Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

High-level production of nervonic acid in the oleaginous yeast Yarrowia lipolytica by systematic metabolic engineering.

Nervonic acid benefits the treatment of neurological diseases and the health of brain. In this study, we employed the oleaginous yeast Yarrowia lipolytica to overproduce nervonic acid oil by systematic metabolic engineering. First, the production of nervonic acid was dramatically improved by iterative expression of the genes ecoding ß-ketoacyl-CoA synthase CgKCS, fatty acid elongase gELOVL6 and desaturase MaOLE2. Second, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of glycerol-3-phosphate acyltransferases and diacylglycerol acyltransferases from Malania oleifera in endoplasmic reticulum (ER). Third, overexpression of a newly identified ER structure regulator gene YlINO2 led to a 39.3% increase in lipid production. Fourth, disruption of the AMP-activated S/T protein kinase gene SNF1 increased the ratio of nervonic acid to lignoceric acid by 61.6%. Next, pilot-scale fermentation using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L (17.9% of total fatty acids), the highest reported titer to date. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs).

[Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin].

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

[Determination and Traceability Analysis of Phthalic Acid Esters in Garlic (Allium stivum L.) from Jiangsu Province, China].

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg-1 and 0.167 mg·kg-1, respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 µg·kg-1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Enhancing microalgal lipid accumulation for biofuel production.

Microalgae have high lipid accumulation capacity, high growth rate and high photosynthetic efficiency which are considered as one of the most promising alternative sustainable feedstocks for producing lipid-based biofuels. However, commercialization feasibility of microalgal biofuel production is still conditioned to the high production cost. Enhancement of lipid accumulation in microalgae play a significant role in boosting the economics of biofuel production based on microalgal lipid. The major challenge of enhancing microalgal lipid accumulation lies in overcoming the trade-off between microalgal cell growth and lipid accumulation. Substantial approaches including genetic modifications of microalgal strains by metabolic engineering and process regulations of microalgae cultivation by integrating multiple optimization strategies widely applied in industrial microbiology have been investigated. In the present review, we critically discuss recent trends in the application of multiple molecular strategies to construct high performance microalgal strains by metabolic engineering and synergistic strategies of process optimization and stress operation to enhance microalgal lipid accumulation for biofuel production. Additionally, this review aims to emphasize the opportunities and challenges regarding scaled application of the strategic integration and its viability to make microalgal biofuel production a commercial reality in the near future.

Transition-metal-free three-component coupling approach to QUINAP derivatives.

The aluminum(III) triflate catalyzed three-component coupling reaction of alkynes, amines and phosphorylated aryl aldehydes to access phosphoryl quinoline derivatives has been developed. The reaction proceeds in a simple system without the use of transition metals, ligands or additives, thus making it attractive for the fast preparation of a variety of new potential N-P bidentate ligands.

Biodegradation of dibutyl phthalate by a novel endophytic Bacillus subtilis strain HB-T2 under in-vitro and in-vivo conditions.

The environmental prevalence and potential toxicity of dibutyl phthalate (DBP) motivate the attempt to develop feasible strategies to deal with DBP contamination. In this study, a strain of endphytic bacteria HB-T2 was isolated from sorrel roots and identified as Bacillus sp. by analysing its morphology, physiology, biochemistry and 16S rDNA sequence. The degradation efficiency of DBP by HB-T2 was almost identical under the temperature of 30∼40°C, but was significantly enhanced as the culture pH and inoculum size increases from 6.0 to 8.0, and 1% to 5% respectively. The degradation kinetics of DBP could be well described by the first-order kinetic model, with the degradation half-life ranging from 1.59 to 7.61 h when the initial concentrations of DBP were in the range of 5-20 mg/L. LC-MS analysis of the culture samples taken at varying intervals revealed monobutyl phthalate, phthalic acid and protocatechuic acid as the major metabolic intermediates during the degradation process. HB-T2 exhibited an excellent capability to degrade a wide range of phthalate esters (PAEs), especially butyl benzyl phthalate (BBP), dipentyl phthalate (DPP), and diisobutyl phthalate (DIBP). Inoculation of HB-T2 into Chinese cabbage (Brassica chinensis L.) growing in DBP-contaminated soils could significantly reduce the DBP levels in plant tissues and relieve the phytotoxic effects of DBP. Results of this study highlighted the great potential of this novel endophytic Bacillus subtilis strain HB-T2 for bioremediation of PAEs contamination and improvement of agricultural product safety by reducing PAEs accumulation in edible crops.

