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The development of stable, highly active, and inexpensive catalysts for the ozone catalytic oxidation of volatile organic compounds (VOCs) is challenging but of great significance. Herein, the micro-coordination environment of Al in commercial Y zeolite was regulated by a specific dealumination method and then the dealuminated Y zeolite was used as the support of Cu-Mn oxides. The optimized catalyst Cu-Mn/DY exhibited excellent performance with around 95% of toluene removal at 30 °C. Besides, the catalyst delivered satisfactory stability in both high-humidity conditions and long-term reactions, which is attributed to more active oxygen vacancies and acidic sites, especially the strong Lewis acid sites newly formed in the catalyst. The decrease in the electron cloud density around aluminum species enhanced electron transfer at the interface between Cu-Mn oxides. Moreover, extra-framework octahedrally coordinated Al in the support promoted the electronic metal-support interaction (EMSI). Compared with single Mn catalysts, the incorporation of the Cu component changed the degradation pathway of toluene. Benzoic acid, as the intermediate of toluene oxidation, can directly ring-open on Cu-doped catalysts rather than being further oxidized to other byproducts, which increased the rate of the catalytic reaction. This work provides a new insight and theoretical guidance into the rational design of efficient catalysts for the catalytic ozonation of VOCs.

Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C-termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene-recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O-sulfation at C-terminus.An integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein-engineered hirudins.Molecular dynamic analysis showed that modifications of the C-termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C-termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased K

3,4-Dihydroxyphenylacetaldehyde synthase (DHPAAS) catalyzes the direct conversion of 3,4-dihydroxyphenylalanine to 3,4-dihydroxyphenylacetaldehyde (DHPAA), an important intermediate in the formation of flexible insect cuticle. In order to clarify the precise roles DHPAAS plays in insect development and survival, DHPAAS was characterized throughout the physiological to the molecular levels. Extensive in vivo experiments in Aedes aegypti confirm that DHPAAS is essential for blood feeding, egg development and cuticle structure formation. The crystal structure of insect DHPAAS was then solved to reveal the structural basis underlying the catalytic production of the key cuticle intermediate DHPAA. The molecular view shows a DHPAAS active site that is distinct from that of the homologous enzyme 3,4-dihydroxyphenylalanine decarboxylase. Stabilization of the flexible 320–350 region is observed to position the 350–360 loop towards the catalytic asparagine residue, and these distinct features are suggested to promote pyridoxal 5'-phosphate-dependent amine oxidation. Additional molecular dynamics simulations further support the involvement of Phe82, Tyr83 and Asn195 in substrate binding and catalysis, and also shows increased fluctuations limited to loop residues 330–345 in Aedes aegypti DHPAAS.

