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Additional file 2: Figure S1. Representative images of antibody staining by immunohistochemistry are shown, which showed markedly decreased IgG deposition in the glomeruli of ALW-treated MRL/lpr mice, but no difference in IgM deposition between groups. Scale bar = 50 μm, Figure S2. Serum anti-dsDNA antibodies are not altered in MRL/lpr mice. There were no significant differences in the titers of anti-dsDNA IgM (a), anti-dsDNA IgG (b), anti-dsDNA IgG1 (c), anti-dsDNA IgG2a (d), anti-dsDNA IgG2b (e), anti-dsDNA IgG3 (f) (p > 0.05), Figure S3. Tubulointerstitial changes are attenuated in ALW-treated MRL/lpr mice. a Representative kidney sections (stained with H&E, PAS, Masson, and Ki-67) showed less tubulointerstitial damage in ALW-treated MRL/lpr mice. b Representative images of CD3, B220, and Iba-1 staining showed fewer inflammatory cells in ALW-treated MRL/lpr mice. Scale bar = 50 μm, Figure S4. Proteinuria, renal function parameters, and lymph node scores are comparable in different groups of MRL/lpr mice. The urine levels of microalbumin (a), creatinine (b), and urea nitrogen (c) were measured after 6-week treatment. The serum levels of creatinine (d) and urea nitrogen (e) were determined accordingly. At the same time point, lymph nodes were scored in all mice (f). There were no significant differences in any parameter between these four groups (p > 0.05)., Figure S5. Representative images of immunohistochemical staining demonstrated evidently decreased expressions of TGF-β1 and collagen I in kidneys of ALW-treated mice. Scale bar = 50 μm, Figure S6. Profibrotic cytokines were attenuated in serum of ALW-treated MRL/lpr mice. Serum of TGF-β1 (a), PDGF-B (b), and CTGF (c) were much lower in the mice of the ALW group. The serum levels of TGF-β1 (d), PDGF-B (e), and CTGF (f) correlated positively with renal chronicity index. *p

We provide the first study on estimating the causal effect of air pollution on body weight. Using the China Health and Nutrition Survey (CHNS), which provided detailed longitudinal health and socioeconomic information for 13,226 adult individuals over 1989-2011, we find significantly positive effect of air pollution, instrumented by thermal inversions, on body mass index (BMI). Specifically, a 1 µg/m3 (1.59%) increase in average PM2.5 concentrations in the past 12 months increases the BMI by 0.31%, and further increases the overweight and obesity rates by 0.89 and 0.19 percentage points respectively. Our paper identifies a new cause of obesity, and shed light on the morbidity cost of air pollution.

Large membrane proteins such as G protein-coupled receptors (GPCRs) are difficult for NMR study due to severe signal overlaps and unfavorable relaxation properties. We used a trimethylsilyl (TMS) group as a reporter group for 1 H NMR study of conformational changes in proteins, utilizing high-intensity 1 H NMR signals near 0 p.p.m. The β2 -adrenergic receptor was labeled with TMS groups at two cysteines located at the cytoplasmic ends of helices VI and VII. Binding of various ligands led to changes in 1 H NMR signals, which manifested that helix VI is sensitive to G protein-specific activation, whereas helix VII is sensitive to β-arrestin-specific activation. Thus, the TMS group is a useful reporter group in NMR for studying conformational changes in membrane proteins such as GPCRs.

