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Hypoxic-ischemic brain damage (HIBD) usually induces chronic neurological disorder and even acute death, but effective neuroprotective strategy is still limited. Herein, we performed this study to clarify the mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) containing microRNA-93 (miR-93) in influencing this damage via regulation of the histone deacetylase 4 (HDAC4)/B-cell lymphoma-2 (Bcl-2) axis. Initially, differentially expressed Bcl-2 was identified in middle cerebral artery occlusion (MCAO), and the upstream regulatory miR-93 and its potential target HDAC4 were also predicted through bioinformatics analysis. HIBD was modeled in vitro by exposing hippocampal neurons to oxygen-glucose deprivation (OGD) and in vivo by MCAO in rats. EVs were isolated from the bone marrow MSCs of well-grown rats. Our experimental data validated that HDAC4 was highly expressed while miR-93 and Bcl-2 were poorly expressed in MCAO rats. Furthermore, HDAC4 overexpression, through inhibiting Bcl-2 via deacetylation, promoted the infarct volume and pathological changes in hippocampal tissues and neuron apoptosis, and impaired neurobehavioral ability of MCAO rats. Of note, miR-93 was found to target HDAC4. Importantly, MSC-derived EVs overexpressing miR-93 suppressed HDAC4 expression and subsequently impeded the apoptosis of OGD-exposed hippocampal neurons in vitro, and also ameliorated HIBD in vivo. Taken together, miR-93 delivered by MSC-derived EVs can ameliorate HIBD by suppressing hippocampal neuron apoptosis through targeting the HDAC4/Bcl-2 axis, a finding which may be of great significance in the treatment of HIBD.

In this paper, we investigate the wellposedness of the non-isentropic compressible Navier-Stokes/Allen-Cahn system with the heat-conductivity proportional to a positive power of the temperature. This system describes the flow of a two-phase immiscible heat-conducting viscous compressible mixture. The phases are allowed to shrink or grow due to changes of density in the fluid and incorporates their transport with the current. We established the global existence and uniqueness of strong solutions for this system in 1-D, which means no phase separation, vacuum, shock wave, mass or heat or phase concentration will be developed in finite time, although the motion of the two-phase immiscible flow has large oscillations and the interaction between the hydrodynamic and phase-field effects is complex. Our result can be regarded as a natural generalization of the Kazhikhov-Shelukhin's result ([Kazhikhov-Shelukhin. J. Appl. Math. Mech. 41 (1977)]) for the compressible single-phase flow with constant heat conductivity to the non-isentropic compressible immiscible two-phase flow with degenerate and nonlinear heat conductivity.

This paper is devoted to the partial regularity of suitable weak solutions to the system of the incompressible shear-thinning flow in a bounded domain Ω ⊂ ℝn, n ≥ 2. It is proved that there exists a suitable weak solution of the shear-thinning fluid in the n-D smooth bounded domain (for n ≥ 2). For 3D model, it is proved that the singular points are concentrated on a closed set whose 1 dimensional Hausdorff measure is zero.

This paper is concerned with the large-time behavior of solutions to the outflow problem of full compressible Navier-Stokes equations in the half line. This is one of the series of papers by the authors on the stability of nonlinear waves to the outflow problem. We show the time asymptotic stability of degenerate (transonic) stationary solution for the general gas including ideal polytropic gas. The key point of the proof is based the new property of the degenerate stationary solution and the delicate energy estimates.

We study the large-time behavior of strong solutions to the one-dimensional, compressible Navier-Stokes system for a viscous and heat conducting ideal polytropic gas, when the viscosity is constant and the heat conductivity is proportional to a positive power of the temperature. Both the specific volume and the temperature are proved to be bounded from below and above independently of time. Moreover, it is shown that the global solution is nonlinearly exponentially stable as time tends to infinity. Note that the conditions imposed on the initial data are the same as those of the constant heat conductivity case ([Kazhikhov-Shelukhin. J. Appl. Math. Mech. 41 (1977); Kazhikhov. Boundary Value Problems for Hydrodynamical Equations, 50 (1981)] and can be arbitrarily large. Therefore, our result can be regarded as a natural generalization of the Kazhikhov's ones for the constant heat conductivity case to the degenerate and nonlinear one., 21

