[Advances of studies on culture and product functions of Euglena gracilis].

Euglena gracilis is a unicellular eukaryote between animal and plant cells, which is widely distributed in nature. E. gracilis has both plant and animal characteristics, and can grow photoautotrophically, heterotrophically and mixotrophically. E. gracilis also features on abundant and various cellular composition. Recently, extensive researches on unique cellular components of E. gracilis have revealed its application in the field of medicine, food, and feedstuff, in terms of improving immunity, fighting inflammation, and lowering uric acid levels. The application prospects of paramylon in biomedical area were also discovered. As food ingredients, food additives, feedstuffs and cosmetic ingredients, E. gracilis has been certified domestically and overseas. A series of products have been developed overseas, especially in Japan. However, the research and development of E. gracilis are still in its infancy in China, and there is huge space for development. At present, the research and potential application of cultivation and product functions of E. gracilis have been rarely reviewed. This review systematically examines both the domestic and abroad research of cultivation and production of E. gracilis, as well as the biological activity of E. gracilis powder and paramylon. The existing problems in the application, exploitation, and possible development direction of E. gracilis in the future are prospected. This review might be useful for establishing and optimizing large-scale and efficient heterotrophic technology, as well as developing related products of E. gracilis with specific functions.

Characterization, Semirational Design for pH Robustness, and the Application in Bioactive Peptide Production of a X-Prolyl Dipeptidyl Aminopeptidase from Lactococcus lactis MY-3.

PepXLcMY-3, an X-prolyl dipeptidyl aminopeptidase derived from Lactobacillus lactis MY-3, was screened and recombinantly expressed in Escherichia coli. The enzyme could exhibit about 40% activity within the pH range of 6.0-10. To further improve the pH robustness, site E396 located in the active pocket was discovered through alanine scanning. The mutant E396I displayed both developed activity and kcat/Km. The optimal pH of E396I shifted from 6.0 to 10 compared to WT, with the relative activity within the pH range of 6.0-10 significantly increased. The site K648 was then proposed by semirational design. The activity of mutant E396I/K648D reached 4.03 U/mg. The optimal pH was restored to 6.0, and the pH stability was further improved. E396I/K648D could totally hydrolyze ß-casomorphin 7 within 30 min. The hydrolysate showed 64.5% inhibition on angiotensin I converting enzyme, which was more efficient than those produced by E396I and WT, 23.2 and 44.7%, respectively.

Lactiplantibacillus plantarum X7022 Plays Roles on Aging Mice with Memory Impairment Induced by D-Galactose Through Restoring Neuronal Damage, Relieving Inflammation and Oxidative Stress.

In this study, Lactiplantibacillus plantarum X7022 was applied to ameliorate memory impairment of aging mice induced by D-galactose. The strain showed specific choloylglycine hydrolysis ability based on in vitro investigation. Morris water maze test showed L. plantarum X7022 administration improved learning ability and spatial memory of aging mice. The gavage of L. plantarum X7022 displayed a promising ability of relieving cerebral oxidative stress and hippocampal inflammatory condition according to the increased GSH level and SOD activity and decreased MDA level, as well as decreased TNF-α, IL-1ß, and IL-6 levels. The intervention with the strain could protect neuron by regulating cell apoptosis and AChE overexpression and inhibiting amyloid-ß deposition, as well as affect neuron functions by regulating CREB-BDNF signaling pathways and iNOS expression. Besides, the strain could improve fecal SCFA contents and increase the abundance of anti-inflammatory and antioxidant-related genera such as Lactobacillus, Akkermansia, and Adlercreutzia. These results suggest that L. plantarum X7022 could be a prospective therapeutic alternative for the improvement of memory impairment among the elderly.

The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory strain, Lactiplantibacillus plantarum X7022.