To investigate the clinical characteristics and predictors of mortality in patients with candidemia in intensive care unit (ICU).The patients with candidemia admitted to ICU of Peking University People's Hospital from January 2010 to December 2017 were enrolled. The general clinical data, indicators related to Candidia infection and prognosis were collected, and the clinical characteristics, infection characteristics and prognosis of patients with candidiasis were analyzed. Patients were divided into death group and survival group according to hospital survival status. The differences of each index were compared between two groups. The independent risk factors of mortality in patients with candidemia were analyzed by multivariate Logistic regression analysis.A total of 95 patients (55 males) with candidemia were included, with an average age of (69.3±16.5) years, acute physiology and chronic health evaluation II (APACHE II) was 24.7±3.6, sequential organ failure assessment (SOFA) was 6.6±2.7. Candida albicans accounted for the largest proportion of Candida infections (n = 56, 58.9%). Thirty-two (33.7%) patients received inadequate antifungal therapy and 38 (40.0%) patients received inadequate source control. Fifty-five (57.9%) patients were died in hospital. Compared with the survival group, patients in the death group was older (years: 72.5±14.6 vs. 64.9±18.0, P0.05), had higher APACHE II and SOFA scores (26.6±2.2 vs. 22.1±3.6, 7.9±2.0 vs. 4.7±2.4, both P0.01), higher rate of glucocorticoid treatment (18.2% vs. 10.0%, P0.05), and higher proportion of Candida albicans and Candida glabrata (69.1% vs. 45.0%, 10.9% vs. 7.5%, both P0.05), the rate of multi-site Candida infection also significantly increased (47.3% vs. 17.5%, P0.05). Intra-abdominal infection was the primary infection site and more common in death group (49.1% vs. 35.0%, P0.05). The rates of sepsis (87.3% vs. 62.5%), inadequate antifungal therapy (49.1% vs. 10.0%), inadequate source control (60.0% vs. 12.5%) in death group were all higher than those in survival group (all P0.01). It was shown by multivariate Logistic regression analysis that APACHE II [odds ratio (OR) = 1.605, P = 0.002, β = 0.473], SOFA (OR = 1.501, P = 0.029, β = 0.406), inadequate antifungal therapy (OR = 12.084, P = 0.006, β = 2.492) and inadequate source control (OR = 7.332, P = 0.024, β = 1.992) were independent risk factors for mortality in ICU patients with candidemia.Candidemia patients were severe and had poor prognosis. APACHE II, SOFA, inadequate antifungal therapy and inadequate source control were independent risk factors of mortality.

To identify the impact of non-opioid analgesics as adjuvants to opioid on opioid consumption and its side effects, as well as the analgesic effectiveness in adult patients in the ICU.Only randomized clinical trials using non-opioid analgesics for analgesia in the ICU were included. Pooled analyses with 95% CI were determined.Twelve studies (mainly surgical and Guillain-Barre syndrome patients) were included. Non-opioid analgesics as adjuvants to opioid were associated with a significant reduction in the consumption of opioids when compared with opioid use alone at Day 1 (MD -15.40; 95% CI -22.41 to -8.39; P .001) and Day 2 (MD -22.93; 95% CI -27.70 to -18.16; P .001). Non-opioid analgesics as adjuvants to opioid were associated with a significantly lower incidence of nausea and vomiting when compared with opioid use alone (RR 0.46; 95% CI 0.30 to 0.68; P .001). Non-opioid analgesics as adjuvants to opioid significantly decreased the pain score at Day 1 (MD -0.68; 95% CI -1.28 to -0.08; P = .03) and Day 2 (MD -1.36; 95% CI -2.47 to -0.24; P = .02).Non-opioid analgesics as adjuvants to opioid reduced the consumption and the side effects of opioids in adult surgical and Guillain-Barre syndrome patients in the ICU.PROSPERO international prospective register of systematic reviews on January 23, 2017, registration number CRD42017055768.

Macroporous magnetic Fe3O4 microparticles, which might act as both drug carriers and magnetocaloric media, were expected to have broad application prospects on magnetocaloric-responsively controlled drug release systems. A kind of macroporous magnetic Fe3O4 microparticle was prepared by an organic matter assisted open-cell hollow sphere (hollow sphere with holes on shell) assembly method in this study. 1-vinyl-2-pyrrolidinone (NVP) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) were selected as the template and the binder, respectively. Ferrous ions were specifically bound to carbonyl groups on NVP and were then reduced by NaBH4. The reduced irons underwent heterogeneous nucleation and grain growth to form Fe0/Fe3O4 microspheres consisting of a lot of nano-Fe0 grains, and were then assembled into Fe0/Fe3O4 microparticles wrapped by AMPS. Results indicate that NVP binding with ferrous ions can promote a self-polymerization process and the formation of Fe0/Fe3O4 microspheres, while AMPS enwrapping around the resultant microspheres can facilitate their assembly into larger aggregates. As a result, macroporous Fe3O4 microparticles composed of several open-cell hollow Fe3O4 microspheres can be obtained under a Kirkendall-controlled oxidation. Moreover, these as-prepared macroporous Fe3O4 microparticles possess a narrow particle size distribution and exhibit ferromagnetism (Ms = 66.14 emu/g, Mr = 6.33 emu/g, and Hc = 105.32 Oe). Our work, described here, would open up a novel synthesis method to assemble macroporous magnetic Fe3O4 microparticles for potential application in magnetocaloric-responsively controlled drug release systems.

Reversible protein acetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) is an essential post-translational modification (PTM) mechanism which correlates largely with epigenetic gene regulation such as transcriptional activation, DNA replication, histone deposition, and DNA repair. Dysfunction of histone acetylation and the aberrant activity of HATs/HDACs is often associated with the pathogenesis of numerous diseases, especially cancer. Therefore, developing potent and specific analytical methods for HATs/HDACs is important for fundamental biochemical research, disease diagnosis and treatment, and drug development. This paper briefly summarizes the general design strategies used in HAT/HDAC sensors, gives a systematic overview of recent advances in the analytical methods for HAT/HDAC enzymatic analysis, classifies these methods by their biorecognition mechanisms and relative applications either in vitro or in living cells, then outlines challenges faced by these bioanalytical methods and offers perspectives on future developments.

