Search

OBJECTIVE: To detect plasma levels of receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) in patients with chronic heart failure and explore the expression pattern of programmed necrosis signaling pathway RIP1/RIP3-MLKL in the progression of heart failure. METHODS: The patients with chronic heart failure (NYHA class Ⅱ-Ⅳ) admitted in our hospital between February, 2020 and March, 2021 were prospectively enrolled in this study, with 21 healthy volunteers as the control group. The enrolled patients included 20 with grade Ⅱ, 33 with grade Ⅲ, and 43 with grade Ⅳ cardiac function. Fasting venous blood was collected from all the participants for detecting plasma levels of RIP1, RIP3, and MLKL and protein expressions of RIP1/RIP3-MLKL pathway using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The patients with grade Ⅳ cardiac function were followed up for 5 months to evaluate the clinical prognostic indicators. RESULTS: Compared with the healthy volunteers, the patients with grade Ⅱ, Ⅲ and Ⅳ cardiac function had significantly increased plasma levels of RIP1, RIP3, and MLKL (P < 0.01), and their levels were significantly higher in grade Ⅲ/Ⅳ patients than in those with grade Ⅱ cardiac function (P < 0.01); the plasma levels of RIP1 and MLKL were significantly higher in grade Ⅳ patients than in grade Ⅲ patients (P < 0.05). The results of Western blotting also showed increased expressions of the proteins in the RIP1/RIP3-MLKL pathway in patients with heart failure. Pearson correlation analysis suggested that in patients with heart failure, the expression levels of RIP1, RIP3, and MLKL were positively correlated with SCR, AST, LVEDD and NT-proBNP (P < 0.05). Follow-up study of the patients with grade Ⅳ cardiac function showed that higher expression levels of RIP1/RIP3-MLKL were associated with a poorer prognosis of the patients. CONCLUSION: The expressions of RIP1, RIP3 and MLKL are significantly upregulated in patients with heart failure in positive correlation with the severity of the disease condition, and the activation of the RIP1/RIP3-MLKL signaling pathway may contribute to the occurrence, development and prognosis of chronic heart failure.

OBJECTIVE: To investigate the molecular mechanism of quercetin in the treatment of heart failure (HF) based on network pharmacology and molecular docking. METHODS: Quercetin and HF-related targets were obtained using TCMSP, PharmMapper, CTD and GeneCards databases, and quercetin-HF intersection targets were obtained through the online website Venn; the protein interaction network was constructed and imported into Cytoscape 3.7.2 to identify the core targets of quercetin in the treatment of HF.GO and KEGG pathway enrichment analyses were performed using R package, and molecular docking was performed using Auto Dock Vina.The protein levels of AKT1, phospho-AKT(Ser473), eNOS, MMP9, and caspase-3 in quercetin-treated HF cell models were detected using protein immunoblotting. RESULTS: We identified 80 quercetin-HF intersectional targets (AKT1, CASP3, MAPK1, MMP9, and MAPK8) and 5 core targets of quercetin for treatment of HF.GO analysis suggested that the therapeutic effect of quercetin for HF was mediated mainly by such biological processes as responses to peptide hormones, phosphatidylinositol-mediated signalling, responses to lipopolysaccharides, responses to molecules of bacterial origin and regulation of inflammatory responses.KEGG pathway enrichment analysis identified lipid and atherosclerosis pathway, proteoglycans in cancer, PI3K-AKT signaling pathway, diabetic cardiomyopathy and MAPK signaling pathway as the most significantly enriched signaling pathways.Molecular docking showed a good binding activity of quercetin to the 5 core targets.The results of protein immunoblotting showed that 100 μmol/L quercetin significantly reduced AKT1, phospho-AKT (Ser473), eNOS, MMP9 and caspase-3 levels in the cell models of HF (P < 0.01). CONCLUSION: Quercetin improves the pathological changes in HF possibly by regulating the AKT1-eNOS-MMP9 pathway to inhibit cell apoptosis.

