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A new gold(i) self-relay catalysis consisting of a 3,3-rearrangement, Nazarov cyclization and Michael addition cascade of 1,3-enyne acetates with aurones and their derived azadienes is reported, producing functionalized cyclopentenones.

The high comorbidity between obesity and mental disorders, such as depression and anxiety, often exacerbates metabolic and neurological symptoms significantly. However, neural mechanisms that underlie reciprocal control of feeding and mental states are largely elusive. Here we report that melanocortin 4 receptor (MC4R) neurons located in the dorsal bed nucleus of the stria terminus (dBNST) engage in the regulation of mentally associated weight gain by receiving GABAergic projections from hypothalamic AgRP neurons onto α5-containing GABAAreceptors and serotonergic afferents onto 5-HT3receptors. Chronic treatment with a high-fat diet (HFD) significantly blunts the hyperexcitability of AgRP neurons in response to not only hunger but also anxiety and depression-like stimuli. Such HFD-mediated desensitization reduces GABAergic outputs from AgRP neurons to downstream MC4RdBNSTneurons, resulting in severe mental dysregulation. Genetic enhancement of the GABAAR-α5 or suppression of the 5-HT3R within the MC4RdBNSTneurons not only abolishes HFD-induced anxiety and depression but also robustly reduces body weight by suppression of food intake. To gain further translational insights, we revealed that combined treatment of zonisamide (enhancing the GABAAR-α5 signaling) and granisetron (a selective 5-HT3R antagonist) alleviates mental dysfunction and yields a robust reversal of diet-induced obesity by reducing total calorie intake and altering food preference towards a healthy low-fat diet. Our results unveil a neural mechanism for reciprocal control of appetite and mental states, which culminates in a novel zonisamide-granisetron cocktail therapy for potential tackling the psychosis-obesity comorbidity.

Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders., Neuronal signaling has an important role in the regulation of energy expenditure and body weight, however, the underlying mechanisms are incompletely understood. Here, the authors report a AgRP-MC4R-serotonin expressing neuronal circuit that regulate energy expenditure without affecting feeding.

Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here, neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI–inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.

Clinical studies have highlighted an association between retinoid treatment and depressive symptoms. As we had shown before that chronic application of all-trans retinoic acid (RA) potently activated the hypothalamus-pituitary-adrenal (HPA) stress axis, we here questioned whether RA also induced changes in adult hippocampal neurogenesis, a form of structural plasticity sensitive to stress and implicated in aspects of depression and hippocampal function. RA was applied intracerebroventricularly (i.c.v.) to adult rats for 19 days after which animals were subjected to tests for depressive-like behavior (sucrose preference) and spatial learning and memory (water maze) performance. On day 27, adult hippocampal neurogenesis and astrogliosis was quantified using BrdU (newborn cell survival), PCNA (proliferation), doublecortin (DCX; neuronal differentiation), and GFAP (astrocytes) as markers. RA was found to increase retinoic acid receptor-α (RAR-α) protein expression in the hippocampus, suggesting an activation of RA-induced signaling mechanisms. RA further potently suppressed cell proliferation, newborn cell survival as well as neurogenesis, but not astrogliosis. These structural plasticity changes were significantly correlated with scores for anhedonia, a core symptom of depression, but not with water maze performance. Our results suggest that RA-induced impairments in hippocampal neurogenesis correlate with depression-like symptoms but not with spatial learning and memory in this design. Thus, manipulations aimed to enhance neurogenesis may help ameliorate emotional aspects of RA-associated mood disorders. © 2016 Wiley Periodicals, Inc.

