Search

A system of fractional differential equations (FDEs) with fractional derivatives of diverse orders is called an incommensurate system of FDEs. In this paper, the well-posedness of the initial value problem for incommensurate systems of FDEs is obtained on the space of continuous functions. Three different methods for this analysis are used and compared. The complexity of such analysis is reduced by new techniques. Strong existence results are obtained by weaker conditions. The uniqueness and the continuous dependency of the solution on initial values are investigated using the Gronwall inequality. [ABSTRACT FROM AUTHOR]

This paper proposes a logging data reconstruction method based on migration learning, which can reduce the dependence on labeled data and also help to improve the generalization ability of data-driven models. Reconstruction experiments are carried out using data from a block in the Junggar Basin of Xinjiang, and compared with the conventional data-driven long short-term memory network and recurrent neural network methods. The results show that the reconstruction results based on migration learning improve the accuracy by 21%, which is significantly better than the remaining two methods, and proves the feasibility of the method. [ABSTRACT FROM AUTHOR]

The skew tent map T is a chaotic map with rich dynamic properties. We present some interesting dynamical properties of the forts and the index function ε of skew tent maps. Using the coordinates of of forts of Tn, we present the exact expression of Tn(x) for n ∈ ℕ . Further, we obtain the coordinates of all fixed points of Tn, and give a necessary and sufficient condition for the fixed point of Tn to be a p-periodic point of T for any p|n. This condition is so simple that we can easily present the exact expressions of all periodic points of T. We give the exact expressions of the coordinates of all forts and periodic points of this map. [ABSTRACT FROM AUTHOR]

The article presents a study which explores how global beta-diversity of angiosperm trees have been shaped by Quaternary climate change. It mentions that results of the study suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide.

Objectives: To investigate the changes in the expression levels of peripheral blood immunoregulatory T lymphocytes in children with bronchial asthma accompanied by recurrent infection. Methods: Eighty children with bronchial asthma admitted to the Third Outpatient Department of General Hospital of Northern Theater Command from January 2017 to January 2019 were retrospectively selected and divided into two groups according to whether they had recurrent infection: the asthma group (n=49) and the recurrent infection group (n=31). Another 40 children in the same age group who had a health checkup or a surgical hospital preoperative examination were selected as the control group. Peripheral venous blood of each group was taken to measure the expression levels of T lymphocyte subsets (CD3 +, CD4 +, CD8 +, CD4 + /CD8 + ), and regulatory T cells (Treg) and helper T lymphocytes (Th1, Th2, Th17) in CD4+ subsets were detected at the same time. Moreover, Th1/Th2 values were calculated, and the levels of interleukin-4 (IL-4), interleukin-17 (IL-17), and interleukin-21 (IL-21) were measured. Results: The expression levels of CD3+ lymphocyte subsets were similar among the recurrent infection group, the asthma group, and the control group (P>0.05), and there were statistically significant differences in CD3 +, CD4 +, CD8 +, CD4 + /CD8 + lymphocyte subsets among the three groups (P<0.05). Statistically significant differences were observed in Treg, Th1, Th2, Th17 and Th1/Th2 values among the recurrent infection group, asthma group and control group (CD3 +, CD4 +, CD8 +, CD4 + /CD8 + <0.05), and the expression levels of IL-4, IL-17 and IL-21 in the three groups also showed statistically significant differences (P<0.05). Conclusion: Bronchial asthma with recurrent infection may have a close bearing on the expression level of peripheral blood immunoregulatory T lymphocytes, and indirect examination of peripheral blood T lymphocyte level in children can be used clinically to determine the incidence of the disease, which is of high clinical application value. [ABSTRACT FROM AUTHOR]

In this paper, a strategy of time-delayed feedback control based on wheel displacement and an optimization method of time-delayed feedback control parameters based on "equivalent harmonic excitation" are proposed for vehicle active suspension system with time-delayed feedback control. In this way, the optimal values of time-delayed feedback control parameters of the vehicle suspension system in the effective frequency band are obtained. Finally, through the stability analysis of suspension system and the numerical simulation analysis of the time-domain response of the suspension system performance evaluation index, the effectiveness of the time-delayed feedback control strategy based on the wheel displacement and the superiority of the optimization method based on the "equivalent harmonic excitation" are verified. Therefore, it provides a theoretical basis for the selection of time-delayed feedback control strategy and the optimal design of time-delayed feedback control parameters of vehicle active suspension system. [ABSTRACT FROM AUTHOR]

The intrusion of debris avalanches into reservoirs frequently occurs in mountainous regions and is a complex solid-fluid interaction. A coupled discrete element method (DEM) and smooth particle hydrodynamics (SPH) method is developed to forecast the entire process of disaster chains including landslide motion, wave generation, and wave propagation on Kaiding slopes at the Houziyan Reservoir, Sichuan Province, China. The sliding masses are treated as granular assemblies with collisions instead of rigid solid. The simulation results indicate that the maximum velocity of debris avalanches when swarming into the water surface is beyond 30 m/s, and the maximum wave elevation on the watercourse and the maximum run-up wave elevation generated by landslides reach 1867.4 m and 1883.0 m, respectively, and the minimum wave trough is 1822.1 m occurring near opposite bank of landslide. Furthermore, the range of landslide-generated waves is estimated to be approximately a propagation distance of 800.0 m along the axis of the river. The coupled DEM-SPH simulation method provides important inspiration for hazard prevention on reservoir landslides. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: The limited availability of highly valuable arenesulfonyl fluorides seriously hinders their further application in many research fields including medicinal chemistry and chemical biological, organic synthesis, polymer preparation, etc. We report herein a mild and efficient copper‐free Sandmeyer‐type fluorosulfonylation reaction of various arenediazonium salts to prepare valuable arenesulfonyl fluorides using K2S2O5 as both a reductant and a practical sulfonyl source in combination with N‐fluorobenzenesulfonimide as an effective fluorine source. This methodology provides an attractive route to diverse important arenesulfonyl fluorides given the overall practicality and scope. [ABSTRACT FROM AUTHOR]

