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.
•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
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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
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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
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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.
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.
ObjectiveThe 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.DesignDeep 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.ResultsIn UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales 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. Escherichia phage and Enterobacteria phage 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.ConclusionWe demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales 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.
In order to enhance the performance of the latent heat storage (LHS) process and provide the criterion for the selection and match of the multistage PCMs, the effects of PCMs melting temperatures on ...the heat storage rate, entransy dissipation rate and heat storage quality were numerically analyzed based on the entransy theory. For the single stage LHS unit, although decreasing the PCM melting temperature can augment the heat storage rate, the lower melting temperature causes larger entransy dissipation and reduces the heat storage quality. The larger heat storage rate results in the larger entransy dissipation rate, which is accordant with the entransy dissipation extremum theory. For the two-stage LHS unit with reasonably matching the PCMs melting temperature, the heat storage rate can be augmented and the entransy dissipation rate can be reduced. Then the optimization for the match of the two-stage PCMs melting temperatures was performed based on the entransy theory. The results show that there is an optimal match of the two-stage PCMs melting temperatures to achieve the maximum heat transfer rate or the minimum entransy dissipation rate. And the formulas for the optimum two-stage PCMs temperatures were presented, which can provide the criterions for the selection and match of the PCMs.
The potential of punched winglet type vortex generator (VG) arrays used to enhance air-side heat-transfer performance of finned tube heat exchanger is numerically investigated. The arrays are ...composed of two delta-winglet pairs with two layout modes of continuous and discontinuous winglets. The heat transfer performance of two array arrangements are compared to a conventional large winglet configuration for the Reynolds number ranging from 600 to 2600 based on the tube collar diameter, with the corresponding frontal air velocity ranging from 0.54 to 2.3m/s. The effects of different geometry parameters that include attack angle of delta winglets (β=10deg, β=20deg, β=30deg) and the layout locations are examined. The numerical results show that for the punched VG cases, the effectiveness of the main vortex to the heat transfer enhancement is not fully dominant while the “corner vortex” also shows significant effect on the heat transfer performance. Both heat transfer coefficient and pressure drop increase with the increase of attack angle β for the side arrangements; the arrays with discontinuous winglets show the best heat transfer enhancement, and a significant augmentation of up to 33.8–70.6% in heat transfer coefficient is achieved accompanied by a pressure drop penalty of 43.4–97.2% for the 30deg case compared to the plain fin. For the front arrangements of VGs higher heat transfer enhancement and pressure drop penalty can be obtained compared to that of the side arrangement cases; the case with front continuous winglet arrays has the maximum value of j/f, a corresponding heat transfer improvement of 36.7–81.2% and a pressure drop penalty of 60.7–135.6%.
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