Integrated metabolomic and transcriptomic analysis reveals perturbed glycerophospholipid metabolism in mouse neural stem cells exposed to cadmium.

Cadmium (Cd) is a ubiquitous heavy metal with neurotoxicity. Our previous study reported that Cd could inhibit the proliferation of mouse neural stem cells (mNSCs). However, the underlying mechanisms are obscure. In recent years, the rapid growth of multi-omics techniques enables us to explore the cellular responses that occurred after toxicant exposure at the molecular level. In this study, we used a combination of metabolomics and transcriptomics approaches to investigate the effects of exposure to Cd on mNSCs. After treatment with Cd, the metabolites and transcripts in mNSCs changed significantly with 110 differentially expressed metabolites and 2135 differentially expressed genes identified, respectively. The altered metabolites were mainly involved in glycerophospholipid metabolism, arginine and proline metabolism, arginine biosynthesis, glyoxylate and dicarboxylate metabolism. Meanwhile, the transcriptomic data demonstrated perturbed membrane function and signal transduction. Furthermore, integrated analysis of metabolomic and transcriptomic data suggested that glycerophospholipid metabolism might be the major metabolic pathway affected by Cd in mNSCs. More interestingly, the supplementation of lysophosphatidylethanolamine (LPE) attenuated Cd-induced mitochondrial impairment and the inhibition of cell proliferation and differentiation in mNSCs, further supporting our analysis. Overall, the study provides new insights into the mechanisms of Cd-induced neurotoxicity.

[Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure].

OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION: Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.

Effect of carboxylation cellulose nanocrystal and grape peel extracts on the physical, mechanical and antioxidant properties of konjac glucomannan films.

Active bionanocomposite films were prepared by incorporating konjac glucomannan (KGM) as a matrix, with carboxylation cellulose nanocrystal (C-CNC) as a reinforcement agent and grape peel extracts (GPE) as a natural antioxidation agent. The effects of C-CNC and/or GPE addition on the structural, morphological, barrier, thermal, mechanical and antioxidant properties of the bionanocomposite films were investigated. The rheological results of film forming solutions revealed that C-CNC and GPE were well dispersed in the KGM matrix. Scanning electron micrographs observed the addition of C-CNC had little effect on the microstructure, while more roughness and unevenness were observed on the film surface and cross-section with the C-CNC and GPE. Furthermore, the water vapor barrier property and transparency of the films improved by the addition of the C-CNC and GPE. Notably, the incorporating of C-CNC or GPE significantly alter the mechanical of the KGM/C-CNC/GPE bionanocomposite films. The highest tensile strength was achieved for the KGM/GPE bionanocomposite film with 10 wt% C-CNC, indicating C-CNC and GPE had synergistic effect on enhancing the TS of KGM film. Moreover, the KGM/C-CNC/GPE films exhibited strong antioxidant activity. These results suggested that KGM/C-CNC/GPE bionanocomposite films can be used as an active food packaging for increasing shelf life of packaged foods.

Natural variation and selection in GmSWEET39 affect soybean seed oil content.

Soybean (Glycine max) is a major contributor to the world oilseed production. Its seed oil content has been increased through soybean domestication and improvement. However, the genes underlying the selection are largely unknown. The present contribution analyzed the expression patterns of genes in the seed oil quantitative trait loci with strong selective sweep signals, then used association, functional study and population genetics to reveal a sucrose efflux transporter gene, GmSWEET39, controlling soybean seed oil content and under selection. GmSWEET39 is highly expressed in soybean seeds and encodes a plasma membrane-localized protein. Its expression level is positively correlated with soybean seed oil content. The variation in its promoter and coding sequence leads to different natural alleles of this gene. The GmSWEET39 allelic effects on total oil content were confirmed in the seeds of soybean recombinant inbred lines, transgenic Arabidopsis, and transgenic soybean hairy roots. The frequencies of its superior alleles increased from wild soybean to cultivated soybean, and are much higher in released soybean cultivars. The findings herein suggest that the sequence variation in GmSWEET39 affects its relative expression and oil content in soybean seeds, and GmSWEET39 has been selected to increase seed oil content during soybean domestication and improvement.

Biological nutrient removal in the anaerobic side-stream reactor coupled membrane bioreactors for sludge reduction.

