Brainstem dominant form of X-linked adrenoleukodystrophy with a novel ABCD1 missense variant: A case report and literature review.

BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder attributed to ABCD1 mutations. Case reports with predominant brainstem involvement are rare. CASE PRESENTATION: In this study, we reported a plateau male worker of X-ALD characterized by progressive weakness accompanied by gait instability, mild nystagmus, and constipation. After 2 years of onset, a brain Magnetic Resonance Image (MRI) scan showed no abnormality but genetic analysis revealed a heterozygous mutation (c.1534G>A) in the ABCD1 gene. After 7 years of onset, although the patient was given aggressive dietary and symptomatic treatment in the course of the disease, a brain MRI scan showed predominantly brainstem damage, but serum concentrations of very long-chain fatty acids were normal, and he had been bedridden for almost 2 years with severe bladder dysfunction, forcing him to undergo cystostomy. The patient was discharged with improved urinary retention and renal function. CONCLUSIONS: We reported an X-ALD patient with a novel ABCD1 variation characterized by brainstem damage and retrospectively summarized the clinical manifestation, MRI features, and genetic features of X-ALD patients with brainstem damage.

Effect of SO2, glutathione, and glutathione-rich inactive dry yeast on the color, phenolic compounds, ascorbic acid, and antioxidant activity of Roxburgh rose wine.

Conventional methods for inhibiting browning in wine are not suitable for cili (Roxburgh rose) wine, which is naturally rich in ascorbic acid and subject to restrictions on SO2 addition. In this study, the capacity of various additives to suppress the browning of cili wine caused by ascorbic acid degradation was investigated. SO2, pure reduced glutathione (GSH), regular inactive dry yeast (IDY), and IDY with various levels of glutathione enrichment (g-IDY) were separately introduced into cili wine following the completion of alcoholic fermentation. Over a period of 12 months, the color parameters, levels of ascorbic acid, phenolic compounds, antioxidant activity, and GSH content of the aged cili wine were analyzed. Among the investigated additives, g-IDY exhibited the strongest inhibitory effect on browning. Moreover, adding 800 mg L-1 g-IDY increased the total reducing power and residual GSH content by factors of 1.52 and 2.44, respectively, with respect to those of the SO2-treated cili wine, thus enhancing its antioxidant capacity. Using ultra-performance liquid chromatography-tandem mass spectrometry analysis, a total of 22 monomeric phenolic compounds were identified. After g-IDY treatment, the contents of 15 easily oxidizable o-diphenols decreased, preventing the depletion of ascorbic acid as an antioxidant. As a result, the levels of ascorbic acid and total phenolics were 1.5-fold and 1.17-fold higher than those in the SO2-treated wine, respectively. This study demonstrates that g-IDY provides a new approach to preventing the browning of wine caused by ascorbic acid degradation. PRACTICAL APPLICATION: Cili wine, characterized by its high ascorbic acid content, can decelerate cellular senescence and bolster immune function, which has contributed to its popularity. Ascorbic acid, a potent antioxidant, can be spiked into white wines to significantly enhance their antioxidative properties. Nevertheless, the high ascorbic acid content in cili wine renders it susceptible to oxidation under both aerobic and anaerobic conditions, which alters the wine's hue from golden to dark brown, thus diminishing its commercial value. Overcoming this browning associated with ascorbic acid degradation is therefore of considerable importance and could facilitate the advancement of the cili industry.

Transcriptomics combined with metabolisms reveals the effect of light-exclusive films on the quality and polyphenols of 'Cabernet Sauvignon' grapes.

The grape quality might be affected if the solar intensity (SI) was too strong. In this study, the influence of light-exclusive films on the transcriptomic properties and metabolic substances of grapes were evaluated. The results showed that films, especially polycarbonate (PC), could significantly decrease the SI. The sugar content was obviously decreased, while the acid content was increased. The anthocyanin content was decreased, in contrast to the total polyphenols, flavonoids and tannins. The corresponding derivatives owned the same trend. Lots of differentially expressed genes (DEGs) were detected, especially under PC. The expression pattern and GO function enrichment of DEGs from PC significantly differed from other groups. DEGs enrichment also proved that films, especially PC, could significantly improve the contents of tannins, flavonoids and other polyphenols. VvUFGT, VvF3'5'H, VvLDOX, VvLAR1 and VvANR were confirmed to be the key genes in the biosynthetic pathway of polyphenols under different films.

