Serum SERCA2a levels in heart failure patients are associated with adverse events after discharge.

Calcium homeostasis imbalance is one of the important pathological mechanisms in heart failure. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), a calcium ATPase on the sarcoplasmic reticulum in cardiac myocytes, is a myocardial systolic-diastolic Ca2 + homeostasis regulating enzyme that is not only involved in cardiac diastole but also indirectly affects cardiac myocyte contraction. SERCA2a expression was found to be decreased in myocardial tissue in heart failure, however, there are few reports on serum SERCA2a expression in patients with heart failure, and this study was designed to investigate whether serum SERCA2a levels are associated with the occurrence of adverse events after discharge in patients hospitalized with heart failure. Patients with heart failure hospitalized in the cardiovascular department of the Second Affiliated Hospital of Guangdong Medical University, China, from July 2018 to July 2019 were included in this study, and serum SERCA2a concentrations were measured; each enrolled patient was followed up by telephone after 6 months (6 ±â€…1 months) for general post-discharge patient status. The correlation between serum SERCA2a levels and the occurrence of adverse events (death or readmission due to heart failure) after hospital discharge was assessed using multiple analysis and trend analysis. Seventy-one patients with heart failure were finally included in this study, of whom 38 (53.5%) were men and 33 (46.5%) were women (All were postmenopausal women). Multiple analysis revealed no correlation between serum SERCA2a levels and the occurrence of adverse events in the total study population and in male patients, but serum SERCA2a levels were associated with the occurrence of adverse outcome events after hospital discharge in female patients (OR = 1.02, P = .047). Further analysis using a trend analysis yielded a 4.0% increase in the risk of adverse outcomes after hospital discharge for each unit increase in SERCA2a in female patients (OR = 1.04; P = .02), while no significant difference was seen in men. This study suggests that serum SERCA2a levels at admission are associated with the occurrence of post-discharge adverse events in postmenopausal female patients hospitalized with heart failure.

[The Effect of SP1 on the Progression of T-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To study the transcriptional regulation of SP1 on the scaffold protein ARRB1 and its influence on the progression of T-cell acute lymphoblastic leukemia (T-ALL). METHODS: pGL3-ARRB1-luc, pCDNA3.1-SP1 and other transcription factor plasmids that might be combined were constructed, and the binding of transcription factors to the promoter of ARRB1 was identified by dual luciferase reporter gene assay. Stable cell lines with over-expressed SP1 (JK-SP1) was constructed by lentiviral transfection, and the expression correlation of SP1 with ARRB1 was demonstrated by RT-PCR and Western blot. Further, the apoptosis, cell cycle and reactive oxygen species (ROS) were detected by flow cytometry. The effect of SP1 on propagation of leukemic cells was observed on NCG leukemic mice. RESULTS: The expression of fluorescein were enhanced by co-transfection with pCDNA3.1-SP1 and pGL3-ARRB1-luc plasmids in HEK293T cell line (P<0.001), meanwhile, compared with the control group, the expression of ARRB1 mRNA and protein were increased in JK-SP1 cells (both P<0.01). Further in vitro experiments showed that, compared with the control group, the apoptosis rate was higher (x=22.78%) , the cell cycle was mostly blocked in G1 phase (63.00%), and the content of reactive oxygen species increased in JK-SP1 cells. And in vivo experiments showed that the mice injected with JK-SP1 cells through tail vein had a favorable overall survival time (average 33.8 days), less infiltration in liver and spleen tissue. CONCLUSION: Transcription factor SP1 promotes the transcription and expression of ARRB1 by binding the the promoter of ARRB1 directly, thus delays the progress of T-ALL in vitro and in vivo. The study improves the pathogenesis of ARRB1 regulating the initiation and development of T-ALL, and provides theoretical basis for the development of new possible targeted drugs.

Bifunctional Metal-Organic Framework Functionalized by Dimethylamine Cations: Proton Conduction and Iodine Vapor Adsorption.

A metal-organic framework, {Zn3(BTB)2(µ3-OH)[(CH3)2NH2](H2O)}n (1), was synthesized based on H3BTB (1,3,5-tri(4-carboxyphenyl)benzene). An AC impedance test proves that 1 has a relatively high conductivity performance of 1.52 × 10-3 S·cm-1 at 338 K and 98% RH. The proton conductivity of the composite film 1@CS-9 (CS = chitosan) reaches 1.84 × 10-1 S·cm-1 at 328 K and 98% RH. In addition, 1 is discovered to have a good adsorption effect on iodine vapor, and the adsorption capacity reaches 726 mg·g-1. The multifunctionality caused by dimethylamine cations was investigated for the first time, which has implications for multifunctionality generated by host-guest molecules.

