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Single-walled carbon nanotube (SWCNT) is a promising candidate for strengthening nanocomposite. As the matrix of nanocomposite, a single crystal of copper is designed to be in-plane auxetic along the crystal orientation [1 1 0]. In that way, the nanocomposite could also be auxetic when enhanced by (7, 2) a single-walled carbon nanotube with relatively small in-plane Poisson’s ratio. A series of molecular dynamics (MD) models of the nanocomposite metamaterial are then established to study mechanical behaviors of the nanocomposite. In the modelling, the gap between copper and SWCNT is determined following the principle of crystal stability. The enhanced effect for different content and temperature in different directions is discussed in detail. This study provides a complete set of mechanical parameters of nanocomposite including thermal expansion coefficients (TECs) from 300 K to 800 K for five weight fractions, which is essential for a wide range of applications of auxetic nanocomposites in the future.

Single-walled carbon nanotubes (SWCNTs) have superior mechanical properties which originate from a strong C-C covalent bond and unique nanostructure. Chirality, one of the helical structural parameters of SWCNTs, leads to differences in mechanical performance. In this work, molecular dynamics (MD) simulation was performed to analyze engineering Poisson’s ratio (EPR) and incremental Poisson’s ratio (IPR) of SWCNTs with different chiral angles, respectively, under tensile and compressive load, as well as the chiral effect on rigidity. We reported the minimum EPR for (4, 1) SWCNT and obtained the distribution and trend of EPR which is dependent on chiral index m. In addition, a new observation showed two exactly opposite trends of EPR existing not only in tension and compression but also in the longitudinal and radial directions. Furthermore, we found that the critical strain, over which SWCNT would be auxetic, ranged from 6% to 18% and was also chirality-dependent. Three representative SWCNTs with chiral angle of 0° (zigzag), 10.89° (chiral), and 30° (armchair) were selected for the mechanism study of auxeticity. Finally, a method of the contribution to radial strain for two main deformation modes proposed in this paper could well explain the negative IPR phenomenon.

A Cp*-Rh based D-shaped binuclear metallacycle and a template-free molecular Borromean ring (BR) were obtained in high yield using the semi-rigid thioether dipyridyl ligand 1,4-bis[(pyridin-4-ylthio)methyl]benzene (Bptmb). The topological transformation from a binuclear metallacycle and a BR to tetranuclear metallacycles was realized via the controlled oxidation of thioethers. The strategy used in this work can be regarded as a new form of stimuli-responsive post-synthesis modification (PSM).

Two molecular metalla-knots containing over 500 non-hydrogen atoms (especially 16 RhIII ions) and one molecular Borromean ring were obtained in high yields facilitated by multiple intermolecular interactions between their components. The syntheses rely on the strategic selection of the nonlinear dipyridyl ligand 2,7-di(pyridin-4-yl)-9H-fluorene (L1) as precursor, and the structures of the assemblies were confirmed by detailed X-ray crystallographic analysis. Subsequently, replacing L1 with the bulkier ligand 4,4'-(9,9-dimethyl-9H-fluorene-2,7-diyl)dipyridine (L2) led to the formation of three tetranuclear metallocycles in high yields on account of the weakened π-π stacking interactions between the naphthacene/anthracene and fluorene moieties, which in turn confirmed the significance of stacking interactions in the construction of the molecular 818 metalla-knots and the molecular Borromean ring.

Dementia and cognitive impairment can be attributed to both genetic and modifiable risk factors. Recently, considerable evidence emerged and urgently require standardized evaluation. To address it, we conducted an umbrella review of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors to evaluate the strength and validity of the existing evidence. We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies. Mendelian randomization studies were reviewed to assess the causality for these associations. For each association, we analyzed the summary effect size, 95% confidence interval, 95% prediction interval, heterogeneity, small study effect and excess significance bias. Based on these estimates, the evidence was graded into levels of convincing, highly suggestive, suggestive, or weak. In total, 12015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, body mass index, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for associations of dementia and cognitive impairment with midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified genetic predicted causal relationships for education and plasma glucose with Alzheimer's disease. Modifiable factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Trial registration: PROSPERO CRD42020195729.

