Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
A highly efficient thermal strategy to manage a high-powered Li-ion battery package within the required safe temperature range is of great demand for electric vehicles (EVs) applications. A ...sandwiched cooling structure using copper metal foam saturated with phase change materials was designed. The thermal efficiency of the system was experimentally evaluated and compared with two control cases: a cooling mode with pure phase change materials and an air-cooling mode. The results showed that the thermal management with air natural convection cannot fulfill the safety demand of the Li-ion battery. The use of pure PCM can dramatically reduce the surface temperature and maintain the temperature within an allowable range due to the latent heat absorption and the natural convection of the melted PCM during the melting process. The foam-paraffin composite further reduced the battery's surface temperature and improved the uniformity of the temperature distribution caused by the improvement of the effective thermal conductivity. Additionally, the battery surface temperature increased with an increase in the porosity and the pore density of the metal foam.
•Cooling structure for Li-ion battery using foam-paraffin composite was designed.•Thermal management by air natural convection cannot fulfill battery safety demand.•Employment of pure PCM dramatically reduced battery surface temperature.•Integration of copper foam and paraffin further reduced battery temperature.•Battery surface temperature increased with increase in porosity and pore density.
•Effects of metal foams parameters on PCM LHS were investigated by LBM.•Increasing PPI improves heat conduction, but weakens natural convection.•Decreasing porosity improves TES rate, but decreases ...TES density.•An optimum structure with porosity of 0.94 and PPI of 45 is recommended.•An enhancement method with nonuniform porosity was proposed.
Lattice Boltzmann method (LBM) was used to investigate the latent heat storage (LHS) performance of metal foams/paraffin composite phase change material (CPCM). The effects of metal foams PPI (number of pores per inch) and porosity on PCM melting rate, heat storage capacity and heat storage density were investigated. The results show that the CPCM heat transfer performance is determined by both heat conduction and natural convection. Increasing PPI can enhance heat conduction, but weaken natural convection. When the porosity is small, increasing PPI can enhance LHS performance. When the porosity is large, decreasing PPI can enhance the performance. With porosity decreasing, CPCM heat storage rate is improved and the maximum heat storage capacity almost keeps constant, but the heat storage density dramatically reduces. An optimum metal foams structure with porosity of 0.94 and PPI of 45 is recommended. Further, a performance enhancement scheme with nonuniform metal foams porosity was proposed and numerically validated. The results show that the proposed scheme can improve the uniformity of the heat transfer process and enhance the heat transfer performance.
Aims/hypothesis
Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP-activated protein kinase (AMPK), and ...the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated.
Methods
2-Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and
ob
/
ob
mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system.
Results
Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in
ob
/
ob
mice.
Conclusions/interpretation
This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in
ob
/
ob
mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes.
► A more detailed three-dimensional model of PTC was proposed by combining FVM and MCRT method. ► Corresponding codes and solving methods were developed and applied to an LS2 PTC. ► Numerical results ...proved that the model and method is feasible and reliable. ► More details of the characteristics in the receiver were revealed and discussed. ► Typical HTF types and residual gas conditions were further studied.
In this paper, a more detailed three-dimensional computational model of the whole parabolic trough solar collector (PTC) system and corresponding numerical simulations by combining the Finite Volume Method (FVM) and the Monte Carlo Ray-Trace (MCRT) method were presented. Corresponding codes and solving methods were also developed and applied to simulate and analyze the total involuted photo-thermal conversion process of an experimental LS2 PTC system. The numerical results were compared with experimental data and good agreement was obtained, proving that the model and method used in the present study is feasible and reliable. More details of the characteristics of solar concentrating, solar collecting, fluid dynamics, coupled heat transfer and the whole flow and temperature fields in the receiver were also revealed and discussed. Then some typical heat transfer fluid (HTF) types and residual gas conditions were further studied. It was revealed that the properties of these HTFs/conditions and their varying relations of the fluid temperature affected the characteristics of fluid dynamics, coupled heat transfer and the whole temperature distributions in the receiver, thus affected the thermal loss and the collector efficiency synthetically.
