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Simultaneously enhancing the strength, plasticity, and toughness of metal materials has been a prominent research objective. In this study, the precipitation of nano-scale vanadium carbide particles at a lower tempering temperature is controlled to achieve three key benefits: reducing lattice distortion in bainitic ferrite, strengthening through precipitation, and enhancing the toughness of bainitic ferrite, while also maintaining the content and stability of retained austenite. The adopted procedure increases the comprehensive mechanical properties of steel by 17%. In particular, the room-temperature impact toughness is increased by 41%. This comprehensive microstructure optimization endows bainitic steel with an excellent combination of mechanical properties.

A coupled model of micro-segregation and macro-heat transfer was established to study the solute micro-segregation behaviour of bainite rail steel in the continuous casting process. The effects of solute elements, effective cooling rate of the mushy zone (Ceff), and MnS precipitation on the solute micro-segregation and characteristic solidification temperatures were analysed. The results show that Ceff gradually decreases from the surface of the bloom to the centre as the solidification of the molten steel progresses, and the maximum effective cooling rate is in the corner of the bloom. During the solidification of bainite rail steel, the micro-segregation degree of P and S is more serious, followed by C, Si, Mo, etc. At the later stage of solidification, the precipitation of MnS leads to a decrease in the micro-segregation degree of S and Mn. Carbon mainly affects the solute micro-segregation behaviour by changing the solidification mode of molten steel, while the initial S and Mn contents in molten steel have no obvious effect on the micro-segregation degree of C, Si, Cr, Ni, Mo, and P. Ceff has different effects on the micro-segregation behaviors of different solute elements. An increase in C, Mn, and S content and in Ceff will advance the MnS precipitation time and lead to an increase in the amount of MnS precipitation. Increasing the initial C, Mn, and S content in molten steel leads to a decrease in both ZST and ZDT.

Abstract We report an Arase‐all sky imager (ASI) conjugate event in which the pulsating aurora (PsA) has a one‐to‐one correspondence with chorus bursts. Wavelet analysis displayed three peaks at ∼0.3 Hz, 4 Hz, and >10 Hz, corresponding to the main pulsation, internal modulation, and fast modulation, respectively. These correspond to the old terms of ∼5–15 s pulsations, chorus risers/elements and subelements/subpackets, respectively. Electron “microbursts” correspond to the 4‐Hz peak. The internal and fast modulations are further verified by the analysis based on fast Fourier transform analyses. Moreover, the spatial distributions of the Fourier spectral amplitude show that the internal and fast modulations are well‐structured within auroral patches. The above results indicate a paradigm shift away from quasilinear theory which implicitly assumes diffuse wave generation. The three time‐scale modulations are consistent with coherent chorus which has been theoretically argued to lead to pitch angle transport three orders of magnitude faster.

Abstract Magnetosheath jets with enhanced dynamic pressure are common in the Earth's magnetosheath. They can impact the magnetopause, causing deformation of the magnetopause. Here we investigate the 3‐D structure of magnetosheath jets using a realistic‐scale, 3‐D global hybrid simulation. The magnetosheath has an overall honeycomb‐like 3‐D structure, where the magnetosheath jets with increased dynamic pressure surround the regions of decreased dynamic pressure resembling honeycomb cells. The magnetosheath jets downstream of the bow shock region with θBn ≲ 20° (where θBn is the angle between the upstream magnetic field and the shock normal) propagate approximately along the normal direction of the magnetopause, while those downstream of the bow shock region with θBn ≳ 20° propagate almost tangential to the magnetopause. Therefore, some magnetosheath jets formed at the quasi‐parallel shock region can propagate to the magnetosheath downstream of the quasi‐perpendicular shock region.

Rapid tempering at high temperature is beneficial to release residual stress. However, the evolution of microstructure and mechanical properties of ultrafine bainitic steel after rapid tempering at high temperature is still unclear. In this research, the effect of rapid tempering at high temperature on microstructure, mechanical properties and mechanical stability of retained austenite (RA) of a medium-carbon ultrafine bainitic steel were studied in detail. Results show that after a rapid tempering at 550 °C, the volume fraction of RA decreased gradually, and the carbon atoms in bainitic ferrite (BF) gradually diffused out of the lattice and finally formed carbides, and the BF plate gradually coarsened. When the tempering time is only 2 min, the carbon clusters formed, strengthening the matrix and stabilizing the RA, which result in the highest yield strength, and the highest impact toughness of the steel. With the extension of tempering time, nano-carbides precipitated and gradually grew up, and the dislocation density in steel decreased, resulting in a gradual decrease in the yield strength of the steel and the mechanical stability of RA. However, the deformation ability and strain hardening ability of the BF matrix gradually increase, so that the tensile strength of the steel gradually increases. The decomposition of RA and the formation of brittle martensite making the impact toughness of the steel gradually decrease. This study can provide theoretical support for the development of rapid tempering process of ultrafine bainitic steel.

