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Two o-carborane-based π-conjugated macrocycles are synthesized via oxidative coupling of acetylene-terminated o-carborane precursors. The single-crystal X-ray diffraction analysis unambiguously revealed their unique porous supramolecular structures, which display micropore characteristics. The...

To determine the impact of visual impairment (VI) on health-related quality of life (HRQoL) and to compare the health burden of VI in different areas in mainland China. A cohort of 6830 people from rural villages and a cohort of 3251 people from an urban city were included to receive comprehensive ophthalmologic examinations and complete the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. For urban and rural populations, a unified VI grouping standard was adopted: the eyes were classified into normal group, mild–moderate group, and severe group according to WHO standards, and then divided into 6 groups considering both eyes. We estimated the effects of VI on the EQ-5D index score using linear regression models and the association between VI and self-reported EQ-5D health problems using logistic regression models. Associations were assessed by the Spearman correlation coefficient. The prevalence of VI and the index scores of EQ-5D-3L for each subgroup of VI were higher for the rural cohort. In these two cohorts, the severity of VI in rural population (Spearman r = 0.205; p

A series of D–π–A type azobenzenes with a ferrocenyl/ferrocenylethynyl electron donor at the para/meta-position have been synthesized and characterized by electrochemistry and UV-vis spectroscopy. Compared to the D–π type meta-ferrocenyl/ferrocenylethynyl azobenzenes, the photoisomerization properties of D–π–A type meta-ferrocenyl/ferrocenylethynyl azobenzene are significantly improved. The photoisomerization properties of D–π–A type meta-ferrocenyl azobenzene are significantly different from those of D–π–A type para-ferrocenyl azobenzene, due to the electronic communication influenced by the substitution position of the redox center on the azobenzene moiety. Among the derivatives, compound 17 exhibits the highest amount of the cis form (97%) in the photostationary state (PSS) upon UV light (365 nm) irradiation. Compounds 13 and 15–17 exhibit excellent fatigue resistance and reversibility upon several reversible isomerization cycles.

The M-type phospholipase A2 receptor (PLA2R) is the major autoantigen of primary membranous nephropathy (MN). Despite many studies on B-cell epitopes recognized by antibodies, little is known about T-cell epitopes. Herein, we synthesized 123 linear peptides, each consisting of 15-22 amino acids with 8-12 amino acid overlaps, across ten domains of PLA2R. Their binding capacity to risk (DRB1*1501, DRB1*0301) and protective (DRB1*0901, DRB1*0701) HLA molecules was then assessed by flow cytometry. Proliferation of CD4+ T cells from patients with anti-PLA2R positive MN was analyzed after peptide stimulation. Cytokines produced by activated peripheral blood mononuclear cells were measured by cytometric bead arrays. We identified 17 PLA2R peptides that bound to both DRB1*1501 and DRB1*0301 molecules with high capacity. Some of these peptides showed decreased binding to heterozygous DRB1*1501/0901 and DRB1*0301/0701. Ten of the 17 peptides (CysR1, CysR10, CysR12, FnII-3, CTLD3-9, CTLD3-10, CTLD3-11, CTLD5-2-1, CTLD7-1 and CTLD7-2) induced significant proliferation of CD4+ T cells from patients with MN than cells from healthy individuals. Upon activation by these peptides, peripheral blood mononuclear cells from patients with MN produced higher levels of pro-inflammatory cytokines, predominantly IL-6, TNF-α, IL-10, IL-9 and IL-17. Thus, we mapped and identified ten peptides in the CysR, FnII, CTLD3, CTLD5, CTLD7 domains of PLA2R as potential T-cell epitopes of MN. These findings are a first step towards developing peptide-specific immunotherapies.

The reaction between alkynyl bridged bisferrocenyl derivatives and decaborane results in new symmetrical ferrocenyl substituted carboranes 8–11. All the new compounds have been identified and fully characterized by means of NMR and HRMS. The molecular structures of target compounds 8–11 were determined by single-crystal X-ray analysis. The electrochemistry studies of the ferrocenyl substituted carboranes are reported, and the results suggest that there is a considerable amount of electronic communication between the two ferrocenyls in these symmetrical conjugated oligomers. The thermodynamic stability of the mixed-valent species increases in the order 11 < 8 < 10 < 9.

TMEM16A Ca2+-activated chloride channel (CaCC) plays an essential role in vascular homeostasis. In this study we investigated the molecular mechanisms underlying downregulation of TMEM16A CaCC activity during hypertension. In cultured basilar artery smooth muscle cells (BASMCs) isolated from 2k2c renohypertesive rats, treatment with angiotensin II (0.125−1 μM) dose-dependently increased endophilin A2 levels and decreased TMEM16A expression. Similar phenomenon was observed in basilar artery isolated from 2k2c rats. We then used whole-cell recording to examine whether endophilin A2 could regulate TMEM16A CaCC activity in BASMCs and found that knockdown of endophilin A2 significantly enhanced CaCC activity, whereas overexpression of endophilin A2 produced the opposite effect. Overexpression of endophilin A2 did not affect the TMEM16A mRNA level, but markedly decreased TMEM16A protein level in BASMCs by inducing ubiquitination and autophagy of TMEM16A. Ubiquitin-binding receptor p62 (SQSTM1) could bind to ubiquitinated TMEM16A and resulted in a process of TMEM16A proteolysis in autophagosome/lysosome. These data provide new insights into the regulation of TMEM16A CaCC activity by endophilin A2 in BASMCs, which partly explains the mechanism of angiotensin-II-induced TMEM16A inhibition during hypertension-induced vascular remodeling.

