Carboxypeptidase E conditional knockout mice exhibit learning and memory deficits and neurodegeneration.

Carboxypeptidase E (CPE) is a multifunctional protein with many nonenzymatic functions in various systems. Previous studies using CPE knock-out mice have shown that CPE has neuroprotective effects against stress and is involved in learning and memory. However, the functions of CPE in neurons are still largely unknown. Here we used a Camk2a-Cre system to conditionally knockout CPE in neurons. The wild-type, CPEflox/-, and CPEflox/flox mice were weaned, ear-tagged, and tail clipped for genotyping at 3 weeks old, and they underwent open field, object recognition, Y-maze, and fear conditioning tests at 8 weeks old. The CPEflox/flox mice had normal body weight and glucose metabolism. The behavioral tests showed that CPEflox/flox mice had impaired learning and memory compared with wild-type and CPEflox/- mice. Surprisingly, the subiculum (Sub) region of CPEflox/flox mice was completely degenerated, unlike the CPE full knockout mice, which exhibit CA3 region neurodegeneration. In addition, doublecortin immunostaining suggested that neurogenesis in the dentate gyrus of the hippocampus was significantly reduced in CPEflox/flox mice. Interestingly, TrkB phosphorylation in the hippocampus was downregulated in CPEflox/flox mice, but brain-derived neurotrophic factor levels were not. In both the hippocampus and dorsal medial prefrontal cortex, we observed reduced MAP2 and GFAP expression in CPEflox/flox mice. Taken together, the results of this study demonstrate that specific neuronal CPE knockout leads to central nervous system dysfunction in mice, including learning and memory deficits, hippocampal Sub degeneration and impaired neurogenesis.

Highly crosslinking core-shell magnetic nanocomposites based catalyst and heat free polymerization for isolation of glycoprotein.

New approaches for the engineering of well-defined, pore modality, and multi-chemical functionality nanocomposites are crucial to generate the next generation of functional materials with recoverable and easy preparation properties. Here, a catalyst and heat free polymerization reaction is exploited and fabricated zwitterionic system around magnetic nanoparticles. N-aminoethyl piperazine propane sulfonate (AEPPS) and dopamine (DA) are introduced as the zwitterionic system, which provided abundant zwitterionic groups (NH2, SO3-, N+) and strong adhesion and various oxidation state properties. And that, the zwitterionic engineering will assemble between AEPPS and DA whereby Schiff base formation or Michael type addition. Whereafter, a series of sophisticated array of microscopic, spectroscopic, and structure techniques verify the formation of highly crosslinking internal zwitterionic architectures, well-defined core-shell structure, and better porosity. The zwitterionic structure-function relationships and striking porous structure are explored in a multi-interaction adsorption assay. The adsorption capacity of the magnetic nanocomposites was 1065.8 mg/g. And that, the system exhibited with hydrophilic-hydrophobic activity towards glycoprotein and better performance to bioactive protein (Ig-G) isolation form human whole blood sample. The synergistic enhancement interaction in hydrophilic target enrichment, easy preparation, and soft substrate properties of the AEPPS-DA zwitterionic materials make them intriguing candidates for sustainable biomedical loading and chromatographic separation.

Altered Peripheral Immune Profiles in First-Episode, Drug-Free Patients With Schizophrenia: Response to Antipsychotic Medications.

Previous research has demonstrated aberrations in the levels of inflammatory cytokines in patients with schizophrenia (SCZ), but most of the respective studies have tested a narrow set of inflammatory cytokines. Here, we aimed to analyze broad immune profiles in the peripheral blood of the first-episode drug-free (FEDF) patients with SCZ at baseline and after an 8-week treatment with atypical antipsychotics. Serum samples from 24 FEDF patients with SCZ and 25 healthy control (HC) subjects were tested using Luminex multiplex analysis for 30 cytokines, chemokines, and growth factors. Multiple comparison tests demonstrated that interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-γ), monokine induced by IFN-γ, and granulocyte colony-stimulating factor (G-CSF) levels were significantly increased, whereas those of the epidermal growth factor were significantly decreased in the FEDF patients with SCZ. Moreover, the levels of the 6 dysregulated cytokines as well as those of 12 additional soluble factors in FEDF patients with SCZ were significantly decreased after 8 weeks of antipsychotic treatment. Furthermore, the transcription of G-CSF and IFN-γ was significantly increased in FEDF patients with SCZ when compared with controls, and G-CSF and IFN-γ mRNA levels were highly correlated with their respective protein concentrations. Receiver operating characteristic curves showed that G-CSF and IFN-γ had good performance in differentiating between FEDF patients with SCZ and HC subjects. Taken together, our data revealed that FEDF patients with SCZ were accompanied by a unique pattern of immune profile, and antipsychotic medications seemed to suppress the immune function in these patients, which could be used to develop novel targets for the diagnosis and treatment of SCZ.

