Blood cell count-derived inflammation indices as predictors of the osteoporotic risk of postmenopausal women.

OBJECTIVE: We investigated the associations between osteoporosis (OP) and systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in postmenopausal women. PATIENTS AND METHODS: This retrospective study included 966 postmenopausal women. Logistic regression and receiver operating characteristic curve (ROC) analyses were applied to explore the relationships between SII, NLR, MLR, and PLR with the bone mineral density (BMD) and risk of OP. RESULTS: Logistic regression analyses showed that SII, PLR, NLR, and MLR had independent negative associations with the OP risk. The ROC curve analysis showed that SII, NLR, and MLR predicted a low BMD, with NLR having the highest predictive value (area under the curve = 0.624). SII > 504.09, PLR > 131.87, NLR > 2.02, and MLR > 0.12 correlated with a particularly high OP risk. CONCLUSIONS: High levels of SII, PLR, NLR, and MLR were associated with a high OP risk. In particular, NLR > 2.02 strongly predicted the risk of OP, thereby representing a valuable and convenient inflammatory marker of the OP risk.

Serum CTRP3 concentrations are positively correlated with disease severity in women with postmenopausal osteoporosis: a population-based cross-sectional study.

OBJECTIVE: Osteoporosis is a leading public health problem that contributes to increasingly high rates of osteoporotic vertebral compression fractures among older adults. This study was developed with the goal of assessing serum C1q/TNF-related protein-3 (CTRP3) levels in postmenopausal osteoporosis (PMOP) patients and exploring the correlations between these levels and PMOP severity. PATIENTS AND METHODS: A population-based cross-sectional study of old women with osteoporosis was conducted. All women underwent both clinical and dual-energy X-ray absorptiometry examinations. Serum CTRP3, procollagen type I N propeptide (P1NP), and C-terminal telopeptide of type I collagen (CTX-1) concentrations in these patients were measured via ELISA. Bone tumor markers were additionally assessed. Receiver operating characteristic (ROC) analyses were utilized to assess the diagnostic performance of CTRP3 when identifying PMOP. RESULTS: This study included 54 PMOP patients, 62 patients with osteopenia, and 60 age-matched patients without PMOP. Serum CTRP3 concentrations in PMOP patients were significantly lower than in the other two groups. Bone mineral density (BMD) was positively correlated with serum CTRP3 levels in all study participants, whereas it was negatively correlated with levels of P1NP and CTX-1. ROC analyses also suggested that reductions in serum CTRP3 levels may offer value as a diagnostic indicator of PMOP. CONCLUSIONS: Present data highlight a close relationship between CTRP3 and PMOP, with lower serum CTRP3 levels being closely associated with BMD, such that they may represent a protective marker for PMOP.

Energetic Electron Precipitation Driven by Electromagnetic Ion Cyclotron Waves from ELFIN's Low Altitude Perspective.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

Ambient air pollution exposure and telomere length: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide evidence of the associations between pre- and post-birth and adulthood air pollution exposure with telomere length. STUDY DESIGN: The databases of PubMed, Embase, and Web of Science were searched up to June 1st, 2022 in order to include relevant observational studies and perform a systematic review and meta-analysis. METHODS: The random-effects meta-analysis was grouped by air pollutant and exposure window (pre- and post-birth and adulthood) to evaluate the summary effect estimate. Cochran's Q and I2 statistics were used to evaluate the heterogeneity among the included studies. The quality of individual studies was evaluated using the national toxicology program/office of health assessment and translation risk of bias rating tool. RESULTS: We identified 18 studies, covering 8506 children and 2263 adults from multiple countries. We found moderate evidence that particulate matter less than 2.5 µm (PM2.5) exposure during the entire pregnancy (-0.043, 95% CI: -0.067, -0.018), nitrogen dioxide (NO2) exposure during the first trimester (-0.016, 95% confidence interval [CI]: -0.027, -0.005), long-term adulthood PM2.5 exposure were associated with shortening telomere length. Mild to high between-study heterogeneity was observed for the most tested air pollutant-telomere length combinations in different exposure windows. CONCLUSIONS: This systematic review and meta-analysis provides the evidence which strongly supports that prenatal PM2.5 and NO2 exposures were related to reduced telomere length, while prenatal sulfur dioxide (SO2) and carbon monoxide (CO) exposures, childhood PM2.5, particulate matter less than 10 µm (PM10), NO2 exposures and short-term adulthood PM2.5 and PM10 exposures were not associated with telomere length. Further high-quality studies are needed to elaborate our suggestive associations.

