Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism,inflammation reaction and bile acid metabolism in ApoE^(-/-)mice

Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.

The Future of Plasticizers: Biobased and Oligomeric

The deficiencies of popular phthalate plasticizers(ready migration from a polymer matrix into which they have been incorporated,flammability,environmental pollution,human health risks)have stimulated efforts to develop new effective,nonmigrating,low-cost,nontoxic replacements.In the main,these have been based on readilyavailable,nontoxic biobased precursors.Some,including those prepared from plant oils,have been generated from biomaterials themselves.However,the more numerous and generally more effective have been generated from discrete compounds produced from various biomaterials.Several structural features of effective plasticizers have been recognized.Polar functionality is required to assure compatibility with a wide range of polymeric materials,including poly(vinyl chloride)(PVC),the most heavily plasticized polymer.A branched structure greatly enhances the effectiveness of compounds used as plasticizers.An oligomeric structure may strongly limit or prevent migration from a polymer matrix.Hyperbranched oligomers of defined structure derived from the readilyavailable,inexpensive,nontoxic biomonomers,glycerol and adipic acid contain all these features and are excellent plasticizers.They contain ester functionality,are highly branched,and display a large number of end groups,all of which contribute to their effectiveness as plasticizers.

Altered serum level of cartilage oligomeric matrix protein and its association with coronary calcification in patients with coronary heart disease

Background Cartilage oligomeric matrix protein （COMP） is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease （CHD） patients, and the relationship between serum COMP and the calcification of coronary artery. Methods A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed to- mography （MSCT） within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages： CHD group （diameter narrowing 〉 50%, n = 194） and control group （diameter narrowing 〈 50%, n = 39）. The Gen- sini score, Syntax score and coronary artery calcium score （CACs） were calculated. The serum COMP level was determined using ELISA. Results The levels of COMP were significantly higher in the CHD group than in the control group 155.7 （124.5-194.5） ng/mL vs. 128.4 （113.0-159.9） ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis 〉 50%. The serum COMP was correlated with age （r = 0.294, P 〈 0.001）, fasting glucose （r = 0.163, P = 0.015）, HbAlc （r = 0.194, P = 0.015） and CACs （r = 0.137, P = 0.037）. Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients （fl = 0.402, t = 2.612, P = 0.015; fl = 0.472, t = 3.077, P = 0.005）. Performance of COMP for predicting CHD was shown as area under curve （AUC）： 0.632, 95% CI： 0.549-0.715 and upper tertile CACs was AUC： 0.602, 95% CI： 0.5264）.678 in receiver operating characteristic （ROC） curve analysis. Conclusion Calcification of coronary artery was an independent predictor of serum COMPs.

Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis

The death of retinal ganglion cells is a hallmark of many optic neurodegenerative diseases such as glaucoma and retinopathy. Oxidative stress is one of the major reasons to cause the cell death. Oligomeric proanthocyanidin has many health beneficial effects including antioxidative and neuro- protective actions. Here we tested whether oligomeric proanthocyanidin may protect retinal gan- glion cells against oxidative stress induced-apoptosis in vitro. Retinal ganglion cells were treated with hydrogen peroxide with or without oligomeric proanthocyanidin. 3-（4,5-Dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTT） assay showed that treating retinal ganglion cell line RGC-5 cells with 20 pmol/L oligomeric proanthocyanidin significantly decreased the hydrogen peroxide （H202） induced death. Results of flow cytometry and Hoechst staining demonstrated that the death of RGC-5 cells was mainly caused by cell apoptosis. We further found that expression of pro-apoptotic Bax and caspase-3 were significantly decreased while anti-apoptotic Bcl-2 was greatly increased in H202 damaged RGC-5 cells with oligomeric proanthocyanidin by western blot assay. Furthermore, in retinal explant culture, the number of surviving retinal ganglion cells in H202-damaged retinal ganglion cells with oligomeric proanthocyanidin was significantly increased. Our studies thus demonstrate that oligomeric proanthocyanidin can protect oxidative stress-injured retinal ganglion cells by inhibiting apoptotic process.

Persistent elevation of fibrosis biomarker cartilage oligomeric matrix protein following hepatitis C virus eradication

Serum levels of cartilage oligomeric matrix protein(COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated.