Obligate bacterial endosymbionts are critical to the existence of many eukaryotes. Such endobacteria are usually characterized by reduced genomes and metabolic dependence on the host, which may cause difficulty in isolating them in pure cultures. Family Burkholderiaceae-related endofungal bacteria affiliated with the Mycoavidus-Glomeribacter clade can be associated with the fungal subphyla Mortierellomycotina and Glomeromycotina. In this study, a cultivable endosymbiotic bacterium, Mycoavidus sp. strain B2-EB, present in the fungal host Mortierella parvispora was obtained successfully. The B2-EB genome (1.88 Mb) represents the smallest genome among the endofungal bacterium Mycoavidus cysteinexigens (2.64 –2.80 Mb) of Mortierella elongata and the uncultured endosymbiont “Candidatus Glomeribacter gigasporarum” (1.37 to 2.36 Mb) of arbuscular mycorrhizal fungi. Despite a reduction in genome size, strain B2-EB displays a high genome completeness, suggesting a nondegenerative reduction in the B2-EB genome. Compared with a large proportion of transposable elements (TEs) in other known Mycoavidus genomes (7.2 to 11.5% of the total genome length), TEs accounted for only 2.4% of the B2-EB genome. This pattern, together with a high proportion of single-copy genes in the B2-EB genome, suggests that the B2-EB genome reached a state of relative evolutionary stability. These results represent the most streamlined structure among the cultivable endofungal bacteria and suggest the minimal genome features required by both an endofungal lifestyle and artificial culture. This study allows us to understand the genome evolution of Burkholderiaceae-related endosymbionts and to elucidate microbiological interactions. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to study the frictional performance of reciprocating pair with high velocity by using hydrodynamic lubrication principle and fish scale textured piston model. Design/methodology/approach: Based on the idea of function characteristic approximation and coordinate change, a mathematical representation model of imitating fish scale texture pit section is established. According to the principle of dynamic pressure lubrication of the textured fluid, a three-dimensional numerical model of flow field for fish scale texture is established without considering cavitation. Numerical analysis of the model carp scale texture unit by orthogonal experimental design and FLUENT software is carried out. Findings: Effects of fish scale pit texture on friction properties for a reciprocating pair piston surface with high velocity (impact piston) are acquired. Effects of texture characterization parameters and flow rate on the surface friction performance for impact piston are found. Effects of different characteristic parameters combination of imitating fish scale texture on friction performance for impact piston surface are obtained. Originality/value: The model is an effective tool to study the friction and wear of reciprocating pair with high velocity. The effects of fish scale textured piston pair supply a theory lead to design the reciprocating pair with better friction performance. Peer review: The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-09-2019-0398 [ABSTRACT FROM AUTHOR]

We propose a hybrid magnetic-electric quantum dot defined by a missing magnetic flux and an electrostatic dot potential in a same circular region, which can be realized through an electrode-controlled (Vg) superconducting disk deposited atop a two-dimensional electron gas in a homogeneous perpendicular magnetic field (Ba). We find that when Vg/Ba=eh/4m*, all ground states with m the (angular momentum) ≤0 recover the degeneracy Landau levels (LLs), although for general cases m-dependent energy deviations from the LLs happen. We also find that the magnetic-field-dependent energy spectrum exhibits quite different features for dot potentials with different signs, e.g., angular momentum transitions occurring in the positive case and coexistence of quantum-dot-kind and LL-kind levels for a small Ba in the negative one. Moreover, as the dot potential varies in a middle range, the energy spectrum shows step-type profiles, which are related to the nonmonotonous change in the probability for the electron to stay in the dot region. At the zero magnetic-field limit, the electron eigenenergy can jump between two adjacent LLs with a little change in the dot potential around special |m|-dependent values. [ABSTRACT FROM AUTHOR]

Spin-polarized transport properties have been investigated in diluted-magnetic-semiconductor/semiconductor quantum wires. We stress the effects introduced by the structural configuration and geometric parameters as well as the external magnetic field. It is found that the symmetric quantum wire shows quite different spin-dependent transport characteristics from the asymmetric one. It is also found that the spin-up component of the conductance can be considerably suppressed when the magnetic field is large enough, and thus nearly 100% spin polarization can be obtained in such kind of quantum wire. Moreover, one can effectively modulate the spin-dependent conductance in the quantum wire structure by varying the geometric parameters and the Fermi energy. [ABSTRACT FROM AUTHOR]

We investigate spin-filtering effect in multilayered ferromagnetic (F)/semiconductor (S) heterostructures within the Landauer framework of ballistic transport. Spin-dependent transmission and polarization are calculated and analyzed for different magnetizations of three ferromagnetic layers in a F/S/F/F structure proposed in this work. The results indicate that in such a multilayered configuration and when the magnetizations of the middle and the right ferromagnetic layers are antiparallel, the transmission for spin-up and spin-down electrons can be separated, which is quite different from the transport properties in the F/S/F structure, where electrons of different spin orientations have exactly the same contributions to transmission if the magnetic moments of the two ferromagnetic layers are antiparallel. It is also shown that the F/S/F/F structure can have big values of the polarization than the F/S/F structure. The quantum size effect of the length of the middle ferromagnetic layer and that of the semiconductor layer are discussed. Moreover, the polarization can be reversed when we switch the magnetizations of the middle and the right ferromagnetic layers. [ABSTRACT FROM AUTHOR]