To determine the impact of visual impairment (VI) on health-related quality of life (HRQoL) and to compare the health burden of VI in different areas in mainland China.A cohort of 6830 people from rural villages and a cohort of 3251 people from an urban city were included to receive comprehensive ophthalmologic examinations and complete the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. For urban and rural populations, a unified VI grouping standard was adopted: the eyes were classified into normal group, mild-moderate group, and severe group according to WHO standards, and then divided into 6 groups considering both eyes. We estimated the effects of VI on the EQ-5D index score using linear regression models and the association between VI and self-reported EQ-5D health problems using logistic regression models. Associations were assessed by the Spearman correlation coefficient.The prevalence of VI and the index scores of EQ-5D-3L for each subgroup of VI were higher for the rural cohort. In these two cohorts, the severity of VI in rural population (Spearman r = 0.205; p 0.0001) and urban population (Spearman r = 0.164; p 0.0001) is correlated with the EQ-5D index score. In the rural cohort, the difference in index scores with bilateral severe VI compared to those without VI, after adjusting for covariates, was - 0.053 for the rural cohort and - 0.084 for the urban cohort, respectively. In the rural cohort, the odds ratio for bilateral severe VI was 4.39 for mobility, 6.33 for self-care, and 5.88 for usual activities. The incidence of anxiety or depression and pain or discomfort in the urban cohort was greater; the OR for bilateral severe VI in the urban cohort was 4.75.VI has a negative impact on HRQoL in the rural and urban areas of China, especially in urban population. It is also more likely to cause anxiety or depression among the urban cohort, which deserves special attention.

In this work, we report a series of cyclophane fluorescent sensors based on acridine combining with imidazolium through ether linkages. X-ray crystal structures demonstrated the self-assembly behavior of these cyclophanes in the solid state driven by hydrogen bond and π–π interactions. Sensors showed excellent selectivity towards Fe3+ in aqueous solution (H2O/CH3CN = 49:1, v/v) and H2PO4− in acetonitrile solution with notable color change under UV light, evident changes were also noticed in fluorescence spectra. In fluorescence emission, the obvious turn-off was induced by Fe3+ in aqueous solution and the obvious turn-on as well as bathochromic-shift was induced by H2PO4− in acetonitrile solution.

Background TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, β, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Cl-current and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Cl-current was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Cl-current. Phosphomimetic mutation S727D markedly decreased TMEM16A Cl-current and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice. Conclusions Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10−9–10−6 g/ml) concentration-dependently depolarized the resting potential, diminished the action potential, and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes, AgNPs (10−9–10−7 g/ml) concentration-dependently decreased the Na+ currents (INa), accelerated the activation, and delayed the inactivation and recovery of Na+ channels from inactivation within 5 min. AgNPs at 10−8 g/ml also rapidly decreased the inwardly rectifying K+ currents (IK1) and delayed the activation of IK1 channels. Intravenous injection of AgNPs at 3 mg/kg only decreased the heart rate, while at ≥4 mg/kg sequentially induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole. AgNPs at 10−10–10−6 g/ml did not increase reactive oxygen species (ROS) generation and only at 10−6 g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5 min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5 min, but was observed 1 h after exposing to AgNPs. Comparative Ag+ (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level, but not caused by Ag+, ROS, and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.

After a short-term intraocular pressure (IOP) elevation, the central retinal vein caliber may be widened at lower IOP rise levels, while be compressed at higher IOP rise values.The purpose of this study was to investigate changes in the calibers of the central retinal vein trunk (CRVT) and central retinal artery trunk (CRAT) trunk during a short-term elevation of IOP.A prospective observational study. Acute primary angle-closure suspects underwent a dark room prone provocative test (DRPPT) for 2 hours. Before and at the end of the test, tonometry, swept-source optical coherence tomography, and nonmydriatic fundus photography were performed. The calibers of the CRVT and CRAT were measured on the fundus photos taken at baseline and at the end of the DRPPT.The study included 101 eyes (61 individuals; mean age: 54.8±9.3 y; range: 30 to 70 y) which showed an increase in IOP by 9.6±9.0 mm Hg (range: 2.3 to 46.7 mm Hg). From baseline to the end of the DRPPT, the mean CRVT caliber increased from 101.8±25.9 to 107.7±26.6 μm (P0.001), while the CRAT caliber did not differ significantly (110.3±24.2 vs. 109.7±21.5 μm; P=0.54) during the test. The CRVT widening was larger in the subgroup with IOP rise of6 mm Hg than in the subgroup with an IOP rise of 6 to 15 mm Hg, while in the subgroup with an IOP rise of15 mm Hg the CRVT caliber did not change significantly (P=0.20) during the test.A physiological short-term IOP rise at lower levels of IOP elevation led to a widening of the CRVT, while at higher IOP values, the further IOP-rise may have compressed the retinal vein. Because of higher intraluminal pressure values, the retinal artery diameters were not affected by the IOP-rise.