Yechun Pei,1– 3,* Zhengpan Xiao,1,2,* Shuangshuang Wei,1,2 Meiqi Peng,1,2 Chenghui Luo,1,2 Dayong Wang2,3 1School of Life Sciences, Hainan University, Haikou, People’s Republic of China; 2Laboratory of Biopharmaceuticals and Molecular Pharmacology, School of Pharmaceutical Sciences, Hainan University, Haikou, People’s Republic of China; 3One Health Institute, Hainan University, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yechun Pei, Department of Biosciences, School of Life Sciences, Hainan University, 58 People’s Road, Haikou, Hainan, 570228, People’s Republic of China, Email ycpei@hainanu.edu.cn Dayong Wang, Laboratory of Biopharmaceuticals and Molecular Pharmacology, School of Pharmaceutical Sciences, Hainan University, 58 People’s Road, Haikou, Hainan, 570228, People’s Republic of China, Email wangdy@hainanu.edu.cnBackground: In tropical and subtropical areas, allergens from the dust mite species Blomia tropicalis are common causes of allergic rhinitis and asthma. Blomia tropicalis has two main allergens: Blo t 5 and Blo t 21.Aim: To generate a chimeric virus-like particle containing HBcAg, Blo t 5 and Blo t 21 that can treat allergies caused by Blomia tropicalis.Methods: To produce allergic asthma in mice, prokaryotic expression and purification of Blomia tropicalis allergens rBlo t 5, rBlo t 21, and recombinant fusion allergen rBlo t 5– 21 were utilized in the study. We created a hepatitis B core antigen (HBcAg) and rBlo t 5– 21 fusion prokaryotic expression plasmid. HBcAg-rBlo t 5– 21 was purified after expression and tested by transmission electron microscopy (TEM). Furthermore, the protein HBcAg-rBlo t 5– 21 was employed as a protein vaccination.Results: In allergy-induced mouse model experiments, the fusion allergen rBlo t 5– 21 was more effective than the individual allergens rBlo t 5 and rBlo t 21 at inducing allergy. We found that vaccinating allergic mice with the recombinant fusion protein vaccine HBcAg-rBlo t 5– 21 alleviated allergy symptoms elicited by the rBlo t 5– 21 allergen. Vaccination with HBcAg-rBlo t 5– 21 resulted in a decrease in total serum IgE levels, suppression of anaphylaxis, and reduction of inflammatory cell infiltration into lung tissue as compared to the PBS group.Conclusion: HBcAg-rBlo t 5– 21, a protein vaccine containing both the hepatitis B core antigen and the Blomia tropicalis fusion allergen rBlo t 5– 21, could be a suitable vaccination for preventing allergy disorders caused by Blomia tropicalis.Keywords: Blomia tropicalis, vaccine, hepatitis B core antigen, asthma

Background: Temporin is one family of the shortest antimicrobial peptides found in Ranidae frogs. Staphylococcus aureus is one of the main pathogens of suppurative diseases and food contamination, causing severe local or systemic infections in humans. Temporin-GHa (GHa) was previously obtained from Hylarana guentheri, showing weak antibacterial activity against S. aureus. Most temporin peptides are positively charged by arginine and lysine; however, GHa contains histidine. Objective: In order to investigate the impact of positively charged amino acid on its antibacterial and antibiofilm activity, GHa4R was designed and synthesized by replacing histidine with arginine in GHa. Method: The antibacterial activity and efficacy against S. aureus were detected by minimum inhibitory concentration, minimum bactericidal concentration, and time-killing kinetics assays. The action mechanism was determined by propidium iodide uptake and scanning electron microscopy assays. The antibiofilm activity was measured by the MTT method. Eradication of biofilm was observed by fluorescence microscope. Results: Compared to GHa, GHa4R had stronger antibacterial activity and bactericidal efficacy against S. aureus. Impressively, GHa4R presented antibacterial activity against methicillin-resistant S. aureus (MRSA). It was barely affected by temperature, pH, and storage period, showing high stability. Furthermore, it increased the permeability of the cell membrane and damaged the membrane integrity, leading to cell death. In addition, GHa4R did not induce antibiotic resistance in S. aureus in 30 days, but the MIC of vancomycin was doubled. It not only inhibited S. aureus biofilm formation but also eradicated 24 h-biofilms. Conclusion: The above-mentioned characteristics make GHa4R a promising candidate for the treatment of S. aureus infections.

Antimicrobial peptides (AMPs) show broad-spectrum microbicidal activity against bacteria, fungi, and viruses, and have been considered as one of the most promising candidates to overcome bacterial antimicrobial resistance. Structural modification of AMPs is an effective strategy to develop high-efficiency and low-toxicity antibacterial agents. A series of peptides GHaR6R, GHaR7R, GHaR8R, and GHaR9W with arginine replacement of histidine (His) derived from temporin-GHa of Hylarana guentheri were designed and synthesized. These derived peptides exhibit antibacterial activity against Staphylococcus aureus, and GHaR8R exerts bactericidal effect within 15 min at 4 × MIC (25 µm). The derived peptides caused rapid depolarization of bacteria, and the cell membrane damage was monitored using quartz crystal microbalance with dissipation assay, which suggests that they target cell membranes to exert antibacterial effects. The derived peptides can effectively eradicate mature biofilms of S. aureus. Taken together, the derived peptides are promising antibacterial agent candidates against S. aureus.