PURPOSE: Probiotics have been reported to effectively alleviate hyperuricemia and regulate the gut microbiota. The aim of this work was to study the in vivo anti-hyperuricemic properties and the mechanism of a novel strain, Lactiplantibacillus plantarum X7022. METHODS: Purine content and mRNA expression of purine assimilation related enzymes were determined by HPLC and qPCR, respectively. Hyperuricemic mice were induced by potassium oxonate and hypoxanthine. Uric acid (UA), blood urea nitrogen, creatinine and renal inflammation were examined by kits. The expression of renal UA transporters was subjected to western blotting. Kidney tissues were sectioned for histological analysis. The fecal short-chain fatty acids (SCFAs) were determined by HPLC, and gut microbiota was investigated using the 16S rDNA metagenomic sequencing. RESULTS: L. plantarum X7022 possesses a complete purine assimilation pathway and can exhaust xanthine, guanine, and adenine by 82.1%, 33.1%, and 12.6%, respectively. The strain exhibited gastrointestinal viability as 44% at the dose of 109 CFU/mL in mice. After four-week administration of the strain, a significant decrease of 35.5% in the serum UA level in hyperuricemic mice was achieved. The diminished contents of fecal propionate and butyrate were dramatically boosted. The treatment also alleviated renal inflammation and restored renal damage. The above physiological changes may due to the inhibited xanthine oxidase (XO) activity, as well as the expressional regulation of UA transporters (GLUT9, URAT1 and OAT1) to the normal level. Notably, gut microbiota dysbiosis in hyperuricemic mice was improved with the inflammation and hyperuricemia related flora depressed, and SCFAs production related flora promoted. CONCLUSION: The strain is a promising probiotic strain for ameliorating hyperuricemia.

Dynamics of an SEIR model with media coverage mediated nonlinear infectious force.

Media coverage can greatly impact the spread of infectious diseases. Taking into consideration the impacts of media coverage, we propose an SEIR model with a media coverage mediated nonlinear infection force. For this novel disease model, we identify the basic reproduction number using the next generation matrix method and establish the global threshold results: If the basic reproduction number $ \mathcal{R}_{0} < 1 $, then the disease-free equilibrium $ P_{0} $ is stable, and the disease dies out. If $ \mathcal{R}_{0} > 1 $, then the endemic equilibrium $ P^{*} $ is stable, and the disease persists. Sensitivity analysis indicates that the basic reproduction number $ \mathcal{R}_{0} $ is most sensitive to the population recruitment rate $ \Lambda $ and the disease transmission rate $ \beta _{1} $.

TRIM59 attenuates ox-LDL-induced endothelial cell inflammation, apoptosis, and monocyte adhesion through AnxA2.

Background: Atherosclerosis (AS), a chronic inflammatory vascular disease, is a cause of heart attack and ischemic stroke. Tripartite motif-containing protein 59 (TRIM59), a member of the tripartite motif family, has been reported to be involved in inflammatory diseases. This study was to investigate the role of TRIM59 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cells and examine the mechanism of TRIM59. Methods: To simulate a cellular model of AS in vitro, varying concentrations of ox-LDL (i.e., 20, 40, 60, 80, and 100 µg/mL) were used to treat the human umbilical vein endothelial cells (HUVECs) for 24 h. The messenger ribonucleic acid (RNA) and protein levels of TRIM59, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and annexin 2 (AnxA2) were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. The transfection efficacy of overexpression (Ov)-TRIM59 and small-interfering RNA-AnxA2 was examined by RT-qPCR and western blot. Cell counting kit-8 assays, lactate dehydrogenase (LDH) assays, enzyme-linked immunosorbent assays, and terminal-deoxynucleotidyl transferase mediated nick end labeling staining were used to examine viability, LDH expression, inflammation, and apoptosis in HUVECs. The protein levels of B-cell lymphoma 2, Bcl-2-associated X (BAX), cleaved caspase3, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were assessed by western blot. Additionally, the adhesion of THP-1 to ox-LDL-induced HUVECs was detected using monocyte adhesion assays and the binding of TRIM59 and AnxA2 was verified by co-immunoprecipitation. Results: This study showed that TRIM59 expression was decreased in the ox-LDL-induced HUVECs while LOX-1 expression was increased. After transfection with Ov-TRIM59, TRIM59 in ox-LDL-induced HUVECs was increased, and TRIM59 overexpression alleviated the viability damage, inflammation, and apoptosis of the ox-LDL-induced HUVECs. In addition, THP-1 adhesion to the ox-LDL-induced HUVECs was also suppressed by TRIM59 overexpression. This study also showed that TRIM59 could bind to AnxA2 and promote AnxA2 expression in ox-LDL-stimulated HUVECs. Moreover, the rescue experiments revealed that TRIM59 suppressed the viability damage, inflammation, apoptosis, and monocyte adhesion of the ox-LDL-induced HUVECs via AnxA2. Conclusions: TRIM59 protected against ox-LDL-induced AS by binding to AnxA2.

