Disturbance of suprachiasmatic nucleus function improves cardiac repair after myocardial infarction by IGF2-mediated macrophage transition.

Suprachiasmatic nucleus (SCN) in mammals functions as the master circadian pacemaker that coordinates temporal organization of physiological processes with the environmental light/dark cycles. But the causative links between SCN and cardiovascular diseases, specifically the reparative responses after myocardial infarction (MI), remain largely unknown. In this study we disrupted mouse SCN function to investigate the role of SCN in cardiac dysfunction post-MI. Bilateral ablation of the SCN (SCNx) was generated in mice by electrical lesion; myocardial infarction was induced via ligation of the mid-left anterior descending artery (LAD); cardiac function was assessed using echocardiography. We showed that SCN ablation significantly alleviated MI-induced cardiac dysfunction and cardiac fibrosis, and promoted angiogenesis. RNA sequencing revealed differentially expressed genes in the heart of SCNx mice from D0 to D3 post-MI, which were functionally associated with the inflammatory response and cytokine-cytokine receptor interaction. Notably, the expression levels of insulin-like growth factor 2 (Igf2) in the heart and serum IGF2 concentration were significantly elevated in SCNx mice on D3 post-MI. Stimulation of murine peritoneal macrophages in vitro with serum isolated from SCNx mice on D3 post-MI accelerated the transition of anti-inflammatory macrophages, while antibody-mediated neutralization of IGF2 receptor blocked the macrophage transition toward the anti-inflammatory phenotype in vitro as well as the corresponding cardioprotective effects observed in SCNx mice post-MI. In addition, disruption of mouse SCN function by exposure to a desynchronizing condition (constant light) caused similar protective effects accompanied by elevated IGF2 expression on D3 post-MI. Finally, mice deficient in the circadian core clock genes (Ckm-cre; Bmal1f/f mice or Per1/2 double knockout) did not lead to increased serum IGF2 concentration and showed no protective roles in post-MI, suggesting that the cardioprotective effect observed in this study was mediated particularly by the SCN itself, but not by self-sustained molecular clock. Together, we demonstrate that inhibition of SCN function promotes Igf2 expression, which leads to macrophage transition and improves cardiac repair post-MI.

2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.

CXADR-like membrane protein protects against heart injury by preventing excessive pyroptosis after myocardial infarction.

Myocardial infarction (MI) results in cardiomyocyte death and ultimately leads to heart failure. Pyroptosis is a type of the inflammatory programmed cell death that has been found in various diseased tissues. However, the role of pyroptosis in MI heart remains unknown. Here, we showed that CXADR-like membrane protein (CLMP) was involved in pyroptosis in the mouse MI heart. Our data showed that CLMP was strongly expressed in fibroblasts of the infarcted mouse hearts. The Clmp+/- mice showed more serious myocardial fibrosis and ventricular dysfunction post-MI than wild-type (Clmp+/+ ) mice, indicating a protective effect of the fibroblast-expressed CLMP against MI-induced heart damage. Transcriptome analyses by RNA sequencing indicated that Il-1ß mRNA was significantly increased in the MI heart of Clmp+/- mouse, which indicated a more serious inflammatory response. Meanwhile, cleaved caspase-1 and Gasdermin D were significantly increased in the Clmp+/- MI heart, which demonstrated enhanced pyroptosis in the Clmp knockdown heart. Further analysis revealed that the pyroptosis mainly occurred in cardiac fibroblasts (CFs). Compared to wild-type fibroblasts, Clmp+/- CFs showed more serious pyroptosis and inflammatory after LPS plus nigericin treatment. Collectively, our results indicate that CLMP participates in the pyroptotic and inflammatory response of CFs in MI heart. We have provided a novel pyroptotic insight into the ischaemic heart, which might hold substantial potential for the treatment of MI.

Dicyanamide Bridged Cu(II)36-Metallacrown-6 Complex with 1,4,7-Triisopropyl-1,4,7-Triazacyclononane and Binding Properties with DNA.

A novel 36-metallacrown-6 complex [CuL(N(CN)2)(PF6)]6∙0.5H2O 1 was achieved using a tridendate ligand, 1,4,7-triisopropyl-1,4,7-triazacyclononane (L), and a flexible ligand, dicyanamide in MeOH. The µ1,5 bridging models of the dicyanamide ligand linked the macrocycle to form in a specific size with the chair conformation. The anion was important to form this 36-metallacrown-6 complex, as change was obtained with the larger anion BPh4-, binuclear copper compound 2. The magnetic property indicates that slightly ferromagnetic interactions resulted from a superexchange mechanism. DNA binding properties were also studied. UV and fluorescence spectra showed that complex 1 could bind with DNA.

