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Sleep disorder (SD) has a high incidence and seriously affects quality of life, mental health and even the manifestation of physical diseases. The combination of Pinellia ternata (Chinese name: banxia) and Prunella vulgaris (Chinese name: xiakucao), known as the Banxia–Xiakucao Chinese herb pair (BXHP), is a proven Chinese herbal medicine that has been used to treat SD for thousands of years due to its significant clinical effects. However, its active pharmacological components and sedative–hypnotic mechanisms have not been fully elucidated. Thus, the present study used a systematic pharmacological approach to develop pharmacokinetic screens and target predictions via construction of a protein–protein interaction network and annotation database for SD-related and putative BXHP-related targets. Visualization, screening and integrated discovery enrichment analyses were conducted. The BXHP chemical database contains 166 compounds between the two herbal ingredients, and of these, 22 potential active molecules were screened by pharmacokinetic evaluation. The targets of 114 of the active molecules were predicted, and 34 were selected for further analysis. Finally, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that BXHP can reduce inflammatory responses. and mediate immune-related and central nervous system neurotransmitters via regulation of multiple targets and pathways. The use of a systematic pharmacology-based approach in the present study further elucidated the mechanisms of action underlying BXHP for the treatment of SD from a holistic perspective and sheds light on the systemic mechanisms of action of Chinese herbal medicines in general.

Utility mining considers high-utility itemsets as useful by combining item quantities and item benefits. Its mining results do not, however, include the quantity information such as large amounts or small amounts. Fuzzy utility mining is thus proposed to fuzzify the results of utility mining and obtain linguistic high-utility itemsets. However, fuzzy utility measurement is not fair to evaluate itemsets because the fuzzy utility value of an itemset in a transaction may be higher than those of its subsets. In the past, we defined the fuzzy average utility mining to solve the above problem and proposed a two-phase method to solve the fuzzy average-utility mining problem and find high fuzzy average-utility itemsets. However, its execution is slow. In this paper, an efficient algorithm is proposed, which uses a tree structure to solve fuzzy average-utility mining. The proposed tree-structure method is compared with the previous two-phase approach. Experimental evaluation shows that the efficiency of the proposed method is better than that of the two-phase algorithm in execution time and numbers of candidates.

Group I metabotropic glutamate receptors (mGlu(1) and mGlu(5)) are promising targets for multiple psychiatric and neurodegenerative disorders. Understanding the subtype selectivity of mGlu(1) and mGlu(5) allosteric sites is essential for the rational design of novel modulators with single- or dual-target mechanism of action. In this study, starting from the deposited mGlu(1) and mGlu(5) crystal structures, we utilized computational modeling approaches integrating docking, molecular dynamics simulation, and efficient post-trajectory analysis to reveal the subtype-selective mechanism of mGlu(1) and mGlu(5) to 10 diverse drug scaffolds representing known negative allosteric modulators (NAMs) in the literature. The results of modeling identified six pairs of non-conserved residues and four pairs of conserved ones as critical features to distinguish the selective NAMs binding to the corresponding receptors. In addition, nine pairs of residues are beneficial to the development of novel dual-target NAMs of group I metabotropic glutamate receptors. Furthermore, the binding modes of a reported dual-target NAM (VU0467558) in mGlu(1) and mGlu(5) were predicted to verify the identified residues that play key roles in the receptor selectivity and the dual-target binding. The results of this study can guide rational structure-based design of novel NAMs, and the approach can be generally applicable to characterize the features of selectivity for other G-protein-coupled receptors.

We present the first space flight use of the electrostatically actuated Next Generation MicroShutter Array systems (NGMSA) as multiple celestial object selectors developed for NASA space telescope missions at the NASA Goddard Space Flight Center. The NGMSA assembly was installed in the Next Generation Far-ultraviolet Off Rowland-circle Telescope for Imaging and Spectroscopy (NG-FORTIS) and successfully launched recently from the White Sands Missile Range in October 2019. We started to investigate this electrostatic NGMSA technology at the late stages of James Webb Space Telescope (JWST) in 2009 to strategically align with requirements of larger field of view for future telescopes in space. The NGMSA in NG-FORTIS is a 128 X 64 programable 2-D addressing microfabricated shutter array while the current NGMSA system under development is a 736 X 384 large format. The new microshutter array (MSA) features several unique designs aiming at performance improvements: electrostatic actuation, thinned microshutters, better electrical wall insulation and anti-stiction surface coating. To ensure reliable operation in the space environment, NGMSA systems have passed a series of critical environment tests including acoustic, random vibration, life cycle of operation, thermal cycling, and optical contrast tests. The successful launch of the NG-FORTIS sounding rocket equipped with NGMSA demonstrates our NGMSA technology have achieved the highest NASA Technical Readiness Level 9 for sounding rocket space applications.

