Recent advances in seafood bioactive peptides and their potential for managing osteoporosis.

Marine biodiversity provides a range of diverse biological resources, including seafoods that are rich in protein and a well-balanced amino acid composition. Previous studies have shown that peptides can improve bone formation and/or inhibit bone resorption, suggesting the potential for seafood bioactive peptides (SBPs) in development of food and pharmaceuticals for management of osteoporosis. In this review, we provided an up-to-date overview of the anti-osteoporosis activity of SBPs and describe their underlying molecular mechanisms. We focus on SBPs' development, broadening the scope and depth of research, as well as strengthening in vivo and clinical research. In vitro cell cultures and in vivo animal osteoporosis models have demonstrated the potential for seafood-derived SBPs, including fish, mollusks, crustaceans, seaweed and microalgae, in preventing osteoporosis. These peptides may act by activating the signaling pathways, such as BMP/Smads, MAPK, OPG/RANKL/RANK, and NF-κB, which are associated with modulation bone health.

Relationship between Neuroprotective Effects and Structure of Procyanidins.

This study evaluated the relationship between the neuroprotective effects of procyanidins and their structural characteristics. In vitro, a rat pheochromocytoma cell line (PC12) was exposed to the grape seed-derived procyanidin monomers: catechin (C), epicatechin (EC), and epicatechin gallate (ECG); the procyanidin dimers: procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-O-gallate (B1-G), and procyanidin B2-3-O-gallate (B2-G); and the procyanidin trimers: procyanidin C1 (C1) and N-acetyl-l-cysteine (NAC) for 24 h. Cells were then incubated with 200 µM H2O2 for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization were incubated with NAC or procyanidins (C, EC, ECG, B1, B2, B3, B4, B1-G, B2-G, C1) in 300 µM H2O2 for 4 days. Different grape seed procyanidins increased the survival of PC12 cells challenged with H2O2, improved the movement behavior disorder of zebrafish caused by H2O2, inhibited the increase of ROS and MDA and the decrease of GSH-Px, CAT, and SOD activities, and up-regulated the Nrf2/ARE pathway. The neuroprotective effects of the procyanidin trimer C1 treatment group were greater than the other treatment groups. These results suggest that the neuroprotective effect of procyanidins is positively correlated with their degree of polymerization.

The Relationship between Procyanidin Structure and Their Protective Effect in a Parkinson's Disease Model.

This study evaluated the effect of grape seed-derived monomer, dimeric, and trimeric procyanidins on rat pheochromocytoma cell line (PC12) cells and in a zebrafish Parkinson's disease (PD) model. PC12 cells were cultured with grape seed-derived procyanidins or deprenyl for 24 h and then exposed to 1.5 mm 1-methyl-4-phenylpyridinium (MPP+) for 24 h. Zebrafish larvae (AB strain) 3 days post-fertilization were incubated with deprenyl or grape seed-derived procyanidins in 400 µM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days. The results showed that the procyanidin dimers procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-O-gallate (B1-G), procyanidin B2-3-O-gallate (B2-G), and the procyanidin trimer procyanidin C1 (C1) had a protective effect on PC12 cells, decreasing the damaged dopaminergic neurons and motor impairment in zebrafish. In PC12 cells and the zebrafish PD model, procyanidin (B1, B2, B3, B4, B1-G, B2-G, C1) treatment decreased the content of reactive oxygen species (ROS) and malondialdehyde (MDA), increased the activity of antioxidant enzymes glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD), and upregulated the expression of nuclear factor-erythroid 2-related factor (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1). These results suggest that in PC12 cells and the zebrafish PD model, the neuroprotective effects of the procyanidins were positively correlated with their degree of polymerization.

Neuroprotective Effects and Mechanisms of Procyanidins In Vitro and In Vivo.

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 µg/mL) or N-Acetyl-L-cysteine (NAC) (20 µM) for 24 h, and then incubated with 200 µM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 µM) or PCs (4, 8 or 16 µg/mL) in the absence or presence of 300 µM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.

Protective Effects and Mechanisms of Procyanidins on Parkinson's Disease In Vivo and In Vitro.

