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Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.

The B6Ca2 and B8Ca2 clusters adopt interesting inverse sandwich architectures, featuring a prolate B6 (or perfect B8) ring jammed with two capping Ca atoms. Both clusters show the high thermodynamic stability due to the double (σ and π) electronic delocalization. In present paper, we computationally studied the hydrogen storage of them. The results suggest that each Ca site in B6Ca2 and B8Ca2 clusters could store up six H2, yielding a gravimetric density of 14.2 wt% for B6Ca2 and 12.6 wt% for B8Ca2. The average adsorption energy for H2-adsorbed B6Ca2 and B8Ca2 complexes is within the scope of 0.12–0.15 eV per H2 at wB97XD level, hinting that two clusters could reversibly store and release hydrogen, which is positively confirmed by the Born-Oppenheimer molecular dynamics simulations. Both B6Ca2 and B8Ca2 nanoclusters are feasible hydrogen storage media under the ambient condition.

Hierarchical organic-inorganic nanocomposites derived from polyethersulfone (PES) nanofibrous membranes with a post-modification of dopamine (DA) and polyethylenimine (PEI), comprising a high content (33 wt%) of MgO nanoparticles of smaller dimensions (12.7 ± 3.0 nm), were successively fabricated using electrospinning and DA/PEI self-polymerization methods. The obtained hybrid membranes have a rapid capture and great destructive capacity towards paraoxon-ethyl toxin degradation with a relatively short interaction time (up to 92% within 40 min) for effective environmental remediation.

Linear detection algorithms require a series of sequential and complex process that needs high-performance processors to reduce computing time when the software is implemented. In this paper, we design a linear detection hardware accelerator with parallel computing capability through our proposed pipelined multiprocessor system-on-a-chip (SoC) design methodology; it contains an upper pipelined controller that controls the operation of the underlying Canny edge detection module and the Hough transform module. That is, we first use the edge detection module to get the edge information, and then use Hough transform to improve the accuracy of linear detection results. Finally, the pipeline control is adopted to enhance the effectiveness of the module. Based on the Canny process and the Gaussian blurring method, this study can reduce the false detection caused by noise, and decrease the number of operations and resource usage without affecting the straight line detection. Compared with Xu and Chen [14] [21] [34] [35], the proposed method can reduce 84% and 74% of the circuit resources, respectively. The hardware function circuit generated from our methodology has a good decentralized architecture and scalability, and it is easier to use in all kinds of embedded systems.

Skin photoaging (SP) is a premature skin-aging damage after repeated exposure to ultraviolet (UV) radiation, mainly characterized by oxidative stress and inflammatory disequilibrium, which makes skin show the typical symptoms of photoaging such as coarse wrinkling, dryness, irregular pigmentation and laxity. Chitosan oligosaccharide (COS), a natural polysaccharide with good humectant property, is the depolymerized product of chitosan with various biological activities, among which the antioxidant and anti-inflammatory effects have been frequently reported in recent years. However, no existing invivo study indicates whether COS has direct protective effect on UV-induced SP. In the current research, we investigated the potential preventive effect of COS against UV-caused damage in hairless mouse dorsal skin. The data showed that COS, by topical application after each UV-radiation for 10weeks, effectively inhibited the undesirable changes on the skin induced by UV. To be specific, COS obviously alleviated the macroscopic and histopathological damages of mice skin, via mitigating the disrupted collagenous fibers, as well as improving the relative content of type I collagen and the amount of total collagen. Furthermore, COS effectively inhibited the levels of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, and markedly improved the activities of antioxidant enzymes (SOD, GSH-Px, CAT), as well as the content of skin hydroxyproline and moisture. These findings demonstrated that this natural polysaccharide attenuated UV-induced SP, at least in part, by virtue of favorable regulation of antioxidant and anti-inflammatory status, which presumably worked in concert to maintain the morphology and level of dermal collagen.

