Cyclocodon lancifolius fruit prolongs the lifespan of Caenorhabditis elegans via antioxidation and regulation of purine metabolism.

Cyclocodon lancifolius fruit is a promising commercial fruit with antioxidant activity and is rich in polyphenolic compounds. In this study, the anti-aging activity of C. lancifolius fruit extract (CF) on Caenorhabditis elegans (C. elegans) was evaluated by observing the longevity, stress response, reproduction, oscillation, lipofuscin, and antioxidant enzymes of worms. Moreover, the effects and potential mechanisms of CF on delaying C. elegans senescence at the mRNA and metabolite levels were investigated. The results showed that CF treatment significantly increased the lifespan and stress resistance, decreased the levels of lipofuscin and reactive oxygen species (ROS), and improved the antioxidant system of C. elegans. The extension of the lifespan of C. elegans was remarkably correlated with the upregulation of mtl-1 and Hsp-16.2, along with the downregulation of age-1, daf-2, and akt-1. Metabolomics analysis revealed that purine metabolism is a key regulatory pathway for CF to exert anti-aging effects. The present study suggests that C. lancifolius fruit has potential for use as a functional food to enhance antioxidant capacity and delay aging.

[Reliability Thermal Design, Simulation and Experimental Verification of Electronic Monitoring Unit for Magnetic Resonance System].

The monitoring unit used in the nuclear magnetic resonance system, as an important unit of the system, faces a high thermal risk during its entire life cycle. This paper ensures the high efficiency and reliability of the thermal design of the product module from the two dimensions of structural design and device derating design. In order to reduce the risk of thermal design of electronic modules and comprehensively verify the effectiveness of thermal design of electronic modules, the design verification is carried out by combining simulation and experiment. In the simulation process, by establishing a thermal simulation model at the circuit board level, the crustal temperature of the core device is numerically calculated, and the index is compared with the thermal design index value and the test value, on the one hand, to verify the correctness of the simulation model. On the other hand, the validity of thermal design is verified. In the testing process, a thermal test platform for product modules is built, and the thermal characteristics test values of the core components of the module under extreme electrical conditions are obtained, and the corresponding conversion methods are used to predict the thermal performance and thermal design margin of the product at different altitudes. The results show that the electronic module can meet the thermal design requirements in terms of structural design and derating design of core components, and can ensure that the product module can work safely and reliably during the entire life cycle of the NMR system.

Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling.

Diabetes has become a significant disease threatening human health and social development. Food intervention is considered an essential strategy to prevent early diabetes development sustainably. The natural product, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG), commonly found in fruits and diets, has many potential antihypoglycemic, antibacterial, and antitumor activities. We found that PGG can promote glucose uptake in whole-organism zebrafish screening, which help in downregulating the glucose levels. We investigated the metabolome and transcriptome changes in zebrafish exposed to high glucose and PGG intervention. The differential genes and metabolites were screened out based on the comparisons of blank, hyperglycemic, and the PGG-exposed groups of zebrafish larvae. Combined with RT-qPCR validation, we found that PGG mainly restored four genes (fthl27, LOC110438965, plat, and aacs) and six metabolites abnormally invoked by high glucose. These validated genes are related with the key metabolites sphingosine and (R)-3-hydroxybutanoate involving the pathways of apelin, apoptosis, necroptosis, and butanoate metabolism. Our findings provided a new mechanistic basis for understanding the hypoglycaemic function of the commonly present dietary molecule (PGG) and offered a new perspective for the rational utilization of PGG to regulate metabolic disorders.

A New Mechanism for Ginsenoside Rb1 to Promote Glucose Uptake, Regulating Riboflavin Metabolism and Redox Homeostasis.

Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).

Metabolomics Mechanism and Lignin Response to Laxogenin C, a Natural Regulator of Plants Growth.

