Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as ...plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications.
Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component of this delicate mechanism are ...quite harmful, characterized by a cascade of premature aging that injures a variety of organs, including the nervous system. One part of the nervous system that is impaired in certain DNA repair disorders is the peripheral nerve. Chronic motor, sensory, and sensorimotor polyneuropathies have all been observed in affected individuals, with specific physiologies associated with different categories of DNA repair disorders. Cockayne syndrome has classically been linked to demyelinating polyneuropathies, whereas xeroderma pigmentosum has long been associated with axonal polyneuropathies. Three additional recessive DNA repair disorders are associated with neuropathies, including trichothiodystrophy, Werner syndrome, and ataxia‐telangiectasia. Although plausible biological explanations exist for why the peripheral nerves are specifically vulnerable to impairments of DNA repair, specific mechanisms such as oxidative stress remain largely unexplored in this context, and bear further study. It is also unclear why different DNA repair disorders manifest with different types of neuropathy, and why neuropathy is not universally present in those diseases. Longitudinal physiological monitoring of these neuropathies with serial electrodiagnostic studies may provide valuable noninvasive outcome data in the context of future natural history studies, and thus the responses of these neuropathies may become sentinel outcome measures for future clinical trials of treatments currently in development such as adeno‐associated virus gene replacement therapies.
Human mesenchymal stem cells (hMSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and ...expanded as plastic adherent cells, hMSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates that improve a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. While cell-cell contacts and cell-extracellular matrix interactions mediate 3D cell aggregation, the adaptive changes of hMSC cytoskeleton during self-assembly and associated metabolic reconfiguration may also influence aggregate properties and functional activation. In this study, we investigated the role of actin in regulating 3D hMSC aggregate compaction, fusion, spreading and functional activation. Individual hMSC aggregates with controlled initial cell number were formed by seeding a known number of hMSCs (500, 2000, and 5000 cells/well) in multi-well plates of an ultra-low adherent surface to form multicellular aggregates in individual wells. To assess the influence of actin-mediated contractility on hMSC aggregation and properties, actin modulators, including cytochalasin D (cytoD), nocodazole, lysophosphatidic acid (LPA), and Y-27632, were added at different stages of aggregation and their impacts on hMSC aggregate compaction and apoptosis were monitored. The results suggest that actin-mediated contractility influences hMSC aggregation, compaction, fusion, and spreading on adherent surface. Formation of multi-cellular aggregates significantly upregulated caspase 3/7 expression, expression of C-X-C chemokine receptor type 4 (CXCR-4), cell migration, secretion of prostaglandin E2 (PGE-2) and interleukin 6 (IL-6), and resistance to in vitro ischemic stress. The functional enhancement, however, is dependent on caspase activation, because treatment with Q-VD-OPh, a pan-caspase inhibitor, attenuated CXCR-4 and cytokine secretion. Importantly, comparable ATP/cell levels and significantly reduced mitochondrial membrane potential in aggregates of different sizes suggest that altered mitochondria bioenergetics on 3D aggregation is the primary inducer for apoptosis. Together, the results suggest multicellular aggregation as an effective and nongenetic strategy for hMSC functional activation.
Physical literacy is a concept that is expected to encompass the mind and body in an integrated way to explain, promote, and help sustain human beings＇ fundamental function： movement. According to ...Whitehead（2010）, physical literacy is defined by motivation, especially by competence-based and interest-based motivation. This point of view is consistent with vast amount of research evidence on children and adolescents＇ physical activity behavior. In the article I attempt to interpret and operationalize physical literacy from a perspective that children＇s motivation in physical education is both an innate mental disposition and an acquired/learned attribute. Particularly I rely on the conceptual learning theory and motivation regulation mechanisms of the self-determination theory to argue that in physical education, children should experience tasks that inspire them to embody competence and interest along with self-regulation strategies necessary for developing and sustaining the motivation to move.
Ultrathin nickel-metal-organic framework (Ni-MOF) nanobelts, Ni
20
(C
5
H
6
O
4
)
20
(H
2
O)
8
·40H
2
O (Ni-MIL-77), have been exploited successfully for the fabrication of a non-enzymatic urea ...sensor. Ni-MOF ultrathin nanobelts in alkaline media can be used as an efficient catalyst for urea electrooxidation. As a non-enzymatic urea sensor, Ni-MOF ultrathin nanobelts exhibit a high sensitivity of 118.77 μA mM
−1
cm
−2
, wide linear range of 0.01-7.0 mM, and low detection limit of 2.23 μM (S/N = 3). The selectivity, stability and reliability of ultrathin Ni-MOF nanobelts towards urea oxidation are also investigated. Moreover, Ni-MOF ultrathin nanobelts were further used to detect urea in human body fluids. All these findings confirm that the urea sensor based on Ni-MOF ultrathin nanobelts is successfully prepared and promising for applications in medical diagnostics and environmental monitoring.
Ni-MOF ultrathin nanobelts in alkaline media can be used as an efficient catalyst for urea electrooxidation.
