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Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

Stress-induced depression is common worldwide. NAc, a “reward” center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5.SIGNIFICANCE STATEMENTStress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.

Overactivation of N-methyl-D-aspartate receptor (NMDAR) in the spinal cord dorsal horn (SDH) in the setting of injury represents a key mechanism of neuropathic pain. However, directly blocking NMDAR or its downstream signaling, interaction between postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS), causes analgesic tolerance, mainly due to GABAergic disinhibition. The aim of this study is to explore the possibility of preventing analgesic tolerance through co-targeting NMDAR downstream signaling and γ-aminobutyric acid type A receptors (GABAARs). Methods: Mechanical/thermal hyperalgesia were quantified to assess analgesic effects. Miniature postsynaptic currents were tested by patch-clamp recording to evaluate synaptic transmission in the SDH. GABA-evoked currents were tested on HEK293 cells expressing different subtypes of recombinant GABAARs to assess the selectivity of (+)-borneol and ZL006-05. The expression of α2 and α3 subunits of GABAARs and BDNF, and nNOS-PSD-95 complex levels were analyzed by western blotting and coimmunoprecipitation respectively. Open field test, rotarod test and Morris water maze task were conducted to evaluate the side-effect of ZL006-05. Results: (+)-Borneol selectively potentiated α2- and α3-containing GABAARs and prevented the disinhibition of laminae I excitatory neurons in the SDH and analgesic tolerance caused by chronic use of ZL006, a nNOS-PSD-95 blocker. A dual-target compound ZL006-05 produced by linking ZL006 and (+)-borneol through an ester bond blocked nNOS-PSD-95 interaction and potentiated α2-containing GABAAR selectively. Chronic use of ZL006-05 did not produce analgesic tolerance and unwanted side effects. Conclusion: By targeting nNOS-PSD-95 interaction and α2-containing GABAAR simultaneously, chronic use of ZL006-05 can avoid analgesic tolerance and unwanted side effects. Therefore, we offer a novel candidate drug without analgesic tolerance for treating neuropathic pain.

The pathogenesis of post-traumatic stress disorder (PTSD) remains largely unclear. A large body of evidence suggests that the abnormal level of serotonin (5-HT) is closely related to the onset of PTSD. Several reports reveal that nitric oxide (NO) affects extracellular 5-HT levels in various brain regions, but no consistent direction of change was found and the underlying mechanisms remain unknown. The most of serotonergic neurons in dorsal raphe nucleus (DRN), a major source of serotonergic input to the forebrain, co-expresses neuronal nitric oxide synthase (nNOS), a synthase derived nitric oxide (NO) in the central nervous system. Here, we found that the excessive expression of nNOS and thereby the high concentration of NO followed by single-prolonged stress (SPS) caused suppression of the activity of DRN 5-HT neurons, inducing PTSD-like phenotype including increased anxiety-like behaviors, enhanced contextual fear memory, and fear generalization. Our study uncovered an important role of DRN nNOS-NO pathway in the pathology of PTSD, which may contribute to new understanding of the molecular mechanism of PTSD.

The DArk Matter Particle Explorer (DAMPE) is a satellite-borne experiment, in operation since 2015, aimed at studying high-energy gamma rays and cosmic nuclei fluxes. Of the various sub-detectors in the DAMPE payload, the Silicon-Tungsten tracKer-converter (STK) plays a significant role in the charge measurement of incoming ions. Depending on the angle of inclination of the impinging particle and its position of impact on these strips, the collected charge can spread between the strips which results in some fractional signal loss. The $\eta$ variable is used to identify this spread of charge across the strips and correct for the associated charge loss. This brings us closer to accurate determination of particle charge which is crucial for ensuring a good discrimination between particles. The $\eta$-correction is, therefore, expected to play an important role in the determination of heavy ions by the DAMPE detector. It has helped reduce the proton background for the helium identification in STK by a factor of 1.5 for MIP tracks. It has been sucessfully applied to carbon nuclei and its application to heavier nuclei is currently being studied.

The DArk Matter Particle Explorer (DAMPE), a space-based high energy particle detector, has been operated on-orbit for more than five years. The large geometric factor and good charge resolution enable DAMPE to have very good potential to measure cosmic-rays up to 100 TeV. Knowledge of the boron to carbon (B/C) flux ratio is very important in understanding the prop- agation of cosmic rays, especially in TeV energy range. In this contribution, the latest progress of the B/C flux ratio analysis based on the flight data collected by DAMPE during the 5 years of operation, is presented.

The magnetically separable ternary polyetherimide/titanate@Fe3O4 (PTF) photocatalysts of special heterostructure between magnetite (Fe3O4) microspheres and titanates nanosheets modified by polyetherimide (PEI) were successfully fabricated via a simple facile hydrothermal deposition method. The as-prepared photocatalysts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, Transmission electron microscopy and UV-vis diffuse reflectance spectroscopy etc. The results showed that the as-fabricated material had a structure of Fe3O4 microspheres coated with titanates nanosheets modified by PEI. The special interfacial contact between 3D microsphere and 2D nanosheets in the nanoarchitectures was formed via electrostatic attraction. Furthermore, the resulted photocatalysts were tested by degradation reaction of methylene blue under visible light irradiation and demonstrated an enhanced performance than the pure Fe3O4 microspheres, and the photocatalytic activity enhanced with the molar ratio of Fe3O4 microspheres and modified titanate gradually, which was attributed to the expansion of the surface area and the different electrostatic contact between the Fe3O4 microspheres and titanate nanosheets. Moreover, the obtained results revealed the high yield magnetic separation and efficient reusability of PTF-5 (96.7%) over 3 times reuse.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the DArk Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of $4.3\sigma$. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out., Comment: 11 pages, 13 figures, published in Phys. Rev. Lett. Add one more digit for first three columns in Table S2

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.