Laxogenin C (LGC) is a natural spirostanol deriving from plant hormone which has shown growing regulation similar to those of brassinosteroids. In the present study, LGC showed a promoting effect on tomato seed germination and seedling growth in a dose-dependent manner. We applied LC-MS/MS to investigate metabolome variations in the tomato treated with LGC, which revealed 10 differential metabolites (DMs) related to KEGG metabolites, associated with low and high doses of LGC. Enrichment and pathway mapping based on the KEGG database indicated that LGC regulated expressions of 2-hydroxycinnamic acid and l-phenylalanine to interfere with phenylalanine metabolism and phenylpropanoids biosynthesis. The two pathways are closely related to plant growth and lignin formation. In our further phenotypic verification, LGC was confirmed to affect seedling lignification and related phenylpropanoids, trans-ferulic acid and l-phenylalanine levels. These findings provided a metabolomic aspect on the plant hormone derivates and revealed the affected metabolites. Elucidating their regulation mechanisms can contribute to the development of sustainable agriculture. Further studies on agrichemical development would provide eco-friendly and efficient regulators for plant growth control and quality improvement.

Association study of the functional variants of the GLIS3 gene with risk of knee osteoarthritis.

INTRODUCTION/OBJECTIVES: Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population. METHODS: In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated. RESULTS: We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69-0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61-0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63-0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren-Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46-0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6-0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001). CONCLUSIONS: These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together. Key Point • Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids.

Eight drimane sesquiterpenoids including (-)-drimenol and (+)-albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1-carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor of the three, (at concentrations of 8 - 64 µg/ml, causing 100% death of various fungi), acts not only against C. albicans in a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, Pneumocystis, Blastomyces, Saksenaea and fluconazole resistant strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest that drimenol is a broad-spectrum antifungal agent. At a high concentration (100 µg/ml) drimenol caused rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive in metazoans. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections revealed putative genes and pathways affected by drimenol. Using a C. albicans mutant spot assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and orf19.759, orf19.1672, and orf19.4382 were revealed to be involved in drimenol's mechanism of action. The three orfs identified in this study are novel and appear to be linked with Crk1 function. Further, computational modeling results suggest possible modifications of the structure of drimenol, including the A ring, for improving the antifungal activity.

Silica-Coated Gold-Silver Nanocages as Photothermal Antibacterial Agents for Combined Anti-Infective Therapy.

Because of the abuse of antibiotics and threats of antibiotic resistance, bacterial infection is still one of the most difficult issues to be resolved. Thus, it is of great significance to explore novel antibacterial agents. In this paper, we investigated a type of silica-coated gold-silver nanocages (Au-Ag@SiO2 NCs) as antibacterial candidates. Their intrinsic characteristics of photothermal property and sustained release of Ag ions were fully exploited for near-infrared (NIR)-induced combined anti-infective therapy. The broad-spectrum antibacterial property of the as-prepared Au-Ag@SiO2 NCs was confirmed in vitro against Gram-positive Staphylococcus aureus ( S. aureus) and Gram-negative bacteria Escherichia coli ( E. coli). In addition, Au-Ag@SiO2 NCs exhibit effective treatment of the S. aureus biofilm with the assistance of NIR irradiation. More importantly, we assessed the in vivo antibacterial efficacy of Au-Ag@SiO2 NCs against S. aureus, which demonstrated sustainably enhanced therapeutic effects on a rat model with wound infection.

Maternal dietary exposure to selenium nanoparticle led to malformation in offspring.

Selenium (Se) is an essential element and its biological activity is related to its speciation. It is also well-known that in excess it can cause teratogenesis in fish and birds. In this study we compared dietary toxicity of elemental selenium nanoparticles (SeNPs) with selenite and selenomethionine (Se-Met). Japanese medaka (Oryzias latipes) was used as a laboratory model to determine Se effects on adults and their offspring. Adult females were individually exposed using a dry diet fortified with 0, 10 or 20 µg/g of the three Se species for 7 days and then allowed to breed for 3 days. Fertilization rate and the proportion of malformed offspring were examined. The three Se diets led to significant increase in maternal tissue Se concentration in the order of Se-Met >>selenite > SeNP. However, in terms of proportion of malformed offspring, the effect of Se-Met = selenite > SeNP. The malformations included pericardial edema and craniofacial changes, which were typical for Se toxicity. The mismatch of maternal ovary Se concentration and proportion of malformed offspring suggested total Se concentration is a poor predictor of toxicity and teratogenesis. Comparing expression of four genes related to oxidative stress in maternal tissue also showed that there were significant differences in expression patterns between three Se diets in the order of selenite = SeNP > Se-Met. Our results showed that SeNPs cause similar toxicity as other Se species but require further study to elucidate the underlying mechanism.