A template-free Cp*Ir-based molecular Solomon link and an unusual trefoil knot induced by stacking interactions were realized via selection of the nonrigid dipyridyl ligand 4,4'-bis(pyridin-4-ylmethyl)-1,1'-biphenyl (BpmBp). In addition, a novel heterobimetallic tetranuclear (IrIII2 + AgI2) complex featuring argentophilic interaction was synthesized in high yield. Remarkably, the reversible topological transformation between the Solomon link and an unusual trefoil knot can be achieved by utilizing the chemical reactivity of silver(I) ions under mild conditions, as demonstrated by a detailed X-ray crystallographic study.

The rational design and facile construction of discrete heterometallic supramolecular catalysts have precipitated a surge of research interest in emulating sophisticated natural catalysts with well-defined cavities and inlaid active sites, allowing conversion of encapsulated substrates with high chemo-, regio-, and stereoselectivity. This review briefly highlights such discrete, heterometallic, coordination-driven metallacycles and metallacages obtained by the strategic utilization of a range of predesigned building blocks in the supramolecular chemist’s toolkit. The two major synthetic strategies toward these metalla-architectures are presented, and special attention has been paid to discussing both the fascinating structures and the unique catalytic performance of various heterometallic macrocycles and cages.

Two Cp*-RhIII based trefoil knots were obtained in high yield under ambient conditions via the coordination-driven self-assembly of semi-rigid thioether dipyridyl ligand 1,4-bis[(pyridin-4-ylthio)methyl]benzene (L1 ), ligand chloranilic acid (H2 -CA) and 6,11-dihydroxytetracene-5,12-dione (H2 -TtDo) with Cp*RhIII metal corner units, respectively. Furthermore, using the bulkier 4,4'-{[(2,5-dimethyl-1,4-phenylene)bis(methylene)]bis(sulfanediyl)}dipyridine (L2 ) in the place of ligand L1 in the construction process resulted in the formation of a teranuclear metallacycle and a template-free Borromean ring in high yields thanks to significantly altered intermolecular forces between the constituent ligands induced by the sterically-hindering methyl groups of L2 , as demonstrated via a detailed X-ray crystallographic analysis and NMR spectroscopy.

Two molecular metalla-knots containing over 500 non-hydrogen atoms (especially 16 Rh

Herein, we describe the utilization of isomeric pyridyl-substituted ligands featuring different coordination vectors to rationally design and construct a series of discrete organometallic assemblies with specific space conformations. In the case of tetranuclear macrocycles constructed from the ligand 3-bpb, different conformations of these assemblies with C2v and C2 h point symmetry were revealed by single-crystal X-ray diffraction. These complexes were further characterized by X-ray crystallography, 1H NMR, DOSY NMR, IR spectroscopy, and elemental analyses.

In this work, five ruthenium complexes [Ru(p-cymene)LCl] containing phenolate-oxazoline ligands [L = 2-(4,5-dihydrooxazol-2-yl)phenol (1); L = 2-(4-methyl-4,5-dihydrooxazol-2-yl)phenol (2); L = 2-(4-ethyl-4,5-dihydrooxazol-2-yl)phenol (3); L = 2-(4-phenyl-4,5-dihydrooxazol-2-yl)phenol (4); and 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenol (5)] were synthesized and characterized. The solid-state structures of all ruthenium complexes were determined by single-crystal X-ray diffraction. The catalytic activities of these complexes in the transfer hydrogenation reaction of nitroarene to aniline were investigated. Aniline and their derivatives were obtained in good to excellent yields with isopropanol as the hydride source. The present protocol provides an environmentally benign synthetic method for the reduction of nitroarenes to anilines without employing harsh reaction conditions. Theoretical studies employing density functional theory were carried with the aim to propose a feasible reaction mechanism and to...