An anoxic-aerobic membrane bioreactor (AO-MBR), an anaerobic side-stream reactor (ASSR) coupled MBR (A-MBR), and an MBR with ASSR packed with carriers (AP-MBR) were operated parallelly to investigate biological nutrient removal, microbial community structure and mass balance of nutrients in sludge reduction systems. Compared to AO-MBR, A-MBR and AP-MBR were both efficient in COD and NH4+-N removal, had significantly higher nitrogen removal, reduced sludge production by 35.0% and 45.9%, but deteriorated biological phosphorus removal. Nitrosomonadaceae and Nitrospira were major bacteria responsible for ammonium and nitrite oxidation in the three systems. Inserting ASSR and packing carriers both favored denitrifying bacteria enrichment and organic substances release, and thus resulted in higher nitrate uptake rate (NUR) in the anoxic tank. Higher endogenous NUR in ASSR than in anoxic tank also indicated that ASSR and carriers both accelerated sludge decay. Denitrification and sludge reduction occurred in ASSR played important roles in biological nutrient removal.

Synthesis and characterization of porous tree gum grafted copolymer derived from Prunus cerasifera gum polysaccharide.

Porous grafted copolymer with excellent thermal stability and swelling capacity was synthesized from water soluble Prunus cerasifera gum polysaccharide (PG) and acrylamide (AM). The monosaccharide compositions and the structure of Prunus cerasifera tree gum were detected by a high-performance anion exchange chromatography (HPAEC) system and 1H NMR and 13C NMR, and the obtained PG-AM copolymer was characterized by Fourier transform infrared (FT-IR), scanning electron microscope (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), respectively. The results indicated that the water soluble polysaccharides obtained from Prunus cerasifera tree gum were mainly composed of l-arabinose (39.78%) and d-galactose (40.59%) with minor amount of xylose, mannose and uronic acids. The maximum percent and the grafting efficiency of grafting acrylamide (AM) onto PG to form PG-AM were obtained by copolymerization between polysaccharide and 3 times (weight) acrylamide with 3 mmol/L potassium persulfate initiator at 50 °C for 1 h. In addition, lots of isolated and conjoint pores were observed in the prepared PG-AM materials, with a diameters distribution between 2 and 10 µm. Compared with PG, the synthesized copolymer PG-AM showed an excellent performance in thermal stability and swelling capacity. The detailed structural characteristic together with excellent thermal stability and swelling properties will benefit efficient utilization of the synthesized copolymer as a precursor for preparation of large-scale environmentally friendly advanced materials with various potential applications.

A pH-indicating intelligent packaging composed of chitosan-purple potato extractions strength by surface-deacetylated chitin nanofibers.

The goal of the study is to develop a novel pH-indicating intelligent packaging by using purple potato extractions (PPE), chitosan and surface-deacetylated chitin nanofibers (CN). Since the major pH-sensitive pigment of PPE was anthocyanin (24.3 mg/g), whether anthocyanins could be loaded on a solid phase to prevent its color fading was further tested. The results of Fourier transform infrared spectrophotometry (FT-IR) and differential scanning calorimetry (DSC) indicated that PPE was efficiently attached into the chitosan film. Meanwhile, adding CN (0.450%, w/v) into chitosan film could significantly enhance the tensile strength (TS), the water-resistant ability and the roughness of chitosan film. Whereas higher content of CN (0.600%, w/v) did not further improve mechanical properties and CN would distribute unevenly due to aggregation in the films. In addition to pH-indicating ability, CS-CN-PPE exhibited the extraordinary antioxidant activities and this provides another advantage of packaging readily oxidizable substances. Taken together, the current study provided a novel and biocompatible packaging with strengthened mechanical property and intelligent pH indicator.

Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis.