Temporin-GHa (GHa) was cloned from , showing a weak antimicrobial activity. In order to improve its bactericidal efficacy, GHaR6R, GHaR7R, GHaR8R and GHaR9W were designed and synthesized. Compared to the parent peptide, the GHa-derived peptides show potent antimicrobial activities against methicillin-resistant (MRSA), which is the main pathogen with high morbidity and mortality that causes various infections in humans. These peptides exert bactericidal actions on MRSA by permeabilizing the cytoplasmic membranes and damaging membrane integrity. All of the four peptides exhibit excellent stability under harsh conditions, including extreme temperature and salts. Furthermore, they inhibit the formation of biofilm and eradicate mature biofilm of MRSA. The GHa-derived peptides decrease bacterial surface hydrophobicity, autoaggregation and polysaccharide intercellular adhesion synthesis in concentration-dependent manner. Real-time quantitative reverse transcription PCR analysis revealed that the peptides downregulate the expression of adhesion genes involved in biofilm formation. Except for GHaR7R, the other three peptides have low hemolytic toxicity against human erythrocytes. In the presence of human erythrocytes, GHaR7R, GHaR8R and GHaR9W interact with MRSA preferentially. GHaR6R, GHaR8R and GHaR9W show less toxicity toward normal cells HL-7702 and hFOB1.19. These results suggest that the GHa-derived peptides may be promising antimicrobial candidates against MRSA infections.

Oxidative stress is one of the causes of aging and other diseases. Nrf2 is the main transcription factor regulating antioxidant gene expression. In recent years, it has been found that inhibiting Nrf2 activity or increasing oxidative pressure can replicate premature aging defects, and reactivating Nrf2 activity can reverse nuclear aging defects and restore cell vitality. SIRT6 is one of the few proteins that can regulate life span and aging at the same time. SIRT6 gene deficient mice show degenerative changes similar to human premature aging 3 weeks after birth and eventually die. SIRT6 deficient cells show the characteristics of accelerated aging, while the deletion of SIRT6 in human cells does not directly lead to the damage of genetic material in the nucleus and genomic instability, but significantly reduces the antioxidant capacity of cells and causes the accumulation of intracellular reactive oxygen species and DNA oxidation products. At present, the interaction between Nrf2 and SIRT6 protein and its mechanism are not clear. In this study, yeast two-hybrid and tag pulldown methods were used to analyze the protein interaction domain between Nrf2 and SIRT6. The experiment found that SIRT6 directly interacts with Nrf2, SIRT6 Interacts with the Neh1 and Neh3 domains of Nrf2.

Objective: To investigate the influence of education level in the peri-menopausal symptoms and quality of life (QoL) among Chinese women.Methods: We carried out a cross-sectional study of 1632 peri...

BaTi4O9/ZrMgMo3O12 composites were prepared by a solid state method according to the relationship between their coefficient of thermal expansion (CTE) and dielectric property. Their phase analysis, thermal expansion, microstructure and dielectric properties were studied in detail. The results showed that the CTE of BaTi4O9/ZrMgMo3O12 composites decreased as the content of ZrMgMo3O12 increasing. And when the content of ZrMgMo3O12 reached 50%, the CTE would be 2.79 × 10−6/K, which was 32% of that of BaTi4O9. Besides, the temperature coefficient of resonance frequency (τf) was 4.29 × 10−6/K. The changes in dielectric properties of composite samples can be mainly attributed to the changes of microstructure and complex polarization mechanism. And temperature coefficient of resonance frequency (τf) was regulated by the CTE owing to τ f = − ( α + 1 2 τ e ) .

