The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China.

BACKGROUND: Intervertebral disc degeneration (IDD) and vertebral endplate Modic changes (MCs) are common lumbar degenerative phenotypes related to low back pain (LBP). Dyslipidemia has been linked to LBP but its associations with IDD and MCs have not been fully elucidated. The present study aimed to address the possible link between dyslipidemia, IDD and MCs in the Chinese population. METHODS: 1035 citizens were enrolled in the study. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were collected. IDD was evaluated based on the Pfirrmann grading system and subjects with an average grade ≥ 3 were defined as having degeneration. MCs were classified into typical types 1, 2 and 3. Covariables, including age, sex, BMI and fasting plasma glucose, were included for the adjustment of the logistic analyses. RESULTS: The degeneration group included 446 subjects while the nondegeneration group included 589 subjects. The degeneration group had significant higher levels of TC and LDL-C (p < 0.001) whereas TG and HDL-C were not significantly different between the two groups. TC and LDL-C concentrations were significantly positively correlated with average IDD grades (p < 0.001). Multivariate logistic regression revealed that high TC (≥ 6.2 mmol/L, adjusted OR = 1.775, 95% CI = 1.209-2.606) and high LDL-C (≥ 4.1 mmol/L, adjusted OR = 1.818, 95% CI = 1.123-2.943) were independent risk factors for IDD. Type 1 MC presented in 84 (8.12%) subjects, type 2 MC presented in 244 (23.57%) subjects, type 3 MC presented in 27 (2.61%) subjects and no MC was observed in the remaining 680 (65.70%) subjects. The type 2 MC group demonstrated a higher level of TC, but the association between serum lipids and MCs could not be confirmed in further multivariate logistic regression. CONCLUSIONS: High TC (≥ 6.2 mmol/L) and LDL-C (≥ 4.1 mmol/L) concentrations were independent risk factors for IDD for citizens in China. However, the association between dyslipidemia and MCs could not be determined. The effect of excess serum cholesterol may be critical for IDD and cholesterol lowering treatment may provide new opportunities in the management of lumbar disc degeneration.

Single Line-to-Ground Fault Type Multilevel Classification in Distribution Network Using Realistic Recorded Waveform.

The further identification of fault types for single line-to-ground faults (SLGFs) in distribution networks is conducive to determining the cause of grounding faults and formulating targeted measures for hidden danger treatment and fault prevention. For the six types of SLGFs generated in the actual power grid, this paper deeply studies their fault characteristics. Firstly, the classification criterion of fault transition resistance is derived by the generation mechanism of fault zero sequence voltage (ZSV). At the same time, by comparing and analyzing the same and different characteristics between faults, three criteria for fault classification are obtained. Based on the above four criteria, a multilevel and multicriteria fault classification method is proposed to judge six types of SLGFs. Then, the proposed method is verified by various fault state simulations of the distribution network model with a balanced topology and unbalanced topology. The engineering application of the method is demonstrated by the verification of actual power grid data. Finally, noise and data loss interference test results show the robustness of the method.

Extraction, purification, structural characterization, and hepatoprotective effect of the polysaccharide from purple sweet potato.

BACKGROUND: Purple sweet potato Ipomoea batatas (L.) has long been used as a medicine and a food. It contains various bioactive substances such as polysaccharides, anthocyanins, and flavonoids. Purple sweet potato polysaccharides are known to have anti-oxidant, anti-tumor, and immunomodulatory functions. Nevertheless, studies on the structural characterization of purple sweet potato polysaccharides and their ability to prevent non-alcoholic fatty liver disease (NAFLD) have rarely been reported. RESULTS: A novel polysaccharide (PSPP-A) was extracted and isolated from purple sweet potato, and its structural characteristics and preventive effects on NAFLD were investigated. The results indicated that PSPP-A was composed of l-rhamnose, d-arabinose, d-galactose, d-glucose, and d-glucuronic acid with molar ratios of 1.89:8.45:1.95:1.13:1. Its molecular weight was 2.63 × 103 kDa. Methylation and nuclear magnetic resonance (NMR) analysis indicated that the glycosidic linkages were →3)-α-L-Araf-(1→, α-L-Araf-(1→, →2,4)-α-L-Rhap-(1→, 4-O-Me-ß-D-GlcAp-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Galp-(1→, and →6)-ß-D-Galp-(1→. Scanning electron microscopy (SEM) indicated that the structure of PSPP-A was irregular. Subsequently, the protective effect of PSPP-A on NAFLD was investigated. The results indicated that bodyweight, liver index, and triglyceride (TG), total cholesterol (TC), aspartate transaminase (AST), and alanine transaminase (ALT) content were significantly reduced by intervention of purple sweet potato polysaccharide-A (PSPP-A) compared with the - high-fat diet group. Liver histopathological analysis indicated that PSPP-A attenuated irregular hepatocyte patterns and excessive lipid vacuoles. CONCLUSIONS: The novel polysaccharide, PSPP-A, mainly contains arabinose, which has certain preventive effects on NAFLD. This study provides a theoretical basis for further elucidating the hepatoprotective effect of purple sweet potatoes as a functional food. © 2022 Society of Chemical Industry.

