Identification of multiple plasma lipids as diagnostic biomarkers of hypercholesterolemia and the underlying mechanisms based on pseudo-targeted lipidomics.

RATIONALE: Hypercholesterolemia is an important risk factor for cardiovascular diseases and death. This study performed pseudo-targeted lipidomics to identify differentially expressed plasma lipids in hypercholesterolemia, to provide a scientific basis for the diagnosis and pathogenesis of hypercholesterolemia. METHODS: Pseudo-targeted lipidomic analyses of plasma lipids from 20 patients with hypercholesterolemia and 20 normal control subjects were performed using liquid chromatography-mass spectrometry. Differentially expressed lipids were identified by principal component analysis and orthogonal partial least squares discriminant analysis. Receiver operating characteristic curves were used to identify differentially expressed lipids with high diagnostic value. The Kyoto Encyclopedia of Genes and Genomes pathway database was used to identify enriched metabolic pathways. RESULTS: We identified 13 differentially expressed lipids in hypercholesterolemia using variable importance of projection > 1 and p < 0.05 as threshold parameters. The levels of eight sphingomyelins and cholesterol sulfate were higher and those of three triacylglycerols and lysophosphatidylcholine were reduced in hypercholesterolemia. Seven differentially expressed plasma lipids showed high diagnostic value for hypercholesterolemia. Functional enrichment analyses showed that pathways related to necroptosis, sphingolipid signaling, sphingolipid metabolism, and steroid hormone biosynthesis were enriched. CONCLUSIONS: This pseudo-targeted lipidomics study demonstrated that multiple sphingomyelins and cholesterol sulfate were differentially expressed in the plasma of patients with hypercholesterolemia. We also identified seven plasma lipids, including six sphingomyelins and cholesterol sulfate, with high diagnostic value.

Stability and gastrointestinal behavior of curcumin-loaded emulsion stabilized by multi-conformation soy proteins: Influence of oil volume fraction.

The aim of this work was to assess the potential of nanoemulsions stabilized by mixed soy protein with multi-conformation as curcumin carrier, and the influence of oil volume fraction on stability and gastrointestinal behavior of curcumin-loaded emulsion was investigated. Loading efficiency showed a slight increase with higher oil content, though the difference was not statistically significant. With the increase of oil, the viscosity (Pa‧s), thixotropy (area of hysteresis loop) and particle size of the emulsion increased, which facilitated the physical and chemical stability of curcumin-loaded emulsion. However, the free fatty acid release rate and bioaccessibility of curcumin was negatively correlated with the oil volume fraction and the particle size of emulsion after gastric digestion. Notably, the digestion in stomach did not affect the structure of interfacial protein, demonstrating that protein-based nanoemulsions exhibited resistance to gastric digestion. This study provides theoretical guidance for the application of protein-based emulsion in curcumin delivery.

Resource availability drives bacteria community resistance to pathogen invasion via altering bacterial pairwise interactions.

Microbial interactions within resident communities are a major determinant of resistance to pathogen invasion. Yet, interactions vary with environmental conditions, raising the question of how community composition and environments interactively shape invasion resistance. Here, we use resource availability (RA) as a model parameter altering the resistance of model bacterial communities to invasion by the plant pathogenic bacterium Ralstonia solanacearum. We found that at high RA, interactions between resident bacterial species were mainly driven by the direct antagonism, in terms of the means of invader inhibition. Consequently, the competitive resident communities with a higher production of antibacterial were invaded to a lesser degree than facilitative communities. At low RA, bacteria produced little direct antagonist potential, but facilitative communities reached a relatively higher community productivity, which showed higher resistance to pathogen invasion than competitive communities with lower productivities. This framework may lay the basis to understand complex microbial interactions and biological invasion as modulated by the dynamic changes of environmental resource availability.

Correction of a digital micromirror device lithography system for fabrication of a pixelated liquid crystal micropolarizer array.