Organoarsenical antibiotics pose a severe threat to the environment and human health. In aquatic environment, dissolved organic matter (DOM)-mediated photochemical transformation is one of the main processes in the fate of organoarsenics. Dicarbonyl is a typical redox-active moiety in DOM. However, the knowledge on the photoconversion of organoarsenics by DOM, especially the contributions of dicarbonyl moieties is still limited. Here, we systematically investigated the photochemical transformation of three organoarsenics with the simplest β-diketone, acetylacetone (AcAc), as a model dicarbonyl moiety of DOM. The presence of AcAc significantly enhanced the photochemical conversion of roxarsone (ROX), whereas only minor effects were observed for 3-amino-4-hydroxyphenylarsonic acid (HAPA) and arsanilic acid (ASA), because the latter two (with an amino (-NH

Demyelination is observed in animal models of intractable epilepsy (IE). Epileptogenesis damages the myelin sheath and dysregulates oligodendrocyte precursor cell (OPC) development. However, the molecular pathways regulating demyelination in epilepsy are unclear. Here, we predicted the molecular mechanisms regulating demyelination in a rat model of lithium-pilocarpine hydrochloride-induced epilepsy. We identified DGKA/Mboat2/Inpp5j and NOS/Keratin 28 as the main target molecules that regulate demyelination via glycerolipid and glycerophospholipid metabolism, phosphatidylinositol signaling, and estrogen signaling in demyelinated forebrain slice cultures (FSCs). In seizure-like FCSs, the actin cytoskeleton was regulated by Cnp and MBP via Pak4/Tmsb4x (also known as Tβ4) and Kif5c/Kntc1. Tβ4 possibly prevented OPC differentiation and maturation and inhibited MBP phosphorylation via the p38MAPK/ERK1/JNK1 pathway. The MAPK signaling pathway was more likely activated in seizure-like FCSs than in demyelinated FCSs. pMBP expression was decreased in the hippocampus of lithium-pilocarpine hydrochloride-induced acute epilepsy rats. The expression of remyelination-related factors was suppressed in the hippocampus and corpus callosum in lithium-pilocarpine hydrochloride-induced epilepsy rats. These findings suggest that the actin cytoskeleton, Tβ4, and MAPK signaling pathways regulate the decrease in pMBP in the hippocampus in a rat model of epilepsy. Our results indicate that regulating the actin cytoskeleton, Tβ4, and MAPK signaling pathways may facilitate the prevention of demyelination in IE.

Controllable thermal expansion dielectric ceramic of SrTiO3/ZrMgMo3O12 has been fabricated by solid-state method. The experimental results indicate that the coefficient of thermal expansion (CTE) of the composites could be adjusted from 10.13 × 10−6 to 4.06 × 10−6 K−1. At 10 MHz, dielectric constants of composites are in the range of 40.70–21.17, while dissipation factors changed from 1.17 × 10−4 to 79.7 × 10−4. The composite wherein the volume fraction of ZrMgMo3O12 was 40%, showed the following excellent properties: low CTE (6.53 × 10−6 K−1), moderate dielectric constants (28.95) and low dissipation factor (tanδ, 1.17 × 10−4) at 10 MHz. Therefore, this composite could be used as a high-frequency dielectric ceramic.

Translocation of RNA across the nuclear envelope relies on transport receptors. Receptor nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1 [also called p15 or p15-1]) shuttles between the nucleus and cytoplasm of metazoan cells and contributes to the nuclear export of a diverse spectrum of RNAs. NXT2 (also called p15-2), a paralog of NXT1 in eutherians, also has implications for RNA nuclear export. A comprehensive description is currently lacking as to the genetic signature of these molecules. In this study, we analyzed genetic changes in the NXT1 and NXT2 genes in primates and murine rodents, including the commonly used model organisms Macaca spp., Mus musculus, and Rattus norvegicus. The results show that NXT1 has been subject to functional constraints in both phylogenetic lineages. Conversely, NXT2 exhibits discrepant patterns of genetic changes between these taxa. Murine NXT2 has evolved conservatively; by contrast, adaptive selection has frequently contributed to genetic changes in primate NXT2. The genetic discrepancy of the NXT2 orthologs leads to the suggestion that they had experienced quite different evolutionary fates potentially constituting different functional implementations in these taxa. These findings raise awareness of further study on different organisms to comprehensively understand their functional characteristics.

