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Context: Qi‐dan‐dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. Objective: This study reveals the mechanism by which QDD ameliorates DKD. Materials and Methods: The compounds in QDD were identified by high‐performance liquid chromatography and quadrupole‐time‐of‐flight tandem mass spectrometry (HPLC‐Q‐TOF‐MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD‐low (QDD‐L), and 2% QDD‐high (QDD‐H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose‐treated HK‐2 and NRK‐52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. Results: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mitogen‐activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial‐mesenchymal transition (EMT) via the p38MAPK and AKT‐mammalian target of rapamycin (mTOR) pathways. Discussion and Conclusion: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Ilex pubescens Hook et Arn mainly contains triterpenoids that possess antithrombotic, anti‐inflammatory and analgesic effects. Quantitative and qualitative analyses of the triterpenoids in I. pubescens can be useful for determining the authenticity and quality of raw materials and guiding its clinical preparation. Objectives: To establish a method for rapid and comprehensive analysis of triterpenoids in I. pubescens using ultra‐high‐performance liquid chromatography coupled to electrospray ionisation and quadrupole time‐of‐flight‐mass spectrometry (UPLC‐ESI‐QTOF‐MS), which will also be applied to evaluate the contents of nine triterpenoids among root, root heartwood and root bark of I. pubescens to judge the value of the root bark to avoid wastage. Methods: UPLC‐ESI‐QTOF‐MS data from the extracts of I. pubescens in negative mode were analysed using Peakview and Masterview software that provided molecular weight, mass errors, isotope pattern fit and MS/MS fragments for the identification of triterpenoids. The quantification of nine investigated compounds of I. pubescens was accomplished using MultiQuant software. Results: A total of 33 triterpenoids, five phenolic acids, two lignans and a flavonol were characterised in only 14 min. The total content of the nine compounds in the root bark was generally slightly higher than that of the root and root heartwood, which has not been reported before. Conclusion: The developed UPLC‐ESI‐QTOF‐MS method was proven to be rapid and comprehensive for simultaneous qualitative and quantitative analyses of the characteristic triterpenoids in I. pubescens. The results may provide a basis for holistic quality control and metabolic studies of I. pubescens, as well as serve as a reference for the analysis of other Ilex plants. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study aimed to identify fungal species associated with trunk diseases of sweet cherries (Prunus avium) in several commercial cherry orchards in Beijing, Guizhou and Shandong provinces, China. In total, eighteen fungal strains that fitted well into the species concept of Diaporthe were isolated. Based on both morphological and multi-locus phylogenetic analyses of internal transcribed spacer region (ITS), beta-tubulin (tub-2), calmodulin (Cal) and translation elongation factor 1-α (tef1–α) sequencing data, fourteen isolates were identified as Diaporthe eres, while four isolates were classified as D. hongkongensis. Here, we report D. hongkongensis causing sweet cherry branch dieback disease and, further, we confirmed the host association of D. eres with sweet cherries in China. A pathogenicity assay revealed the ability of both D. eres and D. hongkongensis to cause shoot necrosis and stem lesions on Prunus avium cv. 'Brooks' (mean lesion lengths of 1.86 cm and 1.56 cm, respectively). The optimal temperature for the growth of both Diaporthe species was tested. The optimal growth temperature for D. hongkongensis was 30 °C, and the 25–28 °C temperatures were the most favorable for the growth of D. eres strains. This research advances the understanding of fungal trunk diseases in fruit crops, particularly gummosis and branch dieback disease in Chinese cherry orchards, and will aid growers in making decisions about cultural practices and disease management. [ABSTRACT FROM AUTHOR]

Ultra-high temperature ceramic coatings have ultra-high melting points, excellent mechanical properties and high temperature ablation resistance. These unique performance combinations turn it into a promising material for use in extreme environment structures in rockets and hypersonic vehicles, particularly nozzles, leading edges and engine components. In this paper, various preparation methods of ultra-high temperature ceramic coatings were reviewed, including plasma spraying, chemical vapor deposition, pack cementation, slurry sintering, hot pressing and their research progress. Meanwhile, some new preparation methods of high temperature coatings, such as ion beam deposition, ultrasonic spraying, metal organic frame work coating, and magnetron sputtering, were introduced. The development trend of ultra-high temperature coatings was prospected as well. [ABSTRACT FROM AUTHOR]