The pathophysiological mechanism of ischemic stroke after hypobaric hypoxia simulation at high altitude.

Tibet is an area in China with a high incidence of stroke, typically attributed to hypobaric hypoxia. The present study aimed to observe the neuronal injury of ischemic stroke after hypobaric hypoxia and explore the mechanism by which N-methyl-D-aspartate receptor (NMDAR) and its downstream pathways are involved. This study employed a hypobaric chamber to imitate high altitude at 4000 m. After hypoxia, the middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke. Behavioral tests and measurements of infarct area were used to observe neuronal injuries. The expression of NMDAR, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII (Threonine 286) (P-CaMKII) was tested by western blot, and hematological tests were used to count the number of red blood cells (RBCs) and hemoglobin. Compared with the plain+MCAO group, the neurological deficit scores and infarct area of rats in the 4000 m + MCAO group were all decreased, and the protein expression of NMDAR, CaMKII and P-CaMKII was reduced. Compared with the plain group, the numbers of RBCs, hemoglobin and hematocrit were increased in the 4000 m group; compared with the 4000 m groups, the three indexes were increased in the 4000 m + MCAO groups. The neuronal injuries after hypoxia were not more serious than those in rats enduring ischemia and reperfusion in plain. The underlying mechanisms were related to the decreased expression of NMDAR and CaMKII; furthermore, the increased numbers of RBCs and hemoglobin may be crucial mechanisms for the incidence and development of ischemic stroke at high altitude.

Adaptive regulation of virulence genes by microRNA-like RNAs in Valsa mali.

MicroRNAs play important roles in the regulation of gene expression in plants and animals. However, little information is known about the action mechanism and function of fungal microRNA-like RNAs (milRNAs). In this study, combining deep sequencing, molecular and histological assays, milRNAs and their targets in the phytopathogenic fungus Valsa mali were isolated and identified. A critical milRNA, Vm-milR16, was identified to adaptively regulate the expression of virulence genes. Fourteen isolated milRNAs showed high expression abundance. Based on the assessment of a pathogenicity function of these milRNAs, Vm-milR16 was found to be a critical milRNA in V. mali by regulating sucrose non-fermenting 1 (VmSNF1), 4,5-DOPA dioxygenase extradiol (VmDODA), and a hypothetical protein (VmHy1). During V. mali infection, Vm-milR16 is downregulated, while its targets are upregulated. Overexpression of Vm-milR16, but not mutated Vm-milR16, significantly reduces the expression of targets and virulence of V. mali. Furthermore, deletion of VmSNF1, VmDODA and VmHy1 significantly reduce virulence of V. mali. All three targets seem to be essential for oxidative stress response and VmSNF1 is required for expression of pectinase genes during V. mali-host interaction. Our results demonstrate Vm-milRNAs contributing to the infection of V. mali on apple trees by adaptively regulating virulence genes.

Identification and expression analysis of genes related to calyx persistence in Korla fragrant pear.

BACKGROUND: The objective of this study was to increase understanding about genetic mechanisms affecting calyx persistence in Korla fragrant pear (Pyrus brestschneideri Rehd). Flowers were collected at early bloom, full bloom, and late bloom. The RNA was extracted from the flowers and then combined according to calyx type. Transcriptome and digital gene expression (DGE) profiles of flowers, ovaries, and sepals with persistent calyx (SC_hua, SC_ep, and SC_zf, respectively) were compared with those of flowers, ovaries, and sepals with deciduous calyx (TL_hua, TL_ep, and TL_zf, respectively). Temporal changes in the expression of selected genes in floral organs with either persistent or deciduous calyx were compared using real-time quantitative PCR (qRT-PCR). RESULTS: Comparison of the transcriptome sequences for SC_hua and TL_hua indicated 26 differentially expressed genes (DEGs) with known relationship to abscission and 10 DEGs with unknown function. We identified 98 MYB and 21 SPL genes from the assembled unigenes. From SC_zf vs TL_zf, we identified 21 DEGs with known relationship to abscission and 18 DEGs with unknown function. From SC_ep vs TL_ep, 12 DEGs with known relationship to abscission were identified along with 11 DEGs with unknown function. Ten DEGs were identified by both transcriptome sequencing and DGE sequencing. CONCLUSIONS: More than 50 DEGs were observed that were related to calyx persistence in Korla fragrant pear. Some of the genes were related to cell wall degradation, plant hormone signal transduction, and stress response. Other DEGs were identified as zinc finger protein genes and lipid transfer protein genes. Further analysis showed that calyx persistence in Korla fragment pear was a metabolic process regulated by many genes related to cell wall degradation and plant hormones.