Revealing the Pathogenesis of Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats through Integrated Multi-Omics Analysis.

Salt-induced renal metabolism dysfunction is an important mechanism of salt-sensitive hypertension. Given that the gut-liver axis is the first hit of a high-salt diet (HSD), we aimed to identify the extra-renal mechanism from hepatic metabolism and gut microbiota, and attempted to relieve the salt-induced metabolic dysfunctions by curcumin. Untargeted metabolomics analysis was performed to identify the changes in hepatic metabolic pathways, and integrated analysis was employed to reveal the relationship between hepatic metabolic dysfunction and gut microbial composition. HSD induced significant increase in fumaric acid, l-lactic acid, creatinine, l-alanine, glycine, and l-cysteine levels, and amino acids metabolism pathways associated with glycolysis were significantly altered, including alanine, aspartate, and glutamate metabolism; glycine, serine, and threonine metabolism, which were involved in the regulation of blood pressure. Integrated multi-omics analysis revealed that changes in Paraprevotella, Erysipelotrichaceae, and genera from Clostridiales are associated with metabolic disorders. Gene functional predication analysis based on 16S Ribosomal RNA sequences showed that the dysfunction in hepatic metabolism were correlated with enhanced lipopolysaccharide (LPS) biosynthesis and apoptosis in gut microbes. Curcumin (50 mg/kg/d) might reduce gut microbes-associated LPS biosynthesis and apoptosis, partially reverse metabolic dysfunction, ameliorate renal oxidative stress, and protect against salt-sensitive hypertension.

Physiological and transcriptomic analysis of Cabernet Sauvginon (Vitis vinifera L.) reveals the alleviating effect of exogenous strigolactones on the response of grapevine to drought stress.

Drought stress can significantly affect the growth and yield of grapevine. The application of exogenous strigolactone can relieve the drought symptoms of grapevine; however, little is known about the transcription levels in grapevine under drought stress following exogenous strigolactone application. The mitigative effect of exogenous strigolactone on grapevine leaves under drought stress was studied by transcriptome analysis based on RNA sequencing. On the 10th day of drought stress, the strigolactone treatment group had a higher relative water content and lower electrical conductivity, which significantly alleviated the drought damage. Compared to the drought (D) group, a total of 5955 differentially expressed genes (DEGs) (2966 up-regulated genes and 2989 down-regulated genes) were detected in the exogenous strigolactone (DG) groups. Based on Gene Ontology analysis, the DEGs in the D and DG treatments were enriched in the processes of photosynthesis and organic acid catabolism. Pathway analysis showed that the DEGs in the D and DG treatments were enriched in carbon metabolism, ribosome, starch and sucrose metabolism, flavonoid biosynthesis, and circadian rhythm. Additionally, in the DG group, the antioxidant enzyme genes of CAT1, GSHPX1, GSHPX2, POD42, APX6, and SODCP were up-regulated, two NAC, three WRKY, and four MYB transcription factor genes were down-regulated, and the key gene of strigolactone synthesis D14 was up-regulated, compared with that in the D group. The results provide a new perspective for studying the adaptation of plants to drought stress.

Effect of foliar application of fulvic acid antitranspirant on sugar accumulation, phenolic profiles and aroma qualities of Cabernet Sauvignon and Riesling grapes and wines.