Adjacent segment degeneration (ASD) is known to occur after anterior cervical arthrodesis. However, it is not known whether cervical canal stenosis enhances the risk of ASD. The purpose of this study was to explore whether congenital stenosis could be used as a predictor of ASD after anterior cervical decompression and fusion (ACDF). We enrolled 141 patients who had undergone ACDF for cervical myelopathy and/or radiculopathy, and had at least 6 years of follow-up. In standard radiographs of cervical spine in lateral view, bony congenital stenosis was evaluated and all patients were divided into two groups: stenosis (n = 63) and non-stenosis (n = 78). Radiographic ASD was assessed according to the criteria of Kellgren and Lawrence and correlated with symptomatic ASD. Clinical and radiological parameters were compared between the groups. The primary outcome was the rate of radiographic ASD after initial ACDF. The incidence of symptomatic ASD was assessed by Kaplan–Meier method. Radiographic ASD and symptomatic ASD developed in 46.8 % and 18.4 % of all patients, respectively. There was a significant association between congenital stenosis and radiographic ASD. The area under the receiver operating characteristic curve of preoperative anteroposterior (AP) diameter of cervical canal for predicting radiographic ASD was 0.756. 13.0 mm was the cutoff value of preoperative AP diameter of cervical canal predicting radiographic ASD. Kaplan–Meier analysis predicted a disease-free survival rate of symptomatic ASD in 97.2 % of patients at 5 years and 78.0 % at 10 years after ACDF. There was no significant difference in survival rates of the adjacent segment between the two groups via log-rank analysis (P = 0.102). Congenital stenosis can increase the rate of radiographic ASD after initial ACDF. The cutoff value of 13.0 mm for preoperative AP diameter of cervical canal had the highest validity for predicting radiographic ASD.

Land ecological security research has gradually become concerned field on global. Using on the Haba Snow Mountain as an example try to discuss the evaluation of ecological security based on change of the landscape ecological pattern in the paper. In GIS, RS and GPS support and accordance with the principles of landscape ecology and using new grid map method has been 1993 and 2006 Haba Snow Mountain ecological safety evaluation and space differentiation. There are temperate coniferous forest, grassland, sclerophyll broad-leaved forest, warm coniferous forest, water area, residential land, semi-humid evergreen broad-leaved forest, ice and snow land nine landscape types, and temperate coniferous forest and grassland are dominant landscape in the study area, both area has accounted about 67% of the total area. The results show that from 1993 to 2006 the whole landscape pattern has changed less in the area. Land ecological security level space differentiation is very obvious. Ecological security level high altitude area is superior to low altitude area, the core area is superior to the edge area, north area is superior to the southern area. Land ecological security in the study area whole is in good level. From 1993 to 2006 years land ecological security level has declined in the area. Research on ecological safety planning to provide basis for ecological safety planning and for similar high mountain canyon area also has reference value.

AlN-SiC ceramics were prepared at 1950°C by hot pressing (HP) of AlN/SiC powders in stoichiometric proportion. The sintered product was characterized using X-ray diffraction (XRD). Scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS) were utilized to investigate the morphology characteristics. The results show that AlN-SiC phase is well-developed with a close and lamellar structure. The grains are plate-like with the size of 1-3μm, the thickness of 3-5μm and elongated dimension. The results showed that the products had the density of 99 percent of the theoretical, bending strength of 550-800 MPa and fracture toughness of 5-6 MPa·m1/2. The distribution of AlN-SiC grains is relatively uniform.

sothermal oxidation behavior of the AlN-TiB2 conductive ceramics prepared by self-propagating high-temperature synthesis and hot isostatic pressing (SHS-HIP) was evaluated in a temperature range from 900 to 1400 °C for exposure times from 1 to 16 h in air. The oxidation experimental results show that the conductive ceramics have a good oxidation resistance below 1200 °C. The oxidation products on the sample surfaces are mainly composed of Al2TiO5, TiO2 and aluminum borate phases.

Distress in mass concrete is a problem in highway and bridge engineering. These mass concrete structures craze not by external loads, the temperature variation caused by heat of hydration and the temperature stress caused by concrete shrinkage are the main causes () for the leaks [1]. Therefore, the thermal stress and the temperature control have significant meaning in the mass concrete structures. Thermal cracks will break the structure globality and also decrease the durability of the structures during the construction time. In addition, the temperature variation will have a remarkable affection on the stresses variation of the structures during the service time [2]. This paper will discuss the temperature monitoring and the crack control projects of the mass concrete based on the cushion cap of an extradosed cable-stayed bridge which is being constructed.

