New horizons for the role of selenium on cognitive function: advances and challenges.

Cognitive deficits associated with oxidative stress and the dysfunction of the central nervous system are present in some neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Selenium (Se), an essential microelement, exhibits cognition-associated functions through selenoproteins mainly owing to its antioxidant property. Due to the disproportionate distribution of Se in the soil, the amount of Se varies greatly in various foods, resulting in a large proportion of people with Se deficiency worldwide. Numerous cell and animal experiments demonstrate Se deficiency-induced cognitive deficits and Se supplementation-improved cognitive performances. However, human studies yield inconsistent results and the mechanism of Se in cognition still remains elusive, which hinder the further exploration of Se in human cognition. To address the urgent issue, the review summarizes Se-contained foods (plant-based foods, animal-based foods, and Se supplements), brain selenoproteins, mechanisms of Se in cognition (improvement of synaptic plasticity, regulation of Zn2+ level, inhibition of ferroptosis, modulation of autophagy and de novo synthesis of L-serine), and effects of Se on cognitive deficits, as well as consequently sheds light on great potentials of Se in the prevention and treatment of cognitive deficits.

Advances and challenges in serine in the central nervous system: physicochemistry, physiology, and pharmacology.

Neurological disorders are the primary cause of human disability and mortality globally, however, current medications slightly alleviate some symptoms of degenerative diseases. Serine is an important amino acid for the brain function and involved in a variety of biosynthetic pathways and signal transduction processes. The imbalance of serine metabolism is associated with neurodegeneration, including neuroinflammation, oxidative stress and apoptosis. Altered activities of serine metabolizing enzymes and accumulation of serine metabolites affect the survival and function of nerve cells. Abnormal serine levels are observed in animal models with neurological diseases, but not all human studies, therefore, the maintenance of serine homeostasis is a potentially therapeutic strategy for neurological disorders. To date, physiological and pharmacological roles of serine in neurological diseases have not been systemically recapitulated, and the association between serine and neurological diseases is controversial. In this review, we summarize physicochemical properties of serine, biological processes of serine in the brain (source, biotransformation, and transport), and the application of serine in neurological diseases including Alzheimer's disease, schizophrenia, and depression. Here, we highlight physicochemistry, physiology, pharmacology, and therapeutic potentials of serine in the prevention and treatment of neurological dysfunction. Our work provides valuable hints for future investigation that will lead to a comprehensive understanding of serine and its metabolism in cellular physiology and pharmacology. Although broad by necessity, the review helps researchers to understand great potentials of serine in the prevention and treatment of neurological dysfunction.

Selenium intake is an effective strategy for the improvement of cognitive decline in low cognition older Americans.

Age-related cognitive decline is a prominent concern in older adults and selenium (Se) deficiency has been found to be associated with cognitive deficits. For the first time, the present study explored the association between Se intake and cognitive performance in older people with/without cognitive impairment using the data from the National Health and Nutrition Examination Survey 2011-2014. Weighted linear regression models were conducted to evaluate the association between dietary Se/total Se intakes and cognitive assessments. A total of 2387 participants were included. The significant positive association between dietary Se/total Se intakes and total scores of cognitive functioning tests existed only in the older people with low cognitive performance (p < 0.001), not in those with normal cognitive performance. In conclusion, Se intake was beneficial for cognitive decline only in the low cognition older people but failed in normal cognition older people.

Investigation on water and air characteristics in Helicoidal Ramp Dropshafts.

Plunge dropshafts are widely used in urban drainage systems, but they can carry large amounts of air into the system, endangering the safety of the system. In this paper, a 3D numerical model is established to investigate the water flow configuration and air characteristics in a helicoidal ramp dropshaft. The simulations under different outlet pressures and water flow rates were simulated, and the results show that the air demand decreases with the increase of outlet pressure, especially in the case of low water flow. In the case of higher outlet pressure, the air demand first increases then decreases with the increase of the water flow rate. The dragging force of water has little effect on the pressure gradient in the dropshaft. The increase of ramp turns leads to the increase of terminal velocity at the same flow rate, and the air demand first increases and then decreases with the increase of ramp turns.