A Climatology of Long-Duration High 2-MeV Electron Flux Periods in the Outer Radiation Belt.

Since the advent of the Space Age, the importance of understanding and forecasting relativistic electron fluxes in the Earth's radiation belts has been steadily growing due to the threat that such particles pose to satellite electronics. Here, we provide a model of long-duration periods of high time-integrated 2-MeV electron flux deep inside the outer radiation belt, based on the significant correlation obtained in 2001-2017 between time-integrated electron flux measured by satellites and a measure of the preceding time-integrated homogenized aa H geomagnetic index. We show that this correlation is likely due to a stronger cumulative chorus wave-driven acceleration of relativistic electrons and a stronger cumulative inward radial diffusion of such electrons during periods of higher time-integrated geomagnetic activity. Return levels of 2-MeV electron flux are provided based on Extreme Value analysis of time-integrated geomagnetic activity over 1868-2017, in rough agreement with estimates based on 20-year data sets of measured flux. A high correlation is also found between our measure of time-integrated geomagnetic activity averaged over each solar cycle and averaged sunspot numbers, potentially paving the way for forecasts of time-integrated relativistic electron flux during future solar cycles based on predictions of solar activity.

Short Chorus Wave Packets: Generation Within Chorus Elements, Statistics, and Consequences on Energetic Electron Precipitation.

Short and intense lower-band chorus wave packets are ubiquitous in the Earth's outer radiation belt. In this article, we perform various Vlasov hybrid simulations, with one or two triggering waves, to study the generation of short chorus packets/subpackets inside long rising tone elements. We show that the length of the generated short wave packets is consistent with a criterion of resonance non-overlap for two independent superposed waves, and that these chorus packets have similar characteristics as in Van Allen Probes observations. We find that short wave packets are mainly formed near the middle/end of long rising tones for moderate linear growth rates, and everywhere for stronger linear growth rates. Finally, we analyze an event characterized by Time History of Events and Macroscale Interactions during Substorms spacecraft measurements of chorus rising tones near the equator and simultaneous measurements by low altitude ELFIN CubeSats of precipitating and trapped electron fluxes in the same sector. The measured precipitating electron fluxes are well recovered by test particle simulations performed using measured plasma and wave properties. We show that short chorus wave packets of moderate amplitudes (160-250 pT) essentially lead to a more diffusive-like transport of 50-200 keV electrons toward the loss cone than long packets. In contrast, long chorus packets are found to produce important nonlinear effects via anomalous trapping, which significantly reduces electron precipitation below 150 keV, especially for higher wave amplitudes.

Extreme Energy Spectra of Relativistic Electron Flux in the Outer Radiation Belt.

Electron diffusion by whistler-mode chorus waves is one of the key processes controlling the dynamics of relativistic electron fluxes in the Earth's radiation belts. It is responsible for the acceleration of sub-relativistic electrons injected from the plasma sheet to relativistic energies as well as for their precipitation and loss into the atmosphere. Based on analytical estimates of chorus wave-driven quasi-linear electron energy and pitch-angle diffusion rates, we provide analytical steady-state solutions to the corresponding Fokker-Planck equation for the relativistic electron distribution and flux. The impact on these steady-state solutions of additional electromagnetic ion cyclotron waves, and of ultralow frequency waves are examined. Such steady-state solutions correspond to hard energy spectra at 1-4 MeV, dangerous for satellite electronics, and represent attractors for the system dynamics in the presence of sufficiently strong driving by continuous injections of 10-300 keV electrons. Therefore, these analytical steady-state solutions provide a simple means for estimating the most extreme electron energy spectra potentially encountered in the outer radiation belt, despite the great variability of injections and plasma conditions. These analytical steady-state solutions are compared with numerical simulations based on the full Fokker-Planck equation and with relativistic electron flux spectra measured by satellites during one extreme event and three strong events of high time-integrated geomagnetic activity, demonstrating a good agreement.