The phytochemical investigation of the ethanol extract from the stems of Entada phaseoloides (L.) Merr (also called "Guo Gang Long") led to the isolation of eleven triterpene saponins (1-11). Their structures were elucidated by extensive spectroscopic methods including 1D- ((1)H and (13)C) and 2D-NMR ((1)H-(1)H COSY, HSQC, HMBC, HSQC-TOCSY and ROESY) experiments as well as ESIMS analysis and hydrolysis. These saponins comprised entagenic acid as the main aglycon, saccharide moieties at C-3 and C-28, and esterification of C-2 or C-3 hydroxyl group of the terminal β-d-glucopyranose unit with a monoterpenic acid. To further explain the clinical applications of "Guo Gang Long" for its anti-inflammatory effect, the inhibitory activities on the production of NO of the saponins and the related aglycon, entagenic acid (12), were evaluated in vitro. The compounds containing a free hydroxyl at C-3 of aglycon (1 and 4) and entagenic acid showed significant activities against NO production in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells with IC50 values of 25.08, 20.13 and 23.48 μM, respectively. And the three compounds could also inhibit the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and IL-8.

Background The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Material/Methods Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I2 index. Results Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of −6.87 (−10.98, −2.77; P

A molecular dynamics (MD) simulation is employed to investigate the effects of the concentration and size of silica particles on the diffusion behavior of water in poly(vinylidene fluoride) (PVDF)/SiO2 hybrid membranes. The membranes with different concentrations of SiO2 particles (class I) and with different sizes of SiO2 particles (class II) are designed and studied. The X-ray diffraction patterns and mean-square displacement (MSD) values of PVDF, the fractional free volume (FFV) characteristics and diffusion coefficients of water are discussed. The results revealed that the incorporation of silica particles into PVDF increased the polymer chain mobility and FFV in PVDF/SiO2 hybrid membranes. The diffusion coefficient of water presented an increase as the concentration of SiO2 increased (0–14.6 wt%). With the same concentration of SiO2, when the sizes of the SiO2 particles are different, the diffusion coefficient of water presented an increase first and then decreased as the size of the silica increased (radius: 0.794–1.26 nm). When the radius of the silica is nearly 1 nm, the diffusion coefficient of water in the membranes is at its largest (4.50 × 10−12 m2 s−1).

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving injuries in multiple organs and systems. Exaggerated inflammatory responses are characterized as end-organ damage in patients with SLE. Although the explicit pathogenesis of SLE remains unclear, increasing evidence suggests that dysregulation of cytokine signals contributes to the progression of SLE through the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway. Activated STAT proteins translocate to the cell nucleus and induce transcription of target genes, which regulate downstream cytokine production and inflammatory cell infiltration. The suppressor of cytokine signaling 1 (SOCS1) is considered as a classical inhibitor of cytokine signaling. Recent studies have demonstrated that SOCS1 expression is decreased in patients with SLE and in murine lupus models, and this negatively correlates with the magnitude of inflammation. Dysregulation of SOCS1 signals participates in various pathological processes of SLE such as hematologic abnormalities and autoantibody generation. Lupus nephritis is one of the most serious complications of SLE, and it correlates with suppressed SOCS1 signals in renal tissues. Moreover, SOCS1 insufficiency affects the function of several other organs, including skin, central nervous system, liver, and lungs. Therefore, SOCS1 aberrancy contributes to the development of both systemic and local inflammation in SLE patients. In this review, we discuss recent studies regarding the roles of SOCS1 in the pathogenesis of SLE and its therapeutic implications.

We estimate the impact of the Great Recession of 2007–2009 on health outcomes in the United States. We show that a one percentage point increase in the unemployment rate resulted in a 7.8–8.8% increase in reports of poor health. In addition, mental health was adversely impacted. These effects were concentrated among those with strong labor force attachments. Whites, the less educated, and women were the most impacted demographic groups.

Using mathematical method to model Web workload locality characteristics is established based on the study of entropy and coefficient of variation. Experiments show that these metrics can depict locality characteristics more properly and are much easier to use.

