Altered glutamate metabolism contributes to antiepileptogenic effects in the progression from focal seizure to generalized seizure by low-frequency stimulation in the ventral hippocampus.

As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays. Additionally, the concentrations of glutamate, GABA, and glutamine (a product of GS) were measured using high-performance liquid chromatography (HPLC) in the same subregions. The results indicated that a transiently promoted glutamate cycle was closely involved in the progression from focal to generalized seizure. Low-frequency stimulation (LFS) delivered to the ventral hippocampus had an antiepileptogenic effect in rats exposed to amygdaloid-kindling stimulation. Simultaneously, LFS could partly reverse the effects of the promoted glutamate cycle, including increased GS function, accelerated glutamate-glutamine cycling, and an unbalanced glutamate/GABA ratio, all of which were induced by amygdaloid kindling in the DG when seizures progressed to stage 4. Moreover, glutamine treatment reversed the antiepileptic effect of LFS with regard to both epileptic severity and susceptibility. Our results suggest that the effects of LFS on the glutamate cycle may contribute to the antiepileptogenic role of LFS in the progression from focal to generalized seizure.

[Study on Chemical Constituents and Content Determination of Feifukang Mistura].

Objective: To identify the main chemical constituents and to determine the content in Feifukang mistura. Methods: HPLC-MS technique was used to profile and identify the chemical constituents by comparing the retention time,MS data with the reference standard. The content determination of all the chemical constituents were carried on a HPLC system. Results: Five compounds were separated from Feifukang mistura,which were identified as neomangiferin,mangiferin,calycosin-7-O-glucoside,calycosin,and schizandrol A. The standard curves of them showed good linearity on the range of 2. 08 ~ 104. 0 µg/m L,2. 00 ~ 100. 0 µg/m L,2. 00 ~ 100. 0µg/m L,2. 09 ~ 104. 5 µg/m L,and 1. 98 ~ 99. 0 µg/m L,respectively. The average recoveries were all in the range of 91. 3 ~ 103. 8%. Conclusion: The methods of chemical constituents identification and content determination were established,which may offer better revealing the material basis and controlling quality of Feifukang mistura.

Excellent Dielectric Properties and Finite Element Simulation of Al-Epoxy Composites with Constructed Ultrathin Al2O3 Parallel-Plate Microcapacitors.

Metal-polymer dielectric composites show promising potential as embedded capacitors, whereas it remains a great challenge to achieve a high dielectric constant (εr) and low dielectric loss (tan δ) simultaneously. This work demonstrates a strategy for overcoming this challenge. Al nanoparticles with self-passivated ultrathin Al2O3 shells are compacted under the uniaxial pressure (P), and Al-epoxy composites are prepared by curing the liquid epoxy monomer that infiltrates into Al compacts. The contacting regions between adjacent Al nanoparticles are flattened and enlarged during the compacting process, so that the ultrathin Al2O3 parallel-plate microcapacitors are constructed by the insulating Al2O3 shells and conductive Al cores. The composite with P of 100 MPa and Al volume fraction (υAl) of 53.7% exhibits the εr of 189 at 10 kHz, which is much higher than the εr (48-102) of 0-3 type Al-polymer composites with similar υAl and even higher than the highest εr (160) reported in the Al-polymer composite with υAl > 80%. Furthermore, the present composites show low tan δ (<0.03) and good frequency and temperature stability of εr. The finite element simulation proves that the construction and enlargement of ultrathin Al2O3 parallel-plate microcapacitors dramatically increase the electric energy stored in Al2O3 and therefore greatly improve the εr.

Obtaining Greatly Improved Dielectric Constant in BaTiO3-Epoxy Composites with Low Ceramic Volume Fraction by Enhancing the Connectivity of Ceramic Phase.

Ceramic-polymer dielectric composites show promising potential as embedded capacitors, whereas it is a great challenge to obtain a high dielectric constant (εr) at a low ceramic volume fraction (Vc). This work demonstrates a strategy for overcoming this challange. By employing a high sintering temperature (Ts) and introducing porogen, BaTiO3 ceramics with both great connectivity and high porosity are obtained, and the composites with improved εr at a low Vc are prepared after curing the epoxy monomer, which is infiltrated into the porous ceramic bodies. For the composite with a Ts of 1300 °C and a Vc of 38.1%, the εr is as high as 466.8 at 1 kHz, which is improved by about nine times compared to the 0-3 counterpart with a higher Vc of 60.8%. Furthermore, the composite exhibits low dielectric loss and good frequency and temperature stability of εr, indicating the great potential for practical applications. Finite element simulation shows that the enhanced connectivity of BaTiO3 increases the electric field intensity in high-εr BaTiO3 dramatically and therefore plays a key role in the dielectric response of the composite. This work not only sheds light on the high-εr ceramic-polymer composites but also deepens the understanding on the relationship between their properties and microstructures.

