Apigenin C-glycosides of Microcos paniculata protects lipopolysaccharide induced apoptosis and inflammation in acute lung injury through TLR4 signaling pathway

Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening conditions with high morbility and mortality, underscoring the urgent need for novel treatments. Leaves of the medicinal herb Microcos paniculata have been traditionally used for treating upper airway infections, by virtue of its content of flavonoids such as apigenin C-glycosides (ACGs). C-glycosides have been shown to exert strong anti-inflammatory properties, although their mechanism of action remains unknown. Herein, hypothesizing that ACGs from M. paniculata inhibit progression of ALI, we used the experimental model of lipopolysaccharide (LPS)-induced ALI in BALB/c mice to evaluate the therapeutic potential of purified ACGs. Our results showed that M. paniculata ACGs inhibited lung inflammation in animals undergoing ALI. The protective effects of ACGs were assessed by determination of cytokine levels and in situ analysis of lung inflammation. ACGs reduced the pulmonary edema and microvascular permeability, demonstrating a dose-dependent down-regulation of LPS-induced TNF-α, IL-6 and IL-1β expression in lung tissue and bronchoalveolar lavage fluid, along with reduced apoptosis. Moreover, metabolic profiling of mice serum and subsequent Ingenuity Pathway Analysis suggested that ACGs activated protective protein networks and pathways involving inflammatory regulators and apoptosis-related factors, such as JNK, ERK1/2 and caspase-3/7, suggesting that ACGs-dependent effects were related to MAPKs and mitochondrial apoptosis pathways. These results were further supported by evaluation of protein expression, showing that ACGs blocked LPS-activated phosphorylation of p38, ERK1/2 and JNK on the MAPKs signaling, and significantly upregulated the expression of Bcl-2 whilst down-regulated Bax and cleaved caspase-3. Remarkably, ACGs inhibited the LPS-dependent TLR4 and TRPC6 upregulation observed during ALI. Our study shows for the first time that ACGs inhibit acute inflammation and apoptosis by suppressing activation of TLR4/TRPC6 signaling pathway in a murine model of ALI. Our findings provide new evidence for better understanding the anti-inflammatory effects of ACGs. In this regard, ACGs could be exploited in the development of novel therapeutics for ALI and ARDS

The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability

人类与其他动物相比的重要区别在于人类拥有高等认知能力，这种能力集中体现在学习记忆和语言表达方面。厦门大学医学院神经科学研究所王鑫教授团队发现人科动物特异性基因USP6作为一个新的NMDA受体调控因子，可通过去泛素化途径调节NMDA型谷氨酸受体的降解和稳定性，进而调控突触可塑性和学习记忆能力。 本研究工作由王鑫教授指导完成，博士生曾凡伟、马学海与硕士生朱琳为共同第一作者，王鑫教授为通讯作者。Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report that USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulates N-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP6 enhances NMDAR stability to promote synaptic function and cognition.This work was partially supported by the National Natural Science Foundation of China (31871077, 81822014, 81571176 to XW; 81701349 to Hongfeng Z.; 81701130 to QZ; and 81471160 to HS), the National Key R&D Program of China (2016YFC1305900 to XW and HS), the Natural Science Foundation of Fujian Province of China (2017J06021 to XW), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to XW and 20720180040 to ZS), Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University (SKLCSB2019KF012 to QZ), and China Postdoctoral Science Foundation (2017M612130 to QZ).该研究得到了国家自然科学基金面上项目和优秀青年基金项目的支持

Sulfuric acid dissolution of 4A and Na-Y synthetic zeolites and effects on Na-Y surface and particle properties

Sodium rich synthetic zeolites 4A and Na-Y have different silicon-to-aluminium (Si/Al) ratios and are widely used as molecular sieves, catalysts and adsorbents. This study investigates the changes in 4A and Na-Y synthetic zeolites treated by H2SO4 at room temperature. Both zeolite types are examined before and after treatment by following the dissolution and re-crystallisation processes, and Na-Y by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and particle size analysis. Na-Y zeolite (high Si/Al ratio) has stronger acid-resistivity than 4A zeolite (low Si/Al ratio) and can be treated with H2SO4 up to 5 M without complete dissolution, whereas 4A zeolite is completely dissolved by 0.5 M acid. For both zeolites, the treatment generates dissolution (of both Si and Al) of first order fast kinetics, followed by re crystallization. XRD studies of Na-Y zeolite indicate that acid treatment leads to structural changes where cations are removed and as dissolution progresses de-alumination takes place, thereby altering the main tetrahedral structure. XPS analysis shows the Si/Al atomic ratio for Na-Y zeolite increases from 2.94 at 0 M to 8.18 at 0.1 M, and a significant binding energy (BE) shift of Si and 0 occurs even at a high Si/Al ratio. The acid treatment increases the surface intermediate electronegativity of Na-Y zeolite, and the BE of each main structural element changes in the same way as the electronegativity ratio (element electronegativity to total surface electronegativity) as the acid concentration increases. Particle size analysis indicates that a recrystallization process occurs during acid treatment, as shown by a shift of the coarse particle distribution peak size to progressively smaller sizes with increasing acid concentration. (C) 2016 Elsevier B.V. All rights reserved