The social and occupational consequences of the COVID-19 pandemic among patients with multiple sclerosis in three distinct populations: A web-based cross-sectional survey.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease COVID-19, has caused a pandemic that has rapidly affected the whole world and caused a significant threat to public health. The aim of this study was to investigate and analyze the social and occupational effects of the COVID-19 pandemic on patients with multiple sclerosis (MS) in three different countries: China, Spain, and Cuba. Methods: A cross-sectional survey was designed to assess the social and occupational effects of the COVID-19 pandemic in MS patients in these three countries, using a 25-item anonymous online questionnaire, structured into three sections. Quantitative data are expressed as mean (standard deviation), and quantitative data as absolute frequency and percentage. Results: A total of 361 participants responded to the questionnaire: 194 from China, 104 from Spain, and 63 from Cuba. We found no cases of COVID-19 among Chinese patients with MS, and few cases in Spain and Cuba. Respondents reported different levels of impact on relationships with friends, family, and colleagues, and patients in all three countries described increased use of digital or social media platforms. Spanish patients reported a significantly less negative impact than those in Cuba and China. Mental and cognitive effects were similar in all three countries, although China seemed to have a better situation. We also found that the time spent exercising decreased at specific points during the pandemic, but with few changes in dietary habits. Patients reported little or no change in their means of transport in all three countries. Most patients in all three countries reported little or no physical deterioration, especially in Chinese patients (82.47%), compared to the Spanish (70.20%) and Cuban respondents (73.02%). In general, patients from all three countries demonstrated confidence in overcoming the COVID-19 pandemic, although to a lesser extent among Spanish respondents. Conclusions: During the pandemic, family support was more effective in China than in Cuba and Spain. Neither COVID-19 infections nor the number of MS relapses increased significantly during lockdown in any of the three countries. Regarding their economic situation, Spanish MS patients reported a significantly less severe negative impact than those in Cuba and China. Patients from all three countries used digital or social media platforms more frequently, probably to maintain personal relationships. Chinese and Cuban respondents were more confident of the control of the pandemic than the Spanish, who were more pessimistic.

