Water-Soluble Lanthanide-Titanium-Oxo Cluster, a Precursor for Biocompatible Nanomaterial.

Titanium-oxo clusters (TOCs) are attractive as a rapidly growing class of molecular materials due to their use as molecular models and precursors of nano-titanium-oxide. However, most TOCs can only be dissolved in nonaqueous solvents, which largely limits their potential applications in biological or environmental situations. Very few water-soluble TOCs were reported, which can be used directly in aqueous biomedical systems. However, until now, no research studies of such TOCs involved in biomedical fields have been documented. We report here a series of lanthanide-titanium-oxo clusters (LnTOCs) formulated as {H2@[Ln2Ti8(µ3-O)8(µ2-O)4(Ac)16]}3·24CH3CN·23H2O (Ln = Eu(III) 1, Tb(III) 2, and Yb(III) 3). The compounds are easily soluble in water and form a stable solution of the cluster aggregates (LnTOC-a). Therefore, nano-biocompatible TiO materals can be prepared from these LnTOCs just by dissolving them in water. The nanoscale aggregates in water solutions were characterized by SEI-MS, 1H NMR, XPS, IR, and EDS mapping. Using the EuTOC-a solution, excellent fluorescence sensor properties for biomolecule ascorbic acid were found. Furthermore, biocompatibility and fluorescent labeling properties of the EuTOC-a for HeLa cells were evaluated. The results indicated that water-soluble LnTOCs can be used to prepare biocompatible fluorescent Ln-Ti-O nanomaterials.

Molecular Model of Dye Sensitized Titanium Oxides Based on Aryl-Amine Dye Anchored Titanium Oxo Clusters.

Model studies on dye sensitized titanium oxides have attracted wide interest with respect to their importance in understanding photoelectric and photophysical processes. Ligand modified titanium oxo clusters (TOCs) have been considered as the most appropriate models for dye sensitized solar cells (DSSCs) on the basis of their atomically precise structures. However, the ligands used previously in TOC models were seldom the dyes that really applied in DSSCs due to the difficulty with which the crystals of the dye anchored TOCs are obtained. We report herein a series of TOCs with the popularly used arylamine-cyanoacrylate dyes. As the closest model of DSSCs, the TOCs were studied by DFT calculations based on their accurate structural information. They have also been applied to photoelectric conversion evaluation by a solar cell device. Both the theoretical and application results showed that the synergistic effect of intradye molecular charge transfer (ICT) and dye to TiO cluster charge transfer (LMCT) is important in increasing the power conversion efficiency.

Effects of the Ligand Structures on the Photoelectric Activities, a Model Study Based on Titanium-Oxo Clusters Anchored with S-Heterocyclic Ligands.

Titanium oxo clusters (TOCs) have become one of the worldwide hot research topics because they are excellent molecular TiO materials having unique photoactive properties and can been used as models of dye-sensitized solar cells (DSSCs). S-Heterocyclic ligands such as thiophene (Th) and tetrathiafulvalene (TTF) derivatives have been widely used in electronic or photoelectronic devices and solar cells. However, a study of the synthesis and properties of TOCs anchored with Th and TTF derivatives is missing. Herein four such TOCs as single crystals were synthesized and structurally characterized: [Ti3O(OiPr)8(LTh)2] (1), [Ti4O2(OiPr)10(LTTF)2] (2), [Ti6O4(OiPr)10(LTh)2(O3PPh)2] (3), and [Ti6O4(OiPr)10(LTTF)2(O3PPh)2] (4). Charge transfer from the Th or TTF electron donor to the TOC core was evaluated by electronic spectra and theoretical calculations. This work first systematically investigated the photoelectrochemistry of TOCs with different conjugated S-heterocyclic ligands in molecular levels. The photocurrent densities of these cluster-modified TiO2 electrodes were examined using DSSCs, which were well responsive to irradiation. The photocurrents of TTF cluster-modified electrodes are higher than those of the Th cluster-modified electrodes because of the sulfur-rich conjugated system.

Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice.