The conductive paths formed by fractures and cave in complex reservoirs differ from those formed by pores and throats in clastic rocks. In this paper, a new formation model based on fractured and caved reservoirs is established, and the electrical characteristics of rocks are analyzed with different pore structures using resistance law to understand their effects on rock resistivity. The ratio of fracture width to cave radius (C e value) and fracture dip are employed to depict pore structure in this model. Our research shows that the electrical characteristics of rocks in fractured and caved reservoirs are strongly affected by pore structure and porous fluid distribution. Although the rock electrical properties associated with simple pore structure agree well with Archie formulae, the relationships between F and or between I and S w , in more complicated pore structures, are nonlinear in double logarithmic coordinates. The parameters in Archie formulae are not constant and they depend on porosity and fluid saturation. Our calculations suggest that the inclined fracture may lead to resistivity anisotropy in the formation. The bigger dip the inclining fracture has, the more anisotropy the formation resistivity has. All of these studies own practical sense for the evaluation of oil saturation using resistivity logging data.

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the elderly and the leading cause of dementia in humans. Evidence shows that cellular trafficking and recycling machineries are associated with AD risk. A recent study found that the coat protein complex I (COPI)–dependent trafficking in vivo could significantly reduce amyloid plaques in the cortex and hippocampus of neurological in the AD mouse models and identified 12 single-nucleotide polymorphisms in COPI genes to be significantly associated with increased AD risk using 6,795 samples. Here, we used a large-scale GWAS dataset to investigate the potential association between the COPI genes and AD susceptibility by both SNP and gene-based tests. The results showed that only rs9898218 was associated with AD risk with P = 0.017. We further conducted an expression quantitative trait loci (eQTLs) analysis and found that rs9898218 G allele was associated with increased COPZ2 expression in cerebellar cortex with P = 0.0184. Importantly, the eQTLs analysis in whole blood further indicated that 11 of these 12 genetic variants could significantly regulate the expression of COPI genes. Hence, these findings may contribute to understand the association between COPI genes and AD susceptibility.

Three neutral pyridine-based selone compounds, 2,6-bis(1-methylimidazole-2-selone)pyridine (Bmsp), 2,6-bis(1-ethylimidazole-2-selone)pyridine (Besp) and 2,6-bis(1-isopropylimidazole- 2-selone)pyridine (Bpsp) have been synthesized and characterized. Reactions of HAuCl4 with pyridine-based selone ligands result in the formation of the complexes [Au(L)Cl2]+[AuCl2]− (L = Bmsp (1); L = Besp (2) and L = Bpsp (3)), respectively. All compounds have been characterized by elemental analysis, NMR IR spectra and electrospray ionization mass spectroscopic (ESI-MS). The molecular structure of 2 has been determined by X-ray crystallography. Moreover, the gold complexes are efficiently catalyzed nitroarenes reduction to aromatic amines in the presence of sodium tetrahydroborate reducing agent in water.

Nuclear magnetic resonance (NMR) T 2 distributions can be employed to understand the geometry of pores, but they are not sensitive enough to determine pore connectivity. In this paper, the pore space in reservoirs is regarded as a series of different sizes of the combination of spherical pores and cylinder pores based on the pore network model and Sphere–Cylinder model. In terms of the optimized T 2 inversion method, T 2 spectral distribution is decomposed into two groups, sphere pore distribution and cylinder pore distribution. It is assumed that cylinder pore controls the connectivity and permeability of the reservoir and the sphere pore is the main place of fluid storage. The more cylinder pores that exist, the better the connectivity and permeability are. The data of eight core plugs are analyzed using this method, and the results are in accordance with those of core analysis, which proves the practicability of our research and provides a basis for the direct evaluation of reservoir pore structure using NMR T 2 distribution.

