Electroacupuncture of scalp acupoint alleviates cerebral ischemic inflammatory injury by down-regulating RORγt and promoting balance of IL-17A+Th17/FOXP3+Treg in MCAO rats. / 电头针调控RORγt促进IL-17A+Th17/FOXP3+Treg细胞平衡缓解MCAOå¤§é¼ è„‘ç¼ºè¡€ç‚Žæ€§æŸä¼¤çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) of scalp acupoint (Dingnieqian-xiexian, MS6) on expression of retinoid-related orphan receptor γT (ROR γ t), interleukin (IL)-17A, IL-10, transfor-ming growth factor-ß1 (TGF-ß1), IL-6, IL-21, and IL-17A+ Thelper cells(Th) 17 and forkhead transcription factor P3 (FOXP3)+ regulatory T cells (Treg) differentiation of ischemic cortex in ischemic stroke rats, so as to explore its molecular mechanisms underlying relief of inflammatory injury of ischemic stroke. METHODS: A total of 120 male SD rats were randomly assigned to sham operation, model, EA, inhibitor, agonist and EA+agonist groups, with 15 rats in each group. The ischemic stroke model was established by occlusion of the left middle cerebral artery according to Longa's methods. For rats of the EA group and EA+agonist group, EA (2 Hz/100 Hz, 1 mA) was applied to bilateral MS6 for 30 min, once daily for 7 days. Rats of the inhibitor group received intraperitoneal injection of solution of SR1001 (RORγt inhibitor) (2.5 mg/mL, 10 mg/kg), once daily for 7 days. Rats of the agonist and EA+agonist groups received intraperitoneal injection of solution of SR1078 (RORγt agonist) (5 mg/mL, 5 mg/kg) before EA, once daily for 7 days. Rats of the sham operation and model groups were grabbed and fixed in the same way with the other groups. The Zea-longa's score, modified neurological severity score (mNSS) and the neurobehavioral score were assessed before and after the intervention. At the end of experiments, the ischemic cortex tissue was collected. The 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction. The expression of RORγt mRNA was detected by real-time quantitative PCR；the protein expression levels of RORγt, IL-17A, IL-10 and TGF-ß1 were detected by Western blot；the immunoactivity of IL-6 and IL-21 were detected by immunohistochemistry；the fluorescence areas of IL-17A+Th17 and FOXP3+Treg cells were measured by immunofluorescence and their ratio was calculated in the tissue of ischemic cortex. RESULTS: Relevant to the sham operation group, the model group had a significant increase in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01), and an obvious decrease in the expression levels of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.01). In contrast to the model group, both EA and inhibitor groups had a significant decrease in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01, P<0.05), and a marked increase in the expression levels of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.05, P<0.01), while the above indicators of the agonist group were all reversed (P<0.01, P<0.05). Comparison between the agonist and EA+agonist groups showed that the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg were significantly lower (P<0.01, P<0.05), and the expression of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity were obviously higher (P<0.01, P<0.05) in the EA+agonist group than in the agonist group, suggesting that EA intervention can effectively weaken the effects of RORγt agonist. CONCLUSIONS: EA of scalp acupoint MS6 can effectively improve the neurological function, behavior reaction and reduce cerebral infarct volume in ischemic stroke rats, which may be associated with its functions in down-regulating the expression of RORγt and promoting the balance of IL-17A+Th17/FOXP3+Treg to alleviate inflammatory injury after ischemic stroke.

Endothelial cell Orai1 is essential for endothelium-dependent contraction of mouse carotid arteries in normotensive and hypertensive mice.