Rationale: Transmembrane member 16A (TMEM16A) is a component of calcium-activated chloride channels that regulate vascular smooth muscle cell (SMC) proliferation and remodeling. Autophagy, a highly conserved cellular catabolic process in eukaryotes, exerts important physiological functions in vascular SMCs. In the current study, we investigated the relationship between TMEM16A and autophagy during vascular remodeling. Methods: We generated a transgenic mouse that overexpresses TMEM16A specifically in vascular SMCs to verify the role of TMEM16A in vascular remodeling. Techniques employed included immunofluorescence, electron microscopy, co-immunoprecipitation, and Western blotting. Results: Autophagy was activated in aortas from angiotensin II (AngII)-induced hypertensive mice with decreased TMEM16A expression. The numbers of light chain 3B (LC3B)-positive puncta in aortas correlated with the medial cross-sectional aorta areas and TMEM16A expression during hypertension. SMC-specific TMEM16A overexpression markedly inhibited AngII-induced autophagy in mouse aortas. Moreover, in mouse aortic SMCs (MASMCs), AngII-induced autophagosome formation and autophagic flux were blocked by TMEM16A upregulation and were promoted by TMEM16A knockdown. The effect of TMEM16A on autophagy was independent of the mTOR pathway, but was associated with reduced kinase activity of the vacuolar protein sorting 34 (VPS34) enzyme. Overexpression of VPS34 attenuated the effect of TMEM16A overexpression on MASMC proliferation, while the effect of TMEM16A downregulation was abrogated by a VPS34 inhibitor. Further, co-immunoprecipitation assays revealed that TMEM16A interacts with p62. TMEM16A overexpression inhibited AngII-induced p62-Bcl-2 binding and enhanced Bcl-2-Beclin-1 interactions, leading to suppression of Beclin-1/VPS34 complex formation. However, TMEM16A downregulation showed the opposite effects. Conclusion: TMEM16A regulates the four-way interaction between p62, Bcl-2, Beclin-1, and VPS34, and coordinately prevents vascular autophagy and remodeling.

Cai-Xia Lin,1,2Jing-Li Gu,2 Ji-Min Cao11Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of ChinaBackground: Platinum nanoparticles (PtNPs) have been considered a nontoxic nanomaterial and been clinically used in cancer chemotherapy. PtNPs can also be vehicle exhausts and environmental pollutants. These situations increase the possibility of human exposure to PtNPs. However, the potential biotoxicities of PtNPs including that on cardiac electrophysiology have been poorly understood.Methods: Ion channel currents of cardiomyocytes were recorded by patch clamp. Heart rhythm was monitored by electrocardiogram recording. Morphology and characteristics of PtNPs were examined by transmission electron microscopy, dynamic light scattering and electrophoretic light scattering analyses.Results: In cultured neonatal mice ventricular cardiomyocytes, PtNPs with diameters 5 nm (PtNP-5) and 70 nm (PtNP-70) concentration-dependently (10–9, – 10–5, g/mL) depolarized the resting potentials, suppressed the depolarization of action potentials and delayed the repolarization of action potentials. At the ion channel level, PtNPs decreased the current densities of INa, IK1 and Ito channels, but did not affect the channel activity kinetics. In vivo, PtNP-5 and PtNP-70 dose-dependently (3–10 mg/kg, i.v.) decreased the heart rate and induced complete atrioventricular conduction block (AVB) at higher doses. Both PtNP-5 and PtNP-70 (10–9, – 10–5, g/mL) did not significantly increase the generation of ROS and leak of lactate dehydrogenase (LDH) from cardiomyocytes within 5 mins after exposure except that only very high PtNP-5 (10–5, g/mL) slightly increased LDH leak. The internalization of PtNP-5 and PtNP-70 did not occur within 5 mins but occurred 1 hr after exposure.Conclusion: PtNP-5 and PtNP-70 have similar acute toxic effects on cardiac electrophysiology and can induce threatening cardiac conduction block. These acute electrophysiological toxicities of PtNPs are most likely caused by a nanoscale interference of PtNPs on ion channels at the extracellular side, rather than by oxidative damage or other slower biological processes.Keywords: platinum nanoparticle, transmembrane potential, ion channel, arrhythmia, nanotoxicity, heart &nbsp

A new anion receptor that utilized boron–fluoride interaction and (C H) + ⋯F − -type ionic hydrogen bonding in the binding of F ions had been synthesized and characterized by IR, MS, HRMS, 11 B, 1 H, and 13 C NMR spectra. The signaling process was confirmed by UV–vis, electrochemistry measurements as well as 1 H, 19 F, and 11 B NMR spectroscopy. Among the tested anions: F − , Cl − , Br − , OAc − , H 2 PO 4 − , HSO 4 − , only F − induced a remarkable red-shift (29 nm) in the absorption spectrum which was concomitant with a color change from pink to faint yellow. This receptor provided a new approach for naked-eyed detection of F − and the detection limit was calculated to be 1.26 μM. Besides, Cyclic Voltammetry (CV) showed that the receptor had unique selectivities for F − with a remarkable phenomenon in merging of the two reduction peaks in response to the increment addition of the anions. 1 H, 19 F, and 11 B NMR titrations demonstrated that the receptor showed affinity and high selectivity for F − and provided the evidence of interaction between the receptor and F − .