Constituents from solid-cultured Antrodia camphorata.

Antrodia camphorata is a rare and precious traditional food and medicine for improving health-related conditions in Taiwan. The phytochemical research of the mushroom led to the isolation of a new naphthalenecarboxaldehyde, named as 1-Naphthalenecarboxaldehyde,3,4,4a,5,6,7,8,8a-octahydro-2-(hydroxymethyl)-5,5,8a-trimethyl (1). Meanwhile, seven other known compounds of nerolidol (2), cadinol (3), herbarulide (4), 3ß-Hydroxy-5a,8a-epidioxyergosta-6,22-diene (5), ergosta-7,22-diene-3,6-dione (6) 2,3-dimethoxy-5-methyl-p-benzoquinone (7) and ß-sitosterol (8) were also obtained from A. camphorata for the first time except compound (8). The new compound was elucidated by 2D NMR techniques (COSY, HMBC, HSQC, NOESY) and HRMS while those known compounds deduced by comparing 1H NMR and 13C NMR data with other literatures. Then, the hepG2 cell toxicity screening was conducted and the results demonstrated that only compound 7 and 8 exhibited significant toxicity to hepG2 cell at the concentration of 50 µg/mL.

Structure-activity relationship of brassinosteroids and their agricultural practical usages.

Brassinosteroids (BRs) control several important agronomic traits, such as strengthening resistance to diverse adversity, improving the quality, and increasing crop yield. Their chemical structures and varieties, specific methods for the evaluation of bioactivities, structure-activity relationships, potential novel compounds, and practical agricultural uses were summarized. The findings allow the examination of brassinosteroids in two important issues: 1) Do the results of different bioevaluation protocols provide similar activities for BRs? and 2) which bioevaluated compounds would proof to have a greater potential for application in agricultural usages?

Structure based in silico identification of potentially non-steroidal brassinosteroids mimics.

Brassinosteroids (BRs) are a class of plant steroid hormones that play indispensable roles in cell elongation, division and plant development. To date, the numerous synthesis of BRs analogs and structure-activity relationship investigations have clearly revealed the key substituent groups relevant to the steroidal activity of BRs. However, due to the limited chemical space studied, the efforts for alternative non-steroidal compounds have produced no remarkable results. To identify potentially non-steroidal BR mimics in this study, vital interacting pharmacophore features were extracted starting from several complex structures of BRs that bound with the receptor Brassinosteroid-Insentive 1 (BRI1) and co-receptor BRI1-associated kinase 1 (BAK1), which were characterized and merged into one comprehensive pharmacophore model. In silico screening of a commercial compound database was carried out by combing pharmacophore modeling, molecular docking and visual analysis. Finally, six non-steroidal molecules were identified and subjected to the in vivo radish hypocotyl elongation assay. As a positive control, the hypocotyls elongation for the naturally most active BR brassinolide (BL) is 152 ± 3% at 100 nM. Moreover, two candidates (4 and 6) show good BRs-like activity with the hypocotyls elongation of 143 ± 1% and 128 ± 3% at the same dose, respectively. Most remarkably, compounds 4 and 6, which have different structures, are predicted to share similar binding modes and proven to exhibit potential BRs-like activity. The two compounds obtained could be valuable leads for the development of BRs-like plant growth regulators.

NIR-Responsive Polycationic Gatekeeper-Cloaked Hetero-Nanoparticles for Multimodal Imaging-Guided Triple-Combination Therapy of Cancer.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

Synthesis of brassinosteroids analogues from laxogenin and their plant growth promotion.

Four steroid saponins (2-5) and three derivatives (6-8) were synthesised from laxogenin. Four of them were new compounds: (25R)-3ß-(2,3,4,6-tetra-O-acetyl-ß-D-galactopyranosyloxy)-5α-spirostan-6-one (3), (25R)-3ß-(ß-D-galactopyranosyloxy)-5α-spirostan-6-one (5), 3ß,16-diacetyl-26-hydroxy-5α-cholestan-6,22-dione (6) and 16-acetyl-3ß,26-dihydroxy-5α-cholestan-6,22-dione (7). All the compounds showed plant growth-promoting activity in the radish hypocotyl elongation and cotyledon expansion bioassay. Above all, 2 and 6 were found to be more active.