A capillary electrophoresis method for the determination of soluble monosaccharides in Ginkgo biloba leaves.

A method for the simultaneous determination of six monosaccharides by pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone and capillary electrophoresis was developed in this work. The derivatization (i.e., reaction temperature, capillary electrophoresis duration, and extraction number) and separation (i.e., pH and buffer concentration) conditions for capillary electrophoresis were optimized. Results showed that the limits of detection under optimal conditions were in the range of 0.036-0.35 mg/L with a mean correlation coefficient >0.99. The recoveries were in the range of 87.3-108.49%, and the relative standard deviations of intra- and inter-day variations were in the ranges of 2.2-3.8 and 3.2-5.0%, respectively. The method was successfully applied to the analysis of six free monosaccharides in three types of Ginkgo biloba leaves.

Cefoperazone sodium/sulbactam sodium vs piperacillin sodium/tazobactam sodium for treatment of respiratory tract infection in elderly patients.

BACKGROUND: Respiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life. AIM: To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODS: Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed. RESULTS: In the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 µg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 109/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 µg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 109/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 µg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 109/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 µg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 109/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708). CONCLUSION: Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.

Covalent organic frameworks with tunable pore sizes enhanced solid-phase microextraction direct ionization mass spectrometry for ultrasensitive and rapid analysis of tetrabromobisphenol A derivatives.

Selective adsorption via the size matching effect is one of the most effective strategies for separating and analyzing low levels of organic molecules. Herein, multicomponent covalent organic frameworks (MC-COFs) with tunable pore sizes are constructed by using one knot (1,3,5-triformylphloroglucinol, Tp) and two organic linkers (p-phenylenediamine, Pa; benzidine, BD). The pore sizes of the MC-COFs composed of TpPaBDX (X = [BD]/([Pa] + [BD]) × 100 = 0, 25, 50, 75, and 100) range from 0.5-1.5 to 0.5-2.2 nm due to variations in the initial organic linker ratios. When coupling TpPaBDX-based solid-phase microextraction (SPME) with constant flow desorption ionization mass spectrometry (CFDI-MS), these MC-COFs feature better selective adsorption performance for tetrabromobisphenol A (TBBPA) derivatives than TpPa with a smaller pore size, TpBD with a larger pore size and even some commercial fibers (e.g., polydimethylsiloxane/divinylbenzene (PDMS/DVB)-, polyacrylate (PA)- and PDMS-coated fibers). The improved method involving MC-COF TpPaBD50 also presents favorable stability with relative standard deviations (RSD, 1 µg L-1) for single fibers of 5.5-7.9% (n = 7) and fiber-to-fiber of 6.6-7.8% (n = 7). Due to the decreased limits of detection and quantification (0.5-12 and 1.6-40 ng L-1), and reduced separation and detection time (7 min), ultratrace levels of TBBPA derivatives in real water samples are successfully detected. The proposed method shows great potential for the rapid tracing of the distribution, transportation and transformation of TBBPA derivatives to better understand their ecotoxicological effects in environmental media.

Simultaneous Detection of Anions and Carbohydrates in Cyanobacteria by Two-Dimensional Ion Chromatography.