We investigate the asymmetric effect in a spin-filter device, which is based on the Rashba spin-orbit coupling effect and uses a nonmagnetic tunneling diode. The structural asymmetry is introduced by unequivalence of the two quantum wells in the spin-filter device. It is found that the structural asymmetry can greatly change spin-filtering efficiency. For some asymmetric spin-filter structures, one can see spin-dependent enhancement in the transmission. Moreover, the current density can increase or decrease greatly depending on the degree of the structural asymmetry. [ABSTRACT FROM AUTHOR]

Background: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. Methods: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. Results: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-y (P=0.038), IL-13 (P0.027), IL-17/IL-17 A (P=0.012), and IL-4 (P=0.025). No significant dif ferences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P=0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P=0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P0.013) and IL-17/11-17 A (P=0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes, Conclusion: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Addi tionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflam- matory mediators in the aqueous humor. [ABSTRACT FROM AUTHOR]

With the development of the oil industry, the accuracy of the conventional well structure design method will be lower and lower. In order to ensure the smooth progress of drilling construction, this paper proposes a risk assessment method for the formation be drilled based on the equivalent drilling fluid density matrix, which reduces the use of empirical coefficients in the well structure design and realizes the fine design of the well structure. [ABSTRACT FROM AUTHOR]

This paper presents three in situ tests about down-hole dynamic compaction pile of 35 m, down-hole dynamic compaction pile of 50 m and pipe sinking compaction pile. To develop a method on improvement of collapsible loess foundation with large thickness and investigate improvement effect and quality control of the method. The tests results showed that (1) down-hole dynamic compaction pile can improve collapsible loess at a thickness of 50 m under reasonable design and required construction quality, improvement effect can be guaranteed; (2) for three tests, collapsible coefficients of soil between piles are all less than.015 in range of improvement depth, the collapsibility elimination effect has a downtrend along depth, whereas the compacting range and extent have no obvious difference, the depth is not a major factor influencing compacting effect; (3)the hammer intersection angle can influence improvement effect of down-hole dynamic compaction pile (4) a calculation formula of tamping number is given, which can simplify pre-tamping work because of acquiring tamping number only through field measurement to meet quality requirement. The tests results confirm a useful method for improvement project of collapsible loess foundation with large thickness, and to make those areas become improved and usable engineering construction site. [ABSTRACT FROM AUTHOR]

This paper investigates the linear functional equation with constant coefficients φ t = κ φ λ t + f t , where both κ > 0 and 1 > λ > 0 are constants, f is a given continuous function on ℝ , and φ : ℝ ⟶ ℝ is unknown. We present all continuous solutions of this functional equation. We show that (i) if κ > 1 , then the equation has infinite many continuous solutions, which depends on arbitrary functions; (ii) if 0 < κ < 1 , then the equation has a unique continuous solution; and (iii) if κ = 1 , then the equation has a continuous solution depending on a single parameter φ 0 under a suitable condition on f. [ABSTRACT FROM AUTHOR]

Apoptosis and autophagy are dynamic processes that determine the fate of cells. Vitamin D receptor (VDR) deficiency in the intestine leads to abnormal Paneth cells and impaired autophagy function. Here, we will elucidate the mechanisms of the intestinal epithelial VDR regulation of autophagy and apoptosis. We used in vivo VDRlox and VDR∆IEC mice and ex vivo organoids generated from small intestine and colon tissues. We found that VDR deficiency induced more apoptotic cells and significantly increased cell death in the small intestine and colon of VDR∆IEC mice. The proapoptotic protein B-cell lymphoma 2 (BCL-2) associated X protein (Bax) was enhanced, whereas autophagy related 16 like 1 (ATG16L1) and Beclin-1 were decreased in the intestines of VDRΔIEC mice. Apoptosis induced by Bax reduced autophagy by decreasing Beclin-1. Physical interactions between Beclin-1 and Bcl-2 were increased in the VDR-deficient epithelia from mice. The growth of VDR∆IEC organoids was significantly slower with fewer Paneth cells than that of VDR+/+ organoids. The expression levels of Beclin-1 and lysozyme were decreased in VDR∆IEC organoids. Bacterial endotoxin levels were high in the serum from VDR∆IEC mice and made mice susceptible to colitis. In the organoids and colitis IL-10-/- mice, vitamin D3 treatment increased VDR and ATG16L1 protein expression levels, which activated autophagic responses. In summary, intestinal epithelial VDR regulates autophagy and apoptosis through ATG16L1 and Beclin-1. Our studies provide fundamental insights into the tissue-specific function of VDR in modulating the balance between autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

The Feigenbaum–Kadanoff–Shenker (FKS) equation for universal scaling in circle maps characterizes the quasiperiodic route to chaos. We reduce the FKS equation to another type of equation, and prove that they are equivalent to each other in the sense of unimodal solutions. We present some properties of these solutions. According to the range of parameters, we give two algorithms to obtain all unimodal solutions. [ABSTRACT FROM AUTHOR]

Antitumor activity of Capsaicin has been studied in various tumor types, but its potency in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Here, we explored themolecular mechanism of the capsaicin-induced antitumor effects on ESCC Eca109 cells. Eca109 cells were treated with capsaicin in vitro, the migration and invasion capacities were significantly decreased by scratch assay and transwell invasion assay. Meanwhile, matrix metalloproteinase (MMP)-9 (MMP-9) expression levels were also obviously down-regulated by Western blot. However, phosphorylated AMPK levels were significantly up-regulated, and this effect was eliminated by the AMPK inhibitor Compound C treatment. In addition, capsaicin can enhance sirtuin1 (SIRT1) expression, which could activate nuclear factor-κB (NF-κB) through deacetylation, and activate AMPK inducing the phosphorylation of IκBα and nuclear localization of NF-κB p65. Overall, these results revealed that Capsaicin can inhibit the migration and invasion of ESCC cells via the AMPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