Endothelium-dependent contraction (EDC) exists in blood vessels of normotensive animals, but is exaggerated in hypertension. An early signal in EDC is cytosolic Ca2+ rise in endothelial cells. In this study we investigated the functional role of Orai1, a major endothelial cell Ca2+ entry channel, in EDC. Hypertension model was established in WT mice by intake of L-NNA in the drinking water (0.5 g/L) for 4 weeks or osmotic pump delivery of Ang II (1.5 mg·kg-1·d-1) for 2 weeks. In TRPC5 KO mice, the concentration of L-NNA and Ang II were increased to 1 g/L or 2 mg·kg-1·d-1, respectively. Arterial segments were prepared from carotid arteries and aortas, and EDC was elicited by acetylcholine in the presence of Nω-nitro-L-arginine methyl ester. We showed that low concentration of acetylcholine (3-30 nM) initiated relaxation in phenylephrine-precontracted carotid arteries of both normotensive and hypertensive mice, while high concentration of acetylcholine (0.1-2 µM) induced contraction. Application of selective Orai1 inhibitors AnCoA4 (100 µM) or YM58483 (400 nM) had no effect on ACh-induced relaxation but markedly reduced acetylcholine-induced EDC. We found that EDC was increased in hypertensive mice compared with that of normotensive mice, which was associated with increased Orai1 expression in endothelial cells of hypertensive mice. Compared to TRPC5 and TRPV4, which were also involved in EDC, endothelial cell Orai1 had relatively greater contribution to EDC than either TRPC5 or TRPV4 alone. We identified COX-2, followed by PGF2α, PGD2 and PGE2 as the downstream signals of Orai1/TRPC5/TRPV4. In conclusion, Orai1 coordinates together with TRPC5 and TRPV4 in endothelial cells to regulate EDC responses. This study demonstrates a novel function of Orai1 in EDC in both normotensive and hypertensive mice, thus providing a general scheme about the control of EDC by Ca2+-permeable channels.

Thioridazine protects against disturbed flow-induced atherosclerosis by inhibiting RhoA/YAP-mediated endothelial inflammation.

Atherosclerotic diseases remain the leading cause of adult mortality and impose heavy burdens on health systems globally. Our previous study found that disturbed flow enhanced YAP activity to provoke endothelial activation and atherosclerosis, and targeting YAP alleviated endothelial inflammation and atherogenesis. Therefore, we established a luciferase reporter assay-based drug screening platform to seek out new YAP inhibitors for anti-atherosclerotic treatment. By screening the FDA-approved drug library, we identified that an anti-psychotic drug thioridazine markedly suppressed YAP activity in human endothelial cells. Thioridazine inhibited disturbed flow-induced endothelial inflammatory response in vivo and in vitro. We verified that the anti-inflammatory effects of thioridazine were mediated by inhibition of YAP. Thioridazine regulated YAP activity via restraining RhoA. Moreover, administration of thioridazine attenuated partial carotid ligation- and western diet-induced atherosclerosis in two mouse models. Overall, this work opens up the possibility of repurposing thioridazine for intervention of atherosclerotic diseases. This study also shed light on the underlying mechanisms that thioridazine inhibited endothelial activation and atherogenesis via repression of RhoA-YAP axis. As a new YAP inhibitor, thioridazine might need further investigation and development for the treatment of atherosclerotic diseases in clinical practice.

[Adjuvant therapy of Wentong acupuncture for elderly patients of primary osteoporosis with intestinal dysfunction: a randomized controlled trial].

OBJECTIVE: To observe the effects of Wentong acupuncture on bone mineral density (BMD), bone metabolism and intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction. METHODS: A total of 128 elderly patients of primary osteoporosis with intestinal dysfunction were randomly divided into an observation group and a control group, 64 cases in each group. Patients in the control group were treated with oral administration of vitamin D calcium chewable tablets (0.6 g, once a day) and calcitriol capsules (0.25 µg, three times a day); the treatment was given for 6 months. On the basis of the treatment in the control group, patients in the observation group were additionally treated with Wentong acupuncture at Shenshu (BL 23), Mingmen (GV 4), Pishu (BL 20), Dachangshu (BL 25), Tianshu (ST 25) and Zusanli (ST 36), etc. for 30 min each time, once a day. After 1-week treatment, the patients took a rest for 2 days; the treatment was given for 6 months. Before and after treatment, the BMD of lumbar spine, femoral neck and femoral trochanter was detected by dual energy X-ray absorptiometry, and the serum levels of bone alkaline phosphatase (NBAP), osteocalcin (OC), matrix metalloproteinase-2 (MMP-2) and calcitonin (CT) were detected by ELISA method. The primary symptom scores of intestinal function, serum diamine oxidase (DAO) and D-lactic acid (D-Lac) levels were compared between the two groups before and after treatment, and the clinical efficacy of the two groups was evaluated. RESULTS: The total effective rate was 85.9% (55/64) in the observation group, which was higher than 71.9% (46/64) in the control group (P<0.05). After treatment, BMD were increased (P<0.05), and serum bone metabolism indexes were improved in the two groups (P<0.05); the BMD and serum bone metabolism indexes in the observation group were better than those in the control group (P<0.05). After treatment, the primary symptom scores of intestinal function, serum DAO and D-Lac levels in the observation group were decreased (P<0.05), and the indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The adjuvant therapy of Wentong acupuncture could increase BMD, improve bone metabolism and regulate intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction.