Introducción: El nuevo coronavirus de tipo 2, causante del síndrome respiratorio agudo severo o COVID-19, se ha expandido rápidamente a nivel mundial, convirtiéndose en una grave amenaza para la salud pública en forma de pandemia. El objetivo de este estudio es analizar los efectos sociolaborales de la pandemia de COVID-19 en pacientes con esclerosis múltiple (EM) en 3 países diferentes (China, España y Cuba). Métodos: Diseñamos un estudio transversal para valorar los efectos sociolaborales de la pandemia de COVID-19 en pacientes con EM procedentes de China, España y Cuba mediante un cuestionario digital de 25 preguntas divididas en 3 apartados. Los datos cuantitativos se expresan como medias y desviaciones estándar, mientras que los datos cualitativos se expresan mediante valores y porcentajes. Resultados: Un total de 361 pacientes respondieron al cuestionario (194 de China, 104 de España y 63 de Cuba). No encontramos ningún paciente chino con EM que hubiera padecido COVID-19, y los casos diagnosticados en España y Cuba fueron muy infrecuentes. A raíz de la pandemia, se observaron cambios en las relaciones con amigos, familiares y compañeros; además, los pacientes con EM usaron plataformas digitales y redes sociales con más frecuencia en los 3 países. El impacto negativo fue significativamente menor en España que en Cuba o China. Los efectos mentales y cognitivos de la pandemia fueron similares en los 3 países, aunque parece que la situación previa era mejor en China. Igualmente, observamos que el tiempo dedicado al ejercicio se redujo en momentos específicos durante la pandemia. Por el contrario, no se detectaron grandes cambios en los hábitos alimentarios. Los pacientes de los 3 países consideraron que no se produjeron cambios en su medio de transporte, o que estos fueron escasos. La mayoría de los pacientes ha experimentado poco o ningún deterioro físico, particularmente los pacientes chinos (82,47%) en comparación con los españoles (70,20%) y cubanos (73,02%). En líneas generales, todos los pacientes se mostraron esperanzados en superar la pandemia, aunque los pacientes españoles en menor grado. Conclusiones: Durante la pandemia, el apoyo familiar fue más importante en China que en Cuba o España. En ninguno de los 3 países se observó un aumento significativo en el número de casos de COVID-19 ni de brotes o recaídas durante el periodo de confinamiento. En términos económicos, los pacientes con EM españoles sufrieron un impacto negativo significativamente menor que los cubanos y chinos. Todos los pacientes usaron plataformas digitales o redes sociales con más frecuencia, probablemente con el fin de mantener relaciones personales. Los pacientes chinos y cubanos mostraron mayor confianza en el control de la pandemia que los españoles, que resultaron ser más pesimistas.

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi.

BACKGROUND: Verrucous epidermal naevi (VEN) are benign skin tumours, considered keratinocytic epidermal naevi, that appear at birth or early childhood. VEN may display a range of appearances, depending on patient age. Although the number of studies regarding VEN is increasing, the exact mechanism of VEN is still unknown. OBJECTIVES: The aim of this study was to analyse the changes in the expression of protein factors in lesions of VEN children by TMT labelling-based quantitative proteomics. METHODS: A total of 8 children with VEN (5 for experiment and 3 for validation) and 8 healthy children (5 for experiment and 3 for validation) presented to the Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Boao Super Hospital, between January 2019 and November 2019. The lesions and lesion-adjacent tissues from children with VEN and naevus-adjacent normal skin tissues from children with pigmented naevi were defined as the VEN group, VENC group and C group, respectively. We performed a proteomics analysis to screen for differentially expressed proteins in the lesions of these individuals. We further performed Western blotting to validate the relative expression levels of nine targeted proteins in the validation group. RESULTS: According to the proteomics results, a total of 4970 proteins were identified, and 4770 proteins were quantified. Among these proteins, 586 proteins were up- or downregulated at least 1.3-fold with a P-value < 0.05 (upregulated: 399, downregulated: 187) in lesions between the VEN group and the C group. These proteins played important roles in multiple biological functions, such as cornification, epidermal cell differentiation and neutrophil activation, and formed a complicated protein-protein interaction network. Of the 586 up- or downregulated proteins, nine were selected for further validation. According to Western blotting analysis results, the relative expression levels of Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A (Cytokeratin 6A), BRAF, Filaggrin, S100A7 and Desmocollin-3 were significantly upregulated in VEN children and may be associated with skin barrier dysfunction, epidermal cell overgrowth and differentiation, inflammation and immune and oxidative phosphorylation, which are involved in the pathogenesis of VEN. CONCLUSIONS: According to TMT-based proteomics and Western blotting results, we identified eight noteworthy proteins, Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A, BRAF, Filaggrin, S100A7 and Desmocollin-3, that were upregulated in the lesions of VEN children and may be associated with the pathogenesis of VEN. Our findings provide new starting points for identifying precise pathogenic mechanisms or therapeutic targets for VEN.

Detection of CTCs and CSCs in the staging and metastasis of non-small cell lung cancer based on microfluidic chip and the diagnostic significance.

