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As a new type of gas-liquid microreactors, the gas-liquid mini-bubble column have potential applications. However, few studies on the flow fields in the mini-bubble column can be found at present. In this work, Particle Image Velocimetry (PIV) was first used to visually study the velocity fields, vorticity fields and bubble dynamics in the gas-liquid mini-bubble columns with column inner diameters of 1to 3 mm and mini-bubble diameters ranged from 0.7 to 1.3 mm. It is found that with the increase of superficial liquid velocity, bubbles rose from almost straight line to Z-shaped or S-shaped trajectory, and the bubble trajectory changed from 1-D to 3-D; when the bubble velocity changed, the bubble size and gas holdup decreased; bubble terminal velocity was controlled by bubble buoyancy and flow resistance, and increased slightly with bubble coalescence. These findings may provide basic reference for the design and scale-up of such mini-bubble column reactor.

We investigated the mediating effect of burnout and depression on the relationship between adolescent academic stress and sleep quality. Participants comprised 757 adolescents aged 12–18 years, who completed self-report questionnaires assessing academic stress, sleep quality, school burnout, and depression. Results showed that adolescent academic stress was negatively correlated with sleep quality, and that depression and school burnout were also negatively associated with sleep quality. Results of a multiple mediation model showed that adolescent academic stress was not only directly correlated with sleep quality, but was also indirectly associated with sleep quality through the mediating effect of school burnout and depression, as well as through the sequential mediating effect from school burnout to depression. Theoretical and practical implications are discussed.

Summary Aims Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti‐inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia‐induced neuroinflammation and to explore the mechanisms underlying its anti‐inflammation effects. Methods To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin‐1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation‐mediated neuron apoptosis in vivo and in vitro using Western blot, RT‐PCR, ELISA, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti‐inflammation mechanisms underlying the effects of BAI, the protein expression of NLRP3 inflammasomes and the expression of proteins involved in the TLR4/NF‐κB signaling pathway were measured using Western blot and immunofluorescence. Results The results indicated that BAI treatment attenuated spatial memory dysfunction in APP/PS1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation‐mediated neuron apoptosis, in APP/PS1 mice and LPS (lipopolysaccharides)/Aβ‐stimulated BV2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia‐induced neuroinflammation via suppression of the activation of NLRP3 inflammasomes and the TLR4/NF‐κB signaling pathway. Conclusion Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia‐mediated neuroinflammation during AD progression.

The traditional weak signal detection makes it difficult to detect nV level signal under strong noise background, so it proposes a new detection method of improving fractional order Duffing oscillator (IMFR-Duffing). Using variable substitution method for improving conventional fractional order Duffing equation obtained a mathematical model of IMFR-Duffing oscillator. It studied anti-noise performance of applying this mathematical model to low frequency nV level weak signal detection in the Gaussian and non-Gaussian noise background. The detection results of contrasting the IMFR-Duffing with the integer order Duffing oscillator verify the effectiveness of the proposed method, and the minimum signal-to-noise ratio (SNR) threshold is reduced by 10 dB. The simulation results show that the lowest SNR threshold of the IMFR-Dufffing oscillator reaches -73 dB in Gaussian white noise, -57 dB in Gaussian colored noise and -153 dB in symmetric Alpha stable distribution noise, and the amplitude detection has higher precision.

Manganese (Mn) is one of the most studied environmental heavy metals linked to Alzheimer’s disease (AD). However, it remains unclear whether serum Mn levels are associated with AD and mild cognition impairment (MCI, a prodromal stage of AD). We conducted a metaanalysis to analyze the serum Mn levels in patients with AD and MCI. A systematic database search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) identified 17 studies, including 836 cases and 1254 health controls (HC). Random‐effects meta‐analysis showed that patients with AD had significantly reduced serum Mn levels compared with HC subjects (SMD = −0.39; 95% CI (−0.71, −0.08); p = 0.015). MCI individuals had a tendency toward reduced serum Mn levels compared with HC subjects (SMD = −0.31; 95% CI (−0.70, 0.08); p = 0.117). A significant decrease in serum Mn levels was found in patients with cognitive impairment (including both AD patients and MCI patients) (SMD = −0.37, 95% CI (−0.60; −0.13); p = 0.002). Finally, no significant differences were observed between AD and MCI patients in serum levels (SMD = 0.24; 95% CI (−0.23, 0.72); p = 0.310). Our findings show that the serum Mn levels are lower in AD patients, and Mn deficiency may be a risk factor for AD.

