Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase ...patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.
To compete with conventional heat-to-power technologies, such as thermal power plants, Concentrated Solar Power (CSP) must meet the electricity demand round the clock even if the sun is not shining. ...Thermal energy storage (TES) is able to fulfil this need by storing heat, providing a continuous supply of heat over day and night for power generation. As a result, TES has been identified as a key enabling technology to increase the current level of solar energy utilisation, thus allowing CSP to become highly dispatchable. This article aims to review different TES technologies that have been investigated and deployed over the past two decades. The review will give a comprehensive overview of TES technologies investigated, demonstrated and/or deployed in CSP plants with a specific emphasis on TES materials perspective. A thorough analysis will also be given on the state-of-the-art of the CSP technologies including commercial development and research innovation. An attempt is also made to use the information gathered along this review to postulate future technology evolution of CSP plants in terms of CSP configurations, TES technologies and location of CSP plants, and to assess the current and future role of TES in CSP field.
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•Thermal energy storage is a key enable technology to increase the CSP installed capacity levels in the world.•The two-tank molten salt configuration is the preferred storage technology, especially in parabolic trough and solar tower.•By 2020, the plants without storage will be just 30% of the total installed capacity.•Molten salt technology will be used in the 67% of the plants, followed by concrete, steam and packed bed.•To increase TES deployement level, diversified alternatives must be found, specific for each CSP configuration requirements.
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•A standalone liquid air energy storage (LAES) plant with packed bed is studied.•The dynamic behaviour of the system was evaluated using an algebraic/differential model.•The link ...between components and system performance is elucidated.•The round trip efficiency of the plant reaches 50%.•Packed bed allow recycle of cold thermal energy increasing efficiency.
Energy storage is more important today than ever. It has a key role in storing intermittent electricity from renewable sources – wind, solar and waves – enabling the decarbonisation of the electricity sector. Liquid air energy storage (LAES) is a novel technology for grid scale energy storage in the form of liquid air with the potential to overcome the drawbacks of pumped-hydro and compressed air storage. In this paper we address the performance of next generation LAES standalone plants. Starting our experience with LAES pilot plant at Birmingham (UK), we developed for the first time a validated model to address the dynamic performance of LAES. The model allows us to understand the relationship between component and system level performance through dynamic modelling. We found that the temporary storage of cold thermal energy streams using packed beds improves efficiency of LAES by ∼50%. However, due to dynamic cycling charge/discharge, packed beds can bring an undesired 25% increase in the energy expenditure needed to liquefy air. In summary, this work points outs that (a) dynamics of LAES should not be neglected; (b) novel design for cold thermal storage are needed and (c) linking component and system level performance is crucial for energy storage.
Robust wall apposition for flow-diverter stents may be important for endothelialization. Using a large series of experimental aneurysms treated with the Pipeline Embolization Device, the objectives ...of this study were to 1) assess interobserver agreement for the evaluation of wall apposition on posttreatment DSA and evaluate its association with aneurysm occlusion, and 2) measure the relationship between wall apposition assessed with histology and aneurysm occlusion rate after treatment.
Saccular aneurysms were created in 41 rabbits and treated with the Pipeline Embolization Device. DSA was performed just after the deployment of the device and at follow-up. Three investigators independently graded wall apposition on posttreatment DSA as good or poor. A histopathologist blinded to the angiographic results graded the wall apposition on histologic samples. We examined the correlation between angiographic occlusion and wall apposition with histology and angiography.
Wall apposition evaluated on histology was strongly associated with saccular aneurysm occlusion. Sensitivity and specificity of wall apposition to predict complete occlusion at follow-up were 76.9% and 84.0%, respectively, with an overall accuracy of 81.6%. In this experimental study, DSA was suboptimal to assess flow-diverter apposition, with moderate interobserver agreement and low accuracy.
Good wall apposition is strongly associated with complete occlusion after flow-diverter therapy. In this study, DSA was suboptimal for assessing wall apposition of flow-diverter stents. These findings suggest that improved tools for assessing flow diverter-stent wall apposition are highly relevant.
It is a huge challenge in both classical and quantum physics to solve analytically the equation of motion in a strongly anharmonic confinement. For an isolated nanoring, we propose a continuous and ...bounded potential model, which patches up the disadvantages of the usual square-well and parabolic potentials. A fully nonlinear and nonperturbative approach is developed to solve analytically the equation of motion, from which various frequency shifts and dynamic displacements are exactly derived by an order-by-order self-consistent method. A series of new energy levels and new energy states are found, indicating an alternative magnetic response mechanism. In nominally identical rings, especially, we observe a diamagnetic-paramagnetic transition in the period-halving Φ
/2-current with Φ
the flux quantum and a large increase in the Φ
-current at least one order of magnitude, which explain well the experimental observations. This work opens a new way to solve the strong or weak nonlinear problems.