INTRODUCTION: Low vitamin D status has been found to be associated with impaired glycemic control in patients who suffer from type 2 diabetes; however, whether vitamin D supplementation is associated with improved glycemic status remains controversial. The aim of this study was to summarize evidence from randomized controlled trials (RCTs) to assess the efficacy of vitamin D supplementation in reducing glycosylated haemoglobinA1c (HbA1c) and fasting blood glucose (FBG) levels. MATERIALS/METHODS: We searched PubMed, Web of Science and the Cochrane Library for reports published up to March 2017. We selected parallel RCTs investigating the effect of vitamin D or vitamin D analogues on HbA1c or FBG levels in type 2 diabetes patients. Cohen's d was calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95%confidence intervals (CIs) were pooled using a random effects model. RESULTS: Twenty-four studies were included that evaluated HbA1c levels and 18 studies were included that evaluated FBG levels. Meta-analyses showed that vitamin D supplementation was associated with reduced HbA1c levels (standardized mean difference (SMD) -0.25 [-0.45 to -0.05]) but had no influence on FBG levels (SMD -0.14 [-0.31 to 0.03]). However, the subgroup analyses suggested that vitamin D supplementation was associated with reduced HbA1c levels (SMD -0.39 [-0.67 to -0.10]) and FBG (SMD -0.27 [-0.46 to -0.07]) among patients with 25-hydroxyvitamin D (25(OH) D) deficiency at baseline. Significantly reduced HbA1c levels were also observed in association with vitamin D supplementation in the subgroup including type 2 diabetes patients with a body mass index (BMI) <30kg m-2 (SMD -0.30 [-0.54 to -0.07]). CONCLUSIONS: Vitamin D supplementation could be effective at improving glycemic control in vitamin D deficient or non-obese type 2 diabetes patients.

Effects of preparation methods on potato microstructure and digestibility: An in vitro study.

The effects of preparation method (boiled, cooled, and reheated) on the structural characteristics and in vitro digestibility of potato were investigated. The highest equilibrium starch hydrolysis was obtained after boiling (82.21%), followed by reheating (66.98%) and cooling (54.31%). The potato after cooling treatment exhibited a narrower melting temperature range and a higher melting enthalpy compared with the potatoes after boiling and the microwave reheating. X-ray diffraction patterns revealed that the relative crystallinity of the cooled potato was higher than those of the reheated and boiled potatoes, consistent with the results in melting enthalpy. Moreover, compared with the boiled potato, a large number of wrinkles were observed on the surface of the cooled potato, whereas after microwave reheating, larger clearances of starch granule regions were found. This study demonstrated that cooling and microwave reheating significantly affected the potato's microstructure and digestibility and were suggested as alternative choices to prepare potato dishes.

New secoiridoids from the fruits of Ligustrum lucidum Ait with triglyceride accumulation inhibitory effects.

Five new secoiridoids, nuzhenal C (1), 6'-O-trans-cinnamoyl iso-8-epikingisidic acid (2), ligulucidumosides A (3), B (4), and C (5), were obtained from the fruits of Ligustrum lucidum Ait. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compound 3 is the first 1-OCH3 substituent secoiridoid obtained from plant kingdom. Furthermore, activity screening results showed that all of the isolates had triglyceride accumulation inhibitory effects in HepG2 cells.

Rare syringyl acylated flavonol glycosides from the aerial parts of Leonurus japonicus Houtt.

Five new syringyl acylated flavonol glycosides, named leonurusoides A (1), B (2), C (3), D (4), and E (5), together with one known one 6 were obtained from the aerial parts of Leonurus japonicus. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Compounds 1-6 showed triglyceride (TG) accumulation inhibitory effects in free fatty acid-induced HepG2 cells.

Isolation, structural elucidation, MS profiling, and evaluation of triglyceride accumulation inhibitory effects of benzophenone C-glucosides from leaves of Mangifera indica L.

Seventy percent ethanol-water extract from the leaves of Mangifera indica L. (Anacardiaceae) was found to show an inhibitory effect on triglyceride (TG) accumulation in 3T3-L1 cells. From the active fraction, six new benzophenone C-glucosides, foliamangiferosides A(3) (1), A(4) (2), C(4) (3), C(5) (4), C(6) (5), and C(7) (6) together with 11 known benzophenone C-glucosides (7-17) were obtained. In this paper, isolation, structure elucidation (1-6), and MS fragment cleavage pathways of all 17 isolates were studied. 1-6 showed inhibitory effects on TG and free fatty acid accumulation in 3T3-L1 cells at 10 µM.

Triglyceride accumulation inhibitory effects of phenylpropanoid glycosides from Boschniakia rossica Fedtsch et Flerov.

Bioassay-guided fractionation led to isolation of five new phenylpropanol glycosides, rossicasides G (1), H (2), I (3), J (4), and K (5), together with seven known compounds (6-12) from Boschniakia rossica. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Activity screening results showed that some isolates had TG accumulation inhibitory effects in HepG2 cells. Furthermore, the structure-activity relationship was partly clarified.

[Induction of adventitious roots of Echinacea pallida and accumulation of caffeic acid derivatives].