The combination of a digital micromirror device (DMD) lithography system and a rotatable polarizer provides a simple and convenient method to achieve the pixelated liquid crystal micropolarizer (LCMP) array for polarization imaging. In this paper, two crucial problems restricting the high-precision fabrication of LCMP array are pointed out and settled: the dislocation of LCMP pixels caused by parallelism error of the rotating polarizer and the grid defect caused by the gap between micromirrors. After correction, the maximum deviation of the fabricated LCMP pixels was reduced from 3.23 µm to 0.11 µm and the grid defect is eliminated. The correction method reported here lays a good foundation for the fine processing of liquid crystal devices with arbitrary photoalignment structure by using the DMD system.

The relationship between solid-liquid interface interaction and gelling capacity of h-BN 2D material: a rheological study.

Diurea modified h-BN nanosheet is a novel kind of 2D gelator that could gel the lubricating oils under the stimulus of ultrasound. Morphological analyzations in previous study confirmed that the ultrasound induced layer-by-layer (LBL) structure of BN gelator is critical for the gelation. However, the elastic response in LBL structure, which is crucial for the formation of a stable gel system, has not been explicitly illustrated yet. The challenge is that the LBL gelator structure is based on 2D material and thus lacks vertical linkage between gelator layers, which is significantly different from the traditional gel systems that generally possess highly crosslinked gelator network. In this work, by investigating the viscoelastic behavior of the BN-based gel via rheometer, it is found the solid-liquid interface interaction, which is regulated by the diurea molecular structure in the BN gelator, is the key factor for triggering the stable elastic response in the LBL structure, and the elasticity mainly originates from the interface interaction induced bending deformation of h-BN 2D material. The findings further elucidate the gelling mechanism of BN gelators and enlighten the structure design of ultrasound-responsive gelator based on 2D materials.

Modulation of the Tomato Rhizosphere Microbiome via Changes in Root Exudation Mediated by the Ethylene Receptor NR.

Plant hormones have been recently shown to exert an indirect influence on the recruitment of plant-associated microbiomes. However, it remains unclear the extent to which the disruption of the ethylene (ET) signaling pathway affects the assembly and functioning of plant-root microbiomes. In this study, the Never-ripe tomato mutant (Nr) was profiled for differences compared to the wild type (control). Tomato plants were subjected to root exudate profiling and the characterization of bacterial and fungal communities. Compared to the control, Nr revealed differences in the composition of root exudates, including lower amounts of esculetin, gallic acid, L-fucose, eicosapentaenoic acid, and higher amounts of ß-aldehyde. Interestingly, Nr significantly differed in the composition and functioning of the rhizosphere bacterial community. We also identified the taxa that occurred at relatively higher abundances in Nr, including the genus Lysobacter, which displayed a significant negative correlation with changes in eicosapentaenoic acid and esculetin, and a significant positive correlation with changes in ß-aldehyde. Taken together, our study provides evidence that a mutation in the ET receptor exerts predictable changes in the root-associated microbial taxa of tomato plants. These indirect effects can potentially be explored towards new strategies to engineer beneficial plant microbiomes via targeted changes in plant genetics and physiology.

Selectively hydrolyzed soy protein as an efficient quality improver for steamed bread and its influence on dough components.

Selectively hydrolyzed soy protein (SHSP) has the potential to improve the quality of steamed bread. To clarify its underlying mechanism, the influence of SHSP on dough properties and components was investigated and compared with that of soy protein isolate (SPI). The results showed that SHSP addition resulted in steamed bread with higher loaf volume, lower hardness, and higher viscoelasticity. In contrast, SPI addition had the opposite effect. Nevertheless, both soy proteins decreased melting enthalpy and increased starch particle exposure due to competition for water. By analyzing molecular weight distribution and the secondary structure, we determined that the GMP content of fermented dough decreased by 10.04% following 1% SPI addition; however, it was enhanced by 7.90% following 1% SHSP addition. Moreover, the content of ß-turns decreased with SHSP addition. The present study provides a theoretical basis for the exploitation of soy proteins as a nutritious and technofunctional dough improver.