N-(arylmethylene)-benzimidazole/imidazole-borane compounds (7-10) based on ferrocene/benzene were synthesized in a cost-effective way by reacting N-(arylmethylene)-benzimidazole/imidazoles with ammonium sulfate ((NH4)2SO4) and sodium borohydride (NaBH4). The structures of compounds 7-9 were determined by X-ray crystallography. Four compounds displayed high thermal decomposition temperatures (182-256°C) according to the thermogravimetry (TG) measurements. Interestingly, these compounds showed promising applications as potential propellant due to their spontaneous combustion upon contact concentrated HNO3 (≥ 95 %) and catalytic effect on the thermal degradation of ammonium perchlorate (AP).

Background and purpose Angiotensin II (AngII) induces migration and growth of vascular smooth muscle cell (VSMC), which is responsible for vascular remodelling in some cardiovascular diseases. Ang II also activates a Cl(-) current, but the underlying mechanism is not clear. Experimental approach The A10 cell line and primary cultures of VSMC from control, ClC-3 channel null mice and WT mice made hypertensive with AngII infusions were used. Techniques employed included whole-cell patch clamp, co-immunoprecipitation, site-specific mutagenesis and Western blotting, Key results In VSMC, AngII induced Cl(-) currents was carried by the chloride ion channel ClC-3. This current was absent in VSMC from ClC-3 channel null mice. The AngII-induced Cl(-) current involved interactions between ClC-3 channels and Rho-kinase 2 (ROCK2), shown by N- or C-terminal truncation of ClC-3 protein, ROCK2 siRNA and co-immunoprecipitation assays. Phosphorylation of ClC-3 channels at Thr(532) by ROCK2 was critical for AngII-induced Cl(-) current and VSMC migration. The ClC-3 T532D mutant (mutation of Thr(532) to aspartate), mimicking phosphorylated ClC-3 protein, significantly potentiated AngII-induced Cl(-) current and VSMC migration, while ClC-3 T532A (mutation of Thr(532) to alanine) had the opposite effects. AngII-induced cell migration was markedly decreased in VSMC from ClC-3 channel null mice that was insensitive to Y27632, an inhibitor of ROCK2. In addition, AngII-induced cerebrovascular remodelling was decreased in ClC-3 null mice, possibly by the ROCK2 pathway. Conclusions and implications ClC-3 protein phosphorylation at Thr(532) by ROCK2 is required for AngII-induced Cl(-) current and VSMC migration that are involved in AngII-induced vascular remodelling in hypertension.

A series of xylyl ( ortho , meta , and para ) linked N -ferrocenylmethylene-substituted bis-imidazolium salts ( 3a–3c ) and bis-benzimidazolium salts ( 4a–4c ) were synthesized and structurally characterized. Their binding properties for anions were investigated by electrochemistry and 1 H NMR spectroscopy. The structure of 3b , 3c , 4a and 4b were confirmed by X-ray crystallography. As expected, all salts were good electrochemistry-signaling receptors for several anions (F − , AcO − , HSO 4 − , Cl − , Br − and I − ), that in one receptor the imidazolium/benzimidazolium units offer binding sites for anion and the ferrocenyl units offer electrochemistry response sites. Furthermore, the results showed that they were highly selective and sensitive to F − and receptors 3b and 4b featuring a meta -xylene spacer were more effective receptors for F − compared to receptors linked by an orth or a para -xylene spacer. 1 H NMR titrations demonstrated that fluoride ion was recognized by receptors through (C–H) + ···X − hydrogen bonds.

The reaction of ferrocenecarboxaldehyde with (2-aminoethoxy)diphenylborane led to the formation of ferrocenyl-substituted boronate receptor 1 , which was characterized by IR, MS, HRMS, 11 B, 1 H and 13 C NMR spectra. The signaling process was confirmed by UV–vis, electrochemistry measurements as well as 1 H and 19 F NMR spectroscopy. The receptor 1 exhibited high selectivity for F − in CH 3 CN solution over all the other anions in the DPVs (differential pulse voltammetry). 1 H NMR titrations indicated that F − ion induced tautomerism of E - and Z -isomer transformations of the receptor 1 and there were three kinds of protons showing obvious highfield shifts for receptor 1 in DMSO- d 6 . UV–vis titrations demonstrated that the receptor 1 could bind F − ion forming 1:1 stoichiometric complexes and show high selectivity and sensitivity towards F − ion.