The importance of CF3-containing molecules in pharmaceuticals, agrochemicals and materials intrigues the intense interest in synthetic methodology of these compounds. With a purpose to enrich trifluoromethylation methodology, we carefully examined the substrate scope of hydroxytrifluoromethylation of alkenes using iodotrifluoromethane, and the reaction provided β-trifluoromethyl alcohols in good yields under extremely mild conditions without catalysts. We found that our reaction can be applied to not only styrenes but also various aliphatic alkenes with excellent selectivity; no ketone was detected in most of our cases. Another feature of our discovery is “simple”. The reaction was carried out in air, irradiated by visible light, at room temperature and most importantly no catalyst was needed. A solution of CF3I in DMSO was used as the facile trifluoromethylating reagent, which simplified the utilization of gaseous CF3I. Based on 19F NMR spectroscopy, we observed a halogen bond between CF3I and tertiary amine in this reaction. The interaction may promote single electron transfer by the visible light irradiation. [ABSTRACT FROM AUTHOR]

As it produces large quantities of allergenic pollen that has a serious effect on human health Ambrosia artemisiifolia (common ragweed) is among the most noxious invasive plant species in Europe. It is most widespread in southern parts of Eastern and Central Europe and likely to spread into other regions. Thus its suppression is highly desirable. To identify species with a potential to suppress this invasive species, we carried out a growth chamber experiment to investigate the performance (height and weight) of A. artemisiifolia and 10 native Central-European species (six grasses and four herbaceous plants), growing in similar habitats and hence potential competitors of ragweed. Two factors were investigated in order to determine the processes that are likely to affect the future spread of A. artemisiifolia in Central Europe, i.e. increasing temperatures and winter treatment with salt of roads that serve as dispersal corridors. The plants were reared at five temperatures ranging from 10 to 26 °C and three levels of salinity. The height and weight of A. artemisiifolia increased with increasing temperature over the whole range of temperatures tested, with most native species growing best at 22 °C. This indicates that A. artemisiifolia will perform better in a warming climate and its spread will be facilitated by the poor performance of native species growing at suboptimal temperatures. As the largest differences in size between A. artemisiifolia and the native species were recorded at 10 and 14 °C we recommend that native seed mixtures are sown at ragweed invaded sites early in spring, or the previous autumn, to provide the competitors with a growth advantage at lower temperatures when A. artemisiifolia plants are still small and thus competitively weak. With respect to the other factor tested, A. artemisiifolia was suppressed similarly by high salinity as most of the native species tested, which indicates that the ragweed spread along roads is not primarily facilitated by its high tolerance of salinity. Different tolerances of native species to salinity indicates that this should be reflected in the selection of species for roadside seeding. [ABSTRACT FROM AUTHOR]

The increasing demand of urban distribution aggravates urban congestion and environmental pollution. In view of the growing serious environmental problems, the urban distribution of electric vehicles (EVs) can alleviate the pollution caused by vehicle emissions to a certain extent. However, in practical application, this urban distribution is affected by the scarce distribution of public charging piles and the limited mileage per charge, which bring difficulties to the operation scheduling. An optimization method considering the distribution of public charging piles and carbon emissions was proposed to improve the efficiency of the urban distribution of EVs. With the minimum total distribution cost as the optimization objective, an optimization model based on the distribution of the public charging pile network and considering the restriction of mileage per charge was established. Hill-climbing algorithm was introduced in accordance with the requirements and characteristics of the optimization model to improve the standard genetic algorithm (SGA) and its local solving capability. The feasibility and validity of the model and hill-climbing genetic algorithm (HCGA) were verified by solving small- and large-scale numerical examples. Results demonstrate that the optimization model and HCGA proposed can effectively provide optimized solutions for the urban distribution of EVs. The designed HCGA has a better searching capability than SGA. For the small-scale numerical example, the average total cost of the feasible solutions obtained by HCGA is 18.2% less than that by SGA, whereas for the large-scale example, the cost is 6% less than that by SGA. This study provides references for saving on the distribution cost and guiding the urban distribution scheduling and optimization of EVs. [ABSTRACT FROM AUTHOR]

This note investigates the conjugacy from Farey map to the skew tent map. We present two explicit expressions of the conjugacy with two kinds of representations for real numbers, and estimate the Hölder exponent of the conjugacy. [ABSTRACT FROM AUTHOR]

Graphical abstract Three isostructural 1D coordination polymers were constructed from a new 3-position substituted imidazo[1,2- a ]pyridine ligand, which reveal interesting phosphorescent or magnetic properties. Abstract A new 3-position substituted imidazo[1,2- a ]pyridine ligand, namely, 5-(2-chloroimidazo[1,2- a ]pyridine-3-carboxamido) isophthalic acid (H 2 L) was synthesized and characterized by 1H NMR spectroscopy. Based on this ligand, three isostructural one-dimensional coordination polymers, [ML(H 2 O) 2 ] n (M = Zn (1), Ni (2) and Co (3)) were synthesized under the solvothermal conditions, and structurally characterized by single crystal X-ray diffraction, infrared spectroscopy, powder X-ray diffraction and elemental analyses. The coordination polymer 1 reveals similar photoluminescent spectrum to H 2 L ligand, but possesses the enhanced phosphorescent emission and higher phosphorescent quantum yield, compared to H 2 L ligand. Furthermore, the magnetic properties of coordination polymers 2 and 3 have been investigated, the results show there are antiferromagnetic interactions between the NiII ions or CoII ions in 2 or 3. [ABSTRACT FROM AUTHOR]