Influence of the Interface Composition to the Superconductivity of Ti/PdAu Films.

In this work, the interface composition of the superconducting Ti/PdAu bilayer is tuned by an annealing process in N2 from 100 to 500 °C to control the superconducting transition temperature (Tc). This Ti-PdAu composition layer is characterized with a high-resolution transmission electron microscopy (HRTEM) and energy-dispersive spectrometer (EDS) to show the infiltration process. The surface topography, electrical, and cryogenic properties are also shown. The inter-infiltration of Ti and PdAu induced by the thermal treatments generates an intermixed layer at the interface of the bilayer film. Due to the enforced proximity effect by the annealing process, the Tc of Ti (55 nm)/PdAu (60 nm) bilayer thin films is tuned from an initial value of 243 to 111 mK which is a temperature that is suitable for the application as the function unit of a superconducting transition edge sensor.

Association between plasma exosome neurogranin and brain structure in patients with Alzheimer's disease: a protocol study.

INTRODUCTION: Neurogranin is known to be significantly elevated in patients with Alzheimer's disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD. METHODS AND ANALYSIS: In this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples. ETHICS AND DISSEMINATION: The ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029055.

MiR-107 overexpression attenuates neurotoxicity induced by 6-hydroxydopamine both in vitro and in vivo.

Alzheimer's disease (AD), the most common form of dementia, is a neurodegenerative disease characterized by neuronal atrophy in various brain regions. The expression of miR-107 is down-regulated in AD patients and target genes of miR-107 have been shown to directly involved in AD. In this study, we aimed to investigate the potential neuroprotective effects of miR-107. We first assessed brain activity in health controls and patients with AD. Then we examined miR-107 expression in SH-SY5Y and PC12 cells treated with 6-hydroxydopamine (6-OHDA), and investigated its function in cytotoxicity induced by 6-OHDA. We predicted a potential miR-107 target and assessed its role in miR-107 mediated effects and explored the intracellular signaling pathways downstream of miR-107. Finally, we assessed the function of miR-107 in the mouse model insulted by 6-OHDA. We found that 6-OHDA suppressed miR-107 expression and miR-107 played neuroprotective effects against 6-OHDA mediated cytotoxicity. We showed that miR-107 targeted programmed cell death 10 (PDCD10). MiR-107 suppressed PDCD10 expression and exogenous expression of PDCD10 inhibited miR-107 mediated neuroprotection. Additionally, we found that Notch signal pathway was downstream of miR-107/PDCD10. Finally, we found that 6-OHDA treatment suppressed miR-107 in mice and restoration of miR-107 alleviated motor disorder in the mouse model. Our study shows that miR-107 plays important neuroprotective roles against neurotoxicity both in vitro and in vivo by inhibiting PDCD10. Our findings confirm that miR-107 may be involved in AD pathogenesis and may be a therapeutic target for the treatment of AD-related impairments.

Mulberrin attenuates 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced Parkinson's disease by promoting Wnt/ß-catenin signaling pathway.

Abnormal neuroinflammation and oxidative stress has been shown to cause neuronal loss in the progressive neurodegenerative Parkinson's disease (PD). Mulberrin is the key component of Ramulus Mori that has various biological activities. This study was to investigate the functions and mechanisms of mulberrin in PD. PD models were established by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Sprague Dawley rats in vivo and Lipopolysaccharide (LPS) treatment on microglial BV2 cells in vitro. Rota-rod test was applied to investigate the roles of mulberrin on MPTP-induced behavioral impairment. The effects of mulberrin on neuronal number and microglia activation were assessed by tyrosine hydroxylase (TH) immunohistochemistry and ionized calcium binding adaptor molecule-1 (Iba-1) immunofluorescence. Inflammatory cytokines and oxidative markers were measured by qRT-PCR. Wnt/ß-catenin components were compared by Western blot. Mulberrin alleviated MPTP-induced impairment of motor coordination in a dose-dependent manner, and partially restored neuronal and microglial population. Neuroinflammation and oxidative stress were suppressed after mulberrin treatment both in vivo and in vitro. Wnt/ß-catenin pathway was partially restored in BV2 cells. Finally, mulberrin rescued MPTP-induced abnormality in tracer elimination by MRI. Our study indicates that mulberrin is a potent suppressor of PD abnormalities and warrants further investigations in the clinical application of mulberrin for treating PD.