Background: Resting-state function MRI (rs-fMRI) research on successful aging can provide insight into the mechanism of aging with a different perspective from aging-related disease. Objective: rs-fMRI research was used to analyze the brain function characteristics of successful aging. Methods: A total of 47 usual aging individuals and 26 successful aging (SA) individuals underwent rs-fMRI scans and neuropsychological tests. Volume-based rs-fMRI data analysis was performed with DPASF to obtain ALFF, ReHo, DC, and VMHC. Results: The SA group showed increased ALFF in right opercular part of inferior frontal gyrus (Frontal_Inf_Oper_R) and right supramarginal gyrus; increased ReHo in right middle temporal pole gyrus and decreased ReHo in left superior frontal gyrus and middle occipital gyrus; increased DC in right medial orbitofrontal gyrus and pulvinar part of thalamus; decreased DC in left fusiform gyrus and right medial frontal gyrus; increased VMHC in right medial orbitofrontal gyrus; and decreased VMHC in the right superior temporal gyrus, right and left middle temporal gyrus, right and left triangular part of inferior frontal gyrus. ALFF in Frontal_Inf_Oper_R were found to be significantly correlated with MMSE scores (r = 0.301, p = 0.014) and ages (r = –0.264, p = 0.032) in all subjects, which could be used to distinguish the SA (AUC = 0.733, 95% CI: 0.604–0.863) by ROC analysis. Conclusion: The brain regions with altered fMRI characteristics in SA group were concentrated in frontal (6 brain regions) and temporal (4 brain regions) lobes. ALFF in Frontal_Inf_Oper_R was significantly correlated to cognitive function and ages, which might be used to distinguish the SA. [ABSTRACT FROM AUTHOR]

Background: For community-dwelling elderly individuals without enough clinical data, it is important to develop a method to predict their dementia risk and identify risk factors for the formulation of reasonable public health policies to prevent dementia.Objective: A community elderly survey data was used to establish machine learning prediction models for dementia and analyze the risk factors.Methods: In a cluster-sample community survey of 9,387 elderly people in 5 subdistricts of Wuxi City, data on sociodemographics and neuropsychological self-rating scales for depression, anxiety, and cognition evaluation were collected. Machine learning models were developed to predict their dementia risk and identify risk factors.Results: The random forest model (AUC = 0.686) had slightly better dementia prediction performance than logistic regression model (AUC = 0.677) and neural network model (AUC = 0.664). The sociodemographic data and psychological evaluation revealed that depression (OR = 3.933, 95% CI = 2.995-5.166); anxiety (OR = 2.352, 95% CI = 1.577-3.509); multiple physical diseases (OR = 2.486, 95% CI = 1.882-3.284 for three or above); "disability, poverty or no family member" (OR = 1.859, 95% CI = 1.337-2.585) and "empty nester" (OR = 1.339, 95% CI = 1.125-1.595) in special family status; "no spouse now" (OR = 1.567, 95% CI = 1.118-2.197); age older than 80 years (OR = 1.645, 95% CI = 1.335-2.026); and female (OR = 1.214, 95% CI = 1.048-1.405) were risk factors for suspected dementia, while a higher education level (OR = 0.365, 95% CI = 0.245-0.546 for college or above) was a protective factor.Conclusion: The machine learning models using sociodemographic and psychological evaluation data from community surveys can be used as references for the prevention and control of dementia in large-scale community populations and the formulation of public health policies. [ABSTRACT FROM AUTHOR]