Synthesis and Luminescent Property of Polycarbazole/Polyhedral Oligomeric Silsesquioxane Nanocomposites

Polyvinylcarbazole（PVK） composites containing organic-inorganic hybrid polyhedral oligomeric silse-squioxane（POSS） PVK-POSS were prepared by free radical polymerization. POSS monomers reacted with vinylcarbazole and were completely dispersed at molecular level in PVK matrix and PVK-POSS nanocomposites display higher glass transition temperature（Tg） in comparison with neat PVK. Optical properties of PVK/POSS nanocomposites were investigated by UV-spectrum and PL-spectrum and the results show that the PVK-POSS nanoparticles have a good interface effect and improve color purity effectively. The maximum absorption wavelength bathochromically shifts gradually with the increasing of the content of POSS. The luminescent intensity becomes higher and higher with the increase of POSS content, and reaches its maximum luminescent intensity when the POSS content is 3% （mass fraction）, while some POSS-rich nanoparticles are present in matrix when contents of POSS are beyond 5%.

Functional foods effective for hepatitis C: Identification of oligomeric proanthocyanidin and its action mechanism

Hepatitis C virus(HCV)is a major cause of viral hepatitis and currently infects approximately 170 million people worldwide.An infection by HCV causes high rates of chronic hepatitis(】75%)and progresses to liver cirrhosis and hepatocellular carcinoma ultimately.HCV can be eliminated by a combination of pegylatedα-interferon and the broad-spectrum antiviral drug ribavirin;however,this treatment is still associated with poor efficacy and tolerability and is often accompanied by serious side-effects.While some novel direct-actingantivirals against HCV have been developed recently,high medical costs limit the access to the therapy in cost-sensitive countries.To search for new natural anti-HCV agents,we screened local agricultural products for their suppressive activities against HCV replication using the HCV replicon cell system in vitro.We found a potent inhibitor of HCV RNA expression in the extracts of blueberry leaves and then identified oligomeric proanthocyanidin as the active ingredient.Further investigations into the action mechanism of oligomeric proanthocyanidin suggested that it is an inhibitor of heterogeneous nuclear ribonucleoproteins(hn RNPs)such as hn RNP A2/B1.In this review,we presented an overview of functional foods and ingredients efficient for HCV infection,the chemical structural characteristics of oligomeric proanthocyanidin,and its action mechanism.

Hydration effect on the electronic transport properties of oligomeric phenylene ethynylene molecular junctions

A first-principles computational method based on the hybrid density functional theory is developed to simulate the electronic transport properties of oligomeric phenylene ethynylene molecular junctions with H2O molecules accumulated in the vicinity as recently reported by Na et al. [Nanotechnology 18 424001 （2007）]. The numerical results show that the hydrogen bonds between the oxygen atoms of the oligomeric phenylene ethynylene molecule and H2O molecules result in the localisation of the molecular orbitals and lead to the lower transition peaks. The H2O molecular chains accumulated in the vicinity of the molecular junction can not only change the electronic structure of the molecular junctions, but also open additional electronic transport pathways. The obvious influence of H2O molecules on the electronic structure of the molecular junction and its electronic transport properties is thus demonstrated.

Study of Flame Retardation of Polycarbonate Modified by Polyhedral Oligomeric Silsesquioxane and Caged Bicyclic Phosphate

The flame-retarded polycarbonate（PC） has been made with octaphenyl polyhedral silsesquioxane（OPS） and/or caged bicyclic phosphate（Trimer）.Thermal gravimetric analysis（TGA）,Fourier-transform infrared（FTIR）,TGA-FTIR,limiting oxygen index（LOI）,and mechanical tests have been employed to characterize the modified PC.The additives of OPS and Trimer in PC have been proved to be effective flame-retardants because of the synergistic interaction between the elements of P and Si.The role of OPS and Trimer in PC degradation are different：OPS participates in the charring of PC,while Trimer makes PC degrade in advance.In addition,OPS and Trimer induced obvious differences in the mechanical properties of PC.