Numerical study on effects of chamber design and multi-inlet on storm geyser.

Storm geysers increasingly occur in sewer systems under climate change and rapid urbanization. Mitigation measures are in great demand to avoid safety problems. In this study, three-dimensional computational fluid dynamics models of single-inlet and multi-inlet systems were established to investigate geysering induced by rapid filling and assess the effectiveness of potential mitigation methods. The modeling results suggest that increasing the capacity of the downstream pipe before the inflow front reaches the chamber can effectively reduce the maximum geyser pressure. The peak pressure can be significantly mitigated when the chamber size is designed with care and the drop height between the upstream and downstream pipes is reduced. A diversion deflector with air vents and an orifice plate at the riser top end can alleviate the maximum pressure by about 65% with about 75% of the entrapped air being released. The peak pressure during the geyser event in the multi-inlet model is less than that of a single-inlet model under the same total inflow condition, but more water can be released.

Breast milk selenocystine as a biomarker for selenium intake in lactating women at differential geographical deficiency risk in China.

BACKGROUND AND OBJECTIVES: A reliable biomarker for optimal selenium (Se) intake in lactating women is not currently available. METHODS AND STUDY DESIGN: Daily dietary Se intake in lactating women was calculated from a 24-hour meal record survey for over 3 days. Se levels in plasma and breast milk were measured through inductively coupled plasma mass spectrometry. Plasma selenoprotein P 1 levels and glutathione peroxidase 3 activity were measured using an enzyme-linked immunosorbent assay. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze proteinaceous Se species in enzymatically digested breast milk. RESULTS: Dietary Se intakes of lactating women from Liangshan, Beijing, and Enshi were 41.6±21.2 ng/d, 51.1±22.6 ng/d, and 615±178 ng/d, respectively (p<0.05). The Se levels in the blood and breast milk were significantly associated with the dietary Se intake (p<0.05). The proteinaceous Se species in breast milk were SeMet and SeCys2. The levels of SeMet in the lactating women from Liangshan, Beijing, and Enshi were 3.31±2.44 ng Se/mL, 7.34±3.70 ng Se/mL, and 8.99±9.64 ng Se/mL, while that of SeCys2 were 13.7±12.0 ng Se/mL, 35.6±20.9 ng Se/mL, and 57.4±13.2 ng Se/mL, respectively. Notably, the concentration of SeCys2, the metabolite of unstable SeCys, reached a saturation platform, whereas no similar phenomenon were found for the total Se SeMet from Secontaining proteins. CONCLUSIONS: SeCys2 in breast milk is a potential biomarker for determining the optimal Se intake in lactating women.

Quantitative and Discriminative Evaluation of Contents of Phenolic and Flavonoid and Antioxidant Competence for Chinese Honeys from Different Botanical Origins.

Phenolics and flavonoids in honey are considered as the main phytonutrients which not only act as natural antioxidants, but can also be used as floral markers for honey identification. In this study, the chemical profiles of phenolics and flavonoids, antioxidant competences including total phenolic content, DPPH and ABTS assays and discrimination using chemometric analysis of various Chinese monofloral honeys from six botanical origins (acacia, Vitex, linden, rapeseed, Astragalus and Codonopsis) were examined. A reproducible and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was optimized and validated for the simultaneous determination of 38 phenolics, flavonoids and abscisic acid in honey. Formononetin, ononin, calycosin and calycosin-7-O-ß-d-glucoside were identified and quantified in honeys for the first time. Principal component analysis (PCA) showed obvious differences among the honey samples in three-dimensional space accounting for 72.63% of the total variance. Hierarchical cluster analysis (HCA) also revealed that the botanical origins of honey samples correlated with their phenolic and flavonoid contents. Partial least squares-discriminant analysis (PLS-DA) classification was performed to derive a model with high prediction ability. Orthogonal partial least squares-discriminant analysis (OPLS-DA) model was employed to identify markers specific to a particular honey type. The results indicated that Chinese honeys contained various and discriminative phenolics and flavonoids, as well as antioxidant competence from different botanical origins, which was an alternative approach to honey identification and nutritional evaluation.