Neuropathic pain is usually persistent due to maladaptive neuroplasticity-induced central sensitization and, therefore, necessitates long-term treatment. N-methyl-D-aspartate receptor (NMDAR)-mediated hypersensitivity in the spinal dorsal horn represents key mechanisms of central sensitization. Short-term use of NMDAR antagonists produces antinociceptive efficacy in animal pain models and in clinical practice by reducing central sensitization. However, how prolonged use of NMDAR antagonists affects central sensitization remains unknown. Surprisingly, we find that prolonged blockage of NMDARs does not prevent but aggravate nerve injury-induced central sensitization and produce analgesic tolerance, mainly due to reduced synaptic inhibition. The disinhibition that results from the continuous decrease in the production of nitric oxide from neuronal nitric oxide synthase, downstream signal of NMDARs, leads to the reduction of GABAergic inhibitory synaptic transmission by upregulating brain-derived neurotrophic factor expression and inhibiting the expression and function of potassium-chloride cotransporter. Together, our findings suggest that chronic blockage of NMDARs develops analgesic tolerance through the neuronal nitric oxide synthase–brain-derived neurotrophic factor–potassium-chloride cotransporter pathway. Thus, preventing the GABAergic disinhibition induced by nitric oxide reduction may be necessary for the long-term maintenance of the analgesic effect of NMDAR antagonists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00883-w) contains supplementary material, which is available to authorized users.

Exposure therapy based on the extinction of fear memory is first-line treatment for post-traumatic stress disorder (PTSD). However, fear extinction is relatively easy to learn but difficult to remember, extinguished fear often relapses under a number of circumstances. Here, we report that extinction learning-induced association of neuronal nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the infralimbic (IL) subregion of medial prefrontal cortex negatively regulates extinction memory and dissociating nNOS-CAPON can prevent the return of extinguished fear in mice. Extinction training significantly increases nNOS-CAPON association in the IL. Disruptors of nNOS-CAPON increase extracellular signal-regulated kinase (ERK) phosphorylation and facilitate the retention of extinction memory in an ERK2-dependent manner. More importantly, dissociating nNOS-CAPON after extinction training enhances long-term potentiation and excitatory synaptic transmission, increases spine density in the IL, and prevents spontaneous recovery, renewal and reinstatement of remote fear of mice. Moreover, nNOS-CAPON disruptors do not affect other types of learning. Thus, nNOS-CAPON can serve as a new target for treating PTSD.

Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF-κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying the role of NF-κB in stress-induced anxiety behaviors are poorly understood. In this study, we show that chronic mild stress (CMS) and glucocorticoids dramatically increased the expression of NF-κB subunits p50 and p65, phosphorylation and acetylation of p65, and the level of nuclear p65 in vivo and in vitro, implicating activation of NF-κB signaling in chronic stress-induced pathological processes. Using the novelty-suppressed feeding (NSF) and elevated-plus maze (EPM) tests, we found that treatment with pyrrolidine dithiocarbamate (PDTC; intra-hippocampal infusion), an inhibitor of NF-κB, rescued the CMS- or glucocorticoid-induced anxiogenic behaviors in mice. Microinjection of PDTC into the hippocampus reversed CMS-induced up-regulation of neuronal nitric oxide synthase (nNOS), carboxy-terminal PDZ ligand of nNOS (CAPON), and dexamethasone-induced ras protein 1 (Dexras1) and dendritic spine loss of dentate gyrus (DG) granule cells. Moreover, over-expression of CAPON by infusing LV-CAPON-L-GFP into the hippocampus induced nNOS-Dexras1 interaction and anxiety-like behaviors, and inhibition of NF-κB by PDTC reduced the LV-CAPON-L-GFP-induced increases in nNOS-Dexras1 complex and anxiogenic-like effects in mice. These findings indicate that hippocampal NF-κB mediates anxiogenic behaviors, probably via regulating the association of nNOS-CAPON-Dexras1, and uncover a novel approach to the treatment of anxiety disorders.

Fear extinction depends on N-methyl-D-aspartate glutamate receptors (NMDARs) and brain-derived neurotrophic factor (BDNF) activation in the limbic system. However, postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) coupling, the downstream signaling of NMDARs activation, obstructs the BDNF signaling transduction. Thus, we wondered distinct roles of NMDAR activation and PSD-95-nNOS coupling on fear extinction. To explore the mechanisms, we detected protein-protein interaction using coimmunoprecipitation and measured protein expression by western blot. Contextual fear extinction induced a shift from PSD-95-nNOS to PSD-95-TrkB association in the dorsal hippocampus and c-Fos expression in the dorsal CA3. Disrupting PSD-95-nNOS coupling in the dorsal CA3 up-regulated phosphorylation of extracellular signal-regulates kinase (ERK) and BDNF, enhanced the association of BDNF-TrkB signaling with PSD-95, and promoted contextual fear extinction. Conversely, blocking NMDARs in the dorsal CA3 down-regulated BDNF expression and hindered contextual fear extinction. NMDARs activation and PSD-95-nNOS coupling play different roles in modulating contextual fear extinction in the hippocampus. Because inhibitors of PSD-95-nNOS interaction produce antidepressant and anxiolytic effect without NMDAR-induced side effects, PSD-95-nNOS could be a valuable target for PTSD treatment.