[The Simulation Experiment of Control System for Left Ventricular Assist Device].

Objective: To test the accuracy, the reliability and the stability of flow-controlling method of a new percutaneous left ventricular assist device. Methods: With the AMEsim to set up a simulation model, analysis the variations of motor speed, flow and pressure by adjusting the size of valve. and we test the improved-theoretical model with outside experiment. Results: In the simulation experiment, with the variations of pressure from A, the system can regulate the motor speed to maintain the pump outlet pressure 1.1×105 Pa~1.2×105 Pa and control the flow. With the B valve size changes, the flow-controlling by the system identify and change the motor speed, to maintain the pump inlet pressure from-0.25×105 Pa to-0.10×105 Pa. In outside experiment, with the variations of the size of valve A and valve B, the pump can change the voltage by self-regulation, maintain the entrance and exit of pressure is relatively stable and control the flow. Conclusions: It is a fast-responding and better robust way, by adding the pressure sensor to adjust the speed of motor, to control the flow accurately.

von Willebrand factor as a novel noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis.

OBJECTIVE: At present, there is no perfect noninvasive method to assess portal hypertension and esophageal varices. Early predicting esophageal varices can provide evidence for managing cirrhotic patients. We aimed to further investigate von Willebrand factor (vWF) as a noninvasive predictor of portal hypertension, especially of esophageal varices. MATERIAL AND METHODS: A total of 60 hepatitis B patients with cirrhosis and 45 healthy subjects were enrolled in this study. Levels of six markers were examined. All patients underwent hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy. We evaluated the performance of six factors for diagnosis of portal hypertension and esophageal varices. The vWF levels in liver tissues were observed by immunohistochemistry. Correlations between the level of vWF in liver tissues and HVPG and between levels of vWF in tissues and plasma were examined. RESULTS: Cutoff values of plasma vWF (1510.5 mU/mL and 1701 mU/mL) showed high positive predictive value (PPV, 90.2% and 87.5%) in predicting clinically significant portal hypertension and severe portal hypertension. Cutoff values of vWF (1414 mU/ml and 1990 mU/mL, PPV 90.3% and 86.3%, respectively) were provided to detect the presence and degree of esophageal varices. Linear correlations were observed between levels of vWF in liver tissues and HVPG (r(2) = 0.552, p < 0.001) and between the level of vWF in liver tissues and in plasma (r(2) = 0.461, p < 0.001). CONCLUSION: The vWF is a noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis. Increased levels of vWF in liver tissues may induce the elevated plasma vWF levels, but molecular mechanism is needed for further study.

Evaluation of a Novel Left Ventricular Assist Device for Resuscitation in an Animal Model of Ventricular Fibrillation Cardiac Arrest.

We evaluated an independently developed novel percutaneous implantable left ventricular assist device for resuscitation in a pig model of ventricular fibrillation cardiac arrest. The model was established in 10 domestic pigs by blocking the anterior descending coronary artery with a balloon after anesthesia. With ventilator-assisted ventilation, the independently developed percutaneous implantable left ventricular assist device was inserted via the femoral artery to assist circulation. According to whether effective circulatory support was achieved, the pigs were randomly divided into an experimental group and a control group. The experimental group was subjected to insertion of the assist device and received continuous circulatory support. The control group underwent insertion of the assist device; however, it did not start it within 15 minutes. For all animals, if successful rescue was achieved (sinus rhythm restoration within 15 minutes and maintenance for over 5 minutes), circulatory support was stopped, and the arterial blockage was removed. If sinus rhythm was not restored within 15 minutes, electric defibrillation, adrenaline injection, and removal of the arterial blockage were performed, and circulatory support was provided until sinus rhythm recovered. A determination of failed rescue was made when sinus rhythm was not restored after 1 hour. All successfully rescued animals were fed for 1 week. There were no significant differences in baseline data between the groups. All animals underwent successful novel left ventricular assist device implantation through the femoral artery. The rescue rate was significantly higher in the experimental group than in the control group (80% vs. 0%, [Formula: see text]). All successfully rescued animals survived after 1 week of feeding, and no eating or movement abnormalities were observed. We conclude that this independently developed percutaneous implantable left ventricular assist device can be conveniently and rapidly implanted through the femoral artery and can maintain basic circulatory perfusion during resuscitation in an animal model of cardiac arrest.