[Grassland vegetation phenology change and its response to climate changes in North China]. / ä¸­å›½åŒ—æ–¹è‰åœ°æ¤è¢«ç‰©å€™å˜åŒ–åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Understanding phenological change of grasslands has scientific significance to reveal their responses to global climate change. Based on the data of GIMMS NDVI 3g, climate data from 1983 to 2015 and digital elevation model (DEM), dynamic threshold method was used to extract the phenological information of northern grassland [the start of growth season (SOS), the end of growth season (EOS), and the length of growth season (LOS)]. We analyzed the temporal and spatial variation of phenology of grassland vegetation and the influence of climate on LOS. The results showed that 88.9% of SOS occurred from late March to late May (90-150 d), and 68.1% of pixels were advanced with a rate of -1.5-0 d·(32 a)-1. 79.7% of EOS occurred from early October to late October (270-300 d), with a delay rate of 0-1.5 d·(32 a)-1, accounting for 70.3% of the pixel number. LOS lasted for 100-140 days and became longer (73.7%), with a rate of 0-1.5 d·(32 a)-1. LOS was significantly positively correlated with temperature (R=0.628) and weakly negatively correlated with precipitation (R=-0.091). There was a significant spatial variation. The 2000 m line above sea level was recognized as the demarcation line. LOS had a weak positive correlation with altitude under 2000 m (R=0.235) and a significant negative correlation with altitude above 2000 m (R=-0.861). Above 3000 m altitude, LOS decreased by about 10 d for every 1000 m elevation.

[Effect of scalp acupuncture stimulation on expression of pentraxin 3 in striatum in acute ische-mic cerebrovascular disease rats].

OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of pentraxin 3 (PTX3), Interleukin (IL)-1ß, zonula occludens-1(ZO-1) mRNA and Occludin mRNA in striatum in acute ischemic cerebrovascular disease (AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to control, model, IL-1Ra and IL-1Ra+scalp-acupuncture groups (n=12 rats in each group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the IL-1Ra group and IL-1Ra+scalp-acupuncture group received intraperitoneal injection of IL-1Ra (0.05 mg·kg-1·d-1), once daily for 6 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 6 days for rats in IL-1Ra+scalp-acupuncture group. Before and after intervention, the neurologic deficit score (NDS) was evalua-ted according to Longa's method. The expression of striatum PTX3 and IL-1ß was detected by immunohistochemistry, and ZO-1 mRNA and Occludin mRNA in the striatum tissue were detected by fluorescence quantitative real-time PCR. The Evans Blue (EB) tracer method was used to monitor the degree of blood-brain barrier (BBB) damage. RESULTS: Following modeling, the NDS, EB content and the expression of PTX3 and IL-1ß in the striatum tissue were significantly increased, and the ZO-1 mRNA and Occludin mRNA expression was considerably decreased in the model group compared with the control group (P<0.05). After the interventions and compared with the model group, the NDS, EB content in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra group were significantly down-regulated (P<0.05), while the striatum ZO-1 mRNA and Occludin mRNA expression in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra+scalp acupuncture group were obviously up-regulated (P<0.05), and the expression of IL-1ß was obviously down-regulated in the IL-1Ra+scalp acupuncture group (P<0.05) rather than in the IL-1Ra group (P>0.05). The effects of scalp acupuncture combined with IL-1Ra were obviously superior to that of IL-1Ra in down-regulating NDS, EB content and IL-1ß expression level, and in up-regulating PTX3, ZO-1 mRNA and Occludin mRNA expression levels (P<0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce the degree of BBB injury in AICD rats, which may be associated with its function in up-regulating the expression of PTX3 and in promoting the expression of ZO-1 mRNA and Occludin mRNA.

High-Performance Photoelectrochemical Water Oxidation with Phosphorus-Doped and Metal Phosphide Cocatalyst-Modified g-C3 N4 Formation Through Gas Treatment.