Low-lying states of Cd-98 have been populated by the two-nucleon removal reaction (In-100, Cd-98+gamma) and studied using in-beam gamma-ray spectroscopy at the Radioactive Isotope Beam Factory at RIKEN. Two new gamma transitions were identified and assigned as decays from a previously unknown state. This state is suggested to be based on a pi 1g(/9/2)(-1)2p(1/2)(-2) configuration with J(pi) = 5(-). The present observation extends the systematics of the excitation energies of the first 5(-) state in N = 50 isotones toward Sn-100. The determined energy of the 5(- )state in Cd-98 continues a smooth trend along the N = 50 isotones. The systematics are compared with shell-model calculations in different model spaces. Good agreement is achieved when considering a model space consisting of the pi(1f(5/2), 2p(3/2), 2p(1/2), 1g(9/2)) orbitals. The calculations with a smaller model space omitting the orbitals below the Z = 38 subshell could not reproduce the experimental energy difference between the ground and first 5(-) states in N = 50 isotones, because proton excitations across Z = 38 subshell yield a large amount of correlation energy that lowers the ground states. (Less)

According to the overall requirements of ecological construction and environmental protection, rely on the national key ecological engineering, strengthen ecological environmental restoration and protection, improve forest cover, control soil erosion, construct important ecological security barrier in poor areas, inhibit poverty alleviation through ecological security in this area from environmental damage to the vicious cycle of poverty. Obviously, the dynamic monitoring of ecological security in contiguous destitute areas of Sichuan province has a policy sense of urgency and practical significance. This paper adopts RS technology and GIS technology to select the Luhe region of Jinchuan county and Ganzi prefecture as the research area, combined with the characteristics of ecological environment in poor areas, the impact factors of ecological environment are determined as land use type, terrain slope, vegetation cover, surface water, soil moisture and other factors. Using the ecological environmental safety assessment model, the ecological environment safety index is calculated. According to the index, the ecological environment safety of the research area is divided into four levels. The ecological environment safety classification map of 1990 in 2009 is obtained. It can be seen that with the human modern life and improve their economic level, the surrounding environment will be destroyed, because the research area ecological environment is now in good, the ecological environment generally tends to be stable. We should keep its ecological security good and improve local economic income. The relationship between ecological environmental security and economic coordinated development in poor areas has very important strategic significance.

We present the first direct measurement of the atomic mass of a superheavy nuclide. Atoms of $^{257}$Db ($Z$=105) were produced online at the RIKEN Nishina Center for Accelerator-Based Science using the fusion-evaporation reaction $^{208}$Pb($^{51}$V, 2n)$^{257}$Db. The gas-filled recoil ion separator GARIS-II was used to suppress both the unreacted primary beam and some transfer products, prior to delivering the energetic beam of $^{257}$Db ions to a helium gas-filled ion stopping cell wherein they were thermalized. Thermalized $^{257}$Db$^{3+}$ ions were then transferred to a multi-reflection time-of-flight mass spectrograph for mass analysis. An alpha particle detector embedded in the ion time-of-flight detector allowed disambiguation of the rare $^{257}$Db$^{3+}$ time-of-flight detection events from background by means of correlation with characteristic $\alpha$-decays. The extreme sensitivity of this technique allowed a precision atomic mass determination from 11 events. The mass excess was determined to be $100\,063(231)_\textrm{stat}(132)_\textrm{sys}$~keV/c$^2$. Comparing to several mass models, we show the technique can be used to unambiguously determine the atomic number as $Z$=105 and should allow similar evaluations for heavier species in future work., Comment: Submitted to PRC as Rapid Comm., 5 pages, 4 figures

