BACKGROUND AND PURPOSE In this study, we compared the different effect of Dimethyl-2-ketoglutarate (DMKG) on energy metabolism, autophagy, and apoptosis between parental and doxorubicin-resistant liver cancer cell lines. EXPERIMENTAL APPROACH In the energy metabolism section, cell viability, adenosine triphosphate (ATP) level, doxorubicin (DOX) content, energy metabolism phenotype, and enzymes expression were measured. In the autophagy part, autophagy vesicles were observed, enzymes expression and cell viability were detected. Apoptosis rate and expression of enzymes were detected in the apoptosis part. KEY RESULTS DMKG can directly act on ATP synthase and prolyl hydroxylase, affecting the cellular oxidative phosphorylation and glycolysis levels, respectively, in both SMMC-7721 and SMMC-7721/DOX cells. However, its practical effects depend on the function of the mitochondrial malate-aspartate shuttle. Furthermore, ATP-reduced cell autophagy had partial anti-apoptotic effects in SMMC-7721 cells, which is an important reason for the weak inhibition of cell viability observed at low doses of DMKG. In contrast, DMKG showed no significant effect on autophagy but a high cell death rate in SMMC-7721/DOX cells. Induced high expression levels of p-AMPK, p-mTOR, and Bcl-2 could inhibit DMKG-induced apoptosis in SMMC-7721 cells. However, activation of Caspase-3 was the most important molecular effect that was observed in relation to the DMKG-induced apoptosis in SMMC-7721/DOX cells. CONCLUSIONS AND IMPLICATIONS These results suggest that inhibition of energy metabolism can reduce the effects of autophagy in DOX resistant cells, which could improve the therapeutic outcomes and reverse the resistance to chemotherapeutic drugs. This article provides a new idea and method for reversing tumor resistance.

Background and purposes Preeclampsia(PE) is associated with abnormal function of various factors in placentas. 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is abundantly expressed in placenta and controls the local availability of glucocorticoids. We aimed to elucidate the role of 11β-HSD2 in the pathogenesis of PE. Experimental approach Pregnant rats were administrated with 11β-HSD2 inhibitor carbenoxolone (CBX) subcutaneously or by placenta-targeted delivery system. The blood pressure, renal and placental morphology, placental blood flow and circulatory levels of fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were subsequently examined. Cultured human trophoblasts were used to investigate the role of 11β-HSD2 in migration and invasion function and sFlt1 release in vitro. Key results Subcutaneous administration and placenta-targeted delivery of CBX resulted in the hallmark of PE-like features including hypertension, proteinuria, renal damages, elevated circulatory sFlt1 level and increased sFlt1/ PlGF in pregnant rats. These animals displayed reduced trophoblast invasion in uterus, impaired spiral artery remodeling and reduced placental blood flow. In vitro study showed that 11β-HSD2 dysfunction inhibited migration and invasion of the extravillous trophoblasts and promoted sFlt1 release in syncytiotrophoblasts. Mechanically, sFlt1 release induced by 11β-HSD2 dysfunction is mediated by enhancement of a disintegrin and metalloprotease (ADAM)17 transcription in placenta.

Background and purpose: Amphetamine use disorder is a serious health concern, but surprisingly little is known about the vulnerability to the moderate and compulsive use of this psychostimulant and its underlying mechanisms. Previous research showed that inherited serotonin transporter (SERT) down-regulation increases the motor response to cocaine, as well as moderate and compulsive intake of this psychostimulant. Here we sought to investigate whether these findings generalize to amphetamine and the underlying mechanisms in the nucleus accumbens. Experimental Approach: In serotonin transporter knockout (SERT−/−) and wild-type control (SERT+/+) rats we assessed the locomotor response to acute amphetamine (AMPH) and intravenous AMPH self-administration under short access (ShA: 1 hr daily sessions) and long access (LgA: 6 hr daily sessions) conditions. 24 hrs after AMPH self-administration we analysed the expression of glutamate system components in the nucleus accumbens shell and core. Key results: We found that SERT−/− animals displayed an increased AMPH-induced locomotor response and increased AMPH self-administration under LgA, but not ShA conditions. Further, we observed changes in the vesicular and glial glutamate transporters, NMDA and AMPA receptor subunits and their respective postsynaptic scaffolding proteins as function of serotonin transporter genotype, AMPH exposure (baseline, ShA and LgA) and nucleus accumbens sub region. Conclusion and implications: We demonstrate that SERT gene deletion increases the psychomotor and reinforcing effects of AMPH, and that the latter is potentially mediated, at least in part, by homeostatic changes in the glutamatergic synapse of the nucleus accumbens shell and/or core.