OBJECTIVE: Dynamic monitoring of CTCs/CSCs can assist in the diagnosis and prognosis of tumors. This study explores the diagnostic significance of microfluidic chip technology in the detection of CTCs/CSCs in clinical staging and metastasis of patients with non-small cell lung cancer (NSCLC). That lays a solid foundation for the use of microfluidic chips to monitor CTCs/CSCs for the stage and metastasis of patients with non-small cell lung cancer. PATIENTS AND METHODS: This study collected 80 patients with lung cancer from October 2017 to October 2018. Meanwhile, 30 healthy people and 30 patients with benign lung diseases were selected during the same period as the control group 1 and the control group 2, respectively. CellSearch (Huntington Valley, PA, USA) and microfluidic chip were used to detect CTCs, the sensitivities were recorded. ELISA methods were used to detect the concentrations of tumor markers VEGF-C, CEA, and CA125 in serum, and their association with CTCs and CSCs was analyzed. In addition, after 3 months, we followed up 40 patients with lung cancer, recorded their prognosis, and extracted peripheral blood to detect changes in their CTCs and CSCs. The CellSearch (Huntington Valley, PA, USA) system and the microfluidic chip system were used to detect the CTCs in patients with lung cancer, and the sensitivity and specificity of the patients were analyzed. The changes in CTCs and CSCs in the peripheral blood of the patient were recorded. RESULTS: It can be seen that the positive rate of CTCs and CSCs is not significantly correlated with the patients' age, gender, pathological type (adenocarcinoma, squamous cell carcinoma), etc. They are significantly correlated with clinical stage (I + II and III + IV) and metastasis (metastasis and non-metastasis) (p<0.01). Then, we divided the patients into groups for testing, and analyzed the association between different groups of patients and CTCs and CSCs. Compared with control group 1 and control group 2, the positive rates of CTCs and CSCs in lung cancer metastasis group and non-metastasis group were significantly different (p<0.05). Compared with the control group 1 and control group 2, the positive rates of CTCs and CSCs in stage I + II and III + IV of lung cancer were significantly different (p<0.05). The positive rate was significantly higher in the cancer metastasis group (p<0.05). The concentrations of tumor markers VEGF-C, CEA, CA125 in the serum of patients were consistent with CTCs-negative and CTC-positive lung cancer, with significant differences (p<0.05). CSCs negative and CSCs positive patients have similar results. Subsequently, we analyzed the sensitivity and specificity of CSCs, CTCs, and tumor markers for the diagnosis of NSCLC. The results showed that the sensitivity of CSCs and CTCs to diagnose patients was significantly higher than that of tumor markers. CONCLUSIONS: This study shows that our microfluidic chip device can exhibit relatively good performance and can better detect CTCs and CSCs. Monitoring CTCs and CSCs of patients can provide a basis for judging the stage and metastasis of patients.

Magnetotail reconnection onset caused by electron kinetics with a strong external driver.

Magnetotail reconnection plays a crucial role in explosive energy conversion in geospace. Because of the lack of in-situ spacecraft observations, the onset mechanism of magnetotail reconnection, however, has been controversial for decades. The key question is whether magnetotail reconnection is externally driven to occur first on electron scales or spontaneously arising from an unstable configuration on ion scales. Here, we show, using spacecraft observations and particle-in-cell (PIC) simulations, that magnetotail reconnection starts from electron reconnection in the presence of a strong external driver. Our PIC simulations show that this electron reconnection then develops into ion reconnection. These results provide direct evidence for magnetotail reconnection onset caused by electron kinetics with a strong external driver.

Juno Observations of Heavy Ion Energization During Transient Dipolarizations in Jupiter Magnetotail.