Anti-Hyperuricemic, Nephroprotective, and Gut Microbiota Regulative Effects of Separated Hydrolysate of α-Lactalbumin on Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice.

SCOPE: This study aims to investigate the anti-hyperuricemic and nephroprotective effects and the potential mechanisms of the separated gastrointestinal hydrolysates of α-lactalbumin on hyperuricemic mice. METHODS AND RESULTS: The gastrointestinal hydrolysate of α-lactalbumin, the hydrolysate fraction with molecular weight (MW) < 3 kDa (LH-3k), and the fragments with smallest MW among LH-3K harvested through dextran gel chromatography (F5) are used. Hyperuricemia mice are induced via daily oral gavage of potassium oxonate and hypoxanthine. F5 displays the highest in vitro xanthine oxidase (XO) inhibition among all the fractions separated from LH-3k. Oral administration of F5 significantly reduces the levels of serum uric acid (UA), creatinine, and urea nitrogen. F5 treatment could ameliorate kidney injury through alleviating oxidative stress and inflammation. F5 alleviates hyperuricemia in mice by inhibiting hepatic XO activity and regulating the expression of renal urate transporters. Gut microbiota analysis illustrates that F5 administration increases the abundance of some SCFAs producers, and inhibits the growth of hyperuricemia and inflammation associated genera. LH-3k exhibits similar effects but does not show significance as those of the F5 fraction. CONCLUSION: The anti-hyperuricemia and nephroprotective functions of F5 are mediated by inhibiting hepatic XO activity, ameliorating oxidative stress and inflammation, regulating renal urate transporters, and modulating the gut microbiota in hyperuricemic mice.

The effects of angiotensin I-converting enzyme inhibitory peptide VGINYW and the hydrolysate of α-lactalbumin on blood pressure, oxidative stress and gut microbiota of spontaneously hypertensive rats.

VGINYW is a highly active angiotensin I-converting enzyme (ACE) inhibitory peptide discovered from α-lactalbumin by an in vitro-in silico high throughput screening strategy. The aim of this study was to evaluate the antihypertensive effect of the peptide and the α-lactalbumin hydrolysates under 3 kDa (LH-3k), and illustrate the possible mechanism in spontaneously hypertensive rats (SHRs). SHRs were administered with VGINYW and LH-3k at doses of 5 mg per kg BW and 100 mg per kg BW, respectively. VGINYW and LH-3k could markedly decrease the systolic blood pressure (SBP) of the SHRs, and the maximal drops of 21 mmHg (2 h after administration) and 17 mmHg (4 h after administration) were achieved during the 8 hour test, respectively. When the agents were given once per day for 4 weeks, they caused a long-term decrease of 16 mmHg of SBP. VGINYW and LH-3k control the blood pressure through regulating the renin-angiotensin system by inhibiting the ACE activity and diminishing the angiotensin II level, and further upregulating the expression levels of the angiotensin-converting enzyme 2 and angiotensin type 2 receptor, and downregulating the expression of the angiotensin type 1 receptor. VGINYW and LH-3k could notably ameliorate the oxidative stress in the SHR as well. It is more important that the gavage of VGINYW and LH-3k could alleviate hypertension-associated intestinal microbiota dysbiosis by recovering the diversity of the gut microbiota and altering the key floras which are short chain fatty acid producers. In conclusion, VGINYW and LH-3k are effective functional ingredients for blood pressure control.