Designable Guest-Molecule Encapsulation in Metal-Organic Frameworks for Proton Conductivity.

Metal-organic frameworks (MOFs), as a porous frame material, exhibit considerable electrical conductivity. In recent decades, research on the proton conductivity of MOFs has made gratifying progress. In this review, the designable guest molecules encapsulated into MOFs are summarized and generalized into four types in terms of promoting proton conductive performance, and then recent progress in the promotion of proton conductivity by MOFs encapsulating guest molecules is discussed. The existing challenges and prospects for the development of this strategy for promoting MOFs' proton conductivity are also listed.

Dual-Functional Coordination Polymer with High Proton Conductivity and a Low-Detection-Limit Fluorescent Probe.

A coordination polymer with dual functions of high proton conductivity and highly sensitive fluorescent sensors demonstrates a great application potential. In this work, a cadmium-based coordination polymer (denoted as CP 1) with hydrothermal stability was synthesized. The abundant coordination water, lattice water, and amino groups make an extended hydrogen-bonding pathway for efficient proton migration, which endows CP 1 with the highest proton conductivity of 2.41 × 10-3 S·cm-1 at 353 K and 98% RH. Especially, the proton conductivity of the chitosan (CS) hybrid membrane containing CP 1 reaches a maximum value of 2.62 × 10-2 S·cm-1 under 343 K and 98% RH, which increases almost 7 times higher than that of the pure CS membrane due to the host-guest collaboration. Furthermore, luminescence studies revealed that CP 1 is a high-sensitivity and good-selectivity fluorescent probe for the detection of trace amounts of l-histidine with a lowest detection limit of 1.0 × 10-8 M.

[ß-arrestin1 Promotes the Concentration of Mitochondrial Reactive Oxygen in T-ALL Cells via MiR-652-5p].

OBJECTIVE: To investigate the effect of ß-arrestin1 on the concentration of reactive oxygen species (ROS) in the mitochondria of acute T-lymphocytic leukemia (T-ALL) cells and its possible mechanisms. METHODS: The stable T-ALL cell line with knocked down ß-arrestin1 (Jurkat Siß1) was constructed. Flow cytometry and probe assays were used to detect ROS content in cell and mitochondrial, respectively. The relationship between ß-arrestin1 and microRNA was detected, analyzed and Q-PCR confirmed by microRNA microarray. The target genes of microRNA were predicated by miRbase software, identified by Western blot, and validated by Dual luciferase reporter gene. RESULTS: Jurkat Siß1 stable cell line was successfully constructed and it was found that ROS content was slightly reduced in Jurkat Siß1 at the whole cell level, and the ROS content was also significantly reduced in mitochondria. MicroRNA microarray analysis revealed that multiple T-ALL related microRNAs showed differentially expressed, in which the expression of miR-652-5p was significantly increased in Jurkat Siß1 (P<0.05 fold>2.0), and Q-PCR showed that miR-652-5p was nearly 5-fold up-regulated in Jurkat Siß1. miRbase predicted that the P62 gene was the target gene of miR-652-5p which could regulates mitochondrial function. P62 protein showed highly expressed in stably knocked down miR-652-5p in Jurkat cells. Dual luciferase reporter gene assay confirms that P62 was the target gene of miR-652-5p. CONCLUSION: ß-arrestin1 can decreases the expression of miR-652-5p and deregulates the translational inhibition of P62 mRNA, thus to increase ROS content in mitochondria of T-ALL cells.

Promotion of Proton Conductivity by Encapsulation of Metal-Organic Polyhedra in Metal-Organic Frameworks.

A Zr-based metal-organic polyhedron (MOP) was self-assembled in a porous MOF host, DUT-68, successfully to synthesize MOP-1@DUT-68. The MOP guest (MOP-1) has a diameter of about 20 Å, larger than that of the square windows (pore sizes of ∼14 Å) of DUT-68 but smaller than that of the rhombicuboctahedral cage (27.7 Å), which means that the migration and leaching of MOP-1 could be effectively prohibited if MOP-1 is encapsulated in the MOF's cavities. The proton conductivity of MOP-1@DUT-68 is 1.14×10-3  S cm-1 (at 80 °C under 98 % relative humidity), which is three orders of magnitude higher than that of DUT-68. Compared with MOP-1⊂DUT-68, which was synthesized by impregnation, MOP-1@DUT-68 is more prone to form faster proton-conduction pathways and thus provides higher proton conductivity.