Tumorigenesis is the cumulative result of multiple gene mutations. The mutant proteins that are expressed by mutant genes in cancer cells are secreted into the blood and are useful biomarkers for the early diagnosis of cancer. However, some difficulties exist; for example, the same gene will express different protein mutants in different patients, and early tumors secrete only small amounts of mutant protein. Thus, the presence of mutant proteins in plasma has not previously been exploited for the early diagnosis of cancer. Proximity ligation assay is a protein-detection method that has been developed in recent years and has been widely used because of its high sensitivity. However, this approach still suffers from some shortcomings that should be addressed. In this paper, we develop a covalent-bonding tube-based proximity ligation assay (TB-PLA). The limit of detection of TB-PLA for 0.001 pM, and the method exhibited a broad dynamic range of up to seven orders of magnitude. Furthermore, we coupled the conformation-specific antibody PAb240 of p53 mutants to PCR tubes for TB-PLA. The assay was capable of detecting an approximately 500-fold lower concentration of mutant p53 in serum compared with sandwich ELISA. Thus, we demonstrate TB-PLA to be a highly sensitive and effective approach that is suitable for the early clinical diagnosis of cancer using the conformation-specific antibodies of protein mutants.

The seasonal changes in leaf particulate matter (PM) accumulation, surface wettability and micromorphology in urban tree species, including Sophora japonica (S. japonica), Platanus acerifolia (P. acerifolia) and Cedrus deodara (C. deodara), were studied during a single growing season. The three species showed distinct seasonal trends in PM accumulation, increasing from spring to autumn (or winter) even during the rainy season, but at different rates. During the study, the leaf PM retention amount of P. acerifolia, a species with ridged leaf surfaces, was significantly higher than that of S. japonica and C. deodara, species with waxy leaf surfaces. The contact angles of water droplets on leaves decreased with leaf age except on the abaxial surface of S. japonica, which remained non-wettable or highly non-wettable throughout the growing season; the decrease in the contact angle on adaxial surface of S. japonica was greater when compared with P. acerifolia and C. deodara. A significant and negative relationship existed between leaf PM retention amounts and contact angles on adaxial surface of leaves of all three species. The increase in wettability, probably caused when epicuticular wax was destroyed by mechanical and chemical abrasion, seemed to be the main factor leading to seasonal variations in leaf PM accumulation.

Eggerâ s regression figures for primary or secondary outcomes of HFNC versus COT. a Intubaiton rate. b Mechanical ventilation rate. c Escalation rate. d Mortality. (PDF 433 kb)

Table of studies excluded from the meta-analysis. (DOCX 19 kb)

Persistent halogenated organic compounds, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and dechlorane plus (DP), were determined in human serum collected in Weifang and Nanning, China, and the relationships between their concentrations and thyroid hormone concentrations were determined. The total PBDE (Σ10PBDEs), total PCB (Σ14PCBs), and total DP (ΣDP) concentrations were higher in Weifang (medians 220, 4.3, and 2.2 ng/g lipid, respectively) than in Nanning (medians 180, 1.9, and 1.5 ng/g lipid, respectively). The donors’ ages correlated with Σ14PCBs but not with Σ10PBDEs or ΣDP in Weifang. Age positively correlated with Σ10PBDEs but not Σ14PCBs and ΣDP in Nanning. The correlations between the individual PBDE, PCB, and DP congener and thyroid hormone concentrations were analyzed by stepwise multiple linear regression after log2-transforming the variables. Triiodothyronine (T3) concentrations were associated with BDE-99 concentrations and ΣDP in Weifang but with BDE-153 concentrations and Σ10PBDEs in Nanning. A positive correlation was found, for the first time, between anti-DP and free-T3 concentrations in Weifang, but free-T3 concentrations correlated with PCB-118 and PCB-170 concentrations in Nanning. Thyroxine (T4) concentrations correlated with total dioxin-like PCB concentrations in Weifang but with PCB-156 concentrations in Nanning. No significant correlations were found between the analyte and free-T4 concentrations in Weifang, but negative correlations were found between free-T4 and total dioxin-like PCB and BDE-190 concentrations in Nanning. No significant correlations were found between the analyte and thyroid-stimulating hormone (TSH) concentrations in Weifang but negative correlations were found between Σ10PBDEs and the TSH concentrations in Nanning. The correlations between the analyte and thyroid hormone concentrations followed different trends in Weifang and Nanning but were similar to those that have been found in animal and epidemiological studies.