Summary Objective To investigate the association between smoking and the risk for knee osteoarthritis (OA). Design Cohort, case–control, and cross-sectional studies were obtained from the Medline, Embase, and Web of Science databases. Estimates were calculated using a random-effects model. Subgroup analyses and meta-regression models were performed to investigate potential sources of heterogeneity. We further analyzed the dose–response relationship between cigarette consumption and risk of knee OA. Results Thirty-eight independent observational studies that included 481,744 participants were analyzed. Those who had ever smoked had a significantly decreased risk of developing knee OA relative to those who had never smoked (RR = 0.80; 95% CI 0.73–0.88). This was unaffected by study design, and the pooled relative risks (RRs) were 0.79 (95% CI, 0.65–0.96), 0.71 (95% CI, 0.61–0.84) and 0.83 (95% CI, 0.73–0.94) for cohort, case–control, and cross-sectional studies, respectively. Analysis of subgroups stratified by gender reduced the heterogeneity from moderate to low in both males and females. The lower risk for developing knee OA was more apparent in male smokers (RR = 0.69; 95% CI 0.58–0.80) than female smokers (RR = 0.89; 95% CI 0.77–1.02) and dose–response analysis showed a linear decrease in knee OA with increased cigarette consumption. Conclusions We found an inverse association between cigarette smoking and risk of knee OA, irrespective of study design. This association was more apparent in males. However, we have not demonstrated a causal relationship between smoking and OA, and further investigations are needed.

Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

Chemical vapor deposition (CVD) is an effective method of preparing silicon carbide whiskers or films and chemical vapor infiltration (CVI) can be successfully used as the preparation of SiC composites. In this paper, silicon carbides whiskers were firstly deposited on substrates of RB-SiC by CVD process and then silicon carbide composites were prepared by chemical vapor infiltration in the SiC whiskers in an upright chemical vapor deposition furnace of Φ150mm×450mm with methyltrichloride silicane (MTS) as precursor gas, H2 as carrier gas and Ar as dilute gas. The morphologies of the SiC whiskers grown on RB-SiC substrate and SiC composites infiltrated in SiC whiskers were determined by scanning electron microscope (SEM), and the crystalline phase of the final deposits were confirmed with X-ray diffractometry (XRD) As a result, the curly defects of whiskers decrease with the addition of dilute gas. And by chemical vapor infiltration in SiC whiskers the, SiC composites were successfully prepared. Finally the deposits were determined as β-SiC.

Previous studies have demonstrated that apolipoprotein E (ApoE) genotype and melatonin are closely associated with Alzheimer's disease (AD). However, the relationship between ApoE genotype and melatonin remains unclear. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In the current study, we investigated the effect of ApoE genotype on melatonin biosynthesis. C6 cells with stable expression of ApoE isoforms (ApoE 2, 3 and 4) were established. A higher level of melatonin was demonstrated in cultured ApoE4-C6 cells than that in ApoE3-C6 cells. In addition, we found that N-acetyltransferase (NAT) protein level was up-regulated in ApoE4-C6 cells compared with ApoE3-C6 cells. Further study suggested that mRNA expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) decreased in ApoE4-C6 cells. In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin.

One of the world natural heritage Three Parallel Rivers core region Yunnan Baima snow mountain national nature reserve as the study area, on the basis of full consideration natural and social factors of reserve, we have established the ecology risk evaluation index system and model in the study area, and has put forward type alpine canyon regional ecological risk assessment of the theory and technical route. We have evaluated risk of the area, and obtained distribution of the risk degrees, and replenished alpine canyon type area demonstration for regional ecological risk assessment. Based on the ecological risk assessment, we put forward the ecological planning in the study area.