Dual-functional coordination polymers with high proton conduction behaviour and good luminescence properties.

Two coordination polymers, [M(5-hip)(H2O)3]n (M = Cd2+ (1), Zn2+ (2), 5-hip = 5-hydroxyisophthalic acid), have been synthesized under hydrothermal conditions. The crystal structure reveals that complexes 1 and 2 have 1D chain structures by the coordination of metal ions and 5-hip. 1D chains are connected by hydrogen bonds to form a 3D structure. AC impedance analysis shows that the proton conductivity of complexes 1 and 2 comes up to 1.58 × 10-3 S cm-1 (98%RH, 343 K) and 5.27 × 10-4 S cm-1 (98%RH, 353 K), respectively. To further improve the proton conductivity, a hybrid membrane was prepared by the solution casting method with complexes as fillers and sulfonated polyether ether ketone (SPEEK) as the organic matrix. The proton conductivity of hybrid membranes 1@SPEEK-5 and 2@SPEEK-5 is 1.97 and 1.58 times higher than that of pure SPEEK membranes, respectively. Furthermore, the two complexes are excellent fluorescent sensors, which could detect Cr2O72- in aqueous solution with high sensitivity and selectivity. Both of them have low detection limits for Cr2O72- in aqueous solution, where the detection limit of complex 1 is 0.8 µM and that of complex 2 is 1 µM. The above work demonstrates that the two complexes are dual-functional materials with high proton conduction and good fluorescence properties.

A dual-functional MOF for high proton conduction and sensitive detection of ascorbic acid.

A new metal-organic framework (MOF), [Eu2(HBDPP)2(H2O)2(DMF)2](H2O)2 (H4BDPP = 3,5-bis(3,5-dicarboxylphenyl) pyridine; DMF = N,N-dimethylformamide) (Eu-MOF), has been successfully synthesized under solvothermal conditions. A 1D chain was formed by the adjacent Eu2(COO)24+ dinuclear cluster and HBDPP3-, and further connected by HBDPP3- to form an infinitely extended 3D structure. In order to further improve the proton conductivity of the Eu-MOF, imidazole was encapsulated in its pores to form a composite material named Im@Eu-MOF. AC impedance analysis shows that the highest proton conductivity of the Im@Eu-MOF reaches up to 4.53 × 10-4 S cm-1 at 348 K and 98% RH, which is about 10 times higher than that of the Eu-MOF. In addition, the Eu-MOF can be considered an excellent luminescence-based sensor with a high sensitivity and low detection limit (0.1 µM) for the detection of trace amounts of ascorbic acid.

Complete Genome Sequence of Clostridium kluyveri JZZ Applied in Chinese Strong-Flavor Liquor Production.

Chinese strong-flavor liquor (CSFL), accounting for more than 70% of both Chinese liquor production and sales, was produced by complex fermentation with pit mud. Clostridium kluyveri, an important species coexisted with other microorganisms in fermentation pit mud (FPM), could produce caproic acid, which was subsequently converted to the key CSFL flavor substance ethyl caproate. In this study, we present the first complete genome sequence of C. kluyveri isolated from FPM. Clostridium kluyveri JZZ contains one circular chromosome and one circular plasmid with length of 4,454,353 and 58,581 bp, respectively. 4158 protein-coding genes were predicted and 2792 genes could be assigned with COG categories. It possesses the pathway predicted for biosynthesis of caproic acid with ethanol. Compared to other two C. kluyveri genomes, JZZ consists of longer chromosome with multiple gene rearrangements, and contains more genes involved in defense mechanisms, as well as DNA replication, recombination, and repair. Meanwhile, JZZ contains fewer genes involved in secondary metabolites biosynthesis, transport, and catabolism, including genes encoding Polyketide Synthases/Non-ribosomal Peptide Synthetases. Additionally, JZZ possesses 960 unique genes with relatively aggregating in defense mechanisms and transcription. Our study will be available for further research about C. kluyveri isolated from FPM, and will also facilitate the genetic engineering to increase biofuel production and improve fragrance flavor of CSFL.

Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16.

The proliferation and migration of vascular smooth muscle cells are significant in the development and progression of atherosclerosis and plaque rupture. Metformin is a widely used antidiabetic drug, which has been reported to inhibit cell growth and migration. The antiproliferative and antimigratory effects of metformin have been attributed to 5' adenosine monophosphate-activated protein kinase (AMPK) activation. The purpose of the present study was to investigate the effects of metformin on primary human aortic muscle cells (HASMCs) in vitro and to clarify the underlying mechanism. We investigated the effectiveness of metformin in inhibiting the proliferation and migration of HASMCs in vitro using RNA extraction and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell number counting, cell viability assay, cell cycle assay and cell migration assay. Through transfection with small interfering (si)RNA targeting p53 and interferon­inducible protein 16 (IFI16), the roles of p53 and IFI16 in these processes were evaluated. The present study demonstrated that p53, IFI16 and AMPK were upregulated in senescent primary HASMCs, which exhibited a decrease in proliferation and migration. In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs. Furthermore, siRNA­mediated knockdown of p53 and IFI16 attenuated AMPK activation and reversed the suppressive effects of metformin. Notably, in response to metformin, the activation of AMPK was not observed in p53­ and IFI16­silenced HASMCs. These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16. These findings suggested that metformin may have potential use in the treatment of atherosclerosis.

Direct observation of turbulent magnetic fields in hot, dense laser produced plasmas.

Turbulence in fluids is a ubiquitous, fascinating, and complex natural phenomenon that is not yet fully understood. Unraveling turbulence in high density, high temperature plasmas is an even bigger challenge because of the importance of electromagnetic forces and the typically violent environments. Fascinating and novel behavior of hot dense matter has so far been only indirectly inferred because of the enormous difficulties of making observations on such matter. Here, we present direct evidence of turbulence in giant magnetic fields created in an overdense, hot plasma by relativistic intensity (10(18) W/cm(2)) femtosecond laser pulses. We have obtained magneto-optic polarigrams at femtosecond time intervals, simultaneously with micrometer spatial resolution. The spatial profiles of the magnetic field show randomness and their k spectra exhibit a power law along with certain well defined peaks at scales shorter than skin depth. Detailed two-dimensional particle-in-cell simulations delineate the underlying interaction between forward currents of relativistic energy "hot" electrons created by the laser pulse and "cold" return currents of thermal electrons induced in the target. Our results are not only fundamentally interesting but should also arouse interest on the role of magnetic turbulence induced resistivity in the context of fast ignition of laser fusion, and the possibility of experimentally simulating such structures with respect to the sun and other stellar environments.

Relativistic collisional current-filamentation instability and two-stream instability in dense plasma.

The collisional effects on the current-filamentation instability (CFI) and the two-stream instability (TSI), which appear as a relativistic intense electron beam penetrating into a cold dense plasma, are investigated. It is shown that the growth rate of the CFI mode is first attenuated and then enhanced by the collisional effects as the density ratio of the background plasma to the beam increases. Meanwhile, the maximum CFI growth rate is shifted to the long-wavelength region due to both the bulk plasma density increase and the collisional effects, resulting in larger filaments formation. On the other hand, collisional effects mainly attenuate the TSI and finally stabilize it. Numerical solutions under parameters close to the fast ignition scenario (FIS) are given, which show that the CFI growth rate can be enhanced by 2 orders of magnitude instead of being suppressed in the dense region. Therefore, the CFI-induced electron filaments formation and the resultant kinetic anomalous heating are potentially significant for the target heating in the FIS.

Plasma thermal effect on the relativistic current-filamentation and two-stream instabilities in a hot-beam warm-plasma system.

Based on fully kinetic model using drift-Maxwellian distributions and taking into account the transverse electrostatic field (TEF), it is shown that the current-filamentation instability (CFI) grows unexpectedly with the plasma temperature. The growth is attributed to the decreasing of the TEF as the plasma becomes hot. In the low-temperature plasma regime where the TEF is strong, it is identified that the TEF can dominate over the thermal pressure in suppressing the CFI. Since the TEF originates from the temperature difference between the beam and the plasma, the plasma temperature plays a significant role for the development of the CFI and the quasistatic magnetic fields in a hot-beam warm-plasma system. Particle-in-cell simulations verify the above results.