Hydrogen sulfide (H2S) is a gasotransmitter that regulates cellular homeostasis and impacts on multiple physiological and pathophysiological processes. However, it exerts many of its biological actions indirectly via the formation of H2S-derived sulfane sulfur species/polysulfides. Because of the high reactivity of sulfur species, the detection of H2S-derived polysulfides in biological systems is challenging and currently used methods are neither sensitive nor quantitative. Herein, we describe a LC-MS/MS-based method that makes use of Sulfane Sulfur Probe 4 to detect endogenously generated polysulfides in biological samples in a selective, sensitive and quantitative manner. The results indicate a large variability in the activity of the H2S-generating enzymes in different murine organs, but the method described was able to detect intracellular levels of polysulfides in the nanomolar range and identify cystathionine γ-lyase as the major intracellular source of sulfane sulfur species/polysulfides in murine endothelial cells and hearts. The protocol described can be applied to a variety of biological samples for the quantification of the H2S-derived polysulfides and has the potential to increase understanding on the control and consequences of this gaseous transmitter. © 2018 The Authors

We have investigated the effects of O2, ethanol, and KI on the photocatalytic efficiency of Bi2Fe4O9 nanoparticles towards the degradation of methylene blue (MB). It is observed that O2 has a negligible effect on the photocatalytic degradation rate of the dye, whereas ethanol and KI exhibit a strong suppression of the dye degradation, with a stronger effect observed for the latter. Hydroxyl radicals are shown, by the photoluminescence technique using coumarin as a probe molecule, to be produced on the irradiated Bi2Fe4O9, and are scavenged on addition of ethanol and KI. The mechanisms involved are discussed in detail. Based on the experimental results, hydroxyl radicals and photogenerated holes are suggested to be the two main active species in the photocatalytic degradation of MB by Bi2Fe4O9 nanoparticles.

In order to design a High Temperature Superconducting (HTS) machine that is able to operate safely and reliably, studies on the characterization of Second Generation (2G) HTS tapes are of paramount importance. This paper presents an experimental setup to measure critical current of 2G HTS tapes in high DC magnetic fields (up to 5 Tesla) with an AC current ripple superimposed, as well as various temperatures ranging from 25 K to 77 K. The 2G tape measured is the SGS12050 coated conductor made by SuperPower. The critical current is measured by a flux vector with reference to the widest sample face from 0 to 90 degrees in 10 degree steps. Smaller steps are required close to 0°. A Variable Temperature Insert (VTI) is utilized to control temperature change.

As we known, the high temperature (77 K) superconducting (HTS) motor is considered as a competitive electrical machine by more and more people. There have been various of designs for HTS motor in the world. However, most of them focus on HTS tapes rather than bulks. Therefore, in order to investigate possibility of HTS bulks on motor application, a HTS magnet synchronous motor which has 75 pieces of YBCO bulks surface mounted on the rotor has been designed and developed in Cambridge University. After pulsed field magnetization (PFM) process, the rotor can trap a 4 poles magnetic field of 375 mT. The magnetized rotor can provide a maximum torque of 49.5 Nm and a maximum power of 7.8 kW at 1500 rpm.

This paper begins with introducing the winding techniques of two superconducting double-pancake coils wound using 2G coated conductors. These winding techniques are able to guarantee a good performance for the superconducting coils. Then the coil critical currents were measured and compared with a simulation model. The results were consistent. Finally the coil AC losses were measured using an experimental circuit including a compensation coil. The simulation results are close to the experiment results.

High temperature superconductors, such as melt-processed YBCO bulks, have great advantages on trapping strong magnetic fields in liquid nitrogen. To enable them to function well, there are some traditional ways of magnetizing them, in which the YBCO bulks are magnetized instantly under a very strong source of magnetic field. These ways would consume great amounts of power to make the superconductors trap as much field as possible. Thermally Actuated Magnetization (TAM) Flux pump has been proved a perfect substitution for these expensive methods by using a relatively small magnet as the source. In this way, the field is developed gradually over many pulses. Unlike conventional flux pumping ways, the TAM does not drive the superconductor normal during the process of magnetization. In former experiments for the flux pump, some fundamental tests were done. In this paper, the experiment system is advanced to a new level with better temperature control to the thermal waves moving in the Gadolinium and with less air gap for the flux lines sweeping through the superconductor. This experiment system leads to a stronger accumulation of the magnetic field trapped in the YBCO bulk. We also tried different ways of sending the thermal waves and found out that the pumping effect is closely related to the power of the heaters and the on and off time.