Hexagonal Lu1-xInxFeO3 Room-Temperature Multiferroic Thin Films.

The hexagonal rare earth ferrites h-RFeO3(R = rare earth element) have been recognized as promising candidates for a room-temperature multiferroic system, and the primary issue for these materials is how to get a stable hexagonal structure since the centrosymmetric orthorhombic structure is generally stable for most RFeO3 at room-temperature, while the hexagonal phase is only stable under some strict conditions. In the present work, h-Lu1-xInxFeO3 (x = 0-1) thin films were prepared on a Nb-SrTiO3 (111) single-crystal substrate by a pulsed laser deposition (PLD) process, and the multiferroic characterization was performed at room temperature. With the combined effects of chemical pressure and epitaxial strain, the stable hexagonal structure was achieved in a wide composition range (x = 0.5-0.7), and the results of XRD (X-ray diffraction) and SAED (selected area electron diffraction) indicate the super-cell match relations between the h-Lu0.3In0.7FeO3 thin film and substrate. The saturated P-E hysteresis loop was obtained at room temperature with a remanent polarization of about 4.3 µC/cm2, and polarization switching was also confirmed by PFM measurement. Furthermore, a strong magnetoelectric coupling with a linear magnetoelectric coefficient of 1.9 V/cm Oe was determined, which was about three orders of magnitude larger than that of h-RFeO3 ceramics. The present results indicate that the h-Lu1-xInxFeO3 thin films are expected to have great application potential for magnetoelectric memory and detection devices.

[Treatment of unresectable pancreatic carcinoma by radiofrequency ablation with 'cool-tip needle': report of 18 cases].

OBJECTIVE: To explore the effects of treatment of unresectable pancreatic tumors by radiofrequency ablation (RFA) with "cool-tip needle". METHODS: 18 patients with unresectable pancreatic tumors, 8 with pancreatic head carcinoma and 10 with pancreatic body and tail carcinomas, 12 males and 6 females, aged 66.2, underwent RFA under laparotomy for 3 times and simultaneous infusion of iced normal saline. The clinical data were retrospectively analyzed. RESULTS: The level of CA19-9, a tumor marker, returned to normal after RF in 2 patients. Back pain was alleviated in 14 patients. B mode ultrasonography or CT examination showed decrease of tumor volume in 14 patients after RF. Pancreatic fistula occurred in 3 patients (16.7%) and then healed smoothly in 7 - 10 days with after routine abdominal drainage. The mortality was 22.2% (4/18). In the 4 death cases, tumors were all located in the pancreatic head; three patients died suddenly of massive gastrointestinal hemorrhage at Days 4, 30, and 40 days postoperative respectively after RF and the other patient died of acute renal failure at Day 2 postoperative days after RF. 8 patients died 1 - 8 months after RF. After 51 months, 1 patient still survived. CONCLUSION: RFA is effective in relieving the back pain for in unresectable pancreatic tumor patients efficiently relieving the back pain. Standard use of cool-tip RFA is dangerous for pancreatic head tumor carcinoma close to portal vein, but safe for those located in the body and tail of the pancreas. Making the Infusion of iced cooling-water flow via a gastric tube into the duodenum and changing change of the parameters of the RF system can reduce the associated complications.

Structural distortions, orbital ordering and physical properties of double perovskite R2CoMnO6 calculated by first-principles.

