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Nickel (Ni) isotopes have been developed as a potential biosignature and proxy for tracing the occurrence of the Great Oxidation Event. However, the precise measurement of Ni isotopes is still hindered by the costly operation, complicated procedures and/or high procedural blanks of the chemical purification schemes. Here, a novel purification scheme, utilizing only dimethylglyoxime (DMG) and acetone as organic reagents, is proposed to separate Ni from samples through a four-step procedure with five chromatographic columns. Steps I, II and III are designed to effectively eliminate major matrix elements, including 99% Fe, Ca, Ti, and Al, 85% Mn, 55% K, even for samples with [Ca]/[Ni] ≈ 4600 and [Mg]/[Ni] ≈ 1900. Step IV utilizes the formation of Ni(DMG)2 complexes in an aqueous medium containing 0.5 M HCl, 95% acetone and 0.1 M DMG, which can remove residual elements such as 45% K; this step avoids the use of Ni-specific resin, which requires careful pH tuning. Steps III and I can be repeated to obtain high-purity Ni. The Ni yield through these four steps is greater than 92%, with a maximum loss of ∼8% occurring in Step II for low-Ni samples. The total procedural blank is 0.4 to 1.2 ng. When double spiking (61Ni–60Ni) is used to correct for instrument mass bias and purification-related isotope fractionation, small sample sizes (600–800 ng) are sufficient for achieving high-precision Ni isotope determination. Nickel isotopes for standards such as SRM 986 and geological reference materials (GRMs) such as BHVO-2, NOD-P-1, and NOD-A were determined on a Nu Plasma III MC-ICP-MS. The long-term reproducibility is 0.05‰ (2SD, n = 134) for pure solution and 0.06‰ (2SD, n = 18) for GRMs, and the average δ60Ni values are in excellent agreement with previous studies. These results show that our new purification method can be applied to various samples. Using this new method, we measured a set of granite, sediment, diamictite and loess samples and preliminarily constrained the δ60Ni of the upper continental crust to be 0.11 ± 0.14‰ (2SD, n = 17). [ABSTRACT FROM AUTHOR]

Isotope disequilibrium is increasingly recognized during crustal anatexis, which is usually attributed to stoichiometry or peritectic phases of melting reactions. Instead, whether fluid influx can contribute to isotope disequilibrium during fluid-fluxed melting remains poorly constrained. Here we report combined Mg-O-Sr isotopic data for migmatites in the Dabie orogen. Leucosomes show considerably lower δ26Mg (−0.71‰ ∼ −0.23‰) and δ18O (3.7‰ ∼ 7.9‰) but higher 87Sr/86Sr(i) (0.7089–0.7131) than the corresponding melanosomes (−0.29‰ ∼ −0.11‰, 6.9‰ ∼ 10.6‰ and 0.7080–0.7119, respectively). Such isotopic difference between leucosomes and melanosomes cannot result from either fractional crystallization, equilibrium, incongruent to non-modal melting or accumulation. Instead, co-variations of δ18O, δ26Mg and 87Sr/86Sr(i) of leucosomes indicate influx of external fluids and their preferential partition into melts. The external fluids could have low δ18O and δ26Mg but high 87Sr/86Sr(i) and were most likely derived from dehydration of the surrounding eclogites and gneisses with Neoproterozoic protoliths experienced meteoric-hydrothermal exchange. One leucosome is plotted off the major trend by its rather low δ26Mg (∼ −0.71‰), and may have been overprinted by inter-diffusion. Simple diffusion modeling shows that the preservation of Mg-O-Sr isotope disequilibrium in the Dabie migmatites requires a short duration from fluid-fluxed anatexis to re-solidification (i.e., < 103–104 years). This study highlights that a combination of multiple isotopes may be conducive to understand the mechanism of disequilibrium melting. • Mg-O-Sr isotope disequilibrium during crustal anatexis is identified in migmatites. • Isotope disequilibrium is formed by fluid influx instead of stoichiometry control. • Fluids result from dehydration of subducted and deeply seated supracrustal basement. [ABSTRACT FROM AUTHOR]

Near equatorial (fast) magnetosonic waves, characterized by high magnetic compressibility, are whistler‐mode emissions destabilized by proton shell/ring distributions. In the past, substorm proton injections are widely known to intensify magnetosonic waves in the inner magnetosphere. Here we report the unexpected observations by the Van Allen Probes of the magnetosonic wave quenching associated with the substorm proton injections under both high‐ and low‐density conditions. The enhanced proton thermal pressure distorted the background magnetic field configuration and the cold plasma density distribution. The reduced phase velocities locally allowed the weak growth or even damping of magnetosonic waves. Meanwhile, the spatially irregularly varying refractive indices might suppress the cumulative growth of magnetosonic waves. For intense injections, this wave quenching region could extend over 2 hr in magnetic local time and 0.5 Earth radii in radial distance. These results provide a new understanding of the generation and distribution of magnetosonic waves. Plain Language Summary: Magnetosonic waves are the near‐equatorially confined electromagnetic emissions between the proton gyrofrequency and the lower hybrid frequency in the magnetosphere. Theoretical and observational studies have demonstrated the potential of the magnetosonic waves to accelerate the radiation belt electrons. It is therefore important to understand the generation process and the spatiotemporal distribution of the magnetosonic waves. The substorm activities injecting hot protons into the inner magnetosphere are conventionally considered to intensify the magnetosonic waves. By analyzing the wave and particle data of the Van Allen Probes, we find a magnetosonic wave quenching region related to the distortion of the background magnetic field configuration and the cold plasma density distribution closely following the substorm injection front. We propose two possible causes for this phenomenon: (1) local weak growth or even damping of the magnetosonic waves with the reduced phase velocities and (2) suppression of the magnetosonic wave cumulative growth in the disturbed medium. This new finding may help refine the modeling of the magnetosonic waves and then the radiation belt electrons. Key Points: The enhanced thermal pressure of hot protons can distort the geomagnetic field configuration and the cold plasma density distributionThe magnetosonic wave quenching region can emerge closely following the substorm injection front under both high‐ and low‐density conditionsThe magnetosonic wave quenching region can extend over 2 hr in magnetic local time and 0.5 Earth radii in radial distance [ABSTRACT FROM AUTHOR]