Loss of functional cardiomyocytes by cell death after myocardial infarction is most critical for the subsequent left ventricular remodeling, cardiac dysfunction and heart failure. Numerous studies have implicated that dysregulation of autophagy might contribute to cardiomyocyte death. However, the underlying mechanisms by which autophagy dysregulation-mediated cell death remains to be elusive. Herein, we showed that, in response to myocardial ischemic damage in vivo and in vitro, autophagy activity was increased quickly but followed by the process of impaired autophagic degradation as evidenced by the sustained higher level of beclin1 until 12 weeks after myocardial infarction, while, increased accumulation of LC3 and p62. The results from both tandem mRFP-GFP-LC3 adenovirus and lysosomal inhibitor chloroquine supported defective autophagy induction by ischemia injury. Importantly, we found that the impaired autophagy flux, induced not only pharmacologically by CQ but also genetically by beclin1 knockdown, upregulated the expression of RIP3 and aggravated OGD-induced necroptotic cardiomyocyte death and cardiac dysfunction. While, upregulation of autophagy by cardiac-specific beclin1 overexpression partially ameliorated cardiac dysfunction after MI. Furthermore, constitutive activation of necroptosis by forced cardiac-specific overexpression of RIP3 aggravated necrotic cardiomyocyte death, post-MI cardiac remodeling and cardiac dysfunction, but all of which could be ameliorated by inhibition of necroptosis by RIP3 knockdown. In conclusion, these results suggested that autophagy dysfunction-mediated necroptosis mechanistically contributed to loss of cardiomyocytes, adverse ventricular remodeling and progressive heart failure after myocardial Infarction. Inhibition of necroptosis might be the potential target for preventing post-infarction cardiac remodeling and heart failure.

A series of metallosupramolecular architectures have been prepared, including rectangles, prisms and cages, that feature half-sandwich rhodium(III) fragments at the vertices. Remarkably, a stable cage-like heteropolymetallic complex possessing eight rhodium(III) and two silver(I) metal ions (3) has been obtained following a multistep procedure. The RhIII /AgI mixed macrocage enables the separation of dihalogenated benzene derivatives with high selectivity. Furthermore, a detailed X-ray crystallographic study confirmed that the discriminative encapsulation of para-dihalobenzene (dichlorobenzene, dibromobenzene and diiodobenzene) is favored by Ag-π interactions and steric effects.

Depression is a common mental disorder that is associated with memory dysfunction. Ketamine has recently been demonstrated to be a rapid antidepressant. The mechanisms underlying how depression induces memory dysfunction and how ketamine relieves depressive symptoms remain poorly understood. This work compared three groups of male C57BL/6J mice: mice exposed to chronic social defeat stress (CSDS) to induce a depression-like phenotype, depression-like mice treated with ketamine, and control mice that were not exposed to CSDS or treated with ketamine. Spatial working memory and long term memory were assessed by spontaneous alternation Y-maze and fear conditioning tests, respectively. We used western blot to analyze the density of N-methyl-D-aspartate receptor (NMDAR) subunits in the hippocampus. We recorded long term potentiation (LTP) and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices. We observed that compared with control mice, depression-like mice had significant reductions in spatial working memory and contextual fear memory. The level of NR2B, LTP and NMDA receptor-mediated EPSCs of depression-like mice were decreased. Ketamine treatment attenuated the memory impairment, and increased the density of NR2B and the amplitude of LTP and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice. In conclusion, depression-like mice have deficits in working memory and contextual fear memory. The decrease of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus may be involved in this process. Ketamine can improve expression of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice, which might be part of the reason why ketamine can alleviate the memory dysfunction induced by depression.

According to the characteristics of electrical haulage shearer in the process of coal mining and the basic principle of cutting constant power speed-adjusting of electrical haulage shearer, taking the traction motor as the controlled object, and cutting constant power speed-adjusting control method of electrical haulage shearer based on RBF neural network PID control is proposed. Adaptive control method to achieve the electrical haulage shearer constant power speed-adjusting and high precision control. At the same time, improve the efficiency of coal mining, to ensure the safety of the shearer. The modeling and simulation analysis of the cutting constant power speed-adjusting control system of electrical haulage Shearer are carried out by Matlab/Simulink, and the system through the field experiment and the comparative analysis with traditional fuzzy PID control. The results show that the system based on RBF neural network PID control has stronger anti-interference ability, higher control precision, faster response time, stronger practicability and stability.

