Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes ...from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia‐preconditioned MSCs (PC‐MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC‐MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR‐21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down‐regulate proinflammatory cytokines (TNF‐α and IL‐1β); and could up‐regulate anti‐inflammatory cytokines (IL‐4 and ‐10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF‐κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC‐MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth‐associated protein 43, synapsin 1, and IL‐10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium‐binding adaptor molecule 1, TNF‐α, IL‐1β, and activation of STAT3 and NF‐κB were sharply decreased. More importantly, exosomes from PC‐MSCs effectively increased the level of miR‐21 in the brain of AD mice. Additionally, replenishment of miR‐21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC‐MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR‐21.—Cui, G.‐H., Wu, J., Mou, F.‐F., Xie, W.‐H., Wang, F.‐B., Wang, Q.‐L., Fang, J., Xu, Y.‐W., Dong, Y.‐R., Liu, J.‐R., Guo, H.‐D. Exosomes derived from hypoxia‐preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 32, 654–668 (2018). www.fasebj.org
Thermal turbulence is well known as a potent means to convey heat across space by a moving fluid. The existence of the boundary layers near the plates, however, bottlenecks its heat-exchange ...capability. Here, we conceptualize a mechanism of thermal vibrational turbulence that breaks through the boundary-layer limitation and achieves massive heat-transport enhancement. When horizontal vibration is applied to the convection cell, a strong shear is induced to the body of fluid near the conducting plates, which destabilizes thermal boundary layers, vigorously triggers the eruptions of thermal plumes, and leads to a heat-transport enhancement by up to 600%. We further reveal that such a vibration-induced shear can very efficiently disrupt the boundary layers. The present findings open a new avenue for research into heat transport and will also bring profound changes in many industrial applications where thermal flux through a fluid is involved and the mechanical vibration is usually inevitable.
This study investigates the effect of vibration on the flow structure transitions in thermal vibrational convection (TVC) systems, which occur when a fluid layer with a temperature gradient is ...excited by vibration. Direct numerical simulation (DNS) of TVC in a two-dimensional enclosed square box is performed over a range of dimensionless vibration amplitudes $0.001 \le a \le 0.3$ and angular frequencies $10^{2} \le \omega \le 10^{7}$, with a fixed Prandtl number of 4.38. The flow visualisation shows the transition behaviour of flow structure upon the varying frequency, characterising three distinct regimes, which are the periodic-circulation regime, columnar regime and columnar-broken regime. Different statistical properties are distinguished from the temperature and velocity fluctuations at the boundary layer and mid-height. Upon transition into the columnar regime, columnar thermal coherent structures are formed, in contrast to the periodic oscillating circulation. These columns are contributed by the merging of thermal plumes near the boundary layer, and the resultant thermal updrafts remain at almost fixed lateral position, leading to a decrease in fluctuations. We further find that the critical point of this transition can be described nicely by the vibrational Rayleigh number ${{Ra}}_{vib}$. As the frequency continues to increase, entering the so-called columnar-broken regime, the columnar structures are broken, and eventually the flow state becomes a large-scale circulation (LSC), characterised by a sudden increase in fluctuations. Finally, a phase diagram is constructed to summarise the flow structure transition over a wide range of vibration amplitude and frequency parameters.
The flow around a rectangular cylinder exhibits intricate features, encompassing phenomena such as separation, reattachment, boundary layer transition, and relaminarization. This study explores the ...intense transport of turbulent fluctuations in these complex flow phenomena, including momentum and turbulent kinetic energy (TKE) transport, for three aspect ratios (L/D=5,10 and 15) at a medium Reynolds number (Re=1000). The connection between these transports and crucial vortical structures is elucidated for the first time. On the lateral side of the cylinder, strong momentum transport occurs, dominated by ejection and sweep events associated with the hairpin vortex. The generation of the LE vortex also leads to active TKE production. The existence of the LE separation bubble, as well as the relaminarization of the downstream boundary layer at L/D=10 and 15, affects the distribution of production terms. This perspective offers an effective yet novel approach that has not been previously addressed in prior researches. The redistribution of TKE results in a disturbance growth, linked to boundary layer transition. The source term reveals that streamwise TKE carried into the recirculating region is closely related to the frequency prior amplified by the LE shear layer. In the wake behind TE, turbulent transports are influenced by vortex shedding patterns.
•Turbulent transports are studied, shedding light on the impact of geometry on flow dynamics.•Turbulent transports are analyzed, helping enhance RANS closure models.•The connection between transport phenomena and crucial vortical structures is elucidated.•The transition and relaminarization of the boundary layer impact turbulent transports.
The heat transfer enhancement achieved by the additional electric field in Rayleigh–Bénard convection (RBC) of a dielectric fluid is numerically studied beyond the Rayleigh number Ra = 105. We ...carried out direct numerical simulations of RBC in a rectangular enclosure under the strong injection condition with a fixed non-dimensional injection parameter C = 10, a fixed mobility number M = 10, two Rayleigh numbers Ra = 105 and Ra = 106, and two Prandtl numbers Pr = 1 and Pr = 10 to investigate the characteristics of flow structure and heat transfer and evaluate the dependence on these parameters. It is observed that the flow structure exhibits multiple states with various steady or unsteady flow patterns such as four cells, three cells, and two cells (up/down). It is found that the introduction of an electric field is an effective way to achieve heat transfer enhancement. The heat flux is augmented more efficiently for a large Prandtl number and a low Rayleigh number, where the electric field has a strong effect relative to buoyancy. It is also found that heat transfer is most efficient when the flow pattern is in a three cells flow state.
Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western ...populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with ...prostate-specific antigen (PSA) levels ≥4.0 ng ml−1 regardless of digital rectal examination (DRE) results or PSA levels <4.0 ng ml−1 and abnormal DRE results were included from 18 large referral hospitals in China. The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer (PCa) and high-grade prostate cancer (HGPCa) at different cutoff values were evaluated. A total of 5220 patients were included in the study, and 2014 (38.6%) of them were diagnosed with PCa. In patients with PSA levels ranging from 4.0 to 10.0 ng ml−1, PSAD was associated with PCa and HGPCa in both univariate (odds ratio OR = 45.15, P < 0.0001 and OR = 25.38, P < 0.0001, respectively) and multivariate analyses (OR = 52.55, P < 0.0001 and OR = 26.05, P < 0.0001, respectively). The areas under the receiver operating characteristic curves (AUCs) of PSAD in predicting PCa and HGPCa were 0.627 and 0.630, respectively. With the PSAD cutoff of 0.10 ng ml−2, we obtained a sensitivity of 88.7% for PCa, and nearly all (89.9%) HGPCa cases could be detected and biopsies could be avoided in 20.2% of the patients (359/1776 cases). Among these patients who avoided biopsies, only 30 cases had HGPCa. We recommend 0.10 ng ml−2 as the proper cutoff value of PSAD, which will obtain a sensitivity of nearly 90% for both PCa and HGPCa. The results of this study should be validated in prospective, population-based multicenter studies.
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