Guanosine ameliorates positive symptoms of schizophrenia via modulating 5-HT1A and 5-HT2A receptors.

Schizophrenia is a serious mental disorder characterized by hallucinations, delusions, and extremely disordered thinking and behavior. There are several hypotheses of pathogenesis in schizophrenia: dopaminergic, glutamatergic, or serotonergic hyperfunction. Guanosine reportedly protects the central nervous system by modulating the glutamatergic system. Thus, we assumed that guanosine may exert a positive effect on the pathophysiology of schizophrenia. Herein, we demonstrated that guanosine significantly reduced MK-801-induced hyperlocomotion and stereotyped behaviors, but showed no effect on hyperlocomotion induced by d-amphetamine, indicating that guanosine may directly affect the glutamatergic system. Guanosine dose-dependently reduced 5-HTP-induced wet dog shakes (WDS) and other serotonin syndromes (SS) behaviors, indicating that it might block serotonin 5-HT1A or 5-HT2A receptors. Finally, we confirm that that guanosine modulates serotonin 5-HT1A and 5-HT2A receptors and it might be anti-schizophrenic partly through pertussis toxin-sensitive Gi/o-coupled PI3K/Akt signaling. Collectively, this study provides possible compounds and mechanisms for therapeutic effects on schizophrenia.

Metabolism Characteristics of Lactic Acid Bacteria and the Expanding Applications in Food Industry.

Lactic acid bacteria are a kind of microorganisms that can ferment carbohydrates to produce lactic acid, and are currently widely used in the fermented food industry. In recent years, with the excellent role of lactic acid bacteria in the food industry and probiotic functions, their microbial metabolic characteristics have also attracted more attention. Lactic acid bacteria can decompose macromolecular substances in food, including degradation of indigestible polysaccharides and transformation of undesirable flavor substances. Meanwhile, they can also produce a variety of products including short-chain fatty acids, amines, bacteriocins, vitamins and exopolysaccharides during metabolism. Based on the above-mentioned metabolic characteristics, lactic acid bacteria have shown a variety of expanded applications in the food industry. On the one hand, they are used to improve the flavor of fermented foods, increase the nutrition of foods, reduce harmful substances, increase shelf life, and so on. On the other hand, they can be used as probiotics to promote health in the body. This article reviews and prospects the important metabolites in the expanded application of lactic acid bacteria from the perspective of bioengineering and biotechnology.

Surface contacts strongly influence the elasticity and thermal conductivity of silica nanoparticle fibers.

Granular materials are often encountered in science and engineering disciplines, in which controlling the particle contacts is one of the critical issues for the design, engineering, and utilization of their desired properties. The achievable rapid fabrication of nanoparticles with tunable physical and chemical properties facilitates tailoring the macroscopic properties of particle assemblies through contacts at the nanoscale. Models have been developed to predict the mechanical properties of macroscopic granular materials; however, their predicted power in the case of nanoparticle assemblies is still uncertain. Here, we investigate the influence of nanocontacts on the elasticity and thermal conductivity of a granular fiber comprised of close-packed silica nanoparticles. A complete elastic moduli characterization was realized by non-contact and non-destructive Brillouin light spectroscopy, which also allowed resolving the stiffness of the constituent particles in situ. In the framework of effective medium models, the strong enhancement of the elastic moduli is attributed to the formation of adhesive nanocontacts with physical and/or chemical bondings. The nanoparticle contacts are also responsible for the increase in the fiber thermal conductivity that emphasizes the role of interface thermal resistance, which tends to be ignored in most porosity models. This insight into the fundamental understanding of structure-property relationships advances knowledge on the manipulation of granular systems at the nanoscale.