Pitaya is a burgeoningly tropical fruit, there are two common varieties, red peel with red pulp and red peel with white pulp. To investigate the reason of different colors in two kinds of pitaya, explore differencially expressed genes (DEGs), in this study, we profiled transcriptome in flesh of two varieties (Hylocereu polyrhizus and Hylocereu undatus) in green stage and mature stage respectively. 53 240 reads with high quality were obtained. Analysing the DEGs, we found there were bigger differences in different stage rather than different variety. Gene ontology (GO) functional analysis and KEGG pathway analysis were adopted in R1 VS R3 and W3 VS W3. Through GO analysis, we found many genes enriched in protein binding transcription factor activity in molecule founction. Through KEGG pathway analysis, we found most genes were enriched in biosynthesis of secondary metabolism, amino acid and nucleic acid metabolism, and tyrosine metabolism. In addintion, tyrosine was the precursor of betalaines. In conclusion, the development of Hylocereu polyrhizus accompanying by the synthesis of a large amount of betalaines, tyrosine played a key role as a precursor, and the synthesis of this pigment required a mass of amino acids, enzymes, and transcription factors. Betalaines synthesis pathway has not cleared yet, this study explored key genes related to betalaines synthesis and provided useful information for optimizing the betalaines synthesis pathway, which was the basis of later experiments.

Acetylacetone (AA) has proven to be a potent photo-activator for the decolorization of dyes. However, there is very limited information on the quantitative structure-activity relationship (QSAR) and the mechanisms of dye degradation by UV/AA. Herein, the photolysis of 65 aromatic compounds (dyes and dye precursors) was investigated at three pH values (4.0, 6.0, 9.0) by UV/AA and UV/H

The triclinic copper (II) molybdate (α-CuMoO4) was synthesized by a solid state method and its negative thermal expansion (NTE) was systematically studied. The results show that α-CuMoO4 exhibits non-linearly NTE and the coefficient of thermal expansion (CTE) is −4.40 × 10−6/K, when the temperature ranges from room temperature (RT) to 390 K. Its negative expansion behavior may be caused by the charge transferred from O2− to Cu2+, resulting that a part of the CuO6 octahedron transferred to CuO5 hexahedron, and the Cu O bond length in CuO5 hexahedron became shorter than in CuO6 octahedron. The synthetic action of d9Jahn-Teller effect of Cu2+ and small amount of pores may also contribute to the NTE of CuMoO4. CuMoO4 also has excellent photocatalytic properties, luminescent properties, dielectric properties and thermal cycling properties. The NTE and other excellent properties of CuMoO4 make the material have great prospects in application.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β-amyloid peptide 1-42 (Aβ1-42 ), and neuronal loss. The self-association of Aβ1-42 monomers (Aβ-M) into soluble oligomers seems to be crucial for the development of neurotoxicity. Previous publications have shown that Aβ oligomers and dimers might play key roles in inducing AD. The role of Aβ-M was rarely investigated and still unclear in AD. To understand the effects of Aβ-M on neurons and other cell types in the brain could be the key to understand its function. In our study, we found that Aβ-M expression slowly induced cell apoptosis within 48 hours after transfection, β2 adrenergic receptor (β2AR) interacted with Aβ-M in the pull-down and the yeast two-hybrid assays, and Aβ-M played a major role in inducing phosphorylation of Tau at Ser-214, c-Jun N-terminal kinase (JNK) at Thr-183/Tyr-185, p70 ribosomal protein S6 kinase (p70S6K) at Thr-389. We also discovered that β2AR, G protein-coupled receptor kinase 2 (GRK2), and protein kinase A (PKA) mediated the phosphorylation of Tau and JNK. Aβ-M induced phosphorylation of Tau at Ser-214 through both β2AR-cAMP/PKA-JNK and β2AR-GRK signaling pathways. Mitogen-activated protein kinase kinase (MEK) mediated the phosphorylation of p70S6K induced by Aβ-M.