Etomidate (ET) produces sedation by binding on the γ-aminobutyric acid type A (GABAA) receptors. We previously found that ET inhibited cerebellar Purkinje cells activity via both GABAA and glycine receptors in vivo in mice, suggesting that ET modulated sensory information synaptic transmission in cerebellar cortex. In this study, we investigated the effect of ET on the sensory stimulation-evoked responses in the cerebellar granule layer (GL) in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion of ET (100 µmol/L) significantly decreased amplitude and area under the curve (AUC) of the sensory stimulation-evoked excitatory component (N1) in the cerebellar GL. Application of GABAA receptor antagonist, SR95531 (20 µmol/L) significantly attenuated, but not abolished the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. However, application of a mixture of SR95531 (20 µmol/L) and cannabinoid 1 receptor (CB1) antagonist, AM-251 (5 µmol/L), completely blocked the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease in amplitude and AUC of N1 in the absence of GABAA receptors activity, as well occluded the ET-induced depression of N1. Moreover, the ET-induced changes in amplitude and AUC of N1 in absence of GABAA receptors activity were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that ET facilitates CB1 receptors in the absence of GABAA receptors activity, resulting in a depression of the sensory stimulation-evoked synaptic transmission via PKA signaling pathway in mouse cerebellar GL.

A Titanium Oxo Cluster Model Study of Synergistic Effect of Co-coordinated Dye Ligands on Photocurrent Responses.

The use of multiple sensitizers in dye sensitized solar cells has been attractive as a promising way to achieve highly efficient photovoltaic performance. However, except for the complementary absorption, synergistic effects among the dye components have not been well understood. Herein, using ferrocene-1-carboxylate (FcCO2) and catechol (Cat) as dye ligands, two titanium oxo clusters (TOCs), [Ti3O(OiPr)6(Cat)(FcCO2)2] (1) and [Ti7O4(OiPr)8(Cat)5(FcCO2)2] (2), were synthesized and structurally characterized. Another TOC, [Ti7O3(OiPr)12(Cat)4( o-BDC)] (3) ( o-BDC = o-benzene dicarboxylate), was also prepared as a contrast. Electronic spectra and theoretical calculations showed that charge transfer occurs from ligands FcCO2 and Cat to the TiO cluster core and the contribution of redox active FcCO2 is greater than that of Cat. Using the clusters as TiO-dye pre-anchored precursors, multi-dye sensitized TiO2 electrodes were prepared. Although the two dyes FcCO2 and Cat do not complement each other in spectra, a synergistic effect on the enhancement of photocurrent responses was found and discussed in view of the inter-dyes electron communication.

Differences in the perceptions of patients with primary biliary cholangitis and physicians from various hospital departments: An online survey.

OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.

Activation CRF-R2 augments cerebellar climbing fiber-Purkinje cell synaptic transmission via presynaptic PKA pathway in mice.

Corticotropin releasing factor (CRF) type 2 receptor (CRF-R2) is present in climbing fiber (CF) afferents, which involves in modulating the CF-Purkinje cell (PC) synaptic transmission in cerebellar cortex. However, the role of CRF-R2 in regulating CF-PC synaptic transmission is unclear. We here investigate the role of CRF-R2 in modulating PC complex spikes (CSs) activity and CF-PC synaptic transmission using electrophysiological recording techniques and pharmacological methods. Cerebellar surface application of a selective CRF-R2 agonist, urocortin III (UCN III; 300 nM) induced an enhancement of CSs activity, which expressed an increase in number of CSs spikelets and pause of simple spike firing of cerebellar PCs in urethane anesthetized mice. The CSs activity was also enhanced by CRF (300 nM) in the presence of CRF-R1 antagonist, which was abolished by CRF-R2 antagonist. Under in vitro conditions, bath application of UCN III increased CF-PC synaptic transmission, which exhibited a time-dependent increase in amplitude of excitatory postsynaptic currents (EPSCs), accompanied by a decrease in paired-pulse ratio (PPR). In addition, bath application of CRF (100 nM) induced an increase in amplitude of EPSCs and a decrease in PPR in the absence of CRF-R1 activity. UCN-induced enhancement of CF-PC synaptic transmission was abolished by bath application of protein kinase A (PKA) inhibitor, KT5720 (100 nM), but it was not prevented by inhibiting intracellular PKA with PKI (5 µM). These results indicate that activation of CRF-R2 augments CF-PC synaptic transmission through a presynaptic PKA signaling pathway in the mouse cerebellar cortex.

Tetra-kis(triphenyl-phosphane-κP)silver(I) trifluoro-methane-sulfonate dichloro-methane monosolvate.

In the title compound, [Ag(C(18)H(15)P)(4)]CF(3)O(3)S·CH(2)Cl(2), the Ag atom is coordinated by four P atoms from four PPh(3) ligands. The P-Ag-P angles are in the range 108.02 (6)-110.15 (6)°, which confirms the distorted tetra-hedral environment around the Ag atom.

Tris(3-amino-5,6-dimethyl-1,2,4-triazine-κN)silver(I) trifluromethane-sulfonate-3-amino-5,6-dimethyl-1,2,4-triazine (1/1).