A esterase gene was characterized from a halophilic bacterium Chromohalobacter canadensis which was originally isolated from a salt well mine. Sequence analysis showed that the esterase, named as EstSHJ2, contained active site serine encompassed by a conserved pentapeptide motif (GSSMG). The EstSHJ2 was classified into a new lipase/esterase family by phylogenetic association analysis. Molecular weight of EstSHJ2 was 26 kDa and the preferred substrate was p-NP butyrate. The EstSHJ2 exhibited a maximum activity at 2.5 M NaCl concentration. Intriguingly, the optimum temperature, pH and stability of EstSHJ2 were related to NaCl concentration. At 2.5 M NaCl concentration, the optimum temperature and pH of EstSHJ2 were 65 ℃ and pH 9.0, and enzyme remained 81% active after 80 ℃ treatment for 2 h. Additionally, the EstSHJ2 showed strong tolerance to metal ions and organic solvents. Among these, 10 mM K+, Ca2+ , Mg2+ and 30% hexane, benzene, toluene has significantly improved activity of EstSHJ2. The EstSHJ2 was the first reported esterase from Chromohalobacter canadensis, and may carry considerable potential for industrial applications under extreme conditions.

In this study, 39 sediment samples were collected from Qilian Island, Iltis Bank, and Yongxing Island in Xuande Atoll in the South China Sea (SCS), and the microbial community structures and distribution were analyzed. The microbial community was influenced by both natural environmental factors and human activities. The abundance of genera Vibrio and Pseudoalteromonas, which are associated with pathogenicity and pollutant degradation, were significantly higher in Qilian Island than in Yongxing Island and Iltis Bank, suggesting possible contamination of Qilian Island area through human activities. Pathogenic or typical pollutants-degrading bacteria were found to be negatively correlated with most of the commonly occurring bacterial populations in marine sediment, and these bacteria were more likely to appear in the sediment of deep water layer. This co-occurrence pattern may be due to bacterial adaptation to environmental changes such as depth and contaminations from human activities, including garbage disposal, farming, and oil spills from ships. The findings of this study could help in understanding the potential influences of human activities on the ecosystem at the microbial level.

Objective: While liver biopsy is the golden standard for liver-fibrosis diagnosis, it is also invasive and has many limitations. Non-invasive techniques such as Magnetic Resonance Imaging (MRI) need to be further developed for liver fibrosis staging. This study aimed to evaluate the diagnostic accuracy of Gadolinium Ethoxybenzyl Diethylenetriamine Penta-acetic Acid (Gd-EOBDTPA)- enhanced MRI for liver fibrosis through systematic review and meta-analysis. Methods: This study comprehensively searched relevant article in PubMed, Embase, and the Cochrane Library published from 2004 to 2018 to find studies analyzing the diagnostic accuracy of Gd-EOB-DTPA-enhanced MRI for liver fibrosis. Two reviewers independently screened the retrieved articles, extracted the required data from the included studies, and evaluated the methodological quality of the studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and Summary Receiver Operating Characteristics (SROC) curve were assessed. Results: This study finally included 16 studies (n = 1,599) and selected a random-effects model based on the results of the I 2 statistic to combine them. The areas under the SROC curve for the detection of F1 or greater, F2 or greater, F3 or greater, or F4 liver fibrosis were 0.8669, 0.8399, 0.8481, and 0.8858, respectively. Conclusion: Gd-EOB-DTPA-enhanced MRI showed a good diagnostic performance for staging liver fibrosis, especially for F4 liver fibrosis.

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Additional file 1: Table S1. Test of normality (Shapiro–Wilk) for photosynthetic traits of F2 populations. The full name and units of the traits are shown in abbreviations list.

Additional file 3: Table S2. Correlations between the photosynthetic traits of F2 populations. The full name and units of the traits are shown in abbreviations list. The correlations were estimated by the linear model. *Significant at 5% level.

A method is proposed for determining the concentration of albumin (ALB) in human whole blood samples using a 3-dimensional (3D) microfluidic paper-based chip and a smart detection module. In fabricating the paper-based chip, the reaction area is implanted with bromocresol green (BCG) reagent and the device is stored in a nitrogen (N2) environment at a temperature of —15 °C until needed for use. In the detection process, 10 μl of whole blood is dropped onto the entrance area of the chip and the plasma within the sample diffuses through a separation channel into the reaction zone. A reaction is induced between the ALB in the plasma and the BCG reagent in the reaction area by heating the chip at 37 °C for 6 min. The ALB concentration is then detected using a colorimetry technique implemented on a cell phone in the form of a self-written app. It is shown that the detection results obtained for 40 pure ALB samples and 30 whole blood samples are consistent with those obtained using a traditional spectrophotometry method (R2 = 0.9837 and R2 = 0.9968). The proposed detection system thus provides a reliable tool for practical ALB determination purposes.

