The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of ...the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
One of the most promising approaches to reach a high gain in inertial confinement fusion is the fast ignition scheme. In this scheme, a relativistic electron beam is generated; this passes through ...the imploded plasma and deposits parts of its energy in the core. However, the large angular spread of the relativistic electron beam and the poorly controlled compression of the target affect realization of the fast ignition technique. Here, we demonstrate that indirectly driven (that is, driven by X-rays generated inside a gold hohlraum) implosions with a ‘high-foot’ and a short-coast time of less than 200 ps allow us to tightly compress the shell. Furthermore, we show the ability to optimize the symmetry of the imploding shell by changing the hohlraum length, successfully tuning a suitable tube-shaped shell to compensate for the large angular spread of the relativistic electron beam and to enhance the electron-to-core coupling efficiency via resistive magnetic fields. Benefiting from those experimental techniques, a significant enhancement in neutron yield was achieved in our indirectly driven fast ignition experiments. These results pave the way towards high-coupling fast ignition experiments with indirectly driven targets similar to those at the National Ignition Facility.Experiments realizing the indirect-drive fast ignition scheme for inertial confinement fusion are reported. Enabled by a tightly compressed target, an increase of neutron yield is observed.
Adopting self‐healing, robust, and stretchable materials is a promising method to enable next‐generation wearable electronic devices, touch screens, and soft robotics. Both elasticity and ...self‐healing are important qualities for substrate materials as they comprise the majority of device components. However, most autonomous self‐healing materials reported to date have poor elastic properties, i.e., they possess only modest mechanical strength and recoverability. Here, a substrate material designed is reported based on a combination of dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds together in a multiphase separated network. Importantly, this material is able to undergo self‐healing and exhibits excellent elasticity. The polymer network forms a microphase‐separated structure and exhibits a high stress at break (≈1.8 MPa) and high fracture strain (≈900%). Additionally, it is observed that the substrate can achieve up to 98% self‐healing efficiency after 48 h at 25 °C, without the need of any external stimuli. A stretchable and self‐healable dielectric layer is fabricated with a dual‐dynamic bonding polymer system and self‐healable conductive layers are created using polymer as a matrix for a silver composite. These materials are employed to prepare capacitive sensors to demonstrate a stretchable and self‐healable touch pad.
Dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds, are combined in a multiphase separated network, in a new strategy to enable a robust and elastic capacitive sensor with autonomous self‐healing properties.
Soft and conformable wearable electronics require stretchable semiconductors, but existing ones typically sacrifice charge transport mobility to achieve stretchability. We explore a concept based on ...the nanoconfinement of polymers to substantially improve the stretchability of polymer semiconductors, without affecting charge transport mobility. The increased polymer chain dynamics under nanoconfinement significantly reduces the modulus of the conjugated polymer and largely delays the onset of crack formation under strain. As a result, our fabricated semiconducting film can be stretched up to 100% strain without affecting mobility, retaining values comparable to that of amorphous silicon. The fully stretchable transistors exhibit high biaxial stretchability with minimal change in on current even when poked with a sharp object. We demonstrate a skinlike finger-wearable driver for a light-emitting diode.
Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, ...the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.
To study the effect of internal particle size on the microstructure properties and thermal decomposition characteristics of site mixed emulsion explosive at different altitudes. Site mixed emulsion ...explosive was prepared with different shear rate. The particle size, viscosity, sensitized bubbles, detonation velocity and peak pressure of the emulsion explosive were tested after stored at different simulated altitudes. The thermal decomposition characteristics of emulsion matrix prepared at three different rotational speeds were measured by thermogravimetric analyzer and kinetic analysis was performed by non-isothermal model Kissinger-Akah-Sunose (KAS) method. The results show that with the increase in altitude, the internal phase size showed a trend of first increasing and then decreasing, and the number of sensitized bubbles within the emulsion explosive decreases. At an altitude of 0 m, the detonation velocity and peak overpressure of the emulsion explosive prepared by 1600 r min
increased 4.78% and 29.09%, respectively compared with 1200 r min
, and at an altitude of 4500 m, the detonation velocity increased 11.87%, the peak overpressure increased 43.98%. The thermal decomposition activation energy of the emulsion matrix at 1600 r min
increased 13.14% compared to 1200 r min
. It shows that in the production of site mixed emulsion explosive at high altitude, reducing the particle size of the internal phase of emulsion explosives in a certain range can effectively improve the performance of emulsion explosives.
Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ...ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.
Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.
Serum FGF2 levels were higher in patients with heart failure (125.60 88.95, 183.40 pg/mL) than in those with non-heart-failure dyspnea (65.30 28.85, 78.95 pg/mL) and healthy controls (78.90 60.80, 87.20 pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.
Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.