Two pyrrolide-imine chelating Ni(II) complexes {[2-(2-CH3O-C6H4-NCH)C4H3N]2Ni (2a) and [(Fc-NCH)]C4H3N]2Ni (2b, Fc = ferrocenyl)} were prepared via treating corresponding Schiff base with 0.5 equiv. NiCl2·6H2O in moderate yields. The crystal structures of 2a and 2b were determined by single-crystal X-ray diffraction. Atom Ni(II) of 2a was coordinated by two pyrrolide-imine ligands in trans position to display a twisted octahedral coordination geometry. Ni(II) of 2b had a distorted square-planar geometry, bonded with two ferrocenyl pyrrole-imine ligands, each ferrocene and pyrrole of ligands adopting a trans conformation. The UV–vis spectroscopy and electrochemical measurements were investigated. The catalytic efficiency of the complexes on the thermal decomposition of ammonium perchlorate (AP) was studied by differential scanning calorimetry (DSC) and thermogravimetry (TG). Compared with the thermal decomposition of pure AP, the decomposition temperatures were decreased by 27 °C, 77 °C, 88 °C and 172 °C, respectively when 1a, 1b, 2a and 2b were added in AP. The results indicated that the Ni(II) complex 2b bearing ferrocene-based pyrrolide-imine N,N-chelate ligand displayed an excellent catalytic efficiency on the thermal decomposition of AP.

The unsymmetric bis-imidazolium salts ligands 4a and b were prepared by stepwise reactions of 2,6-bis(bromomethylene)-4-( t -butyl)anisole ( 1 ) with two different N-substituted imidazoles. Reaction of the bis-imidazolium ligands with Ag 2 O in acetonitrile gave the dinuclear bis(N-heterocyclic carbene) complexes 5a and b . The molecular structure of complex 5a was determined by single-crystal X-ray diffraction analysis. In complex 5a and b, the two C carbene –Ag–C carbene axes are in a crossed conformation, two O atoms from phenoxyl groups weakly coordinate to different Ag ions and the two p - t -butylphenoxyl groups adopted a staggered conformation. To regulate the molecular shape of the N-heterocyclic carbene Ag(I) macrocyclic complexes, two tetradentate imidazolium ligands ( 9a and b ) were prepared. The bimetallic NHC–Ag(I) complexes 10a and b were obtained by the reaction of 9a and b and Ag 2 O in acetonitrile. Constrained by the chain (the dioxoethylene or dioxomethylenebenzene chain in 10a or 10b , respectively) at the O-position of the phenoxyl group, the two p -methylphenoxyl groups in complexes 10a and b might be predicted to have a cone conformation. The ligands and the corresponding NHC metal complexes have been characterized by elemental analysis, 1 H NMR and 13 C NMR, HRMS spectra, as well as TGA and DTA spectra being determined for complexes 10a and b . The TGA curves show that these NHC–Ag complexes have good thermal stability.

TMEM16A is a critical component of CaSerine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10

A series of novel ferrocene-based benzimidazolium receptors 4–7 were designed and structurally characterized, their crystal structures revealed that these receptors were capable of incorporating anions such as PF6− and Br− and that the molecules were linked by C–H···X hydrogen bonds. The anion binding studies were carried out using various techniques including electrochemistry (CV and SWV), UV–vis and 1H NMR spectroscopy. Electrochemical behavior indicated that all the receptors displayed rather strong electrochemical sensing properties for F− in CH3CN. For receptors 6 and 7, obvious absorption changes were observed when F− was added in CH3CN on the UV–vis spectra. 1H NMR titrations demonstrated that all the receptors could bind anions through (C–H)+···X− hydrogen bonds forming 1:1 stoichiometric complexes and have good fluoride binding ability in DMSO-d6. The anion binding studies indicated that receptors 6 and 7 comprised of the ferrocene-based benzimidazolium fragment and conjugated group showing better affinity for F− than receptors 4 and 5.

Several novel acyclic multi-site receptors comprising of imidazolium moieties were synthesized and structurally characterized. All of these compounds were characterized through 1H NMR, 13C NMR, MS and IR, elemental analysis. The crystal structures of 1,4-bis(1-ferrocenylmethylimidazoliumylethoxy)-benzene hexafluorophosphate (1) and 1,3-bis(1-ferrocenylmethylimidazoliumylethoxy)-benzene hexafluorophosphate (2) were confirmed by X-ray crystallography, it was clear that molecules were linked by C–H⋯F hydrogen bonds interactions between PF6− and cations. The anion binding studies were investigated by electrochemistry and 1H NMR spectroscopy. Electrochemical behaviors indicated that all the receptors displayed unique electrochemical sensing property for F− in CH3CN. 1H NMR titrations demonstrated that all the receptors have good fluoride binding ability in DMSO-d6 through (C–H)+⋯X− hydrogen bonds. The flexible receptors 1 and 2 exhibited higher affinity toward anion than the rigid receptors 3 and 4.