Over the last two decades, interlocked molecular species have received considerable attention, not only because of their intriguing structures and topological importance, but also because of their potential applications as smart materials, nanoscale devices, and molecular machines. Through judicious choice of metal centers and their adjoining ligands, a range of interesting interlocked structures have been realized by coordination-driven self-assembly. In addition, researchers have extensively developed synthetic methodologies for the construction of organized self-assemblies. One fascinating and challenging synthetic target in this field is the family of molecular Borromean rings, which consist of three chemically independent rings that are locked in such a way that no two of the three rings are linked with each other. Toward this goal, we have developed a template-free self-assembly method for synthesizing molecular Borromean rings by rationally designing metal-containing precursors and organic ligands. In this Account, we present our recent work, focusing on interlocked structures comprising half-sandwich iridium- and rhodium-based organometallic assemblies obtained by rational design. We first describe a series of template-free self-assembled organometallic molecular Borromean rings, which we constructed from preorganized binuclear half-sandwich molecular clips and suitable pyridyl ligands. These molecular Borromean rings can be sorted into four types according to their different bridging ligands, including those based on metallaligands, dihalogenated ligands, naphthazarin and π-acceptor ligands. By single-crystal X-ray crystallographic analysis, NMR experiment, and DFT calculation, we discuss their driving forces and the inter-ring interactions. Furthermore, we took advantage of the dissimilarity in their interactions to realize selective, reversible conversions between molecular Borromean rings and monomeric rectangles by the use of suitable solvents or guest molecules. Subsequently, a stepwise chemoseparation method based on molecular Borromean rings was established, with the molecular Borromean rings used in the separation being recoverable and recyclable. Due to their structural complexity and difficult synthesis, useful guidelines or rules to help design complicated interlocked molecules are highly desirable. We also highlight our efforts to develop empirical guidelines to uncover the relationship between the aspect ratio of metallarectangles and the formation or stability of molecular Borromean rings. An empirical formula has further been established to show the approximate ratio of lengths of the short arm and the long arm in molecular Borromean rings based on π-π (or p-π) stacking. We then demonstrate how to use these guidelines to design new molecular Borromean rings and further lead to other interlocked structures, for example, [2]- and [3]catenane structures. Taken together, our results may lead to a promising future for the design of fascinating and useful interlocked structures by coordination-driven self-assembly.

Template-free molecular Borromean rings (BRs) and open-ended molecular capsules were realized by strategic selection of the polypyridyl ligand tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j] phenazine (TPPHZ) with a large surface area and specific geometry. The topology of these intricate architectures was constructed via precisely controlled stacking interactions, as evidenced from single-crystal X-ray analysis.

Three gold complexes with pyridine-based SNS type ligands, 2,6-bis(1-methylimidazole-2-thione)pyridine (Bmtp), 2,6-bis(1-ethylimidazole-2-thione)pyridine (Betp) and 2,6-bis(1-isopropylimidazole-2-thione)pyridine (Bptp) have been synthesized and characterized. Reactions of HAuCl4·H2O with three pyridine-based SNS ligands result in the formation of the complexes [(L)AuCl2]Cl (L = Bmtp (1); L = Betp (2) and L = Bptp (3)). All compounds are investigated by elemental analysis, NMR, MS and UV-Vis as well as IR spectral analysis. The molecular structure of 3 has been confirmed by X-ray crystallography. Moreover, all gold complexes are efficient homogeneous catalysts and catalyze the reduction of 4-nitrophenol (4-NP) to 4-nitroaniline (4-AP) in the presence of NaBH4 reducing agent in water. And complex 3 exhibits an exceptionally high turn over frequency (TOF) of 1.20 min−1 for the reduction of 4-NP.

We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1β in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.

Once the GIS appears screws loose and other phenomena, it will lead to the generation of floating potential, then trigger the floating potential discharge. In order to study the discharge characteristics of the floating potential, this paper artificially built floating potential defects on the GIS malfunction simulation platform, and detected with ultrasound and UHF methods. The results show that once the floating potential discharged, it would produce a larger amplitude signal. And the discharge most concentrated between the zero crossing and the peak point among the entire phase range. Ultrasound and UHF detection has obvious signal.

A new type of proportion cycle temperature control algorithm is proposed in this paper. Controller can automatically identify temperature constant related to the heater power, combined with the real time environmental temperature change, dynamically modify the heating and cooling time, controlled volatility in setting temperature range.When the mutant short time ambient temperature occurs, it can make rapid response, so as to achieve better control effect.