Table of subgroup analysis of HFNC versus COT. (DOCX 18 kb)

Table of quality assessment of the included RCTs using the Cochrane Collaboration tool. (DOCX 17 kb)

Search strategy. (DOCX 16 kb)

We report here a label-free and sensitive electrochemical method for probing Citrate synthase (CS) activity based on detailed investigations into the nucleic acid-mimicking coordination polymer (CP) formed from the coenzyme A (CoA)-Ag(I) repeat units. Our biosensing approach provides an especial and significant detection mechanism: CS can catalyze the essential condensation reaction between acetyl-coenzyme A (Ac-CoA) and oxaloacetate (OAA) to form citrate and CoA; then, in the presence of Ag(I), CoA-Ag(I) CP can be in situ formed because of the strong complexation ability of thiol groups of CoA toward Ag(I). The generated CoA-Ag(I) CP attaches to graphene-modified glassy carbon electrode surface by multiple adenine bases deriving from CoA and acting as the side groups along the polymeric backbone, which displays efficient H 2 O 2 -electrocatalyzing activity. More importantly, by using the formed polymer as signal output, the process is implemented to quantitatively analyze the activity of CS. Under the optimal conditions, CS with a detection limit as low as 0.00165 U/µL could be sensitively probed with a wide linear range from 0.0033 to 0.264 U/µL. Furthermore, with the character of label-free detection, high sensitivity and excellent selectivity, this strategy offers a convenient and specific method for CS activity detection and relevant inhibitors screening, which holds a promising potential in the practical application of CS-based biochemical research, disease diagnosis and drug discovery.

A new strategy based on ionic self-assembly technology was provided for design of solid and hollow nanospheres. Solid azocomplex nanospheres were constructed by ionic self-assembly of statistical ionomer and metanil yellow. The structure of azocomplex and self-assembly behaviors were examined by a variety of techniques including 1H-NMR, 13C-NMR, DSC, FTIR, UV–vis, TEM, and elemental analysis. The azocomplex was subjected to solvent-induced self-assembly to construct a variety of morphologies. Solid polymeric nanospheres with the sizes of 50~100 nm in diameter were formed in aqueous solution. High-resolution transmission electron microscopes and X-ray energy dispersion spectrometer were used to study the morphology and composition of the solid nanospheres. The spherical and ordered structure was destroyed in DMF, and converted into membrane structure. Polymeric hollow nanospheres with azobenzene chromophores were formed in DMF/H2O mixed solvent, with 62.5% H2O in mass. The size of these hollow nanospheres was 50~120 nm in diameter.

In the paper, based on the the minimal projective bimodule resolutions of the system quiver algebras of minimal wild representation type, we calculate explicitly the dimensions of all Hochschild homology groups of the system quiver algebras of minimal wild representation type by means of combinatorics.

Nowadays, sustainable economic development is the key issue in the world. In this paper, we take Shandong Province as an example to analyze the relationship between energy use, environmental quality and economic development. Through the study, we find that the correlation between nominal income per capita and environmental quality can be shown in Kuznets inverted U-shaped curve. After 2020, with per capita income increasing, total amount of environmental pollutants will decline slowly; The relationship between per capita income and discharge amount of sulfur dioxide is consistent with EKC theory and is shown in inverted U-shaped curve, but the per capita income has no similar pattern with the other three environmental indicators; Although efficiency of energy utilization in Shandong Province increased steadily in recent years, but the rapid economic growth heavily depends on natural resources, and extensive mode of economic growth remains. Irrational industrial structure is the main cause for structural unbalance of energy consumption and environmental degradation in Shandong Province. It is argued that readjusting industrial structure and improving environment system of environmental pollution are the primary issuesin the reform.

Based on the mechanism of H2O2-mediated hydrolysis of sulfonates, two fluorescein disulfonates compounds (FS-1 and FS-2) were designed and synthesized as the highly selective and sensitive fluorescent probes for imaging H2O2 in living cells. The probes were detected with elemental analysis, IR, 1H NMR and 13C NMR. Upon reaction with H2O2, the probes exhibit strong fluorescence responses and high selectivity for H2O2 over other reactive oxygen species and some biological compounds. Furthermore, the sulfonate-based probes, as novel fluorescent reagents, are cell-permeable and can detect micromolar changes in H2O2 concentrations in living cells by using confocal microscopy.

Due to the small number of replicates in typical gene microarray experiments, the performance of statistical inference is often unsatisfactory without some form of information-sharing across genes. In this article, we propose an enhanced quantile rank score test (EQRS) for detecting differential expression in GeneChip studies by analyzing the quantiles of gene intensity distributions through probe-level measurements. A measure of sign correlation, delta, plays an important role in the rank score tests. By sharing information across genes, we develop a calibrated estimate of delta, which reduces the variability at small sample sizes. We compare the EQRS test with four other approaches for determining differential expression: the gene-specific quantile rank score test, the quantile rank score test assuming a common delta, a modified t-test using summarized probe-set-level intensities, and the Mack-Skillings rank test on probe-level data. The proposed EQRS is shown to be favorable for preserving false discovery rates and for being robust against outlying arrays. In addition, we demonstrate the merits of the proposed approach using a GeneChip study comparing gene expression in the livers of mice exposed to chronic intermittent hypoxia and of those exposed to intermittent room air.