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis. KEY MESSAGES: miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis.

Cereal cyst nematode (Heterodera avenae) diapause is induced by high temperatures and is broken by low temperatures. In this study, metabolic responses were monitored in diapause and non-diapause H. avenae during exposure to 4°C for 10 weeks. The results showed that there was no difference in total carbohydrate content. The content of glycogen and glycerol at 0 week was relatively high but decreased with increased storage time at 4°C. The content of trehalose of the nematode at 10 weeks was significant lower than that at 5 weeks at 4°C. Protein content increased significantly after incubation for 5 and 10 weeks. Esterase and trehalase activity increased with the increasing period at 4°C and showed a significant difference between treatments for esterase activity but there was no significant difference between 5 and 10 weeks for trehalase activity. The SDS-PAGE pattern indicated that a 15.5 kDa protein was absent at 10 weeks and present at 0 and 5 weeks. Esterase isoenzyme patterns of H. avenae showed that at 10 weeks there were four bands: EST 0.21, EST 0.24, EST 0.30 and EST 0.34 (Rf values). EST 0.24 was the common band in the three treatments. Biochemical tests were conducted to correlate with hatching experiments using the same treatments. 2-DE patterns of H. avenae showed that diapause and non-diapause nematodes had 409 and 412 protein spots, respectively, and 19 protein spots were unique: 11 distinct proteins in non-diapause and eight distinct proteins in diapause. This information could be helpful in understanding the diapause mechanism of the cereal cyst nematode.

Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS) in the brain. Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders, including stroke, depression and anxiety disorders, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, chronic pain, and drug addiction. Due to critical roles of nNOS in learning and memory and synaptic plasticity, direct inhibition of nNOS may cause severe side effects. Importantly, interactions of several proteins, including post-synaptic density 95 (PSD-95), carboxy-terminal PDZ ligand of nNOS (CAPON) and serotonin transporter (SERT), with the PSD/Disc-large/ZO-1 homologous (PDZ) domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain. Therefore, it will be a preferable means to interfere with nNOS-mediated protein-protein interactions (PPIs), which do not lead to undesirable effects. Herein, we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders, and the discovery of drugs targeting the PPIs, which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.

A series of sulfobutyl ether β-Cyclodextrins (SBE-β-CDs) with specific average degree of substitution (DS) were successfully synthesized, using a three-step synthesis method, through the reaction between β-Cyclodextrin (β-CD) and 1, 4-butane sultone in the sodium hydroxide solution. Although the ratio of β-CD and 1, 4-butane sultone is a dominant factor affecting the average degree of substitution of products, a typical optimization on other synthesis parameters is also necessary to precisely obtain these products. The optimization includes the addition of sodium hydroxide solution, the range of pH and reaction time in different reaction stages. Actually, each product is a mixture with various degrees of substitution and different positional isomers. Under the optimal conditions, the average degree of substitution and the characterizations of SBE-β-CDs were investigated by means of FTIR, 1H NMR, 13C NMR, HRMS, Capillary Electrophoresis, DSC and HPLC. The results indicated that the substitution reaction occurred simultaneously on C6–OH and C2–OH in the moderate alkaline solution and the proportion of C2–OH substituted increased with the increase of DS. The DS of SBE-β-CDs had better reproducibility and the distribution of composition analyzed by capillary electrophoresis was a normal distribution. In the novel synthesis process, the yield of the products was significantly improved. For example, the yield of SBE7-β-CD reached up to 80%. Moreover, the DS of SBE7-β-CD was 6.68 and the purity of SBE7-β-CD was 96% in line with quality standards of United States Pharmacopeia.

It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner.

PURPOSE The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. METHODS Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. RESULTS Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). CONCLUSIONS Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

β-Phenethyl isothiocyanate (PEITC) is an important phytochemical from cruciferous vegetables and is being evaluated for chemotherapeutic activity in early phase clinical trials. Moreover, studies in cell culture and in animals found that the anticarcinogenic activities of PEITC involved all the major stages of tumor growth: initiation, promotion, and progression. A number of mechanisms have been proposed for the chemopreventive activities of this compound. Here, we focus on the major molecular signaling pathways for the anticancer activities of PEITC. These include (1) activation of apoptosis pathways; (2) induction of cell cycle arrest; and (3) inhibition of the survival pathways. Furthermore, we also discussed the regulation of drug-metabolizing enzymes, including cytochrome P450s, metabolizing enzymes, and multidrug resistance.

C22H32N4O13S2Zn, triclinic, P1̅ (no. 2), a = 9.496(1) Å, b = 10.016(1) Å, c = 16.334(2) Å, α = 102.297(10)°, β = 93.625(10)°, γ = 111.313(10)°, V = 1397.1 Å3, Z = 2, Rgt(F) = 0.0383, wRref(F2) = 0.1020, T = 296 K.

