Associations between body composition profile and hypertension in different fatty liver phenotypes

BackgroundIt is currently unclear whether and how the association between body composition and hypertension varies based on the presence and severity of fatty liver disease (FLD).MethodsFLD was diagnosed using ultrasonography among 6,358 participants. The association between body composition and hypertension was analyzed separately in the whole population, as well as in subgroups of non-FLD, mild FLD, and moderate/severe FLD populations, respectively. The mediation effect of FLD in their association was explored.ResultsFat-related anthropometric measurements and lipid metabolism indicators were positively associated with hypertension in both the whole population and the non-FLD subgroup. The strength of this association was slightly reduced in the mild FLD subgroup. Notably, only waist-to-hip ratio and waist-to-height ratio showed significant associations with hypertension in the moderate/severe FLD subgroup. Furthermore, FLD accounted for 17.26% to 38.90% of the association between multiple body composition indicators and the risk of hypertension.ConclusionsThe association between body composition and hypertension becomes gradually weaker as FLD becomes more severe. FLD plays a significant mediating role in their association

Cyclotides: disulfide-rich peptide toxins in plants

Cyclotides are a plant-derived family of peptides that comprise approximately 30 amino acid residues, a cyclic backbone and a cystine knot. Due to their unique structure, cyclotides are exceptionally stable to heat or proteolytic degradation and are tolerant to amino acid substitutions in their backbone loops between conserved cysteine residues. Their toxicity to insect pests and their make-up of natural amino acids has led to their applications in eco-friendly crop protection. Furthermore, their stability and cell penetrating properties make cyclotides ideal scaffolds for bioactive epitope grafting. This article gives a brief overview of cyclotide discovery, characterization, distribution, synthesis and mode of action mechanisms. We focus on their toxicities to insect pests and their medical and agricultural applications

Study on the Compatibility of Gas Adsorbents Used in a New Insulating Gas Mixture C4F7N/CO2

An environment-friendly insulating gas, perfluoroisobutyronitrile (C4F7N), has been developed recent years. Due to its relatively high liquefaction temperature (around −4.7 °C), buffer gases, such as CO2 and N2, are usually mixed with C4F7N to increase the pressure of the filled insulating medium. During these processes, the insulating gases may be contaminated with micro-water, and the mixture of H2O with C4F7N could produce HF under breakdown voltage condition, which is harmful to the gas insulated electricity transfer equipment. Therefore, removal of H2O and HF in situ from the gas insulated electricity transfer equipment is significant to its operation security. The adsorbents with the ability to remove H2O but without obvious C4F7N/CO2 adsorption capacity are essential to be used in this system. In this work, a series of industrial adsorbents and desiccants were tested for their compatibility with C4F7N/CO2. Pulse adsorption tests were conducted to evaluate the adsorption performance of these adsorbents and desiccants on C4F7N and CO2. The 5A molecular sieve showed high adsorption of C4F7N (22.82 mL/g) and CO2 (43.86 mL/g); F-03 did not show adsorption capacity with C4F7N, however, it adsorbed CO2 (26.2 mL/g) clearly. Some other HF adsorbents, including NaF, CaF2, MgF2, Al(OH)3, and some desiccants including CaCl2, Na2SO4, MgSO4 were tested for their compatibility with C4F7N and CO2, and they showed negligible adsorption capacity on C4F7N and CO2. The results suggested that these adsorbents used in the gas insulated electricity transfer equipment filled with SF6 (mainly 5A and F-03 molecular sieves) are not suitable anymore. The results of this work suggest that it is a good strategy to use a mixture of desiccants and HF adsorbents as new adsorbents in the equipment filled with C4F7N/CO2

Comparison of Dissolved Gases in Mineral and Vegetable Insulating Oils under Typical Electrical and Thermal Faults

Dissolved gas analysis (DGA) is attracting greater and greater interest from researchers as a fault diagnostic tool for power transformers filled with vegetable insulating oils. This paper presents experimental results of dissolved gases in insulating oils under typical electrical and thermal faults in transformers. The tests covered three types of insulating oils, including two types of vegetable oil, which are camellia insulating oil, Envirotemp FR3, and a type of mineral insulating oil, to simulate thermal faults in oils from 90 °C to 800 °C and electrical faults including breakdown and partial discharges in oils. The experimental results reveal that the content and proportion of dissolved gases in different types of insulating oils under the same fault condition are different, especially under thermal faults due to the obvious differences of their chemical compositions. Four different classic diagnosis methods were applied: ratio method, graphic method, and Duval’s triangle and Duval’s pentagon method. These confirmed that the diagnosis methods developed for mineral oil were not fully appropriate for diagnosis of electrical and thermal faults in vegetable insulating oils and needs some modification. Therefore, some modification aiming at different types of vegetable oils based on Duval Triangle 3 were proposed in this paper and obtained a good diagnostic result. Furthermore, gas formation mechanisms of different types of vegetable insulating oils under thermal stress are interpreted by means of unimolecular pyrolysis simulation and reaction enthalpies calculation

Evaluation of the in vivo aphrodisiac activity of a cyclotide extract from Hybanthus enneaspermus