This paper presents the optimum exponent of Barlat-Lian (1989) yield function which defines the yield surface shape for different materials under plane stress condition. The predictions of the optimum exponents of Barlat-Lian (1989) yield function are derived and then compared with the experimental data for these materials to allow a better representation of the plastic behavior of the orthotropic sheet metals. The results show that contrary to what it was supposed to be up to now the optimum exponent of Barlat-Lian could be have different values for verity of face and body centered cubic types of materials case by case.

Fluctuating resource hypothesis proposed that resource fluctuation facilitates the successful invasion of exotic plant. Biotic resistance hypothesis proposed that more species rich communities should be more resistant to invasion. Here, we synthesize these ideas in a single experiment with the invader, Chromolaena odorata in 315 artificial communities with resident plants from native and non-native ranges. We found that the effects of nutrient fluctuation on invasion success are contingent on resident origin (native vs. non-native range), and this effect was weaker in more species rich communities. Our results suggest a novel twist on the fluctuating resource hypothesis: suggesting that it is more powerful in species poor communities of non-native origin. This also suggests that competition for fluctuating resources may be one mechanism governing biotic resistance hypothesis (e.g. the effects of richness were greater when resources were fluctuating).

Objective: To study the pregnancy outcomes of vaginal delivery and neonatal prognosis during the epidemic of COVID-19, and to summarize the management of vaginal delivery. Design: Retrospective review of medical records Setting: Zhongnan Hospital of Wuhan University, Wuhan, China Sample: Pregnant women (n=63) with vaginal delivery from January 20 to March 02, 2020 Methods: Retrospectively analyzed the outcomes of vaginal delivery in 10 pregnant women with clinical diagnosis of COVID-19 and 53 pregnant women without COVID-19 from January 20 to March 02, 2020. The related laboratory tests, imaging tests and the SARS-CoV-2 nucleic acid tests results were also analyzed in neonates delivered by pregnant woman with clinical diagnosis of COVID-19. Main Outcome Measures: Delivery outcomes and neonatal outcomes Results: (1) There were no significant differences in gestational weeks, postpartum hemorrhage (245±49.72ml vs 237±85.99ml), and perineal resection rates (10% vs 7.55%) between the two groups. (2) There were no significant differences in birth weight of neonates(3283±449g vs 3274±456g) and neonatal asphyxia between the two groups. Results of the blood routine, throat swabs test for nucleic acid of SARS-CoV-2 and chest radiograph of neonates delivered by pregnant woman with clinical diagnosis of COVID-19 showed no signs of the SARS-CoV-2 infection. Conclusions: Pregnant women with mild COVID-19 can delivery vaginally without exacerbation of COVID-19 and without increasing the risk of SARS-CoV-2 infection in the neonates. Keywords: COVID-19；outcomes of vaginal delivery；neonatal prognosis；management Tweetable abstract：Pregnant women with mild COVID-19 can try vaginal delivery