Four new furostanol saponins from the rhizomes and roots of Smilax scobinicaulis and their cytotoxicity.

Four new furostanol saponins 1-4, along with two known furostanol saponins 5 and 6 and one known spirostanol saponin 7 were isolated from the rhizomes and roots of Smilax scobinicaulis. The structures of the new saponins were elucidated as 26-O-ß-D-glucopyranoside-3ß,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one-3-O-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranoside (1), 26-O-ß-D-glucopyranoside-3ß,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one (2), 26-O-ß-D-glucopyranoside-3ß,26-dihydroxy-(25R)-5α-furostan-20(22)-en-6-one (3), 26-O-ß-D-glucopyranoside-3ß,23,26-trihydroxy-(23R, 25R)-5α-furostan-20(22)-en-6-one (4) on the basis of spectroscopic analysis. The isolated saponins were evaluated for cytotoxic activity against two human cancer cell lines including Hela (cervical carcinoma) and SMMC-7221 (hepatocellular carcinoma). Compounds 1 and 7 demonstrated cytotoxicity against the tested cell lines.

[Influence of different processing methods and mature stages on 3,29-dibenzoyl rarounitriol of Trichosanthes kirilowii seeds].

OBJECTIVE: To study the different mature stages and the best processing methods on the quality of Trichosanthes kirilowii seeds. METHODS: The content of 3,29-dibenzoyl rarounitriol in Trichosanthes kirilowii seeds was determined by HPLC. The sample of different mature stages such as immature, near mature and fully mature and processed by different methods were studied. RESULTS: Fully mature Trichosanthes kirilowii seeds were better than the immatured, and the best processing method was dried under 60degrees C, the content of 3,29-dibenzoyl rarounitriol reached up to 131.63microlg/mL. CONCLUSION: Different processing methods and different mature stages had a significant influence on the quality of Trichosanthes kirilowii seeds.

A new flavonoid glycoside from the rhizomes and roots of Smilax scobinicaulis.

A new flavonoid glycoside, hesperetin-7-O-[ß-D-glucopyranosyl-(1 → 3)]-ß-D-glucopyranosyl (1), was isolated from the n-BuOH extract of Smilax scobinicaulis, together with four known flavonoid glycosides, clematine (2), ononin (3), daidzin (4) and puerarin (5). All of the five compounds were reported from this material for the first time. Their structures were determined on the basis of spectroscopic and spectrometric methods.

[Phenylpropanoids and diphenylethene compounds from roots and rhizomes of Smilax scobinicaulis].

The chemical constituents were separated and purified from the roots and rhizomes of Smilax scobinicaulis by various chromatographic methods including silica gel, Sephadex LH-20. Their structures were obtained and identified as resveratrol-3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranoside (1), resveratrol (2), 8-viniferin (3), ethyl caffeate (4), 1-0-caffeoylglycerol (5), 1-O-p-coumaroylglycerol (6), 1-0-feruloylglycerol (7), grossamide (8), moracin M (9) on the analysis of spectroscopic data. Compound 1 was a new compound and compounds 3-5, 8,9 were separated from this plant for the first time.

A new cytotoxic steroidal saponin from the rhizomes and roots of Smilax scobinicaulis.

A phytochemical investigation of the EtOH extract from the rhizomes and roots of Smilax scobinicaulis resulted in the isolation of a new isospirostanol-type steroidal saponin, namely (25 R)-5α-spirostan-3ß,6ß-diol 3-O-ß-D-glucopyranosyl-(1 → 4)-[α-L-arabinopyranosyl-(1 → 6)]-ß-D-glucopyranoside (1), along with four known steroidal saponins (2-5). The structures of these compounds were determined by 1D- and 2D-NMR spectroscopic analysis, FABMS and HR-ESI-MS as well as chemical degradation. The isolated saponins were evaluated for their in vitro cytotoxicity against A549, LAC and Hela human cancer cell lines, which demonstrated that only compound 1 possessed significant cytotoxic activity with IC50 values of 3.70, 5.70 and 3.64 µM, respectively.