OBJECTIVE Letrozole, a next-generation aromatase inhibitor, has become a favored drug for the treatment of breast cancer in postmenopausal women. Although letrozole is generally well tolerated, its adverse effects on the central nervous system have been reported. The present study aimed to assess the behavioural outcomes of letrozole administration in mice to determine its side effects. METHODS C57BL/6J female ovariectomized mice received administration of letrozole (2.5 mg/kg per day) or vehicle by gavage for 3 weeks. Behavioural tasks were used to assess anxiety, depression, as well as learning and memory in mice. RESULTS Letrozole-treated mice showed an increased latency to enter the inner area of the chamber on the third day of the open field test, and traveled a shorter distance in the open arms of the elevated plus maze. No significant difference was found in the light-dark box or forced swimming task between letrozole-treated and vehicle-treated mice. Besides, letrozole did not change the spontaneous alternation behaviour of mice in the Y-maze. In the Morris water maze, mice administered with letrozole exhibited an improvement in spatial learning and memory compared with the vehicle-treated mice. CONCLUSION Our results indicate that the inhibition of oestrogen biosynthesis results in mild anxious behaviour, which may be a consideration in the treatment of breast cancer in postmenopausal women using aromatase inhibitors.

Three new solid ternary lanthanide complexes of [Ln(2-Cl-4-FBA) 3 phen] 2 (Ln = Eu 3+ (1), Tb 3+ (2), Ho 3+ (3), 2-Cl-4-FBA = 2-chloro-4-fluorobenzoate, phen = 1,10-phenanthroline) were synthesized and characterized by means of elemental analysis, IR and UV spectra and XRD. The complexes 1 and 2 emit bright red and green luminescence respectively under the excitation ultraviolet light at room temperature. Thermal analyses of the three complexes were discussed by TG–DTG and IR techniques. The heat capacities of the complexes were measured from 259.15 to 493.02 K by means of Differential scanning calorimetry (DSC). The relationship of the molar heat capacities varying with the reduced temperature ( x ) ( x = [ T − ( T max + T min )/2]/[( T max − T min )/2]) was fitted to a polynomial equation with the least-squares method for each complex. Finally, the derived thermodynamic functions ( H T − H 298.15 ), ( S T − S 298.15 ) and ( G T − G 298.15 ) of the complexes relative to the standard reference temperature 298.15 K were also obtained on the base of the fitted polynomials and thermodynamic relationships.

Flexible polymer stamps are considered as an attractive alternative to rigid, brittle and expensive stamps made of inorganic materials because of their low cost and ease of fabrication. In this paper, we present a nanoimprint process to fabricate large area, high-resolution nanograting patterns using flexible polymer stamp made from fluoropolymer. The flexibility and low surface energy of polymer stamp provide a clean release without fracture or deformation of the stamp and of the replicated nanograting. Large-area, high-density nanograting patterns with good shape homogeneity and size uniformity have been successfully fabricated using the flexible polymer stamp with advantages of its good conformal contact and low adhesion. Using flexible polymer stamps can resolve many serious issues in NIL and therefore can bring it to real industrial applications.

Three lanthanide complexes with a general formula [Ln(2,3-DClBA) 3 phen] 2 (Ln(III) = Eu(1), Tb(2), Ho(3); 2,3-DClBA = 2,3-dichlorobenzoate; phen = 1,10-phenanthroline) were synthesized and characterized by elemental analysis, molar conductance, infrared and ultraviolet spectra and powder X-ray diffraction (XRD). The luminescent properties of the complexes 1 and 2 were studied. The thermal behaviors of the complexes were also discussed by thermogravimetric (TG), differential thermogravimetric (DTG) and infrared spectra (IR) techniques. The heat capacities of the complexes were measured from 259.15 to 493.02 K by means of Differential scanning calorimeter (DSC). The dependence of heat capacity on the reduce temperature x ( x = [ T − ( T max + T min )/2]/[( T max − T min )/2]) was fitted to a polynomial equation with the least squares method for each complex. Furthermore, based on the fitted polynomial, the smoothed heat capacities and the derived thermodynamic functions ( H T − H 298.15 K ), ( S T − S 298.15 K ) and ( G T − G 298.15 K ) in the measured temperature range were obtained with an interval of 10 K.