[Identification of icaritin metabolites in rat plasma by UPLC-QTOF-MS].

OBJECTIVE: To identify metabolites of icaritin in rat plasma by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS). METHODS: Acetonitrile was employed to precipitate protein in rat plasma. The separation was carried out on a BEH C18 column (2.1 mm x 50 mm,1.7 microm) using a gradient mobile phase of acetonitrile, water and ammonium formate. High resolution mass spectrometry was applied for qualitative analysis in positive and negative ion modes, respectively. The metabolites were predicted by the PALLAS software and identified in the UNIFI database. RESULTS: Twenty-four metabolites of icaritin in rat plasma which were generated by reactions of hydroxylation, hydrogenation, epoxidation, acetylation, demethylation, dehydroxylation, sulfation conjugation, glucuronidation and glycosylation, were identified. CONCLUSION: A rapid and efficient UPLC-QTOF-MS method is established for the identification of icaritin metabolites in rat plasma, which provided support for the preclinical safety evaluation of icaritin.

[UPLC-MS / MS for the pharmacokinetics of icariin in rats].

OBJECTIVE: To establish an ultra-performance liquid chromatographytandem mass spectrometry( UPLC-MS / MS) method for the quantification of icariin( ICA), and investigate pharmacokinetics of ICA in rats following multiple oral administration. METHODS: ICA and an internal standard coumestrol( CMT) were extracted from rat plasma using ethyl acetate and separated on a BEH C18( 50 mm × 2. 1mm, 1. 7 µm) column using a gradient mobile phase of acetonitrile containing 0. 1%( V / V)formic acid and water containing 2 mmol / L ammonium formate at a flow rate of 0. 3m L / min. In negative electrospray ionization mode, multiple reaction monitoring of the precursor-product ion transitions of m / z 675. 6→351. 1 for ICA, 267. 0 →211. 1 for CMT was used for the quantification. Plasma was collected after rats were orally administered with ICA at multiple doses of 50 mg / kg. RESULTS: The linear calibration curve was achieved in a concentration range of 0. 5-50 ng / m L with a lower limit of quantification of0. 5 ng / m L. The value of intra- and inter-day precision was less than 11. 3% and accuracy fell in the ranges of 94. 3%-98. 7%. The recovery ranged from 81. 3% to85. 2% and the matrix effects from 94. 3% to 103. 2%. After oral administration of ICA to rats, t1 /2was( 1. 68 ± 0. 29) h, Cmaxwas( 29. 6 ± 5. 3) ng / m L, tmaxwas( 1. 00 ± 0. 00) h, AUC0- twas( 88. 4 ± 13. 9)( h·ng) / m L. CONCLUSION: The method is specific and accurate, suitable for preclinical pharmacokinetics of ICA.

[Determination of free selenomethionine in cow milk by UPLC-MS/MS].

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of free selenomethionine (SeMet), and be applied to the quantification of free SeMet in cow milk. METHODS: The analyte was separated on a BEH C18 column (2.1 mm x 100 mm, 1.7 µm) at 40 degrees C with a mobile phase of water: acetonitrile: formic acid (95: 5: 0.1, V/V) , a flow rate of 0.3 mL/min, and an analysis time of 2. 5 min. At positive electrospray ionization mode, multiple reaction monitoring of the precursor-product ion transitions of m/z 198.0 --> 181.1 was used for the quantification. RESULTS: The linear calibration curve was obtained in a concentration range of 0.5 - 100 ng/mL with a lower limit of quantification of 0.5 ng/mL. The value of intra- and inter-day accuracy for SeMet fell in the range of 97.6%-100.6% and 97.7%-99.2%, and value of intra- and inter-day precision 0.53%-4.49% and 1.03%-4.54%. CONCLUSION: The method is specific, sensitive, rapid, and accurate, suitable for the quantification of free SeMet in cow milk.