Our previous study found that serotonin 1A receptor (5-HT1aR) is an endogenous suppressor of nNOS expression in the hippocampus, which accounts for anxiolytic effect of fluoxetine. However, the precise molecular mechanism remains unknown. By using 8-OH-DPAT, a selective 5-HT1aR agonist, NAN-190, a selective 5-HT1aR antagonist, and U0126, an Extracellular Regulated Protein Kinases (ERK) phosphorylation inhibitor, we investigated the role of ERK in 5-HT1aR-nNOS pathway. Western blots analysis demonstrated that 5-HT1aR activation up-regulated the level of phosphorylated ERK (P-ERK) beginning at 5 min and down-regulated the expression of nNOS beginning at 20 min. Meanwhile, blockage of 5-HT1aR resulted in a decrease in P-ERK beginning at 20 min and caused an increase in nNOS expression beginning at 6 h. Although U0126 itself did not alter nNOS expression and activity, NO level, and anxiety-related behaviors, the treatment totally reversed 8-OH-DPAT-induced reduction in nNOS expression and function, and anxiolytic effect. Besides, our data showed that ERK phosphorylation was essential for 5-HT1aR activation-induced cAMP responsive element binding protein (CREB) phosphorylation, hippocampal neurogenesis and synaptogenesis of newborn neuron. Our study suggests a crucial role of ERK phosphorylation in the regulation of nNOS expression by 5-HT1aR, which is helpful for understanding the mechanism of 5-HT1aR-based anxiolytic treatment.

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to the DNA modification caused by derivatives formed during metabolism. 17β-estradiol (E2), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of the 2-hydroxyestradiol (2-OH E2) and 4-hydroxyestradiol (4-OH E2) through the action of Cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that 2-OH E2 have putative protective effects, while 4-OH E2 is genotoxic and has potent carcinogenic activity. Thus, the ratio of 2-OH E2/4-OH E2 is a critical determinant of the toxicity of E2 in mammary cells. In the present study, we investigated the effects of the berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater inductions of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect E2 metabolism in a more protective pathway in the breast cancer MCF-7 cells.

A monomer 4,4'-bis(β-hydroxyethyl)biphenyl (2BP) was synthesized by the Williamson reaction from 2-chloroethanol and 4,4'-biphenol. Then, the novel dendritic liquid crystal macromolecule (DLCM) containing biphenyl structure was synthesized with 2BP and 1,3,5-benzenetrimethylacylchloride as monomers by dispersion method. The structures of 2BP and the DLCM were characterized by FT-IR and 1H-NMR. The thermal stabilities of he DLCM were measured by TGA and DSC. The results showed that the DLCM had good thermal stability and the DLCM may have a higher phase inversion temperature.

Serotonin 1a-receptor (5-HT1aR) has been specifically implicated in the pathogenesis of anxiety. However, the mechanism underlying the role of 5-HT1aR in anxiety remains poorly understood. Here we show in mice that the transcription factor cAMP response element binding protein (CREB) in the hippocampus functions as an effector of 5-HT1aR in modulating anxiety-related behaviors. We generated recombinant lentivirus LV-CREB133-GFP expressing a dominant negative CREB which could not be phosphorylated at Ser133 to specifically reduce CREB activity, and LV-VP16-CREB-GFP expressing a constitutively active fusion protein VP16-CREB which could be phosphorylated by itself to specifically enhance CREB activity. LV-CREB133-GFP neutralized 5-HT1aR agonist-induced up-regulation of synapse density, spine density, dendrite complexity, neurogenesis, and the expression of synapsin and spinophilin, two well-characterized synaptic proteins, and abolished the anxiolytic effect of 5-HT1aR agonist; whereas LV-VP16-CREB-GFP rescued the 5-HT1aR antagonist-induced down-regulation of synapse density, spine density, dendrite complexity, neurogenesis and synapsin and spinophilin expression, and reversed the anxiogenic effect of 5-HT1aR antagonist. The deletion of neurogenesis by irradiation or the diminution of synaptogenesis by knockdown of synapsin expression abolished the anxiolytic effects of both CREB and 5-HT1aR activation. These findings suggest that CREB-mediated hippoacampus structural plasticity is crucial for the role of 5-HT1aR in modulating anxiety-related behaviors.

The 1st, 2nd and 3rd generations of hydroxyl-terminated hyperbranched polyesters (HBPE-1, HBPE-2, and HBPE-3) were synthesized. A3rd generation hyperbranched polyester (HBPE-3) was used as original crosslinking agent to prepared hyperbranched waterborne polyurethane dispersions (HPU). FTIR spectra confirmed that this reaction really took place. The experimental data indicated that, compared with the linear one, the hyperbranched HPU aqueous dispersions exhibited lower viscosity, and larger particle size. For the hyperbranched HPU films, mechanical properties were obviously enhanced.