Epimedium flavonoids inhibit extravascular lipid deposition during prevention of steroid-associated osteonecrosis. Desmethylicaritin is a bioactive metabolite of Epimedium flavonoids in serum. As it is well known that estrogen inhibits aidpogenesis, so we hypothesized that desmethylicaritin as a phytoestrogen might have the potential to inhibit lipid deposition. This study was designed to investigate the effect of desmethylicaritin on adipogenesis and its underlying mechanism in vitro. Adipogenesis was assessed by Oil Red O staining in 3T3-L1 preadipocytes. Bromodeoxyuridine was used to test the clonal expansion. Further, the mRNA level and protein expression of adipgenic and related factors were detected by qRT-PCR and western blot, respectively. The nuclear location of β-catenin was identified using immunofluoresence assay. Our results showed that desmethylicaritin suppressed the adipogenesis in 3T3-L1 cells in a dose-dependent manner. In addition, desmethylicaritin inhibited clonal expansion during adipogenesis. Desmethylicaritin did not affect CCAAT/enhancer binding protein δ and β mRNA expression, but decreased the mRNA expression of CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte lipid-binding protein and lipoprotein lipase. Desmethylicaritin up-regulated the mRNA expression of Wnt10b that was however down-regulated after adipogenic induction. Desmethylicaritin increased the protein expression of β-catenin both in the cytoplasm and nuclei and immunofluorescence results confirmed that desmethylicaritin increased nuclear translocation of β-catenin. Above findings implied that desmethylicaritin was able to inhibit adipogenesis and Wnt/β-catenin signaling pathway was regulated by desmethylicaritin in the process of suppression of adipogenesis. Above findings supported desmethylicaritin as a novel phytochemical agent for potential prevention of disorders involving lipid metabolism., Graphical abstract

Although several epidemiological studies have investigated the association between ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms and Alzheimer’s disease (AD) susceptibility, controversial results exist. Here, we performed a meta-analysis to assess whether ABCB1 polymorphisms 3435C > T (rs1045642), 2677G > T/A (rs2032582), 1236C > T (rs1128503) and haplotypes were associated with AD risk. Nine independent publications were included and analyzed. Crude odds ratio (OR) and 95% confidence interval (CI) were applied to investigate the strength of the association. Sensitivity analysis was conducted to measure the robustness of our analysis. A funnel plot and trim and fill method were used to test and adjust for publication bias. The results showed a significant association between the 3435C > T single nucleotide polymorphism (SNP) and AD susceptibility (CT vs. CC: OR = 1.24, 95% CI = 1.06–1.45, P = 0.01; CT + TT vs. CC: OR = 1.21, 95% CI = 1.04–1.41, P = 0.01) in the total population, as well as in Caucasian subgroup. The 2677G > T/A SNP was related to a decreased AD risk in Caucasian subgroup (TT + TA + AA vs. GT + GA + GG: OR = 0.68, 95% CI = 0.47–0.98, P = 0.04). Moreover, the ABCB1 haplotype analysis showed that the 1236T/2677T/3435C haplotype was associated with a higher risk of AD (OR = 1.99, 95% CI = 1.24–3.18, P = 0.00). Our results suggest that the ABCB1 3435C > T SNP, the 2677G > T/A SNP and 1236T/2677T/3435C haplotype are significantly associated with AD susceptibility.