Graphitic carbon nitride (g-C3 N4 ) has been widely explored as a photocatalyst for water splitting. The anodic water oxidation reaction (WOR) remains a major obstacle for such processes, with issues such as low surface area of g-C3 N4 , poor light absorption, and low charge-transfer efficiency. In this work, such longtime concerns have been partially addressed with band gap and surface engineering of nanostructured graphitic carbon nitride (g-C3 N4 ). Specifically, surface area and charge-transfer efficiency are significantly enhanced through architecting g-C3 N4 on nanorod TiO2 to avoid aggregation of layered g-C3 N4 . Moreover, a simple phosphide gas treatment of TiO2 /g-C3 N4 configuration not only narrows the band gap of g-C3 N4 by 0.57 eV shifting it into visible range but also generates in situ a metal phosphide (M=Fe, Cu) water oxidation cocatalyst. This TiO2 /g-C3 N4 /FeP configuration significantly improves charge separation and transfer capability. As a result, our non-noble-metal photoelectrochemical system yields outstanding visible light (>420 nm) photocurrent: approximately 0.3 mA cm-2 at 1.23 V and 1.1 mA cm-2 at 2.0 V versus RHE, which is the highest for a g-C3 N4 -based photoanode. It is expected that the TiO2 /g-C3 N4 /FeP configuration synthesized by a simple phosphide gas treatment will provide new insight for producing robust g-C3 N4 for water oxidation.

Tubular morphology preservation and doping engineering of Sn/P-codoped hematite for photoelectrochemical water oxidation.

Tubular hematite with high-concentration, uniform doping is regarded as a promising material for photoelectrochemical water oxidation. However, the high-temperature annealing commonly used for activating doped hematite inevitably causes deformation of the tubular structure and an increase in the trap states. In the present work, Sn-doped tubular hematite on fluorine-doped tin oxide (FTO) is successfully obtained at 750 °C from a Sn-coated FeOOH tube precursor. Sn/P codoping, which is rarely considered for hematite, is also achieved via a gas phase reaction in phosphide atmosphere. The tubular morphology allows the dopant to diffuse from both the inner and outer surfaces, thus decreasing the doping profile in the radial direction. The even distribution of Sn and P synergetically increases the carrier density of hematite by one order of magnitude, which shortens the width of the depletion layer to ca. 2.3 nm (compared with 19.3 nm for the pristine sample) and leads to prolonged carrier lifetime and efficient charge separation. In addition, this codoping protocol does not introduce additional surface trap states, as evidenced by the increased charge injection efficiency and surface kinetic analysis using intensity modulated photocurrent spectroscopy (IMPS). As a result, the morphology- and doping-engineered hematite exhibits photocurrents of 0.9 mA cm-2 at 1.23 V and 3.8 mA cm-2 at 2.0 V vs. RHE under AM 1.5 G illumination (100 mW cm-2) in 1.0 M NaOH, representing 4.5-fold and 4.8-fold enhancements, respectively, compared with the photocurrents of undoped hematite. The present method is shown to be effective for preparing multi-element-doped hematite nanotubes and may find broad application in the development of other nanotubular photoelectrodes with or without doping for efficient and robust water oxidation.

Brand new 1D branched CuO nanowire arrays for efficient photoelectrochemical water reduction.

Developing high surface area nanostructured electrodes with fast charge separation is one of the main challenges for exploring cupric oxide (CuO)-based photocathodes in solar-driven hydrogen production applications. Herein, brand new 1D branched CuO nanowire arrays have been achieved on fluorine-doped tin oxide-coated glass (FTO) through a two-step wet chemical redox reaction. X-ray diffraction patterns, Raman spectra and X-ray photoelectron spectroscopy confirm the pure phase characteristic of the resulting branched CuO. In addition to the enlarged surface area of this advanced functional structure as compared with that of the 1D wire trunk, the charge injection and separation have been improved by rationally controlling the density of defects and size of branches. As a result, the optimized branched CuO exhibits photocurrent as high as 3.6 mA·cm-2 under AM 1.5G (100 mW·cm-2) illumination and 3.0 mA·cm-2 under visible light (λ > 420 nm) at 0.2 V vs. RHE in 0.5 M Na2SO4, which are 2.8- and 3.0-fold greater than those of 1D wire samples, respectively. In addition, the solution-processed approach established herein seems quite favourable for large-scale and low-cost manufacturing.

A cadmium(II) coordination polymer with both polyrotaxane and polycatenane features constructed by a V-shaped semi-rigid ligand: synthesis and fluorescence properties.