[Research progress on chemical constituents and pharmacological activities of seabuckthorn and prediction of its Q-markers].

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.

[Effects of soil matrix potential regulation at various growth states on cotton growth and soil water and salt distribution]. / 不同生育期土壤基质势调控对棉花生长和土壤水盐分布的影响.

Water shortage and soil salinization are two main limiting factors for cotton production in southern Xinjiang. We examined the effects of soil matrix potential (SMP) regulation at various growth stages on cotton growth, soil water and salt distribution, to provide theoretical basis for water saving, salts control, and efficient production in cotton fields. The mulched drip irrigation experiments were conducted to monitor cotton growth, aboveground biomass, cotton yield, soil water and salt distribution and other indicators. Three SMP thresholds, i.e.,W1(-20 kPa), W2(-30 kPa) and W3(-40 kPa) were set at the seedling stage (A), seedling stage + budding stage (B), and seedling stage + budding stage + flowering stage (C), with SMP of -50 kPa at 20 cm soil depth below the emitter as the CK. The results showed that plant height, leaf area index (LAI) and aboveground biomass followed the order of WC>WB>WA>CK, when SMP were changed at various growth stages. Plant height, LAI and aboveground biomass increased with increasing SMP thresholds, with the values under W1C and W2C being significantly higher than the other treatments. The effective bolls per plant, single boll weight and lint percentage all increased with the increases of SMP thresholds. The yields of W1C and W2C were similar, which were significantly higher than those of other treatments. However, the water use efficiency of W2C was significantly higher than that of W1C. Controlling the SMP threshold at -20 or -30 kPa at different growth stages could improve soil moisture status of the primary cotton root zone. All treatments presented shallow salt accumulation (0-40 cm) at the harvest stage, with the bare land having greater salt accumulation than the inner film. The higher the SMP threshold was, the less salt was accumulated in the primary root zone (0-40 cm) under film. The salt accumulation (0-40 cm) under W1C and W2C were reduced by 24% compared with other treatments. Considering the efficient production of cotton, water saving and salt control, it was recommended to maintain the SMP threshold of -30 kPa during irrigation at various growth stages in cotton fields without leaching salts during the local off-crop period.

[Metabolomics study of Danggui Buxue Tang on treatment of type 2 diabetes mice using UHPLC-Q-TOF-MS].

In this paper, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS)-based metabolomics approach was used to explore the mechanism of Danggui Buxue Tang(DBT) in treating type 2 diabetes mellitus(T2 DM). T2 DM mice model was induced by high-sugar and high-fat fodder and streptozotocin(STZ). The routine indexes such as body weight, blood glucose, plasma insulin, IL-6 and related organ indexes were determined. The UHPLC-Q-TOF-MS technique was used to analyze the metabolism profile of serum samples between the control group and model group, and multiple statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to screen and identify biomarkers. Metabolic profiling revealed 16 metabolites as the most potential biomarkers distinguishing mice in model group from those in control group. The metabolomics pathway analysis(MetPA) was used to investigate the underlying metabolic pathways. Seven major metabolic pathways such the valine, leucine and isoleucine biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, fatty acid metabolism and biosynthesis of unsaturated fatty acid. Eleven metabolites such as taurocholic acid and palmitic acid were down-regulated in T2 DM mice, and five metabolites such as L-leucine and leukotriene E4 were up-regulated. Moreover, the sixteen biomar-kers of each administration group had a trend of returning to mice in control group. The significantly-altered metabolite levels indicated that DBT can improve the progression of type 2 diabetes by increasing insulin sensitivity, regulating sugar and lipid metabolism disorders, and relieving inflammation.