Aß regulation-based multitarget strategy for drug discovery against Alzheimer's disease.

Alzheimer's disease (AD) is a progressively neurodegenerative disease that eventually leads to the irreversible loss of neurons and intellectual abilities, including cognition and memory. AD has become the most common cause of dementia in aged people, and the ill-defined pathogenesis of AD is seriously impeding the current drug discovery against this disease. To date, there is still a lack of etiologically therapeutic drugs for AD, although some symptomatic treatments have been successfully developed. The ß-amyloid (Aß)-induced neurodegeneration is determined as the main pathogenesis of AD, and by targeting the regulation of Aß in production inhibition or clearance promotion, many active agents have been designed potentially for AD treatment, but no drug has yet been approved in clinical use. Actually, AD has a complex pathogenic mechanism that involves multiple aberrant signaling genes and pathways, and the idea of 'single target' for anti-AD drug research is thus full of challenges. Recently, with a deep understanding of AD pathogeneses and the development of advanced pharmacological techniques, 'multiple target'-based strategy has been widely applied for the drug discovery against this disease, and many promising results have been achieved. Here, we review the recent multitarget strategies for the drug discovery in the treatment of AD by focusing on the involvement of Aß regulation.

Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both ß-amyloid production and clearance.

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The ß-amyloid (Aß)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aß production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aß production by suppressing ß-site amyloid precursor protein cleavage enzyme 1 expression and promote Aß clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aß formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

An enriched ammonia-oxidizing microbiota enables high removal efficiency of ammonia in antibiotic production wastewater.

High ammonia concentration hinders the efficient treatment of antibiotic production wastewater (APW). Developing effective ammonia oxidation wastewater treatment strategies is an ideal approach for facilitating APW treatment. Compared with traditional nitrification strategies, the partial nitrification process is more eco-friendly, less energy-intensive, and less excess sludge. The primary limiting factor of the partial nitrification process is increasing ammonia-oxidizing bacteria (AOB) while decreasing nitrite-oxidizing bacteria (NOB). In this study, an efficient AOB microbiota (named AF2) was obtained via enrichment of an aerobic activated sludge (AS0) collected from a pharmaceutical wastewater treatment plant. After a 52-day enrichment of AS0 in 250 mL flasks, the microbiota AE1 with 69.18% Nitrosomonas microorganisms was obtained. Subsequent scaled-up cultivation in a 10 L fermenter led to the AF2 microbiota with 59.22% Nitrosomonas. Low concentration of free ammonia (FA, < 42.01 mg L-1) had a negligible effect on the activity of AF2, and the nitrite-nitrogen accumulation rate (NAR) of AF2 was 98% when FA concentration was 42.01 mg L-1. The specific ammonia oxidation rates (SAORs) at 30 °C and 15 °C were 3.64 kg NH4+-N·kg MLVSS-1·d-1 and 1.43 kg NH4+-N·kg MLVSS-1·d-1 (MLVSS: mixed liquor volatile suspended solids). The SAOR was 0.52 kg NH4+-N·kg MLVSS-1·d-1 when the NaCl concentration was increased from 0 to 20 g L-1, showing that AF2 functioning was stable in a high-level salt environment. The ammonia oxidation performance of AF2 was verified by treating abamectin and lincomycin production wastewater. The NARs of AF2 used for abamectin and lincomycin production wastewater treatment were >90% and the SAORs were 2.39 kg NH4+-N·kg MLVSS-1·d-1 and 0.54 kg NH4+-N·kg MLVSS-1·d-1, respectively, which was higher than the traditional biological denitrification process. In summary, AF2 was effective for APW treatment via enhanced ammonia removal efficiency, demonstrating great potential for future industrial wastewater treatment.