Abstract Bursts of electron butterfly distributions at 10s keV correlated with chorus waves are frequently observed in the Earth's magnetosphere. Strictly ducted (parallel) upper‐band chorus waves are proposed to cause them by nonlinear cyclotron trapping. However, chorus waves in these events are probably nonducted or not strictly ducted. In this study, test‐particle simulations are conducted to investigate electron scattering driven by ducted (quasi‐parallel) and nonducted upper‐band chorus waves. Simulation results show butterfly distributions of 10s keV electrons can be created by both ducted and nonducted upper‐band chorus waves in seconds. Ducted upper‐band chorus waves cause these butterfly distributions mainly by accelerating electrons due to cyclotron phase trapping. However, nonducted waves tend to decelerate electrons to form these butterfly distributions via cyclotron phase bunching. Our study provides new insights into the formation mechanisms of electron butterfly distributions and demonstrates the importance of nonlinear interactions in the Earth's magnetosphere.

Magnetosonic (MS) waves, i.e., ion Bernstein mode waves, are one of the common plasma waves in the Earth’s magnetosphere, which are important for regulating charged particle dynamics. How MS waves propagate in the magnetosphere is critical to understanding the global distribution of the waves, but it remains unclear. Although previous studies present that MS waves can be reflected by fine-scale density structures, the dissipation of waves by background plasma has long been neglected. In this study, we perform one-dimensional (1-D) particle-in-cell (PIC) simulations to study the propagation of MS waves through density structures, where both absorption and reflection have been included. We find that absorption is as important as reflection when considering the propagation of MS waves through density structures, and both of them are strongly dependent on the shape of density structures. Specifically, the reflectivity of MS waves is positively and negatively correlated with the height and width of density structures, respectively, while the absorptivity of MS waves has a positive correlation with both the height and width of density structures. Our study demonstrates the significance of absorption during the propagation of MS waves, which may help better understand the distribution of MS waves in the Earth’s magnetosphere.

An improved multi-channel symmetric network (MCSNet) is proposed to reconstruct high-channel-density random images after long-term transmission through multimode fibers (MMFs). Temporal correlation within a period of 25 minutes is calculated to investigate the time-varying characteristics of speckles. The results demonstrated that due to noise accumulation along the MMF path, the quality of speckles deteriorates significantly after long-term transmission. The MCSNet integrates U-Net and ConvNeXt Block, which enables to more fully extract the features of each channel within the entire speckle. After being trained by different random image datasets within the initial moment, tests on random images and realistic scenes of endoscopic surgery after 25 min of transmission are carried out, and all of them demonstrate a near-perfect reconstruction performance and superior scalability, which indicates that MCSNet is suitable for long-term imaging demodulation of endoscopes.

Abstract High‐speed jets (HSJs) are commonly observed in the Earth's magnetosheath. The HSJs can drive shock‐like bow waves when compressing the ambient plasma, which are important for the HSJ's evolution and the energization of charged particles. Here we present the first two‐dimensional hybrid simulation of the formation and evolution of jet‐driven bow waves. The simulated bow waves exhibit localized enhanced magnetic field and ion density, with their peaks separated by the order of ion inertial length. The bow waves are formed when a super‐magnetosonic HSJ encounters a magnetic structure with the magnetic field nearly perpendicular to the HSJ's velocity. The magnetic field structure acts as an obstacle to deflect and decelerate the jet, causing the pile up of ions on the jet side and the compression of the magnetic structure on the downstream side. Our study explains the observed properties of bow waves, and helps to better understand the evolution of HSJs.