This research assessed the molecular mechanism of procyanidins (PCs) against neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium (MPP+) induced Parkinson's disease (PD) models. In vitro, PC12 cells were incubated with PCs or deprenyl for 24 h, and then exposed to 1.5 mM MPP+ for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were incubated with deprenyl or PCs in 400 µM MPTP for 4 days. Compared with MPP+/MPTP alone, PCs significantly improved antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), and decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, PCs significantly increased nuclear Nrf2 accumulation in PC12 cells and raised the expression of NQO1, HO-1, GCLM, and GCLC in both PC12 cells and zebrafish compared to MPP+/MPTP alone. The current study shows that PCs have neuroprotective effects, activate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and alleviate oxidative damage in MPP+/MPTP-induced PD models.

Preparation and Characterization of Microemulsions Based on Antarctic Krill Oil.

Antarctic krill oil is high in nutritional value and has biological functions like anti-inflammation and hypolipidemic effects. But it has and unpleasant smell, and unsaturated fatty acids are prone to oxidative deterioration. Its high viscosity and low solubility in water make it difficult for processing. Microemulsion can be a new promising route for development of krill oil product. We determined a formula of krill oil-in-water microemulsion with krill oil: isopropyl myristate = 1:3 as oil phase, Tween 80:Span 80 = 8:2 as surfactant, ethanol as co-surfactant and the mass ratio of surfactant to co-surfactant of 3:1. After screening the formula, we researched several characteristics of the prepared oil-in-water microemulsion, including electrical conductivity, microstructure by transmission electron microscope and cryogenic transmission electron microscope, droplet size analysis, rheological properties, thermal behavior by differential scanning calorimeter and stability against pH, salinity, and storage time.

TsOH·H2O-mediated N-amidation of quinoline N-oxides: facile and regioselective synthesis of N-(quinolin-2-yl)amides.

An operationally simple method with 100% atom economy has been developed for the synthesis of various N-(quinolin-2-yl)amides via the TsOH·H2O-mediated N-amidation of quinoline N-oxides using inexpensive and commercially available nitriles as the amidation reagents. Mechanistic exploration suggested that the reaction probably proceeds through an acid-assisted 1,3-dipolar cycloaddition and an N-O bond cleavage followed by a dehydro-aromatization process.

Predictive features of ligand-specific signaling through the estrogen receptor.

Some estrogen receptor-α (ERα)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERα ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERα activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types. Such ligands induced breast cancer cell proliferation in a manner that was predicted by the canonical recruitment of the coactivators NCOA1/2/3 and induction of the GREB1 proliferative gene. For some ligand series, a single inter-atomic distance in the ligand-binding domain predicted their proliferative effects. In contrast, the N-terminal coactivator-binding site, activation function-1 (AF-1), determined cell-specific signaling induced by ligands that used alternate mechanisms to control cell proliferation. Thus, incorporating systems structural analyses with quantitative chemical biology reveals how ligands can achieve distinct allosteric signaling outcomes through ERα.

Enhancement of coal gangue performance by surface micro-crystalline glaze derived from mineral powder.

Coal gangue is a waste derived from coal mining, and its unreasonable disposal usually causes serious land occupation and environmental pollution. Using coal gangue as a substitute for natural aggregate is an effective recycling approach, however, the high water absorption and high crushing rate of coal gangue seriously weaken its performance. This study proposed a novel strategy to decrease the water absorption and crushing rate of coal gangue by co-calcining with mineral powders, including K-feldspar, wollastonite, blast furnace slag and fly ash, meanwhile clarified the improvement mechanisms. Results showed that after calcining with mineral powders, the crushing rate of coal gangue decreased from 16.8 % to 16.1-13.2 %, and water absorption decreased from 5.29 % to 2.74-3.90 %, among which the coal gangue treated by K-feldspar and blast furnace slag had the lowest water absorption (2.74 %), reducing by 48.2 % compared to raw coal gangue. Underlying mechanisms were that during calcination, mineral powders generated micro-crystalline glaze on gangue surface, which improved the pore size distribution of coal gangue and strengthened its hardness. Specifically, as for pores with 1-1000 nm diameter, the pore volume percentage decreased from 88.5 % to 43.2-71.3 %. Vickers hardness of coal gangue increased from 0.29 GPa to 6.37-6.79 GPa, and the fracture toughness increased significantly to 41.9-67.6 MPa m1/2. Under K-feldspar and blast furnace slag treatment, the approximate thickness of micro-crystalline glaze was about 32 µm. The main component of micro-crystalline glaze was silicate lattice derived from SiO2 and Al2O3, and abundant Fe2O3 and Fe3O4 crystalline were sealed in the glaze. This study provides an innovative approach to strengthen the performance of coal gangue, which is important to expand the resource utilization of coal gangue and control the environmental pollution.