Danthron functions as a retinoic X receptor antagonist by stabilizing tetramers of the receptor.

Retinoic X receptor (RXR) is a promising target for drug discovery against cancer and metabolic syndromes. Here, we identified a specific RXRα antagonist, danthron, from the traditional Chinese medicine rhubarb. Danthron repressed all tested RXRα-involved response element transcription, including the RXRE, PPRE, FXRE, and LXRE. Results from native PAGE and isothermal titration calorimetry (ITC)-based assays indicated that danthron bound to the tetrameric RXRα-LBD in a specific stoichimetric ratio, and such a binding could influence the corepressor SMRT affinity to the receptor. Additionally, a unique tetrameric structure of the apo-RXRα ligand-binding domain (LBD) was determined, which exhibited a larger tetramer interface and different ligand-binding pocket size compared with the one previously reported. Together with the biochemical and biophysical results, the determined crystal structure of danthron-soaked RXRα-LBD suggested a new mechanism for danthron antagonism to tetrameric RXRα. Moreover, the in vivo efficient improvement of insulin sensitivity by danthron was observed in diet-induced obese (DIO) mice. Thus, our findings were expected to supply new insights into the structural basis of RXRα antagonist for its further potential therapeutic application.

The impact of a novel Chinese yam-derived polysaccharide on blood glucose control in HFD and STZ-induced diabetic C57BL/6 mice.

Chinese yam, as a kind of traditional "medicine and food homologous food" in Asia, could assistance to digestion, nourish the lungs and relieve cough. Some research also suggested that Chinese yam could prevention of hyperglycemia, but the specific mechanism of action was not clear. In this paper, an acidic polysaccharide (CYPB) was isolated from Chinese yam with the molecular weight of 1.55 × 102 kDa. The determination of the monosaccharide composition of CYPB with ion chromatography showed that CYPB was composed of rhamnose, glucose, arabinose, galactose, glucose, xylose and glucuronic acid with the ratio of 6 : 3.73 : 7.31 : 10.95 : 4.56 : 1. The structural analysis indicated that the CYPB contain 1 → 3, 1 → 4, 1 → 2, 1 → 6 and 1 → 3, 6 glycoside bonds. The experimental results of diabetic mice model induced by high-fat diet (HFD) and streptozocin (STZ) indicated that CYPB could improve clinical symptoms and alleviate the glucose tolerance damage symptoms effectively. The underlying mechanism of regulate blood glucose of CYPB may be related to improve the ability of synthesize glycogen, insulin resistance and reduce gluconeogenesis by regulating the expression of InsR, PI3K, Akt and FoxO3, GLUT4 proteins in PI3K/Akt signaling pathway in T2DM mice.

Design, synthesis and SAR study of hydroxychalcone inhibitors of human ß-secretase (BACE1).

According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of ß-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A- and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC(50) = 0.27 µM).

The Protective Effect of Docosahexaenoic Acid on PC12 Cells in Oxidative Stress Induced by H2O2 through the TrkB-Erk1/2-CREB Pathway.

Docosahexaenoic acid (DHA) has attracted plenty of interest in the prevention of neurodegenerative diseases. Although the beneficial effects of DHA on the central nervous system function are recognized, more information on the molecular mechanisms involved in its neuroprotective effects is required. The present study aimed to evaluate the effects of DHA on the function of mitochondria, neurite growth-related proteins signaling pathway, and neural signal transmission. In this study, PC12 cells were treated with H2O2 (400 µM) to establish an oxidative damage model. Results showed that DHA improved the viability and morphology of PC12 cells. DHA significantly increased the antioxidant capacity, mitochondrial membrane potential, and activity of ATPase in the cells. Furthermore, the phosphorylation levels of tyrosine kinase receptor (BTrkB), phospholipase C-γ1 (PLCγ1), calcium/calmodulin-dependent protein kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), and cAMP-response element-binding protein (CREB) were upregulated by DHA. The damage on F-actin induced by H2O2 was reversed by DHA, indicating that DHA could protect neurite outgrowth. In addition, DHA increased the content of acetylcholine and γ-aminobutyric acid while decreasing glutamic acid. These results revealed that DHA could protect PC12 cells from damage induced by H2O2 through the TrkB-ERK1/2-CREB pathway.

Protective effect and mechanism of docosahexaenoic acid on the cognitive function in female APP/PS1 mice.