Three ferrocene-based sulfonyl-substituted dihydropyrazoles 3a–c have been synthesized, from the corresponding α,β-unsaturated diketones, and fully characterized. The crystal structures of 3a–c have been confirmed by X-ray crystallography, and electrochemistry behaviors of 3a–c have been examined by cyclic voltammetry (CV). Representatively, the mechanism of the electron transfer in redox process of 3a has been verified by density functional theory (DFT) calculation. It has been found that the activity of catalytic decomposition of ammonium perchlorate (AP) is significantly lowered (by 62.9–104.7 °C) with an addition of 3a–c. We expect that the ferrocene-based sulfonyl dihydropyrazole derivatives would have a great value in burning rate catalyst as composite solid propellants.

Two diphosphane ligands – 2,5-bis(2-(diphenylphosphino)-5-R)phenyl)-1,3,4-oxadiazole (L1, R = H, L2, R = OMe) and their binuclear complexes, L1Cu and L2Cu, were prepared and characterized. The molecular structures of L1Cu and L2Cu, as perchlorate salts, were established by X-ray crystallography, which showed them to be binuclear complexes with each Cu atom tetrahedrally coordinated by two P atoms and two N atoms. The ligands and their Cu(I) complexes catalyzed Sonogashira coupling reactions of iodobenzene with phenylacetylene in the presence of K2CO3 under Pd-free conditions. Coupling reactions catalyzed by L1 or L2 with Cu(MeCN)4ClO4 in situ exhibited better yields than those by the corresponding Cu(I) complexes L1Cu or L2Cu. Detailed studies showed L1 or L2 with Cu(MeCN)4ClO4 to be suitable catalysts for the coupling reaction of terminal alkynes and aryl halides. The coupling reactions of aryl iodides with electron-withdrawing groups showed better results. Copyright © 2014 John Wiley & Sons, Ltd.

Mono- and dinuclear Hg(II) complexes of bis-( N -heterocyclic carbene) bridged with calixarene fragments, [Hg L ](PF 6 ) 2 ( 4a , 4b ) and [Hg 2 L 2 ](PF 6 ) 4 ( 5a , 5b ), ( L = bis{3-( N -1-naphthylmethyl-imidazol-2-ylidene)methyl-5-R-2-methoxyphenyl}methane, a : R = Me, b : R = t -Bu) were both obtained by treatment of corresponding bis-imidazolium salts with mercuric acetate. The structures of complexes 4a and 5a were established by X-ray diffraction. Mononuclear complex 4a displays a small rigid cavity consisting of a mercury cation and a bis-NHC ligand. Dinuclear complex 5a shows a 28-memebered metallamacrocycle formed by two mercury cations and two bis-NHC ligands. Short mercury–oxygen contacts are found between mercury cations and methoxy groups of ligands in 4a and 5a . Cation–π–arene interactions are present between mercury cations and naphthalene rings of ligands. Additionally, the fluorescent chemosensing behaviors of complex 5a with large cavity to diphenylacetylene, ( E )-azobenzene and ( E )-4,4′-azobispyridine were investigated.

Quinoline bridged imidazolium precursors 5,8-bis(N-R-imidazolylidenylmethylene)quinoline PF6– salts [H2L](PF6)2 [R = Me (1a), R = naphthylmethyl (1b)] were prepared by quaternization of N-methylimidazole and N-naphthylmethylimidazole with 5,8-bis(bromomethyl)quinoline, respectively. Reaction of the imidazolium ligands 1a and 1b with Hg(OAc)2 and Ag2O in acetonitrile gave the macrocyclic transition metal carbene complexes [Hg2L2](PF6)4 (2a and 2b) and [Ag2L2](PF6)2 (3a and 3b), respectively. All the N-heterocyclic carbene complexes were characterized in detail by NMR, ESI-MS, and elemental analysis. Structures of complexes 2a and 3a were determined by X-ray diffraction studies. Structural studies revealed that the coordination arrangement of the central mercury atom in complex 2a displays a tricoordinate mode and the molecular conformation results in a“closed” form with the bridging quinoline functionality in the macrocycle, whereas the silver complex 3a does not show an coordiantion between the bridging quinoline and the AgI ion, which results in an “open” conformation of the macrocycle. The HgII and AgI NHC complexes showed similar UV absorption and luminescence in acetonitrile solutions.