The structural distortions, orbital ordering, magnetic and electronic properties of double perovskite R2CoMnO6 (R = rare-earth element) have been systematically calculated by first-principles. Structural distortions, including Co-O and Mn-O bond length splitting, the antiferroelectric motions of R ions, the tilting of octahedral (the resulted Co-O-Mn bond angle) are obviously affected by the rare-earth ions' radius. The bond length splitting behavior of Co-O and Mn-O are rather different because of the Jahn-Teller active ion Co2+ and the Jahn-Teller nonactive ion Mn4+. Taking Gd2CoMnO6 as an example, the t 2g orbitals of Co ions are predicted to be orbital ordered. That is, the spin down channel of d xz orbital for one Co ion and d yz orbital for another Co ion are basically vacant. Finally, the physical properties, including the magnetic Curie temperature and electronic band gap of R2CoMnO6 are almost linear dependent on the average value of cos2 θ (θ is the Co-O-Mn exchange-angle).

Improper electric polarization in simple perovskite oxides with two magnetic sublattices.

ABO3 perovskite oxides with magnetic A and B cations offer a unique playground to explore interactions involving two spin sublattices and the emergent effects they may drive. Of particular interest is the possibility of having magnetically driven improper ferroelectricity, as in the much studied families of rare-earth orthoferrites and orthochromites; yet, the mechanisms behind such effects remain to be understood in detail. Here we show that the strongest polar order corresponds to collinear spin configurations and is driven by non-relativistic exchange-strictive mechanisms. Our first-principles simulations reveal the dominant magnetostructural couplings underlying the observed ferroelectricity, including a striking magnetically driven piezoelectric effect. Further, we derive phenomenological and atomistic theories that describe such couplings in a generic perovskite lattice. This allows us to predict how the observed effects can be enhanced, and even how similar ones can be obtained in other perovskite families.

[Study on the TLC-SERS of sulfamethoxazole].

The spectra of sulfamethoxazole, the efficient ingredient of sulfanilamide-like medicine, were investigated by combining the TLC and FT-Raman spectroscopy using the surface enhanced Raman spectroscopy technique. The result indicatesthat the main vibrant characteristic spectral band can be obtained by TLC in a samples of just about 1 microg. The difference between the compound sulfamethoxazole and the corresponding spectra picture is analyzed. The analysis shows that the method of combining TLC and FT-Raman spectroscopy by the SERS is practical and advantageous in the highly sensitive measurement of the chemical ingredient in medicine.

Biological significance of PinX1 telomerase inhibitor in esophageal carcinoma treatment.

In the present study, to investigate the expression of PinX1 gene and its functional effects in human esophageal carcinoma (Eca)-109 cell line, expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into Eca-109 cells using Lipofectamine 2000. Firstly, the mRNA expression level of PinX1 was examined using reverse transcription-polymerase chain reaction (RT-PCR). Once successful transfection was achieved, the effects on the mRNA level of human telomerase reverse transcriptase (hTERT), telomerase activity, cell proliferation and apoptosis were examined by semi-quantitative RT-PCR, stretch PCR, MTT assay and flow cytometry, respectively. Analysis of restriction and sequencing demonstrated that the recombining plasmids were successfully constructed. The results also indicated that transfection with pEGFP-C3-PinX1 and PinX1-FAM-siRNA into Eca-109 cells significantly increased PinX1 mRNA, decreased hTERT mRNA by 29.9% (P<0.05), and significantly reduced telomerase activity (P<0.05), inhibited cell growth, and increased the cell apoptotic index from 19.27±0.76 to 49.73±2%. The transfected PinX1-FAM-SiRNA exhibited PinX1 mRNA expression levels that were significantly decreased by 70% (P<0.05), whereas the remaining characteristics of Eca-109 cells, including cell growth, mRNA level of hTERT, telomerase activity and cell apoptotic index were not altered. Exogenous PinX1 has been demonstrated to be highly expressed in human Eca. PinX1 can inhibit human telomerase activity and the expression of hTERT mRNA, reduce tumor cell growth and induce apoptosis. Notably, these inhibitory functions were inhibited by silencing PinX1 in Eca with PinX1-FAM-siRNA. PinX1 was successfully increased and decreased in the present study, demonstrating that it may be a potential telomerase activity inhibitor. As PinX1 is an endogenous telomerase inhibitor, it may be used as a novel tumor-targeted gene therapy.

Piezoelectric and Dielectric Properties of Multilayered BaTiO3/(Ba,Ca)TiO3/CaTiO3 Thin Films.

