Comparative study of differentiating human pluripotent stem cells into vascular smooth muscle cells in hydrogel-based culture methods

Vascular smooth muscle cells (VSMCs), which provides structural integrity and regulates the diameter of vasculature, are of great potential for modeling vascular-associated diseases and tissue engineering. Here, we presented a detailed comparison of differentiating human pluripotent stem cells (hPSCs) into VSMCs (hPSCs-VSMCs) in four different culture methods, including 2-dimensional (2D) culture, 3-dimensional (3D) PNIPAAm-PEG hydrogel culture, 3-dimensional (3D) alginate hydrogel culture, and transferring 3- dimensional alginate hydrogel culture to 2-dimensional (2D) culture. Both hydrogel-based culture methods could mimic in vivo microenvironment to protect cells from shear force, and avoid cells agglomeration, resulting in the extremely high culture efficiency (e.g., high viability, high purity and high yield) compared with 2D culture. We demonstrated hPSC-VSMCs produced from hydrogel-based culture methods had better contractile phenotypes and the potential of vasculature formation. The transcriptome analysis showed the hPSC-VSMCs derived from hydrogel-based culture methods displayed more upregulated genes in vasculature development, angiogenesis and blood vessel development, extracellular matrix compared with 2D culture. Taken together, hPSC-VSMCs produced from hydrogel-based culture system could be applied in various biomedical fields, and further indicated the suitable development of alginate hydrogel for industrial production by taking all aspects into consideration

The associations between body dissatisfaction, exercise intensity, sleep quality, and depression in university students in southern China

BackgroundIn recent years, depression in early adulthood has become an urgent global public health concern. The university years mark a transitional period from adolescence to adulthood. Young people are required to face academic and life pressures independently, which increases the risk of mental health problems in university.PurposeThe main goal of the current study was to explore the sex differences in depression, body dissatisfaction, sleep quality, and exercise intensity among university students in southern China and to analyze the factors affecting the level of depression among university students.MethodsIn total, 1,258 university students aged 18–23 years were recruited for this study. All participants completed anthropometric measurements, the Self-rating Depression Scale, Physical Activity Rating Scale, and Pittsburgh Sleep Quality Index. Body dissatisfaction levels were measured using sex-appropriate silhouettes.ResultsCompared with young women, young men had higher exercise intensity and sleep quality, whereas young women’s body dissatisfaction and depression levels were significantly higher than those of young men. Sleep quality score (β = 0.34, p < 0.01), sex (β = 0.15, p < 0.01), physical activity score (β = −0.14, p < 0.01), and body dissatisfaction (β = 0.14, p < 0.01) were significant predictive factors of the Self-rating Depression Scale score.ConclusionLow levels of physical dissatisfaction have a positive effect on depression, and high levels of physical activity and quality sleep can also improve depressive symptoms. At the same time, increasing body satisfaction has the effect of increasing physical activity and improving sleep quality. Therefore, there is great potential to prevent and ameliorate depression by reducing body dissatisfaction

TFEB Probably Involved in Midazolam-Disturbed Lysosomal Homeostasis and Its Induced β-Amyloid Accumulation

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, and β-amyloid (Aβ) plays a leading role in the pathogenesis of AD. The transcription factor EB (TFEB), a main regulating factor of autophagy and lysosome biosynthesis, is involved in the pathogenesis of AD by regulating autophagy-lysosomal pathways. To date, the choice of anesthetics during surgery in patients with neurodegenerative diseases and evaluation of the effects and underlying mechanisms in these patients have rarely been reported. In this study, the HEK293-APP cells overexpressing APP and Hela cells were used. The cells were treated with midazolam at different concentrations and at different times, then lysosomes were stained by lysotracker and their morphology was observed under a fluorescence microscope. The number and size of lysosomes were analyzed using the ImageJ software. The levels of TFEB in the nucleus and APP-cleaved intracellular proteins were detected by nuclear separation and Western Blot. Finally, ELISA was used to detect the levels of Aβ40 and Aβ42 in the cells after drug treatment. We found that 30 μM midazolam decreased the number of lysosomes and increased its size in HEK293 and HeLa cells. However, 15 μM midazolam transiently disturbed lysosomal homeostasis at 24 h and recovered it at 36 h. Notably, there was no significant difference in the extent to which lysosomal homeostasis was disturbed between treatments of different concentrations of midazolam at 24 h. In addition, 30 μM midazolam prevents the transport of TFEB to the nucleus in either normal or starved cells. Finally, the intracellular C-terminal fragment β (CTFβ), CTFα, Aβ40 and Aβ42 levels were all significantly elevated in 30 μM midazolam-treated HKE293-APP cells. Collectively, the inhibition of TFEB transport to the nucleus may be involved in midazolam-disturbed lysosomal homeostasis and its induced Aβ accumulation in vitro. The results indicated the risk of accelerating the pathogenesis of AD by midazolam and suggested that TFEB might be a candidate target for reduction of midazolam-dependent neurotoxicity

