, while initial temperature elevation and salinity peak dissipate. Thus, our simulations suggest that the near-surface salinity peak and elevated temperatures are a result of transient high-flux gas migration through the GHSZ.

58 GEOSCIENCES↗

Filming movies of attosecond charge migration in single molecules with high harmonic spectroscopy

Electron migration in molecules is the progenitor of chemical reactions and biological functions after light-matter interaction. Following this ultrafast dynamics, however, has been an enduring endeavor. Here we demonstrate that, by using machine learning algorithm to analyze high-order harmonics generated by two-color laser pulses, we are able to retrieve the complex amplitudes and phases of harmonics of single fixed-in-space molecules. These complex dipoles enable us to construct movies of laser-driven electron migration after tunnel ionization of N 2 and CO 2 molecules at time steps of 50 attoseconds. Moreover, the angular dependence of the migration dynamics is fully resolved. By examining the movies, we observe that electron holes do not just migrate along the laser polarization direction, but may swirl around the atom centers. Our result establishes a general scheme for studying ultrafast electron dynamics in molecules, paving a way for further advance in tracing and controlling photochemical reactions by femtosecond lasers.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Boundary migration in a 3D deformed microstructure inside an opaque sample

How boundaries surrounding recrystallization grains migrate through the 3D network of dislocation boundaries in deformed crystalline materials is unknown and critical for the resulting recrystallized crystalline materials. Furthermore, by using X-ray Laue diffraction microscopy, we show for the first time the migration pattern of a typical recrystallization boundary through a well-characterized deformation matrix. The data provide a unique possibility to investigate effects of both boundary misorientation and plane normal on the migration, information which cannot be accessed with any other techniques. Our results show that neither of these two parameters can explain the observed migration behavior. Instead we suggest that the subdivision of the deformed microstructure ahead of the boundary plays the dominant role. Our experimental observations challenge the assumptions of existing recrystallization theories, and set the stage for determination of mobilities of recrystallization boundaries.

36 MATERIALS SCIENCE↗

Extrinsic ion migration in perovskite solar cells

In this study, the migration of intrinsic ions (e.g., MA + , Pb 2+ , I – ) in organic–inorganic hybrid perovskites has received significant attention with respect to the critical roles of these ions in the hysteresis and degradation in perovskite solar cells (PSCs). Here, we demonstrate that extrinsic ions (e.g., Li + , H + , Na + ), when used in the contact layers in PSCs, can migrate across the perovskite layer and strongly impact PSC operation. In a TiO 2 /perovskite/spiro-OMeTAD-based PSC, Li + -ion migration from spiro-OMeTAD to the perovskite and TiO 2 layer is illustrated by time-of-flight secondary-ion mass spectrometry. The movement of Li + ions in PSCs plays an important role in modulating the solar cell performance, tuning TiO 2 carrier-extraction properties, and affecting hysteresis in PSCs. The influence of Li + -ion migration was investigated using time-resolved photoluminescence, Kelvin probe force microscopy, and external quantum efficiency spectra. Other extrinsic ions such as H + and Na + also show a clear impact on the performance and hysteresis in PSCs. Understanding the impacts of extrinsic ions in perovskite-based devices could lead to new material and device designs to further advance perovskite technology for various applications.

14 SOLAR ENERGY↗

Fundamental insights about interlayer cation migration in Li-ion electrodes at high states of charge

We present that one approach to increasing the capacity of Li-ion batteries is to expand the usable voltage range over which the battery is cycled by charging the cathode to higher voltages. Layered intercalation compounds commonly used as cathodes in Li-ion batteries, however, can become susceptible to irreversible structural changes at high states of charge due to cation migration to the emptied Li layers. Here we report on the discovery of a strong correlation between the position of the Fermi level and the energy barrier for cation migration to the Li layers of fully charged layered intercalation compounds. Since the identity of the transition metal strongly influences the Fermi level, this discovery suggests that cation migration can be suppressed at high states of charge using targeted alloying strategies. First-principles calculations indicate that an increase in the concentration of Ni relative to Co or Mn should reduce, or even impede, interlayer migration in layered oxides. Lastly, the insights of this study pave the way for the discovery of layered intercalation compounds that can approach their theoretical capacities in practice.