Abstract Lung cancer, a major contributor to cancer-related fatalities worldwide, involves a complex pathogenesis. Cathepsins, lysosomal cysteine proteases, play roles in various physiological and pathological processes, including tumorigenesis. Observational studies have suggested an association between cathepsins and lung cancer. However, the causal link between the cathepsin family and lung cancer remains undetermined. This study employed Mendelian randomization analyses to investigate this causal association. The univariable Mendelian randomization analysis results indicate that elevated cathepsin H levels increase the overall risk of lung cancer, adenocarcinoma, and lung cancer among smokers. Conversely, reverse Mendelian randomization analyses suggest that squamous carcinoma may lead to increased cathepsin B levels. A multivariable analysis using nine cathepsins as covariates reveals that elevated cathepsin H levels lead to an increased overall risk of lung cancer, adenocarcinoma, and lung cancer in smokers. In conclusion, cathepsin H may serve as a marker for lung cancer, potentially inspiring directions in lung cancer diagnosis and treatment.

Abstract Background The prognosis and survival of lung adenocarcinoma (LUAD) patients are still not promising despite recent breakthroughs in treatment. Endoplasmic reticulum stress (ERS) is a self-protective mechanism resulting from an imbalance in quality control of unfolded proteins when cells are stressed, which plays an active role in lung cancer development, but the relationship between ERS and the pathological characteristics and clinical prognosis of LUAD patients remains unclear. Methods LASSO and Cox regression were applied based on sequencing information to construct the model, which was validated to be robust. The risk scores of the patients were calculated using the formula provided by the model, and the patients were divided into high and low-risk groups according to the median cut-off of risk scores. Cox regression analysis identifies independent prognostic factors for these patients, and enrichment analysis of prognosis-related genes was also performed. The relationship between risk scores and tumor mutation burden (TMB), cancer stem cell index, and drug sensitivity was explored. Results We constructed a 13-gene prognostic model for LUAD patients. Patients in the high-risk group had worse overall survival, lower immune score and ESTIMATE score, higher TMB, higher cancer stem cell index, and higher sensitivity to conventional chemotherapeutic agents. In addition, we constructed a nomogram that predicts 5-year survival in LUAD patients, which helps clinicians to foresee the prognosis from a new perspective. Conclusions Our results highlight the association of ERS with LUAD and the potential use of ERS in guiding treatment.

Lung adenocarcinoma (LUAD) has a poor prognosis. Circadian genes such as TIMELESS have been associated with several pathologies, including cancer. The expression of TIMELESS and the relationship between TIMELESS, infiltration of tumors and prognosis in LUAD requires further investigation. In this study, we investigated the expression of TIMELESS and its association with survival across several types of human cancer using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Program. Noncoding RNAs (ncRNAs) regulating overexpression of TIMELESS in lung adenocarcinoma (LUAD) were explored with expression, correlation, and survival analyses. Immune cell infiltration and biomarkers were analyzed between different TIMELESS expression levels. The relationship between TIMELESS expression and immunophenoscores, which were used to predict response to immunotherapy, was evaluated. TIMELESS was identified as a potential oncogene in LUAD. NcRNA analysis showed MIR4435-2HG/hsa-miR-1-3p may interact with TIMELESS in a competitive endogenous RNA network in LUAD tumor tissues. Most immune cells were significantly decreased in TCGA LUAD tumor tissues with high TIMELESS expression except for CD4+T cells and Th2 cells. TIMELESS expression in LUAD tumor tissues was significantly negatively correlated with neutrophil biomarkers, dendritic cell biomarkers (HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DPA1, CD1C) and an immunophenoscore that predicted outcomes associated with the use of immune checkpoint inhibitors. These findings imply that ncRNAs-mediated TIMELESS overexpression in LUAD tumor tissues correlated with poor prognosis, reduced immune cell infiltration in the tumor microenvironment, and poor response to immune checkpoint inhibitors.

Abstract Using the high‐quality measurements of plasma by the Magnetospheric Multiscale (MMS) spacecraft, we investigate the wave‐particle interaction between cold protons and Electromagnetic ion cyclotron (EMIC) waves of different polarizations in the inner magnetosphere. Both the left‐hand and right‐hand polarized EMIC waves can interact with cold protons via non‐resonance interaction, and energize the cold protons (∼eV) up to suprathermal energies (∼tens of eV), resulting in a series of bridge‐like arcs in the ion energy spectrogram. Cold protons experience different types of phase bunching in left‐hand and right‐hand polarized EMIC waves. However, the relative angles between the velocities of bunched protons and wave magnetic or electric fields are independent of the polarizations of EMIC waves. Thus, the energy transfer process is not affected by the polarization of EMIC waves. The observations indicate that EMIC waves can affect the magnetospheric particle dynamics by energizing the cold protons.