Highlights • SPC exhibits excellent effectiveness in treating soils even at 256 days of curing. • SPC treatment significantly reduces the leachable heavy metals and organics. • Acid neutralization capacity and XRD analyses can interpret leaching mechanisms. • Ex-situ treatment well improves spatial homogeneity of contaminated soil. Abstract This study presents a field trial of ex-situ solidification/stabilization of heavy metal contaminated soils using a new hydroxyapatite based binder SPC (superphosphate and calcium oxide). The field performance including electrical conductivity (EC), heavy metal and chemical oxygen demand (COD) leachability, and penetration resistance of stabilized soils up to 256 days after treatment is investigated. Moreover, acid neutralization capacity (ANC), metal speciation, and soil mineralogy analyses are performed to elucidate the heavy metal immobilization mechanisms. The results indicate that the stabilized soils have lower EC values than untreated soils, indicating the lower soluble salt contents in stabilized soils. Ex-situ treatment can significantly reduce acid soluble fraction contents and leachability of lead, zinc and cadmium in soils as a consequence. Decrease in COD leachability is observed during the curing period up to 256 days. Additionally, SPC stabilized soils give superior mechanical properties as indicated by their higher penetration resistance values as compared to the untreated soils. The improvement in ANC and reduction in acid soluble fraction resulting from the formation of phosphate-based precipitates are mainly responsible for the reduced heavy metal leachability of stabilized soils. Additionally, ex-situ SPC treatment is found to be effective in improving soil spatial homogeneity. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia‐treated TNBC cell lines through the use of high‐throughput sequencing technique. Quantitative real‐time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR‐0009 [derived from transfer RNA (tRNA)Gly‐GCC‐1‐1] and tDR‐7336 (derived from tRNA Gly‐GCC‐1–2) were significantly upregulated when the SUM‐1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)‐6, which may be the underlying mechanism of hypoxia‐induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein–protein interaction network for predicted target genes established by the STRING database manifested that tDR‐0009 (tDR‐7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. Triple negative breast cancer (TNBC) is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. We provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets. [ABSTRACT FROM AUTHOR]

Aims: To determine the factors influencing ultrasound breast tumor size assessment accuracy.Material and Methods:  Five factors (tumor type, molecular subtype, histological size, histological grade, and breast density) were used to assess the measurement accuracy of breast ultrasound in tumor size. Size underestimation was defined as ultrasound index lesion diameter < histological size by at least 5 mm.Results: Breast ultrasound underestimated tumor size significantly, especially in cases with intraductal components (p=0.002). There was a tendency for higher size underestimation in breast cancer tumors with high-histological grade (p=0.03), human epidermal growth factor receptor type 2 (HER2)-overexpressing breast cancer tumors (p=0.02) and hormone receptor (HR)-/HER2+ breast cancer tumors (p=0.008). Furthermore, core biopsy revealedhigher probability of size underestimation with intraductal components (p=0.002). Size underestimation was more frequent with larger histological size (p<0.001). Masses in non-dense breasts were significantly underestimated (p=0.036) compared to dense breasts.Conclusions: The size underestimation was influenced by pathological type, molecular subtype, and histological size. The pathological results of core biopsy were conducive for predicting tumor size pre-surgery in precise breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

The primary power gap of chorus waves is statistically investigated using 7‐year waveform data from THEMIS probes for the first time. Overall, ~2/3 of chorus events have a power gap between the lower and upper bands. Both the gap frequency and the frequency bandwidth of the gap have a broad distribution, which peaks at frequencies of ~0.49fce and ~0.07fce, respectively. The gap frequency tends to increase with increasing |MLAT| (magnetic latitude), while the frequency width gradually increases with L‐shell. In most of banded events, the peak frequency of upper band is roughly twice that of lower band. Two types of events are studied. For Type I events, one population is located around Pup/Plow = 10−1, and the other is around Pup/Plow = 10−3. However, Type II events are roughly concentrated around Pup/Plow = 10−3. The gap frequency positively correlates with the frequency of upper band. Our study provides detailed observational constraints on potential mechanisms of the power gap formation. Key Points: We provide the first statistical study to comprehensively describe this mysterious power gap of chorus waves in the Earth's magnetosphereOverall, there are about 2/3 of events identified to have a power gap between two bands, and 1/3 of events are observed without a power gapWe have studied the distribution of both the gap frequency and frequency width of the power gap and their dependencies on two bands [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New PRB materials prepared by calcium peroxide and straw/biochar. • The PRB system removed almost 100% of phenanthrene. • Self-domestication of PAHs degradation microbes in the PRB system. • Phenanthrene was mainly removed by degradation rather than adsorption. Abstract Permeable reactive barriers (PRBs) are an environmentally-friendly, cost-effective in-situ technology that can be used to remediate polycyclic aromatic hydrocarbons (PAHs)-contaminated groundwater. In this study, PRBs of two different materials (A and B) that relied on microbes self-domestication mechanism were designed and tested. The materials A and B were the same apart from their carbon source: A was based on wheat straw and B was based on coconut shell biochar. We used laboratory batch experiments followed by long-term column tests to assess the capacity of these two materials to remediate PAHs. The results showed that both A and B removed almost 100% of the phenanthrene. More carbon was released from A (80–500 mg/L) than from B (72–195 mg/L), and slightly more oxygen was released from B (7.31–10.31 mg/L) than A (7.15–9.64 mg/L). The release of organic carbon from material B was more stable than that from material A. The bacterial communities of both columns comprised members of the Mycobacterium, Pseudomonas, and Sphingomonas genera that are known to degrade phenanthrene, and Pseudomonas and Sphingomonas were 7 times more abundant in column B than in column A. Material B is more promising for treating PAH-contaminated groundwater than material A. [ABSTRACT FROM AUTHOR]

Magnetospheric quasiperiodic whistler‐mode emissions have long been considered a consequence of the relaxation oscillation or the compressional ultralow‐frequency wave modulation. Here we experimentally demonstrate that the whistler‐mode chorus, exohiss, and magnetosonic emissions can be effectively modulated by the toroidal ultralow‐frequency waves. On 04 August 2017, the solar wind dynamic pressure fluctuations excited the fundamental toroidal standing Alfvén waves in the dayside magnetosphere. These regular toroidal pulsations displayed the approximately same periods as the power variations of the whistler‐mode emissions from 50 Hz to 5 kHz. Along with the decay of the toroidal pulsations, the quasiperiodic feature of these whistler‐mode emissions gradually became indistinct. However, no modulation signatures of background parameters and resonant particles for the whistler‐mode emissions were observable near the equator, and the exact cause for this phenomenon remains to be elucidated. Plain Language Summary: Whistler‐mode emissions contribute significantly to the Van Allen radiation belt electron dynamics, and their power can exhibit quasiperiodic variations on a timescale of tens of seconds to several minutes in the dayside magnetosphere. Since the 1960s, the quasiperiodic whistler‐mode emissions have been considered a consequence of the relaxation oscillation or the compressional ultralow‐frequency wave modulation. Using the Van Allen Probes data, we reveal here new physical mechanism for the quasiperiodic whistler‐mode emissions: The solar wind dynamic pressure fluctuations trigger the magnetospheric fundamental toroidal standing Alfvén waves and then modulate the whistler‐mode chorus, exohiss, and magnetosonic emissions from 50 Hz to 5 kHz. Further investigation of this unexpected phenomenon may deepen our understanding of the growth and propagation of whistler‐mode emissions and facilitate the radiation belt model developments. Key Points: The solar wind dynamic pressure fluctuations excited the fundamental toroidal standing Alfvén waves in the dayside magnetosphereThe regular toroidal pulsations simultaneously modulated the whistler‐mode chorus, exohiss, and magnetosonic emissions from 50 Hz to 5 kHzNo modulation signatures of background parameters and resonant particles for these whistler‐mode emissions were observable near the equator [ABSTRACT FROM AUTHOR]

