Structure and immunomodulatory activity of Lentinus edodes polysaccharides modified by probiotic fermentation

Plant-based fermentations provide an untapped source for novel biotechnological applications.In this study,a probiotic named Lactobacillus fermentum 21828 was introduced to ferment Lentinus edodes.Polysaccharides were extracted from fermented and non-fermented L.edodes and purified via DEAE-52 and Sephadex G-100.The components designated F-LEP-2a and NF-LEP-2a were analyzed by FT-IR,HPGPC,HPAEC,SEM,GC-MS and NMR.The results revealed that probiotic fermentation increased the molecular weight from 1.16×10^(4) Da to 1.87×10^(4) Da and altered the proportions of glucose,galactose and mannose,in which glucose increased from 45.94%to 48.16%.Methylation analysis and NMR spectra indicated that F-LEP-2a and NF-LEP-2a had similar linkage patterns.Furthermore,their immunomodulatory activities were evaluated with immunosuppressive mice.NF-LEP and F-LEP improved immune organ indices,immunoglobulin(Ig G and Ig M)and cytokines concentrations;restored the antioxidation capacity of liver;and maintained the balance of gut microbiota.F-LEP displayed better moderating effects on the spleen index,immunoglobulin,cytokines and the diversity of gut microbiota than NF-LEP(200,400 mg/kg).Our study provides an efficient and environment-friendly way for the structural modification of polysaccharides,which helps to enhance their biological activity and promote their wide application in food,medicine and other fields.

Advances in Research of Biological Activity,Action Mechanism and Structure-Activity Relationship of Lentinan

Lentinula edodes is the second largest edible mushroom in the world and is widely used as food and medicine.Modern research shows that lentinan(LNT)is the main active component of L.edodes.It has anti-cancer,treatment of diabetes,intestinal protection,anti-inflammatory,anti-oxidation,anti-aging,hepatoprotective,immune-regulating effects.In this review,the biological activity,action mechanism and structure-activity relationship of LNT in recent years are reviewed.On this basis,the existing problems were discussed,and the future research and application of LNT were prospected.Finally,it is hoped that this review will promote the in-depth study of LNT and provide a reference for its development as a drug and functional food.

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Structure elucidation,immunomodulatory activity,antitumor activity and its molecular mechanism of a novel polysaccharide from Boletus reticulatus Schaeff

A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.

Studies on the Synthesis, Anticonvulsant Activity, and the Structure-Activity Relationships of Phenyl Pyridazinones and their GABA Derivatives

In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.

Effects of Bamboo Charcoal-based Biochar on Soil Enzyme Activity and Microbial Community Structure

[Objectives]This study was conducted to reveal the effects of bamboo charcoal-based biochar(or bamboo charcoal for short)on soil enzyme activity and microbial community structure.[Methods]The field experiment was carried out at the Modern Agriculture Demonstration Base of Gaoping Village,Gaoping Town,Suichang County,Zhejiang Province.Bamboo charcoal was applied at four different levels:T_(0)(no bamboo charcoal),T_(1)(1125 kg/hm^(2)bamboo charcoal),T_(2)(2250 kg/hm^(2)bamboo charcoal)and T_(3)(3375 kg/hm^(2)bamboo charcoal).Soil physicochemical properties and enzyme activities in different treatments were measured.[Results]The soil fungal,bacterial and actinomycete populations increased significantly in the soils surrounding capsicum roots.The bacterial population,fungal population and fungus/bacterium ratio peaked in Treatment T_(2),up to 7.32×10^(6)cfu/g,2.65×10^(4)cfu/g and 0.36×10^(-2),respectively.The effect of bamboo charcoal in promotingβ-glucoside,catalase,acid phosphatase and sucrase activities was T_(2)>T_(3)>T_(1)>T_(0).With bamboo charcoal increasing,the bacterium population,fungus population,fungus/bacterium ratio,β-glucoside,catalase,acid phosphatase and sucrase activities all increased at first and then decreased.T_(2)treatment showed the best effects in improving soil physicochemical properties and microbial community structure.[Conclusions]Bamboo charcoal significantly improves soil enzyme activity and increases soil microbial population,and thus has important positive effects on the soil ecosystem.

Molecular characteristics and structure–activity relationships of food-derived bioactive peptides

Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.

Determination of structure-activity relationships between fentanyl analogs and human μ-opioid receptors based on active binding site models

Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.

Quantitative Structure-activity Relationship Study on the Antioxidant Activity of Carotenoids

Carotenoids are a family of effective active oxygen scavengers, which can reduce the danger of occurrence of chronic diseases such as cardiovascular disease, cataract, cancer, and so on. The quantitative structure-activity relationship （QSAR） equation between carotenoids and antioxidant activity was established by quantum chemistry AM1, molecular mechanism （MM＋） and stepwise regression analysis methods, and the model was evaluated by leave-one-out approach. The results showed that the significant molecular descriptors related to the antioxidant activity of carotenoids were the energy difference （E_HL） between the lowest unoccupied molecular orbital （LUMO） and the highest occupied molecular orbital （HOMO） and ionization energy （Eiso）. The model showed a good predictive ability （Q^2 〉 0.5）.