The asymmetric unit of the title compound, [Ag(C(5)H(8)N(4))(3)](CF(3)O(3)S)·C(5)H(8)N(4), contains two cations, two anions and two uncoordinated 3-amino-5,6-dimethyl-1,2,4-triazine (admt) ligands. It was prepared from the reaction of silver trifluoro-methane-sulfonate and admt in a 2:3 molar ratio. Both silver(I) ions are bonded to three admt mol-ecules via their 2-position triazine N atoms in almost regular trigonal-planar geometries. Three intra-molecular N-H⋯N hydrogen bonds between adjacent admt mol-ecules in each cation help to maintain their overall near planarities (r.m.s. deviations for the 28 non-H atoms = 0.139 and 0.153 Å). In the crystal, numerous N-H⋯N, N-H⋯O, C-H⋯O, C-H⋯N and C-H⋯F hydrogen-bonding interactions link the components into a three-dimensional network.

Poly[bis-[µ-1,3-bis-(diphenyl-phosphan-yl)propane-κP:P']-di-µ-thio-cyanato-κS:N;κN:S-disilver(I)].

In the title coordination polymer, [Ag(2)(NCS)(2)(C(27)H(26)P(2))(2)](n), two centrosymmetrically related Ag(+) cations are linked by two thio-cyanate anions into binuclear eight-membered macrocycles. The Ag⋯Ag separation within the macrocycle is 5.4400 (6) Å. The distorted tetra-hedral coordination about each metal atom is completed by the P atoms of two bridging 1,3-bis-(diphenyl-phosphan-yl)propane ligands, forming polymeric ribbons parallel to the a axis.

Effect of Noradrenaline on the Facial Stimulation-Evoked Mossy Fiber-Granule Cell Synaptic Transmission in Mouse Cerebellar Cortex.

Noradrenaline is an important neuromodulator in the cerebellum. We previously found that noradrenaline depressed cerebellar Purkinje cell activity and climbing fiber-Purkinje cell synaptic transmission in vivo in mice. In this study, we investigated the effect of noradrenaline on the facial stimulation-evoked cerebellar cortical mossy fiber-granule cell synaptic transmission in urethane-anesthetized mice. In the presence of a γ-aminobutyrateA (GABAA) receptor antagonist, air-puff stimulation of the ipsilateral whisker pad evoked mossy fiber-granule cell synaptic transmission in the cerebellar granular layer, which expressed stimulus onset response, N1 and stimulus offset response, N2. Cerebellar surface perfusion of 25 µM noradrenaline induced decreases in the amplitude and area under the curve of N1 and N2, accompanied by an increase in the N2/N1 ratio. In the presence of a GABAA receptor blocker, noradrenaline induced a concentration-dependent decrease in the amplitude of N1, with a half-maximal inhibitory concentration of 25.45 µM. The noradrenaline-induced depression of the facial stimulation-evoked mossy fiber-granule cell synaptic transmission was reversed by additional application of an alpha-adrenergic receptor antagonist or an alpha-2 adrenergic receptor antagonist, but not by a beta-adrenergic receptor antagonist or an alpha-1 adrenergic receptor antagonist. Moreover, application of an alpha-2 adrenergic receptor agonist, UK14304, significantly decreased the synaptic response and prevented the noradrenaline-induced depression. Our results indicate that noradrenaline depresses facial stimulation-evoked mossy fiber-granule cell synaptic transmission via the alpha-2 adrenergic receptor in vivo in mice, suggesting that noradrenaline regulates sensory information integration and synaptic transmission in the cerebellar cortical granular layer.

Complement 3 and the Prognostic Nutritional Index Distinguish Kawasaki Disease from Other Fever Illness with a Nomogram.

OBJECTIVE: This study aimed to establish a model to distinguish Kawasaki disease (KD) from other fever illness using the prognostic nutritional index (PNI) and immunological factors. METHOD: We enrolled a total of 692 patients (including 198 with KD and 494 children with febrile diseases). Of those, 415 patients were selected to be the training group and 277 patients to be the validation group. Laboratory data, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), and immunological factors, were retrospectively collected for an analysis after admission. We used univariate and multivariate logistic regressions and nomograms for the analysis. RESULT: Patients with KD showed significantly higher C3 and a lower PNI. After a multivariate logistic regression, the total leukocyte count, PNI, C3, and NLR showed a significance (p < 0.05) and then performed well with the nomogram model. The areas under the ROC in the training group and the validation group were 0.858 and 0.825, respectively. The calibration curves of the two groups for the probability of KD showed a near agreement to the actual probability. CONCLUSIONS:  Compared with children with febrile diseases, patients with KD showed increased C3 and a decreased nutritional index of the PNI. The nomogram established with these factors could effectively identify KD from febrile illness in children.

catena-Poly[silver(I)-bis-[µ-bis-(diphenyl-phosphino)methane-κP:P']-µ-thio-cyanato-κS:S-silver(I)-µ-thio-cyanato-κS:N].