Spontaneous aggregation and the associated enhancement of stemness have been observed in many anchorage dependent cells. Recently, aggregation of human mesenchymal stem cells (hMSCs) in nonadherent ...culture has been shown to reverse expansion-induced heterogeneity and loss of stemness and reprogram the hMSC to reacquire their primitive phenotype, a phenomenon that can significantly enhance therapeutic applications of hMSC. The objective of this study was to investigate the mechanistic basis underlying the connection between multicellular aggregation and stemness enhancement in hMSC by testing the hypothesis that cellular events induced during three-dimensional aggregation on nonadherent substratum induces changes in mitochondrial metabolism that promote the expression of stem cell genes Oct4, Sox2, and Nanog. Our results show that aggregation changes mitochondrial morphology and reduces mitochondrial membrane potential, resulting in a metabolic reconfiguration characterized by increased glycolytic and anaplerotic flux, and activation of autophagy. We further demonstrate that interrupting mitochondrial respiration in two-dimensional planar culture with small molecule inhibitors partially recapitulates the aggregation-mediated enhancement in stem cell properties, whereas enhancement of mitochondrial oxidative phosphorylation in the aggregated state reduces the aggregation-induced upregulation of Oct4, Sox2, and Nanog. Our findings demonstrate that aggregation-induced metabolic reconfiguration plays a central role in reacquisition of primitive hMSC phenotypic properties. Stem Cells 2017;35:398-410.
Non‐iridescent structural colors of high color visibility are produced by amorphous photonic structures, in which natural cuttlefish ink is used as an additive to break down the long‐range order of ...the structures. The color hue and its spectral purity can be tuned by adjusting the diameter of the polystyrene (PS) spheres and the proportion of ink particles.
•100 ppm of silicon oxide shows improvement in ignition delay and cylinder pressure.•Brake thermal efficiency improvement of 15.4% is achieved by 25 ppm silicon oxide.•Carbon nanotubes show increase ...in carbon monoxide with the increase of its amount.•Silicon oxide shows 0.88 vol% reduction of carbon dioxide is achieved at all loads.•All fuel blends show large reduction of unburned hydrocarbon.
This research investigates the effect of nanoparticle-diesel fuel blends on combustion characteristics, performances and exhaust emissions of a four-stroke single-cylinder diesel engine. Three types of nanoparticles employed in this experiment were aluminium oxide, carbon nanotubes and silicon oxide. The nanoparticles were dispersed in a dosage of 25 ppm, 50 ppm and 100 ppm with pure diesel and were labelled as DA25, DA50, DA100 (aluminium oxide blends), DC25, DC50, DC100 (carbon nanotubes blends) and DS25, DS50, DS100 (silicon oxide blends). The ultraviolet-visible spectrophotometer analysis was done for 200 h to quantify the stability of the nanoparticle-diesel fuel blends. The blended fuels were experimentally tested with YANMAR TF120M diesel engine at engine loads of 0%, 25%, 50%, 75% and 100% at a constant 1800 rpm engine speed. The results revealed that the brake specific fuel consumption reduced by up to 19.8% and brake thermal efficiency enhanced by 18.8%. Silicon oxide blends show better results than aluminium oxide blends in many aspects, such as higher combustion pressure, lower brake specific fuel consumption and lower carbon monoxide emissions. Aluminium oxide and silicon oxide show stable blend conditions with 28.1% and 22.0% absorption ratio at 200 h sedimentation time, while carbon nanotube blends were least stable with absorption ratio reducing to less than 30% after 10 h. Combustion analysis of carbon nanotube blends with diesel show that carbon nanotubes have the potential to be further researched as an additive for diesel fuel due to significant combustion improvement in NOx emissions. However, the issue on the stability of carbon nanotube blends must be resolved before its potential can be fully utilized.
A high configurational entropy, achieved through a proper design of compositions, can minimize the Gibbs free energy and stabilize the quasi‐equilibrium phases in a solid‐solution form. This leads to ...the development of high‐entropy materials with unique structural characteristics and excellent performance, which otherwise could not be achieved through conventional pathways. This work develops a high‐entropy nonlinear dielectric system, based on the expansion of lead magnesium niobate–lead titanate. A dense and uniform distribution of nano‐polar regions is observed in the samples owing to the addition of Ba, Hf, and Zr ions, which lead to enhanced performance of nonlinear dielectrics. The fact that no structural phase transformation is detected up to 250 °C, and no noticeable change or a steep drop in structural and electrical characteristics is observed at high temperatures suggests a robust thermal stability of the dielectric systems developed. With these advantages, these materials hold vast potential for applications such as dielectric energy storage, dielectric tunability, and electrocaloric effect. Thus, this work offers a new high‐entropy configuration with elemental modulation, with enhanced dielectric material features.
This work creates a high‐entropy nonlinear dielectric system based on the expansion of lead magnesium niobate–lead titanate with the additive Ba, Hf, and Zr ions. The structural phase transformation is not detected up to 250 °C, accompanied by excellent thermal stability at high temperatures on the structural and electrical characteristics. With these advantages, these materials hold vast potential applications.
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