Transient magnetic reconnection and associated fast plasma flows led by dipolarization fronts play a crucial role in energetic particle acceleration in planetary magnetospheres. Despite large statistical observations on this phenomenon in the Earth's magnetotail, many important characteristics (e.g., mass or charge dependence of acceleration efficiency and acceleration scaling with the spatial scale of the system) of transient reconnection cannot be fully investigated with the limited parameter range of the Earth's magnetotail. The much larger Jovian magnetodisk, filled by a mixture of various heavy ions and protons, provides a unique opportunity for such investigations. In this study, we use recent Juno observations in Jupiter's magnetosphere to examine the properties of reconnection associated dipolarization fronts and charged particle acceleration. High-energy fluxes of sulfur, oxygen, and hydrogen ions show clear mass-dependent acceleration with energy ~ m 1/3. We compare Juno observations with similar observations in the Earth's magnetotail and discuss possible mechanism for the observed ion acceleration.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

The role of hsa_circ_0000285 in metastasis of hepatocellular carcinoma.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of hsa_circ_0000285 in metastasis of hepatocellular carcinoma, by X.-J. Zhang, G. Cao, J. Fu, H.-J. Zhuang, J. Shi, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3579-3585-DOI: 10.26355/eurrev_202004_20819-PMID: 32329832" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20819.

Identification of serum exosomal miR-148a as a novel prognostic biomarker for breast cancer.

OBJECTIVE: Breast cancer (BC) is one of the most common malignanciesD. Li, J. Wang, L.-J. Ma, H.-B. Yang, J.-F. Jing, M.-M. Jia, X.-J. Zhang, F. Guo, J.-N. Gao affecting females. Aberrant expression of microRNAs (miRNAs) has been associated with carcinogenesis of BC. The aim of our study was to investigate the correlation of serum exosomal miR-148a expression and the clinical outcome of patients with BC. PATIENTS AND METHODS: Quantitative Real Time-Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was applied to evaluate the expression level of serum exosomal miR-148a in patients with BC, patients with benign breast tumors, and healthy controls. Then, the clinical value of serum exosomal miR-148a in BC was evaluated. RESULTS: Serum exosomal miR-148a levels were gradually downregulated from healthy controls patients with benign breast tumors to BC patients. Serum exosomal miR-148a could well distinguish BC patients from healthy volunteers. The expression level of serum exosomal miR-148a in BC patients was significantly upregulated following surgery, while dropped in the cases with disease relapse. A significant association was found between serum exosomal miR-148a levels and the tumor-node-metastasis (TNM) stage, differentiation, and lymph node metastasis in BC. In addition, BC patients with lower expression of serum exosomal miR-148a levels suffered worse overall survival and disease-free survival than those with higher expression of serum exosomal miR-148a levels. Furthermore, serum exosomal miR-148a was an independent risk factor for BC. CONCLUSIONS: Our data have demonstrated that serum exosomal miR-148a is significantly reduced in patients with BC and downregulation of serum exosomal miR-148a is closely associated with unfavorable clinical outcome of BC, indicating that serum exosomal miR-148a might serve as a promising diagnostic and prognostic biomarker for BC.

The role of hsa_circ_0000285 in metastasis of hepatocellular carcinoma.

OBJECTIVE: The importance of circular RNAs in malignant tumors causes more attention in researchers. Hepatocellular carcinoma (HCC) is one of the most ordinary malignant tumors. Hsa_circ_0000285 was explored to identify how it functions in the metastasis of HCC. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect hsa_circ_0000285 expression in HCC patients' tissues. Hsa_circ_0000285 lentivirus and shRNA was constructed for the transfection of HCC cells. Wound healing assay, transwell assay, and Matrigel assay were conducted to identify the function of hsa_circ_0000285 in HCC cells. Furthermore, mechanism assays were performed to uncover the interaction between hsa_circ_0000285 and miR-599. RESULTS: Hsa_circ_0000285 was significantly higher-expressed in HCC samples compared to that in adjacent samples. The migrated length of HCC cells was reduced after hsa_circ_0000285 was silenced, while the migrated length of HCC cells was increased after hsa_circ_0000285 was overexpressed. Moreover, the number of migrated and invaded HCC cells was reduced after hsa_circ_0000285 was silenced, while the number of migrated and invaded HCC cells was increased after hsa_circ_0000285 was overexpressed. Moreover, RT-qPCR results revealed that miR-599 was downregulated via overexpression of hsa_circ_0000285, while miR-599 was upregulated via knockdown of hsa_circ_0000285. Further experiments showed that miR-599 was a direct target of hsa_circ_0000285 in HCC. CONCLUSIONS: Hsa_circ_0000285 could enhance cell metastasis of HCC by targeting miR-599 and might be a potential therapeutic target in HCC.