Background: Studies show that rapid access to high altitude, the body inevitably will be different degrees of injury, more significant damage to heart and lung [1 ~ 3]. The high altitude hypoxia on the lung tissue to adapt to structural changes and hypoxia inducible factor-1α (HIF-1α) expression of the study rarely reported. The experimental area for a short time brought by the near sea level to higher altitudes rat lung tissue by light, electron microscopy and the expression of hypoxia inducible factor-1α changes were studied.Objective: To observe the altitude hypoxia on the ultrastructure of lung tissue and the hypoxia inducible factor-la (HIF-1α) expression.Methods: 50 rats were randomly divided into 5 groups, namely group 1 d Golmud (altitude 2 700 m), 2 d Tanggula group (altitude 5 000 m), 3 d Nagqu group (altitude 4 500 m) and 30 d Nagqu group (altitude 4 500 m), the control group (in Xi'an, elevation 5 m). 4 time-consuming experimental animals 1 d from Xi'an to the Golmud, Qinghai (altitude 2 700 m), 2 d to the Tibetan Tanggula (altitude 5 000 m), 3 d to the Naqu (altitude 4500 m), 30 d in Tibet Nagqu. Light and electron microscopy of the lung tissue samples, Western Blot method to detect the lung tissue of hypoxia inducible factor-1α expression, RT-PCR method for detection of high altitude hypoxic group, lung tissue expression of hypoxia inducible factor-1αmRNA change. Results and Conclusions: Acute hypoxia 2d Tanggula microstructure and ultrastructure of lung tissue apparent high altitude pulmonary edema, and 30d after hypoxic Nagqu group after high altitude pulmonary edema was significantly reduced lung tissue Western blotting, not Canon See HIF-1α protein expression, RT-PCR detection of HIF-1αmRNA in the 30d Nagqu group, a certain amount of expression, the other three experimental groups HIF-1αmRNA expression was not significant (P> 0.05), 30d Nagqu group HIF-lamRNA expression was significantly higher In the control group (P

The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly understood. We report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial mediator. Chronic mild stress and glucocorticoids exposures caused hippocampal nNOS overexpression via activating mineralocorticoid receptor. In turn, hippocampal nNOS-derived nitric oxide (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)/cGMP and peroxynitrite (ONOO−)/extracellular signal-regulated kinase signal pathways, and therefore elevated hypothalamic corticotrophin-releasing factor, a peptide that governs the hypothalamic-pituitary-adrenal axis. More importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive behaviors. In addition, directly delivering ONOO−donor into hippocampus caused depressive-like behaviors. Our findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.

Oxidation kinetic of a Zr55Cu30Al10Ni5 bulk metallic glass (BMG) and its crystalline counterpart were studied under dry artificial air (20% of O2 and 80% of N2) at 673 K by thermogravimetry analysis (TGA) method. According to TGA profiles, the oxidation kinetic in both amorphous and crystalline states followed a protective parabolic law. However, the oxidation rates for the amorphous alloy were obviously higher than those for the crystalline alloy. Pseudo-grazing incident X-Ray diffraction (GIXRD) has been carried out to identify the oxides nature and their crystalline structure. Tetragonal-ZrO2 dominated the oxide scale formed on both alloys (BMG and crystalline) at T = 673 K; meanwhile, a slight amount of Cu was detected on the oxide surface of studied BMG alloy. The atomic diffusion mechanism was investigated using a two-stage oxidation treatment to study oxide scale growth kinetics. The studied specimens were oxidized firstly under dry artificial air and then under 18O2 isotopic tracer gas for 1.5 hours respectively at 673 K. The evident solute penetration zone and ion diffusion characteristic through the oxide scale were determined by Cs+ secondary ion mass spectrometry (SIMS) depth profile. The results showed the mechanism of the oxide layer formation of both alloys was not only due to Oxygen ions diffusion from oxide surface to interior scale, but also to an outward diffusion of Zirconium ions from substrate to oxide layer and the ZrO2 oxide growth seemed to occur at the oxide/gas interface in our studied case.

A novel azobenzene optically polymer (P-DA) was synthesized based on the azo chromophore molecule, chiral reagent L(-)-tartaric acid, acryloyl chloride and methacrylate. The P-DA was characterized by FT-IR, UV-Vis spectroscopy, 1H NMR, DSC and TGA. The P-DA had high thermal stability up to its glass-transition temperature (Tg) of 110 oC and 5 % heat weight loss temperature of 199 oC. The UV-induced trans/cis photoisomerization and reflex-isomerization behaviors were investigated. The results indicated that the P-DA solution could undergo photochromism after irradiated by 365 nm UV light. The optical parameters: refractive index (n), the dielectric constant (ε) and thermal volume expansion coefficient (β) of P-DA were obtained. The thermo-optic coefficients are one order of magnitude larger than those of the inorganic materials, such as SiO2 (1.1×10−5 oC -1 and LiNbO3 (4×10−5 oC -1) and was larger than the organic material such as polystyrene (-1.23×10-4 oC -1) and PMMA (-1.20×10-4 oC -1). The conclusion had a little significance to develop optical communication.

A novel polyelectrolyte (PLJY) was synthesized based on the azobenzene chromophore containing functional groups (-C=C-) and α-methacrylic acid by radical polymerization. The PLJY was characterized by FT-IR and UV-vis spectroscopy. The thermal property was characterized using the differential scanning calorimeter (DSC). The glass transition temperatures (Tg) was 179.1 oC and showed that the PLJY had excellent thermal stability. Influences of pH values on the UV-Vis absorption spectra of PLJY were studied and polyelectrolyte solution had good pH-sensitivity and H-aggregation behavior. The photoresponsive and thermochromism behaviors were investigated for the azo polyelectrolyte PLJY solution or film. By 256 nm excitation wavelength, the PLJY solution or film appeared photo responsive behavior. At high temperature, the PLJY solution had thermochromic behavior. These results showed that the polyelectrolyte had potential applications in optical information storage and optical switch.