Conditioned taste preference (CTP) is a taste learning reflex by which an animal learns to prefer a substance which tastes not well and has been studied with much interest in recent years. However, the neural substrates of CTP are less known. This study aimed to determine the possible neural path- ways of CTP and whether serum leptin level and the leptin receptor (OB-Rb) in the hind brain are involved following CTP formation.We established CTP of quinine in rats with a 2-bottle preference test. The serum leptin concentrations were detected, the expression of c-fos in the rat brain was tested to determine the nuclei in relation with establishment of CTR Finally, the OB-Rb mRNA expression was examined by RT-qPCR assay in parabrachial nucleus (PBN) and the nucleus of the solitary tract (NST) of the hind brain.Compared with control group, the level of serum leptin was higher in the CTP group (4.58 ± 0.52 vs 1.67 ± 0.25 µg/L, P0.01); increased c-fos positive cells were found in the anterior hypothalamus (AH, 221.75 ± 4.96 vs. 178.50 ± 6.63 cells/mm², P0.05), the basal lateral amygdala (BLA, 70.75 ± 6.17 vs 56.50 ± 3.62 cells/ mm², P0.05) and the nucleus of the solitary tract (NST, 41.25 ± 1.32 vs 32.50 ± 1.02 cells/mm², P0.05). But in ventromedial nucleus of the hypothalamus (VMH, 20.75 ± 2.73 vs 38.5 ± 1.54 per 1 mm², P005), PBN (21.50 ± 2.24 vs 36.25 ± 1.49 cells/mm², P0.05) and the central nucleus of the amygdala (CeA, 22.25 ± 1.53 vs 35.50 ± 2.11 cells/mm², P0.05), the number of c-fos positive cells was decreased in the CTP group. In addition, we found OB-Rb mRNA expression in PBN of CTP group rats was higher than that of control group (0.95 ± 0.055 vs 0.57 ± 0.034, P0.05), while there was no significant difference of OB-Rb mRNA expression in NST between the two groups.Nuclei AH, BLA, NST, VMH, PBN and CeA participate in the formation of CTP. Leptin and its receptor in PBN may be involved in the formation and maintenance of CTP.

The reaction of α,β-unsaturated ketones of 2,2-diferrocenylpropane with hydrazine led to the formation of 2,2-diferrocenylpropane-substituted dihydropyrazole. The further reaction of dihydropyrazole with p-pyridinecarboxylic acid chloride or benzoyl chloride resulted in the isolation of two novel 2,2-diferrocenylpropane-substituted acyl dihydropyrazole derivatives. All of these compounds were analyzed by MS, IR and 1H NMR spectra. The crystal structure of representative compound, 1-p-pyridine acyl-3-ferrocenyl-5-(2,2-diferrocenylpropane)-4,5-dihydropyrazole (5a) has been elucidated by X-ray diffraction. The electrochemical behaviours of all the compounds have been examined.

Brown and beige adipose tissues dissipate energy in the form of heat via mitochondrial uncoupling protein 1, defending against hypothermia and potentially obesity. The latter has prompted renewed interest in understanding the processes involved in browning to realize the potential therapeutic benefits. To characterize the temporal profile of cold-induced changes and browning of brown and white adipose tissues in mice. Methods: Male C57BL/6J mice were singly housed in conventional cages under cold exposure (4°C) for 1, 2, 3, 4, 5 and 7days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological, immunohistochemical, gene and protein expression analysis. Results: Upon cold exposure, food intake increased, whilst body weight and adipocyte size were found to be transiently reduced. iBAT mass was found to be increased, whilst sWAT and eWAT were found to be transiently decreased. A combination of morphological, genetic (Ucp-1, Pgc-1α and Elov13) and biochemical (UCP-1, PPARγ and aP2) analyses demonstrated the depot-specific remodelling in response to cold exposure. Conclusion: Our results demonstrate the differential responses to cold-induced changes across discrete BAT and WAT depots and support the notion that the effects of short-term cold exposure are achieved by expansion, activation and increasing thermogenic capacity of iBAT, as well as browning of sWAT and, to a lesser extent, eWAT. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd

Purpose To investigate the effect of femtosecond laser-assisted cataract surgery (FLACS) on aqueous humour and lens capsule. Methods This prospective randomized comparative study enrolled 19 eyes that underwent FLACS as the trial group and 20 eyes that underwent conventional phacoemulsification as the control group. The femtosecond laser platform (LLS-fs 3D; LensAR, Orlando, FL, USA) was used to generate capsulotomy (laser energy 8 μJ) and lens fragmentation (laser energy 10 μJ). Morphology of the cutting edge and cells of anterior capsule was assessed by light microscopy. The proteins in the aqueous humour were identified by mass spectrometry (Ultraflex III TOF/TOF; Bruker Dalton, Bremen, Germany). Electrolyte in the aqueous humour was detected by a chemistry analyzer (Aeroset Clinical Chemistry Analyzer; Abbott Laboratories, Abbott Park, IL, USA). Results The cutting edge of anterior capsule was saw-tooth-shaped under magnification of 200× and 400× in the trial group, while it was smooth in the control group. Intact cells were found in the boundary area next to the cutting edge of anterior capsule in both groups. β-Crystallin B1, γ-crystallin S and transferrin were detected in the aqueous humour in the trial group. The concentrations of K+, Na+ and Cl− in the aqueous humour in the trial group differed significantly from those in the control group (p = 0.02, 0.03 and 0.04, respectively). Conclusion Femtosecond laser-assisted cataract surgery (FLACS) causes release of transferrin and crystallin from lens to aqueous humour and results in significant changes in the concentrations of K+, Na+ and Cl− in aqueous humour. However, these changes due to FLACS have no clinical significance or toxicity.

A structurally simple, 2,2-diferrocenylpropane-based ion pair receptor 1 was synthesized and characterized by (1)H NMR, (13)C NMR, HRMS, elemental analyses, and single-crystal X-ray diffraction. The ion pair receptor 1 showed excellent selectivity and sensitivity towards Pb(2+) with multi-channel responses: a fluorescence enhancement (more than 42-fold), a notable color change from yellow to red, redox anodic shift (ΔE1/2 = 151 mV), while HSO4(-) promoted fluorescence enhancement when Pb(2+) or Zn(2+) was bonded to the cation binding-site. (1)H NMR titration and density functional theory were performed to reveal the sensing mechanism based on photo-induced electron transfer (PET).