Steroid-induced osteonecrosis of the femoral head (SONFH) is difficult to be diagnosed at the early stages when it can be administrated effectively. Yet, to date no study has been performed to identify diagnostic biomarkers and to develop diagnostic models for SONFH. In the current study, a total of 60 SONFH patients with Association Research Circulation Osseous (ARCO) stages I-IV, and 20 controls were enrolled and divided into the discovery and validation cohorts. The serum samples were collected and the gene expression profiles were detected by microarray analysis based on the discovery cohort. Then, eight genes (BIRC3, CBL, CCR5, LYN, PAK1, PTEN, RAF1 and TLR4) were identified as the candidate serum biomarkers of SONFH due to the significant differential expression patterns and the topological importance in the interaction network of SONFH-related differentially expressed genes. Functionally, these candidate serum biomarkers were significantly involved into several pathological processes during SONFH progression, such as the immune regulation and inflammation, bone metabolism and angiogenesis. After that, a prediction model for the early diagnosis of SONFH was constructed using Partial least squares regression based on the serum levels of the candidate biomarkers. Notably, both the 10-fold cross-validation and the independent dataset test demonstrated the good performance of this model. In conclusion, our study identified eight promising serum biomarkers and developed the circulating gene-based prediction model as a new, efficient and non-invasive diagnostic tool for the early detection of SONFH, as well as benefit the administration of SONFH in a daily clinical setting. Funding Statement: This study is funded by National Natural Science Foundation of China (No 81373656 & 81473695). Declaration of Interests: The authors declare that there is no conflict of interests regarding the publication of this paper. Ethics Approval Statement: The study was approved by the Research Ethics Committee of Institute of Chinese Materia Medica, Wangjing Hospital, China (SFDA approval number: 81473695). The informed consent was obtained from all patients.

Over 90% of autoimmune diseases risk variants are located in the noncoding region, leading to great challenge in deciphering the underlying causal functional variants/genes and biological mechanisms. Here we devised an integrative analysis strategy named fGWASAD for identifying not only noncoding functional variants but also gene targets, and underlying biological mechanisms as well as functional roles and clinical implications of gene targets on 20 autoimmune diseases. We demonstrated the credibility of our approach, and further decoded immunologically functional clues for 72.2% of target genes and regulatory mechanisms underlying 71.2% of functional variants. By leveraging pleiotropic effect among target genes, we predicted many candidate drug target genes and new indications for known drugs on several autoimmune diseases. We also suggested the crucial regulatory roles of super enhancers on autoimmune diseases network involving several key master TFs. Together, our analysis provided valuable comprehensive resource for autoimmune diseases, which are freely available online.

Offline network traffic analysis is very important for an in-depth study upon the understanding of network conditions and characteristics, such as user behavior and abnormal traffic. With the rapid growth of the amount of information on the Internet, the traditional stand-alone analysis tools face great challenges in storage capacity and computing efficiency, but which is the advantages for Hadoop cluster. In this paper, we designed an offline traffic analysis system based on Hadoop (OTASH), and proposed a MapReduce-based algorithm for TopN user statistics. In addition, we studied the computing performance and failure tolerance in OTASH. From the experiments we drew the conclusion that OTASH is suitable for handling large amounts of flow data, and are competent to calculate in the case of single node failure.

The aim to raise customer loyalty in telecom market requires an emphasis on one-to-one marketing and personalized services. To this end, it is essential to understand individual customer preferences for services. In this paper an improved fast hierarchical clustering algorithm (IFHCA) is proposed firstly. Then a method for identifying dial-up user preferences based on IFHCA is presented, in order to discover the pattern of users' preferences and recommend the most appropriate services. Finally, this paper analyses the relationship between users' preferences with on-line duration and traffic. Experiment result shows that IFHCA is of advantages such as analyzing on preference patterns of asymmetric digital subscriber line (ADSL) users accurately, lower time complexity than the classical hierarchical clustering algorithm (CHCA) to mining large dataset efficiently. Besides, the result is provided for selective management and commercial package customization.