Collisionless shocks with low Alfvénic Mach numbers are expected to accelerate electrons, but the underlying physics are still unsolved. Two-dimensional particle-in-cell simulation of low-Mach-number quasi-perpendicular shock in low-β is performed to study the physics of formation of beam-like components with respect to background magnetic fields. The incoming electrons can be trapped and scattered to have velocities along the shock surface by the electrostatic wave in the foot region owing to the free energy in the relative drift between shock reflected ions and upstream electrons. Then fractional electrons can be reflected by the mirror force at the shock overshoot when escaping from the loss cone. The reflection by the mirror force makes the electrons gain quasi-parallel velocities, and the electrons are accelerated in the quasi-parallel direction during trapping in the immediate downstream, forming a beam-like component with respect to magnetic fields. Our results shown in this paper explain the physics of beam formation and could be helpful for accounting for type II radio bursts.

A flexible fiber-optic sensor enabled by deep learning is proposed and experimentally demonstrated for highly efficient curvature sensing application. This sensing modulation system combines a deep optical neural network based on a small training dataset, aiming to simplify speckle data capture and sensor model evaluation. The multimode fiber concatenated with a section of single stress-applying fiber serves as a sensing unit as well as an image transport medium. A type of hybrid scattering speckle images is collected and employed to provide more freedom to identify the bending curvature with and without external disturbances. In a perturbed environment, the trained optical classification model is suitable for the speckle dataset recognition with high accuracy rate of 98.3%. Moreover, the deep-learning-enabled fiber curvature sensor shows great potential for practical applications in real-time structural safety test, including studies on health monitoring of infrastructure equipment and aerospace wings.

Kinetic simulation is a powerful tool to study the excitation and propagation of whistler-mode waves in the Earth’s inner magnetosphere. This method typically applies a scaled-down dipole magnetic field to save computational time. However, it remains unknown whether whistler wave propagation in the scaled-down dipole field is consistent with that in the realistic dipole field. In this work, we develop a ray-tracing code with a scalable dipole magnetic field to address this concern. The simulation results show that parallel whistler waves at different frequencies gradually become oblique after leaving the equator and propagate in different raypaths in a dipole magnetic field. During their propagation, the higher frequency waves tend to have larger wave normal angles at the same latitude. Compared with the wave propagation in a realistic dipole field, the wave raypath and wave normal remain the same, whereas the wave amplification or attenuation is smaller because of the shorter propagation time in a scaled-down dipole field. Our study provides significant guidance for kinetic simulations of whistler-mode waves.

Shock drift acceleration (SDA) plays an important role in generating high-energy electrons at quasi-perpendicular shocks, but its efficiency in low-beta plasmas is questionable. In this article, we perform a two-dimensional particle-in-cell simulation of a low-Mach-number, low-plasma-beta quasi-perpendicular shock, and find that the electron cyclotron drift instability is unstable at the leading edge of the shock foot, which is excited by the relative drift between the shock-reflected ions and the incident electrons. The electrostatic waves triggered by the electron cyclotron drift instability can scatter and heat the incident electrons, which facilitates their escape from the shock’s loss cone. These electrons are then reflected by the shock and energized by SDA. In this way, the acceleration efficiency of SDA at low-plasma-beta quasi-perpendicular shocks is highly enhanced.

Magnetic holes, characterized as magnetic field depressions, have been widely observed in space plasma. Two large-scale magnetic holes, MH1 and MH2, were reported in this paper and the energetic electrons up to 100 keV were detected for the first time inside both holes. The two holes showed many similar features, comparable spatial scale, temperature and total pressure increase, and energetic electrons up to 100 keV with a power-law distribution inside them. On the other hand, distinct features were also found between these two holes. A potential ion flow vortex was detected inside the MH1 and an ion-scale magnetic structure was observed in its core region. The electron flux enhancements were associated with this ion-scale structure and the energetic electrons were nonadiabatic around the ion-scale structure inside MH1, while the energetic electrons were adiabatic inside the MH2. The mirror-mode instability was unstable around MH1 while stable around MH2, which suggested that the two holes might be in a different phase of the mirror-mode instability. The observations suggested that the electrons could be significantly accelerated inside magnetic holes in the different phases.