Alzheimer’s disease (AD) is a lifelong progressive neurodegenerativa disease related with accumulation of amyloid β peptide (Aβ) produced by processing of amyloid precursor protein (APP) in the brain. In spite of several-decades effort on AD, there is still no medicine used to intervene with its pathological processes. Our previous studies made in transgenic animal models harboring familial AD genes of mutant presenilin 1 and amyloid precursor protein (APP) showed that β(2)AR gene knock-out (β(2)AR-KO) is beneficial in senile AD animals. Consistently, an epidemiological study lasted for two decades showed that the sole usage of β blockers as antihypertensive medicines is associated with fewer brain lesions and less brain shrinkage seen in senile AD patients. In order to understand why senile β(2)AR-KO AD mice had better learning and memory, genomic effects of β(2)AR-KO in the double transgenic AD mice were investigated. In the analysis, major genomic significance of β(2)AR-KO was directed to influence protein-processing and presentation involving membrane structure and MHC class I and II protein complex, and lysosome and hydrolase activity for protein degradation, which are critical for accumulation of amyloid β peptide, the hallmark of AD.

Acetylacetone (AA) has proven to be a potent photo-activator for the decolorization of dyes. However, there is very limited information on the quantitative structure-activity relationship (QSAR) and the mechanisms of dye degradation by UV/AA. Herein, the photolysis of 65 aromatic compounds (dyes and dye precursors) was investigated at three pH values (4.0, 6.0, 9.0) by UV/AA and UV/H2O2. The obtained pseudo-first-order photodegradation rate constants (k1) were processed using statistical analysis. The correlation between the k1 values and the number of photons absorbed by AA, together with the observed pH effect, suggested that the protonated enol structure of AA plays a crucial role in the photodecolorization of dyes. According to quantum chemical computation, photo-induced direct electron transfer between the excited state of AA and the dye was the main mechanism in the UV/AA process. QSAR models demonstrated that the molecular size and stability were the key factors that determined the efficiency of UV/H2O2 for dye degradation. Statistically, the UV/AA process was target-selective and suffered less from the inner filter effect, which made it more effective than the UV/H2O2 process for dye degradation. The selectivity of the UV/AA process was mainly embodied in the substituent effects: dyes with hydroxyl groups in conjugated systems decomposed faster than those with nitro-substitution or ortho-substituted sulfonate groups. The results can be used for the selection of appropriate photochemical approaches for the treatment of dye-contaminated water.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with complicated pathogeny. There could be obvious alterations of metabolism in the patients with RA and the discovery of metabolic signature may be helpful for the accurate diagnosis of RA. In order to explore the distinctive metabolic patterns in RA patients, a gas chromatography-mass spectrometry (GC-MS) method was employed. Serum samples from 33 RA patients and 32 healthy controls were collected and analyzed. Acquired metabolic data were assessed by the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the data analysis results showed RA patients and healthy controls have very different metabolic profiles. Variable importance for project values (VIP) and Student's t-test were combined to screen the significant metabolic changes caused by RA. Serums from RA patients were featured by decreased levels of amino acids and glucose, increased levels of fatty acids and cholesterol, which were primarily associated with glycolytic pathway, fatty acid and amino acid metabolism, and other related pathways including TCA cycle and the urea cycle. These preliminary results suggest that GC-MS based metabolic profiling study appears to be a useful tool in the exploration of the metabolic signature of RA, and the revealed disease-associated metabolic perturbations could help to elucidate the pathogenesis of RA and provide a probable aid for the accurate diagnosis of RA.