Relationship between Coordination Structure and Biological Activity of Copper(II) Nicotinate

The copper（Ⅱ） complexes of pyridine-3-carboxylic acid （nicotinic acid） and pyridine-2-carboxylic acid （isonicotinic acid） were synthesized, and their structures were characterized by elemental analysis, infrared spectrum, powder X-ray diffraction and so on. The results show that under experimental conditions, the ligands of synthesized copper nicotinate and copper isonicotinate are coordinated simultaneity with copper（Ⅱ） via the nitrogen of pyridine group and an oxygen of carboxylic acid group to form bidentate chelates. The crystal of copper nicotinate with two six-membered chelate rings belongs to monoclinic system, while that of copper isonicotinate having two five-membered chelate rings is of triclinic system. The tests show that the biological activities, such as the improvement of feed utilization, growth, anti-oxidation ability of organism and disease-resistant power, are different when copper nicotinate, copper inicotinate, copper-lysine chelate, copper-methionine chelate and copper sulphate are added in pig＇s feed, respectively. Due to its higher biological activity, less pollution and lower toxicity, copper nicotinate has wide potential applications as a feed additive.

Structure-activity relationships of oxime compounds as flotation collectors by DFT calculations

The relationships between the structure of oxime compounds(R^(1)R^(2)C=NOH,R^(1)/R^(2)=alkyl groups) with different substituents and their corresponding flotation performances were studied. The analyses of density functional theory(DFT) calculations illustrated that the introduced phenyl group at the R^(1) position could enhance the acidity,while the heptyl group could effectively increase the hydrophobicity and benefit van der Waals interactions. Meanwhile,the introduced amino group at the R^(2) position could provide cationic sites to interact with negatively charged surfaces of minerals, while the introduced hydroxyl group could provide additional action sites to form stable chelates with metal ions. Based on the structure-activity relationships, structural optimization was carried out to obtain three efficient collectors, which possessed superior flotation separation performances, proving the effectiveness of the structural modification to oxime compounds in this work.

Quantitative Structure-activity Relationship Studies on the Antioxidant Activity and Gap Junctional Communication of Carotenoids

The antioxidant and gap junctional communication（GJC） activities of carotenoids are known to be the two main anticancer mechanisms.Quantitative structure-activity relationship（QSAR） models of the two activities were developed using stepwise regression and multilayer perceptron neural network based on the calculated descriptors of quantum chemistry.The results showed that the significant molecular descriptor related to the antioxidant activity of carotenoids was the HOMO-LUMO energy gap（EHL） and the molecular descriptor related to the GJC was the lowest unoccupied molecular orbital energy（ELUMO）.The two models of antioxidant activity both showed good predictive power,but the predictive power of the neural network QSAR model of antioxidant activity was better.In addition,the two GJC models have similar,moderate predictive power.The possible mechanisms of antioxidant activity and GJC of carotenoids were discussed.

Quantitative structure-activity relationship study on the biodegradation of acid dyestuffs

Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.

Bone morphogenetic proteins:Relationship between molecular structure and their osteogenic activity

Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying functions such as embryogenesis,skeletal formation,hematopoiesis and neurogenesis have been identified in human body.BMPs are unique growth factors that can induce the formation of bone tissue individually.BMPs can induce the differentiation of bone marrow mesenchymal stem cells into osteoblastic lineage and promote the proliferation of osteoblasts and chondrocytes.BMPs stimulate the target cells by specific membrane-bound receptors and signal transduced through mothers against decapentaplegic(Smads)and mitogen activated protein kinase(MAPK)pathways.It has been demonstrated that BMP-2,BMP-4,BMP-6,BMP-7,and BMP-9 play an important role in bone formation.This article focuses on the molecular characterization of BMPs family members,mechanism of osteogenesis promotion,related signal pathways of osteogenic function,relationships between structure and osteogenetic activity,and the interactions among family members at bone formation.

Relationship between the regional tectonic activity and crustal structure in the eastern Tibetan plateau discovered by gravity anomaly

The eastern Tibetan plateau has been getting more and more attention because it combines active faults,uplifting, and large earthquakes together in a high-population region. Based on the previous researches, the most of Cenozoic tectonic activities were related to the regional structure of the local blocks within the crustal scale. Thus,a better understanding of the crustal structure of the regional tectonic blocks is an important topic for further study. In this paper, we combined the simple Bouguer gravity anomaly with the Moho depths from previous studies to investigate the crustal structure in this area. To highlight the crustal structures, the gravity anomaly caused by the Moho relief has been reduced by forward modeling calculations. A total horizontal derivative（THD） had been applied on the gravity residuals. The results indicated that the crustal gravity residual is compatible with the topography and the geological settings of the regional blocks,including the Sichuan basin, the Chuxiong basin, the Xiaojiang fault, and the Jinhe fault, as well as the Longmenshan fault zone. The THD emphasized the west margin of Yangtze block, i.e., the Longriba fault zone and the Xiaojiang fault cut through the Yangtze block. The checkboard pattern of the gravity residual in the SongpanGarze fold belt and Chuandian fragment shows that the crust is undergoing a southward and SE-directed extrusion,which is coincident with the flowing direction indicatedfrom the GPS measurements. By integrating the interpretations, the stepwise extensional mechanism of the eastern Tibetan plateau is supported by the southeastward crustal deformation, and the extrusion of Chuandian fragment is achieved by Xianshuihe fault.