ABSTRACT
The observation of the transient sky through a multitude of astrophysical messengers has led to several scientific breakthroughs in the last two decades, thanks to the fast evolution of the ...observational techniques and strategies employed by the astronomers. Now, it requires to be able to coordinate multiwavelength and multimessenger follow-up campaigns with instruments both in space and on ground jointly capable of scanning a large fraction of the sky with a high-imaging cadency and duty cycle. In the optical domain, the key challenge of the wide field-of-view telescopes covering tens to hundreds of square degrees is to deal with the detection, identification, and classification of hundreds to thousands of optical transient (OT) candidates every night in a reasonable amount of time. In the last decade, new automated tools based on machine learning approaches have been developed to perform those tasks with a low computing time and a high classification efficiency. In this paper, we present an efficient classification method using convolutional neural networks (CNNs) to discard many common types of bogus falsely detected in astrophysical images in the optical domain. We designed this tool to improve the performances of the OT detection pipeline of the Ground Wide field Angle Cameras (GWAC) telescopes, a network of robotic telescopes aiming at monitoring the OT sky down to R = 16 with a 15 s imaging cadency. We applied our trained CNN classifier on a sample of 1472 GWAC OT candidates detected by the real-time detection pipeline.
Background
Various minimally invasive approaches have been described for infected necrotizing pancreatitis. This article describes a modified minimal‐access retroperitoneal pancreatic necrosectomy ...(MARPN) procedure assisted by gas insufflation.
Methods
This retrospective, observational study documented patients who had undergone a step‐up MARPN between 1 January 2010 and 31 December 2016. A minimum follow‐up of 1 year was required for inclusion. The step‐up approach involved percutaneous catheter drainage followed by the modified MARPN and necrosectomy. If more than one access site was needed it was categorized as complex MARPN.
Results
Of 212 patients with infected necrotizing pancreatitis, 164 (77·4 per cent) underwent a step‐up approach. The median number of percutaneous catheter drains and MARPN procedures was 3 (range 1–7) and 1 (1–6) respectively. Ninety patients (54·9 per cent) underwent complex MARPN. For residual necrosis after MARPN, three patients (1·8 per cent) underwent sinus tract gastroscopy, and 11 (6·7 per cent) had sinography combined with a tube change. However, operations in 13 patients (7·9 per cent) required conversion to open surgery. Postoperative complications developed in 103 patients (62·8 per cent). The mortality rate was 6·1 per cent (10 deaths).
Conclusion
A step‐up approach using a modified MARPN for infected necrotizing pancreatitis is a reasonable option.
Antecedentes
Los procedimientos mínimamente invasivos se han convertido en los más frecuentes para el tratamiento de necrosis pancreáticas infectadas. El objetivo de este estudio fue presentar un procedimiento de necrosectomía pancreática retroperitoneal de acceso mínimo (minimal‐access retroperitoneal pancreatic necrosectomy, MARPN) modificado y asistido mediante insuflación de gases, así como evaluar su seguridad y eficacia.
Métodos
Se realizó un análisis retrospectivo y observacional de los datos de un hospital desde el 1 de enero de 2010 hasta el 31 de diciembre de 2016. Se incluyeron en el análisis todos los pacientes en los que realizó un abordaje por etapas, que consistía en el drenaje percutáneo mediante la colocación de un catéter seguido de un procedimiento MARPN modificado, en los que se dispusiese de un seguimiento postoperatorio mínimo de 1 año. El MARPN en el lado derecho y la necrosectomía realizada a través de más de un acceso se clasificaron como MARPN complejo. Se evaluaron los resultados radiológicos y quirúrgicos.
Resultados
De 212 pacientes con necrosis pancreática infectada, en 164 (77,4%) se realizó un abordaje por etapas. La mediana del número de drenajes percutáneos y procedimientos MARPN fue 3 (rango, 1‐7) y 1 (rango, 1‐6), respectivamente. En 90 pacientes (54,9%) se realizó un MARPN complejo. Para la exéresis de necrosis residual después de un MARPN, en 3 pacientes (1,8%) se realizó mediante gastroscopia y en 11 pacientes (6,7%) con un recambio de drenaje bajo control radiológico. En 13 pacientes (7,9%) fue necesaria la reconversión a cirugía abierta. Hubo complicaciones postoperatorias en 103 pacientes (62,8%). La tasa de mortalidad fue del 6,1% (n = 10).
Conclusión
El abordaje por etapas con un MARPN modificado es seguro y efectivo en el tratamiento de la necrosis pancreática infectada.
Minimally invasive approaches have been used increasingly in the management of infected necrotizing pancreatitis. This study presents a modified minimal‐access retroperitoneal pancreatic necrosectomy procedure assisted by carbon dioxide insufflation, instead of saline. A clear field of view without necrotic debris floating in saline makes the technique safe and efficient.
High degree of success
VIDEO
Presented in part to the Joint Congress of the Sixth Biennial Congress of the Asian–Pacific Hepato‐Pancreato‐Biliary Association and the 29th Meeting of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery, Yokohama, Japan, June 2017
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