This study investigated the effects of foliar application of fulvic acid antitranspirant (FA-AT) on Cabernet Sauvignon (CS) and Riesling grapes and wines in a warm viticulture region of China. FA-AT controlled the contents of total soluble solids, fructose and glucose in mature grapes and alcohol in wines. FA-AT improved total phenols and flavonoids in Riesling grapes, and total tannin and individual flavanols in CS grapes and wine, while reducing total individual phenolic acids and flavonols in CS wine. Increased volatiles in CS grapes (hexyl acetate, linalool) and wine (isoamyl alcohol, 1-hexanol, 2-phenylethanol) detected by SPME-GC-MS can contribute to the fruity and floral aroma. FA-AT reduced the accumulation of anthocyanins in CS grapes and wine without an eventual reduction in the tonality of wine by sensory analysis, and improved the taste and balance of Riesling wine. Overall, FA-AT can improve the quality of grapes and wines produced in warm viticulture regions.

Using the Chou's 5-steps rule, transient overexpression technique, subcellular location, and bioinformatic analysis to verify the function of Vitis vinifera O-methyltranferase 3 (VvOMT3) protein.

3-Isobutyl-2-methoxypyrazine (IBMP) is an important odor compound that revives unripe grapes or poor-quality wine. The biosynthesis of IBMP in grape berries is under the catalysis of Vitis vinifera O-methyltranferase 3 (VvOMT3). The homologous verification in this paper was carried out with the transient overexpression technique. The results showed that both the expression levels of the VvOMT3 gene and the IBMP concentration in 'Red globe' grapes increased significantly, which suggested that VvOMT3 could function in the biosynthesis of IBMP. Based on ß-glucuronidase (GUS) staining results, blue color was only observed in grape pulp, not in grape skin, which indicated that VvOMT3 was expressed in grape pulp. The outcomes of the subcellular location examination performed on the protoplasts of Arabidopsis thaliana showed that the VvOMT3 protein was located on the inner surface of the cytoplasmic membrane. In summary, the VvOMT3 enzyme may function at the inner surface of the cytoplasmic membrane of pulp cells during grape development. These results will provide a background for future research on the catalytic mechanisms of VvOMT3.

Overexpression of grapevine VvNAC08 enhances drought tolerance in transgenic Arabidopsis.

NAC [No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)] transcription factors (TFs) play an important role in plant growth and response to various environmental stress. Drought stress is the primary factor limiting the growth and fruit quality of grapevines worldwide. However, the biological function of the NAC family members in grapevine is not clear. In this study, we reported that VvNAC08, a novel NAC transcription factor gene, was expressed after drought, salicylic acid (SA) and abscisic acid (ABA), jasmonic acid (JA) and melatonin (MT) treatments in grapevine. VvNAC08 was expressed in various tissues. The open reading frame (ORF) of VvNAC08 was 792 bp, encoding 263 amino acids. The VvNAC08 protein could bind to NACRS [CGTA/CACG] in yeast. When subjected to drought and dehydration stress, VvNAC08-overexpression (OE) Arabidopsis had a higher survival rate and a lower water loss rate than wild type (WT) plants. Under drought conditions, transgenic Arabidopsis overexpressing VvNAC08 had a lower malondialdehyde (MDA), H2O2 contents, but a higher peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) activities as well as more proline content. Moreover, the expressions of marker genes, including ABI5, AREB1, COR15A, COR47, P5CS, RD22, and RD29A, were up-regulated in VvNAC08-overexpression lines when subjected to drought treatments. The results suggest that the transgenic Arabidopsis overexpressing VvNAC08 enhances resistance to drought while up-regulating the expressions of ABA- and stress-related genes.

VvNAC17, a novel stress-responsive grapevine (Vitis vinifera L.) NAC transcription factor, increases sensitivity to abscisic acid and enhances salinity, freezing, and drought tolerance in transgenic Arabidopsis.

