Effects of glycation with chitooligosaccharide on digestion and fermentation processes of lactoferrin in vitro.

This study aimed to investigate the digestion and fermentation processes of lactoferrin (LF) glycated with chitooligosaccharide (COS) under a controlled Maillard reaction, utilizing the in vitro digestion and fermentation model, and to compare the results of these processes to LF undertaken without glycation. After gastrointestinal digestion, the products of the LF-COS conjugate were found to have more fragments with lower molecular weight than LF, and the antioxidant capabilities (via ABTS and ORAC assay) of the LF-COS conjugate digesta also increased. In addition, the undigested fractions could be further fermented by the intestinal microbiota. Compared with LF, more short-chain fatty acids (SCFAs) were generated (from 2397.40 to 2623.10 µg/g), and more species of microbiota (from 451.78 to 568.10) were observed in LF-COS conjugate treatment. Furthermore, the relative abundance of Bacteroides and Faecalibacterium that could utilize carbohydrates and metabolic intermediates to produce SCFAs also increased in LF-COS conjugate than that of LF. Our results demonstrated that glycation with COS under the controlled wet-heat treatment Maillard reaction could modify the digestion of LF and have a potentially positive influence on the intestinal microbiota community.

Intracellular zinc protects Kv7 K+ channels from Ca2+/calmodulin-mediated inhibition.

Zinc (Zn) is an essential trace element; it serves as a cofactor for a great number of enzymes, transcription factors, receptors, and other proteins. Zinc is also an important signaling molecule, which can be released from intracellular stores into the cytosol or extracellular space, for example, during synaptic transmission. Amongst cellular effects of zinc is activation of Kv7 (KCNQ, M-type) voltage-gated potassium channels. Here, we investigated relationships between Kv7 channel inhibition by Ca2+/calmodulin (CaM) and zinc-mediated potentiation. We show that Zn2+ ionophore, zinc pyrithione (ZnPy), can prevent or reverse Ca2+/CaM-mediated inhibition of Kv7.2. In the presence of both Ca2+ and Zn2+, the Kv7.2 channels lose most of their voltage dependence and lock in an open state. In addition, we demonstrate that mutations that interfere with CaM binding to Kv7.2 and Kv7.3 reduced channel membrane abundance and activity, but these mutants retained zinc sensitivity. Moreover, the relative efficacy of ZnPy to activate these mutants was generally greater, compared with the WT channels. Finally, we show that zinc sensitivity was retained in Kv7.2 channels assembled with mutant CaM with all four EF hands disabled, suggesting that it is unlikely to be mediated by CaM. Taken together, our findings indicate that zinc is a potent Kv7 stabilizer, which may protect these channels from physiological inhibitory effects of neurotransmitters and neuromodulators, protecting neurons from overactivity.

Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Aß) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Aß generation and senile plaque deposition via activating Nrf2 and downregulating the expression of ß-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-κB (NF-κB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Aß, TS could significantly inhibit the aggregation of Aß and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-κB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-κB through Nrf2, thereby reducing the generation of Aß and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress.

Optimization of cerebral organoids: a more qualified model for Alzheimer's disease research.

Alzheimer's disease (AD) is a neurodegenerative disease that currently cannot be cured by any drug or intervention, due to its complicated pathogenesis. Current animal and cellular models of AD are unable to meet research needs for AD. However, recent three-dimensional (3D) cerebral organoid models derived from human stem cells have provided a new tool to study molecular mechanisms and pharmaceutical developments of AD. In this review, we discuss the advantages and key limitations of the AD cerebral organoid system in comparison to the commonly used AD models, and propose possible solutions, in order to improve their application in AD research. Ethical concerns associated with human cerebral organoids are also discussed. We also summarize future directions of studies that will improve the cerebral organoid system to better model the pathological events observed in AD brains.

Astragaloside IV Ameliorates Cognitive Impairment and Neuroinflammation in an Oligomeric Aß Induced Alzheimer's Disease Mouse Model via Inhibition of Microglial Activation and NADPH Oxidase Expression.