[Heterogeneity and optimal sampe size of soil physicochemical properties in subtropical forest.] / äºšçƒ­å¸¦æ£®æž—åœŸå£¤ç†åŒ–æ€§è´¨çš„å¼‚è´¨æ€§å’Œæœ€ä½³å–æ ·é‡.

Selecting the optimal sample size accurately is important for improving the measurement precision of soil physicochemical properties. In this study, we examined the within-site heterogeneity of soil physical and chemical properties in an evergreen broad-leaved forest and a Chinese fir (Cunninghamia lanceolata) plantation in subtropical China. We applied both traditional and bootstrapping technique to determine the optimal sample size, the number of observation (n), for predicting soil nutrient content with an allowable error of 10% at a 95% confidence level for both forest types. The results showed that soil pH and C/N had low variation, while the soil nutrients had a moderate variation in both forests. The coefficients of variation (CV) of total element concentration in the evergreen broad-leaved forest, such as total carbon and total nitrogen, were significantly larger than those in the Chinese fir plantation, while the CVs of available nutrients were similar between two forests. The evaluation error of all soil properties in two forests showed a stable trend after a sharp decline with the increase of sample size. The mean values also changed from violent fluctuation to stable, and extravagant sample could not effectively improve the accuracy of mean value measurement. The sample sizes of soil water content, total carbon, total nitrogen, nitrate (NO3--N), total potassium, total calcium, and total magnesium in the evergreen broad-leaved forest were signifi-cantly larger than those in the Chinese fir plantation, while the sample size for ammonium (NH4+-N) showed opposite pattern, and the others had no significant difference. In addition, the sample sizes of different soil physicochemical properties varied significantly in the same forest. The available elements, such as NH4+-N and NO3--N, needed a larger sample size than total elements in both forests. Accordingly, we proposed that the heterogeneity and sample size of soil physicochemical properties should be considered before soil survey. An adequate sample size may be varied according to the purpose of sample and the site-specific variation of soil characters.

Thinning effect on photosynthesis depends on needle ages in a Chinese fir (Cunninghamia lanceolata) plantation.

Canopies in evergreen coniferous plantations often consist of various-aged needles. However, the effect of needle age on the photosynthetic responses to thinning remains ambiguous. Photosynthetic responses of different-aged needles to thinning were investigated in a Chinese fir (Cunninghamia lanceolata) plantation. A dual isotope approach [simultaneous measurements of stable carbon (δ13C) and oxygen (δ18O) isotopes] was employed to distinguish between biochemical and stomatal limitations to photosynthesis. Our results showed that increases in net photosynthesis rates upon thinning only occurred in the current-year and one-year-old needles, and not in the two- to four-year-old needles. The increased δ13C and declined δ18O in current year needles of trees from thinned stands indicated that both the photosynthetic capacity and stomatal conductance resulted in increasing photosynthesis. In one-year-old needles of trees from thinned stands, an increased needle δ13C and a constant needle δ18O were observed, indicating the photosynthetic capacity rather than stomatal conductance contributed to the increasing photosynthesis. The higher water-soluble nitrogen content in current-year and one-year-old needles in thinned trees also supported that the photosynthetic capacity plays an important role in the enhancement of photosynthesis. In contrast, the δ13C, δ18O and water-soluble nitrogen in the two- to four-year-old needles were not significantly different between the control and thinned trees. Thus, the thinning effect on photosynthesis depends on needle age in a Chinese fir plantation. Our results highlight that the different responses of different-aged needles to thinning have to be taken into account for understanding and modelling ecosystem responses to management, especially under the expected environmental changes in future.

Inhibition of Neuropathic Pain by a Single Intraperitoneal Injection of Diazepam in the Rat: Possible Role of Neurosteroids.