Abstract
A quantum thermal machine is an open quantum system coupled to hot and cold thermal baths. Thus, its dynamics can be well understood using the concepts and tools from non-Hermitian quantum ...systems. A hallmark of non-Hermiticity is the existence of exceptional points where the eigenvalues of a non-Hermitian Hamiltonian or a Liouvillian superoperator and their associated eigenvectors coalesce. Here, we report the experimental realization of a single-ion heat engine and demonstrate the effect of Liouvillian exceptional points on the dynamics and the performance of a quantum heat engine. Our experiments have revealed that operating the engine in the exact- and broken-phases, separated by a Liouvillian exceptional point, respectively during the isochoric heating and cooling strokes of an Otto cycle produces more work and output power and achieves higher efficiency than executing the Otto cycle completely in the exact phase where the system has an oscillatory dynamics and higher coherence. This result opens interesting possibilities for the control of quantum heat engines and will be of interest to other research areas that are concerned with the role of coherence and exceptional points in quantum processes and in work extraction by thermal machines.
Background
Sarcopenia is an age-related disease, which is characterized by a decline in muscle mass and function. It is one of the most important health issues in the elderly and often leads to a ...high rate and variety of adverse outcomes.
Objectives
To evaluate the screening accuracy of SARC-F for sarcopenia in the elderly.
Design
We conducted a meta-analysis using articles available in 6 databases including PubMed (Medline), Web of Science, Embase, Cochrane Controlled Register of Trials (CENTRAL), China Knowledge Resource Integrated Database (CNKI), and Wanfang databases from inception to May 2020. Participants: Adults aged 60 years and older.
Measurements
Sarcopenia was defined by EWGSOP2, EWGSOP, AWGS, FNIH and IWGS. Two authors independently extracted data based on predefined criteria. Where data were available we calculated pooled summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence interval (CI) based on different criteria using the hierarchical logistic regression modeling including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling.
Results
We included 20 studies, with the prevalence of sarcopenia ranging from 6.42% to 21.56%. The number of the literatures using EWGSOP, EWGSOP2, AWGS, IWGS and FNIH as diagnostic criteria was 13, 4, 13, 8, 7, respectively. Bivariate analysis yielded a pooled sensitivity of 32% (95%CI: 19%–47%), 77% (95%CI: 49%–92%), 27% (95%CI: 16%–42%), 39% (95%CI: 27%–52%), 35% (95%CI: 23%–49%) and a pooled specificity of 86% (95%CI:77%–92%), 63% (95%CI: 43%–79%), 91% (95%CI: 85%–95%), 86% (95%CI: 76%–92%), 89% (95%CI: 81%–93%), respectively. The area under the HSROC curve were 0.68 (95%CI: 0.64–0.72), 0.75 (95%CI: 0.71–0.78), 0.73 (95%CI: 0.69–0.77), 0.67 (95%CI: 0.62–0.71), 0.70 (95%CI: 0.65–0.73), respectively.
Conclusions
The screening accuracy of SARC-F was various based on different diagnostic criteria. There were some limitations for SARC-F, however, considering the higher practicability and specificity for screening sarcopenia in practice, SARC-F was still an effective screening tool for sarcopenia in the elderly. And the screening accuracy of SARC-F needs further exploration when EWGSOP2 is applied as diagnostic criteria and geriatric inpatients are the target participants.
The increasing severity of droughts/floods and worsening air quality from increasing aerosols in Asia monsoon regions are the two gravest threats facing over 60% of the world population living in ...Asian monsoon regions. These dual threats have fueled a large body of research in the last decade on the roles of aerosols in impacting Asian monsoon weather and climate. This paper provides a comprehensive review of studies on Asian aerosols, monsoons, and their interactions. The Asian monsoon region is a primary source of emissions of diverse species of aerosols from both anthropogenic and natural origins. The distributions of aerosol loading are strongly influenced by distinct weather and climatic regimes, which are, in turn, modulated by aerosol effects. On a continental scale, aerosols reduce surface insolation and weaken the land‐ocean thermal contrast, thus inhibiting the development of monsoons. Locally, aerosol radiative effects alter the thermodynamic stability and convective potential of the lower atmosphere leading to reduced temperatures, increased atmospheric stability, and weakened wind and atmospheric circulations. The atmospheric thermodynamic state, which determines the formation of clouds, convection, and precipitation, may also be altered by aerosols serving as cloud condensation nuclei or ice nuclei. Absorbing aerosols such as black carbon and desert dust in Asian monsoon regions may also induce dynamical feedback processes, leading to a strengthening of the early monsoon and affecting the subsequent evolution of the monsoon. Many mechanisms have been put forth regarding how aerosols modulate the amplitude, frequency, intensity, and phase of different monsoon climate variables. A wide range of theoretical, observational, and modeling findings on the Asian monsoon, aerosols, and their interactions are synthesized. A new paradigm is proposed on investigating aerosol‐monsoon interactions, in which natural aerosols such as desert dust, black carbon from biomass burning, and biogenic aerosols from vegetation are considered integral components of an intrinsic aerosol‐monsoon climate system, subject to external forcing of global warming, anthropogenic aerosols, and land use and change. Future research on aerosol‐monsoon interactions calls for an integrated approach and international collaborations based on long‐term sustained observations, process measurements, and improved models, as well as using observations to constrain model simulations and projections.
Key Points
The fast‐developing Asia has suffered severe air pollution problem
Aerosol affects the Asian monsoon
Aerosol‐monsoon interactions dictate the climate change in the region
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy ...in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.
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