Electrostatic solitary (ES) structures have been frequently observed in the solar wind, Earth's and other planetary magnetosphere and are the most widely theoretically studied waves in literature. However, there are very few studies in which simulations and theoretical studies have been performed simultaneously. In this paper, we perform 1-D electrostatic Particle-in-Cell (PIC) simulations of electrostatic solitary (ES) waves in a plasma which consists of immobile ions, and cold, beam and hot electrons. It is found that for a small value of electron beam velocity, ES structures are formed due to the steepening of initially quasi monochromatic electron acoustic (EA) waves. We interpret these ES structures as electron acoustic solitary (EAS) structures, which agree with the rarefactive (negative electrostatic potential) electron acoustic solitary structures obtained theoretically as a solution of the Korteweg de-Vries (KdV) equation. We found that polarity of solitary structures depends on the drift velocity of electron beam and formation of electric field spikes are consistent with the ES waves observations from Earth's magnetosphere. [ABSTRACT FROM AUTHOR]

Purpose: To determine the characteristics of ultrasound (US) imaging of completely ablated cases and the effects of duration and clinical experience on accurate microwave ablation (MWA) for the treatment of benign breast tumours. Methods: With written informed consent and approval of the institutional ethics committee, patients with symptomatic or palpable benign breast tumours (longest diameter, 7-32 mm), to whom MWA (2450 MHz) was performed, were enrolled in this prospective nonrandomised study. US and contrast-enhanced US (CEUS) images were applied for follow-up and analysed. Results: Forty-seven consecutive patients with 52 completely ablated tumours were enrolled. Of these 52 tumour ablations in US, 16 ablations were defined as concentric type, and 36 were defined as nonconcentric type. Of these 52 ablations, 7 cases were defined as nonaccurate ablation with the largest margin ≥10 mm in US. The nonaccurate ablation rate in the training group (the first consecutive 30 cases, 7/30) was significant higher than that (the last 22 cases, 0/22) in the practiced group (p = 0.016). Of 38 completely ablated cases (9 mm < the longest diameter <20 mm), the average largest margin in >70 s group was significant larger than that in <70 s group (p = 0.019). Conclusions: Experience was important for accurate MWA in the treatment of benign breast tumour, and at least 30 cases training was recommended. Nevertheless, clinical trials are still required to validate our findings in the future. [ABSTRACT FROM AUTHOR]

Background: The wide adoption of electronic health record systems (EHRs) in hospitals in China has made large amounts of data available for clinical research including breast cancer. Unfortunately, much of detailed clinical information is embedded in clinical narratives e.g., breast radiology reports. The American College of Radiology (ACR) has developed a Breast Imaging Reporting and Data System (BI-RADS) to standardize the clinical findings from breast radiology reports.Objectives: This study aims to develop natural language processing (NLP) methods to extract BI-RADS findings from breast ultrasound reports in Chinese, thus to support clinical operation and breast cancer research in China.Methods: We developed and compared three different types of NLP approaches, including a rule-based method, a traditional machine learning-based method using the Conditional Random Fields (CRF) algorithm, and deep learning-based approaches, to extract all BI-RADS finding categories from breast ultrasound reports in Chinese.Results: Using a manually annotated dataset containing 540 reports, our evaluation shows that the deep learning-based method achieved the best F1-score of 0.904, when compared with rule-based and CRF-based approaches (0.848 and 0.881 respectively).Conclusions: This is the first study that applies deep learning technologies to BI-RADS findings extraction in Chinese breast ultrasound reports, demonstrating its potential on enabling international collaborations on breast cancer research. [ABSTRACT FROM AUTHOR]

Abstract: The excitation of magnetosonic waves in the meridian plane of a rescaled dipole magnetic field is investigated, for the first time, using a general curvilinear particle‐in‐cell simulation. Our simulation demonstrates that the magnetosonic waves are excited near the equatorial plane by tenuous ring distribution protons. The waves propagate nearly perpendicularly to the background magnetic field along both radially inward and outward directions. Different speeds of inward and outward propagation result in the asymmetrical distribution about the source region. The waves are accompanied by energization of both cool protons and electrons near the wave source region. The cool protons are heated perpendicularly, while the cool electrons can be heated in the parallel direction and also experience enhanced perpendicular drift at the presence of intense wave power. The implications of simulation results to the observations of magnetosonic waves and related particle heating in the inner magnetosphere are also discussed. [ABSTRACT FROM AUTHOR]

irculating tumor cells (CTCs) dissemination is involved in tumor metastasis and is an independent prognostic factor in patients with primary and metastatic breast cancer. Regulatory T cells (Tregs) and cluster of differentiation (CD)8+ T lymphocytes are the main types of immune cells in the tumor microenvironment and exert opposite roles on the progression and outcome of breast cancer. The aim of the present study was to evaluate the associations between CTCs and intratumoral/peritumoral Tregs and CD8+ T lymphocytes in breast cancer. Peripheral CTCs were detected by a multi‑marker quantitative polymerase chain reaction platform in 167 patients with invasive breast cancer. Intratumoral/peritumoral Tregs and CD8+ T lymphocytes were assessed by immunohistochemistry in 167 patients with invasive breast cancer to establish an association between these cell types and detection of peripheral CTCs. CTCs were detected in 55% of the patients with breast cancer. The prevalence of CTCs was positively associated with the number of intratumoral (P=0.002) and peritumoral Tregs (P=0.045), and the primary tumor size (P=0.012). This result was verified by analyzing intratumoral Tregs (P=0.044) and primary tumor size (P=0.044) with multivariate analysis, which indicated that the CTC‑positive rate increased with an increasing number of intratumoral Tregs and a larger tumor size In the multivariate analysis, other variables including menopause, tumor‑node‑metastasis stage and peritumoral Tregs were not associated with the prevalence of CTCs. The prevalence of CTCs was inversely and weakly associated with the number of peritumoral CD8+ T lymphocytes using the univariate analysis, however this result was not statistically significant (P=0.470). In conclusion, regulatory T cells and CD8+ T lymphocytes may be involved, at least in part, in the CTCs dissemination of breast cancer, whereby Tregs appear to exert the dominant effect. Furthermore, the role of Tregs in the progression of breast cancer may be mediated by suppressing the dissemination of CTCs, which is primarily determined by intratumoral Tregs. [ABSTRACT FROM AUTHOR]

Abstract: Although magnetosonic waves in the Earth's magnetosphere have been well understood by the linear theory, low harmonic magnetosonic waves, which often lack of free energy, can be unusually present. By employing a 1‐D particle‐in‐cell simulation model, we have investigated the generation of those unusual lower harmonic magnetosonic waves in a plasma containing a proton ring distribution. In our simulation, the higher harmonic magnetosonic waves (from ~9Ωh to ~12Ωh) are firstly excited due to the unstable proton ring, which can be well explained by the linear theory. Several lower harmonic magnetosonic waves (below 5Ωh), which well separates away from the higher harmonics, soon appear in the system. Those lower harmonics, which do not have any positive linear growth rates, can be generated by a nonlinear mechanism. The bicoherence analysis demonstrates that there is a strong phase coupling among the unusual lower harmonic magnetosonic waves and the magnetosonic waves generated due to the proton ring, supporting the idea that the lower harmonic waves could be driven by the wave‐wave couplings of the generated magnetosonic waves. This wave‐wave coupling generation mechanism is further confirmed by another two simulations, where two or three pump magnetosonic waves are initially injected. The lower‐frequency waves, that is, the fundamental wave and its second harmonic, are also successfully reproduced due to the nonlinear coupling of pump magnetosonic waves. Our simulations not only propose a potential generation mechanism of unusual lower harmonic magnetosonic waves in the Earth's magnetosphere, but also give some new insights on the evolution of magnetosonic spectra. [ABSTRACT FROM AUTHOR]