Diazepam binds with the same high affinity to the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor, which has been renamed translocator protein (TSPO). Both receptors could promote neurosteroid synthesis. In the present study, we investigated whether a single dose of diazepam could inhibit neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), and whether CBR and TSPO mediated this effect. We found that a single intraperitoneal injection of diazepam 9 d after L5 SNL significantly depressed the established mechanical allodynia and thermal hyperalgesia, which persisted until the end of the experiments. Furthermore, the effects were mimicked by a single intraperitoneal injection of Ro5-4864, a specific TSPO agonist and pregnenolone, a neurosteroid precursor. In addition, we found that the inhibitory effect of diazepam was also completely blocked by pretreatment with a specific CBR antagonist, flumazenil. The effects of diazepam or Ro5-4864 on neuropathic pain were completely blocked by pretreatment with a neurosteroid synthesis inhibitor, aminoglutethimide (AMG). Finally, any one of the three drugs, diazepam, Ro5-4864 and pregnenolone, could reduce the activation of astrocytes and the production of interleukin-1beta (IL-1ß) in the L5 spinal dorsal horn 14 d after L5 SNL. These results suggest that in addition to exerting effects on CBR, diazepam may inhibit neuropathic pain via TSPO, which promotes neurosteroid formation, subsequently reducing the activation of astrocytes and production of cytokines.

Hypolipidaemic effects of fenofibrate and fasting in the herbivorous grass carp ( Ctenopharyngodon idella) fed a high-fat diet.

We investigated whether the hypolipidaemic effect of fenofibrate and fasting observed in most omnivorous mammals may also apply to herbivorous fish. Grass carp (Ctenopharyngodon idella) fed a high-fat (8 %) diet exhibited a marked increase in blood lipids and body fat after 6 weeks. They were then treated with fenofibrate (100 mg/kg body weight) in the same high-fat diet for 2 weeks, followed by fasting for 1 week. Plasma lipid concentration, body fat amount, fatty acid composition, plasma thiobarbituric acid-reactive substances and some parameters related to hepatic fatty acid oxidation were measured, and liver samples were stained for histological examination. Fenofibrate treatment decreased TAG and cholesterol concentrations in plasma, total lipids of the whole body and liver, and EPA and DHA contents in tissues. Further, a mobilisation of mesenteric fat concomitant with an increase in hepatic peroxisomal fatty acid oxidation and lipid peroxidation was observed. Compared with fenofibrate treatment, fasting decreased body weight and plasma TAG, but not plasma cholesterol. It also reduced the fat content of the whole body and increased the EPA and DHA contents in the liver and other tissues. Fatty acid oxidation was stimulated by fasting in mitochondria, but not in peroxisomes. These data suggest that fenofibrate and fasting regulate the lipid metabolism in grass carp through different metabolic pathways. The grass carp is moderately responsive to a fibrate derivative in comparison with the well-known excess responsiveness of the rat model, and so it could be used for the study of lipid abnormalities as a herbivorous model.

Biochemical hepatic alterations and body lipid composition in the herbivorous grass carp (Ctenopharyngodon idella) fed high-fat diets.

High-fat diets may have favourable effects on growth of some carnivorous fish because of the protein-sparing effect of lipids, but high-fat diets also exert some negative impacts on flesh quality. The goal of the study was therefore to determine the effects of fat-enriched diets in juvenile grass carp (Ctenopharyngodon idella) as a typical herbivorous fish on growth and possible lipid metabolism alterations. Three isonitrogenous diets containing 2, 6 or 10 % of a mixture of lard, maize oil and fish oil (1:1:1, by weight) were applied to fish for 8 weeks in a recirculation system. Data show that feeding diets with increasing lipid levels resulted in lowered feed intake, decreased growth and feed efficiency, and increased mesenteric fat tissue weight. Concomitantly, alteration of lipoprotein synthesis and greater level of lipid peroxidation were apparent in blood. In liver, muscle and mesenteric fat tissue, the percentages of alpha-linolenic acid and DHA were significantly increased or tended to increase with higher dietary lipid levels. Biochemical activity measurements performed on liver showed that, with the increase in dietary lipid level, there was a decrease in both mitochondrial and peroxisomal fatty acid oxidation capacities, which might contribute, at least in part, to the specific accumulation of alpha-linolenic acid and DHA into cells more active in membrane building. On the whole, grass carp have difficulty in energetically utilising excess dietary fat, especially when enriched in n-3 PUFA that are susceptible to peroxidation.