This paper presents an SMES coil which has been designed and tested by University of Cambridge. The design gives the maximum stored energy in the coil which has been wound by a certain length of second-generation high-temperature superconductors (2G HTS). A numerical model has been developed to analyse the current density and magnetic field distribution and calculate the AC losses during the charge and discharge process of the coil. A cryostat has been designed and a test of the I-V curve measurement of the coil has been accomplished. In addition, the power electronics control of the SMES coil has been simulated.

It is particularly attractive for High Temperature Superconductors (HTS), such as the melt-processed YBCO single-grain bulks, to trap strong magnetic fields at cryogenic temperatures. With the flux density orders of magnitude much greater than the rare earth magnets, the YBCO bulks can be formed as small and as compact as them. As a result, YBCO bulks are used as magnets in magnetic bearings, MRI scanners and motors, etc. The trapped field by the YBCO magnet is decided by the magnetization, which normally includes three different ways. However, the traditional ways to magnetize the YBCO will always need the applied field to be as high as the expected field on the superconductor or much higher than it. In this paper, we will describe a technique which facilitates the creation of the high magnetic field and utilize a normal permanent magnet in stead. By using this rare earth permanent magnet which is not as strong, this technique involves the superconducting flux pump concept, which means that a much larger field being trapped by the superconductor bulk is caused by a small field repeatedly applied to it. To achieve such pumping effect, an intermedia material is necessary and in the related experiments, Gadolinium is used as such an important thermally actuated material. Traveling magnetic field through it will magnetize the YBCO in such a way that the flux density will be accumulated step by step on the surface on the bulk.

General formulae for coherent/incoherent nucleation fields have been obtained as functions of the thickness of the hard and soft layers within a self-contained micromagnetic model for a hard/soft trilayer. The nucleation modes are determined reliably by direct comparison of the nucleation fields for different modes. It is shown that coherent nucleation cannot take place no matter how small the layer thickness. For small soft layer thickness, the magnetic reversal mode is an incoherent nucleation. As the soft layer thickness increases, the dominant magnetic reversal process is domain-wall motion/pinning. Analyses demonstrate that negative nucleation field and very small coercivity occur when the easy axes of neighboring layers are perpendicular. The results could shade light on Brown's coercivity paradox (where the measured coercivity is much smaller than the one given by the previous theories).

This paper describes in detail the magnetization process of a synchronous motor, constructed with High Temperature Superconducting (HTS) elements on the rotor. The Pulse Field Magnetization (PFM) method is considered to magnetize the HTS rotor as a four-pole trapped flux magnet. A 2D model is built for the magnetization process. During the machine operation, intolerable torque ripples occur, which are mainly caused by the irregular field distribution from the magnetized HTS rotor. In order to suppress the large torque ripples, an iterative learning control method is used in addition to the traditional field-oriented control method.

The effects of Ga content on the electrochemical behavior of Mg-5 at%Hg alloys which contain a small amount of Ga was investigated by the measurement of polarization curves and galvanostatic test. The microstructure of the alloys and the surface of the specimens corroded in galvanostatic test were observed by using scanning electron microscopy, energy spectrum analysis and X-ray diffraction analysis. It can be concluded that with the content of Ga increasing, the alloys come into Mg-Mg 3 Hg, Mg-Mg 7.2 (Hg, Ga) 2.8 and Mg-Mg 5 Ga 2 binary phase fields sequentially. The best electrochemical activity occur in the Mg-5 at%Hg -1 at%Ga alloy, with open circle potential -2.124V and mean potential -1.992 V. The corrosion resistance of the alloys is in the sequential order from big to small: Mg-5 at%Hg-5 at%Ga, Mg-5 at%Hg-22 at%Ga, Mg-5 at%Hg-1 at%Ga, Mg-5 at%Hg. The lowest corrosion current density is 0.418 mA·cm -2 . The activation mechanism of the magnesium alloy produced by Hg and Ga was concluded: the dissolution of Hg and Ga atoms leads to the back accumulation of liquid Hg and Ga, which makes a true metallic contact with a-Mg. Magnesium atoms diffuse through the liquid mercury and gallium to form magnesium amalgam and undergo severe oxidation at the amalgam/electrolyte interface. The reaction produces pure Hg and Ga again which continue the activation process.