Microglial activation and neuroinflammation induced by amyloid ß (Aß) play pivotal roles in Alzheimer's disease (AD) pathogenesis. Astragaloside IV (AS-IV) is one of the major active compounds of the traditional Chinese medicine Astmgali Radix. It has been reported that AS-IV could protect against Aß-induced neuroinflammation and cognitive impairment, but the underlying mechanisms need to be further clarified. In this study, the therapeutic effects of AS-IV were investigated in an oligomeric Aß (oAß) induced AD mice model. The effects of AS-IV on microglial activation, neuronal damage and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression were further studied. Different doses of AS-IV were administered intragastrically once a day after intracerebroventricularly oAß injection. Results of behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test revealed that AS-IV administration could significantly ameliorate oAß-induced cognitive impairment in a dose dependent manner. Enzyme linked immunosorbent assay (ELISA) results showed that increased levels of reactive oxygen species (ROS), tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in hippocampal tissues induced by oAß injection were remarkably inhibited after AS-IV treatment. OAß induced microglial activation and neuronal damage was significantly suppressed in AS-IV-treated mice brain, observed in immunohistochemistry results. Furthermore, oAß upregulated protein expression of NADPH oxidase subunits gp91phox, p47phox, p22phox and p67phox were remarkably reduced by AS-IV in Western blotting assay. These results revealed that AS-IV could ameliorate oAß-induced cognitive impairment, neuroinflammation and neuronal damage, which were possibly mediated by inhibition of microglial activation and down-regulation of NADPH oxidase protein expression. Our findings provide new insights of AS-IV for the treatment of neuroinflammation related diseases such as AD.

Enantioselective dearomative [3+2] cycloaddition of 2-nitrobenzofurans with aldehyde-derived Morita-Baylis-Hillman carbonates.

The phosphine-catalyzed asymmetric dearomative [3+2] cycloaddition of 2-nitrobenzofurans with aldehyde-derived Morita-Baylis-Hillman (MBH) carbonates or allenoate was developed. The reaction with MBH carbonates resulted in a series of cyclopentabenzofurans containing three contiguous stereocenters with good to high yields, diastereoselectivities and enantioselectivities. The use of allenoate also gave the target product with moderate enantioselectivity.

Electrical control of spatial resolution in mixed-dimensional heterostructured photodetectors.

Low-dimensional nanomaterials, such as one-dimensional (1D) nanomaterials and layered 2D materials, have exhibited significance for their respective unique electronic and optoelectronic properties. Here we show that a mixed-dimensional heterostructure with building blocks from multiple dimensions will present a synergistic effect on photodetection. A carbon nanotube (CNT)-[Formula: see text]-graphene photodetector is representative on this issue. Its spatial resolution can be electrically switched between high-resolution mode (HRM) and low-resolution mode (LRM) revealed by scanning photocurrent microscopy (SPCM). The reconfigurable spatial resolution can be attributed to the asymmetric geometry and the gate-tunable Fermi levels of these low-dimensional materials. Significantly, an interference fringe with 334 nm in period was successfully discriminated by the device working at HRM, confirming the efficient electrical control. Electrical control of spatial resolution in CNT-[Formula: see text]-graphene devices reveals the potential of the mixed-dimensional architectures in future nanoelectronics and nano-optoelectronics.

Facile synthesis of chiral [2,3]-fused hydrobenzofuran via asymmetric Cu(i)-catalyzed dearomative 1,3-dipolar cycloaddition.

Intermolecular asymmetric dearomative 1,3-dipolar cycloaddition of 2-nitrobenzofurans with azomethine ylides was enabled by using a chiral Cu(i)/(S,Sp)-iPr-Phosferrox catalyst. As a result, a series of highly stereoselective chiral [2,3]-fused hydrobenzofurans possessing four contiguous stereogenic centers were obtained with good to high yields, diastereoselectivities and enantioselectivities. The reaction has broad substrate scope tolerating various functional groups.

Carbon Nanotube Film Gate in Vacuum Electronic Devices.

A superaligned carbon nanotube (SACNT) film can act as an ideal gate electrode in vacuum electronics due to its low secondary electron emission, high electron transparency, ultrasmall thickness, highly uniform electric field, high melting point, and high mechanical strength. We used a SACNT film as the gate electrode in a thermionic emission electron tube and field emission display prototype. The SACNT film gate in a thermionic emission electron tube shows a larger amplification factor. A triode tube with the SACNT film gate is used in an audio amplification circuit. The SACNT film gate electrode in field emission devices shows better field uniformity. The field emission display prototype is demonstrated to dynamically display Chinese characters.