Cervical cancer is the second most commonly diagnosed type of cancer and the third leading cause of cancer-associated mortality in women. The current study aimed to determine the genes associated with cervical cancer development. Microarray data (GSE55940 and GSE46306) were downloaded from Gene Expression Omnibus. Overlapping genes between the differentially expressed genes (DEGs) in GSE55940 (identified by Limma package) and the differentially methylated genes were screened. Gene Ontology (GO) enrichment analysis was subsequently performed for these genes using the ToppGene database. In GSE55940, 91 downregulated and 151 upregulated DEGs were identified. In GSE46306, 561 overlapping differentially methylated genes were obtained through the differential methylation analysis at the CpG site level, CpG island level and gene level. A total of 5 overlapping genes [dipeptidyl peptidase 4 (DPP4); endothelin 3 (EDN3); fibroblast growth factor 14 (FGF14); tachykinin, precursor 1 (TAC1); and wingless-type MMTV integration site family, member 16 (WNT16)] between the 561 overlapping differentially methylated genes and the 242 DEGs were identified, which were downregulated and hypermethylated simultaneously in cervical cancer samples. Enriched GO terms were receptor binding (involving DPP4, EDN3, FGF14, TAC1 and WNT16), ameboidal-type cell migration (DPP4, EDN3 and TAC1), mitogen-activated protein kinase cascade (FGF14, EDN3 and WNT16) and cell proliferation (EDN3, WNT16, DPP4 and TAC1). These results indicate that DPP4, EDN3, FGF14, TAC1 and WNT16 may be involved in the pathogenesis of cervical cancer.

Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and PKCζ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.

To study the effect and mechanism of (-)-Epigallocatechin-3-gallate (EGCG) on the degeneretive changes of the brain in Alzheimer's disease (AD) model mice induced with chemical drugs.AD model mice were established by subcutaneously injecting with 3% D-gal at the dose of 150 mg/kg body weight once daily for 6 weeks. From the third week, the mice of D-gal + V(E) 280 U/kg group, D-gal + EGCG 2 mg/(kg x d) group and D-gal + EGCG 6 mg/(kg x d) group were intragastricly given with 5.6% V(E) at the dose of 280 IU/kg and EGCG at the dose of 2 mg/kg x d or 6 mg/kg x d respectively after injection of D-gal. The mice of control group, D-gal + dd H2O group and D-gal + oil group were administered with same volume vehicle distilled water and soybean oil respectively. The pathological changes of the brain in AD model mice were observed by HE staining analysis, the immunohistochemical analysis of beta-amyloid (Abeta) and evaluating the expression of amyloid precursor protein (APP) in the hippocampus of mice by Western blot analysis.EGCG 2 mg/(kg x d) or 6 mg/(kg x d) 4 weeks, ig evidently released neuronal injury in the hippocampus of the AD mice induced by D-gal, and significantly reduced the express of Abeta and APP in the hippocampus of AD model mice induced by D-gal (P0.01).EGCG has a protective effect on AD model mice induced by D-gal by decreasing the expression of APP and beta-Amyloid in the hippocampus of mice.

