Large‐amplitude (Bw > 1 nT) electromagnetic ion cyclotron (EMIC) waves can cause the rapid loss of >1 MeV electrons, greatly impacting radiation belt dynamics. With long‐term Van Allen Probe B ...observations from 2013 to 2018, we conducted a statistical survey to reveal the amplitude‐dependent EMIC wave properties and excitation mechanisms in the Earth's inner magnetosphere. Statistical results show that large‐amplitude EMIC waves prefer to occur in the afternoon‐dusk sector in the northern hemisphere and tend to be more left‐hand polarized with smaller wave normal angles. In addition, the high proton beta parallel conditions also favor the generation of larger‐amplitude EMIC waves. From the variations of EMIC wave occurrence rate as a function of SuperMAG electrojet (SME) index and solar wind dynamic pressure, we find that the small‐amplitude EMIC waves are generally triggered by high solar wind dynamic pressure, while large‐amplitude EMIC wave generation is both affected by substorm activity and solar wind dynamic pressure. The normalized magnetic field perturbations during EMIC wave appearance, which enable us to distinguish the relative roles of magnetospheric compression and substorm injection in the excitation of different‐amplitude EMIC waves, provide further evidence that as wave amplitude increases, substorm injection plays a more important role in EMIC wave excitation, and magnetospheric compression is also an indispensable trigger.
Plain Language Summary
Electromagnetic ion cyclotron (EMIC) waves, one of the most commonly observed electromagnetic waves in the Earth's inner magnetosphere, can scatter relativistic electrons through cyclotron resonance and cause their loss to the atmosphere, which greatly affects radiation belt dynamics. In recent years, large‐amplitude EMIC waves have attracted much attention due to their ability to cause the rapid loss of >1 MeV electrons. This study aims to reveal the amplitude‐dependent wave properties and excitation mechanisms of EMIC waves in the Earth's inner magnetosphere. It is shown that large‐amplitude EMIC waves are more likely to be left‐hand polarized with smaller wave normal angles under high proton beta parallel β∥,p, which is the ratio of parallel thermal pressure and magnetic pressure. Through analyzing EMIC wave occurrence rate as a function of SME index and solar wind dynamic pressure, together with the normalized magnetic field perturbations during EMIC wave appearance, which can be used to quantify the effects of magnetospheric compression and substorm injection on EMIC wave excitation, we conclude that substorm injection plays a more important role in large‐amplitude EMIC wave excitation, while magnetospheric compression is an indispensable trigger for all EMIC waves.
Key Points
The amplitude‐dependent properties and excitation mechanisms of electromagnetic ion cyclotron (EMIC) waves are investigated with Van Allen Probe B data from 2013 to 2018
Large‐amplitude EMIC waves tend to be more left‐hand polarized with smaller wave normal angles under high proton beta parallel conditions
Substorm injection is vital in large‐amplitude EMIC wave excitation, while magnetospheric compression is indispensable for all EMIC waves
M2-polarized macrophages are tumor-associated-macrophages (TAMs), which are important contents of tumor-infiltrating immune cells. Toll-like receptor 4 (TLR4) is a molecular biomarker of tumor ...aggressiveness and poor prognosis. Toll-like receptors (TLRs) have important roles in the immune system and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized macrophages.
THP-1 cells were induced to differentiate into M2-like macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the HCC cell lines SMMC-7721 and MHCC97-H cultured in conditioned medium from M2-like macrophages (M2-CM) to investigate the migration potential of HCC cells and epithelial-mesenchymal transition (EMT)-associated molecular genetics. Signaling pathways that mediated M2-CM-promoted HCC migration were detected using western blotting.
HCC cells cultured with M2-CM displayed a fibroblast-like morphology, an increased metastatic capability, and expression of EMT markers. TLR4 expression was markedly increased in M2-CM-treated HCC cells. TLR4 overexpression promoted HCC cell migration, and a TLR4-neutralizing antibody markedly inhibited HCC EMT in cells cultured with M2-CM. Furthermore, the TLR4/(signal transducer and activator of transcription 3 (STAT3) signaling pathway contributed to the effects of M2-CM on HCC cells.
Taken together, M2-polarized macrophages facilitated the migration and EMT of HCC cells via the TLR4/STAT3 signaling pathway, suggesting that TLR4 may be a novel therapeutic target. These results improve our understanding of M2-polarized macrophages.
Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the ...increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat‐treated residual HCC cells were cultured on tailorable 3D gel with different matrix stiffness, simulating the changed physical environment after thermal ablation, and then the mechanical alterations of matrix stiffness on cell phenotypes were explored. Increased stiffness was found to significantly promote the proliferation of the heat‐treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness‐dependent regulation of ERK phosphorylation. Heat‐exposed HCC cells cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness‐dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat‐treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerates HCC development. Vitamin K1 plus sorafenib can reverse this protumor effect.