The title compound, [Ag(NCS)(C(25)H(22)P(2))](n), contains two Ag(+) ions, two thio-cyanate ions and two bis-(diphenyl-phosphino)methane (dppm) ligands in the asymmetric unit. One of the thiocyanate ions bridges the two Ag(+) ions in a µ(2)-mode from its S atom and the two dppm ligands bridge the silver ions in a µ(1),µ(1) mode. The remaining SCN(-) ion bridges the binuclear units via its N and S atoms, generating a one-dimensional polymer propagating in [01]: the resulting AgP(2)SN and AgP(2)S(2) coordination geometries could be described as distorted tetra-hedral.

(Perchlorato-κO)tris-(triphenyl-phosphine-κP)silver(I).

In the title complex, [Ag(C(18)H(15)P)(3)(ClO(4))], the silver coord-ination environment is dominated by the distorted P(3)AgO tetra-hedron in which Ag-O = 2.608 (12) Šand the Ag-P bond lengths are 2.5663 (17), 2.5076(16) and 2.5450 (17) Å. The perchlorate O-atoms are disordered over two positions in a 0.584 (14):0.416 (14) ratio.

(Methanol-κO)(perchlorato-κO)bis-(triphenyl-phosphine-κP)silver(I).

In the title complex, [Ag(ClO(4))(CH(3)OH)(C(18)H(15)P)(2)], the angles around the central Ag(+) ion indicate that it is in a distorted tetrahedral coordination. The coordination sphere of silver is formed by two P atoms of two triphenyl-phosphine ligands, one O atom of a perchlorate anion and one O atom of a methanol mol-ecule. The crystal structure is stablized by a bifurcated inter-molecular O-H⋯O hydrogen bond, involving the O-H donor from methanol and two acceptor O atoms from the perchlorate anion, so forming a zigzag chain propagating in [010].

Bis(2,2'-bi-1H-imidazole-κN,N)bis-(dimethyl sulfoxide-κO)copper(II) bis-(tetra-fluoridoborate).

In the title copper(II) salt, [Cu(C(6)H(6)N(4))(2)(C(2)H(6)OS)(2)](BF(4))(2), the Jahn-Teller distorted octa-hedral coordination sphere of copper is formed from four 2,2'-bi-1H-imidazole N atoms and two dimethyl sulfoxide O atoms. The Cu atom lies on a center of inversion. N-H⋯O and N-H⋯F hydrogen bonds give rise to a one-dimensional structure. The BF(4) (-) anion is disordered over two sites in a 0.671 (10):0.329 (10) ratio.

[A new monoclonal antibody selectively distributes on hepatocellular membrane].

OBJECTIVE: Screening monoclonal antibodies selectively distribute on hepatocellular membrane by hybridoma technology and exploring their relationship with liver diseases. METHODS: Plasma membrane vesicles of rat hepatocytes were prepared using density gradient centrifugation and BALB/c mice were immunized with the membrane vesicles. Monoclonal antibodies were made with hybridoma technology. The immunizing valences and monoclonal antibodies were detected and screened by ELISA. Mh7 antigen was identified by immunoprecipitation method. Liver tissues of carbon tetrachloride injured rat models and diabetic rat models were used to detect the pathology value of mh7-antigen. RESULTS: Hepatocellular membrane vesicles were obtained successfully. Several monoclonal antibodies were yielded by hybridoma technology. Immunofluorescence and pre-embedding immunogold-silver cytochemistry confirmed that mh7-antigen was a membrane molecule and with a 200KD molecular weight. Immunohistochemistry results indicated mh7 selectively distributed on hepatocellular membrane. Results with rat models demonstrated that mh7-antigen was dramatically reduced in fatty degenerated hepatocyte of carbon tetrachloride injured rat models and distributed as straps in diabetic rat models. CONCLUSIONS: Mh7 is a new hepatocellular membrane monoclonal antibody and may closely related with liver diseases.

Nuclear receptor coactivator 6 promotes HTR-8/SVneo cell invasion and migration by activating NF-κB-mediated MMP9 transcription.