Magnetospheric relativistic electrons are accelerated during substorms and strong convection events that occur during high-intensity long-duration continuous auroral electrojet activity (HILDCAA) events, associated with solar wind high-speed streams (coming from coronal holes). From an analysis of ∼2–20 MeV electrons at L ∼ 2–7 measured by the Van Allen Probe satellite, it is shown that ∼3.4–4.1 days long HILDCAA events are characterized by ∼7.2 MeV electron acceleration in the L ∼ 4.0–6.0 region, which occurs ∼2.9–3.4 days after the onset of HILDCAA. The dominant acceleration process is due to wave–particle interactions between magnetospheric electromagnetic chorus waves and substorm-injected ∼100 keV electrons. The longer the HILDCAA and chorus last, the higher the maximum energy of the accelerated relativistic electrons. The acceleration to higher and higher energies is due to a bootstrap mechanism.

With the help of a two-dimensional particle-in-cell simulation model, we investigate the long-time evolution (near $100{{\rm{\Omega }}}_{i0}^{-1}$ , where Ω _i _0 is the ion gyrofrequency in the upstream) of a quasi-parallel shock. Some of the upstream ions are reflected by the shock front, and their interactions with the incident ions excite low-frequency magnetosonic waves in the upstream. Detailed analyses have shown that the dominant wave mode is caused by the resonant ion–ion beam instability, and the wavelength can reach tens of ion inertial lengths. Although these plasma waves are directed toward the upstream in the upstream plasma frame, they are brought by the incident plasma flow toward the shock front, and their amplitude is enhanced during the approaching. The interaction of the upstream plasma waves with the shock leads to the cyclic reformation of the shock front, and the reformation period is slightly larger than 10 ${{\rm{\Omega }}}_{i0}^{-1}$ . When crossing the shock front, these large-amplitude plasma waves are compressed and evolve into current sheets in the transition region of the shock. At last, magnetic reconnection occurs in these current sheets, accompanying the generation of magnetic islands. Simultaneously, there still exist plasma waves of another kind, with the wavelength of several ion inertial lengths in the ramp of the shock, which are excited by the nonresonant ion–ion beam instability. The current sheets in the transition region are distorted and broken into several segments when the plasma waves of this kind are transmitted into the downstream, where magnetic reconnection and the generated islands have a much smaller size. No obvious ion flow can be observed around some X-lines produced in the magnetic reconnection, and this implies that electron-only reconnection may occur.

Abstract The frequency chirping of chorus waves is commonly observed in the Earth’s inner magnetosphere, but its generation remains an open question. Recently, Liu et al. (2021), https://doi.org/10.1029/2021JA029258 reported two unusual rising‐tone (upward chirping) chorus elements. Although the central frequency of constituent subpackets rises, the frequency of a single subpacket is surprisingly downward chirping. With a gcPIC‐δf simulation in the dipole field, we successfully reproduce this kind of substructure, which contains alternating signs of chirping. Interestingly, both hole and hill structures are formed around the theoretical resonant velocities in the electron phase space, no matter whether the chirping is upward or downward. However, during each chirping interval, only one structure (either a hole or a hill) is associated with wave excitation: the upward chirping is related to the hole, while the hill contributes to the downward chirping. Our study provides a fresh perspective on the theory of frequency chirping in chorus waves.

Abstract The power gap of chorus waves at ∼0.5fce has been discovered for decades, but its generation mechanism is still under debate. Previous studies have revealed that electron plateau distributions are vitally important for the gap formation. By analyzing over one‐year Van Allen Probes data, we have studied chorus waves with (banded events) and without a power gap (no‐gap events), and their correlations with the electron plateau distribution. Although there is no significant difference in the morphology of velocity distributions in banded and no‐gap events, banded chorus events are typically accompanied by a plateau component with about one order higher number density than no‐gap events. The plateau components can cause severe damping at ∼0.5fce through cyclotron resonance rather than Landau resonance, and the gap frequency is roughly determined by the bulk velocity of plateau components. Our study provides new observational constraints on the generation mechanisms of power gap.

