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

A Novel Remaining Useful Life Prediction Method for Hydrogen Fuel Cells Based on the Gated Recurrent Unit Neural Network

The remaining useful life (RUL) prediction for hydrogen fuel cells is an important part of its prognostics and health management (PHM). Artificial neural networks (ANNs) are proven to be very effective in RUL prediction, as they do not need to understand the failure mechanisms behind hydrogen fuel cells. A novel RUL prediction method for hydrogen fuel cells based on the gated recurrent unit ANN is proposed in this paper. Firstly, the data were preprocessed to remove outliers and noises. Secondly, the performance of different neural networks is compared, including the back propagation neural network (BPNN), the long short-term memory (LSTM) network and the gated recurrent unit (GRU) network. According to our proposed method based on GRU, the root mean square error was 0.0026, the mean absolute percentage error was 0.0038 and the coefficient of determination was 0.9891 for the data from the challenge datasets provided by FCLAB Research Federation, when the prediction starting point was 650 h. Compared with the other RUL prediction methods based on the BPNN and the LSTM, our prediction method is better in both prediction accuracy and convergence rate

The Predictive Value of CD3+/CD8+ Lymphocyte Infiltration and PD-L1 Expression in Colorectal Cancer

Aim: The immune system plays an important role in tumor development and treatment. In this study, we aimed to determine the relationships among the expressions of PD-L1, CD3, CD8, MMR proteins, clinicopathological features, and prognosis of CRC. Methods: Immunohistochemistry was used to determine the expression of PD-L1, CD3, and CD8 in 771 patients with CRC. Results: The expression of PD-L1 in TC was related to the right colon, adenocarcinoma, and dMMR, and in IC, it was related to younger CRC patients and the TNM stage. The expression of CD3 and CD8 in tumor-infiltrating lymphocytes was related to lymph node metastasis and the TNM stage. The expression of PD-L1 in TC and IC was correlated with the infiltration of CD3+ and CD8+ lymphocytes. Univariate survival analysis showed that the expression of PD-L1 in TC, IC, and dMMR was related to a better prognosis. Multivariate survival analysis showed that age, TNM stage, and dMMR were independent prognostic factors for CRC. The OS of the chemotherapy was significantly higher than that of the non-chemotherapy in III-IV TNM stage patients; CRC patients with positive PD-L1 expression in TC or IC and dMMR did not benefit from chemotherapy. Conclusions: PD-L1 expression in TC and IC was closely related to the density of CD3 and CD8 infiltration in tumor-infiltrating lymphocytes. The expression of CD3 and CD8 in tumor-infiltrating lymphocytes and the expression of PD-L1 in IC were linked to the TNM stage of CRC patients. PD-L1 expression in TC and IC and MMR status may act as an important biomarker for guiding the postoperative treatment of III-IV TNM stage CRC patients

A preliminary study on the formation conditions and weathering leaching enrichment mechanism of secondary phosphorite in the Xinhua phosphate mining area, Zhijin, Guizhou

The Xinhua phosphate mining are alocated in Zhijin County, Guizhou Province, is a famous superlarge low-grade phosphate deposit containing rare earth elements in the southwest of China.The average P2O5 grade of the deposit is 17.22%.The proven phosphorite ore resources are 1.348 billion tons, and the rare earth resources are 3 500 kilotons.In recent years, experts and scholars have found that the fluctuation of Xinhua phosphorite ore grade is closely related to weathering, leaching and enrichment effects.To further clarify the influence of weathering and leaching on the element geochemistry as well as the secondary enrichment of phosphate rock, the author focuses on the Gezhongwu ore block and carries out field observations and descriptions of phosphate rock series.A total of 19 chemical analysis samples were collected using block knocking method and 16 rock ore samples were identified through polarizing microscope.On these basis, identification and comprehensive research on the samples were conducted.The results show that the contents of P2O5 in the weathered phosphate rock are 8%-18%, higher than that in the primary phosphate rock, while the contents of MgO are 4%-7%, lower than that in the primary phosphate rock.The weathering intensity of phosphate rock is in the weak to mature stage.The formation of Xinhua weathered phosphate rock in Zhijin County is controlled by lithology, geological structure and hydrological conditions.The purpose of this paper is to provide new information for the further study of the influences of the secondary weathering mineralization of the ore deposit on the chemical composition of phosphate rock, to enrich the metallogenic theories of weathering eluvial phosphate mining in China and to provide the oretical guidance for the rational development and utilization of weathering phosphate resources in the mining area

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

Fault Detection and Diagnosis for Nonlinear and Non-Gaussian Processes Based on Copula Subspace Division

A novel copula subspace division strategy is proposed for fault detection and diagnosis. High-dimensional industrial data are analyzed in two elemental subspaces: margin distribution subspace (MDS) modeled by joint margin distribution, and dependence structure subspace (DSS) modeled by copula. The highest density regions of two submodels are introduced and quantified using probability indices. To improve the robustness of the monitoring index, a hyperrectangular control boundary in MDS is designed, and the equivalent univariate control limits are estimated. Two associated contribution indices are also constructed for fault diagnosis. The interactive relationships among the root-cause variables are investigated via a proposed state chart. The effectiveness and superiority of the proposed approaches (double-subspace and multisubspace) are validated using a numerical example and the Tennessee Eastman chemical process. Better monitoring performance is achieved compared with some conventional approaches such as principal component analysis, independent component analysis, kernel principal component analysis and vine copula-based dependence description. The proposed multisubspace approach fully utilizes univariate-based alarm data with a dependence restriction modulus, which is promising for industrial application

UPLC-QTOF/MS-Based Lipidomic Profiling of Liver Qi-Stagnation and Spleen-Deficiency Syndrome in Patients with Hyperlipidemia

Hyperlipidemia is a common disease caused by abnormal plasma lipid metabolism. Lipidomics is a powerful and efficient technology to study the integration of disease and syndrome of Chinese medicine. This study investigated specific changes in lipid metabolites from hyperlipidemia patients with syndrome of liver qi-stagnation and spleen-deficiency (SLQSD). Lipid profiles in plasma samples from 29 hyperlipidemia patients including 10 SLQSD and 19 non-SLQSD and 26 healthy volunteers (NC) were tested by UPLC-QTOF/MS. PLS-DA analysis and database searching were performed to discover differentiating metabolites. Differences in lipid metabolites between hyperlipidemia and healthy people mainly include phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, and ceramides. Hyperlipidemia patients with SLQSD and non-SLQSD could be differentiated by using identified lipid metabolites including phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, triglycerides, diacylglycerols, lysophosphatidylethanolamines, sphingomyelins, lysophosphatidylcholines, and lactosylceramides. There were significant differences of lipid metabolism between between different syndromes of the same disease such as hyperlipidemia which showed significant differences between SLQSD and non-SLQSD