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Doxorubicin (DOX) is a chemotherapeutic drug for a variety of malignancies, while its application is restricted by the cardiovascular toxic effects characterized by oxidative stress. Ferroptosis is a novel iron-dependent regulated cell death driven by lipid peroxidation. Our study aimed to investigate the role of Elabela (ELA) in DOX-induced oxidative stress and ferroptosis. In cultured rat aortic adventitial fibroblasts (AFs), stimulation with DOX dramatically induced cytotoxicity with reduced cell viability and migration ability, and enhanced lactate dehydrogenase (LDH) activity. Importantly, ELA and ferrostatin-1 (Fer-1) mitigated DOX-mediated augmentation of reactive oxygen species (ROS) in rat aortic AFs, accompanied by upregulated levels of Nrf2, SLC7A11, GPX4, and GSH. In addition, ELA reversed DOX-induced dysregulation of apoptosis- and inflammation-related factors including Bax, Bcl2, interleukin (IL)-1β, IL6, IL-10, and CXCL1. Intriguingly, knockdown of Krüppel-like factor 15 (KLF15) by siRNA abolished ELA-mediated alleviation of ROS production and inflammatory responses. More importanly, KLF15 siRNA impeded the beneficial roles of ELA in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.

MicroRNAs (miRNAs) have emerged as essential regulators that could have pivotal roles in cardiac homeostasis and pathological remodeling of various cardiovascular diseases. We previously demonstrated that miRNA-122-5p overexpression exacerbated the process of vascular hypertrophy, fibrosis, and dysfunction in hypertensive rats and rat aortic adventitial fibroblasts. However, the exact roles and underlying mechanisms of miRNA-122-5p in myocardial fibroblasts remain largely unknown. In this work, neonatal rat cardiofibroblasts (CFs) were isolated and primarily cultured from the hearts of 2- to 3-d-old Sprague-Dawley rats. Stimulation of angiotensin II (Ang II) resulted in marked increases in cellular proliferation and migration and levels of collagen I, collagen III, CTGF, and TGF-β1 in cultured CFs. Furthermore, Ang II led to promoted expression of P62, Bax, and phosphorylated mTOR as well as downregulation of LC3II, beclin-1, and AMPK-phosphorylated levels, thereby contributing to imbalance of autophagy and apoptosis, and cellular injury in CFs, which were significantly ameliorated by treatment with miRNA-122-5p inhibitor. These changes were associated with decreased levels of collagen I, collagen III, CTGF, and TGF-β1. Furthermore, Ang II-induced loss of autophagy and promotion of apoptosis in CFs were prevented by the treatment with Pyr

Cardiovascular disease (CVD) is the leading cause of death worldwide and encompasses diverse diseases of the vasculature, myocardium, cardiac electrical circuit, and cardiac development. Forkhead box protein P1 (Foxp1) is a large multi-domain transcriptional regulator belonging to the Fox family with winged helix DNA-binding protein, which plays critical roles in cardiovascular homeostasis and disorders. The broad distribution of Foxp1 and alternative splicing isoforms implicate its distinct functions in diverse cardiac and vascular cells and tissue types. Foxp1 is essential for diverse biological processes and has been shown to regulate cellular proliferation, apoptosis, oxidative stress, fibrosis, angiogenesis, cardiovascular remodeling, and dysfunction. Notably, both loss-of-function and gain-of-function approaches have defined critical roles of Foxp1 in CVD. Genetic deletion of Foxp1 results in pathological cardiac remodeling, exacerbation of atherosclerotic lesion formation, prolonged occlusive thrombus formation, severe cardiac defects, and embryo death. In contrast, activation of Foxp1 performs a wide range of physiological effects, including cell growth, hypertrophy, differentiation, angiogenesis, and cardiac development. More importantly, Foxp1 exerts anti-inflammatory and anti-atherosclerotic effects in controlling coronary thrombus formation and myocardial infarction (MI). Thus, targeting for Foxp1 signaling has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of CVD, and an increased understanding of cardiovascular actions of the Foxp1 signaling will help to develop effective interventions. In this review, we focus on the diverse actions and underlying mechanisms of Foxp1 highlighting its roles in CVD, including heart failure, MI, atherosclerosis, congenital heart defects, and atrial fibrillation.