Quantifying the influences of factors on Normalized Difference Vegetation Index (NDVI) changes is critical to understanding the functions of terrestrial ecosystems. However, identification of the causes responsible for vegetation changes is still limited. We applied the Geographic Detector to quantify the individual and interactive influences of human and natural factors on the change in the vegetation NDVI,and determined the optimal characteristics of factors that are beneficial to vegetation growth. Our results show that vegetation cover for 2000 and 2015 is in good condition, and regions with NDVI > 0.6 showed a significant transformation, whereas areas with mid-high vegetation or lower and areas with high vegetation increased and decreased, respectively. Vegetation cover changes were mainly in the upper reaches of the Minjiang River and its tributaries. We illustrated that the elevation, annual average temperature, and soil type can satisfactorily account for the vegetation changes with explanatory powers of 60%, 52% and 39% or larger, respectively. Land use types and distance from the road had enhanced influences in the NDVI changes with explanatory powers of less than 16% and 12%, respectively. We proposed that there are interactive effects between the impact factors on vegetation NDVI, and the synergistic effects of the impact factors showed mutual enhancement and nonlinear enhancement. The interaction between the two factors strengthens the influence of each individual factor on the vegetation changes. This study provides important references that policymakers can use to intervene and promote vegetation change for ecological protection and vegetation restoration, while alleviating environmental degradation.

This study investigates the trunnion crack of a 50 MW hydraulic turbine in the generator guide bearing. The crack area has been examined metallographically and the fixing method for the the trunnion crack has been explained. Result of the study shows that the reason for the formation of the bearing trunnion crack can be the thermal stresses that occur during the mounting of the bearing trunnion to the turbine shaft and the material fatigue that occurs during the operation of the hydraulic turbine.

In this paper we consider a class of chemotaxis models with two arbitrary constitutive functions g(u) and f(v). After having performed a complete symmetry group classification with respect to them the reduced systems are derived. By considering g(u) of the logistic form wide classes of exact solutions are found.

In this paper, we mainly focus on the theory of evolution of wave polarization in the normal direction of the curved path, which is assumed to be the trajectory of the propagated light beam. The polarization state of the wave is described by the unit complex transverse field component by eliminating the longitudinal field component, which reduces the dimension of the problem. A Coriolis term is also effectively used to describe the relationship between the geometric phase and the parallel transport law of the wave polarization vector of the evolving light beam in the normal direction of the curved path. We further present a unified geometric interpretation of the binormal evolution of the wave polarization vector in the normal direction of the curved path via the nonlinear Schrodinger equation of repulsive type. Finally, we can sum up these discussions by investigating the analytic solutions of the nonlinear Schrodinger equation of repulsive type, which represents binormal evolution of the polarization vector in the normal direction of the curved path trajectory, for some special cases by using the traveling wave hypothesis approach.

The paper investigates exact solutions of the resonant nonlinear Shr¨odinger’s equation (RNLSE) with Kerr law nonlinearity by using the extended direct algebraic method. Graphs of some obtained solutions are presented with dierent values of parameters to describe their propagation. In order to understand the bifurcation structure of nonlinear and super-nonlinear travelling wave solutions of the considered equation, bifurcation analysis has been practiced. Moreover, a set of non-trivial and rst-order conserved quantities are computed by multiplier approach.

By means of the techniques of the real analysis and the weight functions, a few equivalent conditions of a Hilbert-type integral inequality with the general nonhomogeneous kernel in the whole plane are obtained. The constant factor is proved to be the best possible. As applications, a few equivalent conditions of a Hilbert-type integral inequality with the general homogeneous kernel in the whole plane are deduced. We also consider the operator expressions, a few particular cases and some examples. KEY WORDS: Hilbert-type integral inequality; weight function; equivalent form; operator; norm 2000 MATHEMATICS SUBJECT CLASSIFICATION. 26D15

This paper analyzes a SIS model for infectious diseases with two classes of individuals with different susceptibilities. It focuses in a transition function between both classes of susceptible individuals depending on the density of the infected population. A classification of all the possible bifurcation diagrams that the model can present is done. Specifically, some conditions for the simultaneous existence of backward bifurcation and multiple endemic states are shown.