Two novel cyanide-bridged bimetallic magnetic chains derived from manganese(III) Schiff bases and hexacyanochromate(III) building blocks.

Two novel complexes, [{Mn(salen)}(2){Mn(salen)(CH(3)OH)}{Cr(CN)(6)}](n)·2nCH(3)CN·nCH(3)OH (1) and [Mn(5-Clsalmen)(CH(3)OH)(H(2)O)](2n)[{Mn(5-Clsalmen)(µ-CN)}Cr(CN)(5)](n)·5.5nH(2)O (2) (salen(2-) = N,N'-ethylene-bis(salicylideneiminato) dianion; 5-Clsalmen(2-) = N,N'-(1-methylethylene)-bis(5-chlorosalicylideneiminato) dianion), were synthesized and structurally characterized by X-ray single-crystal diffraction. The structural analyses show that complex 1 consists of one-dimensional (1D) alternating chains formed by the [{Cr(CN)(6)}{Mn(salen)}(4){Mn(salen)(CH(3)OH)}(2)](3+) heptanuclear cations and [Cr(CN)(6)](3-) anions. While in complex 2, the hexacyanochromate(III) anion acts as a bis-monodentate ligand through two trans-cyano groups to bridge two [Mn(5-Clsalmen)](+) cations to form a straight chain. The magnetic analysis indicates that complex 1 shows three-dimensional (3D) antiferromagnetic ordering with the Néel temperature of 5.0 K, and it is a metamagnet displaying antiferromagnetic to ferromagnetic transition at a critical field of about 2.6 kOe at 2 K. Complex 2 behaves as a molecular magnet with Tc = 3.0 K.

Bimetallic materials derived from manganese(III) Schiff base complexes and pentacyanidonitrosylferrate(II) precursor: structures and magnetic properties.

Three complexes, [Mn(salphen)(H(2)O)](2)[Fe(CN)(5)(NO)] x 2 CH(3)OH (1) (salphen = N,N'-phenylenebis(salicylideneiminato) dianion), [Mn(naphtmen)(CH(3)OH)](2)[Fe(CN)(5)(NO)] (2) (naphtmen = N,N'-(1,1,2,2-tetramethylethylene)bis(naphthylideneiminato) dianion), and {[Mn(salen)](2)[Fe(CN)(5)(NO)] x H(2)O}(n) (3) (salen = N,N'-ethylene-bis(salicylideneiminato) dianion), were synthesized and structurally characterized by X-ray single-crystal diffraction. The structural analyses show that complexes 1 and 2 consist of the discrete linear trinuclear [Mn(SB)](2)[Fe(CN)(5)(NO)] units (SB = salphen for 1, naphtmen for 2); in complex 3, the nitroprusside anion coordinates to the axial sites of the four [Mn(salen)](+) entities through its four cyano nitrogen atoms, providing a two-dimensional network. The magnetic analysis indicates that the nitroprusside bridging ligand propagates a very weak antiferromagnetic exchange and single-ion anisotropy (D) plays an important role in the overall magnetic properties. Different from complexes 2 and 3, complex 1 shows a typical spin-flop transition with a critical field of 20 kOe.

Spin canting and slow relaxation in a 3D pillared nickel-organic framework.

A 3D nickel-organic framework formulated as {[Ni(2)(fum)(2)(bpt)(2)(H(2)O)] x 3 H(2)O}(n) (1), built from a mixed fumaric ion (fum), 1H-3,5-bis(4-pyridyl)-1,2,4-triazole (bpt), and nickel salt, has been hydrothermally synthesized and characterized. Compound 1, having a Ni-fum chain structure in which the chains are pillared by the bpt spacers in a 3D "brick-wall"-like architecture, exhibits canted antiferromagnetism at 5.0 K. Below this temperature, slow relaxation is observed from the alternating-current susceptibility measurements corresponding to the spin-glass-like behavior.

A porous 3D heterometal-organic framework containing both lanthanide and high-spin Fe(ii) ions.

The first porous 3D [Ln-Fe] heterometal-organic frameworks incorporating high-spin Fe(ii) ions were structurally characterized with fascinating 1D channels and higher thermal stability: the robust frameworks still keep intact on removing free H(2)O or adsorbing C(2)H(5)OH, and the luminescence of [Eu-Fe] complex displays selective detection of Mg(2+).

Four new lanthanide-nitronyl nitroxide (Ln(III) = Pr(III), Sm(III), Eu(III), Tm(III)) complexes and a Tb(III) complex exhibiting single-molecule magnet behavior.