IntroductionAccording to the principle, thymomas combined with myasthenia gravis (MG) require surgical treatment. However, patients with non-MG thymoma rarely develop MG and early- or late-onset MG after surgery is called postoperative MG (PMG). Our study used a meta-analysis to examine the incidence of PMG and risk factors.MethodsRelevant studies were searched for in the PubMed, EMBASE, Web of Science, CNKI,and Wanfang databases. Investigations that directly or indirectly analyzed the risk factors for PMG development in patients with non-MG thymoma were included in this study. Furthermore, risk ratios (RR) with 95% confidence intervals (CI) were pooled using meta-analysis, and fixed-effects or random-effects models were used depending on the heterogeneity of the included studies.ResultsThirteen cohorts containing 2,448 patients that met the inclusion criteria were included. Metaanalysis revealed that the incidence of PMG in preoperative patients with non-MG thymoma was 8%. Preoperative seropositive acetylcholine receptor antibody (AChR-Ab) (RR = 5.53, 95% CI 2.36 – 12.96, P

As breast cancer is a multistage progression disease resulting from a genetic sequence of mutations, understanding the genes whose expression values increase or decrease monotonically across pathologic stages can provide insightful clues about how breast cancer initiates and advances. Utilizing variational autoencoder (VAE) networks in conjunction with traditional statistical testing, we successfully ascertain long non-coding RNAs (lncRNAs) that exhibit monotonically differential expression values in breast cancer. Subsequently, we validate that the identified lncRNAs really present monotonically changed patterns. The proposed procedure identified 248 monotonically decreasing expressed and 115 increasing expressed lncRNAs. They correspond to a total of 65 and 33 genes respectively, which possess unique known gene symbols. Some of them are associated with breast cancer, as suggested by previous studies. Furthermore, enriched pathways by the target mRNAs of these identified lncRNAs include the Wnt signaling pathway, human papillomavirus (HPV) infection, and Rap 1 signaling pathway, which have been shown to play crucial roles in the initiation and development of breast cancer. Additionally, we trained a VAE model using the entire dataset. To assess the effectiveness of the identified lncRNAs, a microarray dataset was employed as the test set. The results obtained from this evaluation were deemed satisfactory. In conclusion, further experimental validation of these lncRNAs with a large-sized study is warranted, and the proposed procedure is highly recommended.

Using the test particle simulation method, we investigate the stochastic motion of electrons with energy of 300 keV in a monochromatic magnetosonic (MS) wave field. This study is motivated by the violation of the quasi-linear theory assumption, when strong MS waves (amplitude up to ~1 nT) are present in the Earth’s magnetosphere. First, electron motion can become stochastic when the wave amplitude exceeds a certain threshold. If an electron initially resonates with the MS wave via bounce resonance, as the bounce resonance order increases, the amplitude threshold of electron stochastic motion increases until it reaches the peak at about the 11th order in our study, then the amplitude threshold slowly declines. Further, we find that the coexistence of bounce and Landau resonances between electrons and MS waves will significantly reduce the amplitude threshold. In some cases, the electron motion can become stochastic in the field of an MS wave with amplitudes below 1 nT. Regardless, if neither the bounce nor Landau resonance condition is satisfied initially, then the amplitude threshold of stochastic motion shows an increasing trend for lower frequencies and a decreasing trend for higher frequencies, even though the amplitude threshold is always very large (> 5 nT). Our study suggests that electron stochastic motion should also be considered when modeling electron dynamics regulated by intense MS waves in the Earth’s magnetosphere.

Esophageal cancer (EC) is a common tumor of the gastrointestinal system and a major threat to human health. The etiology and incidence of EC vary depending on the type of pathology. Owing to the unique physiological structure of the esophagus and the poor biological behavior of EC, the treatment modalities available are limited, and the prognosis of patients is relatively poor. Curcumin is a type of natural phytochemical belonging to the class of phenolic compounds. It exerts favorable anticancer effects on various cancers. A growing body of evidence indicates that curcumin suppresses tumor development and progression by inhibiting tumor cell proliferation, invasion, and migration, thus inducing apoptosis, regulating microRNA expression, reversing multidrug resistance, and inducing sensitivity to the therapeutic effect of chemoradiotherapy. Multiple cellular molecules, growth factors, and genes encoding proteins participating in different signaling pathways interact with each other to contribute to the complex and orderly anticancer effect. The efficacy and safety of curcumin have been established in preclinical studies for EC and clinical trials for other cancers. However, the low bioavailability of curcumin limits its clinical application. Therefore, the modification of curcumin analogs, the combination of curcumin with other drugs or therapies, and the use of novel nanocarriers have been widely investigated to improve the clinical effects of curcumin in EC.