The Changes of Intrinsic Excitability of Pyramidal Neurons in Anterior Cingulate Cortex in Neuropathic Pain

To find satisfactory treatment strategies for neuropathic pain syndromes, the cellular mechanisms should be illuminated. Central sensitization is a generator of pain hypersensitivity, and is mainly reflected in neuronal hyperexcitability in pain pathway. Neuronal excitability depends on two components, the synaptic inputs and the intrinsic excitability. Previous studies have focused on the synaptic plasticity in different forms of pain. But little is known about the changes of neuronal intrinsic excitability in neuropathic pain. To address this question, whole-cell patch clamp recordings were performed to study the synaptic transmission and neuronal intrinsic excitability 1 week after spared nerve injury (SNI) or sham operation in male C57BL/6J mice. We found increased spontaneous excitatory postsynaptic currents (sEPSC) frequency in layer II/III pyramidal neurons of anterior cingulate cortex (ACC) from mice with neuropathic pain. Elevated intrinsic excitability of these neurons after nerve injury was also picked up, which was reflected in gain of input-output curve, inter-spike interval (ISI), spike threshold and Refractory period (RP). Besides firing rate related to neuronal intrinsic excitability, spike timing also plays an important role in neural information processing. The precision of spike timing measured by standard deviation of spike timing (SDST) was decreased in neuropathic pain state. The electrophysiological studies revealed the elevated intrinsic excitation in layer II/III pyramidal neurons of ACC in mice with neuropathic pain, which might contribute to central excitation

Use of Slag Concrete in Construction of Underground Structures and Mines

The paper considers the possibility of using slag concrete in underground construction. Technological parameters for production of slag concrete with the set properties are defined. The influence of the composition of slag concrete used in the conditions of mine construction on the change of physical and mechanical characteristics, durability and stability is determined. The limits of technological parameters of slag concrete preparation are established. The possibilities of combined use of blast-furnace slags and clinkers for concrete in mine construction are substantiated. The chemical composition of blast furnace slag and the possibility of its application in the composition of concrete is described, the interaction of an aggregate - Portland cement with blast furnace slag is studied. The technique for conducting experiments to determine the rate of strength gain of different types of concrete is described. The rate of strength gains of heavy concrete and the rate of strength gain of slag concrete with additives and without additives have been compared. The possibility of application of this slag concrete in the process of concreting with the use of sliding formwork has been studied

Minimum-Effort Waypoint-Following Differential Geometric Guidance Law Design for Endo-Atmospheric Flight Vehicles

To improve the autonomous flight capability of endo-atmospheric flight vehicles, such as cruise missiles, drones, and other small, low-cost unmanned aerial vehicles (UAVs), a novel minimum-effort waypoint-following differential geometric guidance law (MEWFDGGL) is proposed in this paper. Using the classical differential geometry curve theory, the optimal guidance problem of endo-atmospheric flight vehicles is transformed into an optimal space curve design problem, where the guidance command is the curvature. On the one hand, the change in speed of the flight vehicle is decoupled from the guidance problem. In this way, the widely adopted constant speed hypothesis in the process of designing the guidance law is eliminated, and, hence, the performance of the proposed MEWFDGGL is not influenced by the varying speed of the flight vehicle. On the other hand, considering the onboard computational burden, a suboptimal form of the MEWFDGGL is proposed to solve the problem, where both the complexity and the computational burden of the guidance law dramatically increase as the number of waypoints increases. The theoretical analysis demonstrates that both the original MEWFDGGL and its suboptimal form can be applied to general waypoint-following tasks with an arbitrary number of waypoints. Finally, the superiority and effectiveness of the proposed MEWFDGGL are verified by a numerical simulation and flight experiments

A new equivalent method to obtain the stoichiometric fuel-air cloud from the inhomogeneous cloud based on FLACS-dispersion

ABSTRACT: The fuel-air cloud resulting from an accidental discharge event is normally irregular in shape and varying in concentration. Performance of dispersion simulations using the computational fluid dynamics (CFD)-based tool FLACS can get an uneven and irregular cloud. For the performance of gas explosion study with FLACS, the equivalent stoichiometric fuel-air cloud concept is widely applied to get a representative distribution of explosion loads. The Q9 cloud model that is employed in FLACS is an equivalent fuel-air cloud representation, in which the laminar burning velocity with first order SL and volume expansion ratio are taken into consideration. However, during an explosion in congested areas, the main part of the combustion involves turbulent flame propagation. Hence, to give a more reasonable equivalent fuel-air size, the turbulent burning velocity must be taken into consideration. The paper presents a new equivalent cloud method using the turbulent burning velocity, which is described as a function of SL, deduced from the TNO multi-energy method. Keywords: Explosion, Equivalent approach, Homogenous stoichiometric fuel-air cloud, TNO multi-energy metho