The development of landslide hazards is spatially scattered, temporally random, and poorly characterized. Given the advantages of the large spatial scale and high sensitivity of InSAR observations, InSAR is becoming one of the main techniques for active landslide identification. The difficult problem is how to quickly extract landslide information from extensive InSAR image data. Since the instance segmentation model (Mask R-CNN) in deep learning can provide highly robust target recognition, we select the landslide-prone eastern edge of the Tibetan Plateau as a specific test area. Introducing and optimizing this model achieves high-speed and accurate recognition of InSAR observations. First, the InSAR patch landslide instance segmentation dataset (SLD) is established by developing a common object in context (COCO) annotation format conversion code based on InSAR observations. The Mask R-CNN+++ is found by adding three functions of the ResNext module to increase the fineness of the network segmentation results and enhance the noise resistance of the model, the DCB (deformable convolutional block) to improve the feature extraction ability of the network for geometric morphological changes of landslide patches, and an attention mechanism to selectively enhance usefully and suppress features less valuable to the native Mask R-CNN network. The model achieves 92.94% accuracy on the test set, and the active landslide recognition speed based on this model under ordinary computer hardware conditions is 72.3 km2/s. The overall characteristics of the results of this study show that the optimized model effectively enhances the perceptibility of image morphological changes, thereby resulting in smoother recognition boundaries and further improvement of the generalization ability of segmentation detection. This result is expected to serve to identify and monitor active landslides in complex surface conditions on a large spatial scale. Moreover, active landslides of different geometric features, motion patterns, and intensities are expected to be further segmented. [ABSTRACT FROM AUTHOR]

Lasiodiplodia theobromae is a causal agent of grapevine trunk disease, and it poses a significant threat to the grape industry worldwide. Fungal effectors play an essential role in the interaction between plants and pathogens. However, few studies have been conducted to understand the functions of individual effectors in L. theobromae. In this study, we identified and characterized a candidate secreted effector protein, LtCSEP1, in L. theobromae. Gene expression analysis suggested that transcription of LtCSEP1 in L. theobromae was induced at the early infection stages in the grapevine. Yeast secretion assay revealed that LtCSEP1 contains a functional signal peptide. Transient expression of LtCSEP1 in Nicotiana benthamiana suppresses BAX-trigged cell death and significantly inhibits the flg22-induced PTI-associated gene expression. Furthermore, the ectopic expression of LtCSEP1 in N. benthamiana enhanced disease susceptibility to L. theobromae by downregulating the defense-related genes. These results demonstrated that LtCSEP1 is a potential effector of L. theobromae, which contributes to suppressing the plant's defenses. [ABSTRACT FROM AUTHOR]

Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing, SYQ) has traditionally been used to treat inflammation, high fever and improve immune function of patients. Polysaccharides have been proved to be one of the important components of SYQ. Previous studies have confirmed the antipyretic and antitumor effects of polysaccharides from SYQ (SYQP), and clarified that SYQP could enhance immunity through TLR4 signalling pathway. However, there were more possibilities for the mechanism by which SYQP exerted immunomodulatory effects and the role of SYQP in acute respiratory distress syndrome (ARDS) is elusive. The purpose of this study was further to explain the bidirectional modulation of immunity mechanism of SYQP in vitro and its effect in LPS-induced ARDS in vivo. Experimental results showed that SYQP significantly stimulated gene expressions of TLR1, TLR2 and TLR6 and secretion of cytokines in RAW264.7 cells. Individual or combined application of TLR2 antagonist C29 and TLR4 antagonist TAK-242 could reduce SYQP-mediated stimulation of cytokine secretion in RAW264.7 cells and mouse peritoneal macrophages (MPMs) to varying degrees. On the other hand, SYQP markedly inhibited the expression levels of inflammatory cytokines, NO, iNOS and COX-2 in LPS-treatment RAW264.7 cells. Moreover, in vivo results indicated that SYQP significantly reduced LPS-induced damage in ARDS mice through alleviating LPS-induced pulmonary morphological damage, inhibiting myeloperoxidase (MPO) expression levels, ameliorating the inflammatory cells in bronchoalveolar lavage fluid (BALF) and improving hematological status. Meanwhile, SYQP evidently reduced IL-6, TNF-α and IFN-γ secretion, the overexpression levels of TLR2 and TLR4, as well as the phosphorylation of NF-κB p65. In addition, SYQP reduced the phosphorylation of JAK2 and STAT1 and the overexpression of NLRP3, caspase-1, caspase-3 and caspase-8 in lung tissues of ARDS mice. In summary, our study confirmed that SYQP induced bidirectional immunity and ameliorated LPS-induced acute respiratory distress syndrome in mice through TLR2/TLR4-NF-κB, NLRP3/caspase and JAK/STAT signaling pathways, which provided a theoretical basis for further use of SYQP. [ABSTRACT FROM AUTHOR]