Characterization and rational design for substrate specificity of a prolyl endopeptidase from Stenotrophomonas maltophilia.

A novel prolyl endopeptidase from Stenotrophomonas maltophilia, SmPEP, was discovered and characterized. The specific activity of the recombinant SmPEP expressed by Escherichia coli BL21 (DE3), was 68.3 U/mg at pH 8.0 and 37 °C. In order to improve the substrate specificity for long-chain peptide, rational design was applied based on the structure constructed by homology modeling. Inter-domain sites within the ß-propeller domain were chosen for the mutation to weaken the inter-domain interaction and form an open conformation for long-chain substrate entering into the active site. The substrate specificity on a designed long-chain substrate, PQPQLPYPQPQLP, of the mutants F263A and E184 G increased 8.77 and 5.75 times respectively versus wild-type. After the saturated mutation of the both sites, the reactive rate of mutant F263 V on 13-mer peptide was 10.2 times higher than that of the wild-type. Then the mutant F263 V was used in the hydrolysis of casein, and the ACE inhibitory activity of the hydrolysate was significantly improved compared with wild type enzyme, which verified the efficiency of the design strategy.

Structural diversity of metal-organic frameworks based on a chalcone dicarboxylic acid ligand.

Using chalcone dicarboxylic acid ligands, three different metal-organic frameworks have been successfully obtained. Interestingly, structural diversity has been observed. The difference between compounds 2 and 3 is the inconsistent orientation of the adjacent binuclear Cd clusters. In addition, the photocatalytic properties of compounds 1 and 2 for the degradation of several organic dyes have been explored.

Selective Adsorption of C60 in the Supramolecular Nanopatterns of Donor-Acceptor Porphyrin Derivatives.

The nanostructure of active layers consisting of donor and acceptor molecules is responsible for the separation and transfer processes of charge carriers, which may result in different photoelectric conversion efficiencies of organic photovoltaic cells (OPVCs). Therefore, intensive study on the relationships among nanostructures, intermolecular interactions, and molecular chemical skeletons is necessary for preparing controlled nanostructures of active layers by designing photovoltaic molecules. In this research, the self-assembled nanopatterns of three (DPP-ZnP-E)2-based molecules on highly oriented pyrolytic graphite surface were probed by scanning tunneling microscopy and analyzed by density functional theory calculations. The results indicated that different bridges, diethynylene, diethynylene-dithienyl, and diethynylene-phenylene, in (DPP-ZnP-E)2-based molecules not only made a difference to intermolecular interactions and cooperated with molecule-substrate interactions, consequently affecting the packed nanopattern, but also influenced the adsorption of fullerene acceptors in the nanopatterns of (DPP-ZnP-E)2-based molecules. C60 molecules were found to be selectively adsorbed atop the dithienyl groups of (DPP-ZnP-E)2-2T donor molecules probably by S···π interactions compared with (DPP-ZnP-E)2 or (DPP-ZnP-E)2-Ph molecules. This study on the assembled nanopatterns of the three (DPP-ZnP-E)2-based molecules would be conductive to (DPP-ZnP-E)2-based optoelectronic materials design in OPVCs.

Correction: Isopolymolybdate-based inorganic-organic hybrid compounds constructed by multidentate N-donor ligands: syntheses, structures and properties.

Correction for 'Isopolymolybdate-based inorganic-organic hybrid compounds constructed by multidentate N-donor ligands: syntheses, structures and properties' by Haiyang Guo et al., Dalton Trans., 2019, DOI: 10.1039/c9dt00119k.

Isopolymolybdate-based inorganic-organic hybrid compounds constructed by multidentate N-donor ligands: syntheses, structures and properties.