Exogenous H2 S donor, sodium hydrosulfide (NaHS), can influence the bleomycin-induced pulmonary fibrosis by attenuating the epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but whether NaHS affects paraquat (PQ)-induced EMT and the molecular mechanisms remain unclarified. The aim of the present study is to examine the effect of exogenous NaHS on PQ-induced EMT in human alveolar epithelial cells (A549 cells) and assess if this effect occurs through regulating transforming growth factor (TGF)-β1/Smad2/3 signaling pathway. The expressions of endogenous H2 S producing enzymes, namely cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfur transferase, were detected by reverse transcription-polymerase chain reaction and western blotting. The induced EMT was assessed by morphological and phenotypic characterizations, and the protein level of E-cadherin and vimentin were detected by western blotting. To investigate the effect of NaHS on PQ-induced EMT and potential mechanism, A549 cells were pretreated with NaHS before incubating with PQ and then evaluated by morphological changes, cell migration ability, the expression of EMT markers and TGF-β1/Smad2/3 signaling pathway related proteins. PQ significantly downregulated the expression levels of cystathionine β-synthase and cystathionine γ-lyase, but not 3-mercaptopyruvate sulfur transferase, in a time-dependent manner in A549 cells. Exogenous NaHS could significantly retard PQ-induced morphological changes and cell migration ability. Furthermore, exogenous NaHS significantly upregulated the expression of E-cadherin, whereas it downregulated the expression of vimentin. In addition, exogenous NaHS could also significantly attenuates PQ-induced TGF-β1, phosphorylated Smad2/3 proteins expression, which induced by PQ in a time-dependent manner. This study provides the first evidence that exogenous NaHS attenuates PQ-induced EMT and migration of human alveolar epithelial cells through regulating the TGF-β1/Smad2/3 signaling pathway.

Marginal water-use efficiency plays a critical role in plant carbon–water coupling relationships. We investigated the ecosystem marginal water-use efficiency (λ) of a tropical seasonal evergreen forest to (1) determine the general pattern of λ across time, (2) compare different models for calculating λ, and (3) address how λ varies with soil water content during different seasons. There was a U-shaped diurnal pattern in λ, which was higher in the early morning and late afternoon. At other times of the day, λ was lower and remained constant. Ecosystem λ was higher in the wet season than in the dry season. All three models successfully captured the diurnal and seasonal patterns of λ but differed in the calculated absolute values. The idea that λ is constant on a subdaily scale was partly supported by our study, while a constant λ was only true when data from the early morning and late afternoon were not included. The λ increases with soil water content on a seasonal scale, possibly because early morning λ remained low in dry conditions when the soil water content was low.

The X-ray integral field unit (X-IFU) is a cryogenic spectrometer for the Advanced Telescope for High ENergy Astrophysics (ATHENA). ATHENA is a planned next-generation space-based X-ray observatory with capabilities that surpass the spectral resolution of prior missions. Proposed device designs contain up to 3840 transition edge sensors, each acting as an individual pixel on the detector, presenting a unique challenge for wiring superconducting leads in the focal plane assembly. In prototypes that require direct wiring, the edges of X-IFU focal plane have hosted aluminum wirebonding pads; however, indium (In) ‘bumps’ deposited on an interface layer such as molybdenum nitride (MoN) can instead be used as an array of superconducting interconnects. We investigated bumped MoN:In structures with different process cleans and layer thicknesses. Measurements of the resistive transitions showed variation of transition temperature T(c) as a function of bias and generally differed from the expected bulk T(c) of In (3.41 K). Observed resistance of the In bump structures at temperatures below the MoN transition (at 8.0 K) also depended on the varied parameters. For our proposed X-IFU geometry (10 μm of In mated to a 1-μm In bump), we measured a minimum T(c) of 3.14 K at a bias current of 3 mA and a normal resistance of 0.59 mΩ per interconnect. We also investigated the design and fabrication of superconducting niobium (Nb) microstrip atop flexible polyimide. We present a process for integrating In bumps with the flexible Nb leads to enable high-density wiring for the ATHENA X-IFU focal plane.

Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus can provide cross-protection against distantly related strains, but they are generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are induced under subimmunogenic conditions peripherally, although their development and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated primary vaccination with peptides alone significantly induced antigen-specific Foxp3+ Treg cells, which were further expanded by repeated vaccination with unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction and expansion of antigen-specific Treg cells by peptide vaccination. Interestingly, secondary influenza virus infection significantly increased the frequency of preexisting antigen-specific Treg cells, although primary infection barely induced them. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells promoted influenza viral clearance, indicating their inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the subcutaneous prime-intranasal-boost strategy restricted the recruitment and accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell immunity. Finally, subcutaneous prime-intranasal-boost immunization with CpG-adjuvanted peptides or whole-inactivated influenza vaccines protected mice from heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg cells induced by peptide vaccines attenuate the antiviral immunity against influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic influenza protection probably by inhibiting Treg development and enhancing T cell immunity.

β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice