Purification, Identification, and Mechanistic Investigation of Novel Selenium-Enriched Antioxidant Peptides from Moringa oleifera Seeds.

In this study, five novel Se-enriched antioxidant peptides (FLSeML, LSeMAAL, LASeMMVL, SeMLLAA, and LSeMAL) were purified and identified from Se-enriched Moringa oleifera (M. oleifera) seed protein hydrolysate. The five peptides showed excellent cellular antioxidant activity, with respective EC50 values of 0.291, 0.383, 0.662, 0.1, and 0.123 µg/mL. The five peptides (0.025 mg/mL) increased the cell viability from 78.72 to 90.71, 89.16, 93.92, 83.68, and 98.29%, respectively, effectively reducing reactive oxygen species accumulation and significantly increasing superoxide dismutase and catalase activities in damaged cells. Molecular docking results revealed that the five novel Se-enriched peptides interacted with the key amino acid of Keap1, thus directly blocking the interaction of Keap1-Nrf2 and activating the antioxidant stress response to enhance the ability of scavenging free radicals in vitro. In conclusion, Se-enriched M. oleifera seed peptides exhibited significant antioxidant activity and can be expected to find widespread use as a highly active natural functional food additive and ingredient.

Supporting nanoscale zero-valent iron onto shrimp shell-derived N-doped biochar to boost its reactivity and electron utilization for selenite sequestration.

Nanoscale zero-valent iron (nZVI) has been widely used in the reductive removal of contaminants from water, yet it still fights against the inherent passive cover and the raise of medium pH. In this study, nZVI was supported onto a nitrogen-doped biochar (NBC) that was prepared by pyrolyzing shrimp shell for efficiently sequestrating aqueous selenite (Se(IV)). The resultant composite (NBC-nZVI) revealed a higher reactivity and electron utilization efficiency (EUE) than the bare nZVI in Se(IV) sequestration because of the positive charge, the buffering effect and the good conductivity of NBC. The kinetic rate and EUE of NBC-nZVI were increased by 143.4% and 15.3% compared to the bare nZVI, respectively, at initial pH of 3.0. The high removal capacity of 605.4 mg g-1 for NBC-nZVI was obtained at Se(IV) concentration of 1000 mg L-1, initial pH of 3.0, NBC-nZVI dosage of 1.0 g L-1 and contact time of 12 h. Moreover, NBC-nZVI exhibited a strong tolerance to solution pHs and coexisting compounds (e.g., humic acid) and could reduce the Se(IV) concentration from 5.0 mg L-1 to below the limit of drinking water (50 µg L-1) in real-world samples. This work exemplified a utilization of shrimp shell-derived NBC to simultaneously enhance the reactivity and EUE of nZVI for reductively removing contaminants.

Solvent effects on the motion of a crown ether/amino rotaxane.

Solvents have been recognized as a significant factor for modulating the shuttle of rotaxanes and regulating their functions regarding molecular machines by a lot of published studies. The mechanism of the effects of solvents on the motion of crown ether/amino rotaxanes, however, remains unclear. In this work, a rotaxane, formed by dibenzo-24-crown-8 (C[8]) and a dumbbell-shaped axle with two positively charged amino groups, was investigated at the atom level. Two-dimensional free-energy landscapes characterizing the conformational change of C[8] and the shuttling motions in chloroform and water were mapped. The results indicated that the barriers in water were evidently lower than those in chloroform. By analyzing the trajectories, there was no obvious steric effect during shuttling. Instead, the main driving force of shuttling was verified from electrostatic interactions, especially strong hydrogen bonding interactions between the axle and water, which resulted in the fast shuttling rate of the rotaxane. All in all, the polarity and hydrogen bond-forming ability of solvents are the main factors in affecting the shuttling rate of a crown ether/amino rotaxane. In addition, C[8] would adopt S-shaped conformations during shuttling except for situating in the amino sites with C-shaped ones adopted due to π-π stacking interactions. The results of this research improve the comprehension of the solvent modulation ability for shuttling in crown ether-based rotaxanes and illustrate the effects of structural modifications on motions. These new insights are expected to serve the efficient design and construction of molecular machines.

Resource utilization of pig hair to prepare low-cost adsorbents with high density of sulfhydryl for enhanced and trace level removal of aqueous Hg(II).

Pig hair (PH), a keratinous waste, was modified by ammonium thioglycolate in a ball milling to promote its performance of Hg(II) sequestration. The ball milling broke the hydrophobic cuticle sheath and enhanced the reduction of disulfide bond, which increased the sulfydryl content of the modified PH (BTPH) from 0.07 to 11.05 µmol/g. BTPH exhibited a significantly higher capture capacity of Hg(II) (415.4 mg/g) than PH (3.1 mg/g), as well as the commercial activated carbon (219.7 mg/g), and persisted its performance over a wide range of solution pH. Meanwhile, BTPH with a distribution coefficient of 5.703 × 105 mL/g could selectively capture Hg(II) from the water with the coexisting metal ions such as Mg(II), Cd(II) and Pb(II). Moreover, the low-cost BTPH could reduce the Hg(II) from 1.0 mg/L to well below the limit of drinkable water (2 µg/L) in real-world samples. Density functional theory (DFT) calculations and state-of-the-art characterizations illustrated that the binding of Hg(II) to sulfydryl groups was the main adsorption mechanism. Notably, BTPH decreased the mercury content of water spinaches from 24.1 to 0.50 mg/kg and thereby significantly reduced the phytotoxicity of Hg(II). This work therefore provides a sustainable way to utilize keratinous wastes for the remediation of aqueous Hg(II).

Genome-Wide Association Study Identified a Quantitative Trait Locus and Two Candidate Genes on Sus scrofa Chromosome 2 Affecting Vulvar Traits of Suhuai Pigs.

Vulvar size and angle are meaningful traits in pig production. Sows with abnormal vulva generally show reproductive disorders. In order to excavate candidate loci and genes associated with pig's vulvar traits, 270 Suhuai pigs with vulvar phenotype were genotyped by a porcine single nucleotide polymorphisms (SNP) Chip. Then, Chip data were imputed using resequenced data of 30 Suhuai pigs as a reference panel. Next, we estimated the heritability and performed a genome-wide association study (GWAS) for vulvar traits. The heritabilities for the traits vulvar length (VL), vulvar width (VW) and vulvar angle (VA) in this pig population were 0.23, 0.32 and 0.22, respectively. GWAS based on Chip data identified nine significant SNPs on the Sus scrofa chromosomes (SSC) 2, 7, 9 and 13 for VL or VW. GWAS based on imputed data identified 11 new quantitative trait loci (QTL) on SSC1, 2, 7, 8, 9, 11, 13, 16 and 17 for VL or VW. The most significant QTL for VL on SSC2 were refined to a 3.48-3.97 Mb region using linkage disequilibrium and linkage analysis (LDLA). In this refined region, FGF19 and CCND1, involved in the development of the reproductive tract, cell growth and vulvar cancer, could be new candidate genes affecting VL. Our results provided potential genetic markers for the breeding of vulvar traits in pigs and deepened the understanding of the genetic mechanism of vulvar traits.

Purification, identification, and antioxidative mechanism of three novel selenium-enriched oyster antioxidant peptides.

Natural organic selenium (Se) has multiple physiological health benefits and has become a hotspot of research in recent years. In this study, the Se-enriched antioxidant peptides were purified from Se-enriched oyster hydrolysate. Three novel Se-enriched antioxidant peptides LLVSeMY (685.2953 Da), MMDSeML (687.1875 Da) and VSeMDSeML (703.1599 Da) were identified from fraction F6-4, which all exhibited strong cellular antioxidant activity (CAA) with EC50 values of 0.739, 0.423, and 0.395 µg/mL, respectively. These three Se-enriched antioxidant peptides (0.025 mg/mL) could significantly enhanced cell viability to 84.60 ± 3.32% âˆ¼ 86.18 ± 1.36% compared with the AAPH injury group (75.99 ± 0.79%), and the cytoprotective effects were even better than that of GSH (80.47 ± 2.78%). Moreover, these three Se-enriched peptides also significantly protected HepG2 cells from AAPH-induced oxidative injury by inhibiting ROS production and enhancing the activities of antioxidant enzymes. The molecular docking results showed that these three Se-enriched peptides can form stable hydrogen and hydrophobic bonds with key amino acid residues of Keap1 protein, thereby potentially regulating the Keap1-Nrf2 pathway. In conclusion, the three novel Se-enriched oyster antioxidant peptides are expected to be used in medicine or functional food, providing a new theoretical basis for the high-value utilization of natural organic Se.

Preparation and catalytic behavior of antioxidant cassava starch with selenium active sites and hydrophobic microenvironments.

The preparation of antioxidant starch with the activity of glutathione peroxidase (GPx) for scavenging free radicals can not only enrich the types of modified starch but also alternate native GPx to overcome its drawbacks. In this work, an antioxidant cassava starch (AO-ca-starch) was prepared by the sequential esterification and selenylation of cassava starch. The process was optimized based on the selenium content. Various characterizations for the AO-ca-starch indicated that the catalytic center of GPx, the selenium, was anchored on the starch. The catalytic activity of AO-ca-starch, a starch-based biomimetic GPx, was about 4.95 × 105 times higher than that of the typical artificial selenoenzyme (diphenyl diselenide, PhSeSePh), and it exhibited a typical saturation kinetic catalytic behavior. The surface changes of the starch during the modification were conducive to the formation of hydrophobic microenvironments, which played an important role in the catalytic reaction of biomimetic GPx due to the binding of the hydrophobic substrates. The match of the catalytic center and the hydrophobic microenvironments was the key factor for maintaining the high catalytic activity of AO-ca-starch. Without cytotoxicity, AO-ca-starch exemplified a new and promising modified starch as a selenium-enriched functional food and antioxidant drug.

Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity.

Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Akt1. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells. Low micromolar doses of 10h induced cell apoptosis and cell cycle arrest in G2/M phase, and significantly downregulated the phosphorylation of Akt downstream effectors GSK3ß and S6 in Jeko-1 cells.

Discovery of 4-(Piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Akt Inhibitors.

A series of 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead (1). Typically, compounds 5q and 5t significantly improved the Akt1 inhibitory potency with IC50 values of 18.0 and 21.3 nM, respectively, with desirable antiproliferative effect against the cell lines LNCaP and PC-3. The inhibitors 5q and 5t might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents.

Synthesis and biological evaluation of novel indoline-2,3-dione derivatives as antitumor agents.

A new series of 1,5-disubstituted indolin-2,3-diones was synthesized and their inhibition of the growth of a human acute promyelocytic leukemia (HL-60) cell line was evaluated. These compounds had promising inhibition of HL-60 cell growth in vitro. Results indicated that compounds with a benzyl substituent at the N-1 position on the indolin-2,3-dione ring had more potent antiproliferative activity than those with a (4-fluorobenzyl) amino-2-oxoethyl substituent at the N-1 position. Among the compounds synthesized, compound 8l inhibited half of cell growth at a concentration of 0.07 µM and compound 8p did so at a concentration of 0.14 µM. These compounds may serve as lead compounds for further optimization in order to develop novel anticancer agents.

Incorporation of glutathione peroxidase active site into polymer based on imprinting strategy.

Glutathione peroxidase (GPx, EC 1.11.1.9) is a key enzyme involved in scavenging of reactive oxygen species in biological system. For developing an efficient GPx-like antioxidant, catalytically necessary amino acid derivatives which located near the GPx active center were prepared as functional monomers. Via predetermined imprinting with substrate glutathione (GSH), a polymer-based GPx mimic with a similar structure of catalytic center of natural GPx was developed, and it demonstrated high-catalytic efficiency and substrate specificity. The imprinting polymer (I-PEM) exhibits GPx-like activity about three times higher than that of 2-SeCD, a cyclodextrin-based GPx mimic. The detailed studies on kinetics revealed that not only the substrate binding but also positional arrangement of reacting groups contribute significantly to the catalytic efficiency of the peroxidase model.