Drought stress is the primary factor limiting the growth and fruit quality of grapevines worldwide. However, the biological function of the NAC [No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)] transcription factor (TF) in grapevine is not clear. In this study, we reported that VvNAC17, a novel NAC transcription factor, was expressed in various tissues following drought, high temperature (45 °C), freezing (4 °C), salicylic acid (SA), and abscisic acid (ABA) treatments in grapevine. The VvNAC17 protein was localized in the nucleus of Arabidopsis thaliana protoplasts and demonstrated transcriptional activation activities at its C-terminus in yeast. The VvNAC17 gene was overexpressed in Arabidopsis thaliana. Under mannitol and salt stress, the germination rates of the VvNAC17-overexpression lines were higher than those of the wild-type plants, as were the root lengths. The VvNAC17-overexpression lines showed greater tolerance to freezing stress along with a higher survival rate. Following ABA treatment, the seed germination rate and the root length of the VvNAC17-overexpression lines were inhibited, and the stomatal opening and stomatal density were reduced. When subjected to drought and dehydration stress, the VvNAC17-overexpression lines showed improved survival and reduced water loss rates in comparison to the wild-type plants. Under drought conditions, the VvNAC17-overexpression lines had lower malondialdehyde and H2O2 contents, but higher peroxidase, superoxide dismutase, and catalase activities as well as higher proline content. Moreover, the expression of marker genes, including ABI5, AREB1, COR15A, COR47, P5CS, RD22, and RD29A, was up-regulated in the VvNAC17-overexpression lines when subjected to ABA and drought treatments. The results suggest that in transgenic Arabidopsis over-expression of VvNAC17 enhances resistance to drought while up-regulating the expression of ABA- and stress-related genes.

Investigation on seroprevalence of Toxoplasma gondii infections among neonates in Fujian Province / 中国血吸虫病防治杂志

Objective To investigate the seroprevalence of Toxoplasma gondii infections among neonates in Fujian Province, so as to provide insights into the development of interventions for the prevention and control of congenital toxoplasmosis. Methods A total of 1 045 neonates delivered in Fujian Province from 2017 to 2018 were recruited, including 387 preterm infants and 658 full-term infants. Umbilical cord blood was sampled from all neonates, and the seroprevalence of anti-T. gondii IgG antibody was detected and compared between preterm and full-term infants. In addition, elbow venous blood samples were collected from neonates’mothers, and the seroprevalence of anti-T. gondii IgG antibody was detected and compared between preterm and full-term infants’mothers. Results The overall seroprevalence of anti-T. gondii IgG antibody was 9.38% among the 1 045 neonates in Fujian Province. The seroprevalence of anti-T. gondii IgG antibody was 18.35% in the 387 preterm infants, and there was no significant difference in the seroprevalence of anti-T. gondii IgG antibody between male and female infants (17.69% vs. 18.75%, χ2 = 0.07, P > 0.05). The seroprevalence of anti-T. gondii IgG antibody was 4.10% in the 658 full-term infants, and there was no significant difference in the seroprevalence of anti-T. gondii IgG antibody between male and female infants (4.14% vs. 4.08%, χ2 = 0, P > 0.05). In addition, the overall seroprevalence of anti-T. gondii IgG antibody was 15.02% in all neonates’ mothers, and the seroprevalence was significantly greater in preterm infants’mothers than in full-term infant’s mothers (20.93% vs. 11.55%, χ2 = 16.79, P < 0.01). Conclusions The seroprevalence of T. gondii infections is significantly higher in preterm infants and their mothers than in full-term infants and their mothers. Prenatal detection of T. gondii infections and health education pertaining to toxoplasmosis prevention and control knowledge are required to be strengthened to effectively reduce the incidence of congenital toxoplasmosis.

Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology.

Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cell from oxidative stress. The antioxidant activity suggests that MSRB2 may play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, MSRB2 protein levels were decreased in the hippocampus at both young (6 mon) and old (18 mon) age, and in the cortex only at an old age, respectively. In HEK293 cells that stably express human full-length ß-amyloid precursor protein (APP, HEK/APP), MSRB2 reduced the protein and mRNA levels of APP and ß-amyloid converting enzyme 1 (BACE1), and the consequent amyloid beta peptide (Aß) 1-40 and Aß1-42 levels. MSRB2 overexpression or knockdown also oppositely affected Tau phosphorylation at selective sites, with the concomitant alteration of the phosphorylated extracellular signal regulated kinase (p-ERK) and AMP-activated protein kinase (p-AMPK) levels. Moreover, in cells treated with long-term (24 h) hydrogen peroxide, the alterations of APP processing and Tau phosphorylation were reversed by MSRB2 overexpression. We further found that MSRB2-mediated regulation of APP transcription involved JNK and ERK signaling, as MSRB2 also reduced the levels of phosphorylated JNK (p-JNK), and JNK or ERK inhibitor attenuated the effect of MSRB2 on APP proteins and transcripts. Finally, MSRB2 reduced apoptosis-related proteins Bax and caspase3 and enhanced the anti-apoptotic protein Bcl2. These results indicated that the role for MSRB2 in AD-like pathology was closely associated with its antioxidant activity. By attenuating both amyloidogenesis and Tau phosphorylation, MSRB2 may serve as a potential therapeutic target for AD.