OBJECTIVE: To investigate the effect of auxins 2,4-D,IAA,IBA,NAA on induction of adventitious roots as well as that of IBA concentrations on the growth of adventitious roots and the accumulation of caffeic acid derivatives, with test-tube seedling leaves Echinacea pallida as the explant, and cultivate adventitious roots in bioreactors. RESULT: 1.0 mg x L(-1) IBA was found the best for the induction of adventitious roots, with the numer of induced adventitious roots up to 22. 5 in each culture dish. Among different concentrations for suspension cultivation of IBA tested, 1.0 mg x L(-1) IBA was found the most suitable for the growth of adventitious roots and the accumulation of caffeic acid derivatives. In a 5 L balloon type bubble bioreactor, 8.98 g x L(-1) dry weight was achieved after one month, which was 2.05 times of 4.38 g x L(-1) dry weight cultivated in a triangular flask. The content of echinacoside cultivated in a bioreactor was 14.08 mg x g(-1) DW, which was 2.4 times of cultivated roots. The contents of chlorogenic acid, chicoric acid and total caffeic acid derivatives were 4.0-25.6 times of ultivated roots. CONCLUSION: The study can provide high-quality biomedical drugs containing such caffeic acid derivatives as echinacoside for mass production of Echinacea purpurea medicines.

Large-scale cultivation of adventitious roots of Echinacea purpurea in airlift bioreactors for the production of chichoric acid, chlorogenic acid and caftaric acid.

Adventitious roots of Echinacea purpurea were cultured in airlift bioreactors (20 l, 500 l balloon-type, bubble bioreactors and 1,000 l drum-type bubble bioreactor) using Murashige and Skoog (MS) medium with 2 mg indole butyric acid l(-1) and 50 g sucrose l(-1) for the production of chichoric acid, chlorogenic acid and caftaric acid. In the 20 l bioreactor (containing 14 l MS medium) a maximum yield of 11 g dry biomass l(-1) was achieved after 60 days. However, the amount of total phenolics (57 mg g(-1) DW), flavonoids (34 mg g(-1) DW) and caffeic acid derivatives (38 mg g(-1) DW) were highest after 50 days. Based on these studies, pilot-scale cultures were established and 3.6 kg and 5.1 kg dry biomass were achieved in the 500 l and 1,000 l bioreactors, respectively. The accumulation of 5 mg chlorogenic acid g(-1) DW, 22 mg chichoric acid g(-1) DW and 4 mg caftaric acids g(-1) DW were achieved with adventitious roots grown in 1,000 l bioreactors.

Arbuscular mycorrhizae enhance metal lead uptake and growth of host plants under a sand culture experiment.

A sand culture experiment was conducted to investigate whether mycorrhizal colonization and mycorrhizal fungal vesicular numbers were influenced by metal lead, and whether mycorrhizae enhance host plants tolerance to metal lead. Metal lead was applied as Pb(NO3)2 in solution at three levels (0, 300 and 600 mg kg(-1) sand). Five mycorrhizal host plant species, Kummerowia striata (Thunb.) Schindl, Ixeris denticulate L., Lolium perenne L., Trifolium repens L. and Echinochloa crusgalli var. mitis were used to examine Pb-mycorrhizal interactions. The arbuscular mycorrhizal inoculum consisted of mixed spores of mycorrhizal fungal species directly isolated from orchard soil. Compared to the untreated control, both Pb concentrations reduced mycorrhizal colonization by 3.8-70.4%. Numbers of AM fungal vesicles increased by 13.2-51.5% in 300 mg Pb kg(-1) sand but decreased by 9.4-50.9% in 600 mg Pb kg(-1) sand. Mycorrhizae significantly enhanced Pb accumulation both in shoot by 10.2-85.5% and in root by 9.3-118.4%. Mycorrhizae also enhanced shoot biomass and shoot P concentration under both Pb concentrations. Root/shoot ratios of Pb concentration were higher in highly mycorrhizal plant species (K.striata, I. denticulate, and E. crusgalli var. mitis) than that in poorly mycorrhizal ones (L. perenne and T. repens,). Mycorrhizal inoculation increased the root/shoot ratio of Pb concentration of highly mycorrhizal plant species by 7.6-57.2% but did not affect the poorly mycorrhizal ones. In the treatments with 300 Pb mg kg(-1) sand, plant species with higher vesicular numbers tended to show higher root/shoot ratios of the Pb concentration. We suggest that under an elevated Pb condition, mycorrhizae could promote plant growth by increasing P uptake and mitigate Pb toxicity by sequestrating more Pb in roots.