Crystalline multiwall carbon nanotubes and their application as a field emission electron source.

Using super-aligned carbon nanotube (CNT) film, we have fabricated van der Waals crystalline multiwall CNTs (MWCNT) by adopting high pressure and high temperature processing. The CNTs keep parallel to each other and are distributed uniformly. X-ray diffraction characterization shows peaks at the small angle range, which can be assigned to the spacing of the MWCNT crystals. The mechanical, electrical and thermal properties are all greatly improved compared with the original CNT film. The field emission properties of van der Waals crystalline MWCNTs are tested and they show a better surface morphology stability for the large emission current. We have further fabricated a field emission x-ray tube and demonstrated a precise resolution imaging ability.

Structural characterization and evaluation of the antioxidant activities of polysaccharides extracted from Qingzhuan brick tea.

The crude tea polysaccharides (CTPS) from Qingzhuan brick tea(QZBT) were extracted and fractionated to afford two fractions, namely TPS-1 and TPS-2. Analyses were conducted concerning the structural characterization and antioxidant activities of these samples. Component analysis revealed that the carbohydrate, uronic acid, protein and polyphenol contents of these samples differed significantly. Fourier transform infrared analysis showed that these samples showed similar characteristic absorption peaks for polysaccharides. Ultraviolet-visible spectroscopy, circular dichroism, scanning electron microscopy and thermogravimetric analyses indicated that there were considerable differences in the presence of protein, surface features, conformational characteristics and thermodynamic behaviors. For antioxidant activities in vitro, CTPS, TPS-1 and TPS-2 exhibited concentration-dependent antioxidant activities, with TPS-2 showing significantly higher antioxidant activity than CTPS and TPS-1. These results provide a scientific and strong foundation for the use of tea polysaccharides(TPS) from QZBT and further research towards the relationships between the characteristics and antioxidant activities of TPS.

Effect of glucosamine and chitooligomer on the toxicity of arsenite against Escherichia coli.

Escherichia coli was selected as the sample to study the toxicity of arsenite in the presence of saccharides. The effect of glucosamine, N-acetylglucosamine, glucose, lactose, sucrose, glucosamine and cyclodextrin on the toxicity of arsenite against E. coli was investigated by microcalorimetry. The glucosamine and the tested chitooligomer decreased the toxicity of arsenite on cells of E. coli, and the effect of glucosamine was stronger than that of the chitooligomer. These results suggest that the glucosamine and chitooligomer may be employed as the assistant antidote for arsenite.

Proteomic analysis of young leaves at three developmental stages in an albino tea cultivar.

BACKGROUND: White leaf No.1 is a typical albino tea cultivar grown in China and it has received increased attention in recent years due to the fact that white leaves containing a high level of amino acids, which are very important components affecting the quality of tea drink. According to the color of its leaves, the development of this tea cultivar is divided into three stages: the pre-albinistic stage, the albinistic stage and the regreening stage. To understand the intricate mechanism of periodic albinism, a comparative proteomic approach based on two-dimensional electrophoresis (2-DE) and mass spectrometry was adopted first time to identify proteins that changed in abundance during the three developmental periods. RESULTS: The 2-DE results showed that the expression level of 61 protein spots varied markedly during the three developmental stages. To analyze the functions of the significantly differentially expressed protein spots, 30 spots were excised from gels and analyzed by matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry. Of these, 26 spots were successfully identified. All identified protein spots were involved in metabolism of carbon, nitrogen and sulfur, photosynthesis, protein processing, stress defense and RNA processing, indicating these physiological processes may play crucial roles in the periodic albinism. Quantitative real-time RT-PCR analysis was used to assess the transcriptional level of differentially expressed proteins. In addition, the ultrastructural studies revealed that the etioplast-chloroplast transition in the leaf cell of White leaf No. 1 was inhibited and the grana in the chloroplast was destroyed at the albinistic stage. CONCLUSIONS: In this work, the proteomic analysis revealed that some proteins may have important roles in the molecular events involved in periodic albinism of White leaf No. 1 and identificated many attractive candidates for further investigation. In addition, the ultrastructural studies revealed that the change in leaf color of White leaf No. 1 might be a consequence of suppression of the etioplast-chloroplast transition and damage to grana in the chloroplast induced by temperature. These results provide much useful information to improve our understanding of the mechanism of albinism in the albino tea cultivar.