In this article we consider testing for differentially expressed genes in GeneChip studies by modeling and analyzing the quantiles of gene expression through probe level measurements. By developing a robust rank score test for linear quantile models with a random effect, we propose a reliable test for detecting differences in certain quantiles of the intensity distributions. By using a genomewide adjustment to the test statistic to account for within-array correlation, we demonstrate that the proposed rank score test is highly effective even when the number of arrays is small. Our empirical studies with real experimental data show that detecting differences in the quartiles for the probe level data is a valuable complement to the usual mixed model analysis based on Gaussian likelihood. The methodology proposed in this article is a first attempt to develop inferential tools for quantile regression in mixed models.

When acquiring a spoken language, speakers adapt their speech organs to the articulatory manners and places and thus form a specific articulatory space. For second language (L2) learning, the acquisition process is essentially the one for the learners to approach the standard speech of native speakers in articulatory and acoustical domains by overcoming interferences from their first language. Based on this view, this study investigates learning trajectories in L2 acquisition by measuring the changes in the distance between vowel structures observed from L2 learners and the natives. The vowel structures were constructed for six Mandarin vowels from about 7,200 tokens using the Laplacian eigenmaps. Each vowel was described by a vector with the phase and amplitude of its cluster center and its standard deviation in the vowel structure, and the distance was defined by the difference of the vectors between the learners and the natives. 30 Tibetan Mandarin learners with three Mandarin proficiency levels and 10 Mandarin native speakers participated in this study. The results showed that: i) the higher the Mandarin proficiency of Tibetan speakers is, the closer the structure of their Mandarin vowels is to that of the natives, and ii) the learning trajectory of the six Mandarin vowels, except for vowel /o/, shows a monotonic tendency, that is, as the Tibetan speakers' Mandarin proficiency level increases, the distance reduces for each vowel.

Protein acetylation of histone is an essential post-translational modification (PTM) mechanism in epigenetic gene regulation, and its status is reversibly controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Herein, we have developed a sensitive and label-free time-resolved luminescence (TRL) biosensor for continuous detection of enzymatic activity of HATs and HDACs, respectively, based on acetylation-mediated peptide/DNA interaction and Tb(3+)/DNA luminescent probes. Using guanine (G)-rich DNA-sensitized Tb(3+) luminescence as the output signal, the polycationic substrate peptides interact with DNA with high affinity and subsequently replace Tb(3+), eliminating the luminescent signal. HAT-catalyzed acetylation remarkably reduces the positive charge of the peptides and diminishes the peptide/DNA interaction, resulting in the signal on detection via recovery of DNA-sensitized Tb(3+) luminescence. With this TRL sensor, HAT (p300) can be sensitively detected with a wide linear range from 0.2 to 100 nM and a low detection limit of 0.05 nM. The proposed sensor was further used to continuously monitor the HAT activity in real time. Additionally, the TRL biosensor was successfully applied to evaluating HAT inhibition by two specific inhibitors, anacardic acid and C464, and satisfactory Z'-factors above 0.73 were obtained. Moreover, this sensor is feasible to continuously monitor the HDAC (Sirt1)-catalyzed deacetylation with a linear range from 0.5 to 500 nM and a detection limit of 0.5 nM. The proposed sensor is a convenient, sensitive, and mix-and-read assay, presenting a promising platform for protein acetylation-targeted epigenetic research and drug discovery.