Silicon carbide prepared by chemical vapor deposition (CVD) is one of the important candidate materials for space mirror and high-power mirror such as laser mirror, because of its superior performances such as low density, high melting point and homogeneity. In this paper, the SiC coatings were deposited on the substrates of reaction bonded silicon carbide (RB-SiC) by CVD process. Then, the morphologies of the deposits were examined with scanning electron microscopy. The crystalline phase of the as-deposited films was confirmed with X-ray diffractometry. And the adhesion between the CVD film and the substrate was rated with scraping method. As a result, the morphologies of the deposits, i.e. whiskers at 1050°C or films at 1100°C, are different from that of the substrate. And the mean diameter of the deposits at 1100°C is larger than that at 1050°C. Furthermore, the crystalline phase of the as-deposited film is determined as β-SiC and the adhesion is firm enough not to be peeled off with the scraping test.

In the version of this article initially published, the Simons Foundation was missing from the list of sources of support to P.T.T. in the Acknowledgments. The error has been corrected in the HTML and PDF versions of the article.

Previous studies reported that environmental enrichment might induce various beneficial effects in the central nervous system. However, the effect of environmental factors on endogenous estrogen level was not investigated. The present study was designed to examine the effect of enriched environment on endogenous estrogen in hippocampus and behavioral outcomes.Behavioural measurements, including open field, elevated plus maze and Morris water maze, were used to evaluate anxiety and learning and memory of the male C57BL/6J mice that were housed in enriched environment for five months. In addition, the estrogen and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were measured.We found that environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. In addition, the mice raised in enriched environment showed decreased endogenous estrogen levels both in the hippocampus and plasma compared to controls. Furthermore, our results indicated that environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus.In conclusion, environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. Lastly, environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus and decreased plasma estrogen level. The possible mechanism remained to be determined.

The association between intramedullary increased signal intensity (ISI) on T2-weighted magnetic resonance imaging and surgical outcome in cervical spondylotic myelopathy (CSM) remains controversial. The purpose of this study is to assess the impact of quantitative signal change ratio (SCR) on the surgical outcome for CSM. The prospective study included 108 consecutive patients who underwent surgical treatment for CSM. The Japanese Orthopaedic Association (JOA) score and recovery rate were used to evaluate clinical outcomes. JOA recovery rate less than 50 % was defined as a poor clinical result. The SCR was defined as the signal intensity at the level of ISI or severely compressed cord (in cases with no ISI) divided by the signal intensity at the C7–T1 disc level. Age, sex, body mass index, duration of symptoms, surgical technique, preoperative JOA score, levels of compression, preoperative SCR, preoperative C2–7 angle, preoperative C2–7 range of motion were assessed. Forty patients (37.0 %) had a recovery rate of less than 50 %. Multivariate logistic regression analysis revealed that a higher preoperative SCR and a longer duration of symptoms were significant risk factors for a poor clinical outcome. Receiver operating characteristic (ROC) curve analysis showed that the optimal preoperative SCR cutoff value as a predictor of poor clinical result was 1.46. The area under the ROC curve of preoperative SCR for predicting a poor surgical outcome was 0.844. Preoperative SCR significantly reflected the surgical outcome in patients with CSM. Patients with SCR greater than or equal to 1.46 can experience poor recovery after surgery.

The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.

Relatively Uniform-sized biodegradable poly(lactide) (PLA) microcapsules were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and multiple emulsion-solvent evaporation method. An aqueous phase containing lysozyme was used as the internal water phase (w1), and PLA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores (5.25 microm) of an SPG membrane into the external water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. Then, the solid polymer microcapsules were obtained by simply evaporating the solvent. It is necessary to avoid the phase separation of primary emulsion during the SPG membrane emulsification. It was found that when the density difference of the internal water phase and oil phase was reduced to nearly zero and Arlacel 83 was used as the oil emulsifier, the phase separation was not observed within 24 h. The w1/o/w2 emulsion with uniform diameter was obtained only when Arlaecl 83 concentration was limited below 2.5 wt.% based on oil phase. The drug encapsulation efficiency was found to be related to several factors including PLA molecular weight, additive type and its concentration in the internal water phase, the emulsifier type and concentration in the oil phase, the NaCl concentration and the pH value in the external water phase. Comparing with the stirring method, it was found that the size was more uniform and the drug encapsulation efficiency was much higher when the microcapsules were prepared by SPG membrane emulsification technique and the highest drug encapsulation efficiency of 92.20% was obtained. This is the first study to prepare PLA microcapsules by combining an SPG membrane emulsification technique and multiple emulsion-solvent evaporation method.