Abstract: Magnetosonic waves play a potentially important role in the complex evolution of the radiation belt electrons. These waves typically appear as discrete emission lines along the proton gyrofrequency harmonics, consistent with the prediction of the local Bernstein mode instability of hot proton ring distributions. Magnetosonic waves are nearly dispersionless particularly at low harmonics and therefore have the roughly unchanged frequency time structures during the propagation. On the basis of Van Allen Probes observations, we here present the first report of magnetosonic harmonic falling and rising frequency emissions. They lasted for up to 2 hr and occurred primarily in the dayside plasmatrough following intense substorms. These harmonic emission lines were well spaced by the proton gyrofrequency but exhibited a clear falling (rising) frequency characteristic in a regime with the temporal increase (decrease) of the proton gyrofrequency harmonics. Such unexpected structures might be produced by the nonlinear interactions between the locally generated magnetosonic waves at the proton gyrofrequency harmonics and a constant frequency magnetosonic wave propagating away from the Earth. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. The reference #27 in the reference list is incorrect in that the individual chapter should be cited instead of the whole book. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Chemoresistance has been a major reason for the drug therapy failure. The present study performed a microarray analysis between MCF-7 and MCF-7/adriamycin (ADR) cells, and intended to identify long non-coding (lnc)RNA expression character in drug resistant breast cancer cells. MCF-7/ADR cells were induced from MCF-7 cells via pulse-selection with doxorubicin for 4 weeks, and the resistance to doxorubicin of ADR cells was confirmed by MTT assay. Microarray analysis was performed between MCF-7 and MCF-7/ADR cells. Total RNA was extracted from the two cell lines respectively and was transcribed into cDNA. The results of the microarray were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathways analysis were conducted to enrich the dysregulated lncRNAs presented in the microarray results. Compared to the MCF-7 cells, 8,892 lncRNAs were differentially expressed in MCF/ADR cells (absolute fold-change >2.0). A total of 32 lncRNAs were selected for RT-qPCR by fold-change filtering, standard Student's t-test, and multiple hypothesis testing. Among the dysregulated lncRNAs, AX747207 was prominent because its associated gene RUNX3 was previously reported to be relative to malignant tumor chemoresistance. GO analysis results also indicated some biological processes and molecular functions linked to chemoresistance. The pathway enrichment results provided some potential pathways associated with chemoresistance. In the present study, the authors intended to identify lncRNA expression character in drug resistant cell line MCF-7/ADR, corresponding to the parental MCF-7 cell line. In addition, the study identified the lncRNA AX747207, and its potential targeted gene RUNX3, may be related to chemoresistance in breast cancer. These results may new insights into exploring the mechanisms of chemoresistance in breast cancer. [ABSTRACT FROM AUTHOR]

Depression is a mental illness comorbid risk factor for glucose intolerance worldwide. Chaihu-shugan san, a ‘Shu-Gan’ formula in traditional Chinese medicine, is clinically used in the treatment of depression. The aim of this study was to investigate whether Chaihu-shugan san improved glucose tolerance with its antidepressant activity in rat model of depression and explore the mechanisms underlying its action on liver-brain inflammation axis. After 6 weeks of chronic unpredictable mild stress (CUMS) procedure, male Wistar rats were given Chaihu-shugan san water extract (925 and 1850 mg/kg) by gavage for the next 6 consecutive weeks. Sucrose consumption test was used to assess animal depressive-like behaviors. Oral glucose tolerance test (OGTT) was employed to define the status of glucose tolerance in rats. Serum alanine aminotransferase (ALT) and interleukin-1 beta (IL-1β) were measured by commercial kits, respectively. Western blot was used to detect the expression of key proteins in inflammatory signaling cascades including toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), Nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and IL-1β, as well as insulin signaling in liver and prefrontal cortex of rats. Immunohistochemical staining or immunofluorescence staining of NF-κB, and nuclear/cytoplasmic ratio of NF-κB by Western blot were used to describe its nuclear entry in liver and prefrontal cortex of rats. RT-qPCR and Western blot analysis, as well as microRNA-155 (miR-155) mimic or inhibitor transfection were used to explore possible association of MyD88 and miR-155. In this study, Chaihu-shugan san increased sucrose consumption and reduced serum glucose levels in CUMS rats, showing its antidepressant activity with glucose tolerance improvement. Chaihu-shugan san reduced serum levels of ALT and IL-1β in this animal model. Furthermore, this formula inhibited hepatic and prefrontal cortical inflammatory response by suppressing TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome activation, and improved insulin signaling in CUMS rats. More importantly, Chaihu-shugan san up-regulated miR-155 expression in liver and prefrontal cortex of CUMS rats. These results provide direct evidence that Chaihushugan San can ameliorate depressive-like behaviors by inhibiting liver-brain inflammation axis. [ABSTRACT FROM AUTHOR]

Whistler mode waves in the Earth's magnetosphere have already been widely investigated in the linear or quasi-linear regime, but there is still lack of research on nonlinear physical processes. In this paper, with a 2-D PIC simulation model, we have studied the parametric decay of oblique whistler waves for the first time. The parametric decay of an oblique whistler wave first occurs along its propagating direction, which involves a backward daughter whistler wave and a forward ion acoustic mode. This is quite similar to the parametric decay of parallel whistler waves in 1-D simulations. Interestingly, the parametric decay will then take place along the perpendicular direction, which can generate a family of daughter whistler waves along the perpendicular direction with the nearly same parallel wave number. Meanwhile, the highly oblique whistler waves will also be excited during this perpendicular decay, whose wave normal angle can even reach up to the resonant cone angle. Moreover, the parametric decay tends to be stronger for the pump whistler wave with a larger frequency or larger amplitude. But the growth rate of the parametric decay has little change when the wave normal angle of the pump whistler wave varies within a limited range. Interestingly, parallel whistler waves can also experience the similar decay process, which may suggest that the parametric decay of whistler waves should be a multi-dimensional process in nature. During the decay process, the generated ion acoustic waves can accelerate a part of protons through the Landau resonance. Our simulation results not only uncover the evolution pattern of whistler waves during the parametric decay in a two-dimensional regime but also propose a potential nonlinear physical process related to whistler waves in the Earth's magnetosphere. [ABSTRACT FROM AUTHOR]