Background: Arbidol is an antiviral drug indicated for the prevention and treatment of all types of influenza infection and some other kinds of acute respiratory infections, specifically against influenza groups A and B, and severe acute respiratory syndrome. It is used to help prevent influenza infection as long as necessary with little risk for influenza mutation rendering it less effective. Objective: The aim of this study was to compare the pharmacokinetic properties and tolerability, and to determine bioequivalence, of a newly developed generic dispersible tablet formulation (test) and a branded capsule formulation (reference) of arbidol 200 mg in healthy Chinese fasted male volunteers. Methods: This open-label, single-dose, randomized-sequence, 2-period crossover study was conducted in healthy native Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. After the study drug administration, serial blood samples were collected for 72 hours after administration. Plasma drug concentrations were determined using high-performance liquid chromatography coupled with tandem mass spectrometry. Several pharmacokinetic pararameters, including Cmax, Tmax, t½, AUC0-t, and AUC0-∞, were determined from the plasma concentrations of the 2 formulations of arbidol using noncom-partmental analysis. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration (SFDA) of the People's Republic of China. Tolerability was assessed by monitoring vital signs (blood pressure, heart rate, temperature, and electrocardiography), laboratory analysis (hematology, blood biochemistry, hepatic function, and urinalysis), and subject interview on adverse events. Results: Twenty subjects were enrolled and completed the study (mean [SD] age, 21.1 [1.1] years; weight, 64.7 [5.1] kg; and height, 172.3 [3.1] cm). Neither period nor sequence effect was observed. The main pharmacokinetic properties with the test and reference formulations were as follows: Cmax, 417.4 (107.6) and 414.8 (95.1) ng/mL, respectively (P = NS); median (range) Tmax, 0.63 (0.25–1.0) and 0.75 (0.5–1.5) hours (P = 0.035); AUC0-t, 2033.6 (564.9) and 1992.0 (483.3) ng/mL/h (P = NS); AUC0-∞, 2285.4 (597.7) and 2215.2 (604.0) ng/mL/h (P = NS); and t1/2, 6.9 (4.2) and 6.1 (5.2) hours (P = NS). The 90% CIs for the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were 91.7% to 109.7%, 91.0% to 112.8%, and 92.0% to 116.3%, respectively (all, P < 0.05), which were within the predetermined range for bioequivalence. No adverse events were found on analysis of vital signs or laboratory tests or reported by subjects in this study. Conclusion: In this study in healthy Chinese male volunteers, the dispersible tablet formulation and the 200-mg capsule formulation of arbidol met the SFDA's regulatory definition of bioequivalence based on the rate and extent of absorption.

In order to be better for color image edge detection,this paper analyze the existing problems of gradient algorithm with HSV color image characteristics and the separation by color hue, saturation and brightness information and proposes a color image edge detection method based on gradient extreme value of the local region. The algorithm extracts the edge pixels directly in the local area boundary detection window, first calculate the distance of hue, saturation and brightness between two pixels and then take their sum as the final color distance. The experimental results indicate that this method could obtain more real edges with better continuity.