Most research on biomass-filled plastic composites (BFPCs) mainly focuses on their formulation and physical/mechanical properties, but studies on the connection performance of BFPCs are very rare. However, such performance is vital in the quality assessment of BFPCs products and plays an important role in improving product quality and promoting its application in the field of architecture and furniture. Therefore, the behavior of L-type BFPCs structure under the interaction of fatigue-creep was investigated. Results suggested that the fatigue-creep curve is a typically three-region curve at 80% and 60% failure load, and only first two stages at 40% failure load. But the damage caused by fatigue-creep interaction was not a simple superposition. Fatigue damage dominated when the holding time was short, and creep damage occupied a dominant position gradually when the holding time was longer. In addition, the lifespan of the BFPC component increased initially and then decreased as holding time increased. The component joint exhibited the least integrated damage when the holding time was 60 s and the lifespan was longer. [ABSTRACT FROM AUTHOR]

The dynamic traffic equilibrium problem has been a pivotal area of research in transportation for a few decades. The current state-of-the-art research in this area generally considers simultaneous departure time and route choice. In this paper, we theoretically prove that, in the simplest standard bottleneck model with a sufficient number of commuters, a dynamic user equilibrium (DUE) cannot be reached through a day-to-day evolution process of travelers' departure rate--a central idea behind the iterative dynamic traffic equilibrium algorithms prevalent in the literature. We carry out our exploration with the proportional swap system and then extend our analysis to other typical dynamic equilibrium algorithms such as the network tatonnement process, the simplex gravity flow dynamics, the projected dynamical system, and the evolutionary traffic dynamics. Our investigation indicates that any algorithm analogous to the five categories of systems must be cautious in terms of convergence when it is applied to solve the DUE problem with a departure time choice, and hence puts forward a general question: Are we really solving the DUE problem with a departure time choice? [ABSTRACT FROM AUTHOR]

The association between vitamin D receptor (VDR) polymorphisms (rs731236, rs1544410, rs2228570, and rs7975232) and the risk of autoimmune thyroid disease (AITD) had been investigated in previous studies. However, the results of these studies remained controversial. Thus, a meta-analysis was performed to derive a more precise conclusion. All related articles were systematically searched by PubMed, Embase, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. The overall results indicated that VDR rs731236 and rs2228570 polymorphisms were significantly associated with a reduced risk of AITD. However, a stratification analysis based on clinical types showed that VDR rs731236 and rs2228570 polymorphisms were associated only with a reduced risk of HT. A stratification analysis by ethnicity showed that VDR rs731236 polymorphism was significantly associated with a reduced risk of AITD in Asian and African populations. VDR rs2228570 polymorphism was associated with a reduced risk of AITD in Asian populations. VDR rs1544410 polymorphism was associated with a reduced risk of AITD in European and African populations, but with an increased risk of AITD in Asian populations. VDR rs7975232 polymorphism was significantly associated with an increased risk of AITD in African populations. In conclusion, the present study suggested that VDR rs731236, rs1544410, rs2228570, and rs7975232 polymorphisms were significantly associated with AITD risk. However, more well-designed studies should be performed to verify the current results. [ABSTRACT FROM AUTHOR]

Identifying the factors that influence spatial genetic structure among populations can provide insights into the evolution of invasive plants. In this study, we used the common reed (Phragmites australis), a grass native in Europe and invading North America, to examine the relative importance of geographic, environmental (represented by climate here), and human effects on population genetic structure and its changes during invasion. We collected samples of P. australis from both the invaded North American and native European ranges and used molecular markers to investigate the population genetic structure within and between ranges. We used path analysis to identify the contributions of each of the three factors—geographic, environmental, and humanrelated—to the formation of spatial genetic patterns. Genetic differentiation was observed between the introduced and native populations, and their genetic structure in the native and introduced ranges was different. There were strong effects of geography and environment on the genetic structure of populations in the native range, but the human-related factors manifested through colonization of anthropogenic habitats in the introduced range counteracted the effects of environment. The between-range genetic differences among populations were mainly explained by the heterogeneous environment between the ranges, with the coefficient 2.6 times higher for the environment than that explained by the geographic distance. Human activities were the primary contributor to the genetic structure of the introduced populations. The significant environmental divergence between ranges and the strong contribution of human activities to the genetic structure in the introduced range suggest that invasive populations of P. australis have evolved to adapt to a different climate and to human-made habitats in North America. [ABSTRACT FROM AUTHOR]