•Nanocomposite phase change materials were prepared and characterized.•Larger specific surface area is more efficient to enhance specific heat.•Columnar structure is more efficient to enhance thermal ...conductivity.•Thermal conductivity enhancement is the key.•Single walled carbon nanotube is the optimal nanomaterial additive.
To enhance the performance of high temperature salt phase change material, four kinds of carbon nanomaterials with different microstructures were mixed into binary carbonate eutectic salts to prepare carbonate salt/nanomaterial composite phase change material. The microstructures of the nanomaterial and composite phase change material were characterized by scanning electron microscope. The thermal properties such as melting point, melting enthalpy, specific heat, thermal conductivity and total thermal energy storage capacity were characterized. The results show that the nanomaterial microstructure has great effects on composite phase change material thermal properties. The sheet structure Graphene is the best additive to enhance specific heat, which could be enhanced up to 18.57%. The single walled carbon nanotube with columnar structure is the best additive to enhance thermal conductivity, which could be enhanced up to 56.98%. Melting point increases but melting enthalpy decreases with nanomaterial specific surface area increase. Although the additives decrease the melting enthalpy of composite phase change material, they also enhance the specific heat. As a combined result, the additives have little effects on thermal energy storage capacity. So, for phase change material performance enhancement, more emphasis should be placed on thermal conductivity enhancement and single walled carbon nanotube is the optimal nanomaterial additive.
► Increasing HTF inlet parameters can improve PCTES performance. ► The inlet parameters restrict each other for the rated solar collector. ► The PCTES performance can be effectively enhanced by ...enhanced tubes. ► The pressure drops caused by the enhanced tubes could almost be neglected.
Based on enthalpy method, numerical studies were performed for high temperature molten salt phase change thermal energy storage (PCTES) unit used in a dish solar thermal power generation system. Firstly, the effects of the heat transfer fluid (HTF) inlet temperature and velocity on the PCTES performance were examined. The results show that although increasing the HTF inlet velocity or temperature can enhance the melting rate of the phase change material (PCM) and improve the performance of the PCTES unit, the two parameters will restrict each other for the fixed solar collector heat output. Then three enhanced tubes were adopted to improve the PCTES performance, which are dimpled tube, cone-finned tube and helically-finned tube respectively. The effects of the enhanced tubes on the PCM melting rate, solid–liquid interface, TES capacity, TES efficiency and HTF outlet temperature were discussed. The results show that compared with the smooth tube, all of the three enhanced tubes could improve the PCM melting rate. At the same working conditions, the melting time is 437.92min for the smooth tube, 350.75min for dimpled tube which is reduced about 19.9% and 320.25min for cone-finned tube which is reduced about 26.9% and 302.75min for helically-finned tube reduced about 30.7%. As a conclusion, the thermal performance of PCTES unit can be effectively enhanced by using enhanced tube instead of smooth tube. Although, the HTF pressure drops for the enhanced tubes are also larger than that of the smooth tube, the largest pressure drop (1476.2Pa) is still very lower compared with the working pressure (MPa magnitude) of the dish solar generation system. So, the pressure drops caused by the enhanced tubes could almost be neglected.
Abstract We report the phase-resolved spectral results of the first Galactic pulsating ultraluminous X-ray source (PULX) Swift J0243.6+6124, modeling its 2017–2018 outburst peak using data collected ...by the Hard X-ray Modulation Telescope (Insight-HXMT). The broad energy coverage of Insight-HXMT allows us to obtain a more accurate spectral continuum to reduce the coupling of broad iron line profiles with other components. We use three different continuum spectrum models but obtain similar iron line results. For the first time, we detect the pulse characteristics of the broad iron line in a PULX. The variation in the width and intensity of this iron line with σ ∼ 1.2–1.5 keV has a phase offset of about 0.25 from the pulse phase. We suggest that the uneven irradiation of the thick inner disk by the accretion column produces the modulated variation of the broad iron line. In addition, the nonpulsed narrow line is suggested to come from the outer disk region.
The pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study ...aims to characterise the mucosal virome and their functions in health and UC.
Deep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2.
In UC, there was an expansion of mucosa viruses, particularly
bacteriophages, and a decrease in mucosa
diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls.
and
were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC.
We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of
bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.