Present contribution has consisted of a construction of a class of new shooting methods and application to Darcy Forchheimer fluid flow over the linearly stretching sheet under the influence of thermal radiations. Governing equations of the flow phenomena are presented in the form of partial differential equations, and these governing partial differential equations are reduced into ordinary differential equations. The final ordinary differential equations are resolved by the present given shooting method based on the class of Adam Moulton's techniques with the Gauss-Siedel iterative method. Since the system of the first-order differential is discretized by the Adam Moulton method with the Gauss-Siedel iterative method containing some unknown initial conditions, a shooting approach is employed for finding unknown initial conditions. Also, it is proved that the Adam Moulton methods using Gauss-Seidel iterative method are unconditionally stable for any system of differential equations. In additions to this, finite element simulations containing velocity profile, streamlines, temperature profile and temperature contours are deliberated with the help of graphs, and tables. Thus, the main aim of the current paper is to calculate the unique results for a coupling approach based on Adams Moulton's method for the boundary layer flow problem with the effect of heat transfer.

Potato is among one of the most important food crops, yet maintaining plant productivity in this drought-sensitive crop has become a challenge. Competition for scarce water resources and the continued effects of global warming exacerbate current constraints on crop production. While plants’ response to drought in above-ground tissues has been well documented, the regulatory cascades in developing tubers have been largely unexplored. Using the commercial Canadian cultivar ‘Vigor’, plants were subjected to a drought treatment under high-tunnels causing a 4 ℃ increase in canopy temperature when compared to the well-watered control. Tubers were sampled for RNAseq and metabolite analysis. Approximately 2600 genes and 3898 transcripts were differentially expressed by at least four-fold in drought-stressed potato tubers, with 75 % and 69 % being down-regulated respectively. A further 229 small RNAs were implicated in gene regulation during drought. The comparison of protein homologues between Solanum tuberosum L. and Arabidopsis thaliana L. indicates that downregulated genes are associated with phenylpropanoid, carotenoid and patatin biosynthesis. This suggests that there are nutritive implications to drought stress occurring during the potato tuber bulking phase in sensitive cultivars.

We are proposing a new hypothesis for the antiviral mechanism of hydroxychloroquine (HCQ), based on our computer aided docking studies. HCQ is a clinical trial drug under investigation for the treatment of Covid-19 pandemic. SARS-CoV-2 is the causative agent of the Covid-19 and it binds to host’s bromodomain proteins BRD-2/4. The bromodomain proteins are readers of acetylated histones and play a critical role for host’s hype-immune response to this pathogen. Covid-19 virus protein E mimics acetylated histones and binds at the same site on BRD-2. We propose that the hijacking of BRD-2/4 by SARS-CoV-2, can be thwarted by the use of inhibitors of BRD-2/4. Preliminaryin-silico docking studies with HCQ, indicates that it binds to the same pocket on BRD-2 where viral envelope protein E binds. Therefore, HCQ may acts as a BRD-2 inhibitor, thereby preventing “cytokine storm” initiated by SARS-CoV-2 virus. Another FDA approved drug celecoxib (Celebrex) binds in the same pocket of BRD-2 and the key amino acid interactions between the drug and protein are conserved. Thus, celecoxib may offer innovative path for controlling the Covid-19 pandemic.

In this paper, we consider a laminated beams system with frictional damping and an internal distributed delay feedback on the effective rotational angle. With appropriate assumptions on the weight of the delay feedback and wave speeds, we prove that the dissipation through the frictional damping is sufficiently strong to uniformly stabilize the system even in the presence of delay.

A document by Sezai KIZILTUĞ, written on Authorea.

In this paper, we define a non-iterative transformation method for an Extended Blasius Problem. The original non-iterative transformation method, which is based on scaling invariance properties, was defined for the classical Blasius problem by T\”opfer in 1912. This method allows us to solve numerically a boundary value problem by solving a related initial value problem and then rescaling the obtained numerical solution. In recent years, we have seen applications of the non-iterative transformation method to several problems of interest. The obtained numerical results are improved by both a mesh refinement strategy and Richardson’s extrapolation technique. In this way, we can be confident that the computed six decimal places are correct.