Highly oriented multilayered BaTiO3-(Ba,Ca)TiO3-CaTiO3 thin films were fabricated on Nb-doped (001) SrTiO3 (Nb:STO) substrates by pulsed laser deposition. The configurations of multilayered BaTiO3-(Ba,Ca)TiO3-CaTiO3 thin films are designed with the thickness ratio of 1:1:1 and 2:1:1 and total thickness ∼300 nm. Microstructural characterization by X-ray diffraction indicates that the as-deposited thin films are highly c-axis oriented and large in-plane strain is determined in BaTiO3 and CaTiO3 layers. Piezoresponse force microscopy (PFM) studies reveal an intense in-plane polarization component, whereas the out-of-plane shows inferior phase contrast. The optimized combination is found to be the BaTiO3-(Ba0.85Ca0.15)TiO3-CaTiO3 structure with combination ratio 2:1:1, which displays the largest domain switching amplitude under DC electric field, the largest room-temperature dielectric constant ∼646, a small dielectric loss of 0.03, and the largest dielectric tunability of ∼50% at 400 kV/cm. These results suggest that the enhanced dielectric and tunability performance are greatly associated with the large in-plane polarization component and domain switching.

A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague­Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

Construction and application of a yeast expression system for thymosin alpha1.

We want to construct a yeast expression system for thymosin alpha1 (Talpha1) to make the orally administered Talpha1 preparation possible. The whole Talpha1 DNA fragment was obtained by PCR. After being digested with restriction enzymes, it was cloned into pYES2 vector. Sequencing was performed to identify the recombinant. The sequence of Talpha1 in recombinant coincided with the original one reported in Genbank. When pYES2-Talpha1 plasmid was transformed into yeast, galactose instead of glucose was used to induce Talpha1 expression. Western blot was performed to identify the quality of the expressed Talpha1. Dried yeast containing pYEST2-Talpha1 was fed to Balb/c mice whose immunities were inhibited by cyclophosphamide in advance. Synthesized Talpha1 peptide was used as positive control and empty yeast was used as negative control. Compared with the negative control group, both dried yeast containing pYEST2-Talpha1 and synthesized Talpha1 peptide can significantly increase the CD8+ level (22.74 +/- 1.09 and 18.77 +/- 4.72 vs 7.49 +/- 2.14, p < 0.01), while both of them had little effect on the CD4+ lymphocytes (61.86 +/- 6.94 and 65.91 +/- 4.78 vs 57.93 +/- 10.40,p > 0.05). We concluded that a high effective yeast expression system for Talpha1 was constructed successfully and the Talpha1 protein expressed by this system can improve CD8+ level in immune inhibited mice.

Construction of a eukaryotic expression plasmid of Humanin.

OBJECTIVE: To construct a eukaryotic expression plasmid pcDNA3.1(-)-Humanin. METHODS: The recombinant plasmid pGEMEX-1-Humanin was digested with restriction endonucleases BamH I and Hind III and the Humanin gene fragments, about 100 bp length, were obtained. Then the Humanin gene fragments were inserted into eukaryotic expression vector pcDNA3.1(-) and the recombinant plasmids pcDNA3.1(-)-Humanin were identified by sequencing. RESULTS: Recombinant plasmid DNA successfully produced a band which had the same size as that of the Humanin positive control. The sequence of recombinant plasmids accorded with the Humnain gene sequence. CONCLUSIONS: A eukaryotic expression plasmid of Humanin was successfully constructed.

Immunomodulatory function of orally administered thymosin alpha1.

OBJECTIVE: To investigate the immunological function of a yeast expression system for thymosin alpha1 (Talpha1). METHODS: A constructed Talpha1 yeast expression system was used to investigate the immunological function of orally administered Talpha1. Dried yeast containing three different concentration of Talpha1 was fed to normal Balb/c mice and other Balb/c mice whose immunities were inhibited in advance by cyclophosphamide. Synthesized Talpha1 peptide was used as positive control and dried yeast with empty plasmid was used as negative control. CD4(+) and CD8(+) levels were detected by flow cytometry assay. TNF-alpha, IFN-gamma, IL-2, IL-6 and IL-10 levels were detected by liquid chip. RESULTS: In normal Balb/c mice or immune inhibition Balb/c mice, CD8(+) levels were significantly increased. Especially in immune inhibition Balb/c mice, CD8(+) levels in synthesized Talpha1 group (18.77%+/-4.72%), small dose group (13.48%+/-6.17%) and large dose group (22.74%+/-1.09%) were significantly higher than that in empty yeast control group (7.49%+/-2.14%). CONCLUSION: Orally administered Talpha1 has its certain immunomodulatory function.