Putting forward a kind of star identification algorithm based on SOFM neural network. Firstly, using dynamic threshold selection algorithm what is based on supporting vector machine select guide stars to composite the navigation star database, then a recognition system what contain multiple parallel SOFM subnets for star map recognition is designed. Simulated recognition results show that the SOFM network can extract complex feature recognition navigation star from the chart. Compared with the traditional triangle algorithm, this algorithm has better recognition accuracy, robustness and real-time.

Harmonic transfer between different levels of ac systems increases the difficulty in harmonic identification and governance. From the view of harmonic transfer coefficients, the paper firstly establishes a harmonic infiltration equivalent model of different voltage levels, and then analyzes the formula of harmonic transfer coefficients. Finally, the computational and simulation analysis are carried out in MATLAB software to study the factors that affect the harmonic transfer coefficients between different voltage levels.

As the development of high voltage direct current (HVDC) transmission, the problems of harmonic instability become more prevalent. Besides, harmonic instability in exceedingly weak HVDC systems is particularly serious. The modulation of the DC converter based on switching function is deduced. By considering the whole process of harmonic transferring at the AC and DC side through converters from the perspective of circuit, the generation conditions of harmonic instability are analyzed. Then an exceedingly weak HVDC system model is established and simulated in PSCAD/EMTDC software to verify the theoretical analysis. The study results provide theoretical basis and computational methods to solve the problems of harmonic instability in HVDC systems.

In order to satisfy the need for vehicle dynamic weighing in over-loading detection, the software and hardware of system are designed. The system uses CS5530, which can achieve 24-bit performance, as its AD converter. Apply with the technology of the radio frequency(RF) and embedded operate system, the system can collect, send, display, store and print the information of vehicles in time.

The crude polysaccharides of Laminaria japonica (LP) were extracted with the optimal conditions as follows: raw materials to water 1:50 (w/v), extraction temperature 60 °C and extraction time 60 min. Trypsinase (6 U/ml) in combination with sevag reagent was beneficial to the removal of proteins from crude LP. Three fractions of LP1, LP2 and LP3 were obtained from the crude LP by using a final concentration of 40%, 60% and 80% ethanol to precipitate in turn. The three fractions showed obvious differences in monosaccharide compositions, molecular weight distribution, viscosity, IR spectroscopy and glycosyl linkages. In comparison with the control group, crude LP at a dose of 400 mg/kg/day caused a reduction in total serum cholesterol, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol in serum by 80.6%, 63.4%, 43.8% and 79.8%, respectively. Moreover, crude LP exhibited good potential of enhancing antioxidant enzyme activities in serum of atherosclerosis mice.

Emerging evidence indicates that myocardial inflammation plays a key role in the pathogenesis of cardiac diseases. But the exact mechanisms for this chronic inflammatory disorder have not been elucidated. Glucocorticoids (GCs) are the most effective anti-inflammatory treatments available for many inflammatory diseases. However, it is unknown whether endogenous GCs are able to exert anti-inflammatory effect on myocardial inflammation. In this study, the potential role of endogenous GCs in the regulation of myocardial inflammation was investigated. We showed that the reduction of endogenous GC level by adrenalectomy promoted the production of basal and lipopolysaccharide (LPS)-induced proinflammatory cytokines, which could be partly reversed by supplementing with exogenous physiological level of hydrocortisone. Inhibition of GC receptor (GR) signaling pathway with GR antagonist mifepristone (RU486) or histone deacetylase inhibitor trichostatin A (TSA) also increased the levels of basal and LPS-induced proinflammatory cytokines. Moreover, blockade of GC-GR signaling pathway by adrenalectomy, RU486 or TSA enhanced LPS-induced myocardial nuclear factor-κB activation and histone acetylation but inhibited myocardial histone deacetylase expression and activity. Cardiac function studies demonstrated that blockade of the GC-GR signaling pathway aggravated inflammation-induced cardiac dysfunction. These findings indicate that endogenous GCs are able to inhibit myocardial inflammation induced by LPS. Endogenous GCs represent an important endogenous anti-inflammatory mechanism for myocardium in rats and such mechanism injury may be an important factor for pathogenesis of cardiac diseases.