Hybanthus enneaspermus is an Indian folk medicinal herb that has been widely used as a libido enhancer. This plant belongs to the Violaceae plant family, which ubiquitously contains disulfide-rich cyclic peptides named cyclotides. Cyclotides are an expanding plant-derived peptide family with numerous interesting bioactivities, and their unusual stability against proteolysis has attracted much attention in drug design applications. Recently, H. enneaspermus has been reported to be a rich source of cyclotides, and hence, it was of interest to investigate whether cyclotides contribute to its aphrodisiac activity. In this study, we evaluated the in vivo aphrodisiac activity of the herbal powder, extract, and the most abundant cyclotide, hyen D, extracted from H. enneaspermus on rats in a single dose regimen. After dosing, the sexual behaviors of male rats were observed, recorded, analyzed, and compared with those of the vehicle group. The results show that the extract and hyen D significantly decreased the intromission latency of sexually naïve male rats and the extract improved a range of other measured sexual parameters. The results suggest that the extract could enhance libido as well as facilitate erectile function in male rats and that the cyclotide hyen D could contribute to the libido-enhancing activity of this ethnomedicinal herb

Enabling Efficient Folding and High-Resolution Crystallographic Analysis of Bracelet Cyclotides

Cyclotides have attracted great interest as drug design scaffolds because of their unique cyclic cystine knotted topology. They are classified into three subfamilies, among which the bracelet subfamily represents the majority and comprises the most bioactive cyclotides, but are the most poorly utilized in drug design applications. A long-standing challenge has been the very low in vitro folding yields of bracelets, hampering efforts to characterize their structures and activities. Herein, we report substantial increases in bracelet folding yields enabled by a single point mutation of residue Ile-11 to Leu or Gly. We applied this discovery to synthesize mirror image enantiomers and used quasi-racemic crystallography to elucidate the first crystal structures of bracelet cyclotides. This study provides a facile strategy to produce bracelet cyclotides, leading to a general method to easily access their atomic resolution structures and providing a basis for development of biotechnological applications

Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus

Cyclotides are plant-derived peptides characterized by an ∼30-amino acid-long cyclic backbone and a cystine knot motif. Cyclotides have diverse bioactivities, and their cytotoxicity has attracted significant attention for its potential anticancer applications. Hybanthus enneaspermus (Linn) F. Muell is a medicinal herb widely used in India as a libido enhancer, and a previous study has reported that it may contain cyclotides. In the current study, we isolated 11 novel cyclotides and 1 known cyclotide (cycloviolacin O2) from H. enneaspermus and used tandem MS to determine their amino acid sequences. We found that among these cyclotides, hyen C comprises a unique sequence in loops 1, 2, 3, 4, and 6 compared with known cyclotides. The most abundant cyclotide in this plant, hyen D, had anticancer activity comparable to that of cycloviolacin O2, one of the most cytotoxic known cyclotides. We also provide mechanistic insights into how these novel cyclotides interact with and permeabilize cell membranes. Results from surface plasmon resonance experiments revealed that hyen D, E, L, and M and cycloviolacin O2 preferentially interact with model lipid membranes that contain phospholipids with phosphatidyl-ethanolamine headgroups. The results of a lactate dehydrogenase assay indicated that exposure to these cyclotides compromises cell membrane integrity. Using live-cell imaging, we show that hyen D induces rapid membrane blebbing and cell necrosis. Cyclotide-membrane interactions correlated with the observed cytotoxicity, suggesting that membrane permeabilization and disintegration underpin cyclotide cytotoxicity. These findings broaden our knowledge on the indigenous Indian herb H. enneaspermus and have uncovered cyclotides with potential anticancer activity.</p

Nematicidal Activity of Cyclotides: Toxicity Against <i>Caenorhabditis elegans</i>

Cyclotides are a unique family of stable and cyclic mini-proteins found in plants that have nematicidal and anthelmintic activities. They are distributed across the Rubiaceae, Violaceae, Fabaceae, Cucurbitaceae, and Solanaceae plant families, where they are posited to act as protective agents against pests. In this study, we tested the nematicidal properties of extracts from four major cyclotide-producing plants, Oldenlandia affinis, Clitoria ternatea, Viola odorata, and Hybanthus enneaspermus, against the free-living model nematode Caenorhabditis elegans. We evaluated the nematicidal activity of the cyclotides kalata B1, cycloviolacin O2, and hyen D present in these extracts and found them to be active against the larvae of C. elegans. Both the plant extracts and isolated cyclotides exerted dose-dependent toxicity on the first-stage larvae of C. elegans. Isolated cyclotides caused death or damage upon interacting with the worms’ mouth, pharynx, and midgut or membrane. Cycloviolacin O2 and hyen D produced bubble-like structures around the C. elegans membrane, termed blebs, implicating membrane disruption causing toxicity and death. All tested cyclotides lost their toxicity when the hydrophobic patches present on them were disrupted via a single-point mutation. The present results provide a facile assay design to measure and explore the nematicidal activities of plant extracts and purified cyclotides on C. elegans