Abstract Electron cyclotron harmonic (ECH) waves are one of the most common plasma waves in the Earth's magnetosphere, and they are considered to be excited by the electron loss‐cone distributions near the magnetic equator. Using the Magnetospheric Multiscale data, we report an unusual event of ECH waves at L = ∼12.4 and MLT = ∼16.0 hr, where the ECH waves are locally excited inside non‐propagating magnetic oscillations, that is, mirror mode structures. The observation reveals that the mirror mode structures are generated by anisotropic ions (Ti⊥/Ti∥ ∼ 1.3 – 1.7), and electron mirror loss‐cone distributions are formed due to the magnetic configuration of the mirror mode structures. Combing with the linear instability analysis, we confirm that the ECH waves are locally excited by the electron mirror loss‐cone distributions inside the mirror mode structures. Therefore, we propose that the mirror mode structures provide another potential source region for ECH waves in the Earth's magnetosphere.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with many important functions in normal and transformed cells. STAT3 regulatory activities are highly complex as they are involved in various signaling pathways in different cell types under different conditions. Biologically, STAT3 is a regulative factor for normal and cancer stem cells (CSCs). Tumor protein p63 (p63), a member of the p53 protein family, is involved in these biological processes and is also physically and functionally associated with STAT3. STAT3 activation occurs during various aspects of carcinogenesis, including regulation of CSCs properties. In combination with p63, STAT3 is a possible biological marker of CSCs and a major regulator of maintenance of stemness in CSCs. We summarized the STAT3 functions and regulation and its role in CSC properties and highlight how these are affected by its associations with p63.

From the Ulysses observation of the solar wind between the heliocentric distance r _h of ∼1.0 and ∼5.4 au during 1990–2009, we identified 53 intervals when the solar wind exhibited extreme rarefaction, ∼2 orders of magnitude decreases in the solar wind proton density N _p from their ambient values. These extremely low-density solar wind (ELDSW) events, characterized by an average (median) N _p of ∼0.28 ± 0.09 (∼0.30) cm ^−3 , ram pressure of ∼0.07 ± 0.04 (∼0.07 nPa) and mass flux of ∼166 ± 84 (∼159) 10 ^−22 kg cm ^−2 s ^−1 all normalized to 1 au, have an average (median) duration of ∼6.0 ± 3.5 days (∼5.5 days), and radial extent of ∼1.9 ± 1.1 au (∼1.9 au). A clear hemispheric asymmetry is noted in their solar/interplanetary origin, with 70% being identified in the south hemisphere, and 30% in the north hemisphere of the heliosphere. About 23% of the events were encountered between r _h of 2.25 and 4 au, and 77% at r _h > 4 au, indicating that these are not intrinsic properties of the Sun/solar corona but are created by the evolution of the solar wind with increasing radial distance from the Sun. The majority (49%) of the events occurred during magnetic clouds, 34% in solar wind high-speed stream (HSS) tails, 11% during the proper HSSs, and 6% during interplanetary sheaths. The identification of ELDSWs will have important consequences for their interaction with the magnetospheres of Jupiter and Saturn.

Turbulent magnetic reconnection has been observed by spacecraft to occur commonly in terrestrial magnetosphere and the solar wind, providing a new scenario of kinetic scale magnetic reconnection. Here by imposing a turbulent forcing on ions in particle-in-cell simulations, we simulate kinetic scale turbulent magnetic reconnection. We find formation of fluctuated electric and magnetic fields and filamentary currents in the diffusion region. Reconnection rate does not change much compared to that in laminar Hall reconnection. At the X-line, the electric and magnetic fields both exhibit a double power-law spectrum with a spectral break near local lower-hybrid frequency. The energy conversion rate is high in turbulent reconnection, leading to significant electron acceleration at the X-line. The accelerated electrons form a power-law spectrum in the high energy range, with a power-law index of about 3.7, much harder than one can obtain in laminar reconnection.

Perioperative myocardial injury is a common complication caused by major surgery. Many pharmacological and nonpharmacological studies have investigated perioperative cardioprotection. However, the methods are insufficient to meet the increasing clinical needs for cardioprotection. The application of Mesenchymal Stem Cell-Derived Exosomes (MSC-Exos) is a novel cell-free therapeutic strategy and has significantly benefitted patients suffering from various diseases. In this review, we comprehensively analyzed the application of MSC-Exos to prevent myocardial infarction/injury by regulating inflammatory reactions, inhibiting cardiomyocyte apoptosis and autophagy, promoting angiogenesis, and mediating cardiac remodeling. Finally, we assessed the therapeutic effects and the challenges associated with the application of MSC-Exos from a clinical perspective.