In this paper, with a two-dimensional particle-in-cell simulation model, we study the formation of power-law spectra of energetic electrons in multiple X line magnetic reconnection with a strong guide field. The processes of both magnetic reconnection and electron acceleration can be separated into two stages. In the first stage, two X lines appear at the border and center of the simulation domain, and then, two magnetic islands are formed. In this stage, electrons are accelerated mainly by parallel electric fields, and a power-law spectrum of energetic electrons is generated with the appearance of the second X line. In the second stage, the two magnetic islands are merged into one big island. Besides parallel electric fields, the Fermi mechanism also plays an important role in the production of energetic electrons, and its contribution is comparable to that of parallel electric fields when the electron energy is sufficiently large. In this stage, the generated power-law spectrum of energetic electrons becomes hard. In general, the acceleration efficiencies by both the parallel electric fields and Fermi mechanism become higher with the increase in electron energy, and the tendency is more obvious for the Fermi mechanism. Therefore, both the parallel electric fields and Fermi mechanism are important in the formation of power-law spectra of energetic electrons during multiple X line reconnection. We also investigate the influences of the ion-electron temperature ratio, guide field, and initial flux perturbation on the formed power-law spectra of energetic electrons. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of cancer‑associated mortality, and metastatic breast cancer is responsible for 90% of patient mortalities. Given that JWA represses the proliferation, invasion and metastasis of a number of other human tumor cells, including melanoma, esophageal, hepatocellular and gastric carcinomas, via mitogen‑activated protein kinase or integrin signaling, the present study investigated the expression and function of JWA in human breast cancers. The results showed that the expression level of JWA was significantly reduced in human primary breast cancers when compared with the paired adjacent tissues. Downregulating JWA enhanced, while overexpressing JWA suppressed, the migration and invasion abilities of the two breast cancer cell lines, MDA‑MB‑468 and MDA‑MB‑231, without affecting their proliferations in vitro. In addition, JWA negatively regulated the surface expression of CXCR4 in the two cell lines via proteasome degradation, though not via transcriptional inhibition. Functionally, normalizing the disturbed expressions of CXCR4 largely reversed the inhibitory effect of JWA on cell invasion. These data demonstrated that JWA suppressed the migration/invasion of breast carcinoma cells by downregulating the expression of CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in patients with breast cancer. [ABSTRACT FROM AUTHOR]

In this paper, by taking advantage of a two-dimensional particle-in-cell simulation model, we study the structure of the out-of-plane magnetic field (Hall magnetic field) during asymmetric magnetic reconnection without a guide field, and the associated in-plane current system is also analyzed. The evolution of asymmetric reconnection has two stages. At the first stage, the electrons move toward the X line along the separatrix in the magnetosheath side, and depart from the X line along the separatrix in the magnetosphere side. Another electron flow toward the X line exists above the separatrix in the magnetosphere side. The resulted in-plane current system, which is mainly determined by electron dynamics, generates the quadrupolar structure of the Hall magnetic field, where the two quadrants in the magnetosheath side are much stronger than those in the magnetosphere side. At the second stage, besides these electron flows, an additional electron flow away from the X line is formed along the magnetic field below the separatrix in the magnetosheath side. A hexapolar structure of the Hall magnetic field is then generated by such a current system. [ABSTRACT FROM AUTHOR]

Abstract: Observations of a current sheet as thin as the electron scale are extremely rare in the near‐Earth magnetotail. By measurement from the novel Magnetospheric Multiscale mission in the near‐Earth magnetotail, we identified such an electron‐scale current sheet and determined its detailed properties. The electron current sheet was bifurcated, with a half‐thickness of nine electron inertial lengths, and was sandwiched between the Hall field. Because of the strong Hall electric field, the super‐Alfvénic electron bulk flows were created mainly by the electric field drift, leading to the generation of the strong electron current. Inevitably, a bifurcated current sheet was formed since the Hall electric field was close to zero at the center of the current sheet. Inside the electron current sheet, the electrons were significantly heated while the ion temperature showed no change. The ions kept moving at a low speed, which was not affected by this electron current sheet. The energy dissipation was negligible inside the current sheet. The observations indicate that a thin current sheet, even as thin as electron scale, is not the sufficient condition for triggering bursty reconnection. [ABSTRACT FROM AUTHOR]

The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo , oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo . [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NCT) is the standard treatment for locally advanced breast cancer (LABC). Pathological complete response (pCR) is commonly used as a valid predictor of NCT long-term outcomes. Blood-based tumor biomarkers have the potential to predict response to NCT at early stage non-invasively. We believed plasma CCL5 could be a potential marker to predict NCT of LABC. Its efficiency and possible mechanism was studied in this work. Human Cytokine Antibody Microarray was applied to screen different cytokine concentration in plasma between low histological regression (Low-R) and high histological regression (High-R) patients. LABC patients were divided into two groups according to pathological reactivity. The concentration of plasma CCL5 in different groups was determined by ELISA analysis. CCK8 assay was performed to analyze epirubicin susceptibility of breast cancer cells. Transwell assay was performed to determine the effect of CCL5 on breast cancer cells’ migration and invasion. qRT-PCR and western blot were used to verify the EMT (epithelial-mesenchymal transition) markers in CCL5-treated and epirubicin-treated breast cancer cells. The concentration of plasma CCL5 of Low-R group was higher than High-R group before NCT. The plasma levels of CCL5 were significantly reduced after NCT in the group of high histological regression (High-R). Epirubicin susceptibility decreased in the breast cancer cells treated by recombinant CCL5. Migration and invasion were significantly enhanced in breast cancer cells treated by recombinant CCL5. E-cadherin expression was decreased whereas vimentin increased significantly in CCL5-treated breast cancer cells. The phosphorylation of ezrin in Y-567 and its downstream protein cortactin increased significantly in CCL5-treated breast cancer cells. Plasma CCL5 level could be a promised candidate to predict chemotherapy response of breast cancer. Plasma CCL5 plays an important role in EMT process of breast cancer. [ABSTRACT FROM AUTHOR]

The spatial distribution and source-region size of chorus waves are important parameters for understanding their generation. In this work, we analyze over 3 years of continuous wave burst-mode data from the Van Allen Probes mission and build a data set of rising-tone and falling-tone chorus waves. For the L shell range covered by Van Allen Probes data (3:5 ≥ L ≥ 7), statistical results demonstrate that the sector where rising tones are most likely to be observed is the dayside during geomagnetically quiet and moderate times and the dawn side during active times. Moreover, rising-tone chorus waves have a higher occurrence rate near the equatorial plane, while the falling-tone chorus waves have a higher possibility to be observed at lower L shell and higher magnetic latitudes. By analyzing the direction of the Poynting wave vector, we statistically investigate the chorus sourceregion size along a field line, and compare the results with previous theoretical estimates. Our analysis confirms previous conclusions that both rising-tone and falling-tone chorus waves are generated near the equatorial plane, and shows that previous theoretical estimates roughly agree with the observation within a factor of 2. Our results provide important insights into further understanding of chorus generation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Magnetosonic waves are highly oblique whistler mode emissions transferring energy from the ring current protons to the radiation belt electrons in the inner magnetosphere. Here we present the first report of prompt disappearance and emergence of magnetosonic waves induced by the solar wind dynamic pressure variations. The solar wind dynamic pressure reduction caused the magnetosphere expansion, adiabatically decelerated the ring current protons for the Bernstein mode instability, and produced the prompt disappearance of magnetosonic waves. On the contrary, because of the adiabatic acceleration of the ring current protons by the solar wind dynamic pressure enhancement, magnetosonic waves emerged suddenly. In the absence of impulsive injections of hot protons, magnetosonic waves were observable even only during the time period with the enhanced solar wind dynamic pressure. Our results demonstrate that the solar wind dynamic pressure is an essential parameter for modeling of magnetosonic waves and their effect on the radiation belt electrons. [ABSTRACT FROM AUTHOR]