It has been demonstrated that neuronal nitric oxide synthase (nNOS) negatively regulates adult neurogenesis. However, the cellular and molecular mechanisms underlying are poorly understood. Here, we show that nNOS from neural stem cells (NSCs) and from neurons play opposite role in regulating neurogenesis. The NSCs treated with nNOS inhibitor N5-(1-imino-3-butenyl)-L- ornithine (L-VNIO) or nNOS gene deletion exhibited significantly decreased proliferation and neuronal differentiation, indicating that NSCs-derived nNOS is essential for neurogenesis. The NSCs cocultured with neurons displayed a significantly decreased proliferation, and deleting nNOS gene in neurons or scavenging extracellular nitric oxide (NO) abolished the effects of coculture, suggesting that neurons-derived nNOS, a source of exogenous NO for NSCs, exerts a negative control on neurogenesis. Indeed, the NSCs exposed to NO donor DETA/NONOate displayed decreased proliferation and neuronal differentiation. The bidirectional regulation of neurogenesis by NSCs- and neurons-derived nNOS is probably related to their distinct subcellular localizations, mainly in nuclei for NSCs and in cytoplasm for neurons. Both L-VNIO and DETA/NONOate inhibited telomerase activity and proliferation in wild-type (WT) but not in nNOS−/− NSCs, suggesting a nNOS-telomerase signaling in neurogenesis. The NSCs exposed to DETA/NONOate exhibited reduced cAMP response element binding protein (CREB) phosphorylation, nNOS expression, and proliferation. The effects of DETA/NONOate were reversed by forskolin, an activator of CREB signaling. Moreover, disrupting CREB phosphorylation by H-89 or LV-CREB133-GFP simulated the effects of DETA/NONOate, and inhibited telomerase activity. Thus, we conclude that NSCs-derived nNOS stimulates neurogenesis via activating telomerase, whereas neurons-derived nNOS represses neurogenesis by supplying exogenous NO that hinders CREB activation, in turn, reduces nNOS expression in NSCs.

A novel azobenzene polyelectrolyte (ABAPE) was synthesized based on chromophore 4-(4’-nitrophenylazo) naphthol (NPAN), epoxychloropropane and α-methacrylic acid. The ABAPE was characterized by FT-IR and UV-vis spectroscopy. The aggregation behaviors of ABAPE were investigated based on different pH values by the UV-vis spectroscopy. The isomerization behavior of the ABAPE in DMAC solution was studied by 256 nm UV irradiation light. Attenuated total reflection (ATR) method was adopted and carried out the measurement of refractive index of the thin film. The thermo-optic coefficient (dn/dT) was -2.9228×10-4°C-1 and was bigger than inorganic materials such as silica glass, zinc silicate glass, borosilicate glass and the organic materials of polystyrene and PMMA. These results showed that the polyelectrolyte could be used to carry out optical storage and thermo-optic switch.

Increasing evidence suggests that 5-HT1Areceptor (5-HT1AR) is implicated in anxiety disorders. However, the mechanism underlying the role of 5-HT1AR in these diseases remains unknown. Here, we show that 5-HT1AR-selective agonist 8-OH-DPAT and selective serotonin reuptake inhibitor (SSRI) fluoxetine downregulated hippocampal neuronal nitric oxide synthase (nNOS) expression, whereas 5-HT1AR-selective antagonist NAN-190 upregulated hippocampal nNOS expression. By assessing anxiety-related behaviors using the novelty suppressed feeding, open-field, and elevated plus maze tests, we show that mice lacking nNOS gene [knock-out (KO)] or treated with nNOS-selective inhibitor 7-nitroindazole (7-NI; i.p., 30 mg/kg/d for 28 d; or intrahippocampal microinjection, 16.31 μg/1.0 μl) displayed an anxiolytic-like phenotype, implicating nNOS in anxiety. We also show that, in wild-type (WT) mice, administrations of 8-OH-DPAT (i.p., 0.1 mg/kg/d) or fluoxetine (i.p., 10 mg/kg/d) for 28 d caused anxiolytic-like effects, whereas NAN-190 (i.p., 0.3 mg/kg/d for 28 d) caused anxiogenic-like effects. In KO mice, however, these drugs were ineffective. Moreover, intrahippocampal infusion of 8-OH-DPAT (45.963 μg/100 μl) using 14 d osmotic minipump produced anxiolytic effects. Intrahippocampal microinjection of 7-NI (16.31 μg/1.0 μl) abolished the anxiogenic-like effects of intrahippocampal NAN-190 (4.74 μg/1.0 μl). Additionally, NAN-190 decreased and 8-OH-DPAT increased phosphorylated cAMP response element-binding protein (CREB) levels in WT mice but not in KO mice. Blockade of hippocampal CREB phosphorylation by microinjection of H89 (5.19 μg/1.0 μl), a PKA (protein kinase A) inhibitor, abolished the anxiolytic-like effects of 7-NI (i.p., 30 mg/kg/d for 21 d). These findings indicate that both hippocampal nNOS and CREB activity mediate the anxiolytic effects of 5-HT1AR agonists and SSRIs.

Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia. Inhibiting oxidative stress has been considered as an effective approach for stroke treatment. Edaravone, a free radical scavenger, has been shown to prevent cerebral ischemic injury. However, the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions (O2·−). Here, we report that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, a novel small-molecule compound structurally related to edaravone, showed a stronger inhibitory effect on oxidative stress in vitro. In vivo, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde, two proteins crucial for oxidative stress, suggesting a strengthened antioxidant system. Moreover, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability. Then, we found that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone. More importantly, 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period, indicating enhanced neuroprotection, sensorimotor function and spatial memory. Together, these findings suggest that 2-methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.

NR2A-containing N-methyl- d -aspartate (NMDA) receptors have important roles in influencing the long-term potentiation and spatial memory. Here using Morris water maze, we found that inhibition of NR2A-containing NMDA receptors by [(R)-[(S)-1-(4-bromophenyl)-ethylamino]-(2, 3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077) hindered the formation of spatial memory. An increasing number of reports suggest that adult hippocampal neurogenesis is involved in hippocampal-mediated learning. To explore the possible mechanisms understanding the reduced spatial memory by NVP-AAM077, we investigated the effects of NVP-AAM077 on neurogenesis. We found that NVP-AAM077 inhibited progenitor cells proliferation in the subventricular zone and dentate gyrus and reduced the survival of newborn cells in the dentate gyrus in the adult mice. In null mutant mice lacking neuronal nitric oxide synthase (nNOS) gene (nNOS−/−), the effects of NVP-AAM077 on neurogenesis disappeared. In addition, NVP-AAM077 increased nNOS enzymatic activity. Our findings suggest that NVP-AAM077 reduced spatial learning through down-regulating neurogenesis in the adult hippocampus.

Nitric oxide (NO), a free gaseous signaling molecule, is involved in the regulation of the cardiovascular, nervous and immune system. The neurotransmitter function of nitric oxide is dependent on dynamic regulation of its biosynthetic enzyme, nitric oxide synthase (NOS). There are three types of NOS, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). Of the three NOS, we focus on nNOS in the present review. Brain nNOS exists in particulate and soluble forms and the differential subcellular localization of nNOS may contribute to its diverse functions. Proteins bearing PDZ domains can interact directly with the PDZ domain of nNOS, influencing the subcellular distribution and/or activity of the enzyme. During the past several years, an increasing number of reports have demonstrated the importance of nNOS in a variety of synaptic signaling events. nNOS has been implicated in modulating physiological functions such as learning, memory, and neurogenesis, as well as being involved in a number of human diseases. In this review we concentrate on recent findings regarding the structural features, subcellular localization and factors regulating nNOS function. In particular, we conclude with a section discussing the role of nNOS in a wide range of physiological and pathological conditions.

Intercalation nonlinear-optical (NLO) polyimide and polyimide/silica hybrid material were synthesized by the sol–gel technique. The results showed that the interpenetrating hybrid polymer networks were formed and showed excellent thermal stability. The electro-optic property suggests that this hybrid material has potential for applications in high performance optical devices.

Layered nanocomposite PEG/WS2, intercalating oligomeric poly(ethylene glycol) (PEG6000) into the tungsten disulfide host galleries, was synthesized using the exfoliation-adsorption technique. X-ray diffraction revealed that the intercalated oligomer within the host galleries is in a double-layer arrangement with an interlayer expansion of about 8.8 A. The optimum conditions were explored to prepare the single-phase product with a composition of Li0.12(PEG)1.51WS2. Thermal analyses suggested that the resulting material shows good thermal stability, with the decomposition of the interacted oligomeric chains within the disulfide galleries occurring at around 258 °C. Despite high conductivity of the host material, those of the PEG/WS2 nanocomposite were found to be high in the order of 1 × 10−2 S cm−1 at ambient temperature, resulted from the host guest–host charge transfers.

Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage.

Utilizing the solvothermal synthesis technique, lithium intercalated tungsten disulfide LixWS2 with x > 1 was obtained, which was allowed to react with water to the formation of single-molecule-layer suspension of tungsten disulfide. The layered nanocomposites PEG, PEO/WS2, intercalating poly(ethylene glycol) (PEG, MW ≈ 1 × 103, 6 × 103, 1 × 104) and poly(ethylene oxide) (PEO, MW ≈ 3 × 105) into the tungsten disulfide host galleries, were prepared using the improved exfoliation–adsorption technique. It was revealed that the intercalated polymers within the host galleries are in a double-layer arrangement with an interlayer expansion of about 9 A. Despite high conductivity of the host material, those of the PEG, PEO/WS2 nanocomposites were found to be high in the order of 1 × 10−2 to 10−3 S cm−1 at ambient temperature, resulted from the guest–host charge transfers.

A series of layered nanocomposites constructed from MoS2 and hydroxy-NiAl oligocations with various Ni/Al ratios were prepared. The interlayer expansions of 8.11–9.03 A with Ni/Al ≤ 0.8 indicate that the intercalated species should mainly be [AlO4Al12(OH)24(H2O)12]7+ or substituted [Al13−xNixO4(OH)24(H2O)12](7−x)+ Keggin oligocations. In the presence of molecular oxygen, the composites exhibit good catalytic activities in the oxidization of sulfide ions into thiosulfate ions, and their catalytic activities have been enhanced upon irradiation with visible light.