Taking advantage of isopolymolybdate [(NH4)6Mo7O24·4H2O] as a POM building block with multidentate N-donor molecules (tris[(2-pyridyl)methyl]amine = TPMA, 1-(tetrazo-5-yl)-3-(triazo-1-yl)benzene = 1,3-ttb) as organic ligands, five different inorganic-organic hybrid compounds were synthesized and characterized by single-crystal X-ray diffraction, infrared spectroscopy (IR) and powder X-ray diffraction (PXRD). Compound 1 is a Mo(vi)-based structure in which the TPMA ligand shows a tridentate coordination mode, which bears an uncoordinated pyridyl arm, and can further react with transition metals. Compound 2 exhibits a Cu(ii)-based zero-dimensional (0D) structure consisting of the TPMA ligand and [ß-Mo8O26] polyanion. Compounds 3 and 4 have the same molecular formula with slight structural differences; both have the Co(ii)-based one-dimensional (1D) chain structure. Compared to the ß-Mo8O26 polyanion in compound 3, the [Mo8O28]8- units condense via sharing two common terminal O atoms to form infinite [Mo8O26]n4n- chains in compound 4. Compound 5 is a Cu(ii)-based two-dimensional (2D) layer structure consisting of TPMA and 1,3-ttb mixed ligands and [ß-Mo8O26]. In addition, the electrochemical properties and photocatalytic activities for the degradation of two types of organic dyes were explored for several compounds.

Identification of the enzymes responsible for 3-hydroxypropionic acid formation and their use in improving 3-hydroxypropionic acid production in Gluconobacter oxydans DSM 2003.

Gluconobacter oxydans can be efficiently used to produce 3-hydroxypropionic acid (3-HP) from 1,3-propanediol (1,3-PDO). However, the enzymes involved remain unclear. In this study, transcription analysis of two mutants of strain DSM 2003, obtained by UV-mutagenesis, revealed that membrane-bound alcohol dehydrogenase (mADH) and membrane-bound aldehyde dehydrogenase (mALDH) might be the main enzymes involved. Through deletion and complementation of the genes adhA and aldh, mADH and mALDH were verified as the main enzymes responsible for 3-HP production. Then mALDH was verified as the rate-limiting enzyme in 3-HP production. Since that overexpression of mADH had no effect on 3-HP production, whereas overexpression of mALDH increased 23.6% 3-HP production. Finally, the 3-HP titer of 45.8 g/L and the highest productivity 1.86 g/L/h were achieved when the two mutants DSM 2003/adhAB and DSM 2003/aldh were mixed at a ratio of 1:2 (cell density) and used as whole cell catalysts for 3-HP production.

Flexible and rigid dicarboxylic acids enable the assembly of achiral and chiral 3D Co(ii) metal-organic frameworks.

Two novel 3D Co(ii) metal-organic frameworks induced by flexible and rigid dicarboxylic acids [Co3(µ3-OH)(1,4-ttb)3(sa)]·3H2O (1) and Co2(µ3-OH)(1,4-ttb)(4,4'-bpdc) (2) (1,4-ttb = 1-(tetrazo-5-yl)-4-(triazo-1-yl)benzene, sa = succinic acid and 4,4'-bpdc = biphenyl-4,4'-dicarboxylic acid) have been successfully synthesized and characterized via X-ray single-crystal diffraction, powder X-ray diffraction (PXRD), FT-IR spectroscopy and TG analyses. In the structures of the compounds 1 and 2, the main ligand 1,4-ttb coordinates with Co(ii) ions to form 3D host frameworks with different cavities, and the auxiliary ligands sa and 4,4'-bpdc fill the 3D cavities. More strikingly, compound 2 is a chiral 3D metal-organic framework, in which 4,4'-bpdc acts as a rigid achiral ligand. Additionally, the electrochemical properties and magnetic properties of compounds 1 and 2 have been investigated.