ABCB1 is an important gene that closely related to analgesic tolerance to opioids, and plays an important role in their postoperative treatment. Recent studies have demonstrated that ABCB1 genotype is significantly associated with the chemico-resistance and chemical sensitivity in breast cancer patients. So, it is become very important to investigate the important role of ABCB1 for predicting drug response in breast cancer patients. In this study, by conducting the Cox proportional hazards regression analysis in breast cancer patients, significant differences were found in prognosis between the ABCB1 high- and low-expression subtypes. Meanwhile, by using immune infiltration profiles as well as transcriptomics datasets, the ABCB1 high subtype was found to be significantly enriched in many immune-related KEGG pathways and biological processes, and was characterized by the high infiltration levels of immune cell types. Furthermore, bioinformatics inference revealed that the ABCB1 subtypes were associated with the therapeutic effect of immunotherapy, which would be important for patient prognosis. In conclusion, these findings may provide useful help for recognizing the diversity between ABCB1 subtypes in tumor immune microenvironment, and may unravel prognosis outcomes and immunotherapy utility for ABCB1 in breast cancer.

Background Sustained morphine treatment for cancer pain has been limited due to analgesic tolerance. Opioid receptor internalization and desensitization mediated by downregulation of mu-opioid receptor (MOR) expression have been confirmed as one of the mechanisms of chronic morphine tolerance. In addition to the opiate system, the α2-adrenergic system is involved in the development of morphine tolerance. Several studies reported that co-administration of α2-adrenoceptor agonist dexmedetomidine inhibits morphine tolerance in normal or neuropathic pain animals. However, the effect of dexmedetomidine on morphine tolerance has not been studied in cancer pain. Therefore, we investigated the effect of intrathecal injection of dexmedetomidine on the development of morphine tolerance in cancer pain and on the expression of MOR in the spinal cord of morphine-tolerant cancer pain rats. Methods The model was established using a rat's right hind paw injection of Walker 256 cancer cells. Subcutaneous morphine (10mg/kg) was administrated twice daily for 7 days; meanwhile, the rats received intrathecal α2-adrenoceptor agonist dexmedetomidine (10μ/kg) or antagonist MK-467 (0.25mg/kg) in test groups. Rats receiving drug vehicle served as the control group. Antinociception was detected by von Frey filaments and hot-plate tests. The expression of MOR in the spinal cord was examined through real-time reverse transcription polymerase chain reaction and Western blotting. The data were analyzed via analysis of variance followed by Student t-test with Bonferroni correction. Results Seven-day chronic morphine administration elicited notable analgesic tolerance in the rats with cancer pain. Co-administration of α2-adrenoceptor agonist dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance, which could be blocked by α2-adrenoceptor antagonist MK-467. Furthermore, pre-treatment of dexmedetomidine significantly upregulated MOR protein expression without a notable change in MOR mRNA expression in the spinal cord. Conclusion Our findings suggest that intrathecal injection of dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance in cancer pain, potentially by upregulating MOR expression in the spinal cord. The α2-adrenoceptor agonist may provide a more versatile analgesia option for morphine treatment for cancer pain.

This paper is concerned with the evolution of the periodic boundary value problem and the mixed boundary value problem for a compressible mixture of binary fluids modeled by the Navier–Stokes–Cahn–Hilliard system in one dimensional space. The global existence and the large time behavior of the strong solutions for these two systems are studied. The solutions are proved to be asymptotically stable even for the large initial disturbance of the density and the large velocity data. We show that the average concentration difference for the two components of the initial state determines the long time behavior of the diffusive interface for the two-phase flow.

In this paper, we study the asymptotic behavior of solution to the initial boundary value problem for the two-fluid non-isentropic Navier–Stokes–Poisson system in a half line ( 0 , ∞ ) . We consider an inflow problem where the gas enter into the region through the boundary for general gases including ideal polytropic gas. On account of the quasineutral assumption and the absence of the electric field for the large time behavior, we show the existence of the stationary solutions with the aid of the center manifold theory, and then we give the rigorous proof of the stability theorem on the stationary solutions under small perturbations for the corresponding initial boundary value problem of the Navier–Stokes–Poisson system. Note that it is the first result for the stability of nonlinear waves on the inflow problem of the Navier–Stokes–Poisson system.

The full Navier-Stokes-Fourier system with mixed boundary condition that describes the motion of shear-thinning and incompressible viscous fluid in a rotating multi-screw extruder is investigated. The viscosity is assumed to depend on the shear rate and the temperature. The global existence of suitable weak solutions is established. The fictitious domain method which consists in filling the moving rigid screws with the surrounding fluid and taking into account the boundary conditions on these bodies by introducing a well-chosen distribution of boundary forces is used.