Newly Generated Ca-Feldspar during Sintering Processes Enhances the Mechanical Strength of Coal Gangue-Based Insulation Bricks.

Coal gangue is a solid waste with low carbon content discharged during the course of the coal mining process. The resource utilization of coal gangue could solve environmental problems caused by its excessive production, such as soil contamination and land occupation. This study proposed to produce high-strength thermal insulation bricks using coal gangue as the primary material and three other mineral powders as auxiliary materials, including K-feldspar, CaCO3 and fly ash. A systematic analysis was conducted to explore the optimum raw material addition ratio and optimum sintering temperature; then, the intrinsic structure of thermal insulation bricks and their sintering formation mechanisms were revealed. The results showed that the optimal ratios of coal gangue, K-feldspar, CaCO3 and fly ash were 65 wt%, 15 wt%, 10 wt% and 10 wt%, respectively; the compressive strength of the thermal insulation brick produced under this ratio was 22.5 MPa; thermal conductivity was 0.39 W m-1 k-1. During sintering processes, mineral powders sufficiently fused to form a skeleton, and the CO2 derived from CaCO3 formed pores. The optimum sintering temperature was 1150 °C, because at this temperature, K-feldspar had the best effect in promoting the conversion of CaCO3 to Ca-feldspar. The high level of the relative crystallinity of Ca-feldspar (about 76.0%) helped raise the Si-O network's polymerization degree (NBO/T = 1.24), finally raising the compressive strength of thermal insulation bricks. The innovative method of using coal gangue to make thermal insulation bricks not only solved the environmental pollution caused by coal gangue but also provided excellent construction materials with high practical application value.

Discovery of novel SERMs with a ferrocenyl entity based on the oxabicyclo[2.2.1]heptene scaffold and evaluation of their antiproliferative effects in breast cancer cells.

We have synthesized a series of novel SERMs bearing a ferrocenyl unit based on a three-dimensional oxabicyclo[2.2.1]heptene core scaffold. These compounds displayed high receptor binding affinities as well as ERα or ERß selectivity. In cell proliferation assays, we found that these ligands were cytotoxic at micromolar concentrations in both ER-positive and ER-negative breast cancer cells. On further examination, we found that the antiproliferative effects of compounds 9b, 10h and 11b on MCF-7 cells line does not arise from antiestrogenicity, but rather proceeds through a cytotoxic pathway. Possible mechanisms for the unique activities of these ligands were also investigated by molecular modeling. These new ligands could act as scaffolds for the development of novel anti-breast cancer agents.

Bicyclic core estrogens as full antagonists: synthesis, biological evaluation and structure-activity relationships of estrogen receptor ligands based on bridged oxabicyclic core arylsulfonamides.

Compounds that block estrogen action through the estrogen receptor (ER) or downregulate ER levels are useful for the treatment of breast cancer and endocrine disorders. In our search for structurally novel estrogens having three-dimensional core scaffolds, we found some compounds with a 7-oxabicyclo[2.2.1]heptene core that bound well to the ERs. The best of these compounds, a phenyl sulfonate ester (termed OBHS for oxabicycloheptene sulfonate), was a partial antagonist on both ERα and ERß. Although OBHS bears no structural resemblance to other estrogen antagonists, it appears to achieve its partial antagonist character by stabilizing a novel conformation of the ER that involves a significant distortion of helix-11. To enhance the antagonist properties of these oxabicyclo[2.2.1]heptane core ligands, we expanded the functional diversity of OBHS by replacing the sulfonate with secondary or tertiary sulfonamides (-SO(2)NR-), isoelectronic and potentially isostructural molecular replacements. An array of 16 OBHS sulfonamide analogues were prepared through a Diels-Alder reaction of a 3,4-diarylfuran using various N-aryl vinyl sulfonamide dienophiles. While the more polar secondary sulphonamides were weak ligands, certain of the tertiary sulfonamides had very good ER binding affinity. In HepG2 cell reporter gene assays, the sulphonamides had moderate potency, but they showed lower intrinsic transcriptional activity on ERα than the selective estrogen receptor modulator (SERM) hydroxytamoxifen or OBHS, and they were inverse agonists on ERß. Thus, the behaviour of these OBH-sulfonamides more closely mirrors the activity of full antagonists like the drug fulvestrant (ICI 182 780), and their greater antagonist biocharacter appears to arise from an accentuated distortion of helix-11.

Catalytic Preparation of Carbon Nanotubes from Waste Polyethylene Using FeNi Bimetallic Nanocatalyst.

In this work, carbon nanotubes (CNTs) were synthesized by catalytic pyrolysis from waste polyethylene in Ar using an in-situ catalyst derived from ferric nitrate and nickel nitrate precursors. The influence factors (such as temperature, catalyst content and Fe/Ni molar ratio) on the formation of CNTs were investigated. The results showed that with the temperature increasing from 773 to 1073 K, the carbon yield gradually increased whereas the aspect (length-diameter) ratio of CNTs initially increased and then decreased. The optimal growth temperature of CNTs was 973 K. With increasing the Fe/Ni molar ratio in an FeNi bimetallic catalyst, the yield of CNTs gradually increased, whereas their aspect ratio first increased and then decreased. The optimal usage of the catalyst precursor (Fe/Ni molar ratio was 5:5) was 0.50 wt% with respect to the mass of polyethylene. In this case, the yield of CNTs reached as high as 20 wt%, and their diameter and length were respectively 20-30 nm, and a few tens of micrometers. The simple low-cost method developed in this work could be used to address the environmental concerns about plastic waste, and synthesize high value-added CNTs for a range of future applications.

Synthesis of Carbon Nanotube Arrays with High Aspect Ratio via Ni-Catalyzed Pyrolysis of Waste Polyethylene.

Carbon nanotube (CNT) arrays 30⁻50 nm in diameter and with a length of several micrometers were prepared by catalytic pyrolysis of waste polyethylene in Ar at 773-1073 K using nickel dichloride as a catalyst precursor. X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectrometry (Raman), a vibrating-sample magnetometer (VSM), and nitrogen adsorption/desorption were used to investigate the effects of the pyrolysis temperature and catalyst contents on the preparation of the aligned CNTs. As results, the as-obtained CNTs had an outer diameter of 30 nm, a wall thickness of 10 nm, and a length of about 50 µm, and their aspect ratio was high up to 1500. The aligned CNTs containing 0.75 wt% Ni prepared at 973 K exhibited good adsorption performance for methylene blue (MB); furthermore, benefiting from the special magnetic properties of residual Ni catalysts, the as-obtained CNTs could be easily magnetically recycled from the treated solution after adsorption.

Influences of climate change on area variation of Qinghai Lake on Qinghai-Tibetan Plateau since 1980s.

Qinghai-Tibetan Plateau is the most sensitive region to global warming on Earth. Qinghai Lake, the largest lake on the plateau, has experienced evident area variation during the past several decades. To quantify the area changes of Qinghai Lake, a satellite-based survey based on Landsat images from the 1980s to 2010s has been performed. In addition, meteorological data from all the seven available stations on Qinghai-Tibetan Plateau has been analyzed. Area of Qinghai Lake shrank ~2% during 1987-2005, and then increased ~3% from 2005-2016. Meanwhile, the average annual temperature increased 0.319 °C/10 y in the past 50 years, where the value is 0.415 °C/10 y from 2005-2016. The structural equation modeling (SEM) shows that precipitation is the primary factor influencing the area of Qinghai Lake. Moreover, temperature might be tightly correlated with precipitation, snow line, and evaporation, thereby indirectly causes alternations of the lake area. This study elucidated the significant area variation of water body on the Qinghai-Tibetan Plateau under global warming since 1980s.

Lotus-Seedpod-Bioinspired 3D Superhydrophobic Diatomite Porous Ceramics Comodified by Graphene and Carbon Nanobelts.

Hydrophobic and oleophilic sorbents play an important role in the remediation processes of oil spills/leakages occurring globally from time to time. In this work, for the first time, lotus-seedpod-bioinspired 3D superhydrophobic diatomite porous ceramics with good mechanical strength and thermal stability were fabricated, using inexpensive porous diatomite as a substrate, and graphene/carbon nanobelts as modifiers. Thanks to the presence of graphene coating and in situ formed carbon nanobelts, the surface energy of the final porous ceramics was reduced and their surface roughness increased, conferring superhydrophobicity on them. As-prepared porous ceramics demonstrated 3-30 times higher adsorption capacity in oil/water separation than their conventional inorganic sorbent materials, and had compressive strength 70-270 times higher than that of a sponge/graphene-based sorbent material. The present work could additionally offer a new strategy for the treatment/recycle of waste plastics, the so-called "white pollution".

Effects of elevated atmospheric CO2 on dissolution of geological fluorapatite in water and soil.

Most of phosphorus (P) is present as insoluble phosphorus-bearing minerals or organic forms in soil. Geological fluorapatite (FAp) is the dominant mineral-weathering source of P. In this study, FAp was added into water and soil under elevated CO2 to investigate the pathway of P release. Two types of soils (an acidic soil from subtropical China and a saline-alkali soil from Tibet Plateau, China) with similar total P content were studied. In the solution, increased CO2 in air enhanced the dissolution of FAp, i.e., from 0.04 to 1.18ppm for P and from 2.48 to 13.61ppm for Ca. In addition, release of Ca and P from FAp reached the maximum (2.14ppm for P and 13.84ppm for Ca) under the combination of elevated CO2 and NaCl due to the increasing ion exchange. Consistent with the results from the solution, CO2 elevation promoted P release more significantly (triple) in the saline-alkali soil than in the acidic soil. Therefore, saline-alkali soils in Tibet Plateau would be an important reservoir of available P under the global CO2 rise. This study sheds the light on understanding the geological cycle of phosphorus.

Identification and structure-activity relationships of a novel series of estrogen receptor ligands based on 7-thiabicyclo[2.2.1]hept-2-ene-7-oxide.

To develop estrogen receptor (ER) ligands having novel structures and activities, we have explored compounds in which the central hydrophobic core has a more three-dimensional topology than typically found in estrogen ligands and thus exploits the unfilled space in the ligand-binding pocket. Here, we build upon our previous investigations of 7-oxabicyclo[2.2.1]heptene core ligands, by replacing the oxygen bridge with a sulfoxide. These new 7-thiabicyclo[2.2.1]hept-2-ene-7-oxides were conveniently prepared by a Diels-Alder reaction of 3,4-diarylthiophenes with dienophiles in the presence of an oxidant and give cycloadducts with endo stereochemistry. Several new compounds demonstrated high binding affinities with excellent ERα selectivity, but unlike oxabicyclic compounds, which are transcriptional antagonists, most thiabicyclic compounds are potent, ERα-selective agonists. Modeling suggests that the gain in activity of the thiabicyclic compounds arises from their endo stereochemistry that stabilizes an active ER conformation. Further, the disposition of methyl substituents in the phenyl groups attached to the bicyclic core unit contributes to their binding affinity and subtype selectivity.

Development of selective estrogen receptor modulator (SERM)-like activity through an indirect mechanism of estrogen receptor antagonism: defining the binding mode of 7-oxabicyclo[2.2.1]hept-5-ene scaffold core ligands.

Previously, we discovered estrogen receptor (ER) ligands with a novel three-dimensional oxabicyclo[2.2.1]heptene core scaffold and good ER binding affinity act as partial agonists via small alkyl ester substitutions on the bicyclic core that indirectly modulate the critical switch helix in the ER ligand binding domain, helix 12, by interactions with helix 11. This contrasts with the mechanism of action of tamoxifen, which directly pushes helix 12 out of the conformation required for gene activation. We now report that a much larger substitution can be tolerated at this position of the bicyclic core scaffold, namely a phenyl sulfonate group, which defines a novel binding epitope for the estrogen receptor. We prepared an array of 14 oxabicycloheptene sulfonates, varying the phenyl sulfonate group. As with the parent compound, 5,6-bis-(4-hydroxyphenyl)-7-oxabicyclo[2.2.1]hept-5-ene-2-sulfonic acid phenyl ester (OBHS), these compounds showed preferential affinity for ERα, and the disposition and size of the phenyl substituents were important determinants of the binding affinity and selectivity of these compounds, with those having ortho substituents giving the highest, and para substituents the lowest affinities for ERα. A few analogues exhibit ERα binding affinities that are comparable to or, in the case of the ortho-chloro analogue, higher than that of OBHS itself. In cell-based studies, we found several compounds with activity profiles comparable to tamoxifen, but acting entirely as indirect antagonists, allosterically interfering with recruitment of coactivator proteins to the receptor. Thus, the OBHS binding epitope represents a novel approach to the development of estrogen receptor antagonists via an indirect mechanism of antagonism.