Leucine-rich repeat kinase 2 (LRRK2) S1647T has been identified as a risk variant for Parkinson's disease (PD) in Han Chinese.To replicate the association of LRRK2 S1647T with risk of PD, we conducted a case-control study of this variant involving 406 PD subjects and 412 controls from southern mainland China.The results showed that the frequency of A allele was higher in patients with PD (OR=1.238, 95% CI: 1.015-1.510, P=0.035) compared to controls. In a multivariate logistic regression analysis with the disease group (patients with PD vs. controls) as the dependent variable and genotype as an independent factor adjusting for the effect of age and gender, the homozygous S1647T genotype (AA) was associated with an increased risk of PD (OR=1.815, 95% CI:1.270-2.594, P=0.001). The pooled analysis of present data and the data from the previous work demonstrated that the frequency of A allele was higher in patients with PD (OR=1.2, 95% CI: 1.09-1.32, P0.0001).LRRK2 S1647T increases the risk of Parkinson's disease in southern China.

Wind power generation as one of the most popular renewable energy applications is absorbing more and more attention all over the world. However, output power fluctuations of wind farm due to random variations of wind speed can cause network frequency and voltage flicker in power systems. The power quality consequently declines, particularly in an isolated power system such as the power system in a remote community or a small island. This paper proposes an application of superconducting magnetic energy storage (SMES) to minimize output fluctuations of an isolated power system with wind farm. The isolated power system is fed by a diesel generator and a wind generator consisting of a wind turbine and squirrel cage induction machine. The control strategy is detailed and the proposed system is evaluated by simulation in Matlab/Simulink.

We have built a four-pole high temperature superconducting (HTS) permanent magnet synchronous motor (PMSM) in our lab. At this stage, the HTS PMSM uses two 2G HTS racetrack coils, which are YBCO wires, type 344 from AMSC, and four conventional copper coils as stator windings. 75 YBCO bulks are mounted on the surface of the rotor. After the pulsed field magnetization system had been developed and tested in our lab in 2011, the rotor can trap a four-pole magnetic field. This makes HTS bulks possible for motor application, other than HTS coils. The HTS PMSM can successfully run at a low speed of around 150 rpm for an initial test. This paper states theoretical and practical works on the HTS PMSM's operation including HTS motor drive development and its application.

The present study was designed to further investigate the role of the epidermal growth factor receptor (EGFr) in mouse skin tumor promotion by evaluating the status of the EGFr in tumor promoter-treated mouse epidermis and in mouse skin tumors. Female SENCAR mice received three topical treatments of either the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or the nonphorbol esters okadaic acid and chrysarobin. Membrane proteins from SENCAR mouse epidermis were isolated 6 h after the last treatment, and the phosphotyrosine content of the EGFr and several potential substrates were examined by Western blot analysis. The results indicated that multiple applications of all three tumor promoters led to an increase in the phosphotyrosine content of the EGFr and also of several lower molecular weight proteins (M(r) approximately 80,000-85,000). Phosphorylation of PLC gamma 1 on tyrosine residues could not be detected in tumor promoter-treated mouse epidermis when the phosphotyrosine content of the EGFr was elevated or in cultured keratinocytes exposed to exogenous EGF. When two tyrosine kinase inhibitors (tyrphostins RG50864 and RG13022) were incorporated into the treatment regimens, the TPA-induced epidermal hyperplasia and cell proliferation were effectively blocked, and the TPA-stimulated EGFr tyrosine phosphorylation was significantly reduced. Examination of the phosphotyrosine content of epidermal membrane proteins isolated from skin papillomas revealed that the EGFr also had elevated phosphotyrosine levels. These results demonstrate that multiple topical treatments with both phorbol ester and nonphorbol ester tumor promoters lead to activation of the EGFr tyrosine kinase in mouse epidermis. In addition, these data suggest that signaling through the EGFr pathway plays an important role in the tumor promotion stage of multistage carcinogenesis in mouse skin.