Five new complexes based on rare-earth-radical [Ln(hfac)(3)(NIT-5-Br-3py)](2) (Ln = Pr (1), Sm (2), Eu (3), Tb (4), Tm (5); hfac = hexafluoroacetylacetonate; NIT-5-Br-3py = 2-(4,4,5,5-tetramethyl-3-oxylimidazoline-1-oxide)-5-bromo-3-pyridine) have been synthesized and characterized by X-ray crystal diffraction. The single-crystal structures show that these complexes have similar structures, in which a NIT-5-Br-3py molecule acts as a bridging ligand linking two Ln(III) ions through the oxygen atom of the N-O group and nitrogen atom from the pyridine ring to form a four-spin system. Both static and dynamic magnetic properties were measured for complex 4, which exhibits single-molecule magnetism behavior.

LncRNA-Safe contributes to cardiac fibrosis through Safe-Sfrp2-HuR complex in mouse myocardial infarction.

Rationale: As a hallmark of various heart diseases, cardiac fibrosis ultimately leads to end-stage heart failure. Anti-fibrosis is a potential therapeutic strategy for heart failure. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of heart diseases that promise to serve as therapeutic targets. However, few lncRNAs have been directly implicated in cardiac fibrosis. Methods: The lncRNA expression profiles were assessed by microarray in cardiac fibrotic and remote ventricular tissues in mice with myocardial infarction. The mechanisms and functional significance of lncRNA-AK137033 in cardiac fibrosis were further investigated with both in vitro and in vivo models. Results: We identified 389 differentially expressed lncRNAs in cardiac fibrotic and remote ventricular tissues in mice with myocardial infarction. Among them, a lncRNA (AK137033) we named Safe was enriched in the nuclei of fibroblasts, and elevated in both myocardial infarction and TGF-ß-induced cardiac fibrosis. Knockdown of Safe prevented TGF-ß-induced fibroblast-myofibroblast transition, aberrant cell proliferation and secretion of extracellular matrix proteins in vitro, and mended the impaired cardiac function in mice suffering myocardial infarction. In vitro studies indicated that knockdown of Safe significantly inhibited the expression of its neighboring gene Sfrp2, and vice versa. The Sfrp2 overexpression obviously disturbed the regulatory effects of Safe shRNAs in both the in vitro cultured cardiac fibroblasts and myocardial infarction-induced fibrosis. Dual-Luciferase assay demonstrated that Safe and Sfrp2 mRNA stabilized each other via their complementary binding at the 3'-end. RNA electrophoretic mobility shift assay and RNA immunoprecipitation assay indicated that RNA binding protein HuR could bind to Safe-Sfrp2 RNA duplex, whereas the knockdown of HuR dramatically reduced the stabilization of Safe and Sfrp2 mRNAs, down-regulated their expression in cardiac fibroblasts, and thus inhibited TGF-ß-induced fibrosis. The Safe overexpression partially restrained the phenotype change of cardiac fibroblasts induced by Sfrp2 shRNAs, but not that induced by HuR shRNAs. Conclusions: Our study identifies Safe as a critical regulator of cardiac fibrosis, and demonstrates Safe-Sfrp2-HuR complex-mediated Sfrp2 mRNA stability is the underlying mechanism of Safe-regulated cardiac fibrosis. Fibroblast-enriched Safe could represent a novel target for anti-fibrotic therapy in heart diseases.

The self-assembly and magnetic properties of a Ni(II)8(micro4-hydroxo)6 cube with micro2-pyrazolate as an exogeneous ancillary ligand.

A novel octanuclear hydroxonickel(II) complex possessing a unprecedented cube molecular structure with eight Ni(II) ions at each vertex, six micro4-OH- groups closing each face and twelve exo-bidentate pyrazolate ligands (micro2-pz) spanning each edge, has been synthesized and its magnetic properties investigated.

Template synthesis of lanthanide (Pr, Nd, Gd) coordination polymers with 2-hydroxynicotinic acid exhibiting ferro-/antiferromagnetic interaction.