Abstract: Whistler‐mode extremely low frequency hiss emissions commonly exist in the plasmasphere and the plasmaspheric plume and contribute to the precipitation loss of the radiation belt electrons. How these hiss waves are generated remains a critical unanswered question. Here we report the large‐amplitude (up to 1.5 nT) hiss waves in the plasmaspheric plumes, nearly an order of magnitude stronger than previous observations. These waves are found to propagate toward higher latitudes, and the corresponding frequency dependence of wave power can be qualitatively (but not quantitatively) explained by the modeled linear instability of hot electrons near the equator. At the high‐frequency end of hiss spectra, the discrete rising tones are shown to emerge, similar to the situation of whistler‐mode chorus in the plasmatrough. These data and modeling suggest that these large‐amplitude hiss waves were generated within the plasmaspheric plume probably through a combination of linear and nonlinear instabilities of hot electrons. [ABSTRACT FROM AUTHOR]

The hydrothermal epitaxy of ZnO films on a patterned GaN layer with a honeycomb etching hole array is demonstrated. Through m -planes of the GaN layer exposed on the vertical walls of the etching holes, highly crystalline ZnO films via multiple lateral growth stages can be realized. It is found that higher concentrations of zinc nitrate hexahydrate (ZNH) and hexamethylenetetramine (HMT) in hydrothermal solution yield a larger number of ZnO molecules to speed up ZnO growth during the initial stage of hydrothermal growth, also create secondary crystals and initialize further lateral growth stages to bridge neighboring ZnO prisms after smooth surfaces formed on the m -plane of a ZnO prism. A successive lateral growth mechanism that strongly depends on ZNH and HMT concentrations in the hydrothermal solution is proposed and discussed. [ABSTRACT FROM AUTHOR]

This work is aimed to develop the key algorithms used in medical robots, which can detect alcohol use disorder from structural magnetic resonance imaging of brains. We enrolled 30 alcoholic participants and 30 nonalcoholic participants. In the algorithm stage, we suggested to use Hu moment invariant to extract global features, and use single-hidden layer neural-network as the classifier. Afterwards, we proposed a novel predator–prey adaptive-inertia chaotic particle swarm optimization algorithm to train the classifier. The ten-fold stratified cross validation showed that our method achieves a sensitivity of 90.67 ± 3.16%, a specificity of 91.33 ± 3.06%, and an accuracy of 91.00 ± 1.41%. Our results are better than genetic algorithm, firefly algorithm, and particle swarm optimization. This proposes algorithm is effective in alcoholism detection. It can be installed on medical robots. [ABSTRACT FROM AUTHOR]

Magnetosonic whistler mode waves play an important role in the radiation belt electron dynamics. Previous theory has suggested that these waves are excited by the ring distributions of hot protons and can propagate radially and azimuthally over a broad spatial range. However, because of the challenging requirements on satellite locations and data processing techniques, this theory was difficult to validate directly. Here we present some experimental tests of the theory on the basis of Van Allen Probes observations of magnetosonic waves following substorm injections. At higher L shells with significant substorm injections, the discrete magnetosonic emission lines started approximately at the proton gyrofrequency harmonics, qualitatively consistent with the prediction of linear proton Bernstein mode instability. In the frequency-time spectrograms, these emission lines exhibited a clear rising tone characteristic with a long duration of 15-25 min, implying the additional contribution of other undiscovered mechanisms. Nearly at the same time, the magnetosonic waves arose at lower L shells without substorm injections. The wave signals at two different locations, separated by Δ L up to 2.0 and by ΔMLT up to 4.2, displayed the consistent frequency-time structures, strongly supporting the hypothesis about the radial and azimuthal propagation of magnetosonic waves. [ABSTRACT FROM AUTHOR]

Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels. Furthermore, magnesium isoglycyrrhizinate modulated lipid metabolism-related genes characterized by up-regulating peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1), and down-regulating sensor for fatty acids to control-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of fructose-fed rats, resulting in the reduction of triglyceride and total cholesterol levels. These effective actions were further confirmed in fructose-exposed BRL-3A and HepG2 cells. The molecular mechanisms underpinning these observations suggest that magnesium isoglycyrrhizinate may inhibit NF-κB/NLRP3 inflammasome activation to reduce immunological-inflammatory response, which in turn may prevent liver lipid metabolic disorder and accumulation under high fructose condition. Thus, blockade of NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury with metabolic syndrome in clinic. [ABSTRACT FROM AUTHOR]

Purpose:Non-surgical treatments for benign breast tumours have clinical goals of stopping growth and/or reducing (removing) palpable tumours effect without leaving a surgical scar. The purpose of this non-randomised prospective clinical trial was to assess imaging and clinical outcomes of microwave ablation (MWA) in the treatment of benign breast tumours regardless of the distance from the tumour to the skin and chest wall. Methods:With approval of the institutional ethics committee and written informed consent, 39 patients with 44 core-biopsy-proved benign breast tumours 3.0 cm or less in diameter assessed by using ultrasound (US) and contrast-enhanced ultrasound (CEUS) were prospectively recruited. US-guided MWA was performed under local anaesthesia. The patients were followed up with physical examination, ultrasound elastography and CEUS. Results:The MWA procedure with a mean duration of 74.3 s ± 26.5 was well accepted and tolerated in 41 cases except for three cases. Of 41 tumours with follow-up data, 40 (97.5%; 95% confidence interval: 87.1%, 99.9%) showed complete ablation assessed by using CEUS. The mean volume of the ablated tumours decreased significantly (p = .005) during follow-up. The strain ratio 1-3 months after ablation was higher than that before ablation, and became low 6 months after ablation (p = .022). No epidermal burn was observed in all cases with a mean distance of 7.5 mm ±3.3 from the tumour to the skin. Conclusions:MWA is a safe and effective minimally invasive “patient-friendly” procedure with a very short duration for the treatment of benign breast tumours. [ABSTRACT FROM AUTHOR]