Increased matrix stiffness after thermal ablation accelerates the progression of heat‐exposed residual HCC cells. Vitamin K1 and sorafenib disrupt the stiffness‐induced ERK activation to reverse the pro‐tumor effect as the potential therapeutic drugs. This new finding will help design strategy to treat the local tumor progression and prevent its rapid progression after RFA in the treatment of medium or large HCC.
Drug resistance is one of the major concerns in the treatment of hepatocellular carcinoma (HCC). The aim of the present study was to determine whether aberrant high expression of the inhibitor of ...differentiation 1(ID1) confers oxaliplatin-resistance to HCC by activating the pentose phosphate pathway (PPP).
Aberrant high expression of ID1 was detected in two oxaliplatin-resistant cell lines MHCC97H-OXA(97H-OXA) and Hep3B-OXA(3B-OXA). The lentiviral shRNA or control shRNA was introduced into the two oxaliplatin-resistant cell lines. The effects of ID1 on cell proliferation, apoptosis and chemoresistance were evaluated in vitro and vivo. The molecular signaling mechanism underlying the induction of HCC proliferation and oxaliplatin resistance by ID1 was explored. The prognostic value of ID1/G6PD signaling in HCC patients was assessed using the Cancer Genome Atlas (TCGA) database.
ID1 was upregulated in oxaliplaitin-resistant HCC cells and promoted HCC cell proliferation and oxaliplatin resistance. Silencing ID1 expression in oxaliplaitin-resistant HCC cell lines inhibited cell proliferation and sensitized oxaliplaitin-resistant cells to death. ID1 knockdown significantly decreased the expression of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme of the PPP. Silencing ID1 expression blocked the activation of G6PD, decreased the production of PPP NADPH, and augmented reactive oxygen and species (ROS), thus inducing cell apoptosis. Study of the molecular mechanism showed that ID1 induced G6PD promoter transcription and activated PPP through Wnt/β-catenin/c-MYC signaling. In addition, ID1/G6PD signaling predicted unfavorable prognosis of HCC patients on the basis of TCGA.
Our study provided the first evidence that ID1 conferred oxaliplatin resistance in HCC by activating the PPP. This newly defined pathway may have important implications in the research and development of new more effective anti-cancer drugs.
Epithelial-mesenchymal transition (EMT) is regarded as a critical event during tumor metastasis. Recent studies have revealed changes and the contributions of proteins in/on exosomes during EMT. ...Besides proteins, microRNA (miRNA) is another important functional component of exosomes. We hypothesized that the miRNA profile of exosomes may change following EMT and these exosomal miRNAs may in return promote EMT, migration and invasion of cancer cells.
The small RNA profile of exosomes was altered following EMT. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the specific miRNAs of M-exosomes have the potential to drive signal transduction networks in EMT and cancer progression. Co-culture experiments confirmed that M-exosomes can enter epithelial cells and promote migration, invasion and expression of mesenchymal markers in the recipient cells.
Our results reveal changes in the function and miRNA profile of exosomes upon EMT. M-exosomes can promote transfer of the malignant (mesenchymal) phenotype to epithelial recipient cells. Further, the miRNAs specifically expressed in M-exosomes are associated with EMT and metastasis, and may serve as new biomarkers for EMT-like processes in lung cancer.
Magnetic cavities, also known as magnetic holes, are ubiquitous in space plasmas characterized by depressed magnetic strength and enhanced plasma pressure. Most of the observed cavities are ...associated with anisotropic particle distributions with higher fluxes in the direction perpendicular to the magnetic field. Recent observations of kinetic‐scale magnetic cavities have identified another type of electron distributions in the pitch angle spectrum, the so‐called donut‐shaped distributions, although their formation mechanism remains unclear. Here, we present a simplistic model of cavity shrinkage and deepening, in which electrons are traced backward in time to the initial, equilibrium‐state cavity. The resulting electron distributions, determined from Liouville's theorem, agree with the observations in the presence of donut‐shaped pitch angle structures. The model also enables a quantitative evaluation on the roles of betatron cooling, radial transport, and pitch angle variations in the formation of donut‐shaped electron distributions within evolving magnetic cavities.
Plain Language Summary
Satellite observations of the space plasma environments have identified many localized structures with reduced magnetic field amplitude in an otherwise unperturbed background. These structures, referred to as magnetic cavities or holes, are usually observed in association with anisotropic particle distributions, with higher fluxes in the direction perpendicular to the magnetic field. It is these anisotropic distributions that provide the strongest support to the prevalent understanding that magnetic cavities are generated via mirror or electron‐mirror instabilities. However, recent observations have identified a different type of electron distributions in kinetic‐scale magnetic cavities, the so‐called donut‐shaped distributions after their characteristic appearances in the electron pitch angle spectrum. In this paper, we examine the hypothesis that donut‐shaped electron distributions originate from the simultaneous deepening and shrinkage of magnetic cavities, a process identified in recent observations. To do so, we carry out a particle‐tracing simulation to analyze the electron behavior within the evolving magnetic cavity, which includes the adiabatic betatron cooling, radial transport, and pitch angle variations. The variations of the electron phase space densities are then computed based on Liouville's theorem, which results in donut‐shaped distributions consistent with observations from NASA's Magnetospheric Multiscale mission.