MicroRNA-326 inhibits cell proliferative capacity and invasiveness through inhibiting the expression of ETS1 in nasopharyngeal carcinoma.

OBJECTIVE: This study aims to detect microRNA-326 expression in nasopharyngeal carcinoma (NPC) tissues and cell lines and to explore the potential mechanism of microRNA-326 inhibiting the proliferative capacity and invasiveness of NPC cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-326 expression in 40 cases of NPC tissue samples and cell lines. Meanwhile, microRNA-326 mimics were transfected into NPC cells to up-regulate microRNA-326 level. Next, the influence of microRNA-326 mimics on the proliferation and invasiveness of NPC cells was observed by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. Bioinformatics analysis was applied to search for target genes which may have direct effects on microRNA-326. An EST1 luciferase reporter vector containing microRNA-326 binding site was constructed and the binding relation between ETS1 and microRNA-326 was detected by Dual-Luciferase reporting assay. Lastly, the underlying mechanism of microRNA-326 and ETS1 in NPC was further verified via cell reverse experiments. RESULTS: Compared with control group, microRNA-326 expression was found remarkably decreased both in NPC tissue specimens and cell lines. The low expression of microRNA-326 could predict poor prognosis of patients with NPC. In vitro cell experiments revealed that overexpression of microRNA-326 remarkably inhibited the proliferative capacity and invasiveness of NPC cells. Bioinformatics analysis and Dual-Luciferase assay results suggested that microRNA-326 may bind to ETS1. Cell reverse assay indicated that inhibiting ETS1 expression partially reversed the changes in cell biological behavior induced by the down-regulation of microRNA-326 in CNE1 and 5-8F cell lines. CONCLUSIONS: Overexpression of microRNA-326 in NPC cells could remarkably inhibit the proliferative capacity and invasiveness of NPC cells. In addition, microRNA-326 may participate in the development of NPC by inhibiting ETS1 expression.

Glutamine protects myocardial ischemia-reperfusion injury in rats through the PI3K/Akt signaling pathway.

OBJECTIVE: To study the protective mechanism of glutamine (Gln) on myocardial ischemia-reperfusion (IR) injury in rats through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy SD rats weighing 200-300 g were used in this experiment. They were randomly divided into 3 groups: sham group (n=10), myocardial IR injury group (IR group, n=10), IR+Gln group (n=10). The protein expression levels of phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), mTOR, proliferating cell nuclear antigen (PCNA), P21, and Tubulin were determined by Western blotting (WB). Quantitative Polymerase Chain Reaction (qPCR) was applied to detect the messenger ribonucleic acid (mRNA) levels of Akt and mTOR. 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyl tetrazolium bromide (MTT) test was utilized to examine the proliferation ability of cardiomyocytes in vitro. Besides, the contents of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA). Cell apoptosis in each group was examined through Hoechst staining. RESULTS: Compared with those in the sham group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA extremely significantly decreased, but the level of P21 notably increased in IR group (p<0.01). In comparison with those in the IR group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA were remarkably raised, while the level of P21 was remarkably reduced in IR+Gln group (p<0.05). QRT-PCR results manifested that there were no significant differences in the mRNA levels of Akt and mTOR among the three groups [no significant difference (NS)]. Moreover, the cell proliferation ability in IR group was remarkably lower than that in the sham group (p<0.01), while it was enhanced in the IR+Gln group compared with that in the IR group (p<0.05). Additionally, IR group had significantly elevated expression levels of TNF-α and IL-6 compared with the sham group (p<0.01), whereas the IR+Gln group had notably decreased expression levels of TNF-α and IL-6 compared with IR group (p<0.05). In comparison with that in the sham group, the apoptosis in IR group was significantly raised (p<0.01), and compared with that in the IR group, the apoptosis in the IR+Gln group prominently decreased (p<0.05). The contents of the inflammatory cytokines, TNF-α, and IL-6 presented the same trends among the three groups. CONCLUSIONS: Gln activates the PI3K/Akt signaling pathway by increasing the levels of p-AKT and p-mTOR. Gln can increase the PCNA level and reduce the P21 level, so as to enhance the proliferation ability of cardiomyocytes. Besides, Gln reduces the levels of inflammatory cytokines, TNF-α, and IL-6, and inhibits cell apoptosis. Finally, Gln can protect cells from myocardial IR injury by activating the PI3K/Akt signaling pathway.