Elderly females, particularly those carrying the apolipoprotein E (ApoE)-e4 allele, have a higher risk of developing Alzheimer's disease (AD). However, the underlying mechanism for this increased susceptibility remains unclear. In this study, we investigated the effects of the ApoE genotype and gender on the proteome of synaptosomes. We isolated synaptosomes and used label-free quantitative proteomics, to report, for the first time, that the synaptosomal proteomic profiles in the cortex of female human-ApoE4 mice exhibited significantly reduced expression of proteins related to energy metabolism, which was accompanied by increased levels of oxidative stress. In addition, we also first demonstrated that the proteomic response in synaptic termini was more susceptible than that in the soma to the adverse effects induced by genders and genotypes. This suggests that synaptic mitochondria might be 'older' than mitochondria in the soma of neurons; therefore, they might contain increased cumulative damage from oxidative stress. Furthermore, female human-ApoE4 mice had much lower oestrogen levels in the cortex and treatment with oestrogen protected ApoE3 stable transfected C6 neurons from oxidative stress. Overall, this study reveals complex ApoE- and gender-dependent effects on synaptic function and also provides a basis for future studies of candidates based on specific pathways involved in the pathogenesis of AD. The lack of oestrogen-mediated protection regulated by the ApoE genotype led to synaptic mitochondrial dysfunction and increased oxidative stress, which might make older females more susceptible to AD.

Silicon carbide is one of the best materials for satellite mirror and chemical vapor deposition (CVD) is an effective method of preparing SiC whiskers and films. In this paper, SiC whiskers or films were deposited on substrates of RB-SiC in an upright chemical vapor deposition furnace of Φ150mm × 450 mm with methyltrichloride silicane (MTS) as precursor gas and H2 as carrier gas under dilute gases of different H2/Ar ratio and different deposition temperature between 1050°C and 1150°C. The morphology and composition of the CVD-SiC grown on RB-SiC substrate were determined by scanning electron microscope (SEM) and X-ray diffraction (XRD) respectively. As a result, whisker-like, worm-like or ball-like SiC can be respectively obtained dependent on different deposition conditions such as H2/Ar ratio and deposition temperature, and the composition of the productions are determined as β-SiC by XRD. Furthermore, the deposition mechanisms of different morphologies of SiC are introduced.

Melatonin not only plays an important role in regulating circadian rhythms, but is also involved in antioxidative defense and immunomodulation. Circulating melatonin levels are derived primarily from the pineal gland while other sources of melatonin have also been reported. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In addition, apolipoprotein E genotype influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells.Here, we investigated the expression of genes and enzymes that is responsible for the multistep conversion of tryptophan to serotonin and further to melatonin in mouse embryonic fibroblasts NIH3T3 cells by radioimmunoassay, Immunofluorescence staining, real-time PCR and Western blotting techniques.Our results showed that cultured NIH3T3 cells could synthesize melatonin and serotonin. Serotonin N-acetyltransferase (NAT), the key enzyme in the pathway of melatonin synthesis, was also detectable using both by western blot and PCR methods. In addition, two other key enzymes, tryptophan hydroxylase (TPH1 and TPH2) for serotonin synthesis and the metabolic enzyme monoamine oxidase A (MAOA) for 5-HT, were present in NIH3T3 cell line.In conclusion, we provided evidence that the NIH3T3 cells can synthesize intrinsic serotonin and melatonin and express key enzymes related biosynthetic pathways.