We are concerned with the Cauchy problem of the two-dimensional (2D) nonhomogeneous incompressible Navier-Stokes equations with vacuum as far-field density. It is proved that if the initial density decays not too slow at infinity, the 2D Cauchy problem of the density-dependent Navier-Stokes equations on the whole space $\mathbb{R}^2$ admits a unique global strong solution. Note that the initial data can be arbitrarily large and the initial density can contain vacuum states and even have compact support. Furthermore, we also obtain the large time decay rates of the spatial gradients of the velocity and the pressure which are the same as those of the homogeneous case., 14 pages. arXiv admin note: text overlap with arXiv:1506.02156; text overlap with arXiv:1310.1673 by other authors

In this article, we use a relaxation scheme for conservation laws to study liquid-vapor phase transition modeled by the van der Waals equation, which introduces a small parameter $e$ and a new variable. We solve the relaxation system in Lagrangian coordinates for one dimension and solve the system in Eulerian coordinates for two dimension. A second order TVD Runge-Kutta splitting scheme is used in time discretization and upwind or MUSCL scheme is used in space discretization. The long time behavior of the fluid is numerically investigated. If the initial data belongs to elliptic region, the solution converges to two Maxwell states. When the initial data lies in metastable region, the solution either remains in the same phase or converges to the Maxwell states depending to the initial perturbation. If the initial state is in the stable region, the solution remains in that region for all time.

This paper is concerned with the large-time behavior of solutions to the outflow problem of full compressible Navier–Stokes equations for the general gas including ideal polytropic gas in the half ...

In this paper, we present a fully discrete local discontinuous Galerkin (LDG) finite element method combined with scalar auxiliary variable (SAV) approach for the compressible Navier–Stokes–Allen–Cahn (NSAC) system. We start with a linear and first order scheme for time discretization and the minimal dissipation LDG for spatial discretization, which is based on the SAV approach and is proved to be unconditionally energy stable for one dimensional case. The velocity, the density and the mass concentration of fluid mixture can be solved separately. In addition, a semi-implicit spectral deferred correction (SDC) method combined with the first order scheme is employed to improve the temporal accuracy. Due to the local properties of the LDG methods, the resulting algebraic equations at the implicit level are easy to implement. In particular, we use efficient and practical multigrid solvers to solve the resulting algebraic equations. Although there is no proof of stability for the semi-implicit SDC with LDG spatial discretization, numerical experiments of the accuracy and long time simulations are presented to illustrate the high order accuracy in both time and space, the discretized energy stablity, the capability and efficiency of the proposed method. Numerical results show that the initial state determines the long time behavior of the diffusive interface for the two–phase flow, which are consistent with theoretical asymptotic stability results in Chen et al. (2018)[1].

In this paper, we study the relaxation limit of interacting shock waves for non-isentropic gas dynamics, such a model is introduced by Jin and Xin for numerical analysis and named as Jin–Xin relaxation system. Given any entropy solution of non-isentropic gas dynamics which consists of two different families of shocks interacting at some positive time, we show that such solution is the relaxation limit for a family of smooth global solutions of the Jin–Xin relaxation system. We remark that, after the interacting time, not only shocks but also contact discontinuity is generated.

In this paper, we develop a fictitious domain method with Distributed Lagrange Multipliers for simulating 2D unsteady shear-thinning non-newtonian incompressible flow in a single-screw and twin-screw extruder. The advantage of the fictitious domain method is that one can use a fixed mesh even as the fluid domain changes in time (as the screws are rotating), eliminating the need for repeated remeshing and projection. The method uses a finite element discretization in space and an operator-splitting technique for discretization in time. Numerical results are given for the flow inside a single-screw extruder or twin-screw extruder, which show that the fictitious domain method is efficient for the problem.

We study the large-time behavior of strong solutions to the equations of a planar magnetohydrodynamic compressible flow with the heat conductivity proportional to a nonnegative power of the temperature. Both the specific volume and the temperature are proved to be bounded from below and above independently of time. Moreover, it is shown that the global strong solution is nonlinearly exponentially stable as time tends to infinity. Our result can be regarded as a natural generalization of the previous ones for the compressible Navier-Stokes system to MHD system with either constant heat-conductivity or nonlinear and temperature-dependent heat-conductivity., 27 pages

In this paper, we study the vanishing viscosity limit for non-isentropic gas dynamics with interacting shocks. Given any entropy solution of non-isentropic gas dynamics which consists of two different families of shocks interacting at some positive time, we show that such solution is the vanishing viscosity limit of a family of smooth global solutions for a viscous system of conservation law. We remark that, after the interacting time, not only shocks but also contact discontinuity are generated.

The unsteady flow of viscous incompressible shear-thinning non-Newtonian fluid with mixed boundary is investigated. The boundary condition on the outflow is the modified natural boundary condition, it contains the additional nonlinear term, which enables us to control the kinetic energy of the backward flow. The global existence of weak solution is proved. The fictitious domain method which consists in filling the moving rigid screws with the surrounding fluid and taking into account the boundary conditions on these bodies by introducing a well-chosen distribution of boundary forces is used.