The GlobalFiler™ PCR Amplification Kit is a single multiplex assay that amplifies a set of 24 markers, which encompass the European Standard Set and CODIS (Combined DNA Index System) recommended composite set of loci. In addition to more loci and a 6-dye chemistry format, the Master Mix has been formulated to allow higher sample loading volume for trace DNA samples. The GlobalFiler™ Kit has been optimized to deliver high performance on casework samples, while also delivering fast thermal cycling, with an amplification time of approximately 80 min. Here, we report the results of the developmental validation study which followed the SWGDAM (Scientific Working Group on DNA Analysis Methods) guidelines and includes data for PCR-based studies, sensitivity, species specificity, stability, precision, reproducibility and repeatability, concordance, stutter, DNA mixtures, and performance on mock casework samples. The results validate the multiplex design as well as demonstrate the kit’s robustness, reliability, and suitability as an assay for human identification with casework DNA samples. Electronic supplementary material The online version of this article (10.1007/s00414-018-1817-5) contains supplementary material, which is available to authorized users.

From the perspective of the cost analysis of commodity marketing, the logistics cost accounts for about 30% of the final price of commodities, and the cost of storage selection accounts for about 75% of all logistics costs. This means that the management of the operation efficiency of storage is an essential part of logistics management. With four different modified fruit fly optimization algorithms, this study aimed to optimize the logistics storage selection. First, this study selected 10, 20, and 30 freight sections in a random manner; second, four fruit fly optimization algorithms were used to create some populations and fruit flies, which were taken as freight section spots; third, the algorithms were adopted to seek the logistics storage selection that costs the shortest time. According to analysis of the result, the chaos fruit fly algorithm, out of the four, was the one that took the shortest time and created the greatest effect when 10, 20, or 30 freight sections were considered. The 100 repetitious experiments also demonstrated that the chaos fruit fly algorithm cost the shortest time in the selection, and had the lowest time value variable.

The study of logistics network of Yangtze River Delta city group can enable us to understand the logistics integration status. There are 25 cities in Yangtze River Delta Urban Agglomerations selected as the study object of this paper. The values of logistics links to those cities are calculated on the basis of the gravity model. Then, social network analysis method is used to analyze the logistics network density, centrality, cohesive subgroup and core–periphery structure. The research finds that the logistics connection between those cities is low; a few nodes have high degree of centrality and most of these nodes have little difference; there exists subgroup in the network, and the link density inside and between those subgroup are weak; the network has the core–periphery structure; both links inside the marginal area and links between the core area and the edge area are weak, so the network has vulnerabilities. Therefore, some measures need to be taken in in order to realize coordinative development of logistics in Silk Road Economic belt, including breaking the administrative constraints, taking the lead on the core nodes and strengthening the interaction between the edge region and the core region.

In this paper, robust UDE-based linear control strategy is developed for a class of second-order nonlinear uncertain systems with disturbances. After revealing the control structure and performing stability analysis, the robust control strategy is used to suppress wing rock motion. The approach is based on the uncertainty and disturbance estimator, which calculates and robustly cancels system uncertainties and input disturbances via appropriate filtering. The information regarding the known part of the linear plant dynamics is used by the controller; the terms containing the nonlinear functions are treated as additional uncertainties to the system. The algorithm provides excellent performance in suppressing the wing rock dynamics and rejecting disturbances. Simulations are given to show the effectiveness of the strategy via an application to an experimentally derived delta wing rock model.

In this paper, the synchronization problem of general complex networks is investigated by using adaptive control schemes. Time-delay coupling, derivative coupling, nonlinear coupling etc. exist universally in real-world complex networks. The adaptive synchronization scheme is designed for the complex network with multiple class of coupling terms. A criterion guaranteeing synchronization of such complex networks is established by employing the Lyapunov stability theorem and adaptive control schemes. Finally, an illustrative example with numerical simulation is given to show the feasibility and efficiency of theoretical results.

In order to study bearing characteristics of bridge pile at steep slope under complex loads in mountians, according to double pile-column bridge piers engineering at steep slope and test models in laboratory, finite element analysis of pile-column bridge piers was carried out using software ADINA under different loadings, such as horizontal loading in the longitudinal direction along bridge, vertical loadings, slope top loadings and complex loadings. The numerical simulation results show that displacements of front pile pier top and back pile pier top are different under horizontal loadings in the longitudinal direction along bridge or vertical loadings, the displacements of front pile pier top are higher than those of back pile pier top, and its difference increases with the increase of loadings. Vertical displacements will also appear under slope top loadings, and displacements of front pier top are higher than those of back pier top too, while its difference reduces with the increase of loadings. Displacements of both front pile pier top and back pile pier top under comlex loading are larger than those under single loading.