Synthesis of Nonionic Oligomeric Manganese(Ⅱ) Complexes and Investigation of Their Toxicity andΤ_1-Relaxation Enhancement

Six nonionic oligomeric manganese （ Ⅱ ） complexes with oligomeric phosphate-polyglycol-EDTA ester ligands were synthesized and characterized. The longitudinal relaxivities of these complexes were measured. One of these complexes, which showed the highest relaxivity, was chosen to be used in the acute toxicity test and the T1-weighted imaging experiment. It has been found that compared to Gd-DTPA, this nonionic oligomeric Mn（ Ⅱ ） complex exhibits no acute toxicity, generates highly enhanced MRI signals and increases the intention time in the rat liver tissue.

Flame-retardant oligomeric electrolyte additive for self-extinguishing and highly-stable lithium-ion batteries:Beyond small molecules

Preparing both safe and high-performance lithium-ion batteries(LIBs) based on commonly used commercial electrolytes is highly desirable,yet challenging.To overcome the poor compatibility of conventional small-molecular flame-retardants as electrolyte additives for safe LIBs with graphite anodes,in this study,we propose and design a novel low-cost flame-retardant oligomer that achieves an accurate and complete reconciliation of fire safety and electrochemical performance in LIBs.Owing to the integration of phosphonate units and polyethylene glycol(PEG) chains,this oligomer,which is a phosphonatecontaining PEG-based oligomer(PPO),not only endows commercial electrolytes with excellent flame retardancy but also helps stabilize the electrodes and Li-ion migration.Specifically,adding 15 wt% of PPO can reduce 70% of the self-extinguishing time and 54% of total heat release for commercial electrolytes.Moreover,LiFePO_(4)/lithium and graphite/lithium cells as well as LiFePO_(4)/graphite pouch full cells exhibit good long-term cycling stability.

Fabrication of Layer-by-layer Films of Polyhedral Oligomeric Silsesquioxanes

Layer-by-layer (LBL) self-assembly method was used to fabricate siliceous ultrathin films by using polyhedral oligomeric silsesquioxanes as building blocks. Ammonium salt of octasilsesquioxane acid (OSi8) and poly(diallyldimethylammonium chloride) (PDDA) were alternately assembled onto CaF2 slide to form nanocomposite multilayers. Linear build-up of the LBL films was confirmed by UV-Vis spectroscopy. IR spectrum suggests existence of OSi8 and PDDA in the LBL films. Atomic force microscopic surface topography of the LBL films indicates the OSi8 covers the entire surface of the topmost layer and shows a granular morphology.

Effects of Temperature and Energy on Stability of Oligomeric Enzyme Probed on Electrospray Ionization Mass Spectrometry

Escherichia coli 3-Deoxy-D-manno-octulosonate 8-phosphate（KDO8P） synthase catalyzed the condensation reaction between D-arabinose 5-phosphate（A5P） and phosphoenolpyruvate（PEP） to form KDO8P and inorganic phosphate（Pi）. The noncovalent tetrameric association ofKDO8P synthase was observed and dissociated in gas phase by means of electrospray ionization mass spectrometry under the very ＂soft＂ conditions. The results indicate that PEP-bound enzyme generated abundant tetrameric species as well as monomeric species at the ＂soft＂ conditions, whereas, the unbound enzyme favored the formation of a dimeric species. The mass spectra of the mixture of the enzyme with one of substrates, PEP, and A5P or one of products, KDO8P and Pi show that the complex of the unbound enzyme with PEP or Pi was prone to the formation of a monomeric species, whereas, that of the unbound enzyme with A5P or KDO8P was similar to the unbound enzyme. The intensity of the dimeric species increased with the increase of temperature at a collision voltage of 10 V. Taken together, the results presented here suggest that mass spectrometry will be a powerful tool to explore subtile conformational changes and/or subunit-subunit interactions of multiprotein assembly induced by ligand-binding and/or the changes of environmental conditions.

A Test for Stabilization of an Oligomeric Protein by Introduction of Aromatic Residues into the Interface

The design of variants to enhance conformational stability of proteins is an important aspect of protein engineering. Oligomeric proteins are often stabilized by aromatic clusters located within the subunit interfaces. In the present study, the authors constructed five variants of Ps3aHSD （Pseudomonas sp. B-0831 3a-hydroxysteroid dehydrogenase） in which one or two residues at the dimer interface were replaced with aromatic residues, and examined the effects of introducing aromatic residues in this region on protein thermostability. Under their experimental conditions, all variants formed dimers, similar to wild-type Ps3aHSD. Thermal denaturation experiments indicated that Tm of all variants was 0.2-16.2 °C lower than that of wild-type protein, indicating less stable thanwild-type protein. The results collectively suggest that aromatic residues of natural oligomeric proteins are strictly posted in the interface to facilitate optimal interactions and avoid conformational strain.