The study of liquid crystals is one of the active areas of research in physics. In this paper, the MLPG and direct MLPG (DMLPG) methods are used for the numerical study of the coupled nonlinear sine-Gordon equations in two dimensions arising from the modeling of some phenomena in the liquid crystals and superconductors. A comparison of numerical results between the MLPG and DMLPG methods highlight the precision and speed of the DMLPG method.

in this work, we introduce an efficient meshless technique for solving the two-dimensional variable-order time-fractional mobile/immobile advection-diffusion model with Dirichlet boundary conditions. The main advantage of this scheme is to obtain a global approximation for this problem which reduces such problems to a system of algebraic equations. To approximate the first and fractional variable-order against the time, we use the finite difference relations. The proposed method is based on the Moving Kriging (MK) interpolation shape functions. To discretization this model in space variables, we use the MK interpolation. Duo to the fact that the shape functions of MK have Kronecker’s delta property, boundary conditions are imposed directly and easily. To illustrate the capability of the proposed technique on regular and irregular domains, several examples are presented in different kinds of domains and with uniform and nonuniform nodes. Also, we use this scheme to simulating anomalous contaminant diffusion in underground reservoirs.

The current work is devoted for operating the Lie symmetry approach, to coupled complex short pulse equation. The method reduces the coupled complex short pulse equation to a system of ordinary differential equations with the help of suitable similarity transformations. Consequently, these systems of nonlinear ordinary differential equations under each subalgeras are solved for traveling wave solutions. Further, with the help of similarity variable, similarity solutions and traveling wave solutions of nonlinear ordinary differential equation, complex soliton solutions of the coupled complex short pulse equation are obtained which are in form of sinh, cosh, sin and cos functions.

Mahavier and Montgomery construct a Sobolev space for approximate solution of linear initial value problems in a finite difference setting in SINGLE-ITERATION SOBOLEV DESCENT FOR LINEAR INITIAL VALUE PROBLEMS, Mahavier, Montgomery, MJMS, 2013. Their Sobolev space is constructed so that gradient-descent converges to a solution in a single iteration, demonstrating the existence of a best Sobolev gradient for finite difference approximation of solutions of linear initial value problems. They then ask if there is a broader class of problems for which convergence in a single iteration in an appropriate Sobolev space occurs. We use their results to show the existence of single-step iteration to solution in a lower dimensional Sobolev space for their examples and then a class of problems for single-step convergence.

Background and Purpose - Growing evidence supports a central role of NADPH oxidases (NOXs) in the regulation of platelets. Experimental Approach - Here, we characterise the NOX inhibitor 2-acetylphenothiazine (2APT) and nine of its chemical derivatives for their selectivity, their effect on platelet activation in response to different stimuli ex vivo, and their modulation of carotid thrombosis and hemostasis in vivo. Key Results - Using Nox1-/- mice, we proved that NOX1 is critical for collagen-dependent platelet aggregation and carotid thrombosis, while it does not affect thrombin-dependent aggregation or haemostasis. 2APT selectively inhibits NOX1 over NOX2 (IC50 141 nM and >10 µM, respectively). In agreement with a central role of NOX1 in collagen signalling, 2APT and its most potent derivative 1-(10H-phenothiazin-2-yl)vinyl tert-butyl carbonate (or 2APT-D6) inhibit collagen-dependent platelet aggregation with negligible effects on thrombin responses. 2APT-D6 displays higher potency compared to 2APT (52 vs 141 nM, respectively). Platelet adhesion to collagen in static and flow conditions, superoxide anion generation and surface maker expression in response to collagen were also inhibited by 2APT and 2APT-D6. Administration of 2APT or 2APT-D6 (200mg/kg) in diet for 48 hours led to inhibition of platelet aggregation, oxygen radical output, and thrombus formation, and carotid occlusion in vivo, while tail hemostasis was not affected. Conclusion and Implications - In summary, this study suggests that NOX1 inhibition by 2APT or 2APT-D6 is a viable strategy to control collagen-induced platelet activation and reduce thrombosis in vivo without acute deleterious effects on hemostasis or other aspects of mouse health.