Morbidity of hyperuricemia has constantly increased in population in decades, and hyperuricemia has proved to be an important risk factor for gout, cardiovascular diseases and others. Many urate-lowering drugs have unfavorable side effects and drug interactions. Quzhuotongbi decoction (QZTBD) is an empirical traditional Chinese medicine prescription for clinical therapy of hyperuricemia without serious adverse effects. In the study, we investigated the effects of QZTBD on urate and other metabolites in the sera of hyperuricemia model rats. Hyperuricemia model was established by orally administering yeast extract paste, and allopurinol served as a positive control drug. Serum metabolomics was performed by using a gas chromatography-mass spectrometry (GC-MS) method. Student's t-test and the principal component analysis (PCA) were employed to find the metabolic perturbations in hyperuricemia model rats. The levels of urate, lactate, pyruvate and ornithine were significantly increased, and xanthine, glyconic acids (ribonate, galactonate), amino acids (aspartate, proline, glutamine, serine, pyroglutamate, glutamate) and glucose were down-regulated greatly in the model rats. It demonstrated that nucleotide metabolism, amino acid metabolism and glycolytic pathway were disturbed by yeast administration. An orthogonal signal correction-partial least-squares discriminant analysis (OSC-PLS DA) was performed to assess the effects of yeast administering and drug treatment. 11 significantly distinctive metabolites among four groups were defined according to the variable importance for project values (VIP>1) and univariate ANOVA (p value

Keap1 is deemed as a suppressor of Nrf2 in cytoplasm by sequestrating Nrf2 to proteolysis as an adapter of the Cul3-Rbx1 E3 ubiquitin ligase complex. In the study, it was proposed that post-translational modification might affect the interaction between Nrf2 and Keap1, and the profiles of the phosphorylation of amino acid residues of Keap1 and its effects on the binding of Keap1 to Nrf2 was investigated. A mass spectrometry analysis revealed that S53 and S293 were phosphorylated upon an oxidative stress. Using Keap1 proteins with amino acid residues mutated to glutamate to simulate the introduction of a negative charge by phosphorylation, it was found that a potential phosphorylation of S53 affected Keap1-Nrf2 binding in the pull-down assay, and induced nuclear translocation of Nrf2 in the electrophoretic mobility shift assay. Sequence homology analysis showed that S53 was highly conserved. Structural modeling around BTB domain of wild type and S53E-mutant Keap1 showed that the negative charge introduced by S53E mutation generates a salt bridge between E53 and ionized guanidine group of Arg50. Real-time qRT-PCR for transcription levels of antioxidant genes that are modulated by Nrf2 further proved the effects of the potential phosphorylation of S53 under an oxidative stress condition. In summary, S53 is a potential phosphorylation site of Keap1, and the phosphorylation could enhance the antioxidative capacity of cells in response to an oxidative stress.

Alzheimer's disease (AD) is a lifelong progressive neurodegenerativa disease related with accumulation of amyloid β peptide (Aβ) produced by processing of amyloid precursor protein (APP) in the brain. In spite of several-decades effort on AD, there is still no medicine used to intervene with its pathological processes. Our previous studies made in transgenic animal models harboring familial AD genes of mutant presenilin 1 and amyloid precursor protein (APP) showed that β2AR gene knock-out (β2AR-KO) is beneficial in senile AD animals. Consistently, an epidemiological study lasted for two decades showed that the sole usage of β blockers as antihypertensive medicines is associated with fewer brain lesions and less brain shrinkage seen in senile AD patients. In order to understand why senile β2AR-KO AD mice had better learning and memory, genomic effects of β2AR-KO in the double transgenic AD mice were investigated. In the analysis, major genomic significance of β2AR-KO was directed to influence protein-processing and presentation involving membrane structure and MHC class I and II protein complex, and lysosome and hydrolase activity for protein degradation, which are critical for accumulation of amyloid β peptide, the hallmark of AD.