Ni/ZSM-5 Catalysts for Light Olefin Oligomerization:Effects of Supports and Ni Sites on Activity and Selectivity

A series of Ni/ZSM-5 containing a small amount of Ni was prepared by an ion exchanged method.The impact of the n(SiO_(2))/n(Al_(2)O_(3))ratio on the catalytic activity was studied using the samples 0.09Ni/ZSM-5(60)and 0.09Ni/ZSM-5(130).To determine the interaction between the Ni species and acid sites on the surface of the catalyst,the catalysts were characterized by N2 adsorption-desorption,X-ray diffraction(XRD),scanning electron microscopy(SEM),and UV-vis spectroscopy.The performance of the catalysts for the catalytic oligomerization of 1-hexene was investigated in detail.The nickel species were found to be uniformly distributed in all the catalysts.It was discovered that the oligomerization activity of the catalyst can be improved using Ni species;however,the contribution of Brønsted acids in oligomerization reactions is greater than that of Ni sites and Lewis acids.

Human islet amyloid polypeptide oligomers stabilized and probed by MAS NMR

The capture and characterization of oligomers are extremely important in the studies of amyloid aggregation of proteins and peptides.Oligomers are critical intermediates that can impact the structures of amyloid fibrils.Moreover,it is widely accepted that oligomers are the most toxic species along the aggregation pathway[1e4].The studies of oligomers are believed to shed light on the molecular mechanism of amyloid fibrillation and probably the medical clues for related diseases.In vitro investigations of amyloid oligomers are challenging due to their transient and polymorphic nature[5].This is particularly evident in the case of human type-2 diabetes-associated islet amyloid polypeptide(hIAPP),which tends to rapidly form polymorphic fibrils within minutes[6].Notably,hIAPP demonstrates a higher propensity for rapid aggregation compared to other amyloid proteins such as a-synuclein[7].

Optical Properties of Oligo（fluorene-vinylene） Functionalized Anthracene Linear Oligomers： Effect of π-extension

The photo-physical properties of oligo（fluorene-vinylene） functionalized anthracene linear oligomers （An-OFVn （n=1-4）） have been systemically investigated through experimental and theoretical methods. The steady-state spectral measurement shows that the increasing of fluorene-vinylene （FV） group could lead to the red shift of absorption spectra and restrain the excimer formation between oligomers. Quantum chemical calculations exhibit that the energy levels of HOMO, LUMO, and the band gap gradually converge to a constant in accompany with the increasing of FV unit. Meanwhile, the electronic cloud which distributes on the branch arms, also gradually enhances and makes the absorption spectral shape of oligomers become similar to that of branch arms step by step. The time-resolved fluorescence tests exhibits that the lifetime of excimer emission would be almost invariable after the number of FV group in oligomer is ≥2. In nonlinear optical test, the two-photon photoluminescence efficiency and two-photon absorption cross-section will both gradually enhance and be close to an extremum after the number of FV unit is equal to 4. These results will provide a guideline for the design of novel photo-electronic materials.

Effect of acid density of HZSM-5 on the oligomerization of ethylene in FCC dry gas

The oligomerization of ethylene in FCC dry gas over HZSM-5 catalyst with different Si/A12 ratios was studied. The effect of acid density of catalyst on the oligomerization of ethylene was discussed. By increasing the acid density of catalyst, ethylene conversion showed a linear increase, while the yields of olefins decreased when the acid density of catalyst exceeded 0.14mmolNH3/g owing to a promotion of hydrogen transfer reaction. Through comparing the average distance between acid sites on catalyst with kinetic diameters of olefins, it was found that the dimerization of ethylene was not restrained by the sparse distribution of acid sites, while the hydrogen transfer reaction of C3 and C4 olefins was limited. On these bases, a conclusion is proposed that the dimerization of ethylene proceeded via Eley-Rideal mechanism, while the hydrogen transfer reaction of C3 and C4 olefins followed the Langmuir-Hinshelwood mechanism.