BACKGROUND: The simultaneous analysis of several anions and carbohydrates by one-dimensional chromatography with a single detector is often complicated by the presence of overlapping peaks. To overcome this problem, analytes are usually analyzed separately making analysis long and tedious. OBJECTIVE: A method combining two-dimensional ion chromatography (2D-IC) and valve switching was developed for the simultaneous determination of anions (F-, Cl-, NO2-, SO42-, NO3-, and PO43-) and carbohydrates (glycerin, glucosyl glycerol, trehalose, mannose, glucose, galactose, fructose, ribose, and sucrose) in cyanobacteria. METHOD: Interfering color compounds were removed by first passing the sample through graphitized carbon solid phase extraction (SPE) cartridges. Samples were applied to an AS11-HC column, which was used to separate the anions followed by quantification using a conductance detector. Carbohydrates eluted from the AS11-HC column were trapped and separated on a MA1 column and simultaneously quantified using electrochemical detection in the second dimension with valve switching. RESULTS: The following parameters were established: LOD, 0.001-0.030 (mg/L); LOQ, 0.001-0.010 (mg/L); linearity (R2), 0.9940; repeatability, 0.39-3.02%; and spiked recovery, 90.1-107%. CONCLUSIONS: The proposed method is adequately linear, accurate, and repeatable. The 2D-IC method provides fast, high-resolution, and completely automated procedure for the simultaneous determination of anions and carbohydrates without co-elution compared to the 1D ion chromatography method. This study provides application perspectives for use in biotechnology and other research fields. HIGHLIGHTS: An accurate and effective 2D-IC method was developed for determining anions and carbohydrates in cyanobacteria. The method includes pre-treating samples with graphitized carbon SPE cartridges.

Overcoming the Biological Contamination in Microalgae and Cyanobacteria Mass Cultivations for Photosynthetic Biofuel Production.

Microalgae and cyanobacteria have shown significant potential for the development of the next biofuels innovation because of their own characteristics as photosynthetic microorganisms. However, it is confronted with a lot of severe challenges on the economic scaling-up of the microalgae- and cyanobacteria-based biofuels production. One of these major challenges is the lack of a reliable preventing and controlling culture system of biological contamination, which can attack the cell growth or product accumulation causing crashing effects. To increase the commercial viability of microalgae- and cyanobacteria-based biofuels production, overcoming the biological contaminations should be at the top of the priority list. Here, we highlight the importance of two categories of biological contaminations and their controlling strategies in the mass cultivations of microalgae and cyanobacteria, and outline the directions that should be exploited in the future.

Effects of Genetic Background and Environmental Conditions on Amylopectin Chain-Length Distribution in a Recombinant Inbred Line of an Inter-subspecies Rice Cross.

Amylopectin is an essential starch property, and the chain-length distribution of amylopectin (APCLD) is closely associated with the eating and cooking quality of rice. In this study, a series of recombinant inbred lines derived from an indica/japonica cross were planted in four areas with distinct ecological conditions (LN, SC, JS, and GD), and the relationship among APCLD, environmental factors, and genetic background was analyzed. The results showed that APCLD was strongly influenced by environmental factors, which dynamically changed from heading to the mature stage. The solar radiation, luminous flux, and light hours were positively correlated with Fa but negatively correlated with Fb1 and Fb2. The temperature was negatively correlated with Fa and Fb1 but positively correlated with Fb2 and Fb3. The temperature was the primary factor affecting APCLD, followed by humidity and light. There was no significant correlation between the indica pedigree percentage and APCLD. Furthermore, we detected six quantitative trait loci related to Fa, Fb1, Fb2, and Fb3 chains, several of which shared a similar region to previously reported loci, including DENSE AND ERECT PANICLE 1 (DEP1). The truncated dep1 allele increased Fa, Fb2, and Fb3 but decreased Fb1 in LN, whereas Fa was decreased but Fb1 and Fb2 were increased in JS. Elucidating the effects of climate factors and genetic background on APCLD could provide a theoretical basis and technical guidance for high-quality rice breeding.

[Progress in separation and purification of nattokinase and its enzyme activity determination].

In this paper, the separation and purification of nattokinase have been reviewed by primarily focusing on solvent precipitation, adsorption column chromatography, magnetic microspheres, expanded bed, reverse micelle, and three-phase separation methods. The different methods for determination of the enzyme activity have been discussed and compared. Finally, the feasibility that the nucleic acid-based identification techniques can be used for nattokinase purification and enzyme activity assay has been proposed.

Signature MicroRNA expression profile is associated with lipid metabolism in African green monkey.