Chengjie Gao, Bo Li, Lufeng Xu, Fubin Lv, Guimao Cao, Huixia Wang, Fei Wang, Guanghan WuDepartment of Anesthesiology, General Hospital of Jinan Military Command, Jinan, People’s Republic ofChinaBackground: Postoperative nausea and vomiting is a common side effect of general anesthesia. In this study, we performed a meta-analysis on the efficacy and safety of ramosetron versus ondansetron in the prevention of postoperative nausea and vomiting using the most recently published randomized controlled clinical studies.Methods: PubMed and EMBASE were searched for randomized controlled clinical trials comparing the efficacy and safety of ramosetron and ondansetron. The meta-analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous outcomes are presented as the relative risk (RR) with a 95% confidence interval (CI).Results: A total of 898 patients from nine selected studies were treated with antiemetics after surgery, including 450 patients who received ondansetron 4 mg and 448 patients who received ramosetron 0.3 mg. The meta-analysis showed no statistically significant difference between the two groups with regard to prevention of postoperative nausea (PON) during different time periods in the 48 hours after surgery. When comparing the efficacy of ramosetron and ondansetron in the prevention of postoperative vomiting (POV), at various time intervals in the 24 hours after surgery, ramosetron was significantly more efficient than ondansetron: 0–6 hours (RR 0.46, 95% CI 0.24–0.92; P=0.03), 0–24 hours (RR 0.72, 95% CI 0.52–1.00; P=0.05), and 6–24 hours (RR 0.51, 95% CI 0.31–0.84; P=0.008). At other time periods between 24 and 48hours after surgery, ramosetron did not show better efficacy than ondansetron. When comparing the safety profiles of ramosetron and ondansetron, fewer side effects were recorded in the ramosetron group (RR 0.65, 95% CI 0.47–0.91; P=0.01).Conclusion: Our meta-analysis demonstrates that ramosetron was more effective than ondansetron in the prevention of early POV (0–24 hours) with fewer recorded side effects. However, our study did not reveal any statistically significant differences in efficacy between ramosetron and ondansetron in the prevention of PON or late POV (at 24–48 hours).Keywords: ramosetron, ondansetron, postoperative nausea and vomiting, general anesthesia, meta-analysis

Supplemental Digital Content is available in the text, Many studies have reported the beneficial effects of dexmedetomidine on postoperative neurocognitive function but overall evidence is not as clear. We examined this conundrum by meta-analyzing studies that used dexmedetomidine in perioperative conditions or as intensive care unit (ICU) sedation and utilized reliable neurocognitive assessment tests. The literature search was undertaken across several electronic databases including EBSCO, Embase, Google Scholar, Ovid SP, PubMed, Scopus, and Web of Science. Literature search was carried out across several electronic databases and relevant studies were selected after following précised inclusion criteria. Meta-analysis of risk differences (RDs) was carried out and subgroup analyses were performed. Twenty studies were selected from which data of 2612 individuals were used. Initial dexmedetomidine dose was 0.68 ± 0.27 and maintenance dose was 0.54 ± 0.32 in the trials. Dexmedetomidine treatment was associated with significantly lower risk of postoperative/postanesthesia neurocognitive dysfunction both in comparison with saline-treated controls (RD [95% confidence interval, CI]: −0.17 (−0.30, −0.04); P = 0.008) and comparators (−0.16 [−0.28, −0.04]; P = 0.009). In the subgroups analyses, however, there was no significant differences between dexmedetomidine and controls/comparators when studies with confusion assessment method for ICU only (RD: −0.10 (−0.22, 0.02); P = 0.1) or midazolam as comparator only (RD: −0.26 (−0.60, 0.07); P = 0.12) were meta-analyzed. Dexmedetomidine use in the perioperative conditions or as ICU sedation is associated with lower risk of neurocognitive dysfunction. There can be some impact of neurocognitive assessment method, drug interactions, and clinical heterogeneity on the overall outcomes of this meta-analysis.

Estrogen regulates thymic development and involution and modulates immune function. Despite its critical role in thymus, as well as in autoimmune disorders, the mechanism by which estrogen affects the thymus is not well understood. We previously reported that the estrogenic soy isoflavone genistein, as well as 17beta-estradiol (E2), could induce thymic involution, but genistein effects were only partially mediated through estrogen receptors. To provide insights into mechanisms of estrogenic effects in the thymus, we investigated thymic gene expression changes induced by E2 (125 ng/day) and genistein (1500 ppm in feed) in weanling mice using high-density DNA arrays. We identified several E2-responsive genes involved in thymic development and thymocyte signaling during selection and maturation. Functional characterization indicated effects on genes involved in transcription, apoptosis, and the cell cycle. This study also identified changes in several E2-regulated transcripts essential to maintain immune self-tolerance. E2 upregulated more genes than genistein, while genistein downregulated more genes than E2. Though each treatment regulated several genes not altered by the other, there was considerable overlap in the genes regulated by E2 and genistein. Changes in transcription factors and cell cycle factors were consistent with decreases in cell proliferation induced by both genistein and E2. As indicated by the regulation of non-E2-responsive genes, genistein also induced unique effects through non-estrogenic mechanisms. The specific downregulation of the CD4 coreceptor transcript by genistein was consistent with the decline of CD4+ thymocytes in genistein-treated mice in our previous study. This is the first study identifying E2 and genistein target genes in the thymus. These findings provide new mechanistic insights toward explaining estrogen action on thymocyte development, selection, and maturation, as well as the effects of genistein on prenatal and neonatal thymic development and function.