The mouse skin model of multistage carcinogenesis continues to serve as a major in vivo model for studying the sequential and stepwise evolution of the cancer process by chemical and physical carcinogens. The initiation stage of mouse skin carcinogenesis involves genetic damage in the form of DNA adducts or initiator-induced DNA base changes. These changes ultimately lead to mutations in critical target genes of epidermal stem cells. The rasHa gene, and to a limited extent the N-ras gene, have been identified as target genes for certain tumor initiators in this model system (reviewed in DiGiovanni 1992). The promotion stage of mouse skin carcinogenesis involves the production and maintenance of a chronic state of hyperplasia and cell proliferation and ultimately the selective clonal expansion of initiated cells. The hallmark of all tumor promoters that have been adequately tested is their ability to induce a potentiated hyperplasia after several treatments that is greater than that observed after a single application. Tumor promoters produce many effects when applied topically to mouse skin. Many of the effects that occur after a single application of phorbol esters such as TPA appear to be mediated by its interaction with PKC (Nishizuka 1989). An important question is whether the activation of PKC per se is responsible for tumor promotion by TPA. Because repetitive treatments with TPA lead to a sustained loss of PKC, it is possible that other effects not mediated by PKC but produced by phorbol esters and related compounds may play an important role in the production and maintenance of chronic hyperplasia and cell proliferation in the skin and for skin tumor promotion. More attention should be placed on studying the promoting actions of other compounds outside of the most commonly studied phorbol esters. Investigations of some of these compounds already have and will continue to provide important clues regarding possible common pathways shared by diverse promoting agents. One such pathway may involve the EGFr and its ligand TGF alpha. As discussed in this review, it is now evident that many different types of promoting agents increase production of TGF alpha (Ellem et al. 1988, Pittelkow et al. 1989, Choi et al. 1991, Imamoto et al. 1991, J. DiGiovanni unpublished studies). Although many tumor promoters initially decrease the binding of 125I-EGF to EGFr in specific cell types, including mouse epidermal cells, the long-term effects of tumor promoters, especially after repetitive treatments, may be considerably different.+4

A high temperature superconducting (HTS) permanent magnet synchronous motor (PMSM) is designed and developed in Cambridge University. It is expected to become cost competitive with the conventional PMSM owing to its high efficiency, high power density, high torque density, etc. The structure and parameters of HTS PMSM are detailed. Both AC losses by transport current and applied filed in stator armature winding of HTS PMSM are also analyzed. Computed and simulated results of the characteristics of the HTS PMSM and conventional PMSM are compared. The improvement on stability of direct torque control (DTC) on the HTS PMSM is estimated, and proved by simulation on Matlab/Simulink.

This paper describes in detail the method of magnetization of a superconducting permanent magnet synchronous motor. The rotor of the motor consists of 60 superconducting pucks, which are magnetized by two additional copper windings. The pulse field magnetization (PFM) method is considered and the resulted distribution of the magnetizing flux linkage from the rotor is not a perfect sine wave in the air gap, which leads to a large torque ripple and harmonics of the stator currents. In order to suppress the torque ripple, an iterative learning control (ILC) algorithm is used in addition to the former field-oriented control method. The results show the ILC algorithm can largely reduce the torque ripple.