Hydrodynamic effects play a very important role in the contaminants release from sediments. Experiments were performed to study contaminants releasing characteristics due to resuspension. The time-dependent variation of COD concentration and relative roles under static and dynamic state of the overlying water were analyzed. Experimental results showed that COD concentration in the water column got a striking increment on the dynamic conditions, mainly by reducing the thickness of concentration boundary layer near sediment-water interface and destructing the surface structure of sediment. Hydrodynamics increased contaminants release rates and flux in unit time. Before reaching an equilibrium stage, the dynamic release caused by the resuspension was more effective than static one due to molecular diffusion. The release rate of COD increased with flow velocity and decreased with water depth. But at a shallow water depth, wave effects would dominate the causing resuspension, resulting in contaminants release in large quantity. The intensity of pollutant release increased with time in a rather circuitous process. The diffusion of pollutant from internal sediment to the sediment-water interface would maintain the endogenous release effects.

In this paper, the bottom of the Dianshan Lake was selected as a test sample. The dynamic release of contaminated sediments into the overlying water column was experimentally investigated in an open water channel under different hydrodynamic conditions. The experimental results indicate that the Total Phosphorus (TP) release process can be divided into three stages: rapid release, slow release and equilibration release. In the initial release stage the measured TP concentration changes along the depth. The TP concentration near the sediment-water interface is higher than that near the water surface, but the TP concentration becomes uniform along the depth after 3 h. The dynamic release of re-suspension sediment pollutants is about 6 times higher than the static release of sediment-water interface. There are three main types of release mechanism: diffusion release, re-suspended pore water mixing release and re-suspended particles desorbing release.

The yellow catfish (Pelteobagrus fulvidraco) is one of the important economic freshwater fish in China and widely distributed along Yangtze River. In this survey, we have developed eighteen polymorphic dinucleotide microsatellite markers. They were characterized using 36 samples collected from Chishui and Leshan fragment of Yangtze River. Number of alleles per locus ranged from 2 to 11. Mean observed heterozygosity over all eighteen loci was 0.559 (Chishui population) and 0.848 (Leshan population), respectively. Mean expected heterozygosity was 0.562 (Chishui population) and 0.613 (Leshan population), respectively. These microsatellite markers will be useful in studies of population genetic structure, genome mapping and marker-assisted selection of yellow catfish.

Background The renin-angiotensin system (RAS) has been implicated in atherosclerotic lesions and progression to chronic kidney diseases. We examined regulatory roles of angiotensin-converting enzyme 2 (ACE2) in the apolipoprotein E (ApoE) knockout (KO) kidneys. Methods The 3-month-old wild-type, ApoEKO, ACE2KO and ApoE/ACE2 double-KO (DKO) mice in a C57BL/6 background were used. The ApoEKO mice were randomized to daily deliver either Ang II (1.5 mg/kg) and/or human recombinant ACE2 (rhACE2; 2 mg/kg) for 2 weeks. We examined changes in pro-inflammatory cytokines, renal ultrastructure, and pathological signaling in mouse kidneys. Results Downregulation of ACE2 and nephrin levels was observed in ApoEKO kidneys. Genetic ACE2 deletion resulted in modest elevations in systolic blood pressure levels and Ang II type 1 receptor expression and reduced nephrin expression in kidneys of the ApoE/ACE2 DKO mice with a decrease in renal Ang-(1-7) levels. These changes were linked with marked increases in renal superoxide generation, NADPH oxidase (NOX) 4 and proinflammatory factors levels, including interleukin (IL)-1beta, IL-6, IL-17A, RANTES, ICAM-1, Tumor necrosis factor-alpha (TNF-alpha) and TNFRSF1A. Renal dysfunction and ultrastructure injury were aggravated in the ApoE/ACE2 DKO mice and Ang II-infused ApoEKO mice with increased plasma levels of creatinine, blood urea nitrogen and enhanced levels of Ang II in plasma and kidneys. The Ang II-mediated reductions of renal ACE2 and nephrin levels in ApoEKO mice were remarkably rescued by rhACE2 supplementation, along with augmentation of renal Ang-(1-7) levels. More importantly, rhACE2 treatment significantly reversed Ang II-induced renal inflammation, superoxide generation, kidney dysfunction and adverse renal injury in ApoEKO mice with suppression of the NOX4 and TNF-alpha-TNFRSF1A signaling. However, rhACE2 had no effect on renal NOX2 and TNFRSF1B expression and circulating lipid levels. Conclusions ACE2 deficiency exacerbates kidney inflammation, oxidative stress and adverse renal injury in the ApoE-mutant mice through modulation of the nephrin, NOX4 and TNF-alpha-TNFRSF1A signaling. While rhACE2 supplementation alleviates inflammation, renal dysfunction and glomerulus injury in the ApoE-mutant mice associated with upregulations of Ang-(1-7) levels and nephrin expression and suppression of the TNF-alpha-TNFRSF1A signaling. Strategies aimed at enhancing the ACE2/Ang-(1-7) actions may have important therapeutic potential for atherosclerotic renal injury and kidney diseases.