One of the most interesting phenomena in coordination polymers (CPs) is the co-existence of different interlaced motifs. However, CPs having two different interlaced motifs at the same time are still rare. Colourless block-shaped crystals of the two-dimensional polymer poly[[aqua(µ2-naphthalene-2,6-dicarboxylato){µ2-4,4'-[oxybis(4,1-phenylene)]dipyridine}cadmium(II)] monohydrate], {[Cd(C12H6O4)(C22H16N2O)(H2O)]·H2O}n, (I), was synthesized under hydrothermal conditions by the self-assembly of 4,4'-[oxybis(4,1-phenylene)]dipyridine (OPY) with CdII in the presence of naphthalene-2,6-dicarboxylic acid (H2ndc). Each CdII ion is six-coordinated by two N atoms from the pyridine rings of two OPY ligands and by four O atoms, three of which are from two ndc2- ligands and one of which is from a water molecule. In (I), every two identical two-dimensional (2D) 63 layers are interpenetrated in a parallel fashion, resulting in an interesting 2D→2D framework with both polyrotaxane and polycatenane characteristics. The extension of these sheets into a three-dimensional supramolecular net is via O-H...O hydrogen bonds. The solid-state photoluminescence properties of (I) are also discussed.

Two new two-dimensional coordination polymers based on isophthalate and a flexible N-donor ligand containing benzimidazole and pyridine rings: synthesis, crystal structures and a solid-state UV-Vis study.

In coordination chemistry and crystal engineering, many factors influence the construction of coordination polymers and the final frameworks depend greatly on the organic ligands used. N-Donor ligands with diverse coordination modes and conformations have been employed to assemble metal-organic frameworks. Carboxylic acid ligands can deprotonate completely or partially when bonding to metal ions and can also act as donors or acceptors of hydrogen bonds and are thus good candidates for the construction of supramolecular architectures. Two new transition metal complexes, namely poly[diaqua(µ4-1,4-bis{[1-(pyridin-3-ylmethyl)-1H-benz[d]imidazol-2-yl]methoxy}benzene)bis(µ2-isophthalato)dicobalt(II)], [Co(C8H4O4)(C34H28N6O2)0.5(H2O)]n, (1), and poly[diaqua(µ4-1,4-bis{[1-(pyridin-3-ylmethyl)-1H-benz[d]imidazol-2-yl]methoxy}benzene)bis(µ2-isophthalato)dicadmium(II)], [Cd(C8H4O4)(C34H28N6O2)0.5(H2O)]n, have been constructed using a symmetric N-donor ligand and a carboxylate ligand under hydrothermal conditions. X-ray crystallographic studies reveal that complexes (1) and (2) are isostructural, both of them exhibiting three-dimensional supramolecular architectures built by hydrogen bonds in which the coordinated water molecules serve as donors, while the O atoms of the carboxylate groups act as acceptors. Furthermore, (1) and (2) have been characterized by elemental, IR spectroscopic, powder X-ray diffraction (PXRD) and thermogravimetric analyses. The UV-Vis absorption spectrum of complex (1) has also been investigated.

Translocation of PKG1α acts on TRPV4-C1 heteromeric channels to inhibit endothelial Ca(2+) entry.

AIM: TRPV4-C1 heteromeric channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. However, the negative regulation of these channels is not fully understood. This study was conducted to investigate the inhibitory effect of PKG1α on TRPV4-C1 heteromeric channels. METHODS: Immuno-fluorescence resonance energy transfer (FRET) was used to explore the spatial proximity of PKG1α and TRPC1. Phosphorylation of endogenous TRPC1 was tested by phosphorylation assay. [Ca(2+)]i transients and cation current in MAECs were assessed with Fura-2 fluorescence and whole-cell recording, respectively. In addition, rat mesenteric arteries segments were prepared, and vascular relaxation was examined with wire myography. RESULTS: In immuno-FRET experiments, after exposure of these cells to 8-Br-cGMP, more PKG1α was observed in the plasma membrane, and PKG1α and TRPC1 were observed to be in closer proximity. TAT-TRPC1(S172) and TAT-TRPC1(T313) peptide fragments, which contain the PKG targeted residues Ser172 and Thr313, respectively, were introduced into isolated endothelial cells to abrogate the translocation of PKG1α. Furthermore, a phosphorylation assay demonstrated that PKG directly phosphorylates TRPC1 at Ser172 and Thr313 in endothelial cells. In addition, PKG activator 8-Br-cGMP markedly reduced the magnitude of the 4αPDD-induced and 11,12-EET-induced [Ca(2+)]i transients, the cation current and vascular relaxation. CONCLUSION: This study uncovers a novel mechanism by which PKG negatively regulates endothelial heteromeric TRPV4-C1 channels through increasing the spatial proximity of TRPV4-C1 to PKG1α via translocation and through phosphorylating Ser172 and Thr313 of TRPC1.