[Quantitative investigation of glucuronidated icaritin metabolite in rats].

OBJECTIVE: To establish an ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous quantification of icairitin(ICT) and its major metabolite glucuronidated icaritin (GICT), and investigate metabolism of ICT in rats following a single intraperitoneal administration. METHODS: ICT, GICT and an internal standard coumestrol (CMT) were extracted from rat plasma using acetonitrile and separated on a C18 column using a gradient mobile phase of acetonitrile, water, ammonium formate and formic acid. In the negative electrospray ionization mode, selected reaction monitoring of the precursor-product ion transitions of m/z 367.1 --> 297.1 for ICT, 543.3 --> 367.1 for GICT and 267.0 - 211.1 for CMT was used for the quantification. Plasma was collected for the determination of ICT and GICT after rats were intraperitoneally administered with ICT at a single dose of 10 mg/kg. RESULTS: The calibration curves were linear over the concentration range of 0.2 - 20 ng/ml for ICT and 2 -200 ng/ml for GICT with the respective lower limit of quantification at 0.2 and 2 ng/ml. The intra- and inter-day accuracy values fell in the range of 95.1 - 103.7%, and precisions were within 10.3%. Recovery and matrix effect were 89.1 - 92.4% and 93.2 - 104.2%, respectively. CONCLUSION: The UHPLC-MS/MS method was specific and accurate, suitable for the metabolism study of ICT. ICT was rapidly metabolized to GICT in rats.

[Tissue distribution of glucuronidated icaritin metabolite in rats].

OBJECTIVE: To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS )method for the quantification of glucuronidated icaritin (GICT), and investigate tissue distribution of GICT in rats following a single intraperitoneal administration. METHODS: Acetonitrile was employed to precipitate protein in tissue homogenate after rat tissues were homogenized. The separation was carried out on a BEH C18 column using a gradient mobile phase of acetonitrile, water, ammonium formate and formic acid. The quantification was achieved by the selected reaction monitoring in the negative electrospray ionization mode. Rat tissues were collected for the quantification of GICT after rats were intraperitoneally administered with ICT at a single dose of 10 mg/kg. RESULTS: The calibration curves were linear over the concentration range of 2-200 ng/ml with the lower limit of quantification of 2 ng/ml. The accuracy values at the levels of 5, 80 and 150 ng/ml fell in the range of 93.2-102.9%, and precisions were within 8.9%. CONCLUSION: The UHPLC-MS/MS method was specific and accurate, suitable for the tissue distribution of GICT. GICT was widely distributed in rat's various tissues, in which the content of GICT remained relatively high in kidney and liver, and GICT was reached the highest in tissues at 8 h.

[Inhibition of antisense VEGF gene on the growth of glioma cells BT325].

OBJECTIVE: To investigate the inhibitory effect of antisense VEGF gene on growth of human glioma BT325 and induced apoptosis in cells. METHODS: The pcDNA3.1/anti-VEGF eukaryotic expression vector was constructed and transfected into human glioma BT325. The ELISA assay was used to assess the expression of VEGF gene. Soft agar colony formation, MTT assay and electron microscope were used to evaluate the proliferation, apoptosis and the morphological changes of BT325. RESULTS: Compared with a control group, the level of VEGF expression was significantly decreased and was almost completely suppressed. The amount in soft agar colony at vector group and antisense VEGF gene group were 21 and 2, respectively. The growth of BT325 was significantly inhibited to 38.23% and resulted in the apoptotic morphology by antisense VEGF gene under electron microscope, compared to vector group. CONCLUSION: Antisense VEGF gene inhibited the growth and proliferation, induced cell apoptosis, played an efficient role of anti-cancer in BT325 cells.