[Combination of lamivudine with thymosin alpha1 in treatment of duck hepatitis B].

OBJECTIVE: To explore the inhibitory effect of combination of lamivudine with thymosin alpha1 (Talpha1) on the replication of duck hepatitis B virus (DHBV). METHODS: Peking ducks of 1 d old were challenged with DHBV-positive serum and used as a duck hepatitis B model. After treated with lamivudine for three months, the ducks were randomly grouped and treated with or without Talpha1 for 8 d. Serum DHBV titrate was observed by semi-quantitative PCR, and inflammation and degeneration of hepatocytes were observed by pathology examination. RESULTS: The serum DHBV titrate was significantly reduced (4483.2+/-5193.4 compared with 9351.8+/-5059.6) after lamivudine treatment, and it was reduced more significantly(1692.2+/-589.2) after combination treatment with Talpha1. Lamivudine reduced the degeneration degree of hepatocytes (3.2+/-0.8 compared with 4.6+/-0.5) and the inflammation degree of liver (6.2+/-3.3 compared with 8.6+/-2.8). The combination treatment with Talpha1 increased liver inflammation degree (9.0+/-5.2). CONCLUSION: Both Talpha1 and lamivudine may reduce the replication of DHBV in Peking ducks and combination treatment may have the better anti-virus effect and enhance immune response in liver.

Predicted pressure-induced spin and electronic transition in double perovskite R2CoMnO6 (R = rare-earth ion).

Specific first-principles calculations are performed to predict structural, magnetic and electronic properties of seven double perovskite R2CoMnO6 materials, with R being a rare-earth ion, under hydrostatic pressure. All these compounds are found to undergo a first-order transition from a high spin (HS) to low spin (LS) state at a critical pressure (whose value is dependent on the R ion). Such transition not only results in a significant volume collapse but also yields a dramatic change in electronic structure. More precisely, the HS-to-LS transition is accompanied by a transition from an insulator to a half-metallic state in the R2CoMnO6 compounds having the largest rare-earth ionic radius (i.e., Nd, Sm, Gd and Tb) while it induces a change from an insulator to a semiconductor having a narrow band gap for the smallest rare-earth ions (i.e., R = Dy, Ho and Er). Experiments are called for to confirm these predictions.

Predicted energetics and properties of rare-earth ferrites films grown on cubic (111)- and hexagonal (0001)-oriented substrates.

First-principles calculations are performed to compare the energetics of several phases, including hexagonal polar P6(3)cm and perovskite non-polar Pbnm-like states, of epitaxial RFeO3 films (with R = Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er and Lu) grown on different cubic (1 1 1)- and hexagonal (0 0 0 1)-oriented substrates. The P63cm phase is found to be the ground state for large enough in-plane lattice parameters in all investigated RFeO3 films, and its polarization is tunable by the amount of epitaxial strain. Series of available substrates allowing the growth of hexagonal polar RFeO3 films, as well as other phenomena of fundamental and technological importance (e.g. different ground states and coexistence between several phases) are also predicted.

Creating multiferroics with large tunable electrical polarization from paraelectric rare-earth orthoferrites.

The quest for materials possessing both a magnetic ordering temperature above room temperature and a large electrical polarization is an important research direction in order to design novel spintronic and memory devices. Up to now, BiFeO3 and related systems are the only known compounds simultaneously possessing such characteristics. Here, first-principles calculations predict that another family of materials, namely epitaxial films made of rare-earth orthoferrites (RFeO3), can also exhibit such desired features. As a matter of fact, applying a large enough strain to these compounds, which are nominally paraelectric and have a high magnetic transition temperature, is predicted to render them ferroelectric, and thus multiferroic. At high compressive strain, the resulting ferroelectric phase of RFeO3 systems having large rare-earth ions is even a tetragonal state characterized by a giant polarization and axial ratio. For large tensile strain, two striking inhomogenous ferroelectric phases--including one never observed before in any perovskite--are further predicted as having significant polarization. A multiphase boundary also occurs, which may lead to optimization of properties or unusual features. Finally, many quantities, including electrical polarization and magnetic ordering temperature, are tunable by varying the epitaxial strain and/or chemical pressure.