A small synthetic molecule functions as a chloride-bicarbonate dual-transporter and induces chloride secretion in cells.

A C2 symmetric small molecule composed of l-phenylalanine and isophthalamide was found to function as a Cl(-)/HCO3(-) dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers.

A small synthetic molecule forms selective potassium channels to regulate cell membrane potential and blood vessel tone.

In living cell membranes, K(+) permeability is higher than that of other ions such as Na(+) and Cl(-) owing to abundantly expressed K(+) channels. Polarized membrane potential is mainly established by K(+) outward flow because the K(+) concentration in the intracellular side is much higher than that in the extracellular side. We have found that the small synthetic molecule 1 is capable of self-assembling into selective K(+) channels, enhancing K(+) permeability and hyperpolarizing liposome membrane potential. Interestingly, molecule 1 also functions as K(+) channel hyperpolarizing living cell membrane potential and relaxing agonist-induced blood vessel contraction. Therefore, it may have the potential to become a lead compound for the treatment of human diseases associated with K(+) channel dysfunction.

Activation of canonical transient receptor potential channels preserves Ca2+ entry and endothelium-derived hyperpolarizing factor-mediated function in vitro in porcine coronary endothelial cells and coronary arteries under conditions of hyperkalemia.

OBJECTIVES: Although membrane depolarization by hyperkalemia is known to reduce Ca2+ influx in endothelial cells, the mechanism by which endothelial Ca2+ channel is affected by hyperkalemia remains poorly studied. We studied the effect of hyperkalemia on canonical transient receptor potential channels, in particular canonical transient receptor potential channel 3, in modulation of endothelial intracellular Ca2+ concentration. Endothelium-derived hyperpolarizing factor-mediated function is Ca2+ dependent, and hyperkalemic cardioplegia/organ preservation solutions impair endothelium-derived hyperpolarizing factor-mediated function. We explored the role of canonical transient receptor potential channel 3 in endothelium-derived hyperpolarizing factor-mediated function and investigated whether modulation of these channels preserves endothelial Ca2+ influx and endothelium-derived hyperpolarizing factor-mediated function under the condition of hyperkalemic/cardioplegic exposure. METHODS: Intracellular Ca2+ concentration was measured with fluorescent dye in primary cultured porcine coronary endothelial cells exposed to hyperkalemic/cardioplegic solutions containing mild to extreme high K+ concentration. Endothelium-derived hyperpolarizing factor-mediated relaxation under hyperkalemic/cardioplegic exposure was studied in small porcine coronary arteries in a myograph in the presence of cyclooxygenase and nitric oxide synthase inhibitors and nitric oxide scavenger. RESULTS: Canonical transient receptor potential channel 3 blocker inhibited bradykinin-induced Ca2+ influx and attenuated endothelium-derived hyperpolarizing factor-mediated response. Hyperkalemic exposure inhibited canonical transient receptor potential channel 3-mediated Ca2+ influx in a K+ concentration-dependent manner (120>20>10 mmol/L). Ca2+ influx decreased in porcine coronary endothelial cells exposed to histidine-tryptophan-ketoglutarate, St Thomas' Hospital, and University of Wisconsin solutions that contained mild (10 mmol/L), moderate (20 mmol/L), and extreme high (125 mmol/L) K+ concentration, respectively. Canonical transient receptor potential channel activator prevented the reduction of Ca2+ influx in porcine coronary endothelial cells exposed to solutions containing mild to moderate high [K+]o and restored endothelium-derived hyperpolarizing factor-mediated response that was impaired by hyperkalemic exposure. CONCLUSIONS: Canonical transient receptor potential channel 3 is involved in endothelium-derived hyperpolarizing factor-mediated function in coronary arteries. Hyperkalemia inhibited canonical transient receptor potential channel 3-mediated Ca2+ influx in endothelial cells. Canonical transient receptor potential channel activation restores Ca2+ influx suppressed by hyperkalemia and prevents dysfunction of endothelium-derived hyperpolarizing factor.