Diseases cause a significant loss in both yield and quality of spinach. The cell cycle signalling pathway plays a central role in balancing development and immunity of plants. Cyclin-Dependent Kinase Inhibitor (CKI) is a core cell cycle regulator. It has been found that two Arabidopsis CKIs, SIAMESE (SIM) and SMR1 (SIAMESE-Related 1), function redundantly not only as negative regulators of cell proliferation but also as positive regulators of plant immunity. In the spinach genome, we identified a homologue of Arabidopsis SIM, referred to asSpinacia oleraceaSIAMESE (SoSIM). To investigate the function of SoSIM, we introduced the35Spromoter-drivenSoSIM(35S:SoSIM) into Arabidopsissim smr1double mutants. Over-expression ofSoSIMphenocopied RNA interference ofCyclin-Dependent Kinase A1(CDKA1) which exhibited dwarf and serrated leaves, confirming that SIM is a CDK inhibitor. Arabidopsis wild-type trichomes are single and unicellular, whereassim smr1mutant trichomes are clustered and multicellular. SoSIM restored wild-type trichome phenotype ofsim smr1mutant. Thesim smr1mutants were susceptible to the avirulent pathogenPseudomonas syringaepv.maculicolaas compared with wild-type plants. Our data showed that the resistance of35S:SoSIM-transgenicsim smr1lines to the pathogen was fully restored, indicating that SoSIM activates plant immunity. These data verify that SoSIM functions as its Arabidopsis counterpart in inhibition of plant development and activation of plant immunity. Therefore, SoSIM can be explored to control the balance between development and immunity in spinach. [ABSTRACT FROM PUBLISHER]

Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.Methods: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.Results: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.Conclusions: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity. [ABSTRACT FROM AUTHOR]

Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models. In human luminal tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was positively correlated with CD31-positive microvascular density, induced angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial cell tube formation in vitro. VASH2 expression was absent in the concentrated conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing luminal breast cancer cells. Further, VASH2 regulated the expression of fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2 neutralization in vitro. Additionally, dual luciferase reporter assay and Chromatin immunoprecipitation analysis results showed that FGF2 promoter was transcriptionally activated by VASH2 via histone modifications. In conclusion, VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms. [ABSTRACT FROM AUTHOR]

Modern dolomite formation is conditional and restricted in specific environmental and geochemical conditions, accordingly cannot be used as the analog of ancient dolostones, which normally have platform-wide distribution. The key to understand ancient dolostone formation is to find a dolomitization process that is independent of physical/geochemical environments. It is well-known that ribbon rock (one type of calcareous rhythmites, sensu stricto referring to the alternating limestone and marlstone layers or the limestone-marl alternations) that are deposited in nearly all marine environments throughout the Earth's history, are exclusively, though normally partially, dolomitized. Thus, understanding ribbon rock dolomitization may provide valuable insight into the ‘dolomite problem’. In this study, we measured Mg isotopic compositions ( δ 26 Mg) of ribbon rock samples collected from the Ediacaran Doushantuo Formation in South China. The marlstone layers contain higher dolomite contents and are characterized by higher δ 26 Mg (ranging from − 2.68‰ to − 1.84‰) than the limestone layers (varying between − 3.21‰ and − 2.53‰). A numerical model calculation indicates that clay minerals cannot provide enough Mg for dolomitization, arguing against the traditional interpretation that dolomitization is resulted from diagenetic Mg release from clays. Instead, contemporaneous seawater might provide sufficient Mg for dolomitization, because both Mg isotopes and dolomite content can be simulated by the Diffusion-Advection-Reaction model. Contemporaneous seawater dolomitization requires kinetic barrier be overcome at shallow depth of sediments. We propose the ribbon rock dolomitization is attributed to differential diagenesis of the clay-rich and clay-poor sediment layers, in which Ca 2 + -Mg 2 + exchange elevates porewater Mg/Ca in clay-rich layers. [ABSTRACT FROM AUTHOR]

Aiming at understanding N 2 O formation in a low-temperature SCR process, mechanistic studies regarding the synergistic removal of NO and inhibition of N 2 O formation by the addition of Ce and V into MnO x /Ti based catalysts prepared by the sol-gel method were conducted and analyzed by various techniques, including BET, XRD, XPS, NH 3 -TPD, and FTIR. The results show that the addition of Ce raises the NO conversion efficiency and shifts the high performance region toward the low temperature range, while the addition of V generates less N 2 O. As an optimal formula, Mn(0.4)Ce(0.1)V(0.01)/Ti ensures a high NO conversion efficiency and low N 2 O formation. N 2 O mainly originates from (1) the direct oxidation of NH 3 with O 2 and (2) the reaction of NO and adsorbed NH 3 in the low-temperature SCR process. The latter plays a dominant role at temperatures below 240 °C. The strong redox properties on the MnO x /Ti catalyst surface result in a high NO conversion efficiency and generates numerous NH(ads) species that cause N 2 O formation. The slight addition of V promotes the formation of acid by bringing Lewis acid sites to the catalyst surface and effectively restricts N 2 O formation. Lewis acid sites have a positive function in maintaining a high NO conversion and inhibiting N 2 O formation compared to Brønsted acid sites. In addition, the well-dispersed V on the surface of Mn(0.4)Ce(0.1)V(0.01)/Ti results in improved textural properties, more lattice oxygen and less labile oxygen, as well as comparable Mn 4+ /Mn 3+ , which also improves the catalyst performance at low temperature. [ABSTRACT FROM AUTHOR]

Objectives: Investigate the effectiveness of alcohol septal ablation (ASA) and transaortic extended myectomy (TEM) in hypertrophic cardiomyopathy (HCM) with midventricular obstruction (MVO).Background: MVO is less common than subaortic obstruction. Data on the effectiveness of ASA and TEM in MVO are lacking.Methods: The clinical profiles of 22 patients undergoing ASA and 37 patients undergoing TEM were compared. No patient had apical aneurysm, abnormal chordae, mitral valve replacement or repair.Results: Baseline midventricular pressure gradient and symptoms were comparable between the ASA and TEM groups. During follow-up, both groups demonstrated substantial reduction in pressure gradient (the ASA group: 79.7 ± 21.2 mm Hg to 43.7 ± 28.9 mm Hg, P < 0.001; the TEM group: 69.0 ± 23.9 mm Hg to 15.0 ± 16.9 mm Hg, P < 0.001). The reduction in pressure gradient was greater (78.9 ± 18.6% vs. 46.4 ± 33.4%, P < 0.001) and the residual pressure gradient was lower after TEM versus ASA (P < 0.001). Patients with New York Heart Association class III/IV dyspnea decreased from 59.1 to 18.2% (P = 0.022) in the ASA group and from 56.8 to 5.6% (P < 0.001) in the TEM group. Patients with Canadian Cardiovascular Society class III/IV angina decreased from 40.9 to 9.1% (P = 0.016) in the ASA group and from 32.4 to 0% (P < 0.001) in the TEM group.Conclusions: While ASA and TEM both improve gradients and symptoms, TEM may provide a more reliable reduction in gradients compared to ASA. [ABSTRACT FROM AUTHOR]