OBJECTIVES: NCOA6 is a transcription coactivator; its deletion in mice results in growth retardation and lethality between 8.5 and 12.5 dpc with defects in the placenta. However, the transcription factor(s) and the mechanism(s) involved in the function of NCOA6 in placentation have not been elucidated. Here, the roles of NCOA6 in human cytotrophoblast invasion and migration were studied. MATERIALS AND METHODS: Human placenta tissues were collected from normal pregnancies and pregnancies complicated by early-onset severe preeclampsia (sPE). Immunofluorescence, RT-qPCR and Western blotting were used to determine NCOA6 expression. Transwell invasion/migration assays were performed to explore whether NCOA6 knockdown affected human placenta-derived HTR-8/SVneo cell invasion/migration. Gelatin zymography was performed to examine the change in the gelatinolytic activities of secreted MMP2 and MMP9. Luciferase reporter assays were used to explore whether NCOA6 coactivated NF-κB-mediated MMP9 transcription. RESULTS: NCOA6 is mainly expressed in the human placental trophoblast column, as well as in the EVTs. HTR-8/SVneo cell invasion and migration were significantly attenuated after NCOA6 knockdown, and the secretion of MMP9 was decreased due to transcriptional suppression. NCOA6 was further found to coactivate NF-κB-mediated MMP9 transcription. Moreover, expression of NCOA6 was impaired in placentas of patients complicated by early-onset sPE. CONCLUSIONS: Thus, we demonstrated that NCOA6 is important for cytotrophoblast invasion/migration, at least partially, by activating NF-κB-mediated MMP9 transcription; the downregulation of NCOA6 may contribute to the pathogenesis of early-onset sPE.

Noradrenaline inhibits complex spikes activity via the presynaptic PKA signaling pathway in mouse cerebellar slices.

Norepinephrine (NA) is an important neurotransmitter of the cerebellum that regulates synaptic transmission, motor regulation and motor learning under certain conditions via adrenergic receptors (ARs). We previously found that NA depressed cerebellar climbing fiber-Purkinje cell (CF-PC) synaptic transmission via α2-ARs in vivo in mice. We here investigated the mechanisms of NA inhibited CF-PC synaptic transmission in acute cerebellar slices using the whole-cell recording technique and pharmacological methods. Bath application of NA (10 µM) depressed CF-PC synaptic transmission, which exhibited a time-dependent decrease in amplitude of excitatory postsynaptic currents (N1), accompanied by an increase in the paired-pulse ratio (PPR). The NA-induced depression of CF-PC synaptic transmission was significantly prevented by inhibition of protein kinase A (PKA) with either H-89 or KT5720. Furthermore, the NA-induced inhibition of CF-PC synaptic transmission was rescued by activation adenylate cyclase (AC), and the AC-induced enhancement of CF-PC synaptic transmission was depressed by NA. Moreover, inhibition of AC with SQ22536, produced a significant depression of CF-PC synaptic transmission and abrogated the NA-induced depression of CF-PC synaptic transmission. However, the NA-induced depression of CF-PC synaptic transmission was not blocked by intracellular inhibition of PKA with a cell impermeable PKA inhibitor, PKI, or by extracellular inhibition of protein kinase C. These results indicate that NA activates presynaptic α2-AR, resulting in a depression of mouse cerebellar CF-PC synaptic transmission through the AC-PKA signaling pathway.

NMDARs contribute to the facial stimuli-evoked mossy fiber-granule cell synaptic transmission in vivo in mice.

N-methyl-D-aspartate receptors (NMDARs) are expressed in granule cell and involve in mossy fiber-granule cell (MF-GC) synaptic transmission in cerebellar cortex. In the absence GABAA receptor activity, we here studied the role of NMDARs during the facial stimulation evoked MF-GC synaptic transmission in urethane-anesthetized mice using electrophysiological recording technique and pharmacological methods. Our results showed that facial stimuli train (20 Hz, 5 pulses) evoked 5 field potential responses (N1-N5) in mouse cerebellar granular layer, which identified MF-GC synaptic transmission. Blocking NMDARs induced significant depression in the amplitude of N2 to N5, accompanied with significant decrease in pulse ratios, area under the curve (AUC) and half-width of N1. A selective GluN2A antagonist, PEAQX (10 µM) also produced significant depression in the amplitude of N2 to N5, and decreases in pulse ratios. However, a selective GluN2B antagonist, TCN-237 (10 µM) did not significantly attenuate the facial stimuli train-induced mossy fiber-granule cell synaptic transmission. Application of NMDA (1 µM) produced increases in the AUC and half-width of Ron, as well the amplitude and AUC of Roff, which was reversed by following application of PEAQX. Our present results indicated that NMDARs, especially GluN2A contribute to the facial stimulation-evoked MF-GC synaptic transmission, suggesting that the NMDARs play an important role during the lateral sensory information synaptic transmission in the cerebellar granular layer in vivo in mice.