Layered composites, Zr-intercalated MoS2, have been prepared utilizing the exfoliation and restacking properties of Li x MoS2 under mild conditions and characterized by X-ray powder diffraction, differential scanning calorimetry and BET surface measurements. It showed the formation of two distinct products depending on the employed Zr:MoS2 reaction stoichiometry. The interlayer expansions of about 4.4 A and 9.2 A suggested mono- or bi-layer arrangements of the hydroxyl–Zr oligocations into the interlayer galleries between the MoS2 host layers. The composites exhibit good catalytic activities in the hydrogenation of nitrobenzene into aniline, due to their intercalated structures and great specific surface areas.

A series of polyester-based poly(urethane urea) (PUU) aqueous dispersions with well-defined hard segments were prepared from polyester polyol, 4,4'-diphenylmethane diisocyanate, dimethylolpropionic acid, 1,4-butanediol, isophorone diisocyanate, and ethylenediamine. These anionic-type aqueous dispersions had good dispersity in water and were stable at the ambient temperature for more than 1 year. For these aqueous dispersions, the particle size decreased as the hard-segment content increased, and the polydispersity index was very narrow (

A new hybrid organic–inorganic compound [Cd(en) 3 ]MoO 4 was prepared from the hydrothermal reaction of (NH 4 ) 6 Mo 7 O 24 ·4H 2 O, CdCl 2 ·2.5H 2 O, H 2 C 2 O 4 , ethylenediamine and H 2 O at 120 °C. The compound crystallizes in the trigonal system, space group P 3 ¯ c 1 with a =16.2087(14) A, c =9.8816(17) A, V =2248.3(5) A 3 , Z =6 and R 1=0.0240 for 1627 observed reflections. Single crystal X-ray diffraction revealed that the structure is composed of MoO 4 2− anions and [Cd(en) 3 ] 2+ complex cations, which are held together into a three-dimensional network via hydrogen-bonding interactions. The [Cd(en) 3 ] 2+ cations in the crystal structure exhibit two configurations, Λ ( δδδ ) and Δ ( λλλ ), as a pair of enantiomers due to the D 3 d symmetry. Other characterizations by elemental analysis, IR and thermal analysis are also described.

Cytokines have been implicated in pancreatic beta-cell destruction leading to type 1 diabetes. Exposure to interleukin-1beta (IL-1beta) of pancreatic beta-cells induces expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent formation of nitric oxide (NO) and prostaglandin E2 (PGE2) may impair beta-cell function. Using NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA), we have further investigated the relation between NO formation and COX-2 expression. IL-1beta stimulated the formation of NO and PGE2 by pancreatic beta-cells. L-NMMA completely inhibited IL-1beta-induced NO formation and attenuated PGE2 production. COX-2 gene transcription level and protein expression were determined by real-time PCR, Western blot and luciferase analysis. L-NMMA inhibited IL-1beta-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic beta-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic beta-cells. The identification of a novel interaction of NO on the COX signaling pathway in beta-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.

CA1 pyramidal neurons degenerate after transient global ischemia, whereas neurons in other regions of the hippocampus remain intact. A step in this selective injury is Ca 2+ and/or Zn 2+ entry through Ca 2+ -permeable AMPA receptor channels; reducing Ca 2+ permeability of AMPA receptors via expression of Ca 2+ -impermeable GluR2(R) channels or activation of CRE transcription in the hippocampus of adult rats in vivo using shutoff-deficient p SFV-based vectors rescues vulnerable CA1 pyramidal neurons from forebrain ischemic injury. Conversely, the induction of Ca 2+ and/or Zn 2+ influx through AMPA receptors by expressing functional Ca 2+ -permeable GluR2(Q) channels causes the postischemic degeneration of hippocampal granule neurons that otherwise are insensitive to ischemic insult. Thus, the AMPA receptor subunit GluR2 gates entry of Ca 2+ and/or Zn 2+ that leads to cell death following transient forebrain ischemia.

Up-conversion processes for the blue, green and red emissions were found two-photon phenomenon, known as the cooperative phenomenon. This phenomenon was assisted by Nd3+ → Yb3+ → Ho3+ energy transfer. The strong green emission due to the Ho3+ : (5F4, 5S2)→ 5I8 transitions was observed in Nd3+-Ho3+ co-doped ZrF4-based fluoride glasses under 800 nm excitation. As an attempt to enhance Ho3+ up-conversion luminescences in the Nd3+ – Ho3+ co-doped ZrF4-based glasses, Yb3+ ions were added to the glasses. As a result it was found that, in 800 nm excitation of 60 ZrF4. 30BaF2. (8-x)LaF3. lNdF3. xYbF3. 1HoF3 glasses (x=0 to 7), sensitized up-conversion luminescences are observed at around 490 nm (blue), 545 nm (green), and 650 nm (red), which correspond to the Ho3+ : 5F3 → 5I8, ( 5F4, 5S2)→5I8 and 5F5→ 5I8 transitions respectively. The intensities of the green and red emissions in a 3 mol % YbF3-containing glass were about 50 times stronger than those glasses without YbF3. This is based on sensitization due to Yb3+ ions. In particular, the green emission was extremely strong and the Nd3+-Yb3+-Ho3+ co-doped ZrF4-based glasses have a high possibility of realizing a green up-conversion laser glass. In this paper the up-conversion mechanism in the glasses is discussed in detail.