Preparation of TiO₂/SnO₂ Electron Transport Layer for Performance Enhancement of All-Inorganic Perovskite Solar Cells Using Electron Beam Evaporation at Low Temperature

SnO2 has attracted much attention due to its low-temperature synthesis (ca. 140 °C), high electron mobility, and low-cost manufacturing. However, lattice mismatch and oxygen vacancies at the SnO2/CsPbI3−xBrx interface generally lead to undesirable nonradiative recombination in optoelectronic devices. The traditional TiO2 used as the electron transport layer (ETL) for all-inorganic perovskite solar cells (PSCs) requires high-temperature sintering and crystallization, which are not suitable for the promising flexible PSCs and tandem solar cells, raising concerns about surface defects and device uniformity. To address these challenges, we present a bilayer ETL consisting of a SnO2 layer using electron beam evaporation and a TiO2 layer through the hydrothermal method, resulting in an enhanced performance of the perovskite solar cell. The bilayer device exhibits an improved power conversion efficiency of 11.48% compared to the single-layer device (8.09%). The average fill factor of the bilayer electron transport layer is approximately 15% higher compared to the single-layer electron transport layer. Through a systematic investigation of the use of ETL for CsPb3−xBrx PSCs on optical and electronic properties, we demonstrate that the SnO2/TiO2 is an efficient bilayer ETL for PSCs as it significantly enhances the charge extraction capability, suppresses carrier recombination at the ETL/perovskite interface, facilitates efficient photogenerated carrier separation and transport, and provides high current density and reduced hysteresis

A Pyridine Diketopyrrolopyrrole-Grafted Graphene Oxide Nanocomposite for the Sensitive Detection of Chloramphenicol by a Direct Electrochemical Method

A novel direct electrochemical sensor, based on a pyridine diketopyrrolopyrrole/graphene oxide nanocomposite-modified glass carbon electrode (PDPP/GO/GCE), was developed herein for chloramphenicol (CAP) detection. In this research, PDPP was grafted onto GO by C-N bonds and π-π conjugation, which were synergistically confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The morphology study shows that PDPP was uniformly dispersed on the GO in the form of particles. The constructed PDPP/GO/GCE showed the strongest response signal to CAP in the evaluation of electrocatalytic activity by cyclic voltammetry compared to that of GO-modified and unmodified GCE, revealing that the introduction of PDPP can effectively improve the electrocatalytic activity of sensors. Moreover, PDPP/GO/GCE had a noticeable current signal when the concentration of CAP was as low as 0.001 uM and had a wide line range (0.01–780 uM) with a low limit of detection (1.64 nM). The sensor properties of the as-obtained PDPP/GO/GCE involved anti-interference, reproducibility, and stability, which were also evaluated and revealed satisfactory results

CUT&tag-seq analysis of heat stress response in broiler liver provides novel insights into the improved thermotolerance by dietary phloretin

This work aimed to study the effect of phloretin on antioxidant profiles through nuclear factor erythroid 2–related 2 (Nrf2)-DNA interactions in the liver of heat-stressed broilers by Cleavage Under Targets and Tagmentation combined with high-throughput sequencing (CUT&Tag-seq). One hundred and sixty 22-day-old Arbor Acres broilers were divided into four groups: a normal temperature group (NT: 22.8–23.4 °C and 46–55.8 % humidity) was fed a basal diet and three high temperature groups (China Summer condition: 29.7–31.7 °C and 77.9–94.8 % humidity) were fed the basal diet supplemented with 0 (HT group), 100 mg/kg (LT group) and 200 mg/kg (PT group) phloretin. Liver samples were taken from 42-day-old broilers. High temperature condition increased (P ≤ 0.05) the malondialdehyde (MDA) level, but decreased (P ≤ 0.05) the activities and mRNA expression levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and Nrf2. Dietary 200 mg/kg phloretin decreased (P ≤ 0.05) the MDA level, but increased (P ≤ 0.05) the activities and mRNA expression levels of GSH-Px, SOD, CAT and Nrf2 in the liver of heat-stressed broilers. CUT&Tag-seq showed that 4042 DEPs were up-regulated, while 2322 DEPs were down-regulated in the PT group compared with the HT group. The Nrf2-binding gene of DEPs contained SOD3, CAT, SOD2, and p38 mitogen-activated protein kinase. Most TOP20 significant KEGG pathways were associated with “Environmental Information Processing”. Summary, phloretin could improve oxidative damage by Nrf2 and its downstream DNA-sites including genes and Nrf2-bingding non-coding RNAs in the liver of heat-stressed broilers

Effect of Glutamine on the Growth Performance, Oxidative Stress, and Nrf2/p38 MAPK Expression in the Livers of Heat-Stressed Broilers

The purpose of this work was to study the effects of glutamine (Gln) on the growth performance, oxidative stress, Nrf2, and p38 MAPK pathway in the livers of heat-stressed broilers. In total, 300 broilers were divided into five groups, including a normal temperature (NT, without dietary Gln) group and four cyclic high temperature groups (HT, GHT1, GHT2, and GHT3) fed with 0%, 0.5%, 1.0%, and 1.5% Gln, respectively. High temperature conditions increased (p p p p p p < 0.05) in the GHT3 group than that in the HT group. In summary, Gln improved oxidative damage through the activation of Nrf2 and p38 MAPK expression in the livers of heat-stressed broilers