Efficient Display of Aspergillus niger ß-Glucosidase on Saccharomyces cerevisiae Cell Wall for Aroma Enhancement in Wine.

The aim of this study was to evaluate the potential application of cell-surface-displayed ß-glucosidase (BGL) in wine aroma enhancement. Gene cassettes for the surface display of Aspergillus niger BGL were constructed using different promoters ( GPD and SED1) and glycosylphosphatidylinositol (GPI) anchoring regions (Sag1, Sed1, and Cwp2). The differences in surface-display cassettes, the tolerance of the displayed BGL to typical winemaking conditions, and the hydrolysis capacity for the liberation of grape aroma glycosides were analyzed. Results revealed that simultaneous utilization of GPD promoter and Sed1 anchoring domain achieved the highest BGL activity. The displayed BGL exhibited relatively high activity at pH 3.0 and at glucose concentration below 2.5% (w/v), compared to commercial enzyme (AR 2000), but exhibited no significant difference under varying ethanol concentrations. Furthermore, the surface-displayed BGL presented better ability to release free terpenols compared to AR 2000. Therefore, a surface-display system could provide a new viable solution for enhancing wine aroma.

Identification and expression analysis of ERECTA family genes in grape (Vitis vinifera L.).

BACKGROUND: ERECTA family (ERf) genes are found in many dicots and monocots, and play important roles in plant developmental processes and stress responses. However, there is little known on ERf genes in grape (Vitis vinifera L.). OBJECTIVES: The primary objective of this study was to identify the ERf genes in grape, and to analyze their expression profiles in different organs, during development, and in response to hormone treatments and abiotic/biotic stresses. METHODS: ERf protein sequences of dicots were aligned in the grape genome (V. vinifera cv. Pinot Noir, PN40024, 12X) with Blast server. The locus tags obtained were inputted in NCBI to retrieve corresponding nucleotide and protein accession numbers. The subcellular localization experiment was performed by the transient expression of VvERECTA-GFP and VvERL2-GFP in mesophyll protoplasts of Arabidopsis. The expression levels of ERf genes in grape leaves were detected by qRT-PCR after hormone treatments and abiotic/biotic stresses. RESULTS: We first identified the ERf genes in the grape genome, including VvERECTA and VvERL2. Their cDNA full-length sequences were obtained with the accession numbers MG601756 and MG601757. The result of subcellular localization indicated that the fusion proteins of VvERECTA and VvERL2 were localized in the plasma membrane. There were four conserved domains identified in VvERECTA and VvERL2, including a LRRNT-2, a LRR, a transmembrane and a protein kinase domain. The grape ERf genes expressed highly in young aboveground organs. As grape leaves or berries becoming mature, VvERECTA expressed in a declining trend. The transcript abundance of VvERL2 decreased during leaves development, but showed no significant differences during berries development. The hormone treatments of ABA, SA, MeJA and BR could induce the expression of VvERECTA and VvERL2. The treatments of heat, drought, downy and powdery mildew significantly increased the expression levels of the grape ERf genes. CONCLUSION: The grape ERECTA gene family might play crucial roles in response to abiotic and biotic stresses. We provide the first description of the grape ERf genes and the most comprehensive analysis of their expressions in different biological processes.