Application of PCA and HCA to the Structure-activity Relationship(SAR) Study of Fluoroquinolones

Density functional theory （DFT） was used to calculate a set of molecular descri ptors （properties） for 14 fluoroquinolones with anti-B.fragilis activity. Principal component analysis （PCA） and hierarchical cluster analysis （HCA） were employed in order to reduce dimensionality and investigate which subset of variables should be more effective for classifying fluoroquinolones according to their an-B.fragilis activity degree. The PCA shows that the variables of ELUMO, AEHL, μ, Q2, Q3, Q5, Q6, QB, LogP, MR and MP are responsible for the separation between compounds with higher and lower anti-B.fragilis activities. The HCA results are similar to those obtained with PCA. By using the chemometric results, 4 synthetic compounds were analyzed through PCA and HCA, and 2 of them are proposed as active molecules against B.fragilis, which is consistent with the results of clinic experiments. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-B.fragilis activity.

New Descriptors of Amino Acids and Its Applications to Peptide Quantitative Structure-activity Relationship

A new set of descriptors, HSEHPCSV （component score vector of hydrophobic, steric, and electronic properties together with hydrogen bonding contributions）, were derived from principal component analyses of 95 physicochemical variables of 20 natural amino acids separately according to different kinds of properties described, namely, hydrophobic, steric, and electronic properties as well as hydrogen bonding contributions. HSEHPCSV scales were then employed to express structures of angiotensin-converting enzyme inhibitors, bitter tasting thresholds and bactericidal 18 peptide, and to construct QSAR models based on partial least square （PLS）. The results obtained are as follows： the multiple correlation coefficient （R2cum） of 0.846, 0.917 and 0.993, leave-one-out cross validated Q2cm of 0.835, 0.865 and 0.899, and root-mean-square error for estimated error （RMSEE） of 0.396, 0.187and 0.22, respectively. Satisfactory results showed that, as new amino acid scales, data of HSEHPCSV may be a useful structural expression methodology＇for the studies on peptide QSAR （quantitative structure-activity relationship） due to many advantages such as plentiful structural information, definite physical and chemical meaning and easy interpretation.

Genotoxicity of substituted nitrobenzenes and the quantitative structure－activity relationship

The genotoxicity of 22 substituted nitrobenzenes were evaluated by the chromosome aberrations test in in vitro human peripheral lymphocytes.18 of 22 compounds exhibit genotoxic activities.Quantitative structure-activity relationship model was established to correlate the genotoxicity of substituted nitrobenzenes with the characteristics of the substituents on benzene ring.

Quantitative Structure-activity Relationship(QSAR) Study of Toxicity of Substituted Aromatic Compounds to Photobacterium Phosphoreum

With the artificial neural network（ANN） method combined with the multiple linear regression（MLR）,based on a series of quantum chemical descriptors and molecular connectivity indexes,quantitative structure-activity relationship（QSAR） models to predict the acute toxicity（-lgEC50） of substituted aromatic compounds to Photobacterium phosphoreum were established.Four molecular descriptors that appear in the MLR model,namely,the second order valence molecular connectivity index（2XV）,the energy of the highest occupied molecular orbital（EHOMO）,the logarithm of n-octyl alcohol/water partition coefficient（logKow） and the Connolly molecular area（MA）,were inputs of the ANN model.The root-mean-square error（RMSE） of the training and validation sets of the ANN model are 0.1359 and 0.2523,and the correlation coefficient（R） is 0.9810 and 0.8681,respectively.The leave-one-out（LOO） cross validated correlation coefficient（Q L2OO） of the MLR and ANN models is 0.6954 and 0.6708,respectively.The result showed that the two methods are complementary in the calculations.The regression method gave support to the neural network with physical explanation,and the neural network method gave a more accurate model for QSAR.In addition,some insights into the structural factors affecting the acute toxicity and toxicity mechanism of substituted aromatic compounds were discussed.

A Systematic Review of Uric Acid Transporter 1(URAT1) Inhibitors for the Treatment of Hyperuricemia and Gout and an Insight into the Structure-activity Relationship(SAR)

Gout is caused by the deposition of uric acid as monosodium urate（MSU）. Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Renal under-excretion of uric acid accounts for greater than 90% of the patients with hyperuricemia, making URAT1 inhibitors, which act through uricosuric effect a promising class of urate-lowering therapy（ULT）. This review aims at the summary and discussion of the latest development of URAT1 inhibitors for the treatment of hyperuricemia and gout and providing an insight into their structure-activity relationship（SAR）, which will be helpful to the design of URAT1 inhibitors for both academic research and pharmaceutical industry. The current development pipeline of URAT1 inhibitors is promising and encouraging.