The supramolecular self-assembly formed by newly synthesized mono-6-(4-cyano-phenyl)-β-cyclodextrin through the molecular interpenetration has been investigated and compared in both solution and the solid state, which was characterized by X-ray crystallography, fourier transform infrared spectroscopy, NMR spectroscopy and atomic force microscopy. The crystal structure clearly revealed that the benzonitrile group is consecutively inserted into the adjacent cyclodextrin cavity from the second side, thus giving rise to an unusual interlocked helical supramolecular self-assembly in which the benzonitrile group acts as bridge between the cyclodextrin units. As compared with crystal, the conformation in aqueous solution indicates that the benzonitrile group prefer to be self-assembled included into another cavity from the second side of cyclodextrin to form the self-assembly.

This paper studied the effects of different carbon and nitrogen sources on the removal of iron impurities from kaolin using dissimilatory Fe(III)-reducing bacteria (DIRB). Iron impurities in the kaolin were removed using glucose, sucrose, food-sugar, maltose and soluble starch as different carbon sources with removal efficiencies in the order: monosaccharide > disaccharide > polysaccharide. More than 50% of the iron impurities were removed from kaolin with an increase of whiteness index from 61% to 82% at 5% (mass/mass) of food-sugar, indicating that food-sugar could alternatively be used as a bulk carbon source to reduce the operational cost of bioleaching. Addition of (NH4)2SO4 to the bioleaching medium accelerated the bioleaching rate. The samples before and after bioleaching were examined by X-ray diffraction (XRD), X-ray fluorescence analysis (XRF) and scanning electron microscope (SEM). Iron was selectively leached from the kaolin without formation of a secondary mineral phase, structural changes were not observed but the crystallinity was improved.

Our hospital (Shanghai Skin Diseases & STD Hospital) started to study 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in 1996. So far, we have treated 76 cases of skin cancer and pre-cancer using topical ALA-PDT. They included squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), mammary and extramammary Paget disease, actinic keratosis (AK) and erythroplasia of Queyrat. In this overview article, we would like to present several representative cases and discuss our experience.

The weak inclusion complex of cyclomaltoheptaose (beta-cyclodextrin, betaCD) with p-nitrobenzoic acid was investigated in the solid state. Crystallography shows that two betaCD molecules co-crystallize with two p-nitrobenzoic acids and 28.5 water molecules [2(C(42)H(70)O(35))x2(C(7)H(5)NO(4))x28.5H(2)O] in the triclinic system.

Enterovirus 71 (EV71) has led to recent outbreaks of hand, foot and mouth disease (HFMD) in China, resulting in high mortality. In this study, several monoclonal antibodies were generated by immunizing mice with two synthetic peptides, SP55 and SP70, containing amino acids 163-177 and 208-222 of VP1. The specificities of the anti-EV71 peptide monoclonal antibodies were confirmed by Western blot analysis and immunocytochemistry against EV71 virus. Most importantly, we have identified a monoclonal antibody, clone 22A12, which shows strong neutralizing activity against EV71 in an in vitro neutralization assay. Because there is no vaccine available and treatment is very limited, mouse anti-EV71 monoclonal antibody, clone 22A12, could be a promising candidate to be humanized and used for treatment of EV71 infection.

As 1.398 neutral proteinase (from B. subtilis As 1.398) was immobilized on the loose chitosan-precipitate by simultaneous adsorption and covalent bonding. The optimum activity of the chitosan-immobilized proteinase to soybean protein is at pH 8.O. The profiles of proteolytic activity with regard to temperature, as with soybean protein as substrate, show two peaks at 40 and 60 °C, respectively. The proteolytic activity toward soybean protein at 60 °C is significantly higher than that at 40 °C. The maximum extent of hydrolysis of soybean protein by the immobilized proteinase is about 23% which is substantially lower than that of casein. Heating increases the susceptibility of soybean protein to the immobilized proteinase, but not the maximum extent of hydrolysis. In addition, the composition of free amino acids in hydrolyzed soybean protein was analyzed.