Anthocyanin accumulation and biosynthesis are modulated by regulated deficit irrigation in Cabernet Sauvignon (Vitis Vinifera L.) grapes and wines.

Anthocyanins contents and compositions play an important role in grape berries and wines. Grapevines are widely cultivated in arid and semi-arid areas, and water shortage restricts the development of wine industry. The aim of this work was to gain insight on the effect of regulated deficit irrigation (RDI) on the accumulation and biosynthesis of anthocyanins in Cabernet Sauvignon (Vitis Vinifera L.) grapes and wines. High-performance liquid chromatography (HPLC) was used for anthocyanins profiles analyses and real-time quantitative PCR (qRT-PCR) was used for the genes expressions measurement. The grapevines were treated with 60% (RDI-1), 70% (RDI-2), 80% (RDI-3), 100% (CK, traditional drip irrigation) of their estimated evapotranspiration (ETc) respectively. RDI treatments significantly reduced titration acid and increased pH with higher total soluble solids. RDI-1 treatment increased total anthocyanins contents in berries and wines in both two vintages. RDI-1 and RDI-2 treatments significantly increased the contents of acylated anthocyanins in berries and wines, especially Malvidin-3-acetly-glucoside. RDI treatments significantly increased non-acylated anthocyanins contents in wines, such as Delphinidin-3-gliucoside and Malvidin-3-glucoside. RDI treatments upregulated the expressions of VvPAL, VvC4H, VvCHS, VvF3'H, VvF3'5'H, VvLDOX, and VvOMT in both two vintages. Correlation analysis showed the accumulation of anthocyanins was closely related to the key genes expressions, including VvPAL, VvF3'H, VvF3'5'H etc. The present results provided direct evidence and detailed data to explain that RDI treatments regulated the accumulation of anthocyanins by regulating genes expressions in the anthocyanin synthesis pathway.

Alleviation of drought stress in grapevine by foliar-applied strigolactones.

Drought is one of the major abiotic stress factors that affect grape growth and yield, which in turn negatively affects the grape and wine production industry. Developing effective approaches to improve grapevine tolerance to drought stress is a priority for viticulture. Strigolactones, a newly discovered class of carotenoid-derived phytohormones, have been found to participate in various physiological processes. Herein, the effect of strigolactones (SLs) on grape seedlings under drought stress was investigated. Two-year-old grape seedlings (Vitis vinifera L.) were sprayed with 3 doses of rac-GR24 (1 µM, 3 µM and 5 µM), a synthesized strigolactone, and then were subjected to 7% (w/v) polyethylene glycol (PEG-6000) to simulate the drought conditions. Synthetic GR24 treated plants showed higher tolerance to drought stress with regard to lower electrolyte leakage, stomatal opening, reactive oxygen species (ROS), and higher relative water content, chlorophyll content, photosynthesis rate and malondialdehyde (MDA) content. GR24 application also decreased the levels of indoleacetic acid (IAA) and zeatin riboside (ZR), while increasing the level of abscisic acid (ABA), both in the roots and leaves under drought stress. These results suggested that foliar application of GR24 could ameliorate the adverse effects of drought due to its regulation of stomatal closure through ABA or ROS, and modulation of chlorophyll components and photosynthesis, as well as activation of the antioxidant defense capacity. Cross-talk with other hormones, especially ABA, was also suggested to be one of the important mechanism during this process. This study contributes to our current understanding of GR24-induced drought tolerance in grapevines.

Preliminary observation and analysis of the characteristics of gut microbiota in patients with schizophrenia / 中国神经精神疾病杂志

Objective To investigate the characteristics of gut microbiota in patients with schizophrenia. Methods The composition of the fecal microbiota in 16 schizophrenia patients and 20 healthy controls was analyzed by 16S rRNA sequencing. Results At the phylum level, TM7 was increased in the patients (P<0.05). At the class level, the abundance of Peptostreptococcaceae, Lactobacillaceae and Actinomycetaceae in the patients increased (P<0.05), whereas the abundance of Tissierellaceae decreased relative to health controls (P<0.05). At the genus level, Actinomyces, Scardovia, Atopobium, Moryella, G07 and Lactobacillus were increased in the patients relative to healthy controls (P<0.05). Prediction of functional properties of bacterial flora showed that the metabolic pathways of fatty acids and pyruvate were different between the patients and healthy controls (P<0.05). Conclusion The present study reveals an alteration in the characteristics of gut microbiota in schizophrenia patients which may be an auxiliary diagnosis marker for clinical diagnosis of schizophrenia.

Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5'UTR and PI3K Signaling.

The α-secretase "a disintegrin and metalloproteinase domain-containing protein" (ADAM10) is involved in the processing of amyloid precursor protein (APP). Upregulation of ADAM10 precludes the generation of neurotoxic ß-amyloid protein (Aß) and represents a plausible therapeutic strategy for Alzheimer's disease (AD). In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma) cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5'-untranslated region (5'UTR). This has led to the discovery of cosmosiin (apigenin 7-O-ß-glucoside). Here, we report that in human cell lines (SH-SY5Y and HEK293), cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5'UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5'UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5'UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K) because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aß generation because the levels of Aß40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5'UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression of ADAM10 protein. These results suggest that cosmosiin may be a potential therapeutic agent in the treatment of AD.

Gold surface plasmon crystal structure based-on polystyrene template for biosensor application.

In this communication, we assembled ordered polystyrene (PS) microsphere array as a template with the drop-coating method, and the oxygen plasma was used to etch the template to adjust the spacing between the PS microspheres. Nano-triangular gold array and silver nano-pyramid array were obtained by ion beam sputtering to deposit precious metal gold and silver. We observed the surface morphology of Au and Au/Ag composite films by scanning electron microscope and characterized the films by X-ray diffraction and ultraviolet/visible light spectrophotometer. The results show that the etching time of oxygen plasma has an obvious effect in adjusting the spacing between PSs and has a significant effect on the morphology of Au structure.

The origin, type and hydrocarbon generation potential of organic matter in a marine-continental transitional facies shale succession (Qaidam Basin, China).

This organic-rich shale was analyzed to determine the type, origin, maturity and depositional environment of the organic matter and to evaluate the hydrocarbon generation potential of the shale. This study is based on geochemical (total carbon content, Rock-Eval pyrolysis and the molecular composition of hydrocarbons) and whole-rock petrographic (maceral composition) analyses. The petrographic analyses show that the shale penetrated by the Chaiye 2 well contains large amounts of vitrinite and sapropelinite and that the organic matter within these rocks is type III and highly mature. The geochemical analyses show that these rocks are characterized by high total organic carbon contents and that the organic matter is derived from a mix of terrestrial and marine sources and highly mature. These geochemical characteristics are consistent with the results of the petrographic analyses. The large amounts of organic matter in the Carboniferous shale succession penetrated by the Chaiye 2 well may be due to good preservation under hypersaline lacustrine and anoxic marine conditions. Consequently, the studied shale possesses very good hydrocarbon generation potential because of the presence of large amounts of highly mature type III organic matter.

Estrogen-related receptor alpha is involved in Alzheimer's disease-like pathology.

Estrogen-related receptor alpha (ERRα) is a transcriptional factor associated with mitochondrial biogenesis and energy metabolism. However, little is known about the role of ERRα in Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, ERRα protein and mRNA were decreased in a region- and age-dependent manner. In HEK293 cells that stably express human full-length ß-amyloid precursor protein (APP), overexpression of ERRα inhibited the amyloidogenic processing of APP and consequently reduced Aß1-40/1-42 level. ERRα overexpression also attenuated Tau phosphorylation at selective sites, with the concomitant reduction of glycogen synthase kinase 3ß (GSK3ß) activity. Interestingly, alterations of APP processing and Tau phosphorylation induced by hydrogen peroxide were reversed by ERRα overexpression in HEK/APP cells. These results indicated that ERRα plays a functional role in AD pathology. By attenuating both amyloidogenesis and Tau phosphorylation, ERRα may serve as a potential therapeutic target for AD.