A retrospective study of Ganoderma Lucidum Spore Powder for patients with epilepsy.

This study firstly investigated the feasibility effect and safety of Ganoderma Lucidum Spore Powder (GLSP) for treating patients with epilepsy.Eighteen eligible patients with epilepsy were included. They all received GLSP treatment for a total of 8 weeks. The primary outcome included weekly seizure frequency. The secondary outcomes consisted of each seizure episode, and quality of life, measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), as well as the adverse events (AEs).After treatment, GLSP can significant reduce the weekly seizure frequency, compared with it before the treatment (P = .04). However, GLSP did not exert promising effect in each seizure episode (P = .13), and quality of life, measured by the QOLIE-31 scale (P = .11). Additionally, only minor AEs occurred during the treatment period.The results of this study showed that GLSP may be effective for reducing the weekly seizure frequency. Further studies are still needed to warrant this result.

Analysis of genetic variants of the poly(ADP-ribose) polymerase-1 gene in breast cancer in French patients.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that catalyzes the poly(ADP-ribosyl)ation of target proteins in response to DNA damage and has been proposed to play a role in DNA repair, recombination, transcription, cell death, cell proliferation, as well as in stabilization of the genome. We have recently shown that PARP-1 deficiency causes mammary tumorigenesis in mice. In the present study, we investigated whether genetic variants and single nucleotide polymorphisms (SNPs) of PARP-1 contribute to human breast cancer. To this end, we screened all PARP-1 exons, 7.1kb of intron-exon junction and 1.0-kb promoter sequences in 83 French patients with breast cancer and 100 controls by direct sequencing of genomic DNA. Twenty rare genetic variants of PARP-1, including c.1148C>A (Ser383Tyr), c.1354C>A (Arg452Arg), c.2819A>G (Lys940Arg) were detected in nine (10.8%) breast cancers of these patients. Among 31 polymorphic sites examined, five haplotype-tagging SNPs (htSNPs) of PARP-1 were identified. Interestingly, the genotype distribution of htSNP c.852T>C (Ala284Ala) was likely associated with loss of estrogen- and progesterone-receptor expression. The present study implies that genetic variants of PARP-1 may contribute to breast cancerogenesis and that PARP-1 htSNP c.852T>C (Ala284Ala) may influence hormonal therapy of breast cancer.

CD40 function in squamous cell cancer of the head and neck.

CD40 is expressed on basal keratinocytes and Squamous Cell Cancer of the Head and Neck (SCCHN) tumor cells in vivo and in vitro. CD40 ligation reduces proliferation of SCCHN cell lines and enhances EGFr mediated inhibition of proliferation. We investigated the mechanisms of CD40 function and EGFr cross-communication in SCCHN cell lines. CD40 ligation inhibited spontaneous and Fas-induced apoptosis. CD40 ligation specifically increased the secretion of IL-8, VEGF and PGE(2) but not IL-6, IL-10, FasL, GM-CSF, or TGFalpha. Co-ligation with EGFr further increased IL-8, VEGF and PGE(2) secretion. CD40 ligation also induced delayed activation and tyrosine phosphorylation of EGFr. CD40 induces secretion of specific proinflammatory and proangiogenic cytokines, inhibits spontaneous and Fas-induced apoptosis and increases EGFr phosphorylation. CD40 signaling may enhance the survival of SCCHN and tumor stroma.