Background Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD. Methods RNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database. Results Five differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched. Conclusion A novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.

In this paper, we analyze one reconnection event observed by the Magnetospheric Multiscale (MMS) mission at the earth’s magnetopause. In this event, the spacecraft crossed the reconnection current sheet from the magnetospheric side to the magnetosheath side, and whistler waves were observed on both the magnetospheric and magnetosheath sides. On the magnetospheric side, the whistler waves propagated quasi-parallel to the magnetic field and toward the X-line, while on the magnetosheath side they propagated almost anti-parallel to the magnetic field and away from the X-line. Associated with the enhancement of the whistler waves, we find that the fluxes of energetic electrons are concentrated around the pitch angle 90° when their energies are higher than the minimum energy that is necessary for the resonant interactions between the energetic electrons and whistler waves. This observation provides in situ observational evidence of resonant interactions between energetic electrons and whistler waves in the magnetic reconnection.

The characteristics of whistler-mode waves excited by temperature anisotropic electrons, whose velocity distribution is a combination of bi-Maxwellian distribution and beam-like shapes, are investigated by both linear theory analysis and particle-in-cell simulation. A frequency gap is formed between two peaks, which is caused by the mode splitting of beam-like electrons. We have further investigated the influences of different parameters and found that the position of beam-like shape is the key parameter in determining the frequency of power gap. Moreover, the beam-like component on one direction will lead to the gap in the spectra of waves propagating in the opposite direction. Our study can shed light on the effects of beam-like electrons on the spectra of whistler-mode waves.

Whistler-mode waves play a crucial role in controlling electron dynamics in the Earth’s Van Allen radiation belt, which is increasingly important for spacecraft safety. Using THEMIS waveform data, Gao et al. [X. L. Gao, Q. Lu, J. Bortnik, W. Li, L. Chen, and S. Wang, Geophys. Res. Lett., 43, 2343-2350, 2016] have reported two multiband chorus events, wherein upper-band chorus appears at harmonics of lower-band chorus. They proposed that upper-band harmonic waves are excited through the nonlinear coupling between the electromagnetic and electrostatic components of lower-band chorus, a second-order effect called “lower band cascade”. However, the theoretical explanation of lower band cascade was not thoroughly explained in the earlier work. In this paper, based on a cold plasma assumption, we have obtained the explicit nonlinear driven force of lower band cascade through a full nonlinear theoretical analysis, which includes both the ponderomotive force and coupling between electrostatic and electromagnetic components of the pump whistler wave. Moreover, we discover the existence of an efficient energy-transfer (E-t) channel from lower-band to upper-band whistler-mode waves during lower band cascade for the first time, which is also confirmed by PIC simulations. For lower-band whistler-mode waves with a small wave normal angle (WNA), the E-t channel is detected when the driven upper-band wave nearly satisfies the linear dispersion relation of whistler mode. While, for lower-band waves with a large WNA, the E-t channel is found when the lower-band wave is close to its resonant frequency, and the driven upper-band wave becomes quasi-electrostatic. Through this efficient channel, the harmonic upper band of whistler waves is generated through energy cascade from the lower band, and the two-band spectral structure of whistler waves is then formed. Both two types of banded whistler-mode spectrum have also been successfully reproduced by PIC simulations.

An understanding of the development of strong very low frequency chorus elements is important in the study of the rapid MeV electron acceleration observed during radiation belt recovery events. During such events, chorus elements with long-duration (20-40 ms), strong (|Bw| 0.5-2.0 nT) subpackets with smoothly varying frequency and phase capable of producing nonlinear energy gain of 1%-2% for multi-MeV seed electrons. For such strong chorus elements, we examine the consequences of an upstream motion of the chorus wave generation region using Van Allen Probes observations and nonlinear theory. For a given upstream velocity, v[sub s], resonant electron energy (50-350 keV) and pitch angle (105-115 deg) are uniquely determined for each wave frequency. We examine the effect of an upstream v[sub s] on the inhomogeneity factor that controls wave growth. For steadily increasing upstream motion as the chorus element evolves, vs/c ranging over [-0.001, -0.065], nonlinear wave growth takes place at ≥ 50% of the theoretical maximal value during the development of the observed strong subpackets. For the cases examined, resonant electron energies and pitch angles closely match those of the observed injected electron flux enhancements responsible for chorus development and the nonlinear acceleration of MeV radiation belt electrons. [ABSTRACT FROM AUTHOR]