Flavivirus infection of cells induces massive rearrangements of the endoplasmic reticulum (ER) membrane to form viral replication organelles (ROs) which segregates viral RNA replication intermediates from the cytoplasmic RNA sensors. Among other viral nonstructural (NS) proteins, available evidence suggests for a prominent role of NS4B, an ER membrane protein with multiple transmembrane domains, in the formation of ROs and the evasion of the innate immune response. We previously reported a benzodiazepine compound, BDAA, which specifically inhibited yellow fever virus (YFV) replication in cultured cells and in vivo in hamsters, with resistant mutation mapped to P219 of NS4B protein. In the following mechanistic studies, we found that BDAA specifically enhances YFV induced inflammatory cytokine response in association with the induction of dramatic structural alteration of ROs and exposure of double-stranded RNA (dsRNA) in virus-infected cells. Interestingly, the BDAA-enhanced cytokine response in YFV-infected cells is attenuated in RIG-I or MAD5 knockout cells and completely abolished in MAVS knockout cells. However, BDAA inhibited YFV replication at a similar extent in the parent cells and cells deficient of RIG-I, MDA5 or MAVS. These results thus provided multiple lines of biological evidence to support a model that BDAA interaction with NS4B may impair the integrity of YFV ROs, which not only inhibits viral RNA replication, but also promotes the release of viral RNA from ROs, which consequentially activates RIG-I and MDA5. Although the innate immune enhancement activity of BDAA is not required for its antiviral activity in cultured cells, its dual antiviral mechanism is unique among all the reported antiviral agents thus far and warrants further investigation in animal models in future. Author summary: Emergence and re-emergence of yellow fever (YF) caused by the yellow fever virus (YFV) infection have posed a global public health threat in previously non-epidemic as well as endemic regions. The approximately 30% of mortality rate makes the outbreaks particularly devastating. In addition to the vaccination campaign and mosquito controls, antiviral drugs are important components in the toolbox for combating YF outbreaks. However, only two nucleotide analogue drugs developed for the treatment of other RNA virus infections are currently repurposed for the treatment of YF with uncertain clinical efficacy. BDAA is a benzodiazepine compound discovered as a potent YFV-specific antiviral agent in our laboratory. The work reported herein further demonstrates that BDAA interaction with the YFV NS4B protein may impair the integrity of viral RNA replication organelles, which not only inhibits viral RNA replication, but also results in the leakage of viral RNA into the cytoplasm to activate RIG-I-like RNA receptors and enhances the innate antiviral immune response. The unprecedented antiviral mechanism of BDAA highlights the essential role of the NS4B protein in viral RNA replication and the evasion of host cellular innate immunity. [ABSTRACT FROM AUTHOR]

HK853 is a transmembrane protein from Thermotoga maritime, which belongs to HK853/RR468 two-component signal transduction system (TCS) and acts as a sensor histidine kinase. HK853 is mainly composed of a transmembrane domain, dimerization and histidine-containing phosphotransfer domain (HK853DHp), catalytic and ATP-binding domain (HK853CA) and several linkers. HK853 can be completely autophosphorylated, which is the first step for signal transduction of TCS. HK853CA is an essential domain for its kinase function, since HK853CA could bind with ATP and convert it to ADP. Here, we report the backbone and part of side chain assignments of HK853CA. By analyzing the chemical shifts of HN, N, CO, Cα and Cβ, the secondary structure was predicted and contrasted with the published crystal structure of HK853CA. The result showed that our predicted structure could basically fit into the crystal structure. Thus, the chemical shift assignments of HK853CA are the starting point for further structural and dynamics study. [ABSTRACT FROM AUTHOR]