The authors study the Cauchy problem of the magnetohydrodynamic equations for viscous compressible barotropic flows in two or three spatial dimensions with vacuum as far field density. For two spatial dimensions, we establish the global existence and uniqueness of strong solutions (which may be of possibly large oscillations) provided the smooth initial data are of small total energy, and obtain some a priori decay with rates (in large time) for the pressure, the spatial gradient of both the velocity field and the magnetic field. Moreover, for three spatial dimensions case, some similar decay rates are also obtained.

In this paper, we study the vanishing mean free path limit for interacting shock waves of Broadwell equation. Given any entropy solution of Broadwell model system which consists of two different families of shocks interacting at some positive time, we show that such solution is the vanishing mean free path limit of a family of smooth global solution for the Broadwell model system.

[This corrects the article DOI: 10.21037/atm.2020.04.28.].

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, has been reported to increase the malignancy of breast cancer cells in vitro and stimulate tumor growth in mice. Transmembrane protease serine 2 (TMPRSS2) demonstrates proteolytic activity, resulting in degradation of the extracellular matrix (ECM). This study investigated whether and how TMPRSS2 regulates migration of DEX-treated breast cancer cells. METHODS: Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with DEX and scratch assay was performed. Expressions of TMPRSS2, α2-adrenergic receptor, phospho-STAT3(Tyr705), Rab11, and ECM components were assessed using real-time polymerase chain reaction (real-time PCR), Western blotting, and immunofluorescence staining. ELISA and ultracentrifugation were used to quantify secreted exosomal proteins. Knockdown assay was used to inhibit the expression of TMPRSS2 and Rab11. RESULTS: DEX significantly increased the migration of MCF-7 and MDA-MB-231, which was accompanied by the upregulation and colocalization of TMPRSS2 and α2-adrenergic receptor. Nuclear phospho-STAT3(Tyr705) was increased dramatically following DEX treatment, and TMPRSS2 upregulation was significantly suppressed by the STAT3 inhibitor WP1066. Meanwhile, TMPRSS2 knockdown decreased DEX-induced cellular migration. TMPRSS2 and Rab11 were significantly detected in the media and the isolated exosomes from DEX-treated cells, and their colocalization was also revealed. Rab11 knockdown prevented exosomal TMPRSS2 from increasing in DEX-treated cells. In normal cultured MDA-MB-231, migration was increased by Rab11-positive exosomes isolated from DEX-treated MCF-7. Moreover, transmission electron microscopy showed that Rab11-positive exosomes enriched more components than Rab11-negative exosomes. Additionally, a reduction in ECM components fibronectin, collagen IV, matrix metallopeptidase 16, and Tenascin C was detected after DEX treatment, but was prohibited when TMPRSS2 or Rab11 were knocked down. CONCLUSIONS: This study provides evidence that DEX upregulates TMPRSS2 expression via the activation of α2-adrenergic receptor/STAT3 signaling and promotes TMPRSS2 secretion in exosomes through Rab11, thus resulting in degradation of the ECM, which is responsible for DEX-induced migration of breast cancer cells.

We consider the compressible Navier-Stokes system where the viscosity depends on density and the heat conductivity is proportional to a positive power of the temperature under stress-free and thermally insulated boundary conditions. Under the same conditions on the initial data as those of the constant viscosity and heat conductivity case ([Kazhikhov-Shelukhin. J. Appl. Math. Mech. 41 (1977)], we obtain the existence and uniqueness of global strong solutions. Our result can be regarded as a natural generalization of the Kazhikhov's theory for the constant heat conductivity case to the degenerate and nonlinear one under stress-free and thermally insulated boundary conditions., 13. arXiv admin note: text overlap with arXiv:1809.00467

We deal with the equations of a planar magnetohydrodynamic compressible flow with the viscosity depending on the specific volume of the gas and the heat conductivity proportional to a positive power of the temperature. Under the same conditions on the initial data as those of the constant viscosity and heat conductivity case ([Kazhikhov (1987)], we obtain the global existence and uniqueness of strong solutions which means no shock wave, vacuum, or mass or heat concentration will be developed in finite time, although the motion of the flow has large oscillations and the interaction between the hydrodynamic and magnetodynamic effects is complex. Our result can be regarded as a natural generalization of the Kazhikhov's theory for the constant viscosity and heat conductivity case to that of nonlinear viscosity and degenerate heat-conductivity., Comment: 16. arXiv admin note: text overlap with arXiv:1809.02498

This paper is concerned with the asymptotic stability of the periodic solution to a one-dimensional model system for the compressible viscous van der Waals fluid in Eulerian coordinates. If the initial density and initial momentum are suitably close to the average density and average momentum, then the solution is proved to tend toward a stationary solution as t→∞.