Reactions performed in the presence of the ligand MOD succeed with slightly higher yields than the ones performed in the presence of ligand HOD.

In the present paper, the authors make a summary on the clinical application of acu-moxibustion therapy in the treatment of gouty arthritis in recent 10 years. Acupuncture needles often used are filiform needle, red-hot needle, moxibustion-warmed needle and three-edged needle. Clinical studies have showed that acupuncture therapy has a definite efficacy in relieving gouty arthritis and has its clinical characteristics, such as faster efficacy, lower relapse rate, etc. in comparison with medication.

To observe the effect of electroacupuncture (EA) on hippocampal apoptosis protein caspase-9 expression and neuroethology in hyperlipemia plus cerebral ischemia (HL-CI) rats.Seventy male SD rats were randomized into control, hyperlipemia (HL), CI, HL-CI, CI + EA, HL-CI + EA I , and HL-CI + EA II groups, with 10 cases in each. HL model was established by feeding the animals with high fat forage for 6 weeks and CI model was established by occlusion of the unilateral middle cerebral artery. EA (1-3 mA, 15 Hz) was applied to bilateral "Sanyinjiao" (SP 6) and "Fenglong" (ST 40) for 20 min every time; and "Baihui" (GV 20) and "Shuigou" (GV 26) were punctured and stimulated by twirling the acupuncture needle with hand continuously for 1 min. Acupuncture was given once daily for 17 days (beginning from the 10th day on before CI) in HL-CI + EA I group, and for 7 days (beginning after CI) in HL-CI + EA II group. The expression of hippocampal Caspase-9 was detected with immunohistochemistry. The score of neuroethology was also measured according to modified Bederson's method.In comparison with normal control and hyperlipemia model groups, Caspase-9 immune reaction (IR) positive cells in the hippocampus in HL-CI group increased significantly (P0.01). After acupuncture Caspase-9 IR-positive cells decreased remarkably. In comparison with group HL-CI + EA II, Caspase-9 IR-positive cells decreased significantly in HL-CI + EA I (P0.01). The score of neuroethology also degraded obviously.Acupuncture can improve neuroethology symptom, lessen over expression of hippocampal Caspase-9, and prevent CI injury in hyperlipemia rats with concurrent CI.

This paper analyzes the palmprint textures with a multi-resolution method. Texture feature vectors of palmprint are extracted by wavelet transformation. With the texture feature, isodata clustering method is used to achieve classification of the Feature vectors. Based on the classification, euclidean distance within-class and between-class are calculated to match the feature. Experimental result illustrates that the proposed approach for palmprint recognition is effective.

Dinuclear Ag(I) metallamacrocycles containing bis-N-heterocyclic carbene units and calixarene fragments [{1,1′-R2-3,3′-CH2{(p-R1-C6H2OMe)CH2}m-bisimidazol-2-ylidene}2-Ag2](PF6)2 (6a–f), (6a: m = 1, R1 = Me, R2 = Me; 6b: m = 1, R1 = t-Bu, R2 = Me; 6c: m = 1, R1 = Me, R2 = naphthylmethyl; 6d: m = 1, R1 = Me, R2 = anthrylmethyl; 6e: m = 2, R1 = Me, R2 = anthrylmethyl; 6f: m = 3, R1 = t-Bu, R2 = anthrylmethyl) were synthesized by reacting silver oxide with the corresponding bis-imidazolium salts (5a–f). Single crystal structural analyses reveal that metallamacrocycles of diverse sizes consisting of two NHC–Ag(I)–NHC units and two calixarene fragments are found in the structures of these dinuclear complexes. These complexes show different configurations with the change of the upper-rims (R1) of the calixarene fragments or N-substituents (R2) of the NHC rings. The two bis-NHC ligands in the complexes generally adopt trans-conformations except for the pair in 6b. Complexes 6a and 6c–d, in which R1 are methyl groups, show rectangular cavities in their structures. Complex 6b, in which R1 are tert-butyl groups of great steric hindrance, adopts cone conformation analogous to that of the calixarene. Interestingly, cation–π interactions are present between Ag(I) and the π–electron rich arene ring of R2 in the structures of complexes 6c–f. Intermolecular C–H⋯F hydrogen bonds exist in the crystal packing of all these complexes. Moreover, intermolecular Ag⋯Ag interactions are found in complex 6a and intermolecular π–π interactions are observed in complexes 6c–f. These intermolecular interactions lead to the formation of 2D supramolecular layers in complex 6c and 3D supramolecular networks in complexes 6a–b and 6d–f, respectively. The fluorescent chemosensing behaviors of these metallamacrocycles were explored for some neutral molecules. The results showed that 6d can behave as an efficient fluorescent chemosensor for p-benzoquinone and 6e–f exhibit fluorescent quenching behaviors for C60 or C70 fullerenes.