MiR-373 promotes proliferation and metastasis of oral squamous cell carcinoma by targeting SPOP.

OBJECTIVE: To explore the biological function of microRNA-373 (miR-373) in regulating the progression of oral squamous cell carcinoma (OSCC) and the related mechanism. PATIENTS AND METHODS: 50 patients who were diagnosed as OSCC in the Department of Stomatology of the Stomatological Hospital of Chongqing Medical University were enrolled as the cancer group. 20 healthy oral mucosa specimens were obtained as the control group. The miR-373 level in both OSCC clinical samples and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The binding relationship between speckle-type POZ protein (SPOP) and miR-373 was detected through online prediction software and luciferase reporter assay. RESULTS: MiR-373 was upregulated in OSCC samples and cell lines. It could negatively regulate the protein expression of SPOP. However, it did not affect the mRNA expression of SPOP. The up-regulation of miR-373 promoted proliferation, invasion, and migration ability of the OSCC cells. However, the effects of miR-373 were abolished by the over-expression of SPOP in cells. CONCLUSIONS: Up-regulated miR-373 promotes proliferation, invasion, and migration of OSCC by targeting SPOP. MiR-373/SPOP axis could be a potential therapeutic target for OSCC.

MiR-34b-5p knockdown attenuates bleomycin-induced pulmonary fibrosis by targeting tissue inhibitor of metalloproteinase 3 (TIMP3).

OBJECTIVE: To examine the effects of microRNA-34b-5p (miR-34b-5p) on bleomycin-induced lung fibrosis in mice and the underlying mechanism. MATERIALS AND METHODS: TIMP3-deficient (Timp3-/-) and wild-type mice were administered with bleomycin before to detect the miR-34b-5p expression using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Luciferase reporter assay was used to identify the target of miR-34b-5p in human lung fibroblast MRC-5. MiR-34b-5p was then silenced in vivo before lung histologic analysis and evaluation of extracellular matrix (ECM) genes as well as myofibroblast marker. The protein and mRNA expression levels were detected by Western blot and qRT-PCR, respectively. RESULTS: We found that miR-34b-5p was significantly increased in lung tissues from bleomycin-stimulated mice. TIMP3 was identified as a direct target of miR-34b-5p by using dual-luciferase reporter assay, and enhanced expression of miR-34b-5p led to a decrease in TIMP3 whereas miR-34b-5p knockdown was responsible for TIMP3 elevation in MRC-5 cells. MiR-34b-5p knockdown in vivo attenuated the bleomycin-induced pulmonary fibrosis in wild-type mice, displayed by a reduced expression of Col1A1, fibronectin (Fn), and α-SMA. Furthermore, histological examination of lung sections also verified a diminishing fibrotic phenotype caused by the miR-34b-5p knockdown. But in Timp3-/- mice, down-regulation of miR-34b-5p did not exert an effect on the severe fibrotic lung injury after bleomycin exposure. CONCLUSIONS: MiR-34b-5p knockdown appears to enhance the resistance to bleomycin by regulating its target gene TIMP3 during the pathogenesis of lung fibrosis.