Summary 1. Inflammation-induced proliferation of cardiac fibroblasts plays an important role in cardiac remodelling. Pharmacological doses of exogenous glucocorticoids (GC) are the most effective therapy for inflammatory diseases. Similarly, physiological concentrations of endogenous GC have recently been shown to have anti-inflammatory effects. Therefore, the aim of the present study was to determine whether a physiological concentration of GC could inhibit pro-inflammatory cytokine-stimulated proliferation of cardiac fibroblasts and to explore the mechanisms involved. 2. Cardiac fibroblasts were isolated from adult male Sprague-Dawley rats and cell proliferation was measured using a CCK-8 kit. Western blotting was used to detect protein expression of extracellular-regulated kinase (ERK) 1/2 and nuclear factor (NF)-κB. 3. Cardiac fibroblast proliferation was significantly increased by tumour necrosis factor-α, interleukin (IL)-1β and angiotensin II and was accompanied by upregulated protein expression of ERK1/2 and NF-κB. A physiological concentration of hydrocortisone (127 ng/mL) not only inhibited the proliferation of cardiac fibroblasts, but also suppressed activation of ERK1/2 and NF-κB. These effects of hydrocortisone were abrogated by the glucocorticoid receptor (GR) antagonist RU-486 (100 nmol/L). Furthermore, inflammation-induced cardiac fibroblast proliferation was also blocked by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 (100 nmol/L) and the NF-κB inhibitor pyrrolidine dithiocarbamate (1 μmol/L). Cytokine-induced ERK1/2 phosphorylation and cyclin D1 expression were attenuated by U0126, suggesting that the ERK1/2 and NF-κB signalling pathways were involved in cardiac fibroblast proliferation. 4. In conclusion, the results of the present study indicate that a physiological concentration of hydrocortisone can inhibit inflammation-induced proliferation of cardiac fibroblasts by preventing the activation of ERK1/2 and NF-κB.

The primary afferent neurons are enriched for F-actin in the peripheries, giving rise to ring-like appearances when stained with fluorescence probes for actin. A variety of data, mainly obtained from in vitro experiments, suggested that the satellite cell (SC) envelopes around sensory neurons may be a candidate for the F-actin positive structures. However, immunohistochemical studies on dorsal root ganglia (DRGs) suggested that F-actin was located exclusively within the cortical regions of the sensory neurons. Given this discrepancy, the present study has reexamined the distribution of F-actin in the DRGs at both the fluorescence light and electron microscopic levels. Double staining of F-actin with S-100 beta and neural cell adhesion molecule showed that the fluorescence signals for F-actin around the DRG neurons were restricted to the inner margins of the SC envelope. Subsequent ultrastructural observations, by use of a modified anti-FITC system, demonstrated that the F-actin-positive sites corresponded mostly to the adneuronal SC lamellae, while the cortical cytoskeletons in the neurons seemed to contribute little to the typical F-actin staining. The high concentration of F-actin in the SC envelope has not yet described before, and is thought to assist in understanding the functions of the SCs in the ganglia.

1. Our previous study has shown that leptin induces cardiomyocyte hypertrophy; however, the mechanisms are poorly understood. Recent studies have shown that peroxisome proliferator-activated receptor α (PPARα) activation might be responsible for pathological remodeling and severe cardiomyopathy. Leptin, as an endogenous activator of PPARα, regulates energy metabolism through activating PPARα in many cells. Therefore, we hypothesized that leptin induces cardiomyocyte hypertrophy through activating the cardiac PPARα pathway. 2. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of PPARα on hypertrophy. The selective PPARα antagonist GW6471 concentration-dependently decreased atrial natriuretic factor mRNA expression by 23%, 36%, 44% and 59%, and significantly decreased total RNA levels, protein synthesis and cell surface areas, all of which were elevated by 72 h of leptin treatment. The augmentation of reactive oxygen species levels in leptin treated cardiomyocytes was reversed by 0.1-10 μmol/L GW6471 (40%, 52% and 58%). After 24 h of treatment, leptin concentration-dependently enhanced mRNA expression by 7%, 93%, 100% and 256%, and protein expression by 31.2%, 64.2%, 143% and 199%, and the activity of PPARα. Meanwhile, cardiomycytes receiving 72 h of treatment with the PPARα agonist, fenofibrate, concentration-dependently increased total RNA levels, atrial natriuretic factor mRNA expression, protein synthesis and cell surface area. Treatment of fenofibrate for 4 h also elevated oxygen species levels in a concentration-dependent manner. 3. In conclusion, these findings show that leptin induces hypertrophy through the activation of the PPARα pathway in cultured neonatal rat cardiomyocytes.