Docosahexaenoic acid (DHA) has been studied for many years owing to its protective effect on the decline in brain function. DHA intake reduces the risk of Alzheimer's disease (AD) and decreases amyloid deposition; however, the underlying molecular mechanism has not been completed elucidated. In this study, the effect of DHA on the cognitive function of amyloid precursor protein (APP)/PS1 in wild-type mice and its related mechanism were investigated. Results from the Morris water maze test showed that DHA improved learning and memory function in mice. Moreover, DHA reduced neuronal damage in mice brains, as determined using Nissl staining. Unsaturated fatty acid levels in the brain of mice increased (p < 0.01) after DHA administration and saturated fatty acid levels decreased (p < 0.01). The deposition of amyloid-beta (Aß) plaques and tau protein neurofibrillary tangles was significantly inhibited. The mechanism of action of DHA was attributed to the upregulation of the expression of ß-secretase (BACE)2, which competed with BACE1 to cleave APP, thus decreasing the production of extracellular Aß fragments (p < 0.01). The expression level of insulin-degrading enzyme was not significantly different. The expression of N-methyl-D-aspartate receptors was further downregulated and the phosphorylation of glycogen synthase kinase-3ß and tau protein was inhibited (p < 0.01). These data indicated that DHA could protect cognitive function in mice by reducing Aß plaque formation and decreasing tau phosphorylation levels.

Draft genome of the blister beetle, Epicauta chinensis.

Existence of cantharidin (CTD) in blister beetles is a significant ecological adaptive mechanism that defends against predators and regulates courtship and mating behaviors. To better understand CTD biosynthetic information as well as its biology and pharmacology, we assembled a genome of 151.88 Mb for Epicauta chinensis using PacBio sequencing technology. Gene annotation yielded 249,238 repeats, 527 non-coding RNAs and 12,520 protein-coding genes. Compared to other 11 insects, expansions of gene families in E. chinensis for most core gene families likely associated with environmental adaptation, such as chemoreception, immunity, and detoxification. We further annotated P450s and immune-related genes, a total of 117 putative P450s comprising 7 CYP2, 67 CYP3, 36 CYP4, and 7 mitochondrial P450s and 281 immune-related genes were identified. Comparative analysis of the insect immune repertoires indicated presence of immune genes detected only from Coleopteran insects such as MD2-like. This suggested a lineage-specific gene evolution for Coleopteran insects. Based on the gene family evolution analysis, we identified two probable candidate genes including CYP4TT1 and phytanoyl-CoA dioxygenase for CTD biosynthesis. The high-quality reference genome of E. chinensis provides the genetic basis for further investigation of CTD biosynthesis and in-depth studies of the development and evolution of blister beetles.

Identification and validation of key miRNAs and miRNA-mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep.

MicroRNAs (miRNAs) are widely expressed in different mammalian tissues and exert their biological effects through corresponding target genes. miRNA target genes can be rapidly and efficiently identified and screened by combining bioinformatics prediction and experimental validation. To investigate the possible molecular regulatory mechanisms involving miRNAs during uterine involution in postpartum ewes, we used Illumina HiSeq sequencing technology to screen for the number and characteristics of miRNAs in faster uterine involution and normal uterine involution group. A total of 118 differentially expressed miRNAs, including 33 known miRNAs and 85 new miRNAs, were identified in the hypothalamic library, whereas 54 miRNAs, including 5 known miRNAs and 49 new miRNAs, were identified in the uterine library. Screening with four types of gene prediction software revealed 73 target genes associated with uterine involution, and subsequently, GO annotation and KEGG pathway analysis were performed. The results showed that, in the hypothalamic-uterine axis, uterine involution in postpartum ewes might primarily involve two miRNA-target gene pairs, namely, miRNA-200a-PTEN and miRNA-133-FGFR1, which can participate in GnRH signal transduction in the upstream hypothalamus and in the remodeling process at the downstream uterus, through the PI3K-AKT signaling pathway to influence the recovery of the morphology and functions of the uterus during the postpartum period in sheep. Therefore, identification of differentially expressed miRNAs in this study fills a gap in the research related to miRNAs in uterine involution in postpartum ewes and provides an important reference point for a comprehensive understanding of the molecular mechanisms underlying the regulation of postpartum uterine involution in female livestock.

Comparative analysis of differentially expressed miRNAs related to uterine involution in the ovine ovary and uterus.