Objective: This study consisted of 2 phases: development of a liquid chromatography-tandem mass spectrometry (LC/MS) method for determination of memantine in human plasma and characterization of single-dose and multiple-dose pharmacokinetic profiles of memantine in healthy Chinese volunteers using the LC/MS method. Methods: An analytic method of LC/MS for determination of memantine in human plasma was developed and validated and was applied to this singlecenter, open-label, single-dose and multiple-dose pharmacokinetic study conducted in healthy native Chinese volunteers. Subjects were randomized to receive a single dose of 5, 10, or 20 mg of memantine to study the linear characteristics of pharmacokinetics, or a multiple dose of 5 mg once daily for 14 days to study the drug accumulation. The pharmacokinetic parameters calculated included C max , T max , AUC, t 1/2 ,mean residence time (MRT), maximum steady-state plasma concentration (C ssmax ), minimum steady-state plasma concentration ( ssmin ), average steady-state plasma concentration (C ssav ), and fluctuation percentage (DF). All values were expressed as mean (SD). Sequential blood samples were collected from 0 to 360 hours for single-dose pharmacokinetic determinations after the dose on day 1; in the multiple-dose pharmacokinetic arm, the sequential blood samples were also obtained from 0 to 360 hours on day 14 after collecting the predose samples at 0 hour on days 11, 12, and 13. Memantine concentrations in plasma were determined by LC/MS method. A calibration curve was constructed by 7 memantine concentrations and processed by least-squares linear regression analysis (w = 1/x 2 ). Safety assessments, including adverse events (AEs), were performed at all study visits. Results: The LC/MS method for determination of memantine in human plasma was developed and validated. The standard calibration curve for spiked human plasma containing memantine was linear in the concentration range of 0.2 to 200.0 ng/mL. The correlation coefficient was greater than 0.9960 (n = 6). The lower limit of quantification for memantine in human plasma was 0.2 ng/mL, and the intraday and interday coefficients of variation were all lower than 15%. The mean recoveries of the 0.4, 20.0, and 180.0 ng/mL levels were 78.87%, 81.55%, and 81.98%, respectively. The coefficients of variation were all lower than 15% after being treated at room temperature for 24 hours, for 45 days at -40°, and within 3 freeze-and-thaw cycles in plasma samples. Forty native Chinese subjects (10 [5 men, 5 women] subjects per group; mean [SD] age, 21.6 [1.6] [range, 19-27] years; weight, 63.0 [7.7] [range, 52-82] kg; height, 170.0 [7.0] [range, 155-185] cm) were enrolled in the study. After singledose oral administration, the main pharmacokinetic parameters found for memantine at doses of 5, 10, and 20 mg were as follows: C max , 6.20 (0.75), 11.60 (1.95), and 25.34 (8.34) ng/mL, respectively; T max , 5.70 (1.64), 6.00 (1.33), and 6.89 (1.41) h; AUC 0-t , 486.19 (80.00), 889.32 (239.49), and 1772.91 (784.07) ng · h/mL; AUC 0-∞ , 540.05 (89.68), 932.07 (230.82), and 1853.29 (776.85) ng · h/mL; t 1/2 , 66.86 (11.75), 63.57 (12.58), and 62.06 (9.26) h; and MRT, 99.37 (16.96), 91.73 (18.16), and 89.56 (13.77) h. The main pharmacokinetic parameters found for memantine at doses of 5 mg once daily for 14 days were as follows: T max , 6.80 (2.46) h; C ssmax , 19.69 (2.00) ng/mL; C ssmin , 12.76 (2.80) ng/mL; C ssav , 16.10 (2.46) ng/mL; t 1/2 , 64.57 (15.78) h; MRT, 93.17 (23.38) h; AUC ss ,386.37 (59.00) ng · h/mL; and DF, 44.47% (15.27%). One female subject withdrew from the study after a single 20-mg dose due to an AE (dizziness and vomiting); no other subjects experienced an AE. Conclusions: In these healthy Chinese subjects, the t 1/2 and MRT values were fixed and did not increase following the increased dose, and the AUC ∞ and C max values increased following the increasing dosage of memantine. Linear pharmacokinetics was found at doses from 5 to 20 mg. The multiple-dose pharmacokinetic parameters (other than C max ) were nearly similar compared with the single-dose administration. The maximum plasma concentration of memantine after multiple-dose administration was greater than that after a single-dose administration, suggesting memantine accumulation with multiple-dose administration of 5 mg and requiring further confirmation in larger studies.

The concentration of extract of traditional Chinese medicine (TCM) is one of the important unit operations that affect the quality of the pharmaceutical products. However, there are some problems to be solved. The concentration process has the shortages of relatively high temperature, relatively long time or low efficient, some losses of active and volatile ingredients, more operation steps, easy fouling and emission of waste water. In order to solve these problems, many new technologies and installations have been developed in the past thirty years, including suspension freeze-concentration, progressive freeze-concentration, single- or multi-effect evaporation with an external natural circulating flow, on-line preventing fouling evaporation with vapor-liquid-solid flow, reverse osmosis concentration, membrane distillation, osmotic distillation, macro-porous resin adsorption etc. The system of the extract of TCM is very complex. The extract includes water and alcohol extracts. The composition of TCM is made of active and inactive ingredients. Hence, it is necessary to master the features of every concentration technologies and installations, including their merits and demerits, flexibilities, degree of maturations of techniques and so on to get a wise choice for the industry applications. New concentration technologies and installations of the extract of TCM developed recently are reviewed in this paper. The characteristics of each method are analyzed and discussed in order to guide the industry applications. At the same time, the further research directions of concentration techniques of extract of TCM are also given.