BACKGROUND: Non-human primates (NHPs) are important models of medical research on obesity and cardiovascular diseases. As two of the most commonly used NHPs, cynomolgus macaque (CM) and African green monkey (AGM) own different capacities in lipid metabolism of which the mechanism is unknown. This study investigated the expression profiles of lipid metabolism-related microRNAs (miRNAs) in CM and AGM and their possible roles in controlling lipid metabolism-related gene expression. METHODS: By small RNA deep sequencing, the plasma miRNA expression patterns of CM and AGM were compared. The lipid metabolism-related miRNAs were validated through quantitative reverse-transcription (RT) polymerase chain reaction (PCR). Related-target genes were predicted by TargetScan and validated in Vero cells. RESULTS: Compared to CM, 85 miRNAs were upregulated with over 1.5-fold change in AGM of which 12 miRNAs were related to lipid metabolism. miR-122, miR-9, miR-185, miR-182 exhibited the greatest fold changes(fold changes are 51.2, 3.8, 3.7, 3.3 respectively; all P < 0.01). And 77 miRNAs were downregulated with over 1.5-fold change in AGM of which 3, miR-370, miR-26, miR-128 (fold changes are 9.3, 1.8, 1.7 respectively; all P < 0.05) were related to lipid metabolism. The lipid metabolism-related gene targets were predicted by TargetScan and confirmed in the Vero cells. CONCLUSION: We report for the first time a circulating lipid metabolism-related miRNA profile for CM and AGM, which may add to knowledge of differences between these two non-human primate species and miRNAs' roles in lipid metabolism.

Simultaneous detection of anions and cations in mineral water by two dimensional ion chromatography.

A two dimensional ion chromatography (2D-IC) method was improved for the simultaneous determination of six cations and seven anions using one-valve switching after injection and conductivity detector. The trap conditions and valve-switch timing were optimized. The method has good accuracy and sensitivity for the simultaneous separation of inorganic anions and cations with a mean correlation coefficient of >0.99, repeatability of 0.60%-3.0% for eight replicates, reproducibility of 0.78%-3.1%, and spiked recovery rate of 88.7%-110%. The method was successfully applied to the analysis of inorganic anions and cations in four kinds of mineral water and can completely satisfy the demand of water quality monitoring.

Source Apportionment of Polycyclic Aromatic Hydrocarbons in Sediment by the Application of Non-Negative Factor Analysis: A Case Study of Dalian Bay.

An improved method, factor analysis with non-negative constraints (FA-NNC) was adopted to apportion the sources of sediment polycyclic aromatic hydrocarbons (PAHs) in Dalian Bay, China. Cosine similarity and Monte Carlo uncertainty analysis were used to assist the FA-NNC source resolution. The results identified three sources for PAHs, which were overall traffic, diesel engine emissions and residential coal combustion. The contributions of these sources were quantified as 78 ± 4.6% from overall traffic, 12 ± 3.2% from diesel engine emissions, and 10 ± 1.9% from residential coal combustion. The results from the Monte Carlo uncertainty analysis indicated that the model was robust and convergent.

Color and alcohol removal for the simultaneous detection of amino acids and sugars in wine by two-dimensional ion chromatography.

An effective pretreatment method for wine color removal by a PS-DVB SPE cartridge and online alcohol elimination by valve switching was presented. The optimum parameters for color removal were investigated: 40-µm and 100Å poly (styrene)-divinylbenzene (PS-DVB) (0.4g) was selected as the color removal material and 5mL of ethanol (10%) as the elution solvent for sample pretreatment under given condition. Moreover, an accurate and automated two-dimensional ion chromatography method for the simultaneous detection of amino acids and sugars was achieved with two valves after injection without alcohol interference. The method had a mean correlation coefficient of >0.99 and a repeatability of 0.92%-4.30% for eight replicates. The mean recovery of six red wine samples were 97.6%, 96.6%, 96.1%, 95.9%, 97.3% and 96.4% respectively. And this method successfully analyzed the amino acid and sugar contents of six wine samples of different origins.

HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.

OBJECTIVE: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions. METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes. RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10-15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10-5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association. CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.