To examine the possible miRNA molecular regulatory mechanisms during maternal uterine involution after delivery, we selected ovary and uterus tissues that are structurally connected as experimental materials. We employed Illumina HiSeq sequencing to screen and analyze the quantity and characteristics of miRNA in postpartum ewes in the methylergometrine-treated group and physiological saline control group. Results showed that 16 miRNAs were identified in the ovary libraries, including 4 known miRNAs and 12 novel miRNAs. In the uterus libraries, 54 miRNAs were identified, which included 5 known miRNAs and 49 novel miRNAs. At the same time, target gene prediction, GO annotation, and KEGG signaling pathway enrichment analysis were employed. We found that maternal uterine involution after delivery may involve two miRNA-target gene pairs, i.e., miRNA-200a-ZEB1 and YAP1. The YAP1/Hippo signaling pathway is used to construct an ovary-uterine axial regulatory mechanism to regulate the restoration of postpartum maternal uterine morphology and function. In view of this, the identification of miRNAs with significant differences in this study fills a gap in research on miRNAs associated with regulation of postpartum uterine recovery in ewes and provided an important reference for comprehensive understanding and in-depth research on the regulatory molecular network mechanism for postpartum uterine involution in small ruminants.

2,2',4'-trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice.

Alzheimer's disease (AD) characterizes a progressive neurodegenerative disorder of the brain, while AD patients are afflicted with irreversible loss of neurons and further the intellectual abilities including memory and reasoning. One of the typical hallmarks of AD is the deposition of senile plaque that is contributed mainly by amyloid-beta (Abeta), whose production is initiated by beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1). Inhibition of BACE1 is thereby regarded as an attractive strategy for anti-AD drug discovery. Here, we reported that the natural product 2,2',4'-trihydroxychalcone (TDC) from Glycyrrhiza glabra functioned as a specific non-competitive inhibitor against BACE1 enzyme, and potently repressed beta-cleavage of APP and production of Abeta in human embryo kidney cells-APPswe cells. Moreover, the amelioration ability of this compound against the in vivo memory impairment was further evaluated by APP-PS1 double transgenic mice model. It is discovered that treatment of 9 mg/kg/day of TDC could obviously decrease Abeta production and Abeta plaque formation, while efficiently improve the memory impairment based on Morris water maze test. Our findings thus demonstrated that the natural product TDC as a new BACE1 inhibitor could ameliorate memory impairment in mice, and is expected to be potentially used as a lead compound for further anti-AD reagent development.

Leukamenin F suppresses liver fibrogenesis by inhibiting both hepatic stellate cell proliferation and extracellular matrix production.

AIM: To investigate the inhibitory effect of the natural product Leukamenin F on liver fibrosis and explore its potential underlying mechanisms. METHODS: Carbon tetrachloride (CCl(4))-treated mouse model in vivo and in hepatic stellate cells (HSC) in vitro were used. The effect on CCl(4)-induced liver fibrosis was studied using histochemical and biochemical analysis, while the inhibition on HSC was assessed using cell proliferation/apoptosis assay and collagen I production using real-time PCR. The inhibitory effects of Leukamenin F on Akt/mTOR/p70S6K and TGFbeta/Smad pathways was studied using Western blot and cell image analysis. RESULTS: Leukamenin F (0.1-1 mg/kg, ip, q.d.x28) significantly reduced alpha-SMA and collagen specific Sirius red staining areas in CCl(4) -treated mouse livers. This compound at 1-2 micromol/L dose-dependently inhibited alpha-SMA expression, cell proliferation and type I procollagen mRNA expression in activated HSC. Furthermore it inhibited the Akt/mTOR/p70S6K pathway and suppressed TGFbeta -induced Smad2/Smad3 phosphorylation and nuclear translocation in HSC. CONCLUSION: Our results demonstrated that Leukamenin F could attenuate CCl(4)-induced liver fibrogenesis in mice as an efficient inhibitor against both HSC proliferation and ECM production. This natural product provides a valuable structural hint for the development of anti-liver fibrosis reagents.

Study of the corrosion behavior of Aspergillus niger on 7075-T6 aluminum alloy in a high salinity environment.

In this study, the corrosion behavior of 7075-T6 aluminum alloy in a high salinity environment containing Aspergillus niger was investigated using high-performance liquid chromatography tandem mass spectrometry, gas chromatography, surface analysis and electrochemical measurement. Results demonstrated that uniform and localized corrosion rates of the alloy in the presence of A. niger were approximately 3.7 and 22.4 times, respectively, of that in the absence A. niger. This higher corrosion rate was attributed to accelerated anode and cathode reactions from the actions of A. niger biofilm. Additionally, organic acid corrosion caused by the presence of A. niger was confirmed to be the main cause for the corrosion of aluminum alloy.