A cellulase with wide range of pH resistance and high salt tolerance was isolated from the digestive gland of the oyster Crassostrea rivularis living in mangrove forests. The 27 kDa cellulase named as CrCel was purified 40.6 folds by anion exchange chromatography and extraction from the gel after non-reducing sodium dodecylsufate-polyacrylamide gel electrophoresis. The specific activity of the purified cellulase was 23.4 U/mg against carboxymethyl cellulose (CMC). The N-terminal amino acid sequence of CrCel was determined to be NQKCQANSRV. CrCel preferably hydrolyzes β-1,4-glucosidic bonds in the amorphous parts of cellulose materials and displays degradation activity toward xylan. The Km and Vmax values of CrCel for CMC were determined to be 2.1% ± 0.4% and 73.5 ± 3.3 U mg(-1), respectively. The optimal pH value and temperature of CrCel were 5.5 and 40°C, respectively. The enzyme was stable in a wide range of pH, retaining over 60% activity after incubation for 80 min in the pH range of 3.0-9.0. In addition, CrCel showed remarkable tolerance to salt and remained active at high NaCl concentrations, but also retained over 70% activity after incubation in 0.5-2 M NaCl for up to 24 h. On the basis of the N-terminal sequence alignment and its similar properties to other animal cellulases, CrCel was regarded as a member of glycosyl hydrolase family 45 β-1,4-glucanases. CrCel is the first reported cellulase isolated from mangrove invertebrates, which suggests that it may participate in the assimilation of cellulolytic materials derived from the food sources of the oyster and contribute to the consumption of mangrove primary production. The unique properties of this enzyme make it a potential candidate for further industrial application.

In the present study, the risk coefficients of serum homocysteine (hcy), lipid levels, C-reactive protein (CRP), neutrophils to lymphocyte ratio (NLR) in postmenopausal osteopenic women were determined.We enrolled 269 patients with postmenopausal women from Hangzhou No.1 Hospital gynecological clinic, who aged 45 to 60 years old and never received menopause hormone therapy. According to the bone mineral density determination results, subjects were divided into normal group (n = 128), osteopenia group (n = 141). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). Serum hcy, CRP and lipid indexes were determined by enzyme chemiluminescence immunoassay.The odds ratios (OR) and 95% confidence intervals (CI) of those variables (menopausal age, duration of menopause, LDL, CRP, hcy and NLR) were found significant (p 0.05). Menopausal age, duration of menopause, LDL, CRP, hcy and NLR variables were found statistically significant in the analysis of receiver operating characteristic (ROCs).The present study shows that menopause age, duration of menopause, serum LDL, CRP, hcy and NLR levels are risk factors for postmenopausal osteopenic women, which may be used as the indicators of bone loss in postmenopausal women.

Troxerutin, a semi-synthetic derivative of the natural bioflavanoid rutin, has been reported to possess many beneficial effects in human bodies, such as vasoprotection, immune support, anti-inflammation and anti-aging. However, the effects of troxerutin on genome-wide transcription in blood cells are still unknown. In order to find out effects of troxerutin on gene transcription, a high-throughput RNA sequencing was employed to analysis differential gene expression in blood cells consisting of leucocytes, erythrocytes and platelets isolated from the mice received subcutaneous injection of troxerutin. Transcriptome analysis demonstrated that the expression of only fifteen genes was significantly changed by the treatment with troxerutin, among which 5 genes were up-regulated and 10 genes were down-regulated. Bioinformatic analysis of the fifteen differentially expressed genes was made by utilizing the Gene Ontology (GO), and the differential expression induced by troxerutin was further evaluated by real-time quantitative PCR (Q-PCR).

Numerous studies have focused on the impact of biotic factors under the role of organic matter in the dynamics of mangrove ecosystems during the last decades, but an overall view of the role of macrobenthic fauna in organic matter processing has not yet been established. Cellulase and hemicellulase (xylanase and laminarinase) activities were measured in the extracts from eight native mangrove macrobenthic species (two gastropods, three crabs and three bivalves) of southern China with plate assay and colorimetric assay. All enzyme activities were detected in the eight species except for negligible exoglucanase activity in the crabs and the bivalves. The crabs generated the largest halo zones in the plate assays, but produced the lowest amount of reducing sugar in the colorimetric assays. The highest endoglucanase, β-1,4-glucosidase and xylanase activities were detected in Crassostrea rivularis with colorimetric assays. For each mangrove macrobenthic species, the laminarinase activity was highest am...