A three-dimensional polycatenation framework: catena-poly[[diaquabis(4-{4-[4-(pyridin-4-yl)phenoxy]phenyl}pyridine)nickel(II)]-µ2-naphthalene-2,6-dicarboxylato].

In the title compound, [Ni(C12H6O4)(C22H16N2O)2(H2O)2]n, the Ni(2+) cation resides on a centre of inversion in a slightly distorted octahedral [N2O4] environment. The two carboxylate groups of each naphthalene-2,6-dicarboxylate (NDC(2-)) ligand, which reside on centres of inversion, link the Ni(II) cations into a one-dimensional chain. Identical chains are linked by intermolecular hydrogen bonds between coordinated water molecules and the uncoordinated N atoms of 4-{4-[4-(pyridin-4-yl)phenoxy]phenyl}pyridine ligands to form (4,4)-topological sheets, and then the different sheets are interlocked in an inclined fashion to give a three-dimensional polycatenation network. The stability of the structure is further enhanced by π-π stacking interactions between pyridine and benzene rings.

1-(2-Carb-oxy-eth-yl)-3-(carboxyl-atometh-yl)-2-ethyl-benzimidazol-1-ium monohydrate.

In the title compound, C14H16N2O4·H2O, three substituent groups are located on the same side of the benzimidazole ring plane. In the crystal, O-H⋯O hydrogen bonds and π-π stacking between parallel imidazole rings [centroid-centroid distance = 3.858 (4) Å] link the mol-ecules into a three-dimensional supra-molecular structure.

The GmCLC1 protein from soybean functions as a chloride ion transporter.

Soil salinization is a global issue that hampers agricultural production. Chloride is one of the prominent anions on saline land that cause toxicity to the plant. We previously identified the GmCLC1 gene from soybean (Glycine max) that encodes a putative tonoplast-localized chloride transporter. In this study, using electrophysiological analysis, we demonstrated the chloride transport function of GmCLC1. Interestingly, this chloride transport activity is pH dependent, suggesting that GmCLC1 is probably a chloride/proton antiporter. When the cDNA of GmCLC1 was expressed in tobacco BY-2 cells under the control of a constitutive promoter, the protective effect against salinity stress in transgenic tobacco BY-2 cells was also found to be pH sensitive. In the native host soybean, the expression of GmCLC1 gene is regulated by pH. All these findings support the notion that the function of GmCLC1 is regulated by pH.

Poly[diaqua-[µ-1,4-bis-(1H-imidazol-1-yl)benzene-κ(2)N(3):N(3')](µ-fumarato-κ(2)O(1):O(4))nickel(II)].

In the title compound, [Ni(C(4)H(2)O(4))(C(12)H(10)N(4))(H(2)O)(2)](n), the Ni(II) ion has a distorted octa-hedral coordination geometry. The asymmetric unit is composed of an Ni(2+) ion, located on a twofold rotation axis, one half of a 1,4-bis-(1H-imidazol-1-yl)benzene (BIMB) ligand and one half of a fumarte (fum(2-)) dianion, both ligands being located about inversion centers, and a coordinating water mol-ecule. The Ni(II) ions are linked by two BIMB ligands and two fum(2-) dianions, forming a four-connected layered structure parallel to (010) with a 4(4)-sql topology. Within each layer, there are rhombic grids with dimensions of ca 13.5 × 9.0 Šand approximate angles of 109 and 70°. The crystal packing features a two-dimensional → two-dimensional parallel/parallel interpenetration in which one undulating layer is catenated to another equivalent one, forming a new bilayer. Moreover, the entangled two-dimensional layers are connected by O-H⋯O and C-H⋯O hydrogen bonds, generating a three-dimensional structure.

Three self-penetrated, interlocked, and polycatenated supramolecular isomers via one-pot synthesis and crystallization.

Three supramolecular isomers, {[Cd(2)(TPOM)(hfipbb)(2)]·x/y/zsolvent}(n) (1-3), have been synthesized and characterized by one-pot reaction. Even though the compositions of 1-3 are the same, they generate different structures. Reactions over various time periods were found to influence the formation of supramolecular isomers, and there is little influence on this system under other conditions.