Previous studies have demonstrated that apolipoprotein E (ApoE) genotype and melatonin are closely associated with Alzheimer's disease (AD). However, the relationship between ApoE genotype and melatonin remains unclear. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In the current study, we investigated the effect of ApoE genotype on melatonin biosynthesis. C6 cells with stable expression of ApoE isoforms (ApoE 2, 3 and 4) were established. A higher level of melatonin was demonstrated in cultured ApoE4-C6 cells than that in ApoE3-C6 cells. In addition, we found that N-acetyltransferase (NAT) protein level was up-regulated in ApoE4-C6 cells compared with ApoE3-C6 cells. Further study suggested that mRNA expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) decreased in ApoE4-C6 cells. In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin.

Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47–80 years) and 825 (young group, aged 15–25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P = 0.008, P = 0.002, and P = 0.023, respectively). One-way ANOVA analysis revealed that the ApoE genotype was significantly associated with age at natural menopause (ANM; P = 0.010). Compared with ApoE e3/3 carriers, ApoE e3/4 females showed a 1.8-year delay in ANM (P = 0.002). Single ApoE allele-positive/allele-negative analysis also showed that the age at menopause of ApoE e4 carriers was delayed compared with those who were not carriers (P = 0.023). In the young group, no statistical difference was found in the age of menarche between the carriers of ApoE e3/3 and e3/4. Single ApoE allele-positive/allele-negative analysis showed that the age at menarche in ApoE e4 carriers was slightly earlier than in those who were not carriers (P = 0.048). Meanwhile, univariate association analysis revealed that the ApoE genotypes were not significantly associated with the age at menarche using age as a covariate in the pooled group (young + elderly) (P = 0.143). We demonstrated that the ApoE genotype is significantly linked to the age at natural menopause.

The effect of SUMO on the promoter activity and mRNA expression of BACE gene was investigated to find the connection between sumoylation and APP processing.The BACE promoter activity was measured by reporter gene analysis and BACE mRNA level was investigated using real-time RT-PCR method.BACE gene promoter activity was inhibited by the over-expression of SUMO proteins and was blocked by disrupting the SP1 site. Endogenous BACE mRNA level was also negatively regulated by the induction of SUMO proteins. Using a specific inhitor of SP1, BACE promoter activity was coordinately inhibited.SUMO negatively regulates the BACE expression and SP1 is involved in the process.

Tau phosphorylation and hypoxia are both linked to the pathology of Alzheimer's disease. To find out the possible connection between hypoxia and tau phosphorylation, we performed this study to evaluate the level of phosphorylated tau under hypoxic or normal condition. We found in our study that hypoxia promoted the phosphorylation of tau protein via ERK pathway, which suggest hypoxia might be involved in the process of tau pathology.

Methoxypoly (ethylene glycol)- block-poly (DL-lactide) (PELA) microcapsules containing bovine hemoglobin (BHb) were prepared by a W/O/W double emulsion-solvent diffusion process. The P50 and Hill coeffcient were 3466 Pa and 2.4 respectively, which were near to the natural bioactivity of bovine hemoglobin. The results suggested that polymer composition had significant influence on encapsulation efficiency and particle size of microcapsules. The encapsulation efficiency could reach 90% and the particle size 3 - 5 microm when the PELA copolymer containing MPEG 2000 block was used. The encapsulation efficiency and particle size increased with the concentration of PELA. Increasing the concentrations of NaCl in outer aqueous solution resulted in the increase of encapsulation efficiency and the decrease of particle size. As the concentration of stabilizer in outer aqueous solution increased in the range of 10 g/L to 20 g/L, the particle size reduced while encapsulation efficiency was increased, further increase of the stabilizer concentration would decrease encapsulation efficiency. Increasing of primary emulsion stirring rate was advantageous to the improvement of encapsulation efficiency though it had little influence on the particle size. The influence of re-emulsion stirring rate was complicated, which was not apparent in the case of large volume of re-emulsion solution. When the wall polymer and primary emulsion stirring rate were fixed, the encapsulation efficiency decreased as the particle size reduced.