Background Postoperative nausea and vomiting (PONV) is a common complication after thyroidectomy. The aim of this article was to evaluate the efficacy of dexamethasone for prevention of PONV and pain in patients undergoing thyroidectomy. Material/Methods We performed this meta-analysis based on the QUORUM (Quality of Reporting of Meta-analyses) guidelines. Our study included randomized controlled trials (RCTs) that compared preoperative single-dose administration of dexamethasone with no dexamethasone in patients undergoing thyroidectomy. The primary outcome was occurrence and severity of PONV, and the secondary outcomes included pain, use of analgesics, and steroid-related complications. Results Seven RCTs were included, with a total of 611 patients. A statistically and clinically significant difference in the incidence and severity of PONV was found in favor of dexamethasone (SMD, 0.23; 95% CI, 0.13–0.41; P

This study is to compare the effectiveness of combinational use of bupivacaine with fentanyl (BUPI-FEN) and sufentanil (BUPI-SUF) in epidural/intrathecal analgesia for labor. Electronic databases were searched for relevant research papers published between 1985 and 2014. Meta-analyses of mean differences or odds ratios were performed and statistical heterogeneity between the studies tested by I(2) index. Ten studies recruiting a total of 728 women in labor were selected. Concentrations of the anesthetics used as mean ± sd were bupivacaine 0.115 ± 0.056%, fentanyl 0.0007 ± 0.001%, and sufentanil 0.00017 ± 0.00022%. Duration of analgesia was not significantly different between BUPI-SUF and BUPI-FEN administered mothers (mean difference [95%CI] of -33.55 [-74.94, 7.83] minutes; P = .11) under random effects. The onset of analgesia was also not significantly different between both groups (mean difference [95%CI] of -0.61 [-1.38, 0.16] minutes; P = .12). The number of neonates with Apgar score < 7 was significantly lower in BUPI-FEN group (odd ratio [95%CI] of 0.31 [0.10, 0.95]; P

The adhesion of water droplets to leaves is important in controlling rainfall interception, and affects a variety of hydrological processes. Leaf water drop adhesion (hereinafter, adhesion) depends not only on droplet formulation and parameters but also on the physical (leaf roughness) and physico-chemical (surface free energy, its components, and work-of-adhesion) properties of the leaf surface. We selected 60 plant species from Shaanxi Province, NW China, as experimental materials with the goal of gaining insight into leaf physical and physico-chemical properties in relation to the adhesion of water droplets on leaves. Adhesion covered a wide range of area, from 4.09 to 88.87 g/m(2) on adaxial surfaces and 0.72 to 93.35 g/m(2) on abaxial surfaces. Distinct patterns of adhesion were observed among species, between adaxial and abaxial surfaces, and between leaves with wax films and wax crystals. Adhesion decreased as leaf roughness increased (r = -0.615, p = 0.000), but there were some outliers, such as Salix psammophila and Populus simonii with low roughness and low adhesion, and the abaxial surface of Hyoscyamus pusillus and the adaxial surface of Vitex negundo with high roughness and high adhesion. Meanwhile, adhesion was positively correlated with surface free energy (r = 0.535, p = 0.000), its dispersive component (r = 0.526, p = 0.000), and work of adhesion for water (r = 0.698, p = 0.000). However, a significant power correlation was observed between adhesion and the polar component of surface free energy (p = 0.000). These results indicated that leaf roughness, surface free energy, its components, and work-of-adhesion for water played important roles in hydrological characteristics, especially work-of-adhesion for water.

In the paper, we first put forward an uncertain transportation model for transhipment permitted when the pessimistic value criterion is true. Secondly, balanced condition of an uncertain transportation model is presented. Lastly, we conduct the numerical experiments.

In the paper, we first put forward an uncertain transportation model for transhipment not permitted when the pessimistic value criterion is true. Secondly, balanced condition of an uncertain transportation model is presented. Thirdly, we conduct the numerical experiments. Lastly, we analyze the changes of the total cost, the total number of shipping products and the average cost of shipping one unit product with the change of the confidence level, respectively.

On the basis of the current situation of streaming media application, this article analyses the limitations of traditional streaming video service platform. Seeing that present defect oft application of traditional streaming media. On the one hand, it introduces IPV6 network into Public Video Service Platform, which guarantees the reliable transmission of streaming media. On the other hand, this paper sets out from the construction status of public video service platform, aiming to create a logical clearness and complete functions public video service platform with leisure, entertainment and study in one body on the Internet, which will provide video on demand services for online users free of charge.

In the paper, we put forward the linear weighting method for solving a type of non-differentiable multiobjective programming problem, and use it to solve an example.