Key Points
Magnetic cavity electrons sometimes display donut‐shaped pitch angle distributions, which differ from their usual, 90°‐concentrated form
Numerical simulations show that donut‐shaped electron distributions originate from the shrinkage and deepening of magnetic cavities
The donut‐shaped distributions are formed by the combined effects of betatron cooling, radial transport, and pitch angle variations
Abstract
NASA’s Magnetospheric Multi-Scale (MMS) mission is designed to explore the proton- and electron-gyroscale kinetics of plasma turbulence where the bulk of particle acceleration and heating ...takes place. Understanding the nature of cross-scale structures ubiquitous as magnetic cavities is important to assess the energy partition, cascade and conversion in the plasma universe. Here, we present theoretical insight into magnetic cavities by deriving a self-consistent, kinetic theory of these coherent structures. By taking advantage of the multipoint measurements from the MMS constellation, we demonstrate that our kinetic model can utilize magnetic cavity observations by one MMS spacecraft to predict measurements from a second/third spacecraft. The methodology of “observe and predict” validates the theory we have derived, and confirms that nested magnetic cavities are self-organized plasma structures supported by trapped proton and electron populations in analogous to the classical theta-pinches in laboratory plasmas.
Magnetic cavities are sudden depressions of magnetic field strength widely observed in the space plasma environments, which are often accompanied by plasma density and pressure enhancement. To ...describe these cavities, self‐consistent kinetic models have been proposed as equilibrium solutions to the Vlasov‐Maxwell equations. However, observations from the Magnetospheric Multi‐Scale (MMS) constellation have shown the existence of helical magnetic cavities characterized by the presence of azimuthal magnetic field, which could not be reconstructed by the aforementioned models. Here, we take into account another invariant of motion, the canonical axial momentum, to construct the particle distributions and accordingly modify the equilibrium model. The reconstructed magnetic cavity shows excellent agreement with the MMS1 observations not only in the electromagnetic field and plasma moment profiles but also in electron pitch‐angle distributions. With the same set of parameters, the model also predicts signatures of the neighboring MMS3 spacecraft, matching its observations satisfactorily.
Plain Language Summary
Magnetic cavities, also referred to as magnetic holes, are ubiquitous in the space plasma environment characterized by depressed magnetic field strength and enhanced plasma pressure. These structures are usually believed to result from plasma instabilities, although recent observations and simulations have suggested their quasi‐stationary nature. Kinetic models of magnetic cavities have been also proposed, which show excellent agreement with spacecraft observations to indicate the formation of quasi‐equilibrium cavities during the turbulent evolution of space plasmas. These models, however, apply only to magnetic cavities with straight field lines, and therefore cannot describe the helical magnetic cavities recently discovered by NASA's Magnetospheric Multi‐Scale (MMS) constellation. In this paper, we propose a revised model by incorporating the canonical axial momentum as an additional invariant of particle motion into the particle distributions, to resolve the self‐consistent profiles of the electromagnetic field and particle distributions within the magnetic cavity. This revision accommodates the field‐aligned current to support the helical field lines, which shows remarkable agreement with the observations from the MMS constellation.
Key Points
Spacecraft observations of magnetic cavities are sometimes accompanied by azimuthal magnetic field indicating the helical structure
Kinetic, equilibrium model of helical magnetic cavities is developed based on four invariants of particle motion
The model reproduces the MMS observations of helical magnetic cavities in both electromagnetic field and particle distributions
Abstract
Magnetic flux ropes with helical field lines and a strong core field are ubiquitous structures in space plasmas. Recently, kinetic-scale flux ropes have been identified by high-resolution ...observations from the Magnetospheric Multiscale (MMS) spacecraft in the magnetosheath, which have drawn a lot of attention because of their nonideal behavior and internal structures. Detailed investigation of flux rope structure and dynamics requires the development of realistic kinetic models. In this paper, we generalize an equilibrium model to reconstruct a kinetic-scale flux rope previously reported via MMS observations. The key features in the magnetic field and electron pitch-angle distribution measurements of all four satellites are simultaneously reproduced in this reconstruction. Besides validating the model, our results also indicate that the anisotropic features previously attributed to asymmetric magnetic topologies in the magnetosheath can be alternatively explained by the spacecraft motion in the flux rope rest frame.
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