Lanthanide coordination polymers were synthesized from Pr(III), Nd(III), and Gd(III) salts; 2-hydroxynicotinic acid (Hnica); and MnSO 4.H 2O under hydrothermal conditions. In the absence of (CH 3) 3CCOONa, 1D polymers with an infinite Ln(III)-O-Ln(III) chain structure, [Pr(Hnica)(H 2O) 2SO 4] n ( 1), [Nd(Hnica)(H 2O) 2SO 4] n ( 2), and [Gd(Hnica)(H 2O) 2SO 4] n ( 3), were generated. When (CH 3) 3CCOONa was added to the synthetic systems, 2D coordination polymers {[Pr 3(Hnica) 6(H 2O) 9].3H 2O.SO 4.NO 3} n ( 4), {[Nd 3(Hnica) 6(H 2O) 9].3H 2O.SO 4.NO 3} n ( 5), and {[Gd(Hnica) 2(H 2O) 2]ClO 4.H 2O} n ( 6) were obtained. Complexes 4 and 5 both exhibit Kagome lattice structure, while 6 displays a rhombic grid structure. All complexes were characterized by elemental analysis, IR spectra, UV-vis spectra, and X-ray single-crystal diffraction. The variable-temperature magnetic susceptibility studies reveal ferromagnetic interactions between gadolinium(III) ions in 3 and 6 and antiferromagnetic interactions in 1, 2, 4, and 5.

Structures and magnetic properties of ferromagnetic coupling 2D Ln-M heterometallic coordination polymers (Ln = Ho, Er; M = Mn, Zn).

Four new heterometallic coordination polymers have been successfully synthesized, namely, {[Ho(2)(HCAM)(6)Mn(3)(H(2)O)(12)].17.5H(2)O}(n) (1), {[Er(2)(HCAM)(6)Mn(3)(H(2)O)(12)].17.5H(2)O}(n) (2), {[Ho(2)(HCAM)(6)Zn(3)(H(2)O)(12)].26H(2)O}(n) (3), and {[Er(2)(HCAM)(6)Zn(3)(H(2)O)(12)].26H(2)O}(n) (4) (H(3)CAM = chelidamic acid). X-ray crystallographic studies reveal that coordination polymers 1-4 are isostructural and crystallized in the rhombohedral crystal system, space group R3. These compounds comprise a 2D honeycomb-type framework. A 2D water sheet is first found in 3 and 4, which exhibits a novel topological motif. The magnetic results for 1-4 show that ferromagnetic interactions take place between the Ho(3+)/Er(3+) and Mn(2+) ions within 1 and 2.

2D warp-and-woof interwoven networks constructed by helical chains with different chirality.

Two unprecedented 2D entangled layers of warp-and-woof threads interwoven by left- and right-handed helical chains, {[Mn(salen)Au(CN)2]4(H2O)}n (salen = N,N'-ethylenebis(salicylideneaminato)) and {Mn(acacen)Ag(CN)2}n (acacen = N,N'-ethylenebis(acetylacetonylideneiminate)) 2, have been synthesized and characterized.

Synthesis, crystal structure, magnetic property and nuclease activity of a new binuclear cobalt(II) complex.

One new binuclear Co(II) complex of N,N,N',N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxyl-1,3-diaminopropane (HL), [Co(2)L(mu(2)-Cl)](ClO(4))(2) x 3CH(3)CN x C(2)H(5)OC(2)H(5) (1), has been synthesized and its crystal structure and magnetic properties are shown. In 1, each Co(II) atom has a distorted trigonal bipyramidal geometry with a N(3)OCl donor set. The central two Co(II) atoms are bridged by one alkoxo-O atom and one Cl atom with the Co1-Co2 separation of 3.239 A. Susceptibility data of 1 indicate strong intramolecular antiferromagnetic coupling of the high-spin Co(II) atoms. In this paper, the interaction with calf thymus DNA was investigated by UV absorption and fluorescent spectroscopy. Results show the complex binds to ct-DNA with a intercalative mode. The interaction between complex 1 and pBR322 DNA has also been investigated by submarine gel electrophoresis, noticeably, the complex exhibits effective DNA cleavage activity in the absence of any external agents.

In vivo insulin-mimetic activity of [N,N'-1,3-propyl-bis(salicyladimine)]oxovanadium(IV).

[N,N'-1,3-Propyl-bis(salicyladimine)]oxovanadium(IV) - an oxovanadium complex has been tested for bioactivity as an insulin-enhancing agent. Its structure reveals that the vanadium(IV) ion is hexacoordinated and situated in a distorted octahedral environment. The complex was administered intragastrically to both normal and streptozotocin (STZ)-diabetic rats for two weeks. The results showed that the complex, at a dose of 10.0 and 20.0mgV.kg(-1), could lower the blood glucose level in STZ-diabetic rats and improve the response to an oral glucose challenge. This complex did not alter these parameters in normal rats. It was suggested that the complex exerted an antidiabetic effect in STZ-diabetic rats.