The two spotted spider mite, Tetranychus urticae Koch, is an important herbivore pest of apple trees in Northwest China. This spider mite and another less damaging spider mite, Eotetranychus pruni Oudemans, are attacked by a common and often effective phytoseiid predator, Euseius finlandicus (Oudemans). Functional relationships were studied in the field to evaluate the impact of E. pruni and E. finlandicus on T. urticae. The results from this study showed that the predator-mediated apparent competition strongly affected the population dynamics of T. urticae. The addition of the apparent competitor E. pruni alone had little impact on T. urticae densities. Although the release of the predator E. finlandicus alone could result in reduction in T. urticae densities, the greatest reduction in T. urticae densities occurred in plots where both the predator E. finlandicus and apparent competitor E. pruni were released. In apple orchards, the early introduction of both the apparent competitor E. pruni and predator E. finlandicus would evidently increase the population size of the predator E. finlandicus and consequently significantly enhance the control of T. urticae populations. It is concluded from the study that the predator and apparent competitor release might be an appropriate control for the target species.

Background Interactions between dendritic cells (DCs) and T cells play a critical role in the development of glomerulonephritis, which is a common cause of chronic kidney disease. DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), an immune-regulating molecule of the C-type lectin family, is mainly expressed on DCs and mediates DC adhesion and migration, inflammation, activation of primary T cells. DC-SIGN triggers immune responses and is involved in the immune escape of pathogens and tumours. In addition, ligation of DC-SIGN on DCs actively primes DCs to induce Tregs. Under certain conditions, DC-SIGN signalling may result in inhibition of DC maturation, by promoting regulatory T cell (Treg) function and affecting Th1/Th2 bias. Methods A rat model of nephrotoxic nephritis was used to investigate the therapeutic effects of an anti-lectin-epidermal growth factor (EGF) antibody on glomerulonephritis. DCs were induced by human peripheral blood mononuclear cells in vitro. The expression of DC surface antigens were detected using flow cytometry; the levels of cytokines were detected by ELISA and qPCR, respectively; the capability of DCs to stimulate T cell proliferation was examined by mixed lymphocyte reaction; PsL-EGFmAb targeting to DC-SIGN on DCs was identified by immunoprecipitation. Results Anti-Lectin-EGF antibody significantly reduced global crescent formation, tubulointerstitial injury and improved renal function impairment through inhibiting DC maturation and modulating Foxp3 expression and the Th1/Th2 cytokine balance in kidney. Binding of anti-Lectin-EGF antibody to DC-SIGN on human DCs inhibited DC maturation, increased IL-10 production from DCs and enhanced CD4+CD25+ Treg functions. Conclusions Our results suggest that treatment with anti-Lectin-EGF antibody modulates DCs to suppressive DCs and enhances Treg functions, contributing to the attenuation of renal injury in a rat model of nephrotoxic nephritis.

In practical computation of the discrete best uniform approximation, we usually only get “near best” (i.e., with the “e-near alteration property”) approximation. We need to estimate the error between the (unknown) best approximation and the achieved approximation. In this paper we estimate the parameter error by means of the generalized strong unicity constants.

Fluorescent metal nanoclusters, which consist of collections of small numbers of noble metal atoms, are of great interest in photochemistry and photophysics due to their strong size-dependent emission. Historically their generation was confined to gaseous and solid phases; however, recently a unique organic/inorganic hybrid materials approach was developed that utilizes dendrimers as templates to protect nanoclusters from solution based fluorescence quenching. These hybrid dendrimer/gold nanoclusters are water-soluble and highly fluorescent. Yet there are several intrinsic deficiencies in their synthetic method: first, NaBH4, a toxic chemical, was used as reducing agent in the reaction; and second, the reaction yield was low due to the concurrent formation of large, non-emissive, gold particles. Here we report a particle-free method to produce dendrimer-encapsulated gold nanoclusters in high-yield. Proof of concept is demonstrated using OH-terminated poly(amidoamine) dendrimer and Au(PX3)3Cl (X = Ph, Me), but the approach can also be extended to the combination of other dendrimers and organic noble metal salts. Our approach yields fluorescent clusters with homogeneous size distribution. These clusters can be transferred to aqueous solution and used directly for biological applications.