We have investigated the ballistic spin-polarized transport through a diluted magnetic semiconductor heterostructure with the inclusion of a nonmagnetic barrier. It is found that at suitable magnetic fields, the output current of the system exhibits a nearly 100% spin polarization and large values under the forward bias, while under the reverse bias it is small and shows a weak polarization. Such current and spin-filtering dual diode functions are robust under the change of the nonmagnetic barrier width. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A novel zwitterionic polymer ionic liquid functionalized magnetic nanospheres, shortly as Fe3O4@PCL-PILs, is synthesized by grafting ionic liquid VimCOOHBr onto polymer ε-caprolactone (PCL) modified magnetic nanospheres via esterification and surface-initiated free radical polymerization. This established synthesis strategy offers the obtained magnetic nanospheres with well-defined core-corona structure, compact grafting layer, favorable zwitterionic and negative-charged surface, and high magnetic susceptibility. The as-prepared Fe3O4@PCL-PILs nanospheres exhibit typical "zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC)" behaviors toward protein binding, and selectively adsorption of glycoprotein is achieved. The adsorption capacity of the magnetic nanospheres toward Immunoglobulin G is high up to 1136.4 mg g-1, and the captured Immunoglobulin G could be efficiently recovered by using 0.5% NH3 H2O (v/v) as stripping reagent, providing a recovery of 80.5%. Fe3O4@PCL-PILs nanospheres are then employed as sorbent for the selective isolation of Immunoglobulin G from human whole blood, obtaining high-purity Immunoglobulin G as demonstrated by polyacrylamide gel electrophoresis assays. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL kinase. Recent efforts focused on the development of more potent tyrosine kinase inhibitors (TKIs) that also inhibit mutant tyrosine kinases such as nilotinib and dasatinib. Although major advances in the treatment of this aggressive disease with potent inhibitors of the BCR/ABL kinases, patients in remission frequently relapse due to drug resistance possibly mediated, at least in part, by compensatory activation of growth-signaling pathways and protective feedback signaling of leukemia cells in response to TKI treatment. Continuous activation of AKT/mTOR signaling and inactivation of p53 pathway were two mechanisms of TKI resistance. Here, we reported that nutlin-3 plus tanshinone IIA significantly potentiated the cytotoxic and apoptotic induction effects of imatinib by down-regulation of the AKT/mTOR pathway and reactivating the p53 pathway deeply in Ph+ ALL cell line. In primary samples from Ph+ ALL patients, nutlin-3 plus tanshinone IIA also exhibited synergetic cytotoxic effects with imatinib. Of note, three samples from Ph+ ALL patients harboring T315I mutation also showed sensitivity to the combined treatment of imatinib, nutlin-3 plus tanshinone IIA. In Ph+ ALL mouse models, imatinib combined with nutlin-3 plus tanshinone IIA also exhibited synergetic effects on reduction in leukemia burden. These results demonstrated that nutlin-3 plus tanshinone IIA combined TKI might be a promising treatment strategy for Ph+ ALL patients. [ABSTRACT FROM AUTHOR]

Background: Hypotheses on the development of postoperative delirium (PD) include "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," and "neuroendocrine." Here, we employed metabolomics to determine the serum metabolites in the baseline associated with an increased risk of PD.Methods: Two hundred and nine elderly hip-fracture patients who had undergone hemiarthroplasty and had completed our assessments were selected. Fasting venous blood was collected at 7:00 on the morning of surgery and a serum sample bank was created for analysis. On the first 3 postoperative days, the patients were assessed twice daily using the Confusion Assessment Method - Chinese Revision. Ultimately, 43 patients were diagnosed with PD, who comprised the PD group. Meanwhile, 43 matched non-PD patients were selected based on age, sex, and body mass index. Serum samples from the two groups were analyzed by gas chromatography-time-of-flight mass spectrometry and Acquity ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.Results: The demographic characteristics of the groups were matched. Four metabolites associated with an increased risk of PD were identified, including S-methylcysteine, linolenic acid, eicosapentaenoic acid, and linoleic acid.Conclusions: Multiple metabolic pathways in the PD group altered before surgery, including deficiency of ω3 and ω6 fatty acids, energy metabolism and oxidative stress with interactions between hypoxia and mitochondrial dysfunction, in addition to glutamate-glutamine cycle dysfunction. These metabolic abnormalities could possibly increase the fragility of the brain and then contribute to PD. [ABSTRACT FROM AUTHOR]

Carbonyl reductase 1 (CBR1) is theorized to participate in various cellular processes, such as signal transduction, apoptosis, carcinogenesis and drug resistance, and is highly expressed in certain malignancies, including lung tumors. Several studies have provided evidence that gene polymorphisms may affect susceptibility to non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the CBR1 single-nucleotide polymorphisms (SNPs) rs3787728 and rs2835267, and NSCLC in a Chinese population. The data indicated that the allele frequency in CBR1 rs3787728 was significantly different between patients with NSCLC and the controls [odds ratio (OR)=1.209; 95% confidence interval (CI)=1.013-1.442; P=0.0349], and was significantly different between male patients with NSCLC and the corresponding controls (OR=1.278; 95% CI=1.016-1.607; P=0.0358). The CBR1 rs3787728 thymine (T)/T allele homozygote was associated with an increased risk of NSCLC in all patients (OR=1.382; 95% CI=1.019-1.875; P=0.037), and patients possessing the rs3787728 T/T major allele homozygote exhibited a 1.537-fold greater risk with respect to developing lung squamous-cell carcinoma (SCC) in all patients (95% CI=1.019-2.318; P=0.0395). The CBR1 rs3787728 cytosine (C)/C allele homozygote was associated with a decreased risk of adenocarcinoma (ADC) in male patients (OR=0.633; 95% CI=0.413-0.969; P=0.0348); however, no significant association was observed in CBR1 rs2835267 between SNPs and SCC or ADC-type NSCLC. In conclusion, the results revealed that genetic polymorphisms of CBR1 rs3787728 were associated with susceptibility to NSCLC. Additional studies are required to identify the functional impact of CBR1 expression and activity in NSCLC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to perform comparative genomics using gene expression profile datasets of mice and humans who had been treated with anticancer drugs, to determine the similarities and differences in the antitumor mechanisms in the two mammals. This involved data mining of antitumor gene expression regulation, and screening of genetic loci from experimental mouse models of antitumor targets, to provide a theoretical basis of drug design. Subsequently, 9 overlapping genes with opposite expression patterns were identified across mouse and human cell lines that were treated with a specific cyclin‑dependent kinase 4/6 inhibitor, PD0332991. These genes included LIM homeobox 2, adenomedullin, bone marrow stromal cell antigen 1, caveolin 1, histone cluster 1 (HIST1) H2B family member C, HIST1 H3 family member F, low density lipoprotein‑receptor related protein 11, prolyl 4‑hydroxylase subunit α1 and torsin family 3 member A. In addition, the janus kinase‑signal transducer and activator of transcription signaling pathway, Toll‑like receptor signaling pathway, T cell receptor signaling pathway and the nucleotide‑binding oligomerization domain‑like receptor signaling pathway were identified as candidate pathways for explaining antitumor mechanisms. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing lesions on magnetic resonance imaging that were discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm in diameter without ring-enhancement or mass effect, and homogenous T2 signal abnormality not significantly exceeding the T1 enhancement. Brain neuropathology on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B-lymphocyte and moderate macrophage infiltrates, with perivascular predominance as well as diffuse parenchymal infiltration (14/14), present in meninges, white and grey matter, associated with variable tissue destruction, astrogliosis and secondary myelin loss. Clinical, radiological and pathological feature define CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by neuroradiological and neuropathological findings. [ABSTRACT FROM AUTHOR]