We establish a catalog of interplanetary coronal mass ejections (ICMEs) during the period from 1995 to 2015 using the in-situ observations from the Wind and ACE spacecraft. Based on this catalog, we extend the statistical properties of ICMEs to the maximum phase of Solar Cycle 24. We confirm previous results that the yearly occurrence frequencies of ICMEs and shocks, the ratios of ICMEs driving shocks are correlated with the sunspot numbers. For the magnetic cloud (MC), we confirm that the yearly occurrence frequencies of MCs do not show any correlation with sunspot numbers. The highest MC ratio of ICME occurred near the solar minimum. In addition, we analyzed the yearly variation of the ICME parameters. We found that the ICME velocities, the magnetic-field strength, and their related parameters are varied in pace with solar-cycle variation. At the solar maximum, ICMEs move faster and carry a stronger magnetic field. By comparing the parameters between MCs and non-MC ejecta, we confirm the result that the magnetic-field intensities of MC are higher than those in non-MC ejecta. Furthermore, we also discuss the forward shocks driven by ICMEs. We find that one half of the ICMEs have upstream shocks and ICMEs with shocks have faster speed and higher magnetic-field strength than the ICMEs without shocks. The magnetic-field parameters and solar-wind plasma parameters in the shock sheath regions are higher than those in the ejecta regions of ICMEs from a statistical point of view. [ABSTRACT FROM AUTHOR]

Mammalian p53 is a super tumor suppressor and plays a key role in guarding genome from DNA damage. However, p53 has not been found in plants which do not bear cancer although they constantly expose to ionizing radiation of ultraviolet light. Here we introduced p53 into the model plant Arabidopsis and examined p53-conferred phenotype in plant. Most strikingly, p53 caused early senescence and fasciation. In plants, fasciation has been shown as a result of the elevated homologous DNA recombination. Consistently, a reporter with overlapping segments of the GUS gene (1445) showed that the frequency of homologous recombination was highly induced in p53-transgenic plants. In contrast to p53, SUPPRESSOR OF NPR1-1 INDUCIBLE 1 (SNI1), as a negative regulator of homologous recombination in plants, is not present in mammals. Comet assay and clonogenic survival assay demonstrated that SNI1 inhibited DNA damage repair caused by either ionizing radiation or hydroxyurea in human osteosarcoma U2OS cancer cells. RAD51D is a recombinase in homologous recombination and functions downstream of SNI1 in plants. Interestingly, p53 rendered the sni1 mutants madly branching of inflorescence, a phenotype of fasciation, whereas rad51d mutant fully suppressed the p53-induced phenotype, indicating that human p53 action in plant is mediated by the SNI1-RAD51D signaling pathway. The reciprocal species-swap tests of p53 and SNI1 in human and Arabidopsis manifest that these species-specific proteins play a common role in homologous recombination across kingdoms of animals and plants. [ABSTRACT FROM AUTHOR]

Finding an appropriate and accurate technology for early detection of disease is significantly important to research early treatments. We proposed some novel automatic classification systems based on the stationary wavelet transform (SWT) and the improved support vector machine (SVM). Magnetic Resonance Imaging (MRI) is commonly used for brain imaging as a non-invasive diagnostic tool to assist the pre-clinical diagnosis. However, MRI generates a large information set, which poses a challenge for classification. To deal with this problem we proposed a new approach, which combines SWT and Principal Component Analysis for feature extraction. In our experiments, three different datasets and four kinds of classifiers of the SVM were employed. The results over 5×6-fold stratified cross-validation (SCV) for Dataset-66, and 5×5-fold SCV for the other two datasets show that the average accuracy is almost 100.00%. [ABSTRACT FROM AUTHOR]

A comprehensive field study was conducted to evaluate the environmental performance of a roadway subgrade consisting of contaminated soil solidified/stabilized with a hydroxyapatite-based binder (termed as SPC in this study). Traditional Portland cement (PC) was used as a control binder for comparison purposes. The environmental properties including soil pH, soil leachability, and chemical speciation of target contaminants including nickel (Ni) and zinc (Zn) were investigated at 1 d, 7 d, 28 d, and 600 d after construction of the roadway subgrade. Furthermore, the field migration distances of Ni and Zn released from the subgrade to the off-site clean soil were investigated after 600-d of exposure to the atmospheric environment. The results showed that SPC solidification/stabilization was not only effective for reducing the soil leachability but improving the chemical stability of Ni and Zn in the contaminated soil. The soil pH was slightly acidic after SPC treatment. The observed maximum distance of Ni and Zn migrated from subgrade to the off-site clean soil was approximately 5 cm at 600 d. The SPC binder exhibited superior performance to PC in terms of immobilization effectiveness of Ni and Zn, soil pH, and curing time. [Display omitted] • A hydroxyapatite-based binder SPC is developed to immobilize Ni and Zn in soil. • Environmental performance of reusing SPC solidified/stabilized soil is evaluated. • Binding intensity of Ni and Zn in soil relates to their leached concentrations. • Migration distance of Ni and Zn from on-site soil to off-site soil is monitored. [ABSTRACT FROM AUTHOR]

In patients with triple-negative breast cancer (TNBC), high tumour mutation burden and aberrant oncogene expression profiles are some of the causes of poor prognosis. Therefore, it is necessary to identify aberrantly expressed oncogenes, since they have the potential to serve as therapeutic targets. Transient receptor potential channel 5 opposite strand (TRPC5OS) has been previously shown to function as a novel tumour inducer. However, the underlying mechanism of TRPC5OS function in TNBC remain to be elucidated. Therefore, in the present study TRPC5OS expression was first measured in tissue samples of patients with TNBC and a panel of breast cancer cell lines (ZR-75-1, MDA-MB-453, SK-BR-3, JIMT-1, BT474 and HCC1937) by using qRT-PCR and Western blotting. Subsequently, the possible effects of TRPC5OS on MDA-MB-231 cells proliferation were determined using Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine assays after Lentiviral transfection of MDA-MB-231. In addition, potential interaction partners of TRPC5OS were explored using liquid chromatography-mass spectrometry (LC-MS)/MS. Gene expression patterns following TRPC5OS overexpression were also detected in MDA-MB-231 cells by using High-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis were then used to systematically verify the potential interactions among the TRPC5OS-regulated genes. The potential relationship between TRPC5OS-interacting proteins and gene expression patterns were studied using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis. TRPC5OS expression was found to be significantly higher in TNBC tumour tissues and breast cancer cell lines compared with luminal tumour tissues and ZR-75-1. In addition, the overexpression of TRPC5OS significantly increased cell proliferation. High-throughput sequencing results revealed that 5,256 genes exhibited differential expression following TRPC5OS overexpression, including 3,269 upregulated genes and 1,987 downregulated genes. GO analysis results indicated that the functions of these differentially expressed genes were enriched in the categories of 'cell division' and 'cell proliferation' regulation. KEGG analysis showed that the TRPC5OS-regulated genes were associated with processes of 'homologous recombination' and 'TNF signalling pathways'. Subsequently, 17 TRPC5OS-interacting proteins were found using LC-MS/MS and STRING analysis. The most important protein among interacting proteins was ENO1 which was associated with glycolysis and regulated proliferation of cancer. In summary, data from the present study suggest that TRPC5OS overexpression can increase TNBC cell proliferation and ENO1 may be a potential target protein mediated by TRPC5OS. Therefore, TRPC5OS may serve as a novel therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually. Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment. Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm2± 0.48 (SD), 4.08 cm2± 0.36, respectively;P >0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm2± 0.48 (SD), 1.69 cm2± 0.34 cm2, respectively;p <0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77,p <0.01) or the DOX group (mean 35.17 days ± 7.63,p <0.01). Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin. [ABSTRACT FROM AUTHOR]