36 MATERIALS SCIENCE↗

Interfacial oxygen migration and its effect on the magnetic anisotropy in Pt/Co/MgO/Pt films

This paper reports the interfacial oxygen migration effect and its induced magnetic anisotropy evolution in Pt/Co/MgO/Pt films. During depositing the MgO layer, oxygen atoms from the MgO combine with the neighboring Co atoms, leading to the formation of CoO at the Co/MgO interface. Meanwhile, the films show in-plane magnetic anisotropy (IMA). After annealing, most of the oxygen atoms in CoO migrate back to the MgO layer, resulting in obvious improvement of Co/MgO interface and the enhancement of effective Co-O orbital hybridization. These favor the evolution of magnetic anisotropy from IMA to perpendicular magnetic anisotropy (PMA). The oxygen migration effect is achieved by the redox reaction at the Co/MgO interface. On the contrary, the transfer from IMA to PMA cannot be observed in Pt/Co/Pt films due to the lack of interfacial oxygen migration.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Computational study of inertial migration of prolate particles in a straight rectangular channel

Inertial migration of spherical particles has been investigated extensively using experiments, theory, and computational modeling. Yet, a systematic investigation of the effect of particle shape on inertial migration is still lacking. Herein, we numerically mapped the migration dynamics of a prolate particle in a straight rectangular microchannel using smoothed particle hydrodynamics at moderate Reynolds number flows. After validation, we applied our model to 2:1 and 3:1 shape aspect ratio particles at multiple confinement ratios. Their effects on the final focusing position, rotational behavior, and transitional dynamics were studied. In addition to the commonly reported tumbling motion, for the first time, we identified a new logrolling behavior of a prolate ellipsoidal particle in the confined channel. This new behavior occurs when the confinement ratio is above an approximate threshold value of K = 0.72. Our microfluidic experiments using cell aggregates with similar shape aspect ratio and confinement ratio confirmed this new predicted logrolling motion. In this study, we also found that the same particle can undergo different rotational modes, including kayaking behavior, depending on its initial cross-sectional position and orientation. Furthermore, we examined the migration speed, angular velocity, and rotation period as well as their dependence on both particle shape aspect ratio and confinement ratio. Our findings are especially relevant to the applications where particle shape and alignment are used for sorting and analysis, such as the use of barcoded particles for biochemical assays through optical reading, or the shape-based enrichment of microalgae, bacteria, and chromosomes.

42 ENGINEERING↗

STEADY-STATE PLANET MIGRATION BY THE KOZAI-LIDOV MECHANISM IN STELLAR BINARIES

We study the steady-state orbital distributions of giant planets migrating through the combination of the Kozai-Lidov (KL) mechanism due to a stellar companion and friction due to tides raised on the planet by the host star. We run a large set of Monte Carlo simulations that describe the secular evolution of a star-planet-star triple system including the effects from general relativistic precession, stellar and planetary spin evolution, and tides. Our simulations show that KL migration produces Hot Jupiters (HJs) with semi-major axes that are generally smaller than in the observations and they can only explain the observations if the following are both true: (1) tidal dissipation at high eccentricities is at least ∼150 times more efficient than the upper limit inferred from the Jupiter-Io interaction; (2) highly eccentric planets get tidally disrupted at distances ≳ 0.015 AU. Based on the occurrence rate and semi-major axis distribution of HJs, we find that KL migration in stellar binaries can produce at most ∼20% of the observed HJs. Almost no intermediate-period (semi-major axis ∼0.1 -2 AU) planets are formed by this mechanism—migrating planets spend most of their lifetimes undergoing KL oscillations at large orbital separations (>2 AU) or as HJs.

79 ASTRONOMY AND ASTROPHYSICS↗

Type I planet migration in a magnetized disk. II. Effect of vertical angular momentum transport

We study the effects of a large-scale, ordered magnetic field in protoplanetary disks on Type I planet migration using a linear perturbation analysis in the ideal-magnetohydrodynamic limit. We focus on wind-driving disks, in which a magnetic torque ∝B{sub 0z}∂B{sub 0φ}/∂z (where B{sub 0z} and B{sub 0φ} are the equilibrium vertical and azimuthal field components) induces vertical angular momentum transport. We derive the governing differential equation for the disk response and identify its resonances and turning points. For a disk containing a slightly subthermal, pure-B{sub 0z} field, the total three-dimensional torque is close to its value in the two-dimensional (2D) limit, but remains lower than the hydrodynamic torque. In contrast with the 2D pure-B{sub 0φ} field model considered by Terquem, inward migration is not reduced when the field amplitude decreases with radius. The presence of a subdominant B{sub 0φ} component whose amplitude increases from zero at z = 0 has little effect on the torque when acting alone, but in conjunction with a B{sub 0z} component it gives rise to a strong torque that speeds up the inward migration by a factor ≳200. This factor could, however, be reduced in a real disk by dissipation and magnetic diffusivity effects. Unlike all previously studied disk migration models, in the B{sub 0z}+∂B{sub 0φ}/∂z case the dominant contributions to the torque add with the same sign from the two sides of the planet. We attribute this behavior to a new mode of interaction wherein a planet moves inward by plugging into the disk’s underlying angular momentum transport mechanism.

79 ASTRONOMY AND ASTROPHYSICS↗