Monomethoxypoly (ethylene glycol)-b-poly(DL-lactide) copolymer (PELA) microparticles loading lysozyme were prepared through a modified W/O/W double emulsion-solvent diffusion method using ethyl acetate (EA) as organic solvent. The modified process was divided into five steps: (1) primary emulsification (W-1/O), (2) re-emulsification (W-1/O/W-2), (3) pre-solidification, (4) solidification and (5) purification. The pre-solidification step was carried out in the modified process to control the diffusion rate of EA from oil phase into outer aqueous phase, in order to prevent the wall polymer from precipitation, which usually occurred when the diffusion rate was too fast. The adequately rapid solidification of microparticle caused by controlled fast diffusion of EA and the use of amphiphilic copolymer PELA as wall material, facilitated a high protein entrapment (always above 94%) and full preservation of bioactivity of entrapped lysozyme. It was found that the volume of the outer aqueous phase in the re-emulsification step and the shear stress in the pre-solidification step had a significant effect on the diffusion rate of EA from the droplets into outer aqueous solution, and thereby on the characteristics of the resultant microparticles. With the volume or the shear stress increasing, the removal rate of EA increased, resulting in rapid solidification of the microparticles. This result led to a lower burst effect and a slower lysozyme release from the microparticles. This study suggests that the modified W/O/W double emulsion-solvent diffusion method with EA as organic solvent is a prospective technique to prepare biodegradable microparticles containing water-soluble sensitive agents. (C) 2003 Elsevier B.V. All rights reserved.

Methoxypoly(ethylene glycol)-b-poly-DL-lactide (PELA) microcapsules containing bovine hemoglobin (bHb) were prepared by a W/O/W double emulsion-solvent diffusion process. bHb solution was used as the internal aqueous phase, PELA/organic solvent as the oil phase, and polyvinyl alcohol (PVA) solution as the external aqueous phase. This W/O/W double emulsion was added into a large volume of water (solidification solution) to allow organic solvent to diffuse into water. The optimum preparative condition for PELA microcapsules loaded with bovine hemoglobin was investigated. It was found that homogenization rate, type of organic solvent, and volume of the solidification solution influenced the activity of bovine hemoglobin encapsulated. When the homogenization rate was lower than 9000 rpm and ethyl acetate was used as the organic solvent, there was no significant influence on the activity of hemoglobin. High homogenization rate as 12 000 rpm decreased the P50 and Hill coefficient. Increasing the volume of solidification solution had an effect of improving the activity of microencapsulated hemoglobin. The composition of the PELA had the most important influence on the success of encapsulation. Microcapsules fabricated by PELA with MPEG2k block (molecular weight of MPEG block: 2000) achieved a high entrapment efficiency of 90%, better than PL A homopolymer and PELA with MPEG5k blocks. Hemoglobin microcapsules with native loading oxygen activity (P50 = 26.0 mmHg, Hill coefficient = 2.4), mean size of about 10 microm, and high entrapment efficiency (ca. 93%) were obtained at the optimum condition.

A method of preparing methoxypoly (ethylene glycol)-poly-DL-lactide (PELA) microcapsule containing bovine hemoglobin(BHb) by using W/O/W double emulsion-solvent diffusion process for use as artificial red cells was developed. The results suggested that preparation conditions such as solidification method, stirring rate, type of organic solvent had significant influence on the encapsulation efficiency and the activity of bovine hemoglobin. When ethyl acetate was used as the organic solvent and double emulsion-solvent diffusion process was used, there was no significant influence on the activity of hemoglobin if stirring rate was lower than 9000 r/min. High stirring rate, 12,000 r/min, decreased the P(50) and Hill coefficient of the hemoglobin encapsulated. Increasing the volume of solidification solution had an effect of improving the activity of hemoglobin to carry oxygen.

A simple and efficient method for the synthesis of carboxymethylated polyethylene glycol (CM-PEG) by the oxidation of the corresponding monomethoxy polyethylene glycol (mPEG) with catalytic amounts of TEMPO and hypobromide as a regenerating oxidant and water as solvent was developed.