Rationale: Subacute combined degeneration (SCD) of the spinal cord has been reported to have distinctive characteristics on magnetic resonance imaging (MRI), such as an “inverted V sign”, a “pair of binoculars sign”, and a “dot sign”. We report a 3-point sign as a novel MRI characteristic, expanding the spectrum of imaging signs for SCD. Patient concerns: A 64-year-old female vegetarian presented with a 3-month history of progressive numbness and weakness in the lower extremities. Diagnosis: Laboratory examination showed a reduced serum vitamin B12 level. Spinal MRI showed hyperintensity within the posterior and lateral columns (appearing as a three-point sign) on T2-weighted imaging. Thus, the patient was diagnosed with SCD. Interventions: The patient was treated with intravenous cyanocobalamin and oral vitamin B12. Outcomes: After a follow-up period of 5 months, the symptoms were significantly improved. Lessons: Clinicians should be aware of this atypical MRI pattern, which may facilitate an early diagnosis.

Rationale:We report a rare case of syphilitic meningomyelitis presenting with visceral crisis and possessing characteristic imaging findings.Patient concerns:The patient, a 50-year-old woman, complained of pain in the upper abdomen and back. She then developed numbness in both lower extremit

The present study was performed to evaluate the antihypertensive effects of honokiol in vivo in spontaneously hypertensive rats (SHR). The effects of honokiol were investigated by determination of the blood pressure, vascular reactivity, oxidative parameters, and histologic change in the aorta. Long-term administration of honokiol (400 mg/kg/d) to SHR decreased systolic blood pressure significantly. Honokiol (200, 400 mg/kg/d) enhanced the aortic relaxation in response to acetylcholine after 49-d treatment, but had no significant effects on the relaxation to sodium nitroprusside. The oral administration of honokiol significantly increased the plasma level of NO(2(-))/NO(3(-)), but decreased the level of malondialdehyde in liver of SHR compared with the control vehicle. In addition, SHR administered honokiol showed significant reductions in the elastin bands and media thickness in the aorta. These results suggest that chronic treatment with honokiol exerts an antihypertensive effect in SHR, and its vasorelaxant action and antioxidant properties may contribute to reducing the elevated blood pressure.

Aim: To study the pharmacokinetics and accumulation of an Escherichia coliexpressed His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus monkeys. Methods: Rh-endostatin was iv or sc injected in Rhesus monkeys, and the rh-endostatin concentration in serum samples was determined by an enzyme immunoassay (EIA) method. The serum drug concentration-time data were analyzed by compartmental analysis using the practical pharmacokinetic program 3p97. Results: Following iv administration at a dose rate of 1.5, 4.5, and 13.5 mg/kg in rhesus monkeys, the concentration-time curves of rh-endostatin were best fitted to a three-compartment open model. AUC (0-∞) linearly increased with dose, while Cl s exhibited no significant difference among different dose groups. The terminal half-lives (λ 3 ) were 8±8, 3.1±1.4, and 20±14 h, respectively. After sc administration at a dose rate of 1.5 mg/kg, the concentration-time curve was best fitted to a two-compartment open model, with a terminal half-life ( T 1/2β ) of 8±3 h. Bioavailability following sc injection was approximately 70%±3%. After consecutive iv injection of rh-endostatin at a dose rate of 1.5 mg•kg -1 •d -1 for 7 d, the AUC (0-24 h) substantially increased from 22±13 mg•h•L -1 (d 1) to 50±29 mg•h•L -1 (d 7), with an accumulation factor of 2.3±0.6 (P Conclusion: The pharmacokinetic behavior of rh-endostatin in Rhesus monkeys complies with linear kinetics within the examined dose range. It tends to be accumulated in bodies after repeated administration at a dose level of 1.5 mg•kg -1 •d -1 for more than 7 consecutive days.