Rarefaction wave solutions for a one-dimensional model system associated with non-Newtonian compressible fluid are investigated in terms of asymptotic stability. The rarefaction wave solution is proved to be asymptotically stable, provided the initial disturbance is suitably small. The proof is given by the elemental L 2 energy method.

We study the blowup phenomena of solutions to the compressible Navier–Stokes equations with density-dependent viscosity coefficients in arbitrary dimensions. By constructing a family of self-similar analytical solutions with spherical symmetry, some interesting information including the blowup and expanding properties are shown. In addition, the case of constant viscosity coefficients is also considered. The approach is based on the phase plane method.

Integrin-linked kinase (ILK), a multidomain focal adhesion protein serine/threonine kinase, plays an essential role in ovarian carcinoma. There are reports that the expression and activity of ILK are increased in ovarian cancer.To test the hypothesis that ILK pathway mediates the apoptosis of ovarian carcinoma SKOV3 cell influencing the cell survival, we performed these studies.We applied lentivirus transfection, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), apoptotic proteins expressions assay, and Hoechst to study our hypothesis.We found that silencing of the ILK increases the cell cytotoxic, growth inhibition, and apoptosis. Moreover, after blocking the activation of ILK with ILK shRNA, up-regulation of pro-apoptotic bax expression and down-regulation of the anti-apoptotic bcl-2 expression were found in ovarian cancer SKOV3 cell line. These were associated with an increasing cleaved caspase-3 activity and chromatin condensation of cell nuclear. Furthermore, the expressions of fas and fas ligand (fasL), belonging to the tumor necrosis factor family and controlling the cell apoptosis, were also enhanced.Thus, these findings indicate that both the intrinsic pathway and the extrinsic death receptor pathway are involved in the process that silencing of the ILK gene induces the apoptosis in ovarian carcinoma SKOV3 cell.

A free boundary problem for the one-dimensional compressible Navier-Stokes equations is investigated. The asymptotic stability of the viscous shock wave is established under some smallness conditions. The proof is given by an elementary energy estimate., Comment: 20 pages

The one-dimensional motion of compressible viscous and heat-conductive fluid is investigated in the half space. By examining the sign of fluid velocity prescribed on the boundary, initial boundary value problems with Dirichlet type boundary conditions are classified into three cases: impermeable wall problem, inflow problem and outflow problem. In this paper, the asymptotic stability of the rarefaction wave, boundary layer solution, and their combination is established for both the impermeable wall problem and the inflow problem under some smallness conditions. The proof is given by an elementary energy method.

We continue to study the large time behavior of the solution to a gas-solid free boundary problem for a one-dimensional model system of compressible viscous gas proposed by us in [SIAM J. Math. Anal., 34 (2003), pp. 1331--1355], where the travelling wave and the rarefaction wave were investigated. In this paper we prove the asymptotic stability of the superposition of a travelling wave and a viscous shock wave under some smallness conditions. The asymptotic behavior of the free boundary is also obtained. The proof is given by the elementary energy estimate.

The inflow problem for a one-dimensional compressible viscous gas on the half line (0,+∞) is investigated. The asymptotic stability on both the viscous shock wave and a superposition of the viscous shock wave and the boundary layer solution is established under some smallness conditions. The proofs are given by an elementary energy method.

The inflow problem in the supersonic case for a one-dimensional compressible viscous gas on the half line (0,+∞) is investigated. A stability theorem concerning the long time behavior of rarefaction wave is established.

In this paper we propose a gas-solid free boundary problem for a one-dimensional model system of a compressible viscous gas associated with the inflow problem, where the solid constantly changes into the gas and produces the inflow of the gas on the free boundary. We first show the existence of the traveling wave solution and its asymptotic stability. We further discuss the case in which the asymptotic state of the solution is given by a combination of the traveling wave solution and rarefaction wave.

This paper analyzes the requirement of a real-life assembly job-shop scheduling, which is different from the classical scheduling problems, ensuring not only the sequences having the minimization makespan as possible, but also the operations processed with the a period. Solving the conflicts of the equipments on which many process will be operated be used at the same time in actual production. First modeling the kind of assembly job-shop schedule problem by timed colored Petri nets, then resolves it in a Branch and Bound way with heuristic rules which gives a near optimization. At the end of the paper, a practical example is described, and the results show that the proposed method is effective.