The Janus kinase/signal transducers and activators for transcription (JAK/STAT) pathway plays crucial roles in regulating apoptosis, proliferation, differentiation, and the inflammatory response. The JAK/STAT families are composed of four JAK family members and seven STAT family members. STAT3 plays a key role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment. Recent evidence suggests that STAT3 regulates diverse biological functions in pathogenesis of diseases, such as infection and cancer. In the current review, we will summarize the research progress of STAT3 activation in infection and cancers. We highlight our recent study on the novel role of STAT3 in Salmonella infection-associated colon cancer. Infection with bacterial AvrA-expressing Salmonella activates the STAT3 pathway, which induces the β-catenin signals and enhances colonic tumorigenesis. STAT3 may be a promising target in developing prevention and treatment for infectious diseases and infection-associated cancers. [ABSTRACT FROM AUTHOR]

The conjugacy problem is one of the central questions in dynamical systems. Many works have devoted to conjugacy problems of horseshoe maps with the same number of laps, which is a kind of continuous, piecewise monotone interval maps. This paper considers semi-conjugacies fromm-horseshoe maps ton-horseshoe maps for. We first give new orientation-preserving/reversing partition on their domains. Then by Matkowski’s fixed point principle we prove the existence of semi-conjugacies fromm-horseshoe maps ton-horseshoe maps. We construct some sequences of functions to approximate these semi-conjugacies. Finally, an example is given for a piecewise linear 4-horseshoe maps and a piecewise linear 3-horseshoe map. [ABSTRACT FROM PUBLISHER]

Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)- mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p2l (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, a-smooth muscle actin (a-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Numerous aberrantly expressed microRNAs (miRNAs/miRs) have been identified in gastric cancer (GC); however, only a fraction of these have been functionally investigated and novel deregulated miRNAs in GC remain to be explored. Through examining two public miRNA expression profile datasets, the present study identified aberrantly expressed miRNAs in GC. One of these miRNA, miR-564, was identified to be downregulated in GC, which was validated in tissue samples from patients with GC by reverse transcription-quantitative polymerase chain reaction analysis. Targets of miR-564 were then predicted bioinformatically, including transcription factor E2F3 (E2F3), which was identified to be functionally enriched in several cancer signaling pathways. Furthermore, overexpression of miR-564 decreased the activity of a luciferase reporter carrying the 3'-untranslated region of E2F3, in addition to the mRNA and protein level of E2F3, indicating that miR-564 directly targets E2F3. These data suggest that by targeting E2F3, miR-564 may act as a tumor suppressor gene in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

We report the first example of reversible encapsulation of micron-sized particles by oppositely charged submicron smaller colloids. The reversibility of this encapsulation process is regulated by pH-responsive poly(acrylic acid) (PAA) present in solution. The competitive adsorption between the small colloids and the poly(acrylic acid) on the surface of the large colloids plays a key role in the encapsulation behavior of the system. pH offers an experimental knob to tune the electrostatic interactions between the two oppositely charged particle species via regulation of the charge density of the poly(acrylic acid). This results in an increased surface coverage of the large colloids by the smaller colloids when decreasing pH. Furthermore, the poly(acrylic acid) also acts as a steric barrier limiting the strength of the attractive forces between the oppositely charged particle species, thereby enabling detachment of the smaller colloids. Finally, based on the pH tunability of the encapsulation behavior and the ability of the small colloids to detach, reversible encapsulation is achieved by cycling pH in the presence of the PAA polyelectrolytes. The role of polyelectrolytes revealed in this work provides a new and facile strategy to control heteroaggregation behavior between oppositely charged colloids, paving the way to prepare sophisticated hierarchical assemblies. [ABSTRACT FROM AUTHOR]

This paper investigates two robust finite-time controllers for the attitude control of spacecraft based on rotation matrix. The first controller can compensate external disturbances with known bounds, whereas the second one can deal with both external disturbances and input saturation by using the hyperbolic tangent function and auxiliary system. Both controllers can avoid the singularity and converge to zero in finite time by using novel fast nonsingular terminal sliding mode control. Because the controllers are designed based on a rotation matrix that represents the set of attitudes both globally and uniquely, the system can overcome the drawbacks of unwinding. Numerical simulations are presented to demonstrate the effectiveness of the proposed control schemes. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of static magnetic field (SMF) on cutaneous wound healing of Streptozotocin- (STZ-) induced diabetic rats. Methods. 20 STZ-induced diabetic rats were randomly divided into two groups (10 in each group): diabetic rats with SMF exposure group which were exposed to SMF by gluing one magnetic disk of 230 mT intensity and diabetic rats with sham SMF exposure group (sham group). 10 normal Wistar rats were used as the control group. One open circular wound with 2 cm diameter in the dorsum was generated on both normal and diabetic rats and then covered with sterile gauzes. Wound healing was evaluated by wound area reduction rate, mean time to wound closure, and wound tensile strength. Results. The wound area reduction rate in diabetic rats in comparison with the control group was significantly decreased (P<0.01). Compared with sham magnet group, diabetic rats under 230 mT SMF exposure demonstrated significantly accelerated wound area reduction rate on postoperative days 7, 14, and 21 and decreased gross time to wound closure (P<0.05), as well as dramatically higher wound tissue strength (P<0.05) on 21st day. Conclusion. 230 mT SMF promoted the healing of skin wound in diabetic rats and may provide a non-invasive therapeutic tool for impaired wound healing of diabetic patients. [ABSTRACT FROM AUTHOR]

In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group ( n = 8), survival group ( n = 15) and death group ( n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult ( P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult ( P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo ( P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock. [ABSTRACT FROM AUTHOR]

Purpose Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS. Here we present evidence that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology. Methods We used G93A transgenic mice as a model of human ALS. The G93A mice show abnormal intestinal microbiome and damaged tight junctions before ALS disease onset. The mice were given 2% butyrate, a natural bacterial product, in the drinking water. Results In mice fed with butyrate, intestinal microbial homeostasis was restored, gut integrity was improved, and life span was prolonged compared with those in control mice. At the cellular level, abnormal Paneth cells—specialized intestinal epithelial cells that regulate the host–bacterial interactions—were significantly decreased in the ALS mice treated with butyrate. In both ALS mice and intestinal epithelial cells cultured from humans, butyrate treatment was associated with decreased aggregation of the G93A superoxide dismutase 1 mutated protein. Implications The findings from this study highlight the complex role of the gut microbiome and intestinal epithelium in the progression of ALS and present butyrate as a potential therapeutic reagent for restoring ALS-related dysbiosis. [ABSTRACT FROM AUTHOR]

Background Axin1 is a scaffold protein in the β-catenin destruction complex, which, if disrupted, contributes to pathogenesis of various human diseases, including colorectal carcinogenesis and inflammatory bowel diseases (IBD). We have previously demonstrated that Salmonella infection promotes the degradation and plasma sequestration of Axin1, leading to bacterial invasiveness and inflammatory responses. Vitamin D and the vitamin D receptor (VDR) appear to be important regulators of IBD and colon cancer. Although VDR and Axin1 are all involved in intestinal inflammation, it remains unclear whether these processes are related or function independently. In the current study, we hypothesize that VDR is an important regulator for the maintenance of physiological level of Axin1. Methods Using the intestinal epithelial conditional VDR knockout mouse model (VDR ΔIEC ) and cultured cell lines, influences of VDR status on the expression of Axin1 was evaluated by Western blots and real-time PCR. Loss- and gain-of-function assays were used to investigate the regulation of VDR on Axin1 at the transcriptional and translational levels. Cells were treated with cycloheximide or actinomycin for molecular mechanistic studies. Candidate genomic VDR binding sites for Axin1 were tested by chromatin immunoprecipitation (ChIP) assay. Physical interactions among VDR, Axin1, and β-catenin were tested by immunoprecipitation. Cellular localization of Axin1 with different VDR status was determined by fractionation and immunohistochemistry. Results We found that VDR deletion led to lower protein and mRNA levels of Axin1 , whereas knockdown of Axin1 did not change the expression level of VDR protein. Immunoprecipitation data did not support physical interaction between VDR and Axin1. The VDR regulation of Axin1 was through a VDR genomic binding site for Axin1 gene on the regulatory region. Fractionation data showed that cytosolic Axin1 was significantly reduced due to VDR deletion, leaving the nuclear fraction unchanged. In ileum, Axin1 was distributed in the cytosol of apical epithelium and crypts. Conclusion VDR is important for the maintenance of physiological level of Axin1. The discovery of Axin1 as a VDR target gene provides novel and fundamental insights into the interactions between the VDR and β-catenin signaling pathways. [ABSTRACT FROM AUTHOR]

Salmonella pathogenesis studies to date have focused on Salmonella typhimurium, and the pathogenesis of a second major serotype, Salmonella enteritidis, is poorly understood. Salmonella spp. possess effector proteins that display biochemical activities and modulate host functions. Here, we generated a deletion mutant of the effector AvrA, S.E-AvrA-, and a plasmidmediated complementary strain, S.E-AvrA-/pAvrA+ (S.EAvrA +), in S. Enteritidis. Using in vitro and in vivo infection models, we showed that AvrA stabilizes epithelial tight junction (TJ) proteins, such as ZO-1, in human intestinal epithelial cells. Transepithelial electrical resistance was significantly higher in cells infected with S.E-AvrA+ than in cells infected with S.EAvrA -. Inhibition of the JNK pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA inhibited JNK activity in cells infected with wild type or S.E-AvrA+ strains. Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of the JNK pathway. Furthermore, the S.EAvrA - strain led to enhanced bacterial invasion, both in vitro and in vivo. Taken together, our data reveal a novel role for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and attenuates bacterial invasion. The manipulation of JNK activity and TJs in microbial-epithelial interactions may be a novel therapeutic approach for the treatment of infectious diseases. [ABSTRACT FROM AUTHOR]